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# Wikijunior:Solar System/The Sun ## What is the Sun? {{/Coolfacts\|= 1\|!☉︎.svg "☉︎"){width="80"}\|= 2\|Sun Facts\ WARNING: Never look directly at the Sun; it can hurt and damage your eyes.\|= 3\| - If you looked at the Sun in a telescope, you could risk blindness. - The Sun is 150,000,000 km (93 million miles) away from Earth. - The Sun\'s light takes 8 minutes to reach us on Earth. That means that if the Sun blew up, we wouldn\'t see it blow up until 8 minutes later! - Every second, the Sun turns over 4 million metric tons of gas into energy. That\'s 881,849,000,000 pounds! - The Sun is as wide as 109 Earths. }} The Sun is a star --- the closest star to Earth. It is a large ball of very hot gas in a (plasma) state. The air we breathe and the helium in a balloon are both gases. It is over 5,500 °C at the surface, and much hotter at the center, about 15 million °C. The Sun is made of mostly hydrogen (70%) and helium (28%). It turns many tons of hydrogen into helium every second, thus creating heat and light. The Sun makes light and heat that warms the surface of the Earth and allows plants to grow. We can get food from plants, and we can burn wood and other parts of plants to cook, warm our houses, and make cars go. Without the Sun there could not be any life on Earth. ### How big is the Sun? The Sun is very big --- much, MUCH bigger than the Earth! Even the mighty planet Jupiter is small by comparison. It is more than a million km (109 Earths) across and contains about 99.86% of the Solar System\'s mass. If you could stand on the surface of the Sun, you would weigh 28 times as much as you do on Earth because the Sun has more mass and therefore more gravitational pull than earth. More than a million Earths could fit beneath the surface of the Sun. It doesn\'t look that big from Earth, though. That\'s because the Sun is so far away. Compared to other stars, the Sun is about average-sized. There are much bigger stars, and much smaller stars. A very thin *solar wind* of charged particles blows from the Sun all the way to the edge of the Solar System. When it gets there, the gases mix with those coming from other stars. ### What is the surface like? The Sun doesn\'t have a crust like the Earth that you can stand on. The whole Sun is made out of gases, fire, and plasma. The gas becomes thinner as you go farther from the center of the Sun. The outer-part we see when we look at the Sun is called the photosphere, which means \"ball of light\". We call it the surface of the Sun because that\'s where most of the light we see comes from. There is actually a lot of material from the Sun above the photosphere, and some of the gas is even blasted away to great distances. ## How does the sun make light and heat? The Sun is the main source of energy for the Earth. This energy is made deep inside the Sun in a process called *nuclear fusion*. Four hydrogen `<b>`{=html}atoms`</b>`{=html} are fused together to make one helium atom. Some of the leftover matter turns into energy. This is the same way energy is released in a hydrogen bomb.\ {{ }} upright=1.5\|thumb\|What is going inside the Sun. The different colors show the different regions. **Core**: The center of the Sun is very dense. It\'s about 12 times as dense as lead. That means that a gallon of the gas from the core of the Sun would weigh half a ton. It\'s also very hot --- about 15,000,000 °C. This region is where most of the nuclear reactions are taking place. **Radiative zone**: In this zone the light and heat produced in the core fight their way out towards the surface. The gases that make up the zone are very dense and keep absorbing and emitting the rays. Have you ever tried to run through water? That\'s what it\'s like for light waves in this region of the Sun. Light can\'t go very far at all before it runs into something. Then it bounces off in a different direction. The light doesn\'t get very far this way. It can take a single ray of light a million years to get out of this zone. **Convection zone**: Have you ever seen the air shimmer above a fire? Perhaps you\'ve been told it\'s because heat rises? Actually, it is the hot air that is rising. Hot gases get less dense and rise. Cold gases get denser and sink. In this zone, the gases are less dense. They behave like air in a fireplace. Gas at the bottom of the zone gets heated up from below. It rises to the surface, gives off its heat to space, and sinks again. The gas in the convection zone forms currents like those in Earth's oceans and atmosphere. The currents are called *convection cells*. ## What are sunspots? !The dark areas are sunspots Sunspots are dark spots on the Sun, but they are still brighter than lightning. Sunspots look darker than the rest of the Sun because they are a little cooler. Even though sunspots are cooler than the rest of the Sun, they are still hot --- about 4000 °C (7000 °F). Sunspots are caused by changes in the Sun's magnetic field. The magnetic field stops convection, which causes the sunspot areas to cool off and become darker. Sunspots usually form in groups which are carried around the Sun as it rotates. The number of sunspots we see goes up and down in a cycle of average length about 11 years. ## What is the Solar Atmosphere like? Above the photosphere, the Sun's gases are not very dense at all. There are two layers that we can see with special telescopes. Above that, gases stream out as *solar wind* that reaches to the edge of the Solar System. left\|thumb\|A closeup view of a sunspot and prominences ### Prominences and solar flares If you have a telescope with special filters, you can see bumps around the edge of the Sun. Each one of these is called a *prominence*. They look like volcanoes erupting. They are hundreds or thousands of kilometers long. Some are bigger than the Earth. They often seem to come from sunspots. Sometimes they get so far away from the Sun that they fly away from it. Then they are called *solar flares*. ### Chromosphere *Chromosphere* means \"color ball\". It is just above the photosphere. It is not as bright as the photosphere, and you can\'t normally see it. But you can see it just before a solar eclipse (only with special filters!). It looks like a flash of all the colors of light. Surprisingly, the Chromosphere is even hotter than the photosphere, at some parts over 20,000 °C. ### Corona !The Sun\'s corona during an eclipse *Corona* means \"crown.\" That is what pictures of the corona look like. It is just above the chromosphere. It is hotter than the photosphere, and it glows. It is made of thin gases, and blows away as solar wind. It shifts and changes, but it is hard to see, even with special telescopes. ### Solar wind At the top of the corona, some of the gas blows out as solar wind. It blows fast --- about 60 km per second (more than 100,000 miles per hour). But there isn\'t very much of it. The solar wind is strong enough to push dust and gas away from a comet to make a tail. The solar wind can even push big things. In 1960, the satellite Echo I was put into orbit. It was a large balloon. Since it was so large and light, the solar wind pushed it around in its orbit. In the future, some space craft may use the solar wind to travel between planets using *solar sails* similar to the way sailboats use the Earth\'s wind in their sails to cross the ocean. ### Heliopause thumb\|left\|Heliopause: where the solar wind hits the edge of the Solar System *Heliopause* is where the solar wind hits the wind from other stars. Near here, the solar wind slows down suddenly. In May 2005, the Voyager I spacecraft went through this region and felt a big bump. It is now just inside the heliopause. Because this happens so far from Earth, it is hard to study!\ ## What is solar weather? Did you know the Sun has weather? Earth weather is what is going on in Earth's atmosphere. *Solar weather* is what\'s going on in the Sun's atmosphere. Solar weather affects us on Earth. Solar weather (also called space weather) includes sunlight and the solar wind. Solar flares shoot a lot of very hot gas out from the Sun. If a solar flare is aimed towards Earth, protons --- subatomic particles with positive electric charge --- might be shot at Earth at high speed, and a *solar storm* could result. That could cause electrical blackouts or block radio signals. It could damage satellites in orbit. Radiation from a bad solar storm could be very dangerous for astronauts, so they must be protected. The Earth's magnetic field and atmosphere usually protect us from flares. !Northern Lights Solar flares can also cause an *aurora*. Auroras look like beautiful curtains of shimmering light. They are called Northern Lights (Aurora Borealis) if they are near the North Pole. They are called Southern Lights (Aurora Australis) if they are near the South Pole. Solar weather affects other planets, too. We have pictures of auroras on every planet except Mercury and Pluto. Just like we can get Earth weather forecasts, we can get Solar weather forecasts. Forecasters study the Sun to figure out when flares will happen. They try to tell when solar storms will hit Earth. They also try to tell when solar storms will go to other parts of the Solar System. Next Topic: Mercury ## The life cycle of a star upright=3\|thumb\|center\|Life Cycle Of Our Sun A forming sun\'s life starts out as a nebula; this is a cloud of gas made up mostly of hydrogen. Over time the nebula contracts; its core becomes more and more compact and hotter until it can fuse hydrogen to helium. This fusion becomes its power source. After this, the star will look very much like our sun. They fuse hydrogen atoms together to make helium atoms. !A comparison between the sizes of the Sun as it is now, and how it will be as a red giant. After billions of years, this star will die. The star will exhaust its supply of hydrogen in its core, so that there will no longer be any source of heat to support the core against gravity. The core shrinks, and the hydrogen starts to burn in a shell around the core. The outer layers of the star swell and cool, creating a red giant. This is all with an ordinary star and will be the life cycle of our sun, although the process may vary from star to star. When our sun becomes a red giant it will consume Mercury and Venus, and possibly the Earth. The sun will then begin a cycle of expansion and contraction, puffing away its outer atmosphere as the solar system becomes a planetary nebula. Once the sun can not longer sustain fusion, it will collapse down and condense into a white dwarf star. At this stage the light it emits is the left over energy of our dead sun, radiating the residual heat until eventually the white dwarf cools and darkens. ## Exploration of the Sun Early space probes designed to collect information about the sun were NASA\'s Pioneers 5 through 9 and the Helios 1 and 2. Those were in the 1950s, 60s, and 70s. They collected a lot of data about the Sun. Other projects observed the Sun from Earth orbit, such as a Japanese satellite launched in 1991 called Yohkoh, which means *Sunbeam* in English. It told scientists more about solar flares, and activity on the sun\'s surface. Thanks to Yohkoh, they knew more about how to classify solar flares, and whether or not they will cause electrical disturbance on Earth or not. Two important missions to study Sun are called the *Solar and Heliospheric Observatory* (SHO) and the *Solar Dynamics Observatory* (SDO). They have taken many pictures of the Sun, along with discovering many comets near the Sun. All of these observations were across the Sun\'s equator. The first space probe to observe the Sun\'s poles was named *Ulysses*, after a famous Greek king who traveled on a very, very long voyage. The Ulysses probe went all the way to Jupiter before approaching the Sun. It took a famous picture of the comet *Shoemaker-Levy-9* colliding with Jupiter. !The Shoemaker-Levy 9 fragments falling back on Jupiter. ## References NASA. The Chromosphere --- 1\ Col, Jeananda. Enchanted Learning/Zoom Astronomy 2 1998--2005\ `<i>`{=html}Usborne Internet-Linked Science Encyclopedia`</i>`{=html}, Usborne Publishing Ltd. 3\ Dickinson, Terrence. `<i>`{=html}The Universe and Beyond`</i>`{=html} . Firefly Books \ ar:ويكي الأطفال:نظام شمسي/الشمس bs:Wiki junior Sunčev sistem/Sunce de:Wikijunior Sonnensystem/\_Die_Sonne es:Wikichicos Sistema Solar/El Sol nl:Wikijunior:Zonnestelsel/Zon zh:Wikijunior:太阳系/太阳 fr:Wikijunior:Système solaire/Le soleil
# Wikijunior:Solar System/Mercury !Mercury from the MESSENGER spacecraft. \_\_TOC\_\_ {{-}} ## What is Mercury? {{/Coolfacts\|!☿.svg "☿"){width="80"}\|*Mercury Facts*\| - Mercury orbits around the Sun faster than any other planet. - Mercury\'s surface temperature can vary from -180°C (-300°F) to 430°C (800°F). On Earth, the hottest temperature was recorded at 58°C (136°F). - There may be ice on the top and bottom of Mercury. - Mercury is the smallest planet in the solar system. - The ancient Romans named a day of the week after the planet Mercury; even today, in French Wednesday is *Mercredi*, in Spanish *Miércoles*. }} Mercury is the closest planet to the Sun. It is a *terrestrial planet*; that means a planet made from rock like Earth. It does not have a gas atmosphere, so there is no weather. For a long time, only one spacecraft, Mariner 10, had visited Mercury. In January 2008, the MESSENGER spacecraft went by Mercury. It has gone by Mercury two more times, and has started to go around the planet in 2011. ## How big is Mercury? !Comparison of the size of Mercury to the Earth Mercury is 4879 km across. Mercury\'s diameter is just less than half the diameter of the Earth. It is the smallest planet in the Solar System. Only dwarf planets like Pluto are smaller. Because Mercury is much closer to the Sun than the Earth, it can only be seen just after the sun goes down at night or shortly before it rises in the morning.\ ## What is Mercury\'s surface like? !View of the surface of Mercury Mercury has craters like those on the Earth\'s moon. The largest crater on Mercury is the *Caloris Basin*. It is about 1300 km wide. It was created by a huge asteroid hitting Mercury. The asteroid was probably 100 km wide, but it hit Mercury\'s surface so hard that it made a much bigger hole. {{ }} The surface also has big cliffs called *scarps*. They were made long ago when Mercury cooled down. It shrank, causing the surface to get wrinkled in some places. This wrinkling created the scarps. There may also be ice on the top and bottom of Mercury. Like the Earth, these areas (called *poles*) don\'t get much warmth from the Sun. Any ice there won\'t melt. It is very hot during the day (over 400°C) because Mercury is so close to the Sun. At night it is very cold because Mercury loses almost all its heat since there is almost no *atmosphere* to keep the warmth there. The temperature can fall to almost -175°C. ## How long is a day on this planet? Mercury *rotates* (spins around) much more slowly than the Earth. It takes Mercury 58 days to spin once as viewed from a distant star. Because Mercury orbits the sun very quickly, a day on Mercury lasts longer than 58 days. If you were standing on Mercury at the equator and timed how long it took the sun to go from directly overhead to sunset to sunrise and then rise directly overhead again, it would take 176 Earth days. These long days and nights allow for the temperatures to rise as high, and fall as low, as they do. ## How long is a year on Mercury? !Mercury from Mariner 10 Mercury has the shortest year in the Solar System. It is about 88 Earth days long. It used to be believed that the same side of Mercury always faced the Sun. In order for this to be true, Mercury would have to take the same amount of time to rotate (spin around) as it does to circle the sun. From watching it carefully we now know that Mercury\'s rotation is somewhat faster than its orbit. Because of the way the orbit and rotation work together, on Mercury, a day (the time from one sunrise to the next) is actually almost twice as long as a year. ## What is Mercury made of? The center of Mercury is made of iron in partly-molten (liquid) form. We know that there is iron at the center because the planet generates a magnetic field. It contains more iron for its size than any other planet in the Solar System. The rest of Mercury, its thick crust, is made of a special type of rock called *silicate rocks*. There are craters near the poles that are constantly in shadow. Some of these craters contain ice. There is a huge crater on Mercury called Caloris Basin. It was formed when a comet hit the planet and *lava* or molten rock filled the impact crater. The round wall of this crater is over 2km tall. ## How much would Mercury\'s gravity pull on me? If you were on Mercury, it would pull you down less than half (38%)as much as the Earth. An item that weighs 100 pounds on Earth, would only weigh 38 pounds on Mercury. ## Who discovered Mercury? !A computer-generated simulation of MESSENGER orbiting Mercury. Nobody really knows who first discovered Mercury, but the first known recorded observations of it are from tablets in Assyria about three and a half thousand years ago, in the 14th century BCE. This was probably something like an informational article about Mercury\'s movements. In these tablets, Mercury is called (in translation) *The Jumping Planet*. Almost every ancient civilisation had their own written records and names for Mercury. In 1639, an Italian astronomer named Giovanni Zupi observed that Mercury has phases, like the phases of the Moon, as it orbits around the Sun. This is evidence that it *does* orbit around the Sun, an idea that was fairly new at the time, suggested less than a hundred century earlier by Copernicus. Before the twentieth century, it was a mystery to all the astronomers how long it took for Mercury to rotate. They solved this mystery in 1962, when some astronomers sent radar signals to Mercury, which then bounced back to Earth: it takes 59 days for Mercury to rotate. It isn\'t easy to sent a space probe from Earth to Mercury, because Mercury is much closer to the Sun and therefore orbits the Sun much faster than Earth does. So a space probe would have to burn a lot of fuel to match its speed with Mercury, in order to orbit---or land on---the planet. In 1973, a space probe Mariner 10 was sent to take measurements of Mercury and map its surface. Because orbiting Mercury would be so expensive, Mariner 10 orbited the sun instead, and would take pictures each time it got close enough to Mercury. Unfortunately, when Mariner 10 finally ran out of fuel, it had only mapped about 45% of the surface. However, it also discovered that Mercury has an iron-rich core and a magnetic field. 29 years later, in 2004, another probe was launched, named MESSENGER. MESSENGER stands for MErcury Surface, Space ENvironment, GEochemistry, and Ranging. MESSENGER followed a complicated path that would slowly match speeds with Mercury without using much fuel. It passed by Mercury three times, and finally settled into orbit around Mercury more than six years after it was launched. By March 2013, MESSENGER had mapped 100% of the surface of Mercury. ## Who is this planet named after? !A statue of Mercury. In Roman mythology, Mercury (Latin *Mercurius*) was the messenger of the gods. He wore a hat and sandals with wings on them, allowing him to travel around the world very quickly. The planet Mercury was named after him because it moves faster than any other planet in the Solar System. It moves nearly 48 km *every second*! (Of course, the Romans didn\'t know that, but they could see how fast it moved across the sky.)The Greeks called this god Hermes. Next Topic: Venus {{-}} ## References NASA\'s Solar System Exploration1\ Arnett, Bill. The Nine Planets2\ Worldbook Online 3\ Worldbook@NASA, \"Mercury\"4\ NASA Planetary Fact Sheet 5\ Hamilton, Calvin J. . Solarviews.com, \"Mercury\" 6\ Encyclopedia Mythica, \"Mercury\" 7\ Col, Jeananda. Enchanted Learning/Zoom Astronomy 8 1998-2005\ `<i>`{=html}Usborne Internet-Linked Science Encyclopedia`</i>`{=html}, Usborne Publishing Ltd. 9\ Dickinson, Terrence. `<i>`{=html}The Universe and Beyond`</i>`{=html} . Firefly Books \ ar:ويكي الأطفال:نظام شمسي/عطارد bs:Wiki junior Sunčev sistem/Merkur de:Wikijunior Sonnensystem/\_Merkur es:Wikichicos Sistema Solar/Mercurio nl:Wikijunior:Zonnestelsel/Mercurius pl:Wikijunior:Układ Słoneczny/Merkury zh:Wikijunior:太阳系/水星
# Wikijunior:Solar System/Venus ```{=html} <div style="float:right; border:2px solid #aaaaaa; width:250px; margin-left:0.2em; padding:0.4em"> ``` !♀.svg "♀"){width="80"} **Venus Facts**: - Venera 7, the first space probe to land on Venus, was destroyed by the hostile conditions on Venus after only 23 minutes. - Almost all of the surface features on Venus are named after women. - A day on Venus is equal to 117 days on Earth. - It has been proposed that some microbes could live in Venus\'s clouds. ```{=html} </div> ``` Venus is the second closest planet to the Sun. It is a *terrestrial planet*. This means that we think it was created in a similar way to our planet Earth and is made of rock. !Venus. You can\'t see the surface in this picture; the white is the clouds. \ {{ }} ## How big is Venus? !Earth and Venus Comparison Venus is only slightly smaller than the Earth. This is one reason why Venus is sometimes thought of as Earth\'s \"twin\". Venus has a *diameter* of about 12,100 km. It has also been visited by many probes.\ ## What is the surface like on this planet? !Maat Mons on the Surface of Venus, by radar imaging The surface of Venus is very different from the surface of the Earth. It is very dry and hot enough to melt lead. The pressure on the surface is very high. It is the same pressure as being 1 km (3,280 feet) below the surface of the sea on Earth. !Channels on the surface of Venus, looking like river channels on Earth Channels that look like rivers have formed on Venus. Scientists think these channels are formed from erupting lava. The lava flows along as it cools down, creating the channels. One feature only Venus seems to have is unusual volcanoes called *arachnoids*. These are volcanoes that have formed differently from other volcanoes we have found in the Solar System. We don\'t know exactly how they were formed. Venus also has volcanoes like those on Earth. Parts of the surface of Venus look something like continents. The largest of these areas is called *Ishtar Terra* (land of Ishtar, from the Babylonian goddess who was similar to Venus). Deep basins like those under the Earth\'s oceans have also been discovered. On Venus, though, they have no water. Features like mountain ranges and meteor craters have also been found on Venus. One of the highest mountains on Venus, *Maxwell Montes*, is about 11 km taller than Mount Everest, the highest mountain on Earth. On the night side of the planet, there is a strange effect called *Ashen Light*. For some reason, the dark side of Venus has a subtle glow. There are various theories about this. One of the earliest theories --- now disproved, of course --- was that there were aliens on Venus and they were celebrating a new Venusian emperor. Currently, one of the more believed ones is this: There is a high concentration of carbon dioxide. When it is hit by the ultraviolet rays of the sun, they change into carbon monoxide and oxygen, and emit green light. The entire chemical procedure is . !The Venera 13 Lander as depicted on a stamp, which made scientific measurements and sent back pictures from the surface of Venus ## How long is a day on Venus? Venus *rotates* (spins around) even more slowly than Mercury. One full rotation of Venus takes about 243 Earth days. Venus also rotates in the opposite direction to most of the other planets in the Solar System. One day on Venus, from noon to noon, depends on the length of the year as well as the rotation time, and is about 117 earth days. ## How long is a year on Venus? One year on Venus is almost 225 Earth days long. This is less time than it takes Venus to rotate on its axis and less than two Venus days. ## What is Venus made of? The surface of Venus, its crust, is covered in nothing but rock. But, the core of Venus is made of nickel-iron. The atmosphere around Venus is very thick and is made of carbon dioxide, nitrogen, and poisonous gasses that create high pressure and trap in heat. ## How much would Venus\'s gravity pull on me? If you were on Venus, it would pull you down almost as strongly as Earth. The atmosphere exerts a pressure at the surface more than 90 times Earth\'s normal sea-level pressure. ## Who discovered Venus? Because Venus is closer to the sun than we are on Earth, we always see it close to the sun in the sky. So it only appears for us just before sunrise in the eastern sky, or just after sunset in the western sky. Many cultures thought Venus in the morning and Venus in the evening were two separate things. The ancient Romans called the evening object Venus (after the goddess of love) and the morning object *Lucifer* (which means *light bearer* --- a servant who walked ahead of the sun\'s chariot with a torch, to light the way). Nobody knows who first thought the two were a single object. The first known *written* description of them as one object was the Venus Tablet of Ammisaduqa, from about three and a half thousand years ago --- 1581 BCE. !A map of where the Veneras 9-14 and Vegas landed. About three thousand years later, in 1610, Italian astronomer Galileo Galilei used a telescope to observe that Venus has phases, just as the moon does. Phases happen because only the side of Venus (or of the Moon) facing the Sun is lighted. The phases of Venus supported the theory of Copernicus that the planets go around the Sun. Then, a few years later in 1639, an English astronomer named Jeremiah Horrocks observed a *transit of Venus*. That\'s what it\'s called when Venus passes right between the Earth and the Sun, so that Venus is visible from Earth during the day as a tiny dot passing across the Sun. In 1761 a Russian astronomer, Mikhail Lomonsov, watching another transit of Venus, saw that Venus has an atmosphere. Not much more was discovered about Venus until the 1920s. Then, a United States astronomer, Frank Ross, observed Venus using ultraviolet light --- the light that causes sunburn --- and for the first time saw the structure of the clouds on Venus. However, there is only so much that can be learned about Venus by looking at it from Earth. The first successful pictures of Venus by a space probe were taken by Mariner 2 in 1962. Mariner 2 was the first space probe successfully sent to observe another planet. It showed two important things: Venus has practically no magnetic field, and Venus has temperatures of 490 to 590 K --- that\'s as hot as the inside of a working oven on Earth! !The first written record of Venus. It describes Venus\' movement over 21 years. ## Who is this planet named after? Venus is named after the Roman goddess of love. Sometimes it can be seen shining brightly just before dawn or just after sunset, when it is called the Morning Star or Evening Star. Some people, like the Aztecs and the Greeks, gave Venus two names -- one for the morning and one for the evening. Because Venus and the Earth are the same size, scientists call Venus \"Earth\'s sister planet\". For a long time most scientists thought that Venus had plants, animals, and possibly even people. However because Venus is so hot we now know that it is impossible for anything to live there. ## How long would it take people to get there? It could take around a year and a half to get there. But it is very unlikely someone would go to Venus.\ ## References - Volcano World, \"Lava Flows\"1\ - Astronomy Picture of the Day 2\ - Alder Planetarium3\ - Mount Everest 4\ - Windows to the Universe5\ - NASA\'s Solar System Exploration6\ Arnett, Bill. The Nine Planets7\ - Worldbook Online 8\ - Worldbook@NASA, \"Mercury\"9\ - NASA Planetary Fact Sheet 10\ - Hamilton, Calvin J. . Solarviews.com, \"Mercury\" 11\ - Encyclopedia Mythica, \"Mercury\" 12\ - Col, Jeananda. Enchanted Learning/Zoom Astronomy 13 1998-2005\ - `<i>`{=html}Usborne Internet-Linked Science Encyclopedia`</i>`{=html}, Usborne Publishing Ltd. 14\ - Dickinson, Terrence. `<i>`{=html}The Universe and Beyond`</i>`{=html} . Firefly Books \ Next Topic: Earth ar:ويكي الأطفال:نظام شمسي/الزهرة bs:Wiki junior Sunčev sistem/Venera de:Wikijunior Sonnensystem/\_Venus es:Wikichicos/Sistema_Solar/Venus it:Wikijunior_Il_sistema_solare/Venere nl:Wikijunior:Zonnestelsel/Venus pl:Wikijunior:Układ_Słoneczny/Wenus zh:Wikijunior:太阳系/金星
# Wikijunior:Solar System/Earth Earth is the planet we live on. It is the only planet in the Solar System with liquid water on its surface. It is also the only planet we know to have *life* on it. Earth is also known as Terra. ```{=html} <div style="float:right; border:2px solid #000000; width:250px; margin-left:0.2em; padding:0.4em; background-color:#f0f0ff"> ``` !🜨.svg "🜨"){width="80"} **Earth Facts** - The Earth is the only planet we know to have life on it (such as ourselves.) - There is oxygen on Earth, and oxygen is necessary for life. - The Earth is the third planet from the Sun. - The Earth is the only planet we know that has liquid water on the surface, but scientists are trying to find others. - The Earth\'s axis is tilted which is why we have four different seasons. - The Earth is 4.6 billion years old. - The Hoba meteorite in Namibia is the biggest known meteorite to crash on Earth in one piece. ```{=html} </div> ``` !A picture taken by Apollo 17, a space mission. \ == How big is the Earth? == The Earth is nearly 13,000 km wide. It\'s the largest *terrestrial planet* in the Solar System. The Earth\'s mass is about 5,973,700,000,000,000,000,000,000 kg. That\'s a lot. But it is little compared with Jupiter (319 Earths) and tiny compared with the Sun (335,789 Earths) or other stars! ## What is the Earth\'s surface like ? The Earth\'s surface is made of rock. Most of it is underwater, but not all. Islands of rock rise up out of the water. The biggest islands are called *continents*, of which there are seven: North America, South America, Europe, Asia, Africa, Australia, and Antarctica. The largest bodies of water are called *oceans*, of which there are five: Pacific, Atlantic, Indian, Arctic and Antarctic or Southern. thumb\|right\|upright=2\|Anawhata beach, west of Auckland, New Zealand The Earth\'s surface is made up of huge *plates*. They are like huge jigsaw pieces made of rock. These plates move very, very slowly, carrying the continents with them. They can rub beside each other, push against each other, or even move away from each other. If there are gaps between them, hot molten rock can rise up and make *volcanoes*. Where the plates rub or push against each other, *earthquakes* may happen. When two plates push each other\'s rock upwards, *mountains* are formed. !Zabriske Point, Death Valley National Park, CaliforniaEarth has many kinds of *environments*. It is cold and icy in places like Antarctica. It is hot and dry in deserts like the Sahara in Africa and Death Valley in the United States. It is cold and dry in deserts like Siberia in Russia. Where it is warm and wet, rainforests grow. ## Why is there life on Earth? Wherever we have looked on Earth, we have found living things. They may be very small, like *bacteria*, but they are there. We have found bacteria where it is very cold, very hot, very deep, very high or very dark. !Galileo being deployed after being launched by the Space Shuttle *Atlantis*.jpg "Galileo being deployed after being launched by the Space Shuttle Atlantis") What all living things on Earth seem to need is *liquid water*. Wherever you can find some water, there are almost always living things there too, even if you can\'t see them. If we find liquid water somewhere else in the Solar System, scientists think we might find some living things there too. If we don\'t, there is always the rest of the universe to explore! There is another possibility. All the living things we know need liquid water. But maybe somewhere else there are living things that don\'t need water. Perhaps we will need to learn how to recognize them. \ == What about the Earth\'s moon? == Earth has one moon we call\... the Moon!  Sometimes it is called by its name in Latin, *Luna*, so we don\'t get confused with other planets and their *moons*. The Moon has also been called Selene (pronounced \"suh-LEE-nee\") which is Greek for moon and was the name of the Greek moon goddess. Recently we have also found some other objects that are said to go around the Earth. The largest one, called Cruithne (pronounced \"cru-EE-nyuh\"), is three miles wide. In fact, it *orbits* (goes around) the Sun in a way that makes it keep coming close to Earth. There are various ideas about where the Moon came from (no-one was around to see it happen, after all), but the most widely held theory is that when Earth was young, a large body hit Earth and split off a section of the Earth that is now the Moon. ## How long is a day on this planet? A day on Earth is 24 hours long. That\'s daytime *and* night time. A 24 hour day is how long it takes the Earth to spin around once. On the half of the Earth that is facing the sun it is daytime and on the half of the Earth that is facing away from the sun it is nighttime. The spin of the earth is also the reason why the sun appears to rise in the east and to set in the west. Although it looks like the sun is moving from the surface of the earth, it is really the surface of the earth that is moving. The reason we do not feel like we are spinning is because the earth is so big compared to the size of people. Also, the Earth is tilted at about 23°, so there are times that the North or South pole is always facing or turned away from the sun. If you live at one of the poles of Earth it can be light or dark throughout the whole day!\ {{ }} ## How long is a year on this planet? A year on Earth is about 365 and 1/4 days long. That\'s how long it takes the Earth to orbit the Sun once. Approximately every four years we have a leap year. A leap year contains an extra day in our calendar on February 29th in order to account for the 1/4 of a day left over each year. ## What is the Earth made of? ![](Inside_the_Earth.PNG "Inside_the_Earth.PNG")\ When a planet is made of rock, we call its surface the *crust*. Below the Earth\'s crust is hot rock, some of which is molten. It is in a layer called the *mantle*. The hot molten rock is what comes out of volcanoes. It\'s then called *lava*. Under the mantle is the *core* of the Earth. We think it is made from solid iron and nickel, surrounded by hot molten iron. The temperature there is very very hot! The Earth\'s crust is very thin compared to the mantle and the core. But it is very thick to us. Nobody has drilled all the way through it yet. Even the deepest underground mines are far away from reaching its deepest base. ## How much does the Earth\'s gravity pull on me? It\'s easy to find your weight on Earth by using a scale. You have weight because the Earth\'s **gravity** pulls you towards its center. Normally, the ground or the floor get in the way, making you feel \'stuck\' to them. There are several kinds of scales: !A pan balance{width="160"} 1) Comparing of 2 masses (weights). You put the thing(s) you want to weigh on one pan (like some marbles), and then you put several \"weights\" on the other pan until the pointer shows that both pans have equal weights on them. Then you look at the pan with the known weights on it, and add them all up. The total is the mass of the thing(s) you want to weigh. !A spring balance{width="60"} 2) A spring balance usually has a hook on it, with a pan. You put the thing(s) you want to weigh on the pan, the spring is pulled, and the greater the weight, the further the spring is pulled. That distance, calibrated in pounds or kilogram (or whatever), is usually shown either on a dial or on a linear scale. !electronic balance{width="100"} 3) There are also electronic scales that give a properly calibrated reading---grocery stores, for example, use these. NOTE: **Gravity** varies slightly depending on the location where you want to get the weight; spring balances and some electronic scales can, in theory, read slightly different weights at different places because of that, but usually in practice that difference is too small to be noticed. But, because the balance type of scales work differently from the spring or electronic types, they will always read the true, correct mass. They would even give the same mass on the Moon, where gravity is much less than on Earth. ![](Isaac_Newton_cartoon.png "Isaac_Newton_cartoon.png") **Did you know?** that *Sir Isaac Newton* was the first person to realize that the force pulling you down to the ground was the same force that keeps the planets going around the Sun? The story goes that he thought of this when he saw an apple fall from a tree. Gravity is a very important force. As well as keeping you firmly stuck to the Earth, it keeps the Moon going round the Earth, The Earth going around the Sun and the Sun going around the center of the Milky Way **galaxy**. Gravity also makes stars and planets a nice round ball shape. In fact without gravity there wouldn\'t even *be* a Sun, Moon or Earth because the material that they are made of would just float away into space. \ == Who is it named after? == !The Earth seen from the Moon The word earth is used for both planet Earth and soil. Other names had been used for Earth such as Gaia, Tellus and Terra. Gaia is the Greek goddess (meaning Mother Earth) and Terra is the Roman name of the same goddess. Tellus is the Latin for \"Earth\", many scientific words dealing with Earth will be derived form Latin. Next Topic: Moon ## References \"It is also the only planet we know\...\" 1 2\ \"The Earth is nearly\...\" 3 4\ \"The Earth\'s mass\...\" 5\ \"Earth\'s surface is made of\...\" 6 7 ar:ويكي الأطفال:نظام شمسي/أرض bs:Wiki junior Sunčev sistem/Zemlja de:Wikijunior Sonnensystem/ Erde es:Wikichicos Sistema Solar/La Tierra fr:Wikijunior:Système_solaire/La_Terre nl:Wikijunior:Zonnestelsel/Aarde pl:Wikijunior:Układ_Słoneczny/Ziemia zh:Wikijunior:太阳系/地球
# Wikijunior:Solar System/Moon {{/Coolfacts\|= 1\|!☽︎.svg "☽︎"){width="80"}\|= 2\|Moon Facts\|= 3\| - When we look at the Moon from Earth, we always see roughly the same side. Until Luna 3 sent back photos in 1959, no-one knew what the other side looked like. - The Moon is nearly twice as big as ../Pluto/. - The \"Man in the Moon\" isn\'t always seen as a man. People from India see an old woman with a spinning wheel. People from Mexico see a rabbit! - The Moon isn\'t that small compared to the Earth - it\'s actually the largest moon in the solar system, relative to the size of its planet. Sometimes the Earth and Moon together are called a *binary* or *double planet system*. - The Moon is the fifth largest moon in the solar system. - In 2002, another object appearing to be an asteroid was observed orbiting around the Earth. Later it was found to be a rocket booster. }} ! The Moon is our nearest neighbour in space. ## How big is the moon? !Comparison of the size of the Moon and the Earth Most of the planets in the Solar System are much bigger than their moons, but the Earth and the Moon are much closer in size. The Moon is just under 3,500 kilometers (km) wide. That\'s over a quarter of the size of the Earth (about 12,600 km wide) as you can see in the picture below. Because of this, the Earth and Moon together are sometimes called a *binary* or *double planet system*. {{ }} ## What is the moon\'s surface like? !Astronaut Harrison Schmitt collecting rocks from the Moon during the Apollo XVII mission. !A map of the moon. The Moon has no atmosphere. It also has no liquid water on its surface. During the day it becomes very hot, but at night it is icy cold. A person visiting the Moon needs an air supply and a special suit. The Moon has many *craters* on its surface. The largest one is called the *South Pole-Aitken Basin* and is roughly 2500 km across. We think nearly all the craters on moons or planets were made by huge rocks hitting them a long time ago. These collisions are called *impacts.* Some of the craters on the Moon look as if they have rays coming out of them. These rays are rocks thrown across the Moon by the impacts that made the craters. Some of the craters around the poles of the Moon may have ice in them. There are also darker areas called *maria* (said \"MARR-ee-ah\"). These are large pools of lava that cooled a long time ago. Most maria are on the side of the Moon we see from Earth. The lighter areas on the Moon are highlands. ## How long is the Moon\'s revolution? The Moon takes just over 27 Earth days to *rotate* (rotate means spin around) once. ## How long is a year on the moon? The Moon also takes just over 27 days to *orbit* (move around) the Earth. This is why we always see the same side of the Moon when we look from the Earth. We call this side the *near* side. The other side we call the *far* side. In 1959, a probe called *Luna 3* sent back pictures of the far side. That was the first time anyone saw what it looked like. ## What is the Moon made of? The surface of the Moon is made of rocks and dust. The outer layer of the Moon is called the *crust*. The crust is about 70 km thick on the near side and 100 km thick on the far side. It is thinner under the maria and thicker under the highlands. There may be more maria on the near side because the crust is thinner. It was easier for lava to rise up to the surface. We think the Moon has a small *core* (center) about 300 km across. The core is composed of solid iron. Because the core is solid, the Moon does not have its own magnetic field. ## How much would the Moon\'s gravity pull on me? If you were on the Moon, it would pull you down about a sixth as much as the Earth does, so you\'d weigh a sixth as much. So would anything else. That\'s why it was much easier for the astronauts visiting the Moon to pick up rocks there. ## Who is the moon named after? !The goddess Diane, the goddess of the Moon in Roman mythology The names *Moon* and *month* both come from the ancient Greek name for the Moon, *Mene*. There have been other names for the Moon, like *Selene* and *Luna*. Selene was the Greek goddess of the Moon. Luna was the Roman goddess of the Moon. The Roman people also associated their goddess Diana with the Moon. ## Who discovered the Moon? Ancient Greece and Ancient China noted over 2000 years ago that the light from the Moon is reflected from the Sun. Also, Ancient Greece noted that the Moon causes tides on Earth. More recently, Luna 1 was the first spacecraft to perform a flyby of the moon. Luna 2 was the first spacecraft to land on the moon, and Luna 3 was the first to photograph the far side of the Moon which you can not see from Earth. Luna 1 through 3 all were launched in 1959. Surveyor 3, in 1967, was the first to examine the soil of the Moon. It dug to 17.5 cm. In 1969, Apollo 11 was the very first spacecraft to land people on the moon. Next Topic: Mars ## References \"The Moon is just under\...\" 1 2\ \"So the Earth and the Moon together\...\" 3 4\ \"The Moon does not have any atmosphere.\" 5 6\ \"During the day it becomes\...\" 7 8\ \"The largest one is called\...\" 9 10\ \"These rays are rocks\...\" 11\ \"Some of the craters around the bottom\...\" 12 13\ \"There are also darker areas\...\" 14 15\ \"The lighter areas\...\" 16\ \"The Moon takes just over 27\...\" 17 18\ \"We call this side\...\" 19 20 21\ \"The other side we call\...\" 22 23\ \"The surface of the Moon\...\" 24 25 26 27\ \"\...it would pull you down\...\" 28 29\ \"The names \"Moon\" and\...\" 30 31 32\ ar:ويكي الأطفال:نظام شمسي/القمر bs:Wiki junior Sunčev sistem/Mjesec de:Wikijunior Sonnensystem/ Mond zh:Wikijunior:太阳系/月球
# Wikijunior:Solar System/Mars ```{=html} <div style="float:right; border:2px solid #aaaaaa; width:250px; margin-left:0.2em; padding:0.4em"> ``` !♂.svg "♂"){width="80"} **Mars Facts**: - Mars is red because of rust in the surface rocks - A volcano on Mars called *Olympus Mons* is the highest mountain in our Solar System. - Mars has polar ice caps that look like the ones on ../Earth/. - Mars has ancient river beds where scientists think liquid water flowed millions or billions of years ago. - The *Tooting* crater on Mars was named after a suburb in London because the discoverer \"thought \[his\] mum and brother would get a kick out of having their home town paired with a land form on Mars\". ```{=html} </div> ``` Mars is the fourth planet from the Sun. It is called a *terrestrial* planet because its outer layers are made of rocky material like the Earth. ## How big is the planet? !Comparison of the size of Mars and the Earth Mars is the second smallest of the eight major planets in the Solar System. Only Mercury is smaller. It is nearly 7,000 kilometres (km) wide; just over half the width of the Earth. Its volume is about 15% of the Earth. Since a lot of the Earth is covered by water, the total surface area of the Mars is nearly as large as all of the land on the Earth. It is possible that its size may eventually permit human colonies. ## What is its surface like? center\|thumb\|upright=3\|A panorama view from the Mars rover *Spirit*. The surface of Mars is a lot like a desert on Earth; it is very dry and dusty, but it is also very cold. There are a lot of loose rocks and dunes of fine sand. Crater impacts mark the surface, but these are not as common as on the Moon. One of the craters is the huge *Hellas Planitia*. It is about half the size of the continental United States. The southern half of the planet has more craters than in the north. The south is also higher in elevation. !An overhead view of *Olympus Mons*, the highest mountain in the Solar System. There is an area on Mars called the *Tharsis Bulge*, which has four huge volcanoes. These volcanoes have not erupted for millions of years. The largest volcano is called Olympus Mons. It is 27 km tall, making it the highest mountain in the Solar System; *more than three times* higher than Mount Everest on Earth. It is 625 km across and takes up an area as big as the US state of Arizona. Mars also has a huge canyon called the *Valles Marineris*. It is much bigger than the Grand Canyon on Earth. It is 4000 km long, up to 7 km deep and up to 200 km wide. Scientists think that when the *Tharsis Bulge* was created, the surface of Mars cracked to form the *Valles Marineris*. Like the Earth, Mars has ice caps at its poles. However, they are made from frozen carbon dioxide as well as ice. During the Martian winter at each pole, the cap grows as carbon dioxide from the atmosphere freezes. The cap shrinks again during the Martian summer. As on Earth, when it is winter at one pole it is summer at the other. In some places, there are dry *channels* that look like they were made by running water. So, a long time ago Mars may have had lakes and streams made of water. Now all of the water is frozen into ice under the surface. There is an atmosphere on Mars, but it is very thin. There is also much more carbon dioxide in it than oxygen. (Oxygen is the gas we need when we breathe in; carbon dioxide the gas we get rid of when we breathe out.) So, we would need spacesuits to visit Mars. The atmosphere helps protect the surface from smaller meteorites. When Mars comes closest to the Sun, the atmosphere can stir up storms of dust. Some of these storms are gigantic; they can cover the entire planet in clouds of dust. Dust storms on Mars can last for hundreds of days, with wind speeds of up to 200 kilometres per hour. Huge storms like these have been seen from the Earth through telescopes. {{ }} {{/Mars}} ## How long is a day and year on this planet? One day on Mars is only 39 minutes and 35 seconds longer than a day on Earth (1.026 Earth days). A year on Mars is almost two Earth years long (687 Earth days). Much like the Earth, the axis of rotation of Mars is tilted at an angle. This tilt causes seasons on Mars as it travels around the Sun. Summer occurs on the half of the planet that is tilted toward the Sun, and winter on the other half. After half a Martian year has passed, the seasons are reversed. But these seasons are about twice as long as on Earth. ## What is it made of? !visualization of the Martian interior. The outer, rocky surface of Mars is called the crust. Most of the crust is made from basalt, a type of rock made when lava grows cold. Like the Earth, Mars has a thick layer of rock below the crust called the mantle. The mantle is much hotter than the crust, and the mantle rock is partly molten. But the crust on Mars has grown thick, so the lava from the mantle no longer reaches the surface. There are volcanoes on Mars, but they are no longer active. At the center of Mars is a core made of the metals iron and nickel. If Mars were the same size as the Earth, the core of Mars would be smaller than the Earth\'s core. So a larger amount of Mars is made out of rock. Because rock is lighter than the metals in the core, Mars has a lower density than the Earth. ## How heavy would I be on Mars? !Detailed picture of Mars If you were on Mars, you would be lighter, as Mars\' gravity only has a force about two fifths as strong as the that of Earth\'s. You could lift objects that weigh almost three times as much compared to similar objects here on the Earth. You could jump up almost three times higher, and it would take much longer to fall to the ground from the same height. Even though it looks as though you would be like a comic-book hero on Mars, there are some things you couldn\'t do. Although a big rock would *weigh* less and you could pick it up, it would still have the same *mass*. If you tried to catch it, it would knock you over, and if it landed on you it would crush you. A car on the surface of Mars would need the same amount of power to speed up, although going uphill would be less of a problem. It may, however, need more room to stop. Because of the reduced gravity a vehicle would not \"grip\" the ground on Mars as strongly, but the constant mass would keep the vehicle moving just as strongly, making it easy to go into a skid. ## Who was it named after? In Roman mythology, Mars was the god of war and agriculture. The planet Mars was named this because the planet looks red like blood, from rust in its surface rocks. ## Who discovered Mars? Nobody knows, but the earliest records we know of were by Ancient Egyptians, more than 4000 years ago, noting Mars\' movement. On one pharaoh\'s tomb, named *Seti I*, Mars is drawn on the ceiling. The Babylonians (in the Middle East), Chinese, and Greeks also studied Mars more than 3000 years ago. The Greeks learned about Mars from the Babylonians, and since the Babylonians called it their god of war, named *Nergal*, the Greeks called it their own god of war, *Ares*. Exploration of Mars was first attempted in 1960, with Mars 1. It failed, along with several other missions by the Soviet Union in the 1960s. The first successful mission to Mars was in 1964, by Mariner 4, by the U.S. Most of the other Mariner missions to Mars were successful. The last Mariner mission to Mars, Mariner 9, got there in the midst of a dust storm, and orbited the planet for several months before it could get a good look at the surface. So far, all these missions were flybys or orbiters. The first spacecraft to land on Mars was Viking 1 in 1976. Viking 2 landed 19 days later. Together, they took many good pictures of Mars\' surface. <table> <tbody> <tr class="odd"> <td><p><code>{{multiple image</code></p></td> <td><p>align = left</p></td> <td><p>width1 = 100</p></td> <td><p>width2 = 110</p></td> <td><p>width3 = 122</p></td> <td><p>width4 = 123</p></td> <td><p>width5 = 100</p></td> <td><p>width6 = 196</p></td> <td><p>image1 = Mars Viking 11h016.png</p></td> <td><p>caption1 = Viking 1 lander site (February 11, 1978).</p></td> <td><p>image2 = PIA00563-Viking1-FirstColorImage-19760721.jpg</p></td> <td><p>caption2 = Viking 1 lander site (1st color, July 21, 1976).</p></td> <td><p>image3 = First Color Image of the Viking Lander 2 Site.jpg</p></td> <td><p>caption3 = Viking 2 lander site (1st color, September 5, 1976).</p></td> <td><p>image4 = Vl2 22g144-MarsViking2-19770925.gif</p></td> <td><p>caption4 = Viking 2 lander site (September 25, 1977).</p></td> <td><p>image5 = Mars Viking 21i093.png</p></td> <td><p>caption5 = Frost at Viking 2 site (May 18, 1979).</p></td> <td><p>image6 = Mars Viking 12a240.png</p></td> <td><p>caption6 = Martian sunset over Chryse Planitia at Viking 1 site (August 20, 1976).</p> <p><code>}}</code></p></td> </tr> </tbody> </table> Next Topic: Asteroid belt ## References - Steven W. Squyres, *Mars*, World Book Online Reference Center, World Book, Inc., 2004. 1 2 - \"a *terrestrial* planet\" 3 - \"How big is the planet?\" 4 5 - \"How long is a day on this planet?\" 6 7 - \"What is it made of?\" Steven W. Squyres, *ibid.* ar:ويكي الأطفال:نظام شمسي/المريخ bs:Wiki junior Sunčev sistem/Mars de:Wikijunior Sonnensystem/ Mars es:Wikichicos/Sistema_Solar/Marte nl:Wikijunior:Zonnestelsel/Mars pl:Wikijunior:Układ_Słoneczny/Mars fi:Wikijunior_Aurinkokunta/Mars zh:Wikijunior:太阳系/火星
# Wikijunior:Solar System/Asteroid belt !Asteroid belt between Mars & Jupiter.PNG The asteroid belt lies between the planets Mars and Jupiter. It contains lumps of rock and metal much smaller than planets. These lumps are called asteroids or minor planets. They are not visible from Earth with the naked eye, but many may be seen through binoculars or small telescopes. +------------+----------+ | Object\ | Maximum\ | | Name | Size | +============+==========+ | 1 Ceres | 933 km | +------------+----------+ | 4 Vesta | 530 km | +------------+----------+ | 2 Pallas | 525 km | +------------+----------+ | 10 Hygiea | 407 km | +------------+----------+ | 511 Davida | 326 km | +------------+----------+ : Largest bodies in the asteroid belt The largest asteroid in the solar system is called \"2001 KX76.\" In the asteroid belt, the four largest bodies are Ceres (a dwarf planet named after the Roman goddess of agriculture), Vesta (the Roman goddess of the home), Pallas (the granddaughter of Poseidon), and Hygiea (the Greek goddess of health). These four bodies make up about half of the asteroid belt. Some asteroids are less than a kilometer across. Unofficially the limit has been set at 50 meters, and anything smaller than that is going to be simply called a meteoroid. With advances in telescopes and particularly for objects that travel close to the Earth, some objects smaller than 50 metres have indeed been seen passing nearby the Earth. There are probably several million asteroids in the solar system. Over 96,000 asteroids have been given numbers. Almost 12,000 of them have names. But even though there are a lot of asteroids, the asteroid belt is mostly empty space. Traveling through the asteroid belt in a space ship would not be very much like what you see in a science fiction film. This would not be the same in the first 100 million years of the solar system\'s history (had humans evolved and discovered film). The asteroid belt lost 99.99% of its mass in the first 100 million years of the solar system. {{ }} ## What are they named after? The first asteroids were named after mythical heroes and gods much like the major planets. The first to be discovered was named Ceres after the Roman goddess of growing plants (particularly grain) and of motherly love. The second asteroid discovered was called Pallas and was named after one of the Greek gods of wisdom. Asteroids are also given a number in the order of their discovery, so Ceres is 1, Pallas is 2, and so forth. As the number of known asteroids increased, they ran out of mythical names so other names were used instead. Some asteroids were named after countries. For example asteroid number 136 is named Austria. Others were named after plants, for example 978 Petunia. 1620 Geographos was named after the National Geographic Society, in recognition to their efforts at sharing knowledge about the Solar System. Many are named after people, both alive and dead. In a couple of cases, like 2309 Mr. Spock, asteroids were named after the discoverer\'s pet cat. This last type of naming is discouraged, but it still happens from time to time. Even fictional characters have been used. Today, names for asteroids can be suggested by the people who discover them. The names become official after a group of people reviews them to make sure they are not offensive or too much like another name. Because so many asteroids are now being found, most new asteroid discoveries are not even getting a name at all, but rather a numbered code. It is not likely that they will ever be given a formal name, at least in this century. The actual word *Asteroid* can refer to any member of the family of Asteroidea; in other words, a starfish. The etymology of the word comes from Ancient Greek *ἀστεροειδής*, literally meaning star form. The Ancient Greeks probably must have mistook the asteroids for stars. Most of the asteroids have symbols representing them; for example, Ceres has ⚳, representing Ceres\'s scythe, and Pallas has ⚴, reperesenting Athena\'s spear. ## Who discovered them? ```{=html} <div style="float:right; border:2px solid #aaaaaa; width:250px; margin-left:0.2em; padding:0.4em"> ``` **Asteroid Belt Facts**: - The total mass of all the asteroids in the asteroid belt is about 1/35th of that of our moon. - The largest object in the asteroid belt, Ceres, makes about 1/3 of the total weight of all the asteroids. - Ceres is the only dwarf planet in the asteroid belt. - Vesta is the only asteroid that can ever be seen with the naked eye. Its magnitude can reach +5.1, about the same as Uranus. - Although people probably saw Vesta and Uranus thousands of years ago, they were not recognised to orbit the Sun until 200 years ago. ```{=html} </div> ``` The first asteroid to be discovered was Ceres, on 1 January 1801, by Giuseppe Piazzi accidentally. At first he thought this was a comet, then later a planet! When it was realised it was too small Sir William Herschel (the astronomer who discovered Uranus) made up the word \"asteroid\" to describe it, using the Ancient Greek word *aster*, meaning star, and the *-oid*, meaning form or shape. In other words a star-like planet, because he couldn\'t see any details due to the small size of the object. By 1807 another 3 asteroids were discovered, but no more were found until 1845 when a persistent asteroid hunter named Karl Ludwig Hencke found a fifth, and sixth asteroid in 1847. Ever since then at least one new asteroid has been found each year. In 1891, the first pictures of the night sky were taken to find more asteroids. This led to the discovery of many more asteroids. A picture of the same part of the sky is taken on two different nights. When the two pictures are lined up, the stars will be in the same places but an asteroid will have moved. In our modern times, over 280,000 asteroids have been discovered. Many more are being found all the time. Some of these asteroids pass near the earth and astronomers want to find any that come close to our planet. Large numbers of asteroids are now being discovered by machines. ## What are they made of? Three out of four asteroids are made of rock that is rich in carbon. The rest are made of the metals iron and nickel. About half of these are pure iron and nickel; the rest are mixed with compounds of silica, the element that makes up rocks. Each of the larger metal asteroids contains huge amounts of iron: much more than is mined every year on Earth. Vesta, the brightest asteroid, has a very unusual composition - being made of high-density volcanic rocks. Scientists are very interested in what asteroids are made of because it can help them learn how the solar system was formed. Several spacecraft have visited asteroids to learn more about them. ## Are there asteroids outside of the asteroid belt? framed\|right\|All the major asteroid clusters in the solar system. It does look like the asteroid belt is clustered in the picture, but one millimetre of emptiness in the picture means millions of kilometres emptiness.Most asteroids are found in the asteroid belt, but not all. Some asteroids orbit closer to the Sun, and many asteroids orbit beyond Neptune. Asteroids that closely approach Earth are called Near-Earth Asteroids. Sometimes pieces of asteroids strike the Earth, burning in the atmosphere as a meteor. If they are large enough, they might actually hit the surface and become meteorites. !Asteroid Ida and its moon A centaur is a mythical beast having a horse\'s body with a man\'s head and torso in place of the head and neck of the horse. There are some asteroids in the outer solar system that are called Centaurs. It is hard to tell whether any one Centaur is an asteroid, comet, or Kuiper Belt object. For example, the first Centaur to be discovered was Chiron(In Greek Mythology, an important centaur). But some scientists think it is a comet, not an asteroid. Officially it is called both the asteroid 2060 Chiron and the comet 95P/Chiron! In most cases when an asteroid\'s orbit crosses the path of a planet such as Jupiter, at some point the asteroid will either hit the planet or else be hurled into another orbit. Many of the small moons of some planets may have once been asteroids that were captured by the planet\'s gravity when they came too close. However there are two points along the orbit of a planet were an asteroid can safely linger. These are found at a point one-sixth (or 60°) of an orbit ahead of the planet, and the same distance behind the planet. These sites are called Lagrange points, and they are found where the force of gravity from the Sun and the planet balance out with the motion of the asteroid\'s orbit. The asteroids found in these spots are called Trojans, and they move around the Sun at the same velocity as the planet. ## Ceres !The dwarf planet Ceres._(cropped).jpg "The dwarf planet Ceres."){width="150"} Ceres is a large Dwarf Planet like Pluto located in the asteroid field. The difference between Ceres and most other dwarf planets is that it is also an asteroid. Ceres is one of the few asteroids that are shaped like a sphere, and it may have some ice just underneath its dusty surface. It was discovered in 1801 by Giuseppe Piazzi, who was an Italian astronomer. ## Some famous asteroids Ceres the first discovered and biggest asteroid in the solar system. The asteroid Ida has its own moon named Dactyl. A number of asteroid moons have now been found. Next Topic: Jupiter ## References - U.S. Naval Observatory Ephemerides of the Largest Asteroids, USNO. - Near Earth Asteroid Tracking, NASA. - Asteroids: Structure and composition of asteroids, ESA. - Main Asteroid Belt, SolStation. pojas de:Wikijunior Sonnensystem/ Asteroidengürtel es:Wikichicos/Sistema_Solar/Cinturón_de_asteroides nl:Wikijunior:Zonnestelsel/Planetoïdengordel pl:Wikijunior:Układ_Słoneczny/Pas_planetoid fi:Wikijunior_Aurinkokunta/Asteroidivyöhyke zh:Wikijunior:太阳系/小行星带
# Wikijunior:Solar System/Jupiter ```{=html} <div style="float:right; border:2px solid #aaaaaa; width:250px; margin-left:0.2em; padding:0.4em"> ``` !♃.svg "♃"){width="80"} **Jupiter Facts**: - Due to its magnetic field trapping particles from the Sun, Jupiter is surrounded by very powerful radiation belts which would kill anyone who entered them. - Jupiter\'s moon Europa is thought to have a giant ocean below its surface. - Jupiter\'s moon Ganymede is the largest moon in the solar system. - Jupiter is the third brightest object in the night sky, second being Venus and first being the Earth\'s moon. - Jupiter has more than twice the mass of all the other planets in the solar system combined. - Jupiter is considered an almost-star. The smallest red dwarf star was only 30% bigger than Jupiter. - Jupiter\'s red spot and the Earth are close to the same size. That means that there is a storm going on in Jupiter that is as big as the Earth! - *Jovian* in English means anything relating to Jupiter --- the god or the planet. Sometimes the four outer planets are called the Jovian planets. ```{=html} </div> ``` **Jupiter** is by far the largest planet in our Solar System: two and a half times larger than all of the other planets put together. It is the fifth planet from the Sun and one of the brightest planets as seen from Earth. Jupiter, along with Saturn, Uranus and Neptune, is sometimes called a \"gas giant\" because most of these planets are made up of liquid and gas. ## How big is the planet? !Comparing the sizes of the Sun, Jupiter, Earth, and the Moon. Notice the red spot is about the size of the Earth! Jupiter is 142,984 km or about 11 Earths in diameter at the **equator**. That makes it about one tenth as big in diameter as the Sun! You could fit about 1,400 Earths into the volume of Jupiter. It is 133,709 km or 10 Earths in diameter from pole to pole. Jupiter\'s rapid **rotation** (it spins around in under ten hours compared with 24 hours for Earth) makes it bulge out at the equator. Jupiter\'s magnetic field is the largest single planetary thing in the Solar System. It is 26 million kilometers across, making it about 20 times bigger than the Sun. It has a tail that extends past Saturn\'s orbit. If it could be seen from Earth, it would appear to be five times the size of the full moon. ## What is the surface like on Jupiter ? !Jupiter\'s atmosphere The surface we see is not solid. This enormous planet has a relatively small solid and rocky core. Liquids and gases surround this core and blend with the atmosphere. Jupiter is a cloudy, windy and stormy planet. It is always covered by a layer of clouds, and wind speeds of 600 km/h are not uncommon. The storms are visible as swirls, bands and spots. A particularly violent storm, about three times Earth\'s diameter, is known as the Great Red Spot. This storm has been in existence since at least 1831, and maybe since 1665. If the storm has existed since 1665, that would make it more than 300 years old! The layer of clouds is divided into several bands. The lighter colored bands are called **zones** and the darker bands are called **belts**. The colors are caused by small changes in the temperature and chemistry. Each band rotates in the opposite direction from its neighbors. Along the edges where the bands meet, these winds collide and create swirling patterns. The stormy atmosphere of Jupiter has flashes of lightning just like on Earth. However, while Earth\'s lightning strikes may be hotter than 50,000 °C, Jupiter\'s lightning strikes may go over 5,000,000 °C, which is a hundred times more than Earth lightning, and is more than the temperature of the sun\'s corona. The lightning is made by water near the tops of the clouds. ## What are its rings like? !The rings of Jupiter as seen by the Voyager 2 spacecraft Jupiter\'s rings are dark and hard to see. They are made of tiny particles that meteors knocked off Jupiter\'s small inner moons and debris left over from comets and other objects that came close to the surface of Jupiter. In fact, until the Voyager spacecraft arrived near Jupiter and took closeup pictures of the rings of Jupiter, scientists didn\'t even know that it even had rings at all. Two rings are clearly from material that can be associated with two sets of the inner moons of the planet. These are the names of the rings and their sizes: Ring Name Inner Radius Outer Radius ------------------ -------------- -------------- Halo 100,000 km 122,000 km Main 122,000 km 129,000 km Gossamer (inner) 129,000 km 182,000 km Gossamer (outer) 182,000 km 225,000 km : **Rings of Jupiter** Gossamer means in English anything that is delicate, light, and flimsy. {{ }} ## What is the planet\'s atmosphere made of? !Jupiter as seen by the space probe *Cassini*. This is the most detailed color portrait of Jupiter ever assembled. In the outermost layer of Jupiter lie frozen Ammonia crystals. (Ammonia is a compound of hydrogen and nitrogen; its scientific designation is NH~3~.) crystals. Jupiter\'s atmosphere is mainly made of **hydrogen**(H~2~). Near the surface, there is almost 90% hydrogen. Apart from this, the atmosphere has helium(He). Because of the high pressure, helium becomes a liquid further down in the planet. In addition, Jupiter has methane(CH~4~)(0.3%), hydrogen deuteride(HD)(0.003%), ethane(C~2~H~6~)(0.0006%), and least of all, water(H~2~O)(0.0004%). Jupiter\'s temperature is very high. Because of this, scientists cannot tell all the materials the planet is made of. The outer core of Jupiter has hydrogen. The pressure present can make the gas solid. However, because of the very high temperature, the gas melts, and becomes liquid. ## What are its moons like? !A simulation of the orbit paths of the moons of Jupiter. Jupiter has 95 known moons. There are four major moons that were discovered by Galileo in 1610, the first moons ever discovered around another planet. Those moons are Io, Europa, Ganymede and Callisto; they are named from characters in mythology closely associated with Jupiter. They are called the Galilean moons. There are often **eclipses** on Jupiter\'s cloud tops by the Galilean moons. ### Amalthea Group There are four small moons **orbiting** inside Io\'s orbit. That group is called the Amalthea group because Amalthea is the largest one. They are all small and potato shaped. Amalthea is very red. The material of Jupiter\'s rings came from meteors knocking it off of those moons. Amalthea(Greek:Ἀμάλθεια) in Greek mythology is a foster mother of Zeus. ### Io !The four largest moons of Jupiter. From left to right with increasing distance: Io, Europa, Ganymede, Callisto..tif "The four largest moons of Jupiter. From left to right with increasing distance: Io, Europa, Ganymede, Callisto.") Io (pronounced EYE-oh) is Jupiter\'s closest major moon. It is 3643.2 km across, slightly larger than Earth\'s Moon. It has the most spectacular **volcanoes** in the solar system and molten **sulfur** lakes. Any craters formed by asteroids hitting the surface are quickly covered up by the volcanic activity. Io\'s core is made of molten **iron** and is surrounded by a rock shell. Unlike Jupiter\'s other moons, there is very little water on Io. Scientists think that when Jupiter was forming, it was hot enough to dry out Io, but not the other major moons. In Roman mythology, Io(Ancient Greek:Ἰώ) was a beautiful young nymph(Nymphs are divine spirits that animate nature and generally portrayed as beautiful young women.) that Zeus loved. ### Europa Europa (pronounced *Eurṓpē*) is 3,121.6 km across, about 10% smaller than Earth\'s Moon. It is made of silicates and has a layer of smooth water ice 10 to 30 km thick. The ice has long cracks in it and very few craters. It looks like the sea ice on Earth. The ice has slid around at the cracks. We believe there is liquid water under the ice as much as 100 km below the surface. There are also some large spots on the surface. In Roman mythology Europa was courted by Jupiter in the form of a bull. Europa (Ancient Greek:Ευρώπη) in Greek mythology was a Phoenician noblewoman who was abducted by Zeus to Crete (An island of Greece). ### Ganymede !Jupiter and its four largest moons, as seen through a telescope. Ganymede is 5262.4 km across, making it 380 km wider than Mercury. It is Jupiter\'s largest moon and the largest moon in the Solar System. It has **plate tectonics** like Earth. There are older, darker regions and newer areas with grooves where the plates have moved. Newer craters have bright rays around them from material thrown up by impacts. Older craters look flat and faded because the icy surface does not hold the shape of the crater as well as rock does over long periods of time. Ganymede may have an iron and sulfur core with a silicate **mantle** and an icy shell. It may be similar to Io except with a layer of ice on it. In Roman mythology Ganymede was a beautiful young man who Jupiter kidnapped and made cupbearer to the gods on Mt. Olympus. ### Callisto !The orbit paths of the 4 largest moons. Callisto is 4820.6 km across, about the same size as Mercury. It has many craters. Like craters on Ganymede, the older craters have faded. The largest crater is *Valhalla*. It has a bright center 600 km across with rings around it up to 3000 km across. Callisto is made of silicates and ice. There is a 200 km thick icy **crust** with a liquid water sea under it. In Roman mythology Callisto was turned into a bear by Jupiter\'s jealous wife Juno. Later Jupiter placed her in the stars as The Great Bear. ### Other moons The other moons are smaller in several groups outside the orbits of the major moons. There is also a small moon, Themisto and four groups of small moons that orbit very far from Jupiter. ## How long is a day on this planet? One Jupiter day is about 10 Earth hours long. You have to say \"about\" because different parts of Jupiter rotate about its axis at different speeds. This is caused by the fact that Jupiter is mostly gases that are in constant motion and sometimes going in different directions. Some efforts have been made to try and measure the rotation speed of the inner rocky core of Jupiter, but that has proved to be quite difficult to accomplish due to the magnetic fields that surround Jupiter and the very active radio energy that is generated by the atmosphere of Jupiter, which interferes with measuring techniques like radar that has been used to measure the surface of Venus and Mars. ## How long is a year on Jupiter? !The Great Red Spot !Jupiter Eclipses One year on Jupiter is 4,335 Earth days or 11.87 Earth years long. A Jupiter year is about equal to four-tenths (or two-fifths) of a Saturn year. Thus after every two Saturn years, Jupiter has completed five full orbits about the Sun. So after 59 years, Saturn and Jupiter will be back in nearly the same position. When the orbits of two planets are simple ratios of each other like this, it is called a **resonance**.\ ## How much would Jupiter\'s gravity pull on me? If someone were floating close to the cloud tops of Jupiter, it would pull them down with a force about two and a half times as strong as the force of Earth\'s gravity. Jupiter\'s rapid rotation causes the equator to bulge out. This would also cancel out about 10 percent of gravity\'s force on them if they were at the equator. The amount of this counteraction becomes lower the closer they get to the poles. ## Who is it named after? !Statue of Zeus (Jupiter) in Olympia, Greece in Olympia, Greece") Jupiter (Latin *Iuppiter*) is named after the king of the Roman gods, also called Zeus in ancient Greece. The god Jupiter was known for causing lightning strikes on Earth. He is associated with the eagle and the oak tree. Next Topic: Saturn شمسي/المشتري bs:Wiki_junior_Sunčev_sistem/Jupiter de:Wikijunior Sonnensystem/ Jupiter es:Wikichicos/Sistema_Solar/Júpiter nl:Wikijunior:Zonnestelsel/Jupiter pl:Wikijunior:Układ_Słoneczny/Jowisz fi:Wikijunior_Aurinkokunta/Jupiter zh:Wikijunior:太阳系/木星
# Wikijunior:Solar System/Saturn ```{=html} <div style="float:right; border:2px solid #aaaaaa; width:250px; margin-left:0.2em; padding:0.4em"> ``` !♄.svg "♄"){width="80"} **Saturn Facts**: - If you could find a bathtub big enough, Saturn would float in it. - Some of Saturn\'s moons control the width of its rings. These are known as shepherd moons. - Although it is made mostly of gases, scientists believe Saturn has a small rocky core. ```{=html} </div> ``` **Saturn** is the sixth planet from the sun, and is one of the *gas giants*. {{ }} ## How big is the planet? !Comparison of the size of Saturn and the Earth Saturn is 120,536 km or 9.449 Earths wide at the **equator**.[^1] ## What is its surface like? Saturn is mostly gas and liquid.[^2] Saturn may have a small core of rock and ice.[^3] The **atmosphere** has bands, but they are not as colorful as Jupiter\'s. ## What are its rings like? !Saturn casts a shadow on its rings Saturn\'s rings are composed of rock and ice particles ranging in size from specks of dust to the size of a house. Some particles might even be a few kilometers wide! The particles in the rings are actually spaced far apart. It would be easy to pass through the rings.[^4] ## What are its moons like? !Map of the Saturn system (NASA)") Saturn has 56 moons, and many of them have names.[^5]The size of Saturn\'s moons and the size of the chunks of ice in its rings are similar, which means that we can never know the exact number of moons. [^6] New moons are still being discovered. Saturn\'s biggest moon is named Titan, and is large enough to be a planet in its own right! ### Shepherd moons There are small potato-shaped moons in or near Saturn\'s rings. They control the ring particles with their gravity. That is why they are called shepherd moons. Six of them are known, and there may be more.[^7] ### Mimas Mimas is mostly made of water ice with a small amount of rock.[^8] It has a large **crater** for its size called *Herschel*. It is 130 km across, making it about a third as big as Mimas.[^9] The crater makes Mimas look like the Death Star from the *Star Wars* movies. ### Enceladus Enceladus is made of ice. It is **denser** than the other icy moons. That suggests it also has some rock inside.[^10] It has smooth areas, cracks and some craters. The smooth areas are younger. Craters there have been erased within the past 100 million years. Water vapor was found over a smooth area around the south pole. The cracks and grooves suggest **tectonics** similar to Ganymede\'s. Some ridges similar to Europa\'s ridges were also found. Those suggest oceans like Europa\'s under some areas of Enceladus.[^11]**Tidal forces** from Dione could be powering some of this activity. It is because Enceladus orbits Saturn twice for every orbit by Dione. This makes Dione and Saturn tug on Enceladus. This is similar to how Europa and Ganymede\'s tidal forces on Io power Io\'s volcanoes.[^12] ### Tethys !Tethys imaged by the Cassini spacecraft. Tethys is an icy moon that has many craters, including the huge *Odysseus*. It is 400 km across, 1/5th as big as Tethys is. The crater had become flattened because the icy material does not hold its shape as well as rock would. There is also a large valley called *Ithaca Chasma*. It is 3 to 5 km deep, 100 km wide and 2000 km long, three fourths of the way around Tethys.[^13] There are two moons, Telesto and Calypso, which share Tethys\' orbit. Telesto is ahead of Tethys and Calypso is behind it.[^14] ### Dione Dione is made of lots of ice and there may be some rock in its **core**. It has lots of craters. The craters are flattened because the ice does not hold their shape as well as rock. One side has bright white lines that are fractures. Two moons share Dione\'s orbit. Helene is ahead of Dione and Polydeuces is behind it.[^15] ### Rhea Rhea is an icy moon similar to Dione with some rock in the core. It has many craters mostly on one side, and the other side has some bright white icy areas.[^16] ### Titan !Titan imaged by the Cassini spacecraft. Titan is the largest moon of Saturn and the second largest one in the solar system.[^17] It is the only moon in the Solar System that has a thick atmosphere. The atmosphere is made of **nitrogen**, **argon**, **methane** and various **organic compounds**.[^18] Its surface has light and dark areas and few craters. The Cassini probe discovered a huge crater 440 km wide.[^19] ### Hyperion Hyperion is made of water ice with a little rock. It is potato shaped. It wobbles instead of rotating in the same way other moons do.[^20] ### Iapetus !Mosaic of Iapetus images taken by the Cassini spacecraft. Iapetus is almost entirely ice.[^21] It has a light area called *Roncevaux Terra* that has craters.[^22] There is a big dark area called *Cassini Regio* that covers half of Iapetus. The dark material may be from Phoebe. Some of it is on the bottom of craters. Some huge craters and a ridge have been discovered in *Cassini Regio* by the Cassini probe. The ridge stretches 1300 km along the equator. It is up to 20 km high, which is over 2.26 times higher than Mount Everest.[^23] More huge craters were found in *Roncevaux Terra* when Cassini went by Iapetus again.[^24] ### Phoebe Phoebe is made of ice and rock. It looks dark because it has a layer of dark material on the outside. It also looks rough.[^25] ### Other moons There are two groups of small outer moons. Phoebe is part of the second outermost group.[^26] ## How long is a day on this planet? One day on Saturn is about 10 hours and 39 minutes in Earth time.[^27] ## How long is a year on this planet? One year on Saturn is about 29.46 Earth years long. That is 10,760 Earth days![^28] ## What is it made of? Saturn has a rocky core. Around the core, there is ice. Above the ice is liquid metallic **hydrogen**. On top of that is gaseous hydrogen. There is no place where the hydrogen suddenly turns from a gas to a liquid. The gaseous hydrogen makes up most of Saturn\'s atmosphere. Other gases there include **helium** and some other gases. There may be rain made of helium falling through the hydrogen. There is also ammonia on the surface.[^29] ## How much would Saturn\'s gravity pull on me? If you were floating close to the cloud tops of Saturn, it would pull you down with a force only a little stronger than the force of Earth\'s gravity.[^30] The effects of Saturn\'s large **radius** and its **mass** almost cancel each other out, making the force only a little bigger. So, if you weighed 100 lbs. on Earth, you would weigh 106 lbs. on Saturn. ## Who is it named after? Saturn is named after the most important Roman god of agriculture and harvest time. He taught people how to farm. He was the father of Jupiter. Saturday is named after him.[^31] Uranus ar:ويكي الأطفال:نظام شمسي/زحل bs:Wiki junior Sunčev sistem/Saturn de:Wikijunior_Sonnensystem/\_Saturn es:Wikichicos/Sistema_Solar/Saturno fr:Wikijunior:Système_solaire/Saturne nl:Wikijunior:Zonnestelsel/Saturnus pl:Wikijunior:Układ_Słoneczny/Saturn fi:Wikijunior_Aurinkokunta/Saturnus ## References ```{=html} <references/> ``` de:Wikijunior Sonnensystem/ Saturn nl:Wikijunior:Zonnestelsel/Saturnus [^1]: <http://www.nineplanets.org/saturn.html>; <http://nssdc.gsfc.nasa.gov/planetary/factsheet/saturnfact.html> [^2]: <http://solarsystem.nasa.gov/planets/profile.cfm?Object=Saturn&Display=OverviewLong> [^3]: <http://solarsystem.nasa.gov/multimedia/display.cfm?IM_ID=166> [^4]: <http://www.nineplanets.org/saturn.html>; <http://www.solarviews.com/eng/saturnrings.htm>; <http://solarsystem.nasa.gov/planets/profile.cfm?Object=Saturn&Display=Rings> [^5]: <http://www.nineplanets.org/saturn.html> [^6]: <http://www.factmonster.com/ce6/sci/A0860937.html> [^7]: <http://saturn.jpl.nasa.gov/faq/saturn.cfm#q13> [^8]: <http://www.nineplanets.org/mimas.html> [^9]: <http://www.nineplanets.org/mimas.html> [^10]: <http://saturn.jpl.nasa.gov/multimedia/products/pdfs/20050830_CHARM_Esposito.pdf>; <http://www.ifa.hawaii.edu/faculty/jewitt/kb/phoebe.html> [^11]: <http://www.nineplanets.org/enceladus.html>; <http://www.nasa.gov/home/hqnews/2005/jul/HQ_05208_cassini_watery_world.html>; [^12]: <http://www.bbc.co.uk/science/space/solarsystem/saturn/enceladus.shtml>; <http://www.spacedaily.com/news/cassini-01e3.html> [^13]: <http://www.nineplanets.org/tethys.html> [^14]: <http://apod.gsfc.nasa.gov/apod/ap020519.html> [^15]: <http://www.nineplanets.org/dione.html>; <http://solarsystem.nasa.gov/planets/profile.cfm?Object=Dione>; <http://solarsystem.nasa.gov/planets/profile.cfm?Object=Sat_Polydeuces> [^16]: <http://www.nineplanets.org/rhea.html>; <http://solarsystem.nasa.gov/planets/profile.cfm?Object=Sat_Rhea> [^17]: <http://www.nineplanets.org/titan.html>; <http://solarsystem.nasa.gov/planets/profile.cfm?Object=Sat_Titan> [^18]: <http://www.nineplanets.org/titan.html>; <http://solarsystem.nasa.gov/planets/profile.cfm?Object=Sat_Titan> [^19]: <http://www.nineplanets.org/titan.html>; <http://www.nasa.gov/mission_pages/cassini/media/cassini-021605.html> [^20]: <http://www.nineplanets.org/hyperion.html> [^21]: <http://www.nineplanets.org/iapetus.html> [^22]: <http://www.seasky.org/solarsystem/sky3g8.html> [^23]: <http://www.solarviews.com/cap/pia/PIA06166.htm>; <http://www.solarviews.com/eng/iapetus.htm>; <http://www.nineplanets.org/iapetus.html>; <http://antwrp.gsfc.nasa.gov/apod/ap030831.html> [^24]: <http://saturn.jpl.nasa.gov/multimedia/images/image-details.cfm?imageID=2763> [^25]: <http://www.solarviews.com/eng/phoebe.htm> [^26]: <http://www.factmonster.com/ce6/sci/A0860937.html> [^27]: <http://solarsystem.nasa.gov/planets/profile.cfm?Object=Saturn&Display=Facts&System=Metric> [^28]: <http://nssdc.gsfc.nasa.gov/planetary/factsheet/saturnfact.html> [^29]: <http://www.nineplanets.org/saturn.html>; <http://www.solarviews.com/eng/saturn.htm>; <http://www.seasky.org/solarsystem/sky3g1.html> [^30]: <http://nssdc.gsfc.nasa.gov/planetary/factsheet/saturnfact.html> [^31]: <http://www.pantheon.org/articles/s/saturn.html>; <http://coolcosmos.ipac.caltech.edu/cosmic_kids/AskKids/saturn_name.shtml>
# Wikijunior:Solar System/Uranus Uranus, the seventh planet from the Sun, was discovered by William Herschel on March 13, 1781.[^1] !Uranus as seen from Voyager 2 {{/Coolfacts\| !⛢.svg "⛢"){width="80"}\|Uranus Facts:\| - Uranus\'s rings look white in pictures, but they are really made of asphalt-colored material. - When it was first discovered, Uranus was mistaken for a star. It was named \"34 Tauri\". - Uranus rotates on its side It is the only planet to do so. }} ## How big is Uranus? !Comparison of the size of Uranus and the Earth Uranus is 51,118 kilometers or about four Earths wide. It is the third widest and fourth heaviest planet in the Solar System.\ ## What is the surface of Uranus like? Uranus does not have a surface that you could stand on without going deep into the **atmosphere**. Under the atmosphere, there may be an even mixture of rock and ice.[^2] ## What are the rings around Uranus like? Uranus has eleven rings. They are dark in colour and very hard to see. They were discovered by accident in 1977. Scientists were studying a bright star near Uranus. However, the star\'s light was blocked before and after it disappeared behind Uranus. From this, they figured out that Uranus has a ring system.[^3] ## What are its moons like? right\|thumb\|Uranus\'s rings and moons Uranus has 27 known moons, which places it third in the Solar System for number of moons. The five main ones are Miranda, Ariel, Umbriel, Titania and Oberon.[^4] ### Miranda Miranda is the smallest and closest of Uranus\'s major moons. It is mainly made of ice and rock. Miranda\'s surface has grooves, cliffs, and valleys. The moon was named after a character in *The Tempest*, a play by Shakespeare.[^5] ### Ariel Ariel is made of rock and ice. Ariel has many valleys, but not many craters. Ariel was named after a character in the poem *The Rape of the Lock* by Alexander Pope. Ariel is also a spirit in *The Tempest* by Shakespeare.[^6] ### Umbriel Umbriel is made of lots of ices and some rock. It is also the darkest of Uranus\'s major moons. Umbriel was named after a character in the poem *The Rape of the Lock* by Alexander Pope.[^7] ### Titania Titania is the largest moon of Uranus. It is mostly ice and rock. The surface is covered with canyons. It was named after the Queen of the Fairies in *A Midsummer\'s Night Dream*, a play by Shakespeare.[^8] {{ }} ### Oberon Oberon is the outermost of the major moons of Uranus. It is made of the same things as Titania. It has many craters. Some of them have white rays around them and dark crater floors. It was named after the King of the Fairies in *A Midsummer\'s Night Dream*.[^9] ### Other Moons There are 13 tiny moons known to be **orbiting** Uranus inside Miranda\'s orbit. Nine more tiny moons are known to be in big orbits beyond Oberon\'s orbit.[^10] ## How long is a day on Uranus? One day on Uranus is about 17.24 Earth hours long. Uranus spins on its side, maybe because of a big impact early in the history of the Solar System.[^11] ## How long is a year on Uranus? One year on Uranus would be 30,708 days or 84 years on Earth.[^12] ## What is Uranus made of? Unlike Jupiter and Saturn, Uranus is thought to be made mostly of rock and ice. The gases in its atmosphere are 83% **hydrogen**, 15% **helium**, and 2% **methane**. Other gases found in smaller amounts are ammonia, water, and **methane**.[^13] Uranus\' blue color comes from **methane** clouds, which absorb red light and reflect blue light.[^14] ## How much would Uranus\'s gravity pull on me? If you were floating close to the cloud tops of Uranus, you would be pulled down with a force about 89% of Earth\'s gravity.[^15] ## Who is Uranus named after? Uranus was named after Ouranos, the Greek name for the sky. Ouranos was the ancient Greek deity of the heavens, the earliest supreme God. According to Greek mythology, Ouranos was the husband and son of Gaia, Mother Earth.[^16] Next Topic: Neptune ## References ```{=html} <references/> ``` ar:ويكي الأطفال:نظام شمسي/أورانيوس de:Wikijunior Sonnensystem/ Uranus nl:Wikijunior:Zonnestelsel/Uranus pl:Wikijunior:Uklad_Sloneczny/Uran [^1]: <http://www.nineplanets.org/uranus.html> [^2]: <http://www.solarviews.com/eng/uranus.htm>; <http://www.nineplanets.org/uranus.html> [^3]: <http://www.solarsystem.org.uk/uranus/> [^4]: <http://nssdc.gsfc.nasa.gov/planetary/factsheet/index.html>; <http://www.nineplanets.org/uranus.html> [^5]: <http://www.nineplanets.org/miranda.html>; <http://www.bbc.co.uk/science/space/solarsystem/uranus/miranda.shtml> [^6]: <http://www.nineplanets.org/ariel.html>; <http://www.bbc.co.uk/science/space/solarsystem/uranus/ariel.shtml> [^7]: <http://www.nineplanets.org/umbriel.html>; <http://www.bbc.co.uk/science/space/solarsystem/uranus/umbriel.shtml> [^8]: \[<http://www.nineplanets.org/titania.html>; <http://www.nineplanets.org/titania.html>\]; <http://www.bbc.co.uk/science/space/solarsystem/uranus/titania.shtml> [^9]: <http://www.nineplanets.org/oberon.html>; <http://www.bbc.co.uk/science/space/solarsystem/uranus/oberon.shtml> [^10]: <http://nssdc.gsfc.nasa.gov/planetary/factsheet/uraniansatfact.html> [^11]: Gierasch, Peter J., and Philip D. Nicholson. \"Uranus.\" World Book Online Reference Center. 2004. World Book, Inc. <http://www.worldbookonline.com/wb/Article?id=ar577720>; <http://www.nasa.gov/worldbook/uranus_worldbook.html> [^12]: Gierasch, Peter J., and Philip D. Nicholson. \"Uranus.\" World Book Online Reference Center. 2004. World Book, Inc. <http://www.worldbookonline.com/wb/Article?id=ar577720>; <http://www.nasa.gov/worldbook/uranus_worldbook.html> [^13]: <http://www.nineplanets.org/uranus.html>; <http://www.solarviews.com/eng/uranus.htm> [^14]: <http://www.solarviews.com/eng/uranus.htm> [^15]: Gierasch, Peter J., and Philip D. Nicholson. \"Uranus.\" World Book Online Reference Center. 2004. World Book, Inc. <http://www.worldbookonline.com/wb/Article?id=ar577720>; <http://www.nasa.gov/worldbook/uranus_worldbook.html> [^16]: <http://www.nineplanets.org/uranus.html>
# Wikijunior:Solar System/Neptune !Neptune as seen from Voyager 2 {{/Coolfacts\|= 1\|!♆.svg "♆"){width="80"}\|= 2\|Neptune Facts:\|= 3\|\*Wind speeds on Neptune can reach 450 meters per second. - Neptune was discovered because its gravitational field was affecting the orbit of Uranus. - Neptune is sometimes farther from the Sun than Pluto. }} ## How big is this planet ? {{ }} !Comparison of the size of Neptune and the Earth Neptune is very similar to Uranus in size. Its diameter is only slightly smaller, at 49,528 km wide. [^1] It is almost as big as four Earths in length.[^2] ## What is its surface like? The **atmosphere** of Neptune has some dark blue spots. When the Voyager probe went by Neptune in 1989, it saw a large one called the Great Dark Spot. In 1994, it vanished, but later reappeared.[^3] There is also a large white cloud nicknamed \"Scooter.\" It goes around Neptune every 16 hours.[^4] The winds of Neptune are very fast, blowing at up to 2000 km per hour(the fastest in the entire solar system).[^5] That is about four times faster than the fastest recorded tornado on Earth. ## What are its rings like? Neptune has some faint rings that are dark and hard to see. There are clumps in some parts of the rings where the material is **denser**.[^6] ## What are its moons like? Neptune has 13 moons. There could be more.[^7] ### Inner Moons There are five small potato-shaped moons **orbiting** close to Neptune. #### Proteus Proteus is a dark moon about 418 km across. It has an irregular shape. In Roman mythology Proteus was a sea-god who could change into any shape he wanted.[^8] #### Triton Triton is the largest moon of Neptune. Scientists think that it is a lot like Pluto. It is 2700 km across. It is made of rock and ice. It has a surface temperature of −235 °C Triton has a very thin atmosphere made up of **nitrogen** and a little **methane**. There are volcanoes that have eruptions of liquid nitrogen, dust or methane compounds. The eruptions happen because of the seasons. There are few **craters** because the eruptions cover them up. There are ice caps that change sizes with the seasons. There are also **ridges** and **valleys**. They may have formed because of repeated freezing and thawing. An interesting thing about Triton\'s orbit is that it goes around Neptune in the opposite direction that Neptune\'s rotates. Because of this, scientists think that Triton was captured by Neptune long ago. In Roman mythology, Triton was the son of Neptune.[^9] #### Nereid Nereid is an irregularly shaped moon about 340 km across. Its orbit is very eccentric or noncircular. It may have been captured by Neptune or moved into the eccentric orbit by Triton\'s gravity when Triton got captured. In Roman mythology Nereids were sea nymphs.[^10] ### Outer Moons There are five other known moons. They are small potato-shaped moons far from Neptune. There might be more we haven\'t seen yet. ## How long is a day on this planet? A day on Neptune lasts 16 hours and 7 minutes.[^11] ## How long is a year on this planet? One year on Neptune is about 165 Earth years, or 60,265 days.[^12] ## What is it made of? Neptune is made of rock and metal in the **core**. The core is probably bigger than Uranus\'s because Neptune weighs more, but is the same size. Around the core is rock, water, **ammonia** and **methane**. The atmosphere is made of **hydrogen** and **helium**. Lower down in the atmosphere, there is methane and ammonia too. The methane makes Neptune look blue-green.[^13] !Artistic impression of the mythological Neptune.jpg "Artistic impression of the mythological Neptune") ## How much would Neptune\'s gravity pull on me? If you were floating close to the cloud tops of Neptune, it would pull you down with a force only a little stronger than the force of Earth\'s gravity.[^14] The effects of Neptune\'s larger **radius** and its **mass** almost cancel out, making the force only a little bigger. ## Who is it named after? Neptune is named after the Roman god of the seas, also known as Poseidon in ancient Greece. [^15] Next Topic: Pluto ## References ```{=html} <references/> ``` ar:ويكي الأطفال:نظام شمسي/نبتون de:Wikijunior Sonnensystem/ Neptun nl:Wikijunior:Zonnestelsel/Neptunus pl:Wikijunior:Układ_Słoneczny/Neptun [^1]: Smith, Bradford A. \"Neptune.\" World Book Online Reference Center. 2004. World Book, Inc. <http://www.worldbookonline.com/wb/Article?id=ar386900>; <http://www.nasa.gov/worldbook/neptune_worldbook.html> [^2]: <http://nssdc.gsfc.nasa.gov/planetary/factsheet/neptunefact.html> [^3]: Smith, Bradford A. \"Neptune.\" World Book Online Reference Center. 2004. World Book, Inc. <http://www.worldbookonline.com/wb/Article?id=ar386900>; <http://www.nasa.gov/worldbook/neptune_worldbook.html> [^4]: <http://www.nineplanets.org/neptune.html>; <http://www.moreheadplanetarium.org/index.cfm?fuseaction=page&filename=science_resources_neptune.html> [^5]: <http://www.nineplanets.org/neptune.html>; <http://starchild.gsfc.nasa.gov/docs/StarChild/solar_system_level1/neptune.html> [^6]: Smith, Bradford A. \"Neptune.\" World Book Online Reference Center. 2004. World Book, Inc. <http://www.worldbookonline.com/wb/Article?id=ar386900>; <http://www.nasa.gov/worldbook/neptune_worldbook.html> [^7]: <http://www.nineplanets.org/neptune.html> [^8]: <http://www.nineplanets.org/proteus.html> [^9]: <http://www.nineplanets.org/triton.html> [^10]: <http://www.nineplanets.org/nereid.html> [^11]: Smith, Bradford A. \"Neptune.\" World Book Online Reference Center. 2004. World Book, Inc. <http://www.worldbookonline.com/wb/Article?id=ar386900>; <http://www.nasa.gov/worldbook/neptune_worldbook.html> [^12]: <http://nssdc.gsfc.nasa.gov/planetary/factsheet/neptunefact.html>; Smith, Bradford A. \"Neptune.\" World Book Online Reference Center. 2004. World Book, Inc. <http://www.worldbookonline.com/wb/Article?id=ar386900>; <http://www.nasa.gov/worldbook/neptune_worldbook.html> [^13]: <http://www.nineplanets.org/neptune.html>; Smith, Bradford A. \"Neptune.\" World Book Online Reference Center. 2004. World Book, Inc. <http://www.worldbookonline.com/wb/Article?id=ar386900>; <http://www.nasa.gov/worldbook/neptune_worldbook.html> [^14]: Snow, Theodore P. (1996) \"The Outer Planets.\" In *The Dynamic Universe: An Introduction to Astronomy*. pp. 281. West Publishing Company. [^15]: Snow, Theodore P. (1996) \"The Outer Planets.\" In *The Dynamic Universe: An Introduction to Astronomy*. pp. 282. West Publishing Company.
# Wikijunior:Solar System/Pluto Pluto is a dwarf planet that was discovered by the astronomer Clyde W. Tombaugh in Arizona on February 18, 1930.[^1] !Pluto, as seen from the *New Horizons* spacecraft. ```{=html} <div style="float:right; border:2px solid #aaaaaa; width:250px; margin-left:0.2em; padding:0.4em"> ``` !♇.svg "♇"){width="80"} **Pluto Facts**: - Pluto is a dwarf planet, smaller even than Earth\'s Moon. - Pluto sometimes moves closer to the sun than Neptune. ```{=html} </div> ``` ## How big is Pluto? !Comparison of the sizes of Pluto, Charon, the Moon and Earth Pluto\'s **mass** is about 12,500,000,000,000,000,000,000 kilograms.[^2] While this may seem large, it\'s only about 1/500th of the Earth\'s mass. Pluto is between 2200 and 2400 kilometers across.[^3] Its **surface area** is about 17,950,000 square kilometers (or 1/30th of the Earth\'s).[^4] Its **volume** is 7,150,000,000 km^3^ (or 1/150th of the Earth\'s).[^5]\ {{ }} ## What is its surface like? !The surface of Pluto..jpg "The surface of Pluto.") Pluto\'s surface is covered with ice.[^6] It is very cold, at about -230 °C.[^7] Pluto also has a very thin **atmosphere** which freezes when Pluto moves far away from the Sun.[^8] The image above on the right shows Pluto\'s color. ## What are Pluto\'s moons like? Pluto has three known moons. The largest is called Charon. Charon is about half as wide as Pluto. Because Pluto and Charon are so close in size, they are sometimes called a \"double planet\".[^9] Charon\'s surface is covered in water ice.[^10] Two other moons were discovered in 2005. They have been named Nix and Hydra.[^11] ## How long is a day on Pluto? One day on Pluto is about 6.487 Earth days long. Like Uranus, Pluto also spins on its side.[^12] ## How long is a year on Pluto? One year on Pluto would be about 90,613 days or 248 years on Earth![^13] ## What is it made of? Scientists believe Pluto is made mostly of rock and ice,[^14] but they will not be sure until more research is done. The discovery of Charon helped scientists estimate the **density** of Pluto. The information collected told them what Pluto was and was not made out of. If Pluto were made out of heavy solids, it would have a very high density. If it were made of gases, it would have a low density. Pluto is somewhere in between, so it is probably made of rock and ice. ## How much would Pluto\'s gravity pull on me? If you were on Pluto, gravity would be only 0.06 times as strong as it is on Earth. [^15] This means you could do really high jumps---even more than people could on the Moon! ## Who is Pluto named after? Pluto was named after the Roman god of the underworld. In Roman mythology, he kidnapped Proserpina (Persephone) so he could marry her. This made her mother, Ceres, the goddess of agriculture, very sad, causing winter. To end winter, Jupiter, the king of the gods and her brother, decreed that Proserpina could return to the surface as long as she hadn\'t eaten any food of the Underworld. However, she had eaten six pomegranate seeds, so Jupiter decided she had to spend six months in the underworld each year. This is the Roman myth of winter. When she goes to the Underworld, everything stops growing. When she comes back, her mother is happy again, and life returns.[^16] In Roman mythology, Charon took dead souls across the river Acheron to the land of the dead.[^17] ## Is Pluto a planet? Pluto has been officially classified as a dwarf planet, which is different from a regular planet. One reason is its small size - although it is the tenth largest known object that revolves around the sun, it is smaller than many moons, including Earth\'s moon. Scientists used to think that Pluto was a lot larger than it actually is,[^18] and it was thought of as the ninth planet for many years. Another key reason is that Pluto is part of a large group of objects called the Kuiper Belt, which all revolve around the Sun in the area beyond Neptune. In January 2005 another object \"Eris\" was discovered in the Kuiper Belt. Eris is larger than Pluto. Scientists think there are even more Pluto-sized objects in this part of the solar system, as well as millions of smaller objects. Because of this, the International Astronomical Union (IAU) defined the term \'planet\' for the first time. Under the definition, both Eris and Pluto (along with Ceres, Haumea and Makemake) are dwarf planets. In spite of this, some people continue to hold on to the idea that Pluto is a regular planet because of tradition. Also, some textbooks and references are not up to date, and still list Pluto as the ninth planet. Next Topic: Comets ## References ```{=html} <references/> ``` ar:ويكي_الأطفال:نظام_شمسي/بلوتو de:Wikijunior Sonnensystem/ Pluto nl:Wikijunior:Zonnestelsel/Pluto pl:Wikijunior:Układ_Słoneczny/Pluton [^1]: <http://nssdc.gsfc.nasa.gov/planetary/factsheet/plutofact.html> [^2]: Snow, Theodore P. (1996) \"The Outer Planets.\" In *The Dynamic Universe: An Introduction to Astronomy*. pp. 285. West Publishing Company. ; <http://nssdc.gsfc.nasa.gov/planetary/factsheet/plutofact.html> [^3]: Spinrad, Hyron. 2004 \"Pluto.\" World Book Online Reference Center. 2004. World Book, Inc. <http://www.worldbookonline.com/wb/Article?id=ar435500>; <http://www.nasa.gov/worldbook/pluto_worldbook.html>; Snow, Theodore P. (1996) \"The Outer Planets.\" In *The Dynamic Universe: An Introduction to Astronomy*. pp. 285. West Publishing Company. ; <http://amazing-space.stsci.edu/resources/fastfacts/pluto.php.p=Astronomy+basics@,eds,astronomy-basics.php&a=,eds> [^4]: <http://nssdc.gsfc.nasa.gov/planetary/factsheet/plutofact.html> [^5]: <http://nssdc.gsfc.nasa.gov/planetary/factsheet/plutofact.html> [^6]: Snow, Theodore P. (1996) \"The Outer Planets.\" In *The Dynamic Universe: An Introduction to Astronomy*. pp. 287. West Publishing Company. ; <http://www.nasa.gov/worldbook/pluto_worldbook.html> [^7]: <http://nssdc.gsfc.nasa.gov/planetary/factsheet/plutofact.html>; Snow, Theodore P. (1996) \"The Outer Planets.\" In *The Dynamic Universe: An Introduction to Astronomy*. pp. 285. West Publishing Company. ; <http://www.nasa.gov/worldbook/pluto_worldbook.html> [^8]: Snow, Theodore P. (1996) \"The Outer Planets.\" In *The Dynamic Universe: An Introduction to Astronomy*. pp. 287. West Publishing Company. ; <http://nssdc.gsfc.nasa.gov/planetary/factsheet/plutofact.html> [^9]: <http://solarsystem.nasa.gov/planets/profile.cfm?Object=Plu_Charon> [^10]: <http://seds.lpl.arizona.edu/nineplanets/nineplanets/pluto.html> [^11]: <http://www.space.com/scienceastronomy/060621_nix_hydra.html> [^12]: <http://nssdc.gsfc.nasa.gov/planetary/factsheet/plutofact.html>; <http://www.nineplanets.org/pluto.html> [^13]: <http://solarsystem.nasa.gov/planets/profile.cfm?Object=Pluto&Display=Overview> [^14]: <http://seds.lpl.arizona.edu/nineplanets/nineplanets/pluto.html> [^15]: Snow, Theodore P. (1996) \"The Outer Planets.\" In *The Dynamic Universe: An Introduction to Astronomy*. pp. 285. West Publishing Company. ; <http://nssdc.gsfc.nasa.gov/planetary/factsheet/plutofact.html> [^16]: <http://www.windows.ucar.edu/tour/link=/mythology/persephone_seasons.html>; <http://www.pantheon.org/articles/p/persephone.html> [^17]: <http://www.pantheon.org/articles/c/charon.html> [^18]: Sobel, Dava (2005) \"The Planets.\" pp. 220. Harper Perennial Publishing Company.
# Wikijunior:Solar System/Comets {{/Coolfacts\|= 1\|\|= 2\|80px\|☄.svg "wikilink") Comet Facts\|= 3\| - Comets are often described as giant \"dirty snowballs\" because they are mostly made up of ice and some dirt. - Comets have two \"tails\", one made up mostly of rocks and dust, the other mostly made of gas. - Comet tails always point *away* from the Sun. }} ## What is a Comet? !The Hale Bopp comet Think of a comet as a big, dirty, gassy snowball. Comets are formed in the ring of rocks, dust, and ice that orbits the Sun beyond Pluto called the Kuiper Belt. Comets form when rocks, dust, and ice `<i>`{=html}condense`</i>`{=html} -- that is, join together . As a comet grows larger, it starts to be pulled towards and around the Sun. Comets in our Solar System usually take many years to go around the Sun -- from a few dozen years to many thousands of years. This is because they start to orbit the sun from very far away. They make long, egg-shaped orbits around the Sun instead of almost circular ones like the planets.\ ## What does a Comet look like? {{ }} !The strange surface of Churyumov-Gerasimenko, a comet. Photograph taken by the Rosetta space craft. The comets that can be seen in the sky without telescopes are unusual because they are the biggest and brightest comets of all. You might have the chance to see one once or twice during your life. Most comets can only be seen with a telescope. The few that can be seen with human eyes are usually just hazy streaks or faint smudges in the night sky. When comets are very far away from the Sun, they are covered in a coating of icy, black rocks and dust. As a comet approaches the Sun, however, the ice starts to melt. This creates large amounts of water and gas that break through the coating, freeing some of the dust and rocks. Sometimes this water, gas, rocks, and dust can be seen from the Earth as one or two tails streaming away from the comet. Even when only one tail can be seen, there are two, one made from the lighter gas and water, and the other from the rocks, dust, and chunks of ice. Comets themselves are usually between a few kilometres and several hundred kilometres in size, but their tails can be several million kilometres long. ## Seeing Comets in the Sky The \"great comets\" that produce particularly spectacular tails are some of the rarest objects in our solar system. Usually they can only be seen about once every hundred years, so it is very rare to see one of these comets. The last great comet appeared in 1910, but it may still be another hundred years before another one comes near the Earth. Astronomers can\'t predict exactly how or when they will appear as there are still things about our Solar System that they don\'t understand. If you hear about a comet coming into the sky soon, follow the instructions below to watch it! 1. Find out if the comet is going to be in your area of the sky. 2. Get a telescope or binoculars and some chairs to view it. Many of the largest comets have never even needed a telescope to see them. 3. Ask your parents to take you to a park, the woods or another dark place away from city lights. 4. Look up into the sky and enjoy this amazing sight. Usually the dust making up the comet\'s tail is so faint you can\'t see it. However, when the Earth\'s orbit takes it through one of these tails, the dust hits the Earth\'s atmosphere and burns up. These are the recurring **meteor showers** that happen from time to time, and most major meteor showers have now been identified either with an existing comet or the remains of a comet that was observed earlier, usually in previous centuries. When the Earth travels through this \"swarm\" of dust left behind, you can see **shooting stars** or **meteors** at night. ## How many Comets are there? No one really knows. All comets spend most of their orbit so far away from the sun that they can\'t be seen \-- even with a telescope. However, every year amateur astronomers1 discover over 100 never-seen-before comets that have come close enough to be discovered2. As of November 2005, astronomers have discovered 2 857 comets 3. Most of the comets we see either crash into the Sun, or leave the Solar System entirely. There might be millions of these comets that sooner or later will come within range of our telescopes. Of all the comets that have ever been seen, astronomers only expect 253 comets to ever return 4. ## How is a Comet named? !Edmond Halley A comet is usually named after the astronomer who first discovered it. When several people are involved in its discovery, sometimes you will see multiple names on a comet, like Comet Hale-Bopp, or Comet Shoemaker-Levy. It is generally considered to be a great honor to have a comet named after you.\ ## What are some famous Comets in history? right\|thumb\|upright=1.5\|This diagram shows the orbit of Halley\'s comet around the Sun. There are a few things to note about this orbit.\ \*It is much more elongated than a planet\'s orbit.\ \*It is not in the same plane as the planets.\ \*It goes round its orbit in the opposite direction. This is called retrograde motion.\ - Halley\'s Comet - Perhaps the most famous of all comets, and this was the first comet to be identified as a recurring comet. - Comet Encke - The second comet to be identified as a recurring comet. - Comet Shoemaker-Levy 9 - This was the first comet to have been observed hitting another body in the Solar System. In this case, it smashed into the planet Jupiter in what was possibly the most studied astronomical event in history. ## Do comets bring bad luck? In ancient times people didn\'t have a very good understanding of what comets really were or where they came from. They were seen as very unusual objects in the sky, and very temporary in nature as well. In some societies it was often a sign of bad events in the future when a comet arrived, associated with the death of a king or a significant military defeat. In other countries comets were considered to bring good luck, bringing increased fertility and more food. The ancient Chinese astronomers seem to have done the best job of actually recording when comets appeared in the sky, and left detailed descriptions of what they looked like and approximately where in the sky each comet was seen. Even as recently as the 1910 appearance of Halley\'s Comet there was widespread panic when it was discovered that the Earth might pass through the tail of that comet. The panic was over the possibility of gases from the comet flooding the atmosphere of the Earth with poison. The reality was that there is so little gas in a comet tail that there is no measurable effect in the content of the Earth\'s atmosphere when an event like this occurs. Next Topic: Kuiper Belt ## References - \"What is a comet?\" 5 - \"What does a comet look like?\" 6 7 8 9 - \"Seeing comets in the sky\" 10 11 12 - \"How many comets are there?\" - \"How is a comet named?\" 13 14 - \"Do comets bring bad luck?\" 15
# Wikijunior:Solar System/Kuiper Belt ```{=html} <div style="float:right; border:2px solid #aaaaaa; width:250px; margin-left:0.2em; padding:0.4em"> ``` **Kuiper Belt Facts**: - The Kuiper belt is the most recently discovered section of the Solar System. ```{=html} </div> ``` Beyond the **orbit** of Neptune lies the Kuiper belt. It extends outward an additional three billion kilometers away from the Sun. The belt contains different-sized lumps of icy mixtures. These lumps are called Kuiper belt objects. The biggest are called minor planets or dwarf planets. The Kuiper belt may have formed when the gravity of the young planet Jupiter hurled the objects out to where they are now. The Kuiper belt is named after Gerard Kuiper (rhymes with \"viper\"), one of several astronomers who hypothesized about a field of small objects beyond Neptune. ### What are Kuiper belt objects? The objects in the Kuiper belt are frozen mixtures of dirt, ice and **organic compounds**. They are a lot like **comets**. Some of the objects have a reddish color and others are gray. {{ }} ### How big are the Kuiper belt objects? Scientists consider Pluto to be one of the largest Kuiper belt objects. It is 2390 km across and is a dwarf planet. The next largest known Kuiper belt objects are Orcus, 2003 EL61 and 2005 FY9. Orcus is about 1600 km (1,000 miles) across; 2003 EL61 is 70% the size of Pluto and 2005 FY9 is about 50% to 70% of Pluto\'s size. Recently, scientists found another dwarf planet named Eris that is even bigger than Pluto. The scientists don\'t know its exact size, but they think it is about 20% larger than Pluto. At the time it was found, it was almost 100 times further away from the Sun than the Earth. It can come about as close to the Sun as Pluto. Eris has a moon named Dysnomia. The orbit of Eris is tilted almost 45 degrees compared to Earth\'s orbit. Pluto\'s orbit is only tilted by 17 degrees. Other large Kuiper belt objects about or over 1000 km across are Pluto\'s moon Charon, Quaoar, Varuna, Ixion, 1996 TL66, 2002 TX300, 2002 TC302, 2002 UX25 and 2002 AW197. Ceres, the largest **asteroid** in the asteroid belt, is about 950 km across. There are many other Kuiper belt objects that are only a few kilometers or tens of kilometers across. ### How many Kuiper belt objects are there? Over a thousand Kuiper belt objects had been found by astronomers. Scientists think that there might be more than seventy thousand large objects in the Kuiper belt. Even though there are so many objects in the Kuiper belt, it is very light, weighing between ^1^/~25~ and ^1^/~30~ of Earth\'s mass. ### What is it named after? After the first object in the belt other than Pluto and its moon Charon was spotted from the Mauna Kea Observatory in Hawaii in 1992, the belt was named after the astronomer Gerard Kuiper. Back in 1951 this scientist wrote that he thought this belt might exist, but there was no proof at that time. Other astronomers, including Frederick Leonard, Kenneth Edgeworth, and Julio Fernandez, also thought that the belt existed. For this reason some astronomers call it the Edgeworth-Kuiper belt. ### What are the Kuiper belt objects named after? When an object is discovered in space, it is given a temporary name called a \"provisional designation\". This temporary name begins with the year the object was discovered, followed by some letters and numbers that tell in what month and in what order it was discovered. Later on, important objects are given formal names, often taken from mythology. The Kuiper belt objects Orcus, Charon, and Varuna were all named after mythological gods of the underworld. Ixion was named after a mythological person in the underworld. Quaoar was named after a creation god of the Native American Tongva people. Next Topic: Oort Cloud de:Wikijunior Sonnensystem/ Kuipergürtel
# Wikijunior:Solar System/Oort Cloud {{/Coolfacts\|= 1\|\|= 2\|Oort cloud Facts:\|= 3\|\* The Oort cloud is as far from the Sun as you can go without leaving the Solar System. - It is believed that most comets originate in the Oort cloud before \"falling\" toward the Sun. }} The Oort cloud is a huge halo made of millions of comets that lies at the outermost edge of the Solar System. ## What is the Oort Cloud? Scientists say there is a distant group of objects, made of rock and ice, that forms a cloud-like region surrounding our Solar System. It is a cloud of comet-like objects orbiting far away from the Sun. Even though the comets are very widely scattered from each other, there many millions of them. The total mass of all these comets may be up to 100 times the mass of the Earth. The Oort Cloud is named after a Dutch astronomer Jan Oort who took the original idea, improved upon it and made it widely known. !This diagram shows about how far away the Oort cloud might be compared to the planets of the Solar System. Start in the upper left frame, then follow the pictures clockwise. Each picture shows a bigger volume of space.{width="350"} As a comet makes several passes through the solar system, the Sun slowly melts and vaporizes the ice and only little bits of solid debris are left behind. But if the comets are all destroyed when they pass through the system, then new comets will need to appear. Otherwise we would not see any more comets. Jan Oort used the idea of the Oort cloud to explain why new comets keep appearing. ## Where is the Oort Cloud? If you can imagine the distance from the Earth to the Sun, then the comets in the Oort cloud are 50,000 to 100,000 times further away! That is 1,000 times further away from the Sun than is Pluto, and about one fourth the distance to the nearest neighboring star---Proxima Centauri. Light takes a year to travel from the Sun to the outer edge of the Oort Cloud. {{ }} ## How did the Oort Cloud start? The Oort cloud objects may have started closer to the Sun during the Solar System\'s formation. When they passed near the gas giants, the gravity of those planets hurled the objects into very distant orbits. The Oort cloud objects were sent in all directions, making the Oort cloud ball-shaped instead of disk-shaped. The gravity of passing stars also made the orbits of these objects more circular, and pulled them further from the Sun. But sometimes the gravity of other far away stars can send the objects hurtling back toward the Sun. These become the comets. ## What objects are in the Oort Cloud? An object named Sedna has been discovered that may belong to the Oort Cloud (although it is actually between the Kuiper Belt and the Oort Cloud.) It is from 1,180 to 1,800 km across. Its orbit stretches from 76 to 928 times further from the Sun than does the Earth\'s. Sedna orbits the Sun about once every 11,250 Earth years. The last time Sedna was where it is now in its orbit, Earth\'s last Ice Age was ending! Some scientists think that Sedna should be included in the Kuiper Belt, making the belt bigger. Next Page: Glossary de:Wikijunior Sonnensystem/ Oortsche Wolke
# Wikijunior:Solar System/Space exploration ## Space exploration --- A long dream !An illustration of a spacecraft in *From the Earth to the Moon* Going into space was always one of the biggest dreams people had, even thousands of years ago. Many science fiction authors wrote about traveling in space even before the first airplane flight in 1903. One of the most famous science fiction books on space travel is *From the Earth to the Moon* by Jules Verne --- it was written in 1865, more than one hundred years before the first person walked on the moon. Jules Verne\'s idea was to use a giant cannon! That might seem silly today, but it shows how much our ideas on space travel have changed. ## The first exploration of space !Laika: the first space traveller Space begins about 100 km or 62 miles above the earth. A more realistic way to travel in space is with a **rocket**. Within a rocket is a controlled explosion. However, exhaust (things left over after burning) is only allowed to leave the rocket in one direction. As a result, the rocket is pushed in the other direction. In 1942, the German rocket *A-4* became the first to reach that height, but it wasn\'t meant to do anything but fall straight down again and so wasn\'t terribly useful. Still, it was an advance in rocket technology. The Soviets were the first to put anything in space that would stay up: they launched the *Sputnik 1* satellite on October 4, 1957. Within a month, the Soviets launched *Sputnik 2*, and in that spacecraft was the first space traveler: a dog called Laika. The launch of the *Sputnik* started the Space Race, a competition between the United States and the Soviet Union to obtain more and more advanced space technology. Americans were very surprised that the Soviets could have launched \'Sputnik\', and began to design rockets and satellites of their own. The race would last for the next few decades. ## A man in Space !Yuri Gagarin_-_Restoration.jpg "Yuri Gagarin") On April 12, 1961, the first person was sent into space: Yuri Gagarin, a Soviet, riding in the spacecraft *Vostok 1*. The Soviets would send more people into space over the next few decades, and so would the Americans, but it wouldn\'t be until 2003 that a different country would launch their own spacecraft with a person in it: China, with the *Shenzhou 5*. ## The race to the moon !An Astronaut on the Moon. At the beginning of the 1960s, American president John F. Kennedy made a famous speech in which he said that the U.S. was going to send people to the moon within the next 10 years. And that\'s what happened: in July of 1969, Neil Armstrong stepped off the there spacecraft and said \"One small step for \[a\] man and one giant leap for mankind\". He and Buzz Aldrin walked on the moon where they put an American flag. Their footprints are still there because there is no wind or water on the Moon to wash them away. ## The Space Shuttle !Launch of a space shuttle. After the Apollo program that sent people to the Moon, the U.S. built the Space Shuttle, that is like a jet-plane that can go to space and return (with the help of rockets of course)! The Space Shuttle helped to construct the ISS (International Space Station) among another things. The last space shuttle mission was on June 28, 2011, but it will be replaced with new vehicles that will take mankind to the Moon, Mars, and beyond! ## Spaceships of the future Right now, spaceships are not very efficient. The Saturn V rocket was 363 feet or nearly 111 meters tall, and it could only take people to the moon! To get people further, better rockets must be invented. One of the most popular ideas for a rocket is the **antimatter** rocket. This type of rocket collides a small amount of **antimatter** with an equal amount of normal **matter** to create a large amount of energy! Other ideas for going into space, that do not need rockets, have been thought of by scientists and astronomers. One of these is a space elevator. A space elevator is basically a big lift into space. It will cost a lot less to get things up into space if a space elevator is built. !Is this what space travel will look like in the future? Another idea, a bit like the Jules Verne idea, is an electromagnetic catapult. This catapult works by accelerating the spaceship along a rail, similar to a maglev train. Unfortunately, the air on Earth would set spaceships on fire as they launched, but scientists aren\'t thinking of putting one there: one could go on the Moon! The catapult on the moon could send metal and other resources to Earth\'s orbit, where a space station could collect them. ## Exploration beyond the Solar System Many people dream of the day when humans can travel to another star and explore other worlds, some people wonder what\'s out there some belive that aliens or other life may live on another plant. But, if this ever does happen probably won\'t happen for a very long time. The stars are so spread out that there are trillions of miles between stars that are \"neighbors\". Maybe one day, your great grandchildren will be standing atop an alien world wondering about their ancient ancestors? ## The eye beyond Earth !The Hubble Telescope as seen by the space shuttle. Many people say the very best invention ever (not just in space technology) was the Hubble space telescope (HST). Others say it\'s just the space station being selfish having the best technology in the world. The Hubble Space telescope is a giant telescope that is in orbit around the Earth. Because there is no atmosphere, the Hubble Space Telescope has a clear view of even distant galaxies. One of the pictures the Hubble space telescope has made is called the \'Hubble Deep Field\'. The Hubble Deep Field is a picture of some of the most distant galaxies, and it gives a snapshot of what the universe looked like when it was younger. !A futuristic space telescope planned for the year 2021. Even bigger telescopes are also in the planning, so we might be able to see right to the edge of the universe some day soon. de:Wikijunior Sonnensystem/ Raumforschung
# Wikijunior:Solar System/Puzzles ### Crypto Quiz Try to fill in the correct answer for each of the questions below. A letter should go on each blank line. The numbers underneath the lines match the entries in the secret message. What does it say? ![](Solar_System_Crypto_Quiz.png "Solar_System_Crypto_Quiz.png"){width="600"} ### Photo Word Scramble Each of the names of the pictures below have been scrambled. Can you unscramble the letters to find the correct names? ![](Solar_System_Word_Scramble.png "Solar_System_Word_Scramble.png"){width="400"} ### Word Find Each of the words except one in the list to the right can be found along a row, column, or diagonal somewhere inside the box below. See if you can find which one is missing by finding all the others. ![](Solar_System_Word_Find.png "Solar_System_Word_Find.png"){width="600"}
# Wikijunior:Solar System/Glossary {{ }} A glossary of words used in this book: - **Antimatter**: the opposite of normal matter. Not usually found outside of a laboratory. When mixed with matter they cancel each other out and release lots of energy. ```{=html} <!-- --> ``` - **Arachnoid**: a scientific term for something shaped like a spider, like the legend of the weaving contest. ```{=html} <!-- --> ``` - **Asteroid**: a large rocky object that orbits a star, but is too small to be a planet. It is found in space. ```{=html} <!-- --> ``` - **Astronomer**: a person who studies stars and planets. Also a person who explores new planets and solar systems. ```{=html} <!-- --> ``` - **Astronaut**: a person who travels beyond the atmosphere of the Earth. ```{=html} <!-- --> ``` - **Atmosphere**: a layer of gases around a planet. ```{=html} <!-- --> ``` - **Atom**: a very tiny particle that is the basic building block of matter. It is the tiniest thing on Earth. ```{=html} <!-- --> ``` - **Basalt lava**: molten basalt, a kind of rock from a volcano. ```{=html} <!-- --> ``` - **Belt**: A name used for bands of dark-colored cloud layers on Jupiter. ```{=html} <!-- --> ``` - **Binoculars**: a folding pair of small telescopes with an eyepiece for each eye. ```{=html} <!-- --> ``` - **Carbon dioxide**: a gas that animals breathe out and plants take in. ```{=html} <!-- --> ``` - **Carbonaceous chondrite**: A type of meteorite that contains a lot of water and organic compounds. ```{=html} <!-- --> ``` - **Centaur**: an icy planetoid that orbits the Sun between Jupiter and Neptune. ```{=html} <!-- --> ``` - **Channel**: a groove in the surface of something. ```{=html} <!-- --> ``` - **Comet**: a small icy object orbiting a star. ```{=html} <!-- --> ``` - **Conjunction**: when two objects orbiting the same body come closest together. ```{=html} <!-- --> ``` - **Continent**: a huge landmass on a planet, usually made of tectonic plates that have locked together. ```{=html} <!-- --> ``` - **Convection**: a type of movement in a gas or liquid that carries heat toward a cooler location. When the gas or liquid cools, it sinks back down again. ```{=html} <!-- --> ``` - **Core**: the center of a planet or star. ```{=html} <!-- --> ``` - **Corona**: a region of very hot gas that surrounds the photosphere of a star. ```{=html} <!-- --> ``` - **Crater**: a dent in a planet\'s surface made by a meteorite falling on it. ```{=html} <!-- --> ``` - **Crust**: the outermost layer of a planet\'s surface. ```{=html} <!-- --> ``` - **Dwarf planet**: a rounded body that is in orbit around the Sun. It is not a moon and it is not big enough to sweep up the other objects along its orbit. ```{=html} <!-- --> ``` - **Eclipse**: the shadow made when one object comes between another object and the Sun. ```{=html} <!-- --> ``` - **Energy**: what you use to do work. ```{=html} <!-- --> ``` - **Environment**: the conditions on a planet. ```{=html} <!-- --> ``` - **Equator**: an imaginary line around a planet, perpendicular to the axis of rotation. ```{=html} <!-- --> ``` - **Erosion**: the slow wearing away of a surface, usually from wind, water, and temperature changes. ```{=html} <!-- --> ``` - **Galaxy**: a huge mix of gas, dust, stars, planets and other objects that are held together by their own gravity. ```{=html} <!-- --> ``` - **Gas giant**: one of the four outer planets made out of giant balls of gas. ```{=html} <!-- --> ``` - **Gravity**: the force that pulls on anything with mass (see the About gravity, mass, and weight section). ```{=html} <!-- --> ``` - **Hemisphere**: one half of a planet\'s surface. ```{=html} <!-- --> ``` - **Ice cap**: A huge body of ice at the pole of a planet. ```{=html} <!-- --> ``` - **Lagrange point**: the places where the gravity from two orbiting objects balance each other. ```{=html} <!-- --> ``` - **Lava**: molten rock above a planet\'s surface. ```{=html} <!-- --> ``` - **Latin**: the language of the Roman Empire that was later used by scientists to name things. ```{=html} <!-- --> ``` - **Mantle**: a layer of molten rock below a planet\'s crust. ```{=html} <!-- --> ``` - **Maria**: a large sea of magma that has cooled into solid rock. ```{=html} <!-- --> ``` - **Mass**: the amount of matter that something is made of (see the About gravity, mass, and weight section). ```{=html} <!-- --> ``` - **Matter**: a scientific word for \'stuff\'. ```{=html} <!-- --> ``` - **Meteor**: a small or medium-size rock from space that has entered a planet\'s atmosphere but has not reached the ground. ```{=html} <!-- --> ``` - **Meteor shower**: a large number of meteors that enter a planet\'s atmosphere at about the same time. ```{=html} <!-- --> ``` - **Meteorite**: A meteorite that made it through a planet\'s atmosphere and landed on the ground. ```{=html} <!-- --> ``` - **Methane**: a gas that makes up most of the gas giants. ```{=html} <!-- --> ``` - **Near Earth asteroid**: an asteroid that has an orbit that brings it very close to the earth. ```{=html} <!-- --> ``` - **Newton**: a unit of measurement the describes how hard gravity is pulling you down (see the About gravity, mass, and weight section). ```{=html} <!-- --> ``` - **Observatory**: A special building where astronomers keep their telescopes ready for use. ```{=html} <!-- --> ``` - **Orbit**: the path that an object takes around a larger object. ```{=html} <!-- --> ``` - **Orbit System**: a planet and its moons rotating around a star. ```{=html} <!-- --> ``` - **Organic compounds**: compounds (collections of atoms) containing carbon. ```{=html} <!-- --> ``` - **Phase**: how a planet or moon looks to us at some part of its orbit, when it is lit by the Sun. ```{=html} <!-- --> ``` - **Planet**: the celestial body that has a greater mass than all other objects of the same orbit system together and that describes a well-defined, special orbit around a star. ```{=html} <!-- --> ``` - **Planetary nebula**: a great cloud of gas that was blown off by an old star. ```{=html} <!-- --> ``` - **Photosphere**: the layer of a star that releases light and other energy into space. ```{=html} <!-- --> ``` - **Prominence**: an eruption of hot gas at the surface of the Sun. ```{=html} <!-- --> ``` - **Provisional designation**: a temporary name given to a newly-found object. Later a permanent name may be picked. ```{=html} <!-- --> ``` - **Radar**: radio waves used to find distances to and make maps of things. ```{=html} <!-- --> ``` - **Regolith**: loose soil on the Moon created by rocks hitting the surface at very high speed. ```{=html} <!-- --> ``` - **Retrograde motion**: a rotation that is the opposite way from the rotation of most of the Solar System. ```{=html} <!-- --> ``` - **Retrograde orbit**: an orbit that is the opposite way from the orbit of most of the planets and moons in the Solar System. ```{=html} <!-- --> ``` - **Ring**: A flat, circular band of many small, loose objects that orbit a planet. ```{=html} <!-- --> ``` - **Rotate**: to spin around on an axis. ```{=html} <!-- --> ``` - **Satellite**: an object in a stable orbit around a much larger object. ```{=html} <!-- --> ``` - **Scarp**: a type of cliff. ```{=html} <!-- --> ``` - **Sidereal day**: the time for a planet or moon to rotate so that a distant star overhead is again overhead. ```{=html} <!-- --> ``` - **Silicate**: an object composed mostly of the element silicon, which makes rocks. ```{=html} <!-- --> ``` - **Shooting star**: another name for a meteor. ```{=html} <!-- --> ``` - **Solar day**: the time for a planet or moon to rotate so that the Sun is again overhead. ```{=html} <!-- --> ``` - **Solar wind**: a very hot gas that is being blown away from the Sun at a high speed. ```{=html} <!-- --> ``` - **Spacesuit**: A special sealed suit that protects an astronaut. It has its own air supply so the astronaut can breath, and is insulated against the cold of space. ```{=html} <!-- --> ``` - **Spectrum**: the colored band of light made when white light passes through a prism. ```{=html} <!-- --> ``` - **Star**: a huge ball of gas that is so heavy that it causes nuclear reactions inside itself. This produces heat and light. ```{=html} <!-- --> ``` - **Sulfuric acid**: a strong type of acid that is used in car batteries, and contains the element sulphur. ```{=html} <!-- --> ``` - **Supergiant**: a star near the end of its life that puffs out into a huge body many times larger than a normal star. ```{=html} <!-- --> ``` - **Surface area**: the area on the outside of something. ```{=html} <!-- --> ``` - **Tectonic Plate**: a solid part of the crust that very slowly moves across the surface of a planet ```{=html} <!-- --> ``` - **Telescope**: a system of lenses or mirrors that are used to see distant objects. ```{=html} <!-- --> ``` - **Terrestrial planets**: the four planets closest to the Sun. ```{=html} <!-- --> ``` - **Tether**: A cord that is used to keep two things attached to each other, such as an astronaut to a spaceship. ```{=html} <!-- --> ``` - **Tide**: the rise in the surface caused by gravity from another object, such as the Moon or Sun. ```{=html} <!-- --> ``` - **Tidal lock**: when tides have slowed rotation so that a moon or planet is always facing the same side toward the planet or star. ```{=html} <!-- --> ``` - **Transit**: When astronomers observe one object pass in front of a larger object. ```{=html} <!-- --> ``` - **Trojan asteroid**: an asteroid in the same orbit as a planet or moon that always stays the same distance ahead or behind. ```{=html} <!-- --> ``` - **Volcanic**: something that relates to volcanoes. ```{=html} <!-- --> ``` - **Volume**: the size of a three-dimensional object. ```{=html} <!-- --> ``` - **White dwarf**: a star that has run out of fuel to burn and is slowly cooling off. ```{=html} <!-- --> ``` - **Zone**: A name used for bands of light-colored cloud layers on Jupiter. it:Wikijunior Il sistema solare/Glossario de:Wikijunior Sonnensystem/ Glossar fr:Wikijunior:Système solaire/Glossaire
# Wikijunior:Solar System/Test ## Task 1: The Solar System Below are the eight planets of our solar system, each with a description. Fill in the blanks in the descriptions. - First you have to fill in which planet it is from the sun. For example: if you think Jupiter is the seventh planet, fill in *7th*. - Secondly you have to fill in if the planet is bigger or smaller than Earth. The bigger/smaller question for Earth is about the moon! --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- !Venus is the **2nd** planet of our Solar System and it\'s **smaller** than Earth.{width="90"} !Earth is the **3rd** planet of our Solar System and the moon is **smaller** than Earth.{width="90"} !Jupiter is the **5th** planet of our Solar System and it\'s **bigger** than Earth.{width="90"} !Saturn is the **6th** planet of our Solar System and it\'s **bigger** than Earth.{width="90"} !Neptune is the **8th** planet of our Solar System and it\'s **bigger** than Earth._flatten_crop.jpg "Neptune is the 8th planet of our Solar System and it's bigger than Earth."){width="90"} !Uranus is the **7th** planet of our Solar System and it\'s **bigger** than Earth.{width="90"} !Mercury is the **1st** planet of our Solar System and it\'s **smaller** than Earth.{width="90"} !Mars is the **4th** planet of our Solar System and it\'s **smaller** than Earth.{width="90"} --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- *8 points can be earned with this task. Every wrong sentence reduces the score by 1.* ## Task 2: About the planets *8 points can be earned with this task. Every right answer gives 1 point.* ## Task 3: Other astronomical objects Dependent on the previous question: Dependent on the previous question: *8 points can be earned with this task. Every right answer gives 1 point.* ## Task 4: Glossary Define these terms. *8 points can be earned with this task. A wrong or bad description gives 0 points, a reasonable description gives 1 point, a good description gives 2 points.* ## Task 5: Space Flight *8 points can be earned with this task.* nl:Wikijunior:Zonnestelsel/Eindtoets
# Wikijunior:Solar System/How the Solar System was born Our **solar system** is part of an entity called our **universe**. There were many attempts made in the past to explain how our solar system and universe came into existence as we observe it today. Most scientists use the **Big Bang Theory**, though some people have other theories. ## Big Bang Theory This theory is based around the idea that an enormous explosion occurred about 13.7 billion years ago. That is 13,700,000,000 years ago. This is three times the age of Earth! The Big Bang was not a usual explosion in space because space and time themselves were made in the explosion. This explosion caused the formation of the matter and energy in the universe. At first, the universe was very hot. The planets, stars and all other heavenly bodies formed starting some time after the Big Bang after the universe had cooled down. The universe had been expanding and cooling since the Big Bang. Most galaxies are moving further away from our Milky Way galaxy. The exceptions are the few galaxies that are close enough to the Milky Way for gravity to overcome the universe\'s expansion. Scientists can still see the faint light from when the universe was hot. Over time, the universe\'s expansion stretched out the light, turning it into weak microwave light. Scientists can detect this microwave light. ## Milky Way Galaxy Formation ## Solar System Formation The solar system formed out of a big cloud of gas and dust about 4.6 billion years ago. thumb\|250px\|Eagle Nebula (M16) - Birth of New Stars Stars and solar systems that are very similar to the Sun are now forming in the Eagle Nebula (also known as M16). While this is not a picture of our own sun, it can give you an idea of what our solar system looked like billions of years ago. These gas clouds that you see in this image were formed from earlier stars that exploded and left stuff behind. Small finger-like parts of these clouds, especially at the \"top\" of the first column on the left, are the new stars that are forming. Astronomers who have been watching these stars form have seen changes happen in just a few years, which is a very rapid change for the life of a star. Over many millions and billions of years, these stars and any planets formed with them will look like our Solar System today. What astronomers think happened after this initial period when the Sun was created from these huge gas clouds, there were many small and large rocks that gradually came together because of gravity and formed the planets, moons, asteroids, and comets that we know about today. Many of the craters which can be found on the Moon were made when these rocks came crashing on to the surface. While the number of small rocks and other stuff from the early history of the solar system is now less than what it was like right after the Sun formed, the space between the planets still has many of these rocks, and they continue to form craters and even come into the Earth\'s atmosphere. When you see these rocks at night, they are known as either **Shooting Stars** or **Meteorites**. By watching these items come to the Earth, you are directly witnessing the process that created the Earth in the first place.
# Wikijunior:Solar System/What will happen to the Solar System in the future ## The Fate of Our Solar System Just as the Solar System relies on the Sun as its source of energy, so too is its fate linked to that of the Sun. The Sun is right now a middle-aged star. It has existed for about 5 billion years, and will go on shining, pretty much unchanged, for about another 5 billion more. At that time, it will go through major changes that will bring an end to the Solar System as we know it. To understand these changes, we must first understand where the Sun\'s energy comes from. ## The Power of Fusion Like all stars, the Sun is made mostly of hydrogen. This is the simplest of all atoms. Because the Sun is so large and its gravity is so strong, the hydrogen atoms near the center of the Sun - at its core - are under extreme pressure, and are squeezed very close together. Sometimes, four of these atoms are squeezed so tightly together that they collide with enough force to stick together permanently, forming a new, larger, and more complex atom: helium. This process is called **nuclear fusion**, and when it happens, a small amount of energy is released in the form of heat and light. Due to the massive size of the sun, those small amounts of energy add up to an enormous amount and nuclear fusion is what powers the Sun. (The energy output at the sun\'s core per cubic meter is about the same as common reptiles, so it IS size that matters here!) ## Out of Gas Eventually, the Sun will burn all of the hydrogen in its core, and the fusion will stop. Once this happens, the core will shrink under its own gravity, until it becomes so dense that the helium atoms will begin to collide to form carbon (from three helium atoms) and oxygen (from four helium atoms). These collisions produce much more energy than the hydrogen fusion that powers the Sun today. The extra energy will cause big changes in the Sun. The core will become much hotter, causing the Sun to swell to over one hundred times its present size, swallowing up the planets Mercury and Venus. Even though the core will be hotter, the surface will be cooler than it is today, changing in color from yellow to red. A star at this stage is called a **red giant**. What about here on Earth? When the Sun expands, the Earth will not be spared. Like Mercury and Venus, Earth will probably be absorbed by the expanding Sun. But even if it is not, it will be no place to live. The oceans will boil, and the atmosphere will be blown away. What is left will be a charred, barren cinder, unable to sustain life. ## An Unstable Ending !A Planetary Nebula{width="320"}Meanwhile, the helium-burning reaction in the Sun will produce **solar wind** much stronger than it is today. As it leaves the Sun\'s surface, it will carry with it some of the hydrogen in its outermost layers, forming a **planetary nebula**. As more matter is carried away from the Sun, the solar wind will continue to strengthen. Eventually, it will blow away so much of the Sun\'s matter that there will no longer be enough pressure at the core to keep the helium fusion going. At that point, what\'s left of the Sun will contract under its own gravity, becoming a much smaller, very dense star called a **white dwarf**. The white dwarf will radiate off heat that is left over from the earlier nuclear fusion, but it will no longer generate any new energy. ## A New Beginning But will this really be the end? As bleak as this future might sound, there is a silver lining. All of that matter blown away from the Solar System during will eventually be compressed again by gravity, along with the remains of other long-gone stars, into a cloud of gas and dust much like the one that gave birth to our Solar System. In this cloud, many new stars will form with planets of their own, and just possibly, some of these planets may one day produce living beings who will look at the sky and wonder: where did we come from?
# Wikijunior:Solar System/Is there life out there? The short answer is \"Nobody knows\" - but it\'s interesting to try to make some guesses based on what we **do** know! Scientists who have tried to make good guesses use an equation called \'The Drake Equation\' which was named after Doctor Frank Drake who first tried to work this out about forty years ago. The idea is that if you know how likely it was for life to form on Earth - and if you know how many planets there are that are more or less like the Earth - then you can make a good estimate of how much life there is out there. We can try to do that ourselves. ### How many stars are there in the Universe? When you look up at the sky on a really dark night - far from the lights of cities and roads, you can see about five thousand stars and four or five planets. But nearly all of the stars and planets out there are far, far away and much too dim to see. We know that there are eight planets orbiting the Sun and that our sun is a lot like the other stars out there in our galaxy. Our galaxy (which we call \"The Milky Way\" because it looks like a splash of milk across the night sky) has about three hundred **billion** stars in it. But the Milky Way is a rather small galaxy and there are many, many other galaxies. With our very best telescopes we can see about a hundred billion galaxies. With a hundred billion galaxies - each one with hundreds or even thousands of billions of stars - astronomers calculate that there are about fifty thousand, billion, billion stars in the part of the universe that we can see! That\'s a big number. Written out in numbers it\'s 50,000,000,000,000,000,000,000 stars! ### Do all of those stars have planets? Well, it\'s rather hard to tell for sure - but astronomers have looked carefully at some of the stars in our neighborhood and whilst planets that are orbiting other stars are too small to see - even with our very best telescopes, we can sometimes see a slight wobble in the light coming from a star that is caused by the gravity of one or more planets that are orbiting it. Knowing that, we have found that many nearby stars have at least a few planets that are big enough to wobble the lights from the star enough so we know they are there. There are probably other planets too small to produce a big enough wobble for us to measure - so we don\'t know exactly how many planets to expect. But it seems that there are probably more planets than stars in the universe, so there could easily be 50,000,000,000,000,000,000,000 planets for life to try to get started on. That\'s a lot of places and we haven\'t counted moons, asteroids, comets and dust clouds! ### How often does life actually get started on one of these planets? This something we can really only guess at. We know that life formed once on one planet because we are that life and we live on that planet - but how do we know whether the Earth is just an amazingly special place or whether there are Earth-like planets orbiting most of the stars in the sky? Unfortunately, we don\'t know. - Many planets must be too hot - like Venus and Mercury in our own solar system. Life can\'t survive there because the chemicals that life needs don\'t work properly when things are that hot. - Other planets might be too cold - so there would not be enough sunlight for plants and animals to use as energy. The outer planets of our Solar system - Pluto and Neptune - must be far too cold for life to exist there. - It\'s possible that planets might not have the right mixture of life-giving chemicals. There is no life on our Moon because it has no atmosphere - in daytime it\'s too hot and at night too cold. - Other planets may form and then be destroyed before life has had time to form - and on others, life might have formed a long time ago and then died out for some reason, But there are plenty of planets to choose from. Next time you are on a beach or at a playground with a sand lot, take a handful of sand. There are an awful lot of tiny sand grains in a fistful of sand - but there are more stars and planets than there are grains of sand on all the beaches of all the world! Surely they can\'t all be too hot, too cold, too dry or too poisonous? But we humans haven\'t yet looked closely enough in enough places where life might be to really know for sure what life needs. We\'ve found bacteria living in boiling hot water near underwater volcanoes. There are tiny worms who live in the ice near to the South Pole. Bacteria have been found living inside rocks in the deepest mine shafts. There is hardly anywhere on earth where live can\'t survive somehow. Astronauts from Apollo 12 who visited the moon in 1969 visited the Surveyor III lander that had been sitting on the moon for more than two years. They found that bacteria that had hitched a ride on Surveyor when it was launched and were still alive after two years of living on the moon! It seems then that life can survive and even prosper in some fairly hostile places - this shows that a planet may not have to be a comfortable place for humans in order to develop life. However, there doesn\'t seem to be any native life on the Moon beyond what humans have put there by accident and our robotic missions haven\'t found life on Mars or Venus or any of the comets we\'ve looked at closely. With at fifty thousand billion billion planets in the universe, even if each planet only had a one in a trillion chance of having life, there could still be billions of planets teeming with life out there in the universe. But if the chances are that bad then we might be alone in our galaxy with the nearest other creatures living hundreds of millions of light years away. Even if the odds for life are only a million to one for each planet, we humans and our robots might have to travel for thousands of years and search millions of planets and moons before we\'d find them. ### So how many aliens are there? That is where the drake equation comes into play: `<big>`{=html}`<big>`{=html}R^\*^ × f~p~ × n~e~ × f~l~ × f~i~ × f~c~ × L = The number of alien civilisations that we can talk to in our galaxy`</big>`{=html}`</big>`{=html} This equation might look complicated, but it\'s actually quite simple when you understand it. R^\*^ is how many stars appear a year. So, for example, if there was 10 stars being made every year, then you could scrible out R\* and put at \'10\' there instead. f~p~ is the chances that a star has planets. If, on average, there was a 1 in 2 chance that each new star had a planet, then the number that replaced f~p~ would be 0.5 (1÷2). n~e~ is the number of planets in each solar system that can have life. In our solar system, n~e~ would be 1, because we only have one planet that we know has life on it, Earth. f~l~ is the chances that these planets have life. If all planets that could have life have life, then 1 would go in the place of f~l~ f~i~ is the chances that the life on these planets is clever. A 1 in a hundred chance of life would give us 0.01, 1÷100. f~c~ is the chance that they will be able to talk to us. This number might be 1 (100%), because if they are clever they will eventually find out how to talk to other planets. Finally, L is how long each alien civilisation will live (or want to talk to us), in years. Though nobody knows the real value of this, Frank Drake guessed 10,000 years. Now, we can multiply them all together. 10×0.5×1×1×0.01×1×10000 = 500 alien civilisations in our galaxy. The values here are just guesses, though, and other guesses have ranged from only one civilisation in our galaxy to thousands. ### Little Green Aliens If so many planets in the universe does this mean that we should expect little green aliens to be popping out of their flying saucers soon? Well, perhaps not. For beings living in another galaxy outside of the Milky Way, if they noticed that we are here and set out to visit us - traveling at the speed of light, they still wouldn\'t get here for another 300 million years! They couldn\'t have set out millions of years ago to visit us because humans haven\'t been on around for nearly that long. If we\'re going to be visited by aliens, they\'d have to live on a nearby star and know how to fly very fast to get here. That means that if we are to meet alien cultures they must come from within the very few stars that are within a reasonable travel time. Life would have to be very common indeed for there to be intelligent beings close enough to meet us face-to-face. ### SETI - The Search for Extra-Terrestrial Intelligence One group of scientists are searching for other intelligent life in our galaxy by listening to the radio. With large radio telescopes they sweep the stars looking for radio signals with interesting patterns in them that would not come from natural radio sources. So far, they haven\'t found anything - but that may mean that they have to keep on looking - or it might be that the aliens are not transmitting anything in our direction with enough power for SETI\'s sensitive radio telescopes to pick up. ### Panspermia - Life from Space? One other possibility is that life didn\'t just appear on Earth at all. If life were really common throughout the universe, it\'s possible that life arrived on Earth after it developed somewhere else. We know that meteorites found on Earth have come here from the Moon and from Mars - and probably from other planets too. We also know that debris in the form of little bits of rock and ice rain down on the Earth from space all the time. If life existed in that debris when the Earth was young, there is a good chance that we Earthlings originally came from some other planet entirely. It could be that all life on Earth originated on Mars and we are the alien invaders! ### So what **IS** the answer? We still don\'t know for sure that there is life anywhere beyond the earth, and even if life were common in the universe, we don\'t know whether we\'d ever be able to find it if there was. The search for life beyond Earth is a very new thing. Humans have only been searching for about 40 years - and we\'ve only been looking in the most likely places for 10 years. If we humans are going to find signs of life outside the Earth, it will probably happen in your lifetime. You may one day be amongst the first humans to encounter alien life or to hear a message from another world through SETI!
# OpenSSH/Overview The OpenSSH suite provides secure remote access and file transfer. Since its initial release, it has grown to become the most widely used implementation of the SSH protocol. During the first ten years of its existence, ssh has largely replaced older corresponding unencrypted tools and protocols. The OpenSSH client is included by default in most operating system distributions, including MacOS, Linux, BSD, AIX and Solaris. Any day you use the Internet, you are using and relying on dozens if not hundreds of machines operated and maintained using OpenSSH. A survey in 2008 showed that of the SSH servers found running, just over 80% were OpenSSH. [^1] OpenSSH was first released towards the end of 1999. It is the latest step in a very long and useful history of networked commuting, remote access and telecommuting. ## History of OpenSSH The first release of OpenSSH was in December 1999 as part of OpenBSD 2.6. The source code was originally derived from a re-write of the last available open version, ssh 1.2.12 specifically, of SSH[^2]. SSH went on to become Tectia SSH. Ongoing development of OpenSSH is done by the OpenBSD group. Core development occurs first on OpenBSD, then portability teams bring the changes to other platforms. OpenSSH is an integral part of as good as all server systems today and a good many network appliances such as routers, switches and networked storage. The first steps were in many ways the biggest. ### The Early Days of Remote Access Some of the tools that inspired the need for SSH have been around since the beginning, too, or very near the beginning of the Internet. Remote access has been a fundamental part of the concept since the idea stage and the nature and capabilities of this access has evolved as the network has evolved in scale, scope and usage. See the web version of the *Lévénez Unix Timeline*[^3] by Éric Lévénez for an overview of systems development and the web version of *Hobbes\' Internet Timeline*[^4] by Robert H Zakon for an overview of the development of the Internet. **1969** - Telnet was one of the original ARPAnet application protocols, named in RFC 15 from September 1969. It was used to access a host at a remote site locally. Telnet was described starting two years later in RFC 137, RFC 139, RFC 318 and others, including RFC 97. That is as good a turning point as any to delineate Telnet. **1971** - Thompson Shell, by Ken Thompson, was an improvement on the old text-based user interface, the shell. This new one allowed redirects but was only a user interface and not for scripting. - In the same year FTP, the file transfer protocol, was described in RFC 114. A key goal was to promote use of computers over the net by allowing users at any host on the network to use the file system of any cooperating host. **1978** - Bill Joy created BSD\'s C shell which is named for the C-like syntax it uses. It allows job control, history substitution, and aliases, which features we find in today\'s interfaces. - In the same year, the Bourne Shell by Steve Bourne at Bell Labs [^5] was created. It is the progenitor to the default shells used in most distros today: **ksh** and **bash**. **1983** - The remote file copy utility, **rcp**, appeared in 4.2 BSD. **rcp** copied files across the net to other hosts using **rsh**, which also appeared staring 4.2 BSD, to perform its operations. Like **telnet** and **ftp**, all passwords, user names, and data are transmitted unencrypted in clear text. Both **rsh** and **rcp** were part of the **rlogin** suite. **1991** - PGP, written at MIT by Philip Zimmermann[^6], charted new waters for encrypted electronic communications with the goals of preserving civil liberties online, ensuring individual privacy, keeping encryption legal in the USA, and protecting business communications. Like SSH it uses asymmetric encryption with public / private key pairs. **1993** - Kerberos V (RFC 1510) authentication service from MIT\'s project Athena [^7] provides a means for authentication over an open, unsecure network. Kerberos got its original start in 1988. ### SSH - open then closed **1995** - Tatu Ylönen at the then Helsinki University of Technology developed the first SSH protocol and programs, releasing them under an open license[^8] as per the norm in computer science, software engineering, and advanced development. [^9] **1995?** - Björn Grönvall dug out the most recent open version of **ssh**, version 1.2.12[^10] [^11]. He and Holger Trapp did the initial work to free the distribution, resulting in OSSH **1996** - The SSH2 protocol is defined ### OpenSSH **1999** - OpenSSH begins based on OSSH. Niels Provos, Theo de Raadt, Markus Friedl developed the cryptographic components during the port to OpenBSD which became the OpenSSH we know today. Dug Song, Aaron Campbell and many others provided various non-crypto contributions. openssl library issues were sorted by Bob Beck. Damien Miller, Philip Hands, and others started porting OpenSSH to Linux. Finally OpenSSH 1.2.2 was release shipped with OpenBSD 2.6 in December 1, 1999.[^12] **2000** - Markus Friedl added SSH 2 protocol support to OpenSSH version 2.0, which was released in June.[^13] OpenSSH 2.0 shipped with OpenBSD 2.7. Niels Provos and Theo de Raadt did most of the checking. Bob Beck updated OpenSSL. Markus also added support for the SFTP protocol later that same year. - In September of 2000, the long wait in the USA for the patents on the RSA algorithms to expire was over. In the European Union the European Patent Convention of 1972 frees software, algorithms, business methods or literature, unlike the unfortunate, anti-business situation in the USA. This freedom in Europe hangs by a thread at the moment. - SSH Tectia changes licenses again. **2001** - Damien Miller completed the SFTP client which was released in February. - SSH2 became the default protocol **2008** - Built-in chroot support for **sshd**. **2010** - As of OpenSSH 5.4, the legacy protocol SSH1 is finally disabled by default. **2014** - As of OpenSSH 6.7, both the base and the portable versions of OpenSSH can build against LibreSSL instead of OpenSSL for certain cryptographic functions. **2016** - OpenSSH 7.4 removes server support for the SSH1 legacy protocol. **2023** - OpenSSH 9.5 ssh-keygen(1) generates Ed25519 keys by default instead of old RSA keys. Note: OpenSSH can be used anywhere in the whole world because it uses only algorithms unencumbered by software patents, business method patents, algorithm patents, and so on. These types of patents do not apply in Europe, only physical inventions can be patented in Europe, but there are regions of the world where these problems do occur. Small and medium businesses in Europe have been active in politics to keep the advantage. ## Why Use OpenSSH? A lot has changed since the commercialization of the Internet began in 1996. It was once a University and Government research network and if you were on the net back then, odds were you were supposed to be there. Though it was far from being utopia, any misbehavior could usually be quickly narrowed down to the individuals involved and dealt with easily, usually with no more than a phone call or a few e-mails. Few, if any, sessions back then were encrypted and both passwords and user names were passed in clear text. By then, the WWW was more than a few years under way and undergoing explosive growth. The estimated number of web servers online in 1996 grew from 100,000 at the beginning of the year to close to 650,000 by the end of the same year[^14]. When other types of servers are included in those figures, the estimated year-end number was over 16,000,000 hosts, representing approximately 828,000 domains.[^15] Nowadays, hosts are subject to hostile scans from the moment they are connected to the network. Any and all unencrypted traffic is scanned and parsed for user names, passwords, and other sensitive information. Currently, the biggest espionage threats come from private companies, but governments, individuals, and organized crime are not without a presence. Each connection from one host to another goes through many networks and each packet may take the same or a different route there and back again. This example shows thirteen hops among three organizations from a student computer to a search engine: ``` shell-session % /usr/sbin/traceroute -n www.google.com traceroute: Warning: www.google.com has multiple addresses; using 74.125.95.106 traceroute to www.l.google.com (74.125.95.106), 30 hops max, 40 byte packets 1 xx.xx.xx.xx 0.419 ms 0.220 ms 0.213 ms University of Michigan 2 xx.xx.xx.xx 0.446 ms 0.349 ms 0.315 ms Merit Network, Inc. 3 xx.xx.xx.xx 0.572 ms 0.513 ms 0.525 ms University of Michigan 4 xx.xx.xx.xx 0.472 ms 0.425 ms 0.402 ms University of Michigan 5 xx.xx.xx.xx 0.647 ms 0.551 ms 0.561 ms University of Michigan 6 xx.xx.xx.xx 0.945 ms 0.912 ms 0.865 ms University of Michigan 7 xx.xx.xx.xx 6.478 ms 6.503 ms 6.489 ms Merit Network, Inc. 8 xx.xx.xx.xx 6.597 ms 6.590 ms 6.604 ms Merit Network, Inc. 9 216.239.48.154 64.935 ms 6.848 ms 6.793 ms Google, Inc. 10 72.14.232.141 17.606 ms 17.581 ms 17.680 ms Google, Inc. 11 209.85.241.27 17.736 ms 17.592 ms 17.519 ms Google, Inc. 12 72.14.239.193 17.767 ms 17.778 ms 17.930 ms Google, Inc. 13 74.125.95.106 17.903 ms 17.835 ms 17.867 ms Google, Inc.: ``` The net is big. It is not uncommon to find a trail of 15 to 20 hops between client and server nowadays. Any machine on any of the subnets the packets travel over can eavesdrop with little difficulty if the packets are not well encrypted. ### What OpenSSH Does The OpenSSH suite gives the following: - Encrypted remote access, including tunneling insecure protocols. - Encrypted file transfer - Run remote commands, programs or scripts and, as mentioned, - Replacement for **rsh**, **rlogin**, **telnet** and **ftp** More concretely, that means that the following undesirable activities are prevented: - Eavesdropping of data transmitted over the network. - Manipulation of data at intermediate elements in the network (e.g. routers). - Address spoofing where an attack hosts pretends to be a trusted host by sending packets with the source address of the trusted host. - IP source routing As a free software project, OpenSSH provides: - Open Standards - Flexible License - freedom emphasized for developers - Strong Encryption using these ciphers: - AES - ChaCha20[^16] - RSA - ECDSA - Ed25519 - Strong Authentication, supported methods: `gssapi-with-mic, hostbased, keyboard-interactive, none , password` and `publickey`[^17] - Public Key: can authenticate using multiple keys since March 2015 (OpenSSH 6.8)[^18] - Single Use Passwords - Kerberos - Dongles - Built-in SFTP - Data Compression - Port Forwarding - Encrypt legacy protocols - Encrypted X11 forwarding for X Window System - Key Agents - Single Sign-on using - Authentication Keys - Agent Forwarding - Ticket Passing - Kerberos - AFS ### What OpenSSH Doesn\'t Do OpenSSH is a very useful tool, but much of its effectiveness depends on correct use. It cannot protect from any of the following situations. - Misconfiguration, misuse, or abuse. - Compromised systems, particularly where the root account is compromised. - Insecure or inappropriate directory settings, particularly home directory settings. OpenSSH must be properly configured and on a properly configured system in order to be of benefit. Arranging both is not difficult, but since each system is unique, there is no one-size-fits-all solution. The right configuration is dependent on the uses the system and OpenSSH are put to. If you login from a host to a server and an attacker has control of root on either side, he can listen to your session by reading from the pseudo-terminal device because even though SSH is encrypted on the network it must communicate in clear text with the terminal device. If an attacker can change files in your home directory, for example via a networked file system, he may be able to fool SSH. Last but not least, if OpenSSH is set to allow everyone in, whether on purpose or by accident, it will. ## References [^1]: [^2]: [^3]: [^4]: [^5]: [^6]: [^7]: [^8]: [^9]: [^10]: [^11]: [^12]: <https://www.openssh.com/history.html> [^13]: [^14]: [^15]: [^16]: [^17]: <https://linux.die.net/man/5/sshd_config> [^18]: <https://lists.mindrot.org/pipermail/openssh-unix-announce/2015-March/000120.html>
# OpenSSH/Why Use Encryption Encryption has been a hot topic in computing for a long time. It became a high priority item in national and international politics in 1991 when Dr. Phil Zimmermann at the Massachusetts Institute of Technology (MIT) first published Pretty Good Privacy (PGP). With the arrival of the first web shops, encryption went from a specialty to a requirement and increasing volumes of money changed hands online. By 1996, encryption became essential for e-business. By 2000, it became recognized as a general, essential prerequisite in electronic communication. Currently, in 2010, there is almost no chance of maintaining control over or integrity of any networked machine for more than a few minutes without the help of encryption. Nowadays, much communication over computer networks is still done without encryption. That would be most communication, if inadequate encryption is also taken into account. This is despite years of warnings, government recommendations, best practice guidelines and incidents. As a result, any machine connected to the network can intercept communication that passes over that network. The eavesdroppers are many and varied. They include administrators, staff, employers, criminals, corporate spies, and even governments. Corporate espionage alone has become an enormous burden and barrier. Businesses are well aware of dumpster diving and take precautions to shred all paper documents. But what about electronic information? Contracts and negotiations, trade secrets, patent applications, decisions and minutes, customer data and invoicing, personnel data, financial and tax records, calendars and schedules, product designs and production notes, training materials, and even regular correspondence go over the net daily. Archived materials, even if they are not accessed directly, are usually on machines that are available and accessed for other reasons. Many company managers and executives are still unaware that their communications and documents are so easily intercepted, in spite of apparent and expensive access restrictions. In many cases these can be shown to be ineffectual and at best purely cosmetic. Security Theater is one obstacle and in the field of security it is more common to find snake oil than authentic solutions. Still, there is little public demonstration of awareness of the magnitude of corporate espionage nowadays or the cost of failure. Even failure to act has its costs. Not only is sensitive data available if left unencrypted, but also trends in less sensitive data can be spotted with a large enough sampling. A very large amount of information can be inferred even from lesser communications. Data mining is now a well-known concept as is the so-called wireless wiretap. With the increase in online material and activity, encryption is more relevant than ever even if many years have passed since the issues were first brought into the limelight. ## Excerpt of ssh-1.0.0 README from July 12, 1995 Tatu Ylönen, then at the Helsinki University of Technology, wrote the README[^1] accompanying the early versions of his Open Source software, SSH. The following is an excerpt about why encryption is important. ## Phil Zimmermann on encryption and privacy, from 1991, updated 1999 Phil Zimmermann wrote the encryption tool Pretty Good Privacy (PGP) in 1991 to promote privacy and to help keep encryption, and thus privacy, legal around the world. Considerable difficulty occurred in the United States until PGP was published outside and re-imported in a very visible, public manner. ## Original Press Release for OpenSSH Below is the original press release for OpenSSH sent back in 1999.[^2] cvs.openbsd.org\>\ To: Liz Coolbaugh \<lwn{{@}}lwn.net\>\ Subject: OpenBSD Press Release: OpenSSH integrated into operating system PRESS RELEASE OpenSSH: Secure Shell integrated into OpenBSD operating system Source: OpenBSD\ Contacts: : Louis Bertrand, OpenBSD media relations : Bertrand Technical Services : Tel: (905) 623-8925 Fax: (905) 623-3852 : louis{{@}}openbsd.org ```{=html} <!-- --> ``` : Theo de Raadt, OpenBSD lead developer : deraadt{{@}}openbsd.org Project Web site: <http://www.openbsd.org/> OpenSSH: Secure Shell integrated into OpenBSD Secure communications package no longer third-party add-on \[October 25, 1999: Calgary, Canada\] \-- The OpenBSD developers are pleased to announce the release of OpenSSH, a free implementation of the popular Secure Shell encrypted communications package. OpenSSH, to be released with OpenBSD 2.6, is compatible with both SSH 1.3 and 1.5 protocols and dodges most restrictions on the free distribution of strong cryptography. OpenSSH is based on a free release of SSH by Tatu Ylonen, with major changes to remove proprietary code and bring it up to current security and functionality standards. Secure Shell operates like the popular TELNET remote terminal package but with an encrypted link between the user and the remote server. SSH also allows \"tunnelling\" of network services through the scrambled connection for added privacy. OpenSSH has been tested to interoperate with ssh-1.2.27 from SSH Communications, and the TTSSH and SecureCRT Windows clients. \"Network sessions involving strong cryptographic security are a requirement in the modern world,\" says lead developer Theo de Raadt. \"Everyone needs this. People using the telnet or rlogin protocols are not aware of the extreme danger posed by password sniffing and session hijacking.\" In previous releases of OpenBSD, users were urged to download SSH as soon as possible after installing the OS. Without SSH, terminal sessions transmitted in clear text allow eavesdroppers on the Internet to capture user names and password combinations and thus bypass the security measures in the operating system. \"I asked everyone \`what is the first thing you do after installing OpenBSD?\' Everyone gave me the same answer: they installed ssh,\" says de Raadt. \"That\'s a pain, so we\'ve made it much easier.\" All proprietary code in the original distribution was replaced, along with some libraries burdened with the restrictive GNU Public License (GPL). Much of of the actual cryptographic code was replaced by calls to the crypto libraries built into OpenBSD. The source code is now completely freely re-useable, and vendors are encouraged to re-use it if they need ssh functionality. OpenSSH relies on the Secure Sockets Layer library (libssl) which incorporates the RSA public-key cryptography system. RSA is patented in the US and OpenBSD developers must work around the patent restrictions. Users outside the US may download a libssl file based on the patent-free OpenSSL implementation. For US non-commercial users, OpenBSD is preparing a libssl based on the patented RSAREF code. Unfortunately, the US legal framework effectively bans US commercial users from using OpenSSH, and curtails freedom of choice in that market. OpenSSH was developed and integrated into OpenBSD by Niels Provos, Theo de Raadt, Markus Friedl for cryptographic work; Dug Song, Aaron Campbell, and others for various non-crypto contributions; and Bob Beck for helping with the openssl library issues. The original SSH was written by Tatu Ylonen. Bjoern Groenvall and Holger Trapp did the initial work to free the distribution. OpenBSD is an Internet-based volunteer effort to produce a secure multi-platform operating system with built-in support for cryptography. It has been described in the press as the world\'s most secure operating system. For more information about OpenSSH and OpenBSD, see the project Web pages at <http://www.OpenBSD.org/>. Source: OpenBSD\ <http://lwn.net/1999/1028/a/openssh.html> }} ## The European Union (EU) on Encryption During 2000, the European Commission investigated the state of international and industrial electronic espionage. Counter-measures and solutions were investigated as well as the risks. The result was a resolution containing a summary of the findings and a series of recommended actions for Member States to carry out and goals to meet. Recommendations to EU Member States from the European Parliament resolution ECHELON, A5-0264/2001 (emphasis added): : \"29. Urges the Commission and Member States to devise appropriate measures to promote, develop and manufacture European encryption technology and software and above all to support projects at developing user-friendly **open-source encryption** software;\" : . . . : \"33. Calls on the Community institutions and the public administrations of the Member States to provide training for their staff and make their staff familiar with new **encryption technologies and techniques** by means of the necessary practical training and courses;\"[^3] It was found during the investigation that businesses were the most at risk and the most vulnerable and that widespread use of open source encryption technology is to be encouraged. The same can be said even today. ## References [^1]: [^2]: [^3]:
# OpenSSH/SSH Protocols OpenSSH uses the SSH protocol which connects over TCP. Normally, one SSH session per TCP connection is made, but multiple sessions can be multiplexed over a single TCP connection if planned that way. The current set of Secure Shell protocols is SSH2. It is a rewrite of the old, deprecated SSH1 protocol. It contains significant improvements in security, performance, and portability. The default is now SSH2 and SSH1 support has been removed from both the client and server. !Sequence Diagram for SSH Password Authentication The Secure Shell protocol is an open standard. As such, it is vendor-neutral and maintained by the Internet Engineering Task Force (IETF). The current protocol is described in RFC 4250 through RFC 4256 and standardized by the IETF secsh working group. The overall structure of SSH2 is described in RFC 4251, The Secure Shell (SSH) Protocol Architecture. The SSH protocol is composed of three layers: the transport layer, the authentication layer, and the connection layer. : **SSH-CONNECT** -- The connection layer runs over the user authentication protocol. It multiplexes many different concurrent encrypted channels into logical channels over the authenticated connection. It allows for tunneling of login sessions and TCP-forwarding. It provides a flow control service for these channels. Additionally, various channel-specific options can be negotiated. This layer manages the SSH session, session multiplexing, X11 forwarding, TCP forwarding, shell, remote program execution, invoking SFTP subsystem. ```{=html} <!-- --> ``` : **SSH-USERAUTH** -- The user authentication layer authenticates the client-side to the server. It uses the established connection and runs on top of the transport layer. It provides several mechanisms for user authentication. These include password authentication, public-key or host-based authentication mechanisms, challenge-response, pluggable authentication modules (PAM), Generic Security Services API (GSSAPI) and even dongles. ```{=html} <!-- --> ``` : **SSH-TRANS** -- The transport layer provides server authentication, confidentiality and data integrity over TCP. It does this through algorithm negotiation and a key exchange. The key exchange includes server authentication and results in a cryptographically secured connection: it provides integrity, confidentiality and optional compression. [^1] Among the differences between the current protocol, SSH2, and the deprecated SSH1 protocol, is that SSH2 uses host keys for authentication. Whereas SSH1 used both server and host keys to authenticate. There\'s not much which can be added about the protocols which is not already covered with more detail and authority in RFC 4251 [^2]. ## SSH File Transfer Protocol (SFTP) The SSH File Transfer Protocol (SFTP) is a binary protocol to provide secure file transfer, access and management. SFTP was added by Markus Friedl on the server side in time for the 2.3.0 release of OpenSSH in November 2000. Damien Miller added support for SFTP to the client side in time for 2.5.0. Since then, many have added to both the client and the server. ### SFTP is not FTPS For basic file transfer, nothing more is needed than an account on the machine with the OpenSSH server. SFTP support is built into the OpenSSH server package. The SFTP protocol, in contrast to old FTP, has been designed from the ground up to be as secure as possible for both login and data transfer. Unless the use-case calls for publicly available, read-only, downloads, don\'t worry about trying to fiddle with FTP. It is the protocol FTP itself that is inherently insecure. It\'s great for read-only, public data transfer. The programs **vsftpd** and **proftpd**, for example, are secure insofar as the server software itself goes, although the protocol itself is still insecure. In other words the program itself is more or less fine and if you need to provide read-only, publicly available downloads then FTP maybe the right tool. Otherwise forget about FTP. Nearly always when users ask for \"FTP\" they don\'t mean specifically the old file transfer protocol from 1971 as described in RFC 114, but a generic means of file transfer and there are many ways to solve that problem. This is especially true since the next part of their request is usually how to make it secure. The name \"FTP\" is frequently mis-used generically to mean any file transfer utility, much the same way as the term \"Coke\" is used in some of Southern United States to mean any carbonated soft drink, not just Coca-Cola. Consider SFTP or, for larger groups, even SSHFS, Samba "wikilink"), or AFS. While old FTP succeeded very well in achieving its main goal to promote use of networked computers by allowing users at any host on the network to use the file system of any cooperating host, it cannot be made secure. There\'s nothing to be done about that, so it is past time to get over it. Again, it is the protocol itself, FTP, which is the problem.[^3] With FTP, the data, passwords and user name are all sent back and forth unencrypted.[^4] Anyone on the client\'s subnet, the server\'s subnet or any subnet in between can \'sniff\' the passwords and data when FTP is used. With extra effort it is possible to wrap FTP inside SSL or TLS, thus creating FTPS. However, tunneling FTP over SSL/TLS is complex to do and far from an optimum solution. Unfortunately because of name confusion combined with the large number of posts and discussions created by complex, nit-picky tasks like wrapping FTP in SSL to provide FTPS, the wrong way still turns up commonly in web searches regarding file transfer. In contrast, easy, relatively painless solutions vanish because it is rarely necessary to post how to do those. Also, an easy solution can be summed up in very few lines and maybe a single answer. Thus, there is still a lot of talk online about \'securing\' FTP and very little mention of using SFTP. It\'s a vicious cycle that this book hopes to help break: Difficult tasks mean lots of discussion and noise, lots of discussion and noise means strong web presence, strong web presence means high Google ranking. SFTP tools are very common, but might be taken for granted and thus overlooked. SFTP tools are easy to use and more functional than old FTP clients. In fact a lot of improvements have been made in usability. There is no shortage of common, GUI-based SFTP clients to transfer files: Filezilla, Konqueror, Dolphin, Nautilus, Cyberduck, Fugu, and Fetch top the list but there are many more. Most are Free Software. Again, these SFTP clients are very easy to use. For example, in Konqueror, just type in the URL to the sftp server, where the server name or address is xx.yy.zz.aa. sftp://xx.yy.zz.aa If it is desirable to start with a particular directory, then that too can be specified. sftp://xx.yy.zz.aa/var/www/pictures/ One special client worth knowing about is **sshfs**. With **sshfs** as an SFTP client the other machine is accessible as an open folder on your machine\'s local file system. In that way any program you normally have to work with files, such as LibreOffice, Inkscape or Gimp can access the remote machine via that folder. ### Background of FTP FTP is from the 1970s. It\'s a well proven workhorse, but from an era when if you were on the net you were supposed to be there and if there was trouble it could usually be cleared up with a short phone call or an e-mail or two. It sends the login name, password and all of the data unencrypted for anyone to intercept. FTP clients can connect to the FTP server in either passive or active modes. Both active and passive modes for FTP[^5] use two ports, one for control and one for data. In FTP Active mode, after the client makes a connection to the FTP server it then allows an incoming connection to be initiated from the server to for data transfer. In FTP Passive mode, after the client makes a connection to the FTP server, the server then responds with information about a second port for data transfer and the client initiates the second connection. FTP is most relevant now as Anonymous FTP, which is still excellent for read-only downloads without login. FTP is still one way to go for transferring read-only data, as would be using the web (HTTP or HTTPS), or a P2P protocol like Bittorrent. So there are other options than FTP for offering read-only downloads. Preference is given lately to HTTPS for small files and Bittorrent for large files or large groups of files. #### Using tcpdump to show FTP activity An illustration of how the old protocol, FTP, is insecure can be had from the utility **tcpdump**. It can show what is going over the network during an Anonymous FTP session, or for that matter any FTP session. Look at the manual page for **tcpdump** for an explanation of the individual arguments, the usage example below displays the first FTP or FTP-Data packets going from the client to the server and vice versa. The output below shows an excerpt from the output of **tcpdump** which captured packets between an FTP client and the FTP server, one line per packet. ``` shell $ sudo tcpdump -q -s 0 -c 10 -A -i eth0 \ "tcp and (port ftp or port ftp-data)" tcpdump: verbose output suppressed, use -v or -vv for full protocol decode listening on eth0, link-type EN10MB (Ethernet), capture size 65535 bytes … :18:36.010820 IP desk.55227 > server.ftp: tcp 16 E..D..@.@.....1..X.....G.r. ........l..... ."......USER anonymous :18:36.073192 IP server.ftp > desk.55227: tcp 0 E..4jX@.7.3.[.X...1..... ...G.r#........... .....".. :18:36.074019 IP server.ftp > desk.55227: tcp 34 E..VjY@.7.3.[.X...1..... ...G.r#....Y...... ....."..331 Please specify the password. :18:36.074042 IP desk.55227 > server.ftp: tcp 0 E..4..@.@..+..1.[.X.....G.r# ..)........... ."...... :18:42.098941 IP desk.55227 > server.ftp: tcp 23 E..K..@.@.....1.[.X.....G.r# ..)....gv..... .".w....PASS user@example.net :18:42.162692 IP server.ftp > desk.55227: tcp 23 E..KjZ@.7.3.[.X...1..... ..)G.r:........... .....".w230 Login successful. … :18:43.431827 IP server.ftp > desk.55227: tcp 14 E..Bj\@.7.3.[.X...1..... ..SG.rF.....j..... ....."..221 Goodbye. … ``` As can be seen in lines 3 and 7, data such as text from the server is visible. In lines 1 and 5, text entered by the user is visible and in this case it includes the user name and password used to log in. Fortunately the session is Anonymous FTP, which is read-only and used for downloading. Anonymous FTP is a rather efficient way to publish material for download. For Anonymous FTP, the user name is always \"anonymous\" and the password is the user's e-mail address and the server\'s data always read-only. If you have the package for the OpenSSH server already installed, no further configuration of the server is needed to start using SFTP for file transfers. Though comparatively speaking, FTPS is significantly more secure than FTP. If you want remote remote login access, then both FTP and FTPS should be avoided. A very large reason to avoid both is to save work. ### On FTPS FTPS is FTP tunneled over SSL or TLS. A goal of FTP was to encourage the use of remote computers which, along with the web, has succeeded. A goal of FTPS was to secure logins and transfers, and it was a necessary step in securing file transfers with the legacy protocol. However, since SFTP is so much easier to deploy and most systems now include both graphical and text-based SFTP clients, FTPS can really be considered deprecated for most occasions. Some good background material can be found in the Request for Comments (RFCs) for FTP and FTPS. There, SFTP and even HTTPS are better matches and largely supersede FTPS. See the section on [Client Applications for an idea of the SFTP clients available. ## Privilege Separation !Sequence Diagram for OpenSSH Privilege Separation Privilege separation is when a process is divided into sub-processes, each of which have just enough access to just the right services to do their part of the job. An underlying principle is that of least privilege, which is where each process has exactly enough privileges to accomplish a task, neither more nor less. The goal of privilege separation is to compartmentalize any corruption and prevent a corrupt process from accessing other parts of the system. Privilege separation is applied in OpenSSH by using several levels of access, some higher some lower, to run sshd(8) and its subsystems and components. The SSH server ➊ starts out with a privileged process ➋ which then creates an unprivileged process ➌ to work with the network traffic. Once the user has authenticated, another unprivileged process is created ➍ with the privileges of that authenticated user. See the \"Sequence Diagram for OpenSSH Privilege Separation\". As seen in the diagram, a total of four processes get run to create an SSH session. One process, the server, remains and listens for new connections and spawn new child processes. ``` shell $ ps -ax -o user,pid,ppid,state,start,command | awk '/sshd/ || NR==1' USER PID PPID STAT STARTED COMMAND root 1473 1 I 05:44:01 sshd: /usr/sbin/sshd [listener] 0 of 10-10 ``` It is this privileged process that listens for the initial connection from clients. Here it is seen waiting and listening on port 22. ``` shell $ netstat -ntlp | awk '/sshd/ || NR<=2' Active Internet connections (only servers) Proto Recv-Q Send-Q Local Address Foreign Address State PID/Program name tcp 0 0 0.0.0.0:22 0.0.0.0:* LISTEN 1473/sshd tcp6 0 0 :::22 :::* LISTEN 1473/sshd ``` After the initial connection while waiting for password authentication from user \'fred\', a privileged monitor process supervises an unprivileged process by user \'sshd\' which handles the contact with the remote user\'s client. ``` shell $ ps -ax -o user,pid,ppid,state,start,command | awk '/sshd/ || NR==1' USER PID PPID S STARTED COMMAND root 1473 1 S 05:44:12 sshd: /usr/sbin/sshd [listener] 1 of 10-10 root 9481 1473 S 14:40:37 sshd: fred [priv] sshd 9482 9481 S 14:40:37 sshd: fred [net] ``` Then after authentication is completed and a session established for user \'fred\', a new privileged monitor process is created to supervise the process running as user \'fred\'. At that point the other process running as user \'sshd\' has gone away. ``` shell $ ps -ax -o user,pid,ppid,state,start,command | awk '/sshd/ || NR==1' USER PID PPID S STARTED COMMAND root 1473 1 S 05:44:12 sshd: /usr/sbin/sshd [listener] 0 of 10-10 root 9481 1473 S 14:40:37 sshd: fred [priv] fred 9579 9481 S 14:42:02 sshd: fred@pts/30 ``` Privilege separation has been the default in OpenSSH since version 3.3[^6] Since version 5.9, privilege separation further applies mandatory restrictions on which system calls the privilege separated child can perform. The intent is to prevent a compromised privilege separated child from being used to attack other hosts either by opening sockets and proxying or by probing local kernel attack surface. [^7] Since version 6.1, this sandboxing has been the default. ## References [^1]: [^2]: [^3]: [^4]: [^5]: [^6]: [^7]:
# OpenSSH/Other SSH Implementations ## Dropbear Dropbear is a smaller, modular, open source SSH2 client and server available for all regular POSIX platforms. Dropbear is partially a derivative of OpenSSH and it is often used in embedded systems because very small binaries can be produced. Functions that are not needed can be left out of the binary, leaving a lean executable. Thus a working SSH server can be boiled down to 110KB by trimming away various functions. Many distributions and products use Dropbear. This includes OpenWRT, gumstix, Tomato Firmware, PSPSSH, DSLinux, Meego, OpenMoko, Ångström (for Zaurus), ttylinux, Sisela, Trinux, SliTaz, Netcomm, US Robotics, some Motorola phones, and many, many more. - <https://matt.ucc.asn.au/dropbear/dropbear.html> ## Tectia Tectia is from SSH Communications Security Corporation which is based in Finland. It is a closed-source SSH client and server with FIPS support. - <http://www.ssh.com/?option=com_content&view=article&id=236&Itemid=364> ## Solaris Secure Shell (SunSSH) Sun SSH is fork of OpenSSH 2.3, with many subsequent changes. - <http://hub.opensolaris.org/bin/view/Community+Group+security/SSH> ## GlobalSCAPE EFT Server EFT Server is a closed binary that can include SSH and SFTP modules as extensions. - <http://www.globalscape.com/eft/> ## Gravitational Teleport Teleport provides an Apache-licensed SSH server and client written in Golang. It supports only IPv4 and not IPv6 at this time. - <http://gravitational.com/teleport/>
# OpenSSH/Client Applications On the client side, ssh(1), scp(1), and sftp(1) provide a wide range of capabilities. Interactive logins and file transfers are just the tip of the iceberg. : ssh(1) - The basic login shell-like client program. : sftp(1) - FTP-like program that works using the SSH protocol. : scp(1) - File copy program that acts like rcp(1). ```{=html} <!-- --> ``` : ssh_config(5) - The client configuration file. ## The SSH client ssh(1) is a program which provides the client side for secure, encrypted communications between hosts over an insecure network. Its main use is for logging into and running programs on a remote host. It can also be used to secure remote X11 connections and forward arbitrary TCP ports to secure legacy protocols. ssh was made, in part, to replace insecure tools like **rsh** and **telnet**. It has largely succeeded at this goal. **rsh** and **telnet** are rarely seen anymore for interactive sessions or anywhere else. ssh can authenticate using regular passwords or with the help of a public-private key pair. More options, such as use of Kerberos, smartcards, or one-time passwords can be configured. Remote login, authenticating via password: ``` shell $ ssh fred@somehost.example.org ``` Another way of logging in to the same account: ``` shell $ ssh -l fred somehost.example.org ``` Remote programs can be run interactively when the client is run via the shell on the remote host. Or they can be run directly when passed as an argument to the SSH client. They can even be pre-configured in the authentication key or the server configuration. Run uname(1) on the remote machine: ``` shell $ ssh -l fred somehost.example.org "uname -a" ``` See what file systems are mounted and how much space is used there: ``` shell $ ssh -l fred somehost.example.org "mount; df -h" ``` It is possible to configure in great detail which programs are allowed by which accounts. There are many combinations of options that give extra capabilities, such as re-using a single connection for multiple sessions or passing through intermediary machines. The level of granularity can be increased even more with the help of **sudo(8)**. ### SSH Client Environment Variables \-- Server Side Of course the foundation of most SSH activity centers around use of the shell. Upon a successful connection, OpenSSH sets several environment variables. SSH_CLIENT='192.168.223.17 36673 22' SSH_CONNECTION='192.168.223.17 36673 192.168.223.229 22' SSH_TTY=/dev/pts/6 **SSH_CLIENT** shows the address of the client system, the outgoing port number on the client system, and the incoming port on the server. **SSH_CONNECTION** shows the address of the client, the outgoing port on the client, the address of the server and the incoming port on the server. **SSH_TTY** names the pseudo-terminal device, abbreviated PTY, on the server used by the connection. For more information on pseudo-terminals see ptm(4), tty(1) and tty(4). The login session can be constrained to a single program with a predetermined set of parameters using **ForceCommand** in the server configuration or **Command=\"\...\"** in the authorized keys file. When that happens an additional environment variable **SSH_ORIGINAL_COMMAND** gets set. SSH_ORIGINAL_COMMAND=echo "hello, world" If the server has **ExposeAuthInfo** set, then the **SSH_USER_AUTH** environment variable points to a temporary file listing details about the authentication methods used to start the current session. SSH_USER_AUTH=/tmp/sshauth.4JmbYfF0bhF6C17 The file is removed when the session ends. Other variables are set depending on the user\'s shell settings and the system\'s own settings. ### SSH Client Configuration Options Configuration options can be passed to ssh(1) as arguments, see the manual pages for ssh(1) and ssh_config(5) for the full list. Connect very verbose output, GSSAPI authentication: ``` shell $ ssh -vv -K -l account host.example.org ``` A subset of options can be defined on the server host in the user\'s own authorized keys file, in conjunction with specific keys. See sshd(8) for which subset exactly. ``` apache command="/usr/local/sbin/backup.sh",no-pty ssh-rsa AAAAB3NzaC1yc2EAAAQEAsY6u71N... command="/usr/games/wump",no-port-forwarding,no-pty ssh-ed25519 AAAAC3NzaC1lZDI1... environment="gtm_dist=/usr/local/gtm/utf8",environment="gtm_principal_editing=NOINSERT:EDITING" ssh-rsa AAAA8a2s809poloh05yhh... ``` Note that some directives, like setting the environment variables, are disabled by default and must be named in the server configuration before available to the client. More configuration directives can be set by the user in **\~/.ssh/config** or by the system administrator in **/etc/ssh/ssh_config**. These same configuration directives can be passed as arguments using **-o**. See ssh_config(5) for the full list with descriptions. ``` shell $ ssh -o "ServerAliveInterval=60" -o "Compression=yes" -l fred server.example.org ``` The system administrators of the client host can set some global defaults in **/etc/ssh/config**. Some of these global settings can be targeted to a specific group or user by using a **Match** directive. For example, if a particular SSH server is available via port 2022, it may be convenient to have the client try that port automatically. Some of OpenBSD's anonymous CVS servers accept SSH connections on this port. However, compression should not be used in this case because CVS already uses compression. So it should be turned off. So, one could specify something like the following in the **\$HOME/.ssh/config** configuration file so that the default port is 2022 and the connection is made without compression: ``` {.apache .numberLines} Host anoncvs anoncvs.example.org Compression no Port 2022 ``` See ssh_config(5) for the client side and sshd_config(5) for the server side for the full lists with descriptions. ## The SFTP client sftp(1) is an interactive file transfer program which performs all its operations over an encrypted SSH transport channel. It may also use many features of ssh(1), such as public key authentication and compression. It is also the name of the protocol used. The SFTP protocol is similar in some ways to the now venerable File Transfer Protocol (FTP), except that the entire session, including the login, is encrypted. However, SFTP is not FTPS. The latter old-fashioned FTP tunneled over SSH/SSL. In contrast, SFTP is actually a whole new protocol. sftp(1) can also be made to start in a specific directory on the remote host. ``` shell $ sftp fred@server.example.org:/var/www ``` Frequently, SFTP is used to connect and log into a specified host and enter an interactive command mode. See the manual page for sftp(1) for the available interactive commands such as **get**, **put**, **rename**, and so on. Also, the same configuration options that work for ssh(1) also apply to sftp(1). sftp(1) accepts all ssh_config(5) options and these can be passed along as arguments at run time. Some have explicit shortcuts. ``` shell $ sftp -i ~/.ssh/some.key.ed25519 fred@server.example.org:/var/www ``` While others can be specified by naming them in full using the **-o** option. ``` shell $ sftp -o "ServerAliveInterval=60" -o "Compression=yes" fred@server.example.org ``` Another way to transfer is to send or receive files automatically. If a non-interactive authentication method is used, the whole process can be automatic using batch mode. ``` shell $ sftp -b session.batch -i ~/.ssh/some_key_rsa fred@server.example.org ``` Batch processing only works with non-interactive authentication. ## The SCP client scp(1) is used for encrypted transfers of files between hosts and is used a lot like regular cp(1). It is intended as a replacement for **rcp** from the original Berkeley Software Distribution (BSD). Since 9.0[^1] it is based on the SFTP protocol under the hood while the old version is based on. Both the old and the new versions SSH to encrypt the connection. The scp(1) client, unlike the SFTP client, is not based on any formal standard. It has aimed at doing more or less what old **rcp** did and responded the same way. Since with it the same program must be used at both ends of the connection and interoperability is required with other implementations of SSH. Changes in functionality would probably break that interoperability, so new features are more likely to be added to sftp(1) if at all. Thus, it is best to lean towards using sftp(1) instead when possible. However, recent versions are actually a front end for the SFTP protocol instead. Copy from remote to local: ``` shell $ scp myaccount@sftp.example.org:*.txt . ``` Copy from local to remote, recursively: ``` shell $ scp -r /etc/ myaccount@sftp.example.org:. ``` Being a front end for the SFTP protocol now, the new scp(1) client can cover most but not all of the behavior of the old client and is not quite bug-for-bug compatible. One noticeable change which is fixed on the server side in OpenSSH 8.7 or later was the absence of tilde (\~) expansion. So the \"expand-path@openssh.com\" protocol extension has been added to support this. Another area where there can potentially be trouble is when there are shell meta-characters, such as \* or ?, in the file names. See also the section for the SFTP client above. ## GUI Clients There are a great many graphical utilities that support SFTP and SSH. Many started out as transfer utilities with the outdated legacy protocol FTP and grew with the times to include SSH and SFTP support. Sadly, many retain the epithet FTP program despite modernization. Others are more general file managers that include SFTP support as one means of network transparency. Most if not all provide full SFTP support including Kerberos authentication. Below is a partial list to give an idea of the range of options available. **Bluefish** is a website management tool and web page editor with built in support for SFTP. Closed source competitors XMetaL and Dreamweaver are said to have at least partial support for SFTP. No support for SFTP is available for Quanta+ or Kompozer as of this writing. <http://bluefish.openoffice.nl/> **Cyberduck** is a remote file browser for the Macintosh. It supports an impressive range of protocols in addition to SFTP. <http://cyberduck.ch/> **Dolphin** is a highly functional file manager for the KDE desktop, but can also be run in other desktop environments. It includes SFTP support **Fetch**, by Fetch Softworks, is a reliable and well-known SFTP client for the Macintosh. It has been around since 1989 and started life as just an FTP client. It has many useful features combined with ease of use. It is closed source, but academic institutions are eligible for a free of charge site license. <http://fetchsoftworks.com/fetch/> **Filezilla** is presented as a FTP utility, but it has built in support for SFTP. It is available for multiple platforms under the Free Software license, the GPL. <http://filezilla-project.org/> **FireFTP** is a SFTP plugin for Mozilla Firefox. Though it is presented as an FTP add-on, it supports SFTP. It is available under both the MIT license and the GPL. <http://fireftp.mozdev.org/> **Fugu**, developed by the University of Michigan research systems unix group, is a graphical front-end for SFTP on the Macintosh. <http://rsug.itd.umich.edu/software/fugu/> **gFTP** is a multi-threaded file transfer client <http://www.gftp.org/> **JuiceSSH** is an SSH Client for Android/Linux. It uses the jsch Java implementation of SSH2. <https://juicessh.com/> **Konqueror** is a file manager and universal document viewer for the KDE desktop, but can also be run in other environments. It includes SFTP support. <http://www.konqueror.org/> **lftp** is a file transfer program that supports multiple protocols. <http://lftp.yar.ru/> **Midnight Commander** is a visual file manager based on a text interface and thus usable over a terminal or console. It includes SFTP support. <https://midnight-commander.org/> **Nautilus** is the default file manager for the GNOME desktop, but can also be run in other environments. It includes SFTP support **PCManFM** is an extremely fast, lightweight, yet feature-rich file manager with tabbed browsing which is the default for LXDE. It includes SFTP support. <http://wiki.lxde.org/en/PCManFM> **PuTTY** is another FOSS implementation of Telnet and SSH for both legacy and Unix platforms. It is released under the MIT license and includes an SFTP client, PSFTP, in addition to an xterm terminal emulator and other tools like a key agent, Paegent. It is written and maintained primarily by Simon Tatham. <http://www.chiark.greenend.org.uk/~sgtatham/putty/download.html> **Remmina** is a remote desktop client written in GTK+ which supports multiple network protocols, including SSH. <http://www.remmina.org/> **RemoteShell** is the default SSH client for MorphOS, written in C using the GUI library Magic User Interface (MUI). The operating system also contains the command-line tools ssh(1), scp(1) and sftp(1). <http://www.morphos-team.net> **SecPanel** is a GUI for managing and running SSH and scp connections. It is not a new implementation of the protocol or software-suite, but sits on top of either of the SSH software-suites <http://themediahost.de/secpanel/> **Thunar** is the default file manager for the XFCE desktop. It includes SFTP support. <http://docs.xfce.org/xfce/thunar/start> **Transfer** is the default SFTP client for MorphOS, written in C using the GUI library Magic User Interface (MUI). <http://www.morphos-team.net> **Yafc** is Yet Another FTP Client and despite the name supports SFTP. <http://yafc.sourceforge.net/> [^1]:
# OpenSSH/Client Configuration Files Client configuration files can be per user or system wide, with the former taking precedence over the latter and run-time arguments in the shell overriding both. In these configuration files, one parameter per line is allowed. The syntax is the parameter name followed by its value or values. Empty lines and lines starting with the hash (**\#**) are ignored. An equal sign (**=**) can be used instead of whitespace between the parameter name and the values. Values are case-sensitive, but parameter names are not. The first value assigned is used. For key files, the format is different. With either type of file, there is no substitute for reading the relevant manual pages on the actual systems involved, especially because they match the specific versions which are in use. ## System-wide Client Configuration Files System-wide client files set the default configuration for all users of OpenSSH clients on that system. These defaults can be overridden in most cases by the user\'s own default settings in a local configuration file. Both can be overridden, in many cases, by specifying various options or parameters at run time. The prioritization is as follows: 1. run time arguments via the shell 2. user\'s own configuration 3. system-wide configuration The first value obtained is used. The user\'s own configuration file and the system-wide configuration file can also point to additional configuration files to be included using the **Include** directive starting with OpenSSH 7.3. The **Include** directive can be specified anywhere in the configuration file even inside a **Match** or **Host** block. Care should be used when nesting configurations. ### */etc/ssh/ssh_config* This file defines all the default settings for the client utilities for all users on that system. It must be readable by all users. The configuration options are described in detail in ssh_config(5). Below a shortcut is made for connecting to *arc.example.org*. ``` {.apache .numberLines} Host arc Port 2022 HostName arc.example.org User fred IdentityFile ~/.ssh/id_rsa_arc ``` So with that configuration, it is enough to enter `ssh arc` and the rest of the information gets filled in automatically. ### */etc/ssh/ssh_known_hosts* This contains the system-wide list of known host keys used to verify the identity of the remote host and thus hinder impersonation or eavesdropping. This file should be prepared by the system administrator to contain the public host keys of all necessary hosts. It should be world-readable. See **\~/.ssh/known_hosts** below for more explanation or see sshd(8) for further details of the format of this file. ### */etc/ssh/sshrc* This file resides on the server and programs in this file are executed there by ssh(1) when the user logs in, just before the user\'s shell or designated program is started. It is not run as root, but instead as the user who is logging in. See the sshd(8) manual page in the section \"SSHRC\" for more information. If it sends anything to **stdout** that will interfere with SFTP sessions, among others. So if any output is produced at all, it should be sent to **stderr** or else a log file. ## User-specific Client Configuration Files Users can override the default system-wide client settings and choose their own defaults. For situations where the same change is made repeatedly it is recommended to add it to the user\'s local configuration. ### Client-Side Files These files reside on the client machine. #### *\~/.ssh/config* The user\'s own configuration file which, where applicable, overrides the settings in the global client configuration file, **/etc/ssh/ssh_config**. The configuration options are described in detail in ssh_config(5). This file must *not* be accessible to other users in any way. Set strict permissions: read/write for the user, and not accessible by others. It may group-writable if and only if that user is the only member of the group in question. ##### Local Override of Client Defaults The file is usually named **\~/.ssh/config**. However, a different configuration file can be specified at runtime using the **-F** option. General options intended to apply to all hosts can be set by matching all hosts and should be done at the end of the configuration file. The first match takes precedence, therefore more specific definitions must come first and more general overrides at the end of the file. ``` {.apache .numberLines} Host server1 ServerAliveInterval 200 HostName 203.0.113.76 Host * ExitOnForwardFailure yes Protocol 2 ServerAliveInterval 400 ``` Options given as runtime arguments will override even those in the configuration file. However, not all options can be set or overriden by the user. Those options which may not be set or overridden will be ignored. #### *\~/.ssh/known_hosts* This file is local to the user account and contains the known keys for remote hosts. Often these are collected from the hosts when connecting for the first time, but they can be added manually. As with those keys stored in the global file, **/etc/ssh/ssh_known_hosts**, these keys are used to verify the identity of the remote host, thus protecting against impersonation or man-in-the-middle attacks. With each subsequent connection the key will be compared to the key provided by the remote server. If there is a match, the connection will proceed. If the match fails, ssh(1) will fail with an error message. If there is no key at all listed for that remote host, then the key\'s fingerprint will be displayed and there will be the option to automatically add the key to the file. This file can be created and edited manually, but if it does not exist it will be created automatically by ssh(1) when it first connects to a remote host. The **\~/.ssh/known_hosts** file can use either hashed or clear text host names. Even with hashed names, it can still be searched using ssh-keygen(1) using the **-F** option. ``` shell $ ssh-keygen -F server3.example.com ``` The default file to be searched will be **\~/.ssh/known_hosts** and the key is printed if found. A different file can be searched using the **-f** option. If a key must be removed from the file, the **-R** option works similarly to search by host and then remove it if found even if the host name is hashed. ``` shell $ ssh-keygen -R server4.example.com -f ~/.ssh/known_hosts ``` When a key is removed, it will then be appended to the file **\~/.ssh/known_hosts.old** in case it is needed later. Again, see the manual page for sshd(8) for the format of these **known_host** files. If a non-default file is used with either **-F** or **-R** then the name including the path must be specified using **-f**. But **-f** is optional if the default file is intended. If the global file **/etc/ssh/ssh_known_hosts** is used then it should be prepared by the system administrator to contain the public host keys of all necessary hosts and it should be world-readable. ##### Manually Adding Public Keys to \~/.ssh/known_hosts Manually adding public host keys to **known_hosts** is a matter of adding one unbroken line per key. How the key is obtained is not important, as long as it is complete, valid, and **guaranteed to be the real key and not a fake**. The utility ssh-keyscan(1) can fetch a key and ssh-keygen(1) can be used to show the fingerprint for verification. See examples in the cookbook chapter on Public Key Authentication for methods of verification. Again, the corresponding system-wide file is **/etc/ssh/ssh_known_hosts** ##### About the Contents of the known_hosts Files The **known_hosts** file is for verifying the identity of other systems. ssh(1) can automatically add keys to the user\'s file, but they can be added manually as well. The file contains a list of public keys for all the hosts which the user has connected to. It can also include public keys for hosts that the user plans to log into but are not already in the system-wide list of known host keys. Usually when connecting to a host for the first time, ssh(1) adds the remote host\'s public key to the user\'s **known_hosts** file, but this behavior can be tuned. The format is one public key or certificate per unbroken line. Each line in contains a host name, number of bits, exponent, and modulus. At the beginning of the line is either the host name or a hash representing the host name. An optional comment can follow at the end of the line. These can be preceded by an optional marker to indicate a certificate authority, if an SSH certificate is used instead of a SSH key. These fields are separated by spaces. It is possible to use a comma-separated list of hosts in the host name field if a host has multiple names or if the same key is used on multiple machines in a server pool. Here are two examples for hosts with the basic host names: anoncvs.fr.openbsd.org,93.184.34.123 ssh-rsa AAAA...njvPw== anoncvs.eu.openbsd.org ssh-rsa AAAAB3Nz...cTqGvaDhgtAhw== Non-standard ports can be indicated by enclosing the host name with square brackets and following with a colon and the port number. Here are three examples referring to hosts listening for SSH on non-standard ports: [ssh.example.org]:2222 ssh-rsa AAAAB3Nz...AKy2R2OE= [127.0.0.2]:4922 ssh-rsa AAAAB4mV...1d6j= [anga.funkfeuer.at]:2022,[78.41.115.130]:2022 ssh-rsa AAAAB...fgTHaojQ== Host name patterns can be created using \"**\***\" and \"**?**\" as wildcards and \"**!**\" to indicate negation. Up to one optional marker per line is allowed. If present it must be either **\@cert-authority** or **\@revoked**. The former shows that the key is a certificate authority key, the latter flags the key as revoked and not acceptable for use. See sshd(8) for further details on the format of this file and ssh-keygen(1) for managing the keys. ### Server-Side Client Files These client files reside on the server. By default they are kept in the user\'s directory. However, the server can be configured to look for them in other locations if needed. #### *\~/.ssh/authorized_keys* **authorized_keys** is a one-key-per-line register of public ECDSA, RSA, and ED25519 keys that this account can use to log in with. The file\'s contents are not highly sensitive, but the recommended permissions are read/write for the user and not accessible by others. As always, the whole key including options and comments must be on a single, unbroken line. ssh-rsa AAAAB3NzaC1yc2EAAA...41Ev521Ei2hvz7S2QNr1zAiVaOFy5Lwc8Lo+Jk= Lines starting with a hash (#) are ignored and can be used as comments. Whitespace separates the key\'s fields, which are in sequence an optional list of login options, the key type (usually ssh-rsa or better like ecdsa-sha2-nistp256), the key itself encoded as base64, and an optional comment. If a key is followed by an annotation, the comment does not need to be wrapped in quotes. It has no effect on what the key does or how it works. Here is an annotated key, the comment having been generated with the **-C** option ssh-keygen(1): ssh-rsa AAAAB3NzaC1yc2EAAA...zAiVaOFy5Lwc8Lo+Jk= Fred @ Project FOOBAR Keys can be preceded by a comma-separated list of options to affect what happens upon successful login. The first key below forces the session to launch **tinyfugue** automatically, the second forcibly sets the PATH environment variable: command="/usr/bin/tinyfugue" ssh-rsa AAAAB3NzaC1yc2EAAA...OFy5Lwc8Lo+Jk= environment="PATH=/bin:/usr/bin/:/opt/gtm/bin" ssh-rsa AAAAB3N...4Y2t1j= The format of **authorized_keys** is described in the sshd(8) manual page. Old keys should be deleted from the file when no longer needed. The server can specify multiple locations for **authorized_keys**. See the next section, Server-Side Client Key Login Options, for details. #### *\~/.ssh/authorized_principals* By default this file does not exist. If it is specified in sshd_config(5), it contains a list of names which can be used in place of the username when authorizing a certificate. This option is useful for role accounts, disjoint account namespaces and \"user@realm\"-style naming policies in certificates. Principals can also be specified in **authorized_keys**. #### *\~/.ssh/environment* If the server is configured to accept user-supplied, automatic changes to environment variables as part of the login process, then these changes can be set in this file. If the server, the environment file and an authorization key all try to change the same variable, the file **environment** takes precedence over what a key might contain. Either one will override any environment variables that might have been passed by ssh(1) using **SendEnv**. Authentication keys stored in **authorized_keys** can also be used to set variables. See also the **AcceptEnv** and **PermitUserEnvironment** directives in the manual page for sshd_config(5). #### *\~/.ssh/rc* This is a script which is executed by sh(1) just before the user\'s shell or command is started. It is not run if **ForceCommand** is used. The script is run after reading the environment variables. The corresponding global file, **/etc/ssh/sshrc**, is not run if the user\'s **rc** script exists. ### Local Account Public / Private Key Pairs People might have a variety ECDSA, Ed25519, and RSA keys stored in the file system. Since version 8.2, two new key types ECDSA-SK and Ed25519-SK, along with corresponding certificate types are available for keys tied to FIDO/U2F tokens. Though individual accounts can maintain their own list of keys or certificates for authentication or to verify the identity of remote hosts in any directory, the most common location is in the **\~/.ssh/** directory. The naming convention for keys is only a convention but recommended to follow anyway. Public keys usually have the same name as the private key, but with **.pub** appended to the name. Trouble can arise if the names of the public and private keys do not match. If there is more than one key pair, then ssh-keygen(1) can use the **-f** option when generating keys to produce a useful name along with the **-C** option which embeds a relevant comment inside the key pair. People, programs, and scripts can authenticate using a private key stored on the system, or even a private key fetched from a smartcard, if the corresponding public key is stored in **authorized_keys** on the remote system. The **authorized_keys** file is not highly sensitive, but the recommended permissions are read/write for the user, and not accessible by others. The private keys, however, are very sensitive and should not be readable or even visible to other accounts. They should never leave the client and should certainly never be put on the server. See the chapter on Public Key Authentication for more discussion and examples. The keys can be preceded by a comma-separated list of options. The whole key must be on a single, unbroken line. No spaces are permitted, except within double quotes. Any text after the key itself is considered a comment. The **authorized_keys** file is a one-key-per line register of public RSA, Ed25519, ECDSA, Ed25519-SK, and ECDSA-SK keys that can be used to log into a particular account. See the section above on the **authorized_keys** file for more discussion. DSA is considered deprecated. The time has passed for DSA keys and they are no longer considered safe and should be replaced with better keys. Per-account Host-based Authentication Configuration is also possible using the **\~/.shosts**, **\~/.rhosts**, **\~/.ssh/environment**, and **\~/.ssh/rc** files. #### Public Keys: \~/.ssh/id_ecdsa.pub \~/.ssh/id_ed25519.pub \~/.ssh/id_rsa.pub \~/.ssh/id_ecdsa-sk.pub \~/.ssh/id_ed25519-sk.pub \~/.ssh/id_ecdsa-sk_rk.pub \~/.ssh/id_ed25519-sk_rk.pub These are only the default names for the public keys. Again, it can be a good idea to give more relevant names to keys. The **\*-sk.pub** keys are those bound with a hardware security token and the **\*-sk_rk.pub** keys are those generated from resident keys stored within hardware security token. Public keys are mainly used on the remote server for key-based authentication. Public keys are not sensitive and are allowed to be readable by anyone, unlike the private keys, but don\'t need to be. A public key, minus comments and restriction options, can be regenerated from a private key if lost. So while it can be useful to keep backups of the public key, it is not essential unlike for private keys. #### Private Keys: \~/.ssh/id_ecdsa \~/.ssh/id_ed25519 \~/.ssh/id_rsa \~/.ssh/id_ecdsa-sk \~/.ssh/id_ed25519-sk \~/.ssh/id_ecdsa-sk_rk \~/.ssh/id_ed25519-sk_rk These are only the default names for private keys. Private keys are always considered sensitive data and should be readable only by the user and not accessible by others. In other words, they use mode 0600. The directory they are in should also have mode 0700 or 0500. If a private key file is accessible by others, ssh(1) will ignore it. It is possible to specify a passphrase when generating the key which will be used to encrypt the sensitive part of this file using AES128. Until version 5.3, the cipher 3DES was used to encrypt the passphrase. Old keys using 3DES that are given new passphrases will use AES128 when they are modified. Private keys stored in hardware tokens as resident keys can be extracted and automatically used to generate their corresponding public key using ssh-keygen(1) with the **-K** option. Such keys will default to being named **id_ecdsa-sk_rk** or **id_ed25519-sk_rk**, depending on the key type, though the file names can be changed after extraction. A passphrase can be assigned to the private key upon extraction from the token to a file. While public keys can be generated from private keys, new private keys cannot be regenerated from public keys if the private keys are lost. Nor can a new passphrase be set if the current one is forgotten. Gone is gone, unlike the public keys, which can be regenerated from an existing private key if the private key is lost or forgotten then a whole new key pair must be generated and deployed. ### Legacy Files These files might be encountered on very old or out of date systems but not on up-to-date ones. #### *\~/.shosts* #### *\~/.rhosts* **.rhosts** is a legacy from rsh containing a local list of trusted host-user pairs that are allowed to log in. Login requests matching an entry were granted access. See also the global list of trusted host-user pairs, **/etc/hosts.equiv** **rhosts** can be used as part of host-based authentication. Otherwise it is recommended not to use rhosts for authentication, there are a lot of ways to misconfigure the **.rhosts** file. #### Legacy DSA Keys \~/.ssh/id_dsa \~/.ssh/id_dsa.pub Deprecated DSA keys might be found named as **id_dsa** and **id_dsa.pub**, but regardless of the name any usage should be tracked down. Support for DSA both on the server and client was discontinued in OpenSSH 7.0. If DSA keys are found, the pair should be removed and replaced with a better type of key. #### Legacy SSH1 Protocol Keys \~/.ssh/identity \~/.ssh/identity.pub The files **identity** and **identity.pub** were for SSH protocol version 1, and thus deprecated. If found they should be investigated as to what, if anything, uses them and why. Then once any remaining usage is resolved they should be removed and replaced with newer key types. ## Mapping Client Options And Configuration Directives Many run-time options for the SSH client have corresponding configuration directives and vice versa. The following is a quick overview. It is not a substitute for getting familiar with the relevant manual pages, ssh(1) and ssh_config(5) which are the relevant, authoritative, up-to-date resources on the matter. Directive Option Description ------------------------- --------- ---------------------------------------------------------------------------------------------------- AddressFamily -4 / -6 Limit connections to IPv4 or IPv6 only. ForwardAgent -A / -a Forward or block forwarding from the authentication agent. BindInterface -B Bind the outgoing connection to this network interface. BindAddress -b Bind the outgoing connection to this network address. Compression -C Specify whether to compress the data using gzip(1). Ciphers -c Specify which cipher to use. DynamicForward -D Designate a local port to be forwarded, say for SOCKS5. EscapeChar -e Specify an escape character for PTY sessions. ForkAfterAuthentication -f Drop client to background right before command execution. GatewayPorts -g Whether other hosts are allowed to connect to local forwarded ports. PKCS11Provider -I Specify the path to the shared PKCS#11 library. IdentityFile -i Specify a particular certificate or private key to use for authentication. ProxyJump -J Connect to the destination via this host or hosts first. GSSAPIAuthentication -K / -k Enable or disable Generic Security Services Application Program Interface (GSSAPI) authentication. LocalForward -L Specify which local port or socket to forward to the specified remote system. User -l Designate which account on the remote system to try. ControlMaster -M Allow multiplexing of SSH sessions over a single TCP connection. MACs -m Designate which message authentication code (MAC) algorithms to try. SessionType -N / -s Invoke a designated subsystem or even prevent any command execution at all. StdinNull -n Prevent reading from **stdin**. Tag -P Tag for use within **Match**. Port -p Connect to this port on the remote system. LogLevel -q / -v Adjust the verbosity of logging messages from the client. RemoteForward -R Specify which remote port or socket to forward to the specified local system. ControlPath -S Designate the control socket for multiplexing over this connection. RequestTTY -T / -t Prohibit or request a pseudo-TTY for the session. ForwardX11 -X / -x Enable or prohibit X11 forwarding. : Lookup Table of OpenSSH Client Options Versus Configuration Directives As of version 8.7 the **-f**, **-N**, and **-n** options also have corresponding client configuration directives in ssh_config(5). ## Server-Side Client Key Login Options The login options available for use in the local user authorized keys file might be overridden or blocked by the server\'s own settings. However, within that constraint, the following options can be used. **cert-authority** Specifies that the listed key is a certification authority (CA) trusted to validate signed certificates for user authentication. Certificates may encode access restrictions similar to key options. If both certificate restrictions and key restrictions are present, then the most restrictive union of the two is applied. **command=\"*program*\"** Specifies a program and its options to be executed when the key is used for authentication. This is a good way of forcing a program to restrict a key to a single, specific operation such as a remote backup. However, TCP and X11 forwarding are still allowed unless explicitly disabled elsewhere. The program is run on a PTY if the client requests it, otherwise the default is to run without a TTY. The default, running without a TTY, provides an 8-bit clean channel. If the default has been changed, specify **no-pty** to get an 8-bit clean channel. If no programs are allowed, then use an empty string \"\" to prevent anything from running. no-pty,command="" ssh-rsa AAAAB3NzaC1yc2EAAA...OFy5Lwc8Lo+Jk= If only one program is allowed, with specific options, then it can be spelled out explicitly. restrict,command="/usr/bin/svnserve -t --tunnel-user=fred" ssh-ed25519 AAAAC3NzaC1lZDI1NT...skSUlrRPoLyUq Quotes provided in the program\'s options must be escaped using a backslash. (\'\\\') command="sh -c \"mysqldump db1 -u fred1 -p\"" ssh-rsa AAAAB3NzaC1yc...Lwc8OFy5Lo+kU= This option applies to execution of the shell, another program, or a subsystem. Thus any other programs specified by the user are ignored when **command** is present. However, the program originally specified by the client remains available as the environment variable **SSH_ORIGINAL_COMMAND**. That can be used by a script in a multiple-choice case statement, for example, to allow the account to select from a limited range of actions. **environment=\"*NAME*=*value*\"** Sets the value of an environment variable when this key is used to log in. It overrides default values of the variable, if they exist. This option can be repeated to set multiple variables up to 1024 discrete names. First match wins in the case of repetition. This option is only allowed if the **PermitUserEnvironment** option is set in the SSH server\'s configuration. The default is that it is disabled. This option used to be disabled automatically when **UseLogin** was enabled, but **UseLogin** has been deprecated. **expiry-time=\"*timespec*\"** Sets a date or date-time, either as a YYYYMMDD date or a YYYYMMDDHHMM\[SS\], after which the key will not be allowed to authenticate. Otherwise the key will be considered valid indefinitely. The system time zone is used. **from=\"*pattern-list*\"** Either the canonical name of the remote host or its IP address required in addition to the key. Addresses and host names can be listed using a comma-separated list of patterns, see PATTERNS in ssh_config(5) for more information on patterns, or use the CIDR address/masklen notation. **no-agent-forwarding / agent-forwarding** This option forbids the authentication agent from forwarding the key when it is used for authentication. Alternately, it allows agent forwarding even if it was otherwise previously disabled by the **restrict** option. **no-port-forwarding / port-forwarding** Forbids TCP forwarding and any port forward requests by the client will return an error when this key is used for authentication. Alternately, override the **restrict** option and allow port forwarding. See also **permitopen**. **no-pty / pty** TTY allocation is prohibited and any request to allocate a PTY will fail. Alternately, TTY allocation is permitted, even if previously disabled by the **restrict** option. **no-touch-required** FIDO keys which have been created with the **-O no-touch-required** can use this method which makes the client skip the check for user presence. **no-user-rc / user-rc** Use the **no-user-rc** option in **authorized_keys** to disable execution of **\~/.ssh/rc**. Alternately, use **user-rc** to override the **restrict** option. **no-X11-forwarding / x11-forwarding** Prevent X11 forwarding when this key is used for authentication and requests to forward X11 will return an error. Alternately, override the **restrict** option and allow X11 forwarding. *\'permitlisten=\"\[*host*:\]*port\'\'\" **permitopen=\"*host*:*port*\"** The **permitlisten** setting limits remote port forwarding (`ssh -R`) to only the specified port and, optionally, host. In contrast, **permitopen** limits local port forwarding (`ssh -L`) to only the specified host and port. IPv6 addresses can be specified with an alternative syntax: host/port. Multiple **permitopen** or **permitlisten** options may be used and must be separated by commas. No pattern matching is performed on the specified host names, they must be literal host names or IP addresses. Can be used in conjunction with agent-forwarding. **principals=\"*name1*\[,*name2*,\...\]\"** Specify a list of names that may be used in place of the username when authorizing a certificate trusted via the **TrustedCAKeys** option described in sshd_config(5). **restrict** Disable all options, such as TTY allocation, port forwarding, agent forwarding, user-rc, and X11 forwarding all at once. Specific options can then be explicitly allowed on an individual basis. **tunnel=\"*n*\"** Select a specific tun(4) device on the server. Otherwise when a tunnel device is requested without this option the next available device will be used. **verify-required** Require user-verification, such as with a PIN, with FIDO keys. ## Managing Keys When working with keys there are some basic, hopefully common sense, actions that should take place to prevent problems. The two most beneficial approaches are to use sensible names for the key files and to embed comments. The **-f** option for ssh-keygen(1) allows a custom name to be set. The **-C** option allows a comment to be embedded in both the public and private keys. With the comment inside the private key, it can be regenerated automatically if a replacement public key is ever made using the **-y** option. Other than that, there are three main rules of thumb for managing keys: - Keys should use strong passphrases. If autonomous logins are required, then the keys should be first loaded into an agent and used from there. See ssh-add(1) to get started there. It uses ssh-agent(1) which many systems have installed and some have running by default. ```{=html} <!-- --> ``` - Keys should always be stored in protected locations, even on the client side. This is especially important for private keys. The private keys should not have read permissions for any user or group other than their owner. They should also be kept in a directory that is not accessible by anyone other than the owner in order to limit exposure. ```{=html} <!-- --> ``` - Old and unused keys should be removed from the server. In particular, keys without a known, valid purpose should be removed and not allowed to accumulate. Using the comment field in the public key for annotation can help eliminate some of the confusion as to the purpose and owner once some time has passed. Along those lines, keys should be rotated at intervals. Rotation means generating new key pairs and removing the old ones. This gives a chance to remove old and unused keys. It is also an opportunity to review access needs, whether access is required and if so at what level. Following the principle of least privilege can limit the chance for accidents or abuse. If a key is only needed to run a specific application or script, then its login options should be limited to just what is needed. See sshd(8) for the \"AUTHORIZED_KEYS FILE FORMAT\" section on key login options. For root level access, it is important to remember to configure **/etc/sudoers** or **/etc/doas.conf** appropriately. Access there can be granted to a specific application and even limit that application to specific options. One major drawback to keys is that they never expire and are valid indefinitely in principle. In contrast, certificates can be assigned a validity interval with an end date, after which they can no longer be used.
# OpenSSH/Server The OpenSSH Server, sshd(8), listens for connections from clients and starts a new process or two for each new incoming connection to handle key exchange, encryption, authentication, program execution, and data exchange. In the case of multiplexing, some processes are reused. It can run standalone and wait in the background, be run in the foreground, or it can be loaded on demand by any Internet services daemon. Since version 8.2, the listening process title shown in ps(1) also shows the number of connections pending authentication. ``` shell-session $ ps -p $(pgrep -u root sshd) -o pid,user,args PID USER COMMAND 44476 root sshd: /usr/sbin/sshd [listener] 0 of 10-100 startups (sshd) ``` Note that this is the number pending authentication, not the number which of those which have already been authenticated. Those each have their own separate handler process owned by the account which has authenticated. ## sshd sshd(8) is the secure shell daemon and it listens for incoming connections. The standard port for ssh(1) as specified by IANA is 22 [^1]. If sshd(8) does not listen to a privileged port, it does not have to be launched by root. However there are few, if any occasions where a non-standard port should be considered. sshd(8) can be bound to multiple addresses or just certain ones. Multiple instances of sshd(8), each with a different configuration, can be run on the same machine, something which may be useful on multi-homed machines. An absolute path must be given to launch sshd(8), i.e. `/usr/sbin/sshd` Configuration data is parsed first from the arguments and options passed by the shell, the user-specific file, and lastly the system-wide configuration file. : sshd(8) - The SSH daemon that permits you to log in. ```{=html} <!-- --> ``` : sftp-server(8) - SFTP server subsystem, started automatically by sshd(8) when needed. : ssh-keysign(8) - Helper program for hostbased authentication. ```{=html} <!-- --> ``` : sshd_config(5) - The server configuration file. The sshd(8) daemon can be made to parse the configuration file, test it for validity, and then report the effective configuration settings. This is done by running the extended test mode (**-T**). The extended test will print out the actual server settings. It can also report modifications to the settings through use of the **Match** directive when combined with the connection specification (**-C**) parameter. The options for **-C** are **user**, **host**, and **addr**. This is where **host** and **addr** refer to the host running sshd(8) and the address from which the connection is being made, respectively. The following will print out the configurations that will be applied if the user \'fred\' tries to log in to the host *server.example.org* from the address *192.168.100.5*. ``` shell-session $ /usr/sbin/sshd -TC user=fred,host=server.example.org,addr=192.168.100.5 ``` The output is long, so it might be sensible to pipe it through sort(1) and a pager like less(1). See the section on Debugging a Server Configuration for more options. By default, login is allowed for all groups. However, if either **AllowGroups** or **AllowUsers** is specified, then all users or groups not listed are prohibited from logging in. The allow/deny directives are processed in the following order: 1. **DenyUsers**, 2. **AllowUsers**, 3. **DenyGroups**, and finally, 4. **AllowGroups**. The first pattern matched takes effect, so if **AllowUsers** exists it will completely override **AllowGroups** regardless of the order in which they appear in the configuration file. So for the most flexibility, it is recommended to use **AllowGroups**. In contrast, **DenyUsers** and **DenyGroups** do not interfere with each other and may be used together. List group names or patterns of group names, separated by spaces. If specified, login is allowed or denied only for users who are members of a group that matches a group or pattern on the list. Only group or user names are valid; numerical group or user IDs are not recognized. ## sshd under inetd / xinetd An Internet services daemon is a server to launch other servers on demand. xinetd(8) and inetd(8) are two variants, either of which can be used to specify additional parameters and constraints, including running the launched service as a particular user and group. By having a single daemon active, which invokes others as needed, demands on the system can be reduced. Launching sshd(8) this way means inetd(8) waits for an incoming request, launches sshd(8) and then when the SSH session is over, closes sshd(8). Packet Internet --> Filter --> tcpwrappers --> (x)inetd --> sshd (firewall) (aka tcpd) Either can be used for additional logging such as successful or unsuccessful login, access restriction even including time of day, cpu priority, and number of connections. There are many more possibilities. See the manual pages for xinetd.conf(5) or inetd.conf(5) for a full overview of configuration options. inetd(8) was **tcpd**-aware and could make use of **tcpd**\'s tcpwrappers to further control access or logging. So was sshd(8) by itself, up through 6.6. See the manual pages for \ht ormation about how to use the configuration files **hosts.allow** and **hosts.deny**. Since 6.7, OpenSSH itself no longer supports tcpwrappers because current packet filters filters made it mostly redundant. The two main disadvantages of using [inetd(8) or xinetd(8) are that there can be a slight increase in the delay during the start of the connection and that sshd(8) must be configured to allow launching from the services daemon. The delay only affects the initial connection and thus does not get in the way of actual operation. An Internet services daemon should not be used for stateless services like HTTP and HTTPS, where every action is essentially a new connection. Again, see the manual page for xinetd.conf(5) or inetd.conf(5) for more details. Example from xinetd.conf(5) service ssh { socket_type = stream protocol = tcp wait = no user = root server = /usr/sbin/sshd server_args = -i per_source = UNLIMITED log_on_failure = USERID HOST # log_on_success = PID HOST DURATION TRAFFIC EXIT # instances = 10 # nice = 10 # bind = 192.168.0.100 # only_from = 192.168.0.0 # access_times = 08:00-15:25 # no_access = 192.168.54.0 # no_access += 192.168.33.0 # banner = /etc/banner.inetd.connection.txt # banner_success = /etc/banner.inetd.welcome.txt # banner_fail = /etc/banner.inetd.takeahike.txt } Example from inetd.conf(5) ssh stream tcp nowait root /usr/sbin/sshd -i ssh stream tcp6 nowait root /usr/sbin/sshd -i There are several advantages with xinetd(8) over inetd(8) in capabilities but use-cases where either would be useful are rare. ## The SFTP Server Subsystem The SFTP subsystem first appeared in OpenBSD 2.8 / OpenSSH 2.3[^2]. It is called by sshd(8) as needed using the **Subsystem** configuration directive and not intended to operate standalone. There are two forms of the subsystem. One is the regular sftp-server(8). The other is an in-process SFTP server, which requires no support files when used with the **ChrootDirectory** directive. The **Subsystem** configuration directive can be used to pass options: **-d** specifies an alternate starting directory for users, the default is the user\'s home directory. (First in 6.2) ``` text Subsystem sftp internal-sftp -d /var/www ``` **-e** causes logging information to be sent to **stderr** instead of syslog(3). ``` text Subsystem sftp internal-sftp -e ``` **-f** specifies the syslog(3) facility code that is used when logging messages from sftp-server(8). The possible values are: DAEMON, USER, AUTH, LOCAL0, LOCAL1, LOCAL2, LOCAL3, LOCAL4, LOCAL5, LOCAL6, LOCAL7. ``` text Subsystem sftp /usr/libexec/sftp-server -f LOCAL0 ``` **-l** Specifies which messages will be logged by sftp-server(8). The default is AUTH. The other possible values are: QUIET, FATAL, ERROR, INFO, VERBOSE, DEBUG, DEBUG1, DEBUG2, and DEBUG3. INFO and VERBOSE log transactions that sftp-server performs on behalf of the client. DEBUG and DEBUG1 are equivalent while DEBUG2 and DEBUG3 each specify higher levels of debugging output. Log levels DEBUG through DEBUG3 will violate user privacy and should not be used for regular operation. The default log level is ERROR. The actual path will vary depending on distro or operating system. ``` text Subsystem sftp /usr/libexec/sftp-server -l VERBOSE ``` **-p** and **-P** specify whitelisted and blacklisted protocol requests, respectively. The comma separated lists are permitted or prohibited accordingly, the blacklist is applied first if both are used. **-Q** provides a list of protocol features supported by the server. All three are available as of version 6.5. The actual path will vary depending on distro or operating system. In version 6.5 *requests* are the only protocol features queriable. ``` shell-session $ /usr/libexec/sftp-server -Q requests ``` **-R** places the SFTP subsystem in read-only mode. Attempts to change the filesystem, including opening files for writing, will fail. **-u** overrides the user\'s default umask and explicitly sets the umask(2) to be used for creating files and directories. See the manual page for syslog.conf(5) for more information about log level or log facility. sshd(8) must be able to access **/dev/log** for logging to work. Using the sftp-server(8) subsystem in conjunction with the main SSH server\'s **ChrootDirectory** option therefore requires that syslogd(8) establish a logging node inside the chrooted directory. ``` text Subsystem sftp internal-sftp -u 0002 ``` That sets the umask for the SFTP subsystem in OpenSSH 5.4 and later. ## Environment Variables ssh(1) and sshd(8) set some environment variables automatically when logging in. Other variables can be explicitly defined by users in the **\~/.ssh/environment** file if the file exists and if the user is allowed to change the environment. Variables can also be set on a key by key basis in the **authorized_keys** file, again only if the user is allowed to change the environment. In **\~/.ssh/environment**, the format **NAME=value** is used to set the variable. In **\~/.ssh/authorized_keys** and **/etc/ssh/authorized_keys** the format is **environment=\"NAME=value\"** For more information, see the **PermitUserEnvironment** and **AcceptEnv** configuration directives in sshd_config(5) and the **SendEnv** directive in ssh_config(5). The following variables can be set by ssh(1), depending on the situation. **DISPLAY** If X11 is tunneled, this is set so that the **DISPLAY** variable indicates the location of the X11 server. When it is automatically set by ssh(1) it points to a value in the form *hostname*:*n*, where *hostname* indicates the host where the shell runs, and *n* is an integer greater than or equal to one. ssh(1) uses this special value to forward X11 connections over the secure channel. The user should normally not set **DISPLAY** explicitly, as that will render the X11 connection insecure and will require the user to manually copy any required authorization cookies. **HOME** The path of the user\'s home directory. **LOGNAME** Synonym for USER. This is set for compatibility with systems that use this variable. **MAIL** The path of the user\'s mailbox. **PATH** The default PATH, as specified when compiling ssh(1). **SSH_ASKPASS** If **DISPLAY** and **SSH_ASKPASS** are both set, and the SSH session does not have an associated terminal or pseudo-terminal, the program specified by **SSH_ASKPASS** will execute and open an X11 window to read the passphrase when one is needed. This is particularly useful when calling ssh(1) from an xsession or related script. On some machines it may be necessary to redirect the input from **/dev/null** to make this work. **SSH_AUTH_SOCK** The path on the client machine to tell ssh(1) the UNIX-domain socket used to communicate with an SSH key agent. **SSH_CLIENT** Identifies the client end of the connection. It contains three space-separated values: the client IP address, client port number and the server port number. **SSH_CONNECTION** Identifies the client and server ends of the connection. The variable contains four space-separated values: client IP address, client port number, server IP address, and server port number. **SSH_ORIGINAL_COMMAND** If the **ForceCommand** directive was used, or **Command=\"\...\"** in a key, then this variable contains the original command including the original options. It can be used to extract the original arguments. **SSH_TTY** This is set to the name of the TTY (path to the device) associated with the current shell or command. If the current session has no TTY, this variable is not set. **SSH_USER_AUTH** This will contain the name of a temporary file containing the authentication methods used for this particular session if **ExposeAuthInfo** is set in sshd_config(5). **TZ** This variable is set to indicate the present time zone if it was set when the daemon was started. The SSH daemon passes this value on to new connections. **USER** Set to the name of the user logging in. ## References [^1]: [^2]:
# OpenSSH/Pattern Matching in OpenSSH Configuration A pattern consists of zero or more non-whitespace characters. An asterisk (**\***) matches zero or more characters in a row, and a question mark (**?**) matches exactly one character. For example, to specify a set of declarations that apply to any host in the \".co.uk\" set of domains in ssh_config(5), the following pattern could be used: Host *.co.uk The following pattern would match any host in the 192.168.0.1 - 192.168.0.9 range: Host 192.168.0.? A pattern-list is a list of patterns separated by whitespace. The following list of patterns match hosts in both the \".co.uk\" or \".ac.uk\" domains. Host *.co.uk *.ac.uk Individual patterns by themselves or as part of a pattern-lists may be negated by preceding them with an exclamation mark (**!**). The following will match any host from *example.org* except for *gamma*. Host *.example.org !gamma.example.org Pattern lists in ssh_config(5) do not use commas. Pattern lists in keys need commas. For example, to allow a key to be used from anywhere within an organisation except from the dialup pool, the following entry in **authorized_keys** could be used: from="!*.dialup.example.com,*.example.com" See also glob(7)
# OpenSSH/Utilities : ssh-agent(1) - An authentication agent that can store private keys. : ssh-add(1) - A tool which adds or removes keys to or from the above agent. : ssh-keygen(1) - A key generation tool. : ssh-keyscan(1) - A utility for gathering public host keys from a number of hosts. : ssh-copy-id(1) - Install a public key in a remote machine\'s **authorized_keys** register. : ssh-vulnkey(1) - Check a key against blacklist of compromised keys ## ssh-agent ssh-agent(1) is a tool to hold private keys in memory for re-use during a session. Usually it is started at the beginning of a session and subsequent windows or programs run as clients to the agent. The environment variable **SSH_AUTH_SOCK** points applications to the socket used to communicate with the agent. ## ssh-add ssh-add(1) is a tool to load key identities into an agent for re-use. It can also be used to remove identities from the agent. The agent holds the private keys used for authentication. ## ssh-keyscan ssh-keyscan(1) has been part of the OpenSSH suite since OpenSSH version 2.5.1 and is used to retrieve public keys. Keys retrieved using ssh-keyscan(1), or any other method, must be verified by checking the key fingerprint to ensure the authenticity of the key and reduce the possibility of a man-in-the-middle attack. The default is to request a ECDSA key using SSH protocol 2. David Mazieres wrote the initial version of ssh-keyscan(1) and Wayne Davison added support for SSH protocol version 2. ## ssh-keygen ssh-keygen(1) is for generating key pairs or certificates for use in authentication, update and manage keys, or to verify key fingerprints. It works with SSH keys and can do the following activities: - generate new key pairs, either ECDSA, Ed25519, RSA, ECDSA-SK or Ed25519-SK. - remove keys from known hosts - regenerate a public key from a private key - change the passphrase of a private key - change the comment text of a private key - show the fingerprint of a specific public key - show ASCII art fingerprint of a specific public key - load or read a key to or from a smartcard, if the reader is available If the legacy protocol, SSH1, is used, then ssh-keygen(1) can only generate RSA keys. However, SSH1 is long since deprecated and the systems should be re-tooled if found in use. Also, although DSA keys can be generated, they are deprecated and should be replaced if found. One important use for key fingerprints is when connecting to a machine for the first time. A fingerprint is a hash or digest of the public key. Fingerprints can be transferred out of band and loaded into either the **\~/.ssh/known_hosts** or **/etc/ssh/ssh_known_hosts** files in advance of the first connection. The verification data for the key should be sent out of band. It can be sent ahead of time by post, fax, SMS or a phone call instead or otherwise communicated in some way such that you can be sure it is authentic and unchanged. ``` shell-session $ ssh -l fred zaxxon.example.org The authenticity of host 'zaxxon.example.org (203.0.113.114)' can't be established. RSA key fingerprint is SHA256:DnCHntWa4jeadiUWLUPGg9FDTAopFPR0c5TgjU/iXfw. Are you sure you want to continue connecting (yes/no)? ``` If you see that message and the key\'s fingerprint matches the one you were given in advance, then the connection is probably good. If you see that and the key\'s fingerprint is different than what you were given in advance, then stop and disconnect and get on the phone or VoIP to work out the mistake. Once the SSH client has accepted the key from the server, it is saved in **known_hosts**. ``` shell-session $ ssh -l fred galaga.example.org @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ @ WARNING: REMOTE HOST IDENTIFICATION HAS CHANGED! @ @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ IT IS POSSIBLE THAT SOMEONE IS DOING SOMETHING NASTY! Someone could be eavesdropping on you right now (man-in-the-middle attack)! It is also possible that a host key has just been changed. The fingerprint for the ECDSA key sent by the remote host is SHA256:QIWi4La8svQSf5ZYow8wBHN4tF0jtRlkIaLCUQRlxRI. Please contact your system administrator. Add correct host key in /home/fred/.ssh/known_hosts to get rid of this message. Offending ECDSA key in /home/fred/.ssh/known_hosts:1 ECDSA host key for galaga.example.org has changed and you have requested strict checking. Host key verification failed. ``` If you start to connect to a known host and you get an error like the one above, then either the first connection was to an impostor or the current connection is to an impostor, or something very foolish was done to the machine. Regardless, disconnect and don\'t try to log in. Contact the system administrator out of band to find out what is going on.[^1] It is possible that the server was reinstalled, either the whole operating system or just the OpenSSH server, without saving the old keys. That would result in new keys being generated and explain their presence. Either way, check with the system administrator before connecting to be sure. Hashed host names and addresses can be looked up in **known_hosts** using **-F**. Or else **-R** can be used to delete them. ``` shell-session $ ssh-keygen -F sftp.example.org -f ~/.ssh/known_hosts # Host sftp.example.org found: line 7 type RSA |1|slYCk3msDPyGQ8l0lq82IbUTzBU=|KN7HPqVnJHOFX5LFmTXS6skjK4o= ssh-rsa AAAAB3NzaC1yc2EAAAABIwAAAIEA3cqqA6fZtgexZ7+4wxoLN1+YDvPfBtt4/m+N/RI8o95CXqvqZMIQjuVarVKjwRwt9pTJIVzf6bwjcNkrUx9dQqZNpNBkcvBRdmd775opWCAfkHEueKxkNx3Kb1yitz0dUaFkRwfTsXAjh+NleBq2ofAfjowu/zzCnnbAKy2R2OE= ``` ## ssh-copy-id **ssh-copy-id** is included in some distros to install a public key into a remote machine\'s **authorized_keys** file. It is a simple shell script and the **authorized_keys** file should still be checked manually after first login to verify that everything went ok and that the key was copied as it should be. ## ssh-vulnkey **ssh-vulnkey** was included in some versions of some GNU/Linux distros to check a key against a blacklist of compromised keys. The blacklist was made necessary when a broken version of OpenSSL was distributed by some distros[^2], resulting in bad keys that were easily predicted and compromised. Keys made while that broken version was in use that are found to have been compromised cannot be repaired and must be replaced. The problem has since been fixed and new keys should be all right. ## References [^1]: [^2]:
# OpenSSH/Third Party Utilities : autossh - Automatically restart SSH sessions and tunnels : scanssh - a scanner for SSH hosts and some kinds of proxies : sshfs - a user-space file system client based on SFTP : sshfp - generates SSHFP DNS records from **known_hosts** files or ssh-keyscan(1) : keychain - re-use ssh-agent and/or gpg-agent between logins : rsync - synchronizes files and directories using delta encoding : gstm - a graphical front-end for managing SSH-tunneled port redirects : sslh - a protocol demultiplexer : sshguard - an intrusion detection system with packet filtering : ssh-audit - identifies the server\'s banner, key exchange, encryption, MAC, compression, compatibility, and other information. : webcat - can use websockets[^1] for tunneling, is otherwise very similar to netcat and curl. ## scanssh **scanssh** scans hosts and networks for running services[^2]. It checks the version number of the server and displays the results in a list. It detects ssh, sftp and several kinds of SOCKS, HTTP, and telnet proxies. Scan a small subnet for ssh servers: ``` shell-session $ sudo scanssh -n 22 -s ssh 192.168.100.32/26 ``` Scan the same small network for SOCKS proxies: ``` shell-session $ sudo scanssh -s socks5,socks4 192.168.100.32/26 ``` Variable scanning speeds can be set as well as random sampling. Open proxy detection scans to detect open proxies on common ports. Scan 1000 hosts randomly selected from 172.16.1.1 through 172.31.254.254, at a rate of 200 per second : ``` shell-session $ sudo scanssh -r 200 -p random(1000)/172.16.0.0/12 ``` The hosts and networks to be scanned can be either specified as an IPv4 address or an CIDR like IP prefix with ip address and network mask. Ports can be appended by adding a colon at the end of address specification. The sequence of hosts scanned is random, but that can be modified by the following two parameters, **random** and **split**: **random(n\[,seed\])/** selects a sample of *n* random addresses from the range specified as targets for scanning. *n* is the number of address to randomly create in the given network and *seed* is an optional seed for the pseudo random number generator. For example, it is possible to sample 10000 random IPv4 hosts from the Internet by specifying \'random(10000)/0.0.0.0/0\' as the address. **split(s,e)/** selects a specific segment of the address range for use. *e* specifies the number of segments in parallel and *s* is the segment number used by this particular scan. This can be used to scan from several hosts in parallel by scanning a different segment from each host. **-n** Specifies the port numbers to scan. Ports are separated by commas. Each specified scanner is run for each port in this list. The default port is 22. Scan for SSH servers on both port 22 and 2022: ``` shell-session $ sudo scanssh -s ssh -n 22,2022 192.168.0.0/24 ``` ## sshfs **sshfs** builds on the Filesystem in Userspace (FUSE) interface to allow non-privileged users to create a secure, reliable file system framework. It allows a remote file system to be mounted as a local folder by taking advantage of the SFTP subsystem. It uses SFTP to mount a directory from a remote server as a local directory. In that way, all use applications can interact with that directory and its contents as if it were local.As the name implies, this is done in user space and not the kernel as is usually required for file systems. FUSE has a stable API library and bindings to C, C++, and Java. In this case it is specifically the SFTP client that is run over ssh(1) and is then mounted as a file system. See the Cookbook section on SFTP for more regarding **sshfs**. ## sshfp **sshfp** generates SSHFP NS records using the public keys stored in a **known_hosts** file or provided by ssh-keyscan(1) as a means to use DNS to publish SSH key fingerprints. That in turn allows DNSSEC lookups to verify SSH keys before use. SSHFP resource records in DNS are used to store fingerprint of SSH public host keys that are associated with the host names. A record itself consists of an algorithm number, fingerprint type, and the fingerprint of the public host key. See RFC 4255 for details on SSHFP. ## keychain **keychain** is another manager for ssh-agent(1) to allow multiple shells and processes, including cron(8) jobs, to use the keys held by the agent. It is often integrated into desktop-specific tools like Apple Keychain on OS X or kdewallet for KDE. <http://www.funtoo.org/en/security/keychain/intro/> ## rsync **rsync** is a file transfer utility to transfer files between computers very efficiently. It can run on top of SSH or use its own protocol. SSH is the default. <http://rsync.samba.org/> See the Cookbook section on Automated Backup for examples on using **rsync** live or in scripts. ## gstm (Gnome SSH Tunnel Manager) **gstm** is a graphical front-end for managing SSH connections and especially port forwarding. <http://sourceforge.net/projects/gstm/> ## sslh **sslh** is a protocol demultiplexer. It accepts connections on specified ports and forwards them based on the first packet sent by the client. It can be used to share a single port between SSH, SSL, HTTP, OpenVPN, tinc, and XMPP. <http://www.rutschle.net/tech/sslh.shtml> See also the section on Multiplexing for a discussion with examples. ## sshguard **sshguard** is an intrusion prevention system. It monitors logs to detect undesirable patterns of activities and triggers corresponding packet filter rules for increasing periods of time. It can be used with a few other services besides SSH. <http://www.sshguard.net/> ## ssh-audit **ssh-audit** is a python script to gather information about SSH servers. It can identify banners used, key exchange, encryption, Message Authentication Code (MAC) algorithms, compression, compatibility settings, and several other security-related aspects. <https://github.com/arthepsy/ssh-audit> ## Additional Third Party Utilities The following are useful in working with OpenSSH, but outside the scope of this book to go into detail. They are nevertheless worth mentioning enough to warrant a list: : **netstat** -- Show network connections, routing tables, interface statistics, masquerade connections, and multicast memberships : **nc** or **netcat** -- Netcat, the TCP/IP swiss army knife. : **socat** -- SOcket CAT, a multipurpose relay similar to netcat. : **nmap** -- Network exploration tool and security scanner. : **tcpdump** -- Display network traffic real time. : **telnet** -- Unencrypted interaction with another host. : **pagsh** -- Creates a new credential cache sandbox and process authentication group (PAG). : **nohup** -- Invoke a process that ignores HANGUP signals : **sudo** -- Execute programs as another user : **lftp** -- A handy interactive multi-protocol file transfer text-based client supporting SFTP. : **curl** -- A multi-protocol file transfer text-based client supporting SCP and SFTP. : **tmux** -- A terminal multiplexer. ## References [^1]: [^2]:
# OpenSSH/Logging and Troubleshooting Both the OpenSSH client and server offer a lot of choice as to where the logs are written and how much information is collected. A prerequisite for logging is having an accurate system clock using the Network Time Protocol, NTP, or equivalent, service which provides ongoing time synchronization with rest of the world. The more accurate the time stamp in the log is, the faster it is to coordinate forensics between machines or sites or service providers. If you have to contact outside parties like a service provider, progress can usually only be made with very exact times. ## Server Logs By default sshd(8) sends logging information to the system logs using the log level INFO and the system log facility AUTH. So the place to look for log data from sshd(8) is in **/var/log/auth.log**. These defaults can be overridden using the **SyslogFacility** and **LogLevel** directives. Below is a typical server startup entry in the authorization log. ``` text Mar 19 14:45:40 eee sshd[21157]: Server listening on 0.0.0.0 port 22. Mar 19 14:45:40 eee sshd[21157]: Server listening on :: port 22. ``` In most cases the default level of logging is sufficient, but during initial testing of new services or activities it is sometimes necessary to have more information. Debugging info usually goes to **stderr**. Starting with OpenSSH 7.6, **Match** blocks can set alternate log levels for specific conditions. The log excerpt below show the same basic server start up with increased detail. Contrast the log level DEBUG1 below with the default above: ``` text debug1: sshd version OpenSSH_6.8, LibreSSL 2.1 debug1: private host key #0: ssh-rsa SHA256:X9e6YzNXMmr1O09LVoQLlCau2ej6TBUxi+Y590KVsds debug1: private host key #1: ssh-dss SHA256:XcPAY4soIxU2IMtYmnErrVOjKEEvCc3l5hOctkbqeJ0 debug1: private host key #2: ecdsa-sha2-nistp256 SHA256:QIWi4La8svQSf5ZYow8wBHN4tF0jtRlkIaLCUQRlxRI debug1: private host key #3: ssh-ed25519 SHA256:fRWrx5HwM7E5MRcMFTdH95KwaExLzAZqWlwULyIqkVM debug1: rexec_argv[0]='/usr/sbin/sshd' debug1: rexec_argv[1]='-d' debug1: Bind to port 22 on 0.0.0.0. Server listening on 0.0.0.0 port 22. debug1: Bind to port 22 on ::. Server listening on :: port 22. ``` And here is the same startup using the most verbose level, DEBUG3: ``` text debug2: load_server_config: filename /etc/ssh/sshd_config debug2: load_server_config: done config len = 217 debug2: parse_server_config: config /etc/ssh/sshd_config len 217 debug3: /etc/ssh/sshd_config:52 setting AuthorizedKeysFile .ssh/authorized_keys debug3: /etc/ssh/sshd_config:86 setting UsePrivilegeSeparation sandbox debug3: /etc/ssh/sshd_config:104 setting Subsystem sftp internal-sftp debug1: sshd version OpenSSH_6.8, LibreSSL 2.1 debug1: private host key #0: ssh-rsa SHA256:X9e6YzNXMmr1O09LVoQLlCau2ej6TBUxi+Y590KVsds debug1: private host key #1: ssh-dss SHA256:XcPAY4soIxU2IMtYmnErrVOjKEEvCc3l5hOctkbqeJ0 debug1: private host key #2: ecdsa-sha2-nistp256 SHA256:QIWi4La8svQSf5ZYow8wBHN4tF0jtRlkIaLCUQRlxRI debug1: private host key #3: ssh-ed25519 SHA256:fRWrx5HwM7E5MRcMFTdH95KwaExLzAZqWlwULyIqkVM debug1: rexec_argv[0]='/usr/sbin/sshd' debug1: rexec_argv[1]='-ddd' debug2: fd 3 setting O_NONBLOCK debug1: Bind to port 22 on 0.0.0.0. Server listening on 0.0.0.0 port 22. debug2: fd 4 setting O_NONBLOCK debug1: Bind to port 22 on ::. ``` Every failed login attempt is recorded, once the value in directive **MaxAuthTries** is exceeded the connection is broken. Below is a log excerpt showing how the default log looks after some failed attempts: ``` text ... Mar 19 11:11:06 server sshd[54798]: Failed password for root from 122.121.51.193 port 59928 ssh2 Mar 19 11:11:06 server sshd[54798]: Failed password for root from 122.121.51.193 port 59928 ssh2 Mar 19 11:11:07 server sshd[54798]: Failed password for root from 122.121.51.193 port 59928 ssh2 Mar 19 11:11:08 server sshd[54798]: Failed password for root from 122.121.51.193 port 59928 ssh2 Mar 19 11:11:09 server sshd[54798]: Failed password for root from 122.121.51.193 port 59928 ssh2 Mar 19 11:11:10 server sshd[54798]: Failed password for root from 122.121.51.193 port 59928 ssh2 Mar 19 11:11:10 server sshd[54798]: error: maximum authentication attempts exceeded for root from 122.121.51.193 port 59928 ssh2 [preauth] Mar 19 11:11:10 server sshd[54798]: Disconnecting authenticating user root 122.121.51.193 port 59928: Too many authentication failures [preauth] ... ``` It is not usually a good idea to allow root login, at least not root login with authentication via password. Blocking password authentication for root simplifies log analysis greatly, and in particular it eliminates the time consuming question of who is trying to get in and why. People that need full root level access can gain it through su(1) for general activities. Or for specific tasks which need root level access, those can be given those privileges through custom-made entries for **sudo(8)** or doas(1). Note that in those cases, only specific services and programs should be allowed, not blanket access which is an all too common misconfiguration seen with **sudo(8)**. Alternatively, a single-purpose key made using **forced-commands-only** could be used since some argue that providing extra means of privilege escalation, such as su(1), **sudo(8)**, or doas(1), is more dangerous than carefully providing remote root access through a key or certificate tied to a specific function. ### Successful logins By default, the server does not store much information about user transactions. That is a good thing. It is also a good thing to recognize when the system is operating as it should. So here is an example of a successful SSH login: ``` text Mar 14 19:50:59 server sshd[18884]: Accepted password for fred from 192.0.2.60 port 6647 ssh2 ``` And here is an example using a key for authentication. It shows the key fingerprint as a SHA256 hash in base64. ``` text Mar 14 19:52:04 server sshd[5197]: Accepted publickey for fred from 192.0.2.60 port 59915 ssh2: RSA SHA256:5xyQ+PG1Z3CIiShclJ2iNya5TOdKDgE/HrOXr21IdOo ``` And here is an example of successful authentication with a user certificate. The certificate\'s identification string is \"foobar\" and the serial number is \"9624\". In this example the certificate is using ECDSA and the key itself is using Ed25519. The certificate, being a different key of its own, has a different SHA256 fingerprint from the authentication key itself. ``` text May 15 16:28:17 server sshd[50140]: Accepted publickey for fred from 192.0.2.60 port 44456 ssh2: ECDSA-CERT SHA256:qGl9KiyXrG6mIOo1CT01oHUvod7Ngs5VMHM14DTbxzI ID foobar (serial 9624) CA ED25519 SHA256:fZ6L7TlBLqf1pGWzkcQMQMFZ+aGgrtYgRM90XO0gzZ8 ``` Prior to 6.8, the key\'s fingerprint was a hexadecimal MD5 hash. ``` text Jan 28 11:51:43 server sshd[5104]: Accepted publickey for fred from 192.0.2.60 port 60594 ssh2: RSA e8:31:68:c7:01:2d:25:20:36:8f:50:5d:f9:ee:70:4c ``` In older versions of OpenSSH prior to 6.3 the key fingerprint is completely missing from authentication logging. ``` text Jan 28 11:52:05 server sshd[1003]: Accepted publickey for fred from 192.0.2.60 port 20042 ssh2 ``` Here is an example of password authentication for an SFTP session, using the server\'s internal-sftp subsystem. The logging for that subsystem set to INFO. ``` text Mar 14 20:14:18 server sshd[19850]: Accepted password for fred from 192.0.2.60 port 59946 ssh2 Mar 14 20:14:18 server internal-sftp[11581]: session opened for local user fred from [192.0.2.60] ``` Here is an example of a successful SFTP login using an RSA key for authentication. ``` text Mar 14 20:20:53 server sshd[10091]: Accepted publickey for fred from 192.0.2.60 port 59941 ssh2: RSA SHA256:LI/TSnwoLryuYisAnNEIedVBXwl/XsrXjli9Qw9SmwI Mar 14 20:20:53 server internal-sftp[31070]: session opened for local user fred from [192.0.2.60] ``` Additional data, such as connection duration, can be logged with the help of **xinetd**. ### Logging Problems from SSH Certificate Authentication Usually, not much information is given about which certificate failed, just why it failed authentication. Finding the account or actual certificate in question can require some sleuthing. Generally no client side information is disclosed and all investigation must occur server side. If the authentication is attempted again by other means, such as a password, then when the connection is closed there will be a log entry noting which account was involved. That is because so early in the connection sequence the process ID for the disconnection is the same and the account name and the originating address is included, giving a bit of a clue in pursuit of a solution. Sometimes even the account name will be included. ``` text May 5 16:31:38 server sshd[252]: Connection closed by authenticating user fred 192.0.2.60 port 44470 [preauth] ``` However, if the connection is allowed to timeout without first making any other authentication attempts by some other means, then there will be nothing to go on except maybe the time of day. ``` text May 5 16:33:00 server sshd[90593]: fatal: Timeout before authentication for 192.0.2.60 port 44718 ``` Below are some common examples of log entries for failed certificate-based log in attempts. There can be more than one problem with a certificate but only one error will get logged at a time. #### Expired or Not-yet-valid Certificate Certificates which have not yet become valid or which have already expired get a log entry as to the reason but neither the account or certificate involved. ``` text May 5 16:35:20 server sshd[252]: error: Certificate invalid: expired ``` Above is an expired certificate, below is a certificate which has not yet become valid. ``` text May 5 16:58:00 server sshd[90593]: error: Certificate invalid: not yet valid ``` Neither type of event gives more information. #### Valid Certificate but Invalid Principal Like with expired certificates, very little information is given about the actual account or certificate. Here the certificate was tried with the wrong account, one not listed among the certificate\'s principals. ``` text May 5 17:29:52 server sshd[98884]: error: Certificate invalid: name is not a listed principal May 5 17:29:56 server sshd[98884]: Connection closed by authenticating user fred 192.0.2.60 port 45114 [preauth] ``` If the client closes the connection on purpose, there may be some information in the connection closed entry. #### Valid Certificate but Invalid Source Address If the certificate is limited to connecting from specific addresses or host names, the log will complain if the connection comes from a different address or host and identify the incorrect source address. ``` text May 5 17:48:54 server sshd[2420]: cert: Authentication tried for fred with valid certificate but not from a permitted source address (192.0.2.61). May 5 17:48:54 server sshd[2420]: error: Refused by certificate options ``` However, it will not be possible to identify the specific certificate directly. ### Logging SFTP File Transfers SFTP file transfers can be logged using **LogLevel** INFO or VERBOSE. The log level for the SFTP server can be set in sshd_config(5) separately from the general SSH server settings. ``` {.apache .numberLines} Subsystem internal-sftp -l INFO ``` By default the SFTP messages will also end up in *auth.log* but it is possible to filter these messages to their own file by reconfiguring the system logger, usually **rsyslogd(8)** or **syslogd(8)**. Sometimes this is done by changing the log facility code from the default of AUTH. Available options are LOCAL0 through LOCAL7, plus, less usefully, DAEMON and USER. ``` {.apache .numberLines} Subsystem internal-sftp -l INFO -f LOCAL6 ``` If new system log files are assigned, it is important to remember them in log rotation, too. Again, the **Match** directive can be use to change the log level for certain connections. The following log excerpts are generated from using the log level INFO. A session starts with an open and end with a close. The number in the brackets is the process id for the SFTP session and is the only way to follow a session through the logs. ``` text Oct 22 11:59:45 server internal-sftp[4929]: session opened for local user fred from [192.0.2.33] ... Oct 22 12:09:10 server internal-sftp[4929]: session closed for local user fred from [192.0.2.33] ``` Here is an SFTP upload of a small file of 928 bytes named **foo** to the home directory for user \'fred\'. ``` text Oct 22 11:59:50 server internal-sftp[4929]: open "/home/fred/foo" flags WRITE,CREATE,TRUNCATE mode 0664 Oct 22 11:59:50 server internal-sftp[4929]: close "/home/fred/foo" bytes read 0 written 928 ``` And a directory listing in the same session in the directory **/var/www**. ``` text Oct 22 12:07:59 server internal-sftp[4929]: opendir "/var/www" Oct 22 12:07:59 server internal-sftp[4929]: closedir "/var/www" ``` And lastly here is a download of the same small 928-byte file called **foo** from the home directory for the user \'fred\'. ``` text Oct 22 12:08:03 server internal-sftp[4929]: open "/home/fred/foo" flags READ mode 0666 Oct 22 12:08:03 server internal-sftp[4929]: close "/home/fred/foo" bytes read 928 written 0 ``` Successful transfers will be noted by a *close* message. Attempts to download (open) files that do not exist will be followed by a *sent status No such file* message on a line of its own instead of a *close*. Files that exist but that the user is not allowed to read will create a *sent status Permission denied* message. ### Logging Chrooted SFTP Logging with the built-in **sftp-subsystem** inside a chroot jail, defined by **ChrootDirectory**, needs a **./dev/log** node to exist inside the jail. This can be done by having the system logger such as syslogd(8) add additional log sockets inside the chrooted directory when starting up. On some systems that is as simple as adding more flags, like \"**-u -a /chroot/dev/log**\", in **/etc/rc.conf.local** or whatever the equivalent startup script may be. Here is an example of an SFTP login with password to a chroot jail using log level DEBUG3 for the SFTP-subsystem. The log shows a file upload: ``` text Jan 28 12:42:41 server sshd[26299]: Connection from 192.0.2.60 port 47366 Jan 28 12:42:42 server sshd[26299]: Failed none for fred from 192.0.2.60 port 47366 ssh2 Jan 28 12:42:44 server sshd[26299]: Accepted password for fred from 192.0.2.60 port 47366 ssh2 Jan 28 12:42:44 server sshd[26299]: User child is on pid 21613 Jan 28 12:42:44 server sshd[21613]: Changed root directory to "/home/fred" Jan 28 12:42:44 server sshd[21613]: subsystem request for sftp Jan 28 12:42:44 server internal-sftp[2084]: session opened for local user fred from [192.0.2.60] Jan 28 12:42:58 server internal-sftp[2084]: open "/docs/somefile.txt" flags WRITE,CREATE,TRUNCATE mode 0644 Jan 28 12:42:58 server internal-sftp[2084]: close “/docs/somefile.txt” bytes read 0 written 400 ``` Remember that SFTP is a separate subsystem and that like the file creation mode, the log level and log facility are set separately from the SSH server in sshd_config(5): ``` {.apache .numberLines} Subsystem internal-sftp -l ERROR ``` ### Logging Stability of Client Connectivity When **ClientAliveInterval** is set in the server\'s configuration, the server makes periodic probes of the clients which have established connections. At normal log levels, these are not noted in the log until something goes wrong. If the **ClientAliveInterval** is exceeded more times in a row than allowed by **ClientAliveCountMax** the client is officially declared disconnected and the connection dropped. At the default log level of INFO a brief message is logged, identifying the client which has been dropped. ``` text Sep 6 14:42:08 eee sshd[83709]: packet_write_poll: Connection from 192.0.2.97 port 57608: Host is down ``` At log level DEBUG, the client\'s responses to the polls will be logged by the server showing that the session is still connected. ``` text Sep 6 14:27:52 eee sshd[9075]: debug1: Got 100/147 for keepalive ``` Log level DEBUG2 and DEBUG3 will give even more information about the connection. However, even at log level DEBUG3, the specific client being polled will not be identified directly in the log messages and will have to be inferred from the process id of the daemon if such information is needed. ``` text Sep 6 14:30:59 eee sshd[73960]: debug2: channel 0: request keepalive@openssh.com confirm 1 Sep 6 14:30:59 eee sshd[73960]: debug3: send packet: type 98 Sep 6 14:30:59 eee sshd[73960]: debug3: receive packet: type 100 Sep 6 14:30:59 eee sshd[73960]: debug1: Got 100/22 for keepalive ``` Again, when the **ClientAliveCountMax** is exceeded, the connection is broken after the final failure of the client to respond. Here is how that looks with the log level set to DEBUG2. ``` text Sep 6 14:17:55 eee sshd[15780]: debug2: channel 0: request keepalive@openssh.com confirm 1 Sep 6 14:17:55 eee sshd[15780]: debug1: Got 100/22 for keepalive Sep 6 14:18:37 eee sshd[15780]: debug2: channel 0: request keepalive@openssh.com confirm 1 Sep 6 14:18:37 eee sshd[15780]: packet_write_poll: Connection from 192.0.2.97 port 57552: Host is down Sep 6 14:18:37 eee sshd[15780]: debug1: do_cleanup Sep 6 14:18:37 eee sshd[48675]: debug1: do_cleanup Sep 6 14:18:37 eee sshd[48675]: debug1: session_pty_cleanup: session 0 release /dev/ttyp0 ``` The directives **ClientAliveInterval** and **ClientAliveCountMax** normally apply to all clients connecting to the server. However, they can be used inside a **Match** block and thus applied only to specific connections. ### Logging Revoked Keys If the **RevokedKeys** directive is used to point to a list of public keys that have been revoked, sshd(8) will make a log entry when access is attempted using a revoked key. The entry will be the same whether a plaintext list of public keys is used or if a binary Key Revocation List (KRL) has been generated. If password authentication is allowed, and the user tries it, then after the key authentication fails there will be a record of password authentication. ``` text Mar 14 20:36:40 server sshd[29235]: error: Authentication key RSA SHA256:jXEPmu4thnubqPUDcKDs31MOVLQJH6FfF1XSGT748jQ revoked by file /etc/ssh/ssh_revoked_keys ... Mar 14 20:36:45 server sshd[29235]: Accepted password for fred from 192.0.2.10 port 59967 ssh2 ``` If password authentication is not allowed, sshd(8) will close the connection as soon as the key fails. ``` text Mar 14 20:38:27 server sshd[29163]: error: Authentication key RSA SHA256:jXEPmu4thnubqPUDcKDs31MOVLQJH6FfF1XSGT748jQ revoked by file /etc/ssh/ssh_revoked_keys ... ``` The account trying the revoked key remains a mystery though, so it will be necessary to try to look up the key by its fingerprint from your archive of old keys using `ssh-keygen -lf` and read the key\'s comments. Although if a valid account cancels the connection without trying a password after the key attempt fails, the usual message will still be posted to the log. ``` text Mar 14 20:44:04 server sshd[14352]: Connection closed by authenticating user fred 192.0.2.237 port 55051 [preauth] ... ``` That may provide some clue and allow filtering with a short AWK script, if the messages are all in the same log file. ``` shell-session $ awk '/revoked by file/ { pid[$5]++; key[$5]=$9; hash[$5]=$10; next; } pid[$5] && /closed by authenticating user/ { print key[$5], hash[$5], $10, $11; delete key[$5]; delete hash[$5]; delete pid[$5]; }' /var/log/authlog ``` Similarly, if the client makes no attempt at logging in and just times out, the message will say just that. ``` text Mar 18 21:40:25 server sshd[9942]: fatal: Timeout before authentication for 198.51.100.236 port 53728 ... ``` On the client side, no warning or error will be given if a revoked key is tried. It will just fail and the next key or method will be tried. ### Brute force and Hail Mary attacks It's fairly common to see failed login attempts almost as soon as the server is connected to the net. Brute force attacks, where one machine hammers on a few accounts trying to find a valid password, are becoming rare. In part this is because packet filters, like NFables for Linux and PF for the BSDs, can limit the number and rate of connection attempts from a single host. The server configuration directive **MaxStartups** can limit the number of simultaneous, unauthenticated connections. ``` text ... Mar 18 18:54:44 server sshd[54939]: Failed password for root from 201.179.249.231 port 52404 ssh2 Mar 18 18:54:48 server sshd[54939]: Failed password for root from 201.179.249.231 port 52404 ssh2 Mar 18 18:54:49 server sshd[54939]: Failed password for root from 201.179.249.231 port 52404 ssh2 Mar 18 18:54:49 server sshd[54939]: error: maximum authentication attempts exceeded for root from 201.179.249.231 port 52404 ssh2 [preauth] Mar 18 18:54:49 server sshd[54939]: Disconnecting authenticating user root 201.179.249.231 port 52404: Too many authentication failures [preauth] ... ``` Note the \"authenticating user\" is present in the logs from OpenSSH 7.5 and onward when a valid user name is attempted. When an invalid user name is attempted, that is written too. ``` text ... Mar 18 18:55:05 server sshd[38594]: Invalid user ubnt from 201.179.249.231 port 52471 Mar 18 18:55:05 server sshd[38594]: Failed password for invalid user ubnt from 201.179.249.231 port 52471 ssh2 Mar 18 18:55:09 server sshd[38594]: error: maximum authentication attempts exceeded for invalid user ubnt from 201.179.249.231 port 52471 ssh2 [preauth] Mar 18 18:55:09 server sshd[38594]: Disconnecting invalid user ubnt 201.179.249.231 port 52471: Too many authentication failures [preauth] ... ``` The way to deal with brute force attacks coming from a single machine or network is to customize the server host's packet filter to limit the attacks or even temporarily block machines that overload the maximum number or rate of connections. Optionally, one should also contact the attacker's net block owner with the IP address and exact date and time of the attacks. A kind of attack common at the time of this writing is one which is distributed over a large number of compromised machines, each playing only a small role in attacking the server. To deal with Hail Mary attacks, contact the attacker's net block owner. A form letter with a cut-and-paste excerpt from the log is enough if it gives the exact times and addresses. Alternately, teams of network or system administrators can work to pool data to identify and blacklist the compromised hosts participating in the attack. #### Failed None For Invalid User The SSH protocol specifies a number of possible authentication methods[^1]. The methods `password`, `keyboard-interactive`, and `publickey` are fairly common. A lesser known authentication method is `none`, which will only succeed if the server requires no further authentication such as if **PermitEmptyPassword** is set and the account does not actually have a password[^2]. Some SSH clients including OpenSSH\'s start by asking for `none` authentication and then use the list of remaining possible authentication methods to decide what to do next if that doesn\'t work. ``` text ... Aug 10 19:09:05 server sshd[93126]: Failed none for invalid user admin from 125.64.94.136 port 27586 ssh2 ... ``` So in other words, that is a brute force attack trying the `none` authentication method. It is an attack which will only get into accounts which have been explicitly set with an empty password and furthermore have also been set up specifically to allow access by having both the authentication method of `none` and the **PermitEmptyPasswords** configuration directive enabled on the server. Most brute force attacks try only `password` authentication, and some of those even check for the `password` method and then give up if it is not available. Other attackers may just hammer away pointlessly even if the method is not available. ### Connections Seemingly From 127.0.0.1, ::1, or Other localhost Addresses When the SSH server is accessed via a reverse tunnel to another machine, the incoming connections will appear to be from the *localhost* address, which is usually *127.0.0.1* or *::1*. ``` text Mar 23 14:16:16 server sshd[9265]: Accepted password for fred from 127.0.0.1 port 40426 ssh2 ``` If the port at the other end of the reverse tunnel is publicly accessible, it will be probed and possibly attacked. Because of the reverse tunnel, the attacks will then also appear to be coming from the server\'s own loopback address: ``` text Mar 23 14:20:17 server sshd[5613]: Invalid user cloud from ::1 port 57404 Mar 23 14:20:21 server sshd[5613]: Failed password for invalid user cloud from ::1 port 57404 ssh2 Mar 23 14:20:26 server sshd[5613]: Failed password for invalid user cloud from ::1 port 57404 ssh2 Mar 23 14:20:32 server sshd[5613]: Failed password for invalid user cloud from ::1 port 57404 ssh2 Mar 23 14:20:35 server sshd[5613]: Connection closed by invalid user cloud ::1 port 57404 [preauth] ``` Therefore the usual countermeasures like SSHGuard or Fail2Ban or other similar intrusion detection systems cannot be used because the *localhost* address is used by the tunnel for all login attempts, regardless of their real origins. A partial solution would be to bind the incoming connections to a different IP address. The loopback interface would need an additional permanent address, an alias, for that. That alias could then be assigned when establishing the reverse tunnel: ``` shell-session $ ssh -R 2022:127.2.2.1:22 fred@vps.example.org ``` Thus it would designate the source address for all logins coming in over that tunnel. So, in that way, the alias would then show up in the logs instead of the default loopback address when that reverse tunnel is used: ``` text Mar 23 18:00:13 server sshd[8525]: Invalid user cloud from 127.2.2.1 port 17271 Mar 23 18:00:15 server sshd[8525]: Failed password for invalid user cloud from 127.2.2.1 port 17271 ssh2 Mar 23 18:00:19 server sshd[8525]: Failed password for invalid user cloud from 127.2.2.1 port 17271 ssh2 Mar 23 18:01:23 server sshd[8525]: Failed password for invalid user cloud from 127.2.2.1 port 17271 ssh2 Mar 23 18:01:26 server sshd[8525]: Connection closed by invalid user cloud 127.2.2.1 port 17271 [preauth] ``` If the ports do not need to be available to the open Internet, a full solution would be just to ensure that they are not accessible from the outside. This would be done by not using the **-g** option on the client when making the reverse tunnel or else by setting the **GatewayPorts** directive in sshd_config(5) back to the default of **no**, or both. The system\'s built-in packet filter can also be used. Then, even with the forwarded ports closed off from the outside, the **ProxyJump** option can still be used to skip through the jump host and use the setup for SSH access. However, since it is sometimes necessary that these ports be accessible to the outside world, this approach is not always an option. ## Client Logging The OpenSSH client normally sends log information to **stderr**. The **-y** option can be used to send output to the system logs, managed by syslogd(8) or something similar. Client log verbosity can be increased or decreased by changing the **LogLevel** directive and the log facility changed with the **SyslogFacility** directive in ssh_config(5). Both require use of the **-y** run time option and do nothing without it. Alternatively, instead of using the **-y** option, using the **-E** option sends log output to a designated file instead of **stderr**. Working with the system logs or separate log files are something which can be useful when running ssh(1) in automated scripts. Below is an example of a connection to an interactive shell with the normal level of client logging: ``` shell-session $ ssh -l fred server.example.org fred@server.example.org‘s password: Last login: Thu Jan 27 13:21:57 2011 from 192.168.11.1 ``` The same connection at the first level of verbosity gives lots of debugging information, 42 lines more. ``` shell-session $ ssh -v -l fred server.example.org OpenSSH_6.8, LibreSSL 2.1 debug1: Reading configuration data /etc/ssh/ssh_config debug1: Connecting to server.example.org [198.51.100.20] port 22. debug1: Connection established. debug1: key_load_public: No such file or directory debug1: identity file /home/fred/.ssh/id_rsa type -1 debug1: key_load_public: No such file or directory debug1: identity file /home/fred/.ssh/id_rsa-cert type -1 debug1: key_load_public: No such file or directory debug1: identity file /home/fred/.ssh/id_dsa type -1 debug1: key_load_public: No such file or directory debug1: identity file /home/fred/.ssh/id_dsa-cert type -1 debug1: key_load_public: No such file or directory debug1: identity file /home/fred/.ssh/id_ecdsa type -1 debug1: key_load_public: No such file or directory debug1: identity file /home/fred/.ssh/id_ecdsa-cert type -1 debug1: key_load_public: No such file or directory debug1: identity file /home/fred/.ssh/id_ed25519 type -1 debug1: key_load_public: No such file or directory debug1: identity file /home/fred/.ssh/id_ed25519-cert type -1 debug1: Enabling compatibility mode for protocol 2.0 debug1: Local version string SSH-2.0-OpenSSH_6.8 debug1: Remote protocol version 2.0, remote software version OpenSSH_6.7 debug1: match: OpenSSH_6.7 pat OpenSSH* compat 0x04000000 debug1: SSH2_MSG_KEXINIT sent debug1: SSH2_MSG_KEXINIT received debug1: kex: server->client aes128-ctr umac-64-etm@openssh.com none debug1: kex: client->server aes128-ctr umac-64-etm@openssh.com none debug1: expecting SSH2_MSG_KEX_ECDH_REPLY debug1: Server host key: ecdsa-sha2-nistp256 SHA256:CEXGTmrVgeY1qEiwFe2Yy3XqrWdjm98jKmX0LK5mlQg debug1: Host '198.51.100.20' is known and matches the ECDSA host key. debug1: Found key in /home/fred/.ssh/known_hosts:2 debug1: SSH2_MSG_NEWKEYS sent debug1: expecting SSH2_MSG_NEWKEYS debug1: SSH2_MSG_NEWKEYS received debug1: Roaming not allowed by server debug1: SSH2_MSG_SERVICE_REQUEST sent debug1: SSH2_MSG_SERVICE_ACCEPT received debug1: Authentications that can continue: publickey,password,keyboard-interactive debug1: Next authentication method: publickey debug1: Trying private key: /home/fred/.ssh/id_rsa debug1: Trying private key: /home/fred/.ssh/id_dsa debug1: Trying private key: /home/fred/.ssh/id_ecdsa debug1: Trying private key: /home/fred/.ssh/id_ed25519 debug1: Next authentication method: keyboard-interactive debug1: Authentications that can continue: publickey,password,keyboard-interactive debug1: Next authentication method: password debug1: Authentication succeeded (password). Authenticated to server.example.org ([198.51.100.20]:22). debug1: channel 0: new [client-session] debug1: Requesting no-more-sessions@openssh.com debug1: Entering interactive session. debug1: client_input_global_request: rtype hostkeys-00@openssh.com want_reply 0 debug1: client_input_channel_req: channel 0 rtype exit-status reply 0 debug1: client_input_channel_req: channel 0 rtype eow@openssh.com reply 0 debug1: channel 0: free: client-session, nchannels 1 debug1: fd 2 clearing O_NONBLOCK Last login: Sat Mar 14 21:31:33 2015 from 192.0.2.111 ... ``` The same login with the maximum of verbosity, **-vvv**, gives around 150 lines of debugging information. Remember that debugging information is sent to **stderr** rather than **stdout**. This will only capture the session in a file, debugging info goes only to the screen, not to the output log: ``` shell-session $ ssh -vvv -l fred somehost.example.org | tee ~/ssh-output.log ``` The tool tee(1) is like a T-pipe and sends output two directions, one to **stdout** and one to a file. The following will capture both the debugging info and the session text: ``` shell-session $ ssh -vvv -l fred somehost.example.org 2>&1 | tee ~/ssh-output.log ``` ### Capturing Client Debugging Information Separately Regular pipes and redirects work only with **stdout** so that if **-E** is not used to capture debugging output the output on **stderr** must instead be sent to stdout if one is going to capture it at the same time as the actual session. That is done with an extra redirect, **2\>&1** to capture **stderr**. Mind the spaces, or lack of them. ### Changing Client Debugging Levels At Runtime or On The Fly At run time, when establishing a new connection, just use the **-v** option. ``` shell-session $ sftp -v -o "IdentityFile=~/.ssh/weblog.key_rsa" fred@server.example.org ``` The debugging verbosity on the client can be increased just like on the server. ``` shell-session $ sftp -vvv -o "IdentityFile=~/.ssh/weblog.key_rsa" fred@server.example.org ``` The extra information can be useful to see exactly what is being sent to or requested of the server. After the fact, once a connection is established, the escape sequences **\~v** and **\~V** can be used to increase or decrease the verbosity on the fly. Through them it is possible to change the verbosity of the client in an established connection. When increasing, the client raises its log level to VERBOSE, DEBUG, DEBUG2, and DEBUG3, in that order, if starting from the default of INFO. Conversely, when lowering the log level, the client will descend through ERROR, FATAL, to QUIET if starting from the default of INFO. ## Debugging and Troubleshooting The server logs are your best friend when troubleshooting. It may be necessary to turn up the log level there temporarily to get more information. It is then also necessary to turn them back to normal after things are fixed to avoid privacy problems or excessively use of disk space. For example, the SFTP-subsystem logging defaults to ERROR, reporting only errors. To track transactions made by the client, change the log level to INFO or VERBOSE: ``` {.apache .numberLines} Subsystem internal-sftp -l INFO ``` Caution. Again, operating with elevated logging levels would violate the privacy of users, in addition to filling a lot of disk space, and should generally not be used in production once the changes are figured out. Elevated log messages should really be sent to a separate log file during the time they are collected. By default, some systems send only the normal messages to the regular system log files and ignore the elevated messages. Some save all the messages by default. If the elevated system log messages are not showing up in any of the system logs, the former may be the reason. Either way, check the system log configuration and make sure that the extra messages are only sent to a separate log file and not mixed with the regular system logs. Change the configuration if necessary. This helps keep the logs tidy as well as protect privacy. The system log settings are found in the system log daemon\'s configuration file, the exact name of which will vary depending on what is installed, but common ones are syslog.conf(5) and rsyslog.conf(5). Notice that this machine configuration below has the more detailed DEBUG messages for the AUTH facility going to a separate log file from the regular AUTH messages: ``` shell-session $ grep '^auth\.' /etc/syslog.conf auth.info /var/log/authlog auth.debug /var/log/authdebug ``` See syslog(3) for the log facilities and log levels. It is best to limit the time the debugging information is collected and to actively watch while it is collected. However, if it is running for any length of time, and especially if it is left unattended even for a short while, be sure to remeber to add the special log file to the log rotation schedule so that it cannot fill up the partition. **Match** blocks can help further by setting log levels for specific situations and avoid a situation where everything is logged intensely. Also, the manual pages for OpenSSH are very well written and many times problems can be solved by finding the right section within the right manual page. At the very minimum, it is important to skim through the four main manual pages for both the programs and their configuration and become familiar with at least the section headings. - ssh(1) - ssh_config(5) - sshd(8) - sshd_config(5) Then once the right section is found in the manual page, go over it in detail and become familiar with its contents. The same goes for the other OpenSSH manual pages, depending on the activity. Be sure to use the version of OpenSSH available for your system and the corresponding manual pages, preferably those that are installed on your system to avoid a mismatch. In some cases, the client and the server will be of different versions, so the manual pages for each must be looked up separately. It is also a good idea to review OpenSSH\'s release notes when a new version is published. With a few exceptions below, specific examples of troubleshooting are usually given in the cookbook section relevant to a particular activity. So, for example, sorting problems with authentication keys is done in the section on Public Key Authentication itself. ### Debugging a script, configuration or key that uses sudo(8) Usually log levels only need to be changed when writing and testing a script, a new configuration, some new keys, or all three at once. When working with **sudo(8)**, it is especially important to see exactly what the client is sending so as to enter the right pattern into **/etc/sudoers** for safety. Using the lowest level of verbosity, the exact string being sent by the client to the remote server is shown in the debugging output: ``` shell-session $ rsync -e "ssh -v -i /home/webmaint/.ssh/bkup_key -l webmaint" \ -a server.example.org:/var/www/ var/backup/www/ ... debug1: Authentication succeeded (publickey). Authenticated to server.example.org ([192.0.2.20]:22). debug1: channel 0: new [client-session] debug1: Requesting no-more-sessions@openssh.com debug1: Entering interactive session. debug1: Sending command: rsync --server --sender -vlogDtpre.if . /var/www/ receiving incremental file list ... ``` What **sudoers** then needs is something like the following, assuming account \'webmaint\' is in the group \'webmasters\': ``` {.apache .numberLines} %webmasters ALL=(ALL) NOPASSWD: /usr/local/bin/rsync --server \ --sender -vlogDtpre.if . /var/www/ ``` The same method can be used to debug new server configurations or key logins. Once things are set to run as needed, the log level settings can be lowered back to INFO for sshd(8) and to ERROR for **internal-sftp**. Additionally, once the script is left to run in fully automated mode, the client logging information can be set use the syslog(3) system module instead of **stderr** by setting the **-y** option when it is launched. ### Debugging a server configuration Running the server in debug mode provides a lot of information about the connection and a smaller amount about the server configuration. The server\'s debugging level (**-d**) can be raised once, twice (**-dd**) or thrice (**-ddd**). ``` shell-session $ /usr/sbin/sshd -d ``` Note that the server in this case does not detach and become a daemon, so it will terminate when the SSH connection terminates. The server must be started again in order to make a subsequent connection from the client. Though in some ways this is a hassle, it does make sure that session data is a unique set and not mixes of multiple sessions and thus possibly different configurations. Alternately, another option (**-e**) when debugging sends the debugging data to **stderr** to keep the system logs clean. In recent versions of OpenSSH, it is also possible to log the debug data from the system logs directly to a separate file and keep noise out of the system logs. Since OpenSSH 6.3, the option **-E** will append the debug data to a particular log file instead of sending it to the system log. This facilitates debugging live systems without cluttering the system logs. ``` shell-session $ /usr/sbin/sshd -E /home/fred/sshd.debug.log ``` On older versions of OpenSSH, if you need to save output to a file while still viewing it live on the screen, you can use **tee(1)**. ``` shell-session $ /usr/sbin/sshd -ddd 2>&1 | tee /tmp/foo ``` That will save output to the file *foo* by capturing what sshd(8) sent to **stderr**. This works with older versions of OpenSSH, but the **-E** option above is preferable. If the server is remote and it is important to reduce the risk of getting locked out, the experiments on the configuration file can be done with a second instance of sshd(8) using a separate configuration file and listening to a high port until the settings have been tested. ``` shell-session $ /usr/sbin/sshd -dd -p 22222 -f /home/fred/sshd_config.test ``` It is possible to make an extended test (**-T**) of the configuration file. If there is a syntax error, it will be reported, but remember that even sound configurations can still lock you out. The extended test mode can be used by itself, but it is also possible to specify particular connection parameters to use with **-C**. sshd(8) will then process the configuration file in light of the parameters passed to it and output the results. Of particular use, the results of **Match** directives will be shown. So the **-T** option can be supplemented with the **-C** option to show precisely which configuration will be used for various connections. When passing specific connection parameters to sshd(8) for evaluation, *user*, *host*, and *addr* are the minimum required for extended testing. The following will print out the configurations that will be applied if the user *fred* tries to log in to the host *server.example.org* from the address *192.0.2.15*: ``` shell-session $ /usr/sbin/sshd -T -C user=fred,host=server.example.org,addr=192.0.2.15 ``` Two more parameters, *laddr* and *lport*, may also be passed. They refer to the server\'s IP number and port connected to. ``` shell-session $ /usr/sbin/sshd -T -C user=fred,host=server.example.org,addr=192.0.2.15,laddr=192.0.2.2,lport=2222 ``` Those five variables should be able to describe any possible incoming connection. ### Debugging a client configuration Sometimes when debugging a server configuration it is necessary to track the client, too. Since OpenSSH 6.8, the -G option makes ssh(1) print its configuration after evaluating **Host** and **Match** blocks and then exit. That allows viewing of the exact configuration options that will actually be used by the client for a particular connection. ``` shell-session $ ssh -G -l fred server.example.org ``` Client configuration is determined in three ways. The first is by run-time options, then by the account\'s own configuration file, or lastly the system-wide client configuration file. The priority is in that order and whichever value is found first gets used. With sftp(1) the options are also passed to ssh(1). #### Invalid or Outdated Ciphers or MACs A proper client will show the details of the failure. For a bad Message Authentication Code (MAC), a proper client might show something like the following when trying to foist a bad MAC like hmac-md5-96 onto the server: ``` text no matching mac found: client hmac-md5-96 server umac-64-etm@openssh.com,umac-128-etm@openssh.com,hmac-sha2-256-etm@openssh.com,hmac-sha2-512-etm@openssh.com,hmac-sha1-etm@openssh.com,umac-64@openssh.com,umac-128@openssh.com,hmac-sha2-256,hmac-sha2-512,hmac-sha1 ``` And for a bad cipher, a proper client might show something like this when trying to foist an arcfour cipher on the server: ``` text no matching cipher found: client arcfour server chacha20-poly1305@openssh.com,aes128-ctr,aes192-ctr,aes256-ctr,aes128-gcm@openssh.com,aes256-gcm@openssh.com ``` Sometimes when troubleshooting a problem with the client it is necessary to turn to the server logs. In OpenSSH 6.7 unsafe MACs were removed and in OpenSSH 7.2 unsafe ciphers were removed, but some third-party clients may still try to use them to establish a connection. In that case, the client might not provide much information beyond a vague message that the server unexpectedly closed the network connection. The server logs will, however, show what happened: ``` text fatal: no matching mac found: client hmac-sha1,hmac-sha1-96,hmac-md5 server hmac-sha2-512-etm@openssh.com,hmac-sha2-256-etm@openssh.com,umac-128-etm@openssh.com,hmac-sha2-512,hmac-sha2-256,hmac-ripemd160 [preauth] ``` More recent versions would show a simpler error for a bad MAC. ``` text fatal: Unable to negotiate with 192.0.2.37 port 55044: no matching MAC found. Their offer: hmac-md5-96 [preauth] ``` A bad cipher would be reported like this: ``` text fatal: Unable to negotiate with 192.0.2.37 port 55046: no matching cipher found. Their offer: arcfour [preauth] ``` The error message in the server log might not say which MACs or ciphers are actually available. For those, the extended test mode can be used to show the server settings and, in particular, the MACs or ciphers allowed. In its most basic usage the extended test mode would just be -T, as in `/usr/sbin/sshd -T | grep -E 'cipher|macs'` with no other options. For more details and options, see the previous section on \"Debugging a server configuration\" above. One solution there is to upgrade the client to one that can handle the right ciphers and MACs. Another option is to switch to a different client, one that can handle the modern ciphers or MACs. ### Debugging Key-Based Authentication The most common causes of failure for public key authentication seem to be for either of two reasons: - Mangling the public key on the way to getting it into **authorized_keys** on the server - Incorrect permissions for the files and directories involved, ether on the client or the server. These are the directory for the keys, usually **\~/.ssh/**, or its parent directories, or the **authorized_keys** file, or the private key itself. As of the time of this writing, it looks like pretty much every failure of key-based authentication described on mailing lists and forums is solved by addressing either or both of those two situations. So, when encountering the error message \"Permission denied (publickey,keyboard-interactive)\", or similar, see the section on Public Key Authentication. Then see the manual page for sshd(8) and its section on authorized keys. A very rare third case is if the public and private key files don\'t match and are not from the same key pair. As mentioned in the section on Public Key Authentication, the public and private keys need to match and be part of the same key pair. That is because even before the SSH client uses private key cryptographically, it looks at the file name of the proposed private key and then sends the public key matching that same name, if it exists. If the public key that is on the client does not match the public key on the server in **authorized_keys** then the connection will be denied with the error \"Permission denied (publickey,keyboard-interactive)\" or similar. That alone is a very good reason to give unique descriptive file names. Note that as mentioned above there are usually other causes to that same error message besides having mismanaged the public key file on the client machine. The file names for both parts of each key pair have to be kept organized so that the contents match. As for a solution, the way out in the long term is to more carefully manage the keys and their file names. It is solved on the short term by deleting the offending public key file or using the private key to regenerate a new one, overwriting the offending one. Again, this is an unusual edge case and not a common cause of that error. #### SSH Too Many Authentication Failures When there are multiple keys in the authentication agent, the client will try them against the server in an unpredictable order. If the client happens to cycle through enough of the wrong keys first and hits the server\'s **MaxAuthTries** limit before finding the right key, the server will naturally break off the connection with an error message about too many authentication failures: ``` text "Received disconnect from 203.0.113.110 port 22:2: Too many authentication failures Authentication failed." ``` With increased verbosity, the keys tested and rejected will also be shown: ``` shell-session $ ssh -v 203.0.113.110 ... debug1: SSH2_MSG_SERVICE_ACCEPT received debug1: Authentications that can continue: publickey,keyboard-interactive debug1: Next authentication method: publickey debug1: Offering RSA public key: /home/fred/.ssh/key.06.rsa debug1: Authentications that can continue: publickey,keyboard-interactive debug1: Offering RSA public key: /home/fred/.ssh/key.02.rsa debug1: Authentications that can continue: publickey,keyboard-interactive debug1: Offering RSA public key: /home/fred/.ssh/key.03.rsa debug1: Authentications that can continue: publickey,keyboard-interactive debug1: Offering RSA public key: /home/fred/.ssh/key.04.rsa debug1: Authentications that can continue: publickey,keyboard-interactive debug1: Offering RSA public key: /home/fred/.ssh/key.01.rsa debug1: Authentications that can continue: publickey,keyboard-interactive debug1: Offering RSA public key: /home/fred/.ssh/key.05.rsa Received disconnect from 203.0.113.110 port 22:2: Too many authentication failures Authentication failed. ``` Each key in the agent gets an annotation which says whether or not the key file was supplied by the user, either in the configuration file or as a run-time argument. The client prefers keys that were specified in the configuration and are also currently in the agent. Then it will try try them in the order in which they were supplied. [^3] There are two solutions if you see the \"Too many authentication failures\" error: One way around this error is to remove keys from the agent one at a time using ssh-add(1) with the **-d** option until there is just the right key left. Refer to each key by its file system path, for example: `ssh-add -d ~/.ssh/some.key.rsa` Because the private key to be removed is looked up in the agent based on the corresponding public key both files must exist. Without matching a public key file, the private key cannot be removed individually from the authentication agent. Instead the whole lot may be removed all at once using the **-D** option. However, is not always practical to do either when many remote systems are used frequently and the agent needs to be kept well-stocked. This is probably not the most practical way. Another way around this error, and probably the most practical method, is to limit the client to trying only a specific key using the **IdentitiesOnly** configuration directive in conjunction with the **IdentityFile** configuration directive. The latter points explicitly to the right key. Both can be added either as run-time options or in the client\'s configuration file. As a run-time option, they can be used like this: ``` shell-session $ ssh -o IdentitiesOnly=yes -i ~/.ssh/server14.example.org.rsa -l fred server14.example.org ``` Or these two options could be added to the client configuration file in something like the following way instead. ``` {.apache .numberLines} Host server14 server14.example.org HostName server14.example.org IdentitiesOnly yes IdentityFile /home/fred/.ssh/server14.example.org.rsa User fred ``` In that way, the server could be reached with either the short name or the fully qualified domain name, whatever names are listed under the **Host** directive. ``` shell-session $ ssh server14 ``` Remember that options are selected from the client configuration file on a first-match basis. Because the first-match wins, specific rules must come before more general rules. ### Debugging Chrooted SFTP Accounts The most common problem seems to be bad directory permissions. The chroot directory, and all directories above it, must be owned by root and not writable by any other user or group. Even though these directories\' group memberships do not have to be root, if any of them is not root then it must not be group writable either. Failure to use the correct ownership will result in not being able to log in with the affected accounts. The errors when login is attempted will look like this from the client side: ``` shell-session $ sftp fred@192.0.2.206 fred@192.02.206's password: packet_write_wait: Connection to 192.0.2.206: Broken pipe Couldn't read packet: Connection reset by peer ``` The error message is much clearer on the server side: syntaxhighlighting lang=\"text\"\> Aug 4 23:52:38 server sshd\[7075\]: fatal: bad ownership or modes for chroot directory component \"/home/fred/\" `</syntaxhighlighting>`{=html} Check the directory permissions for the chroot target and all directories above it. If even one is off it must be fixed so that it is owned by root and not writable by any others. There are many, many routes to get there. Here are two was to set up chroot permissions: - One quick way to fix the permissions is to change both ownership and group membership of the directory to root. Same for all directories above the chroot target. ``` shell-session $ ls -lhd /home/ /home/fred/ drwxr-xr-x 3 root root 4.0K Aug 4 20:47 /home/ drwxr-xr-x 8 root root 4.0K Aug 4 20:47 /home/fred/ ``` That will work with the **ChrootDirectory** directive set to **%h** but has some drawbacks that will quickly become obvious when adding files or directories. - Another easy way to fix the permissions is to change both the account\'s home directory and the **ChrootDirectory** directive. Arrange the account\'s home directory so that it is under a unique directory owned by root, such as the user name itself: ``` shell-session $ ls -lhd /home/ /home/fred/ /home/fred/fred/ drwxr-xr-x 3 root root 4.0K Aug 4 20:47 /home/ drwxr-x--- 3 root fred 4.0K Aug 4 20:47 /home/fred/ drwxr-x--- 8 fred fred 4.0K Aug 4 20:47 /home/fred/fred/ ``` Then chroot the account to the parent directory and combine that with an alternate starting directory working from the user name token with the **-d** option for the SFTP server. ``` {.apache .numberLines} ChrootDirectory /home/%u ForceCommand internal-sftp -d %u ``` Then when the account connects it will see only its own directory and no other parts of the system. ### Debugging RC Scripts Interfering with SFTP Sessions The SFTP connection will drop if there are any extraneous data either direction on **stdin**, from the client or the server. A common mistake in that area is if **/etc/ssh/sshrc** or **\~/.ssh/rc** send anything at all to **stdout** instead of being quiet. There the output, which would be **stdout** on the server, is received by the client on **stdin**, but matches no correct protocol and thus causes the client to disconnect. So, even in the case of using the RC scripts, the response from the server must remain 8-bit clean or an error will occur: ``` shell-session $ sftp server.example.org Received message too long 1400204832 ``` That one message will be the main clue. Increasing the verbosity of the SFTP client with **-v** won\'t provide more relevant information. Also, the standard logs on the server will only show that the client disconnected and not provide any information why. At higher levels of logging, some extraneous reads and corresponding discards might be noticed but that is all. Below is a log sample recorded at the verbosity DEBUG3 showing such an example. ``` text ... debug2: subsystem request for sftp by user fred debug1: subsystem: exec() /usr/libexec/sftp-server Starting session: subsystem 'sftp' for fred from 198.51.100.38 port 37446 id 0 ... debug2: channel 0: read 13 from efd 12 debug3: channel 0: discard efd debug2: channel 0: read 12 from efd 12 debug3: channel 0: discard efd debug2: channel 0: read 15 from efd 12 debug3: channel 0: discard efd debug2: channel 0: read 18 from efd 12 debug3: channel 0: discard efd ... ``` Again, neither RC script is allowed produce any output on **stdout** during use of SFTP or it will ruin the connection. If an RC script does produce output, it must be redirected to a system log, to a file, or sent to **stderr** instead of **stdout**. Regular interactive SSH connections are not disturbed by use of **stdout** and the client will just display whatever is sent. See the manual page for sshd(8) in the section \"SSHRC\" for more. The same restriction goes for any other part of the SSH service which runs over **stdin** and **stdout**, such as **ProxyJump** or some uses of **ProxyCommand**. So another example of potential interference would be when using **LocalCommand** with the client to specify a command to execute on the local machine after successfully connecting to the server. Any output from it also needs to be redirected to **stderr**. If **LocalCommand** ends up interfering with **ProxyJump** then the connection will appear to hang at the stage when **stdout** gets used. ### Debugging When An SSH Agent Has The Correct Private Key But Does Not Use It In older versions of OpenSSH, the public key must also be available on the client at the time the private key is loaded into the agent. If it is not then without the matching public key the agent will not be able to use a private key unless other arrangements are made. A symptom of this is that while specifying the key via a run-time argument works, the same key does not work via the agent. Upgrading to a more recent version of OpenSSH is a better option. Otherwise a work-around is to specify the private key either as a run-time argument to the client or in the ssh_config(5) file, from there the client will find the correspondingly named public key file. Importantly the client will still use the key in the agent yet use the designated matching public key file, so the private key file does not have to contain anything at all and could even be empty. ``` shell-session $ ssh -i some_key_ed25519 fred@server.example.org ``` However, if it is undesirable to have the private key accessible on the file system or if the private key is only in the agent and not itself available via the file system, then the public key can be specified directly instead. ``` shell-session $ ssh -i some_key_ed25519.pub fred@server.example.org ``` Either way, another way is to name the key in ssh_config(5) instead using the **IdentityFile** configuration directive. If the file with the public key is missing, it can be regenerated from the private key using ssh-keygen(1) with the **-y** option. ## SSH Client Error Messages And Common Causes As rehash of the above, below are some client-side error messages with some of the more common reasons[^4] for those messages. Neither list of errors nor the reasons for the errors are comprehensive. The suggestions for causes just touch on one or two of the commonly seen reasons. There is no substitute for checking the actual logs, especially on the server. The server log files are usually **/var/log/auth.log** on most system or a variant of that name. Occasionally you will find the information in the file **/var/log/secure** instead. **No address associated with name:** ``` shell-session $ ssh nonesuch.example.org ssh: Could not resolve hostname nonesuch.example.org: no address associated with name ``` The destination\'s host name does not exist in DNS. Was it spelled correctly? **Operation timed out:** ``` shell-session $ ssh 198.51.100.89 ssh: connect to host 198.51.100.89 port 22: Operation timed out ``` There\'s not a system associated with that IP address, or else a packet filter is causing trouble. **Connection timed out:** ``` shell-session $ ssh 198.51.100.89 ssh: connect to host 198.51.100.89 port 22: Connection timed out ``` You can\'t get there from here. It is probable that the destination machine is disconnected from the network or that the network which it is on is not reachable. **Connection refused:** ``` shell-session $ ssh www.example.org ssh: connect to host www.example.org port 22: Connection refused ``` The destination system exists but there is no SSH service available at the port being tried. Is the destination right? It might be the wrong system, SSH might not be running at all, SSH might be listening on another port, or a packet filter might be blocking connections. **Permission denied:** ``` shell-session $ ssh www.example.org fred@www.example.org: Permission denied (publickey,keyboard-interactive). ``` That is usually a sign of a problem cause by the wrong user name, wrong authentication method, wrong SSH key or SSH certificate, or wrong file permissions in the authorized keys file on the destination system. If it is a matter of SSH key based authentication, see the chapter on Public Key Authentication for more thorough coverage. If it is a question of SSH certificates, see the corresponding Certificate-based Authentication chapter. It can also be a matter of server-side settings with **AllowGroups**, **DenyGroups**, or similar configuration directives at the destination. Any of those possibilities can really only be identified and solved by checking the log output from sshd(8). **No matching host key type found:** ``` shell-session $ ssh www.example.org Unable to negotiate with 198.51.100.89 port 22: no matching host key type found. Their offer: ssh-rsa,ssh-dss ``` The SSH daemon on that server is really outdated. Contact the system administrator about an upgrade and get them moving. More details can be seen with the **-v** option on the client. ``` shell-session $ ssh -v fred@example.org ... debug1: SSH2_MSG_KEXINIT received debug1: kex: algorithm: diffie-hellman-group-exchange-sha256 debug1: kex: host key algorithm: (no match) Unable to negotiate with 198.51.100.89 port 22: no matching host key type found. Their offer: ssh-rsa,ssh-dss ``` In the above shell session, it is the server which is badly in need of an update as shown by the deprecated key exchange algorithms which it tries to use. Again, for emphasis, the solution is to update the outdated software. If a specific, old version of an particular operating system absolutely must be used for a while longer, see about getting a back port of the SSH daemon. Many GNU/Linux distros even have specific back port repositories. If you would like to see which key exchange algorithms the client supports try using the **-Q** option. ``` shell-session $ ssh -Q kex diffie-hellman-group1-sha1 diffie-hellman-group14-sha1 diffie-hellman-group14-sha256 diffie-hellman-group16-sha512 diffie-hellman-group18-sha512 diffie-hellman-group-exchange-sha1 diffie-hellman-group-exchange-sha256 ecdh-sha2-nistp256 ecdh-sha2-nistp384 ecdh-sha2-nistp521 curve25519-sha256 curve25519-sha256@libssh.org sntrup761x25519-sha512@openssh.com ``` [^1]: [^2]: [^3]: [^4]:
# OpenSSH/Development It is possible to advance OpenSSH through donations of hardware or money. See the OpenSSH project web site at www.openssh.com for details. OpenSSH is a volunteer project with the goal of making quality software. In that way it relies upon hardware and cash donations to keep the project rolling. Funds are needed for daily operation to cover network line subscriptions and electrical costs. If two dollars were given for every download of the OpenSSH source code from the master site in 2015, ignoring the mirrors, or if a penny was donated for every instance of PF or OpenSSH installed with a mainstream operating system or phone in 2015[^1], then funding goals for the year would be met. Hardware is needed for development and porting to new architectures and platforms always requires new hardware. OpenSSH is currently developed by two teams. The first team works to provide code that is as clean, simple and secure as possible. It is part of the OpenBSD project. The second team works using this core version and ports it to a great many other operating systems. Thus there are two development tracks, the OpenBSD core and the portable version. All the work is done in countries that permit export of cryptography. ## Use the Source, Luke The main development branch of OpenSSH is part of the OpenBSD project. So the source code for the \"-current\" branch of OpenBSD is where to look for latest activity. Nightly, bleeding-edge snapshots of OpenSSH itself are thus publicly available from OpenBSD\'s CVS tree. Use a mirror when possible. The source code for the portable releases of OpenSSH are published using anonymous Git, so no password is needed to download source from the read-only repository. The repository is provided and maintained by Damien Miller. git://anongit.mindrot.org/openssh.git We ask anyone wishing to report security bugs in OpenSSH to please use the contact address given in the source and to practice responsible disclosure. ## libssh **libssh** is an independent project that provides a multiplatform C library implementing the SSHv2 and SSHv1 protocols for client and server implementations. With libssh, developers can remotely execute programs, transfer files and use a secure and transparent tunnel for your remote applications. **libssh** is available under LGPL 2.1 license, on the web page <https://www.libssh.org/> Features: - Key Exchange Methods: curve25519-sha256@libssh.org, ecdh-sha2-nistp256, diffie-hellman-group1-sha1, diffie-hellman-group14-sha1 - Hostkey Types: ecdsa-sha2-nistp256, ssh-dss, ssh-rsa - Ciphers: aes256-ctr, aes192-ctr, aes128-ctr, aes256-cbc, aes192-cbc, aes128-cbc, 3des-cbc, des-cbc-ssh1, blowfish-cbc - Compression Schemes: zlib, zlib@openssh.com, none - MAC hashes: hmac-sha1, none - Authentication: none, password, public-key, hostbased, keyboard-interactive, gssapi-with-mic - Channels: shell, exec (incl. SCP wrapper), direct-tcpip, subsystem, auth-agent-req@openssh.com - Global Requests: tcpip-forward, forwarded-tcpip - Channel Requests: x11, pty, exit-status, signal, exit-signal, keepalive@openssh.com, auth-agent-req@openssh.com - Subsystems: sftp(version 3), publickey(version 2), OpenSSH Extensions - SFTP: statvfs@openssh.com, fstatvfs@openssh.com - Thread-safe: Just don't share sessions - Non-blocking: it can be used both blocking and non-blocking - Your sockets: the app hands over the socket, or uses libssh sockets - OpenSSL or gcrypt: builds with either Additional Features: - Client and server support - SSHv2 and SSHv1 protocol support - Supports Linux, UNIX, BSD, Solaris, OS/2 and Windows - Full API documentation and a tutorial - Automated test cases with nightly tests - Event model based on poll(2), or a poll(2)-emulation. ## libssh2 **libssh2** is another independent project providing a lean C library implementing the SSH2 protocol for embedding specific SSH capabilities into other tools. It has a stable, well-documented API for working on the client side with the different SSH subsystems: Session, Userauth, Channel, SFTP, and Public Key. The API can be set to either blocking or non-blocking. The code uses strict name spaces, is C89-compatible and builds using regular GNU Autotools. **libssh2** is available under a modified BSD license. The functions are each documented in their own manual pages. The project web site contains the documentation, source code and examples: `   ``http://www.libssh2.org/`` ` There is a mailing list for **libssh2** in addition to an IRC channel. The project is small, low-key and, as true to the spirit of the Internet, a meritocracy. Hundreds of specific functions allow specific activities and components to be cherry-picked and added to an application: - Shell and SFTP sessions - Port forwarding - Password, public-key, host-based keys, and keyboard-interactive authentication methods. - Key Exchange Methods diffie-hellman-group1-sha1, diffie-hellman-group14-sha1, diffie-hellman-group-exchange-sha1 - Host Key Types: ssh-rsa and ssh-dss - Ciphers: aes256-ctr, aes192-ctr, aes128-ctr, aes256-cbc (rijndael-cbc@lysator.liu.se), aes192-cbc, aes128-cbc, 3des-cbc, blowfish-cbc, cast128-cbc, arcfour, arcfour128, or without a cipher. - Compression Scheme zlib or without compression - Message Authentication Code (MAC) algorithms for hashes: hmac-sha1, hmac-sha1-96, hmac-md5, hmac-md5-96, hmac-ripemd160 (hmac-ripemd160@openssh.com), or none at all - Channels: Shell, Exec -- including the SCP wrapper, direct TCP/IP, subsystem - Channel Requests: x11, pty - Subsystems: sftp version 3, public-key version 2 - Thread-safe, blocking or non-blocking API - Your sockets: the app hands over the socket, calls select() etc. - Builds with either OpenSSL or gcrypt See also the library **libcurl** which supports SFTP and SCP URLs. ## Thrussh **Thrussh** is an SSH library written in Rust and available under the Apache License version 2.0. It is a full implementation of the SSH 2 protocol. The only non-Rust part is the crypto back end, which uses ring instead. It is designed to work on any platform and to use asynchronous I/O. The project web site contains the documentation, source code, and examples. The code is accessible using **darcs**: `darcs get ``https://pijul.org/thrussh` It is not an implementation of an actual server or client, but instead contains all the elements needed to write custom clients and servers using Rust. ## Other language bindings for the SSH protocols What follows is a list of additional independent resources by programming language: ### Perl - \[<http://search.cpan.org/perldoc?Net>::SSH2 Net::SSH2\]: a wrapper module for **libssh2**. - \[<http://search.cpan.org/perldoc?Net>::<SSH::Perl> Net::<SSH::Perl>\]: a full SSH/SFTP implementation in pure Perl. Unfortunately this module is not being maintained any more and has several open bugs. Also, installing it can be a daunting task due to some of its dependencies. - \[<http://search.cpan.org/perldoc?Net>::OpenSSH Net::OpenSSH\]: a wrapper for OpenSSH binaries and other handy programs (**scp**, **rsync**, **sshfs**). It uses OpenSSH multiplexing feature in order to reuse connections. - \[<http://search.cpan.org/perldoc?Net>::OpenSSH::Parallel Net::OpenSSH::Parallel\] a module build on top of **Net::OpenSSH** that allows to transfer files and run programs on several machines in parallel efficiently. - \[<http://search.cpan.org/perldoc?SSH>::Batch <SSH::Batch>\] another module build on top of **Net::OpenSSH** that allows to run programs on several hosts in parallel. - \[<http://search.cpan.org/perldoc?Net>::<SSH::Expect> Net::<SSH::Expect>\]: this module uses Expect to drive interactive shell sessions run on top of SSH. - \[<http://search.cpan.org/perldoc?Net>::SSH Net::SSH\]: a simple wrapper around any SSH client. It does not support password authentication and is very slow as it establishes a new SSH connection for every remote program invoked. - \[<http://search.cpan.org/perldoc?Net>::SCP Net::SCP\] and \[<http://search.cpan.org/perldoc?Net>::SCP::Expect Net::SCP::Expect\]: modules wrapping the **scp** program. Note that **Net::SSH2**, **Net::<SSH::Perl>** and **Net::OpenSSH** already support file transfers via **scp** natively. - \[<http://search.cpan.org/perldoc?Net>::<SFTP::Foreign> Net::<SFTP::Foreign>\]: a full SFTP client written in Perl with lots of bells and whistles. By default is uses **ssh** to connect to the remote machines but it can also run on top of **Net::SSH2** and **Net::OpenSSH**. - \[<http://search.cpan.org/perldoc?GRID>::Machine GRID::Machine\], \[<http://search.cpan.org/perldoc?IPC>::PerlSSH IPC::PerlSSH\] and \[<http://search.cpan.org/perldoc?SSH>::RPC <SSH::RPC>\]: these modules allow to distribute and run Perl code on remote machines through SSH. ### Python Paramiko - <http://www.lag.net/paramiko/> Fabric - <http://docs.fabfile.org/> libssh2 - <http://www.no-ack.org/2010/11/python-bindings-for-libssh2.html> TwistedConch - <https://twistedmatrix.com/trac/wiki/TwistedConch> ### Ruby Net::SSH - <https://github.com/net-ssh> Capistrano - <https://github.com/capistrano/capistrano> ### Java Jaramiko - <http://www.lag.net/jaramiko/> JSch - a pure Java implementation of SSH2. - <http://www.jcraft.com/jsch/> ## References [^1]:
# C Sharp Programming/K-Means++ ``` csharp using System; using System.Collections.Generic; using System.Linq; using System.Text; using System.Drawing; using System.Security.Cryptography; class KMeansPP { //Output object public class PointClusters { private Dictionary<Point, List<Point>> _pc = new Dictionary<Point, List<Point>>(); public Dictionary<Point, List<Point>> PC { get { return _pc; } set { _pc = value; } } } //Intermediate calculation object public struct PointDetails { private Point _seedpoint; private double[] _Weights; private double _Sum; private double _minD; public Point SeedPoint { get { return _seedpoint; } set { _seedpoint = value; } } public double[] Weights { get { return _Weights; } set { _Weights = value; } } public double Sum { get { return _Sum; } set { _Sum = value; } } public double MinD { get { return _minD; } set { _minD = value; } } } /// <summary> /// Basic (non kd-tree) implementation of kmeans++ algorithm. /// cf. http://en.wikipedia.org/wiki/K-means%2B%2B /// Excellent for financial diversification cf. /// Clustering Techniques for Financial Diversification, March 2009 /// cf http://www.cse.ohio-state.edu/~johansek/clustering.pdf /// Zach Howard & Keith Johansen /// Note1: If unsure what value of k to use, try: k ~ (n/2)^0.5 /// cf. http://en.wikipedia.org/wiki/Determining_the_number_of_clusters_in_a_data_set /// </summary> /// <param name="allPoints">All points in ensemble</param> /// <param name="k">Number of clusters</param> /// <returns></returns> public PointClusters GetKMeansPP(List<Point> allPoints, int k) { //1. Preprocess KMeans (obtain optimized seed points) List<Point> seedPoints = GetSeedPoints(allPoints, k); //2. Regular KMeans algorithm PointClusters resultado = GetKMeans(allPoints, seedPoints, k); return resultado; } //Bog standard k-means. private PointClusters GetKMeans(List<Point> allPoints, List<Point> seedPoints, int k) { PointClusters cluster = new PointClusters(); double[] Distances = new double[k]; double minD = double.MaxValue; List<Point> sameDPoint = new List<Point>(); bool exit = true; //Cycle thru all points in ensemble and assign to nearest centre foreach (Point p in allPoints) { foreach (Point sPoint in seedPoints) { double dist = GetEuclideanD(p, sPoint); if (dist < minD) { sameDPoint.Clear(); minD = dist; sameDPoint.Add(sPoint); } if (dist == minD) { if (!sameDPoint.Contains(sPoint)) sameDPoint.Add(sPoint); } } //Extract nearest central point. Point keyPoint; if (sameDPoint.Count > 1) { int index = GetRandNumCrypto(0, sameDPoint.Count); keyPoint = sameDPoint[index]; } else keyPoint = sameDPoint[0]; //Assign ensemble point to correct central point cluster if (!cluster.PC.ContainsKey(keyPoint)) //New { List<Point> newCluster = new List<Point>(); newCluster.Add(p); cluster.PC.Add(keyPoint, newCluster); } else { //Existing cluster centre cluster.PC[keyPoint].Add(p); } //Reset sameDPoint.Clear(); minD = double.MaxValue; } //Bulletproof check - it it come out of the wash incorrect then re-seed. if (cluster.PC.Count != k) { cluster.PC.Clear(); seedPoints = GetSeedPoints(allPoints, k); } List<Point> newSeeds = GetCentroid(cluster); //Determine exit foreach (Point newSeed in newSeeds) { if (!cluster.PC.ContainsKey(newSeed)) exit = false; } if (exit) return cluster; else return GetKMeans(allPoints, newSeeds, k); } /// <summary> /// Get the centroid of a set of points /// cf. http://en.wikipedia.org/wiki/Centroid /// Consider also: Metoid cf. http://en.wikipedia.org/wiki/Medoids /// </summary> /// <param name="pcs"></param> /// <returns></returns> private List<Point> GetCentroid(PointClusters pcs) { List<Point> newSeeds = new List<Point>(pcs.PC.Count); Point newSeed; int sumX = 0; int sumY = 0; foreach (List<Point> cluster in pcs.PC.Values) { foreach (Point p in cluster) { sumX += p.X; sumY += p.Y; } newSeed = new Point(sumX / cluster.Count, sumY / cluster.Count); newSeeds.Add(newSeed); sumX = sumY = 0; } return newSeeds; } private List<Point> GetSeedPoints(List<Point> allPoints, int k) { List<Point> seedPoints = new List<Point>(k); PointDetails pd; List<PointDetails> pds = new List<PointDetails>(); int index = 0; //1. Choose 1 random point as first seed int firstIndex = GetRandNorm(0, allPoints.Count); Point FirstPoint = allPoints[firstIndex]; seedPoints.Add(FirstPoint); for (int i = 0; i < k - 1; i++) { if (seedPoints.Count >= 2) { //Get point with min distance PointDetails minpd = GetMinDPD(pds); index = GetWeightedProbDist(minpd.Weights, minpd.Sum); Point SubsequentPoint = allPoints[index]; seedPoints.Add(SubsequentPoint); pd = new PointDetails(); pd = GetAllDetails(allPoints, SubsequentPoint, pd); pds.Add(pd); } else { pd = new PointDetails(); pd = GetAllDetails(allPoints, FirstPoint, pd); pds.Add(pd); index = GetWeightedProbDist(pd.Weights, pd.Sum); Point SecondPoint = allPoints[index]; seedPoints.Add(SecondPoint); pd = new PointDetails(); pd = GetAllDetails(allPoints, SecondPoint, pd); pds.Add(pd); } } return seedPoints; } /// <summary> /// Very simple weighted probability distribution. NB: No ranking involved. /// Returns a random index proportional to to D(x)^2 /// </summary> /// <param name="w">Weights</param> /// <param name="s">Sum total of weights</param> /// <returns>Index</returns> private int GetWeightedProbDist(double[] w, double s) { double p = GetRandNumCrypto(); double q = 0d; int i = -1; while (q < p) { i++; q += (w[i] / s); } return i; } //Gets a pseudo random number (of normal quality) in range: [0, 1) private double GetRandNorm() { Random seed = new Random(); return seed.NextDouble(); } //Gets a pseudo random number (of normal quality) in range: [min, max) private int GetRandNorm(int min, int max) { Random seed = new Random(); return seed.Next(min, max); } //Pseudorandom number (of crypto strength) in range: [min,max) private int GetRandNumCrypto(int min, int max) { byte[] salt = new byte[8]; RNGCryptoServiceProvider rng = new RNGCryptoServiceProvider(); rng.GetBytes(salt); return (int)((double)BitConverter.ToUInt64(salt, 0) / UInt64.MaxValue * (max - min)) + min; } //Pseudorandom number (of crypto strength) in range: [0.0,1.0) private double GetRandNumCrypto() { byte[] salt = new byte[8]; RNGCryptoServiceProvider rng = new RNGCryptoServiceProvider(); rng.GetBytes(salt); return (double)BitConverter.ToUInt64(salt, 0) / UInt64.MaxValue; } //Gets the weight, sum, & min distance. Loop consolidation essentially. private PointDetails GetAllDetails(List<Point> allPoints, Point seedPoint, PointDetails pd) { double[] Weights = new double[allPoints.Count]; double minD = double.MaxValue; double Sum = 0d; int i = 0; foreach (Point p in allPoints) { if (p == seedPoint) //Delta is 0 continue; Weights[i] = GetEuclideanD(p, seedPoint); Sum += Weights[i]; if (Weights[i] < minD) minD = Weights[i]; i++; } pd.SeedPoint = seedPoint; pd.Weights = Weights; pd.Sum = Sum; pd.MinD = minD; return pd; } /// <summary> /// Simple Euclidean distance /// cf. http://en.wikipedia.org/wiki/Euclidean_distance /// Consider also: Manhattan, Chebyshev & Minkowski distances /// </summary> /// <param name="P1"></param> /// <param name="P2"></param> /// <returns></returns> private double GetEuclideanD(Point P1, Point P2) { double dx = (P1.X - P2.X); double dy = (P1.Y - P2.Y); return ((dx * dx) + (dy * dy)); } //Gets min distance from set of PointDistance objects. If similar then chooses random item. private PointDetails GetMinDPD(List<PointDetails> pds) { double minValue = double.MaxValue; List<PointDetails> sameDistValues = new List<PointDetails>(); foreach (PointDetails pd in pds) { if (pd.MinD < minValue) { sameDistValues.Clear(); minValue = pd.MinD; sameDistValues.Add(pd); } if (pd.MinD == minValue) { if (!sameDistValues.Contains(pd)) sameDistValues.Add(pd); } } if (sameDistValues.Count > 1) return sameDistValues[GetRandNumCrypto(0, sameDistValues.Count)]; else return sameDistValues[0]; } } ```
# Proteomics/Introduction to Proteomics \_\_NOEDITSECTION\_\_ \_\_NOTOC\_\_ ### `<font size=1 color=dimgray>`{=html}Presentation`</font>`{=html} ```{=html} <table height=1 border=1 style="border-collapse:collapse; border-color:LightSkyBlue; background-color:AliceBlue;" width="100%"> ``` ```{=html} <tr> ``` ```{=html} <td align=left> ``` ```{=html} <table width="100%" align=left> ``` ```{=html} <tr> ``` ```{=html} <td> ``` !Introduction{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` ![](Gohome.png "Gohome.png"){width="" height="40"} ```{=html} </td> ``` ```{=html} <td nowrap> ``` `<font size=6 color=teal>`{=html}`</font>`{=html} ```{=html} </td> ``` ```{=html} <td> ``` !Protein Sample Preparation{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td width="99%"> ```   ```{=html} </td> ``` ```{=html} <td> ``` ```{=html} <td> ``` !Protein Sample Preparation{width="" height="40"} ```{=html} </td> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ```   \_\_TOC\_\_ ## What is proteomics? !Information transfer in the central dogma of biology The focus of proteomics is a biological group called the proteome. The proteome is dynamic, defined as the set of proteins expressed in a specific cell, given a particular set of conditions. Within a given human proteome, the number of proteins can be as large as 2 million. Proteins themselves are macromolecules: long chains of amino acids. This amino acid chain is constructed when the cellular machinery of the ribosome translates RNA transcripts from DNA in the cell\'s nucleus. The transfer of information within cells commonly follows this path, from DNA to RNA to protein. Proteins can be organized in four structural levels: :\*Primary (1°): The amino acid sequence, containing members of a (usually) twenty-unit alphabet :\*Secondary (2°): Local folding of the amino acid sequence into α helices and β sheets :\*Tertiary (3°): 3D conformation of the entire amino acid sequence :\*Quaternary (4°): Interaction between multiple small peptides or protein subunits to create a large unit Each level of protein structure is essential to the finished molecule\'s function. The primary sequence of the amino acid chain determines where secondary structures will form, as well as the overall shape of the final 3D conformation. The 3D conformation of each small peptide or subunit determines the final structure and function of a protein conglomerate. There are many different subdivisions of proteomics, including: :\*Structural proteomics \-- in-depth analysis of protein structure :\*Expression proteomics \-- analysis of expression and differential expression of proteins :\*Interaction proteomics \-- analysis of interactions between proteins to characterize complexes and determine function. Proteomics has both a physical laboratory component and a computational component. These two parts are often linked together; at times data derived from laboratory work can be fed directly into sequence and structure prediction algorithms. Mass spectrometry of multiple types is used most frequently for this purpose. ## The importance of proteomics Proteomics is a relatively recent field; the term was coined in 1994, and the science itself had its origins in electrophoretic separation techniques#Molecular_Biology_and_Biochemistry "wikilink") of the 1970\'s and 1980\'s. The study of proteins, however, has been a scientific focus for a much longer time. Studying proteins generates insight on how proteins affect cell processes. Conversely, this study also investigates how proteins themselves are affected by cell processes or the external environment. Proteins provide intricate control of cellular machinery, and are in many cases components of that same machinery. They serve a variety of functions within the cell, and there are thousands of distinct proteins and peptides in almost every organism. This great variety comes from a phenomenon known as alternative splicing, in which a particular gene in a cell\'s DNA can create multiple protein types, based on the demands of the cell at a given time. The goal of proteomics is to analyze the varying proteomes of an organism at different times, in order to highlight differences between them. Put more simply, proteomics analyzes the structure and function of biological systems. For example, the protein content of a cancerous cell is often different from that of a healthy cell. Certain proteins in the cancerous cell may not be present in the healthy cell, making these unique proteins good targets for anti-cancer drugs. The realization of this goal is difficult; both purification and identification of proteins in any organism can be hindered by a multitude of biological and environmental factors. !Protein structural levels of interest in proteomics ## Proteomics Workflows The first step of proteomics is sample preparation. In this step, we are trying to extract protein from cells. In the second step, we use methods such as 2D electrophoresis to separate different proteins. Then we try to cut proteins into peptides since peptides are easier to detect. In the forth step, we use mass spectrometry to detect peptides and peptides fragments. Finally, we can then determine the sequence of the protein by interpreting all the data obtained. ![](targeted_mass_spectrometry.gif "targeted_mass_spectrometry.gif"){width="400" height="400"} ## Broad-Based Proteomics !Broad-based Proteomics Approach vs traditional focused approach{width="600"} Because Proteomics is growing at a very rapid pace, there is a shift in the field away from a specialized/focused way of conducting studies and towards a more global perspective. Broad-based proteomics presents a unique perspective on the field of proteomics because it allows for one to take on this general perspective by setting out to understand the proteome as a whole. A critical aspect to this strategy is planning ahead; and in doing so, the most appropriate plans and technologies can be implemented in the most efficient manner. By developing a strategy tailored to understanding a particular proteome, problems and setbacks can be avoided during the study. The first step when utilizing broad-based proteomics is to develop a hypothesis specific to the proteome being studied. It is best to choose organisms that already have a great deal of genomic information available, since the genome is always a useful supplement to proteomic information. Once the a hypothesis and organism are established, the proper technologies should be chosen; and these technologies should be compatible with whatever biological factors are present (i.e. sample type). Some important and relevant proteomic methods include HPLC, Mass Spectrometry, SDS-PAGE, two-dimensional gel electrophoresis, and perhaps in silico protein modeling. Since there are multitudes of sample type, sample preparation, and analytical technology combinations possible, it is obvious why careful planning from a broad-based proteomic perspective is critical. By planning upfront, an efficient proteomic study can be conducted. And when the efforts of many broad-based proteomic studies are taken together, understanding the proteome in its entirety becomes a realistic possibility. ## References 1. American Medical Association. \"Proteomics.\" <http://www.ama-assn.org/ama/pub/category/3668.html> 2. Hartl, Daniel L., Jones, Elizabeth W. \"Genetics: Analysis of Genes and Genomes\". Jones and Bartlett Publishers: Boston, 2005. 3. Weaver, Robert F. \"Molecular Biology, 2nd Edition\". McGraw Hill: Boston, 2002. 4. Twyman, Richard. \"Proteomics.\" <http://genome.wellcome.ac.uk/doc_wtd020767.html> 5. Colinge, Jacques and Keiryn L. Bennett. \"Introduction to Computational Proteomics\". PLoS Comput Biol. 2007 July; 3(7): e114. 6. \"History of Proteomics.\" Australian Proteome Analysis Facility. <http://www.proteome.org.au/History-of-Proteomics/default.aspx> 7. Graves, P. R., T. A. J. Haystead. \"Molecular Biologist\'s Guide to Proteomics\". Microbiology and Molecular Biology Reviews: Vol.66 No.1, 2002. 8. \"Proteomics Overview.\" <http://www.proteomicworld.org/> 9. van Wijk, K. J. \"Challenges and Prospects of Plant Proteomics\". Plant Physiol. 2001 June; 126(2): 501-508. Chapter Written by J. Reuter (Zel2008) and S. Lafergola (DieselSandwich) ## Articles Summarized ### Advances in Proteomic Workflows for Systems Biology Johan Malmstrom, Hookeun Lee, and Ruedi Aebersold. *Curr Opin Biotechnol* **18(4):**378-384 (2007) **Main Focus** The article summarizes recent improvements as well as some principal limitations of shortgun tandem mass spectrometry based proteomics. Furthermore, it also briefly introduces steps of targeted driven quantitative proteomics. **Summary** In recent years, great improvements have been made in all the parts of non targeted mass spectrometry based proteomics including sample preparation, data acquisition, data processing and analysis. In the sample preparation process, with the introduction of IEF separation method, resolution obtained from classical two dimensional chromatography peptide separation is greatly improved. Improvements are also made in the field of data quality which is increased by the development of highly reproducible capillary chromatography methods and quantitative analysis by stable isotope labeling method. High mass resolution and accuracy could be achieved now by different types of mass spectrometry such as TOF-TOF,Q-TOF in the data acquisition process. Furthermore, different types of mass analyzers and ion sources have been combined to increase the proteome coverage. With the development of database search tools, the quality of proteomics data could be more accurately assessed and estimated in the data processing and analysis process. Despite all these improvements achieved, limitations exist in shotgun approaches. For example, shotgun MS datasets are extremely redundant which greatly affect the identification of peptides present in proteomic samples. The existence of semi-tryptic or non-tryptic peptides in samples made the sample more complex. Saturation effect greatly reduces the discovery rate of new proteins. Many peptides that detected by Mass Spectrometry could not be identified, making it difficult to compare sample to sample. The limitations of shotgun approaches made the development of targeted driven quantitative proteomics necessary. The first step of targeted driven quantitative proteomics is protein and peptide selection. This step could be finished both experimentally and computationally. For the multiple reaction monitoring (MRM) and data analysis step, multiple reaction monitoring was applied to proteomics data analysis. Relevance to the course: this source is a brief overview of recent improvements in targeted mass spectrometry (one method of proteomics) based proteomics as well as some limitations. It also introduced another field of proteomics: targeted driven quantitative proteomics. **New Terms** Electrospray ionization:A technique used in mass spectrometry to produce ions.It is especially useful in producing ions from macromolecules because it overcomes the propensity of these molecules to fragment when ionized (http://en.wikipedia.org/wiki/Electrospray_ionization)\ Matrix-assisted laser desorption/ionization (MALDI):A soft ionization technique used in mass spectrometry, allowing the analysis of biomolecules (biopolymers such as proteins,peptides and sugars) and large organic molecules (such as polymers, dendrimers and other macromolecules), which tend to be fragile and fragment when ionized by more conventional ionization methods(http://en.wikipedia.org/wiki/MALDI-TOF)\ PeptideAtlas:A multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments(http://www.peptideatlas.org/)\ Multiple reaction monitoring:MRM experiments, using a triple quadrupole instrument, are designed for obtaining the maximum sensitivity for detection of target compounds. This type of mass spectrometric experiment is widely used in detecting and quantifying drug and drug metabolites in the pharmaceutical industry(http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2291721)\ FT-ICR mass spectrometry:Fourier transform ion cyclotron resonance mass spectrometry, also known as Fourier transform mass spectrometry, is a type of mass analyzer (or mass spectrometer) for determining the mass-to-charge ratio (m/z) of ions based on the cyclotron frequency of the ions in a fixed magnetic field(http://en.wikipedia.org/wiki/Fourier_transform_ion_cyclotron_resonance) **Course Relevance** : This source is about non targeted mass spectrometry and targeted approaches which are important methods in the identification of proteins(an important step in proteomics). ### Broad-Based Proteomic Strategies: A Practical Guide to Proteomics and Functional Screening Graham David, Elliot Steven, Van Eyk Jennifer. \"Journal of Physiology\" 563: 1-9 (2005) **Main Focus** This article summarizes what broad-based proteomics is and how one can design a study using this global-view strategy. It first briefly looks at the current technology in proteomics and then discusses how these technologies can be incorporated into a study. **Summary** Proteomics as a field is becoming a very daunting one to enter because many studies are getting lost in the complicated focused details. To help assist with this challenge, a researcher can employ broad-based proteomics. Broad-based proteomics is a strategy where careful planning is employed upfront to answer a question about a proteome (for instance, comparisons between a tissue in a diseased state and a normal state) using the most appropriate and applicable technologies available. By developing a strategy at the beginning of a proteomics study, possible setbacks during the study are avoided. The first step is to develop a general hypothesis that is specific to the problem or issue that is being studied. Since proteomics mirrors genomics, a proteomic study is increasingly difficult when the genome of the model organism isn\'t known. For this reason, organisms where the majority of the genome is known (80% or greater) should be chosen. Once a proper organism has been chosen for study, the next factors to consider are the type of data that will be generated and also the sample source. Some proteomic methods yield qualitative data, while others yield quantitative; so the type of data needed should be determined before a method is chosen. At the same time, the source of the sample is important in determining the extraction and purification methods. Typical sample types include: urine, blood (plasma/serum) and mucosal secretions. Protein concentration within the sample is important, and one should expect reasonable extraction if the protein can be visualized on a coomassie blue stained gel (\> 300 ng). The separation technique chosen should reflect the characteristics of the protein(s) of choice (hydrophobic vs hydrophilic, molecular mass, etc). Another major factor in the planning process is estimating the difficulty in the preparation of the fractioned sample for mass spectrometry identification. Each mass spectrometry technique requires varying degrees of preparation, and some are much more complicated than others (2DE with MS/MS analysis requires greater preparation than HPLC with MS, for instance). Since mass spectrometry is often the step where a lot of proteomic studies encounter difficulty (both in preparation and in interpretation of the results), it is very important to choose a method that is appropriate for the protein sample. With the advent of proteomic databases in recent years, bioinformatics has had an increasing presence in proteomic studies. For this reason, almost all proteomic studies should incorporate bioinformatics; and consequently it\'s important for the research team to have some bioinformatics knowledge. And depending on how much data will be received at the end of the study (depending on the analysis methods chosen), the research team can determine how much bioinformatic analysis should be needed. A final factor to consider is whether to bring in outside assistance or to attempt the study in a more self-contained way. Keeping it self-contained allows for the research team to keep its data integrated and also keeps miscommunication to a minimum. Bringing in outside help, on the other hand, could allow a researcher to tackle problems that would be large and normally not solvable with a smaller team. While bringing in outside assistance seems promising, it\'s important to not lose control over the data and to make sure that the team is not spread out trying to accomplish more than it can handle. Since there are many ways to study a cell\'s proteome, careful planning should be implemented at all stages of a proteomics study. Through broad-based proteomics, a researcher can define a test plan before any actual study is performed. And when used appropriately, this strategy can lead to productive and efficient projects that will bring science one step closer to understanding the proteome as a whole. **New Terms** Isoforms: A set of different proteins that form because of single nucleotide polymorphisms in the genomic sequence. ( <http://en.wikipedia.org/wiki/Isoform> )\ Single-nucleotide polymorphism (SNP): a DNA sequence variation occurring when a single nucleotide in the genome differs between members of a species. ( <http://en.wikipedia.org/wiki/Single_nucleotide_polymorphism> )\ Post-translational modification (PTM): the chemical modification of a protein after it has been translated. It is usualy one of the last steps in protein biosynthesis for most proteins. ( <http://en.wikipedia.org/wiki/Posttranslational_modification> )\ Subproteome: a subfractioned subset of the proteome. Often these are linked to area of the cell (organelle for instance) or by chemical properties.\ Peptide mass fingerprinting (PMF): an analytical technique for protein identification. The unknown protein of interest is first cleaved into smaller peptides and after mass is determined using mass spectrometry, their masses are compared to either a database containing known protein sequences or a genome. ( <http://en.wikipedia.org/wiki/Peptide_mass_fingerprinting> ) **Course Relevance** : This article is relevant because a global view of proteomics is becoming more important. As the wealth of information about proteins expands, understanding the proteome from a broad viewpoint is becoming more and more useful. ## Websites Summarized ### The Association of Bimolecular Resource Facilities: Proteomics Research Group (PRG) Website committee: Pamela Scott Adams, Michelle Detwiler, David Mohr James Ee, Dr. Xiaolog Yang, Dr. Len Packman, Dr. Anthony Yeung, <http://www.abrf.org/index.cfm/group.show/Proteomics.34.htm#R_3> (3/25/09) **Main Focus** This web page is about how the Association of Bimolecular Resource Facilities relates to proteomics. Of particular importance is the Proteomics Research Group within the ABRF. **Summary** The Association of Bimolecular Resource Facilities (ABRF) is an international association of research facilities and laboratories that is focused on core research in Biotechnology. The association encourages the sharing of information through conferences, a quarterly journal, and group studies. The ABRF has a heavy influence on the field of proteomics, and there are five main research groups (RG) that deal with proteomics in some way: Protein Expression (PERG), Protein Sequencing (PSRG), Protein Informatics (iPRG), Proteomics (PRG), and Proteomics Standards (sPRG). Of particular importance, the Proteomics Research Group allows for researchers throughout the world in the field of proteomics to share their protein analysis information freely. Obviously, since understanding the proteome is about bringing together information on many different proteins (which is information that requires a great amount of effort/time/money to achieve), the sharing of protein/subproteomic information is imperative to beginning to understand a proteome in its entirety. This website has numerous links to studies performed by research groups throughout the world. **New Terms** De Novo Peptide Sequencing: Peptide sequencing that is performed without any prior knowledge of the amino acid sequence. (http://www.ionsource.com/tutorial/DeNovo/DeNovoTOC.htm)\ Quantitative Proteomics: Has the goal of obtaining quantitative information about all the proteins in a particular sample. This is useful because it allows for one to see the differences in protein samples. (http://en.wikipedia.org/wiki/Quantitative_proteomics) **Course Relevance** : This is an overview of the Association of Biomolecular Resource Facilities (ABRG) and how it relates to proteomics. There is a great deal of relevant information on this website that those in proteomics will find useful. ### Introduction to Proteomics Writer/Producer: Rick Groleau,Subject Matter Expert: Hanno Steen, PhD,Designer: Peggy Recinos,Developer: Jeffrey Testa, <http://www.childrenshospital.org/cfapps/research/data_admin/Site602/mainpageS602P0.html> (28 March 2009) ![](Flowchart_of_proteomics.gif "Flowchart_of_proteomics.gif"){width="250" height="350"} **Main Focus** This web page is about the importance and challenges in proteomics. It also introduces major steps of proteomics briefly. **Summary** Proteomics is important for us to understand biological processes since all the functions are accomplished by proteins in cell.But as the number of proteins are so large and amino acids(which are units of protein) are so small, the study is quite challenging.There are five steps to analyze protein sequences: sample preparation,separation,ionization,mass spectrometry and informatics.First of all, we obtain cells and extract proteins from the cells.Then we use methods such as 2D electrophoresis to separate proteins. Next, we use protease to cut proteins into peptides.Mass spectrometry allows us to identify individual peptides as well as peptides fragments.Finally, by interpreting the data, we are able to determine the sequence of proteins. **New Terms** Biopsy: A biopsy is a medical test involving the removal of cells or tissues for examination. It is the removal of tissue from a living subject to determine the presence or extent of a disease(http://en.wikipedia.org/wiki/Biopsy)\ TOF: The time of flight (TOF) describes the method used to measure the time that it takes for a particle, object or stream to reach a detector while traveling over a known distance(http://en.wikipedia.org/wiki/Time-of-flight)\ Quadrupole mass spectrometry: The quadrupole mass analyzer is one type of mass analyzer used in mass spectrometry.It consists of 4 circular rods, set perfectly parallel to each other.In a quadrupole mass spectrometer the quadrupole mass analyzer is the component of the instrument responsible for filtering sample ions, based on their mass-to-charge ratio (m/z).Ions are separated in a quadrupole based on the stability of their trajectories in the oscillating electric fields that are applied to the rods(http://en.wikipedia.org/wiki/Quadrupole_mass_analyzer)\ Electronspray ionization: Electrospray ionization (ESI) is a technique used in mass spectrometry to produce ions.It is especially useful in producing ions from macromolecules because it overcomes the propensity of these molecules to fragment when ionized(http://en.wikipedia.org/wiki/Electrospray_ionization)\ Dalton: Dalton is the unit of measurement for atomic mass. One Dalton is equal to 1/12th the mass of one atom of carbon12(http://www.childrenshospital.org/cfapps/research/data_admin/Site602/mainpageS602P1.html) **Course Relevance** : This is an overview of proteomics. It summarizes the procedures and importance of proteomics very briefly. ### Introduction to Proteomics Institute of Biology and Medical Genetics of the First Faculty of Medicine of Charles University and the General Teaching Hospital,http://biol.lf1.cuni.cz/ucebnice/en/proteomics.htm (6 April 2009) ![](proteomics.jpg "proteomics.jpg"){width="250" height="350"} **Main Focus** This website discusses the aims and definitions of proteomics. It also introduces two important methods in proteomcis studies - 2D protein electrophoresis and mass spectrometry as well as proteomics in medicine **Summary** Proteomics is a broad field which includes expression proteomics, protein distribution in subcellular compartments of the organelles,post-translational modifications of the proteins,structural proteomics and functional proteomics, clinical proteomics and so on. Even though analysis of the expression on transcripts level is possible with the introduction of RNA/cDNA microarray, proteomics is still important since not all mRNA will be translated and the processes such as RNA splicing, posttranslational protein modifications exist. Two-dimensional (2D) protein electrophoresis is commonly used to separate proteins based on their PI and mass. Mass spectrometry is an important method in proteomics since it cannot only be used for protein identification but can also be used for protein posttranslational modification analysis. One of the major application of proteomics in medicine is the identification of markers in all the steps to treat diseases. Other applications include drug discovery and pharmacoproteomics. **New Terms** Human Proteome Organization(HUPO): The Human Proteome Organisation (HUPO) is an international scientific organization representing and promoting proteomics through international cooperation and collaborations by fostering the development of new technologies, techniques and training(http://www.hupo.org/)\ structural proteomics: Structural proteomics is an international collaboration project for solving 3D protein structures at a proteome scale(http://en.wikipedia.org/wiki/Structural_proteomics)\ Swedish Human Protein Atlas: The Swedish Human Protein Atlas program (HPA), funded by the (non-profit) Knut and Alice Wallenberg Foundation, invites submission of antibodies from both academic and commercial sources to be included in the human protein atlas (http://www.proteinatlas.org)\ Posttranslational modification (PTM): Posttranslational modification (PTM) is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis for many proteins(http://en.wikipedia.org/wiki/Posttranslational_modification)\ Isoelectric point: Isoelectric point is such a pH value, where the overall protein charge equals to zero(http://biol.lf1.cuni.cz/ucebnice/en/proteomics.htm) **Course Relevance** : This website gives brief definition and aims of proteomics.It also introduces principles of 2D-electrophoresis and mass spectrometry which are important methods in proteomics. \ Contact: jxr0084@rit.edu, sfl9376@rit.edu ## References - Johan Malmstrom, Hookeun Lee, and Ruedi Aebersold. \"Advances in Proteomic Workflows for Systems Biology\"*Curr Opin Biotechnol* **18(4):**378-384 (2007)\ - Rick Groleau,Hanno Steen,Peggy Recinos,Jeffrey Testa. \"Introduction to Proteomics\" <http://www.childrenshospital.org/cfapps/research/data_admin/Site602/mainpageS602P0.html> (28 March 2009) - Institute of Biology and Medical Genetics of the First Faculty of Medicine of Charles University and the General Teaching Hospital. \"Introduction to Proteomics\" <http://biol.lf1.cuni.cz/ucebnice/en/proteomics.htm> (06 April 2009)
# Proteomics/Protein Sample Preparation \_\_NOEDITSECTION\_\_ \_\_NOTOC\_\_ ### `<font size=1 color=dimgray>`{=html}Presentation`</font>`{=html} ```{=html} <table height=1 border=1 style="border-collapse:collapse; border-color:LightSkyBlue; background-color:AliceBlue;" width="100%"> ``` ```{=html} <tr> ``` ```{=html} <td align=left> ``` ```{=html} <table width="100%" align=left> ``` ```{=html} <tr> ``` ```{=html} <td> ``` !Introduction to Proteomics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` ![](Gohome.png "Gohome.png"){width="" height="40"} ```{=html} </td> ``` ```{=html} <td nowrap> ``` `<font size=6 color=teal>`{=html}`</font>`{=html} ```{=html} </td> ``` ```{=html} <td> ``` !Experimental Protocols{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td width="99%"> ```   ```{=html} </td> ``` ```{=html} <td> ``` ```{=html} <td> ``` !Experimental Protocols{width="" height="40"} ```{=html} </td> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ```   ## Introduction As technological advances are made in the field of proteomics, it is seen that advances are necessary in the preparation of protein samples prior to any particular procedure. A number of issues arise in this respect; including sample clean-up, fractionation, enrichment, and the also sample condition optimization. Considerations of this nature can be crucial in obtaining relevant results from an experiment; some so much so that experts feel the field of proteomics is currently being limited by the lack of significant advancement in sample preparation techniques. This facet of proteomics is becoming particularly critical in the case of high throughput protocols where the necessary conditions of a sample in one stage may directly conflict with the efficacy of a second stage. For example, during the initial step in 2D electrophoresis, isoelectric focusing, all proteins in a sample are given a net charge of zero; while the second step, gel electrophoresis, requires a negative charge on all products in the sample in order to induce movement through the gel matrix. Many companies offer pre-packaged kits that will allow you to prepare samples for many different techniques. They also offer many protein samples, and other protein technologies. Many of these companies are also on the forefront of protein analysis technology. Some examples are: 1. www.millipore.com 2. www.bio-rad.com 3. www.qiagen.com 4. www.gelifesciences.com 5. www.invitrogen.com 6. www.eksigent.com 7. www.agilent.com 8. www.beckmancoulter.com 9. www.caliperls.com 10. www.glygen.com 11. www.piercenet.com 12. www.bioproximity.com This section is part of an ongoing project at the Rochester Institute of Technology, involving the Bioinformatics department. Currently the project is being worked on by a Proteomics Class taught by Dr. Paul Craig. ## Bibliography - Jörg von Hagen, VCH-Wiley 2008 Proteomics Sample Preparation.
# Proteomics/Plant Proteomics about Two Dimensional Gel Electrophoresis \_\_NOEDITSECTION\_\_ \_\_NOTOC\_\_ ### `<font size=1 color=dimgray>`{=html}Presentation`</font>`{=html} ```{=html} <table height=1 border=1 style="border-collapse:collapse; border-color:LightSkyBlue; background-color:AliceBlue;" width="100%"> ``` ```{=html} <tr> ``` ```{=html} <td align=left> ``` ```{=html} <table width="100%" align=left> ``` ```{=html} <tr> ``` ```{=html} <td> ``` !Protein Sample Preparation{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` ![](Gohome.png "Gohome.png"){width="" height="40"} ```{=html} </td> ``` ```{=html} <td nowrap> ``` `<font size=6 color=teal>`{=html}`</font>`{=html} ```{=html} </td> ``` ```{=html} <td> ``` !Protein Separations - Chromatography{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td width="99%"> ```   ```{=html} </td> ``` ```{=html} <td> ``` ```{=html} <td> ``` !Protein Separations - Chromatography{width="" height="40"} ```{=html} </td> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ```   This page contains protocols that are frequently used in proteomics. You are welcome to add protocols this chapter. 1. /Plant Proteomics about Two Dimensional Gel Electrophoresis/                                                                    
# Proteomics/Protein Separations - Chromatography \_\_NOEDITSECTION\_\_ \_\_NOTOC\_\_ ### `<font size=1 color=dimgray>`{=html}Presentation`</font>`{=html} ```{=html} <table height=1 border=1 style="border-collapse:collapse; border-color:LightSkyBlue; background-color:AliceBlue;" width="100%"> ``` ```{=html} <tr> ``` ```{=html} <td align=left> ``` ```{=html} <table width="100%" align=left> ``` ```{=html} <tr> ``` ```{=html} <td> ``` !Experimental Protocols{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` ![](Gohome.png "Gohome.png"){width="" height="40"} ```{=html} </td> ``` ```{=html} <td nowrap> ``` `<font size=6 color=teal>`{=html}`</font>`{=html} ```{=html} </td> ``` ```{=html} <td> ``` !Protein Separations- Electrophoresis/Introduction to Electrophoresis{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td width="99%"> ```   ```{=html} </td> ``` ```{=html} <td> ``` ```{=html} <td> ``` !Protein Separations- Electrophoresis/Introduction to Electrophoresis{width="" height="40"} ```{=html} </td> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ```   Chapter written by: Laura Grell and Alexander Butarbutar\ Contact llg3875@rit.edu or nbb3924@rit.edu for contributions\ Chapter modified by Kai Burnett and Dalia Ghoneim\ Contact kab9783@rit.edu or dxg6098@rit.edu \_\_FORCETOC\_\_ ## Introduction !HPLC{width="350"} (Res1) To obtain a pure protein sample, a protein must be isolated from all other proteins and cellular components. This can prove to be a difficult task as a single protein often makes up only 1% of the total protein concentration of a cell. Therefore 99% of the protein components of a sample must be removed before it can be classified as pure. A task that is equally challenging is keeping the protein in its active form. When we purify proteins we remove them from their natural environments. As a result, it is necessary to simulate the pH, salt concentration and reducing conditions in which they are normally found. In the process of obtaining an active and pure sample we want to minimize the number of steps taken in order to maximize the yield at the end of the separation. Finally, since proteins are made with the intention of only functioning for a short period of time, it is also critical to obtain our sample as quickly as possible. All these components of protein separations can be successfully achieved by a group of separation methods collectively known as chromatography. There are several properties of proteins that can be taken advantage of to separate proteins. Different types of chromatography take advantage of different properties. Proteins can be separated by: - size - shape - hydrophobicity - affinity to molecules - charge !A Typical Column{width="350"}    In this chapter several different chromatographic methods will be introduced and described. While the methods outlined below all use different characteristics of proteins to separate proteins from one another, they all utilize an insoluble stationary phase and a mobile phase that passes over it. The mobile phase is commonly a liquid solution. It contains the protein we want to isolate. The stationary phase on the other hand is made up of a grouping of beads, usually based on a carbohydrate or acrylamide derivative, that are bound to ionically charged species, hydrophobic characters, or affinity ligands. Much of the success of chromatography is associated with the selection of an appropriate stationary phase.    In column chromatography, when a protein sample is applied to the column, it equilibrates between the stationary phase and the mobile phase. Depending on the type of chromatography, proteins with certain characteristics will bind to the stationary phase while those lacking the sought characteristics will remain in the mobile phase and pass through the column. For example in ion exchange chromatography, a positively charged protein would bind to a negatively charged stationary phase, while the negatively charge protein will be eluted from the column with the mobile phase. The final step involves displacing the protein from the stationary phase, also known as elution, by introducing a particle which will compete with the protein binding site on the stationary phase. Today various commercial column are readily available, specifically Bio-Rad, Sigma-Aldrich,GE Healthcare and Omnifit offers a wide variety of chromatography column. !Common Chromatogram RIT Ion Exchange Site The image above is a chromatogram that shows the results of a separation based on signals interpreted by a detector. t~m~ - the time required for the mobile phase to travel the entire length of the column t~r~ - the time required for a specific protein to elute from the column ## Resources 1. Craig, P. Designing a Separation 2. Florida State University, \"Chromatography\" Michael Blaber\'s Biochemistry Lab 3. GE Healthcare - 1 - \[<http://www.gelifesciences.com/protein-purification>?\] 4. BioPharm International Guide Basics of Chromatography (2003). 5. Bio-Rad Chromatography Protein Purification \|\| Green Fluorescent Protein Chromatography Kit 6. BioForum Topics In Chromatography 7. Journal of Chromatographic Science 8. M.Isabel Pedraza Mayer Chromatography Database ## References 1. Harris, D.C. \"Quantitative Chemical Analysis; 6th Edition\", W.H. Freeman and Company: New York.. 2. Patrick McKay An Introduction to Chromatography Senior Research Associate, Department of Recovery Sciences, Genentech, Inc \*. .\* Denotes Free Article
# Proteomics/Protein Separations- Electrophoresis CurrentPage=Introduction to Electrophoresis| PrevPage=[[Proteomics/Protein Separations - Chromatography|Previous Chapter - Protein Separations: Chromatography]]| NextPage=[[Proteomics/Protein Separations- Electrophoresis/Gel Electrophoresis|Gel Electrophoresis]]}} ``` \_\_TOC\_\_ ## Definitions e•lec•tro•pho•re•sis (ĭ-lĕk\'trō-fə-rē\'sĭs) n. \ 1) The migration of charged colloidal particles or molecules through a solution under the influence of an applied electric field usually provided by immersed electrodes. Also called cataphoresis.\ 2) A method of separating substances, especially proteins, and analyzing molecular structure based on the rate of movement of each component in a colloidal suspension while under the influence of an electric field. \ an•a•lyte (a-nə-līt) n. \ A chemical substance that is the subject of chemical analysis. !Separation under electrophoresis ## Electrophoresis Theory Separation by electrophoresis depends on differences in the migration velocity of ions or solutes through a given medium in an electric field. The electrophoretic migration velocity of an analyte is: `<big>`{=html} $v_p = \mu_p E$ `</big>`{=html} where E is the electric field strength and $\mu_p$ is the electrophoretic mobility. \ The electrophoretic mobility is inversely proportional to frictional forces in the buffer, and directly proportional to the ionic charge of the analyte. The forces of friction against an analyte are dependent on the analyte\'s size and the viscosity (η) of the medium. Analytes with different frictional forces or different charges will separate from one another when they move through a buffer. At a given pH, the electrophoretic mobility of an analyte is: $\mu_p = \frac{z}{6\pi \eta r}$ where r is the radius of the analyte and z is the net charge of the analyte. \ Differences in the charge to size ratio of analytes causes differences in electrophoretic mobility. Small, highly charged analytes have greater mobility, whereas large, less charged analytes have lower mobility. Anionic surfactants are often used to denature proteins before electrophoresis. This gives all proteins approximately the same charge. Since their charges are all equal their mobility is now a function of only their masses. Electrophoretic mobility is an indication of an analyte\'s migration velocity in a given medium. The net force acting on an analyte is the balance of two forces: the electrical force acting in favor of motion, and the frictional force acting against motion. These two forces remain steady during electrophoresis. Therefore, electrophoretic mobility is a constant for a given analyte under a given set of conditions. ## Applications of Electrophoresis Electrophoresis has a wide variety of applications in proteomics, forensics, molecular biology, genetics, biochemistry, and microbiology. One of the most common uses of electrophoresis is to analyze differential expression of genes. Healthy and diseased cells can be identified by differences in the electrophoretic patterns of their proteins. Proteins themselves can also be characterized in this way, and some sense of their structure can be derived from the masses of fragments inside the gel. There are many different types of electrophoresis, and each can be used for something different. Two-dimensional (2-D) electrophoresis, for example, has the ability to discern many more proteins than most of its contemporaries. Many of these methods will be discussed in detail throughout this chapter. ## References 1. The American Heritage Dictionary of the English Language, Fourth Edition. <http://www.bartleby.com/61/> 2. The Merriam-Webster Online Dictionary. <http://www.m-w.com> 3. Mans, Andreas et al. _Bioanalytical Chemistry._ Imperial College Press, 2004. 4. Twyman, Richard. \"Two-dimensional polyacrylamide gel electrophoresis.\" <http://genome.wellcome.ac.uk/doc_wtd021045.html> ------------------------------------------------------------------------ Next page \>
# Proteomics/Protein Separations - Centrifugation \_\_NOEDITSECTION\_\_ \_\_NOTOC\_\_ ### `<font size=1 color=dimgray>`{=html}Presentation`</font>`{=html} ```{=html} <table height=1 border=1 style="border-collapse:collapse; border-color:LightSkyBlue; background-color:AliceBlue;" width="100%"> ``` ```{=html} <tr> ``` ```{=html} <td align=left> ``` ```{=html} <table width="100%" align=left> ``` ```{=html} <tr> ``` ```{=html} <td> ``` !Protein Separations- Electrophoresis/Introduction to Electrophoresis{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` ![](Gohome.png "Gohome.png"){width="" height="40"} ```{=html} </td> ``` ```{=html} <td nowrap> ``` `<font size=6 color=teal>`{=html}`</font>`{=html} ```{=html} </td> ``` ```{=html} <td> ``` !Emerging and Miscellaneous Proteomics Technologies{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td width="99%"> ```   ```{=html} </td> ``` ```{=html} <td> ``` ```{=html} <td> ``` !Emerging and Miscellaneous Proteomics Technologies{width="" height="40"} ```{=html} </td> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ```   \_\_FORCETOC\_\_ ## Introduction to Centrifugation !Tabletop centrifuge{width="150"} Centrifugation is one of the most important and widely applied research techniques in biochemistry, cellular and molecular biology, and in medicine. In the field of proteomics it plays a vital role in the fundamental and necessary process of isolating proteins. This process begins with intact cells or tissues. Before the proteins can be obtained, the cells must be broken open by processes such as snap freezing, sonication, homogenization by high pressure, or grinding with liquid nitrogen. Once the cells have been opened up all of their contents; including cell membranes, RNA, DNA, and organelles will be mixed in the solvent with the proteins. Centrifugation is probably the most commonly used method for separating out all the non protein material. Within the centrifuge samples are spun at high speeds and the resulting force causes particles to separate based on their density. ## Uses of Centrifugation Centrifugation is capable of: - Removing cells or other suspended particles from their surrounding milieu on either a batch or a continous-flow basis ```{=html} <!-- --> ``` - Separating one cell type from another ```{=html} <!-- --> ``` - Isolating viruses and macromolecules, including DNA, RNA, proteins, and lipids or establishing physical parameters of these particles from their observed behavior during centrifugation ```{=html} <!-- --> ``` - Separating from dispersed tissue the various subcellular organelles including nuclei, mitochondria, cholorplasts, golgi bodies, lysosomes, peroxisomes, glyoxysomes, plasma membranes, endoplasmic reticulum, polysomes, and ribosomal subunits. Once the mixture of proteins has been isolated using centrifugation the scientist is then able to use one of several methods to separate out individual proteins for further study. For more information on protein purification/separation see Protein Separations -- Chromatography and Protein Separations-- Electrophoresis. Next section: /History of the Centrifuge/ ## References ### Subscription Based References 1. Sheeler, P. \"Centrifugation in Biology and Medical Science.\" Dept of Biology, California State University, Northridge, California ### Open Access References 1. Claude, A. & Potter, J. S. \"Isolation of Chromatin Threads From The Reasting Nucleus of Leukemic Cells\" The Journal of Experimental Medicine.
# Proteomics/Emerging and Miscellaneous Proteomics Technologies \_\_NOEDITSECTION\_\_ \_\_NOTOC\_\_ ### `<font size=1 color=dimgray>`{=html}Presentation`</font>`{=html} ```{=html} <table height=1 border=1 style="border-collapse:collapse; border-color:LightSkyBlue; background-color:AliceBlue;" width="100%"> ``` ```{=html} <tr> ``` ```{=html} <td align=left> ``` ```{=html} <table width="100%" align=left> ``` ```{=html} <tr> ``` ```{=html} <td> ``` !Protein Separations - Centrifugation{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` ![](Gohome.png "Gohome.png"){width="" height="40"} ```{=html} </td> ``` ```{=html} <td nowrap> ``` `<font size=6 color=teal>`{=html}`</font>`{=html} ```{=html} </td> ``` ```{=html} <td> ``` !Protein Identification - Mass Spectrometry{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td width="99%"> ```   ```{=html} </td> ``` ```{=html} <td> ``` ```{=html} <td> ``` !Protein Identification - Mass Spectrometry{width="" height="40"} ```{=html} </td> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ```   \_\_FORCETOC\_\_ # Emerging and Miscellaneous Technologies in Proteomics This part of the book will be an area where proteomics techniques that have been newly developed will be discussed. Techniques that do not currently fit into any other part of the book can also be added to this page. As chapters or sections are added elsewhere that discuss these techniques in the context of a greater proteomics problem, the information on this page will be moved to those pages. ## X-Ray Tomography **Description and Discussion of X-ray Tomography.** A new branch of X-ray microscopy is being used in proteomics analysis. This is called X-ray Tomography. This method uses projected images to calculate and reconstruct a 3D object. This technology is being used in proteomics to determine the location of labeled proteins or large complexes within a cell. This technique can also be used in conjunction with images of cells from light based microscopes to help identify where a protein is located and how this location factors in to its function and identification. ## Introduction to Proteoinformatics Proteoinformatics is the use of bioinformatics and computational biology techniques solely within the realm of protein identification and proteomics. Proteoinformatics is currently in its infancy and the largest work being done is on standardizing databases and data submission. Other proteoinformatic work is being done on the image analysis of 2D gels and other images in proteomics used to help identify and annotate proteins in the proteome. ### Protein Identification Database #### What are Protein Identification Databases? Protein Identifications Databases such as ProFound at Rockefeller University and Protein Prospector at the UCSF Mass Spectrometry Facility are used to help identify proteins found with proteomics techniques such as mass spectrometry. Digestion of proteins into peptide fragments allows each protein to break apart in a different way, resulting in a unique peptide fingerprint that can be used to identify the protein. The masses of these fragments as well as the molecular weights and isoelectric points are what is stored in many of these databases. This data can be used to perform high-throughput protein identification. #### The Future of Protein Identification Databases In order to continue advancing the cause of mapping the human proteome, international databases need to be established which integrate both transcriptome and proteome data. The Human Proteome Organization is currently working on establishing a defined standard for data submission and annotation for the many different proteomics techniques currently used to identify and annotate proteins. ### New Techniques in Image Analysis According to the Image Analysis Wikipedia page, \"Image analysis is the extraction of meaningful information from images.\" In terms of Proteomics, image analysis can be used to compare different images generated using proteomics techniques, such as 2D-PAGE gel images. New programs are being developed that will help to optomize and automate the process of locating a protein spot between two gel images in order to identify the differences between 2D-PAGE gels. Other programs can be used to help clean up and remove variability between these images as well. ## Laser Capture Microdissection !Diagram of Laser Capture Microdissection Laser capture microdissection or LCM is a process that isolates and removes distinct populations from a tissue. This will facilitate the comparison of diseased tissue with normal tissue from an organism. In LCM, an infrared laser beam melts a thermosensitive polymer film that traps a specific group of cells. This polymer film is then extracted and moved to a test tube where an extraction buffer is used to remove the groups of cells for more advanced proteomics analysis such as 2D-PAGE, Ion Chromatography, etc. This technology will become more useful as systems with higher sensitivity for analysis of smaller amounts of tissue become developed and realized. ## Proteomic Complex Detection using Sedimentation Approaches such as TAP tagging, which require the addition of fusion proteins, can interfere with protein interactions that would have normally occurred. Many times it takes a great deal of work to express these tagged proteins, so this technique is used to give evidence that there is a stable protein complex detected early on in the proteomics experiment before more laborious approaches are used to isolate and identify the protein complexes of interest. Issues also occur in MS and 2D Gel processes where one cannot be sure that a portion of a gel spot is the desired protein because multiple proteins could be traveling together in that spot as a complex. This is where proteomic complex detection using sedimentation (ProCoDeS) is applicable. ProCoDeS is a technique for the high-throughput identification of both soluble and membrane proteins that are found in stable complexes. Relative sizes of protein complexes are estimated via their sedimentation in a gradient. In this case a rate zonal gradient or RZG is used to better estimate the relative size of protein complexes. The distribution of a protein of interest in this sedimentation can be detected using classic techniques such as Western Blotting or newer techniques such as ICAT. This can be done for a large number of proteins. Thus, ProCoDeS can be used to identify stable protein complexes. ProCoDeS is especially well suited for the screening of unrefined cellular material to help find new proteins that cannot be discovered because they exist in protein complexes such as proteins found in protein membranes. Next Chapter: Protein Identification - Mass Spectrometry ## References 1. Hartman, N. T., et al. \"Proteomic Complex Detection Using Sedimentation\" Anal. Chem., 79, 5, 2078 - 2083, 2007. 2. NCT Proteomics Group \"Emerging Technologies\" National Institutes of Environmental Health Sciences 3. NCT Proteomics Group \"ProteoInformatics\" National Institutes of Environmental Health Sciences 4. \"Wikipedia: Image Analysis 5. \"Wikipedia: Proteomics 6. \"Wikipedia: X-ray Tomography
# Proteomics/Protein Identification - Mass Spectrometry \_\_NOEDITSECTION\_\_ \_\_NOTOC\_\_ ### `<font size=1 color=dimgray>`{=html}Presentation`</font>`{=html} ```{=html} <table height=1 border=1 style="border-collapse:collapse; border-color:LightSkyBlue; background-color:AliceBlue;" width="100%"> ``` ```{=html} <tr> ``` ```{=html} <td align=left> ``` ```{=html} <table width="100%" align=left> ``` ```{=html} <tr> ``` ```{=html} <td> ``` !Emerging and Miscellaneous Proteomics Technologies{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` ![](Gohome.png "Gohome.png"){width="" height="40"} ```{=html} </td> ``` ```{=html} <td nowrap> ``` `<font size=6 color=teal>`{=html}`</font>`{=html} ```{=html} </td> ``` ```{=html} <td> ``` !Protein Primary Structure{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td width="99%"> ```   ```{=html} </td> ``` ```{=html} <td> ``` ```{=html} <td> ``` !Protein Primary Structure{width="" height="40"} ```{=html} </td> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ```   !MALDI TOF MS ## Introduction - **Mass Spectrometry Overview** Mass spectrometry is a technique in which gas phase molecules are ionized and their mass-to-charge ratio is measured by observing acceleration differences of ions when an electric field is applied. Lighter ions will accelerate faster and be detected first. If the mass is measured with precision then the composition of the molecule can be identified. In the case of proteins, the sequence can be identified. Most samples submitted to mass Spectrometry are a mixture of compounds. A spectrum is acquired to give the mass-to-charge ratio of all compounds in the sample. Mass spectrometry is also known as \'mass spec\' or MS for short. Mass spectrometry throws light on molecular mechanisms within cellular systems. It is used for identifying proteins, functional interactions, and it further allows for determination of subunits. Other molecules in cells such as lipid components can also be defined. A mass spectrometer is composed of several different parts: a source that ionizes the sample, the analyzer that separates the ions based on mass-to-charge ratio, a detector that \"sees\" the ions, and a data system to process and analyze the results. You can also measure relative abundance of an ion using mass spectrometry. Different compounds have differential ionization capabilities and therefore intensity of your ion is not a direct correlation to concentration. Mass spectrometry can be a high throughput analytical method due to the ability for a mass spectrum to be measured rapidly and with minimal sample handling as compared to gel methods. It is an analytical method which has a variety of uses outside of proteomics, such as isotope and dating, trace gas analysis, atomic location mapping, pollutant detection, and space exploration - **History of Mass Spectrometry** The history of this technique finds its roots in the first studies of gas excitation in a charged environment, more than 100 years ago. This pioneering work led to the identification of two isotopes of neon (neon-20 and neon-22) via mass to charge ration discrimination by J.J Thomson in 1913. Over the next fifty years the fundamental basis of the technique was further developed. After the coupling of gas chromatography to Mass Spectroscopy in 1959 by researches at Dow Chemical, the full potential of the technique as a highly accurate, quantitative method for exploring compounds was realized, spurring a wave of developments which continue to the present day. The precision of mass spectrometry led to the discovery of isotopes. \ \***Implications of Mass Spectrometry for Proteomics Applications** The technique of mass spectrometry is a valuable tool in the field of proteomics. It can be used to identify proteins through variations of mass spectrometry techniques. The most common first approach to proteomics is a bottom-up approach in which the protein is digested by a protease, such a trypsin, and the peptides are then analyzed by peptide mass fingerprinting, collision-induced dissociation, tandem MS, and electron capture dissociation. Once the peptides masses have been determined the mass list can be sent to a database, such as MASCOT, where the list is compared to the masses of all known peptides. If enough peptides match that of a known protein you can identify your protein. If the masses of your peptides do not match a known protein you can sequence your peptide by de novo sequencing using MS/MS methods; where you isolate your peptide and break it along the peptide bond backbone forming y and b ions from which you can determine the sequence. The advantages of the bottom-up approach are that the small size of tryptic peptide ions is easy to handle biochemically than entire protein ions because of their relatively small masses that are easier to be determine. Beside bottom-up approach, another approach is top-down. In top-down approach, the complete proteins are directly analyzed by using mass spectrometer without solution digestion as bottom-up does. The advantages of the top-down approach are that it can sometime provide the complete coverage of the protein. But since whole proteins are hard to handle biochemically compared to small peptide pieces, it makes top-down approach difficult to analyze. Another use of mass spectrometry in proteomics is protein quantification. By labeling proteins with stable heavier isotopes you can in turn determine the relative abundance of proteins. Companies now produce kits, such as iTRAQ (Applied Biosystems), in order to do this at a high-throughput level. One of the most powerful ways to identify a biological molecule is to determine its molecular mass together with the masses of its component building blocks after fragmentation. There are two dominant methods for doing this. The first is electrospray ionization (ESI), in which the ions of interest are formed from solution by applying a high electric field. This is done by applying a high electric field to the tip of a capillary, from which the solution will pass through. The sample will be sprayed into the electric field along with a flow of nitrogen to promote desolvation. Droplets will form and will evaporate in a vacuumed area. This causes an increase in charge on the droplets and the ions are now said to be multiply charged. These multiply charged ions can now enter the analyzer. ESI is a method of choice because of the following properties: (1)The \"softness\" of the phase conversion process allows very fragile molecules to be ionized intact and even in some non-covalent interactions to be preserved for MS analysis. (2)The eluting fractions through liquid chromatography can then be sprayed into the mass spectrometer, allowing for the further analysis of mixtures. (3)The production of multiply charged ions allow for the measurement of high-mass biopolymers. Multiple charges on the molecule will reduce its mass to charge ratio when compared to a single charged molecule. Multiple charges on a molecule also allows for improved fragmentation which in turn allows for a better determination of structure. The second is matrix-assisted laser desorption/ionization (MALDI) in which the molecular ions of interest are formed by pulses of laser light impacting on the sample isolated within an excess of matrix molecules. This enables the determination of masses of large biomolecules and synthetic polymers greater than 200,000 Daltons without degradation of the molecule of interest. The advantages of MALDI are its robustness, high speed, and relative immunity to contaminants and biochemical buffers. A type of mass spectrometer often used with MALD is TOF or Time of Flight mass spectrometry. This enables fast and accurate molar mass determination along with sequencing repeated units and recognizing polymer additives and impurities. This technique is based on an ultraviolet absorbing matrix where the matrix and polymer are mixed together along with excess matrix and a solvent to prevent aggregation of the polymer. This mixture is then placed on the tip of a probe; then the solvent is removed while under vacuum conditions. This creates co-crystallized polymer molecules that are dispersed homogeneously within the matrix. A pulsing laser beam is set to an appropriate frequency and energy is shot to the matrix, which becomes partially vaporized. In turn the homogeneously dispersed polymer within the matrix is carried into the vapor phase and becomes charged. To obtain a superb signal-to-noise ratio, multiple laser shots are executed. The shapes of the peaks are improved and the molar masses determined are more accurate. Fianlly, in the TOF analyzer the molecules from a sample are imparted identical translational kinetic energies because of the electrical potential energy difference. These ionic molecules travel down an evacuated tube with no electrical field and of the same distance. The smallest ions arrive first at the detector, which produces a signal for each ion. The cumulative data from multiple laser shots yield a TOF mass spectrum, which translates the detector signal into a function of time, which in turn can be used to calculate the mass of the ion. In addition to these ionization techniques, highly powerful mass analyzers have been developed. These analyzers measure the mass/charge ratio of intact ionized biomolecules, as well as their fragmentation spectra, with high accuracy and high speed. The measurement of fragmentation spectra is called tandem MS or MS/MS. In conjunction with single stage MS (with intact precursor ions) tandem MS can be utilized to help elucidate a protein since the problem of elucidation will reduce to assembling the puzzle pieces of the fragmented protein. ## References 1. American Society for Mass Spectrometry - What is MS?, <http://www.asms.org/whatisms/p4.html> 2. Mass Spectrometry in the Postgenomic Era 3. Annual Review of Biochemistry Vol. 80: 239-246 (Volume publication date July 2011) DOI: 10.1146/annurev-biochem-110810-095744 <https://ted.ucsd.edu/webapps/portal/frameset.jsp?tab_tab_group_id=_2_1&url=%2Fwebapps%2Fblackboard%2Fexecute%2Flauncher%3Ftype%3DCourse%26id%3D_767_1%26url%3D> 4. University of Illinois at Urbana-Champaign School of Chemical Sciences <http://scs.illinois.edu/massSpec/ion/esi.php> 5. University of Southern Mississippi School of Polymers and High Performance Materials <http://www.psrc.usm.edu/mauritz/maldi.html> fr:Chimie organique/Spectrométrie de masse
# Proteomics/Protein Primary Structure \_\_NOEDITSECTION\_\_ \_\_NOTOC\_\_ ### `<font size=1 color=dimgray>`{=html}Presentation`</font>`{=html} ```{=html} <table height=1 border=1 style="border-collapse:collapse; border-color:LightSkyBlue; background-color:AliceBlue;" width="100%"> ``` ```{=html} <tr> ``` ```{=html} <td align=left> ``` ```{=html} <table width="100%" align=left> ``` ```{=html} <tr> ``` ```{=html} <td> ``` !Protein Identification - Mass Spectrometry{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` ![](Gohome.png "Gohome.png"){width="" height="40"} ```{=html} </td> ``` ```{=html} <td nowrap> ``` `<font size=6 color=teal>`{=html}`</font>`{=html} ```{=html} </td> ``` ```{=html} <td> ``` !Post-translational Modification{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td width="99%"> ```   ```{=html} </td> ``` ```{=html} <td> ``` ```{=html} <td> ``` !Post-translational Modification{width="" height="40"} ```{=html} </td> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ```   ## Introduction                                                                                    
# Proteomics/Post-translational Modification \_\_NOEDITSECTION\_\_ \_\_NOTOC\_\_ ### `<font size=1 color=dimgray>`{=html}Presentation`</font>`{=html} ```{=html} <table height=1 border=1 style="border-collapse:collapse; border-color:LightSkyBlue; background-color:AliceBlue;" width="100%"> ``` ```{=html} <tr> ``` ```{=html} <td align=left> ``` ```{=html} <table width="100%" align=left> ``` ```{=html} <tr> ``` ```{=html} <td> ``` !Protein Primary Structure{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` ![](Gohome.png "Gohome.png"){width="" height="40"} ```{=html} </td> ``` ```{=html} <td nowrap> ``` `<font size=6 color=teal>`{=html}`</font>`{=html} ```{=html} </td> ``` ```{=html} <td> ``` !Protein - Protein Interactions{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td width="99%"> ```   ```{=html} </td> ``` ```{=html} <td> ``` ```{=html} <td> ``` !Protein - Protein Interactions{width="" height="40"} ```{=html} </td> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ```   ## Introduction I. Definition `    A. Spontaneous or enzymatic alteration to one or more of a protein's amino acids`\ `    B. Most often manifests as an addition or deletion to a side-chain`\ `    C. Can occur at any point during or following full translation of a protein`\ `    D. Often drastically effects overall structure and function of protein and associated complexes`\ `    E. Are highly conserved among all living organisms` II\. Types of modifications `    A. Acetylation`\ `    B. Amidation/Deamidation`\ `    C. Glycosylation`\ `    D. Oxidation`\ `         i. S-Glutathionylation`\ `         ii. S-Nitrosylation`\ `    E. Phosphorylation`\ `         i. Histidine`\ `         ii. Serine`\ `         iii. Theronine`\ `         iv. Tyrosine`\ `    F. Proteolysis`\ `    G. Ubiquitinylation/SUMOylation`\ `    H. Others?` III\. Manipulating in-vivo modifications `    A. Modifications can be prevented or induced in organism, tissue, and cell based model systems`\ `    B. May allow for the detection of target proteins or dissection of related processes and pathways`\ `    C. Exogenous introduction of stimuli`\ `         i. endocrine/paracrine signals (aka hormones)`\ `         ii. environmental (temp, UV, heavy-metals, peroxide, etc.)`\ `         iii. antigens (virus, bacteria, allergens, lysates, etc.)`\ `         iv. chemical/medicinal activators and inhibitors`\ `    D. Genetic Approaches`\ `         i. deletion, mutation, or reorganization of genetic elements (enhancers, promoters, genes, etc.)`\ `         ii. gene inactivation or silencing by nucleic acid hybridization`\ `         iii. transgenics (tansformations and transfections)`\ `    E. Advantages and Draw-backs`\ `         i. Qualitative but often hard to quantify`\ `         ii. Often expolaratory in nature (observe and report)`\ `         iii. Often very large scale in terms of available data` IV\. In vitro reconstitution strategies `    A. Often provide a more quantitative, in depth analysis of a particular post-translational modification`\ `    B. The protein in question is added to a reaction with the appropriate reagents and/or enzymes`\ `    C. Reactions can be followed in real-time more readily` V. Methods of detection `    A. Most commonly used detection method of known modifications is through immuno/Western blotting`\ `    B. Unexpected or novel modifications can be detected with a variety of analytical techniques, most notably mass spectrometry`\ `    C. The best specific method of detection depends on many factors including the stability, frequency, and scale of the modification(s)`\ `    D. In practice ease and cost dictate which methods are used first while the more exhaustive, cumbersome, or expensive methods follow as needed`
# Proteomics/Protein - Protein Interactions \_\_NOEDITSECTION\_\_ \_\_NOTOC\_\_ ### `<font size=1 color=dimgray>`{=html}Presentation`</font>`{=html} ```{=html} <table height=1 border=1 style="border-collapse:collapse; border-color:LightSkyBlue; background-color:AliceBlue;" width="100%"> ``` ```{=html} <tr> ``` ```{=html} <td align=left> ``` ```{=html} <table width="100%" align=left> ``` ```{=html} <tr> ``` ```{=html} <td> ``` !Post-translational Modification{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` ![](Gohome.png "Gohome.png"){width="" height="40"} ```{=html} </td> ``` ```{=html} <td nowrap> ``` `<font size=6 color=teal>`{=html}`</font>`{=html} ```{=html} </td> ``` ```{=html} <td> ``` !Protein Chips{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td width="99%"> ```   ```{=html} </td> ``` ```{=html} <td> ``` ```{=html} <td> ``` !Protein Chips{width="" height="40"} ```{=html} </td> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ```   Chapter edited and updated by: Poulami Barman and Sarah Allen Contact pxb2979@rit.edu, sea3016@rit.edu ## Introduction Protein interaction is crucial for every organism. Most proteins function through interaction with other molecules, and often with other proteins. Enzymes interact with their substrates, inhibitors interact with enzymes, transport proteins interact with structural proteins, hormones interact with receptors -- and that's just a few of the interactions that happen in a cell. Some proteins are composed of more than one polypeptide chain, and the interactions between the different peptides are necessary for the whole protein to function. Since they are so essential, protein-protein interactions are an important topic for scientists to understand. There are many characteristics of a protein-protein interaction that are important. Obviously, it is important to know **which proteins are interacting**. In many experiments and computational studies, the focus is on interactions between two different proteins. However, you can have one protein interacting with other copies of itself (oligomerization), or three or more different proteins interacting. The **stoichiometry** of the interaction is also important -- that is, how many of each protein involved are present in a given reaction. Some protein interactions are stronger than others, because they bind together more tightly. The strength of binding is known as **affinity**. Proteins will only bind each other spontaneously if it is energetically favorable. **Energy** changes during binding are another important aspect of protein interactions. Many of the computational tools that predict interactions are based on the energy of interactions. In recent years there has been a strong focus on predicting protein interactions computationally. Predicting the interactions can help scientists predict pathways in the cell, potential drugs and antibiotics, and protein functions. However, it has been an ongoing challenge to decipher those interactions. Proteins are large molecules, and binding between them often involves many atoms and a variety of interaction types, including hydrogen bonds, hydrophobic interactions, salt bridges, and more. Proteins are also dynamic, with many of their bonds able to stretch and rotate leading to different conformations. Therefore, predicting protein-protein interactions requires a good knowledge of the chemistry and physics involved in the interactions. This chapter discusses the characteristics of protein-protein interactions, how they are determined experimentally, and how they are predicted computationally. It also contains a list of databases where you can explore known and predicted protein interactions. The links above will lead you to the various sections.
# Proteomics/Protein Chips \_\_NOEDITSECTION\_\_ \_\_NOTOC\_\_ ### `<font size=1 color=dimgray>`{=html}Presentation`</font>`{=html} ```{=html} <table height=1 border=1 style="border-collapse:collapse; border-color:LightSkyBlue; background-color:AliceBlue;" width="100%"> ``` ```{=html} <tr> ``` ```{=html} <td align=left> ``` ```{=html} <table width="100%" align=left> ``` ```{=html} <tr> ``` ```{=html} <td> ``` !Protein - Protein Interactions{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` ![](Gohome.png "Gohome.png"){width="" height="40"} ```{=html} </td> ``` ```{=html} <td nowrap> ``` `<font size=6 color=teal>`{=html}`</font>`{=html} ```{=html} </td> ``` ```{=html} <td> ``` !Proteomics and Drug Discovery{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td width="99%"> ```   ```{=html} </td> ``` ```{=html} <td> ``` ```{=html} <td> ``` !Proteomics and Drug Discovery{width="" height="40"} ```{=html} </td> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ```   **Introduction:** \_\_TOC\_\_ ## Introduction !A DNA microarray as seen through a microscope. Protein chips look identical, except each spot corresponds to one of the organism\'s thousands of proteins, instead of one of it\'s genes. The intensity of the dot indicates the amount of protein present. Protein chips, also referred to as protein arrays or protein microarrays, are modeled after DNA microarrays. The success of DNA microarrays in large-scale genomic experiments inspired researchers to develop similar technology to enable large-scale, high-throughput proteomic experiments. Protein chips enable researchers to quickly and easily survey the entire proteome of a cell within an organism. They also allow researchers to automate and parallelize protein experiments. Protein chips were first developed in 2000 by researchers at Harvard University.[^1] Today there are many companies manufacturing protein chips using many types of techniques including spotting and gel methods. The types of protein chips available include \"lab on a chip\", antibody arrays and antigen arrays, as well as a wide range of chips containing \"alternative capture agents\" such as proteins, substrates and nucleic acids. Analysis of protein chips comes with many challenges including dynamic protein concentrations, the sheer number of proteins in a cell\'s proteome, and the understanding of the probes for each protein. Steps include the reading of the protein levels off the chip, and then the use of computer software to analyze the massive amounts of data collected. Applications of protein chip experiments include identifying biomarkers for diseases, investigating protein-protein interactions, and testing for the presence of antibodies in a sample. Protein chips have applications in cancer research, medical diagnostics, homeland security and proteomics. This chapter will demonstrate why protein chips are changing the face of proteomics, and why they will have an even larger impact in the future. ## History ### Nucleic Acid Microarrays The use of microarrays for gene expression profiling was first published in 1995.[^2] This technology allowed scientists to analyze thousands of mRNAs in a single experiment to determine whether expression is different in disease states. Unfortunately, mRNA levels within a cell are often poorly correlated with actual protein abundance.[^3] This can be due to many factors including degradation rate of mRNA versus proteins and post-transcriptional controls and modifications. Measuring the amount of protein directly would bypass any mRNA inconsistencies and give a true level of gene function, however traditional protein characterization methods were slow and cumbersome. These combined factors were the impetus behind the creation of protein chips. ### Deficiency of Traditional Protein Characterization Methods !A liquid chromatography / mass spectrometry (LC/MS) instrument. This technique is low throughput compared to protein chips because protein chips can test for thousands of proteins on a single chip in a single experiment. instrument. This technique is low throughput compared to protein chips because protein chips can test for thousands of proteins on a single chip in a single experiment.") Before the advent of protein chips, protein measuring and characterization was done using two different methods: 2D gel electrophoresis coupled with mass spectrometry, and liquid chromatography. These methods can separate and visualize a large number of proteins per experiment, however they are time consuming when compared to protein chips. Their process is very low-throughput because of lack of automation. Reproducibility is also a factor because of the large amount of sample handling. A better, more standardized, higher-throughput method needed to be invented for protein measuring and characterization. ### Protein Chip Precursors to Modern Day !The equipment and reagents used in an Enzyme-linked Immunosorbent Assay (ELISA), a precursor of protein chips., a precursor of protein chips.") Immunoassays, the precursor to protein chips available since the 1980s, exploit the interactions between antibodies and antigens in order to detect their concentrations in biological samples. Their creation, however, is tedious and expensive. As a response to this, researchers at Harvard University combined the technologies of immunoassays and DNA microarrays to develop the protein chip.[^4] In their landmark paper, published in 2000, \"Printing Proteins as Microarrays for High-Throughput Function Determination,\" Gavin MacBeath and Stuart Schreiber described how to create protein chips and demonstrated three types of applications that would benefit from this new technology. The strengths of their approach were the use of readily available materials (i.e. glass slides, polyacrylamide gel), the relative ease of implementation (robotic microarray printers), and compatibility with standard instrumentation. Within the past five years, many companies, including Biacore, Invitrogen, and Sigma-Aldrich, have begun production of industrial level protein array systems that can be used for drug discovery and basic biological research. Commercial entities have made protein chip research a streamlined and standardized process on the same level as DNA microarrays compared to its inception in 2000. Academic research plays a huge role in the development and improvement of these technologies. The collaboration of academic research with systems such as the Affymetrix GeneChip and the Human Genome Initiative has allowed for friendly competition, resulting in the advancement of technologies. With more develops come a better understanding and encourages even more research towards these fields. Affymetrix is a company that has been manufactures microarrays, named GeneChip, since 1992. They have 13 locations across the world with headquarters located in the US (California), UK, Japan, and China.[^5] Next section: Manufacture ## References ```{=html} <references/> ``` Chapter written by: Jonathan Keeling and Eric Foster\ Contact jwk3970@rit.edu, edf3480@rit.edu, ttl5439@rit.edu\ [^1]: MacBeath G, Schreiber S. (2000). Printing Proteins as Microarrays for High-Throughput Function Determination. Science. Sep 08; 289 (5485): 1760-1764. [^2]: Schena M, Shalon D, Davis RW, Brown PO. (1995). Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science. Oct 20; 270 (5235): 467-70. [^3]: Gygi SP, Rochon Y, Franza B, Abersold R: Correlation between protein and mRNA abundance in yeast. Mol. Cell Biol. 19, 1720-1730 (1999). [^4]: MacBeath G, Schreiber S. (2000). Printing Proteins as Microarrays for High-Throughput Function Determination. Science. Sep 08; 289 (5485): 1760-1764. [^5]: \"Affymetrix.\" Wikipedia, The Free Encyclopedia. 5 Feb 2007, 03:19 UTC. Wikimedia Foundation, Inc. Apr 2008 \<<http://en.wikipedia.org/wiki/Affymetrix>\>
# Proteomics/Biomarkers \_\_NOEDITSECTION\_\_ \_\_NOTOC\_\_ ### `<font size=1 color=dimgray>`{=html}Presentation`</font>`{=html} ```{=html} <table height=1 border=1 style="border-collapse:collapse; border-color:LightSkyBlue; background-color:AliceBlue;" width="100%"> ``` ```{=html} <tr> ``` ```{=html} <td align=left> ``` ```{=html} <table width="100%" align=left> ``` ```{=html} <tr> ``` ```{=html} <td> ``` !Proteomics and Drug Discovery{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` ![](Gohome.png "Gohome.png"){width="" height="40"} ```{=html} </td> ``` ```{=html} <td nowrap> ``` `<font size=6 color=teal>`{=html}`</font>`{=html} ```{=html} </td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td width="99%"> ```   ```{=html} </td> ``` ```{=html} <td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ```   ### Mass spectrometry based targeted protein quantification: methods and applications !Cross section of triple Q{width="250"} ### Main Focus The main focus of the paper was a review of the methods and applications of using mass spectrometry to quantify proteins, especially those that are in a concentration of less than µg/ml concentrations, in an attempt to universalize a procedure. ### New terms MALDI TOF/TOF: matrix assisted laser desorption/ionization time-of-flight tandem mass spectrometer. ```{=html} <!-- --> ``` Selected reaction monitoring (SRM): method in which a specific product ion from a specific parent ion is detected. All other ions with masses not specified in a predetermined range are filtered away leaving only ions with the mass in the range we are looking for. (source <http://en.wikipedia.org/wiki/Mass_chromatogram#Selected_reaction_monitoring_.28SRM.29>) ```{=html} <!-- --> ``` Triple quadrupole: type of MS that contains a linear series of three quadrupoles. The first and third set act as mass filters, and the second is a collision cell. This type of MS can "filter" an ion of a known mass. (source <http://en.wikipedia.org/wiki/Quadrupole_mass_analyzer>) ```{=html} <!-- --> ``` Hydrazide: class of organic compounds that share a common functional group characterized by a N-N covalent bond with one of the constituents being an acyl group. (source <http://en.wikipedia.org/wiki/Hydrazide>) ```{=html} <!-- --> ``` Biomarker: biochemical feature that can be used to measure progress of the effects of treatment or a disease. (source <http://www.medterms.com/script/main/art.asp?articlekey=6685>) For this summary, we will focus on protein biomarkers. Some diseases which have protein biomarkers that show promise as a screening tool are breast cancer, Alzheimer\'s, leukemia, ALS, and Parkinson\'s [^1]. A series of six steps must be accomplished in order to successfully validate a biomarker or set of biomakers: discovery, qualification, verification, assay optimization, validation and commercialization[^2]. Once a biomarker is found and accepted, it can be used to possibly predict and prevent the disease it\'s related to. The summary below focuses on the quantification method of proteins in the search for and identification of protein biomarkers. By finding ways in which to universally quantify proteins, one can search for all biomarkers in one screening rather than multiple screenings, once conclusive biomarkers are identified. ### Summary With the recent breakthroughs in technology, it is conceivable that is possible to have a "universal" method or approach with minimal restrictions to quantitatively assay a wide number of proteins in search of potential biomarkers. Once a few potential biomarkers are discovered, further research can be done to confirm or refute its use in clinical applications. Another goal is to easily accumulate multiple detections in a single measurement. Measurements are taken by identifying synthetically stable isotopes attached to their respective proteins or peptides. Each isotope mimics the peptide's endogenous counterparts allowing high selectivity. Mass spectrometry (MS) provides us with a powerful tool to compare two different protein samples. It can be used for comparing the proteome of a diseased sample against a normal sample at a global scale. This is applied to a wide array of human diseases, with the hope that it will lead to identification of biomarkers or even pathogenesis of a disease. Traditionally, ELISA (enzyme-linked immunosorbent assay) has been the major method for the quantification of proteins with good sensitivity. Even today, it is the "gold standard" for targeted protein quantification. The major drawback with ELISA is the lack of availability of antibodies with high specificity. First attempts to determine the amount of specific proteins were done using stable isotope dilution methods and MS approximately 20 years ago, starting with atom bombardment MS and deuterium-labeled synthetic polypeptides. Advances in MS instrumentation has increased our ability to detect candidate proteins in complicated biological samples with high sensitivity. To quantify the results, introduction of a stable isotope (containing ^13^C or ^15^N, for example) to selected amino acids in a reference peptide sequence provides a peptide with the same physicochemical properties, that can be readily distinguished by MS from the peptide in the target tissue or fluid. Studies have shown that full-length proteins with stable isotopes can be used in quantification of biomarkers in urine and water samples with nanomolar and picomolar level sensitivities respectively. There is a variety of MS platforms used for quantitative proteomics, some of which are triple quadrupole (triple Q), matrix assisted laser desorption/ionization time-of-flight tandem mass spectrometer (MALDI TOF/TOF), electrospray ionization (ESI) based on QTOF MS, and an ion trap instrument using selective ion monitoring (SIM) mode. The most popular of the platforms above is the triple Q. Demonstrations have shown that it can multiplex and simultaneously target more than 50 peptides for quantification in plasma in a single measurement. For targeted quantitative analysis, coupling liquid chromatography with MALDI greatly enhances the performance of MALDI bases MS. Some advantages of this application include the ability of the techniques to be performed in parallel with each other, it can be made a highly selective, data-driven procedure, and the preservation of the sample to some degree for repeat analysis. This technique is also highlighted by its potential high throughput and excellent resolution. One of the most important steps in quantification is sample preparation which greatly influences sensitivity. One of the most common steps used is the depletion of highly abundant proteins making it easier to enhance analytical dynamic range and the detection of proteins in low concentrations. One of the techniques performed is strong-cation exchange chromatography (SCX) which has shown to give the ability to detect peptides in the high pg/ml level, giving a 100-fold improvement over direct plasma analysis. Post-translational modification (PTM) is an important process to understand since it is often involved in tumor progression, but can be a problem to mimic due to the complexity and structure of the sugar chains (as in glycosylation PTM). One experiment extracted N-linked glycopeptides and de-glycosylated. This resulted in the conversion of Asn to Asp and a difference in mass. This was utilized to make a synthetic polypeptide to replicate an N-linked glycopeptide in its glycosylated form. Once of the main features of MS based quantification is for clinical applications used to identify biomarkers associated with diseases. For example, 177 protein candidates associated with stroke and cardiovascular disease in plasma have been proposed. Some biomarkers affiliated with stroke are S-100b, B-type neurotrophic growth factor, von Willebrand factor and monocyte chemotactic protein-1[^3]. Other biomarkers have been proposed to rheumatoid arthritis and breast cancer among others. One of the main goals of the ability to quantify proteins and peptides is for personalized medicine. As technology advances, we will be able to create techniques that easily assemble multiples detection in a single measurement. Biomarkers from diseases can also be multiplexed in a single assay, allowing us to possibly diagnose multiple diseases. Ideally, a single-step preparation strategy is key, allowing for high throughput and possible an automated process, reducing the amount of human interaction and the chance of human error. ### Relevance to Proteomics Course The ability to quantify proteins using mass spectrometry is a great tool to compare a large number of proteins from a control sample with a test sample in search of biomarkers. When a noticeable difference is detected, further studies can be performed on those proteins. Major breakthroughs in MS technology give us the capability to universally approach developments to quantify a wide spectrum of proteins with little restriction. It also gives us the ability to make more detections per measurement. In the future, these approaches can give way to personal medicine giving us the ability to screen individuals by detecting multiple biomarkers from a single or multiple diseases. ### References \[1\] Pharmaceutical Outsourcing Decisions. SPG Media Limited. (http://www.pharmaceuticaloutsourcing.com/articles/pod003_014_power3.htm) \[2\] Rifai, Nader, Gillette, Michael A., and Carr, Steven A. \"Protein biomarker discovery and validation: the long and uncertain path to clinical utility\". Nature Biotechnology 24, 971 - 983 (2006) (http://www.nature.com/nbt/journal/v24/n8/abs/nbt1235.html) \[3\] Reynolds, Mark A., et al. \"Early Biomarkers of Stroke\". Clinical Chemistry 49 (2003): 1733-1739. Print. (http://www.clinchem.org/cgi/content/abstract/49/10/1733) [^1]: [^2]: [^3]:
# Proteomics/Experimental Protocols \_\_NOEDITSECTION\_\_ \_\_NOTOC\_\_ ### `<font size=1 color=dimgray>`{=html}Presentation`</font>`{=html} ```{=html} <table height=1 border=1 style="border-collapse:collapse; border-color:LightSkyBlue; background-color:AliceBlue;" width="100%"> ``` ```{=html} <tr> ``` ```{=html} <td align=left> ``` ```{=html} <table width="100%" align=left> ``` ```{=html} <tr> ``` ```{=html} <td> ``` !Protein Sample Preparation{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` ![](Gohome.png "Gohome.png"){width="" height="40"} ```{=html} </td> ``` ```{=html} <td nowrap> ``` `<font size=6 color=teal>`{=html}`</font>`{=html} ```{=html} </td> ``` ```{=html} <td> ``` !Protein Separations - Chromatography{width="" height="40"} ```{=html} </td> ``` ```{=html} <td> ``` !List of Topics{width="" height="40"} ```{=html} </td> ``` ```{=html} <td width="99%"> ```   ```{=html} </td> ``` ```{=html} <td> ``` ```{=html} <td> ``` !Protein Separations - Chromatography{width="" height="40"} ```{=html} </td> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ```   This page contains protocols that are frequently used in proteomics. You are welcome to add protocols this chapter. 1. /Plant Proteomics about Two Dimensional Gel Electrophoresis/                                                                    
# Human Physiology/Physiology Introduction **Physiology** The word *physiology* is from the Ancient Greek φυσιολογία (*phusiología*, \"natural philosophy\") and it is the study of how organisms perform their vital functions. An example is the study of how a muscle contracts or the force contracting muscles exert on the skeleton. It was introduced by French physician Jean Fernery in 1552. Physiology is built upon a tripod of sciences: physics, chemistry, and anatomy. ## Types of human physiology Human physiology is the study of functions of the human body that can be divided into the following types: **Cell physiology**. This is the cornerstone of human physiology; it is the study of the functions of cells. **Special physiology** This is the study of the functions of specific organs. For example, renal physiology is the study of kidney function. **Systemic physiology** It includes all aspects of the function of the body systems, such as cardiovascular physiology, respiratory physiology, reproductive physiology etc.. **Pathophysiology** It is the study of the effects of diseases on organ or system functions (pathos is the Greek word for disease). ## Levels of organization **Atom:** An atom is the smallest particle of an element or a molecule. \[carbon (C), Hydrogen (H), Oxygen (O), etc.\]. **Molecule:** A molecule is a particle composed of two or more joined atoms (carbon dioxide CO2, water H2O). **Macromolecule:** A macromolecule is a large molecule (carbohydrates, lipids, proteins, nucleic acids). **Organelles:** An organelle is a small organ of a cell, which performs a particular function (cell membrane, cytoplasm and nucleus) **Cell:** The cell is the basic unit of structure and function of living organisms. **Tissue:** A tissue is a group of similar cells that perform a specialized function (epithelia, connective, muscle and nervous). **Organ:** An organ is a structure consisting of a group of tissues that perform a specialized function (skin, heart, brain, etc.). **System:** A system is a group of organs that act together to perform a specialized function. 1 . cardiovascular system 2 . respiratory system 3 . urinary system 4 . digestive system 5.nervous system 6.reproductive system 7.endocrine system 8 . musculoskeletal system 9.integument system. **Human body:** A living organism is the most complex level of organization. It consists of all the systems arranged in a discrete manner so as to facilitate functioning of the various organ systems in synchronicity. **The seven characteristics of life** 1\. **Cells:** All living organisms have cells; cells are the building blocks of life. 2\. **Metabolism:** All living organisms eat, drink, breathe and excrete. 3\. **Growth:** All living organisms take in material from the environment to enlarge and sustain. 4\. **Reproduction:** All living organisms are able to produce a copy of themselves. 5\. **Irritability:** All living organisms are able to react to a change in their environment. 6\. **Adaptation:** All living organisms are able to compete with each other for food and space to survive. 7\. **Movement:** All living organisms are able to move. ## Cell physiology The cell is the basic unit of all living organisms. The cell is the functional unit of an organism. Cells are not all the same but all cells share general structures. Cells are organized into three main regions: Nucleus, cytoplasm and plasma membrane. **1) The nucleus :** It is the center of the cell because it contains genetic material (DNA). It consists of three main regions: the nuclear membrane, the nucleolus and chromatin. - **Nuclear membrane :** Nuclear membrane serves as a barrier of nucleus. It consists of a double phospholipid membrane and contains nuclear pores that allow for the exchange of material with the rest of the cell. - **Nucleolus :** Nucleus contains one or more nucleoli. It functions as a site of ribosome production. Ribosomes then migrate to the cytoplasm through nuclear pores. ```{=html} <!-- --> ``` - **Chromatin :** It is composed of DNA and protein scattered throughout the nucleus. Chromatin condenses to form chromosomes when the cell divides. **2) Plasma membrane :** It is the barrier for cell contents. It consists of double phospholipid layer and monolayer of protein scattered around phospholipid layer. Other materials in the plasma membrane include cholesterol and glycoproteins. **3) Cytoplasm :** It is a thick jelly like fluid. It represents the material outside the nucleus and inside the plasma membrane. It consists of Cytosol. - **Cytosol**: It is a fluid that suspends other elements - organelles. ```{=html} <!-- --> ``` - **Organelles:** That perform the metabolic activity of the cell. ```{=html} <!-- --> ``` - **Cytoplasmic organelles :** These are the organelles which are present scattered into the cytoplasm and performs specific functions. These are as follows:- - **Ribosomes :** They represent sites of protein synthesis in the cell. They are found at two locations : Free in the cytoplasm and attached to endoplasmic reticulum. ```{=html} <!-- --> ``` - **Endoplasmic reticulum (ER) :** They are fluid-filled tubules for carrying substances. There are two types of ER : ```{=html} <!-- --> ``` - **Rough endoplasmic reticulum :** They carry ribosomes that represent sites of protein synthesis. ```{=html} <!-- --> ``` - **Smooth endoplasmic reticulum :** They function in cholesterol synthesis and breakdown, fat metabolism, and detoxification of drugs. ```{=html} <!-- --> ``` - **Golgi apparatus :** It modifies and packages proteins, secretes vesicles, plasma membrane components and lysosomes. ```{=html} <!-- --> ``` - **Lysosomes :** They contain enzymes that digest non-usable materials within the cell. ```{=html} <!-- --> ``` - **Peroxisomes :** These are membranous sacs of oxidase enzymes. They detoxify harmful substances and break down free radicals. ```{=html} <!-- --> ``` - **Mitochondria :** The powerhouse of the cell (cells often have multiple mitochondria). They can change shape continuously. They also carry out reactions where oxygen is used to break down food to provide ATP for cellular activities. ```{=html} <!-- --> ``` - **Centrosome** : The centrosome is composed of two centrioles surrounded by an amorphous mass of protein. Centrosomes are associated with the nuclear membrane during prophase of the cell cycle. In mitosis the nuclear membrane breaks down and the centrosome can interact with the chromosomes to build the mitotic spindles. - **Centrioles :** These are self-replicating organelles made up of nine bundles of microtubules. They appear to help in organizing cell division, but aren\'t essential to the process. - **Cytoskeleton :** It\'s a network of protein structures that extend throughout the cytoplasm. It provides the cell with an internal framework. For example, microfilaments and microtubules. - **a-Microfilaments :** Microfilaments are solid rods made of proteins called actin. These filaments are important supports of the cytoskeleton. ```{=html} <!-- --> ``` - **b-Microtubules :** These straight, hollow cylinders are found throughout the cytoplasm of all human cells and carry out a variety of functions, ranging from transport to structural support. Cell membrane is made up of lipids, proteins and carbohydrates.
# Human Physiology/Homeostasis ## Overview The human organism consists of trillions of cells all working together for the maintenance of the entire organism. While cells may perform very different functions, all the cells are quite similar in their metabolic requirements. Maintaining a constant internal environment with all that the cells need to survive (oxygen, glucose, mineral ions, waste removal, and so forth) is necessary for the well-being of individual cells and the well-being of the entire body. The varied processes by which the body regulates its internal environment are collectively referred to as homeostasis. ### What is Homeostasis? **Homeostasis** in a general sense refers to stability or balance in a system. It is the body\'s attempt to maintain a constant internal environment. Maintaining a stable internal environment requires constant monitoring and adjustments as conditions change. This adjusting of physiological systems within the body is called *homeostatic regulation*. Homeostatic regulation involves three parts or mechanisms: 1) the ***receptor***, 2) the***control center***and 3) the***effector***. The ***receptor***receives information that something in the environment is changing. The***control center***or***integration center***receives and processes information from the***receptor***. And lastly, the***effector***responds to the commands of the***control center*** by either opposing or enhancing the stimulus. This is an ongoing process that continually works to restore and maintain homeostasis. For example, in regulating body temperature there are temperature *receptors* in the skin, which communicate information to the brain, which is the *control center,* and the *effector* is our blood vessels and sweat glands in our skin. Because the internal and external environments of the body are constantly changing and adjustments must be made continuously to stay at or near the set point, homeostasis can be thought of as a *synthetic equilibrium.* Since homeostasis is an attempt to maintain the internal conditions of an environment by limiting fluctuations, it must involve a series of negative feedback loops. ### Positive and Negative Feedback When a change of variable occurs, there are two main types of feedback to which the system reacts: - ***Negative feedback***: a reaction in which the system responds in such a way as to reverse the direction of change. Since this tends to keep things constant, it allows the maintenance of homeostasis. For instance, when the concentration of carbon dioxide in the human body increases, the lungs are signaled to increase their activity and expel more carbon dioxide. Thermoregulation is another example of negative feedback. When body temperature rises, receptors in the skin and the hypothalamus sense a change, triggering a command from the brain. This command, in turn, effects the correct response, in this case a decrease in body temperature. : : **Home Heating System Vs. Negative Feedback**\'\' : When you are at home, you set your thermostat to a desired temperature. Let\'s say today you set it at 70 degrees. The thermometer in the thermostat waits to sense a temperature change either too high above or too far below the 70 degree set point. When this change happens the thermometer will send a message to to the \"Control Center\", or thermostat,which in turn will then send a message to the furnace to either shut off if the temperature is too high or kick back on if the temperature is too low. In the home-heating example the air temperature is the \"NEGATIVE FEEDBACK.\" When the Control Center receives negative feedback it triggers a chain reaction in order to maintain room temperature. - ***Positive feedback***: a response is to amplify the change in the variable. This has a destabilizing effect, so does not result in homeostasis. Positive feedback is less common in naturally occurring systems than negative feedback, but it has its applications. For example, in nerves, a threshold electric potential triggers the generation of a much larger action potential. Blood clotting in which the platelets process mechanisms to transform blood liquid to solidify is an example of positive feedback loop. Another example is the secretion of oxytocin which provides a pathway for the uterus to contract, leading to child birth. : : **Harmful Positive Feedback** : Although Positive Feedback is needed within Homeostasis it also can be harmful at times. When you have a high fever it causes a metabolic change that can push the fever higher and higher. In rare occurrences the body temperature reaches 113 degrees Fahrenheit / 45 degrees Celsius and the cellular proteins stop working and the metabolism stops, resulting in death. **Summary**: Sustainable systems require combinations of both kinds of feedback. Generally with the recognition of divergence from the homeostatic condition, positive feedbacks are called into play, whereas once the homeostatic condition is approached, negative feedback is used for \"fine tuning\" responses. This creates a situation of \"metastability,\" in which homeostatic conditions are maintained within fixed limits, but once these limits are exceeded, the system can shift wildly to a wholly new (and possibly less desirable) situation of homeostasis. ***Homeostatic systems have several properties*** - They are ultra-stable, meaning the system is capable of testing which way its variables should be adjusted. - Their whole organization (internal, structural, and functional) contributes to the maintenance of balance. - Physiology is largely a study of processes related to homeostasis. Some of the functions you will learn about in this book are not specifically about homeostasis (e.g. how muscles contract), but in order for all bodily processes to function there must be a suitable internal environment. Homeostasis is, therefore, a fitting framework for the introductory study of physiology. ***Where did the term \"Homeostasis\" come from?*** The concept of homeostasis was first articulated by the French scientist Claude Bernard (1813-1878) in his studies of the maintenance of stability in the \"milieu interior.\" He said, \"All the vital mechanisms, varied as they are, have only one object, that of preserving constant the conditions of life in the internal environment\" (from *Leçons sur les Phénonèmes de la Vie Commune aux Animaux et aux Végétaux*, 1879). The term itself was coined by American physiologist Walter Cannon, author of *The Wisdom of the Body* (1932). The word comes from the Greek *homoios* (same, like, resembling) and *stasis* (to stand, posture). ### Cruise Control on a car as a simple metaphor for homeostasis When a car is put on cruise control it has a set speed limit that it will travel. At times this speed may vary by a few miles per hour but in general the system will maintain the set speed. If the car starts to go up a hill, the systems will automatically increase the amount of fuel given to maintain the set speed. If the car starts to come down a hill, the car will automatically decrease the amount of fuel given in order to maintain the set speed. It is the same with homeostasis- the body has a set limit on each environment. If one of these limits increases or decreases, the body will sense and automatically try to fix the problem in order to maintain the pre-set limits. This is a simple metaphor of how the body operates---constant monitoring of levels, and automatic small adjustments when those levels fall below (or rise above) a set point. ## Pathways That Alter Homeostasis A variety of homeostatic mechanisms maintain the internal environment within tolerable limits. Either homeostasis is maintained through a series of control mechanisms, or the body suffers various illnesses or disease. When the cells in the body begin to malfunction, the homeostatic balance becomes disrupted. Eventually this leads to disease or cell malfunction. Disease and cellular malfunction can be caused in two basic ways: either, *deficiency* (cells not getting all they need) or *toxicity* (cells being poisoned by too much of the things they need, or by things they do not need). When homeostasis is interrupted in your cells, there are *pathways* to correct or worsen the problem. In addition to the internal control mechanisms, there are external influences based primarily on lifestyle choices and environmental exposures that influence our body\'s ability to maintain cellular health. - **Nutrition:** If your diet is lacking in a specific vitamin or mineral your cells will function poorly, possibly resulting in a disease condition. For example, a menstruating woman with inadequate dietary intake of iron will become anemic. Lack of hemoglobin, a molecule that requires iron, will result in reduced oxygen-carrying capacity. In mild cases symptoms may be vague (e.g. fatigue), but if the anemia (British English: *anaemia*) is severe the body will try to compensate by increasing cardiac output, leading to palpitations and sweatiness, and possibly to heart failure. - **Toxins:** Any substance that interferes with cellular function, causing cellular malfunction. This is done through a variety of ways; chemical, plant, insecticides, and/or bites. A commonly seen example of this is drug overdoses. When a person takes too much of a drug their vital signs begin to waver; either increasing or decreasing, these vital signs can cause problems including coma, brain damage and even death. - **Psychological:** Your physical health and mental health are inseparable. Our thoughts and emotions cause chemical changes to take place either for better as with meditation, or worse as with stress. - **Physical:** Physical maintenance is essential for our cells and bodies. Adequate rest, sunlight, and exercise are examples of physical mechanisms for influencing homeostasis. Lack of sleep is related to a number of ailments such as irregular cardiac rhythms, fatigue, anxiety and headaches. - **Genetic/Reproductive:** Inheriting strengths and weaknesses is part of our genetic makeup. Genes are sometimes turned off or on due to external factors which we can have some control over, but at other times little can be done to correct or improve genetic diseases. Beginning at the cellular level a variety of diseases come from mutated genes. For example, cancer can be genetically inherited or can be caused due to a mutation from an external source such as radiation or genes altered in a fetus when the mother uses drugs. - **Medical:** Because of genetic differences some bodies need help in gaining or maintaining homeostasis. Through modern medicine our bodies can be given different aids, from anti-bodies to help fight infections, or chemotherapy to kill harmful cancer cells. Traditional and alternative medical practices have many benefits, but like any medical practice the potential for harmful effects is present. Whether by nosocomial infections, or wrong dosage of medication, homeostasis can be altered by that which is trying to fix it. Trial and error with medications can cause potential harmful reactions and possibly death if not caught soon enough. The factors listed above all have their effects at the cellular level, whether harmful or beneficial. Inadequate beneficial pathways (deficiency) will almost always result in a harmful waver in homeostasis. Too much toxicity also causes homeostatic imbalance, resulting in cellular malfunction. By removing negative health influences, and providing adequate positive health influences, your body is better able to self-regulate and self-repair, thus maintaining homeostasis. ## Homeostasis Throughout the Body Each body system contributes to the homeostasis of other systems and of the entire organism. No system of the body works in isolation, and the well-being of the person depends upon the well-being of all the interacting body systems. A disruption within one system generally has consequences for several additional body systems. Here are some brief explanations of how various body systems contribute to the maintenance of homeostasis: ### Nervous System Since the nervous system does not store nutrients, it must receive a continuous supply from blood. Any interruption to the flow of blood may bring brain damage or death. The nervous system maintains homeostasis by controlling and regulating the other parts of the body. A deviation from a normal set point acts as a stimulus to a receptor, which sends nerve impulses to a regulating center in the brain. The brain directs an effector to act in such a way that an adaptive response takes place. If, for example, the deviation was a lowering of body temperature, the effector acts to increase body temperature. The adaptive response returns the body to a state of normalcy and the receptor, the regulating center, and the effector temporarily cease their activities. Since the effector is regulated by the very conditions it produced, this process is called control by negative feedback. This manner of regulating normalcy results in a fluctuation between two extreme levels. Not until body temperature drops below normal do receptors stimulate the regulating center and effectors act to raise body temperature. Regulating centers are located in the central nervous system, consisting of the brain and spinal cord. The hypothalamus is a portion of the brain particularly concerned with homeostasis; it influences the action of the medulla oblongata, a lower part of the brain, the autonomic nervous system, and the pituitary gland. The nervous system has two major portions: the central nervous system and the peripheral nervous system. The central nervous system consists of the cranial and spinal nerves. The autonomic nervous system is a part of peripheral nervous system and contains motor neurons that control internal organs. It operates at the subconscious level and has two divisions, the sympathetic and parasympathetic systems. In general, the sympathetic system brings about those results we associate with emergency situations, often called fight or flight reactions, and the parasympathetic system produces those effects necessary to our everyday existence. ### Endocrine System The endocrine system consists of glands which secrete hormones into the bloodstream. Each hormone has an effect on one or more target tissues. In this way the endocrine system regulates the metabolism and development of most body cells and body systems. To be more specific, the Endocrine system has sex hormones that can activate sebaceous glands, development of mammary glands, alter dermal blood flow and release lipids from adipocytes. MSH can stimulate melanocytes on our skin. Our bone growth is regulated by several hormones, and the endocrine system helps with the mobilization of calcitonin and calcium. In the muscular system, hormones adjust muscle metabolism, energy production, and growth. In the nervous system, hormones affect neural metabolism, regulate fluid/electrolyte balance and help with reproductive hormones that influence CNS development and behaviors. In the Cardiovascular system, we need hormones that regulate the production of RBC\'s (red blood cells), which elevate and lower blood pressure. Hormones also have anti-inflammatory effects and stimulate the lymphatic system. In summary, the endocrine system has a regulatory effect on basically every other body system. ### Integumentary System The integumentary system (the skin) is involved in protecting the body from invading microbes (mainly by forming a thick impenetrable layer), regulating body temperature through sweating and vasodilation/vasoconstriction, or shivering and piloerection (goose bumps), and regulating ion balances in the blood. Stimulation of mast cells also produce changes in blood flow and capillary permeability which can effect the blood flow in the body and how it is regulated. It also helps synthesize vitamin D which interacts with calcium and phosphorus absorption needed for bone growth, maintenance, and repair. Hair on the skin guards entrance into the nasal cavity or other orifices, preventing invaders from getting further into our bodies. Our skin also helps maintain balance by excretion of water and other solutes (i.e. the keratinized epidermis limits fluid loss through skin). It also provides mechanical protection against environmental hazards. We need to remember that our skin is integumentary; it is our first line of defense. ### Skeletal System As the structural framework for the human body, the skeletal system consists mainly of the 206 or so bones of the skeletal system but also includes cartilages, ligaments, and other connective tissues that stabilize and interconnect them. Bones work in conjunction with the muscular system to aid in posture and locomotion. Many bones of the skeleton function as levers, which change the magnitude and direction of forces generated by skeletal muscle. Protection is a pivotal role occupied by the skeletal system, as many vital organs are encased within the skeletal cavities (e.g. cranial and spinal), and bones form much of the structural basis for other body cavities (ex: thoracic and pelvic cavities). The skeletal system also serves as an important mineral reserve. For example, if blood levels of calcium or magnesium are low and the minerals are not available in the diet, they will be taken from the bones. Also, the skeletal system provides calcium needed for all muscular contraction. Finally, red blood cells, lymphocytes and other cells relating to the immune response are produced and stored in the bone marrow. ### Muscular System The muscular system is one of the most versatile systems in the body. The muscular system contains the heart, which constantly pumps blood through the body. The muscular system is also responsible for actions both involuntary (e.g. goose bumps, digestion, breathing) and voluntary (e.g. walking, picking up objects). Muscles also help protect organs in the body\'s cavities. The muscles in your body use energy, which increases your body heat when you\'re cold. The act of shivering occurs when the internal temperature drops. Muscles around vital organs move, breaking down ATP and thereby releasing heat, which is then distributed to the rest of the body. ### Cardiovascular System The cardiovascular system, in addition to needing to maintain itself within certain levels, plays a role in maintenance of other body systems by transporting hormones (heart secretes Atrial Natriuretic Peptide and Brain Natriuretic Peptide, or ANP and BNP, respectively) and nutrients (oxygen, EPO to bones, etc.), taking away waste products, and providing all living body cells with a fresh supply of oxygen and removing carbon dioxide. Homeostasis is disturbed if the cardiovascular or lymphatic systems are not functioning correctly. Our skin, bones, muscles, lungs, digestive tract, and nervous, endocrine, lymphatic, urinary and reproductive systems use the cardiovascular system as its \"road\" or \"highway\" as far as distribution of things such as nutrients, oxygen, waste products, hormones, drugs, etc. There are many risk factors for an unhealthy cardiovascular system. Some diseases associated are typically labeled \"uncontrollable\" or \"controllable.\" The main uncontrollable risk factors are age, gender, and a family history of heart disease, especially at an early age. The cardiovascular system also contains sensors to monitor blood pressure, called baroreceptors, that work by detecting how stretched a blood vessel is. This information is relayed to the Medulla Oblongata in the brain where action is taken to raise or lower blood pressure via the autonomic nervous system. ### Lymphatic System The lymphatic system has three principal roles. First is the maintenance of blood and tissue volume. Excess fluid that leaves the capillaries when under pressure would build up and cause edema. Secondly, the lymphatic system absorbs fatty acids and triglycerides from fat digestion so that these components of digestion do not enter directly into the blood stream. Third, the lymphatic system is involved in defending the body against invading microbes, and the immune response. This system assists in maintenance, such as bone and muscle repair after injuries. Another defense is maintaining the acidic pH of urine to fight infections in the urinary system. The tonsils are our bodies \"helpers\" to defend us against infections and toxins absorbed from the digestive tract. The tonsils also protect against infections entering into our lungs. ### Respiratory System The respiratory system works in conjunction with the cardiovascular system to provide oxygen to cells within every body system for cellular metabolism. The respiratory system also removes carbon dioxide. Since CO2 is mainly transported in the plasma as bicarbonate ions, which act as a chemical buffer, the respiratory system also helps maintain proper blood pH levels, a fact that is very important for homeostasis. In hyperventilation, CO2 is decreased in blood levels. This causes the pH of body fluids to increase. If pH levels rise above 7.45, the result is respiratory alkalosis and passing out. On the other hand, hypoventilation may causes pH to fall below 7.35 which results in respiratory acidosis. This is the mechanism for death by opioid overdose. The respiratory system also helps the lymphatic system by trapping pathogens and protecting deeper tissues within. Note that when you have increased thoracic space it can provide abdominal pressure through the contraction of respiratory muscles. This can assist in defecation. The organs of the respiratory system include the nose, pharynx, larynx, trachea, bronchi and lungs. Together these organs permit the movement of air into the tiny, thin walled sacs of the lungs called alveoli. It is in the alveoli that oxygen from the air is exchanged for the waste product carbon dioxide, which is carried to lungs by the blood so that it can be eliminated from the body. ### Digestive System Without a regular supply of energy and nutrients from the digestive system, all body systems would soon suffer. The digestive system absorbs organic substances, vitamins, ions, and water that are needed all over the body. In the skin, the digestive tract provides lipids for storage in the subcutaneous layer. Note that food undergoes three types of processes in the body: digestion, absorption, and elimination. If one of these is not working, you will have problems that will be extremely noticeable. Mechanics of digestion can include chemical digestion, movements, ingestion absorption, and elimination. In order to maintain a healthy and efficient digestive system, we have to remember the components involved. If these are disturbed, digestive health may be compromised. ### Urinary System Toxic nitrogenous wastes accumulate as proteins and nucleic acids are broken down and used for other purposes. The urinary system rids the body of these wastes. The urinary system is also directly involved in maintaining proper blood volume (and indirectly blood pressure) and ion concentration within the blood. One other contribution is that the kidneys produce a hormone (erythropoietin) that stimulates red blood cell production. The kidneys also play an important role in maintaining the correct water content of the body and the correct salt composition of extracellular fluid. External changes that lead to excess fluid loss trigger feedback mechanisms that act to inhibit fluid loss. ### Reproductive System The Reproductive System is unique in that it does little to contribute to the homeostasis of the organism. Rather than being tied to the maintenance of the organism, the reproductive system relates to the maintenance of the species. Having said that, the sex hormones do have an effect on other body systems, and an imbalance can lead to various disorders (e.g. a woman whose ovaries are removed early in life is at much higher risk of osteoporosis). ### Excretory System Excretory System is responsible for removing wastes, excess water and salt in the urine. Regulates the volume and pH of the internal environment. The human excretory system maintains homeostasis by removing metabolic waste such as water, salt and metabolite concentrations in the blood. The kidneys, which are the primary excretory organs, are major organs of homeostasis because they excrete nitrogenous wastes, and regulate water-salt balance and acid base balance. This section will examine the kidney in details. ## Thermoregulation The living bodies have been characterized with a number of automated processes, which make them self-sustainable in the natural environment. Among these many processes are that of reproduction, adjustment with external environment, and instinct to live, which are gifted by nature to living beings. The survival of living beings greatly depends on their capability to maintain a stable body temperature irrespective of temperature of surrounding environment. This capability of maintaining body temperature is called thermoregulation. Cold blooded animals, such as reptiles, have somewhat different means of temperature regulation than warm blooded (or homeothermic) animals, such as humans and other mammals. This section is most relevant when considering warm blooded organisms. Body temperature depends on the heat produced minus the heat lost. Heat is lost by radiation, convection, and conduction, but the net loss by all three processes depends on a gradient between the body and the outside. Thus, when the external temperature is low, radiation is the most important form of heat loss. When there is a high external temperature, evaporation is the most important form of heat loss. The balance of heat produced and heat lost maintains a constant body temperature. However, temperature does vary during the day, and this set point is controlled by the hypothalamus. Body temperature is usually about 37.4°C, but does vary during the day by about 0.8°C. The lowest daily temperature is when the person is asleep. Temperature receptors are found in the skin, the great veins, the abdominal organs and the hypothalamus. While the ones in the skin provide the sensation of coldness, the hypothalamic (central core) temperature receptors are the most important. The core body temperature is usually about 0.7-1.0°C higher than axillary or oral temperature. When body temperature drops due to external cold, an important component of protection is vaso-constriction of skin and limb blood vessels. This drops the surface temperature, providing an insulating layer (such as the fat cell layer) between the core temperature and the external environment. Likewise, if the temperature rises, blood flow to the skin increases, maximizing the potential for loss by radiation and evaporation. Thus, if you dilated the skin blood vessels by alcohol ingestion this might give a nice warm glow, but it would increase heat loss (if the external temperature was still low). The major adjustments in cold are to shiver to increase heat production, and constrict blood vessels in the periphery and skin. This helps to minimize heat loss through the skin, and directs blood to the vital internal organs. Besides the daily variation in body temperature, there are other cyclic variations. In women, body temperature falls prior to ovulation and rises by about 1°C at ovulation, largely due to progesterone increasing the set point. Thyroid hormone and pyrogens also increase the set point. The basal metabolic rate (BMR) is about 30 calories/sq m/h. It is higher in children than in adults, partly as a result of different surface area to body mass ratio. Due to this relationship, young children are more likely to drop their temperature rapidly; there is greater temperature variation in children than in adults. It is increased by thyroid hormone and decreased by thyroid hormone lack. Different foods can affect BMR and the Respiratory Quotient of foods differ. Carbohydrate 1.0; Protein = 1.0; Fats = 0.7 ## Body Composition ```{=html} <table border="1" width="100%"> ``` ```{=html} <tr valign="top"> ``` ```{=html} <th width="33%"> ``` \ ```{=html} </th> ``` ```{=html} <th width="33%"> ``` Extracellular Fluid ```{=html} </th> ``` ```{=html} <th width="33%"> ``` Cellular Fluid ```{=html} </th> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Volume ```{=html} </td> ``` ```{=html} <td width="33%"> ``` plasma -- 3 litres interstitial -- 10 litres ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 30 litres ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Osmolality (mOsm) ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 290 ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 290 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Na ^+^ (mmol/l) ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 140 ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 15 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Ca ^2+^ (mmol/l) ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 2.2 ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \< 10 ^-6^ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Cl ^-^ (mmol/l) ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 110 ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 10 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` HCO`<sub>`{=html}3 `     ``</sub>`{=html}^`-`^ (mmol/l) ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 30 ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 10 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` K ^+^ (mmol/l) ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 4 ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 150 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Mg ^2+^`<span style="">`{=html} (mmol/l)`</span>`{=html} ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 1.5 ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 15 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` PO`<sub>`{=html}4 `     ``</sub>`{=html}^`3+`^`<span style="">`{=html}` (mmol/l)``</span>`{=html} ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 2 ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 40 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` pH ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 7.4 ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 7.1 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Potential Difference (mV) ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \ ```{=html} </td> ``` ```{=html} <td width="33%"> ``` -70 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` Blood pressure is expressed as two different numbers. The first number is called the \"systolic\" blood pressure, and the second is the \"diastolic\" blood pressure. Systolic blood pressure is the pressure at the time of the cardiac cycle when the heart contracts, forcing blood out(called systole). This is the time of greatest pressure. The Diastolic number comes from the time in the cardiac cycle when pressure is at its lowest, while the heart is refilling with blood. This phase is called Diastole. The blood pressure in large arteries is about 120/80 mmHg. By the time this comes to the capillaries it has partly lost its pulsatile nature and has a pressure of about 35 mmHg. The pressure falls rapidly along the capillary to 15 mmHg at the venous end. This hydrostatic pressure tends to force fluid out of the capillary into the interstitium (the fluid between cells) but balance is maintained by the colloid osmotic pressure (due to protein, principally albumin) of 26 mmHg. Net water movement is small (about 2%) and thus colloid osmotic pressure is the same at the arterial and venous end of the capillary. At the arterial end of the capillary there is a net outward force of about 11 mmHg while at the venous end the net inward force is about 9 mmHg (ie. -9). There is an imbalance between water movement out and movement back in which leads to an imbalance of about 3 litres/day, which is removed as lymph. There is some albumin in the interstitial tissue and it varies in different organs but the concentration may be up to 10 or 20% of plasma. This gives an interstitial oncotic pressure which causes movement of fluid into the interstitium. However the bulk movement of water is not the way nutrients get to cells. Nutrients diffuse down their concentration gradient as the capillary is very permeable to all small molecules. The extracellular volume is approximately thirteen litres in a seventy kg person. Ten litres are in the interstitial space and three litres in plasma. The capillaries are the interface between the two compartments and are permeable to most substances with a molecular weight less than 20,000. Thus nutrients can readily diffuse across the wall and go from blood to cell. Despite the high permeability of the capillary water is maintained inside due to the oncotic pressure and only about 2% of the plasma flowing through the capillary moves across the wall. The blood volume is about 5 litres of which about 3 litres are plasma and about 2 litres red blood cells. The red blood cell volume (haematocrit) is about 43% and the relationship between plasma and blood volume and haematocrit is Blood Volume = Plasma Volume 100/(100 - Ht). Most of the blood is usually in the veins (70%). Capillaries differ in their permeability throughout the body. Brain capillaries are relatively impermeable due to tight junctions between endothelial cells lining the blood vessels. This is known as the blood brain barrier, or BBB, and helps prevent toxins from entering the brain. In order of less permeability: Brain \< Muscle \< Glomerulus \< Liver sinusoids. The capillaries, while having a large surface area, only contain about 7% of the blood volume. The arteries and arterioles contain about 15%. Most of the blood is in the veins. ## Body Fluid Distribution The cell membrane is a bilipid layer that is permeable to water and lipid soluble particles. However, it is impermeable to charged particles. It is the osmolality controlling factor. Osmolality in the cell and interstitial fluid are the same but the anionic and cationic compositions differ. Made of albumin, the capillary membrane is permeable to everything except proteins. The membranes in different tissues differ. There are fenestrae (or pores) to promote better flow of fluids. Particles weighing over 40,000 Daltons have low permeability. It is the oncotic pressure controlling factor. Capillaries in the brain are relatively impermeable while capillaries in liver sinusoids and glomeruli are extremely permeable. ```{=html} <table border="1" width="100%"> ``` ```{=html} <tr valign="top"> ``` ```{=html} <th width="25%"> ``` \ ```{=html} </th> ``` ```{=html} <th width="25%"> ``` Water (litres) ```{=html} </th> ``` ```{=html} <th width="25%"> ``` Sodium (mmol) ```{=html} </th> ``` ```{=html} <th width="25%"> ``` Potassium (mmol) ```{=html} </th> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="25%"> ``` Total ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 43 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 3700 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 4000 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="25%"> ``` Intracellular ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 30 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 400 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="25%"> ``` Bone ```{=html} </td> ``` ```{=html} <td width="25%"> ``` \- ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 1500 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 300 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="25%"> ``` Extracellular ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 13 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 1820 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 52 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="25%"> ``` Plasma ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 3 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 420 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 12 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="25%"> ``` Interstitial ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 10 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 1400 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 40 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="25%"> ``` Usual Intake ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 1.5 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 180 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 70 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="25%"> ``` Range ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 0.7-5 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 5-400 ```{=html} </td> ``` ```{=html} <td width="25%"> ``` 50-400 ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` ## Dehydration and Volume Depletion Plasma osmolality is about 290 mosmol/l contributed mainly by sodium (140 mmol/l) and it\'s accompanying anions. In dehydration water is lost from the body. The rise in osmolality that occurs in the plasma (also sodium rises) causes water to initially move out of the cells along the osmotic gradient. Thus cell volume is initially reduced but cell homeostatic processes subsequently return it towards normal by taking up solute. In dehydration water is removed from the plasma and thus haematocrit and albumin which have not been lost will have a higher concentration. In volume depletion water and electrolytes are both lost and thus there will be little effect on either sodium concentration or osmolality. As osmolality is not altered there will be no force to pull water out of the cells and cell volume is not affected. In volume depletion due to blood loss the haematocrit acutely is the same but the resultant fall in blood pressure causes fluid to come out of the interstitium into the vascular compartment and albumin and haematocrit both decrease. When there is volume depletion due to electrolyte and water loss by vomiting or diarrhoea there will be little or no effect on plasma osmolality or sodium concentration. However there will be a small increase in haematocrit and plasma albumin because the volume is lost from the extracellular space and as blood cells and albumin are not lost this increases the concentration. In volume depletion forces are activated that retain sodium and water in the body. The sodium retention works to a major extent by the renin-angiotensin-aldosterone system which is activated by a fall in blood pressure caused by volume depletion. In dehydration, the high osmolality activates ADH secretion which causes water retention. As there is also volume depletion, this activates the renin-angiotensin-aldosterone system which causes sodium to be retained. This retention would tend to cause a rise in sodium concentration which is already high but the water retention would correct this. There is no effective receptor that monitors and controls Na concentration by altering sodium excretion. Sodium retaining hormones are predominantly regulated by the volume and blood pressure. Initially in blood loss the haematocrit is not altered but falls as fluid comes in from the interstitial space. ## Water Balance Vasopressin, also called Antidiuretic Hormone (ADH), is the principal compound controlling water balance by decreasing water output by the kidney, and thus decreased urination. It perceives the need by monitoring plasma osmolality and if this is high, vasopressin is secreted. Vasopressin is formed in the hypothalamus and travels down axons to the posterior pituitary where it is stored. Plasma osmolality is the usual factor regulating vasopressin release but other factors alter the release. Pain and emotion release vasopressin together with the other posterior pituitary hormone oxytocin. Alcohol inhibits the release of vasopressin and thus causes a diuresis. A low plasma volume also releases vasopressin which in high concentration can cause vasoconstriction. These different factors can overcome the usual physiological control of osmolality. Osmoreceptors in the hypothalamus monitor the plasma osmolality and send a signal down the axon that releases vasopressin from the posterior pituitary gland. Vasopressin travels by the blood to the kidney and binds to a receptor on the basolateral membrane and by a series of cellular events alters the permeability of the luminal membrane to water, thereby increasing the water permeability of the collecting duct and due to osmotic gradients created in the kidney causes water to be retained by the body (ie. an antidiuresis) which provides the other name for vasopressin of antidiuretic hormone. Vasopressin released by the pituitary binds to a receptor on the basolateral membrane and activates adenyl cyclase which increases cyclic AMP levels in the kidney. This by a series of reactions, some of which involve calcium, cause microfilaments to contract and insert preformed water channels (aquaporins) into the luminal membrane increasing water permeability. A high plasma osmolality is the important physiological stimulus causing vasopressin release. Urea in plasma in a normal person only has a concentration of 6 mmol/l and thus contributes to only a small part of plasma osmolality. Even if plasma urea is elevated to 30 mmol/l it would not have a significant effect on vasopressin release as membranes (including those of the osmoreceptor cells) are permeable to urea. If there is excessive ADH water is retained and the osmolality and sodium concentration would fall (hyponatraemia). If there is no ADH water is lost and osmolality and sodium concentration would rise (hypernatraemia). While ADH is released if the plasma volume falls the most important factor to restore volume is retention of sodium by the renin-angiotensin-aldosterone and other salt retaining systems. ## Sodium Balance ```{=html} <table border="1" width="100%"> ``` ```{=html} <tr valign="top"> ``` ```{=html} <th width="34%"> ``` \ ```{=html} </th> ``` ```{=html} <th width="33%"> ``` Amount ```{=html} </th> ``` ```{=html} <th width="33%"> ``` Concentration ```{=html} </th> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Amount in body ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 3700 mmol ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Intracellular ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 400 mmol ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 15 mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Extracellular ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 1800 mmol ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 140 mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Plasma ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 420 mmol ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 140 mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Interstitial ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 1400 mmol ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 140 mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Bone ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 1500 mmol ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Amount in diet ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \ ```{=html} </td> ``` ```{=html} <td width="33%"> ``` ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Hunter Gatherer ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 20 mmol/day ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Western ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 180 mmol/day ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Japanese ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 300 mmol/day ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Obligatory Need ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \< 5 mmol/day ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` Sodium is an important cation distributed primarily outside the cell. The cell sodium concentration is about 15 mmol/l but varies in different organs and with an intracellular volume of 30 litres about 400 mmol are inside the cell. The plasma and interstitial sodium is about 140 mmol/l with an extracellular volume of about 13 litres, 1800 mmol are in the extracellular space. The total body sodium, however, is about 3700 mmol as there is about 1500 mmol stored in bones. The usual sodium intake of an Australian diet is about 180 mmol/d but varies widely (50-400 mmol/day) depending on habit and cultural influences. The body has potent sodium retaining mechanisms and even if a person is on 5 mmol Na+/day they can maintain sodium balance. Extra sodium is lost from the body by reducing the activity of the renin angiotensin aldosterone system which leads to increased sodium loss from the body. Sodium is lost through the kidney, sweat and faeces. In states of sodium depletion aldosterone levels increase and in states of sodium excess aldosterone levels decrease. The major physiological controller of aldosterone secretion is the plasma angiotensin II level which increases aldosterone secretion. A high plasma potassium also increases aldosterone secretion because besides retaining Na+ high plasma aldosterone causes K+ loss by the kidney. Plasma Na+ levels have little effect on aldosterone secretion. A low renal perfusion pressure stimulates the release of renin, which forms angiotensin I which is converted to angiotensin II. Angiotensin II will correct the low perfusion pressure by causing constriction of blood vessels and by increasing sodium retention by a direct effect on the proximal renal tubule and by an effect operated through aldosterone. The perfusion pressure to the adrenal gland has little direct effect on aldosterone secretion and the low blood pressure operates to control aldosterone via the renin angiotensin system. In addition to aldosterone and angiotensin II other factors influence sodium excretion. Thus in high sodium states due either to excess intake or cardiac disease (+ others) atrial peptide is secreted from the heart and by a series of actions causes loss of sodium by the kidney. Elevated blood pressure will also tend to cause Na+ loss and a low blood pressure usually leads to sodium retention. Aldosterone also acts on the sweat ducts and colonic epithelium to conserve sodium. When aldosterone has been activated to retain sodium the plasma sodium tends to rise. This immediately causes release of ADH which causes water to be retained, thus retaining Na+ and H2O in the right proportion to restore plasma volume. ## Potassium Balance ```{=html} <table border="1" width="100%"> ``` ```{=html} <tr valign="top"> ``` ```{=html} <th width="34%"> ``` \ ```{=html} </th> ``` ```{=html} <th width="33%"> ``` Amount ```{=html} </th> ``` ```{=html} <th width="34%"> ``` Concentration ```{=html} </th> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Amount in body ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 4000 mmol ```{=html} </td> ``` ```{=html} <td width="34%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Intracellular ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 3000 + mmol ```{=html} </td> ``` ```{=html} <td width="34%"> ``` 110 mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Extracellular ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 53 mmol ```{=html} </td> ``` ```{=html} <td width="34%"> ``` 4 mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Plasma ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 12 mmol ```{=html} </td> ``` ```{=html} <td width="34%"> ``` 4 mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Interstitial ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 40 mmol ```{=html} </td> ``` ```{=html} <td width="34%"> ``` 4 mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Bone ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 300 mmol ```{=html} </td> ``` ```{=html} <td width="34%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Amount in diet ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \ ```{=html} </td> ``` ```{=html} <td width="34%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Hunter Gatherer ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 200 -- 400 mmol/day ```{=html} </td> ``` ```{=html} <td width="34%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Western ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 50 -- 100 mmol/day ```{=html} </td> ``` ```{=html} <td width="34%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="34%"> ``` Obligatory Need ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 30 -- 50 mmol/day ```{=html} </td> ``` ```{=html} <td width="34%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` Potassium is predominantly an intracellular ion and most of the total body potassium of about 4000 mmol is inside the cells and the next largest proportion (300-500 mmol) is in the bones. Cell K+ concentration is about 150 mmol/l but varies in different organs. Extracellular potassium is about 4.0 mmol/l and with an extracellular value of about 13 litres, 52 mmol (ie. less than 1.5%) is present here and only 12 mmol in the plasma. In an unprocessed diet potassium is much more plentiful than sodium and is present as an organic salt while sodium is added as NaCl. In a hunter gatherer K+ intake may be as much as 400 mmol/d while in the Western diet it is 70 mmol/d or less if a person has a minimal amount of fresh fruit and vegetables. Processing of foods replaces K+ with NaCl. While the body can excrete a large K+ load it is unable to conserve K+. On a zero K+ intake or in a person with K+ depletion there will still be a loss of K+ of 30-50 mmol/d in the urine and faeces. If there is a high potassium intake, e.g. 100 mmol, this would potentially increase the extracellular K+ level 2 times before the kidney could excrete the extra potassium. The body buffers the extra potassium by equilibrating it within the cells. The acid base status controls the distribution between plasma and cells. A high pH (ie. alkalosis \>7.4) favours movement of K+ into the cells whilst a low pH (ie. acidosis) causes movement out of the cell. A high plasma potassium increases aldosterone secretion and this increases the potassium loss from the body, restoring balance. This change of distribution with the acid base status means that the plasma K+ may not reflect the total body content. Thus a person with an acidosis (pH 7.1) and a plasma K+ of 6.5 mmol/l could be depleted of total body potassium. This occurs in diabetic acidosis. Conversely a person who is alkalotic with a plasma K+ of 3.4 mmol/l may have normal total body potassium. ## Calcium and Phosphate Balance ```{=html} <table border="1" width="100%"> ``` ```{=html} <tr valign="top"> ``` ```{=html} <th width="33%"> ``` \ ```{=html} </th> ``` ```{=html} <th width="33%"> ``` Amount ```{=html} </th> ``` ```{=html} <th width="33%"> ``` Concentration ```{=html} </th> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Amount in body ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \ ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Interstitial (0.9%) ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 270 mmol ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 9 mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Cytoplasm ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \<1 mmol ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 10^-6^ mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Cell organelles ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 270 mmol ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 9 mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Extracellular (0.1%) ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 30 mmol ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 2.2 mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Plasma ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 7 mmol ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 2.2 mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Interstitial ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 23 mmol ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 2.2 mmol/l ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Bone (99%) ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 27.5 mol (1.1 kg) ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Amount in diet ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 1200 mg/day ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 40 mmol/day ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Amount absorbed ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 300 mg/day ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 10 mmol/day ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Amount excreted ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 300 mg/day ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 10 mmol/day ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Obligatory Need ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 100 mg/day ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 3 mmol/day ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} <tr valign="top"> ``` ```{=html} <td width="33%"> ``` Bone =\> Plasma ```{=html} </td> ``` ```{=html} <td width="33%"> ``` 500 mmol/day ```{=html} </td> ``` ```{=html} <td width="33%"> ``` \ ```{=html} </td> ``` ```{=html} </tr> ``` ```{=html} </table> ``` Calcium is a very important electrolyte. 99% or more is deposited in bone but the remainder is importantly associated with nerve conduction, muscle contraction, hormone release and cell signalling. The plasma concentration of Ca++ is 2.2 mmol/l and phosphate 1.0 mmol/l. The solubility product of Ca and P is close to saturation in plasma. The concentration of Ca++ in the cytoplasm is \< 10-6 mmol/l but the concentration of Ca++ in the cell is much higher as calcium is taken up (and is able to be released from) cell organelles. In the Australian diet there is about 1200 mg/d of calcium. Even if it was all soluble it is not all absorbed as it combines with phosphates in the intestinal secretions. In addition absorption is regulated by active Vitamin D and increased amounts increase Ca++ absorption. Absorption is controlled by Vitamin D while excretion is controlled by parathyroid hormones. However, the distribution from bone to plasma is controlled by both the parathyroid hormones and vitamin D. There is a constant loss of calcium by the kidney even if there was none in the diet. The excretion of calcium by the kidney and its distribution between bone and the rest of the body is primarily controlled by parathyroid hormone. Calcium in plasma exists in 3 forms. Ionized, non ionized and protein bound. It is the ionized calcium concentration that is monitored by the parathyroid gland and if low, parathyroid hormone secretion is increased. This acts to increase ionized calcium levels by increasing bone re-absorption, decreasing renal excretion and acting on the kidney to increase the rate of formation of active Vitamin D, and thereby increase gut absorption of calcium. The usual amount of phosphate in the diet is about 1 g/d but not all is absorbed. Any excess is excreted by the kidney and this excretion is increased by parathyroid hormone. Parathyroid hormone also causes phosphate to come out of bone. Plasma phosphate has no direct effect on parathyroid hormone secretion. However if it is elevated it combines with Ca++ decreasing the ionized Ca++ in plasma, thereby increasing parathyroid hormone secretion. ## Case Study **Heat stroke and Heat exhaustion** If you have ever performed heavy manual labor or competed in an athletic event on a very hot day, you may have experienced symptoms of heat exhaustion. Typically these include an elevated core body temperature (above 104F or 40C), profuse sweating, pale color, muscle cramps, dizziness, and in some extreme circumstances, fainting or loss of consciousness. Heat exhaustion occurs as a consequence of disruption of the body\'s own system of thermoregulation, the means by which it adjusts temperature. Sweating is the principal means through which the body cools itself down, but diverting blood from other regions toward the skin also serves this purpose. Although sweat allows excess heat to dissipate as the moisture reaches the skin surface, it can also have dangerous implications for blood pressure and volume. As sweating increases, blood volume can drop precipitously, meaning that the brain and other body systems are at risk for insufficient oxygen and nutrient supplies. Furthermore, diverting blood away from other systems and towards the skin compounds the changes in blood volume and blood pressure induced through sweating. Heat stroke is a far more serious condition. This happens when the body\'s temperature rises out of control due to the failure of the thermoregulating system. If the body is unable to reduce its temperature due to outside or physical influences, the brain will start to malfunction. Delirium and loss of consciousness set in. The center of the brain controlling the sweat glands will stop functioning, halting the production of sweat. This causes the body\'s temperature to rise even faster. Furthermore, with the increase of the body\'s temperature, the metabolic process will speed up causing even more heat in the body. If left untreated this will result in death. One of the easiest ways to spot heat stroke is the skin. If it is flushed due to the increase of blood flow but dry because the sweat glands have stopped secreting, the individual will need prompt medical attention. ## Other Examples - Thermoregulation - The skeletal muscles can shiver to produce heat if the body temperature is too low. - Non-shivering thermogenesis involves the decomposition of fat to produce heat. - Sweating cools the body with the use of evaporation. - Chemical regulation - The pancreas produces insulin and glucagon to control blood-sugar concentration. - The lungs take in oxygen and give off carbon dioxide, which regulates pH in the blood. - The kidneys remove urea, and adjust the concentrations of water and a wide variety of ions. Main examples of homeostasis in mammals are as follows: - The regulation of the amounts of water and minerals in the body. This is known as osmoregulation. This happens primarily in the kidneys. - The removal of metabolic waste. This is known as excretion. This is done by the excretory organs such as the kidneys and lungs. - The regulation of body temperature. This is mainly done by the skin. - The regulation of blood glucose level. This is mainly done by the liver and the insulin and glucagon secreted by the pancreas in the body. Most of these organs are controlled by hormones secreted from the pituitary gland, which in turn is directed by the hypothalamus. ## Review Questions I Answers for these questions can be found here 1\. Meaning of Homeostasis: A\) contributor and provider B\) expand C\) same or constant D\) receiver 2\. What is the normal pH value for body fluid? A\) 7.15-7.25 B\) 7.35-7.45 C\) 7.55- 7.65 D\) 7.00-7.35 E\) 6.5-7.5 3\. An example of the urinary system working with the respiratory system to regulate blood pH would be A\) When you hold your breath the kidneys will remove CO~2~ from your blood B\) If you exercise a lot your urine will become more acidic C\) If you have emphysema the kidneys will remove fewer bicarbonate ions from circulation D\) If you hyperventilate the kidneys will counteract the alkalinity by adding hydrogen ions into the blood stream E\) None of the above-the urinary system never works with the respiratory system 4\. The urge to breathe comes in direct response to: A\) How long it has been since you last took a breath B\) The oxygen concentration of your surrounding environment C\) The build-up of nitrogen within your blood stream D\) The pH of your blood E\) The build-up of blood pressure that occurs when you don\'t breathe 5\. In response to a bacterial infection my body\'s thermostat is raised. I start to shiver and produce more body heat. When my body temperature reaches 101 degrees, I stop shivering and my body temperature stops going up. This is an example of: A\) Negative feedback B\) A malfunctioning control system C\) Positive feedback D\) A negative impact 6\. Which of the following is an example of a positive feedback? A\) Shivering to warm up in a cold winter storm B\) A cruise control set on your car applies more gas when going up a hill C\) You sweat on a hot summer\'s day and the blood vessels in your skin vasodilate D\) You get cut and platelets form a clot. This in turn activates the fibrin clotting system and more blood forms clots 7\. Where is the body\'s \"thermostat\" found? A\) Within the nervous system, in the Hypothalamus B\) Within the integumentary system, in the skin C\) Within the brain, in the corpus callosum D\) Within the Urinary system, in the kidneys 8\. What system has little to contribute to the homeostasis of the organism? A\) Urinary System B\) Reproductive System C\) Respiratory System D\) Nervous System 9\. Select the *phrase(s)* below that best describe(s) homeostasis. A\) Fluctuating within a homeostatic range B\) Maintaining a constant internal environment C\) Dynamic equilibrium D\) Deviating 10\. In which part of the nephron does ADH act? A)PCT B)DCT C)Loop of Henle D)None ### Review Answers - 1=C - 2=B - 3=C - 4=D - 5=A - 6=D - 7=A - 8=B - 9=B - 10=B ## Glossary - **Control Center or Integration Center:** receives and processes information from the receptor - **Effector:** responds to the commands of the control center by either opposing or enhancing the stimulus - **Homeostasis:** refers to stability, balance or equilibrium - **Negative Feedback:** a reaction in which the system responds in such a way as to reverse the direction of change - **Positive Feedback:** a response is to amplify the change in the variable - **Receptor:** receives information that something in the environment is changing fr:Cours de physiologie/Contrôle, régulation et homéostasie
# Human Physiology/Cell physiology ## Cell Structure and Function ### What is a Cell? A **cell** is a structure as well as a functional unit of life. Every living thing has cells: **bacteria, protozoans, fungi, plants, and animals** are the main group of living things. Some organisms are made up of just one cell are called **unicellular**. (e.g. bacteria and protozoans), but animals, including human beings, are **multi-cellular.** An adult human body is composed of about 100,000,000,000,000 cells! Each cell has basic requirements to sustain it, and the body\'s organ systems are largely built around providing the many trillions of cells with those basic needs (such as oxygen, food, and waste removal). There are about 200 different kinds of specialized cells in the human body. When many identical cells are organized together it is called a tissue (such as muscle tissue, nervous tissue, etc). Various tissues organized together for a common purpose are called organs (e.g. the stomach is an organ, and so is the skin, the brain, and the uterus). Ideas about cell structure have changed considerably over the years. Early biologists saw cells as simple membranous sacs containing fluid and a few floating particles. Today\'s biologists know that cells are inconceivably more complex than this. Therefore, a strong knowledge of the various cellular organelles and their functions is important to any physiologist. If a person\'s cells are healthy, then that person is healthy. All physiological processes, disease, growth and development can be described at the cellular level. ### Specialized Cells of the Human Body Although there are specialized cells - both in structure and function - within the body, all cells have similarities in their structural organization and metabolic needs (such as maintaining energy levels via conversion of carbohydrate to ATP and using genes to create and maintain proteins). Here are some of the different types of specialized cells within the human body. - **Nerve Cells**: Also called neurons, these cells are in the nervous system and function to process and transmit information (it is hypothesized). They are the core components of the brain, spinal cord, and peripheral nerves. They use chemical synapses that can evoke electrical signals, called action potentials, to relay signals throughout the body. - **Epithelial cells**: Functions of epithelial cells include secretion, absorption, protection, transcellular transport, sensation detection, and selective permeability. Epithelium lines both the outside (skin) and the inside cavities and lumen of bodies. - **Exocrine cells**: These cells secrete products through ducts, such as mucus, sweat, or digestive enzymes. The products of these cells go directly to the target organ through the ducts. For example, the bile from the gallbladder is carried directly into the duodenum via the bile duct. - **Endocrine cells**: These cells are similar to exocrine cells, but secrete their products directly into the bloodstream instead of through a duct. Endocrine cells are found throughout the body but are concentrated in hormone-secreting glands such as the pituitary. The products of the endocrine cells go throughout the body in the bloodstream but act on specific organs by receptors on the cells of the target organs. For example, the hormone estrogen acts specifically on the uterus and breasts of females because there are estrogen receptors in the cells of these target organs. - **Blood Cells**: The most common types of blood cells are: - **red blood cells (erythrocytes)**. The main function of red blood cells is to collect oxygen in the lungs and deliver it through the blood to the body tissues. Gas exchange is carried out by simple diffusion. - various types of **white blood cells (leukocytes)**. They are produced in the bone marrow and help the body to fight infectious disease and foreign objects in the immune system. White cells are found in the circulatory system, lymphatic system, spleen, and other body tissues. ### Cell Size Cells are the smallest structural & functional living units within our body, but play a big role in making our body function properly. Many cells never have a large increase in size like eggs, after they are first formed from a parental cell. Typical stem cells reproduce, double in size, then reproduce again. Most Cytosolic contents such as the endomembrane system and the cytoplasm easily scale to larger sizes in larger cells. If a cell becomes too large, the normal cellular amount of DNA may not be adequate to keep the cell supplied with RNA. Large cells often replicate their chromosomes to an abnormally high amount or become multinucleated. Large cells that are primarily for nutrient storage can have a smooth surface membrane, but metabolically active large cells often have some sort of folding of the cell surface membrane in order to increase the surface area available for transport functions. ### Cellular Organization Several different molecules interact to form organelles within our body. Each type of organelle has a specific function. Organelles perform the vital functions that keep our cells alive. #### Cell Membranes The boundary of the cell, sometimes called the plasma membrane, separates internal metabolic events from the external environment and controls the movement of materials into and out of the cell. This membrane is very selective about what it allows to pass through; this characteristic is referred to as \"selective permeability.\" For example, it allows oxygen and nutrients to enter the cell while keeping toxins and waste products out. The plasma membrane is a double phospholipid membrane, or a lipid bilayer, with the nonpolar hydrophobic tails pointing toward the inside of the membrane and the polar hydrophilic heads forming the inner and outer surfaces of the membrane. center\|framed\|The molecular structure of the cell membrane.22 #### Protein and Cholesterol Proteins and cholesterol molecules are scattered throughout the flexible phospholipid membrane. Peripheral proteins attach loosely to the inner or outer surface of the plasma membrane. Integral proteins lie across the membrane, extending from inside to outside. A variety of proteins are scattered throughout the flexible matrix of phospholipid molecules, somewhat like icebergs floating in the ocean, and this is termed the *fluid mosaic model* of the cell membrane. The phospholipid bilayer is selectively permeable. Only small, uncharged polar molecules can pass freely across the membrane. Some of these molecules are H~2~O and CO~2~, hydrophobic (nonpolar) molecules like O~2~, and lipid soluble molecules such as hydrocarbons. Other molecules need the help of a membrane protein to get across. There are a variety of membrane proteins that serve various functions: - **Channel proteins**: Proteins that provide passageways through the membranes for certain hydrophilic or water-soluble substances such as polar and charged molecules. No energy is used during transport, hence this type of movement is called facilitated diffusion. - **Transport proteins**: Proteins that spend energy (ATP) to transfer materials across the membrane. When energy is used to provide passageway for materials, the process is called active transport. - **Recognition proteins**: Proteins that distinguish the identity of neighboring cells. These proteins have oligosaccharide or short polysaccharide chains extending out from their cell surface. - **Adhesion proteins**: Proteins that attach cells to neighboring cells or provide anchors for the internal filaments and tubules that give stability to the cell. - **Receptor proteins**: Proteins that initiate specific cell responses once hormones or other trigger molecules bind to them. - **Electron transfer proteins**: Proteins that are involved in moving electrons from one molecule to another during chemical reactions. #### Passive Transport Across the Cell Membrane **Passive transport** describes the movement of substances down a concentration gradient and does not require energy use. - **Bulk flow** is the collective movement of substances in the same direction in response to a force, such as pressure. Blood moving through a vessel is an example of bulk flow. - **Simple diffusion**, or diffusion, is the net movement of substances from an area of higher concentration to an area of lower concentration. This movement occurs as a result of the random and constant motion characteristic of all molecules, (atoms or ions) and is independent from the motion of other molecules. Since, at any one time, some molecules may be moving against the gradient and some molecules may be moving down the gradient, although the motion is random, the word \"net\" is used to indicate the overall, eventual end result of the movement. - **Facilitated diffusion** is the diffusion of solutes through channel proteins in the plasma membrane. Water can pass freely through the plasma membrane without the aid of specialized proteins (though facilitated by aquaporins). - **Osmosis** is the diffusion of water molecules across a selectively permeable membrane. When water moves into a body by osmosis, hydrostatic pressure or osmotic pressure may build up inside the body. - **Dialysis** is the diffusion of solutes across a selectively permeable membrane. #### Active Transport Across the Cell Membrane **Active transport** is the movement of solutes against a gradient and requires the expenditure of energy, usually in the form of ATP. Active transport is achieved through one of these two mechanisms: ##### Protein Pumps - Transport proteins in the plasma membrane transfer solutes such as small ions (Na^+^, K^+^, Cl^-^, H^+^), amino acids, and monosaccharides. - The proteins involved with active transport are also known as **ion pumps**. - The protein binds to a molecule of the substance to be transported on one side of the membrane, then it uses the released energy (ATP) to change its shape, and releases it on the other side. - The protein pumps are specific, there is a different pump for each molecule to be transported. - Protein pumps are catalysts in the splitting of ATP → ADP + phosphate, so they are called **ATPase enzymes**. - The sodium-potassium pump (also called the Na^+^/K^+^-ATPase enzyme) actively moves sodium out of the cell and potassium into the cell. These pumps are found in the membrane of virtually every cell, and are essential in transmission of nerve impulses and in muscular contractions. **Cystic fibrosis** is a genetic disorder that results in a mutated chloride ion channel. By not regulating chloride secretion properly, water flow across the airway surface is reduced and the mucus becomes dehydrated and thick. ##### Vesicular Transport - Vesicles or other bodies in the cytoplasm move macromolecules or large particles across the plasma membrane. Types of **vesicular** **transport** include: 1. **Exocytosis**, which describes the process of vesicles fusing with the plasma membrane and releasing their contents to the outside of the cell. This process is common when a cell produces substances for export. 2. **Endocytosis**, which describes the capture of a substance outside the cell when the plasma membrane merges to engulf it. The substance subsequently enters the cytoplasm enclosed in a vesicle. : There are three kinds of endocytosis: - **Phagocytosis** or cellular eating, occurs when the dissolved materials enter the cell. The plasma membrane engulfs the solid material, forming a phagocytic vesicle. - **Pinocytosis** or cellular drinking occurs when the plasma membrane folds inward to form a channel allowing dissolved substances to enter the cell. When the channel is closed, the liquid is encircled within a pinocytic vesicle. - **Receptor-mediated endocytosis** occurs when specific molecules in the fluid surrounding the cell bind to specialized receptors in the plasma membrane. As in pinocytosis, the plasma membrane folds inward and the formation of a vesicle follows. : **Note:** Certain hormones are able to target specific cells by receptor-mediated endocytosis. ## Parts of the Cell ![](Animal_cell_structure_en.svg "Animal_cell_structure_en.svg") ### Cytoplasm The gel-like material within the cell membrane is referred to as the cytoplasm. It is a fluid matrix, the cytosol, which consists of 80% to 90% water, salts, organic molecules and many enzymes that catalyze reactions, along with dissolved substances such as proteins and nutrients. The cytoplasm plays an important role in a cell, serving as a \"molecular soup\" in which organelles are suspended and held together by a fatty membrane. Within the plasma membrane of a cell, the cytoplasm surrounds the nuclear envelope and the cytoplasmic organelles. It plays a mechanical role by moving around inside the membrane and pushing against the cell membrane helping to maintain the shape and consistency of the cell and again, to provide suspension to the organelles. It is also a storage space for chemical substances indispensable to life, which are involved in vital metabolic reactions, such as anaerobic glycolysis and protein synthesis. The cell membrane keeps the cytoplasm from leaking out. It contains many different organelles which are considered the insoluble constituents of the cytoplasm, such as the mitochondria, lysosomes, peroxysomes, ribosomes, several vacuoles and cytoskeletons, as well as complex cell membrane structures such as the endoplasmic reticulum and the Golgi apparatus that each have specific functions within the cell. - **Cytoskeleton** Threadlike proteins that make up the cytoskeleton continually reconstruct to adapt to the cell\'s constantly changing needs. It helps cells maintain their shape and allows cells and their contents to move. The cytoskeleton allows certain cells such as neutrophils and macrophages to make amoeboid movements. The network is composed of three elements: _microtubules_, actin filaments, and intermediate fibers. - **Microtubules** Microtubules function as the framework along which organelles and vesicles move within a cell. They are the thickest of the cytoskeleton structures. They are long hollow cylinders, composed of protein subunits, called tubulin. Microtubules form mitotic spindles, the machinery that partitions chromosomes between two cells in the process of cell division. Without mitotic spindles cells could not reproduce. Microtubules, intermediate filaments, and microfilaments are three protein fibers of decreasing diameter, respectively. All are involved in establishing the shape or movements of the cytoskeleton, the internal structure of the cell. !A photograph of microfilaments. - **Microfilaments** Microfilaments provide mechanical support for the cell, determine the cell shape, and in some cases enable cell movements. They have an arrow-like appearance, with a fast growing plus or barbed end and a slow growing minus or pointed end. They are made of the protein actin and are involved in cell motility. They are found in almost every cell, but are predominant in muscle cells and in the cells that move by changing shape, such as phagocytes (white blood cells that scour the body for bacteria and other foreign invaders). ### Organelles Organelles are bodies embedded in the cytoplasm that serve to physically separate the various metabolic activities that occur within cells. The organelles are each like separate little factories, each organelle is responsible for producing a certain product that is used elsewhere in the cell or body. Cells of all living things are divided into two broad categories: prokaryotes and eukaryotes. Bacteria (and archea) are prokaryotes, which means they lack a nucleus or other membrane-bound organelles. Eukaryotes include all protozoans, fungi, plants, and animals (including humans), and these cells are characterized by a nucleus (which houses the chromosomes) as well as a variety of other organelles. Human cells vary considerably (consider the differences between a bone cell, a blood cell, and a nerve cell), but most cells have the features described below. center\|framed\|A comparison of Eukaryote and Prokaryote cells. #### Nucleus Controls the cell; houses the genetic material (DNA). The nucleus is the largest of the cells organelles. Cells can have more than one nucleus or lack a nucleus all together. Skeletal muscle cells contain more than one nucleus whereas red blood cells do not contain a nucleus at all. The nucleus is bounded by the nuclear envelope, a phospholipid bilayer similar to the plasma membrane. The space between these two layers is the nucleolemma Cisterna. The nucleus contains the DNA, as mentioned above, the hereditary information in the cell. Normally the DNA is spread out within the nucleus as a threadlike matrix called chromatin. When the cell begins to divide, the chromatin condenses into rod-shaped bodies called chromosomes, each of which, before dividing, is made up of two long DNA molecules and various histone molecules. The histones serve to organize the lengthy DNA, coiling it into bundles called nucleosomes. Also visible within the nucleus are one or more nucleoli, each consisting of DNA in the process of manufacturing the components of ribosomes. Ribosomes are shipped to the cytoplasm where they assemble amino acids into proteins. The nucleus also serves as the site for the separation of the chromosomes during cell division. !A cross-sectional diagram of a nucleus. - **Chromosomes** right\|framed\|A rough sketch of a chromosome. Inside each cell nucleus are chromosomes. Chromosomes are made up of chromatin, which is made up of protein and deoxyribonucleic acid strands. Deoxyribonucleic acid is DNA, the genetic material that is in the shape of a twisted ladder, also called the double helix. Humans have 23 pairs of chromosomes. Down Syndrome and Cri du Chat Syndrome result from having an abnormal number of chromosomes. #### Centrioles Centrioles are rod like structures composed of 9 bundles which contain three microtubules each. Two perpendicularly placed centrioles surrounded by proteins make up the centrosome. Centrioles are very important in cellular division, where they arrange the mitotic spindles that pull the chromosome apart. Centrioles and basal bodies act as microtubule organizing centers. A pair of centrioles (enclosed in a centrosome) located outside the nuclear envelope gives rise to the microtubules that make up the spindle apparatus used during cell division. Basal bodies are at the base of each flagellum and cilium and appear to organize their development. #### Ribosomes center\|framed Ribosomes play an active role in the complex process of protein synthesis, where they serve as the structures that facilitate the joining of amino acids. Each ribosome is composed of a large and small subunit which are made up of ribosomal proteins and ribosomal RNAs. They can either be found in groups called polyribosomes within the cytoplasm or found alone. Occasionally they are attached to the endoplasmic reticulum. !A cutaway view inside a mitochondria. #### Mitochondria Mitochondria are the organelles that function as the cell \"powerhouse\", generating ATP, the universal form of energy used by all cells. It converts food nutrients such as glucose, to a fuel (ATP) that the cells of the body can use. Mitochondria are tiny sac-like structures found near the nucleus. Little shelves called cristae are formed from folds in the inner membrane. Cells that are metabolically active such as muscle, liver and kidney cells have high energy requirements and therefore have more mitochondria. Mitochondria are unique in that they have their own mitochondrial DNA (separate from the DNA that is in the nucleus). It is believed that eukaryotes evolved from one cell living inside another cell, and mitochondria share many traits with free-living bacteria (similar chromosome, similar ribosomes, etc). #### Endoplasmic Reticulum : **Endoplasmic** means \"within the plasm\" and **reticulum** means \"network\". A complex three dimensional internal membrane system of flattened sheets, sacs and tubes, that play an important role in making proteins and shuttling cellular products; also involved in metabolisms of fats, and the production of various materials. In cross-section, they appear as a series of maze-like channels, often closely associated with the nucleus. When ribosomes are present, the rough ER connects polysaccharide groups to the polypeptides as they are assembled by the ribosomes. Smooth ER, without ribosomes, is responsible for various activities, including the synthesis of lipids and hormones, especially in cells that produce these substances for export from the cell. Rough endoplasmic reticulum has characteristic bumpy appearance due to the multitude of ribosomes coating it. It is the site where proteins not destined for the cytoplasm are synthesized. Smooth endoplasmic reticulum provides a variety of functions, including lipid synthesis and degradation, and calcium ion storage. In liver cells, the smooth ER is involved in the breakdown of toxins, drugs, and toxic byproducts from cellular reactions. #### Golgi Apparatus \"Packages\" cellular products in sacs called vesicles so that the products can cross the cell membrane and exit the cell. The **Golgi apparatus** is the central delivery system for the cell. It is a group of flattened sacs arranged much like a stack of bowls. They function to modify and package proteins and lipids into vesicles, small spherically shaped sacs that bud from the ends of a Golgi apparatus. Vesicles often migrate to and merge with the plasma membrane, releasing their contents outside the cell. The Golgi apparatus also transports lipids and creates lysosomes and organelles involved in digestion. #### Vacuoles Spaces in the cytoplasm that sometimes serve to carry materials to the cell membrane for discharge to the outside of the cell. **Vacuoles** are formed during endocytosis when portions of the cell membrane are pinched off. #### Lysosomes Lysosomes are sac-like compartments that contain a number of powerful degradative enzymes. They are built in the Golgi apparatus. They break down harmful cell products and waste materials, cellular debris, and foreign invaders such as bacteria, and then force them out of the cell. Tay-Sachs disease and Pompe\'s disease are just two of the malfunctions of lysosomes or their digestive proteins. #### Peroxisomes Organelles in which oxygen is used to oxidize substances, breaking down lipids and detoxifying certain chemicals. Peroxisomes self replicate by enlarging and then dividing. They are common in liver and kidney cells that break down potentially harmful substances. Peroxisomes can convert hydrogen peroxide, a toxin made of H~2~O~2~ to H~2~O. ### Extracellular structures - **Extracellular matrix** Human cells, like other animal cells, do not have a rigid cell wall. Human cells do have an important and variable structure outside of their cell membrane called the extracellular matrix. Sometimes this matrix can be extensive and solid (examples = calcified bone matrix, cartilage matrix), while other times it consists of a layer of extracellular proteins and carbohydrates. This matrix is responsible for cells binding to each other and is incredibly important in how cells physically and physiologically interact with each other. - **Flagella** Many prokaryotes have flagella, allowing, for example, an *E. coli* bacteria to propel its way up the urethra to cause a UTI (Urinary Tract Infection). Human cells, however (and in fact most eukaryotic cells) lack flagella. This makes sense since humans are multicellular, and individual cells do not need to swim around. The obvious exception to this is with sperm, and indeed each sperm is propelled by a single flagellum. The flagellum of sperm is composed of microtubules. - **Cilia** Cilia are especially notable on the single-celled protozoans, where they beat in synchrony to move the cells nimbly through the water. They are composed of extensions of the cell membrane that contain microtubules. When present in humans they are typically found in large numbers on a single surface of the cells, where rather than moving cells, they move materials. The *mucociliary escalator* of the respiratory system consists of mucus-secreting cells lining the trachea and bronchi, and ciliated epithelial cells that move the mucus ever-upward. In this manner mold spores, bacteria, and debris are caught in the mucus, removed from the trachea, and pushed into the esophagus (to be swallowed into a pit of acid). In the oviducts cilia move the ovum from the ovary to the uterus, a journey which takes a few days. right\|framed\|A magnified view of several cells, with visible cilia. ## Cell Junctions The plasma membranes of adjacent cells are usually separated by extracellular fluids that allow transport of nutrients and wastes to and from the bloodstream. In certain tissues, however, the membranes of adjacent cells may join and form a junction. Three kinds of cell junctions are recognized: - **Desmosomes** are protein attachments between adjacent cells. Inside the plasma membrane, a desmosome bears a disk shaped structure from which protein fibers extend into the cytoplasm. Desmosomes act like spot welds to hold together tissues that undergo considerable stress, such as our skin or heart muscle. ```{=html} <!-- --> ``` - **Tight junctions** are tightly stitched seams between cells. The junction completely encircles each cell, preventing the movement of material between the cell. Tight junctions are characteristic of cells lining the digestive tract, where materials are required to pass through cells,rather than intercellular spaces, to penetrate the bloodstream. ```{=html} <!-- --> ``` - **Gap junctions** are narrow tunnels that directly connect the cytoplasm of two neighbouring cells, consisting of proteins called connexons. These proteins allow only the passage of ions and small molecules. In this manner, gap junctions allow communication between cells through the exchange of materials or the transmission of electrical impulses. ## Cell Metabolism **Cell metabolism** is the total energy released and consumed by a cell. Metabolism describes all of the chemical reactions that are happening in the body. Some reactions, called anabolic reactions, create needed products. Other reactions, called catabolic reactions, break down products. Your body is performing both anabolic and catabolic reactions at the same time and around the clock, twenty four hours a day, to keep your body alive and functioning. Even while you sleep, your cells are busy metabolizing. - **Catabolism**: The energy releasing process in which a chemical or food is used (broken down) by degradation or decomposition, into smaller pieces. ```{=html} <!-- --> ``` - **Anabolism**: Anabolism is just the opposite of catabolism. In this portion of metabolism, the cell consumes energy to produce larger molecules via smaller ones. ### Energy Rich Molecules #### Adenosine Triphosphate (ATP) !Chemical diagram of an ATP molecule. ATP is the currency of the cell. When the cell needs to use energy such as when it needs to move substances across the cell membrane via the active transport system, it \"pays\" with molecules of ATP. The total quantity of ATP in the human body at any one time is about 0.1 Mole. The energy used by human cells requires the hydrolysis of 200 to 300 moles of ATP daily. This means that each ATP molecule is recycled 2000 to 3000 times during a single day. ATP cannot be stored, hence its consumption must closely follow its synthesis. On a per-hour basis, 1 kilogram of ATP is created, processed and then recycled in the body. Looking at it another way, a single cell uses about 10 million ATP molecules per second to meet its metabolic needs, and recycles all of its ATP molecules about every 20-30 seconds. #### Flavin Adenine Dinucleotide (FAD) When two hydrogen atoms are bonded, FAD is reduced to FADH~2~ and is turned into an energy-carrying molecule. FAD accommodates two equivalents of Hydrogen; both the hydride and the proton ions. This is used by organisms to carry out energy requiring processes. FAD is reduced in the citric acid cycle during aerobic respiration #### Nicotinamide Adenine Dinucleotide (NADH) Nicotinamide adenine dinucleotide (NAD^+^) and nicotinamide adenine dinucleotide phosphate (NADP) are two important cofactors found in cells. NADH is the reduced form of NAD^+^, and NAD^+^ is the oxidized form of NADH. It forms NADP with the addition of a phosphate group to the 2\' position of the adenosyl nucleotide through an ester linkage. NAD is used extensively in glycolysis and the citric acid cycle of cellular respiration. The reducing potential stored in NADH can be converted to ATP through the electron transport chain or used for anabolic metabolism. ATP \"energy\" is necessary for an organism to live. Green plants obtain ATP through photosynthesis, while other organisms obtain it by cellular respiration. NADP is used in anabolic reactions, such as fat acid and nucleic acid synthesis, that require NADPH as a reducing agent. In chloroplasts, NADP is an oxidising agent important in the preliminary reactions of photosynthesis. The NADPH produced by photosynthesis is then used as reducing power for the biosynthetic reactions in the Calvin cycle of photosynthesis. !Chemical diagram of an NADH molecule. MH~2~ + NAD^+^ → NADH + H^+^ + M: + energy, where M is a metabolite. Two hydrogen ions (a hydride ion and an H^+^ ion) are transferred from the metabolite. One electron is transferred to the positively-charged nitrogen, and one hydrogen attaches to the carbon atom opposite to the nitrogen. The human body synthesizes NAD from the vitamin niacin in the form of nicotinic acid or nicotinamide. #### Cellular Respiration Cellular respiration is the energy releasing process by which sugar molecules are broken down by a series of reactions and the chemical energy gets converted to energy stored in ATP molecules. The reactions that convert the fuel (glucose) to usable cellular energy (ATP) are glycolysis, the Krebs cycle (sometimes called the citric acid cycle), and the electron transport chain. Altogether these reactions are referred to as \"cellular respiration\" or \"aerobic respiration.\" Oxygen is needed as the final electron acceptor, and carrying out cellular respiration is the very reason we breathe and the reason we eat. center\|framed\|Flowchart of cellular respiration..svg "wikilink") ### Glycolysis The glycolytic pathway (glycolysis) is where glucose, the smallest molecule that a carbohydrate can be broken into during digestion, gets oxidized and broken into two 3-carbon molecules (pyruvates), which are then fed into the Kreb\'s Cycle. Glycolysis is the beginning of cellular respiration and takes place in the cytoplasm. Two molecules of ATP are required for glycolysis, but four are produced so there is a net gain of two ATP per glucose molecule. Two NADH molecules transfer electrons (in the form of hydrogen ions) to the electron transport chain in the mitochondria, where they will be used to generate additional ATP. During physical exertion when the mitochondria are already producing the maximum ATP possible with the amount of oxygen available, glycolysis can continue to produce an additional 2 ATP per glucose molecule without sending the electrons to the mitochondria. However, during this *anaerobic respiration* lactic acid is produced, which may accumulate and lead to temporary muscle cramping. ### Krebs Cycle The Krebs cycle was named after Sir Hans Krebs (1900-1981), who proposed the key elements of this pathway in 1937 and was awarded the Nobel Prize in Medicine for its discovery in 1953. Two molecules of pyruvate enter the Krebs cycle, which is called the aerobic pathway because it requires the presence of oxygen in order to occur. This cycle is a major biological pathway that occurs in humans and every plant and animal. After glycolysis takes place in the cell\'s cytoplasm, the pyruvic acid molecules travel into the interior of the mitochondrion. Once the pyruvic acid is inside, carbon dioxide is enzymatically removed from each three-carbon pyruvic acid molecule to form acetic acid. The enzyme then combines the acetic acid with an enzyme, coenzyme A, to produce acetyl coenzyme A, also known as acetyl CoA. Once acetyl CoA is formed, the Krebs cycle begins. The cycle is split into eight steps, each of which will be explained below. - Step 1: The acetic acid subunit of acetyl CoA is combined with oxaloacetate to form a molecule of citrate. The acetyl coenzyme A acts only as a transporter of acetic acid from one enzyme to another. After Step 1, the coenzyme is released by hydrolysis so that it may combine with another acetic acid molecule to begin the Krebs cycle again. - Step 2: The citric acid molecule undergoes an isomerization. A hydroxyl group and a hydrogen molecule are removed from the citrate structure in the form of water. The two carbons form a double bond until the water molecule is added back. Only now, the hydroxyl group and hydrogen molecule are reversed with respect to the original structure of the citrate molecule. Thus, isocitrate is formed. - Step 3: In this step, the isocitrate molecule is oxidized by a NAD molecule. The NAD molecule is reduced by the hydrogen atom and the hydroxyl group. The NAD binds with a hydrogen atom and carries off the other hydrogen atom leaving a carbonyl group. This structure is very unstable, so a molecule of CO~2~ is released creating alpha-ketoglutarate. - Step 4: In this step, our friend, coenzyme A, returns to oxidize the alpha-ketoglutarate molecule. A molecule of NAD is reduced again to form NADH and leaves with another hydrogen. This instability causes a carbonyl group to be released as carbon dioxide and a thioester bond is formed in its place between the former alpha-ketoglutarate and coenzyme A to create a molecule of succinyl-coenzyme A complex. - Step 5: A water molecule sheds its hydrogen atoms to coenzyme A. Then, a free-floating phosphate group displaces coenzyme A and forms a bond with the succinyl complex. The phosphate is then transferred to a molecule of GDP to produce an energy molecule of GTP. It leaves behind a molecule of succinate. - Step 6: In this step, succinate is oxidized by a molecule of FAD (Flavin adenine dinucleotide). The FAD removes two hydrogen atoms from the succinate and forces a double bond to form between the two carbon atoms, thus creating fumarate. - Step 7: An enzyme adds water to the fumarate molecule to form malate. The malate is created by adding one hydrogen atom to a carbon atom and then adding a hydroxyl group to a carbon next to a terminal carbonyl group. - Step 8: In this final step, the malate molecule is oxidized by a NAD molecule. The carbon that carried the hydroxyl group is now converted into a carbonyl group. The end product is oxaloacetate which can then combine with acetyl-coenzyme A and begin the Krebs cycle all over again. - Summary: In summary, three major events occur during the Krebs cycle. One GTP (guanosine triphosphate) is produced which eventually donates a phosphate group to ADP to form one ATP; three molecules of NAD are reduced; and one molecule of FAD is reduced. Although one molecule of GTP leads to the production of one ATP, the production of the reduced NAD and FAD are far more significant in the cell\'s energy-generating process. This is because NADH and FADH~2~ donate their electrons to an electron transport system that generates large amounts of energy by forming many molecules of ATP. To see a visual summary of \"Kreb Cycle\" please click here. ### Electron Transport System The most complicated system of all. In the respiration chain, oxidation and reduction reactions occur repeatedly as a way of transporting energy. The respiratory chain is also called the electron transport chain. At the end of the chain, oxygen accepts the electron and water is produced. #### Redox Reaction This is a simultaneous oxidation-reduction process whereby cellular metabolism occurs, such as the oxidation of sugar in the human body, through a series of very complex electron transfer processes. The chemical way to look at redox processes is that the substance being oxidized transfers electrons to the substance being reduced. Thus, in the reaction, the substance being oxidized (aka. the reducing agent) loses electrons, while the substance being reduced (aka. the oxidizing agent) gains electrons. Remember: LEO (Losing Electrons is Oxidation) the lion says GER (Gaining Electrons is Reduction); or alternatively: OIL (Oxidation is Loss) RIG (Reduction is Gain). The term redox state is often used to describe the balance of NAD^+^/NADH and NADP^+^/NADPH in a biological system such as a cell or organ. The redox state is reflected in the balance of several sets of metabolites (e.g., lactate and pyruvate, β-hydroxybutyrate and acetoacetate) whose interconversion is dependent on these ratios. An abnormal redox state can develop in a variety of deleterious situations, such as hypoxia, shock, and sepsis. ## Cell Building Blocks What major classes of molecules are found within cells? ### Lipids The term is more-specifically used to refer to fatty-acids and their derivatives (including tri-, di-, and mono-glycerides and phospholipids) as well as other fat-soluble sterol-containing metabolites such as cholesterol. Lipids serve many functions in living organisms including energy storage, serve as structural components of cell membranes, and constitute important signaling molecules. Although the term lipid is sometimes used as a synonym for fat, the latter is in fact a subgroup of lipids called triglycerides and should not be confused with the term fatty acid. ### Carbohydrates Carbohydrate molecules consist of carbon, hydrogen, and oxygen. They have a general formula C~n~(H~2~O)~n~. There are several sub-families based on molecular size. Carbohydrates are chemical compounds that contain oxygen, hydrogen, and carbon atoms, and no other elements. They consist of monosaccharide sugars of varying chain lengths. Certain carbohydrates are an important storage and transport form of energy in most organisms, including plants and animals. Carbohydrates are classified by their number of sugar units: monosaccharides (such as glucose and fructose), disaccharides (such as sucrose and lactose), oligosaccharides, and polysaccharides (such as starch, glycogen, and cellulose). The simplest carbohydrates are monosaccharides, which are small straight-chain aldehydes and ketones with many hydroxyl groups added, usually one on each carbon except the functional group. Other carbohydrates are composed of monosaccharide units and break down under hydrolysis. These may be classified as disaccharides, oligosaccharides, or polysaccharides, depending on whether they have two, several, or many monosaccharide units. ![](Protein-structure.png‎ "Protein-structure.png‎") ### Proteins All proteins contain carbon, hydrogen, oxygen and nitrogen. Some also contain phosphorus and sulfur. The building blocks of proteins are amino acids. There are 20 different kinds of amino acids used by the human body. They unite by peptide bonds to form long molecules called polypeptides. Polypeptides are assembled into proteins. Proteins have four levels of structure - **Primary** Primary structure is the sequence of amino acids bonded in the polypeptide. - **Secondary** The secondary structure is formed by hydrogen bonds between amino acids. The polypeptide can coil into a helix or form a pleated sheet. - **Tertiary** The tertiary structure refers to the three-dimensional folding of the helix or pleated sheet. - **Quaternary** The quaternary structure refers to the spatial relationship among the polypeptide in the protein. - **Hexagonary** The hexagonary structure refers to the carpal relationship among the bipeptide in the person. ### Enzymes A biological molecule that catalyzes a chemical reaction. Enzymes are essential for life because most chemical reactions in living cells would occur too slowly or would lead to different products without enzymes. Most enzymes are proteins and the word \"enzyme\" is often used to mean a protein enzyme. Some RNA molecules also have a catalytic activity, and to differentiate them from protein enzymes, they are referred to as RNA enzymes or ribozymes. ## Review Questions Answers for these questions can be found here 1\. List 2 functions of the cell membrane: Questions 2 - 6 Match the following organelles with their function: 2. Mitochondria 3. Vacuoles 4. Cilia 5. Smooth ER 6. Golgi Apparatus : A. Movement of the cell : B. Lipid synthesis and transport : C. \"Powerhouse\" of the cell, makes ATP : D. Storage areas, mainly found in plant cells : E. Packages and distributes cellular products 7\. The diffusion of H~2~O across a semi permeable or selectively permeable membrane is termed : A. Active transport : B. Diffusion : C. Osmosis : D. Endocytosis 8\. Oxygen enters a cell via? : a\. Diffusion : b\. Filtration : c\. Osmosis : d\. Active transport 9\. The term used to describe, \"cell eating\" is? : a\. Exocytosis : b\. Phagocytosis : c\. Pinocytosis : d\. Diffusion 10\. Which of the following requires energy? : a\. Diffusion : b\. Osmosis : c\. Active transport : d\. Facilitated diffusion 11\. Protein synthesis occurs at the : a\. Mitochondria : b\. Lysosomes : c\. Within the nucleus : d\. Ribosomes 12\. Which of the following is not found in the cell membrane? : a\. Cholesterol : b\. Phospholipids : c\. Proteins : d\. Galactose : e\. Nucleic acids 13\. What is a cell? : a\. The largest living units within our bodies. : b\. Enzymes that \"eat\" bacteria : c\. Microscopic fundamental units of all living things. : d\. All of the above. ## Glossary **Active Transport**: the movement of solutes against a gradient and requires the expenditure of energy **Adenosine Triphosphate (ATP):** a cell's source of energy **Bulk Flow:** the collective movement of substances in the same direction in response to a force **Cells:** the microscopic fundamental unit that makes up all living things **Cell Membrane:** boundary of the cell, sometimes called the plasma membrane **Cytoplasm:** a water-like substance that fills cells. The cytoplasm consists of cytosol and the cellular organelles, except the cell nucleus. The cytosol is made up of water, salts, organic molecules and many enzymes that catalyze reactions. The cytoplasm holds all of the cellular organelles outside of the nucleus, maintains the shape and consistency of the cell, and serves as a storage place for chemical substances. **Cytoskeleton:** made of threadlike proteins, helps cells maintain their shape and allows cells and their contents to move **Dialysis:** the diffusion of solutes across a selectively permeable membrane. Most commonly heard of when a patient has had renal failure. In medicine, dialysis is a type of renal replacement therapy which is used to provide an artificial replacement for lost kidney function due to renal failure. It is a life support treatment and does not treat any kidney diseases. **Endocrine cells:** similar to exocrine cells, but secrete their products directly into the bloodstream instead of through a duct **Endocytosis:** the capture of a substance outside the cell when the plasma membrane merges to engulf it **Endoplasmic Reticulum:** organelle that play an important role in making proteins and shuttling cellular products; also involved in metabolisms of fats, and the production of various materials **Epithelial Cells:** cells that aid in secretion, absorption, protection, trans-cellular transport, sensation detection, and selective permeability **Exocrine Cells:** cells that secrete products through ducts, such as mucus, sweat, or digestive enzymes **Exocytosis:** the process of vesicles fusing with the plasma membrane and releasing their contents to the outside of the cell **Facilitated Diffusion:** the diffusion of solutes through channel proteins in the plasma membrane **Golgi Apparatus:** \"packages\" cellular products in sacs called vesicles so that the products can cross the cell membrane and exit the cell **Glycolysis:** process in which sugars (glucose) are converted to acid **Lysosomes:** sac-like compartments that contain a number of powerful degradative enzymes **Microfilaments:** provide mechanical support for the cell, determine the cell shape, and in some cases enable cell movements **Microtubules:** function as the framework along which organelles and vesicles move within a cell **Mitochondria:** the organelles that function as the cell \"powerhouse\", generating ATP **Nucleus:** controls the cell; houses the genetic material **Organelles:** bodies embedded in the cytoplasm that serve to physically separate the various metabolic activities that occur within cells **Osmosis:** the diffusion of water molecules across a selectively permeable membrane from an area of high solute concentration to an area of low solute concentration. **Passive Transport:** the movement of substances down a concentration gradient and does not require energy use **Peroxisomes:** organelles in which oxygen is used to oxidize substances, breaking down lipids and detoxifying certain chemicals **Phagocytosis:** a form of endocytosis wherein large particles are enveloped by the cell membrane of a (usually larger) cell and internalized to form a phagosome, or \"food vacuole.\" In animals, phagocytosis is performed by specialized cells called phagocytes, which serve to remove foreign bodies and thus fight infection. In vertebrates, these include larger macrophages and smaller granulocytes, types of blood cells. Bacteria, dead tissue cells, and small mineral particles are all examples of objects that may be phagocytosed. **Pinocytosis:** also called cellular drinking, is a form of endocytosis, a process in which small particles are taken in by a cell by splitting into smaller particles. The particles then form small vesicles which subsequently fuse with lysosomes to hydrolyze, or to break down, the particles. This process requires adenosine triphosphate (ATP). **Receptor-mediated Endocytosis:** occurs when specific molecules in the fluid surrounding the cell bind to specialized receptors in the plasma membrane **Red Blood Cells (erythrocytes):** cells that collect oxygen in the lungs and deliver it through the blood to the body tissues **Ribosomes:** play an active role in the complex process of protein synthesis, where they serve as the structures that facilitate the joining of amino acids **Simple Diffusion:** the net movement of substances from an area of higher concentration to an area of lower concentration **Vacuoles:** spaces in the cytoplasm that sometimes serve to carry materials to the cell membrane for discharge to the outside of the cell **White Blood Cells (leukocytes):** produced in the bone marrow and help the body to fight infectious disease and foreign objects in the immune system
# Human Physiology/Integumentary System ## Introduction The **integumentary system** consists of the skin, hair, nails, the subcutaneous tissue below the skin,and assorted glands.The most obvious function of the integumentary system is the protection that the skin gives to underlying tissues. The skin not only keeps most harmful substances out, but also prevents the loss of fluids. A major function of the subcutaneous tissue is to connect the skin to underlying tissues such as muscles. Hair on the scalp provides insulation from cold for the head. The hair of eyelashes and eyebrows helps keep dust and perspiration out of the eyes, and the hair in our nostrils helps keep dust out of the nasal cavities. Any other hair on our bodies no longer serves a function, but is an evolutionary remnant. Nails protect the tips of fingers and toes from mechanical injury. Fingernails give the fingers greater ability to pick up small objects. There are four types of glands in the integumentary system: Sudoriferous glands, Sebaceous glands, Ceruminous glands, and Mammary glands. Sudoriferous glands are sweat producing glands. These are important to help maintain body temperature. Sebaceous glands are oil producing glands which help inhibit bacteria, keep us waterproof and prevent our hair and skin from drying out. Ceruminous glands produce earwax which keeps the outer surface of the eardrum pliable and prevents drying. Mammary glands produce milk. ## Skin In zoology and dermatology, skin is an organ of the integumentary system made up of a layer of tissues that guard underlying muscles and organs. As the interface with the surroundings, it plays the most important role in protecting against pathogens. Its other main functions are insulation and temperature regulation, sensation and vitamin D and B synthesis. Skin is considered one of the most important parts of the body. Skin has pigmentation, melanin, provided by melanocytes, which absorbs some of the potentially dangerous radiation in sunlight. It also contains DNA repair enzymes which reverse UV damage, and people who lack the genes for these enzymes suffer high rates of skin cancer. One form predominantly produced by UV light, malignant melanoma, is particularly invasive, causing it to spread quickly, and can often be deadly. Human skin pigmentation varies among populations in a striking manner. This has sometimes led to the classification of people(s) on the basis of skin color. Damaged skin will try to heal by forming scar tissue, often giving rise to discoloration and depigmentation of the skin. The skin is often known as \"the largest organ in the human body\". This applies to exterior surface, as it covers the body, appearing to have the largest surface area of all the organs. Moreover, it applies to weight, as it weighs more than any single internal organ, accounting for about 15 percent of body weight. For the average adult human, the skin has a surface area of between 1.5-2.0 square meters, most of it is between 2-3 mm thick. The average square inch of skin holds 650 sweat glands, 20 blood vessels, 60,000 melanocytes, and more than a thousand nerve endings. The use of natural or synthetic cosmetics to treat the appearance of the face and condition of the skin (such as pore control and black head cleansing) is common among many cultures. ### Layers The skin has two major layers which are made of different tissues and have very different functions. !Diagram of the layers of human skin{width="400"} Skin is composed of the *epidermis* and the *dermis*. Below these layers lies the *hypodermis or subcutaneous adipose layer*, which is not usually classified as a layer of skin. The outermost epidermis consists of stratified squamous keratinizing epithelium with an underlying basement membrane. It contains no blood vessels, and is nourished by diffusion from the dermis. The main type of cells which make up the epidermis are keratinocytes, with melanocytes and Langerhans cells also present. The epidermis can be further subdivided into the following *strata* (beginning with the outermost layer): corneum, lucidum, granulosum, spinosum, basale. Cells are formed through mitosis at the innermost layers. They move up the strata changing shape and composition as they differentiate, inducing expression of new types of keratin genes. They eventually reach the corneum and become sloughed off (desquamation). This process is called *keratinization* and takes place within about 30 days. This layer of skin is responsible for keeping water in the body and keeping other harmful chemicals and pathogens out. Blood capillaries are found beneath the dermis, and are linked to an arteriole and a venule. Arterial shunt vessels may bypass the network in ears, the nose and fingertips. The dermis lies below the epidermis and contains a number of structures including blood vessels, nerves, hair follicles, smooth muscle, glands and lymphatic tissue. It consists of loose connective tissue otherwise called areolar connective tissue---collagen, elastin and reticular fibers are present. Erector muscles, attached between the hair papilla and epidermis, can contract, resulting in the hair fiber pulled upright and consequentially goose bumps. The main cell types are fibroblasts, adipocytes (fat storage) and macrophages. Sebaceous glands are exocrine glands which produce a mixture of lipids and waxy substances known as sebum. Sebum serves many functions, including lubrication, water-proofing, softening, and also provides antimicrobial properties. Sweat glands open up via a duct onto the skin by a pore. The dermis is made of an irregular type of fibrous connective tissue consisting of collagen and elastin fibers. It can be split into the *papillary* and *reticular* layers. The papillary layer is outermost and extends into the epidermis to supply it with vessels. It is composed of loosely arranged fibers. Papillary ridges make up the lines of the hands giving us fingerprints. The reticular layer is more dense and is continuous with the hypodermis. It contains the bulk of the structures (such as sweat glands). The reticular layer is composed of irregularly arranged fibers and resists stretching. The hypodermis is not part of the skin, and lies below the dermis. Its purpose is to attach the skin to underlying bone and muscle as well as supplying it with blood vessels and nerves. It consists of loose connective tissue and elastin. The main cell types are fibroblasts, macrophages and adipocytes (the hypodermis contains 95% of body fat). Fat serves as padding and insulation for the body. ### Functions ![](Pili.JPG "Pili.JPG") 1. Protection: Skin gives an anatomical barrier between the internal and external environment in bodily defense; Langerhans cells in the skin are part of the immune system 2. Sensation: Skin contains a variety of nerve endings that react to heat, cold, touch, pressure, vibration, and tissue injury; see somatosensory system and touch. 3. Heat regulation: The skin contains a blood supply far greater than its requirements which allows precise control of energy loss by radiation, convection and conduction. Dilated blood vessels increase perfusion and heat loss while constricted vessels greatly reduce cutaneous blood flow and conserve heat. Erector pili muscles are significant in animals. #### Tumors - Benign tumors of the skin: Squamous cell papilloma - Skin cancer - Acne - Keratosis pilaris - Fungal infections such as athlete\'s foot - microbial infections - calcinosis cutis - ulcer ## Hair ### Types of hair Humans have three different types of hair: - Lanugo, the fine, unpigmented hair that covers nearly the entire body of a fetus, although most has been replaced with vellus by the time of the baby\'s birth - Vellus hair, the short, downy, \"peach fuzz\" body hair (also unpigmented) that grows in most places on the human body. While it occurs in both sexes, and makes up much of the hair in children, men have a much smaller percentage (around 10%) vellus whereas 2/3 of a female\'s hair is vellus. - Terminal hair, the fully developed hair, which is generally longer, coarser, thicker, and darker than vellus hair, and often is found in regions such as the axillary, male beard, and pubic. ### Pathological impacts on hair Drugs used in cancer chemotherapy frequently cause a temporary loss of hair, noticeable on the head and eyebrows, because they kill all rapidly dividing cells, not just the cancerous ones. Other diseases and traumas can cause temporary or permanent loss of hair, either generally or in patches. The hair shafts may also store certain poisons for years, even decades, after death. In the case of Col. Lafayette Baker, who died July 3, 1868, use of an atomic absorption spectrophotometer showed the man was killed by white arsenic. The prime suspect was Wallace Pollock, Baker\'s brother-in-law. According to Dr. Ray A. Neff, Pollack had laced Baker\'s beer with it over a period of months, and a century or so later minute traces of arsenic showed up in the dead man\'s hair. Mrs. Baker\'s diary seems to confirm that it was indeed arsenic, as she writes of how she found some vials of it inside her brother\'s suit coat one day. ## Nails {{-}} ### Parts of the fingernail !The parts of a finger nail{width="200"} The fingernail is an important structure made of keratin. The fingernail generally serve two purposes. It serves as a protective plate and enhances sensation of the fingertip. The protection function of the fingernail is commonly known, but the sensation function is equally important. The fingertip has many nerve endings in it allowing us to receive volumes of information about objects we touch. The nail acts as a counterforce to the fingertip providing even more sensory input when an object is touched. ### Nail Structure The structure we know of as the nail is divided into six specific parts - the root, nail bed, nail plate, eponychium (cuticle), perionychium, and hyponychium. **Root** The root of the fingernail is also known as the germinal matrix. This portion of the nail is actually beneath the skin behind the fingernail and extends several millimeters into the finger. The fingernail root produces most of the volume of the nail and the nail bed. This portion of the nail does not have any melanocytes, or melanin producing cells. The edge of the germinal matrix is seen as a white, crescent shaped structure called the lunula. **Nail Bed** The nail bed is part of the nail matrix called the sterile matrix. It extends from the edge of the germinal matrix, or lunula, to the hyponychium. The nail bed contains the blood vessels, nerves, and melanocytes, or melanin-producing cells. As the nail is produced by the root, it streams down along the nail bed, which adds material to the undersurface of the nail making it thicker. It is important for normal nail growth that the nail bed be smooth. If it is not, the nail may split or develop grooves that can be cosmetically unappealing. **Nail Plate** The nail plate is the actual fingernail, made of translucent keratin. The pink appearance of the nail comes from the blood vessels underneath the nail. The underneath surface of the nail plate has grooves along the length of the nail that help anchor it to the nail bed. **eponychium** The cuticle of the fingernail is also called the eponychium. The cuticle is situated between the skin of the finger and the nail plate fusing these structures together and providing a waterproof barrier. **Perionychium** The perionychium is the skin that overlies the nail plate on its sides. It is also known as the paronychial edge. The perionychium is the site of hangnails, ingrown nails, and an infection of the skin called paronychia. **Hyponychium** The hyponychium is the area between the nail plate and the fingertip. It is the junction between the free edge of the nail and the skin of the fingertip, also providing a waterproof barrier. !Nails: left hand, adult human male{width="200"} ### Nail Diseases Nail diseases are in a separate category from diseases of the skin. Although nails are a skin appendage, they have their own signs and symptoms which may relate to other medical conditions. Nail conditions that show signs of infection or inflammation require medical assistance and cannot be treated at a beauty parlor. Deformity or disease of the nails may be referred to as **onychosis**. There are many disease that can occur with the fingernails and toenails. The most common of these diseases are ingrown nails and fungal infections. #### Ingrown Nails **Onychocryptosis**, commonly known as \"ingrown nails\" (unguis incarnatus), can affect either the fingers or the toes. In this condition, the nail cuts into one or both sides of the nail bed, resulting in inflammation and possibly infection. The relative rarity of this condition in the fingers suggests that pressure from the ground or shoe against the toe is a prime factor. The movements involved in walking or other physical disturbances can contribute to the problem. Mild onychocryptosis, particularly in the absence of infection, can be treated by trimming and rounding the nail. More advanced cases, which usually include infection, are treated by surgically excising the ingrowing portion of the nail down to its bony origin and cauterizing the matrix, or \'root\', to prevent recurrence. This surgery is called matricectomy. The best results are achieved by cauterizing the matrix with phenol. Another method, which is much less effective, is excision of the matrix, sometimes called a \'cold steel procedure\' #### Nail Fungus An infection of nail fungus (onychomycosis) occurs when fungi infect one or more of your nails. **Onychomycosis** generally begins as a white or yellow spot under the tip of the fingernail or toenail. As the nail fungus spreads deeper into the nail, it may cause the nail to discolor, thicken and develop crumbling edges --- an unsightly and potentially painful problem. Infections of nail fungus account for about half of all nail disorders. These infections usually develop on nails continually exposed to warm, moist environments, such as sweaty shoes or shower floors. Nail fungus isn\'t the same as athlete\'s foot, which primarily affects the skin of the feet, but at times the two may coexist and can be caused by the same type of fungus. Topical steroid misuse is one of the most common cause now a days. An infection with nail fungus may be difficult to treat, and infections may recur. But medications are available to help clear up nail fungus permanently. ### Clinical Application Nail inspection can give a great deal of information about the internal working of the body as well, and like tongue or iris inspection, has a long history of diagnostic use in cantraditional medical practices such as Chinese medicine. **Pliability:** Brittleness is associated with iron deficiency, thyroid problems, impaired kidney function, circulation problems\[2\], and biotin deficiency\[3\] Splitting and fraying are associated with psoriasis, folic acid, protein and/or Vitamin C deficiency. Unusual thickness is associated with circulation problems. Thinning nails and itchy skin are associated with lichen planus\[4\]. **Shape and texture:** Clubbing, or nails that curve down around the fingertips with nail beds that bulge is associated with oxygen deprivation and lung, heart, or liver disease. Spooning, or nails that grow upwards is associated with iron or B12 deficiency. Flatness can indicate a B12 vitamin deficiency\[5\] or Raynaud\'s disease\[6\] Pitting of the nails is associated with Psoriasis. Horizontal ridges indicate stress, and Beau\'s lines are associated with many serious conditions. Vertical ridges are associated with arthritis\[7\]. Vertical grooves are associated with kidney disorders, aging, and iron deficiency\[8\]. Beading is associated with rheumatoid arthritis\[9\]. Nails that resemble hammered brass are associated with (or portend) hair loss\[10\]. Short small beds are associated with heart disease\[11\]. **Coloration of the nail bed:** Mee\'s lines are associated with arsenic or thallium poisoning, and renal failure. White lines across the nail are associated with heart disease, liver disease, or a history of a recent high fever\[12\]. Opaque white nails with a dark band at the fingertip are associated with cancer, cirrhosis, congestive heart failure, diabetes and aging\[13\]. Paleness or whitening is associated with liver or kidney disease and anemia\[14\]. Yellowing of the nail bed is associated with chronic bronchitis, lymphatic problems, diabetes, and liver disorders. Brown or copper nail beds are associated with arsenic or copper poisoning, and local fungal infection. Grey nail beds are associated with arthritis, edema, malnutrition, post-operative effects, glaucoma and cardio-pulmonary disease\[15\]. redness is associated with heart conditions. dark nails are associated with B12 deficiency. Stains of the nail plate (not the nail bed) are associated with nail polish\[16\], smoking, and henna use. **Markings:** Pink and white nails are associated with kidney disease\[17\]. Parallel white lines in the nails are associated with hypoalbuminemia. red skin at the base of the nail is associated with connective tissue disorders\[18\]. blue lunulae are associated with silver poisoning or lung disorder\[19\]. blue nail beds are (much like blue skin) associated with poor oxygenation of the blood (asthma, emphysema, etc)\[20\]. small white patches are associated with zinc or calcium deficiency or malabsorption, parasites, or local injury\[21\]. receded lunulae (fewer than 8) are associated with poor circulation\[22\], shallow breathing habits or thyroid dysfunction\[23\]. large lunulae (more than 25% of the thumb nail) is associated with high blood pressure. ## Glands ### Sudoriferous(Sweat Glands) !A diagrammatic sectional view of the skin (magnified). Sweat gland labeled as \"sudoriferous gland\" at center right.. Sweat gland labeled as "sudoriferous gland" at center right."){width="350"} In humans, there are two kinds of sweat glands which differ greatly in both the composition of the sweat and its purpose: Also \"**click**\" here\[<http://health.howstuffworks.com/adam-200101.htm>\|\"How our body Sweats\"\] to see a short movie on sweat glands. #### Eccrine (a.k.a. merocrine) **Eccrine sweat glands** are exocrine glands distributed over the entire body surface but are particularly abundant on the palms of hands, soles of feet, and on the forehead. These produce sweat that is composed chiefly of water (99%) with various salts. The primary function is body temperature regulation. Eccrine sweat glands are coiled tubular glands derived leading directly to the most superficial layer of the epidermis (outer layer of skin) but extending into the inner layer of the skin (dermis layer). They are distributed over almost the entire surface of the body in humans and many other species but are lacking in some marine and fur-bearing species. The sweat glands are controlled by sympathetic cholinergic nerves which are controlled by a center in the hypothalamus. The hypothalamus senses core temperature directly, and also has input from temperature receptors in the skin and modifies the sweat output, along with other thermoregulatory processes. Human eccrine sweat is composed chiefly of water with various salts and organic compounds in solution. It contains minute amounts of fatty materials, urea, and other wastes. The concentration of sodium varies from 35--65 mmol/l and is lower in people acclimatized to a hot environment. The sweat of other species generally differs in composition. #### Apocrine Apocrine sweat glands only develop during early- to mid-puberty (approximately age 15) and release more than normal amounts of sweat for approximately a month and subsequently regulate and release normal amounts of sweat after a certain period of time. **Apocrine sweat glands** produce sweat that contains fatty materials. These glands are mainly present in the armpits and around the genital area and their activity is the main cause of sweat odor, due to the bacteria that break down the organic compounds in the sweat from these glands. Emotional stress increases the production of sweat from the apocrine glands, or more precisely: the sweat already present in the tubule is squeezed out. Apocrine sweat glands essentially serve as scent glands. In some areas of the body, these sweat glands are modified to produce wholly different secretions, including the cerumen (\"wax\") of the outer ear. Other glands, such as Mammary glands, are greatly enlarged and modified to produce milk. ### Sebaceous Glands !Schematic view of a hair follicle with sebaceous gland.{width="200"} The **sebaceous glands** are glands found in the skin of mammals. They secrete an oily substance called **sebum** (Latin, meaning *fat* or *tallow*) that is made of fat (lipids) and the debris of dead fat-producing cells. These glands exist in humans throughout the skin except in the palms of the hands and soles of the feet. Sebum acts to protect and waterproof hair and skin, and keep them from becoming dry, brittle, and cracked. It can also inhibit the growth of microorganisms on skin. Sebaceous glands can usually be found in hair-covered areas where they are connected to hair follicles to deposit sebum on the hairs, and bring it to the skin surface along the hair shaft. The structure consisting of hair, hair follicle and sebaceous gland is also known as **pilosebaceous unit**. Sebaceous glands are also found in non haired areas of lips, eyelids, penis, labia minora and nipples; here the sebum reaches the surface through ducts. In the glands, sebum is produced within specialized cells and is released as these cells burst; sebaceous glands are thus classified as holocrine glands. Sebum is odorless, but its bacterial breakdown can produce odors. Sebum is the cause of some people experiencing \"oily\" hair if it is not washed for several days. Earwax is partly sebum, as is mucopurulent discharge, the dry substance accumulating in the corners of the eye after sleeping. !A hair follicle with associated structures.{width="360"} The composition of sebum varies from species to species; in humans, the lipid content consists of about 25% wax monoesters, 41% triglycerides, 16% free fatty acids, and 12% squalene. The activity of the sebaceous glands increases during puberty because of heightened levels of androgens. Sebaceous glands are involved in skin problems such as acne and keratosis pilaris. A blocked sebaceous gland can result in a sebaceous cyst. The prescription drug isotretinoin significantly reduces the amount of sebum produced by the sebaceous glands, and is used to treat acne. The extreme use (up to 10 times doctor prescribed amounts) of anabolic steroids by bodybuilders to prevent weight loss tend to stimulate the sebaceous glands which can cause acne. The sebaceous glands of a human fetus *in utero* secrete a substance called Vernix caseosa, a \"waxy\" or \"cheesy\" white substance coating the skin of newborns. The preputial glands of mice and rats are large modified sebaceous glands that produce pheromones. ### Ceruminous glands !Wet-type human earwax on a cotton swab.{width="200"} **Earwax**, also known by the medical term **cerumen**, is a yellowish, waxy substance secreted in the ear canal of humans and many other mammals. It plays a vital role in the human ear canal, assisting in cleaning and lubrication, and also provides some protection from bacteria, fungus, and insects. A comprehensive review of the physiology and pathophysiology of cerumen can be found in Roeser and Ballachanda. Excess or impacted cerumen can press against the eardrum and/or occlude the external auditory canal and impair hearing. #### Production, composition, and different types Cerumen is produced in the outer third of the cartilaginous portion of the human ear canal. It is a mixture of viscous secretions from sebaceous glands and less-viscous ones from modified apocrine sweat glands. Two distinct genetically determined types of earwax are distinguished \-- the wet-type which is dominant, and the dry type which is recessive. Asians and Native Americans are more likely to have the dry type of cerumen (grey and flaky), whereas Caucasians and Africans are more likely to have the wet type (honey-brown to dark-brown and moist). Cerumen type has been used by anthropologists to track human migratory patterns, such as those of the Inuit. The difference in cerumen type has been tracked to a single base change (an single nucleotide polymorphism) in a gene known as \"ATP-binding cassette C11 gene\". In addition to affecting cerumen type, this mutation also reduces sweat production. The researchers conjecture that the reduction in sweat was beneficial to the ancestors of East Asians and Native Americans who are thought to have lived in cold climates. #### Function !Wet-type earwax fluoresces weakly under ultraviolet light..jpg "Wet-type earwax fluoresces weakly under ultraviolet light."){width="200"} **Cleaning.** Cleaning of the ear canal occurs as a result of the \"conveyor belt\" process of epithelial migration, aided by jaw movement. Cells formed in the center of the tympanic membrane migrate outwards from the umbo (at a rate equivalent to that of fingernail growth) to the walls of the ear canal, and accelerate towards the entrance of the ear canal. The cerumen in the canal is also carried outwards, taking with it any dirt, dust, and particulate matter that may have gathered in the canal. Jaw movement assists this process by dislodging debris attached to the walls of the ear canal, increasing the likelihood of its extrusion. **Lubrication.** Lubrication prevents desiccation and itching of the skin within the ear canal (known as *asteatosis*). The lubricative properties arise from the high lipid content of the sebum produced by the sebaceous glands. In wet-type cerumen at least, these lipids include cholesterol, squalene, and many long-chain fatty acids and alcohols. **Antibacterial and antifungal roles.** While studies conducted up until the 1960s found little evidence supporting an antibacterial role for cerumen, more recent studies have found that cerumen provides some bactericidal protection against some strains of bacteria. Cerumen has been found to be effective in reducing the viability of a wide range of bacteria (sometimes by up to 99%), including *Haemophilus influenzae*, *Staphylococcus aureus*, and many variants of *Escherichia coli*. The growth of two fungi commonly present in otomycosis was also significantly inhibited by human cerumen. These antimicrobial properties are due principally to the presence of saturated fatty acids, lysozyme and, especially, to the relatively low pH of cerumen (typically around 6.1 in normal individuals). ### Mammary Glands !Cross section of the breast of a human female.{width="200"} **Mammary glands** are the organs that, in the female mammal, produce milk for the sustenance of the young. These exocrine glands are enlarged and modified sweat glands and are the characteristic of mammals which gave the class its name. #### Structure The basic components of the mammary gland are the *alveoli* (hollow cavities, a few millimetres large) lined with milk-secreting epithelial cells and surrounded by myoepithelial cells. These alveoli join up to form groups known as *lobules*, and each lobule has a *lactiferous duct* that drains into openings in the nipple. The myoepithelial cells can contract, similar to muscle cells, and thereby push the milk from the alveoli through the lactiferous ducts towards the nipple, where it collects in widenings (*sinuses*) of the ducts. A suckling baby essentially squeezes the milk out of these sinuses. !Dissection of a lactating breast.\ 1 - Fat\ 2 - Lactiferous duct/lobule\ 3 - Lobule\ 4 - Connective tissue\ 5 - Sinus of lactiferous duct\ 6 - Lactiferous duct{width="250"} One distinguishes between a *simple mammary gland*, which consists of all the milk-secreting tissue leading to a single lactiferous duct, and a *complex mammary gland*, which consists of all the simple mammary glands serving one nipple. Humans normally have two complex mammary glands, one in each breast, and each complex mammary gland consists of 10-20 simple glands. (The presence of more than two nipples is known as polythelia and the presence of more than two complex mammary glands as polymastia.) Also, **\"click\"** this;\[<http://health.howstuffworks.com/adam-200040.htm>\|\"Breast tissue\"\], to this a movie visual of the breast. #### Development and hormonal control The development of mammary glands is controlled by hormones. The mammary glands exist in both sexes, but they are rudimentary until puberty when in response to ovarian hormones, they begin to develop in the female. Click this \<http://health.howstuffworks.com/adam-200042.htm%5Dto> see what breast tissue does in a female during menstruation. Estrogen promotes formation, while testosterone inhibits it. At the time of birth, the baby has lactiferous ducts but no alveoli. Little branching occurs before puberty when ovarian estrogens stimulate branching differentiation of the ducts into spherical masses of cells that will become alveoli. True secretory alveoli only develop in pregnancy, where rising levels of estrogen and progesterone cause further branching and differentiation of the duct cells, together with an increase in adipose tissue and a richer blood flow. Colostrum is secreted in late pregnancy and for the first few days after giving birth. True milk secretion (lactation) begins a few days later due to a reduction in circulating progesterone and the presence of the hormone prolactin. The suckling of the baby causes the release of the hormone oxytocin which stimulates contraction of the myoepithelial cells. #### Breast cancer As described above, the cells of mammary glands can easily be induced to grow and multiply by hormones. If this growth runs out of control, cancer results. Almost all instances of breast cancer originate in the lobules or ducts of the mammary glands. **Types of breast cancer** - [DCIS: Ductal Carcinoma in Situ - LCIS: Lobular Carcinoma in Situ - Invasive ductal carcinoma - Invasive lobular carcinoma - Inflammatory breast cancer - Paget\'s disease center\|framed\|Early Signs of Breast Cancer ## Homeostasis As a whole, the integumentary system plays a big part in maintaining homeostasis. The integumentary system is the outermost organ system of the body and many of its functions are related to this location. The skin protects the body against pathogens and chemicals, minimizes loss or entry of water, and blocks the harmful effects of sunlight. Sensory receptors in the skin provide information about the external environment, helping the skin regulate body temperature in response to environmental changes and helping the body react to pain and other tactile stimuli. The large surface area of the skin makes it ideal for temperature regulation. The rate of heat loss can be regulated by the amount of blood flowing through the blood vessels in the dermis close to the surface of the skin. When the body temperature rises, as for example during exercise, sympathetic tone is reduced and this brings about dilation of the blood vessels supplying the skin. The increase in skin blood flow allows heat to be lost more rapidly so that body temperature does not rise above the normal homeostatic range. The rate of heat loss can also be boosted by the production of sweat, which takes up additional heat as it evaporates. Conversely, if heat production is less than required, the dermal vessels constrict, sweating stops, and heat is conserved by the body. ## Glossary Areolar:Areolar connective tissue is a pliable, mesh-like tissue with a fluid matrix and functions to cushion and protect body organs. It acts as a packaging tissue holding the internal organs together and in correct placement. ```{=html} <!-- --> ``` Basal lamina :Basal lamina (often erroneously called basement membrane) is a layer on which epithelium sits. This layer is composed of an electron-dense layer (lamina densa) between two electron-lucid layers (lamina lucida), and is approximately 40-50 nm thick (with exceptions such as the 100-200 nm glomerular basement membrane). ```{=html} <!-- --> ``` Dermis : The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. ```{=html} <!-- --> ``` Epidermis : The epidermis is the outermost layer of the skin. It forms the waterproof, protective wrap over the body\'s surface and is made up of stratified squamous epithelium with an underlying basal lamina. ```{=html} <!-- --> ``` Fibroblasts :A fibroblast is a cell that makes the structural fibers and ground substance of connective tissue. ```{=html} <!-- --> ``` Hair follicle :A hair follicle is part of the skin that grows hair by packing old cells together. ```{=html} <!-- --> ``` Hypodermis : The hypodermis (also called the hypoderm), is the lowermost layer of the integumentary system in vertebrates. It is derived from the mesoderm, but unlike the dermis, it is not derived from the dermatome region of the mesoderm. ```{=html} <!-- --> ``` Impetigo: This is a superficial skin infection most common among children age 2--6 years. People who play close contact sports such as rugby, American football and wrestling are also susceptible, regardless of age. The name derives from the Latin impetere (\"assail\"). It is also known as school sores. ```{=html} <!-- --> ``` Melanocytes :These are cells located in the bottom layer of the skin\'s epidermis and in the middle layer of the eye, the uvea. Through a process called melanogenesis, these cells produce melanin, a pigment in the skin, eyes, and hair. ```{=html} <!-- --> ``` Melanoma : A melanoma is a malignant tumor that originates in melanocytes. It is a highly malignant form of skin cancer, and, though rare, is responsible for the majority of skin cancer-related deaths. ```{=html} <!-- --> ``` Onychosis :Deformity or disease of the nails ```{=html} <!-- --> ``` Papillary : The papillary layer is outermost and extends into the epidermis to supply it with vessels. It is composed of loosely arranged fibres. Papillary ridges make up the lines of the hands. ```{=html} <!-- --> ``` Recticular Layer : The reticular layer is more dense and is continuous with the hypodermis. It contains the bulk of the structures (such as sweat glands). The reticular layer is composed of irregularly arranged fibres and resists stretching. ```{=html} <!-- --> ``` For more fun pictures of other skin diseases and skin problems \"click\" to this cool website: \[<http://tray.dermatology.uiowa.edu/Home.html>\|\"Dermatology Image Database\"\]. Note: From this link then click \"Clinical Skin Diseases Images\". ## Review Questions Answers for these questions can be found here 1\. Name all of the parts of the integumentary system. 2\. Name the cells that produce melanin and describe its function. 3\. Name and describe the importance of the cutaneous senses. 4\. Explain how sweating helps maintain normal body temperature. 5\. Explain where on the body hair has important functions and describe these functions. 6\. What is a melanoma? A\) The outermost layer of skin B\) A type of nail disease C\) A malignant tumor that originates in melanocytes D\) The lower most layer of skin ## References : Brannon, Heather (2006). \"Nail Anatomy\" About, Inc., A part of The New York Times Company. ```{=html} <!-- --> ``` : American Academy of Dermatology - Nail Health ```{=html} <!-- --> ``` : Cobb, Judith. Fingernails, Jewels or Tools? *Nature\'s Field* - Nail diagnosis ```{=html} <!-- --> ``` : Graaff, Van De (2002). *Human Anatomy, Sixth Edition*. New York: McGraw-Hill. ```{=html} <!-- --> ``` : Mader, Sylvia S. (2004). *Human Biology*. New York: McGraw-Hill. ```{=html} <!-- --> ``` : Sorrentino, Sheila A. (2004). *Mosby\'s textbook for Nursing Assistants, 6th Edition*. St. Louis, Missouri: Mosby.
# Human Physiology/The Nervous System The **central nervous system** includes the **brain** and **spinal cord**. The brain and spinal cord are protected by bony structures, membranes, and fluid. The brain is held in the cranial cavity of the skull and it consists of the **cerebrum**, **cerebellum**, and the **brain stem**. The nerves involved are cranial nerves and spinal nerves. thumb\|upright=1.3 ## Overview of the entire nervous system The nervous system has three main functions: sensory input, integration of data and motor output. Sensory input is when the body gathers information or data, by way of neurons, glia and synapses. The nervous system is composed of excitable nerve cells (neurons) and synapses that form between the neurons and connect them to centers throughout the body or to other neurons. These neurons operate on excitation or inhibition, and although nerve cells can vary in size and location, their communication with one another determines their function. These nerves conduct impulses from sensory receptors to the brain and spinal cord. The data is then processed by way of integration of data, which occurs only in the brain. After the brain has processed the information, impulses are then conducted from the brain and spinal cord to muscles and glands, which is called motor output. Glia cells are found within tissues and are not excitable but help with myelination, ionic regulation and extracellular fluid. The nervous system is comprised of two major parts, or subdivisions, the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS includes the brain and spinal cord. The brain is the body\'s \"control center\". The CNS has various centers located within it that carry out the sensory, motor and integration of data. These centers can be subdivided to Lower Centers (including the spinal cord and brain stem) and Higher centers communicating with the brain via effectors. The PNS is a vast network of spinal and cranial nerves that are linked to the brain and the spinal cord. It contains sensory receptors which help in processing changes in the internal and external environment. This information is sent to the CNS via afferent sensory nerves. The PNS is then subdivided into the autonomic nervous system and the somatic nervous system. The autonomic has involuntary control of internal organs, blood vessels, smooth and cardiac muscles. The somatic has voluntary control of skin, bones, joints, and skeletal muscle. The two systems function together, by way of nerves from the PNS entering and becoming part of the CNS, and vice versa. ## General functions of the CNS !Brain, brain stem, and spinal cord. When the central nervous system becomes damaged or peripheral nerves become trapped, it can increase or decrease your internal organs functionality, it can even affect your facial expressions, i.e. make you frown a lot, your smile becomes lopsided, your lungs can overwork, or underwork, the lung capacity is increased or decreased, your bladder can fill , but you are unable to urinate, your bowels become lapsed and you are unable to completely clear them upon each bowel movement, the muscles in your arms, legs, and torso can become weaker and more fatty, not from lack of use, but from the nerves that run from your spine into them being restricted from working properly, you can suffer headaches, earaches, sore throats, blocked sinuses. Even your ability to orgasm can be affected. The central nervous system (CNS) represents the largest part of the nervous system, including the brain and the spinal cord. Together with the peripheral nervous system (PNS), it has a fundamental role in the control of behavior. The CNS is conceived as a system devoted to information processing, where an appropriate motor output is computed as a response to a sensory input. Many threads of research suggest that motor activity exists well before the maturation of the sensory systems, and senses only influence behavior without dictating it. ## Structure and function of neurons ### Structure Neurons are highly specialized for the processing and transmission of cellular signals. Given the diversity of functions performed by neurons in different parts of the nervous system, there is, as expected, a wide variety in the shape, size, and electrochemical properties of neurons. For instance, the soma of a neuron can vary in size from 4 to 100 micrometers in diameter. The soma (cell body) is the central part of the neuron. It contains the nucleus of the cell and therefore is where most protein synthesis occurs. The nucleus ranges from 3 to 18 micrometers in diameter. The dendrites of a neuron are cellular extensions with many branches, and metaphorically this overall shape and structure are referred to as a dendritic tree. This is where the majority of input to the neuron occurs. However, information outflow (i.e. from dendrites to other neurons) can also occur (except in chemical synapse in which backflow of impulse is inhibited by the fact that axon does not possess chemoreceptors and dendrites cannot secrete neurotransmitter chemical). This explains one-way conduction of nerve impulse. The axon is a finer, cable-like projection which can extend tens, hundreds, or even tens of thousands of times the diameter of the soma in length. The axon carries nerve signals away from the soma (and also carry some types of information back to it). Many neurons have only one axon, but this axon may - and usually will - undergo extensive branching, enabling communication with many target cells. The part of the axon where it emerges from the soma is called the \'axon hillock\'. Besides being an anatomical structure, the axon hillock is also the part of the neuron that has the greatest density of voltage-dependent sodium channels. This makes it the most easily-excited part of the neuron and the spike initiation zone for the axon: in neurological terms, it has the greatest hyperpolarized action potential threshold. While the axon and axon hillock are generally involved in information outflow, this region can also receive input from other neurons as well. The axon terminal is a specialized structure at the end of the axon that is used to release neurotransmitter chemicals and communicate with target neurons. Although the canonical view of the neuron attributes dedicated functions to its various anatomical components, dendrites and axons often act in ways contrary to their so-called main function. Axons and dendrites in the central nervous system are typically only about a micrometer thick, while some in the peripheral nervous system are much thicker. The soma is usually about 10--25 micrometers in diameter and often is not much larger than the cell nucleus it contains. The longest axon of a human motor neuron can be over a meter long, reaching from the base of the spine to the toes. Sensory neurons have axons that run from the toes to the dorsal columns, over 1.5 meters in adults. Giraffes have single axons several meters in length running along the entire length of their necks. Much of what is known about axonal function comes from studying the squids\' giant axon, an ideal experimental preparation because of its relatively immense size (0.5--1 millimeter thick, several centimeters long). ## Function Sensory afferent neurons convey information from tissues and organs into the central nervous system. Efferent neurons transmit signals from the central nervous system to the effector cells and are sometimes called motor neurons. Interneurons connect neurons within specific regions of the central nervous system. Afferent and efferent can also refer generally to neurons which, respectively, bring information to or send information from the brain region. Classification by action on other neurons Excitatory neurons excite their target postsynaptic neurons or target cells causing it to function. Motor neurons and somatic neurons are all excitatory neurons. Excitatory neurons in the brain are often glutamatergic. Spinal motor neurons, which synapse on muscle cells, use acetylcholine as their neurotransmitter. Inhibitory neurons inhibit their target neurons. Inhibitory neurons are also known as short axon neurons, interneurons The output of some brain structures (neostriatum, globus pallidus, cerebellum) are inhibitory. The primary inhibitory neurotransmitters are GABA and glycine. Modulatory neurons evoke more complex effects termed neuromodulation. These neurons use such neurotransmitters as dopamine, acetylcholine, serotonin and others. Each synapses can receive both excitatory and inhibitory signals and the outcome is determined by the adding up of summation. ## Excitatory and inhibitory process !Nerve Synapse{width="300"} The release of an excitatory neurotransmitter (e.g. glutamate) at the synapses will cause an inflow of positively charged sodium ions (Na+) making a localized depolarization of the membrane. The current then flows to the resting (polarized) segment of the axon. Inhibitory synapse causes an inflow of Cl- (chlorine) or outflow of K+ (potassium) making the synaptic membrane hyperpolarized. This increase prevents depolarization, causing a decrease in the possibility of an axon discharge. If they are both equal to their charges, then the operation will cancel itself out. This effect is referred to as summation. There are two types of summation: spatial and temporal. Spatial summation requires several excitatory synapses (firing several times) to add up, thus causing an axon discharge. It also occurs within inhibitory synapses, where just the opposite will occur. In temporal summation, it causes an increase of the frequency at the same synapses until it is large enough to cause a discharge. Spatial and temporal summation can occur at the same time as well. The neurons of the brain release inhibitory neurotransmitters far more than excitatory neurotransmitters, which helps explain why we are not aware of all memories and all sensory stimuli simultaneously. The majority of information stored in the brain is inhibited most of the time. ## Summation When excitatory synapses exceed the number of inhibitory synapses there are, then the excitatory synapses will prevail over the other. The same goes with inhibitory synapses, if there are more inhibitory synapses than excitatory, the synapses will be inhibited. To determine all of this is called summation. Classification by discharge patterns: Neurons can be classified according to their electrophysiological characteristics (note that a single action potential is not enough to move a large muscle, and instead will cause a twitch). `<b>`{=html}Tonic or regular spiking:`</b>`{=html} Some neurons are typically constantly (or tonically) active. Example: interneurons in the neostriatum. `<b>`{=html}Phasic or bursting:`</b>`{=html} Neurons that fire in bursts is called phasic. `<b>`{=html}Fast spiking:`</b>`{=html} Some neurons are notable for their fast firing rates. For example, some types of cortical inhibitory interneurons, cells in globus pallidus. `<b>`{=html}Thin-spike:`</b>`{=html} Action potentials of some neurons are more narrow compared to the others. For example, interneurons in the prefrontal cortex are thin-spike neurons. Classification by neurotransmitter released: Some examples are cholinergic, GABAergic, glutamatergic and dopaminergic neurons. ### Central Nervous System The central nervous system is the control center for the body. It regulates organ function, higher thought, and movement of the body. The central nervous system consists of the brain and spinal cord. ## Generation & propagation of an action potential !`Electrical characteristics of a neurochemical action potential.`{width="422"} {{-}} ### The Nerve Impulse ! animated action potential{width="300"} When a nerve is stimulated the resting potential changes. Examples of such stimuli are pressure, electricity, chemicals, etc. Different neurons are sensitive to different stimuli(although most can register pain). The stimulus causes sodium ion channels to open. The rapid change in polarity that moves along the nerve fiber is called the \"action potential.\" In order for an action potential to occur, it must reach threshold. If threshold does not occur, then no action potential can occur. This moving change in polarity has several stages: **Depolarization**: The upswing is caused when positively charged sodium ions (Na+) suddenly rush through open sodium gates into a nerve cell. The membrane potential of the stimulated cell undergoes a localized change from -55 millivolts to 0 in a limited area. As additional sodium rushes in, the membrane potential actually reverses its polarity so that the outside of the membrane is negative relative to the inside. During this change of polarity the membrane actually develops a positive value for a moment(+30 millivolts). The change in voltage stimulates the opening of additional sodium channels (called a voltage-gated ion channel). This is an example of a positive feedback loop.\ **Repolarization**: The downswing is caused by the closing of sodium ion channels and the opening of potassium ion channels. Release of positively charged potassium ions (K+) from the nerve cell when potassium gates open. Again, these are opened in response to the positive voltage\--they are voltage gated. This expulsion acts to restore the localized negative membrane potential of the cell (about -65 or -70 mV is typical for nerves). ! sodium potassium pump ```{=html} <!-- --> ``` **Hyperpolarization** When the potassium ions are below resting potential (-90 mV). Since the cell is hyper polarized, it goes to a refractory phrase. **Refractory phase**: The refractory period is a short period of time after the depolarization stage. Shortly after the sodium gates open, they close and go into an inactive conformation. The sodium gates cannot be opened again until the membrane is repolarized to its normal resting potential. The sodium-potassium pump returns sodium ions to the outside and potassium ions to the inside. During the refractory phase this particular area of the nerve cell membrane cannot be depolarized. This refractory area explains why action potentials can only move forward from the point of stimulation. ### Factors that affect sensitivity and speed **Sensitivity**: Increased permeability of the sodium channel occurs when there is a deficit of calcium ions. When there is a deficit of calcium ions (Ca+2) in the interstitial fluid, the sodium channels are activated (opened) by very little increase of the membrane potential above the normal resting level. The nerve fiber can therefore fire off action potentials spontaneously, resulting in tetany. This could be caused by the lack of hormone from parathyroid glands. It could also be caused by hyperventilation, which leads to a higher pH, which causes calcium to bind and become unavailable.\ **Speed of Conduction**: This area of depolarization/repolarization/recovery moves along a nerve fiber like a very fast wave. In myelinated fibers, conduction is hundreds of times faster because the action potential only occurs at the nodes of Ranvier (pictured below in \'types of neurons\') by jumping from node to node. This is called \"saltatory\" conduction. Damage to the myelin sheath by the disease can cause severe impairment of nerve cell function. Some poisons and drugs interfere with nerve impulses by blocking sodium channels in nerves. See discussion on drug at the end of this outline. ## Brain !A color-coded image of the brain, showing the main sections. The brain is found in the cranial cavity. Within it are found the higher nerve centers responsible for coordinating the sensory and motor systems of the body (forebrain). The brain stem houses the lower nerve centers (consisting of midbrain, pons, and medulla), ### Medulla The medulla is the control center for respiratory, cardiovascular and digestive functions. ### Pons The pons houses the control centers for respiration and inhibitory functions. Here it will interact with the cerebellum. ### Cerebrum The cerebrum, or top portion of the brain, is divided by a deep crevice, called the longitudinal sulcus. The longitudinal sulcus separates the cerebrum in to the right and left hemispheres. In the hemispheres you will find the cerebral cortex, basal ganglia and the limbic system. The two hemispheres are connected by a bundle of nerve fibers called the corpus callosum. The right hemisphere is responsible for the left side of the body while the opposite is true of the left hemisphere. Each of the two hemispheres are divided into four separated lobes: the frontal in control of specialized motor control, learning, planning and speech; parietal in control of somatic sensory functions; occipital in control of vision; and temporal lobes which consists of hearing centers and some speech. Located deep to the temporal lobe of the cerebrum is the insula. ### Cerebellum The cerebellum is the part of the brain that is located posterior to the medulla oblongata and pons. It coordinates skeletal muscles to produce smooth, graceful motions. The cerebellum receives information from our eyes, ears, muscles, and joints about what position our body is currently in (proprioception). It also receives output from the cerebral cortex about where these parts should be. After processing this information, the cerebellum sends motor impulses from the brain stem to the skeletal muscles. The main function of the cerebellum is coordination. The cerebellum is also responsible for balance and posture. It also assists us when we are learning a new motor skill, such as playing a sport or musical instrument. Recent research shows that apart from motor functions cerebellum also has some emotional role. ### **The Limbic System and Higher Mental Functions** ------------------------------------------------------------------------ !Image of the brain, showing the Limbic system. #### **The Limbic System** The Limbic System is a complex set of structures found just beneath the cerebrum and on both sides of the thalamus. It combines higher mental functions, and primitive emotion, into one system. It is often referred to as the emotional nervous system. It is not only responsible for our emotional lives, but also our higher mental functions, such as learning and formation of memories. The Limbic system explains why some things seem so pleasurable to us, such as eating and why some medical conditions are caused by mental stress, such as high blood pressure. There are two significant structures within the limbic system and several smaller structures that are important as well. They are: 1. The Hippocampus 2. The Amygdala 3. The Thalamus 4. The Hypothalamus 5. The Fornix and Parahippocampus 6. The Cingulate Gyrus #### Structures of the Limbic System ##### Hippocampus : The Hippocampus is found deep in the temporal lobe, shaped like a seahorse. It consists of two horns that curve back from the amygdala. It is situated in the brain so as to make the prefrontal area aware of our past experiences stored in that area. The prefrontal area of the brain consults this structure to use memories to modify our behavior. The hippocampus is a primary contributor to memory. ##### Amygdala : The Amygdala is a little almond shaped structure, deep inside the anteroinferior region of the temporal lobe, that connects with the hippocampus, the septi nuclei, the prefrontal area and the medial dorsal nucleus of the thalamus. These connections make it possible for the amygdala to play its important role on the mediation and control of such activities and feelings as love, friendship, affection, and expression of mood. The amygdala is the center for identification of danger and is fundamental for self preservation. The amygdala is the nucleus responsible for fear. ##### Thalamus : Lesions or stimulation of the medial, dorsal, and anterior nuclei of the thalamus are associated with changes in emotional reactivity. However, the importance of these nuclei on the regulation of emotional behavior is not due to the thalamus itself, but to the connections of these nuclei with other limbic system structures. The medial dorsal nucleus makes connections with cortical zones of the prefrontal area and with the hypothalamus. The anterior nuclei connect with the mamillary bodies and through them, via fornix, with the hippocampus and the cingulated gyrus, thus taking part in what is known as the Papez\'s circuit. !Image of the brain showing the location of the hypothalamus.{width="75"} ##### Hypothalamus : The Hypothalamus is a small part of the brain located just below the thalamus on both sides of the third ventricle. Lesions of the hypothalamus interfere with several vegetative functions and some so called motivated behaviors like sexuality, combativeness, and hunger. The hypothalamus also plays a role in emotion. Specifically, the lateral parts seem to be involved with pleasure and rage, while the medial part is linked to aversion, displeasure, and a tendency to uncontrollable and loud laughing. However, in general the hypothalamus has more to do with the expression of emotions. When the physical symptoms of emotion appear, the threat they pose returns, via the hypothalamus, to the limbic centers and then the prefrontal nuclei, increasing anxiety. ##### The Fornix and Parahippocampal : These small structures are important connecting pathways for the limbic system. ##### The Cingulate Gyrus : The Cingulate Gyrus is located in the medial side of the brain between the cingulated sulcus and the corpus callosum. There is still much to be learned about this gyrus, but it is already known that its frontal part coordinates smells and sights, with pleasant memories of previous emotions. The region participates in the emotional reaction to pain and in the regulation of aggressive behavior. {{-}} #### **Memory and Learning** Memory is defined as : The mental faculty of retaining and recalling past experiences, the act or instance of remembering recollection. Learning takes place when we retain and utilize past memories. Overall, the mechanisms of memory are not completely understood. Brain areas such as the hippocampus, the amygdala, the striatum, or the mammillary bodies are thought to be involved in specific types of memory. For example, the hippocampus is believed to be involved in spatial learning and declarative learning (learning information such as what you\'re reading now), while the amygdala is thought to be involved in emotional memory. Damage to certain areas in patients and animal models and subsequent memory deficits is a primary source of information. However, rather than implicating a specific area, it could be that damage to adjacent areas, or to a pathway traveling through the area is actually responsible for the observed deficit. Further, it is not sufficient to describe memory, and its counterpart, learning, as solely dependent on specific brain regions. Learning and memory are attributed to changes in neuronal synapses, thought to be mediated by long-term potentiation and long-term depression. There are three basic types of memory: 1. Sensory Memory 2. Short Term Memory 3. Long Term Memory ##### Sensory Memory : The sensory memories act as a buffer for stimuli through senses. A sensory memory retains an exact copy of what is seen or heard: *iconic memory for visual, echoic memory for aural and haptic memory for touch.* Information is passed from sensory memory into short term memory. Some believe it lasts only 300 milliseconds, it has unlimited capacity. Selective attention determines what information moves from sensory memory to short term memory. ##### Short Term Memory : Short Term Memory acts as a scratch pad for temporary recall of the information under process. For instance, in order to understand this sentence you need to hold in your mind the beginning of the sentence as you read the rest. Short term memory decays rapidly and also has a limited capacity. Chunking of information can lead to an increase in the short term memory capacity, this is the reason why a hyphenated phone number is easier to remember than a single long number. The successful formation of a chunk is known as *closure.* Interference often causes disturbance in short term memory retention. This accounts for the desire to complete a task held in short term memory as soon as possible. Within short term memory there are three basic operations: 1. Iconic memory - the ability to hold visual images 2. Acoustic memory - the ability to hold sounds. Can be held longer than iconic. 3. Working memory - an active attentional process to keep it until it is put to use. Note that the goal is not really to move the information from short term memory to long term memory, but merely to put it to immediate use. The process of transferring information from short term to long term memory involves the encoding or consolidation of information. This is not a function of time, that is, the longer the memory stays in the short term the more likely it is to be placed in the long term memory. On organizing complex information in short term before it can be encoded into the long term memory, in this process the meaningfulness or emotional content of an item may play a greater role in its retention in the long term memory. The limbic system sets up local reverberating circuits such as the Papez\'s Circuit. ##### Long Term Memory : Long Term Memory is used for storage of information over a long time. Information from short to long term memory is transferred after a short period. Unlike short term memory, long term memory has little decay. Long term potential is an enhanced response at the synapse within the hippocampus. It is essential to memory storage. The limbic system isn\'t directly involved in long term memory necessarily but it selects them from short term memory, consolidates these memories by playing them like a continuous tape, and involves the hippocampus and amygdala. There are two types of long term memory: 1. Episodic Memory 2. Semantic Memory Episodic memory represents our memory of events and experiences in a serial form. It is from this memory that we can reconstruct the actual events that took place at a given point in our lives. Semantic memory, on the other hand, is a structured record of facts, concepts, and skills that we have acquired. The information in the semantic memory is derived from our own episode memory, such as that we can learn new facts or concepts from experiences. There are three main activities that are related to long term memory: 1. Storage 2. Deletion 3. Retrieval Information for short term memory is stored in long term memory by rehearsal. The repeated exposure to a stimulus or the rehearsal of a piece of information transfers it into long term memory. Experiments also suggest that learning is most effective if it is distributed over time. Deletion is mainly caused by decay and interference. Emotional factors also affect long term memory. However, it is debatable whether we actually ever forget anything or whether it just sometimes becomes increasingly difficult to retrieve it. Information may not be recalled sometimes but may be recognized, or may be recalled only with prompting. This leads us to the third operation of memory, information retrieval. There are two types of information retrieval: 1. Recall 2. Recognition In recall, the information is reproduced from memory. In recognition the presentation of the information provides the knowledge that the information has been seen before. Recognition is of lesser complexity, as the information is provided as a cue. However, the recall may be assisted by the provision of retrieval cues which enable the subject to quickly access the information in memory. ##### Long-term Potentiation . Long-term potentiation (LTP) is the lasting enhancement of connections between two neurons that results from stimulating them simultaneously. Since neurons communicate via chemical synapses, and because memories are believed to be stored by virtue of patterns of activation of these synapses, LTP and its opposing process, long-term depression, are widely considered the major cellular mechanisms that underlie learning and memory. This has been proven by lab experiments. When one of the chemicals involved (PKMzeta, it will be discussed later) is inhibited in rats, it causes retrograde amnesia with short term memory left intact (meaning they can\'t recall events from before the inhibitor was given). By enhancing synaptic transmission, LTP improves the ability of two neurons, one presynaptic and the other postsynaptic, to communicate with one another across a synapse. The precise mechanism for this enhancement isn\'t known, but it varies based on things like brain region, age and species. This will focus on LTP in the CA1 section of the hippocampus, because that\'s what is well known. The end result of LTP is a well established neural circuit that can be called upon later for memory. LTP in the CA1 hippocampus is called NMDA receptor-dependent LTP. It has four main properties. - Rapid induction : LTP can be rapidly induced by applying one or more brief, high-frequency, stimulus to a presynaptic cell. - Input specificity : Once induced, LTP at one synapse does not spread to other synapses; rather LTP is input specific. LTP is only propagated to those synapses according to the rules of associativity and cooperativity. - Associativity : Associativity refers to the observation that when weak stimulation of a single pathway is insufficient for the induction of LTP, simultaneous strong stimulation of another pathway will induce LTP at both pathways. - Cooperativity : LTP can be induced either by strong tetanic stimulation of a single pathway to a synapse, or cooperatively via the weaker stimulation of many. When one pathway into a synapse is stimulated weakly, it produces insufficient postsynaptic depolarization to induce LTP. In contrast, when weak stimuli are applied to many pathways that converge on a single patch of postsynaptic membrane, the individual postsynaptic depolarizations generated may collectively depolarize the postsynaptic cell enough to induce LTP cooperatively. Synaptic tagging, discussed later, may be a common mechanism underlying associativity and cooperativity. LTP is generally divided into three parts that occur sequentially: Short-term potentiation, early LTP (E-LTP) and late LTP (L-LTP). Short-term potentiation isn\'t well understood and will not be discussed. E-LTP and L-LTP phases of LTP are each characterized by a series of three events: induction, maintenance and expression. Induction happens when a short-lived signal triggers that phase to begin. Maintenance corresponds to the persistent biochemical changes that occur in response to the induction of that phase. Expression entails the long-lasting cellular changes that result from activation of the maintenance signal. Each phase of LTP has a set of mediator molecules that dictate the events of that phase. These molecules include protein receptors, enzymes, and signaling molecules that allow progression from one phase to the next. In addition to mediators, there are modulator molecules that interact with mediators to fine tune the LTP. Modulators are a bit beyond the scope of this introductory book, and won\'t be discussed here. ###### Early Phase Induction E-LTP induction begins when the calcium inside the postsynaptic cell exceeds a threshold. In many types of LTP, the flow of calcium into the cell requires the NMDA receptor, which is why these types of LTP are considered NMDA receptor-dependent. When a stimulus is applied to the presynaptic neuron, it releases a neurotransmitter, typically glutamate, onto the postsynaptic cell membrane where it binds to AMPA receptors, or AMPARs. This causes an influx of sodium ions into the postsynaptic cell, this short lived depolarization is called the excitatory postsynaptic potential (EPSP) and makes it easier for the neuron to fire an action potential. A single stimulus doesn\'t cause a big enough depolarization to trigger an E-LTP, instead it relies on EPSP summation. If EPSPs are reaching the cell before the others decay, they will add up. When the depolarization reaches a critical level, NMDA receptors lose the magnesium molecule they were originally plugged with and let calcium in. The rapid rise in calcium within the postsynaptic neuron trigger the short lasting activation of several enzymes that mediate E-LTP induction. Of particular importance are some protein kinase enzymes, including CaMKII and PKC. To a lesser extent, PKA and MAPK activation also contribute. Maintenance During the maintenance stage of E-LTP, CaMKII and PKC lose their dependence on calcium and become autonomously active. They then carry out phosphorylation that underlies E-LTP expression. Expression CaMKII and PKC phosphorylate existing AMPA receptors to increase their activity, and mediate the insertion of additional AMPA receptors onto the postsynaptic cell membrane. This is achieved by having a pool of nonsynaptic AMPA receptors adjacent to the postsynaptic membrane. When the appropriate stimulus arrives, the nonsynaptic AMPA receptors are brought into the postsynaptic membrane under the influence of protein kinases. AMPA receptors are one of the most common type of receptors in the brain. Their effect is excitatory. By adding more AMPA receptors, and increasing their activity, future stimuli will generate larger postsynaptic responses. ###### Late Phase Late LTP is the natural extension of E-LTP. L-LTP requires gene transcription and protein synthesis in the postsynaptic cell, unlike E-LTP. Late LTP is also associated with the presynaptic synthesis of synaptotagmin and an increase in synaptic vesicle number, suggesting that L-LTP induces protein synthesis not only in postsynaptic cells, but in presynaptic cells as well. This is discussed under \"retrograde messenger\" below. Induction Late LTP is induced by changes in gene expression and protein synthesis brought about by persistent activation of protein kinases activated during E-LTP, such as MAPK. In fact, MAPK\--Specifically the ERK subfamily of MAPKs\--may be the molecular link between E-LTP and L-LTP, since many signaling cascades involved in E-LTP, including CaMKII and PKC, can converge on ERK. Maintenance Upon activation, ERK may phosphorylate a number of cytoplasmic and nuclear molecules that ultimately result in the protein synthesis and morphological changes associated with L-LTP. These chemicals may include transcription factors such as CREB. ERK-mediated changes in transcription factor activity may trigger the synthesis of proteins that underlie the maintenance of L-LTP. PKMzeta is one such molecule. When this molecule is inhibited in rats, they experience retrograde amnesia (where you can\'t recall previous events but short term memory works fine). Expression Aside from PKMzeta, many of the proteins synthesized during L-LTP are unknown. They are though to increase postsynaptic dendritic spine number, surface area and sensitivity to the neurotransmitter associated with L-LTP expression. ###### Retrograde Signaling Retrograde signaling is a hypothesis that attempts to explain that, while LTP is induced and expressed postsynaptically, some evidence suggests that it is expressed presynaptically as well. The hypothesis gets its name because normal synaptic transmission is directional and proceeds from the presynaptic to the postsynaptic cell. For induction to occur postsynaptically and be partially expressed presynaptically, a message must travel from the postsynaptic cell to the presynaptic cell in a retrograde (reverse) direction. Once there, the message presumably initiates a cascade of events that leads to a presynaptic component of expression, such as the increased probability of neurotransmitter vesicle release. Retrograde signaling is currently a contentious subject as some investigators do not believe the presynaptic cell contributes at all to the expression of LTP. Even among proponents of the hypothesis there is controversy over the identity of the messenger. #### Language and Speech Language depends on semantic memory so some of the same areas in the brain are involved in both memory and language. Articulation, the forming of speech, is represented bilaterally in the motor areas. However, for most individuals, language analysis and speech formation take place in regions of the left hemisphere only. The two major cortical regions involved are: 1. Broca\'s Area 2. Wernicke\'s Area Broca\'s area is located just in front of the voice control area of the left motor cortex. This region assembles the motor sequencing of language, speech and writing. For example, patients with lesions in this area: 1. Are unable to understand language perfectly: they are typically able to understand nouns better than verbs or syntactical words and fragments 2. May not be able to write clearly 3. Usually speak in fragmented phrases and sentences, often with effort Wernicke\'s area is part of the auditory and visual associations cortex. This region is responsible for the analysis and formation of language content. For example, patients with lesions in this area: 1. Have difficulty naming objects 2. Have difficulty understand the meaning of words 3. Articulate speech readily but often with distorted or unintelligible meaning #### Diseases of the Limbic System There are several well known diseases that are disorders of the limbic system. Several are discussed here. ##### Schizophrenia An increased dopamine (DA) response in the limbic system results in schizophrenia. DA may be synthesized or secreted in excess, DA receptors may be supersensitive, and DA regulatory mechanism may be defective. Symptoms are decreased by drugs which block DA receptors. Symptoms of schizophrenia are: 1. Loss of touch with reality 2. Decreased ability to think and reason 3. Decreased ability to concentrate 4. Decreased memory 5. Regress in child-like behavior 6. Altered mood and impulsive behavior 7. Auditory hallucinations Symptoms may be so severe that the individual cannot function. ##### Depression Depression is the most common major mental illness and is characterized by both emotional and physical symptoms. Symptoms of depression are: 1. Intense sadness and despair 2. Anxiety 3. Loss of ability to concentrate 4. Pessimism 5. Feelings of low self esteem 6. Insomnia or hypersomnia 7. Increased or decreased appetite 8. Changes in body temperature and endocrine gland function 10 to 15% of depressed individuals display suicidal behavior during their lifetime. The cause of depression and its symptoms are a mystery but we do understand that it is an illness associated with biochemical changes in the brain. A lot of research goes on to explain that it is associated with a lack of amines serotonin and norephinephrine. Therefore pharmacological treatment strategies often try to increase amine concentrations in the brain. One class of antidepressants is monoamine oxidase inhibitors. Mono amine oxidase is an enzyme that breaks down your amines like norephinephrine and serotonin. Because the antidepressants inhibit their degradation they will remain in the synaptic cleft for a longer period of time making the effect just as if you had increased these types of neurotransmitters. A newer class of antidepressants is selective serotonin reuptake inhibitors (SSRI\'s). With SSRI\'s decreasing the uptake of serotonin back into the cell that will increase the amount of serotonin present in the synaptic cleft. SSRI\'s are more specific than the monoamine oxidase inhibitors because they only affect serotonergic synapses. You might recognize these SSRI\'s by name as Prozac and Paxil. ##### Bipolar Disorder Another common form of depression is manic depression. Mania is an acute state characterized by: 1. Excessive elation and impaired judgment 2. Insomnia and irritability 3. Hyperactivity 4. Uncontrolled speech Manic depression, also known as bipolar disorder, displays mood swings between mania and depression. The limbic system receptors are unregulated. Drugs used are unique mood stabilizers. The hippocampus is particularly vulnerable to several disease processes, including ischemia, which is any obstruction of blood flow or oxygen deprivation, Alzheimer's disease, and epilepsy. These diseases selectively attack CA1, which effectively cuts through the hippocampal circuit. ##### An Autism Link A connection between autism and the limbic system has also been noted as well. URL: <http://www.autism.org/limbic.html> ##### Case Study *Central Pain Syndrome* I was 42 years old when my life changed forever. I had a stroke. As an avid viewer of medical programs on television I assumed that I would have physical therapy for my paralyzed left side and get on with my life. No one ever mentioned pain or the possibility of pain, as a result of the stroke. I did experience unusual sensitivity to touch while still in the hospital, but nothing to prepare me for what was to come. The part of my brain that is damaged is the Thalamus. This turns out to be the pain center and what I have now is an out of control Thalamus, resulting in Thalamic Pain syndrome, also called Central Pain Syndrome. This means that 24 hours a day, seven days a week, my brain sends messages of pain and it never goes away. I am under the care of physicians, who not only understand chronic pain, but are also willing to treat it with whatever medications offer some help. None of the medications, not even narcotic medications, take the pain away. They just allow me to manage it so I can function. ## The Peripheral Nervous System !The Cranial Nerves{width="250"} The **peripheral nervous system** includes 12 cranial nerves 31 pairs of spinal nerves. It can be subdivided into the **somatic** and **autonomic** systems. It is a way of communication from the central nervous system to the rest of the body by nerve impulses that regulate the functions of the human body. The twelve cranial nerves are : I **Olfactory Nerve** for smell : II **Optic Nerve** for vision : III **Oculomotor** for looking around : IV **Trochlear** for moving eye : V **Trigeminal** for feeling touch on face : VI **Abducens** to move eye muscles : VII **Facial** to smile, wink, and help us taste : VIII **Vestibulocochlear** to help with balance, equilibrium, and hearing : IX **Glossopharyngeal** for swallowing and gagging : X **Vagus** for swallowing, talking, and parasympathetic actions of digestion : XI **Spinal accessory** for shrugging shoulders : XII **Hypoglossal** for tongue more divided into different regions as muscles 10 out of the 12 cranial nerves originate from the brain stem (I and II are in the cerebrum), and mainly control the functions of the anatomic structures of the head with some exceptions. CN X receives visceral sensory information from the thorax and abdomen, and CN XI is responsible for innervating the sternocleidomastoid and trapezius muscles, neither of which is exclusively in the head. Spinal nerves take their origins from the spinal cord. They control the functions of the rest of the body. In humans, there are 31 pairs of spinal nerves: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 1 coccygeal. The naming convention for spinal nerves is to name it after the vertebra immediately above it. Thus the fourth thoracic nerve originates just below the fourth thoracic vertebra. This convention breaks down in the cervical spine. The first spinal nerve originates above the first cervical vertebra and is called C1. This continues down to the last cervical spinal nerve, C8. There are only 7 cervical vertebrae and 8 cervical spinal nerves. ### Lateral cord The **lateral cord** gives rise to the following nerves: - The lateral pectoral nerve, C5, C6 and C7 to the pectoralis major muscle, or musculus pectoralis major. - The musculocutaneous nerve which innervates the biceps muscle - The median nerve, partly. The other part comes from the medial cord. See below for details. ### Posterior cord !diagram showing human dermatoms, i.e., skin regions with respect to the routing of their nerve connection of their afferent nerves through the spinal cord.{width="300"} The **posterior cord** gives rise to the following nerves: - The upper subscapular nerve, C7 and C8, to the subscapularis muscle, or musculus supca of the rotator cuff. - The lower subscapular nerve, C5 and C6, to the teres major muscle, or the musculus teres major, also of the rotator cuff. - The thoracodorsal nerve, C6, C7 and C8, to the latissimus dorsi muscle, or musculus latissimus dorsi. - The axillary nerve, which supplies sensation to the shoulder and motor to the deltoid muscle or musculus deltoideus, and the teres minor muscle, or musculus teres minor. - The radial nerve, or nervus radialis, which innervates the triceps brachii muscle, the brachioradialis muscle, or musculus brachioradialis,, the extensor muscles of the fingers and wrist (extensor carpi radialis muscle), and the extensor and abductor muscles of the thumb. See radial nerve injuries. ### Medial cord The **medial cord** gives rise to the following nerves: - The median pectoral nerve, C8 and T1, to the pectoralis muscle - The medial brachial cutaneous nerve, T1 - The medial antebrachial cutaneous nerve, C8 and T1 - The median nerve, partly. The other part comes from the lateral cord. C7, C8 and T1 nerve roots. The first branch of the median nerve is to the pronator teres muscle, then the flexor carpi radialis, the palmaris longus and the flexor digitorum superficialis. The median nerve provides sensation to the anterior palm, the anterior thumb, index finger and middle finger. It is the nerve compressed in carpal tunnel syndrome. - The ulnar nerve originates in nerve roots C7, C8 and T1. It provides sensation to the ring and pinky fingers. It innervates the flexor carpi ulnaris muscle, the flexor digitorum profundus muscle to the ring and pinky fingers, and the intrinsic muscles of the hand (the interosseous muscle, the lumbrical muscles and the flexor pollicis brevis muscle). This nerve traverses a groove on the elbow called the cubital tunnel, also known as the funny bone. Striking the nerve at this point produces an unpleasant sensation in the ring and little fingers. ### Other thoracic spinal nerves (T3-T12) The remainder of the thoracic spinal nerves, T3 through T12, do little recombining. They form the **intercostal nerves**, so named because they run between the ribs. For points of reference, the 7th intercostal nerve terminates at the lower end of the sternum, also known as the xyphoid process. The 10th intercostal nerve terminates at the umbilicus, or the belly button. The **somatic nervous system** is that part of the peripheral nervous system associated with the voluntary control of body movements through the action of skeletal muscles, and also reception of external stimuli. The somatic nervous system consists of afferent fibers that receive information from external sources, and efferent fibers that are responsible for muscle contraction. The somatic system includes the pathways from the skin and skeletal muscles to the Central Nervous System. It is also described as involved with activities that involve consciousness. The basic route of the efferent somatic nervous system includes a two neuron sequence. The first is the upper motor neuron, whose cell body is located in the precentral gyrus (Brodman Area 4) of the brain. It receives stimuli from this area to control skeletal (voluntary) muscle. The upper motor neuron carries this stimulus down the corticospinal tract and synapses in the ventral horn of the spinal cord with the alpha motor neuron, a lower motor neuron. The upper motor neuron releases acetylcholine from its axon terminal knobs and these are received by nicotinic receptors on the alpha motor neuron. The alpha motor neurons cell body sends the stimulus down its axon via the ventral root of the spinal cord and proceeds to its neuromuscular junction of its skeletal muscle. There, it releases acetylcholine from its axon terminal knobs to the muscles nicotinic receptors, resulting in stimulus to contract the muscle. The somatic system includes all the neurons connected with the muscles, sense organs and skin. It deals with sensory information and controls the movement of the body. ## The Autonomic System The **Autonomic system** deals with the visceral organs, like the heart, stomach, gland, and the intestines. It regulates systems that are unconsciously carried out to keep our body alive and well, such as breathing, digestion (peristalsis), and regulation of the heartbeat. The Autonomic system consists of the **sympathetic** and the **parasympathetic** divisions. Both divisions work without conscious effort, and they have similar nerve pathways, but the sympathetic and parasympathetic systems generally have opposite effects on target tissues (they are antagonistic). By controlling the relative input from each division, the autonomic system regulates many aspects of homeostasis. One of the main nerves for the parasympathetic autonomic system is Cranial Nerve X, the Vagus nerve. right\|frame\|**Figure 1:** The right sympathetic chain and its connections with the thoracic, abdominal, and pelvic plexuses. (After Schwalbe.) ### The Sympathetic and Parasympathetic Systems The sympathetic nervous system activates what is often termed the fight or flight response, as it is most active under sudden stressful circumstances (such as being attacked). This response is also known as sympathetico-adrenal response of the body, as the pre-ganglionic sympathetic fibers that end in the adrenal medulla (but also all other sympathetic fibers) secrete acetylcholine, which activates the secretion of adrenaline (epinephrine) and to a lesser extent noradrenaline (norepinephrine) from it. Therefore, this response that acts primarily on the cardiovascular system is mediated directly via impulses transmitted through the sympathetic nervous system and indirectly via catecholamines secreted from the adrenal medulla. Western science typically looks at the SNS as an automatic regulation system, that is, one that operates without the intervention of conscious thought. Some evolutionary theorists suggest that the sympathetic nervous system operated in early organisms to maintain survival (Origins of Consciousness, Robert Ornstein; et al.), as the sympathetic nervous system is responsible for priming the body for action. One example of this priming is in the moments before waking, in which sympathetic outflow spontaneously increases in preparation for action. The parasympathetic nervous system is part of the autonomic nervous system. Sometimes called the rest and digest system or feed and breed. The parasympathetic system conserves energy as it slows the heart rate, increases intestinal and gland activity, and relaxes sphincter muscles in the gastrointestinal tract. After high stress situations (ie: fighting for your life) the parasympathetic nervous system has a backlash reaction that balances out the reaction of the sympathetic nervous system. For example, the increase in heart rate that comes along with a sympathetic reaction will result in an abnormally slow heart rate during a parasympathetic reaction. ### Organization Sympathetic nerves originate inside the vertebral column, toward the middle of the spinal cord in the intermediolateral cell column (or lateral horn), beginning at the first thoracic segment of the spinal cord and extending into the second or third lumbar segments. Because its cells begin in the thoracic and lumbar regions of the spinal cord, the SNS is said to have a thoracolumbar outflow. Axons of these nerves leave the spinal cord in the ventral branches (rami) of the spinal nerves, and then separate out as \'white rami\' (so called from the shiny white sheaths of myelin around each axon) which connect to two chain ganglia extending alongside the vertebral column on the left and right. These elongated ganglia are also known as paravertebral ganglia or sympathetic trunks. In these hubs, connections (synapses) are made which then distribute the nerves to major organs, glands, and other parts of the body. \[1\] In order to reach the target organs and glands, the axons must travel long distances in the body, and, to accomplish this, many axons link up with the axon of a second cell. The ends of the axons do not make direct contact, but rather link across a space, the synapse. In the SNS and other components of the peripheral nervous system, these synapses are made at sites called ganglia. The cell that sends its fiber is called a preganglionic cell, while the cell whose fiber leaves the ganglion is called a postganglionic cell. As mentioned previously, the preganglionic cells of the SNS are located between the first thoracic segment and the second or third lumbar segments of the spinal cord. Postganglionic cells have their cell bodies in the ganglia and send their axons to target organs or glands. The ganglia include not just the sympathetic trunks but also the superior cervical ganglion (which sends sympathetic nerve fibers to the head), and the celiac and mesenteric ganglia (which send sympathetic fibers to the gut). ### Information transmission Messages travel through the SNS in a bidirectional flow. Efferent messages can trigger changes in different parts of the body simultaneously. For example, the sympathetic nervous system can accelerate heart rate; widen bronchial passages; decrease motility (movement) of the large intestine; constrict blood vessels; increase peristalsis in the esophagus; cause pupil dilation, piloerection (goose bumps) and perspiration (sweating); and raise blood pressure. Afferent messages carry sensations such as heat, cold, or pain. The first synapse (in the sympathetic chain) is mediated by nicotinic receptors physiologically activated by acetylcholine, and the target synapse is mediated by adrenergic receptors physiologically activated by either noradrenaline or adrenaline. An exception is with sweat glands which receive sympathetic innervation but have muscarinic acetylcholine receptors which are normally characteristic of PNS. Another exception is with certain deep muscle blood vessels, which have acetylcholine receptors and which dilate (rather than constrict) with an increase in sympathetic tone. The sympathetic system cell bodies are located on the spinal cord excluding the cranial and sacral regions, specifically the thoracolumbar region (T1-L3). The preganglionic neurons exit from the vertebral column and synapse with the postganglonic neurons in the sympathetic trunk. The parasympathetic nervous system is one of three divisions of the autonomic nervous system. Sometimes called the rest and digest system, the parasympathetic system conserves energy as it slows the heart rate, increases intestinal and gland activity, and relaxes sphincter muscles in the gastrointestinal tract. ### Relationship to sympathetic While an oversimplification, it is said that the parasympathetic system acts in a reciprocal manner to the effects of the sympathetic nervous system; in fact, in some tissues innervated by both systems, the effects are synergistic. ### Receptors The parasympathetic nervous system uses only acetylcholine (ACh) as its neurotransmitter. The ACh acts on two types of receptors, the muscarinic and nicotinic cholinergic receptors. Most transmissions occur in two stages: When stimulated, the preganglionic nerve releases ACh at the ganglion, which acts on nicotinic receptors of the postganglionic nerve. The postganglionic nerve then releases ACh to stimulate the muscarinic receptors of the target organ. The three main types of muscarinic receptors that are well characterised are: - The M1 muscarinic receptors are located in the neural system. - The M2 muscarinic receptors are located in the heart, and act to bring the heart back to normal after the actions of the sympathetic nervous system: slowing down the heart rate, reducing contractile forces of the atrial cardiac muscle, and reducing conduction velocity of the atrioventricular node (AV node). Note, they have no effect on the contractile forces of the ventricular muscle. - The M3 muscarinic receptors are located at many places in the body, such as the smooth muscles of the blood vessels, as well as the lungs, which means that they cause vasoconstriction and bronchoconstriction. They are also in the smooth muscles of the gastrointestinal tract (GIT), which help in increasing intestinal motility and dilating sphincters. The M3 receptors are also located in many glands that help to stimulate secretion in salivary glands and other glands of the body. ## Nervous Tissue The nervous system coordinates the activity of the muscles, monitors the organs, constructs and also stops input from the senses, and initiates actions. Prominent participants in a nervous system include neurons and nerves, which play roles in such coordination.Our nervous tissue only consists of two types of cells. These cells are neurons and neuroglia cells. The neurons are responsible for transmitting nerve impulses. Neuroglia cells are responsible for supporting and nourishing the neuron cells. ### Types of Neurons ![](Neuron.svg "Neuron.svg") There are three types of neurons in the body. We have sensory neurons, interneurons, and motor neurons. Neurons are a major class of cells in the nervous system. Neurons are sometimes called nerve cells, though this term is technically imprecise, as many neurons do not form nerves. In vertebrates, neurons are found in the brain, the spinal cord and in the nerves and ganglia of the peripheral nervous system. Their main role is to process and transmit information. Neurons have excitable membranes, which allow them to generate and propagate electrical impulses. Sensory neuron takes nerve impulses or messages right from the sensory receptor and delivers it to the central nervous system. A sensory receptor is a structure that can find any kind of change in it\'s surroundings or environment. ### Structure of a neuron Neurons have three different parts to them. They all have an axon, a cell body and dendrites. The axon is the part of the neuron that conducts nerve impulses. Axons can get to be quite long. When an axon is present in nerves, it is called a nerve fiber. A cell body has a nucleus and it also has other organelles. The dendrites are the short pieces that come off of the cell body that receive the signals from sensory receptors and other neurons. ### Myelin Sheath Schwann cells contain a lipid substance called myelin in their plasma membranes. When schwann cells wrap around axons, a myelin sheath forms. There are gaps that have no myelin sheath around them; these gaps are called nodes of Ranvier. Myelin sheathes make excellent insulators. Axons that are longer have a myelin sheath, while shorter axons do not. The disease multiple sclerosis is an autoimmune disease where the body attacks the myelin sheath of the central nervous system. ## Case Study A 35-year-old male in 1986 had been admitted to a hospital in Florida three weeks previous to being diagnosed, with complaints of weakness and spasticity in the right leg, difficulties with balance, and fatigue and malaise. Tests performed at the Florida hospital had revealed abnormalities in spinal fluid and MRI brain scan. The patient complained of being severely depressed and anxious. He had anger at his circumstances and frequent crying spells. One month previously he had noticed aching and loss of vision in the left eye that had since improved. This man was diagnosed with Multiple Sclerosis (MS). MS is a chronic, degenerative, and progressive disorder that affects the nerve fibers in the brain and spinal cord. Myelin is a fatty substance that surrounds and insulates the nerve fibers and facilitates the conduction of the nerve impulse transmissions. MS is characterized by intermittent damage to myelin (called demyelination) caused by the destruction of specialized cells (oligodendrocytes) that form the substance. Demyelination causes scarring and hardening (sclerosis) of nerve fibers usually in the spinal cord, brain stem, and optic nerves, which slows nerve impulses and results in weakness, numbness, pain, and vision loss. Because different nerves are affected at different times, MS symptoms often worsen (exacerbate), improve, and develop in different areas of the body. Early symptoms of the disorder may include vision changes (blurred vision, blind spots) and muscle weakness. MS can progress steadily or cause acute attacks (exacerbations) followed by partial or complete reduction in symptoms (remission). Most patients with the disease have a normal lifespan. There are different types of MS: Multiple sclerosis is classified according to frequency and severity of neurological symptoms, the ability of the CNS to recover, and the accumulation of damage. ![](Types_of_MS.jpg‎ "Types_of_MS.jpg‎") ### Treating Depression Every now and then we all feel a little blue, these feelings can be caused by losing a loved one. Clinical depression goes much further than just feeling down. Depression has many symptoms, including lack of energy, abnormal eating habits (either too much or too little) and sleeping problems (also too much or too little). Often a person can feel worthless and have thoughts of committing suicide. The cause of depression and its symptoms are a mystery but we do understand that it is an illness associated with biochemical changes in the brain. A lot of research goes on to explain that it is associated with a lack of amines serotonin and norephinephrine. Therefore pharmacological treatment strategies often try to increase amine concentrations in the brain. One class of antidepressants is monoamine oxidase inhibitors. Mono amine oxidase is a enzyme that breaks down your amines like norephinephrine and serotonin. Because the antidepressants inhibit their degradation they will remain in the synaptic cleft for a longer period of time making the effect just as if you had increased theses types of neurotransmitters. A newer class of antidepressants is selective serotonin reuptake inhibitors (SSRI\'s). With SSRI\'s decreasing the uptake of serotonin back into the cell that will increase the amount of serotonin present in the synaptic cleft. SSRI\'s are more specific than the monoamine oxidase inhibitors because they only affect serotonergic synapses. You might recognize these SSRI\'s by name as Prozac and Paxil. ## Drugs A drug is, generally speaking, any substance that changes the way your body works. Some drugs have a medicinal effect, and some are used recreationally. They have diverse effects, depending on the drug. Drugs can do anything from diminish pain, to preventing blood clots, to helping a depressed person. Different drugs work in different ways, called the mechanism of action, the drugs covered here will all act on the nervous system via receptors on different neurons. There are also drugs that change how enzymes work, but that\'s not part of the nervous system (at least directly) and will not be discussed here. You\'ve probably heard the terms stimulant (excitatory) and depressant (inhibitory). This is a broad way of classifying drugs that work on the CNS. Depressants slow down neural function, and stimulants speed it up. Most of the common depressants (including alcohol, benzodiazepines, barbiturates and GHB) work on GABA receptors, although there are others. Opiates, for example, work on mu opioid receptors and also produce inhibitory effects, and some antipsychotics block serotonin. See the alcohol section below to see one way this can work. Stimulants work mostly with epinephrine, dopamine or serotonin (or a combination of them). Many of them either mimic one, or stop them from leaving the synapse, causing more action potentials to be fired. Methamphetamine, discussed below, is a fairly typical stimulant drug. ### Drug Abuse ![](Phencyclidine_(PCP).jpg‎ "Phencyclidine_(PCP).jpg‎"){width="60"} Scientists have long accepted that there is a biological basis for drug addiction, though the exact mechanisms responsible are only now being identified. It is believed that addictive substances create dependence in the user by changing the brain\'s reward functions, located in the mesolimbic dopamine system---the part of the brain that reinforces certain behaviors such as eating, sexual intercourse, exercise, and social interaction. Addictive substances, through various means and to different degrees, cause the synapses of this system to flood with excessive amounts of dopamine, creating a brief rush of euphoria more commonly called a \"high". Some say that abuse begins when the user begins shirking responsibility in order to afford drugs or to have enough time to use them. Some say it begins when a person uses \"excessive\" amounts, while others draw the line at the point of legality, and others believe it amounts to chronic use despite degenerating mental and physical health in the user. Some think that any intoxicant consumption is an inappropriate activity. Here are some drugs that are abused frequently: Acid/LSD, Alcohol, various tryptamines and phenethylamines, Cocaine, Ecstasy/MDMA, Heroin, Inhalants, Marijuana, Methamphetamine, PCP/Phencyclidine, Prescription Medications, Smoking/Nicotine and Steroids. ### Alcohol Alcohol is, and has been for thousands of years, one of the most commonly used drugs in the world. It is legal, with some restrictions and exceptions, nearly everywhere. It is a common misconception that somehow alcohol is \'better\' or \'safer\' than other recreational drugs. This is simply NOT the case. Alcohol is a depressant, and as such it has the potential to cause coma, respiratory depression/arrest and possibly death. Compared with some other (illegal in most places) drugs of recreational value (such as marijuana, serotonin based hallucinogens like LSD or psilocybin) alcohol is far more toxic and has more risk of overdose. That doesn\'t mean that moderate drinking will probably hurt you, though, either. Short term effects from drinking (listed roughly as they appear, and as dosage goes up) are: decreased inhibitions and, thus, judgment, flushing of the face, drowsiness, memory problems, severe motor impairment, blurry vision, dizziness, confusion, nausea, possible unconsciousness, coma, and death (due to respiratory arrest or possibly aspiration on vomit). Alcohol produces these effects mainly via the GABA receptors in the brain. When GABA (or in this case alcohol) binds to it\'s receptor, it lets either Cl- ions in, or K+ out. This is called hyperpolarization, or an inhibitory postsynaptic potential (IPSP). It makes it harder for the neuron to depolarize and hence harder for it to fire an action potential, slowing neural function. At higher doses alcohol will start to block NMDA. NMDA is involved in memory (see the long-term potentiation section) so this is thought to account for memory blackouts. ### Methamphetamine In the US, medically prescribed **methamphetamine** is distributed in tablet form under the brand name Desoxyn®, generally for Attention Deficit Hyperactivity Disorder (ADHD) but also for narcolepsy or obesity. Illicit methamphetamine comes in a variety of forms. Most commonly it is found as a colorless crystalline solid, sold on the street under a variety of names, such as: crystal meth or crystal. Methamphetamine may also be referred to as shards, rock, pony, crissie, crystal, glass, ice, Jib, critter, Tina, tweak or crank. Dope may refer to methamphetamine or other drugs, especially heroin or marijuana. The term \"speed\" can denote any stimulant including other amphetamines (e.g. adderall), cocaine and methylphenidate (Ritalin). Methamphetamine can be injected (either subcutaneous, intramuscular or intravenous), smoked, snorted, swallowed, or used rectally or sublingually. The latter two being fairly uncommon. After administration, methamphetamine takes from a few seconds (smoked or injected IV) to around 30 minutes (oral) for effects to arise, lasting around eight hours depending on the route of administration. Effects/side effects include euphoria, anorexia, increased energy, clenching of the jaw/grinding of teeth (bruxism), weight loss, insomnia, tooth decay and psychosis among others. Methamphetamine is neurotoxic to at least some areas of the brain, and owes most of its effects to the neurotransmitters dopamine, norepinephrine and serotonin it releases. It also blocks the reuptake of those neurotransmitters, causing them to stay in the synaptic cleft longer than normal. ### Marijuana !Cannabis sativa.{width="250"} Marijuana contains a myriad of chemicals, called cannabinoids, that have psychoactive and medicinal effects when consumed, the major one being tetrahydrocannabinol (THC). THC serves to mimic the endogenous neurotransmitter anandamide (also found in chocolate) at the CB~1~ receptors in the brain. Other cannabinoids include Cannabidiol (CBD), cannabinol (CBN) and tetrahydrocannabivarin (THCV). Although THC is found in all parts of the plant, the flower of the female plant has the highest concentration, commonly around eight percent. The flowers can be used, or they can be refined. Trichomes contain most of the THC on the flowers and can be removed by a few different methods. These removed trichomes are called kief. Kief can, in turn, be pressed into hashish. By far the most common way to consume any of these products is by smoking, but it can be taken orally as well. Cannabis has a very long, very good safety record. Nobody on record has ever died because of marijuana, directly at least. It is estimated that it would take 1-1.8 kilograms of average potency marijuana, taken orally, to have a fifty percent chance of killing a 68kg human. Despite this, the possession, use, or sale of psychoactive cannabis products became illegal in many parts of the world in the early 20th century. Since then, while some countries have intensified the enforcement of cannabis prohibition, others have reduced the priority of enforcement to the point of de facto legality. Cannabis remains illegal in the vast majority of the world\'s countries. The nature and intensity of the immediate effects of cannabis consumption vary according to the dose, the species or hybridization of the source plant, the method of consumption, the user\'s mental and physical characteristics (such as possible tolerance), and the environment of consumption. This is sometimes referred to as set and setting. Smoking the same cannabis either in a different frame of mind (set) or in a different location (setting) can alter the effects or perception of the effects by the individual. Effects of cannabis consumption may be loosely classified as cognitive and physical. Anecdotal evidence suggests that the Cannabis sativa species tends to produce more of the cognitive or perceptual effects, while Cannabis indica tends to produce more of the physical effects. ## Review Questions Answers for these questions can be found here 1\. The junction between one neuron and the next, or between a neuron and an effector is called: : A ) A synapse : B ) A dendrite : C ) A neuotransmitter : D ) A ventricle : E ) None of the above 2\. A fast excitatory synapses follows this order: : A ) (1) neurotransmitter released (2) diffused across the synaptic cleft to a receptor protein (3) binding of the transmitter opens pores in the ion channels and positive ions move in. : B ) (1) neurotransmitter released (2) diffused across the synaptic cleft to a receptor protein (3) binding of the transmitter opens pores in the ion channels and negative ions move in. : C ) (1) neurotransmitter released (2) diffused across the synaptic cleft to a receptor amino acid (3) binding of the transmitter opens pores in the ion channels and positive ions move in. : D ) (1) diffused across the synaptic cleft to a receptor protein (2) neurotransmitter released (3) binding of the transmitter opens pores in the ion channels and positive ions move in. : E ) None of the above 3\. Resting potential is : A ) excess positive ions accumulate inside the plasma membrane : B ) excess negative ions accumulate inside the plasma membrane : C ) excess positive ions accumulate outside the plasma membrane : D ) both b & c : E ) both a & c 4\. Sensory neurons have: : A ) A short dendrite and a long axon : B ) A short dendrite and a short axon : C ) A long dendrite and a short axon : D ) A long dendrite and a long axon : E ) Their axons and dendrites may be either long or short 5\. \_\_\_\_\_\_\_\_blocks Acetylcholine receptor sites causing muscle relaxation. : A ) Novocain : B ) curare : C ) Nicotine : D ) Nerve gases 6\. Transmission across a synapse is dependent on the release of \_\_\_\_\_\_\_? : A ) neurotransmitters : B ) synaptic vesicle : C ) neuromuscular tissue : D ) receptor proteins 7\. Motor neurons take messages : A ) from the muscle fiber to the central nervous system : B ) away from the central nervous system to the central nervous system : C ) that are classified : D ) away from the central nervous system to muscle fiber 8\. The medulla oblongata helps to regulate which of the following: : A ) Breathing : B ) Heartbeat : C ) Sneezing : D ) Vomiting : E ) All of the above 9\. The nervous systems main components are what? : A\) The Synapses and Sprinal cord : B\) The neurons and the synapses : C\) The bain and the neurons : D)The brain and the spinal cord 10\. Explain what LTP does to enhance communication between two neurons, on the postsynaptic end. 11\. Explain what LTP does to enhance communication between two neurons, on the presynaptic end. ## Glossary **Afferent Messages:** carry sensations such as heat, cold, or pain **Autonomic System:** deals with the visceral organs, like the heart, stomach, gland, and the intestines **Axon:** the part of the neuron that conducts nerve impulses **Cannabis:** a psychoactive drug produced from parts of the cannabis plant **Central Nervous System (CNS):** the system that includes the brain and the spinal cord **Cerebellum:** part of the brain that is located posterior to the medulla oblongata and pons, coordinates skeletal muscles to produce smooth, graceful motions **Cerebrospinal Fluid (CSF):** acts a shock absorber for the central nervous system, protecting the brain and spinal cord from injury; it also has a high glucose content which serves as a nutritional factor **Cerebrum** motor control, learning, speech, somatic sensory functions, vision,hearing and more. **Dendrites:** short pieces that come off of the cell body that receive the signals from sensory receptors and other neurons **Episodic Memory:** represents our memory of events and experiences in a serial form **Excitatory Neurotransmitter:** a neurotransmitter that acts to elicit an action potential by opening sodium ion channels **Longitudinal Sulcus:** separates the cerebrum in to the right and left hemispheres **Long Term Memory:** used for storage of information over a long time **Long-Term Potentiation (LTP)** long term communication enhancement between two neurons. Results in neural pathways that store memoris. **Medulla** control center for respiratory, cardiovascular and digestive functions. **Myelin:** a fatty substance that surrounds and insulates the nerve fibers and facilitates the conduction of the nerve impulse transmissions **Multiple Sclerosis (MS):** disease that affects the CNS by causing hardening and scarring of the myelin **Nodes of Ranvier:** unmyelinated gaps between sections of myelin **Peripheral Nervous System (PNS):** a way of communication from the central nervous system to the rest of the body by nerve impulses that regulate the functions of the human body **Pons** control centers for respiration and inhibitory functions. **Postganglionic Cells:** have their cell bodies in the ganglia and send their axons to target organs or glands **Postsynaptic Cells** the cell on the receiving (second) end of the synapse. **Presynaptic Cell** The cell on the sending (first) end of the synapse. **Proprioception** the sense that indicates whether the body is moving with required effort, as well as where various parts of the body are located in relation to each other. **Sensory Receptor:** structure that can find any kind of change in it\'s surroundings or environment **Somatic Nervous System (SNS):** the part of the peripheral nervous system associated with the voluntary control of body movements through the action of skeletal muscles, and also reception of external stimuli **Synapses:** the gap between two neurons; new synapses lead to learning ## References <http://action.painfoundation.org/site/News2?page=NewsArticle&id=5135&security=1&news_iv_ctrl=1061> Esther Wednesday, October 19, 2005 <http://www.neurologychannel.com/multiplesclerosis/> <http://www.theraj.com/ms/casestudy.html>
# Human Physiology/Senses ## What are Senses? We experience reality through our senses. Senses are the physiological methods of perception, so a sense is a faculty by which outside stimuli are perceived. The senses and their operation, classification, and theory are overlapping topics studied by a variety of fields. Many neurologists disagree about how many senses there actually are due to a broad interpretation of the definition of a sense. Our senses are split into two different groups. Our **exteroceptors** detect stimulation from the outsides of our body. For example smell, taste, and equilibrium. The **interoceptors** receive stimulation from the inside of our bodies. For instance, blood pressure dropping, changes in the glucose and pH levels. Children are generally taught that there are five senses (sight, hearing, touch, smell, taste). However, it is generally agreed that there are at least seven different senses in humans, and a minimum of two more observed in other organisms. Sense can also differ from one person to the next. Take taste for an example: what may taste great to one person will taste awful to someone else. This has to do with how the brain interprets the stimuli that are received. ## Chemoreception The senses of **gustation** (taste) and **olfaction** (smell) fall under the category of **chemoreception**. Specialized cells act as receptors for certain chemical compounds. As these compounds react with the receptors, an impulse is sent to the brain and is registered as a certain taste or smell. Gustation and olfaction are chemical senses because the receptors they contain are sensitive to the molecules in the food we eat, along with the air we breathe. ### Gustatory System In humans, the sense of **taste** is transduced by **taste buds** and is conveyed via three of the twelve cranial nerves. Cranial nerve VII, the facial nerve, carries taste sensations from the anterior two thirds of the tongue (excluding the circumvallate papillae, see lingual papilla) and soft palate. Cranial nerve IX the glossopharyngeal nerve carries taste sensations from the posterior one third of the tongue (including the circumvallate papillae). Also a branch of the vagus nerve carries some taste sensations from the back of the oral cavity (i.e. pharynx and epiglottis). Information from these cranial nerves is processed by the gustatory system. Though there are small differences in sensation, which can be measured with highly specific instruments, all taste buds can respond to all types of taste. Sensitivity to all tastes is distributed across the whole tongue and indeed to other regions of the mouth where there are taste buds (epiglottis, soft palate). #### Papilla **Papilla** are specialized epithelial cells. There are four types of papillae: **filiform** (thread-shape), **fungiform** (mushroom-shape), **foliate** (leaf-shape), and **circumvallate** (ringed-circle). All papillae except the filiform have taste buds on their surface. Some act directly by ion channels, others act indirectly. - **Fungiform papillae** -- as the name suggests, are slightly mushroom shaped if looked at in section. These are present mostly at the apex (tip) of the tongue. - **Filiform papillae** -- these are thin, longer papillae that don\'t contain taste buds but are the most numerous. These papillae are mechanical and not involved in gustation. - **Foliate papillae** -- these are ridges and grooves towards the posterior part of the tongue. - **Circumvallate papillae** -- there are only about 3-14 of these papillae on most people and they are present at the back of the oral part of the tongue. They are arranged in a circular-shaped row just in front of the sulcus terminalis of the tongue. #### Structure of Taste Buds center\|framed\|The mouth cavity. The cheeks have been slit transversely and the tongue pulled forward. left\|framed\|Semidiagrammatic view of a portion of the mucous membrane of the tongue. Two fungiform papillæ are shown. On some of the filiform papillæ the epithelial prolongations stand erect, in one they are spread out, and in three they are folded in. Each taste bud is flask-like in shape, its broad base resting on the corium, and its neck opening by an orifice, the gustatory pore, between the cells of the epithelium. The bud is formed by two kinds of cells: supporting cells and gustatory cells. The supporting cells are mostly arranged like the staves of a cask, and form an outer envelope for the bud. Some, however, are found in the interior of the bud between the gustatory cells. The gustatory cells occupy the central portion of the bud; they are spindle-shaped, and each possesses a large spherical nucleus near the middle of the cell. The peripheral end of the cell terminates at the gustatory pore in a fine hair-like filament, the gustatory hair. The central process passes toward the deep extremity of the bud, and there ends in single or bifurcated varicosities. The nerve fibrils after losing their medullary sheaths enter the taste bud, and end in fine extremities between the gustatory cells; other nerve fibrils ramify between the supporting cells and terminate in fine extremities; these, however, are believed to be nerves of ordinary sensation and not gustatory. {{-}} #### Types of Taste Salt: Arguably the simplest receptor found in the mouth is the salt (NaCl) receptor. An ion channel in the taste cell wall allows Na+ ions to enter the cell. This on its own depolarises the cell, and opens voltage-regulated Ca2+ gates, flooding the cell with ions and leading to neurotransmitter release. This sodium channel is known as enc and is composed of three sub-units. En Ac can be blocked by the drug amiloride in many mammals, especially rats. The sensitivity of the salt taste to amiloride in humans, however, is much less pronounced, leading to conjecture that there may be additional receptor proteins besides EnAC that may not have been discovered yet. ```{=html} <!-- --> ``` Sour: Sour taste signals the presence of acidic compounds (H+ ions in solution). There are three different receptor proteins at work in sour taste. The first is a simple ion channel which allows hydrogen ions to flow directly into the cell. The protein for this is EnAC, the same protein involved in the distinction of salt taste (this implies a relationship between salt and sour receptors and could explain why salty taste is reduced when a sour taste is present). There are also H+ gated channels present. The first is a K+ channel, which ordinarily allows K+ ions to escape from the cell. H+ ions block these, trapping the potassium ions inside the cell (this receptor is classified as MDEG1 of the EnAC/Deg Family). A third protein opens to Na+ ions when a hydrogen ion attaches to it, allowing the sodium ions to flow down the concentration gradient into the cell. The influx of ions leads to the opening of a voltage regulated Ca2+ gate. These receptors work together and lead to depolarization of the cell and neurotransmitter release. ```{=html} <!-- --> ``` Bitter: There are many classes of bitter compounds which can be chemically very different. It is interesting that the human body has evolved a very sophisticated sense for bitter substances: we can distinguish between the many radically different compounds which produce a generally "bitter" response. This may be because the sense of bitter taste is so important to survival, as ingesting a bitter compound may lead to injury or death. Bitter compounds act through structures in the taste cell walls called G-protein coupled receptors (GPCR's). Recently, a new group of GPCR's was discovered, known as the T2R's, which is thought to only respond to bitter stimuli. When the bitter compound activates the GPCR, it in turn releases gustducin, the G-protein it was coupled to. Gustducin is made of three subunits. When it is activated by the GPCR, its subunits break apart and activate phosphodiesterase, a nearby enzyme. It then converts a precursor within the cell into a secondary messenger, which closes potassium ion channels. This secondary messenger can stimulate the endoplasmic reticulum to release Ca2+, which contributes to depolarization. This leads to a build-up of potassium ions in the cell, depolarization, and neurotransmitter release. It is also possible for some bitter tastants to interact directly with the G-protein, because of a structural similarity to the relevant GPCR. ```{=html} <!-- --> ``` Sweet: Like bitter tastes, sweet taste transduction involves GPCR's. The specific mechanism depends on the specific molecule. "Natural" sweeteners such as saccharides activate the GPCR, which releases gustducin. The gustducin then activates the molecule adenylate cyclase, which is already inside the cell. This molecule increases concentration of the molecule cAMP, or adenosine 3\', 5\'-cyclic monophosphate. This protein will either directly or indirectly close potassium ion channels, leading to depolarization and neurotransmitter release. Synthetic sweeteners such as saccharin activate different GPCR's, initiating a similar process of protein transitions, starting with the protein phospholipase A, which ultimately leads to the blocking of potassium ion channels. ```{=html} <!-- --> ``` Umami: Umami is a Japanese word meaning \"savory\" or \"meaty\". It is thought that umami receptors act much the same way as bitter and sweet receptors (they involve GPCR's), but not much is known about their specific function. We do know that umami detects glutamates that are common in meats, cheese and other protein-heavy foods. Umami receptors react to foods treated with monosodium glutamate (MSG). This explains why eating foods that have MSG in them often give a sense of fullness. It is thought that the amino acid L-glutamate bonds to a type of GPCR known as a metabotropic glutamate receptor (mGluR4). This causes the G-protein complex to activate a secondary receptor, which ultimately leads to neurotransmitter release. The intermediate steps are not known. #### Disorders of the Tongue : **Loss of taste** : You may lose your sense of taste if the facial nerve is damaged. Then there is also Sjogren\'s Syndrome where the saliva production is reduced. In most cases the loss of taste is typically a symptom of **anosmia** -- a loss of the sense of smell. ```{=html} <!-- --> ``` : **Sore tongue** : It is usually caused by some form of trauma, such as biting your tongue, or eating piping-hot or highly acidic food or drink. : If your top and bottom teeth don't fit neatly together, tongue trauma is more likely. : Some people may experience a sore tongue from grinding their teeth **(bruxism).** : Disorders such as diabetes, anemia, some types of vitamin deficiency and certain skin diseases can include a sore tongue among the range of symptoms. ```{=html} <!-- --> ``` : **Glossodynia** : A condition characterized by a burning sensation on the tongue. ```{=html} <!-- --> ``` : **Benign migratory glossitis** : This condition is characterized by irregular and inflamed patches on the tongue surface that often have white borders. The tongue may be generally swollen, red and sore. Another name for this condition is geographic tongue. The cause of benign migratory glossitis is unknown. : **Risk factors are thought to include**: - Mineral or vitamin deficiencies - Local irritants, such as strong mouthwashes, cigarettes or alcohol - Certain forms of anemia - Infection - Certain medications - Stress ### Olfactory System **Olfaction** is the sense of smell. In humans, the sense of **Smell** is received in **nasopharynx**. Airborne molecules go into solution on moist epithelial surface of nasal passage. An olfactory receptors neuron sends an impulse via Cranial nerve I the olfactory nerve. Although 80-90% of what we think is \"taste\" actually is due to smell. This is why when we have a head cold or stuffed up nose we have a harder time tasting our foods. #### Receptors Humans have 347 functional odor receptor genes; the other genes have nonsense mutations. This number was determined by analyzing the genome in the Human Genome Project; the number may vary among ethnic groups, and does vary among individuals. For example, not all people can smell androstenone, a component of male sweat. Each olfactory receptor neuron in the nose expresses only one functional odor receptor. Odor receptor nerve cells may function like a key-lock system: if the odor molecules can fit into the lock the nerve cell will respond. According to shape theory, each receptor detects a feature of the odor molecule. Weak-shape theory, known as odotope theory, suggests that different receptors detect only small pieces of molecules, and these minimal inputs are combined to create a larger olfactory perception (similar to the way visual perception is built up of smaller, information-poor sensations, combined and refined to create a detailed overall perception). An alternative theory, the vibration theory proposed by Luca Turin (1996, 2002), posits that odor receptors detect the frequencies of vibrations of odor molecules in the infrared range by electron tunneling. However, the behavioral predictions of this theory have been found lacking (Keller and Vosshall, 2004). An olfactory receptor neuron, also called an olfactory sensory neuron, is the primary transduction cell in the olfactory system. Humans have about 40 million olfactory receptor neurons. In vertebrates, olfactory receptor neurons reside on the olfactory epithelium in the nasal cavity. These cells are bipolar neurons with a dendrite facing the interior space of the nasal cavity and an axon that travels along the olfactory nerve to the olfactory bulb. Many tiny hair-like cilia protrude from the olfactory receptor cell\'s dendrite and into the mucus covering the surface of the olfactory epithelium. These cilia contain olfactory receptors, a type of G protein-coupled receptor. Each olfactory receptor cell contains only one type of olfactory receptor, but many separate olfactory receptor cells contain the same type of olfactory receptor. The axons of olfactory receptor cells of the same type converge to form glomeruli in the olfactory bulb. Olfactory receptors can bind to a variety of odor molecules. The activated olfactory receptor in turn activates the intracellular G-protein GOLF, and adenylate cyclase and production of Cyclic AMP opens ion channels in the cell membrane, resulting in an influx of sodium and calcium ions into the cell. This influx of positive ions causes the neuron to depolarize, generating an action potential. Individual olfactory receptor neurons are replaced approximately every 40 days by neural stem cells residing in the olfactory epithelium. The regeneration of olfactory receptor cells, as one of the only few instances of adult neurogenesis in the central nervous system, has raised considerable interest in dissecting the pathways for neural development and differentiation in adult organisms. #### In the brain The axons from all the thousands of cells expressing the same odor receptor converge in the olfactory bulb. Mitral cells in the olfactory bulb send the information about the individual features to other parts of the olfactory system in the brain, which puts together the features into a representation of the odor. Since most odor molecules have many individual features, the combination of features gives the olfactory system a broad range of odors that it can detect. Odor information is easily stored in long term memory and has strong connections to emotional memory. This is possibly due to the olfactory system\'s close anatomical ties to the limbic system and hippocampus, areas of the brain that have long been known to be involved in emotion and place memory, respectively. !The Olfactory Nerve leading to the brain.{width="250"} #### Pheromonal olfaction Some pheromones are detected by the olfactory system, although in many vertebrates pheromones are also detected by the vomeronasal organ, located in the vomer, between the nose and the mouth. Snakes use it to smell prey, sticking their tongue out and touching it to the organ. Some mammals make a face called flehmen to direct air to this organ. In humans, it is unknown whether or not pheromones exist. #### Olfaction and Gustation Olfaction, taste and trigeminal receptors together contribute to flavor. It should be emphasized that there are no more than 5 distinctive tastes: salty, sour, sweet, bitter, and umami. The 10,000 different scents which humans usually recognize as \'tastes\' are often lost or severely diminished with the loss of olfaction. This is the reason why food has little flavor when your nose is blocked, as from a cold. The key nutrition players in our taste is the olfactory function, 80-90% of what we consider taste is dependent on our senses of smell. With aging our olfactory function declines. In the elderly careful monitoring of appetite is necessary due to the alterations in the olfactory function. Nutritionist suggest giving a dual approach of supplementation of the trace minerals zinc and iron to enhance the smell and taste senses. #### Disorders of Olfaction Anosmia: Anosmia is the lack of olfaction, or a loss of the sense of smell. It can be either temporary or permanent. A related term, hyposmia refers to a decrease in the ability to smell. Some people may be anosmic for one particular odor. This is called \"specific anosmia\" and may be genetically based. Anosmia can have a number of detrimental effects. Patients with anosmia may find food less appetizing. Loss of smell can also be dangerous because it hinders the detection of gas leaks, fire, body odor, and spoiled food. The common view of anosmia as trivial can make it more difficult for a patient to receive the same types of medical aid as someone who has lost other senses, such as hearing or sight. A temporary loss of smell can be caused by a stuffy nose or infection. In contrast, a permanent loss of smell may be caused by death of olfactory receptor neurons in the nose, or by brain injury in which there is damage to the olfactory nerve or damage to brain areas that process smell. The lack of the sense of smell at birth, usually due to genetic factors, is referred as congenital anosmia. Anosmia may be an early sign of degenerative brain diseases such as Parkinson\'s disease and Alzheimer\'s disease. Another specific cause of permanent loss could be from damage to olfactory receptor neurons due to use of nasal sprays. To avoid loss of smell from nasal sprays, use them for only a short amount of time. Nasal sprays that are used to treat allergy related congestion are the only nasal sprays that are safe to use for extended periods of time. ```{=html} <!-- --> ``` Phantosmia: Phantosmia is the phenomenon of smelling odors that aren\'t really present. (AKA Phantom odors) The most common odors are unpleasant smells such as rotting flesh, vomit, feces, smoke etc. Phantosmia often results from damage to the nervous tissue in the olfactory system. The damage can be caused by viral infection, trauma, surgery, and possibly exposure to toxins or drugs. It can also be induced by epilepsy affecting the olfactory cortex. It is also thought the condition can have psychiatric origins. ```{=html} <!-- --> ``` Dysosmia: When things smell differently than they should. ## The Sense of Vision **Vision** needs to have the work of both the eyes and the brain to process any information. The majority of the stimuli is done in the eyes and then the information is sent to the brain by the way of nerve impulses. At least one-third of the information of what the eye sees is processed in the cerebral cortex of the brain. ### Anatomy of the Eye The human eye is a elongated ball about 1-inch (2.5 cm) in diameter and is protected by a bony socket in the skull. The eye has three layers or coats that make up the exterior wall of the eyeball, which are the sclera, choroid, and retina. Sclera: The outer layer of the eye is the sclera, which is a tough white fibrous layer that maintains, protects and supports the shape of the eye. The front of the sclera is transparent and is called the cornea. The cornea refracts light rays and acts like the outer window of the eye. ```{=html} <!-- --> ``` Choroid: The middle thin layer of the eye is the choroid, also known as the choroidea or choroid coat, it is the vascular layer of the eye lying between the retina and the sclera. The choroid provides oxygen and nourishment to the outer layers of the retina. It also contains a nonreflective pigment that acts as a light shield and prevents light from scattering. Light enters the front of the eye through a hole in the choroid coat called the pupil. The iris contracts and dilates to compensate for the changes in light intensity. If the light is bright the iris then contracts making the pupil smaller, and if the light is dim, the iris dilates making the pupil bigger. Just posterior to the iris is the lens, which is composed mainly of proteins called crystallins. The lens is attached by the zonules to the ciliary body that contains the ciliary muscles that control the shape of the lens for accommodation. Along with the ciliary body and iris, the choroid forms the uveal tract. The uvea is the middle of the three concentric layers that make up an eye. The name is possibly a reference to its almost black color, wrinkled appearance and grape-like size and shape when stripped intact from a cadaveric eye. ```{=html} <!-- --> ``` Retina:!Illustration of the \"blind spot.\" Situate your head about one foot from the monitor. Close your right eye and look at the dot on the right with your left eye. Move your head slowly closer. When you get to the correct spot, the dot on the left will disappear. The third or the innermost layer of the eye is call the retina. In adult humans the entire retina is 72% of a sphere about 22 mm in diameter. The retina lays over the back two thirds of the choroid coat, which is located in the posterior compartment. The compartment is filled with vitreous humor which is a clear, gelatinous material. Within the retina there are cells called rod cells and cone cells also known as photoreceptors. The rod cells are very sensitive to light and do not see color, that is why when we are in a darkened room we see only shades of gray. The cone cells are sensitive to different wavelengths of light, and that is how we are able to tell different colors. It is a lack of cones sensitive to red, blue, or green light that causes individuals to have deficiencies in color vision or various kinds of color blindness. At the center of the retina is the optic disc, sometimes known as \"the blind spot\" because it lacks photoreceptors. It is where the optic nerve leaves the eye and takes the nerve impulses to the brain. The cornea and the lens of the eye focuses the light onto a small area of the retina called the **fovea centralis** where the cone cells are densely packed. The fovea is a pit that has the highest visual acuity and is responsible for our sharp central vision -- there are no rods in the fovea. center\|framed *Retina\'s simplified axial organization. The retina is a stack of several neuronal layers. Light is concentrated from the eye and passes across these layers (from left to right) to hit the photoreceptors (right layer). This elicits chemical transformation mediating a propagation of signal to the bipolar and horizontal cells (middle yellow layer). The signal is then propagated to the amacrine and ganglion cells. These neurons ultimately may produce action potentials on their axons. This spatiotemporal pattern of spikes determines the raw input from the eyes to the brain.* Photoreceptors: A photoreceptor, or photoreceptor cell, is a specialized type of neuron found in the eye\'s retina that is capable of phototransduction. More specifically, the photoreceptor sends signals to other neurons by a change in its membrane potential when it absorbs photons. Eventually, this information will be used by the visual system to form a complete representation of the visual world. There are 2 types of photoreceptors: **rods** are responsible for scotopic, or night vision, whereas **cones** are responsible for photopic, or daytime vision as well as color perception. ```{=html} <!-- --> ``` Extraocular muscles: Each eye has six muscles that control its movements: the lateral rectus, the medial rectus, the inferior rectus, the superior rectus, the inferior oblique, and the superior oblique. When the muscles exert different tensions, a torque is exerted on the globe that causes it to turn. This is an almost pure rotation, with only about one millimeter of translation, thus, the eye can be considered as undergoing rotations about a single point in the center of the eye. Five of the extraocular muscles have their origin in the back of the orbit in a fibrous ring called the **annulus of Zinn**. Four of these then course forward through the orbit and insert onto the globe on its anterior half (i.e., in front of the eye\'s equator). These muscles are named after their straight paths, and are called the four rectus muscles, or four recti. They insert on the globe at 12, 3, 6, and 9 o\'clock, and are called the superior, lateral, inferior and medial rectus muscles. (Note that lateral and medial are relative to the subject, with lateral toward the side and medial toward the midline, thus the medial rectus is the muscle closest to the nose). ### Eye Movement The visual system in the brain is too slow to process that information if the images are slipping across the retina at more than a few degrees per second, thus, for humans to be able to see while moving, the brain must compensate for the motion of the head by turning the eyes. To get a clear view of the world, the brain must turn the eyes so that the image of the object of regard falls on the fovea. Eye movements are thus very important for visual perception, and any failure to make them correctly can lead to serious visual disabilities. Having two eyes is an added complication, because the brain must point both of them accurately enough that the object of regard falls on corresponding points of the two retinas; otherwise, double vision would occur. The movements of different body parts are controlled by striated muscles acting around joints. The movements of the eye are no exception, but they have special advantages not shared by skeletal muscles and joints, and so are considerably different. Try This Experiment: Hold your hand up, about one foot (30 cm) in front of your nose. Keep your head still, and shake your hand from side to side, slowly at first, and then faster and faster. At first you will be able to see your fingers quite clearly. But as the frequency of shaking passes about one hertz, the fingers will become a blur. Now, keep your hand still, and shake your head (up and down or left and right). No matter how fast you shake your head, the image of your fingers remains clear. This demonstrates that the brain can move the eyes opposite to head motion much better than it can follow, or pursue, a hand movement. When your pursuit system fails to keep up with the moving hand, images slip on the retina and you see a blurred hand. ### How we see an object - The light rays enter the eye through the cornea (transparent front portion of eye to focus the light rays). - Then, light rays move through the pupil, which is surrounded by Iris to keep out extra light - Then, light rays move through the crystalline lens (Clear lens to further focus the light rays ) - Then, light rays move through the vitreous humor (clear jelly like substance) - Then, light rays fall on the retina, which processes and converts incident light to neuron signals using special pigments in rod and cone cells. - These neuron signals are transmitted through the optic nerve, - Then, the neuron signals move through the visual pathway -- Optic nerve \> Optic Chiasm \> Optic Tract \> Optic Radiations \> Cortex - Then, the neuron signals reach the occipital (visual) cortex and its radiations for the brain\'s processing. - The visual cortex interprets the signals as images and along with other parts of the brain, interpret the images to extract form, meaning, memory and context of the images. ### Depth Perception Depth perception is the visual ability to perceive the world in three dimensions. It is a trait common to many higher animals. Depth perception allows the beholder to accurately gauge the distance to an object. Depth perception is often confused with binocular vision, also known as Stereopsis. Depth perception does rely on binocular vision, but it also uses many other monocular cues. ### Diseases, disorders, and age-related changes There are many diseases, disorders, and age-related changes that may affect the eyes and surrounding structures. As the eye ages certain changes occur that can be attributed solely to the aging process. Most of these anatomic and physiologic processes follow a gradual decline. With aging, the quality of vision worsens due to reasons independent of aging eye diseases. While there are many changes of significance in the non-diseased eye, the most functionally important changes seem to be a reduction in pupil size and the loss of accommodation or focusing capability (presbyopia). The area of the pupil governs the amount of light that can reach the retina. The extent to which the pupil dilates also decreases with age. Because of the smaller pupil size, older eyes receive much less light at the retina. In comparison to younger people, it is as though older persons wear medium-density sunglasses in bright light and extremely dark glasses in dim light. Therefore, for any detailed visually guided tasks on which performance varies with illumination, older persons require extra lighting. !This image contains a two digit number similar to the sample above. Someone who is protanopic might not see this number.\|link=Special:FilePath/Colorblind3.png Color Blindness: Color Blindness or color vision deficiency, in humans is the inability to perceive differences between some or all colors that other people can distinguish. It is most often of genetic nature, but may also occur because of eye, nerve, or brain damage, or due to exposure to certain chemicals. There are many types of color blindness. The most common variety are hereditary (genetic) photoreceptor disorders, but it is also possible to acquire color blindness through damage to the retina, optic nerve, or higher brain areas. There is generally no treatment to cure color deficiencies, however, certain types of tinted filters and contact lenses may help an individual to distinguish different colors better. ```{=html} <!-- --> ``` Night Blindness: Also known as Nyctalopia, is a condition making it difficult or impossible to see in the dark. It is a symptom of several eye diseases. Night blindness may exist from birth, or be caused by injury or malnutrition (for example, a lack of vitamin A). The most common cause of nyctalopia is retinitis pigmentosa, a disorder in which the rod cells in the retina gradually lose their ability to respond to the light. Patients suffering from this genetic condition have progressive nyctalopia and eventually their day-time vision may also be affected. In congenital stationary night blindness the rods do not work from birth, but as the name implies, sufferers do not get worse. Another cause of night blindness is a deficiency of retinol, or vitamin A, found in fish oils, liver and dairy products. ```{=html} <!-- --> ``` Day Blindness: Also known as Hemeralopia is the inability to see clearly in bright light. The daytime vision gets worse and worse. Nighttime vision remains unchanged due to the use of rods as opposed to cones (during the day), which get affected by hemeralopia and in turn degrade the daytime optical response. !Impression of floaters, as seen against a blue sky.{width="110"} Floater: Also known as \"Muscae Volitantes\" are deposits of various size, shape, consistency, refractive index, and motility within the eye\'s normally transparent vitreous humour. Floaters are suspended in the vitreous humour, the thick fluid or gel that fills the eye. Thus, they generally follow the rapid motions of the eye, while drifting slowly within the fluid. Floaters are visible only because they do not remain perfectly fixed within the eye. The shapes are shadows projected onto the retina by tiny structures of protein or other cell debris discarded over the years and trapped in the vitreous humour. They are also common after cataract operations or after trauma. In some cases, floaters are congenital. !Picture of children holding a ball as seen by someone with glaucoma. Glaucoma: A group of diseases of the optic nerve involving loss of retinal ganglion cells in a characteristic pattern of optic neuropathy. Although raised intraocular pressure is a significant risk factor for developing glaucoma, there is no set threshold for intraocular pressure that causes glaucoma. One person may develop nerve damage at a relatively low pressure, while another person may have high eye pressures for years and yet never develop damage. Untreated glaucoma leads to permanent damage of the optic nerve and resultant visual field loss, which can progress to blindness. ```{=html} <!-- --> ``` Visual Agnosia:Visual agnosia is the inability of the brain to make sense of or make use of some part of otherwise normal visual stimulus, and is typified by the inability to recognize familiar objects or faces. This is distinct from blindness, which is a lack of sensory input to the brain due to damage to the eye or optic nerve. Visual agnosia is often due to damage, such as stroke, in posterior parietal lobe in the right hemisphere of the brain. Careful analysis of the nature of visual agnosia has led to improved understanding of the brain\'s role in normal vision. ```{=html} <!-- --> ``` Deadly Nightshade: Deadly Nightshade is a plant oil that can potentially kill you. Atrophine taken from this plant causes your eyes to dilate. This was used in the middle ages by women who wanted to look more attractive for men. To this day, it is still used by opthamologists. How this works is that the atrophine is a competitor with acetylcholine. The Nightshadow goes into your receptors on the postsynaptic membrane of an action potential. This makes it so that the acetylcholine doesn't have any receptor site so the Na ion is not able to be released. ### Critical Thinking **The answers for these critical thinking questions is right here** 1. Explain why you are normally unaware of your blind spot. 2. Stare at a bright light for 10 seconds and then stare at a white sheet of paper. What do you observe and why? 3. What is it that makes things \"disappear\" when you are staring at them at night, and how do you make them reappear? 4. Name what rods are sensitive to and also what cones are sensitive to. 5. Explain how Deadly Nightshade works. ## The Senses Of Hearing The ear is the sense organ that collects and detects sound waves and plays a major role in the sense of balance and body position. The sensory receptors for both hearing and equilibrium are mechanoreceptors found in the inner ear; these receptors are hair cells that have stereocilia (long microvilli) that are extremely sensitive to mechanical stimulations. ### Anatomy of the Ear The ear has three divisions: the outer ear, the middle ear, and the inner ear. !Anatomy of the human ear.{width="250"} Outer Ear (Auricle, Ear Canal, Surface of Ear Drum): The outer ear is the most external portion of the ear. The outer ear includes the pinna (also called auricle), the ear canal, and the very most superficial layer of the ear drum (also called the tympanic membrane). Although the word \"ear\" may properly refer to the pinna (the flesh covered cartilage appendage on either side of the head), this portion of the ear is not vital for hearing. The complicated design of the human outer ear does help capture sound, but the most important functional aspect of the human outer ear is the ear canal itself. This outer ear canal skin is applied to cartilage; the thinner skin of the deep canal lies on the bone of the skull. If the ear canal is not open, hearing will be dampened. Ear wax (medical name -- cerumen) is produced by glands in the skin of the outer portion of the ear canal. Only the thicker cerumen-producing ear canal skin has hairs. The outer ear ends at the most superficial layer of the tympanic membrane. The tympanic membrane is commonly called the ear drum. ```{=html} <!-- --> ``` Middle Ear (Air Filled Cavity behind the Ear Drum, includes most of the Ear Drum, and Ear Bones): The middle ear includes most of the ear drum (tympanic membrane) and the 3 ear bones ossicles: malleus (or hammer), incus (or anvil), and stapes (or stirrup). The opening of the Eustachian tube is also within the middle ear. The malleus has a long process (the handle) that is attached to the mobile portion of the ear drum. The incus is the bridge between the malleus and stapes. The stapes is the smallest named bone in the human body. The stapes transfers the vibrations of the incus to the **oval window**, a portion of the inner ear to which it is connected. It is the final bone in the chain to transfer vibrations from the eardrum to the inner ear. The arrangement of these 3 bones is a sort of Rube Goldberg device: movement of the tympanic membrane causes movement of the first bone, which causes movement of the second, which causes movement of the third. When this third bone pushes down, it causes movement of fluid within the cochlea (a portion of the inner ear). This particular fluid only moves when the stapes footplate is depressed into the inner ear. Unlike the open ear canal, however, the air of the middle ear is not in direct contact with the atmosphere outside the body. The Eustachian tube connects from the chamber of the middle ear to the back of the pharynx. The middle ear in humans is very much like a specialized paranasal sinus, called the tympanic cavity, it, like the paranasal sinuses, is a hollow mucosa lined cavity in the skull that is ventilated through the nose. The mastoid portion of the temporal bone, which can be felt as a bump in the skull behind the pinna, also contains air, which ventilates through the middle ear. ```{=html} <!-- --> ``` Inner Ear (Cochlea, Vestibule, and Semi-Circular Canals):The inner ear includes both the organ of hearing (the cochlea) and a sense organ (the labyrinth or vestibular apparatus) that is attuned to the effects of both gravity and motion. The balance portion of the inner ear consists of three semi-circular canals and the vestibule. The inner ear is encased in the hardest bone of the body. Within this ivory hard bone, there are fluid-filled hollows. Within the cochlea are three fluid filled spaces: the tympanic canal, the vestibular canal, and the middle canal. The eighth cranial nerve comes from the brain stem to enter the inner ear. When sound strikes the ear drum, the movement is transferred to the footplate of the stapes, which attaches to the oval window and presses into one of the fluid-filled ducts of the cochlea. The hair cells in the organ of Corti are stimulated by particular frequencies of sound, based on their location within the cochlea. High pitch sounds are at a higher frequency and, due to the shorter wavelength they \"hit\" the membrane \"faster\" (ie. close to the oval window). In contrast, low frequency sounds have large wavelengths, and will travel further through the scala vestibuli before \"hitting\" the tectorial membrane near the apex of the cochlea. The fluid inside the cochlea is moved, flowing against the receptor (hair) cells of the organ of Corti, which fire in a graded response based on the volume of the sound. The hair cells then stimulate the nerve cells in the Spiral Ganglion, which sends information through the auditory portion of the eighth cranial nerve to the brain. Humans are able to hear sounds between about 20 Hz and 20,000 Hz. Mammals that can hear lower frequency sounds, such as whales and elephants, have a longer cochlea. Humans tend to lose high-frequency hearing first, which has led some teenagers to using high-frequency ring tones (above 17,000 Hz) that may go undetected by their middle-aged teachers. !Cross section of the cochlea{width="250"} Hair Cell: Hair cells are columnar cells, each with a bundle of 100-200 specialized cilia at the top, for which they are named. These cilia are the mechanosensors for hearing. Lightly resting atop the longest cilia is the tectorial membrane, which moves back and forth with each cycle of sound, tilting the cilia and allowing electric current into the hair cell. Hair cells, like the photoreceptors of the eye, show a graded response, instead of the spikes typical of other neurons. Immediately over the hair cells of the organ of Corti is an overhanging "tectorial membrane." When the Bones of the Middle Ear vibrate the oval window, these vibrations are transmitted to the fluid within the cochlea and eventually cause the round window on the cochlea to bulge outward. These vibrations deflect the membrane on which the Organ of Corti is located, causing the three rows of outer hair cells to "rub" against the overhanging tectorial membrane. By their muscle-like activity they amplify the weakest vibrations for the inner hair cells. The louder sounds are not amplified. The disturbed inner hair cells will then activate the cochlear nerve fibers. The current model is that cilia are attached to one another by "tip links", structures which link the tips of one cilium to another. Stretching and compressing the tip links may open an ion channel and produce the receptor potential in the hair cell. These graded potentials are not bound by the "all or none" properties of an action potential. There are far fewer hair cells than afferent (leading to the brain) nerve fibers in the cochlea. The nerve that innervates the cochlea is the cochlear nerve, and forms cranial nerve number VIII with the vestibular nerve from the balance organ. Neuronal dendrites innervate cochlear hair cells. The neurotransmitter itself is thought to be **glutamate**. At the presynaptic juncture, there is a distinct "presynaptic dense body" or ribbon. This dense body is surrounded by synaptic vesicles and is thought to aid in the fast release of neurotransmitter. Efferent projections from the brain to the cochlea also play a role in the perception of sound. Efferent synapses occur on outer hair cells and on afferent dendrites under inner hair cells. ### Process of Hearing Detection of sound motion is associated with the right posterior superior temporal gyrus. The superior temporal gyrus contains several important structures of the brain, including: (1)marking the location of the primary auditory cortex, the cortical region responsible for the sensation of sound. Sections 41 and 42 are called the primary auditory area of the cerebrum, and processes the basic characteristics of sound such as pitch and rhythm. The auditory association area is located within the temporal lobe of the brain, in an area called the Wernicke\'s area, or area 22. This area, near the lateral cerebral sulcus, is an important region for the processing of acoustic energy so that it can be distinguished as speech, music, or noise. It also interprets words that are heard into an associated thought pattern of understanding. The gnostic area of the cerebrum, (areas 5, 7, 39 and 40) helps to integrate all incoming sense patterns so that a common thought can be formed (correlated) using all arriving sensory information. ### Hearing Underwater Hearing threshold and the ability to localize sound sources are reduced underwater. in which the speed of sound is faster than in air. Underwater, hearing is by bone conduction and localization of sound appears to depend on differences in amplitude detected by bone conduction. ### Localization of Sound by Humans Humans are normally able to hear a variety of sound frequencies, from about 20 Hz to 20 kHz. Our ability to estimate just where the sound is coming from, sound localization, is dependent on both hearing ability of each of the two ears, and the exact quality of the sound. Since each ear lies on an opposite side of the head, a sound will reach the closest ear first, and its amplitude will be loudest in that ear. Much of the brain\'s ability to localize sound depends on interaural (between ears) intensity differences and interaural temporal or phase differences. Two mechanisms are known to be used. Bushy neurons can resolve time differences as small as the time it takes sound to pass one ear and reach the other (10 milliseconds). For high frequencies, frequencies with a wavelength shorter than the listener\'s head, more sound reaches the nearer ear. Human echolocation is a technique involving echolocation used by some blind humans to navigate within their environment. ### Process of Equilibrium Equilibrioception or sense of balance is one of the physiological senses. It allows humans and animals to walk without falling. Some animals are better in this than humans, for example allowing a cat (as a quadruped using its inner ear and tail) to walk on a thin fence. All forms of equilibrioception can be described as the detection of acceleration. It is determined by the level of fluid properly called endolymph in the labyrinth -- a complex set of tubing in the inner ear. When the sense of balance is interrupted it causes dizziness, disorientation and nausea. You can temporarily disturb your sense of balance by closing your eyes and turning rapidly in circles five or six times. This starts the fluid swirling in circles inside your ear canal. When you stop turning it takes a few seconds for the fluid to lose momentum, and until then the sense from your inner ear conflicts with the information coming from your vision, causing dizziness and disorientation. Most astronauts find that their sense of balance is impaired when in orbit, because there is not enough gravity to keep the ear\'s fluid in balance. This causes a form of motion sickness called space sickness. ### Disorders with the Ear Deafness: The word deaf can have at least two different meanings. The first term is used to indicate the presence of enough hearing loss such that an individual is not sensitive to sound. Someone with a partial loss of hearing is more likely to be referred to as hearing impaired or the qualified partially deaf by professionals. The second term is used to indicate someone who considers themselves \'culturally deaf\', and they often use a capital D to distinguish this. Deaf people often are signers and consider that their Deafness is not something that needs to be medically fixed. !250 px\|right\|An inflamed Otitis Media. Otitis Media: An inflammation of the middle ear segment. It is usually associated with a buildup of fluid and frequently causes an earache. The fluid may or may not be infected. The typical progress of otitis media is: the tissues surrounding the Eustachian tube swell due to an infection and/or severe congestion. The Eustachian tube remains blocked most of the time. The air present in the middle ear is slowly absorbed into the surrounding tissues. A strong negative pressure creates a vacuum in the middle ear. The vacuum reaches a point where fluid from the surrounding tissues accumulates in the middle ear. Streptococcus pneumoniae and Haemophilus influenzae are the most common bacterial causes of otitis media. As well as being caused by Streptococcus pneumoniae and Haemophilus influenzae it can also be caused by the common cold. ```{=html} <!-- --> ``` Vertigo (dizziness): Vertigo, sometimes called a headrush, is a major symptom of a balance disorder. It is the sensation of spinning while the body is stationary with respect to the earth or surroundings. With the eyes shut, there will be a sensation that the body is in movement, called subjective vertigo; if the eyes are open, the surroundings will appear to move past the field of vision, called objective vertigo. The effects may be slight. It may cause nausea or, if severe, may give rise to difficulty with standing and walking. Vertigo is usually associated with a problem in the inner ear balance mechanisms (vestibular system), in the brain, or with the nerve connections between these two organs. The most common cause is benign paroxysmal positional vertigo, or BPPV. Vertigo can be a symptom of an underlying harmless cause, such as in BPPV or it can suggest more serious problems. These include drug toxicities, strokes or tumors (though these are much less common than BPPV). ```{=html} <!-- --> ``` Motion sickness: Motion sickness is a condition in which the endolymph (the fluid found in the semicircular canals of the inner ears) becomes \'stirred up\', causing confusion between the difference between apparent perceived movement (none or very little), and actual movement. Depending on the cause, it is also referred to as seasickness, carsickness, airsickness, or spacesickness. Nausea is the most common symptom of motion sickness. If the motion causing nausea is not resolved, the sufferer will frequently vomit within twenty minutes. Unlike ordinary sickness, vomiting in motion sickness tends not to relieve the nausea. If you don\'t want to consult a doctor, one common form of relief is to eat mints. ```{=html} <!-- --> ``` Dysacusis: Dysacusis is a hearing impairment characterized by difficulty in processing details of sound, but not primarily a loss of the ability to perceive sound. May also refer to pain or discomfort due to sound. ### Critical Thinking **The answers for these critical thinking questions can be found here.** 1. Explain how the pitch of sound is coded. How is the loudness of sound coded? 2. What do the three semicircular canals in the inner ear enable us to do? How do they accomplish this? 3. What does the eustachian tube do? What does the eustachian tube have to do with a middle ear infection? 4. What is the advantage of having a oval window? ## Touch Touch is the first sense developed in the womb and the last sense used before death. With 50 touch receptors for every square centimeter and about 5 million sensory cells overall, the skin is very sensitive and is the largest and one of the most complex organs in our bodies. These touch receptors are grouped by type and include Mechanoreceptors (sensitive to pressure, vibration and slip), Thermoreceptors (sensitive to changes in temperature), and Nocioreceptors (responsible for pain). ### Pacinian Corpuscles Pacinian corpuscles detect gross pressure changes and vibrations. They are the largest of the receptors. Any deformation in the corpuscle causes action potentials to be generated, by opening pressure-sensitive sodium ion channels in the axon membrane. This allows sodium ions to influx in, creating a receptor potential. Pacinian corpuscles cause action potentials when the skin is rapidly indented but not when the pressure is steady, due to the layers of connective tissue that cover the nerve ending (Kandel et al., 2000). It is thought that they respond to high velocity changes in joint position. ### Meissner\'s Corpuscle Meissner\'s corpuscles are distributed throughout the skin, but concentrated in areas especially sensitive to light touch, such as the fingertips, palms, soles, lips, tongue, face, nipples and the external skin of the male and female genitals. They are primarily located just beneath the epidermis within the dermal papillae. Any physical deformation in the Meissner's corpuscle will cause an action potential in the nerve. Since they are rapidly adapting or phasic, the action potentials generated quickly decrease and eventually cease. If the stimulus is removed, the corpuscle regains its shape and while doing so (ie: while physically reforming) causes another volley of action potentials to be generated. (This is the reason one stops \"feeling\" one\'s clothes.) This process is called **sensory adaption**. Because of their superficial location in the dermis, these corpuscles are particularly sensitive to touch and vibrations, but for the same reasons, they are limited in their detection because they can only signal that something is touching the skin. Meissner\'s corpuscles do not detect pain; this is signaled exclusively by free nerve endings. !Layers of the skin, showing the Merkel\'s Cell.{width="500"} ### Merkel's Discs Merkel's Discs are Mechanoreceptors, making them sensitive to pressure and vibration. In humans, Merkel cells occur in the superficial skin layers, and are found clustered beneath the ridges of the fingertips that make up fingerprints. They're somewhat rigid in structure, and the fact that they are not encapsulated, causes them to have a sustained response (in the form of action potentials or spikes) to mechanical deflection of the tissue. Merkel nerve endings are extremely sensitive to tissue displacement, and may respond to displacements of less than 1 um. Several studies indicate that they mediate high-resolution tactile discrimination, and are responsible for the ability of our fingertips to feel fine detailed surface patterns (e.g. for reading Braille). ### Ruffini corpuscles Ruffini corpuscles are Thermoreceptors, aiding in the detection of temperature changes. Named after Angelo Ruffini, the Ruffini ending is a class of slowly adapting mechanoreceptor thought to exist only in the glabrous dermis and subcutaneous tissue of humans. This spindle-shaped receptor is sensitive to skin stretch, and contributes to the kinesthetic sense of and control of finger position and movement. ### Disorders of Touch Sensory Processing Disorder: In most people sensory integration occurs naturally without a thought process. But in some people the sensory integration does not develop properly and becomes distorted. In these people, the brain and central nervous system misinterprets everyday sensory information such as touch, sound and movement. Research is still being done on this disorder but they are finding direct links to SPD with other disorders like ADD/ADHD, premature birth, Autism, Down's Syndrome and Fragile X.\ Tactile defensiveness:Considered a category of SPD, tactile defensiveness is an overreaction to the sense of touch. Identified by Dr. Jean Ayers in the 1960's. A person with tactile defensiveness will react with a "flight or fight" reaction to touch stimuli that a normal person would interpret as harmless. Most cases are noticed in children or babies due to the fact that they do not want to be touched or cuddled as a normal child would. A child with this disorder will probably have these sign or symptoms: - Does not like to go barefoot or have feet touched - Does not enjoy baths, haircuts, nail clipping - Requires tags to be removed from all clothing - Does not want their face touched - Hard time eating because of textures, temperatures of the food - Does not want to touch anything that is messy or has a sticky texture Congenital insensitivity to pain with anhidrosis or CIPA: Exceedingly rare disease. There are only about 35 known cases in the United States. CIPA is a severe autosomal recessive condition in which the peripheral nerves demonstrate a loss of unmyelinated and small myelinated fibers. The actual physiopathological mechanism is still unknown and being studied- this is an extremely hard disease to study due to the rarity of cases. Most people with the disease will not live long due to injuries received that go untreated because they are unknown and severe ### Case Study **Insensitivity to pain** Wouldn\'t it wonderful if you could no longer feel pain. Is that not something we all would like to have? Or do we have pain for a good reason? Although it is rare there is a disease known as congenital insensitivity to pain. This genetic abnormality cause some people to lack certain components of the sensory system to receive pain. The exact reason for the problem is unknown and varies between people. Sadly people who have the disease often die in childhood. Injuries are very common with people who have congenital insensitivity to pain. They often will lose digits, may suffer from burns and their knees often have sores from kneeling to long. Clearly pain has a purpose, it is our warning signal when things are awry. ## The newborn\'s senses Newborns can feel all different sensations, but respond most enthusiastically to soft stroking, cuddling and caressing. Gentle rocking back and forth will oftentimes calm a crying infant, as will massages and warm baths. Newborns may comfort themselves by sucking their thumbs, or a pacifier. The need to suckle is instinctive and allows newborns to feed. Vision: Newborn infants have unremarkable vision, being able to focus on objects only about 18 inches (45 cm) directly in front of their face. While this may not be much, it is all that is needed for the infant to look at the mother's face when breastfeeding. When a newborn is not sleeping, or feeding, or crying, he or she may spend a lot of time staring at random objects. Usually, anything that is shiny, has sharp contrasting colors, or has complex patterns will catch an infant\'s eye. However, the newborn has a preference for looking at other human faces above all else. ```{=html} <!-- --> ``` Hearing: While still inside the mother, the infant can hear many internal noises, such as the mother\'s heartbeat, as well as many external noises including human voices, music and most other sounds. Therefore, although a newborn\'s ears may have some fluid present, he or she can hear sound from birth. Newborns usually respond to a female\'s voice over a male\'s. This may explain why people will unknowingly raise the pitch of their voice when talking to newborns. The sound of other human voices, especially the mother\'s, can have a calming or soothing effect on the newborn. Conversely, loud or sudden noises will startle and scare a newborn. ```{=html} <!-- --> ``` Taste:Newborns can respond to different tastes, including sweet, sour, bitter, and salty substances, with preference toward sweets. ```{=html} <!-- --> ``` Smell:A newborn has a developed sense of smell at birth, and within the first week of life can already distinguish the differences between the mother\'s own breast milk and the breast milk of another female. Reflex Stimulation Response Age of disappearance Function -------------- ----------------------------------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------- Eye blink Bright light shining in eyes or clap hands by eyes. Closes eyelids quickly. Permanent This reflex protects the infant from an excessive amount of stimulation. Withdrawal Stick sole of foot with a stimulus like a pin. This causes the foot to withdraw. Flexing of the knee to hip occurs. Decreases after the 10th day of birth This protects the infant from excessive unpleasant tactile stimulation. Rooting Touch cheek near the corner of the mouth. The infant\'s head will turn towards the site of stimulation. 3 weeks (due to the voluntary response that is now capable for infant to do at this time) This reflex helps baby to find the mothers\' nipple. Sucking Place fingers in infant\'s mouth. The infant will suck finger rhythmically. 4 months (voluntary sucking will come about) This helps with feeding. Swimming Place the baby in pool of water face down. The baby paddles and kicks in swimming movements. 4 to 6 month This helps baby to survive if dropped into the water. Moro Hold infant in a cradling horizontal position and slightly lower the baby in a fast motion toward the ground while making a loud sound. The baby will make an embracing motion and arch its back extending its legs and throwing its arms outward. Finally, it will bring the arms in toward its body 6 months In the evolutionary past this may have helped the baby cling to the mother. Palmar grasp Place the finger in baby\'s palm and press against the palm. The baby will immediately grasp the finger. 3 to 4 months This prepares infant for voluntary grasping. Tonic neck Turn the baby\'s head to one side while the baby is awake. This will cause the baby to extend one arm in front of its eye or to the side to which the head has been turned. 4 months This may prepare for voluntary reaching. Stepping Hold the baby under the arm and permit the bare feet of the baby to touch a flat surface. The baby will lift one foot after the other in a stepping fashion. 2 months (this applies to a baby who has gained weight. For baby who is not as heavy, this reflex may be submissive.) This prepares the baby for voluntary walking. Babinski Touch the foot in a stroking manner from the toe toward the heel. The baby\'s toes will fan out and curl as the foot twists inward. 8 to 12 months Unknown ## Review Questions Answers for these questions can be found here 1\. Located under the hardest bone in the body, these control not only hearing but also a sense of gravity and motion: A\) The incus and the stapes B\) The pinna and the ear drum C\) the vestibular nerve and the semicircular canals D\) The eustachian tube and the stapes 2\. The retina does the following; A\) allows vision in light and dark, using cones and rods B\) Gives depth perception using binocular vision C\) Contains the ciliary muscles that control the shape of the lens D\) Protects and supports the shape of the eye 3\. This is the reason that we stop feeling the clothes that we are wearing A\) Merkel's Discs are somewhat rigid in structure, and the fact that they are not encapsulated, causes them to have a sustained response B\) Meissner's corpuscle are rapidly adapting or phasic, the action potentials generated quickly decrease and eventually cease C\) Ruffini corpuscles is a class of slowly adapting mechanoreceptor D\) Pacinian corpuscles allow sodium ions to influx in, creating a receptor potential 4\. When eating a piece of candy, I will use the following to sense that it is sweet A\) Fungiform papillae B\) Filiform papillae C\) Foliate papillae D\) Circumvallate papillae E\) All of the above 5\. If I have a cold, food may not taste as good to me because A\) The nerve fibrils are not functioning properly B\) My food will taste the same; taste and smell have nothing in common C\) Papilla become blocked by mucus and are unable to function D\) Olfaction, taste and trigeminal receptors together contribute to the flavor of my food 6\. Walking from a well lit room into a dark room would cause the following to occur A\) The sclera in the eye to open and eventually allow me to see in the dark B\) The extraocular muscles in the eye to open and eventually allow me to see in the dark C\) The cones in the eye to open and eventually allow me to see in the dark D\) the rods in the eye to open and eventually allow me to see in the dark 7\. Hair cells in the ear A\) Are the actual sensory receptors that will fire off action potentials when they are disturbed B\) Show a graded response, instead of the spikes typical of other neurons C\) "Rub" against the overhanging tectorial membrane D\) All of the above 8\. Eyesight decreases with age because A\) Older eyes receive much less light at the retina B\) There are numerous eye diseases that can affect an older eye C\) The extent to which the pupil dilates decreases with age D\) all of the above 9\. Teens walking off of a roller coaster in Magic Mountain seem to have vertigo because A\) The fluid in the auricle has not stopped moving causing conflicts with the information coming from your vision B\) the fluid in the cochlea has not stopped moving causing conflicts with the information coming from your vision C\) The fluid in the tympanic membrane has not stopped moving causing conflicts with the information coming from your vision D\) The fluid in the stirrup has not stopped moving causing conflicts with the information coming from your vision 10\. These receptors react to foods treated with monosodium glutamate A\) Salt B\) Sour C\) Bitter D\) Sweet E\) Umami 11\. What senses fall under the category of chemoreception? A\) Hearing and smell B\) Touch and hearing C\) Vision and taste D\) Taste and smell ## Glossary **Anosmia**: Lack of olfaction, or a loss of the sense of smell **Auditory Canal**: Tube from the auditory meatus or opening of the ear to the tympanic membrane **Auditory Tube**: Either of the paired tubes connecting the middle ears to the nasopharynx; equalizes air pressure on the two sides of the eardrum **Chemoreception**: Physiological response of a sense organ to a chemical stimulus **Choroid**: Vascular layer of the eye lying between the retina and the sclera **Circumvallate papillae**: Papillae that are present on the back of the oral part of the tongue **Cochlea**: Is concerned with hearing, resembling a shell of a snail **Dysosmia**: When things smell differently than they should **Equilibrium**: Sense of balance **Extraocular muscles**: Six muscles that control eye movements: lateral rectus, medial rectus, inferior rectus, superior rectus, inferior oblique and superior oblique **Filiform papillae**: Thin, longer papillae that don\'t contain taste buds but are the most numerous **Foliate papillae**: Ridges and grooves towards the posterior part of the tongue **Fungiform papillae**: These are present mostly at the apex (tip) of the tongue- slightly mushroom shaped **Gustation**: The sense of taste **Hair Cell**: Mechanosensors for hearing, columnar cells each with a bundle of 100-200 specialized cilia at the top **Haptic**: From the Greek Haphe, means pertaining to the sense of touch **Hyposmia**: Decreased ability to smell **Inner Ear**: Innermost part of the ear, contains the cochlea, vestibule and semi-circular canals **Mechanoreceptor**: Sensory receptor that responds to mechanical pressure or distortion **Meissner\'s Corpuscle**: Encapsulated unmyelinated nerve endings, usually found in areas sensitive to light touch **Middle Ear**: Air filled cavity behind the eardrum, includes most of the eardrum and ear bones **Nasopharynx**: Nasal part of the pharynx that lies behind the nose and above the level of the soft palate **Nociception**: The perception of pain **Olfaction**: The sense of smell **Otitis Media**: An inflammation of the middle ear **Outer Ear**: External portion of the ear, includes the auricle, ear canal and surface of the ear drum **Oval Window**: Fenestra that has the base of the stapes attached to it **Pacinian Corpuscles**: Detect gross pressure changes and vibrations **Papilla**: Specialized epithelial cells that are small projections on the top of the tongue **Perception**: The brain's interpretation of a sensation **Phantosmia**: Phenomenon of smelling odors that aren\'t really present (AKA Phantom odors) **Photoreceptors**: Specialized type of neuron found in the eye\'s retina that is capable of phototransduction **Pinna**: Auricle of the ear **Retina**: Thin layer of neural cells that lines the back of the eyeball of vertebrates and some cephalopods **Round Window**: Fenestra leading into the cochlea **Sclera**: White outer coating of the eye- gives the eye its shape and helps to protect the delicate inner parts **Semicircular Canals**: Certain canals of the inner ear **Sensation**: Occurs when nerve impulses arrive in the brain **Sensory adaptation**: A decrease in response to stimuli **Stapes**: One of the small bones in the tympanum of the ear; the stirrups bone **Tactition**: The sense of pressure perception, generally in the skin **Tympanic Membrane**: The membrane in the ear that vibrates to produce sound **Umami**: Japanese word meaning savory or meaty- type of taste signal ## References - Hänig, D.P., 1901. Zur Psychophysik des Geschmackssinnes. Philosophische Studien, 17: 576-623. - Collings, V.B., 1974. Human Taste Response as a Function of Locus of Stimulation on the Tongue and Soft Palate. Perception & Psychophysics, 16: 169-174. - Buck, Linda and Richard Axel. (1991). A Novel Multigene Family May Encode Odorant Receptors: A Molecular Basis for Odor Recognition. Cell 65:175-183.
# Human Physiology/The Muscular System The **muscular system** is the biological system of humans that produces movement. The muscular system, in vertebrates, is controlled through the nervous system, although some muscles, like cardiac muscle, can be completely autonomous. **Muscle** is contractile tissue and is derived from the mesodermal layer of embryonic germ cells. Its function is to produce force and cause motion, either locomotion or movement within internal organs. Much of muscle contraction occurs without conscious thought and is necessary for survival, like the contraction of the heart or peristalsis, which pushes food through the digestive system. Voluntary muscle contraction is used to move the body and can be finely controlled, such as movements of the finger or gross movements that of the biceps and triceps.!Muscle structure{width="300"}Muscle is composed of muscle cells (sometimes known as \"muscle fibers\"). Within the cells are myofibrils; myofibrils contain sarcomeres which are composed of actin and myosin. Individual muscle cells are lined with endomysium. Muscle cells are bound together by perimysium into bundles called fascicles. These bundles are then grouped together to form muscle, and is lined by epimysium. Muscle spindles are distributed throughout the muscles, and provide sensory feedback information to the central nervous system. Skeletal muscle, which involves muscles from the skeletal tissue, is arranged in discrete groups. An example is the biceps brachii. It is connected by tendons to processes of the skeleton. In contrast, smooth muscle occurs at various scales in almost every organ, from the skin (in which it controls erection of body hair) to the blood vessels and digestive tract (in which it controls the caliber of a lumen and peristalsis, respectively).!A top-down view of skeletal muscle{width="300"}There are approximately 640 skeletal muscles in the human body (see list of muscles of the human body). Contrary to popular belief, the number of muscle fibers cannot be increased through exercise; instead the muscle cells simply get bigger. It is however believed that myofibrils have a limited capacity for growth through hypertrophy and will split if subject to increased demand. There are three basic types of muscles in the body (smooth, cardiac, and skeletal). While they differ in many regards, they all use actin sliding against myosin to create muscle contraction and relaxation. In skeletal muscle, contraction is stimulated at each cell by nervous impulses that releases acetylcholine at the neuromuscular junction, creating action potentials along the cell membrane. All skeletal muscle and many smooth muscle contractions are stimulated by the binding of the neurotransmitter acetylcholine. Muscular activity accounts for most of the body\'s energy consumption. Muscles store energy for their own use in the form of glycogen, which represents about 1% of their mass. Glycogen can be rapidly converted to glucose when more energy is necessary. ## Types There are three types of muscles: ![](Illu_muscle_tissues.jpg‎ "Illu_muscle_tissues.jpg‎") - **Smooth muscle** or \"involuntary muscle\" consists of spindle shaped muscle cells found within the walls of organs and structures such as the esophagus, stomach, intestines, bronchi, uterus, ureters, bladder, and blood vessels. Smooth muscle cells contain only one nucleus and no striations. ```{=html} <!-- --> ``` - **Cardiac muscle** is also an \"involuntary muscle\" but it is striated in structure and appearance. Like smooth muscle, cardiac muscle cells contain only one nucleus. Cardiac muscle is found only within the heart. ```{=html} <!-- --> ``` - **Skeletal muscle** or \"voluntary muscle\" is anchored by tendons to the bone and is used to effect skeletal movement such as locomotion. Skeletal muscle cells are multinucleated with the nuclei peripherally located. Skeletal muscle is called \'striated\' because of the longitudinally striped appearance under light microscopy. Functions of the skeletal muscle include: - Support of the body - Aids in bone movement - Helps maintain a constant temperature throughout the body - Assists with the movement of cardiovascular and lymphatic vessels through contractions - Protection of internal organs and contributing to joint stability Cardiac and skeletal muscle are striated in that they contain sarcomere and are packed into highly-regular arrangements of bundles; smooth muscle has neither. Striated muscle is often used in short, intense bursts, whereas smooth muscle sustains longer or even near-permanent contractions. Skeletal muscle is further divided into several subtypes: - Type I, slow oxidative, *slow twitch*, or \"red\" muscle is dense with capillaries and is rich in mitochondria and myoglobin, giving the muscle tissue its characteristic red color. It can carry more oxygen and sustain aerobic activity. - Type II, *fast twitch*, muscle has three major kinds that are, in order of increasing contractile speed: - a\) Type IIa, which, like slow muscle, is aerobic, rich in mitochondria and capillaries and appears red. - b\) Type IIx (also known as type IId), which is less dense in mitochondria and myoglobin. This is the fastest muscle type in humans. It can contract more quickly and with a greater amount of force than oxidative muscle, but can sustain only short, anaerobic bursts of activity before muscle contraction becomes painful (often attributed to a build-up of lactic acid). N.B. in some books and articles this muscle in humans was, confusingly, called type IIB - c\) Type IIb, which is anaerobic, glycolytic, \"white\" muscle that is even less dense in mitochondria and myoglobin. In small animals like rodents or rabbits this is the major fast muscle type, explaining the pale color of their meat. For most muscles, contraction occurs as a result of conscious effort originating in the brain. The brain sends signals, in the form of action potentials, through the nervous system to the motor neuron that innervates the muscle fiber. However, some muscles (such as the heart) do not contract as a result of conscious effort. These are said to be autonomic. Also, it is not always necessary for the signals to originate from the brain. Reflexes are fast, unconscious muscular reactions that occur due to unexpected physical stimuli. The action potentials for reflexes originate in the spinal cord instead of the brain. There are three general types of muscle contractions, skeletal muscle contractions, heart muscle contractions, and smooth muscle contractions. ## Muscular System Working With Other Body Systems - 1\. Homeostasis - 2\. Protection - 3\. Calcium Metabolism - 4\. Maintaining Body Temperature ## Skeletal Muscle Contractions Steps of a skeletal muscle contraction: - An action potential reaches the axon of the motor neuron. - The action potential activates voltage gated calcium ion channels on the axon, and calcium rushes in. - The calcium causes acetylcholine vesicles in the axon to fuse with the membrane, releasing the acetylcholine into the cleft between the axon and the motor end plate of the muscle fiber. - The skeletal muscle fiber is excited by large myelinated nerve fibers which attach to the neuromuscular junction. There is one neuromuscular junction for each fiber. - The acetylcholine diffuses across the cleft and binds to nicotinic receptors on the motor end plate, opening channels in the membrane for sodium and potassium. Sodium rushes in, and potassium rushes out. However, because sodium is more permeable, the muscle fiber membrane becomes more positively charged, triggering an action potential. - The action potential on the muscle fiber causes the sarcoplasmic reticulum to release calcium ions(Ca++). - The calcium binds to the troponin present on the thin filaments of the myofibrils. The troponin then allosterically modulates the tropomyosin. Normally the tropomyosin physically obstructs binding sites for cross-bridge; once calcium binds to the troponin, the troponin forces the tropomyosin to move out of the way, unblocking the binding sites. - The cross-bridge (which is already in a ready-state) binds to the newly uncovered binding sites. It then delivers a power stroke. - ATP binds the cross-bridge, forcing it to conform in such a way as to break the actin-myosin bond. Another ATP is split to energize the cross bridge again. - Steps 7 and 8 repeat as long as calcium is present on thin filament. - Throughout this process, the calcium is actively pumped back into the sarcoplasmic reticulum. When no longer present on the thin filament, the tropomyosin changes back to its previous state, so as to block the binding sites again. The cross-bridge then ceases binding to the thin filament, and the contractions cease as well. - Muscle contraction remains as long as Ca++ is abundant in sarcoplasm. Types of Contractions: - Isometric contraction\--muscle does not shorten during contraction and does not require the sliding of myofibrils but muscles are stiff. - Isotonic contraction\--inertia is used to move or work. More energy is used by the muscle and contraction lasts longer than isometric contraction. Isotonic muscle contraction is divided into two categories: concentric, where the muscle fibers shorten as the muscle contracts (ie. biceps brachialis on the up phase of a biceps curl); and eccentric, where the muscle fibers lengthen as they contract (ie. biceps brachialis on the down phase of a biceps curl). - Twitch\--exciting the nerve to a muscle or by passing electrical stimulus through muscle itself. Some fibers contract quickly while others contract slowly. - Tonic -maintaining postural tone against the force of gravity. The Efficiency of Muscle Contraction: - Only about 20% of input energy converts into muscular work. The rest of the energy is heat. - 50% of energy from food is used in ATP formation. - If a muscle contraction is slow or without movement, energy is lost as maintenance heat. - If muscle contraction is rapid, energy is used to overcome friction. Summation of Muscle Contraction: It is the adding together of individual muscle twitches to make strong muscle movements. - Multiple motor unit summation\--increasing number of motor units contracting simultaneously. - Wave summation\--increasing rapidity of contraction of individual motor units. - Tetanization\--higher frequency successive contractions fuse together and cannot be distinguished from one another. ## Sliding Filament theory When a muscle contracts, the actin is pulled along myosin toward the center of the sarcomere until the actin and myosin filaments are completely overlapped. The H zone becomes smaller and smaller due to the increasing overlap of actin and myosin filaments, and the muscle shortens. Thus when the muscle is fully contracted, the H zone is no longer visible (as in the bottom diagram, left). Note that the actin and myosin filaments themselves do not change length, but instead slide past each other. ### Cellular Action of Skeletal Muscles During cellular respiration the mitochondria, within skeletal muscle cells, convert glucose from the blood to carbon dioxide and water in the process of producing ATP (see cell physiology). ATP is needed for all muscular movement. When the need of ATP in the muscle is higher than the cells can produce with aerobic respiration, the cells will produce extra ATP in a process called anaerobic respiration. The first step of aerobic respiration(glycolysis) produces two ATP per glucose molecule. When the rest of the aerobic respiration pathway is occupied the pyruvate molecule can be converted to lactic acid. This method produces much less ATP than the aerobic method, but it does it faster and allows the muscles to do a bit more than if they relied solely on ATP production from aerobic respiration. The drawback to this method is that lactic acid accumulates and causes the muscles to fatigue. They will eventually stop contracting until the breakdown of lactic acid is sufficient to allow for movement once again. People experience this most noticeably when they repeatedly lift heavy things such as weights or sprint for a long distance. Muscle soreness sometimes occurs after vigorous activity, and is often misunderstood by the general public to be the result of lactic acid buildup. This is a misconception because the muscle does fatigue from lactic acid buildup, but it does not stay in the muscle tissue long enough to cause tissue breakdown or soreness. During heavy breathing, following exercise, the cells are converting the lactic acid either back into glucose or converting it to pyruvate and sending it through the additional steps of aerobic respiration. By the time a person is breathing normally again the lactic acid has been removed. The soreness is actually from small tears in the fibers themselves. After the fibers heal they will increase in size. The number of mitochondria will also increase if there is continued demand for additional ATP. Hence, through exercise the muscles can increase in both strength and endurance. Another misconception is that as the muscle increases in size it also gains more fibers. This is not true. The fibers themselves increase in size rather than in quantity. The same holds true for adipose tissue\--fat cells do not increase in number, but rather the amount of lipids (oil) in the cells increase. Muscle fibers are also genetically programmed to reach a certain size and stop growing from there, so after a while even the hardest working weightlifter will only reach a certain level of strength and endurance. Some people will get around this by taking steroids. The artificial steroids cause all sorts of trouble for the person. They can cause the adrenal glands to stop producing corticosteroids and glucosteroids. This leads to the atrophy of the gland\'s medulla and causes permanent loss of the production of these hormones. The testicles may also atrophy in response to steroids. Eventually the testes will stop making testosterone and sperm, rendering the male infertile. One of the more serious problems associated with abnormal gain of muscle mass is heart failure. While for most people gaining muscle and losing fat is desirable, a body builder is at risk of producing more muscle mass than the heart can handle. One pound of fat contains about 3.5 miles of blood vessels, but one pound of muscle has about 6.5 miles. Hence, additional muscle causes the heart to pump more blood. Some people that have too much muscle will be very strong but will not have a healthy aerobic endurance, in part because of the difficulty of providing oxygenated blood to so much tissue. Sliding filament theory:This link shows the animation of the sliding filament theory.\ explanation and image of sliding filament theory:this link gives a better demonstration of the theory with the explanation. ## Involuntary Muscle Movement Spasms When Smooth and skeletal muscles go through multiple spasms it is referred either as seizure or convulsion. Cramps Strenuous activities can cause painful spasms that are long, this is referred to as cramps. ## Injury Sprain An injury to a joint that involves a stretched or torn ligament. Muscle Strain A strain occurs when a muscle or the tendon that attaches it to the bone is overstretched or torn. Muscle strains are also called pulled muscles. Who gets it? Anyone can strain a muscle. However, people involved in sports or other forms of strenuous exercise are more likely to strain a muscle. *What causes it?* Muscles are bunches of fibers that can contract. Muscle strains usually occur during activities that require the muscle to tighten forcefully. The muscle is strained either because it is not properly stretched, or warmed up, before the activity; it is too weak; or because the muscle is already injured and not allowed time to recover. So, many muscle strains occur during exercise or sports activities. They can also occur when lifting heavy objects. What are the symptoms? When a muscle is strained, it hurts and is difficult to move. You may also feel a burning sensation in the area of the injured muscle, or feel as though something has \"popped.\" Sometimes the area of the strained muscle looks bruised or swells. A strained muscle might spasm, which means it contracts suddenly and involuntarily, causing severe pain. How is it diagnosed? To diagnose a muscle strain, your doctor will examine the painful area, and ask how and when the injury happened. He or she may order other diagnostic tests, such as x-rays, to rule out any injury to the bone. *What is the treatment?* Muscle strains are treated with rest, ice, compression, and elevation, or RICE. You will be told to rest the injured area to reduce pain and swelling. If the strain is in the leg or foot area, you may need to use crutches. Ice packs are recommended at regular intervals (as recommended by your doctor) over the first few days after the injury. Ice causes the blood vessels to constrict, which reduces inflammation and pain. Anti-inflammatory medications might also be used to relieve pain. Compression and elevation help to reduce swelling. Your doctor may also recommend physical therapy to speed your recovery. You should avoid the type of activity that caused the injury until the muscle is completely healed. Self-care tips You can prevent muscle strains by warming up for at least 10 minutes before participating in any strenuous exercise or heavy lifting. When you warm up, you increase the blood circulation to the muscle and prepare it for exercise. When starting any new exercise program or sport, it\'s important to begin gradually so your muscles are conditioned for the activity. ### Steroids Anabolic steroids, which are synthetic versions of the primary male sex hormone testosterone, can be injected, taken orally, or used transdermally. These drugs are Controlled Substances that can be prescribed to treat conditions such as body wasting in patients with AIDS, and other diseases that occur when the body produces abnormally low amounts of testosterone. However, the doses prescribed to treat these medical conditions are 10 to 100 times lower than the doses that are used for performance enhancement. Let me be clear:- while anabolic steroids can enhance certain types of performance or appearance,they are dangerous drugs, and when used inappropriately, they can cause a host of severe, long-lasting, and often irreversible negative health consequences. These drugs can stunt the height of growing adolescents, masculinize women, and alter sex characteristics of men. Anabolic steroids can lead to premature heart attacks, strokes, liver tumors, kidney failure and serious psychiatric problems. In addition, because steroids are often injected, users risk contracting or transmitting HIV or hepatitis. Abuse of anabolic steroids differs from the abuse of other illicit substances because the initial use of anabolic steroids is not driven by the immediate euphoria that accompanies most drugs of abuse, such as cocaine, heroin, and marijuana, but by the desire of the user to change their appearance and performance, characteristics of great importance to adolescents. These effects of steroids can boost confidence and strength leading the user to overlook the potential serious long-term damage that these substances can cause. Government agencies such as NIDA support research that increases our understanding of the impact of steroid use and improves our ability to prevent abuse of these drugs. For example, NIDA funding led to the development of two highly effective programs that not only prevent anabolic steroid abuse among male and female high school athletes, but also promote other healthy behaviors and attitudes. The ATLAS (targeting male athletes) and ATHENA (targeting female athletes) programs have been adopted by schools in 29 states and Puerto Rico. Both Congress and the Substance Abuse and Mental Health Services Administration have endorsed ATLAS and ATHENA as model prevention programs, which could and should be implemented in more communities throughout the country. In addition to these prevention programs and other research efforts, also has invested in public education efforts to increase awareness about the dangers of steroid abuse. We have material on our website about steroid abuse at www.steroidabuse.gov and in April 2005 we again will distribute a \"Game Plan\" public service announcement designed to bring attention to abuse of anabolic steroids. Research has shown that the inappropriate use of anabolic steroids can have catastrophic medical, psychiatric and behavioral consequences. I hope that students, parents, teachers, coaches and others will take advantage of the information on our website about anabolic steroids abuse and join us in our prevention and education efforts. Participating in sports offers many benefits, but young people and adults shouldn\'t take unnecessary health risks in an effort to win.(Nora D. Volkow, M.D.) -Human-made substances related to male sex hormones. Some athletes abuse anabolic steroids to enhance performance. Abuse of anabolic steroids can lead to serious health problems, some of which are irreversible. Major side effects can include liver tumors and cancer, jaundice, high blood pressure, kidney tumors, severe acne, and trembling. In males, side effects may include shrinking of the testicles and breast development. In females, side effects may include growth of facial hair, menstrual changes, and deepened voice. In teenagers, growth may be halted prematurely and permanently. The therapeutic use of steroids can be realized by patients and their doctors by using them in a manner that is beneficial to the person. ### MyoD and other muscular factors MyoD is a protein and a transcription factor that activates muscle cell differentiation by turning on transcription of specific regulatory genes. It turns stem cells into myoblasts, a cell that can turn into many muscle cell, also called \"muscle stem cell\". MyoD belongs to a family of proteins knowns as myogenic regulatory factor(MRFs). MyoD can also turn on transcription of its own regulatory genes (MyoD protein coding genes), and this means that it can produce more of itself. The positive feedback turns on transcription of other muscle proteins, cell cycle blockers, and microRNA-206. One of the main actions of MyoD is to remove cells from the cell cycle by enhancing the transcription of p21The function of MyoD is to commit mesoderm cells to a skeletal lineage. MyoD can also regulate muscle repair. One of the main actions of MyoD is to remove cells from the cell cycle by enhancing the transcription of p21. Bidirectional Signalling- muscle cells and nerves cells send signals back and forth to each other. Amyotrophic Lateral Sclerosis(ALS) is a loss of motor neuron and this blocks the formation of neuromuscular junctions. Therefore, no muscle growth which means a potential of leading to paralysis. Stephen Hawking suffers from this disease. ### Muscle Homeostasis MicroRNA-206 indirectly forms neuromuscular junctions with motor neurons. Neuromuscular junction sends synaptic signals to MyoD and this blocks MyoD and stops or limits muscle development. Myostatin is a protein that also blocks MyoD. Without myostatin, muscle development increases. Myostatin Mutations In Sheep: they can have a mutant myostatin that causes microRNA-206 to block myostatin translation Myostatin Mutations In Humans: humans with mutant myostatin will develop lots of muscle (like a body builder) is possible to create a drug that blocks myostatin production. ## Smooth Muscle Contraction - Contractions are initiated by an influx of calcium which binds to calmodulin. - The calcium-calmodulin complex binds to and activates myosin light-chain kinase. - Myosin light-chain kinase phosphorylates myosin light-chains using ATP, causing them to interact with actin filaments. - Powerstroke. - Calcium is actively pumped out of the cell by receptor regulated channels. A second messanger, IP3, causes the release. - As calcium is removed the calcium-calmodulin complex breaks away from the myosin light-chain kinase, stopping phosphorylation. - Myosin phophatase dephosphorylates the myosin. If the myosin was bound to an actin molecule, the release is slow, this is called a latch state. In this manner, smooth muscle is able to stay contracted for some time without the use of much ATP. If the myosin was not bound to an actin chain it loses its affinity for actin. - It should be noted that ATP is still needed for crossbridge cycling, and that there is no reserve, such as creatine phosphate, available. Most ATP is created from aerobic metabolism, however anaerobic production may take place in times of low oxygen concentrations. ## Cardiac Muscle Cardiac muscle is found in the hearts of humans. They are shaped like skeletal muscles but work like smooth muscles. The cardiac muscle is responsible for the contractility of the heart and, therefore, the pumping action. ## ATP in the Human Body Muscles cells, like all cells, use ATP as an energy source. The total quantity of ATP in the human body at any one time is about 0.1 Mole. The energy used by human cells requires the hydrolysis of 200 to 300 moles of ATP daily. This means that each ATP molecule is recycled 2000 to 3000 times during a single day. ATP cannot be stored, hence its consumption must closely follow its synthesis. On a per-hour basis, 1 kilogram of ATP is created, processed and then recycled in the body. Looking at it another way, a single cell uses about 10 million ATP molecules per second to meet its metabolic needs, and recycles all of its ATP molecules about every 20-30 seconds. ## Lactic Acid Catabolized carbohydrates is known as glycolysis. The end product of glycolysis, pyruvate can go into different directions depending on aerobic or anaerobic conditions. In aerobic it goes through the Krebs cycle and in anaerobic it goes through the Cori cycle. In the Cori cycle pyruvate is converted to lactate, this forms lactic acid, lactic acid causes muscle fatigue. In the aerobic conditions pyruvate goes through the Krebs cycle. For more about Krebs cycle refer to chapter 2 Cell Physiology. ## Muscle Disorders ### Dermatomyositis and Polymyositis Dermatomyositis and polymyositis cause inflammation of the muscles. They are rare disorders, affecting only about one in 100,000 people per year. More women than men are affected. Although the peak age of onset is in the 50s, the disorders can occur at any age. Signs and symptoms --- Patients complain of muscle weakness that usually worsens over several months, though in some cases symptoms come on suddenly. The affected muscles are close to the trunk (as opposed to in the wrists or feet), involving for example the hip, shoulder, or neck muscles. Muscles on both sides of the body are equally affected. In some cases, muscles are sore or tender. Some patients have involvement of the muscles of the pharynx (throat) or the esophagus (the tube leading from the throat to the stomach), causing problems with swallowing. In some cases, this leads to food being misdirected from the esophagus to the lungs, causing severe pneumonia. In dermatomyositis, there is a rash, though sometimes the rash resolves before muscle problems occur. A number of different types of rash can occur, including rashes on the fingers, the chest and shoulders, or on the upper eyelids (show picture 1-3). In rare cases, the rash of dermatomyositis appears but myopathy never develops. Other problems sometimes associated with these diseases include fever, weight loss, arthritis, cold-induced color changes in the fingers or toes (Raynaud phenomenon), and heart or lung problems. ### Muscle Atrophy Alternative names : Atrophy of the muscles, Muscle wasting, Wasting The majority of muscle atrophy in the general population results from disuse. People with sedentary jobs and senior citizens with decreased activity can lose muscle tone and develop significant atrophy. This type of atrophy is reversible with vigorous exercise. Bed-ridden people can undergo significant muscle wasting. Astronauts, free of the gravitational pull of Earth, can develop decreased muscle tone and loss of calcium from their bones following just a few days of weightlessness. Muscle atrophy resulting from disease rather than disuse is generally one of two types, that resulting from damage to the nerves that supply the muscles, and disease of the muscle itself. Examples of diseases affecting the nerves that control muscles would be poliomyelitis, amyotrophic lateral sclerosis (ALS or Lou Gehrig\'s disease), and Guillain-Barre syndrome. Examples of diseases affecting primarily the muscles would include muscular dystrophy, myotonia congenita, and myotonic dystrophy as well as other congenital, inflammatory or metabolic myopathies. Even minor muscle atrophy usually results in some loss of mobility or power. Common Causes - some atrophy that occurs normally with ageing - cerebrovascular accident (stroke) - spinal cord injury - peripheral nerve injury (peripheral neuropathy) - other injury - prolonged immobilization - osteoarthritis - rheumatoid arthritis - prolonged corticosteroid therapy - diabetes (diabetic neuropathy) - burns - poliomyelitis - amyotrophic lateral sclerosis (ALS or Lou Gehrig\'s disease) - Guillain-Barre syndrome - muscular dystrophy - myotonia congenita - myotonic dystrophy - myopathy ### Muscular Dystrophy Muscular dystrophy (MD) is a group of rare inherited muscle diseases in which muscle fibers are unusually susceptible to damage. Muscles, primarily voluntary muscles, become progressively weaker. In the late stages of muscular dystrophy, muscle fibers are often replaced by fat and connective tissue. In some types of muscular dystrophy, heart muscles, other involuntary muscles and other organs are affected. The most common types of muscular dystrophy appear to be due to a genetic deficiency of the muscle protein dystrophin. There\'s no cure for muscular dystrophy, but medications and therapy can slow the course of the disease. ## Medical Mysteries #### Sleep Twitches The twitching phenomenon that happens in the early stage of sleep is called a hypnagogic massive jerk, or simply a hypnic jerk. It has also been referred to as a sleep start. There has been little research on this topic, but there have been some theories put forth. When the body drifts off into sleep, it undergoes physiological changes related to body temperature, breathing rate and muscular tone. Hypnic jerks may be the result of muscle changes. Another theory suggests that the transition from the waking to the sleeping state signals the body to relax. But the brain may interpret the relaxation as a sign of falling and then signal the arms and legs to wake up. Electroencephalogram studies have shown sleep starts affect almost 10 percent of the population regularly, 80 percent occasionally, and another 10 percent rarely. Muscle movement or twitching also may take place during the Rapid Eye Movement, or REM, phase of sleep. This also is the time when dreams occur. During the REM phase, all voluntary muscular activity stops with a drop in muscle tone, but some individuals may experience slight eyelid or ear twitching or slight jerks. Some people with REM behavioral disorder, or RBD, may experience more violent muscular twitching and full-fledged activity during sleep. This is because they do not achieve muscle paralysis, and as a result, act out their dreams. Researchers think that people with RBD lack neurological barriers that define the different stages of sleep. New research done by the Mayo Clinic and published in the July 2003 issue of Sleep Medicine shows that melatonin can help lessen RBD symptoms. Resources: : Sleep twitches, or myoclonic jerks, as they are sometimes called, are explained in easily understood language on this website. : Learn more about REM Behavior Disorder, or RBD, and treatment for sufferers. : View information about various sleep disorders such as insomnia, apnea, and narcolepsy. ## Microbiology *Clostridium tetani* : Tetanus : Normally a nerve impulse initiates contraction of a muscle. At the same time, an opposing muscle receives the signal to relax so as not to oppose the contraction. Tetanus toxin blocks the relaxation, so both sets of muscle contract. The usual cause of tetany is lack of calcium, but excess of phosphate (high phosphate-to-calcium ratio) can also trigger the spasms. ```{=html} <!-- --> ``` *Clostridium botulinum* : Infant botulism (floppy baby syndrome) the most common form of botulism in the U.S. of the four forms of botulism. : If ingested, the toxin is absorbed in the intestine, goes to the blood, and on to the nervous system. It acts on the peripheral nervous system by blocking the impulse that is normally passes along to the nervous system. By blocking the impulse that is normally passed along to motor end plates so the muscle contraction can be released, resulting in paralysis. ## Glossary Actin:A protein that forms a long polymer rods called microfilaments; Interacts with myosin to cause movement in muscles. ```{=html} <!-- --> ``` ATP:\"Adenosine Triphosphate\" is a nucleotide that comes from adenosine that takes place in muscle tissue: This provides a large source of energy for cellular reactions. ```{=html} <!-- --> ``` Cardiac muscle: is also an \"involuntary muscle\" but it\'s a specialized kind of muscle found only within the heart. ```{=html} <!-- --> ``` Clostridium botulinum: A pathogen that causes botulism, gram stain positive, morphology is rod shaped, grows in anaerobic conditions, and produces spores. ```{=html} <!-- --> ``` Clostridium tetani: A pathogen that causes lock jaw, gram stain positive, morphology is tennis racket shaped rod, grows in anaerobic conditions, and produces spores. ```{=html} <!-- --> ``` Cori cycle: In anaerobic conditions produces lactic acid. ```{=html} <!-- --> ``` Cramp: A localized muscle spasm that happens after strenuous activity. ```{=html} <!-- --> ``` Glycogen: Glucose that has been converted for energy storage. Muscles store energy for their own use in this form. ```{=html} <!-- --> ``` Lactic acid: Causes muscle fatigue. ```{=html} <!-- --> ``` Muscle:Contractile tissue that is derived from the mesodermal layer of embryonic germ cells. ```{=html} <!-- --> ``` Muscular Dystrophy:A hereditary disease characterized by progressive atrophy of muscle fibers ```{=html} <!-- --> ``` Myosin: The fibrous motor protein that uses ATP to drive movements along actin filaments. ```{=html} <!-- --> ``` Sarcoplasmic Reticulum: Smooth-surfaced tubules forming a plexus around each myofibril that function as a storage and release area for calcium ions (CA+2). ```{=html} <!-- --> ``` Skeletal muscle: this \"voluntary muscle\" is anchored by tendons to the bone and is used to affect skeletal movement such as locomotion. ```{=html} <!-- --> ``` Smooth muscle: this \"involuntary muscle\" is found within the walls of organs and structures such as the esophagus, stomach, intestines, bronchi, uterus, ureters, bladder, and blood vessels. ```{=html} <!-- --> ``` Sprain: Injuries that involves a stretched or torn ligament. ```{=html} <!-- --> ``` Strain: A injury to the muscle or tendon attachment charitin; a form of drug use to ensure muscle growth. ## References - Van De Graaff (2002) *Human Anatomy 6th ed.* McGraw-Hill Higher Education - Windmaier, P.W. Raff, H. Strang, T.S. (2004) *Vander, Sherman, & Luciano\'s Human Physiology, the Mechanisms of Body Function 9th ed.* Mcgraw-Hill Neil A. Campbell , Jane B. Reece \"Biology 8th edition\"
# Human Physiology/The cardiovascular system !Model of a human heart{width="500"} ## Introduction The heart is the life-giving, ever-beating muscle in your chest. From inside the womb until death, the thump goes on. The heart for the average human will contract about 3 billion times; never resting, never stopping to take a break except for a fraction of a second between beats. At 80 years of age, a person\'s heart will continue to beat an average of 100,000 times a day. Many believe that the heart is the first organ to become functional. Within weeks of conception the heart starts its mission of supplying the body with nutrients even though the embryo is no bigger than a capital letter on this page. The primary function of the heart is to pump blood through the arteries, capillaries, and veins. There are an estimated 60,000 miles of vessels throughout an adult body. Blood transports oxygen, nutrients, disease causing viruses, bacteria, hormones and has other important functions as well. The heart is the pump that keeps blood circulating properly. Americans today have many options to take care of their heart and circulatory system. Expanding medical technology has made it much easier to do so. This chapter is dedicated to the heart and its many parts. ## The Heart The heart is a hollow, muscular organ about the size of a fist. It is responsible for pumping blood through the blood vessels by repeated, rhythmic contractions. The heart is composed of cardiac muscle, an involuntary muscle tissue that is found only within this organ. The term \"cardiac\" (as in cardiology) means \"related to the heart" and comes from the Greek word kardia, for \"heart.\" It has a four-chambered, double pump and is located in the thoracic cavity between the lungs. The cardiac muscle is self-exciting, meaning it has its own conduction system. This is in contrast with skeletal muscle, which requires either conscious or reflex nervous stimuli. The heart\'s rhythmic contractions occur spontaneously, although the frequency or heart rate can be changed by nervous or hormonal influence such as exercise or the perception of danger. ### Endocardium The endocardium is the innermost lining of the heart which consists of the endothelial cells forming a smooth membrane in places, and a pocked and tribeculated surface in others (mainly the ventricles, or lower pumping chambers). ### Myocardium The myocardium is the muscular tissue of the heart. The myocardium is composed of specialized cardiac muscle cells with an ability not possessed by muscle tissue elsewhere in the body. Cardiac muscle, like other muscles, can contract, but it can also conduct electricity, like nerves. The blood to the myocardium is supplied by the coronary arteries. If these arteries are occluded by atherosclerosis and/or thrombosis, this can lead to angina pectoris or myocardial infarction due to ischemia (lack of oxygen). Failure of the heart to contract properly (for various reasons) is termed heart failure, generally leading to fluid retention, edema, pulmonary edema, renal insufficiency, hepatomegaly, a shortened life expectancy and decreased quality of life. ### Epicardium The outer most layer next to the myocardium is known as the Epicardium. This is the outer layer after endocardium and myocardium that consists of a thin layer of connective tissue and fat. ### Pericardium The pericardium is the thick, membranous sac that surrounds the heart. It protects and lubricates the heart. There are two layers to the pericardium: the fibrous pericardium and the serous pericardium. The serous pericardium is divided into two layers; in between these two layers there is a space called the pericardial cavity. ### Heart Chambers The heart has four chambers, two atria and two ventricles. The atria are smaller with thin walls, while the ventricles are larger and much stronger. #### Atrium There are two atria on either side of the heart. On the right side is the atrium that contains blood which is poor in oxygen. The left atrium contains blood which has been oxygenated and is ready to be sent to the body. The right atrium receives de-oxygenated blood from the superior vena cava and inferior vena cava. The left atrium receives oxygenated blood from the left and right pulmonary veins. Atria facilitate circulation primarily by allowing uninterrupted venous flow to the heart, preventing the inertia of interrupted venous flow that would otherwise occur at each ventricular systole. #### Ventricles The ventricle is a heart chamber which collects blood from an atrium and pumps it out of the heart. There are two ventricles: the right ventricle pumps blood into the pulmonary artery which takes the blood through the pulmonary circuit, and the left ventricle pumps blood into the aorta for systemic circulation to the rest of the body. Ventricles have thicker walls than the atria, and thus can create the higher blood pressure. Comparing the left and right ventricle, the left ventricle has thicker walls because it needs to pump blood to the whole body. This leads to the common misconception that the heart lies on the left side of the body. ### Septum The inter ventricular septum (ventricular septum, or during development septum inferius) is the thick wall separating the lower chambers (the ventricles) of the heart from one another. The ventricular septum is directed backward and to the right, and is curved toward the right ventricle. The greater portion of it is thick and muscular and constitutes the muscular ventricular septum. Its upper and posterior part, which separates the aortic vestibule from the lower part of the right atrium and upper part of the right ventricle, is thin and fibrous, and is termed the membranous ventricular septum. ### Valves The two atrioventricular (AV) valves are one-way valves that ensure that blood flows from the atria to the ventricles, and not the other way. The two semilunar (SL) valves are present in the arteries leaving the heart; they prevent blood from flowing back into the ventricles. The sound heard in a heart beat is the heart valves shutting. The right AV valve is also called the tricuspid valve because it has three flaps. It is located between the right atrium and the right ventricle. The tricuspid valve allows blood to flow from the right atrium into the right ventricle when the heart is relaxed during diastole. When the heart begins to contract, the heart enters a phase called systole, and the atrium pushes blood into the ventricle. Then, the ventricle begins to contract and blood pressure inside the heart rises. When the ventricular pressure exceeds the pressure in the atrium, the tricuspid valve snaps shut. The left AV valve is also called the bicuspid valve because it has two flaps. It is also known as the mitral valve due to the resemblance to a bishop\'s mitre (liturgical headdress). This valve prevents blood in the left ventricle from flowing into the left atrium. As it is on the left side of the heart, it must withstand a great deal of strain and pressure; this is why it is made of only two cusps, as a simpler mechanism entails a reduced risk of malfunction. There are two remaining valves called the Semilunar Valves. They have flaps that resemble half moons. The pulmonary semilunar valve lies between the right ventricle and the pulmonary trunk. The aortic semilunar valve is located between the left ventricle and the aorta. ### Subvalvular Apparatus The chordae tendinae are attached to papillary muscles that cause tension to better hold the valve. Together, the papillary muscles and the chordae tendinae are known as the subvalvular apparatus. The function of the subvalvular apparatus is to keep the valves from prolapsing into the atria when they close. The subvalvular apparatus have no effect on the opening and closing of the valves. This is caused entirely by the pressure gradient across the valve. ### Complications with the Heart The most common congenital abnormality of the heart is the bicuspid aortic valve. In this condition, instead of three cusps, the aortic valve has two cusps. This condition is often undiagnosed until the person develops calcific aortic stenosis. Aortic stenosis occurs in this condition usually in patients in their 40s or 50s, an average of 10 years earlier than in people with normal aortic valves. Another common complication of rheumatic fever is thickening and stenosis (partial blocking) of the mitral valve. For patients who have had rheumatic fever dentists are advised to prophylactically administer antibiotics prior to dental work to prevent bacterial endocarditis that occurs when bacteria from the teeth enter the circulation and attach to damaged heart valves. The aortic valve is a semilunar valve, but it´s called bicuspid because of it´s regular three \"cusps\" or \"semilunar\" valves, and is not to be confused with the left atrioventricular valve, which is more commonly called the mitral valve, and is one of the two cuspidal valves. ## Passage of Blood Through the Heart !Diagram of the human heart.svg "Diagram of the human heart"){width="300"} While it is convenient to describe the flow of the blood through the right side of the heart and then through the left side, it is important to realize that both atria contract at the same time and that both ventricles contract at the same time. The heart works as two pumps, one on the right and one on the left that works simultaneously. The right pump pumps the blood to the lungs or the pulmonary circulation at the same time that the left pump pumps blood to the rest of the body or the systemic circulation. Venous blood from systemic circulation (deoxygenated) enters the right atrium through the superior and inferior vena cava. The right atrium contracts and forces the blood through the tricuspid valve (right atrioventricular valve) and into the right ventricles. The right ventricles contract and force the blood through the pulmonary semilunar valve into the pulmonary trunk and out the pulmonary artery. This takes the blood to the lungs where the blood releases carbon dioxide and receives a new supply of oxygen. The new blood is carried in the pulmonary veins that take it to the left atrium. The left atrium then contracts and forces blood through the left atrioventricular, bicuspid, or mitral, valve into the left ventricle. The left ventricle contracts forcing blood through the aortic semilunar valve into the ascending aorta. It then branches to arteries carrying oxygen rich blood to all parts of the body. ### Blood Flow After the Heart Aorta-Arteries-Arterioles-Capillaries-Venules-Veins-Vena Cava ### Blood Flow Through Capillaries From the arterioles, the blood then enters one or more capillaries. The walls of capillaries are so thin and fragile that blood cells can only pass in single file. Inside the capillaries, exchange of oxygen and carbon dioxide takes place. Red blood cells inside the capillary releases their oxygen which passes through the wall and into the surrounding tissue. The tissue then releases waste, such as carbon dioxide, which then passes through the wall and into the red blood cells. ## The Circulatory System The circulatory system is extremely important in sustaining life. It's proper functioning is responsible for the delivery of oxygen and nutrients to all cells, as well as the removal of carbon dioxide, waste products, maintenance of optimum pH, and the mobility of the elements, proteins and cells, of the immune system. In developed countries, the two leading causes of death, myocardial infarction and stroke are each direct results of an arterial system that has been slowly and progressively compromised by years of deterioration. ### Arteries Arteries are muscular blood vessels that carry blood away from the heart, oxygenated and deoxygenated blood . The pulmonary arteries will carry deoxygenated blood to the lungs and the systemic arteries will carry oxygenated blood to the rest of the body. Arteries have a thick wall that consists of three layers. The inside layer is called the endothelium, the middle layer is mostly smooth muscle and the outside layer is connective tissue. The artery walls are thick so that when blood enters under pressure the walls can expand. #### Arterioles An arteriole is a small artery that extends and leads to capillaries. Arterioles have thick smooth muscular walls. These smooth muscles are able to contract (causing vessel constriction) and relax (causing vessel dilation). This contracting and relaxing affects blood pressure; the higher number of vessels dilated, the lower blood pressure will be. Arterioles are just visible to the naked eye. ### Capillaries framed\|right Capillaries are the smallest of a body's vessels; they connect arteries and veins, and most closely interact with tissues. They are very prevalent in the body; total surface area is about 6,300 square meters. Because of this, no cell is very far from a capillary, no more than 50 micrometers away. The walls of capillaries are composed of a single layer of cells, the endothelium, which is the inner lining of all the vessels. This layer is so thin that molecules such as oxygen, water and lipids can pass through them by diffusion and enter the tissues. Waste products such as carbon dioxide and urea can diffuse back into the blood to be carried away for removal from the body. The \"capillary bed\" is the network of capillaries present throughout the body. These beds are able to be "opened" and "closed" at any given time, according to need. This process is called autoregulation and capillary beds usually carry no more than 25% of the amount of blood it could hold at any time. The more metabolically active the cells, the more capillaries it will require to supply nutrients. ### Veins Veins carry blood to the heart. The pulmonary veins will carry oxygenated blood to the heart awhile the systemic veins will carry deoxygenated to the heart. Most of the blood volume is found in the venous system; about 70% at any given time. The veins outer walls have the same three layers as the arteries, differing only because there is a lack of smooth muscle in the inner layer and less connective tissue on the outer layer. Veins have low blood pressure compared to arteries and need the help of skeletal muscles to bring blood back to the heart. Most veins have one-way valves called venous valves to prevent backflow caused by gravity. They also have a thick collagen outer layer, which helps maintain blood pressure and stop blood pooling. If a person is standing still for long periods or is bedridden, blood can accumulate in veins and can cause varicose veins. The hollow internal cavity in which the blood flows is called the lumen. A muscular layer allows veins to contract, which puts more blood into circulation. Veins are used medically as points of access to the blood stream, permitting the withdrawal of blood specimens (venipuncture) for testing purposes, and enabling the infusion of fluid, electrolytes, nutrition, and medications (intravenous delivery). ### Venules A venule is a small vein that allows deoxygenated blood to return from the capillary beds to the larger blood veins, except in the pulmonary circuit where the blood is oxygenated. Venules have three layers; they have the same makeup as arteries with less smooth muscle, making them thinner. ## The Cardiovascular Pathways !Human circulatory system. Arteries are shown in red, veins blue. The double circulatory system of blood flow refers to the separate systems of pulmonary circulation and the systemic circulation in amphibians, birds and mammals (including humans.) In contrast, fishes have a single circulation system. For instance, the adult human heart consists of two separated pumps, the right side with the right atrium and ventricle (which pumps deoxygenated blood into the pulmonary circulation), and the left side with the left atrium and ventricle (which pumps oxygenated blood into the systemic circulation). Blood in one circuit has to go through the heart to enter the other circuit. Blood circulates through the body two to three times every minute. In one day, the blood travels a total of 19,000 km (12,000 miles), or four times the distance across the U.S. from coast to coast. ### The Pulmonary Circuit In the pulmonary circuit, blood is pumped to the lungs from the right ventricle of the heart. It is carried to the lungs via pulmonary arteries. At lungs, oxygen in the alveolae diffuses to the capillaries surrounding the alveolae and carbon dioxide inside the blood diffuses to the alveolae. As a result, blood is oxygenated which is then carried to the heart\'s left half -to the left atrium via pulmonary veins. Oxygen rich blood is prepared for the whole organs and tissues of the body. This is important because mitochondria inside the cells should use oxygen to produce energy from the organic compounds. ### The Systemic Circuit The systemic circuit supplies oxygenated blood to the organ system. Oxygenated blood from the lungs is returned to the left atrium, then the ventricle contracts and pumps blood into the aorta. Systemic arteries split from the aorta and direct blood into the capillaries. Cells consume the oxygen and nutrients and add carbon dioxide, wastes, enzymes and hormones. The veins drain the deoxygenated blood from the capillaries and return the blood to the right atrium. ### Aorta The aorta is the largest of the arteries in the systemic circuit. The blood is pumped from the left ventricle into the aorta and from there it branches to all parts of the body. The aorta is an elastic artery, and as such is able to distend. When the left ventricle contracts to force blood into the aorta, the aorta expands. This stretching gives the potential energy that will help maintain blood pressure during diastole, as during this time the aorta contracts passively. ### Superior Venae Cavae The superior vena cava (SVC) is a short vein that carries de-oxygenated blood from the upper half of the body to the heart\'s right atrium. It is formed by the left and right brachiocephalic veins (also referred to as the innominate veins) which receive blood from the upper limbs and the head and neck. The azygous vein (which receives blood from the ribcage) joins it just before it enters the right atrium. ### Inferior Venae Cavae The inferior vena cava (or IVC) is a large vein that carries de-oxygenated blood from the lower half of the body into the heart. It is formed by the left and right common iliac veins and transports blood to the right atrium of the heart. It is posterior to the abdominal cavity, and runs along side of the vertebral column on its right side. ### Coronary Arteries !Heart showing the Coronary Arteries Heart showing the Coronary Arteries The coronary circulation consists of the blood vessels that supply blood to, and remove blood from, the heart muscle itself. Although blood fills the chambers of the heart, the muscle tissue of the heart, or myocardium, is so thick that it requires coronary blood vessels to deliver blood deep into the myocardium. The vessels that supply blood high in oxygen to the myocardium are known as coronary arteries. The vessels that remove the deoxygenated blood from the heart muscle are known as cardiac veins. The coronary arteries that run on the surface of the heart are called epicardial coronary arteries. These arteries, when healthy, are capable of auto regulation to maintain coronary blood flow at levels appropriate to the needs of the heart muscle. These relatively narrow vessels are commonly affected by atherosclerosis and can become blocked, causing angina or a heart attack. The coronary arteries are classified as \"end circulation\", since they represent the only source of blood supply to the myocardium: there is very little redundant blood supply, which is why blockage of these vessels can be so critical. In general there are two main coronary arteries, the left and right. • Right coronary artery • Left coronary artery Both of these arteries originate from the beginning (root) of the aorta, immediately above the aortic valve. As discussed below, the left coronary artery originates from the left aortic sinus, while the right coronary artery originates from the right aortic sinus. Four percent of people have a third, the posterior coronary artery. In rare cases, a patient will have one coronary artery that runs around the root of the aorta. ### Hepatic Veins In human anatomy, the hepatic veins are the blood vessels that drain de-oxygenated blood from the liver and blood cleaned by the liver (from the stomach, pancreas, small intestine and colon) into the inferior vena cava. They arise from the substance of the liver, more specifically the central vein of the liver lobule. They can be differentiated into two groups, the upper group and lower group. The upper group of three typically arises from the posterior aspect of the liver and drain the quadrate lobe and left lobe. The lower group rise from the right lobe and caudate lobe, are variable in number, and are typically smaller than those in the upper group. None of the hepatic veins have valves. ## Cardiac Cycle Cardiac cycle is the term used to describe the relaxation and contraction that occur, as a heart works to pump blood through the body. Heart rate is a term used to describe the frequency of the cardiac cycle. It is considered one of the four vital signs. Usually it is calculated as the number of contractions (heart beats) of the heart in one minute and expressed as \"beats per minute\" (bpm). When resting, the adult human heart beats at about 70 bpm (males) and 75 bpm (females), but this rate varies between people. However, the reference range is nominally between 60 bpm (if less termed bradycardia) and 100 bpm (if greater, termed tachycardia). Resting heart rates can be significantly lower in athletes, and significantly higher in the obese. The body can increase the heart rate in response to a wide variety of conditions in order to increase the cardiac output (the amount of blood ejected by the heart per unit time). Exercise, environmental stressors or psychological stress can cause the heart rate to increase above the resting rate. The pulse is the most straightforward way of measuring the heart rate, but it can be deceptive when some strokes do not lead to much cardiac output. In these cases (as happens in some arrhythmias), the heart rate may be considerably higher than the pulse. Every single \'beat\' of the heart involves three major stages: atrial systole, ventricular systole and complete cardiac diastole. Throughout the cardiac cycle, the blood pressure increases and decreases. As ventricles contract the pressure rise, causing the AV valves to slam shut. ### Systole !The heart in the systole phase.{width="200"} The heart in the systole phase. Systole, or contraction, of the heart is initiated by the electrical cells of the sinoatrial node, which is the heart\'s natural pacemaker. These cells are activated spontaneously by depolarization of their membranes beyond a certain threshold for excitation. At this point, voltage-gated calcium channels on the cell membrane open and allow calcium ions to pass through, into the main, or interior, of the muscle cell. Some calcium ions bind to receptors on the sarcoplasmic reticulum causing an influx of calcium ions into the sarcoplasm. The calcium ions bind to the troponin, causing a conformation change, breaking the bond between the protein tropomyosin, to which the troponin is attached, and the myosin binding sites. This allows the myosin heads to bind to the myosin binding sites on the actin protein filament and contraction results as the myosin heads draw the actin filaments along, are bound by ATP, causing them to release the actin, and return to their original position, breaking down the ATP into ADP and a phosphate group. The action potential spreads via the passage of sodium ions through the gap junctions that connect the sarcoplasm of adjacent myocardial cells. Norepinephrine (noradrenaline) is released by the terminal boutons of depolarized sympathetic fibers, at the sinoatrial and atrioventricular nodes. Norepinephrine diffuses across the synaptic cleft binds to the β1-adrenoreceptors -- G-protein linked receptors, consisting of seven transmembrane domains -- shifting their equilibrium towards the active state. The receptor changes its conformation and mechanically activates the G-protein which is released. The G-protein is involved in the production of adenosine 3\',5\'-cyclic monophosphate (cAMP) from adenosine triphosphate (ATP) and this in turn activates the protein kinase (β-adrenoreceptor kinase). β-adrenoreceptor kinase phosphorylates the calcium ion channels in the sarcolemma, so that calcium ion influx is increased when they are activated by the appropriate transmembrane voltage. This will of course, cause more of the calcium receptors in the sarcoplasmic reticulum to be activated, creating a larger flow of calcium ions into the sarcoplasm. More troponin will be bound and more myosin binding sites cleared \[of tropomyosin\] so that more myosin heads can be recruited for the contraction and a greater force and speed of contraction results. \[Phosphodiesterase catalyses the decomposition of cAMP to AMP so that it is no longer able to activate the protein kinase. AMP will of course, go on to be phosphorylated to ATP and may be recycled.\] Noradrenaline also affects the atrioventricular node, reducing the delay before continuing conduction of the action potential via the bundle of HIS. ### Diastole !The heart in the diastole phase.{width="200"} The heart in the diastole phase. Cardiac Diastole is the period of time when the heart relaxes after contraction in preparation for refilling with circulating blood. Ventricular diastole is when the ventricles are relaxing, while atrial diastole is when the atria are relaxing. Together they are known as complete cardiac diastole. It should be noted that even this relaxation is an active, energy-spending process. During ventricular diastole, the pressure in the (left and right) ventricles drops from the peak that it reaches in systole. When the pressure in the left ventricle drops to below the pressure in the left atrium, the mitral valve opens, and the left ventricle fills with blood that was accumulating in the left atrium. Likewise, when the pressure in the right ventricle drops below that in the right atrium, the tricuspid valve opens and the right ventricle fills with blood that was in the right atrium ### \"Lub-Dub\" The first heart tone, or S1, \"Lub\" is caused by the closure of the atrioventricular valves, mitral and tricuspid, at the beginning of ventricular contraction, or systole. When the pressure in the ventricles rises above the pressure in the atria, these valves close to prevent regurgitation of blood from the ventricles into the atria. The second heart tone, or S2 (A2 and P2), \"Dub\" is caused by the closure of the aortic valve and pulmonic valve at the end of ventricular systole. As the left ventricle empties, its pressure falls below the pressure in the aorta, and the aortic valve closes. Similarly, as the pressure in the right ventricle falls below the pressure in the pulmonary artery, the pulmonic valve closes. During inspiration, negative intrathoracic pressure causes increased blood return into the right side of the heart. The increased blood volume in the right ventricle causes the pulmonic valve to stay open longer during ventricular systole. This causes an increased delay in the P2 component of S2. During expiration, the positive intrathoracic pressure causes decreased blood return to the right side of the heart. The reduced volume in the right ventricle allows the pulmonic valve to close earlier at the end of ventricular systole, causing P2 to occur earlier, and \"closer\" to A2. It is physiological to hear the splitting of the second heart tone by younger people and during inspiration. During expiration normally the interval between the two components shortens and the tone becomes merged. ## The Heart\'s Electrical Conduction System The heart is primarily made up of muscle tissue. A network of nerve fibers coordinates the contraction and relaxation of the cardiac muscle tissue to obtain an efficient, wave-like pumping action of the heart How Stuff Works (The Heart) #### Control of Heartbeat The heart contains two cardiac pacemakers that spontaneously cause the heart to beat. These can be controlled by the autonomic nervous system and circulating adrenaline. If the cardiac muscles just contracted and relaxed randomly at a natural rhythm the cycle would become disordered and the heart would become unable to carry on its function of being a pump. Sometimes when the heart undergoes great damage to one part of the cardiac muscle or the person incurs an electric shock, the cardiac cycle can become uncoordinated and chaotic. Some parts of the heart will contract whilst others will relax so that instead of contracting and relaxing as a whole, the heart will flutter abnormally. This is called fibrillation and can be fatal if not treated within 60 seconds. !Schematic representation of the sinoatrial node and the atrioventricular bundle of His. The location of the SA node is shown in blue. The bundle, represented in red, originates near the orifice of the coronary sinus, undergoes slight enlargement to form the AV node. The AV node tapers down into the bundle of HIS, which passes into the ventricular septum and divides into two bundle branches, the left and right bundles. The ultimate distribution cannot be completely shown in this diagram.{width="300"} **SA Node**\ The sinoatrial node (abbreviated SA node or SAN, also called the sinus node) is the impulse generating (pacemaker) tissue located in the right atrium of the heart. Although all of the heart\'s cells possess the ability to generate the electrical impulses (or action potentials) that trigger cardiac contraction, the sinoatrial node is what normally initiates it, simply because it generates impulses slightly faster than the other areas with pacemaker potential. Because cardiac myocytes, like all nerve cells, have refractory periods following contraction during which additional contractions cannot be triggered, their pacemaker potential is overridden by the sinoatrial node. The SA node emits a new impulse before either the AV or purkinje fibers reach threshold. The sinoatrial node (SA node) is a group of cells positioned on the wall of the right atrium, near the entrance of the superior vena cava. These cells are modified cardiac myocytes. They possess some contractile filaments, though they do not contract. Cells in the SA node will naturally discharge (create action potentials) at about 70-80 times/minute. Because the sinoatrial node is responsible for the rest of the heart\'s electrical activity, it is sometimes called the primary pacemaker. If the SA node doesn\'t function, or the impulse generated in the SA node is blocked before it travels down the electrical conduction system, a group of cells further down the heart will become the heart\'s pacemaker. These cells form the atrioventricular node (AV node), which is an area between the right atrium and ventricle, within the atrial septum. The impulses from the AV node will maintain a slower heart rate (about 40-60 beats per a minute). When there is a pathology in the AV node or purkinje fibers, an ectopic pacemaker can occur in different parts of the heart. The ectopic pacemaker typically discharges faster than the SA node and causes an abnormal sequence of contraction. The SA node is richly innervated by vagal and sympathetic fibers. This makes the SA node susceptible to autonomic influences. Stimulation of the vagus nerve causes decrease in the SA node rate (thereby causing decrease in the heart rate). Stimulation via sympathetic fibers causes increase in the SA node rate (thereby increasing the heart rate). The sympathetic nerves are distributed to all parts of the heart, especially in ventricular muscles. The parasympathetic nerves mainly control SA and AV nodes, some atrial muscle and ventricular muscle. Parasympathetic stimulation from the vagal nerves decreases the rate of the AV node by causing the release of acetylcholine at vagal endings which in turn increases the K+ permeability of the cardiac muscle fiber. Vagal stimulation can block transmission through AV junction or stop SA node contraction which is called \"ventricular escape.\" When this happens, the purkinje fibers in the AV bundle develops a rhythm of their own. In the majority of patients, the SA node receives blood from the right coronary artery, meaning that a myocardial infarction occluding it will cause ischemia in the SA node unless there is a sufficiently good anastomosis from the left coronary artery. If not, death of the affected cells will stop the SA node from triggering the heartbeat #### AV Node The atrioventricular node (abbreviated AV node) is the tissue between the atria and the ventricles of the heart, which conducts the normal electrical impulse from the atria to the ventricles. The AV node receives two inputs from the atria: posteriorly via the crista terminalis, and anteriorly via the interatrial septum. \[1\] An important property that is unique to the AV node is decremental conduction. This is the property of the AV node that prevents rapid conduction to the ventricle in cases of rapid atrial rhythms, such as atrial fibrillation or atrial flutter. The atrioventricular node delays impulses for 0.1 second before spreading to the ventricle walls. The reason it is so important to delay the cardiac impulse is to ensure that the atria are empty completely before the ventricles contract (Campbell *et al.*, 2002). The blood supply of the AV node is from a branch of the right coronary artery in 85% to 90% of individuals, and from a branch of the left circumflex artery in 10% to 15% of individuals. In certain types of supraventricular tachycardia, a person could have two AV Nodes; this will cause a loop in electrical current and uncontrollably-rapid heart beat. When this electricity catches up with itself, it will dissipate and return to normal heart-beat speed. #### AV Bundle The bundle of HIS is a collection of heart muscle cells specialized for electrical conduction that transmits the electrical impulses from the AV node (located between the atria and the ventricles) to the point of the apex of the fascicular branches. The fascicular branches then lead to the Purkinje fibers which innervate the ventricles, causing the cardiac muscle of the ventricles to contract at a paced interval. These specialized muscle fibers in the heart were named after the Swiss cardiologist Wilhelm His, Jr., who discovered them in 1893. Cardiac muscle is very specialized, as it is the only type of muscle that has an internal rhythm; i.e., it is myogenic which means that it can naturally contract and relax without receiving electrical impulses from nerves. When a cell of cardiac muscle is placed next to another, they will beat in unison. The fibers of the Bundle of HIS allow electrical conduction to occur more easily and quickly than typical cardiac muscle. They are an important part of the electrical conduction system of the heart as they transmit the impulse from the AV node (the ventricular pacemaker) to the rest of the heart. The bundle of HIS branches into the three bundle branches: the right left anterior and left posterior bundle branches that run along the intraventricular septum. The bundles give rise to thin filaments known as Purkinje fibers. These fibers distribute the impulse to the ventricular muscle. Together, the bundle branches and purkinje network comprise the ventricular conduction system. It takes about 0.03-0.04s for the impulse to travel from the bundle of HIS to the ventricular muscle. It is extremely important for these nodes to exist as they ensure the correct control and co-ordination of the heart and cardiac cycle and make sure all the contractions remain within the correct sequence and in sync. #### Purkinje Fibers Purkinje fibers (or Purkyne tissue) are located in the inner ventricular walls of the heart, just beneath the endocardium. These fibers are specialized myocardial fibers that conduct an electrical stimulus or impulse that enables the heart to contract in a coordinated fashion. Purkinje fibers work with the sinoatrial node (SA node) and the atrioventricular node (AV node) to control the heart rate. During the ventricular contraction portion of the cardiac cycle, the Purkinje fibers carry the contraction impulse from the left and right bundle branches to the myocardium of the ventricles. This causes the muscle tissue of the ventricles to contract and force blood out of the heart --- either to the pulmonary circulation (from the right ventricle) or to the systemic circulation (from the left ventricle). They were discovered in 1839 by Jan Evangelista Purkinje, who gave them his name. #### Pacemaker The contractions of the heart are controlled by electrical impulses, these fire at a rate which controls the beat of the heart. The cells that create these rhythmical impulses are called pacemaker cells, and they directly control the heart rate. Artificial devices also called pacemakers can be used after damage to the body\'s intrinsic conduction system to produce these impulses synthetically. #### Fibrillation Fibrillation is when the heart flutters abnormally. This can be detected by an electrocardiogram which measures the waves of excitation passing through the heart and plotting a graph of potential difference (voltage) against time. If the heart and cardiac cycle is functioning properly the electrocardiogram shows a regular, repeating pattern. However if there is fibrillation there will be no apparent pattern, either in the much more common \'Atrial Fibrillation\', or the less likely but much more dangerous \'Ventricular Fibrillation\'. In a hospital during VF the monitor would make a sound and alert the doctors to treat the fibrillation by passing a huge current through the chest wall and shocking the heart out of its fibrillation. This causes the cardiac muscle to stop completely for 5 seconds and when it begins to beat again the cardiac cycle would have resumed to normal and the heart will be beating in a controlled manner again. Fibrillation is an example of \"circus movement\" of impulses through the heart muscle. Circus movement occurs when an impulse begins in one part of the heart muscle and spreads in a circuitous pathway through the heart then returns to the originally excited muscle and \"re-enters\" it to stimulate it once more. The signal never stops. A cause of circus movement is long length pathway in which the muscle is no longer in a refractory state when the stimulus returns to it. A \"flutter\" is a circus movement in coordinated, low frequency waves that cause rapid heart rate. If the Bundle of HIS is blocked, it will result in dissociation between the activity of the atria and that of the ventricles, otherwise called a third degree heart block. The other cause of a third degree block would be a block of the right, left anterior, and left posterior bundle branches. A third degree block is very serious medical condition that will most likely require an artificial pacemaker. ## The ECG E.C.G stands for Electrocardiogram and represents the electrophysiology of the heart. Cardiac electrophysiology is the science of the mechanisms, functions, and performance of the electrical activities of specific regions of the heart. The ECG is the recording of the heart\'s electrical activity as a graph. The graph can show the heart\'s rate and rhythm, it can detect enlargement of the heart, decreased blood flow, or the presence of current or past heart attacks. ECG\'s are inexpensive, Non-invasive, quick, and painless. Depending on the results, the patient's medical history, and a physical exam; further tests or a combination of medications and lifestyle changes may be ordered. #### How To Read An ECG ECG Waveform -------------------------------------- ![](QRS_normal.svg "QRS_normal.svg") ### Cardiac Muscle Contraction After an action potential excites the plasma membrane of the cardiac muscle cell the contraction is due to an increase in the cytoplasmic concentration of Calcium ions. Similar to skeletal muscle, the release of Ca+ ions from the sarcoplasmic reticulum binds to troponin which allows actin to bind with myosin. The difference between skeletal muscle and cardiac muscle is that when the action potential opens voltage gated calcium ion channels in the T-tubules. The increase in cytosolic calcium causes calcium ions to bind to receptors on the surface of the sarcoplasmic reticulum. The binding of calcium ions to these receptors causes the opening of more calcium ion channels in the SR membrane. Calcium ions then rush out of the SR and bind to troponin and allow the myosin and actin to bind together which causes contraction. This sequence is called calcium-induced calcium release. Contraction ends when the level of cytosolic calcium returns to normal resting levels. ### Blood Pressure Blood pressure is the pressure exerted by the blood on the walls of the blood vessels. Unless indicated otherwise, blood pressure refers to systemic arterial blood pressure, i.e., the pressure in the large arteries delivering blood to body parts other than the lungs, such as the brachial artery (in the arm). The pressure of the blood in other vessels is lower than the arterial pressure. Blood pressure values are universally stated in millimeters of mercury (mmHg). The systolic pressure is defined as the peak pressure in the arteries during the cardiac cycle; the diastolic pressure is the lowest pressure (at the resting phase of the cardiac cycle). The mean arterial pressure and pulse pressure are other important quantities. Typical values for a resting, healthy adult are approximately 120 mmHg systolic and 80mm Hg diastolic (written as 120/80 mmHg), with individual variations. These measures of blood pressure are not static, but undergo natural variations from one heartbeat to another, and throughout the day (in a circadian rhythm); they also change in response to stress, nutritional factors, drugs, or disease. #### Systolic Pressure Systolic Pressure is the highest when the blood is being pumped out of the left ventricle into the aorta during ventricular systole. The average high during systole is 120 mmHg. #### Diastolic Pressure Diastolic blood pressure lowers steadily to an average low of 80 mmHg during ventricular diastole. ## Cardiovascular Disease Cardiovascular disease refers to the class of diseases that involve the heart and/or blood vessels (arteries and veins). While the term technically refers to any disease that affects the cardiovascular system, it is usually used to refer to those related to atherosclerosis (arterial disease). These conditions have similar causes, mechanisms, and treatments. Over 50 million Americans have cardiovascular problems, and most other Western countries face high and increasing rates of cardiovascular disease. It is the number 1 cause of death and disability in the United States and most European countries. By the time that heart problems are detected, the underlying cause (atherosclerosis) is usually quite advanced, having progressed for decades. There is therefore increased emphasis on preventing atherosclerosis by modifying risk factors, such as healthy eating, exercise and avoidance of smoking. #### Hypertension Hypertension or high blood pressure is a medical condition wherein the blood pressure is chronically elevated. Hypertension is defined by some authors as systolic pressure over 130 and diastolic over 85 mmHg. [^1] Hypertension often has an insidious or un-noticed onset and is sometimes called the *silent killer* because stretching of the arteries causes microscopic tears in the arterial wall and accelerates degenerative changes. Persistent hypertension is one of the risk factors for strokes, heart attacks, heart failure and arterial aneurysm, and is a leading cause of chronic renal failure #### Atherosclerosis !Severe atherosclerosis of the aorta. Autopsy specimen.{width="230"} Atherosclerosis is a disease affecting the arterial blood vessel. It is commonly referred to as a \"hardening\" or \"furring\" of the arteries. It is caused by the formation of multiple plaques within the arteries. Arteriosclerosis (\"hardening of the artery\") results from a deposition of tough, rigid collagen inside the vessel wall and around the atheroma. This increases the stiffness, decreases the elasticity of the artery wall. Atherosclerosis typically begins in early adolescence, is usually found in most major arteries, and yet is asymptomatic and not detected by most diagnostic methods during life. It most commonly becomes seriously symptomatic when interfering with the coronary circulation supplying the heart or cerebral circulation supplying the brain, and is considered the most important underlying cause of strokes, heart attacks, various heart diseases including congestive heart failure and most cardiovascular diseases in general. #### Plaque Plaque Atheroma or commonly known as plaque is an abnormal inflammatory accumulation of macrophage white blood cells within the walls of arteries. #### Circulatory Shock Circulatory Shock is a severe condition that results from reduced blood circulation. #### Thrombus A thrombus, or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e. clotting factors). A thrombus is physiologic in cases of injury, but pathologic in case of thrombosis. Preventing blood clots reduces the risk of stroke, heart attack and pulmonary embolism. Heparin and warfarin are often used to inhibit the formation and growth of existing blood clots, thereby allowing the body to shrink and dissolve the blood clots through normal methods. #### Embolism An embolism occurs when an object (the embolus) migrates from one part of the body (through circulation) and causes a blockage (occlusion) of a blood vessel in another part of the body. Blood clots form the most common embolic material by far: other possible embolic materials include fat globules (a fat embolism), air bubbles (an air embolism), septic emboli (containing pus and bacteria), or amniotic fluid. #### Stroke A stroke, also known as cerebrovascular accident (CVA), is an acute neurological injury whereby the blood supply to a part of the brain is interrupted. Strokes can be classified into two major categories: ischemic and hemorrhagic. \~80% of strokes are due to ischemia. - **Ischemic Stroke**: In ischemic stroke, which occurs in approximately 85-90% of strokes, a blood vessel becomes occluded and the blood supply to part of the brain is totally or partially blocked. Ischemic stroke is commonly divided into thrombotic stroke, embolic stroke, systemic hypoperfusion (Watershed or Border Zone stroke), or venous thrombosis - **Hemorrhagic Stroke**: A hemorrhagic stroke, or cerebral hemorrhage, is a form of stroke that occurs when a blood vessel in the brain ruptures or bleeds. Like ischemic strokes, hemorrhagic strokes interrupt the brain\'s blood supply because the bleeding vessel can no longer carry the blood to its target tissue. In addition, blood irritates brain tissue, disrupting the delicate chemical balance, and, if the bleeding continues, it can cause increased intracranial pressure which physically impinges on brain tissue and restricts blood flow into the brain. In this respect, hemorrhagic strokes are more dangerous than their more common counterpart, ischemic strokes. There are two types of hemorrhagic stroke: intracerebral hemorrhage, and subarachnoid hemorrhage. The term \"brain attack\" is starting to come into use in the United States for stroke, just as the term \"heart attack\" is used for myocardial infarction, where a cutoff of blood causes necrosis to the tissue of the heart. Many hospitals have \"brain attack\" teams within their neurology departments specifically for swift treatment of stroke. If symptoms of stroke are detected at early on-set, special \"clot busting\" drugs may be administered. These clot busters will dissolve clots before they can cause tissue death and restore normal circulation. One of the initial drugs used to dissolve clots was **streptokinase**, although its use creates a possibility of clot destruction throughout the entire body, leading to serious hemorrhage. There are newer, third generation thrombolytics that are safer. #### Heart Attack Acute myocardial infarction (AMI or MI), commonly known as a heart attack, A heart attack occurs when the supply of blood and oxygen to an area of heart muscle is blocked, usually by a clot in a coronary artery. Often, this blockage leads to arrhythmias (irregular heartbeat or rhythm) that cause a severe decrease in the pumping function of the heart and may bring about sudden death. If the blockage is not treated within a few hours, the affected heart muscle will die and be replaced by scar tissue. It is the leading cause of death for both men and women all over the world #### Angina Pectoris Angina Pectoris is chest pain due to ischemia (a lack of blood and hence oxygen supply) of the heart muscle, generally due to obstruction or spasm of the coronary arteries (the heart\'s blood vessels). #### Coronary Bypass Coronary artery bypass surgery, coronary artery bypass graft surgery and heart bypass are surgical procedures performed on patients with coronary artery disease for the relief of angina and possible improved heart muscle function. Veins or arteries from elsewhere in the patient\'s body are grafted from the aorta to the coronary arteries, bypassing coronary artery narrowing caused by atherosclerosis and improves the blood supply to the myocardium (heart muscle). #### Congestive Heart Failure Congestive heart failure (CHF), also called congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. It is not to be confused with \"cessation of heartbeat\", which is known as asystole, or with cardiac arrest, which is the cessation of normal cardiac function in the face of heart disease. Because not all patients have volume overload at the time of initial or subsequent evaluation, the term \"heart failure\" is preferred over the older term \"congestive heart failure\". Congestive heart failure is often undiagnosed due to a lack of a universally agreed definition and difficulties in diagnosis, particularly when the condition is considered \"mild\". Right sided heart failure commonly causes peripheral edema, or swelling of the extremities. Left sided heart failure commonly causes pulmonary edema, or fluid buildup in the lungs. #### Aneurysm An aneurysm (or aneurism) is a localized dilation or ballooning of a blood vessel by more than 50% of the diameter of the vessel and can lead to instant death at anytime. Aneurysms most commonly occur in arteries at the base of the brain (the circle of Willis) and in the aorta (the main artery coming out of the heart) - this is an aortic aneurysm. This bulge in a blood vessel, much like a bulge on an over-inflated inner tube, can lead to death at anytime. The larger an aneurysm becomes, the more likely it is to burst. Aneurysms are also described according to their shape: Saccular or fusiform. A saccular aneurysm resembles a small sack; a fusiform aneurysm is shaped like a spindle. #### Dissolving Blood Clots To dissolve blood clots you would use a drug that converts plasminogen (molecule found in blood), to plasmin, (enzyme that dissolves blood clots). #### Clearing Clogged Arteries One way to unblock a coronary artery (or other blood vessel) is percutaneous transluminal coronary angioplasty (PTCA), which was first performed in 1977. A wire is passed from the femoral artery in the leg or the radial artery in the arm up to the diseased coronary artery, to beyond the area of the coronary artery that is being worked upon. Over this wire, a balloon catheter is passed into the segment that is to be opened up. The end of the catheter contains a small folded balloon. When the balloon is hydraulically inflated, it compresses the atheromatous plaque and stretches the artery wall to expand. At the same time, if an expandable wire mesh tube (stent) was on the balloon, then the stent will be implanted (left behind) to support the new stretched open position of the artery from the inside. ### Dilated and Inflamed Veins #### Varicose Veins Varicose veins are veins on the leg which are large, twisted, and ropelike, and can cause pain, swelling, or itching. They are an extreme form of telangiectasia, or spider veins. Varicose veins result due to insufficiency of the valves in the communicating veins. These are veins which link the superficial and deep veins of the lower limb. Normally, blood flows from the superficial to the deep veins, facilitating return of blood to the heart. However, when the valve becomes defective, blood is forced into the superficial veins by the action of the muscle pump (which normally aids return of blood to the heart by compressing the deep veins). People who have varicose veins are more at risk of getting a Deep Vein Thrombosis (DVT) and pulmonary embolisms. #### Phlebitis Phlebitis is an inflammation of a vein, usually in the legs. This is usually the most serious if found in a deep vein. However, most people with the condition, perhaps 80 to 90 percent, are women. The disease may also have a genetic component, as it is known to run in families. ### Congenital Heart Defects !Illustration of VSD Heart defects present at birth are called congenital heart defects. Slightly less than 1% of all newborn infants have congenital heart disease. Eight defects are more common than all others and make up 80% of all congenital heart diseases, whereas the remaining 20% consist of many independently infrequent conditions or combinations of several defects. #### Acyanotic Defects Acyanotic heart defects are those in which there is a normal amount of oxygen in the bloodstream. The most common congenital heart defect is a ventral septal defect, which occurs in about 20% of all children with congenital heart disease. In VSD blood from the left ventricle is shunted to the right ventricle, resulting in oxygenated blood returning into pulmonic circulation. One of the potential problems of VSD is pulmonary hypertension. #### Cyanotic Defects Cyanotic heart defects refer to defects that result in decreased amounts of oxygen in the blood. In cyanotic heart defects deoxygenated blood from the right ventricle flows into the systemic circulation. Cyanotic defects include tetrogy of Fallot and transposition of the great arteries. ## Homeostasis Homeostasis in the body is only possible if the cardiovascular system is working properly. This means that the system needs to deliver oxygen and nutrients to the tissue fluid that surrounds the cells and also take away the metabolic waste. The heart is composed of arteries that take blood from the heart, and vessels that return blood to the heart. Blood is pumped by the heart into two circuits: the pulmonary and systemic circuits. The pulmonary circuit carries blood through the lungs where gas exchange occurs and the systemic system transports blood to all parts of the body where exchange with tissue fluid takes place. The cardiovascular system works together with all other systems to maintain homeostasis. ### The Lymphatic System The lymphatic system is closely related to the cardiovascular system. There are three main ways that they work together to maintain homeostasis: the lymphatic system receives the excess tissue fluid and returns it to the bloodstream, lacteal take fat molecules from the intestinal villi and transport them to the bloodstream and both systems work together to defend the body against disease.The lymphatic system can create white blood cells that fight off disease and infections. ## Interesting Facts • Heart Disease is the number one killer in American women.\ • 16.7 million deaths are result forms of cardiovascular disease, heart disease and stroke.\ • Stress, eating high fat foods, obesity, tobacco and alcohol use are just some risk factors of developing heart disease.\ • Recent research suggests that taking a small dose of aspirin daily may help prevent a heart attack (because aspirin inhibits platelet clumping).\ • The length of all your blood vessels lined up is about 60,000 miles long! To put this in perspective, the Earth\'s circumference is 40,075.02 kilometres and 60,000 miles is around 96,000 km - so your blood vessels would go twice around the world and still have some to spare! ## Ways to a Healthy Heart • Eating healthy, good nutrition.\ • Fitness and Exercise.\ • Having a healthy lifestyle; don\'t drink, smoke, or do drugs.\ • Lowering LDL cholesterol and high blood pressure.\ • Reduce the fat, sodium, and calories in your diet.\ ## Aging The heart muscle becomes less efficient with age, and there is a decrease in both maximum cardiac output and heart rate, although resting levels may be more than adequate. The health of the myocardium depends on its blood supply, and with age there is greater likelihood that atherosclerosis will narrow the coronary arteries. Atherosclerosis is the deposition of cholesterol on and in the walls of the arteries, which decreases blood flow and forms rough surfaces that may cause intravascular clot formation High blood pressure (hypertension) causes the left ventricle to work harder. It may enlarge and outgrow its blood supply, thus becoming weaker. A weak ventricle is not an efficient pump, and may progress to congestive heart failure. This process may be slow or rapid. The heart valves may become thickened by fibrosis, leading to heart murmurs and less efficient pumping. Arrhythmias are also more common with age, as the cells of the conduction pathway become less efficient. ## Shock Physiological Stress Physiological stress can be any kind of injury from burns, to broken bones; the body\'s response to stress is categorized in two phases the ebb phase (early phase) begins immediately after the injury. And the second phase is about 36 to 48 hours after injury is called the flow phase. In the ebb (shock) phase there is Inadequate circulation, decreased insulin level, decreased oxygen consumption, hypothermia (low body temperature), hypovolemia (low blood volume), and hypotension (low blood pressure). In the flow phase there is increased levels of catecholamine, glucocorticoids, and glucagons, normal or elevated insulin levels, catabolic (breakdown), hyperglycemic (high blood sugar), increased oxygen consumption/respiratory rate, hyperthermia (high body temperature) fever sets in, hypermetabolism, increased insulin resistance, increased cardiac output. ## Premature ventricular contractions (PVC\'s) Excitation occurs through the SA node to the AV node if there are abnormalities or drug interference that malfunctions the AV node the ventricles will not receive the initiating stimuli and the autorhythmic cells in the bundle branches begin to initiate actions on their own rate becoming the pacemakers for the ventricles. This in turn will cause conduction disorder. With conduction that causes problems with the bundle branches there is the right and the left premature ventricular contractions. Right is most common and may go untreated. Left is always a serious problem and must be treated. ## Intrinsic Control of heartbeat • SA node (located in the right atrium near the entrance of the superior vena cava)\ • AV node (located at the base of right atrium)\ • AV bundle (located in the intraventricular septum between the two ventricles that go in two directions right and left bundle branches that leave the septum to enter the walls of both ventricle)\ • Bundle Branches (the branching off the septum to the walls of the ventricles that run into the purkinje fibers that then make contact with ventricular myocardial cells to spread the impulse to the rest of the ventricles)\ !Animation of a normal ECG wave. ## Electrocardiogram • The P is the atrial depolarization\ • QRS is the ventricular depolarization, as well as atrial repolarization.\ • T is the ventricular repolarization\ !Schematic representation of normal ECG{width="300"} ## Extrinsic Control of Heartbeat Autonomic system with two subdivisions: the sympathetic division and the parasympathetic division. Hormonal control of blood pressure - Epinephrine - Norepinephrine - ANP : Atrial natriuretic peptide - ADH: Antidiuretic hormone - Renin-Angiotension system ## Case Study An example of the ever expanding technology for the heart is best described in this story: In 1955, when I was five years old, I first learned by my family physician that I had a heart murmur and that it would eventually need attention. By the time I was 15 in 1965, I had two cardiac catherizations at Rhode Island Hospital. The tests were inconclusive and I was told to go on with my life and wait and see if I had a problem. It wasn\'t until 1975 that I was told by my family physician that I should have my heart checked again. Dr. David Kitzes of Mariam Hospital performed another catherization. This time, unlike the others, I was told that because of new machine technology, Dr. Kitzes found that I had aortic stenosis, which is a narrowing of the valve passage by build-up of plaque due to the valve being malformed at birth. Dr. Kitzes informed me that I could lead a normal life until I was in my fifties or sixties before I would need corrective surgery. In 1996, I had an echocardiogram and it was determined that my heart was enlarged. My family physician said that I should see a cardiologist. I down played the visit as not being serious after hearing the same thing many times. This time I entered the office of Jon Lambrecht, I had never met him before. Within a few minutes my whole life was turned around. After asking me about my symptoms, which were fatigue, weakness, asthmatic symptoms, as well as ashen skin color and dizziness, he informed me of how serious my condition was and the only salvation was immediate open-heart surgery to replace the aortic valve. I began to cry as I thought my life was over. Dr. Lambrecht studied my reaction and told me that this condition is repairable and that I don\'t have a terminal illness. I didn\'t have a lot of time to think about it. Within 10 days from that visit, I was the recipient of a Meditronic Hall Prosthetic heart valve. The operation was performed by Dr. Robert Indeglia at Miriam Hospital in Providence, R.I. on March 20th, 1996. It has been almost 3 years since the surgery and I am doing better than I could have expected. In 1977 my son Kevin was born with Hypoplastic Left-heart Syndrome and only lived for 2 days because heart surgery wasn\'t performed like today. I am thankful that I lived at a time when medical technology paved the way for a second chance because of my new aortic heart valve. Our goal in this chapter is to take you by the hand and lead you through each part of the cardiovascular system, so that you too may learn and come to respect the greatness of this blood pumping machine we all call the heart. #### Stroke Cerebrovascular disease are those that affect blood vessels in the brain and happen to be the third cause of death in the United States only behind heart disease and cancer. Stroke (also called cerebrovascular accident or CVR) is a cerebrovascular disorder caused by a sudden decrease or stoppage of blood flow to a part of the brain. Decreased blood flow also known as ischemia is dangerous to any tissue but brain tissue is even more vulnerable, mainly due to the high rate of its metabolic reactions. In fact if you stopped blood flow for no more than three minutes it may be sufficient enough to cause death of most brain cells. For this reason a stroke can kill people within minutes or leave them with severe brain damage. Strokes may be classified as either occlusive or hemorrhagic and may happen either in the interior of the brain or on its surface. In a occlusive stroke blood flow through a vessel is blocked. In a hemorrhagic stroke a blood vessel ruptures causing a hemorrhage. ## Summary As with all of the body systems, the cardiovascular system plays a part in maintaining homeostasis. The nervous system regulates the functioning of the heart based on what the heart is supposed to do. The pumping of the heart maintains normal blood pressure and proper oxygenation of tissues. The vascular system forms passageways for the blood, but they aren\'t simply just a pipeline system. The vessels are not passive tubes, but rather active contributors to homeostasis. The arteries and veins help maintain blood pressure, and the capillaries provide sites for the necessary exchanges of materials between the blood and the tissues. ## Review Questions Answers for these questions can be found here 1\. This conducts electricity like nerves : A\) Epicardium : B\) Pericardium : C\) Myocardium : D\) Subvalaular Apparatus : E\) None of these, only nerves conduct electricity 2\. This carries the most blood at any given time in the body : A\) Veins : B\) Capillary Beds : C\) Veins : D\) Aorta : E\) Vena Cava 3\. The following contract together to pump blood : A\) Right atrium with the right ventricle and left atrium with the left ventricle : B\) Right atrium with left atrium and right ventricles with left ventricle : C\) Tricuspid valve and mitral valve : D\) Aorta and pulmonary artery : E\) Aorta, pulmonary artery and pulmonary vein 4\. This is the pacemaker of the heart : A\) AV node : B\) Purkinje fibers : C\) AV Bundle : D\) SA node : E\) None of these, a pacemaker is surgically inserted 5\. When reading an EKG, this letter shows the depolarization from the AV node down to the AV bundle : A\) S : B\) P : C\) U : D\) T : E\) Q 6\. The T wave in an EKG shows : A\) Resting potential : B\) Atrial depolarization : C\) SA node excitation : D\) Ventricle repolarization : E\) Purkinje Excitation 7\. Blood pressure is the measure of : A\) Pressure exerted by the blood on the walls of the blood vessels : B\) Pressure exerted by the blood on the arteries : C\) Pressure exerted by the blood on the veins : D\) Pressure exerted by the blood on the aorta : E\) Pressure exerted by the blood on the capillaries 8\. Systolic Pressure is : A\) An average of 120 mm Hg : B\) Lowers steadily during ventricle systole : C\) The highest when blood is being pumped out of the left ventricle into the aorta : D\) An average of 80 mm Hg : E\) Both A and C : F\) Both B and D 9\. The heart has how many chambers? : A\) One : B\) Two : C\) Three : D\) Four : E\) Five ## Glossary \ **Acute myocardial infarction (AMI or MI)** commonly known as a heart attack, is a disease state that occurs when the blood supply to a part of the heart is interrupted. The resulting ischemia or oxygen shortage causes damage and potential death of heart tissue. **Aorta**: the largest of the arteries in the systemic circuit\ **Aortic Valve**: lies between the left ventricle and the aorta\ **Antidiuretic hormone:** Produced in the posterior pituitary ADH (vasopressin), major function is to regulate blood pressure by water retention by the kidneys.\ **Arteriole:** a small diameter blood vessel that extends and branches out from an artery and leads to capillaries\ **Atrial natriuretic peptide:** Produced in the atria of the heart, it increases urinary excretion of sodium which causes water loss which in turn the viscosity of the blood is lowered and in turn lowers the blood pressure.\ **Atrioventricular Node (abbreviated AV node):** the tissue between the atria and the ventricles of the heart, which conducts the normal electrical impulse from the atria to the ventricles\ **Atrioventricular valves:** large, multi-cusped valves that prevent backflow from the ventricles into the atria during systole\ **AV Bundle:** collection of heart muscle cells specialized for electrical conduction that transmits the electrical impulses from the AV node\ **Barbiturates:** CNS depressants, sedative-hypnotics\ **Blood Pressure:** the pressure exerted by the blood on the walls of the blood vessels\ **Capillaries:** the smallest of a body's vessels, they connect arteries and veins\ **Cardiac Cycle:** term used to describe the sequence of events that occur as a heart works to pump blood through the body\ **Cerebral Vascular Accident (CVA):** Also known as a stroke, is a rapidly developing loss of a part of brain function or loss of consciousness due to an interruption in the blood supply to all or part of the brain. That is, a stroke involves the sudden loss of neuronal function due to a disturbance in cerebral perfusion. There are many different causes for the interruption of blood supply, and different parts of the brain can be affected. Because of this, a stroke can be quite heterogeneous. Patients with the same cause of stroke can have widely differing handicaps. Similarly, patients with the same clinical handicap can in fact have different causes of their stroke.\ **Chordae Tendinae:** cord-like tendons that connect the papillary muscles to the tricuspid valve and the mitral valve in the heart\ **Coronary Arteries:** blood vessels that supply blood to, and remove blood from, the heart muscle itself\ **Continuous Capillaries:** have a sealed epithelium and only allow small molecules, water and ions to diffuse\ **Deep-vein thrombosis (DVT):** is the formation of a blood clot (\"thrombus\") in a deep vein. It commonly affects the leg veins, such as the femoral vein or the popliteal vein or the deep veins of the pelvis. Occasionally the veins of the arm are affected\ **Diastole:** period of time when the heart relaxes after contraction in preparation for refilling with circulating blood\ **Diastolic Pressure:** lowest point in blood pressure where the heart relaxes\ **Edema:** The swelling that forms when too much tissue fluid forms or not enough taken away\ **Electrocardiogram:** the recording of the heart\'s electrical activity as a graph\ **Epinephrine:** Produced in the adrenal medulla of the adrenal glands, major function is vasoconstriction that will in turn increase respiratory rate and increase cardiac out put.\ **Fenestrated Capillaries:** have openings that allow larger molecules to diffuse\ **Fibrous Pericardium:** a dense connective tissue that protects the heart, anchoring it to the surrounding walls, and preventing it from overfilling with blood\ **Heart Rate:** term used to describe the frequency of the cardiac cycle\ **Hepatic Veins:** blood vessels that drain de-oxygenated blood from the liver and blood cleaned by the liver (from the stomach, pancreas, small intestine and colon) into the inferior vena cava\ **Hypertension or High Blood Pressure:** medical condition wherein the blood pressure is chronically elevated\ **Inferior Vena Cava (or IVC):** a large vein that carries de-oxygenated blood from the lower half of the body into the heart\ **Intraventricular Septum:** the stout wall separating the lower chambers (the ventricles) of the heart from one another\ **Left Atrium:**receives oxygenated blood from the left and right pulmonary veins\ **Lub:** first heart tone, or S1; caused by the closure of the atrioventricular valves, mitral and tricuspid, at the beginning of ventricular contraction, or systole\ **Lumen:** hollow internal cavity in which the blood flows\ **Lymph:** originates as blood plasma that leaks from the capillaries of the circulatory system, becoming interstitial fluid, filling the space between individual cells of tissue\ **Mitral valve:** also known as the bicuspid valve; prevents blood flowing from the left ventricle into the left atrium\ **Myocardium:** the muscular tissue of the heart.\ **Norepinephrine:** Produced in the adrenal medulla of the adrenal glands, major function is a strong vasoconstrictor that will in turn increase respiratory rate.\ **Pacemaker Cells:** cells that create these rhythmical impulses of the heart\ **Plaque: an abnormal inflammatory accumulation of macrophage white blood cells within the walls of arteries\ **Pulmonary Valve:**lies between the right ventricle and the pulmonary artery; prevents back-flow of blood into the ventricle\ **Pulse: the number of heartbeats per minute\ **Purkinje Fibers (or Purkinje tissue):** located in the inner ventricular walls of the heart, just beneath the endocardium; specialized myocardial fibers that conduct an electrical stimulus or impulse that enables the heart to contract in a coordinated fashion\ **Renin-Angiotension system:**\ **Right Atrium:** receives de-oxygenated blood from the superior vena cava and inferior vena cava\ **Serous Pericardium:** functions in lubricating the heart to prevent friction from occurring during heart activity\ **Semilunar Valves:** positioned on the pulmonary artery and the aorta\ **Sinoatrial Node:** (abbreviated SA node or SAN, also called the sinus node): the impulse generating (pacemaker) tissue located in the right atrium of the heart\ **Sinusoidal Capillaries:** special forms of fenestrated capillaries that have larger opening allowing RBCs and serum proteins to enter\ **Systole:** contraction of the heart\ \'\'Systolic Pressure:**the highest point in blood pressure when the blood is being pumped out of the left ventricle into the aorta during ventricular systole\ **Superior Vena Cava (SVC):**a large but short vein that carries de-oxygenated blood from the upper half of the body to the heart\'s right atrium\ **Thrombus:**a blood clot in an intact blood vessel\ **Tricuspid Valve:**on the right side of the heart, between the right atrium and the right ventricle; allows blood to flow from the right atrium into the right ventricle when the heart is relaxed during diastole\ **Vasoconstriction:**the constriction of blood vessels\ **Vasodilation: the dilation of blood vessels\ **Veins:**carry de-oxygenated blood from the capillary blood vessels to the right part of the heart\ **Ventricle:** a heart chamber which collects blood from an atrium\ **Venule:** a small blood vessel that allows deoxygenated blood to return from the capillary beds to the larger blood vessels called veins ## References 1. Van De Graaff, Kent M. Human Anatomy. McGraw Hill Publishing, Burr Ridge, IL. 2002. 2. Essentials of Anatomy and Physiology, Valerie C. Scanlon and Tina Sanders 3. Tortora, G. & Grabowski, S. (2000) Principles of Anatomy & Physiology. Wiley & Sons. Brisbane, Singapore & Chichester. 4. Anderson, RM. The Gross Physiology of the Cardiovascular System (1993) \<<http://cardiac-output.info>\>. [^1]: Tortora, G. & Grabowski, S. (2000)Principles of anatomy and physiology. Ninth Edition. Wiley page 733.
# Human Physiology/The Immune System ## Overview The immune system is a complex system that is responsible for protecting us against infections and foreign substances. There are three lines of defense: the first is to keep invaders out (through skin, mucus membranes, etc), the second line of defense consists of non-specific ways to defend against pathogens that have broken through the first line of defense (such as with inflammatory response and fever). The third line of defense is mounted against specific pathogens that are causing disease (B cells produce antibodies against bacteria or viruses in the extracellular fluid, while T cells kill cells that have become infected). The immune system is closely tied to the lymphatic system, with B and T lymphocytes being found primarily within lymph nodes. Tonsils and the thymus gland are also considered lymph organs and are involved in immunity. We often don\'t realize how effective the immune system is until it fails or malfunctions, such as when the lymphocytes are attacked by HIV in an AIDS patient. ## The Immune System as a Castle The immune system is a silent wonder. While we are very aware of our heart beating and the breaths we take, we are much less aware of our immune system that protects us from thousands of potentially deadly attacks every day. In this chapter we will discuss the immune system we each possess that is working around the clock, protecting us from disease and death. ![](Suecia_3-126_;_Tavastehus_slott.png "Suecia_3-126_;_Tavastehus_slott.png") A good way to start understanding the immune system is to liken it to a castle. A castle, like our bodies, is a fortress. A castle has three lines of defense: - *First*, A moat and drawbridge. The first line of defense in our bodies are physical and chemical barriers - our skin, stomach acids, mucus, tears, vaginal opening, of which the last three mostly produce lysozyme to destroy harmful incoming pathogens. - *Second*, Sentries and archers who stand on the castle wall. In our bodies the second line of defense is non-specific immune responses - macrophages, neutrophils, interferons, and complement proteins. This line of defense also includes fever and inflammatory response as nonspecific defenses. - *Third*, Soldiers within the castle. Our third line of defense is specific immune responses - T Cells and B Cells. There are many types of each which work like a close knit team to destroy pathogens. If pathogens (invaders) try and succeed in penetrating the first line of defense, then the second line of defense is ready to act. If both the first and second line of defense fail, then the third line of defense will act. It is when all three lines of defense are breached that we get sick and are subject to disease. So what we are trying to say is that the immune system is a set of mechanisms of defense, protecting an organism from infection by identifying and attacking pathogens. This is a difficult task, since pathogens range from viruses to parasitic worms and must be detected with absolute specificity as they are \"hidden\" amongst normal cells and tissues. Pathogens are also constantly changing themselves to avoid detection and successfully infect and destroy their hosts. ## Lymphatic System right\|framed\|200px\|The human lymphatic system The lymphatic system and the immune system are terms that are used interchangeably to refer to the body\'s ability to defend against pathogens. The lymphatic system comprises three interrelated functions: (1) Removal of excess fluids, lymph, from body tissues, (2) Absorption of fatty acids and subsequent transport of fat, chyle, to the circulatory system and (3) Formation of white blood cells (WBCs), and initiation of immunity through the formation of antibodies, lending specific resistance to pathogens. ### Lymphatic Pathways The lymphatic system acts as a secondary circulatory system, except it collaborates with white blood cells in lymph nodes to protect the body from being infected by cancer cells, fungi, viruses or bacteria. Unlike the circulatory system, the lymphatic system is not closed and has no central pump; the lymph moves slowly and under low pressure due to peristalsis, the operation of semilunar valves in the lymph veins, and the milking action of skeletal muscles. Like veins, lymph vessels have one-way, semi-lunar valves and depend mainly on the movement of skeletal muscles to squeeze fluid through them. Rhythmic contraction of the vessel walls may also help draw fluid into the lymphatic capillaries. This fluid is then transported to progressively larger lymphatic vessels culminating in the right lymphatic duct (for lymph from the right upper body) and the thoracic duct (for the rest of the body); these ducts drain into the circulatory system at the right and left subclavian veins. thumb\|left ### Lymph Lymph originates as blood plasma that leaks from the capillaries of the circulatory system, becoming interstitial fluid, filling the space between individual cells of tissue. Plasma is forced out of the capillaries by hydrostatic pressure, and as it mixes with the interstitial fluid, the volume of fluid accumulates slowly. Most of the fluid is returned to the capillaries by osmosis. The proportion of interstitial fluid that is returned to the circulatory system by osmosis is about 90% of the former plasma, with about 10% accumulating as overfill. The excess interstitial fluid is collected by the lymphatic system by diffusion into lymph capillaries, and is processed by lymph nodes prior to being returned to the circulatory system. Once within the lymphatic system the fluid is called lymph, and has almost the same composition as the original interstitial fluid. ### Edema Edema is the swelling that forms when too much tissue fluid forms or not enough taken away. It can be caused by a variety of conditions such as allergic responses (too much vasodilation), starvation (lack of albumin in blood lowers osmotic pressure and decreases amount of fluid returning to capillaries), and lymphatic disorders (e.g. blockage due to parasite in elephantiasis, or removal of lymph nodes due to a radical mastectomy). Edema is common in the lower extremities when people spend a lot of time sitting, because the fluid return is based largely on the massaging action of skeletal muscles. ### Lymphatic Vessels and Ducts The lymphatic vessels are similar in structure to the cardiovascular veins, meaning they also have valves. They are dependent upon the contraction of skeletal muscle, respiratory movements and valves that do not allow backward flow. The vessels merge before entering one of two ducts. - Thoracic Duct: This duct is much larger than the lymphatic duct. It serves the abdomen, lower extremities and the left side of the upper body (head, neck, and arm) - Right Lymphatic Duct: This duct serves all of the right side of the upper body and thoracic area (head, neck). ## Organs, Tissues and Cells of the Immune System The immune system consists of a network of lymphatic organs, tissues, and cells. These structures are supported by the reticuloendothelial system: loose connective tissue with a network of reticular fibers. Phagocytic cells, including monocytes and macrophages, are located in the reticular connective tissue. When micro-organisms invade the body, or the body encounters antigens (such as pollen), antigens are transported to the lymph. Lymph is carried through the lymph vessels to regional lymph nodes. In the lymph nodes, the macrophages and dendritic cells phagocytose the antigens, process them, and present the antigens to lymphocytes, which can then start producing antibodies or serve as memory cells. The function of memory cells is to recognize specific antigens in the future. **Primary Lymphatic Organs** The primary lymphatic organs are the red bone marrow and the thymus. They are the site of production and maturation of lymphocytes, the type of white blood cell that carries out the most important work of the immune system. - **Red Bone Marrow** Red bone marrow, the soft, spongy, nutrient rich tissue in the cavities of certain long bones, is the organ that is the site of blood cell production. Some of the white blood cells produced in the marrow are: neutrophils, basophils, eosinophils, monocytes, and lymphocytes. Lymphocytes differentiate into B lymphocytes and T lymphocytes. Red bone marrow is also the site of maturation of B lymphocytes. T lymphocytes mature in the thymus. thumb\|Side of thorax, showing surface markings for bones, lungs (purple), pleura (blue), and spleen (green). - **Thymus Gland** The thymus gland is located in the upper thoracic cavity posterior to the sternum and anterior to the ascending aorta. The thymus is an organ that is more active in children, and shrinks as we get older. Connective tissue separates the thymus into lobules, which contain lymphocytes. Thymic hormones such as thymosin are produced in the thymus gland. Thymosin is thought to aid in the maturation of T lymphocytes. **The Thymus** is critical to the immune system. Without a thymus, a person has no ability to reject foreign substances, blood lymphocyte level is very poor, and the body's response to most antigens is either absent or very weak Immature T lymphocytes travel from the bone marrow through the bloodstream to reach the thymus. Here they mature and for the most part, stay in the thymus. Only 5% of T lymphocytes ever leave the thymus. They only leave if they are able to pass the test: if they react with "self" cells, they die. If they have the potential to attack a foreign cell, they leave the thymus. **Secondary Lymphatic Organs** The secondary lymphatic organs also play an important role in the immune system as they are places where lymphocytes find and bind with antigens. This is followed by the proliferation and activation of lymphocytes. The secondary organs include the spleen, lymph nodes, tonsils, Peyer's patches, and the appendix. - **The spleen**, The spleen is a ductless, vertebrate gland that is closely associated with the circulatory system, where it functions in the destruction of old red blood cells in holding a reservoir of blood. Located in the upper left region of the abdominal cavity, it is divided into partial compartments. Each compartment contains tissue known as white pulp and red pulp. The white pulp contains lymphocytes and the red pulp acts in blood filtration. When blood enters the spleen and flows through the sinuses for filtration, lymphocytes react to pathogens , macrophages engulf debris, and also remove old, worn out red blood cells. A person without a spleen is more susceptible to infections and may need supplementary antibiotic therapy for the rest of their life. !Structure of the lymph node.**1.** Efferent lymphatic vessel **2.** Sinus **3.** Nodule **4.** Capsule **5.** Medulla **6.** Valve to prevent backflow **7.** Afferent lymphatic vessel.{width="342"} - **Lymph Nodes** are small oval shaped structures located along the lymphatic vessels. They are about 1-25 mm in diameter. Lymph nodes act as filters, with an internal honeycomb of connective tissue filled with lymphocytes that collect and destroy bacteria and viruses. They are divided into compartments, each packed with B lymphocytes and a sinus. As lymph flows through the sinuses, it is filtered by macrophages whose function is to engulf pathogens and debris. Also present in the sinuses are T lymphocytes, whose functions are to fight infections and attack cancer cells. Lymph nodes are in each cavity of the body except the dorsal cavity. Physicians can often detect the body's reaction to infection by feeling for swollen, tender lymph nodes under the arm pits and in the neck, because when the body is fighting an infection, these lymphocytes multiply rapidly and produce a characteristic swelling of the lymph nodes. ```{=html} <!-- --> ``` - **Tonsils** are often the first organs to encounter pathogens and antigens that come into the body by mouth or nose. There are 3 pairs of tonsils in a ring about the pharynx. ```{=html} <!-- --> ``` - **Peyer's patches**, located in the wall of the intestine and the appendix, attached to the cecum of the large intestine, intercept pathogens that come into the body through the intestinal tract. ## Leukocytes The primary cells of the immune system are the *leukocytes* or white blood cells (WBC). Most leukocytes are much larger than red blood cells, but they are not nearly as numerous. A microliter of whole blood contains about 5 million red blood cells but only about 7000 leukocytes. Although most leukocytes circulate through the blood, they usually leave the capillaries and function extravascularly (outside the vessels). Some types of leukocytes can live out in the tissue for several months, but others may live for only hours or days. Leukocytes can be distinguished from one another in stained tissue samples by the shape and size of the nucleus, the staining characteristics of the cytoplasm and the cytoplasmic inclusions, and the regularity of the cell border. Leukocytes are divided into six basic types eosinophils, basophils, neutrophils, monocytes, lymphocytes, and dendritic cells. One functional group of leukocytes is the **phagocytes**, WBC that engulf and ingest their targets by phagocytosis. This group includes the neutrophils, macrophages, monocytes (which are macrophage precursors), and eosinophils. A second functional group is the **cytotoxic cells**, so named because they kill the cells they attack. This group includes eosinophils and some types of lymphocytes. Lets take a closer look at the six basic types of leukocytes. **Eosinophils** Eosinophils fight parasites and contribute to allergic reactions. They are easily recognized by the bright pink staining granules in their cytoplasm. Normally, there are only a few eosinophils found in the peripheral circulatory. They account for only 1-3% of all leukocytes. The life span of a typical eosinophil in the blood is about 6-12 hours. Eosinophils are known to attach to large parasites and release substances from their granules that damage or kill the parasite. Because eosinophils kill pathogens, they are classified as cytotoxic cells. Eosinophils also participate in allergic reactions, by contributing to inflammation and tissue damage by releasing toxic enzymes. **Basophils** Basophils release histamine and other chemicals. (Histamine is also secreted by other cells called MAST cells.) Basophils are rare in circulation but are easily recognized in a stained blood smear by the large, dark blue granules in their cytoplasm. They also release mediators that contribute to inflammation. The granules contain histamine, heparin(an anticoagulant), cytokines, and other chemicals involved in allergic and immune responses. !Illistration of a cell during phagocytosis. **Neutrophils** Neutrophils \"eat\" bacteria and release cytokines. Neutrophils are the most abundant WBC, 50-70% of the total. They are easily identified by a segmented nucleus. Neutrophils, like other leukocytes are formed in the bone marrow. They are phagocytic cells that typically ingest and kill bacteria. Most neutrophils remain in the blood but can leave the circulation if attracted to an extravascular site of damage or infection. In addition to ingesting bacteria and foreign particles, neutrophils release a variety of cytokines. **Monocytes** Monocytes are the precursor cells of tissue macrophages. Monocytes are not that common in the blood 1-6% of WBC. Once out of the blood, monocytes enlarge and differentiate into macrophages. Some tissue macrophages patrol the tissues, creeping along by amoeboid motion. Others find a location and remain fixed in place. Macrophages are the primary scavengers within tissues. Macrophages also remove larger particles, such as old RBC and dead neutrophils. Macrophages play an important role in the development of acquired immunity. After they ingest and digest molecular or cellular antigens, fragments of processed antigen are inserted into the macrophage membrane as part of surface protein complexes. **Lymphocytes** Lymphocytes are the key cells that mediate the acquired immune response of the body. Only about 5% of lymphocytes are found in circulation. They constitute 20-30% of all WBC. Most lymphocytes are found in lymphoid tissues, where they are more likely to encounter invaders. By one estimate,the adult body contains a trillion lymphocytes at any one time. **Dendritic Cells** Dendritic cells activate lymphocytes. They are antigen-presenting cells characterized by long, thin processes that resemble neuronal dendrites. Dendritic cells are found in the skin called Langerhans cells and also in various organs. When dendritic cells recognize and capture antigens, they migrate to secondary lymphoid tissues, where they present the antigens to lymphocytes. ## The Three Defenses Against Infection ### Innate Defense -- first line of defense Physical and chemical barriers are the body\'s first line of defense. **Physical or Mechanical barriers** - **Skin** One of the body\'s first line of defenses against bacteria and other harmful organisms is the skin. Our skin is a barrier which stops infection from entering the body. Millions of microorganisms live harmlessly on the skin and in the air around us. Sebaceous glands in the skin produce sweat and sebum, which, combined help to protect the skin. Both substances contain antiseptic molecules, primarily lysozyme which breaks down bacterial cell walls. Although our skin is a good defense, it isn't perfect. The skin itself can also become infected by bacteria, viruses, fungi or tiny parasites. Some examples of these are: boils, impetigo; ringworm, athletes foot; cold sore, wart, verucca; and scabies. - **Mucus membranes** Another very important first line of defense is our mucus membranes. The mucous membranes (or mucosae; singular: mucosa) line various body cavities that are exposed to the external environment and internal organs. It is at several places continuous with skin: at the nostrils, the lips, the ears, the genital area, and the anus. The nose and mouth serve as passageways for air going to and from the lungs. As we inhale and exhale, the mucus membranes that line these passageways warm and humidify the air. It has been said that there is more bacteria contained in a human mouth than the sum of all the people that have ever lived on the earth. Mucus membranes serve different functions, however, their more important job is to secrete mucus that traps bacteria and other foreign debris that irritates the lining of the respiratory tract. This mucus is produced and stored in the sinuses by other mucus membranes. We get congested when there is excessive fluid in the sinus cavities. This is a result of an increase in mucus secretions, as well as an increase in the amount of fluids that passes across the blood vessels of the mucus membranes that line the nose and sinus. There are also many chemicals, such as pesticides and anthrax that are absorbed through the skin. Some mucous membranes are ciliated. *Cilia* are thin, tail-like projections extending approximately 5--10 micrometers outwards from the cell body. Their main function is to move things across their surface. - **Mucociliary escalator** The mucociliary clearance of the respiratory tract is an important defense mechanism against foreign debris and inhaled pathogens. The cilia that lines the upper and lower airways are lined with a thin layer of mucus. These beat rapidly to propel particles that are trapped in the mucus layer to the pharynx. Defective mucociliary clearance predisposes our respiratory tracts to recurrent infections. These cilial defects may be either congenital or acquired by infection, toxins or drugs. **Chemical Defenses** - **Tears, saliva** Tears and saliva contain *lysozyme*, an antiseptic enzyme that attacks cell walls of bacteria and breaks them down. - **Stomach acids** Glands in the stomach lining produce hydrocloric acid. This acid kills most invading organisms that are swallowed and take up residence there. ### Non-specific responses to infection - 2nd line of defense We are born with built in nonspecific defenses that all respond in the same way to invading pathogens. The outermost defense our body has is our skin. The sebaceous glands produce sweat and sebum, which contain antiseptic properties which protect. This bacteria-killing substance called lyzosome is also found in tears and saliva. Acidic urine in the urinary tract and friendly bacteria in the genital tract prevent the multiplying of harmful organisms in these areas. Most invading organisms in the stomach are killed by gland production of hydrochloric acid. These are a few examples of how the outer defenses protect us. All outer defenses work together as the body\'s first line of defense. #### Inflammatory response Any break in the skin will allow bacteria to enter the body. These foreign microbes will cause swelling and reddening at the site of injury. This reaction by the body is called an *inflammatory reaction* or *inflammatory response*. - Swelling, redness, heat, and pain Inflammation is characterized by the following quintet: swelling (tumor), redness (rubor), heat (calor), pain (dolor) and dysfunction of the organs involved (functio laesa). When an injury occurs, a capillary and several tissue cells are apt to rupture, releasing histamine and kinins. These cause the capillaries to dilate, become more permeable, and leak fluid into these tissues. Dilation and fluid leaking into the tissues causes swelling, redness, and heat. The swelling and kinins stimulate nerve endings, causing pain. If there has been a break in the skin due to the injury, invading microbes may enter. A common cause of inflammation after surgery is serous fluid. This is a mixture of plasma, lymph and interstitial fluids seeping from the damaged cells and vessels. If enough serous fluid accumulates a mass called a seroma may form. Treatment of a seroma may involve the removal of the fluid with a needle into a syringe, a process called aspiration. - Phagocytosis by neutrophils and macrophages In the event of a break in the skin, neutrophils, monocytes (and macrophages) arrive and attempt to engulf and destroy the invaders. Phagocytosis is receptor-mediated event, which ensures that only unwanted particles are ingested. Stimulated macrophages can bring about an explosive increase in the number of leukocytes by producing Colony Stimulating Factors (CSFs). The CSFs pass by way of the blood to the bone marrow, where they stimulate the production and the release of white blood cells (WBCs), primarily neutrophils. Lymphocytes in nearby lymph nodes produce specific antibodies to attack the microbes. During the conflict, some neutrophils die and become mixed with dead tissue, bacteria, living white cells, etc. This thick yellow-white fluid is called *pus*. When a person has an illness, an examination of the numbers and types of WBC\'s in their blood can be very useful. #### Complement System !Complement protein attacking a cell membrane. The complement system is a biochemical cascade of the immune system that helps clear pathogens from an organism, and promote healing. It is derived from many small plasma proteins that work together to form the primary end result of cytolysis by disrupting the target cell\'s plasma membrane. Complement is activated by antigen-antibody complexes and causes holes to form in the plasma membrane of foreign microbes or cells (lysis). The complement system is considered a nonspecific defense, but it can be activated against specific microbes that have been marked with antibodies. Hemolytic transfusion reactions are caused by complement activation after a person expresses antibodies against the antigens found on the inappropriately donated blood. Hemolytic Disease of the Newborn (HDN) is due to maternal antibodies against the Rh factor crossing the placenta, binding to the baby\'s red blood cells, and stimulating the baby\'s own complement system to lyse its red blood cells. #### Interferon in response to viral infection Interferon (IFNs) are naturally occurring glycoproteins involved in non-specific immune responses. Interferons do just as their name states they \"interfere\" with viral growth. Interferons are initiated from a cell that has been infected by a virus. When a cell has been infected by a virus the virus will then cause the cell to make viral nucleic acid. This nucleic acid acts as a signal and it causes the cell to realize that it has been infected with a virus. So the cell will start making and sending out interferons. The IFN\'s that the cell sends out go to nearby healthy cells and warns them of a virus. The healthy cells then start intracellular changes that help the cells to be more resistant to the virus. ### Adaptive Defense (Specific Defense\--third line of defense) This part of the immune system directly targets invading microbes. Our specific immune defenses respond to *antigens*. An antigen is a protein (or polysaccharide) molecule, typically on the cell membrane, that the body recognizes as *nonself*. They are found on microbes, foreign cells, or on cancer cells. Normally our immune system does not respond to our own antigens (if it does, then this is an autoimmune disease). Sometimes we develop an immune response to a harmless antigen, such as pollen or cat dander (this is an allergic response). #### Lymphocytes Specific immunity is dependent upon two types of lymphocytes, the B cells and the T cells. Their names are based on where in the body they mature. B cells mature in the bone marrow, and T cells mature in the thymus gland. In comparison, both B and T cells can recognize and target antigen-bearing cells, although they go about this in different ways. B and T cell lymphocytes are capable of recognizing an antigen because they have specific receptor molecules on their surface which exactly fit individual antigens (like a lock and a key). Any B or T cell can only respond to one type of antigen. The body does not know ahead of time which antigens it will encounter, but rather makes receptor sites for a huge number of possible antigens. It is estimated that for the million or so antigens we encounter in our lifetime we have an equal number of specific lymphocytes for each possible antigen. ##### B Cells Produce Antibodies *B cell* lymphocytes are responsible for antibody-mediated immunity (humoral immunity). They produce antibodies, which are proteins that bind with and neutralize specific antigens. Antibodies do not directly kill bacteria, but mark them for destruction. When antibodies bind to viruses they can prevent the viruses from infecting cells. When antibodies bind to toxins they can neutralize the toxin (why we get immunized against the tetanus toxin). Humoral immunity works best fighting against target viruses, bacteria, and foreign molecules that are soluble in blood and lymph *before* the bacteria or viruses have entered into cells (extracellular bacteria and extracellular viruses). B cells produce two different types of cells: - plasma cells - memory cells **Plasma cells** As B cells mature during embryonic development, they develop surface receptors that allow them to recognize specific antigens. Then they travel in the bloodstream, distributing throughout the lymph nodes, spleen, and tonsils. Once B cells reach their destination, they remain inactive until they encounter a foreign cell with an antigen that matches their particular receptor site (most B cells remain inactive for your entire life). The foreign antigen can be presented to the B cell directly, but usually macrophages and T cell lymphocytes (helper T cells) interact with B cells as Antigen Presenting Cells to bring about antibody production. Upon such an encounter, the B cell\'s receptors will bind to the antigen. The appropriate B cell is *turned on* or stimulated. It then grows bigger, and rapidly multiplies into a large homogenous group (clone). Most of these cells are *plasma cells*, which actively secrete antibody that will bind with the original stimulating antigen . While most of the B cells remain in the lymphatic system, the antibodies are secreted into the lymph fluid which then enters into the blood plasma to circulate throughout the body. Although the clone cells only live a few days, their antibodies remain and circulate in the blood and lymph, gradually decreasing in number. **Antibody Structure and Function** There are different classes of antibodies, or immunoglobulins (Ig), such as IgA, IgG, IgE, and IgM. They can attach to the surface of a microbe and make it more easily phagocytized by neutrophils, monocytes and macrophages. Anything that simplifies phagocytosis is called an *opsonin.* The process of antibodies attaching to invaders can be termed \'opsonization.\' Some antibodies can bind and inactivate certain poisons or toxins and are called *antitoxins* (tetanus immunizations stimulate your body to produce antibodies against the tetanus toxin rather than against the bacteria that produces the toxin). Still other antibodies can bind to the surface of microbes and prevent their attachment to the body\'s cells (thus preventing viruses from entering host cells). Also, some of them can stimulate nine proteins found in plasma, called *complement*. **Memory B cells** At the time of activation some of the clones become memory B cells. These cells are long lived and have recorded the information about the foreign antigen so antibodies can be made more quickly, and in greater amount, in case a second exposure should occur. Since the second response is much stronger than the first and puts more antibodies into circulation, we often receive \"booster shots\" for immunizations. ##### T Cells Attack Infected Cells thumb\|250px Defending the body against intracellular pathogens is the role of T lymphocytes, which carry out *cell-mediated immunity*(CMI). Macrophages phagocytize invading microbes and present parts of the microbe (antigens) to the T cell lymphocytes. The appropriate T cell is *turned on* or stimulated. The activated T cell rapidly multiplies into a large homogenous group (clone) of *cytotoxic T cells* (Tc cells). - \(a\) Attack organisms directly, Also kill infected cells These cytotoxic T cells migrate to the site of infection (or disease) and produce chemicals which directly kill the invader. Cytotoxic T cells release "perforin" that causes pores to form in the plasma membrane of the target cell, resulting in lysis. - \(b\) T cells develop in the thymus gland from immature precursor cells that migrate there from the bone marrow. - \(c\) Killer and helper T cells - \(d\) Memory T Cells A portion of these activated T cells become *memory* T cells (Tm). These cells record the information about the foreign antigen so T cells can respond more quickly, and more strongly, if a second exposure occurs. A portion of the T cells become *T helper cells* (TH) or *T suppressor cells* (Ts). TH cell stimulate other T cells and B cells by releasing *cytokines* and other stimulatory chemicals. Ts cells suppress the immune response. Experience has shown that cell mediated immunity is most useful to the body by: Protecting against microbes which exist inside of our body\'s cells (intracellular bacteria and intracellular viruses). Protecting against fungal infections. Protecting against protozoan parasites. Protecting against cancer cells. ## Immune Response Pathways The innate response starts first, and it is reinforced by the more specific acquired response. The two pathways are interconnected, so cooperation and communication is essential. ### Inflammation What happens when bacteria invade? If the first line of defense fails, bacteria can reach the extracellular fluid. There they usually cause an inflammatory response. This response coats antigens on the bacterial surface, with antibodies. Then in return the antibodies will ingest the antigens with phagocytic cells. This is characterized by a red, swollen warm area that is tender or painful. In addition to the nonspecific inflammatory response, lymphocytes attracted to the area produce antibodies keyed to the specific type of bacteria. If the infection continues it will produce a fever. - What causes a fever? During an infection macrophages may release *cytokines* (see glossary), such as interleukin-1, that travel to the hypothalamus and induce a change in the *thermostat* setting. When the thermostat is raised to a new normal temperature, the previous body temperature now registers as too cold. To increase the temperature to the new level, our body shunts blood away from the skin (leaving it feeling cold and clammy), the heart rate increases, and we shiver to generate heat until we reach the new set point. The hypothalamus may subsequently lower the thermostat, in which case we suddenly feel hot and start to sweat as our body attempts to cool off. A person may cycle between chills and sweats during the course of an infection. While a fever can be dangerous if it gets too high, or if a patient is weak or has heart trouble, there is some evidence suggesting that the body may overcome an infection faster if a fever is allowed to run its course. ### Intracellular Defense What happens when virus\'s invade the body? First they encounter an extracellular phase just like the bacteria did. In the early stages of a viral infection, innate immune responses and antibodies can help control the invasion of the virus. Once the virus enters the body\'s host cells cytotoxic T lymphocytes are the main defense against intracellular viruses. These cells look for infected host cells, then destroy them. ### Acquired Immunity: Antigen-specific Responses Acquired immunity responses are antigen-specific responses in which the body recognizes a foreign substance and selectively reacts to it. This is mediated primarily by lymphocytes. Acquired immunity overlaps with the process of innate immunity. Acquired immunity can be subdivided into active immunity and passive immunity. **Active Immunity** occurs when the body is exposed to a pathogen and produces its own antibodies. Active immunity is active because it is the \"activation\" of your immune system. Active immunity can occur naturally, when a pathogen invades the body, or artificially, like when we are given vaccinations containing disabled or killed pathogens. The body does require prior exposure to an antigen to develop an active immunity. Some parents expose their children to some antigens so they will have immunity to these diseases later in life. **Passive Immunity** occurs when we acquire antibodies made by another human or animal. Passive immunity is passive because it requires no response from the person\'s immune system. In passive immunity you are not presenting the body with foreign antigens. Therefore your immune system will not need to use B cells, and we know that if the B cells are never introduced your body isn\'t making antibodies and it isn\'t making memory B cells. The transfer of antibodies from mother to fetus across the placenta is one example. Injections containing antibodies are another. Sometimes travelers going abroad may be injected with gamma globulin, but this passive immunity last only about three months. Passive immunizations are used to protect people who have been exposed to infections or toxins, like snake venom or tetanus. ### Allergic Responses/Inflammatory Responses An allergy is an inflammatory immune response to a nonpathogenic antigen. Left alone, the antigen is not harmful to the body, but if someone is sensitive to the antigen, the body produces an inflammatory response designed to get rid of it. Allergic inflammatory responses can range from mild tissue damage to fatal reactions. The immune response in allergies is called *sensitivity* or *hypersensitivity* to the antigen. **Immediate hypersensitivity reactions** are mediated (immune destruction) by antibodies and occur within minutes of exposure to antigens, which are called allergens. **Delayed hypersensitivity reactions** are mediated by helper T cells and macrophages and may take several days to develop. ![](Antigens_presentation.svg "Antigens_presentation.svg") What happens during a immediate hypersensitivity reaction? : 1-Foreign protein or antigen is introduced : 2-Macrophage cell ingests (phagocytosis) : 3- Activation of Th lymphocyte : 4-Th (helper) lymphocyte : 5-Foreign protein bound by membrane antibodies : 6-B lymphocyte : 7-Antigen processing (MHC II type) : 8-Antigen-MHC II complex (antigen presentation) : 9-Production of antigen-specific antibodies : 10-Activation of B lymphocyte with active Th 2\. Upon reexposure, the body reacts more strongly and rapidly. The allergen binds to IgE already present on mast cells, triggering the immediate release of histamine, cytokines, and other mediators that cause allergic symptoms. The severity of the reaction varies, ranging from localized reactions near the site of where the allergen entered, such as a rash. To the most severe allergic reaction called *anaphylaxis*. In an anaphylactic reaction, massive release of histamine and other cytokines cause widespread vasodilation, circulatory collapse, and severe bronchoconstriction. Unless treated promptly, anaphylaxis can result in death. Skin tests for allergies of certain allergens can be injected into the skin. This is a good way to find out what one might be allergic to so they can eliminate further exposure. Allergens that can cause immediate hypersensitivity include bee stings, pollen and certain foods. Allergies that cause chronic allergic rhinitis and asthma are highly due to dust mites (dermatophgoides). It is not their bodies that cause the reaction, but rather it\'s feces. Allergic attacks usually stop when the histamine has been depleted. This can be stopped faster with an antihistamine drug or nasal spray. What happens in a delayed hypersensitivity? It could take hours or days for symptoms to occur in a delayed hypersensitivity. Delayed hypersensitivity is cell mediated with a T lymphocyte response. Secretion of lymphokines, instead of histamine, happens in a delayed hypersensitivity. So, the treatment would be a corticosteroid instead of an antihistamine. Examples of a delayed hypersensitivity would be, poison sumac, poison oak and poison ivy. Skin tests for certain diseases are also considered examples like TB test and the Mantoux test. ## Infectious Organisms and Immunization **Beneficial Organisms** **Intestinal bacteria** - Bacteria are prokaryotic (before nucleus) cells that we see usually as bacilli (rods) or cocci (spheres). While they are the major cause of many diseases both fatal and mild, bacteria are also our friends and can be of great service to us. Many bacteria in our bodies help prevent pathogens from becoming established. \"Good bacteria\" helps protect us from \"bad bacteria\". The large intestine is packed with *normal microflora* that digest substances otherwise indigestible. This process provides our bodies with additional vitamins, fatty acids and nutrients. Another example is the microflora that is in the vagina that helps maintain an acidic pH, which discourages the growth of infectious organisms. These are examples of our immune system\'s first line of defense. **Harmful Organisms** **Viruses** - Viruses are non-living particles consisting of protein and nucleic acid that infect cells in biological organisms. They can reproduce only by invading and taking over other cells as they lack the cellular machinery for self reproduction. A virus is about ten times smaller than a bacteria. Some viruses you will recognize are: *influenza, herpes, measles, and the common cold*. Some viruses are particularly dangerous because they can undergo a period of latency, during which they are hidden in the cell and do not reproduce. *Influenza* and *HIV* are examples of viruses that frequently mutate, thus making it nearly impossible to achieve a long-lasting immunity. **Bacteria** - Bacteria can be deadly. They are the major cause of preventable infections and death. Some well known illnesses are caused by bacteria: *staph infections, strep infections, tuberculosis, food poisoning, tetanus, leprosy, and pneumonia*. Because bacterial cells are different from human cells, compounds can be found that can kill specific bacterial targets while leaving the human patient unharmed. Antibacterial agents can be successful in wiping out a bacterial infection. The problem with antibiotics is that many strains of bacteria are growing resistant to them. Plus, our bodies are not getting the chance to develop immunity to certain bacteria. It may be better to use probiotics (new supplements that promote the growth of healthy and helpful bacteria) rather than depend on antibiotics so much. **Protozoans** - The protozoans are mostly eukaryotic unicellular organisms with organelles and a nucleus. - *Malaria* is the most dangerous disease caused by protozoans and is endemic in about 50% of the populations on Earth. Two to four million people die each year from malaria, a million of these are under the age of five. malaria is caused by one of the protozoan genus \"Plasmodium\" which is carried by the female Anopheles mosquito. **Fungi** - Fungi are more like animals and humans than they are like bacteria because of their eukaryotic cells. Though they produce large, visible colonies on old bread, molds and yeasts are in the category of microscopic fungi. Yeasts are one-celled and reproduce by budding. Molds exist as cell chains, called hyphae. - *Mycoses* are diseases caused by fungi. Because of the similarity between human cells and fungal cells, it has been difficult for scientists to design antibiotics that are effective against fungi and do not harm humans. Some of the diseases caused by fungi are: *tineas*, *vaginal infection* (candidiasis), and *histoplasmosis*. **Diagnosis** Infectious diseases are diagnosed by laboratory techniques such as microscopy and culture. Since many bacteria have no color, scientists have developed special staining procedures to more accurately diagnose. - Culture Bacteria and fungi can be identified by growing them on plates until colonies are visible. Viruses are cultured on eggs or live cells. - Antibiotic sensitivity After colonies of bacteria are grown on plates, discs are placed on the plates that contain different antibiotics. Bacteria will not grow around the most effective antibiotic. - Tests for viruses Since viruses are too small to be seen with a light microscope, viral infections can be diagnosed indirectly by their effects on cells. Some viruses cause changes to the surface of cultured cells, causing them to stick together. **Immunization** While some infectious diseases are common and can occur many times in the same person, others can only occur once in a lifetime thanks to the immune system and it\'s ability to remember the organism and prevent following infections. To avoid an epidemic of a grave disease such as polio, before the disease can be acquired, an immunization can create a man-made \"memory\". - Active immunization A person receives an injection (vaccine) that contains dead or harmless living forms of an organism. The vaccine stimulates the immune system to produce antibodies and memorize the organism. If there is a later exposure to this organism and subsequent infection, the antibodies will stop the infection. - Passive immunization Blood containing antibodies is taken from animals or humans who have recently had an infection. Blood serum is made that contains the antibodies, and then injected into the person. The antibodies either attack an infection that is present or provide short-term protection. - Genetically engineered viruses Genetic engineering is a technique that alters or changes the DNA of a plant or animal by inserting new genetic information from another organism. After these organisms replicate, vaccines and hormones are made that can help fight disease. - Hepatitis B vaccine The gene of the surface antigen of Hepatitis B virus is implanted into the DNA of a single bacterium. The bacteria produces viral antigens which are then implanted to stimulate the immune system. ## Immune System Disorders The immune system is a very complex and highly developed system, yet it has a very simple mission, seek and destroy invaders. When the immune system does not function properly it leaves the body open for attacks from an array of diseases. We classify these into three broad categories; autoimmunity, immunodeficiencies, and hypersensitivities. Anything that can trigger the immune response is called an antigen. An antigen can be a microbe such as a virus, or even a part of a microbe. Tissues of cells from another person also carry nonself markers and act as antigens. This explains why tissue transplants can be rejected. In abnormal situations, the immune system can mistake self for nonself and launch an attack against the body\'s own cells or tissues. The result is called an autoimmune disease. Some forms of arthritis and diabetes are autoimmune diseases. In other cases, the immune system responds to a seemingly harmless foreign substance such as a dust mite. The result is allergy, and this kind of antigen is called an allergen. ## The Allergic response Type 1 hypersensitivity is an allergic reaction provoked by reexposure to a specific antigen. Exposure may be by ingestion, inhalation, injection, or direct contact. The reaction is mediated by IgE antibodies and produced by the immediate release of histamine, tryptase, arachidonate and derivatives by basophils and mast cells. This causes an inflammatory response leading to an immediate (within seconds to minutes) reaction. The reaction may be either local or systemic. Symptoms vary from mild irritation to sudden death from anaphylactic shock. Treatment usually involves epinephrine, antihistamines, and corticosteroids. - **Hay Fever** Hay fever involves an allergic reaction to pollen and results in allergic rhinitis (inflammation of the nasal mucosa). It is most common in the haying season, which is why the ailment was named hay fever. A virtually identical reaction occurs with allergy to mold, animal dander, dust, and similar inhaled allergens. Particulate matter in polluted air and chemicals such as chlorine and detergents, which can normally be tolerated, can greatly aggravate the condition. The pollens that cause hay fever vary from person to person and from region to region; generally speaking, the tiny, hardly visible pollens of wind-pollinated plants are the predominant culprits. ## Autoimmune Disorders For reasons we do not fully understand, sometimes the immune system attacks the body the way it normally would attack a germ or foreign substance. The genes some people inherit can contribute to their susceptibility to develop an autoimmune disease. Most autoimmune diseases affect woman more than men. - In **Juvenile-onset diabetes** the immune system starts attacking and eliminating the cells in the pancreas that make insulin. ```{=html} <!-- --> ``` - **Multiple Sclerosis** is a chronic degenerative disorder of the central nervous system where the immune system starts attacking and destroying vital myelin in the brain and spinal cord. This causes multiple sclerosis (scars) on the myelin sheath resulting in loss of nerve function. ```{=html} <!-- --> ``` - Another fairly known disorder is **Rheumatoid Arthritis** this is when the immune system starts attacking the tissue inside your joints. ```{=html} <!-- --> ``` - There is another disorder, **Organ and Tissue Transplants**, that is classified under immuno-deficiencies but in reality is not a failure of the immune system. In transplants, foreign tissue is placed inside the body. These tissues do not perfectly match the surrounding cells. The body sees this as something that should not be there and sends messages to attack and kill it. This can make transplanting nearly impossible. This problem can not be completely prevented but it can be diminished by making sure the donor tissue is a close match to the recipient tissue. In addition, the recipient is placed on immuno-suppressing drugs to try and prevent the immune system from attacking and rejecting the new organ or tissue. ```{=html} <!-- --> ``` - **Vitiligo** is an autoimmune disorder in which the immune system destroys pigment-making cells called melanocytes. This results in irregularly shaped milky-white patches of skin on different parts of the body. This is the condition which Michael Jackson claims to have had. ## Immunodeficiency Diseases When the immune system is presented with foreign antigens in association with dendritic cells, a vigorous immune response ensues. (Antigens are the molecules on the surface of invader cells that announce them as different from the body\'s cells.). Alternatively, dendritic cells can be exploited during the development of many immune based diseases. - **AIDS and HIV** Acquired immunodeficiency disease (AIDS) is a well-known immune system disease. Acquired Immune Deficiency Syndrome or Acquired immunodeficiency syndrome (AIDS or Aids) is a collection of symptoms and infections resulting from the specific damage to the immune system caused by the human immunodeficiency virus (HIV).The late stage of the condition leaves individuals prone to opportunistic infections and tumors. Although treatments for AIDS and HIV exist to slow the virus\'s progression, there is no known cure. HIV is transmitted through direct contact of a mucous membrane or the bloodstream with a bodily fluid containing HIV, such as blood, semen, vaginal fluid, preseminal fluid, and breast milk.This transmission can come in the form of anal, vaginal or oral sex, blood transfusion, contaminated hypodermic needles, exchange between mother and baby during pregnancy, childbirth, or breastfeeding, or other exposure to one of the above bodily fluids. AIDS is the most severe manifestation of infection with HIV. HIV is a retrovirus that primarily infects vital components of the human immune system such as CD4+ T cells (a subset of T cells), macrophages and dendritic cells. It directly and indirectly destroys CD4+ T cells. CD4+ T cells are required for the proper functioning of the immune system. When HIV kills CD4+ T cells so that there are fewer than 200 CD4+ T cells per microliter (µL) of blood, cellular immunity is lost, leading to the condition known as AIDS. Acute HIV infection progresses over time to clinical latent HIV infection and then to early symptomatic HIV infection and later to AIDS, which is identified on the basis of the amount of CD4+ T cells in the blood and the presence of certain infections. In the absence of antiretroviral therapy, the median time of progression from HIV infection to AIDS is nine to ten years, and the median survival time after developing AIDS is only 9.2 months. However, the rate of clinical disease progression varies widely between individuals, from two weeks up to 20 years. Many factors affect the rate of progression. These include factors that influence the body\'s ability to defend against HIV such as the infected person\'s general immune function. Older people have weaker immune systems, and therefore have a greater risk of rapid disease progression than younger people. Poor access to health care and the existence of coexisting infections such as tuberculosis also may predispose people to faster disease progression. The infected person\'s genetic inheritance plays an important role and some people are resistant to certain strains of HIV. ## Different Types of T Lymphocyte Cells Several different subsets of T cells have been described, each with a distinct function. ***Cytotoxic T cells*** (Tc cells) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8+ T cells, since they express the CD8 glycoprotein at their surface. ***Helper T cells***, (Th cells) are the \"middlemen\" of the adaptive immune system. Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or \"help\" the immune response. These cells (also called CD4+ T cells) are a target of HIV infection; the virus infects the cell by using the CD4 protein to gain entry. The loss of Th cells as a result of HIV infection leads to the symptoms of AIDS. ***Memory T cells*** are a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen, thus providing the immune system with \"memory\" against past infections. Memory cells may be either CD4+ or CD8+. ***Regulatory T cells*** (Treg cells), formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell mediated immunity towards the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Two major classes of regulatory T cells have been described, including the naturally occurring Treg cells and the adaptive Treg cells. ***Treg cells*** (also known as CD4+CD25+FoxP3+ Treg cells) arise in the thymus, whereas the adaptive Treg cells (also known as Tr1 cells or Th3 cells) may originate during a normal immune response. Naturally occurring Treg cells can be distinguished from other T cells by the presence of an intracellular molecule called FoxP3. Mutations of the FOXP3 gene can prevent regulatory T cell development, causing the fatal autoimmune disease IPEX. ***\'Natural** ***Killer T cells****\' (NKT cells) are a special kind of lymphocyte that bridges the adaptive immune system with the innate immune system. Unlike conventional T cells that recognize peptide antigen presented by major histocompatibility complex (MHC) molecules, NKT cells recognize glycolipid antigen presented by a molecule called CD1d. Once activated, these cells can perform functions ascribed to both Th and Tc cells (i.e. cytokine production and release of cytolytic/cell killing molecules). **THE FUNCTIONS OF T LYMPHOCYTES** T lymphocytes cells help with all components of the immune system, including cell elimination by killer T cells and maintaining roles by helper and suppressor T cells. Although the specific mechanisms of activation vary slightly between different types of T cells, the \"two-signal model\" in CD4+ T cells holds true for most. ## The Immune System Pioneers - Ilya Mechnikov and the Phagocyte Cells In 1882, a Russian scientist named Ilya Mechnikov was experimenting with the larvae of the sea star. He stuck a thorn in the larvae and then he noticed that something really weird happened. Strange cells started gathering near the point of insertion. The cells that were surrounding the thorn were eating any foreign substance that was entering through the ruptured skin. Mechnikov decided to name these new cells \"phagocytes\", in Greek meaning \"devouring cells.\" This discovery was very important since it helped scientists understand how the body defends itself against disease. If the phagocyte encountered anything foreign, they attack/arrest or destroy it; all dependent on the foreign substance. Phagocytes also play an important part in activating the immune response in the rest of the body. - Paul Ehrlich and the Side-chain Theory Ehrlich supposed that living cells have side-chains. These side chains can link with a particular toxin, just as Emil Fischer said enzymes must bind to their receptors \"like a key in a lock.\" He theorized that a cell under threat grew additional side-chains to bind the toxin, and that these additional side chains broke off to become the antibodies that circulate through the body. It was these antibodies that Ehrlich first described as \"magic bullets\" in search of toxins. Ehrlich figured that if a compound could be made that selectively targeted a disease causing organism, then a toxin for that organism could be delivered along with the agent of selectivity. Hence, a \"magic bullet\" would be created that killed only the organism targeted. Ehrlich predicted autoimmunity calling it \"horror autotoxicus\". In 1908, Ehrlich and Mechnikov received the Nobel Prize. ## Review Questions Answers for these questions can be found here 1-When neutrophils and macrophages squeeze out of capillaries to fight off infection it is called: : A\) phagocytosis : B\) hemolysis : C\) interleukin : D\) diapedesis : E\) folliculitis 2-During a great battle between your WBC\'s and an aggressive microbe, an inflammatory response has been initiated. Reddness and edema has kicked in what else does the body do to protect itself? : A\) Histamine cause vasodilation : B\) Hypothalmus raises the thermostat : C\) Neutrophils engulf and destroy the microbe : D\) Living and dead WBC and bacteria accumulate : E\) All of the above 3-Specificity and memory are associated with which body defense mechanism? : A\) inflammatory response : B\) phagocytosis by macrophages and neutrophils : C\) interferon : D\) T cell and B cell responses : E\) anatomical barriers in the body 4-An additional chemical defense found in tears and saliva? : A\) T lymphocytes : B\) saline : C\) lysozyme : D\) EFC 5-Which of the following does complement protein perform : A\) They cause antibody release : B\) T cell development : C\) The release if histamine : D\) Promotes tissue repair : E\) Mast cell degranulation 6-Which substance induces fever? : A\) Pyrogen : B\) Pus : C\) Monocytes : D\) Edema : E\) Interferon 7-Major function(s) of the lymphatic system is/are? : A\) provide route for return of extracellular fluid : B\) act as drain off for inflammatory response : C\) render surveillance, recognition , and protection against foreign materials via lymphocytes, phagocytes, and antibodies. : D\) a and c : E\) all of the above 8-An antigen is: : A\) a chemical messenger that is released by virus infected cells : B\) a lymphocyte responsible for cell-mediated immunity : C\) something that coats the inside of lungs, causing infection : D\) a protein or other molecule that is recognized as non-self : E\) a thick yellow-white fluid 9-A foreign substance, usually a protein, that stimulates the immune system to react, such as by producing antibodies is a \_\_\_\_\_\_\_\_\_\_\_\_\_\_. : A\) allergen : B\) antigen : C\) histamine : D\) mast cell : E\) interferon 10-When a macrophage ingests an invading bacteria and takes the antigen to a lymph node, what happens next? : A\) the macrophage will present it to the first B-cell it encounters, and the B-cell will in turn change its surface receptors to match the antigen : B\) a B-cell will only become activated if it already has a match for the antigen : C\) a matching B-cell will become activated into a cytotoxic T-cell : D\) the cells of the lymph node will release histamine : E\) the lymph node will increase production of neutrophils 11-What is the most common portal of entry for diseases, into the body? : A\) Respiratory system : B\) Endocrine system : C\) Hematacrit system : D\) Any opening into the body. 12-This gland shrinks in size during adulthood, and has hormones that function in maturation of T-lymphocytes: : A\) lymph nodes : B\) thymus : C\) spleen : D\) GALT : E\) tonsils 13-Which of the following is not a mechanical factor to protect the skin and mucous membranes from infection? : A\) Layers of cells : B\) Tears : C\) Saliva : D\) Lysozyme : E\) None of the above 14-Where is the site of maturation for a B cell? : A\) thymus : B\) bone marrow : C\) pancreas : D\) cortex 15-Nonspecific resistance is : A\) The body\'s ability to ward off diseases. : B\) The body\'s defenses against any kind of pathogen. : C\) The body\'s defense against a particular pathogen. : D\) The lack of resistance. : E\) None of the above. 16\. What is an Antibody? : A\) An antimicrobial substance applied to a living tissue to prevent infection. : B\) Programmed cell death : C\) A protein generated by the immune system in response to a foreign substance. : D\) A chemical involved in inflammation. # Glossary **Antibody**: Antibody or (immunoglobulin) is a protein generated by the immune system (B cells) in response to a foreign substance (antigen). **Antibody titer**: A test done to check the immunity of vaccination, when identification of a low immunity to a vaccine a booster shot can be given to increase the immunity. **Antigen**: Protein (or polysaccharide) molecule that the body recognizes as nonself. Substance body recognizes as foreign such as, fungi, viruses, protozoans, parasitic worms, pollen, poison ivy plant resin, insect venom, and transplanted organs. **Antiseptic**: Antimicrobial substance applied to living tissue or skin to prevent infection. **Apoptosis**: Programmed cell death **B Cell**: Lymphocytes that are responsible for antibody-mediated immunity **Basophils**: WBC that release histamine and other chemicals **Chemotaxis**: Movement of cells, phagocytes especially, they move in a specific direction in a tumbling fashion like rolling this is all due to a chemical stimulant. **Complement System**: Biochemical cascade of the immune system that helps clear pathogens from an organism, and promote healing **Cytokines**: Regulatory peptides that control cell development,differentiation, and the immune response **Dendritic**: cells that activate lymphocytes **Diapedesis**: The movement of WBC\'s from the blood to the surrounding tissue. A mechanism of the kind phagocyte that will walk or crawl out of the blood stream to site of infection. **Edema**: Swelling that forms when too much tissue fluid forms or not enough taken away **Eosinophils**: WBC that fight parasites and contribute to allergic reactions **Histamine**: Histamine is a chemical involved in inflammation, this chemical makes capillaries leaky, in this it will move more fluid out into the tissue spaces. **IgA**: Found in breast milk, mucus, saliva, and tears. This immunoglobulin functions to stop the pathogens before entry to the internal environment. **IgD**: This immunoglobulin is found on B-cells and function is not known. **IgE**: This immunoglobulin is combined with mast cells that in turn release histamine, this kind of globulin is released in the presence of an allergic response or parasitic infection. **IgG**: This immunoglobulin is the majority of the specific immunity against bacteria and viruses in the extracellular fluid. **IgM**: This immunoglobulin is associated to antibodies that react to incompatibility of ABO and Rh factor grouping. **Immunoglobulins**: Proteins that are antibodies receptors on the surface of B-cells, there are five classes. **Kinins**: Kinins is a chemical involved in inflammation, it is inactive in blood plasma but become activated by tissue damage and in turn stimulate pain receptors in skin. **Leukocytes**: primary cells of the immune system; also called white blood cells **Lymph**: fluid of the lymph system; originates as blood plasma that leaks from the capillaries of the circulatory system, becoming interstitial fluid, filling the space between individual cells of tissue **Lymphocytes**: The key cells that mediate the acquired immune response of the body **Lymph Nodes**: Small oval shaped structures located along the lymphatic vessels **Lysosome**: Organelle containing digestive enzymes (acid hydrolases) that digest viruses, bacteria, food particles and worn out organelles **Lysozyme**: Enzyme that attacks cell walls of bacteria and breaks them down; found and used as an antiseptic property in the body\'s first line of defense (ie. saliva, tears, sweat, etc) **Macrophages**: WBC that are the primary scavengers within tissues **Membrane Attack Complex (MAC)**: Work in the same way as the perforins of the NK cells that is it punches holes in the membrane that causes lysis. **Neutrophils**: WBC that \"eat\" bacteria and release cytokines **Opsonin**: Any substance that promotes a phagocytosis by binding a microbe to a phagocyte. **Perforin**: Protein secreted by cytotoxic T cells, causes pores to form in the plasma membrane of the target cell resulting in lysis. **Peyer's Patches**: located in the wall of the intestine and the appendix, attached to the cecum of the large intestine, intercept pathogens that come into the body through the intestinal tract **Phagocytes**: WBC that engulf and ingest their targets by phagocytosis **Pyrogens**: Foreign substances and or microorganisms that causes hypothalamic thermoregulatory center to increase and causes fever (pyrexia) **Right Lymphatic Duct**: Lymphatic duct that serves all of the right side of the upper body and thorasic area(head,neck) **Spleen**: Ductless, vertebrate gland that is closely associated with the circulatory system, where it functions in the destruction of old red blood cells in holding a reservoir of blood **T Cell**: cells that carry out cell-mediated immunity **Thoracic Duct**: Lymphatic duct that serves the abdomen, lower extremities and the left side of the upper body(head,neck, and arm) **Thymus Gland**: Gland that contains lymphocytes; produces thymosin that is thought to aid in the maturation of T lymphocytes
# Human Physiology/The Urinary System !450 px\|right ## Introduction The **Urinary System** is a group of organs in the body concerned with filtering out excess fluid and other substances from the bloodstream. The substances are filtered out from the body in the form of **urine**. Urine is a liquid produced by the kidneys, collected in the bladder and excreted through the urethra. Urine is used to extract excess minerals or vitamins as well as blood corpuscles from the body. The Urinary organs include the kidneys, ureters, bladder, and urethra. The Urinary system works with the other systems of the body to help maintain homeostasis. The kidneys are the main organs of homeostasis because they maintain the acid base balance and the water salt balance of the blood. ## Functions of the Urinary System One of the major functions of the Urinary system is the process of excretion. Excretion is the process of eliminating, from an organism, waste products of metabolism and other materials that are of no use. The urinary system maintains an appropriate fluid volume by regulating the amount of water that is excreted in the urine. Other aspects of its function include regulating the concentrations of various electrolytes in the body fluids and maintaining normal pH of the blood. Several body organs carry out excretion, but the kidneys are the most important excretory organ. The primary function of the kidneys is to maintain a stable internal environment (homeostasis) for optimal cell and tissue metabolism. They do this by separating urea, mineral salts, toxins, and other waste products from the blood. They also do the job of conserving water, salts, and electrolytes. At least one kidney must function properly for life to be maintained. **Six important roles of the kidneys are:** **Regulation of plasma ionic composition.** Ions such as sodium, potassium, calcium, magnesium, chloride, bicarbonate, and phosphates are regulated by the amount that the kidney excretes. **Regulation of plasma osmolarity.** The kidneys regulate osmolarity because they have direct control over how many ions and how much water a person excretes. **Regulation of plasma volume.** Your kidneys are so important they even have an effect on your blood pressure. The kidneys control plasma volume by controlling how much water a person excretes. The plasma volume has a direct effect on the total blood volume, which has a direct effect on your blood pressure. Salt(NaCl)will cause osmosis to happen; the diffusion of water into the blood. **Regulation of plasma hydrogen ion concentration (pH).** The kidneys partner up with the lungs and they together control the pH. The kidneys have a major role because they control the amount of bicarbonate excreted or held onto. The kidneys help maintain the blood Ph mainly by excreting hydrogen ions and reabsorbing bicarbonate ions as needed. **Removal of metabolic waste products and foreign substances from the plasma.** One of the most important things the kidneys excrete is nitrogenous waste. As the liver breaks down amino acids it also releases ammonia. The liver then quickly combines that ammonia with carbon dioxide, creating **urea** which is the primary nitrogenous end product of metabolism in humans. The liver turns the ammonia into urea because it is much less toxic. We can also excrete some ammonia, creatinine and uric acid. The **creatinine** comes from the metabolic breakdown of creatine phospate (a high-energy phosphate in muscles). **Uric acid** comes from the break down of nucleotides. Uric acid is insoluble and too much uric acid in the blood will build up and form crystals that can collect in the joints and cause gout. **Secretion of Hormones** The endocrine system has assistance from the kidney\'s when releasing hormones. Renin is released by the kidneys. Renin leads to the secretion of aldosterone which is released from the adrenal cortex. Aldosterone promotes the kidneys to reabsorb the sodium (Na+) ions. The kidneys also secrete erythropoietin when the blood doesn\'t have the capacity to carry oxygen. Erythropoietin stimulates red blood cell production. The Vitamin D from the skin is also activated with help from the kidneys. Calcium (Ca+) absorption from the digestive tract is promoted by vitamin D. **CC: Chapter Check: Name the role of the kidneys and how they work?** !700 px\|center ## Organs in the Urinary System ### Kidneys And Their Structure !Kidney Diagram: 1. Renal pyramid 2. Interlobar artery 3. Renal artery 4. Renal vein 5. Renal hylum 6. Renal pelvis 7. Ureter 8. Minor calyx 9. Renal capsule 10. Inferior renal capsule 11. Superior renal capsule 12. Interlobar vein 13. Nephron 14. Minor calyx 15. Major calyx 16. Renal papilla 17. Renal column{width="250"} The **kidneys** are a pair of bean shaped, brown organs about the size of your fist.It measures 10-12 cm long. They are covered by the renal capsule, which is a tough capsule of fibrous connective tissue. Adhering to the surface of each kidney is two layers of fat to help cushion them. There is a concaved side of the kidney that has a depression where a renal artery enters, and a renal vein and a ureter exit the kidney. The kidneys are located at the rear wall of the abdominal cavity just above the waistline, and are protected by the ribcage. They are considered retroperitoneal, which means they lie behind the peritoneum. There are three major regions of the kidney, **renal cortex**, **renal medulla** and the **renal pelvis**. The outer, granulated layer is the renal cortex. The cortex stretches down in between a radially striated inner layer. The inner radially striated layer is the renal medulla. This contains pyramid shaped tissue called the renal pyramids, separated by renal columns. The ureters are continuous with the renal pelvis and is the very center of the kidney. #### Renal Vein The **renal veins** are veins that drain the kidney. They connect the kidney to the inferior vena cava. Because the inferior vena cava is on the right half of the body, the left renal vein is generally the longer of the two. Unlike the right renal vein, the left renal vein often receives the left gonadal vein (left testicular vein in males, left ovarian vein in females). It frequently receives the left suprarenal vein as well. #### Renal Artery The **renal arteries** normally arise off the abdominal aorta and supply the kidneys with blood. The arterial supply of the kidneys are variable and there may be one or more renal arteries supplying each kidney. Due to the position of the aorta, the inferior vena cava and the kidneys in the body, the right renal artery is normally longer than the left renal artery. The right renal artery normally crosses posteriorly to the inferior vena cava. The renal arteries carry a large portion of the total blood flow to the kidneys. Up to a third of the total cardiac output can pass through the renal arteries to be filtered by the kidneys. ### Ureters The **ureters** are two tubes that drain urine from the kidneys to the bladder. Each ureter is a muscular tube about 10 inches (25 cm) long. Muscles in the walls of the ureters send the urine in small spurts into the bladder, (a collapsible sac found on the forward part of the cavity of the bony pelvis that allows temporary storage of urine). After the urine enters the bladder from the ureters, small folds in the bladder mucosa act like valves preventing backward flow of the urine. The outlet of the bladder is controlled by a sphincter muscle. A full bladder stimulates sensory nerves in the bladder wall that relax the sphincter and allow release of the urine. However, relaxation of the sphincter is also in part a learned response under voluntary control. The released urine enters the urethra. ### Urinary Bladder The **urinary bladder** is a hollow, muscular and distendible or elastic organ that sits on the pelvic floor (superior to the prostate in males). On its anterior border lies the pubic symphysis and, on its posterior border, the vagina (in females) and rectum (in males). The urinary bladder can hold approximately 17 to 18 ounces (500 to 530 ml) of urine, however the desire to micturate is usually experienced when it contains about 150 to 200 ml. When the bladder fills with urine (about half full), stretch receptors send nerve impulses to the spinal cord, which then sends a reflex nerve impulse back to the sphincter (muscular valve) at the neck of the bladder, causing it to relax and allow the flow of urine into the urethra. The Internal urethral sphincter is involuntary. The ureters enter the bladder diagonally from its dorsolateral floor in an area called the trigone. The trigone is a triangular shaped area on the postero-inferior wall of the bladder. The urethra exits at the lowest point of the triangle of the trigone. The urine in the bladder also helps regulate body temperature. A bladder when operating normally empties completely upon a complete discharge, otherwise it is a sign that its elasticity is compromised, when it becomes completely void of fluid, it may cause a chilling sensation due to the rapid change of body temperature. ### Urethra !250 px\|thumb\|left\|Female urethra (labeled at bottom right.)") !200 px\|thumb\|right\|Male Sphincter urethrae muscle - The male urethra laid open on its anterior (upper) surface. (Region visible, but muscle not labeled.) surface. (Region visible, but muscle not labeled.)") The **urethra** is a muscular tube that connects the bladder with the outside of the body. The function of the urethra is to remove urine from the body. It measures about 1.5 inches (3.8 cm) in a woman but up to 8 inches (20 cm) in a man. Because the urethra is so much shorter in a woman it makes it much easier for a woman to get harmful bacteria in her bladder this is commonly called a bladder infection or a UTI. The most common bacteria of a UTI is E-coli from the large intestines that have been excreted in fecal matter. **Female urethra** In the human female, the urethra is about 1-2 inches long and opens in the vulva between the clitoris and the vaginal opening. Men have a longer urethra than women. This means that women tend to be more susceptible to infections of the bladder (cystitis) and the urinary tract. **Male urethra** In the human male, the urethra is about 8 inches long and opens at the end of the head of the penis. The length of a male\'s urethra, and the fact it contains a number of bends, makes catheterisation more difficult. The **urethral sphincter** is a collective name for the muscles used to control the flow of urine from the urinary bladder. These muscles surround the urethra, so that when they contract, the urethra is closed. - There are two distinct areas of muscle: the internal sphincter, at the bladder neck and - the external, or distal, sphincter. Human males have much stronger sphincter muscles than females, meaning that they can retain a large amount of urine for twice as long, as much as 800mL, i.e. \"hold it\". ### Nephrons A nephron is the basic structural and functional unit of the kidney. The name nephron comes from the Greek word (nephros) meaning kidney. Its chief function is to regulate water and soluble substances by filtering the blood, reabsorbing what is needed and excreting the rest as urine. Nephrons eliminate wastes from the body, regulate blood volume and pressure, control levels of electrolytes and metabolites, and regulate blood pH. Its functions are vital to life and are regulated by the endocrine system by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone. Each nephron has its own supply of blood from two capillary regions from the renal artery. Each nephron is composed of an initial filtering component (the renal corpuscle) and a tubule specialized for reabsorption and secretion (the renal tubule). The renal corpuscle filters out large solutes from the blood, delivering water and small solutes to the renal tubule for modification. #### Glomerulus The glomerulus is a capillary tuft that receives its blood supply from an afferent arteriole of the renal circulation. The glomerular blood pressure provides the driving force for fluid and solutes to be filtered out of the blood and into the space made by Bowman\'s capsule. The remainder of the blood not filtered into the glomerulus passes into the narrower efferent arteriole. It then moves into the vasa recta, which are collecting capillaries intertwined with the convoluted tubules through the interstitial space, where the reabsorbed substances will also enter. This then combines with efferent venules from other nephrons into the renal vein, and rejoins with the main bloodstream. **Afferent/Efferent Arterioles** The afferent arteriole supplies blood to the glomerulus. A group of specialized cells known as **juxtaglomerular cells** are located around the afferent arteriole where it enters the renal corpuscle. The efferent arteriole drains the glomerulus. Between the two arterioles lies specialized cells called the **macula densa.** The juxtaglomerular cells and the macula densa collectively form the **juxtaglomerular apparatus.** It is in the juxtaglomerular apparatus cells that the enzyme **renin** is formed and stored. Renin is released in response to decreased blood pressure in the afferent arterioles, decreased sodium chloride in the distal convoluted tubule and sympathetic nerve stimulation of receptors (beta-adrenic) on the juxtaglomerular cells. Renin is needed to form Angiotensin I and Angiotensin II which stimulate the secretion of aldosterone by the adrenal cortex. #### Glomerular Capsule or Bowman\'s Capsule **Bowman\'s capsule** (also called the **glomerular capsule**) surrounds the glomerulus and is composed of visceral (simple squamous epithelial cells) (inner) and parietal (simple squamous epithelial cells) (outer) layers. The visceral layer lies just beneath the thickened glomerular basement membrane and is made of podocytes which send foot processes over the length of the glomerulus. Foot processes interdigitate with one another forming filtration slits that, in contrast to those in the glomeruluar endothelium, are spanned by diaphragms. The size of the filtration slits restricts the passage of large molecules (e.g., albumin) and cells (e.g., red blood cells and platelets). In addition, foot processes have a negatively-charged coat (glycocalyx) that limits the filtration of negatively-charged molecules, such as albumin. This action is called electrostatic repulsion. The parietal layer of Bowman\'s capsule is lined by a single layer of squamous epithelium. Between the visceral and parietal layers is Bowman\'s space, into which the filtrate enters after passing through the podocytes\' filtration slits. It is here that smooth muscle cells and macrophages lie between the capillaries and provide support for them. Unlike the visceral layer, the parietal layer does not function in filtration. Rather, the filtration barrier is formed by three components: the diaphragms of the filtration slits, the thick glomerular basement membrane, and the glycocalyx secreted by podocytes. 99% of glomerular filtrate will ultimately be reabsorbed. The process of filtration of the blood in the Bowman\'s capsule is ultrafiltration (or glomerular filtration), and the normal rate of filtration is 125 ml/min, equivalent to ten times the blood volume daily. Measuring the glomerular filtration rate (GFR) is a diagnostic test of kidney function. A decreased GFR may be a sign of renal failure. Conditions that can affect GFR include: arterial pressure, afferent arteriole constriction, efferent arteriole constriction, plasma protein concentration and colloid osmotic pressure. Any proteins that are roughly 30 kilodaltons or under can pass freely through the membrane. Although, there is some extra hindrance for negatively charged molecules due to the negative charge of the basement membrane and the podocytes. Any small molecules such as water, glucose, salt (NaCl), amino acids, and urea pass freely into Bowman\'s space, but cells, platelets and large proteins do not. As a result, the filtrate leaving the Bowman\'s capsule is very similar to blood plasma in composition as it passes into the proximal convoluted tubule. Together, the glomerulus and Bowman\'s capsule are called the renal corpuscle. #### Proximal Convoluted Tubule (PCT) The proximal tubule can be anatomically divided into two segments: the proximal convoluted tubule and the proximal straight tubule. The proximal convoluted tubule can be divided further into S1 and S2 segments based on the histological appearance of it\'s cells. Following this naming convention, the proximal straight tubule is commonly called the S3 segment. The proximal convoluted tubule has one layer of cuboidal cells in the lumen. This is the only place in the nephron that contains cuboidal cells. These cells are covered with millions of microvilli. The microvilli serve to increase surface area for reabsorption. Fluid in the filtrate entering the proximal convoluted tubule is reabsorbed into the peritubular capillaries, including approximately two-thirds of the filtered salt and water and all filtered organic solutes (primarily glucose and amino acids). This is driven by sodium transport from the lumen into the blood by the Na+/K+ ATPase in the basolateral membrane of the epithelial cells. Much of the mass movement of water and solutes occurs in between the cells through the tight junctions, which in this case are not selective. The solutes are absorbed isotonically, in that the osmotic potential of the fluid leaving the proximal tubule is the same as that of the initial glomerular filtrate. However, glucose, amino acids, inorganic phosphate, and some other solutes are reabsorbed via secondary active transport through cotransport channels driven by the sodium gradient out of the nephron. #### Loop of the Nephron or Loop of Henle !The Nephron Loop or Loop of Henle.{width="450"} The loop of Henle (sometimes known as the nephron loop) is a U-shaped tube that consists of a descending limb and ascending limb. It begins in the cortex, receiving filtrate from the proximal convoluted tubule, extends into the medulla, and then returns to the cortex to empty into the distal convoluted tubule. Its primary role is to concentrate the salt in the interstitium, the tissue surrounding the loop. Descending limb:Its descending limb is permeable to water but completely impermeable to salt, and thus only indirectly contributes to the concentration of the interstitium. As the filtrate descends deeper into the hypertonic interstitium of the renal medulla, water flows freely out of the descending limb by osmosis until the tonicity of the filtrate and interstitium equilibrate. Longer descending limbs allow more time for water to flow out of the filtrate, so longer limbs make the filtrate more hypertonic than shorter limbs. ```{=html} <!-- --> ``` Ascending limb:Unlike the descending limb, the ascending limb of Henle\'s loop is impermeable to water, a critical feature of the countercurrent exchange mechanism employed by the loop. The ascending limb actively pumps sodium out of the filtrate, generating the hypertonic interstitium that drives countercurrent exchange. In passing through the ascending limb, the filtrate grows hypotonic since it has lost much of its sodium content. This hypotonic filtrate is passed to the distal convoluted tubule in the renal cortex. #### Distal Convoluted Tubule (DCT) The distal convoluted tubule is similar to the proximal convoluted tubule in structure and function. Cells lining the tubule have numerous mitochondria, enabling active transport to take place by the energy supplied by ATP. Much of the ion transport taking place in the distal convoluted tubule is regulated by the endocrine system. In the presence of parathyroid hormone, the distal convoluted tubule reabsorbs more calcium and excretes more phosphate. When aldosterone is present, more sodium is reabsorbed and more potassium excreted. Atrial natriuretic peptide causes the distal convoluted tubule to excrete more sodium. In addition, the tubule also secretes hydrogen and ammonium to regulate pH. After traveling the length of the distal convoluted tubule, only 3% of water remains, and the remaining salt content is negligible. 97.9% of the water in the glomerular filtrate enters the convoluted tubules and collecting ducts by osmosis. #### Collecting ducts Each distal convoluted tubule delivers its filtrate to a system of collecting ducts, the first segment of which is the connecting tubule. The collecting duct system begins in the renal cortex and extends deep into the medulla. As the urine travels down the collecting duct system, it passes by the medullary interstitium which has a high sodium concentration as a result of the loop of Henle\'s countercurrent multiplier system. Though the collecting duct is normally impermeable to water, it becomes permeable in the presence of antidiuretic hormone (ADH). As much as three-fourths of the water from urine can be reabsorbed as it leaves the collecting duct by osmosis. Thus the levels of ADH determine whether urine will be concentrated or dilute. Dehydration results in an increase in ADH, while water sufficiency results in low ADH allowing for diluted urine. Lower portions of the collecting duct are also permeable to urea, allowing some of it to enter the medulla of the kidney, thus maintaining its high ion concentration (which is very important for the nephron). Urine leaves the medullary collecting ducts through the renal papilla, emptying into the renal calyces, the renal pelvis, and finally into the bladder via the ureter. Because it has a different embryonic origin than the rest of the nephron (the collecting duct is from endoderm whereas the nephron is from mesoderm), the collecting duct is usually not considered a part of the nephron proper. **Renal Hormones** 1\. Vitamin D- Becomes metabolically active in the kidney. Patients with renal disease have symptoms of disturbed calcium and phosphate balance. 2\. Erythropoietin- Released by the kidneys in response to decreased tissue oxygen levels (hypoxia). 3\. Natriuretic Hormone- Released from cardiocyte granules located in the right atria of the heart in response to increased atrial stretch. It inhibits ADH secretions which can contribute to the loss of sodium and water. ## Formation of Urine Urine is formed in three steps: Filtration, Reabsorption, and Secretion. ### Filtration Blood enters the afferent arteriole and flows into the glomerulus. Blood in the glomerulus has both filterable blood components and non-filterable blood components. Filterable blood components move toward the inside of the glomerulus while non-filterable blood components bypass the filtration process by exiting through the efferent arteriole. Filterable Blood components will then take a plasma like form called glomerular filtrate. A few of the filterable blood components are water, nitrogenous waste, nutrients and salts (ions). Nonfilterable blood components include formed elements such as blood cells and platelets along with plasma proteins. The glomerular filtrate is not the same consistency as urine, as much of it is reabsorbed into the blood as the filtrate passes through the tubules of the nephron. ### Reabsorption Within the peritubular capillary network, molecules and ions are reabsorbed back into the blood. Sodium Chloride reabsorbed into the system increases the osmolarity of blood in comparison to the glomerular filtrate. This reabsorption process allows water (H2O) to pass from the glomerular filtrate back into the circulatory system. Glucose and various amino acids also are reabsorbed into the circulatory system. These nutrients have carrier molecules that claim the glomerular molecule and release it back into the circulatory system. If all of the carrier molecules are used up, excess glucose or amino acids are set free into the urine. A complication of diabetes is the inability of the body to reabsorb glucose. If too much glucose appears in the glomerular filtrate it increases the osmolarity of the filtrate, causing water to be released into the urine rather than reabsorbed by the circulatory system. Frequent urination and unexplained thirst are warning signs of diabetes, due to water not being reabsorbed. Glomerular filtrate has now been separated into two forms: Reabsorbed Filtrate and Non-reabsorbed Filtrate. Non-reabsorbed filtrate is now known as tubular fluid as it passes through the collecting duct to be processed into urine. ### Secretion Some substances are removed from blood through the peritubular capillary network into the distal convoluted tubule or collecting duct. These substances are Hydrogen ions, creatinine, and drugs. Urine is a collection of substances that have not been reabsorbed during glomerular filtration or tubular reabsorbtion. ## Maintaining Water-Salt Balance It is the job of the kidneys to maintain the water-salt balance of the blood. They also maintain blood volume as well as blood pressure. Simple examples of ways that this balance can be changed include ingestion of water, dehydration, blood loss and salt ingestion. ### Reabsorption of water Direct control of water excretion in the kidneys is exercised by the anti-diuretic hormone (ADH), released by the posterior lobe of the pituitary gland. ADH causes the insertion of water channels into the membranes of cells lining the collecting ducts, allowing water reabsorption to occur. Without ADH, little water is reabsorbed in the collecting ducts and dilute urine is excreted. There are several factors that influence the secretion of ADH. The first of these happen when the blood plasma gets too concentrated. When this occurs, special receptors in the hypothalamus release ADH. When blood pressure falls, stretch receptors in the aorta and carotid arteries stimulate ADH secretion to increase volume of the blood. ### Reabsorption of Salt The Kidneys also regulate the salt balance in the blood by controlling the excretion and the reabsorption of various ions. As noted above, ADH plays a role in increasing water reabsorption in the kidneys, thus helping to dilute bodily fluids. The kidneys also have a regulated mechanism for reabsorbing sodium in the distal nephron. This mechanism is controlled by aldosterone, a steroid hormone produced by the adrenal cortex. Aldosterone promotes the excretion of potassium ions and the reabsorption of sodium ions. The release of Aldosterone is initiated by the kidneys. The juxtaglomerular apparatus is a renal structure consisting of the macula densa, mesangial cells, and juxtaglomerular cells. Juxtaglomerular cells (JG cells, also known as granular cells) are the site of renin secretion. Renin is an enzyme that converts angiotensinogen (a large plasma protein produced by the liver) into Angiotensin I and eventually into Angiotensin II which stimulates the adrenal cortex to produce aldosterone. The reabsorption of sodium ions is followed by the reapsorption of water. This causes blood pressure as well as blood volume to increase. **Atrial natriuretic hormone (ANH**) is released by the atria of the heart when cardiac cells are stretched due to increased blood volume. ANH inhibits the secretion of renin by the juxtaglomerular apparatus and the secretion of the aldosterone by the adrenal cortex. This promotes the excretion of sodium. When sodium is excreted so is water. This causes blood pressure and volume to decrease. #### Hypernatremia An increase in plasma sodium levels above normal is **hypernatremia**. Sodium is the primary solute in the extracellular fluid. Sodium levels have a major role in osmolarity regulation. For excitable cells the electrochemical gradient for sodium across the plasma membrane is critical for life. Water retention and an increased blood pressure usually are signs of hypernatremia. If the plasma sodium levels are below normal it is called **hyponatremia**. Signs of this are low plasma volume and hypotension. #### Diuretics A diuretic (colloquially called a water pill) is any drug that elevates the rate of bodily urine excretion (diuresis). Diuretics also decrease the extracellular fluid (ECF) volume, and are primarily used to produce a negative extracellular fluid balance. Caffeine, cranberry juice and alcohol are all weak diuretics. In medicine, diuretics are used to treat heart failure, liver cirrhosis, hypertension and certain kidney diseases. Diuretics alleviate the symptoms of these diseases by causing sodium and water loss through the urine. As urine is produced by the kidney, sodium and water -- which cause edema related to the disease -- move into the blood to replace the volume lost as urine, thereby reducing the pathological edema. Some diuretics, such as acetazolamide, help to make the urine more alkaline and are helpful in increasing excretion of substances such as aspirin in cases of overdose or poisoning. The antihypertensive actions of some diuretics (thiazides and loop diuretics in particular) are independent of their diuretic effect. That is, the reduction in blood pressure is not due to decreased blood volume resulting from increased urine production, but occurs through other mechanisms and at lower doses than that required to produce diuresis. Indapamide was specifically designed with this is mind, and has a larger therapeutic window for hypertension (without pronounced diuresis) than most other diuretics. Chemically, diuretics are a diverse group of compounds that either stimulate or inhibit various hormones that naturally occur in the body to regulate urine production by the kidneys. Alcohol produces diuresis through modulation of the vasopressin system. ## Diseases of the Kidney **Diabetic nephropathy** (nephropatia diabetica), also known as Kimmelstiel-Wilson syndrome and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nodular glomerulosclerosis. It is due to longstanding diabetes mellitus, and is a prime cause for dialysis in many Western countries. !An image of a **kidney stone**. In medicine, **hematuria** (or \"haematuria\") is the presence of blood in the urine. It is a sign of a large number of diseases of the kidneys and the urinary tract, ranging from trivial to lethal. **Kidney stones**, also known as nephrolithiases, urolithiases or renal calculi, are solid accretions (crystals) of dissolved minerals in urine found inside the kidneys or ureters. They vary in size from as small as a grain of sand to as large as a golf ball. Kidney stones typically leave the body in the urine stream; if they grow relatively large before passing (on the order of millimeters), obstruction of a ureter and distention with urine can cause severe pain most commonly felt in the flank, lower abdomen and groin. Kidney stones are unrelated to gallstones. **Case Study** I was 34 weeks pregnant when I noticed blood in my urine. I immediately went to my OBGYN where I was told that I had a bladder infection and given an antibiotic. The next morning I experienced the most intense pain. I was rushed to the ER where I was told that I had kidney stones. The doctors explained that there was nothing they could do as long as I was pregnant. The next 3 weeks of my life were filled with intense pain and multiple painkillers. After I delivered my baby, CAT scans were done and I was informed that I had 6 kidney stones. It took three more weeks for me to pass all of the stones the largest measuring 5 mm. The stones were tested and I was informed that my body had been building up calcium due to my pregnancy and this was the cause of the kidney stones. I continued to have kidney pain for 6 months after passing the stones. I now live my life on a low calcium diet and the hope that my body will not develop more kidney stones. **Pyelonephritis** When an infection of the renal pelvis and calices, called pyelitis, spreads to involve the rest of the kidney as well, the result is pyelonephritis. It usually results from the spread of fecal bacterium Escherichia coli from the anal region superiorly through the urinary tract. In severe cases, the kidney swells and scars, abscesses form, and the renal pelvis fills with pus. Left untreated, the infected kidney may be severely damaged, but administration of antibiotics usually achieve a total cure. **glomerulonephritis** Inflammation of the glomerular can be caused by immunologic abnormalities, drugs or toxins, vascular disorders, and systemic diseases. Glomerulonephritis can be acute, chronic or progressive. Two major changes in the urine are distinctive of glomerulonephritis: hematuria and proteinuria with albumin as the major protein. There is also a decrease in urine as there is a decrease in GFR (glomerular filtration rate). Renal failure is associated with oliguria (less than 400 ml of urine output per day). **Renal Failure** Uremia is a syndrome of renal failure and includes elevated blood urea and creatinine levels. Acute renal failure can be reversed if diagnosed early. Acute renal failure can be caused by severe hypotension or severe glomerular disease. Diagnostic tests include BUN and plasma creatinine level tests. It is considered to be chronic renal failure if the decline of renal function to less than 25%. ## Diabetes Insipidus This is caused by the deficiency of or decrease of ADH. The person with (DI) has the inability to concentrate their urine in water restriction, in turn they will void up 3 to 20 liters/day. There are two forms of (DI), neurogenic, and nephrogenic. In nephrogenic (DI) the kidneys do not respond to ADH. Usually the nephrogenic (DI) is characterized by the impairment of the urine concentrating capability of the kidney along with concentration of water. The cause may be a genetic trait, electrolyte disorder, or side effect of drugs such as lithium. In the neurogenic (DI), it is usually caused by head injury near the hypophysisal tract. ## Urinary tract infections (UTI\'s) The second most common type of bacterial infections seen by health care providers is UTI\'s. Out of all the bacterias that colonize and cause urinary tract infections the big gun is *Escherichia coli*. In the hospital indwelling catheters and straight catheterizing predispose the opportunity for urinary tract infections. In females there are three stages in life that predispose urinary tract infections, that is menarche, manipulation between intercourse, and menopause. However, a small percentage of men and children will get urinary tract infections. In men it is usually due to the prostate gland growth which usually occurs in older age men. In children it can occur 3% to 5% in girls and 1% in boys, uncircumcised boys it is more common than circumcised ones to have a urinary tract infection, in girls it may be the result of onset of toilet training, some predispositions for getting urinary tract infection include family history and urinary tract anomalies. In neonates urinary tract infections is most common when bacteremia is present. ## Dialysis and Kidney Transplant !Plugged into dialysis{width="200"} Generally, humans can live normally with just one kidney. Only when the amount of functioning kidney tissue is greatly diminished will renal failure develop. If renal function is impaired, various forms of medications are used, while others are contraindicated. Provided that treatment is begun early, it may be possible to reverse chronic kidney failure due to diabetes or high blood pressure. If creatinine clearance (a measure of renal function) has fallen very low (\"end-stage renal failure\"), or if the renal dysfunction leads to severe symptoms, dialysis is commenced. Dialysis is a medical procedure, performed in various different forms, where the blood is filtered outside of the body. Kidney transplantation is the only cure for end stage renal failure; dialysis, is a supportive treatment; a form of \"buying time\" to bridge the inevitable wait for a suitable organ. The first successful kidney transplant was announced on March 4, 1954 at Peter Bent Brigham Hospital in Boston. The surgery was performed by Dr. Joseph E. Murray, who was awarded the Nobel Prize in Medicine in 1990 for this feat. There are two types of kidney transplants: living donor transplant and a cadaveric (dead donor) transplant. When a kidney from a living donor, usually a blood relative, is transplanted into the patient\'s body, the donor\'s blood group and tissue type must be judged compatible with the patient\'s, and extensive medical tests are done to determine the health of the donor. Before a cadaveric donor\'s organs can be transplanted, a series of medical tests have to be done to determine if the organs are healthy. Also, in some countries, the family of the donor must give its consent for the organ donation. In both cases, the recipient of the new organ needs to take drugs to suppress their immune system to help prevent their body from rejecting the new kidney. ## Review Questions Answers for these questions can be found here 1\. While reading a blood test I notice a high level of creatinine, I could assume from this that : A\) There is a possibility of a UTI : B\) There is a possibility of diabetes : C\) There is a possibility of kidney failure : D\) There is nothing wrong, this is normal 2\. Direct control of water excretion in the kidneys is controlled by : A\) Anti-diuretic hormone : B\) The medulla oblongata : C\) Blood plasma : D\) Sodium amounts in the blood 3\. Nephrons : A\) Eliminate wastes from the body : B\) Regulate blood volume and pressure : C\) Control levels of electrolytes and metabolites : D\) Regulate blood pH : E\) All of the above 4\. If I am dehydrated, my body will increase : A\) ATP : B\) ADP : C\) Diluted urine : D\) ADH 5\. Which part of the nephron removes water, ions and nutrients from the blood? : A ) vasa recta : B ) loop of henle : C ) proximal convoluted tubule : D ) peritubular capillaries : E ) glomerulus 6\. Kidneys have a direct effect on which of the following : A ) Blood pressure : B ) How much water a person excretes : C ) Total blood volume : D ) pH : E ) all of the above 7\. Why do substances in the glomerulus enter the Bowman\'s capsule? : A ) the magnetic charge of the Bowman\'s capsule attracts the substances : B ) the substances are actively transported into the Bowman\'s capsule : C ) blood pressure of the glomerulus is so great that most substances in blood move into capsule : D ) little green men force it in with their ray guns 8\. What happens in tubular excretion? : A ) urine bonds are formed between the wastes : B ) wastes are diffused from the tubule : C ) wastes move into the distal convoluted tubule from the blood : D ) blood pressure forces wastes away from the kidney 9\. The countercurrent exchange system includes\_\_\_\_\_\_\_\_\_and\_\_\_\_\_\_\_\_\_. : A ) glomerulus and macula densa : B ) proximal convoluted tubule and distal convoluted tubule : C ) loop of Henle and collecting tubule : D ) afferent arteriole and efferent arteriole : E ) ureters and bladder 10\. The function of the loop of the nephron in the process of urine formation is: : A ) reabsorption of water : B ) production of filtrate : C ) reabsorption of solutes : D ) secretion of solutes 11\. Name the six important roles of the kidneys. ## Glossary **Antidiuretic:** lessening or decreasing of urine production or an agent that decreases the release of urine. **Catheterisation:** a catheter is a tube that can be inserted into a body cavity, duct or vessel. Catheters thereby allow drainage or injection of fluids or access by surgical instruments. The process of inserting a catheter is catheterisation. In most uses a catheter is a thin, flexible tube: a \"soft\" catheter; in some uses, it is a larger, solid tube: a \"hard\" catheter. **Dehydration:** condition resulting from excessive loss of body fluid. **Diabetes:** a general term for a disease characterized by the beginning stages and onset of renal failure. It is derived from the Greek word diabaínein, that literally means \"passing through,\" or \"siphon\", a reference to one of diabetes\' major symptoms---excessive urine production. **Diuresis:** secretion and passage of large amounts of urine. **Diuretic:** increasing of urine production, or an agent that increases the production of urine. **Erythropoietin:** hormone that stimulates stem cells in the bone marrow to produce red blood cells **Fibrous Capsule:** the kidney\'s loose connective tissue **Glomerulus:** capillary tuft that receives its blood supply from an afferent arteriole of the renal circulation. **Gluconeogenesis:** the cycle of producing a glucose form fat or protein; preformed by the kidney in times of long fasting, initially gluconeogenesis is preformed by the liver **Juxtaglomerular (JG) cells:** Renin-secreting cells that are in contact with the macula densa and the afferent arterioles of the renal nephron. **Juxtaglomerular apparatus (JGA):** A site of juxtaglomerular cells connecting with the macula densa where renin is secreted and sensor for control of secretion of golmerular filtration rate. **Loop of Henle/ Nephron Loop:** u-shaped tube that consists of a descending limb and ascending limb; primary role is to concentrate the salt in the interstitium, the tissue surrounding the loop **Medullary Pyramids or Renal Pyramids:** the cone shaped masses in the kidney **Micturition:** another name for excretions **Nephron:** basic structural and functional unit of the kidney; chief function is to regulate water and soluble substances by filtering the blood, reabsorbing what is needed and excreting the rest as urine **Podocytes:** filtration membrane, in the visceral layer of the bowman\'s capsule **Renal Calculi:** kidney stones, solid crystals of dissolved minerals in urine found inside the kidneys **Renal Cortex:** outer portion of the kidney **Renal Lobe:** each pyramid together with the associated overlying cortex **Renal Pelvis:** a central space, or cavity that transmits urine to the urinary bladder via the ureter **Renin:** hormone released by the Juxtaglomerular (JG) cells of the kidneys when blood pressure falls **TURP:** transurethral resection of the prostate. During TURP, an instrument is inserted up the urethra to remove the section of the prostate that is blocking urine flow. This is most commonly caused by benign prostatic hyperplasia (BPH). A TURP usually requires hospitalization and is done using a general or spinal anesthetic. It is now the most common surgery used to remove part of an enlarged prostate. **Urethra:** a muscular tube that connects the bladder with the outside of the body **Ureters:** two tubes that drain urine from the kidneys to the bladder **Urine:** liquid produced by the kidneys, collected in the bladder and excreted through the urethra **Urinary Bladder:** a hollow, muscular and distensible or elastic organ that sits on the pelvic floor **Urinary System:** a group of organs in the body concerned with filtering out excess fluid and other substances from the bloodstream ## References - Graaff, Van De (2002). \"Human Anatomy, Sixth Edition\". New York: McGraw-Hill. - Mader, Sylvia S. (2004). *Human Biology*. New York: McGraw-Hill. - Smith, Peter (1998). Internet reference, \[<http://www.liv.ac.uk/~petesmif/teaching/1bds_mb/notes/homeo/kidney.htm>\|*The Role of the Kidney*\]. Department of Clinical Dental Sciences,The University of Liverpool. - McCance, Katherine L., Heuther, Sue E. (1994). \"Pathophysiology: The Biological Basis for Disease In Adults and Children, Second Edition\". Mosby-Year Book, Inc.
# Human Physiology/The respiratory system The **Respiratory System** is vital to every human being. Without it, we would cease to live outside of the womb. Let us begin by taking a look at the structure of the respiratory system and how vital it is to life. During inhalation or exhalation air is pulled towards or away from the lungs, by several cavities, tubes, and openings. The organs of the respiratory system make sure that **oxygen** enters our bodies and **carbon dioxide** leaves our bodies. The respiratory tract is the path of air from the nose to the lungs. It is divided into two sections: **Upper Respiratory Tract** and the **Lower Respiratory Tract**. Included in the upper respiratory tract are the **Nostrils**, **Nasal Cavities**, **Pharynx**, **Epiglottis**, and the **Larynx**. The lower respiratory tract consists of the **Trachea**, **Bronchi**, **Bronchioles**, and the **Lungs**. As air moves along the respiratory tract it is warmed, moistened and filtered. !The **lungs** flank the heart and great vessels in the chest cavity. `<small>`{=html}(Source: *Gray\'s Anatomy of the Human Body*, 20th ed. 1918.)`</small>`{=html}"){width="230"} ## Functions In this chapter we will discuss the four processes of respiration. They are: 1. **BREATHING** or ventilation 2. **EXTERNAL RESPIRATION**, which is the exchange of gases (oxygen and carbon dioxide) between inhaled air and the blood. 3. **INTERNAL RESPIRATION**, which is the exchange of gases between the blood and tissue fluids. 4. **CELLULAR RESPIRATION** In addition to these main processes, the respiratory system serves for: - **REGULATION OF BLOOD pH**, which occurs in coordination with the kidneys, and as a - **DEFENSE AGAINST MICROBES** - **Control of body temperature** due to loss of evaporate during expiration ## Breathing and Lung Mechanics **Ventilation** is the exchange of air between the external environment and the alveoli. Air moves by bulk flow from an area of high pressure to low pressure. All pressures in the respiratory system are relative to atmospheric pressure (760mmHg at sea level). Air will move in or out of the lungs depending on the pressure in the alveoli. The body changes the pressure in the alveoli by changing the volume of the lungs. As volume increases pressure decreases and as volume decreases pressure increases. There are two phases of ventilation; inspiration and expiration. During each phase the body changes the lung dimensions to produce a flow of air either in or out of the lungs. The body is able to stay at the dimensions of the lungs because of the relationship of the lungs to the thoracic wall. Each lung is completely enclosed in a sac called the pleural sac. Two structures contribute to the formation of this sac. The parietal pleura is attached to the thoracic wall where as the visceral pleura is attached to the lung itself. In-between these two membranes is a thin layer of intrapleural fluid. The intrapleural fluid completely surrounds the lungs and lubricates the two surfaces so that they can slide across each other. Changing the pressure of this fluid also allows the lungs and the thoracic wall to move together during normal breathing. Much the way two glass slides with water in-between them are difficult to pull apart, such is the relationship of the lungs to the thoracic wall. The rhythm of ventilation is also controlled by the \"Respiratory Center\" which is located largely in the medulla oblongata of the brain stem. This is part of the autonomic system and as such is not controlled voluntarily (one can increase or decrease breathing rate voluntarily, but that involves a different part of the brain). While resting, the respiratory center sends out action potentials that travel along the phrenic nerves into the diaphragm and the external intercostal muscles of the rib cage, causing inhalation. Relaxed exhalation occurs between impulses when the muscles relax. Normal adults have a breathing rate of 12-20 respirations per minute. ### The Pathway of Air When one breathes air in at sea level, the inhalation is composed of different gases. These gases and their quantities are Oxygen which makes up 21%, Nitrogen which is 78%, Carbon Dioxide with 0.04% and others with significantly smaller portions. right\|framed\|Diagram of the **Pharynx**. In the process of breathing, air enters into the nasal cavity through the nostrils and is filtered by coarse hairs (*vibrissae*) and mucous that are found there. The vibrissae filter macroparticles, which are particles of large size. Dust, pollen, smoke, and fine particles are trapped in the mucous that lines the **nasal cavities** (hollow spaces within the bones of the skull that warm, moisten, and filter the air). There are three bony projections inside the nasal cavity. The **superior, middle, and inferior nasal conchae**. Air passes between these conchae via the nasal meatuses. Air then travels past the nasopharynx, oropharynx, and laryngopharynx, which are the three portions that make up the pharynx. The **pharynx** is a funnel-shaped tube that connects our nasal and oral cavities to the larynx. The **tonsils** which are part of the lymphatic system, form a ring at the connection of the oral cavity and the pharynx. Here, they protect against foreign invasion of antigens. Therefore, the respiratory tract aids the immune system through this protection. Then the air travels through the **larynx**. The larynx closes at the epiglottis to prevent the passage of food or drink as a protection to our trachea and lungs. The larynx is also our voicebox; it contains vocal cords, in which it produces sound. Sound is produced from the vibration of the vocal cords when air passes through them. The **trachea**, which is also known as our windpipe, has ciliated cells and mucous secreting cells lining it, and is held open by C-shaped cartilage rings. One of its functions is similar to the larynx and nasal cavity, by way of protection from dust and other particles. The dust will adhere to the sticky mucous and the cilia helps propel it back up the trachea, to where it is either swallowed or coughed up. The **mucociliary escalator** extends from the top of the trachea all the way down to the **bronchioles**, which we will discuss later. Through the trachea, the air is now able to pass into the bronchi, bronchioles and finally alveoli before entering the pulmonary capillaries. There is lots of oxygen and then there is less carbon dioxide when the air comes in, but when it diffuses, the amounts exchange. All of this happens in seconds. ### Inspiration **Inspiration is initiated by contraction of the diaphragm** and in some cases the intercostals muscles when they receive nervous impulses. During normal quiet breathing, **the phrenic nerve stimulates the diaphragm to contract and move downward into the abdomen**. This downward movement of the diaphragm enlarges the thorax. When necessary, the intercostal muscles also increase the thorax by contacting and drawing the ribs upward and outward. As the diaphragm contracts inferiorly and thoracic muscles pull the chest wall outwardly, the volume of the thoracic cavity increases. The lungs are held to the thoracic wall by negative pressure in the pleural cavity, a very thin space filled with a few millilitres of lubricating pleural fluid. The negative pressure in the pleural cavity is enough to hold the lungs open in spite of the inherent elasticity of the tissue. Hence, as the thoracic cavity increases in volume the lungs are pulled from all sides to expand, causing a drop in the pressure (a partial vacuum) within the lung itself (but note that this negative pressure is still not as great as the negative pressure within the pleural cavity\--otherwise the lungs would pull away from the chest wall). Assuming the airway is open, air from the external environment then follows its pressure gradient down and expands the alveoli of the lungs, where gas exchange with the blood takes place. As long as pressure within the alveoli is lower than atmospheric pressure air will continue to move inwardly, but as soon as the pressure is stabilized air movement stops. ### Expiration During quiet breathing, expiration is normally a passive process and does not require muscles to work (rather it is the result of the muscles relaxing). When the lungs are stretched and expanded, stretch receptors within the alveoli send inhibitory nerve impulses to the medulla oblongata, causing it to stop sending signals to the rib cage and diaphragm to contract. The muscles of respiration and the lungs themselves are elastic, so when the diaphragm and intercostal muscles relax there is an elastic recoil, which creates a positive pressure (pressure in the lungs becomes greater than atmospheric pressure), and air moves out of the lungs by flowing down its pressure gradient. Although the respiratory system is primarily under involuntary control, and regulated by the medulla oblongata, we have some voluntary control over it also. This is due to the higher brain function of the cerebral cortex. When under physical or emotional stress, more frequent and deep breathing is needed, and both inspiration and expiration will work as active processes. Additional muscles in the rib cage forcefully contract and push air quickly out of the lungs. In addition to deeper breathing, when coughing or sneezing we exhale forcibly. Our abdominal muscles will contract suddenly (when there is an urge to cough or sneeze), raising the abdominal pressure. The rapid increase in pressure pushes the relaxed diaphragm up against the pleural cavity. This causes air to be forced out of the lungs. Another function of the respiratory system is to sing and to speak. By exerting conscious control over our breathing and regulating flow of air across the vocal cords we are able to create and modify sounds. ### Lung Compliance **Lung Compliance** is the magnitude of the change in lung volume produced by a change in pulmonary pressure. Compliance can be considered the opposite of stiffness. A low lung compliance would mean that the lungs would need a greater than average change in intrapleural pressure to change the volume of the lungs. A high lung compliance would indicate that little pressure difference in intrapleural pressure is needed to change the volume of the lungs. More energy is required to breathe normally in a person with low lung compliance. Persons with low lung compliance due to disease therefore tend to take shallow breaths and breathe more frequently. **Determination of Lung Compliance** Two major things determine lung compliance. The first is the elasticity of the lung tissue. Any thickening of lung tissues due to disease will decrease lung compliance. The second is surface tensions at air water interfaces in the alveoli. The surface of the alveoli cells is moist. The attractive force, between the water cells on the alveoli, is called surface tension. Thus, energy is required not only to expand the tissues of the lung but also to overcome the surface tension of the water that lines the alveoli. To overcome the forces of surface tension, certain alveoli cells (Type II pneumocytes) secrete a protein and lipid complex called \"\"Surfactant"", which acts like a detergent by disrupting the hydrogen bonding of water that lines the alveoli, hence decreasing surface tension. ### Control of respiration #### Central control The medulla oblongata is the primary respiratory control center Its main function is to send signals to the muscles that control respiration to cause breathing to occur. #### Peripheral control CO~2~ is converted to HCO~3~; most CO~2~ produced at the tissue cells is carried to lungs in the form of HCO~3~ - CO~2~ & H~2~O form carbonic acid (H~2~CO~3~) - changes to H CO~3~ & H+ ions - result is H+ ions are buffered by plasma proteins ## Respiratory System: Upper and Lower Respiratory Tracts For the sake of convenience, we will divide the respiratory system in to the upper and lower respiratory tracts: ### Upper Respiratory Tract The upper respiratory tract consists of the nose and the pharynx. Its primary function is to receive the air from the external environment and filter, warm, and humidify it before it reaches the delicate lungs where gas exchange will occur. Air enters through the nostrils of the nose and is partially filtered by the nose hairs, then flows into the nasal cavity. The nasal cavity is lined with epithelial tissue, containing blood vessels, which help warm the air; and secrete mucous, which further filters the air. The endothelial lining of the nasal cavity also contains tiny hairlike projections, called cilia. The *cilia* serve to transport dust and other foreign particles, trapped in mucous, to the back of the nasal cavity and to the pharynx. There the mucus is either coughed out, or swallowed and digested by powerful stomach acids. After passing through the nasal cavity, the air flows down the pharynx to the larynx. ### Lower Respiratory Tract The lower respiratory tract starts with the larynx, and includes the trachea, the two bronchi that branch from the trachea, and the lungs themselves. This is where gas exchange actually takes place. 1. Larynx The larynx (plural larynges), colloquially known as the voice box, is an organ in our neck involved in protection of the trachea and sound production. The larynx houses the vocal cords, and is situated just below where the tract of the pharynx splits into the trachea and the esophagus. The larynx contains two important structures: the epiglottis and the vocal cords. The epiglottis is a flap of cartilage located at the opening to the larynx. During swallowing, the larynx (at the epiglottis and at the glottis) closes to prevent swallowed material from entering the lungs; the larynx is also pulled upwards to assist this process. Stimulation of the larynx by ingested matter produces a strong cough reflex to protect the lungs. Note: choking occurs when the epiglottis fails to cover the trachea, and food becomes lodged in our windpipe. The vocal cords consist of two folds of connective tissue that stretch and vibrate when air passes through them, causing vocalization. The length the vocal cords are stretched determines what pitch the sound will have. The strength of expiration from the lungs also contributes to the loudness of the sound. Our ability to have some voluntary control over the respiratory system enables us to sing and to speak. In order for the larynx to function and produce sound, we need air. That is why we can\'t talk when we\'re swallowing. 1. Trachea 2. Bronchi 3. Lungs ## Homeostasis and Gas Exchange !Gas exchange{width="200"} Homeostasis is maintained by the respiratory system in two ways: gas exchange and regulation of blood pH. Gas exchange is performed by the lungs by eliminating carbon dioxide, a waste product given off by cellular respiration. As carbon dioxide exits the body, oxygen needed for cellular respiration enters the body through the lungs. ATP, produced by cellular respiration, provides the energy for the body to perform many functions, including nerve conduction and muscle contraction. Lack of oxygen affects brain function, sense of judgment, and a host of other problems. ### Gas Exchange Gas exchange in the lungs and in the alveoli is between the alveolar air and the blood in the pulmonary capillaries. This exchange is a result of increased concentration of CO2, and a decrease of oxygen. This process of exchange is done through diffusion. ### External Respiration External respiration is the exchange of gas between the air in the alveoli and the blood within the pulmonary capillaries. A normal rate of respiration is 12-25 breaths per minute. In external respiration, gases diffuse in either direction across the walls of the alveoli. Oxygen diffuses from the air into the blood and carbon dioxide diffuses out of the blood into the air. Most of the carbon dioxide is carried to the lungs **in plasma** as bicarbonate ions (HCO3-). When blood enters the pulmonary capillaries, the bicarbonate ions and hydrogen ions are converted to carbonic acid (H2CO3) and then back into carbon dioxide (CO2) and water. This chemical reaction also uses up hydrogen ions. The removal of these ions gives the blood a more neutral pH, allowing hemoglobin to bind up more oxygen. De-oxygenated blood \"blue blood\" coming from the pulmonary arteries, generally has an oxygen partial pressure (pp) of 40 mmHg and CO2 pp of 45 mmHg. Oxygenated blood leaving the lungs via the pulmonary veins has an O2 pp of 100 mmHg and CO2 pp of 40 mmHg. It should be noted that alveolar O2 pp is 105 mmHg, and not 100 mmHg. The reason why pulmonary venous return blood has a lower than expected O2 pp can be explained by \"Ventilation Perfusion Mismatch\". ### Internal Respiration Internal respiration is the exchanging of gases at the cellular level. #### The Passage Way From the Trachea to the Bronchioles There is a point at the inferior portion of the trachea where it branches into two directions that form the right and left primary bronchus. This point is called the **Carina** which is the keel-like cartilage plate at the division point. We are now at the **Bronchial Tree**. It is named so because it has a series of respiratory tubes that branch off into smaller and smaller tubes as they run throughout the lungs. #### Right and Left Lungs right\|framed\|Diagram of the **lungs** The **Right Primary Bronchus** is the first portion we come to, it then branches off into the **Lobar (secondary) Bronchi**, **Segmental (tertiary) Bronchi**, then to the **Bronchioles** which have little cartilage and are lined by simple cuboidal epithelium (See fig. 1). The bronchi are lined by pseudostratified columnar epithelium. Objects will likely lodge here at the junction of the Carina and the Right Primary Bronchus because of the vertical structure. Items have a tendency to fall in it, where as the Left Primary Bronchus has more of a curve to it which would make it hard to have things lodge there. The **Left Primary Bronchus** has the same setup as the right with the lobar, segmental bronchi and the bronchioles. The lungs are attached to the heart and trachea through structures that are called the **roots of the lungs**. The roots of the lungs are the bronchi, pulmonary vessels, bronchial vessels, lymphatic vessels, and nerves. These structures enter and leave at the **hilus** of the lung which is \"the depression in the medial surface of a lung that forms the opening through which the bronchus, blood vessels, and nerves pass\" (medlineplus.gov). There are a number of **terminal bronchioles** connected to **respiratory bronchioles** which then advance into the **alveolar ducts** that then become **alveolar sacs**. Each bronchiole terminates in an elongated space enclosed by many air sacs called **alveoli** which are surrounded by blood capillaries. Present there as well, are **Alveolar Macrophages**, they ingest any microbes that reach the alveoli. The **Pulmonary Alveoli** are **microscopic**, which means they can only be seen through a microscope, membranous air sacs within the lungs. They are units of respiration and the site of gas exchange between the respiratory and circulatory systems. ### Cellular Respiration First the oxygen must diffuse from the alveolus into the capillaries. It is able to do this because the capillaries are permeable to oxygen. After it is in the capillary, about 5% will be dissolved in the blood plasma. The other oxygen will bind to red blood cells. The red blood cells contain hemoglobin that carries oxygen. Blood with hemoglobin is able to transport 26 times more oxygen than plasma without hemoglobin. Our bodies would have to work much harder pumping more blood to supply our cells with oxygen without the help of hemoglobin. Once it diffuses by osmosis it combines with the hemoglobin to form oxyhemoglobin. Now the blood carrying oxygen is pumped through the heart to the rest of the body. Oxygen will travel in the blood into arteries, arterioles, and eventually capillaries where it will be very close to body cells. Now with different conditions in temperature and pH (warmer and more acidic than in the lungs), and with pressure being exerted on the cells, the hemoglobin will give up the oxygen where it will diffuse to the cells to be used for cellular respiration, also called aerobic respiration. Cellular respiration is the process of moving energy from one chemical form (glucose) into another (ATP), since all cells use ATP for all metabolic reactions. It is in the mitochondria of the cells where oxygen is actually consumed and carbon dioxide produced. Oxygen is produced as it combines with hydrogen ions to form water at the end of the electron transport chain (see chapter on cells). As cells take apart the carbon molecules from glucose, these get released as carbon dioxide. Each body cell releases carbon dioxide into nearby capillaries by diffusion, because the level of carbon dioxide is higher in the body cells than in the blood. In the capillaries, some of the carbon dioxide is dissolved in plasma and some is taken by the hemoglobin, but most enters the red blood cells where it binds with water to form carbonic acid. It travels to the capillaries surrounding the lung where a water molecule leaves, causing it to turn back into carbon dioxide. It then enters the lungs where it is exhaled into the atmosphere. ## Lung Capacity !450 px\|right The normal volume moved in or out of the lungs during quiet breathing is called **tidal volume**. When we are in a relaxed state, only a small amount of air is brought in and out, about 500 mL. You can increase both the amount you inhale, and the amount you exhale, by breathing deeply. Breathing in very deeply is **Inspiratory Reserve Volume** and can increase lung volume by 2900 mL, which is quite a bit more than the tidal volume of 500 mL. We can also increase expiration by contracting our thoracic and abdominal muscles. This is called **expiratory reserve volume** and is about 1400 ml of air. **Vital capacity** is the total of tidal, inspiratory reserve and expiratory reserve volumes; it is called vital capacity because it is vital for life, and the more air you can move, the better off you are. There are a number of illnesses that we will discuss later in the chapter that decrease vital capacity. Vital Capacity can vary a little depending on how much we can increase inspiration by expanding our chest and lungs. Some air that we breathe never even reaches the lungs! Instead it fills our nasal cavities, trachea, bronchi, and bronchioles. These passages aren\'t used in gas exchange so they are considered to be **dead air space**. To make sure that the inhaled air gets to the lungs, we need to breathe slowly and deeply. Even when we exhale deeply some air is still in the lungs,(about 1000 ml) and is called **residual volume**. This air isn\'t useful for gas exchange. There are certain types of diseases of the lung where residual volume builds up because the person cannot fully empty the lungs. This means that the vital capacity is also reduced because their lungs are filled with useless air. ## Stimulation of Breathing There are two pathways of motor neuron stimulation of the respiratory muscles. The first is the control of voluntary breathing by the cerebral cortex. The second is involuntary breathing controlled by the medulla oblongata. There are chemoreceptors in the aorta, the carotid body of carotid arteries, and in the medulla oblongata of the brainstem that are sensitive to pH. As carbon dioxide levels increase there is a buildup of carbonic acid, which releases hydrogen ions and lowers pH. Thus, the chemoreceptors do not respond to changes in oxygen levels (which actually change much more slowly), but to pH, which is dependent upon plasma carbon dioxide levels. **In other words, CO2 is the driving force for breathing**. The receptors in the aorta and the carotid sinus initiate a reflex that immediately stimulates breathing rate and the receptors in the medulla stimulate a sustained increase in breathing until blood pH returns to normal. This response can be experienced by running a 100-meter dash. During this exertion (or any other sustained exercise) your muscle cells must metabolize ATP at a much faster rate than usual, and thus will produce much higher quantities of CO2. The blood pH drops as CO2 levels increase, and you will involuntarily increase breathing rate very soon after beginning the sprint. You will continue to breathe heavily after the race, thus expelling more carbon dioxide, until pH has returned to normal. Metabolic acidosis therefore is acutely corrected by respiratory compensation (hyperventilation). ## Regulation of Blood pH Many of us are not aware of the importance of maintaining the acid/base balance of our blood. It is vital to our survival. Normal blood pH is set at 7.4, which is slightly alkaline or \"basic\". If the pH of our blood drops below 7.2 or rises above 7.6 then very soon our brains would cease functioning normally and we would be in big trouble. Blood pH levels below 6.9 or above 7.9 are usually fatal if they last for more than a short time. Another wonder of our amazing bodies is the ability to cope with every pH change -- large or small. There are three factors in this process: the lungs, the kidneys and buffers. So what exactly is pH? pH is the concentration of hydrogen ions (H+). Buffers are molecules which take in or release ions in order to maintain the H+ ion concentration at a certain level. When blood pH is too low and the blood becomes too acidic (acidosis), the presence of too many H+ ions is to blame. Buffers help to soak up those extra H+ ions. On the other hand, the lack of H+ ions causes the blood to be too basic (alkalosis). In this situation, buffers release H+ ions. Buffers function to maintain the pH of our blood by either donating or grabbing H+ ions as necessary to keep the number of H+ ions floating around the blood at just the right amount. The most important buffer we have in our bodies is a mixture of carbon dioxide (CO2) and bicarbonate ion (HCO3). CO2 forms carbonic acid (H2CO3) when it dissolves in water and acts as an acid giving up hydrogen ions (H+) when needed. HCO3 is a base and soaks up hydrogen ions (H+) when there are too many of them. In a nutshell, blood pH is determined by a balance between bicarbonate and carbon dioxide. **Bicarbonate Buffer System**. With this important system our bodies maintain homeostasis. (Note that H2CO3 is Carbonic Acid and HCO3 is Bicarbonate) CO2 + H2O \<\-\--\> H2CO3 \<\-\--\> (H+) + HCO3 - If pH is too high, carbonic acid will donate hydrogen ions (H+) and pH will drop. - If pH is too low, bicarbonate will bond with hydrogen ions (H+) and pH will rise. Too much CO2 or too little HCO3 in the blood will cause acidosis. The CO2 level is increased when hypoventilation or slow breathing occurs, such as if you have emphysema or pneumonia. Bicarbonate will be lowered by ketoacidosis, a condition caused by excess fat metabolism (diabetes mellitus). Too much HCO3 or too little CO2 in the blood will cause alkalosis. This condition is less common than acidosis. CO2 can be lowered by hyperventilation. So, in summary, if you are going into respiratory acidosis the above equation will move to the right. The body\'s H+ and CO2 levels will rise and the pH will drop. To counteract this the body will breathe more and release H+. In contrast, if you are going into respiratory alkalosis the equation will move to the left. The body\'s H+ and CO2 levels will fall and the pH will rise. So the body will try to breathe less to release HCO3. You can think of it like a leak in a pipe: where ever there is a leak, the body will \"fill the hole\". ## Problems Associated With the Respiratory Tract and Breathing The environment of the lung is very moist, which makes it a hospitable environment for bacteria. Many respiratory illnesses are the result of bacterial or viral infection of the lungs. Because we are constantly being exposed to harmful bacteria and viruses in our environment, our respiratory health can be adversely affected. There are a number of illnesses and diseases that can cause problems with breathing. Some are simple infections, and others are disorders that can be quite serious. **Carbon Monoxide Poisoning**: caused when carbon monoxide binds to hemoglobin in place of oxygen. Carbon monoxide binds much tighter, without releasing, causing the hemoglobin to become unavailable to oxygen. The result can be fatal in a very short amount of time. : Mild Symptoms: flu like symptoms, dizziness, fatigue, headaches, nausea, and irregular breathing : Moderate Symptoms: chest pain, rapid heart beat, difficulty thinking, blurred vision, shortness of breath and unsteadiness : Severe Symptoms: seizures, palpitations, disorientation, irregular heart beat, low blood pressure, coma and death. **Pulmonary Embolism:** blockage of the pulmonary artery (or one of its branches) by a blood clot, fat, air or clumped tumor cells. By far the most common form of pulmonary embolism is a thromboembolism, which occurs when a blood clot, generally a venous thrombus, becomes dislodged from its site of formation and embolizes to the arterial blood supply of one of the lungs. : Symptoms may include difficulty breathing, pain during breathing, and more rarely circulatory instability and death. Treatment, usually, is with anticoagulant medication. ## Upper Respiratory Tract Infections The upper respiratory tract consists of our nasal cavities, pharynx, and larynx. Upper respiratory infections (URI) can spread from our nasal cavities to our sinuses, ears, and larynx. Sometimes a viral infection can lead to what is called a secondary bacterial infection.**\"Strep throat\"** is a primary bacterial infection and can lead to an upper respiratory infection that can be generalized or even systemic (affects the body as a whole). Antibiotics aren\'t used to treat viral infections, but are successful in treating most bacterial infections, including strep throat. The symptoms of strep throat can be a high fever, severe sore throat, white patches on a dark red throat, and stomach ache. Sinusitis:An infection of the cranial sinuses is called **sinusitis**. Only about 1-3% of URI\'s are accompanied by sinusitis. This \"sinus infection\" develops when nasal congestion blocks off the tiny openings that lead to the sinuses. Some symptoms include: post nasal discharge, facial pain that worsens when bending forward, and sometimes even tooth pain can be a symptom. Successful treatment depends on restoring the proper drainage of the sinuses. Taking a hot shower or sleeping upright can be very helpful. Otherwise, using a spray decongestant or sometimes a prescribed antibiotic will be necessary. ```{=html} <!-- --> ``` Otitis Media:Otitis media in an infection of the middle ear. Even though the middle ear is not part of the respiratory tract, it is discussed here because it is often a complication seen in children who has a nasal infection. The infection can be spread by way of the *\'auditory (Eustachian) tube* that leads form the nasopharynx to the middle ear. The main symptom is usually pain. Sometimes though, vertigo, hearing loss, and dizziness may be present. Antibiotics can be prescribed and tubes are placed in the eardrum to prevent the buildup of pressure in the middle ear and the possibility of hearing loss. !Photo of **Tonsillitis**.{width="300"} Tonsillitis:Tonsillitis occurs when the tonsils become swollen and inflamed. The tonsils located in the posterior wall of the nasopharynx are often referred to as adenoids. If you suffer from tonsillitis frequently and breathing becomes difficult, they can be removed surgically in a procedure called a tonsillectomy. ```{=html} <!-- --> ``` Laryngitis:An infection of the larynx is called laryngitis. It is accompanied by hoarseness and being unable to speak in an audible voice. Usually, laryngitis disappears with treatment of the URI. Persistent hoarseness without a URI is a warning sign of cancer, and should be checked into by your physician. {{-}} ## Lower Respiratory Tract Disorders Lower respiratory tract disorders include infections, restrictive pulmonary disorders, obstructive pulmonary disorders, and lung cancer. ### Lower Respiratory Infections Acute bronchitis:An infection that is located in the primary and secondary bronchi is called bronchitis. Most of the time, it is preceded by a viral URI that led to a secondary bacterial infection. Usually, a nonproductive cough turns into a deep cough that will expectorate mucus and sometimes pus.\ Pneumonia:A bacterial or viral infection in the lungs where the bronchi and the alveoli fill with a thick fluid. Usually it is preceded by influenza. Symptoms of pneumonia include high fever & chills, with headache and chest pain. Pneumonia can be located in several lobules of the lung and obviously, the more lobules involved, the more serious the infection. It can be caused by a bacteria that is usually held in check, but due to stress or reduced immunity has gained the upper hand. ### Restrictive Pulmonary Disorders Pulmonary Fibrosis:Vital capacity is reduced in these types of disorders because the lungs have lost their elasticity. Inhaling particles such as sand, asbestos, coal dust, or fiberglass can lead to **pulmonary fibrosis**, a condition where fibrous tissue builds up in the lungs. This makes it so our lungs cannot inflate properly and are always tending toward deflation. Pulmonary fibrosis can be synonymous with interstitial lung disease (ILD), or interstitial pneumonia or pneumonitis. ### Obstructive Pulmonary Disorders !400 px\|Diagram of the lungs during an **asthma attack**. Asthma:Asthma is a respiratory disease of the bronchi and bronchioles. The symptoms include wheezing, shortness of breath, and sometimes a cough that will expel mucus. The airways are very sensitive to irritants which can include pollen, dust, animal dander, and tobacco. Even being out in cold air can be an irritant. When exposed to an irritant, the smooth muscle in the bronchioles undergoes spasms. Most asthma patients have at least some degree of bronchial inflammation that reduces the diameter of the airways and contributes to the seriousness of the attack. ```{=html} <!-- --> ``` Emphysema:Emphysema is a type of chronic obstructive pulmonary disease. Typically characterized by a loss of elasticity and surfactant in the alveoli, a loss of surface area decreases the gas exchange in the lungs. These patients have difficulty with too little expiratory pressure, not retaining inspired air long enough for sufficient gas exchange to happen. ```{=html} <!-- --> ``` Chronic Bronchitis:Another type of chronic obstructive pulmonary disease, Chronic Bronchitis is caused by overproduction of mucus in the airways, causing an inadequate expiration of inspired air. Retention of air in the lungs reduces gas exchange at the alveoli, and can lead to a hypoxic drive. These patients are known as \"blue bloaters\", vulnerable to cyanosis and often have increased thoracic diameters. ## Respiratory Distress Syndrome Pathophysiology At birth the pressure needed to expand the lungs requires high inspiratory pressure. In the presence of normal surfactant levels the lungs retain as much as 40% of the residual volume after the first breath and thereafter will only require far lower inspiratory pressures. In the case of deficiency of surfactant the lungs will collapse between breaths, this makes the infant work hard and each breath is as hard as the first breath. If this goes on further the pulmonary capillary membranes become more permeable, letting in fibrin rich fluids between the alveolar spaces and in turn forms a hyaline membrane. The hyaline membrane is a barrier to gas exchange, this hyaline membrane then causes hypoxemia and carbon dioxide retention that in turn will further impair surfactant production. Etiology Type two alveolar cells produce surfactant and do not develop until the 25th to the 28th week of gestation, in this, respiratory distress syndrome is one of the most common respiratory disease in premature infants. Furthermore, surfactant deficiency and pulmonary immaturity together leads to alveolar collapse. Predisposing factors that contribute to poorly functioning type II alveolar cells in a premature baby are if the child is a preterm male, white infants, infants of mothers with diabetes, precipitous deliveries, cesarean section performed before the 38th week of gestation. Surfactant synthesis is influenced by hormones, this ranges form insulin and cortisol. Insulin inhibits surfactant production, explaining why infants of mothers with diabetes type 1 are at risk of development of respiratory distress syndrome. Cortisol can speed up maturation of type II cells and therefore production of surfactant. Finally, in the baby delivered by cesarean section are at greater risk of developing respiratory distress syndrome because the reduction of cortisol produced because the lack of stress that happens during vaginal delivery, hence cortisol increases in high stress and helps in the maturation of type II cells of the alveoli that cause surfactant. Treatment Today to prevent respiratory distress syndrome are animal sources and synthetic surfactants, and administrated through the airways by an endotracheal tube and the surfactant is suspended in a saline solution. Treatment is initiated post birth and in infants who are at high risk for respiratory distress syndrome. ## Sleep Apnea !CPAP is the most common treatment for obstructive sleep apnea.{width="200"} Sleep apnea or sleep apnoea is a sleep disorder characterized by pauses in breathing during sleep. These episodes, called apneas (literally, \"without breath\"), each last long enough so one or more breaths are missed, and occur repeatedly throughout sleep. The standard definition of any apneic event includes a minimum 10 second interval between breaths, with either a neurological arousal (3-second or greater shift in EEG frequency, measured at C3, C4, O1, or O2), or a blood oxygen desaturation of 3-4 percent or greater, or both arousal and desaturation. Sleep apnea is diagnosed with an overnight sleep test called polysomnogram. One method of treating central sleep apnea is with a special kind of CPAP, APAP, or VPAP machine with a Spontaneous Time (ST) feature. This machine forces the wearer to breathe a constant number of breaths per minute. (CPAP), or continuous positive airway pressure, in which a controlled air compressor generates an airstream at a constant pressure. This pressure is prescribed by the patient\'s physician, based on an overnight test or titration. ## Nutrition for COPD (Chronic Obstructive Pulmonary Disease) Patients Nutrition is particularly important for ventilator-dependent patient. When metabolizing macronutrients carbon dioxide and water are produced. The respiratory quotient (RQ) is a ratio of produced carbon dioxide to amount consumed. Carbohydrates metabolism produces the most amount of carbon dioxide so they have the highest (RQ). Fats produce the least amount of carbon dioxide along with proteins. Protein has a slightly higher RQ ratio. It is recommended that this kind of patient not exceed a 1.0 respiratory quotient (RQ). Lowering carbohydrates and supplementing fat or protein in the diet might not result in maintaining the desired outcome because, excess amounts fat or protein may also result in a respiratory quotient (RQ) higher than 1.0. - Please reference source and fact accuracy. It seems like by definition, it is impossible to exceed a respiratory quotient (RQ) of 1.0. \* ## Case Study **Cystic Fibrosis** This disease is most common in Caucasians and will happen to 1 in every 2500 people. It is most known for its effects on the respiratory tract although it does effect other systems as well. The respiratory passages become clogged with a thick mucus that is difficult to expel even with vigorous coughing. Breathing becomes difficult and affected individuals run the risk of choking to death on their own secretions unless strenuous effort is made to clear the lungs multiple times every day. Victims frequently will die in the 20\'s of pneumonia. All of us secrete mucus by certain cells in the epithelium that line the respiratory passageways. In normal cases the cells also secrete a watery fluid that will dilute the mucus making it easier to pass through the airways. In cystic fibrosis that secretion of watery fluid is impaired. This makes the mucus thicker and difficult to clear from the passageways. A 1989 discovery found that cystic fibrosis is caused by defects in a type of anion channel found in apical membranes of epithelial cells in the respiratory system and elsewhere[^1]. The defects directly impede the chloride ion transport, which will then indirectly effect other exchanges of ions in the cells. This causes the epithelium to not create the osmotic gradient necessary for water secretion. It has been known for a long time that cystic fibrosis is caused by a recessive gene inheritance. This gene codes for the chloride channel protein, which can malfunction in a variety of ways, each with specific treatment required. ## Glossary ## References - Mader, Sylvia S. *Human Biology*. McGraw Hill Publishing, Burr Ridge, IL. 2004. - Van De Graaff, Kent M. *Human Anatomy*. McGraw Hill Publishing, Burr Ridge, IL. 2002. - Department of Environmental Biology, University of Adelaide, Adelaide, South Australia - Wikipedia:Lung - Medlineplus.gov. *Hilus*. <http://www2.merriam-webster.com/cgi-bin/mwmednlm?book=Medical&va=hilum+> - <http://www.an-attorney-for-you.com/legal/carbon-monoxide.htm> - www.ineedtoknow.com - \'\'\"The respiratory system\"Authors Mary Kitteredge,intro. by C. Everett Koop, M.D.,SC.D., foreword by Sandra Thurman ## External Resources - Eastern Kentucky University Gary Ritchison Lecture Notes: Human Respiration (includes videos) - In depth anatomy and physiology of the pulmonary system. pt:Fisiologia/Sistema respiratório [^1]: Riordan,J.R., Rommens,J.M., Kerem,B., Alon,N., Rozmahel,R., Grzelczak,Z., Zielenski,J., Lok,S., Plavsic,N. and Chou,J.L. (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science, 245, 1066--73.
# Human Physiology/The gastrointestinal system ## Introduction Which organ is the most important organ in the body? Most people would say the heart or the brain, completely overlooking the gastrointestinal tract (*GI tract*). Though definitely not the most attractive organs in the body, they are certainly among the most important. The 30+ foot long tube that goes from the mouth to the anus is responsible for the many different body functions which will be reviewed in this chapter. The GI tract is imperative for our well being and our lifelong health. A non-functioning or poorly functioning GI tract can be the source of many chronic health problems that can interfere with your quality of life. In many instances the death of a person begins in the intestines. The old saying \"you are what you eat\" perhaps would be more accurate if worded \"you are what you absorb and digest\". Here we will be looking at the importance of these two functions of the digestive system: digestion and absorption. The **Gastrointestinal System** is responsible for the breakdown and absorption of various foods and liquids needed to sustain life. Many different organs have essential roles in the digestion of food, from the mechanical disrupting by the teeth to the creation of bile (an emulsifier) by the liver. Bile production of the liver plays an important role in digestion: from being stored and concentrated in the gallbladder during fasting stages to being discharged to the small intestine. In order to understand the interactions of the different components we shall follow the food on its journey through the human body. During digestion, two main processes occur at the same time; - **Mechanical Digestion**: larger pieces of food get broken down into smaller pieces while being prepared for chemical digestion. Mechanical digestion starts in the mouth and continues into the stomach. - **Chemical Digestion**: starts in the mouth and continues into the intestines. Several different enzymes break down macromolecules into smaller molecules that can be absorbed. The GI tract starts with the mouth and proceeds to the esophagus, stomach, small intestine (duodenum, jejunum, ileum), and then to the large intestine (colon), rectum, and terminates at the anus. You could probably say the human body is just like a big donut. The GI tract is the donut hole. We will also be discussing the pancreas and liver, and accessory organs of the gastrointestinal system that contribute materials to the small intestine. ## Layers of the GI Tract The GI tract is composed of four layers also known as Tunics. Each layer has different tissues and functions. From the inside out they are called: mucosa, submucosa, muscularis, and serosa. **Mucosa**: The mucosa is the absorptive and secretory layer. It is composed of simple epithelium cells and a thin connective tissue. There are specialized goblet cells that secrete mucus throughout the GI tract located within the mucosa. On the mucosa layer there are Villi and Micro Villi. **Submucosa**: The submucosa is relatively thick, highly vascular, and serves the mucosa. The absorbed elements that pass through the mucosa are picked up from the blood vessels of the submucosa. The submucosa also has glands and nerve plexuses. **Muscularis**: The muscularis is responsible for segmental contractions and peristaltic movement in the GI tract. The muscularis is composed of two layers of muscle: an inner circular and outer longitudinal layer of smooth muscle. These muscles cause food to move and churn with digestive enzymes down the GI tract. **Serosa**: The last layer is a protective layer. It is composed of avascular connective tissue and simple squamous epithelium. It secretes lubricating serous fluid. This is the visible layer on the outside of the organs. ## Accessory Organs !Teeth, Tongue, and Salivary Glands 1\. Salivary glands - Parotid gland, submandibular gland, sublingual gland - Exocrine gland that produces saliva which begins the process of digestion with amylase 2\. Tongue - Manipulates food for chewing/swallowing - Main taste organ, covered in taste buds 3\. Teeth - For chewing food up 4\. Liver - Produces and excretes bile required for emulsifying fats. Some of the bile drains directly into the duodenum and some is stored in the gall bladder. - Helps metabolize proteins, lipids, and carbohydrates. - Urea, chief end product of mammalian metabolism, is formed in liver from amino acids and compounds of ammonia. - Breaks down insulin and other hormones. - Produces coagulation factors. 5\. Gallbladder - Bile storage. 6\. Pancreas - Exocrine functions: Digestive enzyme secretion. - Stores zymogens (inactive enzymes) that will be activated by the brush border membrane in the small intestine when a person eats protein (amino acids). - Trypsinogen -- Trypsin: digests protein. - Chymotypsinogen -- Chymotrypsin: digests proteins. - Carboxypeptidases: digests proteins. - Lipase-lipid: digests fats. - Amylase: digests carbohydrates. - Endocrine functions: Hormone secretion. - Somatostatin: inhibits the function of insulin. Produced if the body is getting too much glucose. - Glucagon: stimulates the stored glycogen in the liver to convert to glucose. Produced if the body does not have enough glucose. - Insulin: made in the beta cells of the Islets of Langerhans of the pancreas. Insulin is a hormone that regulates blood glucose. 7\. Vermiform appendix - There are a few theories on what the appendix does. - Vestigal organ - Immune function - Helps maintain gut flora ## The Digestive System !300 px The first step in the digestive system can actually begin before the food is even in your mouth. When you smell or see something that you just have to eat, you start to salivate in anticipation of eating, thus beginning the digestive process. Food is the body\'s source of fuel. Nutrients in food give the body\'s cells the energy they need to operate. Before food can be used it has to be broken down into tiny little pieces so it can be absorbed and used by the body. In humans, proteins need to be broken down into amino acids, starches into sugars, and fats into fatty acids and glycerol. During digestion two main processes occur at the same time: - **Mechanical Digestion**: larger pieces of food get broken down into smaller pieces while being prepared for chemical digestion. Mechanical digestion starts in the mouth and continues in to the stomach. - **Chemical Digestion**: several different enzymes break down macromolecules into smaller molecules that can be more efficiently absorbed. Chemical digestion starts with saliva and continues into the intestines. The digestive system is made up by the alimentary canal, or the digestive tract, and other abdominal organs that play a part in digestion such as the liver and the pancreas. The alimentary canal is the long tube of organs that runs from the mouth (where the food enters) to the anus (where indigestible waste leaves). The organs in the alimentary canal include the mouth( for mastication),esophagus, stomach and the intestines. The average adult digestive tract is about thirty feet (30\') long. While in the digestive tract the food is really passing `<i>`{=html}through`</i>`{=html} the body rather than being `<i>`{=html}in`</i>`{=html} the body. The smooth muscles of the tubular digestive organs move the food efficiently along as it is broken down into absorb-able atoms and molecules. During absorption, the nutrients that come from food (such as proteins, fats, carbohydrates, vitamins, and minerals) pass through the wall of the small intestine and into the bloodstream and lymph. In this way nutrients can be distributed throughout the rest of the body. In the large intestine there is re absorption of water and absorption of some minerals as feces are formed. The parts of the food that the body passes out through the anus is known as feces. **Mastication** Digestion begins in the mouth. A brain reflex triggers the flow of saliva when we see or even think about food. Saliva moistens the food while the teeth chew it up and make it easier to swallow. Amylase, which is the digestive enzyme found in saliva, starts to break down starch into simpler sugars before the food even leaves the mouth. The nervous pathway involved in salivary excretion requires stimulation of receptors in the mouth, sensory impulses to the brain stem, and parasympathetic impulses to salivary glands. Swallowing your food happens when the muscles in your tongue and mouth move the food into your **pharynx**. The pharynx, which is the passageway for food and air, is about five inches (5\") long. A small flap of skin called the epiglottis closes over the pharynx to prevent food from entering the trachea and thus choking. For swallowing to happen correctly a combination of 25 muscles must all work together at the same time. Salivary glands also produce an estimated three liters of saliva per day. Enzyme Produced In Site of Release pH Level --------------------------------------------------------------------------- ----------------- ----------------- ---------- `<span style="color:red;">`{=html}Carbohydrate Digestion:`</span>`{=html} Salivary amylase Salivary glands Mouth Neutral Pancreatic amylase Pancreas Small intestine Basic Maltase Small intestine Small intestine Basic `<span style="color:red;">`{=html}Protein Digestion:`</span>`{=html} Pepsin Gastric glands Stomach Acidic Trypsin Pancreas Small intestine Basic Peptidases Small intestine Small intestine Basic `<span style="color:red;">`{=html}Nucleic Acid Digestion:`</span>`{=html} Nuclease Pancreas Small intestine Basic align''left''\|Nucleosidases Pancreas Small intestine Basic `<span style="color:red;">`{=html}Fat Digestion:`</span>`{=html} Lipase Pancreas Small intestine Basic ## Esophagus !300 px The **esophagus** (also spelled oesophagus/esophagus) or gullet is the muscular tube in vertebrates through which ingested food passes from the throat to the stomach. The esophagus is continuous with the laryngeal part of the pharynx at the level of the C6 vertebra. It connects the pharynx, which is the body cavity that is common to both the digestive and respiratory systems behind the mouth, with the stomach, where the second stage of digestion is initiated (the first stage is in the mouth with teeth and tongue masticating food and mixing it with saliva). After passing through the throat, the food moves into the esophagus and is pushed down into the stomach by the process of *peristalsis* (involuntary wavelike muscle contractions along the G.I. tract). At the end of the esophagus there is a sphincter that allows food into the stomach then closes back up so the food cannot travel back up into the esophagus. **Histology** The esophagus is lined with mucus membranes, and uses peristaltic action to move swallowed food down to the stomach. The esophagus is lined by a *stratified squamous epithelium*, which is rapidly turned over, and serves a protective effect due to the high volume transit of food, saliva, and mucus into the stomach. The *lamina propria* of the esophagus is sparse. The mucus secreting glands are located in the submucosa, and are connective structures called *papillae*. The muscularis propria of the esophagus consists of *striated* *muscle* in the upper third (superior) part of the esophagus. The middle third consists of a combination of *smooth muscle* and striated muscle, and the bottom (inferior) third is only smooth muscle. The distal end of the esophagus is slightly narrowed because of the thickened circular muscles. This part of the esophagus is called the lower esophageal sphincter. This aids in keeping food down and not being regurgitated. The esophagus has a rich *lymphatic* drainage as well. ## Stomach The **stomach** is a thick walled organ that lies between the esophagus and the first part of the small intestine (the duodenum). It is on the left side of the abdominal cavity, the fundus of the stomach lying against the diaphragm. Lying beneath the stomach is the pancreas. The greater omentum hangs from the greater curvature. A mucous membrane lines the stomach which contains glands (with *chief cells*) that secrete gastric juices, up to three quarts of this digestive fluid is produced daily. The gastric glands begin secreting before food enters the stomach due to the parasympathetic impulses of the vagus nerve, making the stomach also a storage vat for that acid. The secretion of gastric juices occurs in three phases: cephalic, gastric, and intestinal. The cephalic phase is activated by the smell and taste of food and swallowing. The gastric phase is activated by the chemical effects of food and the distension of the stomach. The intestinal phase blocks the effect of the cephalic and gastric phases. Gastric juice also contains an enzyme named **pepsin**, which digests proteins, hydrochloric acid and mucus. Hydrochloric acid causes the stomach to maintain a pH of about 2, which helps kill off bacteria that comes into the digestive system via food. The gastric juice is highly acidic with a pH of 1-3. It may cause or compound damage to the stomach wall or its layer of mucus, causing a peptic ulcer. On the inside of the stomach there are folds of skin call the gastric rugae. Gastric rugae make the stomach very extendable, especially after a very big meal. !350 px The stomach is divided into four sections, each of which has different cells and functions. The sections are: 1) Cardiac region, where the contents of the esophagus empty into the stomach, 2) Fundus, formed by the upper curvature of the organ, 3) Body, the main central region, and 4) Pylorus or atrium, the lower section of the organ that facilitates emptying the contents into the small intestine. Two smooth muscle valves, or sphincters, keep the contents of the stomach contained. They are the: 1) Cardiac or esophageal sphincter, dividing the tract above, and 2) Pyloric sphincter, dividing the stomach from the small intestine. After receiving the **bolus** (chewed food) the process of peristalsis is started; mixed and churned with gastric juices the bolus is transformed into a semi-liquid substance called **chyme**. Stomach muscles mix up the food with enzymes and acids to make smaller digestible pieces. The pyloric sphincter, a walnut shaped muscular tube at the stomach outlet, keeps chyme in the stomach until it reaches the right consistency to pass into the small intestine. The food leaves the stomach in small squirts rather than all at once. Water, alcohol, salt, and simple sugars can be absorbed directly through the stomach wall. However, most substances in our food need a little more digestion and must travel into the intestines before they can be absorbed. When the stomach is empty it is about the size of one fifth of a cup of fluid. When stretched and expanded, it can hold up to eight cups of food after a big meal. **Gastric Glands** There are many different gastric glands and they secrete many different chemicals. Parietal cells secrete hydrochloric acid and intrinsic factor; chief cells secrete pepsinogen; goblet cells secrete mucus; argentaffin cells secrete serotonin and histamine; and G cells secrete the hormone gastrin. **Vessels and nerves** !`Nerves in the lower abdomen.` : **Arteries:** The arteries supplying the stomach are the left gastric, the right gastric and right gastroepiploic branches of the hepatic, and the left gastroepiploic and short gastric branches of the lineal. They supply the muscular coat, ramify in the submucous coat, and are finally distributed to the mucous membrane. ```{=html} <!-- --> ``` : **Capillaries:** The arteries break up at the base of the gastric tubules into a plexus of fine capillaries, which run upward between the tubules, anatomizing with each other, and ending in a plexus of larger capillaries, which surround the mouths of the tubes, and also form hexagonal meshes around the ducts. ```{=html} <!-- --> ``` : **Veins:** From these the veins arise, and pursue a straight course downward, between the tubules, to the submucous tissue; they end either in the lineal and superior mesenteric veins, or directly in the portal vein. ```{=html} <!-- --> ``` : **Lymphatics:** The lymphatics are numerous: They consist of a superficial and a deep set, and pass to the lymph glands found along the two curvatures of the organ. ```{=html} <!-- --> ``` : **Nerves:** The nerves are the terminal branches of the right and left urethra and other parts, the former being distributed upon the back, and the latter upon the front part of the organ. A great number of branches from the celiac plexus of the sympathetic are also distributed to it. Nerve plexuses are found in the submucous coat and between the layers of the muscular coat as in the intestine. From these plexuses fibrils are distributed to the muscular tissue and the mucous membrane. **Disorders of the Stomach** Disorders of the stomach are common. There can be a lot of different causes with a variety of symptoms. The strength of the inner lining of the stomach needs a careful balance of acid and mucus. If there is not enough mucus in the stomach, ulcers, abdominal pain, indigestion, heartburn, nausea and vomiting could all be caused by the extra acid. Erosions, ulcers, and tumors can cause bleeding. When blood is in the stomach it starts the digestive process and turns black. When this happens, the person can have black stool or vomit. Some ulcers can bleed very slowly so the person won\'t recognize the loss of blood. Over time, the iron in your body will run out, which in turn, will cause anemia. There isn\'t a known diet to prevent against getting ulcers. A balanced, healthy diet is always recommended. Smoking can also be a cause of problems in the stomach. Tobacco increases acid production and damages the lining of the stomach. It is not a proven fact that stress alone can cause an ulcer. **Histology of the human stomach** Like the other parts of the gastrointestinal tract, the stomach walls are made of a number of layers. From the inside to the outside, the first main layer is the mucosa. This consists of an epithelium, the lamina propria underneath, and a thin bit of smooth muscle called the muscularis mucosa. The submucosa lies under this and consists of fibrous connective tissue, separating the mucosa from the next layer, the muscularis externa. The muscularis in the stomach differs from that of other GI organs in that it has three layers of muscle instead of two. Under these muscle layers is the adventitia, layers of connective tissue continuous with the omenta. The epithelium of the stomach forms deep pits, called fundic or oxyntic glands. Different types of cells are at different locations down the pits. The cells at the base of these pits are chief cells, responsible for production of pepsinogen, an inactive precursor of pepsin, which degrades proteins. The secretion of pepsinogen prevents self-digestion of the stomach cells. Further up the pits, parietal cells produce gastric acid and a vital substance, intrinsic factor. The function of gastric acid is twofold 1) it kills most of the bacteria in food, stimulates hunger, and activates pepsinogen into pepsin, and 2) denatures the complex protein molecule as a precursor to protein digestion through enzyme action in the stomach and small intestines. Near the top of the pits, closest to the contents of the stomach, there are mucous-producing cells called goblet cells that help protect the stomach from self-digestion. The muscularis externa is made up of three layers of smooth muscle. The innermost layer is obliquely-oriented: this is not seen in other parts of the digestive system: this layer is responsible for creating the motion that churns and physically breaks down the food. The next layers are the square and then the longitudinal, which are present as in other parts of the GI tract. The pyloric antrum which has thicker skin cells in its walls and performs more forceful contractions than the fundus. The pylorus is surrounded by a thick circular muscular wall which is normally tonically constricted forming a functional (if not anatomically discrete) pyloric sphincter, which controls the movement of chyme. **Control of secretion and motility** The movement and the flow of chemicals into the stomach are controlled by both the nervous system and by the various digestive system hormones. The hormone gastrin causes an increase in the secretion of HCL, pepsinogen and intrinsic factor from parietal cells in the stomach. It also causes increased motility in the stomach. Gastrin is released by G-cells into the stomach. It is inhibited by pH normally less than 4 (high acid), as well as the hormone somatostatin. Cholecystokinin (CCK) has most effect on the gall bladder, but it also decreases gastric emptying. In a different and rare manner, secretin, produced in the small intestine, has most effects on the pancreas, but will also diminish acid secretion in the stomach. Gastric inhibitory peptide (GIP) and enteroglucagon decrease both gastric motility and secretion of pepsin. Other than gastrin, these hormones act to turn off the stomach action. This is in response to food products in the liver and gall bladder, which have not yet been absorbed. The stomach needs only to push food into the small intestine when the intestine is not busy. While the intestine is full and still digesting food, the stomach acts as a storage for food. ## Small Intestine framed\|Diagram showing the small intestine The small intestine is the site where most of the chemical and mechanical digestion is carried out. Tiny projections called **villi** line the small intestine which absorbs digested food into the capillaries. Most of the food absorption takes place in the jejunum and the ileum. The functions of a small intestine is, the digestion of proteins into peptides and amino acids principally occurs in the stomach but some also occurs in the small intestine. Peptides are degraded into amino acids; lipids (fats) are degraded into fatty acids and glycerol; and carbohydrates are degraded into simple sugars. The three main sections of the small intestine are *the duodenum, the jejunum, the ileum.* : **The duodenum** In anatomy of the digestive system, the **duodenum** is a hollow jointed tube connecting the stomach to the jejunum. It is the first and shortest part of the small intestine. It begins with the duodenal bulb and ends at the ligament of Treitz. The duodenum is almost entirely retro peritoneal. The duodenum is also where the bile and pancreatic juices enter the intestine. : **The jejunum** The *jejunum* is a part of the small bowel, located between the distal end of duodenum and the proximal part of ileum. The jejunum and the ileum are suspended by an extensive mesentery giving the bowel great mobility within the abdomen. The inner surface of the jejunum, its mucous membrane, is covered in projections called villi, which increase the surface area of tissue available to absorb nutrients from the gut contents. It is different from the ileum due to fewer goblet cells and generally lacks Peyer\'s patches. : **The ileum** Its function is to absorb vitamin B12 and bile salts. The wall itself is made up of folds, each of which has many tiny finger-like projections known as villi, on its surface. In turn, the epithelial cells which line these villi possess even larger numbers of micro villi. The cells that line the ileum contain the protease and carbohydrate enzymes responsible for the final stages of protein and carbohydrate digestion. These enzymes are present in the cytoplasm of the epithelial cells. The villi contain large numbers of capillaries which take the amino acids and glucose produced by digestion to the hepatic portal vein and the liver. The terminal ileum continues to absorb bile salts, and is also crucial in the absorption of fat-soluble vitamins (Vitamin A, D, E and K). For fat-soluble vitamin absorption to occur, bile acids must be present. ## Large Intestine !Large Intestinal Tract The large intestine (colon) extends from the end of the ileum to the anus. It is about 5 feet long, being one-fifth of the whole extent of the intestinal canal. It\'s caliber is largest at the commencement at the cecum, and gradually diminishes as far as the rectum, where there is a dilatation of considerable size just above the anal canal. It differs from the small intestine in by the greater caliber, more fixed position, sacculated form, and in possessing certain appendages to its external coat, the appendices epiploicæ. Further, its longitudinal muscular fibers do not form a continuous layer around the gut, but are arranged in three longitudinal bands or tæniæ. The large intestine is divided into the cecum, colon, rectum, and anal canal. In its course, describes an arch which surrounds the convolutions of the small intestine. It commences in the right iliac region, in a dilated part, the cecum. It ascends through the right lumbar and hypochondriac regions to the under surface of the liver; here it takes a bend, the right colic flexure, to the left and passes transversely across the abdomen on the confines of the epigastric and umbilical regions, to the left hypochondriac region; it then bends again, the left colic flexure, and descends through the left lumbar and iliac regions to the pelvis, where it forms a bend called the sigmoid flexure; from this it is continued along the posterior wall of the pelvis to the anus. There are trillions of bacteria, yeasts, and parasites living in our intestines, mostly in the colon. Over 400 species of organisms live in the colon. Most of these are very helpful to our health, while the minority are harmful. Helpful organisms *synthesize* vitamins, like *B12*, *biotin*, and *vitamin K*. They breakdown toxins and stop proliferation of harmful organisms. They stimulate the immune system and produce short chain fatty acids (SCFAs) that are required for the health of colon cells and help prevent colon cancer. There are many beneficial bacteria but some of the most common and important are *Lactobacillus Acidophilus* and various species of *Bifidobacterium.* These are available as \"probiotics\" from many sources. ## Pancreas, Liver, and Gallbladder The pancreas, liver, and gallbladder are essential for digestion. The pancreas produces enzymes that help digest proteins, fats, and carbohydrates, the liver produces bile that helps the body absorb fat, and the gallbladder stores the bile until it is needed. The enzymes and bile travel through special channels called ducts and into the small intestine where they help break down the food. **Pancreas** The pancreas is located posterior to the stomach and in close association with the duodenum. In humans, the pancreas is a 6-10 inch elongated organ in the abdomen located retro peritoneal. It is often described as having three regions: a head, body and tail. The pancreatic head abuts the second part of the duodenum while the tail extends towards the spleen. The pancreatic duct runs the length of the pancreas and empties into the second part of the duodenum at the ampulla of Vater. The common bile duct commonly joins the pancreatic duct at or near this point. The pancreas is supplied arterially by the pancreaticoduodenal arteries, themselves branches of the superior mesenteric artery of the hepatic artery (branch of celiac trunk from the abdominal aorta). The superior mesenteric artery provides the inferior pancreaticoduodenal arteries while the gastroduodenal artery (one of the terminal branches of the hepatic artery) provides the superior pancreaticoduodenal artery. Venous drainage is via the pancreatic duodenal veins which end up in the portal vein. The splenic vein passed posterior to the pancreas but is said to not drain the pancreas itself. The portal vein is formed by the union of the superior mesenteric vein and splenic vein posterior to the body of the pancreas. In some people (as many as 40%) the inferior mesenteric vein also joins with the splenic vein behind the pancreas, in others it simply joins with the superior mesenteric vein instead. The function of the pancreas is to produce enzymes that break down all categories of digestible foods (exocrine pancreas) and secrete hormones that affect carbohydrates metabolism (endocrine pancreas). - **Exocrine** The pancreas is composed of pancreatic exocrine cells, whose ducts are arranged in clusters called acini (singular acinus). The cells are filled with secretory granules containing the precursor digestive enzymes (mainly trypsinogen, chymotrypsinogen, pancreatic lipase, and amylase) that are secreted into the lumen of the acinus. These granules are termed zymogen granules (zymogen referring to the inactive precursor enzymes.) It is important to synthesize inactive enzymes in the pancreas to avoid auto degradation, which can lead to pancreatitis. The pancreas is near the liver, and is the main source of enzymes for digesting fats (lipids) and proteins - the intestinal walls have enzymes that will digest polysaccharides. Pancreatic secretions from ductal cells contain bicarbonate ions and are alkaline in order to neutralize the acidic chyme that the stomach churns out. Control of the exocrine function of the pancreas are via the hormone gastrin, cholecystokinin and secretin, which are hormones secreted by cells in the stomach and duodenum, in response to distension and/or food and which causes secretion of pancreatic juices. The two major proteases which the pancreas are trypsinogen and chymotrypsinogen. These zymogens are inactivated forms of trypsin and chymotrypsin. Once released in the intestine, the enzyme enterokinase present in the intestinal mucosa activates trypsinogen by cleaving it to form trypsin. The free trypsin then cleaves the rest of the trypsinogen and chymotrypsinogen to their active forms. Pancreatic secretions accumulate in intralobular ducts that drain the main pancreatic duct, which drains directly into the duodenum. Due to the importance of its enzyme contents, injuring the pancreas is a very dangerous situation. A puncture of the pancreas tends to require careful medical intervention. - **Endocrine** Scattered among the acini are the endocrine cells of the pancreas, in groups called the islets of Langerhans. They are: Insulin-producing beta cells (50-80% of the islet cells) Glucagon-releasing alpha cells (15-20%) Somatostatin-producing delta cells (3-10%) Pancreatic polypeptide-containing PP cells (remaining %) The islets are a compact collection of endocrine cells arranged in clusters and cords and are crisscrossed by a dense network of capillaries. The capillaries of the islets are lined by layers of endocrine cells in direct contact with vessels, and most endocrine cells are in direct contact with blood vessels, by either cytoplasmic processes or by direct apposition. **Liver** The liver is an organ in vertebrates, including human. It plays a major role in metabolism and has a number of functions in the body including glycogen storage, plasma protein synthesis, and drug detoxification. It also produces bile, which is important in digestion. It performs and regulates a wide variety of high-volume biochemical reaction requiring specialized tissues. The liver normally weighs between 1.3 - 3.0 kilograms and is a soft, pinkish-brown \"boomerang shaped\" organ. It is the second largest organ (the largest being the skin) and the largest gland within the human body. Its anatomical position in the body is immediately under the diaphragm on the right side of the upper abdomen, The liver lies on the right side of the stomach and makes a kind of bed for the gallbladder. The liver is supplied by two main blood vessels on its right lobe: the hepatic artery and the portal vein. The hepatic artery normally comes off the celiac trunk. The portal vein brings venous blood from the spleen, pancreas, and small intestine, so that the liver can process the nutrients and byproducts of food digestion. The hepatic veins drain directly into the inferior vena cava. The bile produced in the liver is collected in bile canaliculi, which merge from bile ducts. These eventually drain into the right and left hepatic ducts, which in turn merge to form the common hepatic duct. The cystic duct (from the gallbladder) joins with the common hepatic duct to form the common bile duct. Bile can either drain directly into the duodenum via the common bile duct or be temporarily stored in the gallbladder via the cystic duct. The common bile duct and the pancreatic duct enter the duodenum together at the ampulla of Vater. The branching\'s of the bile ducts resemble those of a tree, and indeed term \"biliary tree\" is commonly used in this setting. The liver is among the few internal human organs capable of natural regeneration of lost tissue: as little as 25% of remaining liver can regenerate into a whole liver again. This is predominantly due to hepatocytes acting as unipotential stem cells. There is also some evidence of bio potential stem cells, called oval cell, which can differentiate into either hepatocytes or cholangiocytes (cells that line bile ducts). The various functions of the liver are carried out by the liver cells or hepatocytes. - The liver produces and excretes bile, required for dissolving fats. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder - The liver performs several roles in carbohydrate metabolism: - gluconeogenesis (the formation of glucose from certain amino acids, lactate or glycerol) - Glycogenolysis (the formation of glucose from glycogen) - Glycogenesis (the formation of glycogen from glucose) - The breakdown of insulin and other hormones - The liver is responsible for the mainstay of protein metabolism. - The liver also performs several roles in lipid metabolism: - cholesterol synthesis - The production of triglycerides (fats) - The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, X and XI, as well as protein C, Protein S and antithrombin. - The liver breaks down hemoglobin, creating metabolites that are added to bile as pigment - The liver breaks down toxic substances and most medicinal products in a process called drug metabolism. This sometimes results in toxication, when the metabolite is more toxic than its precursor. - The liver converts ammonia to urea. - The liver stores a multitude of substances, including glucose in the form of glycogen, vitamin B12, iron, and copper. - In the first trimester fetus, the liver is the main site of red blood cell production. By the 32nd weeks of gestation, the bone marrow has almost completely taken over that task. - The liver is responsible for immunological effects; the reticuloendothelial system of the liver contains many immunologically active cells, acting as a \'sieve\' for antigens carried to it via the portal system. **Gallbladder** The gallbladder is a pear shaped organ that stores about 50 ml of bile (or \"gall\") until the body needs it for digestion. The gallbladder is about 7-10cm long in humans and is dark green in appearance due to its contents (bile), not its tissue. It is connected to the liver and the duodenum by the biliary tract. The gallbladder is connected to the main bile duct through the gallbladder duct (cystic duct). The main biliary tract runs from the liver to the duodenum, and the cystic duct is effectively a \"cul de sac\", serving as entrance and exit to the gallbladder. The surface marking of the gallbladder is the intersection of the midclavicular line (MCL) and the trans pyloric plane, at the tip of the ninth rib. The blood supply is by the cystic artery and vein, which runs parallel to the cystic duct. The cystic artery is highly variable, and this is of clinical relevance since it must be clipped and cut during a cholecystectomy. The gallbladder has an epithelial lining characterized by recesses called Aschoff\'s recesses, which are pouches inside the lining. Under the epithelium there is a layer of connective tissue, followed by a muscular wall that contracts in response to cholecystokinin, a peptide hormone synthesized in the duodenum. The gallbladder stores bile, which is released when food containing fat enters the digestive tract, stimulating the secretion of cholecystokinin (CCK). The bile emulsifies fats and neutralizes acids in partly digested food. After being stored in the gallbladder, the bile becomes more concentrated than when it left the liver, increasing its potency and intensifying its effect on fats. ## Anus ![](Gray1078.png "Gray1078.png") The human anus is situated between the buttocks, posterior to the perineum. It has two anal sphincters, one internal, the other external. These hold the anus closed until defecation occurs. One sphincter consists of smooth muscle and its action is involuntary; the other consists of striated muscle and its action is voluntary. In many animals, the anus is surrounded by anal sacs. Role of the anus is when the rectum is full, the increase in intra-rectal pressure forces the walls of the anal canal apart allowing the fecal matter to enter the canal. The rectum shortens as material is forced into the anal canal and peristaltic waves propel the feces out of the rectum. The internal and external sphincters of the anus allow the feces to be passed by muscles pulling the anus up over the exiting feces. ## Conditions Affecting the Esophagus There are two different types of conditions that may affect the esophagus. The first type is called congenital: meaning a person is born with it. The second type is called non-congenital: meaning the person develops it after birth. Some examples of these are: **Tracheoesophageal fistula and esophageal atresia** Both of these conditions are congenital. In *Tracheoesophageal fistula* there is a connection between the esophagus and the wind pipe (trachea) where there shouldn\'t be one. In *Esophageal atresia* the esophagus of a newborn does not connect to the stomach but comes to a dead end right before the stomach. Both conditions require corrective surgery and are usually detected right after the baby is born. In some cases, it can be detected before the baby is born. **Esophagitis** Esophagitis is inflammation of the esophagus and is a non-congenital condition. Esophagitis can be caused by certain medications or by infections. It can also be caused by gastroesophageal reflux disease (gerd), a condition where the esophageal sphincter allows the acidic contents of the stomach to move back up into the esophagus. Gastroesophageal reflux disease can be treated with medications, but it can also be corrected by changing what you eat. ## Conditions Affecting the Stomach and Intestines Everybody has experienced constipation or diarrhea in their lifetime. With constipation, the contents of the large intestines don\'t move along fast enough and waste material stays in the large intestines so long that almost all water is extracted out of the waste and it becomes hard. With diarrhea you get the exact opposite reaction: waste moves along too fast and the large intestines can\'t absorb the water before the waste is pushed through. Common flora bacteria assists in the prevention of many serious problems. Here are some more examples of common stomach and intestinal disorders: !Acute Appendicitis: An exemplary case of acute appendicitis in a 10-year-old boy. The organ is enlarged and sausage-like (botuliform). This longitudinal section shows the angry red inflamed mucosa with its irregular luminal surface. Diagnosed and removed early in the course of the disease, this appendix does not show late complications, like transmural necrosis, perforation, and abscess formation.. This longitudinal section shows the angry red inflamed mucosa with its irregular luminal surface. Diagnosed and removed early in the course of the disease, this appendix does not show late complications, like transmural necrosis, perforation, and abscess formation.") **Appendicitis** Appendicitis is the inflammation of the appendix, the finger-like pouch that extends from the cecum. The most common symptoms are abdominal pain, loss of appetite, fever, and vomiting. Children and teenagers are the most common victims of appendicitis, which must be corrected by surgery. While mild cases may resolve without treatment, most require removal of the inflamed appendix, either by laparotomy or laparoscopy. Untreated, mortality is high, mainly due to peritonitis and shock. **Celiac Disease** Celiac disease is a disorder in which a person\'s digestive system is damaged by the response of the immune system to a protein called gluten, which is found in rye, wheat, and barley, and also in foods like breakfast cereal and pizza crust. People who have celiac disease experience abdominal pain, diarrhea, bloating, exhaustion, and depression when they eat foods with gluten in them. They also have difficulty digesting their food. Celiac disease runs in families and becomes active after some sort of stress, like viral infections or surgery. The symptoms can be managed by following a gluten free diet. Doctors can diagnose this condition by taking a full medical history or with a blood test. **Diverticulitis** !Benign gastric ulcer Diverticulitis is a common disease of the bowel, in particular the large intestine. Diverticulitis develops from diverticulosis, which involves the formation of pouches (diverticula) on the outside of the colon. Diverticulitis results if one of these diverticula becomes inflamed. In complicated diverticulitis, bacteria may subsequently infect the outside of the colon if an inflamed diverticula bursts open. If the infection spreads to the lining of the abdominal cavity (peritoneum), this can cause a potentially fatal peritonitis. Sometimes inflamed diverticula can cause narrowing of the bowel, leading to an obstruction. Also, the affected part of the colon could adhere to the bladder or other organ in the pelvic cavity, causing a fistula, or abnormal communication between the colon and an adjacent organ. **Gastritis and Peptic ulcers** Usually the stomach and the duodenum are resistant to irritation because of the strong acids produced by the stomach. But sometimes a bacteria called Helicobacter pylori or the chronic use of drugs or certain medications, weakens the mucous layer that coats the stomach and the duodenum, allowing acid to get through the sensitive lining beneath. This can cause irritation and inflammation of the lining of the stomach, which is called gastritis, or cause peptic ulcers, which are holes or sores that form in the lining of the stomach and duodenum and cause pain and bleeding. Medications are the best way to treat this condition. **Gastrointestinal Infections** Gastrointestinal infections can be caused by bacteria such as Campylobacter, Salmonella, E. coli, or Shigella. They can also be caused by viruses or by intestinal parasites like amebiasis and Giardiasis. The most common symptoms of gastrointestinal infections are abdominal pain and cramps, diarrhea, and vomiting. These conditions usually go away on their own and don\'t need medical attention. **Inflammatory Bowel Disease** Inflammatory bowel disease is the chronic inflammation of the intestines, which usually affects older children, teens and adults. There are two major types, *ulcerative colitis* and *Crohn\'s* *disease* and indeterminate colitis, which occurs in 10-15% of patients. Ulcerative colitis usually affects just the rectum and large intestine, while Crohn\'s disease can affect the whole gastrointestinal tract from mouth to anus along with some other parts of the body. Patients with these diseases also suffer from extraintestinal symptoms including joint pain and red eye, which can signal a flare of the disease. These diseases are treated with medications and if necessary, Intravenous or IV feeding, or in the more serious cases, surgery to remove the damaged areas of the intestines. **Polyp** A polyp is an abnormal growth of tissue (tumor) projecting from a mucous membrane. If it is attached to the surface by a narrow elongated stalk it is said to be pedunculated. If no stalk is present it is said to be sessile. Polyps are commonly found in the colon, stomach, nose, urinary bladder and uterus. They may also occur elsewhere in the body where mucous membranes exist like the cervix and small intestine. ## Disorders of the Pancreas, Liver, and Gallbladder Disorders of the pancreas, liver, and gallbladder affect the ability to produce enzymes and acids that aid in digestion. examples of these disorders are. **Cystic Fibrosis** Cystic fibrosis is a chronic, inherited illness where the production of abnormally thick mucous blocks the duct or passageways in the pancreas and prevents the digestive fluids from entering the intestines, making it difficult for the person with the disorder to digest protein and fats, which cause important nutrients to pass through without being digested. People with this disorder take supplements and digestive enzymes to help manage their digestive problems. **Hepatitis** Hepatitis is a viral condition that inflames a person\'s liver which can cause it to lose its ability to function. Viral hepatitis, like hepatitis A, B, and C, is extremely contagious. Hepatitis A, which is a mild form of hepatitis, can be treated at home, but more serious cases that involve liver damage, might require hospitalization. **Cholecystitis** Acute or chronic inflammation if the gallbladder causes abdominal pain. 90% of cases of acute cholecystitis are caused by the presence of gallstones. The actual inflammation is due to secondary infection with bacteria of an obstructed gallbladder, with the obstruction caused by the gallstones. Gallbladder conditions are very rare in kids and teenagers but can occur when the kid or teenager has sickle cell anemia or in kids being treated with long term medications. **Cholestasis** Cholestasis is the blockage in the supply of bile into the digestive tract. It can be \"intrahepatic\" (the obstruction is in the liver) or \"extrahepatic\" (outside the liver). It can lead to jaundice, and is identified by the presence of elevated bilirubin level that is mainly conjugated. **Biliary colic** This is when a gallstone blocks either the common bile duct or the duct leading into it from the gallbladder. This condition causes severe pain in the right upper abdomen and sometimes through to the upper back. It is described by many doctors as the most severe pain in existence, between childbirth and a heart attack. Other symptoms are nausea, vomiting, diarrhea, bleeding caused by continual vomiting, and dehydration caused by the nausea and diarrhea. Another more serious complication is total blockage of the bile duct which leads to jaundice, which if it is not corrected naturally or by surgical procedure can be fatal, as it causes liver damage. The only long term solution is the removal of the gallbladder. ## Gastrointestinal Dysfunctions As we age, the amount of digestive enzymes produced by the body drops way down. This leads to decreased and slower digestion, slower absorption of nutrients and increased accumulation of fecal mater in the intestinal tract. Undigested food material and metabolic waste can also build up due to slow elimination, starting a series of health problems. When digestion slows, it turns the intestines into a toxic environment. Helpful organisms cannot live in toxic environments. When the beneficial organisms die they are replaced by harmful organisms, such as yeasts and parasites, the most common being *Candida albicans*. This leads to changes in the intestinal wall which produce *leaky gut syndrome*, which allows many toxic chemicals to be introduced into the bloodstream. As a result, the entire toxic load of the body is increased, causing a bigger burden on the liver, kidneys and other body organs. When this happens the organs that are normally used for eliminating waste and supplying nutrients to the GI tract become a large dump for waste. This problem can be made worse by the use of prescriptions and over-the-counter medications, antibiotics, and a diet that is too low in fiber or contains \'junk food\'. Most people never think about their GI tract. We are concerned about what the outside of our bodies look like, but we completely ignore the inside. Because our bodies a very resilient, deterioration of the digestive system can go on for years with no symptoms or side-effects. When symptoms finally do appear they are usually very non-specific, and include: decreased energy, headaches, diarrhea, constipation, heartburn, and acid reflux. Over the years these symptoms become more serious, including: asthma, food allergies, arthritis, and cancer. Poor digestion, poor absorption, and bacterial imbalance can be traced to many chronic conditions. Every organ in the body receives nutrients from the GI tract; if the GI tract is malfunctioning then the whole body suffers. It is possible to return good health to your GI tract by improving digestion, consuming the right amount of fiber, and cutting out junk food and refined sugars. You can improve the function of the intestines by taking fiber supplements and vitamins (especially B12 and vitamin K). Some doctors suggest herbal or vitamin enemas to cleanse and relieve constipation and to help stimulate *peristaltic movement* which will help to move the bowels. **Irritable Bowel Syndrome** Irritable Bowel Syndrome (IBS) is a disorder with symptoms that are most commonly bloating, abdominal pain, cramping, constipation, and diarrhea. IBS causes a lot of pain and discomfort. It does not cause permanent damage to the intestines and does not lead to serious diseases such as cancer. Most of the people affected with IBS can control their symptoms with stress management, diet, and prescription medication. For others IBS can be debilitating, they may be unable to go to work, travel, attend social events or leave home for even short periods of time. About 20 percent of the adult population has some symptoms of IBS, making it one of the most common intestinal disorders diagnosed by physicians. It is more common in men than women and in about 50 percent of people affected it starts at about age 35. Researchers have not found out what exactly causes IBS. One idea is that people with IBS have a large intestine (colon) that is sensitive to certain foods and stress. The immune system may also be involved. It has also been reported that *serotonin* is linked with normal GI functioning. 95 percent of the body\'s serotonin is located in the GI tract (the other 5 percent is in the brain). People with IBS have diminished receptor activity, causing abnormal levels of serotonin in the GI tract. Because of this, IBS patients experience problems with bowel movement, motility, and the sensation having more sensitive pain receptors in their GI tract. Many IBS patients suffer from depression and anxiety which can make symptoms worse. There is no cure for IBS, but medications are an important part of relieving symptoms. Fiber supplements or laxatives are helpful for constipation. Anti diarrhoeals such as Imodium can help with diarrhea. An antispasmodic is commonly prescribed for colon muscle spasms. Antidepressants and pain medication are also commonly prescribed. \[12\] **Gastrointestinal Stromal Tumor** Gastrointestinal Stromal Tumors or GIST is an uncommon type of cancer in the GI tract (esophagus, stomach, small intestine, and colon). These types of cancers begin in the connective tissue like fat, muscles, nerves, cartilage, etc. GIST originates in the stroma cells. Stroma cells are strung along the GI tract and are part of the system that helps the body to know when to move food through the digestive system. Over half of GISTs occur in the stomach. Most cases occur in people between the ages of forty and eighty, but they can also occur in a person of any age. All GISTs of any size or location have the ability to spread. Even if a GIST is removed, it can reappear in the same area, or may even spread outside of the GI tract. In the early stages, GIST is hard to diagnose because early-stage symptoms cannot be recognized. In the later stages a person can have vague abdominal pain, vomiting, abdominal bleeding that shows up in stool or vomit, low blood counts causing anemia, and having an early feeling of being full, causing a decrease in appetite. GIST is now recognized as an aggressive cancer that is able to spread to other parts of the body. People who have been diagnosed with GIST should get treatment as soon as possible. **Food Allergies** Food allergies occur when the immune system thinks that a certain protein in any kind of food is a foreign substance and will try to fight against it. Only about eight percent of children and two percent of adults actually have a food allergy. A person can be allergic to any kind of food, but the most common food allergies are to nuts, cow\'s milk, eggs, soy, fish, and shellfish. Most people who have a food allergy are allergic to fewer than four different foods. The most common signs of food allergies are hives, swelling, itchy skin, itchiness, tingling or swelling in the mouth, coughing, trouble breathing, diarrhea, and vomiting. The two most common chronic illness that are associated with food allergies are eczema and asthma. Food allergies can be fatal if they cause the reaction called anaphylaxis. This reaction makes it hard for the person to breathe. This can be treated by an epinephrine injection. **GERD, Heartburn, Acid Reflux** GERD, or Gastroesophageal Reflux Disease occurs when the lower esophageal sphincter is not able to close properly. When this happens, contents from the stomach, called reflux, leak back into the esophagus and the stomach. When the stomach refluxes, stomach acid touches the lining of the esophagus and causes it to have a burning feeling in the throat or the chest. This is what heartburn is. When you taste the fluid in the back of your throat, it is called acid indigestion. It is common for a person to get occasional heartburn, but when it occurs more than twice a week it can be considered to be GERD. GERD can occur in people of all ages including infants. Some symptoms of GERD include having a pain in your chest, hoarseness, having trouble swallowing, or having the feeling of food being stuck in your throat. The main symptoms are having persistent heartburn and acid regurgitation. GERD can also cause bad breath and a dry cough. No one knows why people get GERD. Some things that could contribute to GERD are alcohol use, pregnancy, being overweight and smoking. Certain foods might also contribute like citrus fruits, caffeine, spicy, fatty, and dried foods, and also mint flavorings. Over-the-counter antacids or medications that help stop acid production and help the muscles empty the stomach are commonly used to treat GERD. **Constipation** Not everyone is on the same schedule for having a bowel movement. Depending on the person, a \"normal\" schedule can range anywhere from three times a day to three times a week. If you start having bowel movements less than your own personal schedule, then you might be getting the signs of constipation. Constipation is when you have trouble having bowel movements. The stool is very hard, making it difficult to pass and causing a person to strain. You may even feel like you have to have a bowel movement even after you have already had one. When you digest food, the waste products go through your intestines by the muscles contracting. When in the large intestine, most of the water and salt from the waste products are reabsorbed because they are needed by the body for our everyday functions. You can become constipated if too much water is absorbed, or if waste products move too slowly. Not getting enough fluids, a low fiber diet, age, not being physically active, depression, stress and pregnancy can all contribute to constipation. Medications and narcotics can also cause a person to get constipated. Chronic constipation may be a symptom of a liver problem such as a urea cycle disorder. The best way for a person to treat constipation is to make sure that they are getting enough fluids as well as fiber in their diet. By doing this, the bulk of their stool is increased and made softer, so that it can move through the intestines more easily. Being more active and increasing daily exercise also helps keep bowel movements regulated. **Hemorrhoids** Hemorrhoids (also known as haemorrhoids, emerods, or piles) are varicosities or swelling and inflammation of veins in the rectum and anus. Two of the most common types of hemorrhoids are external and internal hemorrhoids. - **External hemorrhoids** are those that occur outside of the anal verge (the distal end of the anal canal). They are sometimes painful, and can be accompanied by swelling and irritation. Itching, although often thought to be a symptom from external hemorrhoids, is more commonly due to skin irritation. - If the vein ruptures and a blood clot develops, the hemorrhoid becomes a **thrombosed hemorrhoid**. ```{=html} <!-- --> ``` - **Internal hemorrhoids** are those that occur inside the rectum. As this area lacks pain sensory receptor\|receptors, internal hemorrhoids are usually not painful and most people are not aware that they have them. Internal hemorrhoids, however, may bleed when irritated. ```{=html} <!-- --> ``` - Untreated internal hemorrhoids can lead to two severe forms of hemorrhoids: prolapsed and strangulated hemorrhoids. - **Prolapsed hemorrhoids** are internal hemorrhoids that are so distended that they are pushed outside of the anus. - If the anal sphincter muscle goes into spasm and traps a prolapsed hemorrhoid outside of the anal opening, the supply of blood is cut off, and the hemorrhoid becomes a **strangulated hemorrhoid**. ## Bleeding in the Gastrointestinal tract Bleeding in the gastrointestinal tract doesn\'t always mean you have a disease, it\'s usually a symptom of a digestive problem. The cause of the bleeding may not be that serious, it could be something that can be cured or controlled such as hemorrhoids. However, locating the source of the bleeding is very important. The gastrointestinal tract contains many important organs like the esophagus, stomach, small intestine, large intestine or colon, rectum, and anus. Bleeding can come from one or more of these area from a small ulcer in the stomach, or a large surface like the inflammation of the colon. Sometimes a person doesn\'t even know they are bleeding. When this happens, it is called hidden, or occult bleeding. Simple tests can detect hidden blood in the stool. **What Causes Bleeding in the Digestive Tract** Esophageal bleeding may be caused by Mallory-Weiss syndrome which is a tear in the esophagus. Mallory-Weiss syndrome is usually caused by excessive vomiting or may be caused by childbirth, a hiatal hernia, or increased pressure in the abdomen caused by coughing. Various medications can cause stomach ulcers or inflammations. Medications containing aspirin or alcohol, and various other medications(mainly those used for arthritis) are some examples of these. Benign tumors or cancer of the stomach may also cause bleeding. These disorders don\'t usually produce massive bleeding. The most common source of bleeding usually occurs from ulcers in the duodenum. Researchers believe that these ulcers are caused by excessive stomach acid and a bacteria called Helicobacter Pylori. In the lower digestive tract, the most common source of bleeding is in the large intestine, and the rectum. Hemorrhoids are the most common cause of bleeding in the digestive tract. Hemorrhoids are enlarged veins in the anal area which produces bright red blood that you see in the toilet or on the toilet paper. **How do you Recognize Bleeding in the Digestive Tract** The signs of bleeding in the digestive tract vary depending on the site and severity of the bleeding. If the blood is coming from the rectum, it would be bright red blood. If it was coming from higher up in the colon or from the small intestine, the blood would be darker. When the blood is coming from the stomach, esophagus, or the duodenum, the stool would be black and tarry. If the bleeding is hidden, or occult, a person may not notice changes in the stool color. If extensive bleeding occurs, a person may feel dizzy, faint, weak, short of breath, have diarrhea or cramp abdominal pain. Shock can also occur along with rapid pulse, drop in blood pressure, and difficulty urinating. Fatigue, lethargy, and pallor from anemia will settle in if the bleeding is slow. Anemia is when the bloods iron-rich substance, hemoglobin, is diminished. **Common Causes of Bleeding in the Digestive Tract** - Hemorrhoids - Gastritis (inflammation) - Inflammation (ulcerative colitis) - Colo rectal Polyps - Colo rectal Cancer - Duodenal Ulcer - Enlarged Veins - Esophagitis (inflammation of the esophagus) - Mallory-Weiss Syndrome - Ulcers Iron and beets can also turn the blood red or black giving a false indication of blood in the stool. **How Bleeding in the Digestive Tract is Diagnosed** To diagnose bleeding in the digestive tract the bleeding must be located and a complete history and physical are very important. Here are some of the procedures that diagnose the cause of bleeding. **Endoscopy** An endoscopy is a common diagnostic technique that allows direct viewing of the bleeding site. Since the endoscope can detect lesions and confirm the absence or presence of bleeding, doctors often use this method to diagnose acute bleeding, the endoscope can also be used to treat the cause of bleeding as well. The endoscope is a flexible instrument that can be inserted through the mouth or rectum. The instrument allows the doctors to see inside the esophagus, stomach, duodenum(esophagoduodenoscopy), sigmoid colon(sigmoidoscopy), and rectum(rectoscopy, to collect small samples of tissues, take pictures, and stop the bleeding. There is a new procedure out using a long endoscope that can be inserted during surgery to locate a source of bleeding in the small intestine. **Capsule Endoscopy** Capsule endoscopy helps doctors to see and examine the lining of the middle part of the gastrointestinal tract, which includes the three parts of the small intestine (duodenum, jejunum, ileum). The capsule is a small pill sized video camera called an endoscope. It has its own lens and light that transfers the images to a monitor so the doctor can view them outside of the body. This process is also referred to as small bowel endoscopy, capsule endoscopy, or wireless endoscopy. The most common reason for doing a capsule endoscopy is to look for the causes of bleeding that is coming from the small intestine. It is also able to help detect ulcers, tumors, and Crohn\'s disease. **Angiography** Angiography is a technique that uses dye to highlight blood vessels. This procedure is used when the patient is bleeding badly enough that it allows the dye to leak out of the blood vessels and identifies the bleeding site. In some situations, Angiography allows the patient to have medication injections that may stop the bleeding. **Radionuclide Scanning** Radionuclide scanning is a non-invasive screening technique used for locating sites of acute bleeding, especially in the lower GI tract. This procedure injects small amounts of radioactive material that either attach to the persons red blood cells or are suspended in the blood. Special pictures are taken that allows doctors to see the blood escaping. Barium x-rays, angiography, and radionuclide scans can be used to locate sites of chronic occult bleeding. **How to Recognize Blood in the Stool and Vomit** - Bright red blood coating the stool - Dark blood mixed with the stool - Black or tarry stool - Bright red blood in the vomit - Grainy appearance in vomit **Symptoms of Acute Bleeding** - Weakness - Shortness of breath - Dizziness - Cramp abdominal pain - Feeling light headed - Diarrhea **Symptoms of Chronic Bleeding** - Fatigue - Shortness of breath - Lethargy - Pallor ## Colonoscopy A colonoscopy is a test to look at the inside of your colon. Everyone should have a colonoscopy by the time they are 50 to check for diseases of the colon. Colonoscopy is best known for its use in early detection of colorectal cancer, the second leading cause of cancer deaths in the United States. Colon cancer develops from growths like polyps within the intestinal wall. These growths often take 5-10 years to develop usually without symptoms. You are at a higher risk to have this disease if you have a close relative who has had it. If you are going to develop a polyp, you will probably do so after age 50. So the American College of Gastroenterology (the digestive specialists) recommends screening examinations every 5 years for early detection and removal of these cancer-causing growths after that age. Don\'t make excuses! It\'s not so bad and it may save your life! ## Case Study Bob had a history of chronic pain in his intestinal area, and wasn\'t sure what it was. His doctor suspected what it was and gave Bob antibiotics, which helped. It so happened that whenever Bob ate popcorn or nuts he would get this pain. Sometimes it would just go away\... other times he had to go on antibiotics. The doctor ordered some tests, and told Bob he would have to stay away from nuts, popcorn, tomatoes, strawberries, and anything else with seeds or hard parts; something in his bowels couldn\'t tolerate those foods. Bob ate a pretty healthy diet so he couldn\'t understand what was happening. A few years later, Bob had another series of painful episodes. The pain was so great Bob could hardly stand, let alone go to work. This time the doctor did more tests and found out that his lower intestine was almost blocked. Surgery was ordered. What did Bob have? ## Glossary Amebiasis : An inflammation if the intestines caused by infestation with Entameba histolytica (a type of ameba) and characterized by frequent loose stools flecked with blood and mucus ```{=html} <!-- --> ``` Amylase : An enzyme produces in the pancreas and salivary glands that help in the digestions of starches. ```{=html} <!-- --> ``` Bile : A bitter, alkaline, brownish-yellow or greenish-yellow fluid that is secreted by the liver, stored in the gallbladder, and discharged into the duodenum and aids in the emulsification, digestion, and absorption of fats. Also called gall. ```{=html} <!-- --> ``` Biotin : Biotin is used in cell growth, the production of fatty acids, metabolism of fats, and amino acids. It plays a role in the Krebs Cycle. Biotin is also helpful in maintaining a steady blood sugar level. It is often recommended for strengthening hair and nails. ```{=html} <!-- --> ``` B12 : A vitamin important for the normal formation of red blood cells and the health of the nerve tissues. Undetected and untreated B12 deficiency can lead to anemia and permanent nerve and brain damage ```{=html} <!-- --> ``` Candida Albicans : Found in animals and in man. Has been isolated from the skin and mucosa of man, but has also been recovered from leaves, flowers, water, and soil. Reported to be allergenic. A common cause of superficial infection, oral and vaginal infection, sepsis, and disseminated disease. Cells from the organism are usually not airborne and are considered to be normal component of the flora of the mouth and other mucous membranes on the body. ```{=html} <!-- --> ``` Chemical digestion: Is a chemical breakdown of food when being in the mouth (oral cavity). Is the digestive secretions of saliva that moistens food and introduces gastric juices and enzymes that are produced in the stimulation to certain macronutrients, such as, carbohydrates. In this, the mouth saliva carries an enzyme called amylase for breaking down carbohydrates. ```{=html} <!-- --> ``` Cholecystokinin (CCK) : Cholecystokinin (also called pancreozymin), this is a hormone in the small intestinal cells (intestinal mucosa) that is produced in response to food. This hormone regulates the release of secretions of many organs that aid digestion, such as, bicarbonate from the pancreas to reduce the acidity of digestive juices like the chyme that enters the small intestine form the stomach that contains hydrochloric acid (HCL). ```{=html} <!-- --> ``` Chylomicrons : The lipoproteins first formed after absorption of lipids form food. ```{=html} <!-- --> ``` Chyme : The thick semi fluid mass of partly digested food that is passed from the stomach to the duodenum. ```{=html} <!-- --> ``` Crohn\'s Disease : Described as skip lessions in the large and small bowel it is a malabsorption disorder that can affect the gastrointestinal tract for the mouth to the anus. ```{=html} <!-- --> ``` Deamination: When an amino acid group breaks off an amino acid that makes a molecule of ammonia and keto acid. ```{=html} <!-- --> ``` Emulsifier : A mixture of two immiscible (unblendable) substances. ```{=html} <!-- --> ``` Gastrin : The stomach mucosa secretes a hormone gastrin that increases the release of gastric juices. ```{=html} <!-- --> ``` GI tract : Gastrointestinal Tract, The tube that extends from the mouth to the anus in which the movement of muscles and release of hormones and enzymes digest food. ```{=html} <!-- --> ``` Hydrochloric : The chemical substance hydrochloric acid is the water-based solution of hydrogen chloride (HCI) gas. It is a strong acid, the major component of stomach acid and of wide industrial use. ```{=html} <!-- --> ``` Lactobacillus Acidophilus : Important resident inhabitant of the human small and large intestines, mouth, and vagina. Secretes natural antibiotic substances which strengthen the body against various disease-causing microbes ```{=html} <!-- --> ``` Leaky gut syndrome : Abnormal level of intestinal permeability ```{=html} <!-- --> ``` Lingual lipase : An enzyme produced only in infancy to aid digestion of long-chain fatty acids. ```{=html} <!-- --> ``` Lipase : An enzyme produced by microorganisms that split the fat molecules into fatty acids which create flavor ```{=html} <!-- --> ``` Mechanical digestion: The crushing of the teeth and rhythms made by the movement of the tongue, the teeth aid in tearing and pulverizing food, while the tongue helps with peristalsis (movement), of food down the esophagus. ```{=html} <!-- --> ``` Micelles : A product of lipids and bile assist in lipid absorption. ```{=html} <!-- --> ``` Microvilli : On the villi in the small intestine is mivrovilli, these projections called brush border microvilli secrete specific enzymes for disaccharide hydrolysis, these further aid the absorption of the carbohydrate by yielding a monosaccharide that then can go through portal circulation to liver circulation to be further processed into immediate use for energy or glycogen storage. ```{=html} <!-- --> ``` Peristalsis : The wavelike muscular contractions of the intestine or other tubular structure that propel the contents onward by alternate contraction and relaxation. ```{=html} <!-- --> ``` Pharynx : ```{=html} <!-- --> ``` Proliferation : The process of reproduction or division of cells ```{=html} <!-- --> ``` Proteases : Protein enzyme ```{=html} <!-- --> ``` Rennin : Only produced during infancy and is a gastric protease and functions with calcium to clot with milk proteins casein, to slow the movement of milk so that digestion is prolonged. ```{=html} <!-- --> ``` Serotonin : chemical messenger in the brain that affects emotions, behavior, and thought ```{=html} <!-- --> ``` Synthesize : To create something, such as chemicals in the body, from simpler, raw materials ```{=html} <!-- --> ``` Ulcerative Colitis : ```{=html} <!-- --> ``` Villi : A minute projection arising from a mucous membrane, especially one of the vascular projections of the small intestine. ```{=html} <!-- --> ``` Vitamin K : A substance that promotes the clotting of blood **Case Study Answer** Bob has diverticulitis. The doctor was afraid that if he had another bad infection that scar tissue would eventually block his colon completely and burst, which would necessitate a colostomy. Bob ended up having to have surgery to remove the damaged part of his colon. The doctor removed almost 18 inches of Bob\'s large intestine. Bob is doing fine now and most importantly, he can now eat his favorite food - nuts! Note: Sometimes a diet rich in fiber can help you avoid this dreaded problem. Sometimes, like in Bob\'s case, the predisposition to have this problem runs in the family. All of his siblings and his father suffered from this same ailment. Stress is another factor that can exacerbate this disease. So.. don\'t worry, be happy and eat fiber! ## External links - Appendicitis Update Review, An updated Issue on Appendicitis ## References 1: Chen Ts, Chen PS. Intestinal autointoxication: A gastrointestinal leitmotive: Journal Clinical Gastroenterology 2: Ernst E. Colonic irrigation and the theory of autointoxication: A triumph of ignorance over science. Journal of Gastroenterology 3: Alvarez WC. Origin of the so-called auto-intoxication symptoms. 4: Donaldson AN. Relation of constipation to intestinal intoxication. 5: Kenney JJ. Fit for Life: Some notes on the book and its roots. Nutrition Forum 6: Use of enemas is limited. FDA consumer 7: Amebiasis associated with colonic irrigation - Colorado. Morbidity and Mortality Weekly Report 8: Istre GR and others. An outbreak of amebiasis spread by colonic irrigation at a chiropractic clinic 9: Benjamin R and others. The case against colonic irrigation 10: Eisele JW, Reay DT. Deaths related to coffee enemas 11: Jarvis WT. Colonic Irrigation. National Council Against Health Fraud. 12: National Digestive Disease Information Clearinghouse (NDDIC)
# Human Physiology/The endocrine system ## Introduction To The Endocrine System The endocrine system is a control system of ductless glands that secrete hormones within specific organs. Hormones act as \"messengers,\" and are carried by the bloodstream to different cells in the body, which interpret these messages and act on them. It seems like a far fetched idea that a small chemical can enter the bloodstream and cause an action at a distant location in the body. Yet this occurs in our bodies every day of our lives. The ability to maintain homeostasis and respond to stimuli is largely due to hormones secreted within the body. Without hormones, you could not grow, maintain a constant temperature, produce offspring, or perform the basic actions and functions that are essential for life. The endocrine system provides an electrochemical connection from the hypothalamus of the brain to all the organs that control the body metabolism, growth and development, and reproduction. There are two types of hormones secreted in the endocrine system: Steroidal (or lipid based) and non-steroidal, (or protein based) hormones. The endocrine system regulates its hormones through negative feedback, except in very specific cases like childbirth. Increases in hormone activity decrease the production of that hormone. The immune system and other factors contribute as control factors also, altogether maintaining constant levels of hormones. ## Types of Glands !Major endocrine glands. (Male left, female on the right.) **1.** Pineal gland **2.** Pituitary gland **3.** Thyroid gland **4.** Thymus **5.** Adrenal gland **6.** Pancreas **7.** Ovary **8.** Testis 1. Pineal gland 2. Pituitary gland 3. Thyroid gland 4. Thymus 5. Adrenal gland 6. Pancreas 7. Ovary 8. Testis"){width="227"} **Exocrine Glands** are those which release their cellular secretions through a duct which empties to the outside or into the lumen (empty internal space) of an organ. These include certain sweat glands, salivary and pancreatic glands, and mammary glands. They are not considered a part of the endocrine system. **Endocrine Glands** are those glands which have no duct and release their secretions directly into the intercellular fluid or into the blood. The collection of endocrine glands makes up the endocrine system. : 1, The main endocrine glands are the pituitary (anterior and posterior lobes), thyroid, parathyroid, adrenal (cortex and medulla), pancreas and gonads. ```{=html} <!-- --> ``` : 2, The pituitary gland is attached to the hypothalamus of the lower forebrain. ```{=html} <!-- --> ``` : 3, The thyroid gland consists of two lateral masses, connected by a cross bridge, that are attached to the trachea. They are slightly inferior to the larynx. ```{=html} <!-- --> ``` : 4, The parathyroid glands are four masses of tissue, two embedded posterior in each lateral mass of the thyroid gland. ```{=html} <!-- --> ``` : 5, One adrenal gland is located on top of each kidney. The cortex is the outer layer of the adrenal gland. The medulla is the inner core. ```{=html} <!-- --> ``` : 6, The pancreas is along the lower curvature of the stomach, close to where it meets the first region of the small intestine, the duodenum. ```{=html} <!-- --> ``` : 7, The gonads (ovaries and testes) are found in the pelvic cavity. ## Hormones and Types A **hormone** is a type of chemical signal. They are a means of communication between cells. The endocrine system produces hormones that are instrumental in maintaining homeostasis and regulating reproduction and development. A hormone is a chemical messenger produced by a cell that effects specific change in the cellular activity of other cells (target cells). Unlike exocrine glands (which produce substances such as saliva, milk, stomach acid and digestive enzymes), endocrine glands do not secrete substances into ducts (tubes). Instead, endocrine glands secrete their hormones directly into the surrounding extra cellular space. The hormones then diffuse into nearby capillaries and are transported throughout the body in the blood. The endocrine and nervous systems often work toward the same goal. Both influence other cells with chemicals (hormones and neurotransmitters). However, they attain their goals differently. Neurotransmitters act immediately (within milliseconds) on adjacent muscle, gland, or other nervous cells, and their effect is short-lived. In contrast, hormones take longer to produce their intended effect (seconds to days), may affect any cell, nearby or distant, and produce effects that last as long as they remain in the blood, which could be up to several hours. In the following table there are the major hormones, their target and their function once in the target cell. Endocrine Gland Hormone Released Chemical Class Target Tissue/Organ Major Function of Hormone ------------------------- ------------------------------------------------ ---------------------- --------------------------------- --------------------------------------------------------------------------------------------- **Hypothalamus** Hypothalamic releasing and inhibiting hormones Peptide Anterior pituitary Regulate anterior pituitary hormone **Posterior Pituitary** Antidiuretic (ADH) Peptide Kidneys Stimulates water reabsorption by kidneys Oxytocin Peptide Uterus, mammary glands Stimulates uterine muscle contractions and release of milk by mammary glands **Anterior Pituitary** Thyroid stimulating (TSH) Glycoprotein Thyroid Stimulates thyroid Adrenocorticotropic (ACTH) Peptide Adrenal cortex Stimulates adrenal cortex Gonadotropic (FSH, LH) Glycoprotein Gonads Egg and sperm production, sex hormone production Prolactin (PRL) Protein Mammary glands Milk production Growth (GH) Protein Soft tissue, bones Cell division, protein synthesis and bone growth **Thyroid** Thyroxine (T4) and Triiodothyronine (T3) Iodinated amino acid All tissue Increase metabolic rate, regulates growth and development Calcitonin Peptide Bones, kidneys and intestine Lowers blood calcium level **Parathyroids** Parathyroid (PTH) Peptide Bones, kidneys and intestine Raises blood calcium level **Adrenal Cortex** Glucocorticoids (cortisol) Steroid All tissue Raise blood glucose level, stimulates breakdown of protein Mineralocorticoids (aldosterone) Steroid Kidneys Reabsorb sodium and excrete potassium Sex Hormones Steroid Gonads, skin, muscles and bones Stimulates reproductive organs and brings on sex characteristics **Adrenal Medulla** Epinephrine and norepinephrine Modified amino acid Cardiac and other muscles Released in emergency situations, raises blood glucose level, "fight or flight" response **Pancreas** Insulin Protein Liver, muscles, adipose tissue Lowers blood glucose levels, promotes formation of glycogen Glucagon Protein Liver, muscles, adipose tissue Raises blood glucose levels **Testes** Androgens (testosterone) Steroid Gonads, skin, muscles and bone Stimulates male sex characteristics **Ovaries** Estrogen and progesterone Steroid Gonads, skin, muscles and bones Stimulates female sex characteristics **Thymus** Thymosins Peptide T lymphocytes Stimulates production and maturation of T lymphocytes **Pineal Gland** Melatonin Modified amino acid Brain Controls circadian and circannual rhythms, possibly involved in maturation of sexual organs Hormones can be chemically classified into four groups: 1. **Amino acid-derived**: Hormones that are modified amino acids. 2. **Polypeptide and proteins**: Hormones that are chains of amino acids of less than or more than about 100 amino acids, respectively. Some protein hormones are actually glycoproteins, containing glucose or other carbohydrate groups. 3. **Steroids**: Hormones that are lipids synthesized from cholesterol. Steroids are characterized by four interlocking carbohydrate rings. 4. **Eicosanoids**: Are lipids synthesized from the fatty acid chains of phospholipids found in plasma membrane. Hormones circulating in the blood diffuse into the interstitial fluids surrounding the cell. Cells with specific receptors for a hormone respond with an action that is appropriate for the cell. Because of the specificity of hormone and target cell, the effects produced by a single hormone may vary among different kinds of target cells. Hormones activate target cells by one of two methods, depending upon the chemical nature of the hormone. - **Lipid-soluble** hormones (steroid hormones and hormones of the thyroid gland) diffuse through the cell membranes of target cells. The lipid-soluble hormone then binds to a receptor protein that, in turn, activates a DNA segment that turns on specific genes. The proteins produced as result of the transcription of the genes and subsequent translation of mRNA act as enzymes that regulate specific physiological cell activity. ```{=html} <!-- --> ``` - **Water-soluble** hormones (polypeptide, protein, and most amino acid hormones) bind to a receptor protein on the plasma membrane of the cell. The receptor protein, in turn, stimulates the production of one of the following second messengers: Cyclic AMP (cAMP) is produced when the receptor protein activates another membrane-bound protein called a G protein. The G protein activates adenylate cyclase, the enzyme that catalyzes the production of cAMP from ATP. Cyclic AMP then triggers an enzyme that generates specific cellular changes. Inositol triphosphate (IP3) is produced from membrane phospholipids. IP3, in turn, triggers the release of CA2+ from the endoplasmic reticulum, which then activates enzymes that generate cellular changes. Endocrine glands release hormones in response to one or more of the following stimuli: 1. Hormones from other endocrine glands. 2. Chemical characteristics of the blood (other than hormones). 3. Neural stimulation. Most hormone production is managed by a negative feedback system. The nervous system and certain endocrine tissues monitor various internal conditions of the body. If action is required to maintain homeostasis, hormones are released, either directly by an endocrine gland or indirectly through the action of the hypothalamus of the brain, which stimulates other endocrine glands to release hormones. The hormones activate target cells, which initiate physiological changes that adjust the body conditions. When normal conditions have been recovered, the corrective action - the production of hormones - is discontinued. Thus, in negative feedback, when the original (abnormal) condition has been repaired, or negated, corrective actions decrease or discontinue. For example, the amount of glucose in the blood controls the secretion of insulin and glucagons via negative feedback. The production of some hormones is controlled by positive feedback. In such a system, hormones cause a condition to intensify, rather than decrease. As the condition intensifies, hormone production increases. Such positive feedback is uncommon, but does occur during childbirth, where hormone levels build with increasingly intense labor contractions. Also in lactation, hormone levels increase in response to nursing, which causes an increase in milk production. The hormone produced by the hypothalamus causing the milk let down and uterine contraction is **oxytocin**. ## Endocrine Glands ### Pituitary gland The hypothalamus makes up the lower region of the diencephalons and lies just above the brain stem. The pituitary gland (hypophysis) is attached to the bottom of the hypothalamus by a slender stalk called the infundibulum. The pituitary gland consists of two major regions, the anterior pituitary gland (anterior lobe or adenohypophysis) and the posterior pituitary gland (posterior lobe or neurohypophysis). The hypothalamus also controls the glandular secretion of the pituitary gland. The hypothalamus oversees many internal body conditions. It receives nervous stimuli from receptors throughout the body and monitors chemical and physical characteristics of the blood, including temperature, blood pressure, and nutrient, hormone, and water content. When deviations from homeostasis occur or when certain developmental changes are required, the hypothalamus stimulates cellular activity in various parts of the body by directing the release of hormones from the anterior and posterior pituitary glands. The hypothalamus communicates directives to these glands by one of the following two pathways: The pituitary gland is found in the inferior part of the brain and is connected by the pituitary stalk. It can be referred to as the master gland because it is the main place for everything that happens within the endocrine system. It is divided into two sections: the **anterior** lobe (adenohypophysis) and the **posterior** lobe (neurohypophysis). The Anterior pituitary is involved in sending hormones that control all other hormones of the body. #### Posterior pituitary Communication between the hypothalamus and the posterior pituitary occurs through neurosecretory cells that span the short distance between the hypothalamus and the posterior pituitary. Hormones produced by the cell bodies of the neurosecretory cells are packaged in vesicles and transported through the axon and stored in the axon terminals that lie in the posterior pituitary. When the neurosecretory cells are stimulated, the action potential generated triggers the release of the stored hormones from the axon terminals to a capillary network within the posterior pituitary. Two hormones, oxytocin and antidiuretic hormone (ADH), are produced and released this way. Decreased ADH release or decreased renal sensitivity to ADH produces a condition known as diabetes insipidus. Diabetes insipidus is characterized by polyuria (excess urine production), hypernatremia (increased blood sodium content) and polydipsia (thirst). Oxytocin is secreted by paraventricular nucleus and a small quantity is secreted by supraoptic nucleus in the hypothalamus. Oxytocin is secreted in both males and females. In females, oxytocin acts on the mammary glands and uterus. In males, oxytocin facilitates release of sperm into the urethra by causing contraction of vas deferens. The posterior lobe is composed of neural tissue \[neural ectoderm\] and is derived from hypothalamus. Its function is to store oxytocin and antidiuretic hormone. When the hypothalamic neurons fire these hormones are release into the capillaries of the posterior lobe. The posterior pituitary is, in effect, a projection of the hypothalamus. It does not produce its own hormones, but only stores and releases the hormones oxytocin and antidiuretic hormone. ADH is also known as arginine vasopressin (AVP) or simply vasopressin. #### Anterior pituitary The anterior lobe is derived from oral ectoderm and is composed of glandular epithelium. Communication between the hypothalamus and the anterior pituitary (adenohypophysis) occurs through hormones (releasing hormones and inhibiting hormones) produced by the hypothalamus and delivered to the anterior pituitary via a portal network of capillaries. It consists of three divisions: 1. pars distalis, 2. pars tuberalis, 3. pars intermedia. The releasing and inhibiting hormones are produced by specialized neurons of the hypothalamus called neurosecretory cells. The hormones are released into a capillary network or primary plexus, and transported through veins or hypophyseal portal veins, to a second capillary network or secondary plexus that supplies the anterior pituitary. The hormones then diffuse from the secondary plexus aunshine into the anterior pituitary, where they initiate the production of specific hormones by the anterior pituitary. Many of the hormones produced by the anterior pituitary are tropic hormones or tropins, which are hormones that stimulate other endocrine glands to secrete their hormones. The anterior pituitary lobe receives releasing hormones from the hypothalamus via a portal vein system known as the hypothalamic-hypophyseal portal system. The anterior pituitary secretes: - thyroid-stimulating hormone (TSH) - adrenocorticotropic hormone (ACH) - prolactin - follicle-stimulating hormone (FSH) - luteinizing hormone (LH) - growth hormone (GH) - endorphins - and other hormones It does this in response to a variety of chemical signals from the hypothalamus, which travels to the anterior lobe by way of a special capillary system from the hypothalamus, down the median eminence, to the anterior lobe. These include: - thyrotropin-releasing hormone (TRH) - corticotropin-releasing hormone (CRH) - dopamine (DA), also called \'prolactin inhibiting factor\' (PIF) - gonadotropin-releasing hormone (GnRH) - growth hormone releasing hormone (GHRH) These hormones from the hypothalamus cause release of the respective hormone from the pituitary. The control of release of hormones from the pituitary is via negative feedback from the target gland. For example homeostasis of thyroid hormones is achieved by the following mechanism; TRH from the hypothalamus stimulates the release of TSH from the anterior pituitary. The TSH, in turn, stimulates the release of thyroid hormones form the thyroid gland. The thyroid hormones then cause negative feedback, suppressing the release of TRH and TSH. The heart, gastrointestinal tract, the placenta, the kidneys and the skin, whose major function is not the secretion of hormones, also contain some specialized cells that produce hormones. In addition, all cells, except red blood cells secrete a class of hormones called eicosanoids. These hormones are paracrines, or local hormones, that primarily affect neighboring cells. Two groups of eicosanoids, the prostaglandins (PGs) and the leukotrienes (LTs), have a wide range of varying effects that depend upon the nature of the target cell. Eicosanoid activity, for example, may impact blood pressure, blood clotting, immune and inflammatory responses, reproductive processes, and the contraction of smooth muscles. ## Antagonistic Hormones Maintaining homeostasis often requires conditions to be limited to a narrow range. When conditions exceed the upper limit of homeostasis, specific action, usually the production of a hormone is triggered. When conditions return to normal, hormone production is discontinued. If conditions exceed the lower limits of homeostasis, a different action, usually the production of a second hormone is triggered. Hormones that act to return body conditions to within acceptable limits from opposite extremes are called **antagonistic hormones**. The two glands that are the most responsible for homeostasis is the thyroid and the parathyroid. The regulation of blood glucose concentration (through negative feedback) illustrates how the endocrine system maintains homeostasis by the action of antagonistic hormones. Bundles of cells in the pancreas called the islets of Langerhans contain two kinds of cells, **alpha cells** and **beta cells**. These cells control blood glucose concentration by producing the antagonistic hormones insulin and glucagon. Beta cells secrete **insulin**. When the concentration of blood glucose raises such in after eating, beta cells secret insulin into the blood. Insulin stimulates the liver and most other body cells to absorb glucose. Liver and muscle cells convert glucose to glycogen, for short term storage, and adipose cells convert glucose to fat. In response, glucose concentration decreases in the blood, and insulin secretion discontinues through negative feedback from declining levels of glucose. Alpha cells secrete **glucagon**. When the concentration of blood glucose drops such as during exercise, alpha cells secrete glucagon into the blood. Glucagon stimulates the liver to release glucose. The glucose in the liver originates from the breakdown of glycogen. Glucagon also stimulates the production of ketone bodies from amino acids and fatty acids. Ketone bodies are an alternative energy source to glucose for some tissues. When blood glucose levels return to normal, glucagon secretion discontinues through negative feedback. Another example of antagonistic hormones occurs in the maintenance of Ca^2+^ ion concentration in the blood. Parathyroid hormone (PTH) from the parathyroid glands increases Ca^2+^ in the blood by increasing Ca^2+^ absorption in the intestines and reabsorption in the kidneys and stimulating Ca^2+^ release from bones. Calcitonin (CT) produces the opposite effect by inhibiting the breakdown of bone matrix and decreasing the release of calcium in the blood. ### Thyroid gland The **Thyroid gland** is one of the largest endocrine glands in the body. It is positioned on the neck just below the Larynx and has two lobes with one on either side of the trachea. It is involved in the production of the hormones T3 (triiodothyronine) and T4 (thyroxine). These hormones increase the metabolic activity of the body's cells. The thyroid also produces and releases the hormone calcitonin (thyrocalcitonin) which contributes to the regulation of blood calcium levels. Thyrocalcitonin or calcitonin decreases the concentration of calcium in the blood. Most of the calcium removed from the blood is stored in the bones. The thyroid hormone consists of two components, thyroxine and iodine. This hormone increases the metabolism of most body cells. A deficiency of iodine in the diet leads to the enlargement of the thyroid gland, known as a simple goiter. Hypothyroidism during early development leads to cretinism. In adults, it produces myxedema, characterized by obesity and lethargy. Hyperthyroidism leads to a condition known as exophthalmic goiter, characterized by weight loss as well as hyperactive and irritable behavior. The thyroid gland is a two-lobed gland that manifests a remarkably powerful active transport mechanism for up-taking iodide ions from the blood. As blood flows through the gland, iodide is converted to an active form of iodine. This iodine combines with an amino acid called tyrosine. Two molecules of iodinated tyrosine then combine to form thyroxine. Following its formation, the thyroxine becomes bound to a polysaccharide-protein material called thyroglobulin. The normal thyroid gland may store several weeks supply of thyroxine in this bound form. An enzymatic splitting of the thyroxine from the thyroglobulin occurs when a specific hormone is released into the blood. This hormone, produced by the pituitary gland, is known as thyroid-stimulating hormone (TSH). TSH stimulates certain major rate-limiting steps in thyroxine secretion, and thereby alters its rate of release. A variety of bodily defects, either dietary, hereditary, or disease induced, may decrease the amount of thyroxine released into the blood. The most popular of these defects is one that results from dietary iodine deficiency. The thyroid gland enlarges, in the continued presence of TSH from the pituitary, to form a goiter. This is a futile attempt to synthesize thyroid hormones, for iodine levels that are too low. Normally, thyroid hormones act via a negative feedback loop on the pituitary to decrease stimulation of the thyroid. In goiter, the feedback loop cannot be in operation - hence continual stimulation of the thyroid and the inevitable protuberance on the neck. Formerly, the principal source of iodine came from seafood. As a result, goiter was prevalent amongst inland areas far removed from the sea. Today, the incidence of goiter has been drastically reduced by adding iodine to table salt. Thyroxine serves to stimulate oxidative metabolism in cells; it increases the oxygen consumption and heat production of most body tissues, a notable exception being the brain. Thyroxine is also necessary for normal growth. The most likely explanation being that thyroxine promotes the effects of growth hormone on protein synthesis. The absence of thyroxine significantly reduces the ability of growth hormone to stimulate amino acid uptake and RNA synthesis. Thyroxine also plays a crucial role in the closely related area of organ development, particularly that of the central nervous system. If there is an insufficient amount of thyroxine, a condition referred to as hypothyroidism results. Symptoms of hypothyroidism stem from the fact that there is a reduction in the rate of oxidative energy-releasing reactions within the body cells. Usually the patient shows puffy skin, sluggishness, and lowered vitality. Other symptoms of hypothyroidism include weight gain, decreased libido, inability to tolerate cold, muscle pain and spasm, and brittle nails. Hypothyroidism in children, a condition known as cretinism, can result in mental retardation, dwarfism, and permanent sexual immaturity. Sometimes the thyroid gland produces too much thyroxine, a condition known as hyperthyroidism. This condition produces symptoms such as an abnormally high body temperature, profuse sweating, high blood pressure, loss of weight, irritability, insomnia and muscular pain and weakness. It also causes the characteristic symptom of the eyeballs protruding from the skull called exophthalmia. This is surprising because it is not a symptom usually related to a fast metabolism. Hyperthyroidism has been treated by partial removal or by partial radiation destruction of the gland. More recently, several drugs that inhibit thyroid activity have been discovered, and their use is replacing the former surgical procedures. Unfortunately thyroid conditions require lifetime treatment and because of the body\'s need for a sensitive balance of thyroid hormone both supplementing and suppressing thyroid function can take months or even years to regulate. #### T3 and T4 Function within the body Iodine and T4 stimulate the spectacular apoptosis (programmed cell death) of the cells of the larval gills, tail and fins Transforming the aquatic, vegetarian tadpole into the terrestrial, carnivorous frog with better neurological, visuospatial, olfactory and cognitive abilities for hunting. Contrary to amphibian metamorphosis, thyroidectomy and hypothyroidism in mammals may be considered a sort of phylogenetic and metabolic regression to a former stage of reptilian life. Indeed, many disorders that seem to afflict hypothyroid humans have reptilian-like features, such as dry, hairless, scaly, cold skin and a general slowdown of metabolism, digestion, heart rate and nervous reflexes, with lethargic cerebration, hyperuricemia and hypothermia ( Venturi, 2000). \]\] The Production of T3 and T4 are regulated by thyroid stimulating hormone (TSH), released by the pituitary gland, a bean shape node in the brain. TSH Production is increased when T3 and T4 levels are too low. The thyroid hormones are released throughout the body to direct the body\'s metabolism. They stimulate all cells within the body to work at a better metabolic rate. Without these hormones the body\'s cells would not be able to regulate the speed at which they performed chemical actions. Their release will be increased under certain situations such as cold temperatures when a higher metabolism is needed to generate heat. When children are born with thyroid hormone deficiency they have problems with physical growth and developmental problems. Brain development can also be severely impaired. #### The significance of iodine Thyroid hormone cannot be produced without an abundant source of iodine. The iodine concentration within the body, although significant, can be as little as 1/25th the concentration within the thyroid itself. When the thyroid is low on iodine the body will try harder to produce T3 and T4 which will often result in a swelling of the thyroid gland, resulting in a goiter. ## Extrathyroidal iodine ![Sequence of 123-iodide human scintiscans after an intravenous injection, (from left) after 30 minutes, 20 hours, and 48 hours. A high and rapid concentration of radio-iodide is evident in the periencephalic and cerebrospinal fluid (left), salivary glands, oral mucosa and the stomach. In the thyroid gland, I-concentration is more progressive, also in the reservoir (from 1% after 30 minutes, to 5.8 % after 48 hours, of the total injected dose. Highest iodide-concentration by the mammary gland is evident only in pregnancy and lactation. High excretion of radio-iodide is observed in the urine.[^1]](Sequence_of_123-iodide_total_body_human_scintiscans.jpg "Sequence of 123-iodide human scintiscans after an intravenous injection, (from left) after 30 minutes, 20 hours, and 48 hours. A high and rapid concentration of radio-iodide is evident in the periencephalic and cerebrospinal fluid (left), salivary glands, oral mucosa and the stomach. In the thyroid gland, I-concentration is more progressive, also in the reservoir (from 1% after 30 minutes, to 5.8 % after 48 hours, of the total injected dose. Highest iodide-concentration by the mammary gland is evident only in pregnancy and lactation. High excretion of radio-iodide is observed in the urine.") Iodine accounts for 65% of the molecular weight of T4 and 59% of the T3. 15--20 mg of iodine is concentrated in thyroid tissue and hormones, but 70% of the body\'s iodine is distributed in other tissues, including mammary glands, eyes, gastric mucosa, the cervix, and salivary glands. In the cells of these tissues iodide enters directly by sodium-iodide symporter (NIS). Its role in mammary tissue is related to fetal and neonatal development, but its role in the other tissues is unknown. It has been shown to act as an antioxidant in these tissues. The US Food and Nutrition Board and Institute of Medicine recommended daily allowance of iodine ranges from 150 micrograms /day for adult humans to 290 micrograms /day for lactating mothers. However, the thyroid gland needs no more than 70 micrograms /day to synthesize the requisite daily amounts of T4 and T3. These higher recommended daily allowance levels of iodine seem necessary for optimal function of a number of body systems, including lactating breast, gastric mucosa, salivary glands, oral mucosa, thymus, epidermis, choroid plexus, etc.[^3][^4][^5] Moreover, iodine can add to double bonds of docosahexaenoic acid and arachidonic acid of cellular membranes, making them less reactive to free oxygen radicals.[^6] #### Calcitonin Calcitonin is a 32 amino acid polypeptide hormone. It is an additional hormone produced by the thyroid, and contributes to the regulation of blood calcium levels. Thyroid cells produce calcitonin in response to high calcium levels in the blood. This hormone will stimulate movement of calcium into the bone structure. It can also be used therapeutically for the treatment of hypercalcemia or osteoporosis. Without this hormone calcium will stay within the blood instead of moving into bones to keep them strong and growing. Its importance in humans has not been as well established as its importance in other animals. ### Parathyroid gland There are four parathyroid glands. They are small, light-colored lumps that stick out from the surface of the thyroid gland. All four glands are located on the thyroid gland. They are butterfly-shaped and located inside the neck, more specifically on both sides of the windpipe. One of the parathyroid glands most important functions is to regulate the body\'s calcium and phosphorus levels. Another function of the parathyroid glands is to secrete parathyroid hormone, which causes the release of the calcium present in bone to extracellular fluid. PTH does this by depressing the production of osteoblasts, special cells of the body involved in the production of bone and activating osteoclasts, other specialized cells involved in the removal of bone. There are two major types of cells that make up parathyroid tissue: - One of the major cells is called **oxyphil cells**. Their function is basically unknown. - The second type are called **chief cells**. Chief cells produce parathyroid hormone. The structure of a parathyroid gland is very different from that of a thyroid gland. The chief cells that produce parathyroid hormone are arranged in tightly-packed nests around small blood vessels, quite unlike the thyroid cells that produce thyroid hormones, which are arranged in spheres called the thyroid follicles. PTH or **Parathyroid Hormone** is secreted from these four glands. It is released directly into the bloodstream and travels to its target cells which are often quite far away. It then binds to a structure called a receptor, that is found either inside or on the surface of the target cells. Receptors bind a specific hormone and the result is a specific physiologic response, meaning a normal response of the body. PTH finds its major target cells in bone, kidneys, and the gastrointestinal system. Calcitonin, a hormone produced by the thyroid gland that also regulates ECF calcium levels and serves to counteract the calcium-producing effects of PTH. The adult body contains as much as 1 kg of calcium. Most of this calcium is found in bone and teeth. The four parathyroid glands secrete the parathyroid hormone (PTH). It opposes the effect of thyrocalcitonin. It does this by removing calcium from its storage sites in bones, releasing it into the bloodstream. It also signals the kidneys to reabsorb more of this mineral, transporting it into the blood. It also signals the small intestine to absorb more of this mineral, transporting it from the diet into the blood. Calcium is important for steps of body metabolism. Blood cannot clot without sufficient calcium. Skeletal muscles require this mineral in order to contract. A deficiency of PTH can lead to tetany, muscle weakness due to lack of available calcium in the blood. The parathyroid glands were long thought to be part of the thyroid or to be functionally associated with it. We now know that their close proximity to the thyroid is misleading: both developmentally and functionally, they are totally distinct from the thyroid. The parathyroid hormone, called parathormone, regulates the calcium-phosphate balance between the blood and other tissues. Production of this hormone is directly controlled by the calcium concentration of the extracellular fluid bathing the cells of these glands. Parathormone exerts at least the following five effects: (1) it increases gastrointestinal absorption of calcium by stimulating the active transport system and moves calcium from the gut lumen into the blood; (2) it increases the movement of calcium and phosphate from bone into extracellular fluid. This is accomplished by stimulating osteoclasts to break down bone structure, thus liberating calcium phosphate into the blood. In this way, the store of calcium contained in bone is tapped; (3) it increases re-absorption of calcium by the renal tubules, thereby decreasing urinary calcium excretion; (4) it reduces the re-absorption of phosphate by the renal tubules (5)it stimulates the synthesis of 1,25-dihydrixycholecalciferol by the kidney. The first three effects result in a higher extracellular calcium concentration. The adaptive value of the fourth is to prevent the formation of kidney stones. If parathyroid glands are removed accidentally during surgery on the thyroid, there would be a rise in the phosphate concentration in the blood. There would also be a drop in the calcium concentration as more calcium is excreted by the kidneys and intestines, and more incorporated into the bone. This can produce serious disturbances, particularly in the muscles and nerves, which use calcium ions for normal functioning. Over activity of the parathyroid glands, which can result from a tumor on the glands, produces a weakening of the bones. This is a condition that makes them much more vulnerable to fracturing because of excessive withdrawal of calcium from the bones. ### Adrenal glands **Adrenal glands** are a pair of ductless glands located above the kidneys. Through hormonal secretions, the adrenal glands regulate many essential functions in the body, including biochemical balances that influence athletic training and general stress response. The glucocorticoids include corticosterone, cortisone, and hydrocortisone or cortisol. These hormones serve to stimulate the conversion of amino acids into carbohydrates which is a process known as gluconeogenesis, and the formation of glycogen by the liver. They also stimulate the formation of reserve glycogen in the tissues, such as in the muscles. The glucocorticoids also participate in lipid and protein metabolism. The cortex of the adrenal gland is known to produce over 20 hormones, but their study can be simplified by classifying them into three categories: glucocorticoids, mineralocorticoids, and sex hormones. They are triangular-shaped glands located on top of the kidneys. They produce hormones such as estrogen, progesterone, steroids, cortisol, and cortisone, and chemicals such as adrenalin (epinephrine), norepinephrine, and dopamine. When the glands produce more or less hormones than required by the body, disease conditions may occur. The adrenal cortex secretes at least two families of hormones, the **glucocorticoids** and **mineral corticoids**. The **adrenal medulla** secretes the hormones **epinephrine** (adrenalin) and **norepinephrine** (noradrenalin). **Adrenal Cortex:** The hormones made by the Adrenal Cortex supply long-term responses to stress. The two major hormones produced are the**Mineral Corticoids** and the **Glucocorticoids.** The Mineral Corticoids regulate the salt and water balance, leading to the increase of blood volume and blood pressure. The **Glucocorticoids** are monitoring the ACTH, in turn regulating carbohydrates, proteins, and fat metabolism. This causes an increase in blood glucose. Glucocorticoids also reduce the body\'s inflammatory response. **Cortisol** is one of the most active glucocorticoids. It usually reduces the effects of inflammation or swelling throughout the body. It also stimulates the production of glucose from fats and proteins, which is a process referred to as **gluconeogenesis**. **Aldosterone** is one example of a mineralocorticoid. It signals the tubules in the kidney nephrons to reabsorb sodium while secreting or eliminating potassium. If sodium levels are low in the blood, the kidney secretes more **renin**, which is an enzyme that stimulates the formation of **angiotensin** from a molecule made from the liver. Angiotensin stimulates aldosterone secretion. As a result, more sodium is reabsorbed as it enters the blood. Aldosterone, the major mineralocorticoid, stimulates the cells of the distal convoluted tubules of the kidneys to decrease re-absorption of potassium and increase re-absorption of sodium. This in turn leads to an increased re-absorption of chloride and water. These hormones, together with such hormones as insulin and glucagon, are important regulators of the ionic environment of the internal fluid. The renin-angiotensin-aldosterone mechanism can raise blood pressure if it tends to drop. It does this in two ways. Angiotensin is a vasoconstrictor, decreasing the diameter of blood vessels. As vessels constrict, blood pressure increases. In addition, as sodium is reabsorbed, the blood passing through the kidney becomes more hypertonic. Water follows the sodium into the hypertonic blood by osmosis. This increases the amount of volume in the blood and also increases the blood pressure. **Adrenal Medulla** The hypothalamus starts nerve impulses that travel the path from the bloodstream, spinal cord, and sympathetic nerve fibers to the Adrenal Medulla, which then releases hormones. The effects of these hormones provide a short-term response to stress. Excessive secretion of the glucocorticoids causes **Cushing\'s syndrome**, characterized by muscle atrophy or degeneration and hypertension or high blood pressure. Under secretion of these substances produces **Addison\'s disease**, characterized by low blood pressure and stress. Epinephrine and norepinephrine produce the \"fight or flight\" response, similar to the effect from the sympathetic nervous system. Therefore, they increase heart rate, breathing rate, blood flow to most skeletal muscles, and the concentration of glucose in the blood. They decrease blood flow to the digestive organs and diminish most digestive processes. left\|framed\|300px\|Suprarenal glands viewed from the front. right\|framed\|300px\|Suprarenal glands viewed from behind. The adrenal sex hormones consist mainly of male sex hormones (androgens) and lesser amounts of female sex hormones (estrogens and progesterone). Normally, the sex hormones released from the adrenal cortex are insignificant due to the low concentration of secretion. However, in cases of excess secretion, masculine or feminine effects appear. The most common syndrome of this sort is \"virilism\" of the female. Should there be an insufficient supply of cortical hormones, a condition known as Addison\'s disease would result. This disease is characterized by an excessive excretion of sodium ions, and hence water, due to lack of mineralocorticoids. Accompanying this is a decreased blood glucose level due to a deficient supply of glucocorticoids. The effect of a decreased androgen supply cannot be observed immediately. Injections of adrenal cortical hormones promptly relieve these symptoms. Hormonal production in the adrenal cortex is directly controlled by the anterior pituitary hormone called adrenocorticotropic hormone (ACTH). The two adrenal glands lie very close to the kidneys. Each adrenal gland is actually a double gland, composed of an inner core like medulla and an outer cortex. Each of these is functionally unrelated. The adrenal medulla secretes two hormones, adrenalin or epinephrine and noradrenalin or norepinephrine, whose functions are very similar but not identical. The adrenal medulla is derived embryologically from neural tissue. It has been likened to an overgrown sympathetic ganglion whose cell bodies do not send out nerve fibers, but release their active substances directly into the blood, thereby fulfilling the criteria for an endocrine gland. In controlling epinephrine secretion, the adrenal medulla behaves just like any sympathetic ganglion, and is dependent upon stimulation by sympathetic preganglionic fibers. Epinephrine promotes several responses, all of which are helpful in coping with emergencies: the blood pressure rises, the heart rate increases, the glucose content of the blood rises because of glycogen breakdown, the spleen contracts and squeezes out a reserve supply of blood, the clotting time decreases, the pupils dilate, the blood flow to skeletal muscles increase, the blood supply to intestinal smooth muscle decreases and hairs become erect. These adrenal functions, which mobilize the resources of the body in emergencies, have been called the fight-or-flight response. Norepinephrine stimulates reactions similar to those produced by epinephrine, but is less effective in conversion of glycogen to glucose. The significance of the adrenal medulla may seem questionable since the complete removal of the gland causes few noticeable changes; humans can still exhibit the flight-or-fight response. This occurs because the sympathetic nervous system complements the adrenal medulla in stimulating the fight-or-flight response, and the absence of the hormonal control will be compensated for by the nervous system. ### Pancreas The **pancreas** is very important organ in the digestion system and the circulatory system because it helps to maintain our blood sugar levels. The pancreas is considered to be part of the gastrointestinal system. It produces digestive enzymes to be released into the small intestine to aid in reducing food particles to basic elements that can be absorbed by the intestine and used by the body. It has another very different function in that it forms insulin, glucagon and other hormones to be sent into the bloodstream to regulate blood sugar levels and other activities throughout the body. It has a pear-shape to it and is approximately 6 inches long. It is located in the middle and back portion of the abdomen. The pancreas is connected to the first part of the small intestine, the duodenum, and lies behind the stomach. The pancreas is made up of glandular tissue: any substance secreted by the cells of the pancreas will be secreted outside of the organ. The digestive juices produced by the pancreas are secreted into the duodenum via a Y-shaped duct, at the point where the common bile duct from the liver and the pancreatic duct join just before entering the duodenum. The digestive enzymes carried into the duodenum are representative of the exocrine function of the pancreas, in which specific substances are made to be passed directly into another organ. The pancreas is unusual among the body\'s glands in that it also has a very important endocrine function. Small groups of special cells called **islet cells** throughout the organ make the hormones of insulin and glucagon. These, of course, are hormones that are critical in regulating blood sugar levels. These hormones are secreted directly into the bloodstream to affect organs all over the body. **Insulin** acts to lower blood sugar levels by allowing the sugar to flow into cells. Glucagon acts to raise blood sugar levels by causing glucose to be released into the circulation from its storage sites. Insulin and glucagon act in an opposite but balanced fashion to keep blood sugar levels stable. A healthy working pancreas in the human body is important for maintaining good health by preventing malnutrition, and maintaining normal levels of blood sugar. The digestive tract needs the help of the enzymes produced by the pancreas to reduce food particles to their simplest elements, or the nutrients cannot be absorbed. Carbohydrates must be broken down into individual sugar molecules. Proteins must be reduced to simple amino acids. Fats must be broken down into fatty acids. The pancreatic enzymes are important in all these transformations. The basic particles can then easily be transported into the cells that line the intestine, and from there they can be further altered and transported to different tissues in the body as fuel sources and construction materials. Similarly, the body cannot maintain normal blood sugar levels without the balanced action of insulin and glucagon. The pancreas contains exocrine and endocrine cells. Groups of endocrine cells, the **islets of Langerhans**, secrete two hormones. The beta cells secrete **insulin**; the alpha cells secrete **glucagon**. The level of sugar in the blood depends on the opposing action of these two hormones. Insulin decreases the concentration of glucose in the blood. Most of the glucose enters the cells of the liver and skeletal muscles. In these cells, this **monosaccharide** is converted to the polysaccharide glycogen. Therefore, insulin promotes **glycogenesis** or glycogen synthesis, in which glucose molecules are added to chains of glycogen. Excess glucose is also stored as fat in adipose tissue cells in response to insulin. Insulin deficiency leads to the development of **diabetes mellitus**, specifically **type I**, juvenile diabetes. As the pancreas does not produce sufficient insulin, it is treated by insulin injections. In **type II** or maturity onset diabetes, the pancreas does produce enough insulin, but the target cells do not respond to it. As already stated, the pancreas is a mixed gland having both endocrine and exocrine functions. The exocrine portion secretes digestive enzymes into the duodenum via the pancreatic duct. The endocrine portion secretes two hormones, insulin and glucagon, into the blood. Insulin is a hormone that acts directly or indirectly on most tissues of the body, with the exception of the brain. The most important action of insulin is the stimulation of the uptake of glucose by many tissues, particularly the liver, muscle and fat. The uptake of glucose by the cells decreases blood glucose and increases the availability of glucose for the cellular reactions in which glucose participates. Thus, glucose oxidation, fat synthesis, and glycogen synthesis are all accentuated by an uptake of glucose. It is important to note that insulin does not alter glucose uptake by the brain, nor does it influence the active transport of glucose across the renal tubules and gastrointestinal epithelium. As stated, insulin stimulates glycogen synthesis. It also increases the activity of the enzyme that catalyzes the rate-limiting step in glycogen synthesis. Insulin also increases triglyceride levels by inhibiting triglyceride breakdown, and by stimulating production of triglyceride through fatty acid and glycerophosphate synthesis. The net protein synthesis is also increased by insulin, which stimulates the active membrane transport of amino acids, particularly into muscle cells. Insulin also has effects on other liver enzymes, but the precise mechanisms by which insulin induces these changes are not well understood. Insulin is secreted by beta cells, which are located in the part of the pancreas known as the islets of Langerhans. These groups of cells, which are located randomly throughout the pancreas, also consist of other secretory cells called alpha cells. It is these alpha cells that secrete glucagon. Glucagon is a hormone that has the following major effects: it increases hepatic synthesis of glucose from pyruvate, lactate, glycerol, and amino acids (a process called gluconeogenesis, which also raises the plasma glucose level); and it increases the breakdown of adipose tissue triglyceride, thereby raising the plasma levels of fatty acids and glycerol. The glucagon secreting alpha cells in the pancreas, like the beta cells, respond to changes in the concentration of glucose in the blood flowing through the pancreas; no other nerves or hormones are involved. It should be noted that glucagon has the opposite effects of insulin. Glucagon elevates the plasma glucose, whereas insulin stimulates its uptake and thereby reduces plasma glucose levels; glucagon elevates fatty acid concentrations, whereas insulin converts fatty acids and glycerol into triglycerides, thereby inhibiting triglyceride breakdown. The alpha and beta cells of the pancreas make up a push-pull system for regulating the plasma glucose level. ### Sex organs The Sex organs (Gonads) are the testes in the male, and the ovaries in the female. Both of these organs produce and secrete hormones that are balanced by the hypothalamus and pituitary glands. The main hormones from the reproductive organs are: **Testosterone** is more prominent in males. It belongs to the family of androgens, which are steroid hormones producing masculine effects. Testosterone stimulates the development and functioning of the primary sex organs. It also stimulates the development and maintenance of secondary male characteristics, such as hair growth on the face and the deep pitch of the voice. **Estrogen** In females, this hormone stimulates the development of the uterus and vagina. It is also responsible for the development and maintenance of secondary female characteristics, such as fat distribution throughout the body and the width of the pelvis. #### Male right\|framed The **testes** produce **androgens** (i.e., \"testosterone\"). **Testosterone** is classified as a steroid and is responsible for many of the physical characteristics in males like. - Broad shoulders - Muscular body - Hair Testosterone increases protein production. Hormones that build up protein are called **anabolic steroids**. Anabolic steroids are available commercially and are being used by athletes because they help improve their physical ability, however, they do have major side effects such as: - Liver and kidney disorders - Hypertension (high blood pressure) - Decreased sperm count and impotency - Aggressive behavior (\"roid rage\") - Balding - Acne {{-}} #### Female !Schematic frontal view of female anatomy.{width="240"} The **ovaries** produce **estrogen** and **progesterone**. Estrogen increases at the time of puberty and causes the growth of the uterus and vagina. Without estrogen egg maturation would not occur. Estrogen is also responsible for secondary sex characteristics such as female body hair and fat distribution. Estrogen and Progesterone are responsible for the development of the breast and for the uterine cycle. Progesterone is a female hormone secreted by the corpus luteum after ovulation during the second half of the menstrual cycle. It prepares the lining of the uterus for implantation of a fertilized egg and allows for complete shedding of the endometrium at the time of menstruation. In the event of pregnancy, the progesterone level remains stable beginning a week or so after conception. {{-}} ### Pineal gland The pineal gland (also called the pineal body or epiphysis) is a small endocrine gland in the brain. It is located near the center of the brain, between the two hemispheres, tucked in a groove where the two rounded thalamic bodies join. It consists of two types of cells 1. parenchymal cells 2. neuroglial cells. The pineal gland is a reddish-gray body about the size of a pea (8 mm in humans) located just rostro-dorsal to the superior colliculus and behind and beneath the stria medullaris, between the laterally positioned thalamic bodies. It is part of the epithalamus. The pineal gland is a midline structure, and is often seen in plain skull X-rays, as it is often calcified. The main hormone produced and secreted by the pineal gland is melatonin. Secretion is highest at night and between the ages of 0-5. Melatonin acts mainly on gonads. {{-}} ## Glossary **Adrenal Gland:** endocrine gland that is located on top of each kidney **Amino Acid-derived:** hormones that are modified amino acids **Antagonistic Hormones:** hormones that act to return body conditions to within acceptable limits from opposite extremes **Calcitonin:** hormone produced by the thyroid; contributes to the regulation of blood calcium levels **Eicosanoids:** lipids that are synthesized from the fatty acid chains of phospholipids found in plasma membrane **Endocrine Glands:** glands that have no duct and release their secretions directly into the intercellular fluid or into the blood **Endocrine System:** a control system of ductless glands that secrete chemical messengers called hormones **Estrogen:** hormone in females; stimulates the development of the uterus and vagina **Exocrine Glands:** glands that release their cellular secretions through a duct which empties to the outside or into the lumen (empty internal space) of an organ **Hormone:** a specific chemical substance produced by certain cells that control, or help to control, cellular processes elsewhere in an organism **Insulin:** hormone that acts to lower blood sugar levels by allowing the sugar to flow into cells **Iodine:** chemical in the body; Thyroid hormone can not be produced with out it **Lipid-soluble Hormones:** diffuse through the cell membranes of target cells **Parathyroid:** four masses of tissue, two embedded posterior in each lateral mass of the thyroid gland **Pancreas:** organ involved with the digestion system and the circulatory system; helps to maintain blood sugar levels **Pineal Gland:** small endocrine gland in the brain located near the center of the brain, between the two hemispheres, tucked in a groove where the two rounded thalamic bodies join **Pituitary Gland:** endocrine gland that is attached to the hypothalamus of the lower forebrain **Polypeptide and Proteins:** hormones that are chains of amino acids of less than or more than about 100 amino acids **Steroids:** hormones that are lipids that are synthesized from cholesterol; characterized by four interlocking carbohydrate rings **Testosterone:** hormone more prominent in males; belongs to the family of androgens, which are steroid hormones producing masculinizing effects **Thyroid Gland:** endocrine gland that consists of two lateral masses that are attached to the trachea **Thyroxine:** serves to stimulate oxidative metabolism in cells; increases the oxygen consumption and heat production of most body tissues **Water-soluble Hormones:** bind to a receptor protein on the plasma membrane of the cell ## Chapter Review Questions Answers for these questions can be found here 1\. My child just fell and was hurt, the anxious feeling that I feel is caused by: : A\) glucagon : B\) insulin : C\) epinephrine : D\) adrenocorticotropic : E\) None of these 2\. All of Bob's life he has had to take insulin shots, this is caused because : A\) his beta cells don't function correctly : B\) his alpha cells don't function correctly : C\) his DA hormone isn't functioning correctly : D\) his GHRH hormone isn't functioning correctly 3\. The reason iodine is in salt is : A\) to prevent diabetes : B\) to prevent simple goiters : C\) to prevent Addison's disease : D\) to prevent Cushing\'s syndrome 4\. All hormones react to a negative feedback except : A\) progesterone : B\) estrogen : C\) prolactin : D\) oxytocin : E\) none of these 5\. If I have a high blood calcium level it may be due to : A\) calcitonin : B\) parathyroid : C\) glucocorticoids : D\) glucagon 6\. Hormones that are lipids that are synthesized from cholesterol : A\) protein : B\) amino acid-derived : C\) polypeptide : D\) steroids : E\) eicosanoids 7\. This type of hormone must bind to a receptor protein on the plasma membrane of the cell : A\) water soluble : B\) lipid soluble : C\) steroid : D\) polypeptide : E\) a and d : F\) b and c 8\. Endocrine glands release hormones in response to : A\) Hormones from other endocrine glands : B\) Chemical characteristics of the blood : C\) Neural stimulation : D\) All of the above 9\. The anterior pituitary secretes : A\) oxytocin : B\) endorphins : C\) ADH : D\) TRH 10\. Chief cells produce : A\) epinephrine : B\) glucagon : C\) insulin : D\) mineralocorticoids : E\) parathyroid hormone 11\. Name the eight major endocrine glands. 12\. Name the four major groups hormones can be chemically classified into. ## References [^1]: [^2]: [^3]: [^4]: [^5]: [^6]: Cocchi, M. and Venturi, S. Iodide, antioxidant function and Omega-6 and Omega-3 fatty acids: a new hypothesis of a biochemical cooperation? Progress in Nutrition, 2000, 2, 15-19
# Human Physiology/The male reproductive system ## Introduction In simple terms, **reproduction** is the process by which organisms create descendants. This miracle is a characteristic that all living things have in common and sets them apart from nonliving things. But even though the reproductive system is essential to keeping a species alive, it is not essential to keeping an individual alive. In human reproduction, two kinds of sex cells or gametes are involved. Sperm, the male gamete, and a secondary oocyte (along with first polar body and corona radiata), the male gamete must meet in the female reproductive system to create a new individual. For reproduction to occur, both the female and male reproductive systems are essential. It is a common misnomer to refer to a woman\'s gametic cell as an **egg or ovum**, but this is impossible. A secondary oocyte must be fertilized by the male gamete before it becomes an \"ovum\" or \"egg\". While both the female and male reproductive systems are involved with producing, nourishing and transporting either the **oocyte or sperm**, they are different in shape and structure. The male has reproductive organs, or genitals, that are both inside and outside the pelvis, while the female has reproductive organs entirely within the pelvis. The male reproductive system consists of the testes and a series of ducts and glands. Sperm are produced in the testes and are transported through the reproductive ducts. These ducts include the epididymis, vas deferens, ejaculatory duct and urethra. The reproductive glands produce secretions that become part of semen, the fluid that is ejaculated from the urethra. These glands include the seminal vesicles, prostate gland, and bulbourethral glands. ## Structure !The human male reproductive system{width="440"} ### Testes The testes (singular, testis) are located in the scrotum (a sac of skin between the upper thighs). In the male fetus, the testes develop near the kidneys, then descend into the scrotum just before birth. Each testis is about 1 1/2 inches long by 1 inch wide. Testosterone is produced in the testes which stimulates the production of sperm as well as give secondary sex characteristics beginning at puberty. **Scrotum** The two testicles are each held in a fleshy sac called the scrotum. The major function of the scrotal sac is to keep the testes cooler than thirty-seven degrees Celsius (ninety-eight point six degrees Fahrenheit). The external appearance of the scrotum varies at different times in the same individual depending upon temperature and the subsequent contraction or relaxation of two muscles. These two muscles contract involuntarily when it is cold to move the testes closer to the heat of the body in the pelvic region. This causes the scrotum to appear tightly wrinkled. On the contrary, they relax in warm temperatures causing the testes to lower and the scrotum to become flaccid. The temperature of the testes is maintained at about thirty-five degrees Celsius (ninety-five degrees Fahrenheit), which is below normal body temperature. Temperature has to be lower than normal in order for *spermatogenesis* (sperm production) to take place. !The scrotum is in a relaxed state.!Penile shrinkage due to low temperatures. The scrotum is in a tense state to regulate testicular temperatures. The two muscles that regulate the temperature of the testes are the dartos and cremaster muscles: - *Dartos Muscle* The dartos muscle is a layer of smooth muscle fibers in the subcutaneous tissue of the scrotum (surrounding the scrotum). This muscle is responsible for wrinkling up the scrotum, in conditions of cold weather, in order to maintain the correct temperature for spermatogenesis. - *Cremaster Muscle* The cremaster muscle is a thin strand of skeletal muscle associated with the testes and spermatic cord. This muscle is a continuation of the internal oblique muscle of the abdominal wall, from which it is derived. **Seminiferous Tubules** Each testis contains over 100 yards of tightly packed seminiferous tubules. Around 90% of the weight of each testes consists of seminiferous tubules. The seminiferous tubules are the functional units of the testis, where spermatogenesis takes place. Once the sperm are produced, they moved from the seminiferous tubules into the rete testis for further maturation. **Interstitial Cells (Cells of Leydig)** In between the seminiferous tubules within the testes, are instititial cells, or, *Cells of Leydig*. They are responsible for secreting the male sex hormones (i.e., testosterone). **Sertoli Cells** A Sertoli cell (a kind of sustentacular cell) is a \'nurse\' cell of the testes which is part of a seminiferous tubule. It is activated by follicle-stimulating hormone, and has FSH-receptor on its membranes. Its main function is to nurture the developing sperm cells through the stages of spermatogenesis. Because of this, it has also been called the \"mother cell.\" It provides both secretory and structural support. Other functions During the Maturation phase of spermiogenesis, the Sertoli cells consume the unneeded portions of the spermatazoa. **Efferent ductules** The sperm are transported out of the testis and into the epididymis through a series of efferent ductules. **Blood Supply** The testes receive blood through the testicular arteries (gonadal artery). Venous blood is drained by the testicular veins. The right testicular vein drains directly into the inferior vena cava. The left testicular vein drains into the left renal vein. ### Epididymis !Anatomy of the testisThe seminiferous tubules join together to become the epididymis. The epididymis is a tube that is about 2 inches that is coiled on the posterior surface of each testis. Within the epididymis the sperm incomplete their maturation (full maturation occur in female genital tract) and their flagella become mobile. This is also a site to store sperm, nourishing them until the next ejaculation. Smooth muscle in the wall of the epididymis propels the sperm into the ductus deferens. Vasa efferentia from the rete testis open into the epididymis which is a highly coiled tubule. The epididymis has three parts- 1)head or caput epididymis- it is the proximal part of the epididymis. It carries the sperms from the testis. 2)body or corpus epididymis- it the highly convoluted middle part of the epididymis 3)tail or cauda epididymis- it is the last part that takes part in carrying the sperms to the vas deferens. The cauda epididymis continues to form less convoluted vas deferens. ### Ductus Deferens The ductus (vas) deferens, also called sperm duct, or, spermatic deferens, extends from the epididymis in the scrotum on its own side into the abdominal cavity through the inguinal canal. The inguinal canal is an opening in the abdominal wall for the spermatic cord (a connective tissue sheath that contains the ductus deferens, testicular blood vessels, and nerves. The smooth muscle layer of the ductus deferens contracts in waves of peristalsis during ejaculation. ### Seminal Vesicles The pair of seminal vesicles are posterior to the urinary bladder. They secrete fructose to provide an energy source for sperm and alkalinity to enhance sperm mobility. The duct of each seminal vesicle joins the ductus deferens on that side to form the ejaculatory duct. ### Ejaculatory Ducts There are two ejaculatory ducts. Each receives sperm from the ductus deferens and the secretions of the seminal vesicle on its own side. Both ejaculatory ducts empty into the single urethra. ### Prostate Gland The prostate gland is a muscular gland that surrounds the first inch of the urethra as it emerges from the bladder. The smooth muscle of the prostate gland contracts during ejaculation to contribute to the expulsion of semen from the urethra. ### Bulbourethral Glands !Pre ejaculate produced by the bulbourethral glandsThe bulbourethral glands also called Cowper\'s glands are located below the prostate gland and empty into the urethra. The alkalinity of seminal fluid helps neutralize the acidic vaginal pH and permits sperm mobility in what might otherwise be an unfavorable environment. ### Penis The penis is an external genital organ. The distal end of the penis is called the glans penis and is covered with a fold of skin called the prepuce or foreskin. Within the penis are masses of erectile tissue. Each consists of a framework of smooth muscle and connective tissue that contains blood sinuses, which are large, irregular vascular channels. ### Urethra The urethra, which is the last part of the urinary tract, traverses the corpus spongiosum and its opening, known as the meatus, lies on the tip of the glans penis. It is both a passage for urine and for the ejaculation of semen. ### Overview of Male Reproductive System Structure and Function STRUCTURE LOCATION & DESCRIPTION FUNCTION ------------------------------------------------ -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Bulbourethral glands (2) Pea sized organs posterior to the prostate on either side of the urethra. Secretion of gelatinous seminal fluid called pre-ejaculate. This fluid helps to lubricate the urethra for spermatozoa to pass through, and to help flush out any residual urine or foreign matter. (\< 1% of semen) Cells of Leydig (Interstitial cells of Leydig) Adjacent to the seminiferous tubules in the testicle. Responsible for production of testosterone. Closely related to nerves. Cremaster muscle Covers the testes. Raises and lowers scrotum to help regulate temperature and promote spermatogenesis. Voluntary and involuntary contraction. Dartos muscle Layer of smooth muscular fiber outside the external spermatic fascia but below the skin Contraction by wrinkling to decrease surface area available for heat loss to testicles, or expansion to increase surface area available to promote heat loss; also helps raise and lower scrotum to help regulate temperature Efferent ductules Part of the testes and connect the rete testis with the epididymis Ducts for sperm to get to epididymis Ejaculatory ducts (2) Begins at the vas deferens, passes through the prostate, and empties into the urethra at the Colliculus seminalis. Causes reflex for ejaculation. During ejaculation, semen passes through the ducts and exits the body via the penis. Epididymis Tightly coiled duct lying just outside each testis connecting efferent ducts to vas deferens. Storage and maturation of sperm. Penis Three columns of erectile tissue: two corpora cavernosa and one corpus spongiosum. Urethra passes through penis. Male reproductive organ and also male organ of urination. Prostate gland Surrounds the urethra just below the urinary bladder and can be felt during a rectal exam. Stores and secretes a clear, slightly alkaline fluid constituting up to one-third of the volume of semen. Raise vaginal pH.(25-30% of semen) Scrotum Pouch of skin and muscle that holds testicles. Regulates temperature at slightly below body temperature. Semen Usually white but can be yellow, gray or pink (blood stained). After ejaculation, semen first goes through a clotting process and then becomes more liquid. Components are sperm, and \"seminal plasma\". Seminal plasma is produced by contributions from the seminal vesicle, prostate, and bulbourethral glands. Seminal vesicles (2) Convoluted structure attached to vas deferens near the base of the urinary bladder. About 65-75% of the seminal fluid in humans originates from the seminal vesicles. Contain proteins, enzymes, fructose, mucus, vitamin C, flavins, phosphorylcholine and prostaglandins. High fructose concentrations provide nutrient energy for the spermatozoa as they travel through the female reproductive system. Seminiferous tubules (2) Long coiled structure contained in the chambers of the testis; joins with vas deferens. Meiosis takes place here, creation of gametes (sperm). Sertoli cells Junctions of the Sertoli cells form the blood-testis barrier, a structure that partitions the interstitial blood compartment of the testis from the abdominal compartment of the seminiferous tubules. Cells responsible for nurturing and development of sperm cells , provides both secretory and structural support; activated by FSH. Also called \"mother cells\" or \"nurse cells\". Testes Inside scrotum, outside of body. Gonads that produce sperm and male sex hormones.Production of testosterone by cells of Leydig in the testicles. Testicular arteries (Gonadal arteries) Branch of the abdominal aorta. It is a paired artery. Each passes obliquely downward and laterally behind the peritoneum. Supplies blood to the testes. Urethra Connects bladder to outside body, about 8 inches long. Tubular structure that receives urine from bladder and carries it to outside of the body. Also passage for sperm. Vas deferens Muscular tubes connecting the left and right epididymis to the ejaculatory ducts to move sperm. Each tube is about 30 cm long. During ejaculation the smooth muscle in the vas deferens wall contracts, propelling sperm forward. Sperm are transferred from the vas deferens into the urethra, collecting fluids from accessory sex glands on route ### Composition of human semen The components of semen come from two sources: sperm, and \"seminal plasma\". Seminal plasma, in turn, is produced by contributions from the seminal vesicle, prostate, and bulbourethral glands. Seminal plasma of humans contains a complex range of organic and inorganic constituents. The seminal plasma provides a nutritive and protective medium for the spermatozoa during their journey through the female reproductive tract. The normal environment of the vagina is a hostile one for sperm cells, as it is very acidic (from the native microflora producing lactic acid), viscous, and patrolled by immune cells. The components in the seminal plasma attempt to compensate for this hostile environment. Basic amines such as putrescine, spermine, spermidine and cadaverine are responsible for the smell and flavor of semen. These alkaline bases counteract the acidic environment of the vaginal canal, and protect DNA inside the sperm from acidic denaturation. **The components and contributions of semen are as follows:** **GLAND** **APPROXIMATE %** **DESCRIPTION** ---------------------- ------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- testes 2-5% Approximately 200- to 500-million spermatozoa (also called sperm or spermatozoans), produced in the testes, are released per ejaculation seminal vesicle 65-75% amino acids, citrate, enzymes, flavins, fructose (the main energy source of sperm cells, which rely entirely on sugars from the seminal plasma for energy), phosphorylcholine, prostaglandins (involved in suppressing an immune response by the female against the foreign semen), proteins, vitamin C prostate 25-30% acid phosphatase, citric acid, fibrinolysin, prostate specific antigen, proteolytic enzymes, zinc (serves to help to stabilize the DNA-containing chromatin in the sperm cells. A zinc deficiency may result in lowered fertility because of increased sperm fragility. Zinc deficiency can also adversely affect spermatogenesis.) bulbourethral glands \< 1% galactose, mucus (serve to increase the mobility of sperm cells in the vagina and cervix by creating a less viscous channel for the sperm cells to swim through, and preventing their diffusion out of the semen. Contributes to the cohesive jelly-like texture of semen.), pre-ejaculate, sialic acid A 1992 World Health Organization report described normal human semen as having a volume of 2 ml or greater, pH of 7.2 to 8.0, sperm concentration of 20x106 spermatozoa/ml or more, sperm count of 40x106 spermatozoa per ejaculate or more and motility of 50% or more with forward progression (categories a and b) of 25% or more with rapid progression (category a) within 60 minutes of ejaculation.[^1] ## Functions ![](Male_reproductive_hormone_chart.gif "Male_reproductive_hormone_chart.gif"){width="550"} ### Hormone Regulation Hormones which control reproduction in males are: Gonadotropin-Releasing Hormone (GnRH): - The hypothalamus secretes this hormone into the pituitary gland in the brain. - There are two gonadotropic hormones, FSH and LH. Luteinizing Hormone (LH): - The pituitary gland secretes this hormone after receiving a GnRH signal from the hypothalamus. - LH stimulates Leydig cells, in the testes, telling them to produce testosterone. Follicle-Stimulating Hormone (FSH): - The pituitary gland also secretes this hormone. - Testosterone helps FSH run through the bloodstream to make Sertoli cells, located in the seminiferous tubules of the testes, to make immature sperm to mature sperm. Testosterone: - Also known as \"the male hormone\" and \"androgen\". - Testosterone is vital for the production of sperm. !150 px\|The constituent cavernous cylinders of the penis. ### Erection !250 px\|Transverse section of the penis. The erection of the penis is its enlarged and firm state. It depends on a complex interaction of psychological, neural, vascular and endocrine factors. The term is also applied to the process that leads to this state. A penile erection occurs when two tubular structures that run the length of the penis, the corpora cavernosa, become engorged with venous blood. This is a result of parasympathetic nerve induced vasodilation. This may result from any of various physiological stimuli. The corpus spongiosum is a single tubular structure located just below the corpora cavernosa, which contains the urethra, through which urine and semen pass during urination and ejaculation, respectively. This may also become slightly engorged with blood, but less so than the corpora cavernosa. Penile erection usually results from sexual stimulation and/or arousal, but can also occur by such causes as a full urinary bladder or spontaneously during the course of a day or at night, often during erotic or wet dreams. An erection results in swelling and enlargement of the penis. Erection enables sexual intercourse and other sexual activities (sexual functions), though it is not essential for all sexual activities. ### Ejaculation Emission is the term used when sperm moves into the urethra. Ejaculation is the term used when sperm is forced out of the urethra and the penis. These are both stimulated by sympathetic nerves. ### Sperm Production A spermatozoon or spermatozoan (pl. spermatozoa), from the ancient Greek σπέρμα (seed) and ζῷον (living being) and more commonly known as a sperm cell, is the haploid cell that is the male gamete. !A mature human Spermatozoon Spermatagonia divides several times during the process of sperm development. The entire process of sperm formation and maturation takes about 9-10 weeks. The separate divisions that take place and what happens in each are as follows: - **First division**: The first division is done by mitosis, and ensures a constant supply of *spermatocytes*, each with the diploid number of chromosomes. ```{=html} <!-- --> ``` - **Second division**: Spermatocytes then undergo a series of two cell divisions during meiosis to become *secondary spermatocytes*. ```{=html} <!-- --> ``` - **Third division**: Secondary Spermatocytes finally become *spermatids*. Spermatids, which are haploid cells, mature slowly to become the male gametes, or *sperm*. The sperm is the main reproductive cell in males. The sperms differ in that each carry a set of chromosomes dividing each into either a male, or female sperm. The females differ in that they carry a X gene, while the male sperm carry a Y gene. The female sperm also differ phenotypically in that they have a larger head in comparison to the male sperms. This contributes to the male sperm being lighter, and therefore faster and stronger swimmers than their female counterparts (although statistically there is still a 50% chance of an either XY or XX embryo forming. Spermatozoan stream lines are straight and parallel. The tail flagellates, which we now know propels the sperm cell (at about 1-3 mm/minute in humans) by rotating like a propeller, in a circular motion, not side to side like a whip. The cell is characterized by a minimum of cytoplasm. During fertilization, the sperm\'s mitochondria gets destroyed by the egg cell, and this means only the mother is able to provide the baby\'s mitochondria and mitochondrial DNA, which has an important application in tracing maternal ancestry. However it has been recently discovered that mitochondrial DNA can be recombinant. Spermatozoa are produced in the seminiferous tubules of the testes in a process called spermatogenesis. Round cells called spermatogonia divide and differentiate eventually to become spermatozoa. During copulation the vagina is inseminated, the spermatozoa move through *chemotaxis* (see glossary) to the ovum inside a Fallopian tube or the uterus. ### Sperm Pathway Spermatogenesis takes place inside a male's testes, specifically in the walls of the seminiferous tubules. The epididymis is a tortuously coiled structure topping the testis, it receives immature sperm from the testis and stores it for several days. When ejaculation occurs, sperm is forcefully expelled from the tail of the epididymis into the ductus deferens. Sperm travels through the ductus deferens and up the spermatic cord into the pelvic cavity, over the ureter to the prostate behind the bladder. Here, the vas deferens joins with the seminal vesicle to form the ejaculatory duct, which passes through the prostate and empties into the urethra. Upon the sperm\'s exit from the testes, into the vas deferens, muscular movements take over. When ejaculation occurs, rhythmic muscle movements of *peristalsis* propel the sperm forward. This continues throughout the remainder of the sperm\'s journey through the male reproductive system. Sperm cells become even more active when they begin to interact with the *fertilizing layer* of an egg cell. They swim faster and their tail movements become more forceful and erratic. This behavior is called \"hyper activation.\" A recent discovery links hyper activation to a sudden influx of calcium ions into the tails. The whip-like tail (flagellum) of the sperm is studded with ion channels formed by proteins called CatSper. These channels are selective, allowing only calcium ion to pass. The opening of CatSper channels is responsible for the influx of calcium. The sudden rise in calcium levels causes the flagellum to form deeper bends, propelling the sperm more forcefully through the viscous environment. !Acrosome reaction on a Sea Urchin cell{width="440"} The sperm use their tails to push themselves into the epididymis, where they complete their development. It takes sperm about 4 to 6 weeks to travel through the epididymis. The sperm then move to the vas deferens, or sperm duct. The seminal vesicles and prostate gland produce a whitish fluid called seminal fluid, which mixes with sperm to form semen when a male is sexually stimulated. The penis, which usually hangs limp, becomes hard when a male is sexually excited. Tissues in the penis fill with blood and it becomes stiff and erect (an erection). The rigidity of the erect penis makes it easier to insert into the female\'s vagina during sexual intercourse, and the extended length allows it to reach deeper into the female\'s *oviduct*, the passage from the ovaries to the outside of the body (allowing a shorter travel distance for the spermatozoa). When the erect penis is stimulated to orgasm, muscles around the reproductive organs contract and force the semen through the duct system and urethra. Semen is pushed out of the male\'s body through his urethra - ejaculation. The speed of the semen is about 70 mph when ejaculation comes and it can contain 100 to 600 million sperm cells. When the male ejaculates during intercourse, semen is deposited into the fornix at the base of the female\'s vagina, near the cervix. From the fornix, the sperm make their way up through the cervix and move through the uterus with help from uterine contractions. Sperm hyperactivity is necessary for breaking through two physical barriers that protect the egg from fertilization. The first barrier to sperm is made up of so-called cumulus cells embedded in a gel-like substance made primarily of hyaluronic acid. The cumulus cells develop in the ovary with the egg and support it as it grows. The second barrier coating the oocyte is a thick shell formed by glycoproteins called the zona pellucida. One of the proteins that make up the zona pellucida binds to a partner molecule on the sperm. This lock-and-key type mechanism is species-specific and prevents the sperm and egg of different species from fusing. There is some evidence that this binding is what triggers the acrosome to release the enzymes that allow the sperm to fuse with the egg. When a sperm cell reaches the egg the acrosome releases its enzymes. These enzymes weaken the shell, allowing the sperm cell to penetrate it and reach the plasma membrane of the egg. Part of the sperm\'s cell membrane then fuses with the egg cell\'s membrane, and the sperm cell sinks into the egg (at which point the sperm tail falls off). Upon penetration, the egg cell membrane undergoes a change and becomes impenetrable, preventing further fertilization. The binding of the sperm to an ovum is called a zygote. A zygote is a single cell, with a complete set of chromosomes, that normally develops into an embryo. ## Puberty !Male pubertyIn addition to producing sperm, the male reproductive system also produces sex hormones, which help a boy develop into a sexually mature man during puberty. When a baby boy is born, he has all the parts of his reproductive system in place, but it isn\'t until puberty that his reproductive organs mature and become fully functional. As an newborn FSH and LH levels are high and after a few weeks levels drop to extremely low. When puberty begins, usually between the ages of 10 and 14, the pituitary gland - which is located in the brain - secretes hormones that stimulate the testicles to produce testosterone. The production of testosterone brings about many physical changes. Although the timing of these changes is different for each individual male, the stages of puberty generally follow a set sequence. - First stage: the scrotum and testes grow larger, the *apocrine glands* develop (see explanation of apocrine glands in glossary). ```{=html} <!-- --> ``` - Second stage: the penis becomes longer, and the seminal vesicles and prostate gland grow. Hair begins to grow in the pubic region. Reproductive capacity has usually developed by this stage. ```{=html} <!-- --> ``` - Third stage: hair begins to appear on the face and underarms. During this time, a male\'s voice also deepens. Fertility continues to increase. ### Testicular size, function, and fertility In boys, testicular enlargement is the first physical manifestation of puberty (and is termed gonadarche). Testes in prepubertal boys change little in size from about 1 year of age to the onset of puberty, averaging about 2--3 cc in volume and about 1.5-2 cm in length. Testicular size continues to increase throughout puberty, reaching maximal adult size about 6 years later. While 18-20 cc is reportedly an average adult size, there is wide variation in the normal population. The testes have two primary functions: to produce hormones and to produce sperm. The Leydig cells produce testosterone (as described below), which in turn produces most of the changes of male puberty. However, most of the increasing bulk of testicular tissue is spermatogenic tissue (primarily Sertoli and interstitial cells). The development of sperm production and fertility in males is not as well researched. Sperm can be detected in the morning urine of most boys after the first year of pubertal changes (and occasionally earlier). ### Genitalia A boy\'s penis grows little from the fourth year of life until puberty. Average prepubertal penile length is 4 cm. The prepubertal genitalia are described as stage 1. Within months after growth of the testes begins, rising levels of testosterone promote growth of the penis and scrotum. This earliest discernible beginning of pubertal growth of the genitalia is referred to as stage 2. The penis continues to grow until about 18 years of age, reaching an average adult size of about 10-16 cm. Although erections and orgasm can occur in prepubertal boys, they become much more common during puberty, accompanied by development of *libido* (sexual desire). Ejaculation becomes possible early in puberty; prior to this boys may experience dry orgasms. Emission of seminal fluid may occur due to masturbation or spontaneously during sleep (commonly termed a *wet dream*, and more clinically called a *nocturnal emission*). The ability to ejaculate is a fairly early event in puberty compared to the other characteristics, and can occur even before reproductive capacity itself. In parallel to the irregularity of the first few periods of a girl, for the first one or two years after a boy\'s first ejaculation, his seminal fluid may contain few active sperm. If the foreskin of a boy does not become retractable during childhood, it normally begins to retract during puberty. This occurs as a result of the increased production of testosterone and other hormones in the body. !Distribution of androgenic hair on female and male body{width="150"} ### Genital Erection The penis contains two chambers called the corpora cavernosa, which run the length of the organ. A spongy tissue, full of muscle, veins, arteries, etc. fills these chambers. The corpora cavernosa are surrounded by a membrane, called the tunica albuginea. Erection begins with sensory or mental stimulation, or both. Impulses from the brain and local nerves cause the muscles of the corpora cavernosa to relax, allowing blood to flow in and fill the spaces. The blood creates pressure in the corpora cavernosa, making the penis expand. The tunica albuginea helps trap the blood in the corpora cavernosa, thereby sustaining erection. When muscles in the penis contract to stop the inflow of blood and open outflow channels, erection is reversed. ### Pubic hair in boys Pubic hair often appears on a boy shortly after the genitalia begin to grow. As in girls, the first appearance of pubic hair is termed pubarche and the pubic hairs are usually first visible at the dorsal (abdominal) base of the penis. The first few hairs are described as stage 2. Stage 3 is usually reached within another 6 to 12 months, when the hairs are too numerous to count. By stage 4, the pubic hairs densely fill the \"pubic triangle.\" Stage 5 refers to spread of pubic hair to the inner thighs and upward towards the umbilicus as part of the developing abdominal hair. ## Sexual Homology !The human male reproductive system{width="440"} !Cross-sectional diagram of the female reproductive organs.{width="440"} In short, this is a known list of sex organs that evolve from the same tissue in a human life. Indifferent Male Female --------------------- ----------------------------------- --------------------------------- Gonad Testis Ovary Mullerian duct Appendix testis Fallopian tubes Mullerian duct Prostatic utricle Uterus, proximal vagina Wolffian duct Rete testis Rete ovarii Mesonephric tubules Efferent ducts Epoophoron Wolffian duct Epididymis Gartner\'s duct Wolffian duct Vas deferens Wolffian duct Seminal vesicle Wolffian duct Prostate Skene\'s glands Urogenital sinus Urinary bladder\|Bladder, urethra Bladder, urethra, distal vagina Urogenital sinus Bulbourethral gland Bartholin\'s gland Genital swelling Scrotum Labia majora Urogenital folds Distal urethra Labia minora Genital tubercle Penis Clitoris Prepuce Foreskin Clitoral hood Bulb of penis Vestibular bulbs Glans penis Clitoral glans Crus of penis Clitoral crura ## Aging For most men, testosterone secretion continues throughout life, as does sperm production, though both diminish with advancing age. Probably the most common reproductive problem for older men is prostatic hypertrophy, enlargement of the prostate gland. This causes the urethra to compress and urination becomes difficult. Residual urine in the bladder increases the chance of urinary tract infections. Prostate hypertrophy is usually benign, but cancer of the prostate is one of the more common cancers in elderly men. A TURP is commonly used to correct this problem if the symptoms do not improve in response to home treatment and medication. Erectile dysfunction (ED) is another common problem seen in aging males. In older men, ED usually has a physical cause, such as disease, injury, or side effects of drugs. Any disorder that impairs blood flow in the penis or causes injury to the nerves has the potential to cause ED. Although it is not an inevitable part of aging, incidences increases with age: About 5 percent of 40-year-old men and between 15 and 25 percent of 65-year-old men experience ED. As discouraging as Erectile dysfunction may be, it is treatable at any age, and awareness of this fact has been growing. More men have been seeking help and returning to normal sexual activity because of improved, successful treatments for ED. ## Things that can go wrong with the male reproductive system Boys may sometimes experience reproductive system problems. Below are some examples of disorders that affect the male reproductive system (Disorders of the Scrotum, Testicles, or Epididymis). Conditions affecting the scrotal contents may involve the testicles, epididymis, or the scrotum itself. - **Testicular trauma.** Even a mild injury to the testicles can cause severe pain, bruising, or swelling. Most testicular injuries occur when the testicles are struck, hit, kicked, or crushed, usually during sports or due to other trauma. Testicular torsion, when 1 of the testicles twists around, cutting off the blood supply, is also a problem that some teen males experience - although it\'s not common. Surgery is needed to untwist the cord and save the testicle. ```{=html} <!-- --> ``` - **Varicocele.** This is a varicose vein (an abnormally swollen vein) in the network of veins that run from the testicles. Varicoceles commonly develop while a boy is going through puberty. A varicocele is usually not harmful, although in some people it may damage the testicle or decrease sperm production, so it helps for you to take your child to see his doctor if he is concerned about changes in his testicles. ```{=html} <!-- --> ``` - **Testicular cancer.** This is one of the most common cancers in men younger than 40. It occurs when cells in the testicle divide abnormally and form a tumor. Testicular cancer can spread to other parts of the body, but if it\'s detected early, the cure rate is excellent. Teen boys should be encouraged to learn to perform testicular self-examinations. ```{=html} <!-- --> ``` - **Epididymitis** is inflammation of the epididymis, the coiled tubes that connect the testes with the vas deferens. It is usually caused by an infection, such as the sexually transmitted disease chlamydia, and results in pain and swelling next to 1 of the testicles. ```{=html} <!-- --> ``` - **Hydrocele.** A hydrocele occurs when fluid collects in the membranes surrounding the testes. Hydroceles may cause swelling of the testicle but are generally painless. In some cases, surgery may be needed to correct the condition. ```{=html} <!-- --> ``` - **Inguinal hernia.** When a portion of the intestines pushes through an abnormal opening or weakening of the abdominal wall and into the groin or scrotum, it is known as an inguinal hernia. The hernia may look like a bulge or swelling in the groin area. It can be corrected with surgery. ### Disorders of Penis Disorders of the Penis Disorders affecting the penis include the following: - **Inflammation of the penis.** Symptoms of penile inflammation include redness, itching, swelling, and pain. Balanitis occurs when the glans (the head of the penis) becomes inflamed. Posthitis is foreskin inflammation, which is usually due to a yeast or bacterial infection. ```{=html} <!-- --> ``` - **Hypospadias.** This is a disorder in which the urethra opens on the underside of the penis, not at the tip. ```{=html} <!-- --> ``` - **Phimosis.** This is a tightness of the foreskin of the penis and is common in newborns and young children. It usually resolves itself without treatment. If it interferes with urination, circumcision (removal of the foreskin) may be recommended. ```{=html} <!-- --> ``` - **Paraphimosis.** This may develop when a boy\'s uncircumcised penis is retracted but doesn\'t return to the unretracted position. As a result, blood flow to the penis may be impaired, and your child may experience pain and swelling. A doctor may try to use lubricant to make a small incision so the foreskin can be pulled forward. If that doesn\'t work, circumcision may be recommended. ```{=html} <!-- --> ``` - **Ambiguous genitalia.** This occurs when a child is born with genitals that aren\'t clearly male or female. In most boys born with this disorder, the penis may be very small or nonexistent, but testicular tissue is present. In a small number of cases, the child may have both testicular and ovarian tissue. ```{=html} <!-- --> ``` - **Micro penis.** This is a disorder in which the penis, although normally formed, is well below the average size, as determined by standard measurements. ```{=html} <!-- --> ``` - **Sexually transmitted diseases.** Sexually transmitted diseases (STDs) that can affect boys include human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), human papillomavirus (HPV, or genital warts), syphilis, chlamydia, gonorrhea, genital herpes, and hepatitis B. They are spread from one person to another mainly through sexual intercourse. ```{=html} <!-- --> ``` - **Erectile dysfunction.** E.D. is the inability to get or keep an erection firm enough for sexual intercourse. This can also called impotence. The word \"impotence\" may also be used to describe other problems that can interfere with sexual intercourse and reproduction, such as problems with ejaculation or orgasm and lack of sexual desire. Using the term erectile dysfunction clarifies that those other problems are not involved. ### Contraceptive for Men Vasectomy: In the procedure the vas deferens of each testes is cut and tied off to prevent the passage of sperm. Sperm is still produced and stored in crypt sites causing inflammation. Because of this inflammatory response the immune system acts on them destroying them and then having antisperm antibodies. This causes a lower possibility if the vasectomy is reversed to becoming fertile again. Condoms: A device, usually made of latex, or more recently polyurethane, that is used during sexual intercourse. It is put on a man\'s penis and physically blocks ejaculated semen from entering the body of a sexual partner. Condoms are used to prevent pregnancy, transmission of sexually transmitted diseases (STDs - such as gonorrhea, syphilis, and HIV), or both. ## Review Questions Answers for these questions can be found here 1\. This is needed to make immature sperm mature : A\) FHS : B\) LH : C\) FSH : D\) HL 2\. These become engorged with blood in an erection : A\) corpora cavernosa : B\) fibrous envelope : C\) septum pectiniforme : D\) integument : E\) dorsal veins 3\. The difference between male and female sperm : A\) female sperm have a larger head : B\) male sperm are lighter : C\) female sperm are faster : D\) male sperm are weaker : E\) A and B : F\) C and D 4\. The entire process of sperm formation takes about : A\) 5-6 weeks : B\) 7-8 weeks : C\) 3-4 weeks : D\) 9-10 weeks 5\. Hyper Activation occurs when : A\) the sperm are introduced into the urethra : B\) the sperm are ejaculated into the vaginal canal : C\) the sperm begin to interact with the fertilizing layer of an egg cell : D\) the sperm reach the cervix 6\. It takes sperm \_\_\_\_\_\_\_\_\_\_\_ weeks to travel through the epididymis : A\) 6-8 : B\) 1-3 : C\) 2-4 : D\) 4-6 7\. While singing in the choir, Ben suddenly notices his voice is constantly cracking. This is caused by : A\) androgens : B\) LH : C\) FSH : D\) Ben's inability to sing 8\. In sexual homology, the glans penis in the male is equal to \_\_\_\_\_\_\_\_\_\_\_\_\_ in the female : A\) clitoral hood : B\) clitoris : C\) clitoral glans : D\) clitoral crura 9\. In sexual homology, the \_\_\_\_\_\_\_\_\_\_\_ in the male is equal to the fallopian tubes in the female : A\) testis : B\) appendix testis : C\) vas deferens : D\) seminal vesicle : E\) efferent ducts 10\. Joe has a bulge in the groin area that seems to get worse when he lifts things. This most likely is : A\) epididymitis : B\) testicular cancer : C\) varicocele : D\) hydrocele : E\) inguinal hernia ## Glossary **Androgen**: The generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of masculine characteristics in vertebrates by binding to androgen receptors. This includes the activity of the accessory male sex organs and development of male secondary sex characteristics. They are also the precursor of all estrogens, the female sex hormones. The primary and most well-known androgen is testosterone. **Apocrine Glands**: Apocrine sweat glands develop during the early to mid puberty ages approximately around the age of 15 and release more than normal amounts of sweat for approximately a month and subsequently regulate and release normal amounts of sweat after a certain period of time. They are located wherever there is body hair. These glands produce sweat that contains fatty materials. Mainly present in the armpits and around the genital area, their activity is the main cause of sweat odor, due to the bacteria that break down the organic compounds in the sweat. **Bulbourethral Glands**: male accessory sex glands that secrete mucus for lubrication **Chemotaxis**: Chemotaxis is a kind of taxis, in which bodily cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food (for example, glucose) by swimming towards the highest concentration of food molecules, or to flee from poisons (for example, phenol). In multicellular organisms, chemotaxis is critical to development as well as normal function. In addition, it has been recognized that mechanisms that allow chemotaxis in animals can be subverted during cancer metastasis. **Corpora Cavernosa**: one of a pair of a sponge-like regions of erectile tissue which contain most of the blood in the male penis during erection **Ductus Deferens**: epididymal ducts from each testis converge to form a large, thick walled, muscular duct **Ejaculatory Ducts**: two ducts, receive sperm from the ductus deferens and secretions from the seminal vesicle; the ducts then empty into the urethra **Epididymis**: comma shaped and loosely attached to the rear surface of each testis **Erectile Tissue**: smooth muscle and connective tissue inside the penis that contain blood sinuses; large, irregular vascular channels **Erection**: the penis at its enlarged and firm state; occurs when the corpora cavernosa become engorged with venous blood **Flagellum**: the whip-like tail of a sperm, propels the sperm towards the egg in hopes of achieving fertilization **Follicle-Stimulating Hormone (FSH)**: hormone that stimulates production of sertoli cells, to make immature sperm to mature sperm **Glans Penis**: distal end of the penis, covered with the foreskin **Gonadotropin-Releasing Hormone (GnRH)**: hormone secreted by the hypothalamus into the pituitary gland; two types, FSH and LH **Libido**: In its common usage, it means sexual desire; however, more technical definitions, such as those found in the work of Carl Jung, are more general, referring to libido as the free creative---or psychic---energy an individual has to put toward personal development, or individuation. **Luteinizing Hormone (LH)**: hormone that stimulates Leydig cells in the testes to produce testosterone **Oviduct**: the passage in females from the ovaries to the outside of the body. **Penis**: external genital organ of the male **Prostate Gland**: male accessory sex gland that secretes an alkaline fluid, which neutralizes acidic vaginal secretions **Puberty**: the period of maturation and arousal of the dormant and nonfunctional reproductive system; usually occurs in males between the ages of 10 and 15 **Scrotum**: skin covered sac that houses the male testicles; keeps the testicles away from the body so that they can stay a few degrees cooler than the body, for better sperm production **Seminal Vesicle**: male accessory sex glands that supply fructose to ejaculated sperm and secrete prostaglandins **Seminiferous Tubules**: highly coiled tubules within the testes that produce spermatozoa **Sertoli Cell**: A Sertoli cell (a kind of sustentacular cell) is a \'nurse\' cell of the testes which is part of a seminiferous tubule. It is activated by follicle-stimulating hormone, and has FSH-receptor on its membranes. Its main function is to nurture the developing sperm cells through the stages of spermatogenesis. Because of this, it has also been called the \"mother cell.\" It provides both secretory and structural support. **Sexual Homology**: sex organs that evolve from the same tissues in both male and females **Sperm**: main reproductive cell in males **Spermatogenesis**: sperm production **Testes**: located in the scrotum, produces testosterone which stimulates production of sperm **Testosterone**: male sex hormone secreted by the leydig cells of the testes, vital for the production of sperm **TURP**: transurethral resection of the prostate. During TURP, an instrument is inserted up the urethra to remove the section of the prostate that is blocking urine flow. This is most commonly caused by benign prostatic hyperplasia (BPH). A TURP usually requires hospitalization and is done using a general or spinal anesthetic. It is now the most common surgery used to remove part of an enlarged prostate. **Urethra**: the last part of the urinary tract; in males, it is the passage for both urine and sperm **Varicocele**: varicose vein of the testicles, sometimes a cause of male infertility **Vasectomy**: most common sterilization procedure in males; small segment of each ductus deferens is surgically removed after it passes from the testis ## Summary Both male and female reproductive systems may seem somewhat isolated from other body systems in that their purpose is to create new life and not just to maintain existing life. There are however significant relationships between the reproductive system and other body systems. All systems relate in one way or another to help our bodies maintain homeostasis. ## References - \"Essentials of Anatomy and Physiology\" by Valerie C. Scanlon and Tina Sanders - \"Web MD\": <http://www.webmd.com> - Wikibook: Sexual Health [^1]: *Male Infertility from A to Z: A Concise Encyclopedia*. Google books
# Human Physiology/The female reproductive system ## Introduction All living things reproduce. This is something that sets the living apart from non-living. Even though the reproductive system is essential to keeping a species alive, it is not essential to keeping an individual alive. This chapter describes the different parts of the female reproductive system: the organs involved in the process of reproduction, hormones that regulate a woman\'s body, the menstrual cycle, ovulation and pregnancy, the female\'s role in genetic division, birth control, sexually transmitted diseases and other diseases and disorders. ### Reproduction Reproduction can be defined as the process by which an organism continues its species. In the human reproductive process, two kinds of sex cells ( gametes), are involved: the male gamete (sperm), and the female gamete (egg or ovum). These two gametes meet within the female\'s uterine tubes located one on each side of the upper pelvic cavity, and begin to create a new individual. The female needs a male to fertilize her egg; she then carries offspring through pregnancy and childbirth. #### Similarities between male and female reproductive systems The reproductive systems of the male and female have some basic similarities and some specialized differences. They are the same in that most of the reproductive organs of both sexes develop from similar embryonic tissue, meaning they are homologous. Both systems have gonads that produce (sperm and egg or ovum) and sex organs. And both systems experience maturation of their reproductive organs, which become functional during puberty as a result of the gonads secreting sex hormones. !The human male reproductive system{width="440"} !Cross-sectional diagram of the female reproductive organs.{width="440"} In short, this is a known list of sex organs that evolve from the same tissues in a human life. Undifferentiated Male Female --------------------- ----------------------------------- -------------------------- Gonad Testis Ovary Müllerian duct Appendix testis Fallopian tubes Müllerian duct Prostatic utricle Uterus, proximal Wolffian duct Rete testis Rete ovarii Mesonephric tubules Efferent ducts Epoophoron Wolffian duct Epididymis Gartner\'s duct Wolffian duct Vas deferens Wolffian duct Seminal vesicle Wolffian duct Prostate Skene\'s glands Urogenital sinus Urinary bladder\|Bladder, urethra Bladder, urethra, distal Urogenital sinus Bulbourethral gland Bartholin\'s gland Genital swelling Scrotum Labia majora Urogenital folds Distal urethra Labia minora Genital tubercle Penis Clitoris Prepuce Clitoral hood Bulb of penis Vestibular bulbs Glans penis Clitoral glans Crus of penis Clitoral crura #### Differences between male and female reproductive systems The differences between the female and male reproductive systems are based on the functions of each individual\'s role in the reproduction cycle. A male who is healthy, and sexually mature, continuously produces sperm. The development of women\'s \"eggs\" are arrested during fetal development. This means she is born with a predetermined number of oocytes and cannot produce new ones. At about 5 months gestation, the ovaries contain approximately six to seven million oogonia, which initiate meiosis. The oogonia produce primary oocytes that are arrested in prophase I of meiosis from the time of birth until puberty. After puberty, during each menstrual cycle, one or several oocytes resume meiosis and undergo their first meiotic division during ovulation. This results in the production of a secondary oocyte and one polar body. The meiotic division is arrested in metaphase II. Fertilization triggers completion of the second meiotic division and the result is one ovum and an additional polar body. The ovaries of a newborn baby girl contain about one million oocytes. This number declines to 400,000 to 500,000 by the time puberty is reached. On average, 500-1000 oocytes are ovulated during a woman\'s reproductive lifetime. When a young woman reaches puberty around age 10 to 13, a promary oocyte is discharged from one of the ovaries every 28 days. This continues until the woman reaches menopause, usually around the age of 50 years. Occytes are present at birth, and age as a woman ages. Female Reproductive System: - Produces eggs (ova) - Secretes sex hormones - Receives the male spermatazoa during - Protects and nourishes the fertilized egg until it is fully developed - Delivers fetus through birth canal - Provides nourishment to the baby through milk secreted by mammary glands in the breast ## External Genitals ![](Gray1229.png "Gray1229.png"){width="250"} **Vulva** The external female genitalia is referred to as vulva. It consists of the labia majora and labia minora (while these names translate as \"large\" and \"small\" lips, often the \"minora\" can protrude outside the \"majora\"), mons pubis, clitoris, opening of the urethra (meatus), vaginal vestibule, vestibular bulbs, vestibular glands. The term \"vagina\" is often improperly used as a generic term to refer to the vulva or female genitals, even though - strictly speaking - the vagina is a specific internal structure and the vulva is the exterior genitalia only. Calling the vulva the vagina is akin to calling the mouth the throat. **Mons Veneris** The **mons veneris**, Latin for \"mound of Venus\" (Roman Goddess of love) is the soft mound at the front of the vulva (fatty tissue covering the pubic bone). It is also referred to as the mons pubis. The mons veneris protects the pubic bone and vulva from the impact of sexual intercourse. After puberty, it is covered with pubic hair, usually in a triangular shape. Heredity can play a role in the amount of pubic hair an individual grows. **Labia Majora** The **labia majora** are the outer \"lips\" of the vulva. They are pads of loose connective and adipose tissue, as well as some smooth muscle. The labia majora wrap around the vulva from the mons pubis to the perineum. The labia majora generally hides, partially or entirely, the other parts of the vulva. There is also a longitudinal separation called the pudendal cleft. These labia are usually covered with pubic hair. The color of the outside skin of the labia majora is usually close to the overall color of the individual, although there may be some variation. The inside skin is usually pink to light brown. They contain numerous sweat and oil glands. It has been suggested that the scent from these oils are sexually arousing. **Labia Minora** Medial to the labia majora are the labia minora. The **labia minora** are the inner lips of the vulva. They are thin stretches of tissue within the labia majora that fold and protect the vagina, urethra, and clitoris. The appearance of labia minora can vary widely, from tiny lips that hide between the labia majora to large lips that protrude. There is no pubic hair on the labia minora, but there are sebaceous glands. The two smaller lips of the labia minora come together longitudinally to form the prepuce, a fold that covers part of the clitoris. The labia minora protect the vaginal and urethral openings. Both the inner and outer labia are quite sensitive to touch and pressure. **Clitoris** !lang=en\|right\|thumb\|133px The **clitoris**, visible as the small white oval between the top of the labia minora and the clitoral hood, is a small body of spongy tissue that functions solely for sexual pleasure. Only the tip or glans of the clitoris shows externally, but the organ itself is elongated and branched into two forks, the crura, which extend downward along the rim of the vaginal opening toward the perineum. Thus the clitoris is much larger than most people think it is, about 4\" long on average. The clitoral glans or external tip of the clitoris is protected by the prepuce, or clitoral hood, a covering of tissue similar to the foreskin of the male penis. However, unlike the penis, the clitoris does not contain any part of the urethra. During sexual excitement, the clitoris erects and extends, the hood retracts, making the clitoral glans more accessible. The size of the clitoris is variable between women. On some, the clitoral glans is very small; on others, it is large and the hood does not completely cover it. **Urethra** The opening to the urethra is just below the clitoris. Although it is not related to sex or reproduction, it is included in the vulva. The **urethra** is actually used for the passage of urine. The urethra is connected to the bladder. In females the urethra is 1.5 inches long, compared to males whose urethra is 8 inches long. Because the urethra is so close to the anus, women should always wipe themselves from front to back to avoid infecting the vagina and urethra with bacteria. This location issue is the reason for bladder infections being more common among females. **Hymen** The hymen is a thin fold of mucous membrane that separates the lumen of the vagina from the urethral sinus. Sometimes it may partially cover the vaginal orifice. The hymen is usually perforated during later fetal development. Because of the belief that first vaginal penetration would usually tear this membrane and cause bleeding, its \"intactness\" has been considered a guarantor of virginity. However, the hymen is a poor indicator of whether a woman has actually engaged in sexual intercourse because a normal hymen does not completely block the vaginal opening. The normal hymen is never actually \"intact\" since there is always an opening in it. Furthermore, there is not always bleeding at first vaginal penetration. The blood that is sometimes, but not always, observed after first penetration can be due to tearing of the hymen, but it can also be from injury to nearby tissues. A tear to the hymen, medically referred to as a \"transection,\" can be seen in a small percentage of women or girls after first penetration. A transection is caused by penetrating trauma. Masturbation and tampon insertion can, but generally are not forceful enough to cause penetrating trauma to the hymen. Therefore, the appearance of the hymen is not a reliable indicator of virginity or chastity. **Perineum** The perineum is the short stretch of skin starting at the bottom of the vulva and extending to the anus. It is a diamond shaped area between the symphysis pubis and the coccyx. This area forms the floor of the pelvis and contains the external sex organs and the anal opening. It can be further divided into the urogenital triangle in front and the anal triangle in back. The perineum in some women may tear during the birth of an infant and this is apparently natural. Some physicians however, may cut the perineum preemptively on the grounds that the \"tearing\" may be more harmful than a precise cut by a scalpel. If a physician decides the cut is necessary, they will perform it. The cut is called an episiotomy. ## Internal Genitals ### Vagina The **vagina** is a muscular, hollow tube that extends from the vaginal opening to the cervix of the uterus. It is situated between the urinary bladder and the rectum. It is about three to five inches long in a grown woman. The muscular wall allows the vagina to expand and contract. The muscular walls are lined with mucous membranes, which keep it protected and moist. A thin sheet of tissue with one or more holes in it, called the hymen, partially covers the opening of the vagina. The vagina receives sperm during sexual intercourse from the penis. The sperm that survive the acidic condition of the vagina continue on through to the fallopian tubes where fertilization may occur. The vagina is made up of three layers, an inner mucosal layer, a middle muscularis layer, and an outer fibrous layer. The inner layer is made of vaginal rugae that stretch and allow penetration to occur. These also help with stimulation of the penis. microscopically the vaginal rugae has glands that secrete an acidic mucus (pH of around 4.0.) that keeps bacterial growth down. The outer muscular layer is especially important with delivery of a fetus and placenta. Purposes of the Vagina: - Receives a male\'s erect penis and semen during sexual intercourse. - Pathway through a woman\'s body for the baby to take during childbirth. - Provides the route for the menstrual blood (menses) from the uterus, to leave the body. - May hold forms of birth control, such as a diaphragm, FemCap, Nuva Ring, or female condom. ### Cervix The **cervix** (from Latin \"neck\") is the lower, narrow portion of the uterus where it joins with the top end of the vagina. Where they join together forms an almost 90 degree curve. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall. Approximately half its length is visible with appropriate medical equipment; the remainder lies above the vagina beyond view. It is occasionally called \"cervix uteri\", or \"neck of the uterus\". During menstruation, the cervix stretches open slightly to allow the endometrium to be shed. This stretching is believed to be part of the cramping pain that many women experience. Evidence for this is given by the fact that some women\'s cramps subside or disappear after their first vaginal birth because the cervical opening has widened. The portion projecting into the vagina is referred to as the portio vaginalis or **ectocervix**. On average, the ectocervix is three cm long and two and a half cm wide. It has a convex, elliptical surface and is divided into anterior and posterior lips. The ectocervix\'s opening is called the external os. The size and shape of the external os and the ectocervix varies widely with age, hormonal state, and whether the woman has had a vaginal birth. In women who have not had a vaginal birth the external os appears as a small, circular opening. In women who have had a vaginal birth, the ectocervix appears bulkier and the external os appears wider, more slit-like and gaping. The passageway between the external os and the uterine cavity is referred to as the **endocervical canal**. It varies widely in length and width, along with the cervix overall. Flattened anterior to posterior, the endocervical canal measures seven to eight mm at its widest in reproductive-aged women. The endocervical canal terminates at the internal os which is the opening of the cervix inside the uterine cavity. During childbirth, contractions of the uterus will dilate the cervix up to 10 cm in diameter to allow the child to pass through. During orgasm, the cervix convulses and the external os dilates. ### Uterus The **uterus** is shaped like an upside-down pear, with a thick lining and muscular walls. Located near the floor of the pelvic cavity, it is hollow to allow a blastocyte, or fertilized egg, to implant and grow. It also allows for the inner lining of the uterus to build up until a fertilized egg is implanted, or it is sloughed off during menses. The uterus contains some of the strongest muscles in the female body. These muscles are able to expand and contract to accommodate a growing fetus and then help push the baby out during labor. These muscles also contract rhythmically during an orgasm in a wave like action. It is thought that this is to help push or guide the sperm up the uterus to the fallopian tubes where fertilization may be possible. The uterus is only about three inches long and two inches wide, but during pregnancy it changes rapidly and dramatically. The top rim of the uterus is called the fundus and is a landmark for many doctors to track the progress of a pregnancy. The uterine cavity refers to the fundus of the uterus and the body of the uterus. Helping support the uterus are ligaments that attach from the body of the uterus to the pelvic wall and abdominal wall. During pregnancy the ligaments prolapse due to the growing uterus, but retract after childbirth. In some cases after menopause, they may lose elasticity and uterine prolapse may occur. This can be fixed with surgery. Some problems of the uterus include uterine fibroids, pelvic pain (including endometriosis, adenomyosis), pelvic relaxation (or prolapse), heavy or abnormal menstrual bleeding, and cancer. It is only after all alternative options have been considered that surgery is recommended in these cases. This surgery is called hysterectomy. Hysterectomy is the removal of the uterus, and may include the removal of one or both of the ovaries. Once performed it is irreversible. After a hysterectomy, many women begin a form of alternate hormone therapy due to the lack of ovaries and hormone production. ![](Gray1161.png "Gray1161.png") ### Fallopian Tubes At the upper corners of the uterus are the **fallopian tubes**. There are two fallopian tubes, also called the uterine tubes or the oviducts. Each fallopian tube attaches to a side of the uterus and connects to an ovary. They are positioned between the ligaments that support the uterus. The fallopian tubes are about four inches long and about as wide as a piece of spaghetti. Within each tube is a tiny passageway no wider than a sewing needle. At the other end of each fallopian tube is a fringed area that looks like a funnel. This fringed area, called the infundibulum, lies close to the ovary, but is not attached. The ovaries alternately release an egg. When an ovary does ovulate, or release an egg, it is swept into the lumen of the fallopian tube by the fimbriae. Once the egg is in the fallopian tube, tiny hairs in the tube\'s lining help push it down the narrow passageway toward the uterus. The oocyte, or developing egg cell, takes four to five days to travel down the length of the fallopian tube. If enough sperm are ejaculated during sexual intercourse and there is an oocyte in the fallopian tube, fertilization will occur. After fertilization occurs, the zygote, or fertilized egg, will continue down to the uterus and implant itself in the uterine wall where it will grow and develop. If a zygote doesn\'t move down to the uterus and implants itself in the fallopian tube, it is called a ectopic or tubal pregnancy. If this occurs, the pregnancy will need to be terminated to prevent permanent damage to the fallopian tube, possible hemorrhage and possible death of the mother. ### Mammary glands !Cross section of the breast of a human female.{width="200"} **Mammary glands** are the organs that produce milk for the sustenance of a baby. These exocrine glands are enlarged and modified sweat glands. #### Structure The basic components of the mammary gland are the **alveoli** (hollow cavities, a few millimetres large) lined with milk-secreting epithelial cells and surrounded by myoepithelial cells. These alveoli join up to form groups known as **lobules**, and each lobule has a **lactiferous duct** that drains into openings in the nipple. The **myoepithelial** cells can contract, similar to muscle cells, and thereby push the milk from the alveoli through the lactiferous ducts towards the nipple, where it collects in widenings (sinuses) of the ducts. A suckling baby essentially squeezes the milk out of these sinuses. The development of mammary glands is controlled by hormones. The mammary glands exist in both sexes, but they are rudimentary until puberty when - in response to ovarian hormones - they begin to develop in the female. Estrogen promotes formation, while testosterone inhibits it. At the time of birth, the baby has lactiferous ducts but no alveoli. Little branching occurs before puberty when ovarian estrogens stimulate branching differentiation of the ducts into spherical masses of cells that will become alveoli. True secretory alveoli only develop in pregnancy, where rising levels of estrogen and progesterone cause further branching and differentiation of the duct cells, together with an increase in adipose tissue and a richer blood flow. Colostrum is secreted in late pregnancy and for the first few days after giving birth. True milk secretion (lactation) begins a few days later due to a reduction in circulating progesterone and the presence of the hormone prolactin. The suckling of the baby causes the release of the hormone oxytocin which stimulates contraction of the myoepithelial cells. The cells of mammary glands can easily be induced to grow and multiply by hormones. If this growth runs out of control, cancer results. Almost all instances of breast cancer originate in the lobules or ducts of the mammary glands. STRUCTURE LOCATION & DESCRIPTION FUNCTION ------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Breasts Upper chest one on each side containing alveolar cells (milk production), myoepithelial cells (contract to expel milk), and duct walls (help with extraction of milk). Lactation milk/nutrition for newborn. Cervix The lower narrower portion of the uterus. During childbirth, contractions of the uterus will dilate the cervix up to 10 cm in diameter to allow the child to pass through. During orgasm, the cervix convulses and the external os dilates Clitoris Small erectile organ directly in front of the vestibule. Sexual excitation, engorged with blood. Fallopian tubes Extending upper part of the uterus on either side. Egg transportation from ovary to uterus (fertilization usually takes place here). Hymen Thin membrane that partially covers the vagina in young females. Labia majora Outer skin folds that surround the entrance to the vagina. Lubrication during mating. Labia minora Inner skin folds that surround the entrance to the vagina. Lubrication during mating. Mons Mound of skin and underlying fatty tissue, central in lower pelvic region Ovaries (female gonads) Pelvic region on either side of the uterus. Provides an environment for maturation of oocyte. Synthesizes and secretes sex hormones (estrogen and progesterone). Perineum Short stretch of skin starting at the bottom of the vulva and extending to the anus. Urethra Pelvic cavity above bladder, tilted. Passage of urine. Uterus Center of pelvic cavity. To house and nourish developing human. Vagina Canal about 10-8 cm long going from the cervix to the outside of the body. Receives penis during mating. Pathway through a womans body for the baby to take during childbirth. Provides the route for the menstrual blood (menses) from the uterus, to leave the body. May hold forms of birth control, such as an IUD, diaphragm, neva ring, or female condom Vulva Surround entrance to the reproductive tract.(encompasses all external genitalia) Endometrium The innermost layer of uterine wall. Contains glands that secrete fluids that bathe the utrine lining. Myometrium Smooth muscle in uterine wall. Contracts to help expel the baby. ## The Female Reproductive Cycle Towards the end of puberty, girls begin to release eggs as part of a monthly period called the female reproductive cycle, or **menstrual cycle** (menstrual referring to \"monthly\"). Approximately every 28 days, during ovulation, an ovary sends a tiny egg into one of the fallopian tubes. Unless the egg is fertilized by a sperm while in the fallopian in the two to three days following ovulation, the egg dries up and leaves the body about two weeks later through the vagina. This process is called menstruation. Blood and tissues from the inner lining of the uterus (the endometrium) combine to form the menstrual flow, which generally lasts from four to seven days. The first period is called **menarche**. During menstruation arteries that supply the lining of the uterus constrict and capillaries weaken. Blood spilling from the damaged vessels detaches layers of the lining, not all at once but in random patches. Endometrium mucus and blood descending from the uterus, through the liquid creates the menstruation flow. !Menstrual cycle{width="300"} The reproductive cycle can be divided into an ovarian cycle and a uterine cycle (compare ovarian histology and uterine histology in the diagram on the right). During the **uterine cycle**, the endometrial lining of the uterus builds up under the influence of increasing levels of estrogen (labeled as estradiol in the image). Follicles develop, and within a few days one matures into an **ovum**, or egg. The ovary then releases this egg, at the time of **ovulation**. After ovulation the uterine lining enters a secretory phase, or the **ovarian cycle**, in preparation for implantation, under the influence of progesterone. Progesterone is produced by the corpus luteum (the follicle after ovulation) and enriches the uterus with a thick lining of blood vessels and capillaries so that it can sustain the growing fetus. If fertilization and implantation occur, the embryo produces Human Chorionic Gonadotropin (HCG), which maintains the corpus luteum and causes it to continue producing progesterone until the placenta can take over production of progesterone. Hence, progesterone is \"pro gestational\" and maintains the uterine lining during all of pregnancy. If fertilization and implantation do not occur the corpus luteum degenerates into a corpus albicans, and progesterone levels fall. This fall in progesterone levels cause the endometrium lining to break down and sluff off through the vagina. This is called menstruation, which marks the low point for estrogen activity and is the starting point of a new cycle. Common usage refers to menstruation and menses as a period. This bleeding serves as a sign that a woman has not become pregnant. However, this cannot be taken as certainty, as sometimes there is some bleeding in early pregnancy. During the reproductive years, failure to menstruate may provide the first indication to a woman that she may have become pregnant. Menstruation forms a normal part of a natural cyclic process occurring in healthy women between puberty and the end of the reproductive years. The onset of menstruation, known as **menarche**, occurs at an average age of 12, but is normal anywhere between 8 and 16. Factors such as heredity, diet, and overall health can accelerate or delay the onset of menarche. **Signs of ovulation** The female body produces outward signs that can be easily recognized at the time of ovulation. The two main signs are thinning of the cervical mucus and a slight change in body temperature. **Thinning of the Cervical Mucus** After menstruation and right before ovulation, a woman will experience an increase of cervical mucus. At first, it will be thick and yellowish in color and will not be very plentiful. Leading up to ovulation, it will become thinner and clearer. On or around the day of ovulation, the cervical mucus will be very thin, clear and stretchy. It can be compared to the consistency of egg whites. This appearance is known as \'spinnbarkeit\'. **Temperature Change** A woman can also tell the time of ovulation by taking her basal body temperature daily. This is a temperature taken with a very sensitive thermometer first thing in the morning before the woman gets out of bed. The temperature is then tracked to show changes. In the uterine cycle, a normal temperature will be around 97.0 -- 98.0. The day of ovulation the temperature spikes down, usually into the 96.0 -- 97.0 range and then the next morning it will spike up to normal of around 98.6 and stay in that range until menstruation begins. Both of these methods are used for conception and contraception. They are more efficient in conception due to the fact that sperm can live for two to three days inside of the fallopian tubes. A woman could be off by a couple of days in her calculations and still become pregnant. **Menopause** is the physiological cessation of menstrual cycles associated with advancing age. Menopause is sometimes referred to as \"the change of life\" or climacteric. Menopause occurs as the ovaries stop producing estrogen, causing the reproductive system to gradually shut down. As the body adapts to the changing levels of natural hormones, vasomotor symptoms such as hot flashes and palpitations, psychological symptoms such as increased depression, anxiety, irritability, mood swings and lack of concentration, and atrophic symptoms such as vaginal dryness and urgency of urination appear. Together with these symptoms, the woman may also have increasingly scanty and erratic menstrual periods. Technically, menopause refers to the cessation of menses; the gradual process through which this occurs, which typically takes a year but may last as little as six months or more than five years, is known as climacteric. A natural or physiological menopause is that which occurs as a part of a woman\'s normal aging process. However, menopause can be surgically induced by such procedures as hysterectomy. The average onset of menopause is 50.5 years, but some women enter menopause at a younger age, especially if they have suffered from cancer or another serious illness and undergone chemotherapy. Premature menopause is defined as menopause occurring before the age of 40, and occurs in 1% of women. Other causes of premature menopause include autoimmune disorders, thyroid disease, and diabetes mellitus. Premature menopause is diagnosed by measuring the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). The levels of these hormones will be higher if menopause has occurred. Rates of premature menopause have been found to be significantly higher in both fraternal and identical twins; approximately 5% of twins reach menopause before the age of 40. The reasons for this are not completely understood. Post-menopausal women are at increased risk of osteoporosis. **Perimenopause** refers to the time preceding menopause, during which the production of hormones such as estrogen and progesterone diminish and become more irregular. During this period fertility diminishes. Menopause is arbitrarily defined as a minimum of twelve months without menstruation. Perimenopause can begin as early as age 35, although it usually begins much later. It can last for a few months or for several years. The duration of perimenopause cannot be predicted in advance. **Premenstrual Syndrome** (PMS) It is common for women to experience some discomfort in the days leading up to their periods. PMS usually is at its worst the seven days before a period starts and can continue through the end of the period. PMS includes both physical and emotional symptoms: acne, bloating, fatigue, backaches, sore breasts, headaches, constipation, diarrhea, food cravings, depression, irritability, difficulty concentrating or handling stress. ## Ovarian and Uterine Cycles in the Nonpregnant Woman thumb\|An ovary about to release an egg. Ovarian Cycle Events Uterine Cycle Events ------------------------------ -------------------------------------- --------------------------------- ------------------------------------------------- Follicular phase - Days 1-13 FSH secretion begins. Menstruation - Days 2-5 Endometrium breaks down. Follicle maturation occurs. Proliferative phase - Days 6-13 Endometrium rebuilds. Estrogen secretion is prominent. Ovulation - Day 14\* LH spike occurs. Luteal phase - Days 15-28 LH secretion continues. Secretory phase - Days 15-28 Endometrial thickens, and glands are secretory. Corpus luteum forms. Progesterone secretion is prominent. (\*)Assuming a 28 day cycle. There are two phases of the ovarian cycle the follicular phase and the luteal phase. In the follicular phase about 10-25 follicles are taken from preantral or early antrial follicles to develop further. Seven days later the dominant follicle is selected to develop to full maturity. This is the pre-cursor for ovulation. Follicles themselves secrete FSH and estrogen, and these two hormones stimulate follicular growth and development. Ovulation marks the beginning of the luteal phase. This is started by the wall of the Graffian follicle to rupture and cause a flow of antral fluid that will carry the oocyte to the ovary\'s surface. The ruptured follicle is then turned into a gland (corpus luteum). Which secretes estrogens and progesterone. This is all triggered by and abrupt change in plasma LH levels. After ovulation the released oocyte enters the uterine tube, where it will be either fertilized or discarded. The uterine cycle operates in sync with the ovarian cycle and is divided into three phases. The first phase in the menstrual phase. It is named the menstrual phase because in corresponds with the shedding the uterine lining or more commonly called menstruation. The corpus luteum degenerates causing plasma estrogen and progesterone levels to decrease and in turn causes menstruation. Blood vessels in the outer most layer of the endometrium constrict and decrease blood flow to the tissues killing these tissues. After the tissues die they start to separate from the underlying endometrial tissues. Eventually the dead tissue is shed. This shedding of the tissues ruptures blood vessels and causes bleeding. Now we have the proliferative phase. During this phase the uterus renews itself and prepares for pregnancy. The endometrial tissue that is left after menstruation begins to grow. The endometrial glands grow and enlarge causing more blood vessels. The cervical canal has glands that secrete a thin mucous that helps deposited sperm. Estrogen promotes uterine changes in this phase. The last phase is the secretory phase. This is where the endometrium is transformed to make it the best environment for implantation and subsequent housing and nourishment of the developing embryo. By doing this the endometrium will do things like have an enriched blood supply, begin to secrete fluids rich in glycogen, and even form a plug at the end of the cervical canal so that microorganisms can not enter. These changes in the uterus are caused by progesterone, due to the corpus luteum. At the end of the secretory phase the corpus luteum degenerates, and progesterone levels fall. This will trigger menstruation. ## Sexual Reproduction **Sexual reproduction** is a type of reproduction that results in increasing genetic diversity of the offspring. In sexual reproduction, genes from two individuals are combined in random ways with each new generation. Sex hormones released into the body by the endocrine system signal the body when it is time to start puberty. The female and male reproductive systems are the only systems so vastly different that each sex has their own different organs. All other systems have \"unisex\" organs. Reproduction is characterized by two processes. The first, meiosis, involves the halving of the 46 of chromosomes. The second process, fertilization, leads the fusion of two gametes and the restoration of the original number of chromosomes: 23 chromosomes from the paternal side and 23 from the maternal side. During meiosis, the chromosomes of each pair usually cross over to achieve genetic recombination. Sexual reproduction cannot happen without the sexual organs called gonads. Both sexes have gonads: in females, the gonads are the ovaries. The female gonads produce female gametes (eggs); the male gonads produce male gametes (sperm). After an egg is fertilized by the sperm, the fertilized egg is called the zygote. The fertilization usually occurs in the oviducts, but can happen in the uterus itself. The zygote then implants itself in the wall of the uterus, where it begins the processes of embryogenesis and morphogenesis. The womens body carries out this process of reproduction for 40 weeks, until delivery of the fetus from the uterus through the vagina (birth canal). Even after birth, the female continues with the reproduction process by supplying the milk to nourish the infant. ## Infertility **Infertility** is the inability to naturally conceive a child or the inability to carry a pregnancy to term. There are many reasons why a couple may not be able to conceive without medical assistance. Infertility affects approximately 15% of couples. Roughly 40% of cases involve a male contribution or factor, 40% involve a female factor, and the remaining 20% involve both sexes. Healthy couples in their mid-20s having regular sex have a one-in-four chance of getting pregnant in any given month. This is called \"Fecundity\". ### Primary vs. secondary According to the American Society for Reproductive Medicine, infertility affects about 6.1 million people in the United States, equivalent to 10% of the reproductive age population. Female infertility accounts for one third of infertility cases, male infertility for another third, combined male and female infertility for another 15%, and the remainder of cases are \"unexplained\'\'. \"Secondary infertility\" is difficulty conceiving after already having conceived and carried a normal pregnancy. Apart from various medical conditions (e.g. hormonal), this may come as a result of age and stress felt to provide a sibling for their first child. Technically, secondary infertility is not present if there has been a change of partners. ### Factors of Infertility Factors relating to female infertility are: - General factors - Diabetes mellitus,thyroid disorders,adrenal disease - Significant liver,kidney disease - Psychological factors - Hypothalamic-pituitary factors: - Kallmann syndrome - Hypothalamic dysfunction - Hyperprolactinemia - Hypopituitarism - Ovarian factors - Polycystic ovary syndrome - Anovulation - Diminished ovarian reserve - Luteal dysfunction - Premature menopause - Gonadal dysgenesis (Turner syndrome) - Ovarian neoplasm - Tubal/peritoneal factors - Endometriosis - Pelvic adhesions - Pelvic inflammatory disease(PID, usually due to chlamydia) - Tubal occlusion - Uterine factors - Uterine malformations - Uterine fibroids (leiomyoma) - Asherman\'s Syndrome - Cervical factors - Cervical stenosis - Antisperm antibodies - Insufficient cervical mucus (for the travel and survival of sperm) - Vaginal factors - Vaginismus - Vaginal obstruction - Genetic factors - Various intersexuality\|intersexed conditions, such as androgen insensitivity syndrome ### Combined Infertility In some cases, both the man and woman may be infertile or sub-fertile, and the couple\'s infertility arises from the combination of these factors. In other cases, the cause is suspected to be immunological or genetic; it may be that each partner is independently fertile but the couple cannot conceive together without assistance. ### Unexplained Infertility In about 15% of cases of infertility, investigation will show no abnormalities. In these cases abnormalities are likely to be present but not detected by current methods. Possible problems could be that the egg is not released at the optimum time for fertilization, that it may not enter the fallopian tube, sperm may not be able to reach the egg, fertilization may fail to occur, transport of the zygote may be disturbed, or implantation fails. It is increasingly recognized that egg quality is of critical importance. ### Diagnosis of Infertility Diagnosis of infertility begins with a medical history and physical exam. The healthcare provider may order tests, including the following: - an endometrial biopsy, which tests the lining of the uterus - hormone testing, to measure levels of female hormones - laparoscopy, which allows the provider to see the pelvic organs - ovulation testing, which detects the release of an egg from the ovary - Pap smear, to check for signs of infection - pelvic exam, to look for abnormalities or infection - a postcoital test, which is done after sex to check for problems with secretions - special X-ray tests ### Treatment - Fertility medication which stimulates the ovaries to \"ripen\" and release eggs (e.g. Clomifene\|clomifene citrate, which stimulates ovulation) - Surgery to restore potency of obstructed fallopian tubes (tuboplasty) - Donor insemination which involves the woman being artificially inseminated or artificially inseminated with donor sperm. - In vitro fertilization (IVF) in which eggs are removed from the woman, fertilized and then placed in the woman\'s uterus, bypassing the fallopian tubes. Variations on IVF include: - Use of donor eggs and/or sperm in IVF. This happens when a couple\'s eggs and/or sperm are unusable, or to avoid passing on a genetic disease. - Intracytoplasmic sperm injection (ICSI) in which a single sperm is injected directly into an egg; the fertilized egg is then placed in the woman\'s uterus as in IVF. - Zygote intrafallopian transfer(ZIFT) in which eggs are removed from the woman, fertilized and then placed in the woman\'s fallopian tubes rather than the uterus. - Gamete intrafallopian transfer(GIFT) in which eggs are removed from the woman, and placed in one of the fallopian tubes, along with the man\'s sperm. This allows fertilization to take place inside the woman\'s body. - Other assisted reproductive technology (ART): - Assisted hatching - Fertility preservation - Freezing (cryopreservation) of sperm, eggs, & reproductive tissue - Frozen embryo transfer (FET) - Alternative and complimentary treatments - Acupuncture Recent controlled trials published in Fertility and Sterility have shown acupuncture to increase the success rate of IVF by as much as 60%. Acupuncture was also reported to be effective in the treatment of female anovular infertility, World Health Organization, Acupuncture: Review and Analysis of Reports on Controlled Trials (2002). - Diet and supplements - Healthy lifestyle ## Types of Birth Control **Birth control** is a regimen of one or more actions, devices, or medications followed in order to deliberately prevent or reduce the likelihood of a woman becoming pregnant. Methods and intentions typically termed birth control may be considered a pivotal ingredient to family planning. Mechanisms which are intended to reduce the likelihood of the fertilization of an ovum by a sperm may more specifically be referred to as contraception. Contraception differs from abortion in that the former prevents fertilization, while the latter terminates an already established pregnancy. Methods of birth control (e.g. the pill, IUDs, implants, patches, injections, vaginal ring and some others) which may prevent the implantation of an embryo if fertilization occurs are medically considered to be contraception. It is advised to talk with a doctor before choosing a contraceptive. If you have genetics problems or blood conditions, such as factor V leiden, certain contraceptives can be deadly. Type Procedure Method Effectiveness Risks ------------------------------------ --------------------------------------------------------------------------------------------------------------------------------------------------------- ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ---------------------------- ------------------------------------------- Abstinence Refrain from sexual intercourse No sperm in vagina 100% None Rhythm Method Intercourse is avoided for about an 8-day span every month in middle of her cycle, from about five days before ovulation to three days after ovulation. fertilization is only possible during 8-day span in middle of menstrual cycle 70-80% None Withdrawal The man withdraws his penis from the vagina at just the right moment before ejaculation. sperm are unable to enter vagina if male penis is removed at the right time 70-80% None Tubal Ligation (Vasectomy) Oviducts are cut and tied No eggs in oviduct Almost 99% About 75% Irreversible Hormonal IUD (intrauterine device) Flexible, plastic coil inserted by physician Releases small amounts of estrogen. In most cases, stops egg from developing and being released, but can also operate by killing a fertilized egg by preventing its implantation About 99% May cause infections, uterine perforation Oral Contraceptive Hormone medication taken daily Stops release of FSH and LH, but can also operate by killing a fertilized egg by preventing its implantation More than 90% Blood clots, especially in smokers Contraceptive Implants Tubes of progesterone implanted under the skin Stops release of FSH and LH, but can also operate by killing a fertilized egg by preventing its implantation More than 90% None known Contraceptive Injections Injections of hormones Stops release of FSH and LH, but can also operate by killing a fertilized egg by preventing its implantation About 99% Possible osteoporosis Diaphragm Latex cup inserted into vagina to cover cervix before intercourse Blocks entrance of sperm into uterus With spermicide, about 90% Latex or spermicide allergy Cervical Cap Latex cup held by suction over cervix Delivers spermicide near cervix Almost 85% UTI, latex or spermicide allergy Female Condom Polyurethane liner fitted inside vagina Blocks entrance of sperm into uterus and prevents STD's Almost 85% None Male Condom soft sheath, made of latex or animal membrane, encloses penis, trapping ejaculated sperm Blocks entrance of sperm into vagina and prevents STD\'s 90% None Jellies, Cream, Foams Spermicidal products inserted before intercourse Kills large number of sperm About 75% UTI, allergy to spermicides Natural Family Planning Keep record of ovulation using various methods Avoid sexual intercourse near ovulation About 70% None known Douche Vagina cleansed after intercourse Washes out sperm Less than 70% None known Plan B Pill Pill taken after intercourse Prevents release of egg, fertilization of egg, but can also operate by killing a fertilized egg by preventing its implantation About 89% Same as oral contraceptive ## Sexually Transmitted Diseases **Sexually transmitted diseases** (STDs) are diseases or infections likely to be transmitted by sexual contact: vaginal intercourse, oral sex, and/or anal sex. Many STDs are (more easily) transmitted through the mucous membranes of the penis, vulva, and (less often) the mouth. The visible membrane covering the head of the penis is a mucous membrane, though, for those who are circumcised it is usually dry and produces no mucus (similar to the lips of the mouth). Mucous membranes differ from skin in that they allow certain pathogens (viruses or bacteria) into the body (more easily). The probability of transmitting infections through sex is far greater than by more casual means of transmission, such as non-sexual contact---touching, sharing cutlery, and shaking hands. Although mucous membranes exist in the mouth as well as in the genitals, many STDs are more likely to be transmitted through oral sex than through deep kissing. Many infections that are easily transmitted from the mouth to the genitals or from the genitals to the mouth, are much harder to transmit from one mouth to another. With HIV, genital fluids happen to contain a great deal more of the pathogen than saliva. Some infections labeled as STDs can be transmitted by direct skin contact. Herpes simplex and HPV are both examples. Depending on the STD, a person who has the disease but has no symptoms may or may not be able to spread the infection. For example, a person is much more likely to spread herpes infection when blisters are present than when they are absent. However, a person can spread HIV infection at any time, even if he/she has not developed symptoms of AIDS. All sexual behaviors that involve contact with the bodily fluids of another person should be considered to hold some risk of transmission of sexually transmitted diseases. Most attention has focused on controlling HIV, which causes AIDS, but each STD presents a different situation. As may be noted from the name, sexually transmitted diseases are transmitted from one person to another by certain sexual activities rather than being actually caused by those sexual activities. Bacteria, fungi, protozoa or viruses are still the causative agents. It is not possible to catch any sexually transmitted disease from a sexual activity with a person who is not carrying a disease; conversely, a person who has an STD received it from contact (sexual or otherwise) with someone who is infected. Although the likelihood of transmitting diseases by sexual activities varies a great deal, in general, all sexual activities between two (or more) people should be considered as being a two-way route for the transmission of STDs (i.e. \"giving\" or \"receiving\" are both risky). ### Prevention of Sexually Transmitted Diseases Although healthcare professionals suggest that safer sex, such as the use of condoms, as the most reliable way of decreasing the risk of contracting sexually transmitted diseases during sexual activity, safer sex should by no means be considered an absolute safeguard. The transfer of and exposure to bodily fluids, such as blood transfusions and other blood products, sharing injection needles, needle-stick injuries (when medical staff are inadvertently jabbed or pricked with needles during medical procedures), sharing tattoo needles, and childbirth are all avenues of transmission. These means put certain groups, such as doctors, haemophiliacs and drug users, particularly at risk. ### **Human Papillomavirus (HPV)** There are over 100 types of this virus which is often asymptomatic. Nearly 3 out of 4 Americans between ages 15 and 49 have been infected. It can be contracted through one partner and remain dormant allowing it to be transmitted to another. Some types can cause cervical cancer. Genital HPV infection is a sexually transmitted disease that is caused by human papillomavirus. Human papillomavirus is the name of a group of viruses that includes more than 100 different strains. More than 30 of these are sexually transmitted and they can infect the genital area of men and women. Approximately 20 million people are currently infected with HPV and at least 50% of sexually active men and women will acquire HPV at some point in their lives. By age 50 at least 80% of women will have acquired HPV and about 6.2 million Americans get a new HPV infection each year. Most people who have HPV don\'t know that they are infected. The virus lives in the skin or mucous membranes and usually causes no symptoms. Commonly some people get visible genital warts or have pre-cancerous changes in the cervix, vulva, anus, or penis. Very rarely, HPV results in anal or genital cancers. Genital warts usually appear soft, moist, pink, or flesh colored swellings. They can be raised, flat, single, or multiple, small or large and sometimes cauliflower shaped. Warts may not appear for weeks or months or not at all and the only way to diagnose them is by visible inspection. Most women are diagnosed with HPV on the basis of abnormal pap tests and there are no tests available for men. There is no cure for HPV. The surest way to eliminate risk for HPV is to refrain from any genital contact with another individual. For those who choose to be sexually active, a long term monogamous relationship with an uninfected partner is the strategy most likely to prevent future HPV infections.The next best way to help reduce risk is using a condom but the effectiveness is unknown. **What is the connection between HPV and cervical cancer?** All types of HPV cause mild pap test abnormalities which do not have serious consequences. Approximately 10 of the 30 identified HPV types can lead to development of cervical cancer. Research as shown that for most women, 90% cervical HPV infection becomes undetectable within two years. Although only a small proportion of women have persistent infection, persistent infection with the high risk types of HPV is the main risk factor for cervical cancer. A pap test can detect pre-cancerous and cancerous cells on the cervix. Regular pap testing and careful medical follow up, with treatment if necessary, can help ensure that pre-cancerous changes in the cervix caused by HPV infection do not develop into life-threatening cervical cancer. The pap test used in the U.S. cervical cancer screening programs is responsible for greatly reducing deaths from cervical cancer. ## **Diseases and Disorders of the Female Reproductive System** Women are commonly dealing with many different diseases and disorders that pertain to the reproductive system. Here are some of the most common: 1. **Vulvovaginitis** (pronounced:vul-vo-vah-juh-ni-tus) is an inflammation of the vulva and vagina. It may be caused by irritating substances such as laundry soap, bubble baths or poor hygiene such as wiping from back to front. Symptoms include redness and itching in these areas and sometimes vaginal discharge. It can also be caused by an overgrowth of candida, a fungus normally present in the vagina. 2. **Nonmenstrual vaginal bleeding** is most commonly due to the presence of a foreign body in the vagina. It may also be due to urethral prolapse, a condition in which the mucous membranes of the urethra protrude into the vagina and forms a tiny, donut shaped mass of tissue that bleeds easily. It can also be due to a straddle injury or vaginal trauma from sexual abuse. 3. **Ectopic Pregnancy** occurs when a fertilized egg or zygote doesn\'t travel into the uterus, but instead grows rapidly in the fallopian tube. Women with this condition can develop severe abdominal pain and should see a doctor because surgery may be necessary. 4. **Ovarian tumors**,although rare, can occur. Women with ovarian tumors may have abdominal pain and masses that can be felt in the abdomen. Surgery may be needed to remove the tumor. 5. **Ovarian cysts** are noncancerous sacs filled with fluid or semi-solid material. Although they are common and generally harmless, they can become a problem if they grow very large. Large cysts may push on surrounding organs, causing abdominal pain. In most cases, cysts will pass or disappear on their own and treatment is not necessary. If the cysts are painful and occur frequently, a doctor may prescribe birth control pills to alter their growth and occurrences. Surgery is also an option if they need to be removed. 6. **Polycystic ovary syndrome** is a hormone disorder in which too many hormones are produced by the ovaries. This condition causes the ovaries to become enlarged and develop many fluid filled sacs or cysts. It often first appears during the teen years. Depending on the type and the severity of the condition, it may be treated with drugs to regulate hormone balance and menstruation. 7. **Trichomonas vaginalis** inflammatory condition of the vagina usually a bacterial infection also called vaginosis. 8. **Dysmenorrhea** is painful periods. 9. **Menorrhagia** is when a woman has very heavy periods with excess bleeding. 10. **Oligomenorrhea** is when a woman misses or has infrequent periods, even though she has been menstruating for a while and is not pregnant. 11. **Amenorrhea** is when a girl has not started her period by the time she is 16 years old or 3 years after puberty has started, has not developed signs of puberty by 14, or has had normal periods but has stopped menstruating for some reasons other than pregnancy. 12. **Toxic shock syndrome** is caused by toxins released into the body during a type of bacterial infection that is more likely to develop if a tampon is left in too long. It can produce high fever, diarrhea, vomiting, and shock. 13. **Candidasis** symptoms of yeast infections include itching, burning and discharge. Yeast organisms are always present in all people, but are usually prevented from \"overgrowth\" (uncontrolled multiplication resulting in symptoms) by naturally occurring microorganisms. At least three quarters of all women will experience candidiasis at some point in their lives. The Candida albicans organism is found in the vaginas of almost all women and normally causes no problems. However, when it gets out of balance with the other \"normal flora,\" such as lactobacilli (which can also be harmed by using douches), an overgrowth of yeast can result in noticeable symptoms. Pregnancy, the use of oral contraceptives, engaging in vaginal sex after anal sex in an unhygienic manner, and using lubricants containing glycerin have been found to be causally related to yeast infections. Diabetes mellitus and the use of antibiotics are also linked to an increased incidence of yeast infections. Candidiasis can be sexually transmitted between partners. Diet has been found to be the cause in some animals. Hormone Replacement Therapy and Infertility Treatment may be factors. There are also cancer\'s of the female reproductive system, such as: 1. Cervical cancer 2. Ovarian cancer 3. Uterine cancer 4. Breast cancer **Endometriosis** Endometriosis is the most common gynecological diseases, affecting more than 5.5 million women in North America alone! The two most common symptoms are pain and infertility. In this disease a specialized type of tissue that normally lines the inside of the uterus,(the endometrium) becomes implanted outside the uterus, most commonly on the fallopian tubes, ovaries, or the tissue lining the pelvis. During the menstrual cycle, hormones signal the lining of the uterus to thicken to prepare for possible pregnancy. If a pregnancy doesn\'t occur, the hormone levels decrease, causing the thickened lining to shed. When endometrial tissue is located in other parts it continues to act in it\'s normal way: It thickens, breaks down and bleeds each month as the hormone levels rise and fall. However, because there\'s nowhere for the blood from this mislocated tissue to exit the body, it becomes trapped and surrounding tissue becomes irritated. Trapped blood may lead to growth of cysts. Cysts in turn may form scar tissue and adhesions. This causes pain in the area of the misplaced tissue, usually the pelvis. Endometriosis can cause fertility problems. In fact, scars and adhesions on the ovaries or fallopian tubes can prevent pregnancy. Endometriosis can be mild, moderate or severe and tends to get worse over time without treatment. The most common symptoms are: 1. **Painful periods** Pelvic pain and severe cramping, intense back pain and abdominal pain. 2. **Pain at other times** Women may experience pelvic pain during ovulation, sharp deep pain in pelvis during intercourse, or pain during bowel movements or urination. 3. **Excessive bleeding** Heavy periods or bleeding between periods. 4. **Infertility** Approximately 30-40% of women The cause of endometriosis remains mysterious. Scientists are studying the roles that hormones and the immune system play in this condition. One theory holds that menstrual blood containing endometrial cells flows back through the fallopian tubes, takes root and grows. Another hypothesis proposes that the bloodstream carries endometrial cells to other sites in the body. Still another theory speculates that a predisposition toward endometriosis may be carried in the genes of certain families. Other researchers believe that certain cells present within the abdomen in some women retain their ability to specialize into endometrial cells. These same cells were responsible for the growth of the woman\'s reproductive organs when she was an embryo. It is believed that genetic or environmental influences in later life allow these cells to give rise to endometrial tissue outside the uterus. Experts estimate that up to one in ten American women of childbearing age have endometriosis. There is some thinking that previous damage to cells that line the pelvis can lead to endometriosis. There are several ways to diagnose endometriosis: 1. **Pelvic exam** 2. **Ultrasound** 3. **Laparoscopy** Usually used, most correct diagnosis 4. **Blood test** Endometriosis can be treated with: 1. **Pain medication** 2. **Hormone therapy** 1. **Oral contraceptives** 2. **Gonadotropin-releasing hormone(Gn-Rh)agonists and antagonists** 3. **Danazol(Danocrine)** 4. **Medroxyprogesterone(Depo-Provera)** 3. **Conservative surgery** which removes endometrial growths. 4. **Hysterectomy** ## Check Your Understanding Answers for these questions can be found here 1\. In homology, the \_\_\_\_\_\_\_\_\_\_\_ in the female is equal to the penis in the male : A\) labia majora : B\) clitoral hood : C\) clitoris : D\) labia minora : E\) none of the above 2\. This contains some of the strongest muscles in the human body : A\) uterus : B\) clitoris : C\) cervix : D\) labia majora 3\. This protects the vaginal and urethral openings : A\) labia majora : B\) labia minora : C\) clitoris : D\) urethra 4\. Sally has noticed that her cervical mucus has changed and now resembles egg whites- from this Sally could assume : A\) her period will begin soon : B\) nothing, this is a normal occurrence : C\) she has a yeast infection : D\) she is ovulating 5\. Debbie recently went to the OBGYN and was diagnosed with PCOD (polycystic ovary syndrome) because of this she has : A\) nothing, its normal in women : B\) antisperm antibodies : C\) an overproduction of LH : D\) leaking of milk from her mammary glands : E\) problems becoming pregnant 6\. Angie went to the doctor because she has had pain in her leg recently- this could be caused by : A\) ovulation pain : B\) her period that will be starting tomorrow : C\) premenstrual syndrome : D\) a blood clot resulting from her birth control pill 7\. Sue recently started her period and has noticed that they are very heavy and painful, and that they are inconsistent in their timing. One explanation could be : A\) endometriosis : B\) ovarian cancer : C\) candidiasis : D\) toxic shock syndrome : E\) amenorrhea 8\. Mary is getting married and is not ready to become a mother- she chooses this birth control because of its high effectiveness : A\) natural family planning : B\) a diaphragm : C\) contraceptive injections : D\) a spermicide foam 9\. The release of LH in woman causes : A\) menstration : B\) ovulation : C\) increase of endometrial lining : D\) decrease of endometrial lining : E\) nothing LH only does something in the male reproductive system 10\. When the ovaries stop producing estrogen, this occurs : A\) ovulation : B\) implantation : C\) premenstrual syndrome : D\) menopause 11\. Infertility affects what percentage of couples? : A\) 5% : B\) 10% : C\) 15% : D\) 20% 12\. What is the only 100% effective form of birth control? : A\) Tubal ligation : B\) IUD : C\) Natural family planning : D\) Abstinence ## Glossary **Adhesions**: Abnormal tissue that binds organs together **Alveoli**: Basic components of the mammary glands; lined with milk-secreting epithelial cells **Birth Control**: regimen of one or more actions, devices, or medications followed in order to deliberately prevent or reduce the likelihood of a woman becoming pregnant **Cervical Mucus**: Mucus secreted by the cervix, near ovulation it helps to lower the acidity of the vagina **Cervix**: Lower, narrow portion of the uterus where it joins with the top of the vagina **Clitoris**: Small body of spongy tissue that functions solely for sexual pleasure **Chromosomes**: Structures in the nucleus that contain the genes for genetic expression **Ectocervix**: Portion of the cervix projecting into vagina **Endocervical Canal**: Passageway between the external os and the uterine cavity **Endometrium**: The inner lining of the uterus **Fallopian Tubes**: Located at the upper end of the vagina, passage way for the egg from the ovary **Factor V Leiden**: This is the name given to a variant of human factor V that causes a hypercoagulability disorder. In this disorder the Leiden variant of factor V, cannot be inactivated by activated protein C. Factor V Leiden is the most common hereditary hypercoagulability disorder amongst Eurasians. It is named after the city Leiden (The Netherlands), where it was first identified in 1994 by Prof R. Bertina et al. **Gamete**: A haploid sex cell; either an egg cell or a sperm cell **Gene**: That portion of the DNA of a chromosome containing the information needed to synthesize a particular protein molecule **Gonad**: A reproductive organ, testis or ovary that produces gametes and sex hormones **Hormone**: A chemical substance produced in an endocrine gland and secreted into the bloodstream that acts on target cells to produce a specific effect **Hymen**: Thin fold of mucous membrane that separates the lumen of the vagina from the urethral sinus **Infertility**: Inability to naturally conceive a child or the inability to carry a pregnancy to term **Labia Majora**: Outer \"lips\" of the vulva, made of loose connective tissue and adipose tissue with some smooth muscle **Labia Minora**: Inner lips of the vulva, folds and protects the vagina, urethra and clitoris **Mammary Glands**: Organs that produce milk for the sustenance of a baby **Meiosis**: A specialized type of cell division by which gametes, or haploid sex cells, are formed **Menarche**: The first menstrual discharge; occurs normally between the ages of 9 and 17 **Menopause**: The period marked by the cessation of menstrual periods in the human female **Menstrual Cycle**: The rhythmic female reproductive cycle characterized by physical changes in the uterine lining **Menstruation**: The discharge of blood and tissue from the uterus at the end of menstrual cycle **Mittelschmerz**: Pain near the lower abdomen site at the time of ovulation; German for ovulation pain **Mons Veneris**: soft mound at the front of the vulva (fatty tissue covering the pubic bone) **Ovarian Cycle**: Last phase of the reproductive cycle; if no implantation occurs, causes the breakdown of the endometrial lining and causes menstruation **Ovulation**: The rupture of an ovarian follicle with the release of an ovum **Perineum**: External region between the scrotum and the anus in a male or between the vulva and anus in a female **Premenstrual Syndrome (PMS)**: Time leading up to menstruation; includes both physical and emotional symptoms: acne, bloating, fatigue, backaches, sore breasts, headaches, constipation, diarrhea, food cravings, depression, irritability, difficulty concentrating or handling stress **Puberty**: The period of development in which the reproductive organs become functional and the secondary sex characteristics are expressed **Reproduction**: Process by which an organism continues its species **Sexually transmitted diseases (STDs)**: diseases or infections that have a significant probability of transmission between humans by means of sexual contact **Urethra**: Located below the clitoris, used for the passage of urine **Uterine Cycle**: First part of the reproductive cycle; the time when the endrometrial lining builds up and follicles develop **Uterus**: Major reproductive organ, receives fertilized eggs which become implanted in the lining, the lining (endometrium) provides nourishment to developing fetus; contains some of the strongest muscles in the female body and is able to stretch during fetus development **Vagina**: Muscular, hollow tube that extends from the vaginal opening to the cervix **Vulva**: External female genitals, includes labia majora, labia minora, mons pubis, clitoris, meatus, vaginal vestibule, vestibule bulbs and vestibular glands ## References - Essentials of Anatomy and Physiology. Fourth Edition. Valerie C. Scanlon and Tina Sanders. - Human Anatomy. Sixth Edition. Van De Graaff. - Wikibook: Sexual Health - <http://www.fda.gov/cder/drug/infopage/planBQandAhtm> - <http://www.goplanb.com/Forconsumers> - American Social Health Association;ashastd.org - <http://www.cdc.gov> - <http://www.mayoclinic.com>
# Human Physiology/Pregnancy and birth ## Introduction In this chapter we will discuss the topics covering pregnancy, from conception to birth. The chapter will cover fertilization, implantation of the zygote, to becoming a fetus, the three trimesters, and the progressive development of the fetus through the weeks of pregnancy. It will cover the topic of birth and different birthing methods. ## Fertilization !A sperm fertilizing an ovum{width="300"} Fertilization is the joining of a sperm and an egg. A sperm is a male gamete that is released into the vagina of a female during intercourse. In order for fertilization to occur there must be a mature ovum present. Every month one of the ovaries releases an egg which will meet one of the A 4 million sperm the male ejaculates into the vagina. The sperm swim through the cervix and into the uterus which lead to the fallopian tubes. This is where fertilization is most likely to take place. The high amount of sperm in the ejaculate is needed because only around 100 survive to enter reach the fertilization site. In order to penetrate the egg the sperm must first break through two barriers surrounding the ovum. The acrosome of sperm comes in contact with the corona radiata and releases digestive enzymes that break down a gelatinous layer around the egg called, the zona pellucida. Once a sperm reaches the plasma membrane of the egg it sets off a reaction that spreads across the membrane of the egg preventing other sperm from breaking through the egg membrane. Once the sperm reaches the inside of the egg it sheds its tail and the two nuclei fuse and now the 23 chromosomes from the egg and the 23 chromosomes of the sperm join and they become a *zygote*. Chromosomes contain all the information needed to determine the genetic structure of the new baby. Normally all human beings have two chromosomes that determine sex: A combination of X and Y makes a male or a combination of X and X makes a female. All ovum have X sex chromosomes where as sperm have both X or Y sex chromosomes. Therefore, the male gametes determine the sex of the baby. !An 8-cell embryo in the process of cleavage.{width="300"} ## Pre-embryonic Period After fertilization, the zygote begins a process of dividing by *mitosis* in a process called *cleavage*. It divides until it reaches 16 cells. It is now referred to as a *morula*. As the morula floats freely within the uterus, it starts to bring nutrients into the cells. The morula fills with fluid and the cells inside start to form two separate groups. At this stage it is now a *blastocyst*. The inner layer of cells is called the embryoblast, and will become the fetus. The outer layer is called a trophoblast which will develop into part of the placenta. At this point the zona pellucida is disintegrating. The trophoblast contains specialized cells that become extensions, like fingers, that grow into the endometrium once in contact with the well thickened endometrium. ### Implantation The blastocyst preserves itself by secreting a hormone that indirectly stops menstruation. The trophoblast cells secrete hCG hormones that help maintain the corpus luteum that would normally regress. In turn, the corpus luteum continues to secrete progesterone, which maintains the endometrium of the uterus in the secretory phase. This helps the blastocyst to continue to grow and stay embedded within the endometrium. The fetal life support system and the placenta begin to form, and eventually the placenta will take over the job of producing progesterone. - Gastrulation and Formation The embryoblast within the blastocyst forms 3 primary germs layers: ectoderm, mesoderm, and endoderm. #### Ectoderm This forms the nervous tissue and the epithelium covering the outer body surface. Epidermis of skin, including hair and nails, glands of skin, linings of oral cavity, nasal cavity, anal canal, vagina, brain, spinal cord, sensory organs, lens of eye and epithelium of conjunctiva (a membrane that covers the sclera and lines the inside of the eyelids), pituitary gland, adrenal medulla, and enamel of teeth. #### Mesoderm This forms all of the muscle tissue and the connective tissue of the body, as well as the kidneys and the epithelium of the serous membranes and blood vessels. All muscle tissue (skeletal, smooth, cardiac), all connective tissue (fibrous connective tissue, bone, blood, cartilage), dentin of teeth, adrenal cortex, kidneys and ureters, internal reproductive viscera, epithelium lining vessels, joint cavities, and the serous body cavities. #### Endoderm Forms the lining epithelium and glands of the visceral body systems. Lining epithelium and glands of digestive, respiratory, and parts of urogenital systems, thyroid and parathyroid glands, and thymus. ## Formation of Placenta As changes to the endometrium occur, cellular growth and the accumulation of glycogen cause fetal and maternal tissue to come together. This formation makes the functional unit called the placenta. The placenta does not mix blood between mother and fetus, but allows nutrients and waste products to diffuse between the two blood systems. The placenta provides protection by filtering out many harmful substances that the mother comes in contact with. The placenta cannot protect against some teratogens including but not limited to: - Thalidomide - Heroin - Cocaine - Aspirin - Alcohol - Chemicals in cigarette smoke - Propecia, also known as Finasteride, which can cause birth defects simply by a woman handling a broken pill during pregnancy. ## Amniotic Fluid Attached to placenta is the membranous sac which surrounds and protects the embryo. This sac is called the amnion. It grows and begins to fill, mainly with water, around two weeks after fertilization. This liquid is called Amniotic fluid, it allows the fetus to move freely, without the walls of the uterus being too tight against its body. Buoyancy is also provided here for comfort. After a further 10 weeks the liquid contains proteins, carbohydrates, lipids and phospholipids, urea and electrolytes, all which aid in the growth of the fetus. In the late stages of gestation much of the amniotic fluid consists of fetal urine. The fetus swallows the fluid and then voids it to prepare its digestive organs for use after birth. The fetus also \"breathes\" the fluid to aid in lung growth and development. !A small part of the placenta is shown at the bottom, while the fluid-filled amnion surrounds it Not enough amniontic fluid, or oligohydramnios, can be a concern during pregnancy. Oligohydramnios can be caused by infection, kidney dysfunction or malformation (since much of the late amniotic fluid volume is urine), procedures such as chorionic villus sampling (CVS), and preterm, premature rupture of membranes (PPROM). One possible outcome of oligohydramnios can cause is underdeveloped, or hypoplastic, lungs. This condition is potentially fatal and the baby can die shortly after birth. Babies with too little amniotic fluid can also develop contractures of the limbs, including clubbing of the feet and hands. As with too little fluid, too much fluid or polyhydramnios, can be a cause or an indicator of problems for the mother and baby. Polyhydramnios is a predisposing risk factor for cord prolapse and is sometimes a side effect of a macrosomic pregnancy. In both cases, however, the majority of pregnancies proceed normally and the baby is born healthy. Preterm, premature rupture of membranes (PPROM) is a condition where the amniotic sac leaks fluid before 38 weeks of gestation. This can be caused by a bacterial infection or by a defect in the structure of the amniotic sac, uterus, or cervix. In some cases the leak can spontaneously heal, but in most cases of PPROM, labor begins within 48 hours of membrane rupture. When this occurs, it is necessary that the mother receive treatment immediately to postpone labor if the fetus is not viable, for as long as is safe, and for antibiotic treatments to avoid possible infection in the mother and baby. If rupture occurs too early in pregnancy little can be done to save the fetus. A very rare and most often fatal obstetric complication is an amniotic fluid embolism, or leakage of amniotic fluid into the mothers vascular systems causing an allergic reation. This allergic reaction results in cardiorespiratory (heart and lung) collapse, developing into a condition known as disseminated intravascular coagulation in which the mothers blood looses it\'s ability to clot. Amniotic band syndrome, or ABS, occurs when the inner fetal membrane (amnion) ruptures without injury to the outer membrane (chorion). Fibrous bands from the ruptured amnion float in the amniotic fluid and can entangle the fetus, reducing blood supply and causing congenital limb abnormalities dysmelia. In some cases a complete \"natural\" amputation of a digit(s) or limb may occur before birth or the digit(s) or limbs may be necrotic (dead) requiring surgical removal. ## Endocrine Function of the Placenta There are pituitary like hormones and steroid hormones secreted from the placenta. The pituitary like hormones are hCG and hCS. HCG is similar to LH and helps maintain the mothers corpus luteum. HCS is like prolactin and growth hormone and help aid in increasing fat breakdown that spares the use of glucose from the mothers tissues. This effect leaves more glucose available to the placenta and the fetus for necessary growth. The steroid hormones are progesterone and estrogen. Progesterone helps maintain the endrometrium and supports the growth of mammary glands. Estrogen also helps maintain the endrometrium and growth of mammary glands as well as inhibits prolactin secretion. ## Developing Baby The womb is expanding, the baby is growing and taking all the nourishment from the mother. What once started as a microscopic two-celled egg, will be formed into a baby in just twelve weeks. The baby develops from conception to term, in a month-to-month progress. ### Overview of Developmental Milestones WEEK CHANGES IN MOTHER DEVELOPMENT OF BABY ------------- ------------------------------------------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- **Pre-embryonic Development** 1 week Ovulation Occurs Fertilization occurs, cell division begins and continues, chorion appears **Embryonic Development** 2 weeks Symptoms of early pregnancy (nausea, breast swelling and tenderness, fatigue); blood pregnancy tests may show positive Implantation occurs; amnion and yolk sac appear; embryo has tissue; placenta begins to form 3 weeks First period missed; urine pregnancy test may show positive; early pregnancy symptoms continue Nervous system begins to develop; allantois and blood vessels are present and placenta is well formed 4 weeks Limb buds form; heart is beating; nervous system further develops; embryo has tail; other systems are forming 5 weeks Uterus is the size of a hen\'s egg; mother may need to urinate frequently Embryo is curved, head is large, limb buds are showing division, nose, ears and eyes are noticeable 6 weeks Uterus is the size of an orange Fingers and toes are present and skeleton is cartilaginous 8 weeks Uterus can be felt above the pubic bone Fetus begins to look human; limbs are developing and major organs forming; facial features are becoming refined **Fetal Development** 12 weeks Uterus is the size of a grapefruit Head grows faster than the rest of the body; facial features are apparent, but there is no layer of fat yet and the skin is translucent; gender can be distinguished via ultrasound; fingernails appear 16 weeks Fetal movement can be felt Fine hair (lanugo) grows over the body; fetus resembles a tiny human being; skeleton is visible 20-22 weeks Uterus reaches up to the level of umbilicus and pregnancy is obvious Vernix caseosa, the protective fatty coating, begins to be deposited; heartbeat can be heard 24 weeks Doctor can tell where baby\'s head, back and limbs are; breasts have enlarged and nipples and areola are darker, colostrum is produced Fully formed but still thin; much larger and very active, all major organs are working, the lungs and digestive system need more time to develop; body is covered in fine hair called lanugo 32 weeks Uterus reaches halfway between umbilicus and rib cage Most babies are in a head down position in the womb; head is more in proportion to the body; eyes are open; babies born at this stage have a good chance of living 36 weeks Weight gain is averaging about a pound a week; standing and walking are becoming very difficult because the center of gravity is thrown forward Body hair begins to disappear, fat is being deposited 40 weeks Uterus is up to the rib cage, causing shortness of breath and heartburn; sleeping is very difficult Not much room to move in the womb; fully mature, baby moves less, and the surrounding fluid reduces and the womb expands its limits ## Embryonic Development at Specific Stages ### First trimester !An embryo this tiny shows very distinct anatomic features, including tail, limb buds, heart (which actually protrudes from the chest), eye cups, cornea/lens, brain, and prominent segmentation into somites. The gestational sac is surrounded by a myriad of chorionic villi resembling elongate party balloons. This embryo is about five weeks old (or seven weeks in the biologically misleading but eminently practical dating system used in obstetrics)., eye cups, cornea/lens, brain, and prominent segmentation into somites. The gestational sac is surrounded by a myriad of chorionic villi resembling elongate party balloons. This embryo is about five weeks old (or seven weeks in the biologically misleading but eminently practical dating system used in obstetrics)."){width="300"} ***4 Weeks*** - There are only the beginnings of facial features. All the major organs are starting to form. Gill-like folds that develop into facial features, beginnings of the spinal cord, skin is translucent, and rudimentary (basic; minimal) heart develops. ***6 Weeks*** - The length from crown to rump is about the size of a finger tip, ¾ \". The beginnings of all the major organs will have formed. - The embryo floats in a fluid filled bubble that will develop into the amniotic sac. The sac is covered by a protective layer of cells, called chorion. The yolk sac supplies the embryo with all its nutrients until the placenta is fully developed and takes over at around the twelfth week. During the first 12 weeks, the embryo will develop features and major organs of a human being. The embryo is susceptible to harmful environmental influences. This is a vital time for the embryo to develop healthily; taking supplements of folic acid, avoiding certain foods, and eliminating alcohol, cigarettes, and any unnecessary drugs or medicines. ***9 Weeks*** - The length from crown to rump approximately 1 1/4\". The facial features are becoming more distinct, and the "tail" has disappeared. The muscles are also developing. Eyes are formed but eyelids are still closed over them. Arms now bend at the elbow and rudimentary hands and fingers develop. Knees will have formed and developing feet with distinct toes. - Heart- is now a four-chambered and fully formed organ; it beats about 180 times per minute. - Brain and nervous system- is four times the size it was at 6 weeks. Special glial cells are being formed within the neural tube; they allow nerve cells to be joined so that messages can be transmitted from the brain to the body. - Digestive system- the mouth, intestine, and stomach are developing very rapidly, but do not function yet. - The fetal life-support system- the placental tissue that initially surrounds the fetus and the amniotic sac is becoming concentrated in one circular area on the womb wall to form the placenta. !Sonogram of a fetus at 14 weeks (Profile)") ***12 Weeks*** - At twelve weeks the fetus looks like a tiny human. It is about 2 1/2\" long and weighs 1/2 oz. Arms and legs are now beginning to move. Skin is red and translucent. Fingers and toes are more defined, and nails are starting to grow. - Heart is complete and working, pumping blood to all parts of the body. Digestive system has formed and is linked to the mouth and intestines. Sexual organs have formed inside the body, but cannot yet establish the sex of the baby. ### Second Trimester ***20 Weeks*** - By 20 weeks the fetus will be about 6 1/3\" long and weighs 12 oz. Movements are for more coordinated. The sexual organs are well developed and are usually visible on ultra sound. - The fetus is growing very quickly. At this stage, the mother should feel the movements of the fetus. Movements are more noticeable as the fetus\'s leg bones achieve their final relative proportions in a process called *quickening*. Quickening is the process of muscles contracting that cause movement at the fetus\'s synovial joints. The joint movement enhances the nutrition of the articular cartilage and prevents the fusion of connective tissues within the joint. It also promotes bone hardening. - From now on, the fully developed placenta will provide all the fetus\' needs until birth; oxygen, nutrients and protective antibodies. !Fetus at 29 weeks gestation in 3D ### Third Trimester ***29 Weeks*** - By 29 weeks the baby is about 10\" long and weighs about 2 lbs. 7 oz. - The brain grows much larger, and fatty protective sheath covers the nerve fibers; this important development allows brain impulses to travel faster, enhancing the ability to learn. The lungs have developed most of their airways and air sacs. The placenta is quite selective in what it allows to pass from the mother to the baby\'s blood, stopping some harmful substances, such as certain drugs, from crossing over. ***40 Weeks*** - The baby is now ready to be born. When the head of the baby moves down from high in the mother\'s abdomen and settles deeper into her pelvis in preparation for birth, it is called engagement. This can happen any time between 36 weeks and labor. - In the last four weeks of pregnancy the baby puts on a lot of weight and develops a thick layer of fat. All organs are completely formed and functioning. ### Umbilical Cord This is the life support for a growing embryo. The umbilical cord stretches between the placenta and the fetus. This cord contains the umbilical arteries and vein. The umbilical cord forms by week 5 of conception. The average cord is close to 22 inches long and may have the appearance of a coil. The umbilical cord is very rich in stem cells and is often used for parents who choose to store their stem cells in a blood bank or donate it to a blood bank. These stem cells can be used to treat over 45 disorders and is an alternative from extracting the stem cells from a donor. !Human placenta shown a few minutes after birth. The side shown faces the baby with the umbilical cord top right. The unseen side connects to the uterine wall. The white fringe surrounding the bottom is the remnants of the amniotic sac. You can see the differences in the umbilical vein and arteries.{width="350"} - *Umbilical Arteries* The exchange of gases, nutrients and oxygen takes place between the maternal blood and fetal blood. There are 2 main arteries. - *Umbilical Vein* Vein that carries nutrients and oxygen away from the placenta to the growing fetus. It also carries oxygen and nutrient rich blood. There is only 1 main vein. - Fetus doesn\'t use its lungs for gas exchange, only a small amount of blood is pumped to fetal lungs in order to support their development. #### Umbilical Abnormalities - *Single Umbilical Artery* One artery instead of two will result in chromosomal abnormalities. Some of these defects include poor fetal growth, preterm delivery, and still births. This can be detected by a routine ultrasound. If an ultrasound is done and no other complications or abnormalities are detected, the baby will usually be born healthy. - *Umbilical Prolapse* This condition usually happens when a cord is too long. The baby may be born prematurely or will be breech. - *Umbilical Nuchal Loops* This condition happens when the umbilical cord is wrapped around the baby\'s head at least one or more times. This can be detected when a baby is in stress or by a simple ultrasound. In most cases the mother will have a cesarean delivery. In other cases the cord may be wrapped around the hands or feet. - *Vasa Previa* This occurs in one in every 3,000 births, which can become life-threatening for the unborn baby. This complication happens when the umbilical cord inserts abnormally in the fetal membranes of the placenta, which appears abnormally shaped or positioned. Major risks include unprotected fetal blood vessels cross the cervix, oftentimes rupturing the membranes. Also, lack of blood pressure due from pressure, causes the loss of oxygen to the baby. Women who will be at risk for this would be those who already have experienced placenta previa or have used in vitro fertilization. - *Umbilical Cord Knots* About 1% of babies are born with one or more knots in their umbilical cord. Some knots happen during labor; others happen from moving around in the womb. Most knots occur when the umbilical cord is too long. In some cases the knots can become tight, cutting off the oxygen supply to the baby. Cord knots result in miscarriages and stillbirth in 5% and 10% of most cases. Most will require a cesarean delivery. - *Umbilical Clotting* This is more common with genetic defects, such as Factor V Leiden. This complication will prevent blood flow to and from the baby and many times will cause the placenta to also clot and die. If this is not caught early enough, the baby will die of starvation in the womb. A simple ultrasound can determine if there are problems with the blood flow. ## Pregnancy from the mother\'s perspective !Growth of the uterus in a pregnant female. An initial sign of pregnancy is amenorrhea, or the absence of menstruation. Menses cease because the blastocyte begins the release of hCG or human chorionic gonadotropin. Most pregnancy tests are specifically designed to recognize the presence of hCG, and hCG levels can be tested through the mothers blood to learn whether or not a pregnancy is progressing normally. Human pregnancy lasts approximately 40 weeks from the time of the last menstrual cycle to childbirth (38 weeks from fertilization). The medical term for a pregnant woman is genetalian, just as the medical term for the potential baby is embryo (early weeks) and then fetus (until birth). A woman who is pregnant for the first time is known as a primigravida or gravida 1: a woman who has never been pregnant is known as a gravida 0; similarly, the terms para 0, para 1 and so on are used for the number of times a woman has given birth. In many societies\' medical and legal definitions, human pregnancy is somewhat arbitrarily divided into three trimester periods, as a means to simplify reference to the different stages of fetal development. The first trimester period carries the highest risk of miscarriage (spontaneous death of embryo or fetus). During the second trimester the development of the fetus can start to be monitored and diagnosed. The third trimester marks the beginning of viability, which means the fetus might survive if an early birth occurs. ### Changing Body !(38 weeks) A fully developed fetus in the mothers abdomen\|250px A fully developed fetus in the mothers abdomen|250px") As soon as a woman becomes pregnant, her body begins to change so that it can support both herself and the unborn baby. All of the body functions start to work much harder. The heart has to pump more blood around the body, in particular to the womb, placenta, and the fetus. As well as physical demands, pregnancy also causes a range of emotional reactions. - The first trimester, the first twelve weeks, little is visible. - The second trimester, 13-27 Weeks, the waistline is rapidly growing, the abdomen becomes noticeably pregnant. - The third trimester, 28-40 weeks, the body expands rapidly and the womb enlarges and presses against the diaphragm. #### First Trimester In the early weeks the mother is likely to be more tired. As the uterus begins to grow, the \"bump\" becomes noticeable. This is a good time to start looking into options on birthing and doctors. - Physical feelings: tiredness, nausea, constipation, frequent urination, food cravings, change in size of breasts, fainting or dizziness, bloated stomach, and high emotions. #### Second Trimester The mother will probably be feeling full of energy and excitement. :\*Physical feelings: More energy, constipation, heartburn, and indigestion. The breasts continue to grow, as does an increase in appetite. There is mild swelling in the feet, ankles, hands, and face. There is also more baby movement. There may be emotional ups and downs in the feeling of pregnancy, and short-term memory may be poor. :\*The hormones estrogen, progesterone, human placental lactogen, oxytocin, and prolactin prepare the body for feeding the baby, and cause the breasts to enlarge, becoming painful and tender. :\*The fetus, placenta, and amniotic fluid account for just over a third of the weight gain during pregnancy. The remaining weight comes from increased blood volume, fluid retention, and extra body fat. The suggested weight gain in most pregnancies is between 25-40 lbs. #### Third Trimester Physical feelings: Shortness of breath, tiredness, difficulty in moving and sleeping, and frequent urination. The emotional mood swings ease off, but the mother begins to feel less enthusiastic about being pregnant. She may become impatient and restless and just wants for the birth to be over. :\*The body is changing to cope with the ever increasing size of the womb. The baby grows and pushes out the lower back of the mother. The breathing rate of the baby is growing very quickly. At this stage, the mother should feel the movements of the fetus. Other signs may be the nipples secreting colostrum, Braxton-Hicks\' contractions may begin, and blood flow to the womb has increased tenfold since conception. ### Prenatal Care Once the female confirms her pregnancy, she will need to find out her physical condition and what to expect in the coming months. Women typically begin pre-natal care at approximately 8-10 weeks gestation, and pregnancy care should continue until approximately 6 weeks postpartum. The main purpose of the prenatal visits is to perform preventative medicine. Most complications in pregnancy are best treated if they are caught early on. A series of tests will be performed throughout the pregnancy to judge the mother and fetus\' well-being including: - Mother\'s history - Urine tests for glucose, protein, and infection - The mother\'s weight - Blood tests such as a complete blood count, HIV test, or the triple screen which is test used most commonly to look for neural tube defects and Downs Syndrome. - Physical examination - Blood pressure - Fetal heart monitoring - Ultrasound scans - Non-stress tests Continuous care is the best way to ensure a healthy mother and baby. ## Labor and Birth Labor is defined as contractions *and* cervical change, contractions alone are not labor. - Pre-Labor Signs: as your body is preparing for labor, there are a few things that should be expected to happen within four to six weeks of labor. 1. Pressure on the pelvic area 2. Occasional brownish discharge 3. Energy level is noticeably increasing or decreasing 4. Loss of the mucus plug (does not always exist)/increasing discharge 5. Braxton Hicks contractions (painless contraction of the uterus) 6. Movement of the baby into the pelvis - False Labor Signs: there are a few signs that indicate false labor. 1. Timing of the contractions are irregular and do not become more frequent or more intense 2. Contractions stop during rest, stopping what the mother is doing, walking, or changing position 3. Inconsistent in strength (strong one minute then weak the next) 4. Location of pain is in the front only - True Labor 1. Pain in the lower back, radiating towards the front abdomen, possibly also the legs 2. Contractions increase in strength and are closer together; coming now on a regular basis, 30 to 70 seconds apart 3. The mucous plug is detached, showing bloody discharge 4. The water breaks (usually this does not break until the doctor does it), when this happens, contractions become much stronger 5. Some women have the sudden need to go to the bathroom, diarrhea is common 6. Contractions continue despite movement 7. The cervix is thinning and dilating When the contractions of labor begin, the walls of the uterus start to contract. They are stimulated by the release of the pituitary hormone *oxytocin*. The contractions cause the cervix to widen and begin to open. As labor progresses the amniotic sac can rupture causing a slow or a fast gush of fluids. Labor usually begins within a 24 hour period after the amniotic sac has ruptured. As contractions become closer and stronger the cervix will gradually start to dilate. The first stage of labor is broken into three parts: - **Early Phase** First is the early phase of labor, when the cervix dilates from 1-4 centimeters, this can be the longest and most exhausting part for the mother. ```{=html} <!-- --> ``` - **Active Phase** The cervix dilates on average 1 cm per hour in the active phase of labor dilating from 4-7 centimeters. If an epidural is requested it is usually given in this phase. ```{=html} <!-- --> ``` - **Transition** This is often considered the most intense part of labor with contractions lasting longer and having shorter rest periods in between them. Dilation from 8-10 centimeters occurs during transition. Some women experience nausea and vomiting during this phase as well as rectal pressure and an urge to push. At this point the labor enters the second stage, or the birth of the baby. The mother begins pushing to aid in the birth of the baby, this part of labor can last minutes, or even hours. A fetus usually delivered head first. \'Crowning\' is the term used when the fetus\' head can be seen between the mothers labia as it emerges. At this point if necessary the birth attendant may perform an episiotomy, which is a small surgical incision on the perineum. This procedure is usually done to deliver the baby more quickly in response to fetal distress. !Diagram showing an episiotomie The third stage of labor is the delivery of the afterbirth (placenta). Oxytocin continues to be released to shrink the size of the uterus and aid in the limiting of blood loss from the site of the placenta. As the uterus shrinks the attachment site blood vessels, some of which can be as large as an adult finger, shrink also. The average blood loss in a routine vaginal delivery is 400-500 cc. There are times when a mother may need outside aid in the delivery of the baby, some of these methods include: - Forceps, an instrument used to cradle the fetus\' head and manipulate the head under the pubic bone to more easily pass through the birth canal. ```{=html} <!-- --> ``` - Vacuum Extraction, a suction cup is applied to the baby\'s head, and a plunger is used to suck any air from between the suction cup and the head to create a good seal. The babies head is then manipulated through the birth canal. This usually leaves a baby\'s head bruised, but the mark fades within weeks after birth. !C-section Birth - Cesarean section, or C-section, is the delivery of a baby through a surgical abdominal incision (Abdominal delivery - Abdominal birth - Cesarean section). A C-section delivery is performed when a vaginal birth is not possible or is not safe for the mother or child. Surgery is usually done while the woman is awake but anesthetized from the chest to the legs by epidural or spinal anesthesia. An incision is made across the abdomen just above the pubic area. The uterus is opened, and often brought through the incision after delivery for better visualization. The amniotic fluid is drained, and the baby is delivered. The baby\'s mouth and nose are cleared of fluids, and the umbilical cord is clamped and cut. After delivery a nursery nurse or pediatrician check the make sure that the baby is breathing and responding. Due to a variety of medical and social factors, C-sections have become fairly common; around 25% of births are performed by C-section. C-sections carry some risks to mother and baby. Compared to a vaginal birth, the risks to mother include increased risk of death, surgical injury, infection, postpartum depression, and hemorrhage, although these are rare. Babies born by c-section are more likely to be admitted to the ICU for breathing problems. Mothers are advised to carefully weigh the risks of C-section versus vaginal birth. !Newborn baby ### Delivery Options Hospital Births: The chances of having natural, uncomplicated birth are optimized by carefully selecting your obstetrician and hospital. Doctors who work with midwives have lower cesarean section rates because midwives handle less complicated pregnancies. Delivering babies by abdominal surgery has been steadily rising in America over the past two decades, so that now 22-30% of births in American hospitals are cesarean section. The U.S., despite having the most advanced technology and highly trained medical personnel, ranks 23rd in infant mortality and 18th in perinatal mortality. ```{=html} <!-- --> ``` : Medical interventions such as epidural anesthesia, pitocin augmentation of labor, vacuum extraction of fetus, episiotomy and separation of newborn and mother are common in American hospitals. There are circumstances where medical procedures such as these are necessary, but many parents and professionals now question the routine use of such interventions. In some cases, the routine use of these procedures have lead to further complications. For example, the epidural anesthetic, while providing pain relief, has shown to increase the operative vaginal delivery rate (i.e. forceps and vacuum extraction rates slightly) especially in first time mothers. Epidurals have not been shown to increase the cesarean section rate in recent well documented studies. ```{=html} <!-- --> ``` Freestanding Birth Centers & Water Birth:\"Freestanding\" Birth Centers are not inside of or affiliated with a hospital. They are run by collaboration of midwives or physicians. This is an alternative choice for the woman who does not wish to birth in a hospital environment yet is not comfortable giving birth at home. Birth centers do not provide any additional measure of safety than most planned home births with qualified midwives; they may provide the expectant couple with the physiological comfort necessary to enable the mother to relax. ```{=html} <!-- --> ``` : Out of hospital birth centers are designed for women having low-risk pregnancies who want drug-free birth with minimal intervention in a home-like environment. Family members may participate in the birth. C-sections rates are lower than most hospitals because the pregnancies are low risk. Freestanding Birth Centers are an alternative choice for a woman who has had a previous cesarean and wishes to maximize her chances of a vaginal delivery. However, vaginal birth attempts after a prior cesarean section have a 1-2% risk of uterine rupture. Health insurance may cover costs. Many birth centers offer birthing tubs where one can give birth in water. ```{=html} <!-- --> ``` Homebirth:Birth at home provides parents with intimacy, privacy, comfort and family-centered experience. Childbirth at home may be a safe option for healthy women having normal pregnancies. It is for those who have a very strong desire for natural childbirth and who are willing to take high degree of responsibility for their health care and baby\'s birth. At home, the parents and midwife are in control of the birthing environment, and strict time perimeters for length of labor are not imposed, or routine medical interventions such as IVs done. However, the World Health Organization (WHO) states that \"giving birth in a health facility (not necessarily a hospital) with professional staff is safer by far than doing so at home.\" (The World Health Report 2005). Also, the American College of Obstetricians and Gynecologists (ACOG) opposes out of hospital births. In choosing the comfort of home parents are also choosing to be further away from lifesaving measures should complications arise. ```{=html} <!-- --> ``` : Homebirth midwives provide complete prenatal care including monthly visits, laboratory tests, screening for infections. They provide nutritional counseling and support for psycho-social issues. There is a chance that a rare, but critical emergency might occur during the birth where hospital services may not be able to be obtained quick enough. Again, the WHO states that \"it is just before, during, and in the very first hours and days after birth that life is most at risk,\" (The World Health Report 2005) and that \"many of the complications that result in maternal deaths and many that contribute to perinatal deaths are unpredictable, and their onset can be both sudden and severe.\" (WHO Birth and Emergency Preparedness in Antenatal Care, 2006) Home birth midwives are trained to know when an emergency requires medical interface and can provide stabilizing measures until critical care can be obtained. While homebirth midwives generally have the training, equipment, and medicine to handle many complications, there is great variation in training and skill level among midwives. In choosing a homebirth midwife one should careful examine credentials and training. !A newborn with umbilical cord still attached (3 minutes.)"){width="200"} ### Postpartum care After the baby is born the umbilical cord is clamped and cut and the baby is looked over by a doctor or nurse. The baby is given an APGAR score at one and five minutes after birth. This is an analysis of how well the baby is performing its vital functions. +-------------+-------------+-------------+-------------+-------------+ |   | Score of 0 | Score of 1 | Score of 2 | Acronym | +=============+=============+=============+=============+=============+ | Skin color | blue all | blue at | normal | **A | | | over | extremities | | **ppearance | +-------------+-------------+-------------+-------------+-------------+ | Heart rate | absent | \<100 | \>100 | **P**ulse | +-------------+-------------+-------------+-------------+-------------+ | Reflex i | no | gri | sneeze/ | **G**rimace | | rritability | response\ | mace/feeble | cough/pulls | | | | to | cry\ | away\ | | | | stimulation | when | when | | | | | stimulated | stimulated | | +-------------+-------------+-------------+-------------+-------------+ | Muscle tone | none | some | active | * | | | | flexion | movement | *A**ctivity | +-------------+-------------+-------------+-------------+-------------+ | Respiration | absent | weak or | strong | **R* | | | | irregular | | *espiration | +-------------+-------------+-------------+-------------+-------------+ : The five criteria of the Apgar score: If tearing, or an episiotomy occurs the wound is closed with absorbable suture. The mother is closely watched for blood loss, infection, or any other possible complications. Breastfeeding should be initiated as soon as possible after delivery as the stimulation of oxytocin in the mother aids in hemostasis. ## Risks in Pregnancy Pregnancies that warrant close attention usually come from an existing medical condition such as asthma, diabetes, epilepsy, or a condition developed because of pregnancy. Conditions that arise during pregnancy will require special treatment. The purpose of prenatal care is to detect these conditions, and to monitor and deal with them before they become serious. - **Preeclampsia** is the medical term for high blood pressure during pregnancy. It is also characterized by edema, blurry vision, liver pain, and can progress into Eclampsia in which the mother can experience seizures, coma or even death. ```{=html} <!-- --> ``` - **Gestational Diabetes** is diabetes mellitus that develops during pregnancy. All women should be tested for the condition at about 28 weeks gestation. Gestational and pre-existing diabetes can cause large for gestational age babies, a sudden drop in a neonates blood sugar after birth, and has a high risk for stillbirth Other serious risks include: - **Teratogens** (substances that cause birth defects including alcohol and certain prescription and recreational drugs) ```{=html} <!-- --> ``` - **Infection** (such as rubella or cytomegalovirus) An infection in the eleventh week is less likely to damage the heart, but the baby may be born deaf. ```{=html} <!-- --> ``` - **Genetics** (such as Factor V Leiden) Diabetes, blood conditions, etc. ```{=html} <!-- --> ``` - **Radiation** (ionizing radiation such as X-rays, radiation therapy, or accidental exposure to radiation) ```{=html} <!-- --> ``` - **Nutritional deficiencies** ```{=html} <!-- --> ``` - **Fetal Alcohol Syndrome** or **FAS** exposure is the leading known cause of mental retardation in the Western world. It is a disorder of permanent birth defects that occurs in the offspring of women who drink alcohol during pregnancy, depending on the amount, frequency, and timing of alcohol consumption. Alcohol crosses the placental barrier and can stunt fetal growth or weight, create distinctive facial stigmata, damage neurons and brain structures, and cause other physical, mental, or behavioral problems. Drinking during pregnancy should be avoided. Women who drink more than 4 or 5 drinks per day may cause permanent damage to their fetus, including, behavioral problems, sight and hearing loss, deformed organs and central nervous system dysfunction. ```{=html} <!-- --> ``` - **Smoking** can cause low birth weight, still birth, birth defects, preterm births and immature lung development. It can also contribute to addiction in the child\'s later teen years. ```{=html} <!-- --> ``` - **Illegal Drugs** can be the most devastating. Risks include SIDS (Sudden Infants Death Syndrome), learning disorders, birth defects, uncontrollable trembling, hyperactive, and drug dependency. Most drugs can be tested by a simple urine or blood test. ```{=html} <!-- --> ``` - **Medications**. All medication use should be discussed with your doctor. Many over the counter and prescription drugs have warning labels. Follow these precautions to help avoid birth defects or other related problems. ### Miscarriage Miscarriage or spontaneous abortion is the natural or spontaneous end of a pregnancy at a stage where the embryo or the fetus is incapable of surviving, generally defined in humans at a gestation of prior to 20 weeks. Miscarriages are the most common complication of pregnancy. Basic Facts: 15-20% of pregnancies end in miscarriage, 70% of the time there is a chromosomal abnormality with the fetus, and one miscarriage does not increase your risk in the next pregnancy. Miscarriage is almost never the mother\'s fault. If the products of conception are not completely expelled after fetal death this is known as a missed abortion and is usually treated surgically by a procedure known as a D&C or dilation and curettage. ### Bleeding During Pregnancy Vaginal bleeding at any stage should be taken seriously. Severe bleeding in the early weeks may be a sign of miscarriage. However, 25% of pregnant patient bleed in the first trimester. After 24 weeks the mother should seek medical advice immediately. Third trimester bleeding in pregnancy is often one of the first signs of placenta previa; placenta is across the opening of the cervix. An ultrasound should be performed to establish the location. Other causes of late term bleeding include: - **Preterm Labor** or labor that occurs before 38 weeks gestation that can have multiple causes ```{=html} <!-- --> ``` - **Placental Abruption** is a condition in which the placenta is torn away from the uterine wall causing loss of oxygen and nutrients to the baby, and hemorrhage of mother and baby from the large blood vessels in the placenta. Most women, but not all experience heavy bleeding and abdominal pain. This is a life threatening emergency as a fetus can only survive as long as 50% of the placenta is still attached. ### Blood Conditions Individuals either have, or do not have, the Rhesus factor (or Rh D antigen) on the surface of their red blood cells. This is usually indicated by \'RhD positive\' (does have the RhD antigen) or \'RhD negative\' (does not have the antigen) suffix to the ABO blood type i.e. A+ B- blood typing. This is a problem only when an Rh-negative woman has a partner who is Rh-positive resulting in an Rh-positive baby. If the mother\'s and the baby\'s blood come into contact during the birth, her body produces antibodies against the baby\'s blood. This problem usually does not affect the current pregnancy but can be dangerous for future pregnancies as the antibodies stay in the blood causing an immune response against future Rh+ fetus. In essence the mother\'s body \"rejects\" the fetus as it would a foreign body. A drug called Rhogam is now given by injection given at 28-30 weeks gestation and given again if there is confirmation that the baby is Rh positive within 24 hours after birth to protect the future pregnancies. Rh isoimmunization is rare in our day. Rh- mothers should also be given the injection after miscarriage or abortion. If a mother is untreated they are at risk to subsequently deliver babies who suffer from hemolytic disease of the newborn. Hemolytic disease of the newborn, also known as HDN, is an alloimmune condition that develops in a fetus, when the IgG antibodies that have been produced by the mother and have passed through the placenta include ones which attack the red blood cells in the fetal circulation. The red cells are broken down and the fetus can develop reticulocytosis and anemia. This fetal disease ranges from mild to very severe, and fetal death from heart failure (hydrops fetalis) can occur. When the disease is moderate or severe, many erythroblasts are present in the fetal blood and so these forms of the disease can be called erythroblastosis fetalis (or erythroblastosis foetalis). Hemolysis leads to elevated bilirubin levels. After delivery bilirubin is no longer cleared (via the placenta) from the neonate\'s blood and the symptoms of jaundice (yellowish skin and yellow discoloration of the whites of the eyes) increase within 24 hours after birth. Like any other severe neonatal jaundice, there is the possibility of acute or chronic kernicterus. Profound anemia can cause high-output heart failure, with pallor, enlarged liver and/or spleen, generalized swelling, and respiratory distress. The prenatal manifestations are known as hydrops fetalis; in severe forms this can include petechiae and purpura. The infant may be stillborn or die shortly after birth. ### Other Abnormalities Physical and Genetic Defects: Physical anomalies are present at birth. Examples are; cardiac, facial (such as cleft palate), club foot, etc. These do not always endanger the baby\'s life. 1-2% of babies are born with a significant congenital abnormality. 4-6% with something relatively minor. - Chromosomal Abnormalities: Occur when there is a problem in the baby\'s genetic makeup; these include conditions such as Down syndrome. Other genetic defects, such as cystic fibrosis, can be inherited from the parents. ## Staying Healthy Pregnancy and childbirth place great demands, it is important to keep healthy. The more healthy and relaxed the mother is, the better it will be to cope with the demands of pregnancy. A healthy lifestyle combines many factors: Balanced Diet: A poor diet can cause a low birth weight. Excessive weight gain during pregnancy can cause back problems, varicose veins, or indicate preeclampsia. Advice on diet often includes to eat foods that are high in nutritional content. Sufficient protein, vitamins, carbohydrates, fats, and minerals, as well as fiber. Limit intake of saturated fats and sugar, and salt. Drink plenty of fluids.\ Regular Exercise: Mild exercise, such as walking or swimming, is beneficial and will help cope with the workload of pregnancy and the demands of labor. Mother\'s should listen to her body and stop exercising when it tells her to. Exercise should never be painful.\ Baby\'s Health: Smoking reduces the oxygen and nutrients passing via the placenta to the baby. Avoid alcohol to avoid serious birth defects. ## In vitro Fertilization and Artificial Implantation !Oocyte is injected with sperm outside of the womb.{width="300"} **An alternative when other methods of achieving contraception have failed.** In vitro fertilization (IVF) is a technique in which egg cells are fertilized by sperm outside the woman\'s womb. IVF is a major treatment in infertility when other methods of achieving conception have failed. The process involves hormonally controlling the ovulatory process, removing ova (eggs) from the woman\'s ovaries and letting sperm fertilize them in a fluid medium. The fertilized egg (zygote) is then transferred to the patient\'s uterus with the intent to establish a successful pregnancy. The term in vitro, from the Latin root, is used, because early biological experiments involving cultivation of tissues outside the living organism from which they came, were carried out in glass containers such as beakers, test tubes, or petri dishes. While the overall live birth rate via IVF in the U.S. is about 27% per cycle (33% pregnancy rate), the chances of a successful pregnancy via IVF vary widely based on the age of the woman (or, more precisely, on the age of the eggs involved). Where the woman\'s own eggs are used as opposed to those of a donor, for women under 35, the pregnancy rate is commonly approximately 43% per cycle (37% live birth), while for women over 40, the rate falls drastically - to only 4% for women over 42. Other factors that determine success rates include the quality of the eggs and sperm, the duration of the infertility, the health of the uterus, and the medical expertise. It is a common practice for IVF programmes to boost the pregnancy rate by placing multiple embryos during embryo transfer. A flip side of this practice is a higher risk of multiple pregnancy, itself associated with obstetric complications. **Embryo cryopreservation** If multiple embryos are generated, patients may choose to freeze embryos that are not transferred. Those embryos are placed in liquid nitrogen and can be preserved for a long time. There are currently 500,000 frozen embryos in the United States. The advantage is that patients who fail to conceive may become pregnant using such embryos without having to go through a full IVF cycle. Or, if pregnancy occurred, they could return later for another pregnancy. ## Embryonic stem cells !Pluripotent, embryonic stem cells originate as inner mass cells with in a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula\'s cells are totipotent, able to become all tissues and a placenta.{width="500"} Embryonic Celtic cell lines (ES cell lines) are cultures of cells derived from the epiblast tissue of the inner cell mass (ICM) of a blastocyst. A blastocyst is an early stage embryo - approximately 4 to 5 days old in humans and consisting of 50-150 cells. ES cells are *pluripotent*, and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta. This means they can become any kind of human tissue (ie. heart tissue, nerve tissue, etc.). When given no stimuli for differentiation, ES cells will continue to divide in vitro and each daughter cell will remain pluripotent. The pluripotency of ES cells has been rigorously demonstrated in vitro and in vivo, thus they can be indeed classified as stem cells. Because of their unique combined abilities of unlimited expansion and pluripotency, embryonic stem cells are a potential source for regenerative medicine and tissue replacement after injury or disease. To date, no approved medical treatments have been derived from embryonic stem cell research. This is not surprising considering that many nations currently have moratoria (suspension of practices) on either ES cell research or the production of new ES cell lines. There exists a widespread controversy over stem cell research that emanates from the techniques used in the creation and usage of stem cells. Embryonic stem cell research is particularly controversial because, with the present state of technology, starting a stem cell line requires the destruction of a human embryo and/or therapeutic cloning. Opponents of the research argue that this practice is a slippery slope to reproductive cloning and tantamount to the instrumentalization of a human being. Contrarily, some medical researchers in the field argue that it is necessary to pursue embryonic stem cell research because the resultant technologies are expected to have significant medical potential, and that the embryos used for research are only those meant for destruction anyway (as a product of in vitro fertilization). This in turn, conflicts with opponents in the pro-life movement, who argue that an embryo is a human being and therefore entitled to dignity even if legally slated for destruction. The ensuing debate has prompted authorities around the world to seek regulatory frameworks and highlighted the fact that stem cell research represents a social and ethical challenge. - **Reproductive Cloning** Reproductive Cloning is a technology used to generate an animal that contains the same nuclear DNA as another currently or previously existing animal. Scientists transfer the genetic material from the nucleus of a donor adult cell to an egg whose nucleus, and thus its genetic material has been removed. The egg containing the DNA, now reconstructed, has to be treated with chemicals or electric current in order to stimulate cell division. Once the cloned embryo reaches a suitable stage, it is transferred to the uterus of a female host to continue development until birth. Currently this is illegal to practice in the United States. - **Therapeutic Cloning** Recent research by researchers led by Anthony Atala of Wake Forest University and a team from Harvard University has found that amniotic fluid, in addition to its main functions of cushioning a growing fetus and providing buoyancy, is also a plentiful source of non-embryonic stem cells. These cells have demonstrated the ability to differentiate into a number of different cell-types, including brain, liver and bone. Therapeutic Cloning refers to a procedure that allows the cloning of specific body parts and organs to be used for medical purposes. Although this has not been realized, much research is being done on the subject. ## Pregnancy and Lactation A mother\'s milk is ideal because it meets the baby\'s specific needs. Lactation is a neuroendocrine response in *milk production*. Sucking stimulates the sensory nerve endings in the nipples and sends stimulus to the hypothalamus. The hypothalamus stimulates anterior pituitary and prolactin is released. In *milk let-down* the sucking stimulates sensory nerves in the nipples. This stimulates the hypothalamus which then stimulates the posterior pituitary and releases oxytocin. Sucking also stimulates contraction of the cells around the alveoli in the mammary cells. Milk then flows into the milk ducts causing milk let-down. Breast milk provides all the nutrients required for the first 4-6 months. It contains carbohydrates (such as lactose), fats (such as linoleic acid), and easily digestible proteins (such as alpha-lactalbumin). Breast milk also contains an adequate supply of vitamins and minerals, digestive enzymes, hormones and immunological factors. The first milk produced after birth is called *colostrum*. This is synthesized during the end of pregnancy and 3-5 days of postpartum. It is very high in protein and low in fat and carbohydrates, and contains immunoglobulins. This help the baby have a first bowel movement and prevent jaundice. The bowel movement that results from the colostrum is a different color and consistency than future bowel movements once the mother\'s milk comes in. In some cultures the colostrum is discarded because of the difference, but what they do not know is that it is the best thing for the baby. The composition varies in breast milk during feeding, and over time with development of the baby. When breastfeeding there are three names for the composition of the milk: the fore milk, present during the beginning of breastfeeding; mid is the middle of feeding; and hind which is toward the end of the feeding and contains a composition high in fat. When breastfeeding the female should consider the types of food that will be consumed. If the mother is on a low fat diet or if foods like garlic, broccoli, and onions are eaten, it may affect the baby\'s preference for breast feeding. Also, the mother should consider not breastfeeding after the consumption of alcohol, caffeine, smoking, and certain medications. Barriers of breastfeeding are lack of professional and social support, misinformation, embarrassment, early discharge form the hospital without instruction, and returning to work or school without adequate lactation rooms and if the mother refuses to tend breastfed infant. When breastfeeding initiate as soon after delivery as possible, position the baby correctly, feed on demand from both breasts at each feeding and at least 10 minutes on each breast. Additionally there should be a good educator in the case the infant is not latching on. A common problem that may happen when breastfeeding is *mastitis*, which is an inflammation of one or both breasts and is usually associated with the infection of a blocked milk duct during lactation. The symptoms include flu-like symptoms, red streaks on the breast, and hot skin. Antibiotics may be necessary to clear the infection. *Thrush* may also happen and could be passed between mom and baby. A symptom of thrush includes white flecks on tongue, and the baby and mother should be treated by a doctor. Breast milk is recommended through the first 12 months. Supplementation of cow\'s milk is not recommended due to the high protein that would cause liver damage to the baby. Why breastfeed? - It is easily digested - Composition changes with infant needs - Changes during a feeding, high in fat at the end of feeding - Antibodies in milk - Breastfeeding moms miss less work because babies are sick less - Fewer allergies - Less spit-up - Less constipation and diarrhea - Better jaw development - Decreased risk of SIDS (Sudden Infant Death Syndrome) - Higher IQ - Decreased risk of diabetes, Crohn\'s Disease, Celiac Sprue - Bonding - Convenient, always at the correct temperature and ready to go - Less expensive - Helps the uterus return to normal size more quickly - Less incidence of postpartum "blues" - Lower risk of breast cancer - Lower risk of osteoporosis ## Postpartum Depression Having a baby is usually one of the happiest times in a woman\'s life, but for some women, it can include times of sadness and depression. More women actually suffer from postpartum depression than we really know. Women usually ignore the emotional and physical signs, dealing with their feelings on their own. Postpartum depression affects approximately 10 to 15 percent of new mothers. It often causes anxiety and obsession about caring for the baby or the cleanliness of the home. It may cause changes in sleep patterns and affect relationships including the ability to form a bond with the baby and other family members. Some mothers with postpartum depression have thoughts of wanting to die or of hurting the baby. If the symptoms are so severe that they keep the mother from being able to function, medical treatment is necessary. Baby blues are common due to rapid hormonal changes but resolve after 1-2 weeks. Postpartum depression is characterized by persisting symptoms, and the mother should notify her provider immediately. ## Testing Your Knowledge Answers for these questions can be found here 1\. Is at this stage that an egg implants in the uterine lining : A\) morula : B\) zygote : C\) blastocyst : D\) embryoblast 2\. Which part of the embryoblast will become the central nervous system in development : A\) ectogerm : B\) mesoderm : C\) endoderm 3\. This hormone is only produced in the human body when a woman is pregnant : A\) estrogen : B\) HCG : C\) progesterone : D\) FSH : E\) LH 4\. By this week of pregnancy, the beginnings of all major organs have formed : A\) 4 : B\) 7 : C\) 5 : D\) 6 : E\) 8 5\. Stem cells are found in the embryoblast and use of them is very controversial, another place to find stem cells that are usable to treat leukemia and other disorders is the : A\) morula : B\) chorion : C\) amnion : D\) amniotic fluid : E\) umbilical cord 6\. The cervix dilates on an average of \_\_\_\_\_\_ per hour in the active phase of labor : A\) 2 mm : B\) 2 cm : C\) 1mm : D\) 1 cm 7\. The contractions of the uterus are stimulated by the release of : A\) oxytocin : B\) FSH : C\) LH : D\) prolactin : E\) estrogen 8\. A sign of pre-labor is : A\) irregular contractions : B\) pain in the front only : C\) loss of the mucus plug : D\) contractions stop during rest 9\. This is the most common complication of pregnancy : A\) preclampcia : B\) miscarriage : C\) smoking : D\) Rh factor : E\) teratogens 10\. Sue decides to breastfeed because she has been told that colostrum contains : A\) high protein : B\) low fat : C\) immunoglobulins : D\) all of the above : E\) none of the above 11\. What is the first milk after birth called? : A\) thrush : B\) mastitis : C\) colostrum : D\) milk let down ## Glossary **Abruption**: Premature separation of the placenta from the wall of the womb **Amnion**: An embryonic membrane that encircles a developing fetus and contains amniotic fluid. **Amniocentesis**: A procedure in which a small sample of amniotic fluid is removed from around the fetus **Amniotic fluid**: The fluid surrounding the fetus **Amniotomy**: (artificial rupture of membranes, ARM) Breaking the membranes using a special plastic hook **Anemia**: Lack of hemoglobin in red blood cells, due to iron deficiency or disease **Antepartum Hemorrhage**: (APH) Vaginal bleeding that happens after 24 weeks of pregnancy and before delivery **Breech**: The baby is lying bottom down in the womb **Celiac sprue**: Nutrient absorption impairment which is improved when gluten is removed form the diet. Characteristic mucosal lesion of the small intestine. **Cephalic**: The baby is lying head down in the womb **Chorion**: The embryonic membrane that forms the outermost covering around the developing fetus. **Chorion Villus Sampling**: (CVS) A method for sampling placental tissue for genetic or chromosome studies. **Colostrum** the fluid that is made late in pregnancy and the first few days postpartum in the breast that contains immunologic substances and essential nutrients. **Cleavage**: The early successive divisions of embryonic cells into smaller and smaller cells. **Cilia**: The fine hairs that line the fallopian tubes\' **Cordocentesis**: The procedure for taking blood from the fetal umbilical cord via a needle through the mother's abdomen **Copulation**: (Coitus, sexual intercourse) is the procreative act of a man\'s erect penis is inserted into a woman\'s vagina. At climax, semen is ejaculated from the penis at the cervix of the uterus. Sperm then propel themselves into the uterine tubes where fertilization may occur if an egg is present. **Crohn\'s disease**: Skip lesions in the colon and is a malabsorptive disease. **Cystitis**: Infection of the bladder **Dizygous**: Not identical (fraternal) twins **Doppler**: A form of ultrasound used specially to investigate blood flow in the placenta or in the fetus **Down Syndrome**: (Trisomy 21) A disorder caused by the presence of an extra chromosome 21 in the cells **Ectopic Pregnancy**: A pregnancy that develops outside of the womb **Edema**: Swelling of the fingers, legs, toes, and face. **Embryo**: The medical term for the baby from conception to about six weeks **Engagement**: The process in which the head of the baby moves down from high in the mother\'s abdomen and settles deeper into her pelvis in preparation for birth. This can happen any time between 36 weeks and labor. **Epidural Anesthesia**: A method of numbing the nerves of the lower spinal cord to ensure a pain-free labor **Episiotomy**: A cut of the perineum and vagina performed to make the delivery easier **External Fetal Monitor**: An electronic monitor used to record the fetal heartbeat and mother's contractions **Fallopian Tubes**: (uterine tubes) Two tubular structures (one on each side of the womb) leading from the ovaries to the uterus **Fertilization**: The union of an egg cell and a sperm cell is present wherein 23 chromosomes from each parent come together to form a zygote. After sperm penetrates, the ovum undergoes a chemical change to prevent other sperm from entering. Multiple births can occur from complete division of the conceptus during early cleavage or from fertilization of multiple ova. Birth control techniques are designed to prevent ovulation or to prevent fertilization by barriers, that keep sperm and ova separated. **Fetus**: Medical term for the baby from six weeks after conception until birth **Forceps**: Metal instruments that fit on either side of the baby\'s head and are used to help deliver the baby **Fundus**: The top of the womb **Germ layer**: Layers of cells within an embryo that form the body organs during development. **Glial Cells** (neuroglia; glia): Non-neuronal cells that provide support and nutrition, maintain homeostasis, form myelin, and participate in signal transmission in the nervous system. In the human brain, glia are estimated to outnumber neurons by about 10 to 1. Glial cells provide support and protection for neurons, the other main type of cell in the central nervous system. They are thus known as the \"glue\" of the nervous system. The four main functions of glial cells are to surround neurons and hold them in place, to supply nutrients and oxygen to neurons, to insulate one neuron from another, and to destroy pathogens and remove dead neurons. **Hemoglobin**: (Hb)The oxygen carrying constituent of red blood cells **Induction of labor**: (IOL) the procedure for initiating labor artificially **In utero death**: (IUD)the death of the unborn fetus after 24 weeks **In vitro fertilization**: (IVF) a method of assisted conception in which fertilization occurs outside the mother\'s and the embryo is replaced in the womb **Lanugo**: fine hair that covers the fetus in the womb **Lochia**: blood loss after birth **Mastitis** inflammation of the breast most frequently in lactation. **Neonatal**: baby less than 28 days old **Nuchal scan**: special ultrasound scan that gives an estimate of the risk of Down syndrome **Oocyte**: one egg that is released from the ovary at each ovulation **Placenta**: The structure by which an unborn child is attached to it\'s mother\'s uterine wall and through which it is nourished. **Postnatal**: After birth **Prenatal**: Before birth **Quickening**: The process that occurs between the seventeenth and twentieth weeks of fetal development, the fetus\'s leg bones achieve their final relative proportions. In this process the muscles contract, causing movement at the fetus\'s sinovial joints. The joint movement enhances the nutrition of the articular cartilage and prevents the fusion of connective tissues within the joint. It also promotes bone hardening. It is this stage, where the fetus\'s bones become more developed and harder, that the mother begins to notice fetal movement. **Rudimentary**: Basic; minimal; with less than, or only the minimum, necessary **Thrush**: Creamy white flakes on a red papillae on tongue and tongue may be enlarged. **Umbilical cord**: The cord like structures that connects the fetus to the placenta. **Zygote**: A cell produced by the fusion of an egg and a sperm; a fertilized egg cell. ## Reference - \'\'\"as your baby grows From Conception to Birth\"published by American Baby ```{=html} <!-- --> ``` - <http://www.babybluesconnection.com> ```{=html} <!-- --> ``` - *\"Pregnancy and Birth\"* authors: Dr. Karina Reynolds, Dr. Christoph Lees, Grainne McCartan ```{=html} <!-- --> ``` - *\"Fundamental Concepts of Human Anatomy\"* authors: M.J. Shively D.V.M., M.S., Ph.D. and D.P. Homan B.S., M.S. - \'\'\"Essentials of Anatomy and Physiology\" authors:Valerie C. Scanlon and Tina Sanders, fourth edition - <http://www.MERLOT.com> Stanford Site - \'\'\"The New Parent\" author DR. Miriam Stoppard - \'\'www.marchofdimes.com - \'\'<http://health.allrefer.com/health/fetal-development-info.html> - *American Pregnancy Association* Internet groups: International Awareness Network: www.ican-online.org
# Human Physiology/Genetics and inheritance ## Introduction Genetics is the science of the way traits are passed from parent to offspring. For all forms of life, continuity of the species depends upon the genetic code being passed from parent to offspring. Evolution by natural selection is dependent on traits being heritable. Genetics is very important in human physiology because all attributes of the human body are affected by a person's genetic code. It can be as simple as eye color, height, or hair color. Or it can be as complex as how well your liver processes toxins, whether you will be prone to heart disease or breast cancer, and whether you will be color blind. Defects in the genetic code can be tragic. For example: Down Syndrome, Turner Syndrome, and Klinefelter\'s Syndrome are diseases caused by chromosomal abnormalities. Cystic fibrosis is caused by a single change in the genetic sequence. Genetic inheritance begins at the time of conception. You inherited 23 chromosomes from your mother and 23 from your father. Together they form 22 pairs of autosomal chromosomes and a pair of sex chromosomes (either XX if you are female, or XY if you are male). Homologous chromosomes have the same genes in the same positions, but may have different alleles (varieties) of those genes. There can be many alleles of a gene within a population, but an individual within that population only has two copies, and can be homozygous (both copies the same) or heterozygous (the two copies are different) for any given gene. Genetics is important to medicine. As more is understood about how genetics affects certain defects and diseases, cures and treatments can be more readily developed for these disorders. The sequence of the human genome (approximately 3 billion base pairs in a human haploid genome with an estimated 20,000-25,000 protein-coding genes) was completed in 2003, but we are far from understanding the functions and regulations of all the genes. In some ways medicine is moving from diagnosis based on symptoms towards diagnosis based on genetics, and we are moving into what many are calling the age of personalized medicine. ### DNA **Deoxyribonucleic acid** (DNA) is the macromolecule that stores the information necessary to build structural and functional cellular components. It also provides the basis for inheritance when DNA is passed from parent to offspring. The union of these concepts about DNA allows us to devise a working definition of a gene. A **gene** is a segment of DNA that codes for the synthesis of a protein and acts as a unit of inheritance that can be transmitted from generation to generation. The external appearance (*phenotype*) of an organism is determined to a large extent by the genes it inherits (*genotype*). Thus, one can begin to see how variation at the DNA level can cause variation at the level of the entire organism. These concepts form the basis of **genetics** and **evolutionary theory**. ### Gene right\|framed\|rotating animation of a DNA molecule. A gene is made up of short sections of DNA which are contained on a chromosome within the nucleus of a cell. Genes control the development and function of all organs and all working systems in the body. A gene has a certain influence on how the cell works; the same gene in many different cells determines a certain physical or biochemical feature of the whole body (e.g. eye color or reproductive functions). All human cells hold approximately 30,000 different genes. Even though each cell has identical copies of all of the same genes, different cells express or repress different genes. This is what accounts for the differences between, let\'s say, a liver cell and a brain cell. Genotype is the actual pair of genes that a person has for a trait of interest. For example, a woman could be a carrier for hemophilia by having one normal copy of the gene for a particular clotting protein and one defective copy. A Phenotype is the organism's physical appearance as it relates to a certain trait. In the case of the woman carrier, her phenotype is normal (because the normal copy of the gene is dominant to the defective copy). The phenotype can be for any measurable trait, such as eye color, finger length, height, physiological traits like the ability to pump calcium ions from mucosal cells, behavioral traits like smiles, and biochemical traits like blood types and cholesterol levels. Genotype cannot always be predicted by phenotype (we would not know the woman was a carrier of hemophilia just based on her appearance), but can be determined through pedigree charts or direct genetic testing. Even though genotype is a strong predictor of phenotype, environmental factors can also play a strong role in determining phenotype. Identical twins, for example, are genetic clones resulting from the early splitting of an embryo, but they can be quite different in personality, body mass, and even fingerprints. ### Genetics **Genetics** (from the Greek *genno* = give birth) is the science of genes, heredity, and the variation of organisms. The word \"genetics\" was first suggested to describe the study of inheritance and the science of variation by prominent British scientist William Bateson in a personal letter to Adam Sedgwick, dated April 18, 1905. Bateson first used the term \"genetics\" publicly at the Third International Conference on Genetics (London, England) in 1906. Heredity and variations form the basis of genetics. Humans apply knowledge of genetics in prehistory with the domestication and breeding of plants and animals. In modern research, genetics provide important tools for the investigation of the function of a particular gene, e.g., analysis of genetic interactions. Within organisms, genetic information is generally carried in *chromosomes*, where it is represented in the chemical structure of particular DNA molecules. !diagram showing the seven characters observed by Mendel Genes encode the information necessary for synthesizing the amino-acid sequences in proteins, which in turn play a large role in determining the final phenotype, or physical appearance of the organism. In diploid organisms, a dominant allele on one chromosome will mask the expression of a recessive allele on the other. While most genes are dominant/recessive, others may be codominant or show different patterns of expression. The phrase \"to code for\" is often used to mean a gene contains the instructions about a particular protein, (as in the gene codes for the protein). The \"one gene, one protein\" concept is now known to be the simplistic. For example, a single gene may produce multiple products, depending on how its transcription is regulated. Genes code for the nucleotide sequence in mRNA and rRNA, required for protein synthesis. Gregor Mendel researched principals of heredity in plants. He soon realized that these principals also apply to people and animals and are the same for all living animals. Gregor Mendel experimented with common pea plants. Over generations of the pea plants, he noticed that certain traits can show up in offspring with out blending any of the parent\'s characteristics. This is a very important observation because at this point the theory was that inherited traits blend from one generation to another. !Mendelian inheritance 1 2 1 Pea plant reproduction is easily manipulated. They have both male and female parts and can easily be grown in large numbers. For this reason, pea plants can either self-pollinate or cross-pollinate with other pea plants. In cross pollinating two true-breeding plants, for example one that came from a long line of yellow peas and the other that came from a long line of green peas, the first generation of offspring always came out with all yellow peas. The following generations had a ratio of 3:1 yellow to green. In this and in all of the other pea plant traits Mendel observed, one form was dominant over another so it masked the presence of the other allele. Even if the phenotype (presence) is covered up, the genotype (allele) can be passed on to other generations. **Time line of notable discoveries** 1859 Charles Darwin publishes \"The Origin of Species\" 1865 Gregor Mendel\'s paper, *Experiments on Plant Hybridization* 1903 Chromosomes are discovered to be hereditary units 1906 The term \"genetics\" is first introduced publicly by the British biologist William Bateson at the Third International Conference on Genetics in London, England 1910 Thomas Hunt Morgan shows that genes reside on chromosomes, and discovered linked genes on chromosomes that do NOT follow Mendel\'s law of independent allele segregation 1913 Alfred Sturtevant makes the first genetic map of a chromosome 1913 Gene maps show chromosomes contain linear arranged genes 1918 Ronald Fisher publishes *On the correlation between relatives on the supposition of Mendelian inheritance* - the modern synthesis starts. 1927 Physical changes in genes are called mutations 1928 Fredrick Griffith discovers a hereditary molecule that is transmissible between bacteria 1931 Crossing over is the cause of recombination 1941 Edward Lawrie Tatum and George Wells Beadle show that genes code for proteins 1944 Oswald Theodore Avery, Colin McLeod and Maclyn McCarty isolate DNA as the genetic material (at that time called transforming principle) 1950 Erwin Chargaff shows that the four nucleotides are not present in nucleic acid in stable proportions, but that some general rules appear to hold. (e.g., the nucleotide bases Adenine-Thymine and Cytosine-guanine always remain in equal proportions) 1950 Barbra McClintock discovers transposons in maize 1952 The Hershey-Chase experiment proves the genetic information of phages (and all other organisms) to be DNA 1953 DNA structure is resolved to be a double helix by James D. Watson and Francis Crick, with help from Rosalind Franklin 1956 Jo Hin Tjio and Albert Levan established the correct chromosome number in humans to be 46 1958 The Meselson-Stahl experiment demonstrates that DNA is semi-conservatively replicated 1961 The genetic code is arranged in triplets 1964 Howard Temin showed using RNA viruses that Watson\'s central dogma is not always true 1970 Restriction enzymes were discovered in studies of a bacterium *Haemophilus influenzae*, enabling scientists to cut and paste DNA 1977 DNA is sequenced for the first time by Fred Sangr, Walter Gilbert, and Allan Maxam working independently. Sanger\'s lab complete the entire genome of sequence of Bacteriophage 1983 Kary Banks Mullis discovers the polymerase chain reaction (PCR) enabling the easy amplification of DNA 1985 Alec Jeffreys discovers genetic finger printing 1989 The first human gene is sequenced by Francis Collin and Lap-Chee Tsui. It encodes the CFTR protein. Defect in this gene causes Cystic Fibrosis 1995 The genome of Haemophilus influenza is the first genome of a free living organism to be sequenced. 1996 Saccharomyces cerevisiae is the first eukaryote genome sequence to be released. 1998 The first genome sequence for a multicellular eukaryote, C. elegans is released. 2001 First draft sequences of the human genome are released simultaneously by the Human Genome Project and Celera Genomic 2003 (14 April) Successful completion of Human Genome Project with 99% of the genome sequenced to a 99.99% accuracy 2006 Marcus Pembrey and Olov Bygren publish *Sex-specifics*, *male line trans-generational responses in humans*, a proof of epigenetics ## Transcription and Translation !300 px **Transcription** is the process of making RNA. In response to an enzyme RNA polymerase breaks the hydrogen bonds of the gene. A gene is a segment of DNA which contains the information for making a protein. As it breaks the hydrogen bonds it begins to move down the gene. Next the RNA polymerase will line up the nucleotides so they are complementary. Some types of RNA will leave the nucleus and perform a specific function. **Translation** is the synthesis of the protein on the ribosome as the mRNA moves across the ribosome. There are eleven basic steps to translation. 1. The mRNA base sequence determines the order of assembling of the amino acids to form specific proteins. 2. Transcription occurs in the nucleus, and once you have completed transcription the mRNA will leave the nuecleus, and go into the cytoplasm where the mRNA will bind to a free floating ribosome, where it will attach to a small ribosomal subunit. 3. Methionine-tRNA binds to the nucleotides AUG. AUG is known as the start codon and is found at the beginning of each mRNA. 4. The complex then binds to a large ribosomal subunit. Methionine-tRNA is bound to the P site of the ribosome. 5. Another tRNA containing a second amino acid (lysine) binds to the second amino acid. Binding to the second codon of mRNA (on the A-site of the ribosome). 6. Peptidyl transferase, forms a peptide3 bond between the two amino acids (methionine and lysine). 7. The first amino tRNA is released and mRNA is translocated one codon carrying the second tRNA (still carrying the two amino acids) to the P site. 8. Another tRNA with attached amino acid (glutamine) moves into the A site and binds to that codon. 9. It will now form a peptide bond with lysine and glutamine. 10. Now the tRNA in the P site will be let go, and mRNA is translocated one codon, (the tRNA with three amino acids) to the P site. 11. This will continue going until it reaches the stop codon (UAG) on the mRNA. Then this codon will tell it to release the polypeptide chain. These are some good sites to visit : **A** <http://www.studiodaily.com/main/technique/tprojects/6850.html> : **B** <http://multimedia.mcb.harvard.edu/media.html> Select **A** the video of the Inner Life of a Cell. If you want to hear the descriptions in this process go to **B** web site and select the Inner Life: view the animation. ## Inheritance Children inherit traits, disorders, and characteristics from their parents. Children tend to resemble their parents especially in physical appearance. However they may also have the same mannerisms, personality, and a lot of the time the same mental abilities or disabilities. Many negatives and positives tend to \"run in the family\". A lot of the time people will use the excuse \"It runs in the family\" for things that have alternative reasons, such as a whole family may be overweight, yes it may \"run in the family\" but it could also be because of all the hamburgers and extra mayo that they all eat. Or the fact that after they eat the hamburgers they all sit on the couch and don\'t move for the rest of the evening. Children may have the same habits (good or bad) as their parents, like biting their nails or enjoying reading books. These things aren\'t inherited they are happening because children imitate their parents, they want to be like mom or dad. Good examples are just as important as good genes. Inheritance pattern Description Examples --------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------- Autosomal dominant Only one mutated copy of the gene is needed for a person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. There is a 50% chance that a child will inherit the mutated gene. Many disease conditions that are autosomal dominant have low penetrance, which means that although only one mutated copy is needed, a relatively small proportion of those who inherit that mutation go on to develop the disease, often later in life. Huntingtons disease, Neurofibromatosis 1, HBOC syndrome, Hereditary nonpolyposis colorectal cancer Autosomal recessive Two copies of the gene must be mutated for a person to be affected by an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Two unaffected people who each carry one copy of the mutated gene have a 25% chance with each pregnancy of having a child affected by the disorder. Cystic fibrosis, Sickle cell anemia, Tay-Sachs disease, Spinal muscular atrophy, Muscular dystrophy X-linked dominant X-linked dominant disorders are caused by mutations in genes on the X chromosome. Only a few disorders have this inheritance pattern. Females are more frequently affected than males, and the chance of passing on an X-linked dominant disorder differs between men and women. The sons of a man with an X-linked dominant disorder will not be affected, and his daughters will all inherit the condition. A woman with an X-linked dominant disorder has a 50% chance of having an affected daughter or son with each pregnancy. Some X-linked dominant conditions, such as Aicardi Syndrome, are fatal to boys, therefore only girls have them (and boys with Klinefelter Syndrome). Hypophosphatemia, Aicardi Syndrome X-linked recessive X-linked recessive disorders are also caused by mutations in genes on the X chromosome. Males are more frequently affected than females, and the chance of passing on the disorder differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the mutated gene. With each pregnancy, a woman who carries an X-linked recessive disorder has a 50% chance of having sons who are affected and a 50% chance of having daughters who carry one copy of the mutated gene. Hemophilia A, Duchenne muscular dystrophy, Color blindness, Turner Syndrome Y-linked Y-linked disorders are caused by mutations on the Y chromosome. Only males can get them, and all of the sons of an affected father are affected. Since the Y chromosome is very small, Y-linked disorders only cause infertility, and may be circumvented with the help of some fertility treatments. Male Infertility Mitochondrial This type of inheritance, also known as maternal inheritance, applies to genes in mitochondrial DNA. Because only egg cells contribute mitochondria to the developing embryo, only females can pass on mitochondrial conditions to their children. Leber\'s Hereditary Optic Neuropathy (LHON) ### Mechanisms of inheritance A person\'s cells hold the exact genes that originated from the sperm and egg of his parents at the time of conception. The genes of a cell are formed into long strands of DNA. Most of the genes that control characteristic are in pairs, one gene from mom and one gene from dad. Everybody has 22 pairs of chromosomes (*autosomes*) and two more genes called sex-linked chromosomes. Females have two X (XX) chromosomes and males have an X and a Y (XY) chromosome. Inherited traits and disorders can be divided into three categories: unifactorial inheritance, sex-linked inheritance, and multifactor inheritance. ### Unifactorial Inheritance !Chart showing the possibilities of contracting a recessive defect, from two carrier parents.{width="400"} Traits such as blood type, eye color, hair color, and taste are each thought to be controlled by a single pair of genes. The Austrian monk Gregor Mendel was the first to discover this phenomenon, and it is now referred to as *the laws of Mendelian inheritance*. The genes deciding a single trait may have several forms (*alleles*). For example, the gene responsible for hair color has two main alleles: red and brown. The four possibilities are thus Brown/red, which would result in brown hair,\ Red/red, resulting in red hair,\ Brown/brown, resulting in brown hair, or\ Red/brown, resulting in red hair.\ The genetic codes for red and brown can be either dominant or recessive. In any case, the dominant gene overrides the recessive. When two people create a child, they each supply their own set of genes. In simplistic cases, such as the red/brown hair, each parent supplies one \"code\", contributing to the child\'s hair color. For example, if dad has brown/red he has a 50% chance of passing brown hair to his child and a 50% of passing red hair. When combined with a mom who has brown/brown (who would supply 100% brown), the child has a 75% chance of having brown hair and a 25% chance of having red hair. Similar rules apply to different traits and characteristics, though they are usually far more complex. ### Multifactorial inheritance Some traits are found to be determined by genes and environmental effects. Height for example seems to be controlled by multiple genes, some are \"tall\" genes and some are \"short\" genes. A child may inherit all the \"tall\" genes from both parents and will end up taller than both parents. Or the child my inherit all the \"short\" genes and be the shortest in the family. More often than not the child inherits both \"tall\" and \"short\" genes and ends up about the same height as the rest of the family. Good diet and exercise can help a person with \"short\" genes end up attaining an average height. Babies born with drug addiction or alcohol addiction are a sad example of environmental inheritance. When mom is doing drugs or drinking, everything that she takes the baby takes. These babies often have developmental problems and learning disabilities. A baby born with *Fetal alcohol syndrome* is usually abnormally short, has small eyes and a small jaw, may have heart defects, a cleft lip and palate, may suck poorly, sleep poorly, and be irritable. About one fifth of the babies born with fetal alcohol syndrome die within the first weeks of life, those that live are often mentally and physically handicapped. ### Sex-linked Inheritance !X-linked recessive inheritance Sex-linked inheritance is quite obvious, it determines your gender. Male gender is caused by the Y chromosome which is only found in males and is inherited from their fathers. The genes on the Y chromosomes direct the development of the male sex organs. The x chromosome is not as closely related to the female sex because it is contained in both males and females. Males have a single X and females have double XX. The X chromosome is to regulate regular development and it seems that the Y is added just for the male genitalia. When there is a default with the X chromosomes in males it is almost always persistent because there is not the extra X chromosome that females have to counteract the problem. Certain traits like colorblindness and hemophilia are on alleles carried on the X chromosome. For example if a woman is colorblind all of her sons will be colorblind. Whereas all of her daughters will be carriers for colorblindness. ### Exceptions to simple inheritance Our knowledge of the mechanisms of genetic inheritance has grown a lot since Mendel\'s time. It is now understood, that if you inherit one allele, it can sometimes increase the chance of inheriting another and can affect when or how a trait is expressed in an individuals phenotype. There are levels of dominance and recessiveness with some traits. Mendel\'s simple rules of inheritance does not always apply in these exceptions. ### Polygenic Traits Polygenic traits are traits determined by the combined effect of more than one pair of genes. Human stature is an example of this trait. The size of all body parts from head to foot combined determines height. The size of each individual body part are determined by numerous genes. Human skin, eyes, and hair are also polygenic genes because they are determined by more than one allele at a different location. ### Intermediate Expressions When there is incomplete dominance, blending can occur resulting in heterozygous individuals. An example of intermediate expression is the pitch of a human male voice. Homozygous men have the lowest and highest voice for this trait (AA and aa). Tay-Sachs, causing death in childhood, is also characterized by incomplete dominance. ### Co-dominance For some traits, two alleles can be co-dominant. Were both alleles are expressed in heterozygous individuals. An example of that would be a person with AB blood. These people have the characteristics of both A and B blood types when tested. ### Multiple-Allele Series There are some traits that are controlled by far more alleles. For example, the human HLA system, which is responsible for accepting or rejecting foreign tissue in our bodies, can have as many as 30,000,000 different genotypes! The HLA system is what causes the rejection of organ transplants. The multiple allele series is very common, as geneticists learn more about genetics, they realize that it is more common than the simple two allele ones. ### Modifying and Regulator Genes Modifying and regulator genes are the two classes of genes that may have an effect on how the other genes function. *Modifying Genes* alter how other genes are expressed in the phenotype. For example, a dominant cataracts gene may impair vision at various degrees, depending on the presence of a specific allele for a companion modifying gene. However, cataracts can also come from excessive exposure to ultraviolet rays and diabetes. *Regulator Genes* also known as homoerotic genes, can either initiate or block the expression of other genes. They also control a variety of chemicals in plants and animals. For example, Regulator genes control the time of production of certain proteins that will be new structural parts of our bodies. Regulator genes also work as a master switch starting the development of our body parts right after conception and are also responsible for the changes in our bodies as we get older. They control the aging processes and maturation. ### Incomplete penetrates Some genes are incomplete penetrate. Which means, unless some environmental factors are present, the effect does not occur. For example, you can inherit the gene for diabetes, but never get the disease, unless you were greatly stressed, extremely overweight, or didn\'t get enough sleep at night. ## Inherited Genetic Disease Some of the most common inherited diseases are *hemochromatosis*, *cystic fibrosis*, *sickle cell* *anemia* and *hemophilia*. They are all passed along from the parents and even if the parents don\'t show signs of the disease they may be carriers which mean that all of the children they have may be born with the disease. There is genetic testing that may be done prenatally to determine if the baby is conflicted with one of these diseases. ### Hemochromatosis !Haemochromatosis types 1-3 are inherited in an autosomal recessive fashion. !Haemochromatosis type 4 is inherited in an autosomal dominant fashion. Even though most people have never heard of hemochromatosis it is the most common inherited disease. About 1 in 300 are born with hemochromatis and 1 in 9 are carriers. The main characteristic is the intake of too much iron into the inflicted body. Iron is crucial to the workings of *hemoglobin* but too much iron is just as bad as too little iron. With hemochromatosis deposits of iron form on almost every major organ especially the liver, heart and pancreas, which causes complete organ failure. Hemochromatosis patients usually absorb two or three times the iron that is needed for normal people. Hemochromatosis was first discovered in 1865 and most patients have Celtic ancestry dating back 60 or 70 generations. #### Treatments for hemochromatosis The most common treatment for hemochromatosis is to induce anemia and maintain it until the iron storage is reduced. This is done by therapeutic phlebotomy. Phlebotomy is the removal of a unit of blood (about 500 mls.) This must be done one to two times a week and can take weeks, months, or years to complete. After this treatment some patients will never have to do it again and others will have to do it many times over the course of their life. Patients who undergo their recommended treatments usually go on to live a long and healthy life. Patients who decide against treatment increase their chances of problems such as organ failure \-- or even death. Along with phlebotomy treatment, patients should stick to a low iron diet and should not cook with iron cookware. ### Cystic Fibrosis (CF) Cystic fibrosis is a disease that causes thick, sticky mucus to build up in the lungs and digestive tract. It is the most common lung disease in children and young adults and may cause early death. The mucus builds up in the breathing passages of the lungs and in the pancreas. The build up of the mucus results in terrible lung infections and digestion problems. Cystic fibrosis may also cause problem with the sweat gland and a man\'s reproductive system. There are more than 1,000 mutations of the CF gene, symptoms vary from person to person. The most common symptoms are: No bowel movements for the first 24 to 48 hours of life, stools that are pale or clay colored, foul smelling or that float, infants that have salty-tasting skin, recurrent respiratory infections like pneumonia, coughing or wheezing, weight loss or low weight gain in childhood, diarrhea, delayed growth, and excessive fatigue. Most patients are diagnosed by their first birthday but less severe cases sometimes aren\'t caught until after 18 years of age. 40% of patients are over 18 years old and the average life span of CF patients is about 35 years old, which is a huge increase over the last 30 years. Patients usually die of lung complications. !**CFTR protein -** Molecular structure of the CFTR protein{width="350"} #### Treatment for cystic fibrosis In 2005 the U.S food and drug administration approved the first DNA based blood test to help detect CF. Other tests to help detect CF include: Sweat chloride test, which is the standard test for CF. High salt levels in the patients sweat is an indication of CF, Fecal fat test, upper GI and small bowel series, and measurements of pancreatic function. After a diagnosis has been made there are a number of treatments available, these include: Antibiotics for respiratory infections, pancreatic enzyme replacement, vitamin supplements (mostly A, D, E, and K), inhalers to open the airways, enzyme replacement therapy which makes it easier to cough up the mucus, pain relievers, and in very severe cases, lung transplants. ### Sickle cell anemia Sickle cell anemia is an inherited disease of the red blood cells which causes abnormally shaped red cells. A typical red blood cell has about 270 million hemoglobin molecules, which bind with oxygen. In a person with sickle cell disease, one amino acid is changed in the hemoglobin molecule, and the end result is misshapen red blood cells. In a patient with sickle cell disease the red blood cells change from the normal round shape to the shape of a sickle or \"C\" shaped. The abnormal shape causes the cells to get stuck in some blood vessels which causes blockage in the vessel. This causes pain and can destroy organs because of the lack of oxygen. Sickle cells live only 10 to 20 days and a normal cell lives about 120 days.left\|framed\|Red blood cells with sickle-cell mutations. This rapid death of blood cells leads to chronic anemia. Complications can include severe pain, terrible infection, swelling of the feet and hands, stroke, damage to the eyes, and damaged body organs. These effects can vary from person to person depending on the type of sickle cell disease they have. Some patients are mostly healthy and others are in the hospital more than they are out. Thanks to diagnosis and treatment advancements, most children born with sickle cell grow up to have a normal and relatively healthy life. The form of sickle cell is determined by which genes they inherit from the parents. When a child inherits a sickle cell gene (hemoglobin gene) from each parent it is called hemoglobin SS disease ( which is the formal name for sickle cell). When a child inherits a sickle cell gene from one parent and a different abnormal gene from the other parent, it is a form of disease called hemoglobin SC disease or hemoglobin S-thalassemia. If a child inherits a normal gene from one parent and a sickle cell gene from the other, the child will not have sickle cell but will be a carrier and may pass it to their children. Sickle cell affects mostly African Americans and some Latino Americans. A person who is a carrier (has one copy of the gene) is resistant to malaria. This heterozygote advantage explains why the gene is more common in people in equatorial regions, or who are descendants of such people (such as African Americans). #### Treatment for Sickle cell anemia Sickle cell is diagnosed at birth with a simple blood test. If the first blood test is positive then a second test is done just for confirmation. Because of the high risk of infections that occur with sickle cell, early diagnosis is very important. Other than a bone marrow transplant there is no known cure for sickle cell. Bone marrow transplants have a high risk of rejection and aren\'t an available option for every patient. The patient would need a bone marrow donor match with a low risk of rejection. Even without a cure, with the use of pain medications and antibiotic treatments, children with sickle cell can live a long and happy life. Blood transfusions are sometimes used to treat episodes of severe pain. For adults who have recurrent pain episodes (at least 3 yearly), a cancer drug, hydroxyurea (marketed as Droxia), has been approved to relieve symptoms. It appears to work by increasing the flexibility of sickle cells. ### Hemophilia About two thirds of people who have Hemophilia have inherited it. For the other third, there is no known cause for possessing the disorder. There are two types of hemophilia, Type A and Type B. Both are caused by a low level or a complete absence of protein in the blood. Without this protein, blood is not able to clot. Some of the symptoms of Hemophilia are bleeding in the joints, knees, and ankles. Stiffness without pain in the joints, stiffness with a lot of warmth,(most ability for movement is lost due to swelling) blood in the urine or stool, excessive bleeding after surgery or loosing a tooth, excessive bruising, abnormal menstrual bleeding, and nose bleeds that last for long periods of time. Hemophiliacs blood does not coagulate like a normal persons. Coagulation controls bleeding, it changes blood from a liquid to a solid. Within seconds of a cut or scrape, platelets, calcium and other tissue factors start working together to form a clot. Over a short time the clot strengthens and then dissolves as the injury heals. Hemophiliacs are missing the clotting factor, or it isn\'t working correctly which causes them to bleed for a longer time. The most common myth is that a person with a bleeding disorder will bleed to death from a minor wound or that their blood flows faster than somebody without a bleeding disorder. Some of the risks hemophilia are: Scarring of the joints or joint disease, vision loss from bleeding of the eyes, chronic anemia from blood loss, a neurological or psychiatric problem, death which may occur from large amounts of blood loss or bleeding in the brain or other vital organs. Most cases of hemophilia are caused from inherited disorders but sometimes people can get it from vitamin K deficiency, liver disease, or treatments like prolonged use of antibiotics or anti coagulation drugs. Hemophilia is the best known bleeding disorder and it has had the most research done on it, so hemophiliacs have a slight advantage over people with other bleeding disorders. #### Treatment for hemophilia To treat Hemophilia, a Clotting Factor is needed. It is in the shape of powder kept in a small, sterile glass bottle. It has to be kept in the fridge. When needed, The Clotting Factor is mixed with sterile water, then one minute later it can be injected into a vein. It may also be mixed with a large amount of water and injected through an IV. There are over 140 centers that specialize in hemophilia. Most of these centers are \"Comprehensive Care Facilities\". Comprehensive care facilities provide all the services needed by a hemophiliac and their family. Services provided include: Primary physician, nurse coordinator, physiotherapist, and dentist. Hemophiliacs require a special dentist because of the higher risk of bleeding. It is recommended that hemophiliacs go to the treatment centers twice a year for a complete check-up. The basic and most common treatment for patients with hemophilia A and B is factor replacement therapy. Factor replacement therapy is the IV injection of Factor VIII and IX concentrates which help control bleeding. This concentrate comes from two sources: human plasma and genetically engineered cells made by DNA technology. This concentrate is what the hemophiliac is lacking in their own genes. After the injection is given the patients blood becomes \"normal\" for a couple of hours which gives time for a clot to from at the site of a damaged blood vessel. This treatment is not a permanent cure, within about 3 days there is no trace left in the system. Today\'s Factor treatments are much more concentrated than they were in the past so very little is required even if the patient is going in for major surgery or has a major injury. Treatments are also very convenient, they can be stored at home in the fridge for up to 6 months. So if the patient is injured they don\'t need to go to the hospital they can give themself an injection at home. After the injection it only takes about 15-20 minutes for the clotting process to begin. There is a risk of contracting other disease such as AIDS from Factor VIII that is made from human plasma, but as technology gets better the cases of AIDS has dropped. There is no possibility of contracting diseases from genetic engineering Factor VIII. Hemophiliacs can live a long life. The most common reason for early death among patients has been from AIDS related complications. ## Non-heritable Genetic Disorders !Karyotype of 21 trisomy-Down syndrome{width="350"} Any disorder caused totally or in part by a fault (or faults) of the genetic material passed from parent to child is considered a genetic disorder. The genes for many of these disorders are passed from one generation to the next, and children born with a heritable genetic disorder often have one or more extended family members with the same disorder. There are also genetic disorders that appear due to spontaneous faults in the genetic material, in which case a child is born with a disorder with no apparent family history. **Down Syndrome,** also known as Trisomy 21, is a chromosome abnormality that effects one out of every 800-1000 newborn babies. During anaphase II of meiosis the sister chromatids of chromosome 21 fail to separate, resulting in an egg with an extra chromosome, and a fetus with three copies (trisomy) of this chromosome. At birth this defect is recognizable because of the physical features such as almond shaped eyes, a flattened face, and less muscle tone than a normal newborn baby. During pregnancy, it is possible to detect the Down Syndrome defect by doing amniocentesis testing. There is a risk to the unborn baby and it is not recommended unless the pregnant mother is over the age of thirty-five. Other non-lethal chromosomal abnormalities include additional osex chromosome abnormalities which is when a baby girl (about 1 in 2,500)is born with one x instead of two (xx) this can cause physical abnormalities and defective reproduction systems. Boys can also be born with extra X\'s (XXY or XXXY) which will cause reproductive problems and sometimes mental retardation. **Chromosomal Abnormalities** In most cases with a chromosomal abnormality all the cells are affected. Defects can have anywhere from little effect to a lethal effect depending on the type of abnormality. Of the 1 in 200 babies born having some sort of chromosomal abnormality, about 1/3 of these results in spontaneous abortion. Abnormalities usually form shortly after fertilization and mom or dad usually has the same abnormality. There is no cure for these abnormalities. Tests are possible early in pregnancy and if a problem is detected the parents can choose to abort the fetus. ## Mutant Genes Mutation is a permanent change in a segment of DNA. Mutations are changes in the genetic material of the cell. Substances that can cause genetic mutations are called mutagen agents. Mutagen agents can be anything from radiation from x-rays, the sun, toxins in the earth, air, and water viruses. Many gene mutations are completely harmless since they do not change the amino acid sequence of the protein the gene codes for. Mutations can be good, bad, or indifferent. They can be good for you because their mutation can be better and stronger than the original. They can be bad because it might take away the survival of the organism. However, most of the time, they are indifferent because the mutation is no different than the original. The not so harmless ones can lead to cancer, birth defects, and inherited diseases. Mutations usually happen at the time of cell division. When the cell divides, one cell contracts a defect, which is then passed down to each cell as they continue to divide. Teratogens refers to any environmental agent that causes damage during the prenatal period. Examples of Common Teratogens: - drugs: prescription, non-prescription, and illegal drugs - tobacco, alcohol, - radiation, - environmental pollution, - infectious disease, - STD\'s, - Aids, - Parasites, Sensitive period to teratogen exposure, in the embryonic period is most vital. Fetal damage is minor. ## Genetic Engineering Genetic engineering is where the DNA or gene gets changed by a scientist to make a gene with the characteristics that they want it to have, and to get rid of the characteristics that they don\'t want the gene to have. This process can be applied towards any plant, animal, or person. The main reason for genetic engineering is to \"mass produce\" a certain protein. Each cell is responsible for producing a certain protein and these proteins can be used for medical treatment and diagnosis. The job of each gene is to control the production of a particular protein in a living cell. If the gene responsible for *synthesizing* an important or useful protein can be found, and if that gene can be inserted into another cell that can be made to reproduce, then a colony of cells containing that gene can be grown and the protein will be manufactured in large quantities. This process is responsible for insulin and growth hormones and it is also used in vaccines to help prevent hepatitis and a treatment to help prevent viral infections. It also helps in genetically engineering Factor VIII which is a treatment for hemophilia. The first step is to find the gene in the DNA of a cell that is responsible for the manufacturing of the desired protein. Then that gene is either extracted or the exact chemical structure is figures out to be synthesized. The last step is to insert the DNA into the recipient which is done by using special enzymes to split a molecule of the recipients cell and inserting the new gene. There have been many steps taken to bring technology closer to being able to fix genetically inherited diseases. Hopefully someday there will be many fewer babies born with genetic diseases and disorders. ## Gene Therapy Gene therapy is a way to correct the defective genes that are the cause of disease development. When the genes are altered proteins are not able to function normally and as a result of this, defects can occur. Current gene therapy is still being experimented with, but in some cases it is very effective. Genes are carried on chromosomes and are the basic physical and functional parts of hereditary. When there is a genetic disorder, gene therapy can help fix the problem either permanently or at least temporarily. The most common form of gene therapy is to insert a gene into a nonspecific place to replace a malfunctioning gene. Another method is gene swapping, where an abnormal gene is replaced by a normal gene. Genes could also be repaired through \"selective reverse mutation\" which returns the gene to it\'s original function. The degree to which a gene is turned on or off can also be altered. Gene therapy works on the principle belief that a virus genome can be manipulated to remove disease causing genes and new therapeutic genes can be inserted in their place. These new genes are called gene therapy vectors. (The virus container is the vector and the new gene is the payload.) !Gene therapy using an Adenovirus vector. A new gene is inserted into an adenovirus vector, which is used to introduce the modified DNA into a human cell. If the treatment is successful, the new gene will make a functional protein.{width="340"} A few of the different viruses used as gene therapy vectors are: **Retroviruses** - A class of viruses that can create double-stranded DNA copies of their original RNA genomes. Theses copies of its genomes can be mixed into the chromosomes of \"host\" cells. HIV is a type of retrovirus. **Adenoviruses** - A class of viruses with double-stranded DNA genome that cause respiratory, intestinal, and eye infections in humans. The common cold is an adenovirus. Adeno-associated viruses - A class of small, single-stranded DNA viruses that can insert their genetic material at a specific site on chromosome 19. (chromosome 19 represents about 2% of the human genome and contains about 1,500 genes. Some of the genes included are genes that code for insulin-dependent diabetes, myotonic dystrophy, migraines, and inherited high blood cholesterol). A class of double-stranded DNA viruses that infect a particular cell type, neurons, called **Herpes simplex viruses** is another common virus used in gene therapy. It is the virus that causes cold sores. Major advancements have been made in gene therapy. There are many new discoveries in helping cure and treat diseases that claim millions of lives. Some of the disease that have cures or treatments because of gene therapy include: Parkinson\'s, Huntington\'s, Cystic Fibrosis, Some cancers, \"Bubble Boy\" syndrome and sickle cell. With technology jumping ahead, maybe someday there will be a cure for every life threatening disease. ## Genetic Regulation of Development and Homeostasis It is very easy to think of genetics as why I have blue eyes while both of my parents have brown eyes. Or how hemophilia is passed down from mother to son, and not mother to daughter. But Genetics is more in depth than that. At conception you started as a single cell. That cell started to divide. You didn't increase in mass just in the number of cells. Once the bundle of cells reached a certain number, things changed. You started gaining mass by acquiring new resources (from your mother) and increasing in cell number. Your cells specialized. Some cells became the liver. Others became heart, lungs, brain, and so forth. Why is this? How did that little bundle of cells \"know\" when it was time to specialize? It is because your DNA has regulatory control over your entire system. If it didn't, that bundle of cells would just keep dividing as undifferentiated cells and never specialize, never gain form or function. Thanks to the genetic regulatory control over your system, your anatomy forms correctly with everything in its proper place. Even after fetal development gene regulation still controls what each cell produces and how it functions. Puberty just doesn't happen at the age of twelve. Puberty happens because genes in your genetic code are triggered by your growth and development, causing your endocrine system to start producing the proper hormones, thus causing you to mature sexually. Even aging is genetically controlled. The mechanisms of genetic regulation are not discussed here, but it is worth noting that any step of gene expression may be modulated, from the DNA-RNA transcription step to post-translational modification of a protein. Gene regulation gives the cell control over structure and function, and is the basis for cellular differentiation. A cell can also respond to changes in its environment by altering gene expression. For example, a pancreatic cell exposed to high glucose levels releases pre-formed insulin that it was storing. Yet, if the high levels of glucose continue, the cell will transcribe additional copies of the gene for making insulin and thus increase insulin production to meet demand. This is homeostasis in action. ## Glossary **Allele:** one member of a pair of genes that occupy a specific position on a specific chromosome **Autosome:** chromosome that is not a sex chromosome **Chromosome:** threadlike strand of DNA and associated proteins in the nucleus of cells that carries the genes and functions in the transmission of heredity information **Cystic Fibrosis:** recessive genetic disorder affecting the mucus lining of the lungs, leading to breathing problems and other difficulties **Fetal Alcohol Syndrome:** combination of birth defects resulting form high (sometimes low) alcohol consumption by the mother during pregnancy **Gene:** is a segment of nucleic acid that contains the information necessary to produce a functional product, usually a protein. **Genetics:** is the science of genes, heredity, and the variation of organisms. **Genome:** complete set of genetic information of an organism including DNA and RNA **Genotype:** actual set of genes an organism has. It is the blue print of gentic material. **Hemochromatosis:** metabolic disorder that causes increased absorption of iron, which is deposited in the body tissues and organs; the iron accumulates in the body where it may become toxic and causes damage **Hemoglobin:** component of red blood cells that carries oxygen **Hemophilia:** group of heredity disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots **Inheritance:** characteristics given to a child by a parent **Modifying Gene:** alters how other genes are expressed in the phenotype **Multifactorial Inheritance:** trait or disorder determined by multiple genes and/or environmental effects **Phenotype:** organisms physical appearance **Polygenic:** trait whose expression is influenced by more than one gene **Regulator Genes:** initiate or block the expression of other genes. **Sex-linked:** pertaining to a trait of a disorder determined by the sex chromosome in a persons cells or by the genes carried on those chromosomes **Sickle Cell Anemia:** recessive disorder in which red blood cells take on an unusual shape, leading to other problems with the blood **Synthesize:** to make using biochemical processes **Unifactorial Inheritance:** trait or disorder determined by a single pair of genes **Zygote:** cell formed by the union of male and female gametes. A Zygote is a cell that is the result of fertilization. ## Review questions Answers for these questions can be found here 1\. DNA is found on : A\) endoplasmic reticulum : B\) ribosomes : C\) chromosomes : D\) cytoplasm 2\. Even though each cell has identical copies of all of the same genes, different cells \_\_\_\_\_\_\_\_\_\_ or \_\_\_\_\_\_\_\_\_\_\_ different genes : A\) express, repress : B\) genotype, phenotype : C\) dominant, recessive 3\. In diploid organisms, a dominant allele on one chromosome will : A\) show the expression of a recessive allele : B\) mask the expression of a recessive allele : C\) show that there are dominant alleles on both chromosomes : D\) none of the above 4\. Transcription occurs in the : A\) cytoplasm : B\) golgi apparatus : C\) mitochondria : D\) nucleus 5\. This is the start codon and is found at the beginning of each mRNA : A\) AGU : B\) GAU : C\) UAG : D\) GUA : E\) AUG 6\. Sara was born with cystic fibrosis, from this we could assume that : A\) all of her siblings also have cystic fibrosis : B\) only her dad is a carrier : C\) only her mom is a carrier : D\) both of her parents are carriers 7\. Jesse was born with a flattened face, almond eyes and less muscle tone; it could be assumed that he has : A\) a chromosome abnormality on chromosome 21 : B\) a chromosome abnormality on chromosome 19 : C\) a chromosome abnormality on chromosome 20 : D\) a chromosome abnormality on chromosome 22 : E\) No chromosome abnormality, these are his inherited traits 8\. The most common inherited disease is : A\) hemochromatosis : B\) cystic fibrosis : C\) sickle cell anemia : D\) hemophilia : E\) all of the above 9\. Being a carrier of sickle cell anemia means that the person will : A\) also be a carrier of hemophilia : B\) be resistant to malaria : C\) have children that all have sickle cell anemia : D\) have children that all have malaria : E\) none of the above 10\. Hemophilia is : A\) a Y linked disease : B\) an XY linked disease : C\) an X linked disease
# Human Physiology/Development: birth through death ## Overview We are born, we grow up, we age, and then we die. Unless disease or trauma occurs, most humans go through the various stages of the life described above. Human Development is the process of growing to maturity and mental ability. Traditionally, theories that explain senescence have generally been divided between the programmed and stochastic theories of aging. Programmed theories imply that aging is regulated by biological clocks operating throughout the life span. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair and defense responses. Stochastic theories blame environmental impacts on living organisms that induce cumulative damage at various levels as the cause of aging. Examples of environmental impacts range from damage to DNA, damage to tissues and cells by oxygen radicals (widely known as free radicals countered by the even more well known antioxidants), and cross-linking. However, aging is now seen as a combination of genetic and environmental processes; a progressive failure of homeostatic mechanisms involving maintenance and repair genes, stochastic events leading to molecular damage and molecular heterogeneity, and chance events determining the probability of death. Homeostasis, as we have seen throughout this book, is maintained through complex and interacting systems, and aging is considered to be a progressive shrinkage of homeostatic capabilities, mainly due to increased molecular heterogeneity. In this chapter we explore the physiology of all stages of human development, with a particular emphasis on the aging process. ## Apoptosis !A cell undergoing apoptosis. In just one of many scenarios of apoptosis, the process is triggered by another neighboring cell; the dying cell eventually transmits signals that tell the phagocytes, which are a part of the immune system, to engulf it.{width="200"} Apoptosis is the process of regulated cell death and removal. In some cases cell damage can trigger apoptosis, but it is usually a normal function of the cell. Apoptosis results in controlled auto digestion of the cells content. The cell membrane stays in place and the cells contents are not dispersed. When this process is near completion, \"eat me\" signals, like phosphatidylserine, appear on the surface of the cell membrane. This in turn attracts phagocytic scavengers that complete the process of removing the dead cell without eliciting an inflammatory response. Unlike necrosis, which is a form of cell death that results from acute cellular injury, apoptosis is carried out in an ordered process that generally confers advantages during an organism\'s life cycle. Apoptosis Rates:The rate at which cells of the body die varies widely between different cell types. Some cells, such as white blood cells, live for only a matter of hours while other cells can live throughout the duration of the lifespan of the individual. ```{=html} <!-- --> ``` Homeostasis:Apoptosis is a regulated function that results in a relatively consistent number of cells in the body. This balancing act is part of homeostasis (see chapter 1) that is required by living organisms. An example for this is that blood cells are constantly being produced and apoptosis takes place to eliminate a similar number of older cells. Homeostasis was discovered by Claude Bernard around the year 1851. ```{=html} <!-- --> ``` Development:Apoptosis also plays a key role in growth and development. An example of how apoptosis enables development is the differentiation of human fingers in a developing embryo. Apoptosis is the function that enables the embryos fingers to separate. ```{=html} <!-- --> ``` Disorders:Too much apoptosis causes cell loss disorders such as osteoporosis, whereas too little apoptosis results in uncontrolled cell proliferation, namely cancer. ## Growth and development Growth and development is an ongoing process that begins at conception and continues through the remainder of our lives. There is a broad spectrum of physical and psychological changes that are part of the maturation and life of the individual. Growth is a physical change that can be weighed and measured. Development is psychological and social changes to the individual such as behaviors and thinking patterns. Growth and development are two complimentary processes that together make up the individual. Examples of this difference are all around us. One notable example involves infants. Infants understand speech much earlier than their bodies have matured enough to physically perform it. Thus it is evident that their speech patterns develop before the physical growth of their vocal chords is adequate to facilitate speech. The rate of development and growth varies dependent on many factors such as age and genetic disposition. Babies grow at roughly the same pace and benchmarks for their physical and social development are roughly standard. However, as any parent can tell you, no two children develop exactly within the same time frame. Thus an appropriate time span should be used. For example: one brother may gain weight faster than another. Growth spurts can vary. Some children can speak entire sentences before their first year while others may not speak at all until two or three. This creates a greater diversity among human beings. The following chart focuses on reflexes of the developing infant. Reflex Stimulation Response Age of disappearance Function ------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------ --------------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------ --------------------------------------------------------------------------------------- Eye blink Bright light shinning in eyes or clap hands by eyes closes eyelids quickly Permanent This reflex protects the infant from a lot of stimulation Withdrawal Stick sole of foot with stimulus like a pin This cause the foot to withdraw, this occurs with the use of flexing of the knee to hip Decreases after the 10th day of birth This is a protection for the infant in the instance of unpleasant tactile stimulation Rooting Touch cheek near the corner of the mouth The infants head will turn towards the site of stimulation 3 weeks (due to the voluntary response that is now capable for infant to do at this time) This reflex helps baby to find the mothers nipple Sucking Place fingers in infant\'s mouth The infant will suck finger rhythmically 4 months (voluntary sucking will come about) This helps with feeding Swimming Place the baby in pool of water face down The baby paddles and kicks in swimming movements 4 to 6 month This helps baby to survive if dropped into the water Moro Hold infant in a cradling horizontal position and slightly lower the baby in a fast motion toward the ground while making a loud sound supporting the baby The baby will make a embracing motion and arch its back extending its legs throwing its arms outward, and finally it will bring arms in toward its body 6 months In the evolutionary past this may have helped the baby cling to the mother Palmar grasp Place the finger in baby\'s palm and press against the palm The baby will immediately grasp the finger 3 to 4 months This prepares infant for when voluntary grasping comes about Tonic neck Turn the baby\'s head to one side while the baby is awake This will cause the baby to extend one arm in front of its eye on one arm to the side to which the head has been turned 4 months This may prepare for voluntary reaching Stepping/marching When you hold the baby under the arm and permit the bare feet of the baby to touch a flat surface The baby will lift one foot after the other in a stepping fashion 2 months (this applies to a baby who has gained weight a baby who is not as heavy this reflex may be submissive) This prepares the baby for voluntary walking Babinski Touch the foot in a stroking manner form the toe toward the heel The baby\'s toes will fan out and curl as the foot twists in 8 to 12 months Unknown ## Neonatal The neonatal period extends from birth to somewhere between 2 weeks and 1 month. Immediately after the baby is born, uterine contractions force blood, fluid, and the placenta from the mother\'s body. The umbilical cord---the baby\'s lifeline to it\'s mother---is now severed. Without the placenta to remove waste, carbon dioxide builds up in the baby\'s blood. This fact, along with the actions of medical personnel, stimulates the control center in the brain, which in turn responds by triggering inhalation. Thus the newborn takes its first breath. As the newborn\'s lungs begin to function, the bypass vessels of fetal circulation begin to close. The bypass connecting the atria of the heart, known as the foramen ovale, normally closes slowly during the first year. During this period the body goes through drastic physiological changes. The most critical need is for the body to get enough oxygen as well as an adequate supply of blood. (The respiratory and heart rate of a newborn is much faster than that of an adult.) !Newborn infant, just seconds after vaginal delivery.{width="260"} ### The newborn\'s appearance A newborn\'s skin is oftentimes grayish to dusky blue in color. As soon as the newborn begins to breathe, usually within a minute or two of birth, the skin\'s color returns to normal tones. Newborns are wet, covered in streaks of blood, and coated with a white substance known as vernix caseosa, which is believed to act as an antibacterial barrier. The newborn may also have Mongolian spots, various other birthmarks, or peeling skin, particularly at the wrists, hands, ankles, and feet. A newborn\'s shoulders and hips are narrow, the abdomen protrudes slightly, and the arms and legs are relatively short. The average weight of a full-term newborn is approximately 7 ½ pounds (3.2kg), but can be anywhere from 5.5--10 pounds (2.7--4.6kg). The average total body length is 14--20 inches (35.6--50.8cm), although premature newborns may be much smaller. The Apgar score is a measure of a newborn\'s transition from the womb during the first ten minutes of life. A newborn\'s head is very large in proportion to the rest of the body, and the cranium is enormous relative to his or her face. While the adult human skull is about 1/8 of the total body length, the newborn\'s is twice that. At birth, many regions of the newborn\'s skull have not yet been converted to bone. These \"soft spots\" are known as fontanels; the two largest are the diamond-shaped anterior fontanel, located at the top front portion of the head, and the smaller triangular-shaped posterior fontanel, which lies at the back of the head. During labor and birth, the infant\'s skull changes shape to fit through the birth canal, sometimes causing the child to be born with a misshapen or elongated head. This will usually return to normal on its own within a few days or weeks. Special exercises sometimes advised by physicians may assist the process. Some newborns have a fine, downy body hair called lanugo. It may be particularly noticeable on the back, shoulders, forehead, ears and face of premature infants. Lanugo disappears within a few weeks. Likewise, not all infants are born with lush heads of hair. Some may be nearly bald while others may have very fine, almost invisible hair. Some babies are even born with a full head of hair. Amongst fair-skinned parents, this fine hair may be blond, even if the parents are not. The scalp may also be temporarily bruised or swollen, especially in hairless newborns, and the area around the eyes may be puffy. !Traces of vernix caseosa on a full term newborn{width="260"} A newborn\'s genitals are enlarged and reddened, with male infants having an unusually large scrotum. The breasts may also be enlarged, even in male infants. This is caused by naturally-occurring maternal hormones and is a temporary condition. Females (and even males) may actually discharge milk from their nipples, and/or a bloody or milky-like substance from the vagina. In either case, this is considered normal and will disappear in time. The umbilical cord of a newborn is bluish-white in color. After birth, the umbilical cord is normally cut, leaving a 1--2 inch stub. The umbilical stub will dry out, shrivel, darken, and spontaneously fall off within about 3 weeks. Occasionally, hospitals may apply triple dye to the umbilical stub to prevent infection, which may temporarily color the stub and surrounding skin purple. Newborns lose many of the above physical characteristics quickly. Thus prototypical older babies look very different. While older babies are considered \"cute\", newborns can be \"unattractive\" by the same criteria and first time parents may need to be educated in this regard. Neonatal jaundice:Neonatal jaundice is usually harmless: this condition is often seen in infants around the second day after birth, lasting until day 8 in normal births, or to around day 14 in premature births. Serum Bilirubin initially increase because a newborn does not need as many red blood cells as it did as a fetus (since there is a higher concentration of oxygen in the air than what was available through the umbilical vein). The newborn\'s liver processes the breakdown of the extra red blood cells, but some bilirubin does build up in the blood. Normally bilirubin levels drop to a low level without any intervention required. In babies where the bilirubin levels are a concern (particularly in pre-term infants), a common treatment is to use UV lights (\"bili lights\") on the newborn baby. ## Changes in body Size and Muscle fat makeup By the end of the first year an infant\'s height is increased by 50% and by the age of 2 the baby will have grown 75% greater. By 5 months a baby will have doubled its weight, and tripled its weight by the first year. By the age of 2, a baby\'s weight will have quadrupled. Infants and toddlers grow in little spurts over the first 21 months of life. A baby can go through periods of 7 to 63 days with no growth but they can add as much as an inch in one 24 hour period. During the day before a growth spurt, parents describe their babies as irritable and very hungry. The best way to estimate a child\'s physical maturity is to use *skeletal age*, a measure of bone development. This is done by having a x-ray of the long bones of the body to see the extent to which soft, pliable cartilage has hardened into bone. - Changes in body Proportions **Cephalocaudal trend** means that growth occurs from head to tail. The head develops more rapidly than the lower part of the body. At birth the head takes up to one fourth of the total body length and legs only one third. The lower body catches up by age 2 and the head accounts for only one fifth and legs for nearly one half of the body length. **Proximodistal trend** means that head growth proceeds literally from near to far or from center of the body outward. At birth the brain is nearer its adult shape and size than any other physical structure. The brain continues to develop at an astounding pace throughout infancy and toddlerhood. - The Brain Development The neurons of infants and adults differ in 2 significant ways: Growth of neural fibers and synapses increases connective structures. When synapses are formed, many surrounding neurons die. This occurs in 20 to 80 percent of the brain region. **Dendrites synapses**: Synapses are tiny gaps between neurons where fiber from different neurons come close together but do not touch. Neurons release chemicals that cross the synapses sending messages to one another. During the prenatal period the neural tube produces far more neurons than the brain will ever need. **Myelinization**: The coating of neural fibers with a fatty sheath called myelin that improves the efficiency of message transfer. Multi-layered lipid cholesterol and protein covering produced by neuralgia cause a rapid gain in overall size of brain due to neural fibers and myelination. **Synaptic pruning**: Neurons seldom stimulated soon loose their synapses. Neurons not needed at the moment return to an uncommitted state so they can support future development. However, if synaptic pruning occurs in old age neurons will lose their synapses. If neurons are stimulated at a young age, even though neurons were pruned, they will be stimulated again. **Cerebral Cortex**: Surrounding the brain, it is the largest most complex brain structure. The cortex is divided into four major lobes: occipital lobe, parietal lobe, temporal lobe, and frontal lobe which is the last to develop. **Brain plasticity**: The brain is highly plastic. Many areas are not yet committed to specific functions. If a part of the brain is damaged, other parts can take over tasks that they would not normally have handled. - Changing states of Arousal How children develop more regular "sleep patterns" around 4 to 6 months of age: Sleep patterns are more developed as the brain develops. It is not until the first year of life that the secretion of *melatonin*, a hormone produced in the brain, affects more drowsiness in the night than in the day. In addition, REM is decreased. ## Infancy !Infant Infancy is the period that follows the neonatal period and includes the first two years of life. During this time tremendous growth, coordination and mental development occur. Most infants learn to walk, manipulate objects and can form basic words by the end of infancy. Another characteristic of infancy is the development of deciduous teeth. **Deciduous Teeth** *Deciduous teeth*, otherwise known as milk teeth, baby teeth, or primary teeth, are the first set of teeth in the growth development of humans and many other animals. They develop during the embryonic stage of development and erupt - become visible in the mouth - during infancy. They are usually lost and replaced by permanent teeth, but in the absence of permanent replacements, they can remain functional for many years. (Concise) Deciduous teeth start to form during the embryo phase of pregnancy. The development of deciduous teeth starts at the sixth week of development as the dental lamina. This process starts at the midline and then spreads back into the posterior region. By the time the embryo is eight weeks old, there are ten areas on the upper and lower arches that will eventually become the deciduous dentition. These teeth will continue to form until they erupt in the mouth. In the deciduous dentition there are a total of twenty teeth: five per quadrant and ten per arch. In most babies the eruption of these teeth begins at the age of six months and continues until twenty-five to thirty-three months of age. The first teeth seen in the mouth are the mandibular centrals and the last are the maxillary second molars. However it is not unheard of for a baby to be born with teeth. right\|framed\|Deciduous teeth. The deciduous dentition is made up of centrals, laterals, canines, first molars, and second molars; there is one in each quadrant, making a total of four of each tooth. All of these are replaced with a permanent counterpart except for the first and second molars; they are replaced by premolars. These teeth will remain until the age of six. At that time, the permanent teeth start to appear in the mouth resulting in mixed dentition. The erupting permanent teeth causes root resorption, where the permanent teeth push down on the roots of the deciduous teeth causing the roots to be dissolved and become absorbed by the forming permanent teeth. The process of shedding deciduous teeth and the replacement by permanent teeth is called exfoliation. This will last from age six until age twelve. By age twelve there are only permanent teeth remaining. Deciduous teeth are considered essential in the development of the oral cavity by dental researchers and dentists. The permanent teeth replacements develop from the same tooth bud as the deciduous teeth; this provides a guide for permanent teeth eruption. Also the muscles of the jaw and the formation of the jaw bones depend on the primary teeth in order to maintain the proper space for permanent teeth. The roots of deciduous teeth provide an opening for the permanent teeth to erupt through. These teeth are also needed in the development of a child's ability to speak and chew their food correctly. ## Adolescence !United States\|American high school students{width="250"} Adolescence is the period of psychological and social transition between childhood and adulthood. Adolescence is the transitional stage of human development in which a juvenile matures into an adult. This transition involves biological, social, and psychological changes, though the biological ones are the easiest to measure objectively. The time is identified with dramatic changes in the body, along with developments in a person\'s psychology and academic career. In the onset of adolescence, children usually complete elementary school and enter secondary education, such as middle school or high school. A person between early childhood and the teenage years is sometimes referred to as a pre-teen or \'tween. Physical maturation resulting from puberty leads to an interest in sexual activities, sometimes leading to teenage pregnancy. Since teens may not be emotionally or mentally mature enough or financially able to support children, sexual activity among adolescents is considered problematic. At this age there is also a greater probability of drug and alcohol use, mental health disorders such as schizophrenia, eating disorders such as anorexia, and clinical depression. The unstable emotions or lack of emotional intelligence among some adolescents may also lead to youth crime. Searching for a unique identity is one of the problems that adolescents often face. Some, but not all, teenagers often challenge the authority or the rules as a way to establish their individuality. They may crave adulthood and be eager to find their place in society. While adolescents are eager to grow up and be treated like adults, they also idolize athletes, movie stars and celebrities. They want to be like these role models - whether or not these role models actually have qualities that should be aspired to. ### Female In females, puberty is caused by alterations in brain functions that result in increased secretion by the hypothalamus of gonadotropin-releasing hormone (GnRH). Increased levels of GnRH stimulate secretion of pituitary gonadatrophins FSH and LH which cause follicle development and estrogen secretion. Estrogen is responsible for accessory sex organs and secondary sex characteristics. Menarche, the first menstrual cycle, occurs at about 12.5 years of age as a result of the release of FSH. **Breast development** The first physical sign of puberty in girls is usually a firm, tender lump under the center of the areola(e) of one or both breasts, occurring on average at about 10.5 years. This is referred to as thelarche. By the widely used Tanner staging of puberty, this is stage 2 of breast development (stage 1 is a flat, prepubertal breast). Within 6-12 months, the swelling has clearly begun in both sides, softened, and can be felt and seen extending beyond the edges of the areolae. This is stage 3 of breast development. By another 12 months (stage 4), the breasts are approaching mature size and shape, with areolae and papillae forming a secondary mound. In most young women, this mound disappears into the contour of the mature breast (stage 5), although there is so much variation in sizes and shapes of adult breasts that distinguishing advanced stages is of little clinical value. **Pubic hair in girls** Pubic hair is often the second unequivocal change of puberty. It is referred to as pubarche and the pubic hairs are usually visible first along the labia. The first few hairs are described as Tanner stage 2. Stage 3 is usually reached within another 6--12 months, when the hairs are too numerous to count and appear on the mons as well. By stage 4, the pubic hairs densely fill the \"pubic triangle.\" Stage 5 refers to spread of pubic hair to the thighs and sometimes as abdominal hair upward towards the umbilicus. In about 15% of girls, the earliest pubic hair appears before breast development begins. **Vagina, uterus, ovaries** The mucosal surface of the vagina also changes in response to increasing levels of estrogen, becoming thicker and a duller pink in color (in contrast to the brighter red of the prepubertal vaginal mucosa). Whitish secretions (physiologic leukorrhea) are a normal effect of estrogen as well. In the next 2 years following thelarche, the uterus and ovaries increase in size. The ovaries usually contain small cysts visible by ultrasound. **Menstruation and fertility** The first menstrual bleeding is referred to as **menarche**. The average age of menarche in American girls is about 12.7 years, usually about 2 years after thelarche. Menses (menstrual periods) are not always regular and monthly in the first 2 years after menarche. Ovulation is necessary for fertility, and may or may not accompany the earliest menses. By 2 years after menarche, most girls are ovulating at least several times a year. Over 90% of girls who experience menarche before age 13 years are experiencing very regular, predictable menses accompanied by ovulation within 2 years, and a higher proportion of those with later menarche may not establish regular ovulation for 4 years or more. However, initiation of ovulation after menarche is not inevitable, and a high proportion of girls with continued irregularity several years from menarche will continue to have prolonged irregularity and anovulation, and are at higher risk for reduced fertility. **Pelvic shape, fat distribution, and body composition** During this period, also in response to rising levels of estrogen, the lower half of the pelvis widens. This prepares the body for the time when she will give birth by enlarging the birth canal. Fat tissue increases to a greater percentage of the body composition than in males, especially in the typical female distribution of breasts, hips, and thighs. This produces the typical female body shape. Also, the fat goes to the buttocks of a girl, giving their buttocks more shape and curve. **Body and facial hair in girls** In the months and years following the appearance of pubic hair, other areas of skin which respond to androgens develop heavier hair (androgenic hair) in roughly the following sequence: underarm (axillary) hair, perianal hair, upper lip hair, sideburn (preauricular) hair, and periareolar hair. Arm and leg hair becomes heavier gradually over a period of 10 years or more. While the appearance of hair in some of these areas is not always wanted, particularly in Western culture, it rarely indicates a hormone imbalance unless it occurs elsewhere as well, such as under the chin and in the midline of the chest. **Height growth in girls** The estrogen-induced pubertal growth spurt in girls begins at the same time the earliest breast changes begin, or even a few months before, making it one of the earliest manifestations of puberty in girls. Growth of the legs and feet accelerates first, so that many girls have longer legs in proportion to their torso in the first year of puberty. The rate of growth tends to reach a peak velocity (as much as 7.5-10 cm or 3-4 inches per year) midway between thelarche and menarche and is already declining by the time menarche occurs. In the 2 years following menarche most girls grow about 5 cm (2 inches) before growth ceases at maximal adult height. This last growth primarily involves the spine rather than the limbs. **Body odor, skin changes, and acne** right\|framed\|**Acne** on the face and body. Rising levels of androgens can change the fatty acid composition of perspiration, resulting in a more \"adult\" body odor. This often precedes thelarche and pubarche by 1 or more years. Another androgen effect is increased secretion of oil (sebum) from the skin. This change increases the susceptibility to acne vulgaris, a characteristic affliction of puberty greatly variable in its severity. ### Male The onset of puberty for males is similar to that of females. GnRH secretion from the hypothalamus results in an increase in pituitary gonadatropins secretion of LH / ICSH and FSH. The pituitary gonadatropins stimulate the seminiferous tubules and testosterone secretion. Testosterone causes changes in the accessory reproductive organs, secondary sex characteristics and male sex drive. **Testicular size, function, and fertility** In boys, testicular enlargement is the first physical manifestation of puberty. It is termed gonadarche. The testes in prepubertal boys change little in size from about 1 year of age to the onset of puberty, averaging about 2--3 cc in volume and about 1.5-2 cm in length. Testicular size continues to increase throughout puberty, reaching maximal adult size about 6 years later. While 18-20 cc is reportedly an average adult size, there is wide variation in the normal population. The testes have two primary functions: to produce hormones and to produce sperm. The Leydig cells produce testosterone (as described below), which in turn produces most of the changes of male puberty. However, most of the increasing bulk of testicular tissue is spermatogenic tissue (primarily Sertoli and interstitial cells). The development of sperm production and fertility in males is not as well documented. Sperm can be detected in the morning urine of most boys after the first year of pubertal changes (and occasionally earlier). **Genitalia** A boy\'s penis grows little from the fourth year of life until puberty. Average prepubertal penile length is 4 cm. The prepubertal genitalia are described as stage 1. Within months after growth of the testes begins, rising levels of testosterone promote growth of the penis and scrotum. This earliest discernible beginning of pubertal growth of the genitalia is referred to as stage 2. The penis continues to grow until about 21 years of age, reaching an average adult size of about 7-15.5 cm. Although erections and orgasms occur in prepubertal boys, they become much more common during puberty, accompanied by a markedly increased libido. Ejaculation becomes possible early in puberty; prior to this boys may experience dry orgasms. Emission of seminal fluid may occur due to masturbation or spontaneously during sleep (commonly termed a wet dream, and more clinically called a nocturnal emission). The ability to ejaculate is a fairly early event in puberty compared to the other characteristics. However, in parallel to the irregularity of the first few periods of a girl, for the first one or two years after a boy\'s first ejaculation, his seminal fluid may contain few active sperm. **Pubic hair in boys** Pubic hair often appears on a boy shortly after the genitalia begin to grow. As in girls, the first appearance of pubic hair is termed pubarche and the pubic hairs are usually first visible at the dorsal (abdominal) base of the penis. The first few hairs are described as stage 2. Stage 3 is usually reached within another 6--12 months, when the hairs are too numerous to count. By stage 4, the pubic hairs densely fill the \"pubic triangle.\" Stage 5 refers to spread of pubic hair to the thighs and upward towards the umbilicus as part of the developing abdominal hair. **Body and facial hair in boys** In the months and years following the appearance of pubic hair, other areas of skin which respond to androgens develop heavier hair (androgenic hair) in roughly the following sequence: underarm (axillary) hair, perianal hair, upper lip hair, sideburn (preauricular) hair, periareolar hair, and the rest of the beard area. Arm, leg, chest, abdominal, and back hair become heavier more gradually. There is a large range in amount of body hair among adult men, and significant differences in timing and quantity of hair growth among different ethnic groups. **Voice change** Under the influence of androgens, the voice box, or larynx, grows in both genders. This growth is far more prominent in boys, causing the male voice to drop, rather abruptly, about one octave, because the larger vocal folds have a lower fundamental frequency. Occasionally, this is accompanied by cracking and breaking sounds in the early stages. Most of the voice change happens during stage 4 of male puberty around the time of peak growth. However, it usually precedes the development of significant facial hair by several months to years. **Height growth in boys** Compared to girls\' early growth spurt, growth accelerates more slowly in boys and lasts longer, resulting in a taller adult stature among males than females (on average about 10 cm or 4 inches). The difference is attributed to the much greater potency of estradiol compared to testosterone in promoting bone growth, maturation, and epiphyseal closure. In boys, growth begins to accelerate about 9 months after the first signs of testicular enlargement and the peak year of the growth spurt occurs about 2 years after the onset of puberty, reaching a peak velocity of about 8.5--12 cm or 3.5--5 inches per year. The feet and hands experience their growth spurt first, followed by the limbs, and finally ending in the trunk. Epiphyseal closure and adult height are reached more slowly, at an average age of about 17.5 years. As in girls, this last growth primarily involves the spine rather than the limbs. **Male musculature and body shape** By the end of puberty, adult men have heavier bones and nearly twice as much skeletal muscle. Some of the bone growth (e.g., shoulder width and jaw) is disproportionately greater, resulting in noticeably different male and female skeletal shapes. The average adult male has about 150% of the lean body mass of an average female, and about 50% of the body fat. This muscle develops mainly during the later stages of puberty, and muscle growth can continue even after a male is biologically adult. The peak of the so-called \"strength spurt,\" the rate of muscle growth, is attained about one year after a male experiences his peak growth rate. **Breast development in boys: pubertal gynecomastia** Estradiol is produced from testosterone in male puberty as well as female, and male breasts often respond to the rising estradiol levels. This is termed gynecomastia. In most boys, the breast development is minimal, similar to what would be termed a \"breast bud\" in a girl, but in many boys, breast growth is substantial. It usually occurs after puberty is underway, may increase for a year or two, and usually diminishes by the end of puberty. It is increased by extra adipose tissue if the boy is overweight. Although this is a normal part of male puberty, breast development for some boys is as unwelcome as upper lip hair in girls. If the boy\'s distress becomes too substantial during development, breast tissue can be removed and corrected surgically. ## Adulthood The term \"adult\" generally refers to a fully developed person from maturity (the end of puberty) onward. The age at which a person is physiologically an adult is age 17 for females and age 18 for males. Adulthood can also refer to a person\'s ability to care for them self independently, and raise a family of their own; or it can simply mean reaching a specified age. Graduating high school, residing in one\'s own residence and attaining financial independence are all synonymous with adulthood in the United States. ### Adult characteristics There are some qualities that symbolize adultness in most cultures. Not always is there a concordance between the qualities and the physical age of the person. The adult character is comprised of: - **Self-control** - restraint, emotional control. - **Stability** - stable personality, strength. - **Independence** - ability to self-regulate. - **Seriousness** - ability to deal with life in a serious manner. - **Responsibility** - accountability, commitment and reliability. - **Method/Tact** - ability to think ahead and plan for the future, patience. - **Endurance** - ability and willingness to cope with difficulties that present themselves. - **Experience** - breadth of mind, understanding. - **Objectivity** - perspective and realism. !This diagram shows Maslow\'s hierarchy of needs, represented as a pyramid with the more primitive needs at the bottom.{width="400"} Abraham Maslow, a psychologist, developed Maslow\'s Hierarchy of Needs. It is a chart outlining basic needs that a person must meet to function and survive in life. It also attempts to explain what motivates people in life. The needs on the lower level must be met before moving up the ladder, as the higher needs only come into focus once all the needs that are lower down in the pyramid are satisfied. People can get stuck on levels and some people may never reach certain levels because of circumstances in their life. When one stage is fulfilled you naturally move to the next. **Physical or Physiological:** These include shelter, oxygen, food, water, rest and elimination, all of which are vital to a person\'s life and essential to survival. **Security or Safety:** This involves not only actually being secure and safe, but also the feeling of safety and security. This is something that people typically learn from their childhood and something that helps lay the groundwork for developing other skills and moving up to the next step in the ladder. **Social (Love/Belonging):** This involves developing friendships and eventually relationships. This involves emotionally-based relationships in general, such as friendship, sexual intimacy, and having a supportive and communicative family. **Esteem:** This is where people learn to develop self-esteem and confidence. According to Maslow, all humans have a need to be respected, to have self-respect, and to respect others. People need to engage themselves in order to gain recognition and have an activity or activities that give the person a sense of contribution, be it in a profession or hobby, **Self-Actualization:** The highest level you can reach according to Maslow. Maslow writes the following of self-actualizing people: - They embrace the facts and realities of the world (including themselves) rather than denying or avoiding them. - They are spontaneous in their ideas and actions. - They are creative. - They are interested in solving problems; this often includes the problems of others. Solving these problems is often a key focus in their lives. - They feel a closeness to other people, and generally appreciate life. - They have a system of morality that is fully internalized and independent of external authority. - They have discernment and are able to view all things in an objective manner. Prejudices are absent. In short, self-actualization is reaching one\'s fullest potential. Most people accomplish the two lower levels in their lifetime, but may get stuck on upper levels. While self-actualization is a useful concept to many, others insist there is no proof that every individual has this capacity or even the goal to achieve it. ## Menopause Menopause occurs as the ovaries stop producing estrogen, causing the reproductive system to gradually shut down. As the body adapts to the changing levels of natural hormones, vasomotor symptoms such as hot flashes and palpitations, psychological symptoms such as increased depression, anxiety, irritability, mood swings and lack of concentration, and atrophic symptoms such as vaginal dryness and urgency of urination appear. Together with these symptoms, the woman may also have increasingly scanty and erratic menstrual periods. Technically, menopause refers to the cessation of menses; whereas the gradual process through which this occurs, which typically takes a year but may last as little as six months or more than five years, is known as climacteric. Popular use, however, replaces climacteric with menopause. A natural or physiological menopause is that which occurs as a part of a woman\'s normal aging process. However, menopause can be surgically induced by such procedures as hysterectomy (when this procedure includes oophorectomy, removal of the ovaries). The average onset of menopause is 50.5 years, but some women enter menopause at a younger age, especially if they have suffered from cancer or another serious illness and undergone chemotherapy. Premature menopause (or premature ovarian failure) is defined as menopause occurring before the age of 40, and occurs in one percent of women. Other causes of premature menopause include autoimmune disorders, thyroid disease, and diabetes mellitus. Premature menopause is diagnosed by measuring the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH); the levels of these hormones will be higher if menopause has occurred. Rates of premature menopause have been found to be significantly higher in both fraternal and identical twins; approximately five percent of twins reach menopause before the age of 40. The reasons for this are not completely understood. Transplants of ovarian tissue between identical twins have been successful in restoring fertility. Post-menopausal women, especially Caucasian women of European descent, are at increased risk of osteoporosis. Animals other than human beings rarely experience menopause, possibly because they simply do not live long enough to reach it. However, recent studies have shown menopause in gorillas, with an average age of 44 at onset. Perimenopause refers to the time preceding menopause, during which the production of hormones such as estrogen and progesterone diminishes and becomes more irregular. During this period fertility diminishes. Menopause is arbitrarily defined as a minimum of twelve months without menstruation. Perimenopause can begin as early as age 35, although it usually begins much later. It can last for a few months or for several years. The duration of perimenopause cannot be predicted in advance. ### Grandmother Hypothesis Human females have the unique distinction of being one of the only species to stop reproduction well before the end of their life span. This evolutionary distinction is odd because most other species continue to reproduce until death, thus maximizing the number of offspring they produce. The grandmother hypothesis essentially states that the presence of a grandmother has beneficial effect on the survival of an infant. Humans are one of the slowest developing species in the animal kingdom, and unlike many species, infants, toddlers and children must be continuously cared for to ensure their survival. (Compare that to the salmon that swims up stream, spawns and dies.) ### Etiology The cessation of menses is the result of the eventual atresia (degeneration and reabsorption) of almost all oocytes in the ovaries. This causes an increase in circulating FSH and LH levels as there are a decreased number of oocytes responding to these hormones and producing estrogen. This decrease in the production of estrogen leads to the post-menopausal symptoms of hot flashes, insomnia, osteoporosis, atherosclerosis, vaginal atrophy and depression. Cigarette smoking has been found to decrease the age of menopause by as much as one year however, premature menopause (before the age of 40) is generally idiopathic. ### Symptoms The clinical features of menopause are caused by the estrogen deficiency. - vasomotor instability - hot flashes, hot flushes - sleep disturbances - Urogenital atrophy - dyspareunia - itching - dryness - bleeding - urinary frequency - urinary urgency - urinary incontinence - skeletal **Breast Atrophy** - skin thinning - decreased elasticity - Psychological **Mood Disturbance** - irritability - fatigue - decreased libido - memory loss - depression **Treatments:** Medical treatments for menopausal symptoms have been developed. Most notably, Hormone Replacement Therapy (HRT), has been used to reduce the weakening of bones (known as osteoporosis). However, some women have resisted the implication that menopause is a disorder, seeing it as a natural stage of life. There has also been scientific controversy over whether the benefits of HRT outweigh the risks. For many years, women were advised to take hormone therapy after menopause to reduce their risk of heart disease and various aspects of aging. However, a large, randomized, controlled trial (the Women\'s Health Initiative) found that women undergoing HRT had an increased risk of Alzheimer\'s disease, breast cancer, heart disease and stroke. ### Osteoporosis Osteoporosis is a skeletal disease resulting in bone loss and changes in the bone quality that leads to diminished bone strength and an increased risk to sustain fractures. The main cause of osteoporosis is a loss estrogen following menopause. Osteoporosis can be prevented and treated using a number of different drugs and lifestyle modifications including proper diet, exercise and hormone replacement therapy. The link to Wikipedia Osteoporosis is a great source of additional information. **Preventing Osteoporosis** The old saying that an ounce of prevention is worth a pound of cure holds true for osteoporosis. In researching osteoporosis I found that while there are some treatments for osteoporosis, a healthy lifestyle throughout your life is a much more effective way of combating the effects of this disease. It is generally acknowledged that a regular weight bearing exercise plan is helpful in maintaining bone mass. Additionally, adequate dietary calcium and vitamin D intake throughout ones life are important factors in building up and maintaining bone mass. Estrogen and progesterone treatments in postmenopausal women have proven to be effective in treating bone loss. There are also two groups of drugs that interfere with the re-absorption of bone by osteoclasts called bisphosphonates and lective estrogen receptor modulators (SERMS). An estimated 52 million men and woman will be afflicted with crumbling, weakened bones by the year 2010. Osteoporosis is three to four times more common in woman than men. While some men do get osteoporosis, they are less likely to do so because men have frames that are 25 percent larger and heavier than women. Women are also more susceptible to the disease because they are more likely than a man to go on crash diets. This kind of diet may interfere with the three main factors associated with osteoporosis and having healthy bones: having enough vitamin D, having enough calcium, and having enough estrogen. There are approximately 1 million to 1.3 million hip fractures every year that are related to osteoporosis. Men on steroids, people with arthritis, people undergoing chemotherapy, along with those suffering from anorexia all have an increased chance of having osteoporosis. #### Osteoporosis related links Wikipedia Osteoporosis Page This is a wikipedia link with a complete discussion of osteoporosis. National Osteoporosis Foundation This page links to the National Osteoporosis Foundation ## Old Age !Hmong women{width="220"} ### Why do people age? Some researchers believe we are programmed by an internal biological clock to age. The idea is that each type of cell, tissue and organ is like a clock that ticks at its own pace. In the body our cells divide 80 to 90 times at the most. At the end of each chromosome there are repeated stretches of DNA called telomeres. These Telomeres prevent Uncontrollable division which might lead to genetic deficits , producing Cancer cells. A bit of each telomere is lost during every cell division. When only a nub remains the cells stop dividing and die. A different hypothesis is that aging is a result of accumulated damage to DNA from environmental attacks and a decline in DNA\'s mechanism of self repair. Things such as free radicals attack DNA and other molecules causing structural changes. These changes in DNA endanger the synthesis of enzymes and other proteins that are required for life. This damage interferes with cell division. Organ wear out (over time) can cause excessive damage to DNA ; unable to repair itself , DNA slowly starts degrading in function thus increasing the chance of mistakes in replication . Most researchers believe that aging is a combination of an internal clock that ticks out the life span of cells and the accumulation damage to DNA. ## Old Age Diseases ### Diabetes Diabetes mellitus is a disease characterized by persistent hyperglycemia (high blood sugar levels), resulting either from inadequate secretion of the hormone insulin, an inadequate response of target cells to insulin, or a combination of these factors. Diabetes is a metabolic disease requiring medical diagnosis, treatment and lifestyle changes Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans of the pancreas. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. This type comprises up to 10% of total cases in North America and Europe, though this varies by geographical location. This type of diabetes can affect children or adults, but has traditionally been termed \"juvenile diabetes\" because it represents a majority of cases of diabetes affecting children. The most common cause of beta cell loss leading to type 1 diabetes is autoimmune destruction, accompanied by antibodies directed against insulin and islet cell proteins. The principal treatment of type 1 diabetes, even from the earliest stages, is replacement of insulin. Without insulin, ketosis and diabetic ketoacidosis can develop. Type 2 diabetes mellitus is due to a combination of defective insulin secretion and defective responsiveness to insulin (often termed reduced insulin sensitivity). In early stages the predominant abnormality is reduced insulin sensitivity, characterized by elevated levels of insulin in the blood. The initial defect of insulin secretion is subtle and initially involves only the earliest phase of insulin secretion. In the early stages, hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver, but as the disease progresses the impairment of insulin secretion worsens, and therapeutic replacement of insulin often becomes necessary. Type 2 diabetes is quite common, comprising 90% or more of cases of diabetes in many populations. There is a strong association with obesity and with aging, although in the last decade it has increasingly begun to affect older children and adolescents. In the past, this type of diabetes was often termed adult-onset diabetes or maturity-onset diabetes. Gestational diabetes, Type III, also involve a combination of inadequate insulin secretion and responsiveness, resembling type 2 diabetes in several respects. It develops during pregnancy and may improve or disappear after delivery. Even though it may be transient, gestational diabetes may damage the health of the fetus or mother, and about 40% of women with gestational diabetes develop type 2 diabetes later in life. ### Congestive Heart Failure Congestive heart failure (CHF), also called congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. It is not to be confused with \"cessation of heartbeat\", which is known as asystole, or with cardiac arrest, which is the cessation of normal cardiac function in the face of heart disease. Because not all patients have volume overload at the time of initial or subsequent evaluation, the term \"heart failure\" is preferred over the older term \"congestive heart failure\". Congestive heart failure is often undiagnosed due to a lack of a universally agreed definition and difficulties in diagnosis, particularly when the condition is considered \"mild\". ### Stroke !Stroke{width="150"} A stroke, also known as cerebrovascular accident (CVA), is an acute neurologic injury whereby the blood supply to a part of the brain is interrupted. Stroke can also be said to be a syndrome of sudden loss of neuronal function due to disturbance in cerebral perfusion. This disturbance in perfusion is commonly on the arterial side of the circulation, but can be on the venous side. The part of the brain with disturbed perfusion can no longer receive adequate oxygen carried by the blood; brain cells are therefore damaged or die, impairing function from that part of the brain. Stroke is a medical emergency and can cause permanent neurologic damage or even death if not promptly diagnosed and treated. It is the third leading cause of death and adult disability in the US and industrialized European nations. On average, a stroke occurs every 45 seconds and someone dies every 3 minutes. Of every 5 deaths from stroke, 2 occur in men and 3 in women. ### Progeria The term Progeria narrowly refers to Hutchinson-Gilford Progeria syndrome, but the term is also used more generally to describe any of the so-called \"accelerated aging diseases\". The word progeria is derived from the Greek for \"prematurely old\". Because the \"accelerated aging\" diseases display different aspects of aging, but never every aspect, they are often called \"segmental progerias\" by biogerontologists. Hutchinson-Gilford Progeria syndrome is an extremely rare genetic condition which causes physical changes that resemble greatly accelerated aging in sufferers. The disease affects between 1 in 4 million (estimated actual) and 1 in 8 million (reported) newborns. Currently, there are approximately 40-45 known cases in the world. There is no known cure. Most people with progeria die around 13 years of age. Progeria is of interest to scientists because the disease may reveal clues about the process of aging. Unlike most other \"accelerated aging diseases\" (such as Werner\'s syndrome, Cockayne\'s syndrome or xeroderma pigmentosum), progeria is not caused by defective DNA repair. It is caused by mutations in a LMNA (Lamin A protein) gene on chromosome 1. Nuclear lamina is a protein scaffold around the edge of the nucleus that helps organize nuclear processes such as RNA and DNA synthesis. ## The effects of Aging on the Body ### **Cardiovascular System** The heart loses about 1% of its reserve pumping capacity every year after we turn 30. Change in blood vessels that serve brain tissue reduce nourishment to the brain, resulting in the malfunction and death of brain cells. By the time we turn 80, cerebral blood flow is 20% less, and renal blood flow is 50% less than when we were age 30. As we age our heart goes through certain structural changes: the walls of the heart thicken and the heart becomes heavier, heart valves stiffen and are more likely to calcify, and the aorta, the major vessel carrying blood out of the heart, becomes larger. Heart Attack / Myocardial infarction:Acute myocardial infarction (AMI or MI), commonly known as a heart attack, is a disease that occurs when the blood supply to a part of the heart is interrupted, causing death of heart tissue. It is the leading cause of death for both men and women all over the world. The term myocardial infarction is derived from myocardium (the heart muscle) and infarction (tissue death). The phrase \"heart attack\" sometimes refers to heart problems other than MI, such as unstable angina pectoris and sudden cardiac death. ```{=html} <!-- --> ``` Congestive Heart Failure: In the elderly, ventricular diastolic stiffness can lead to pulmonary circulatory congestion. Aortic stenosis and aortic insufficiency, elevate left ventricular preload to the point where the left ventricle becomes stiff and noncompliant, and is common in people 75 years of age or older. Elevated pressures are transmitted to the pulmonary vasculature and lead to pulmonary edema. ### **Musculoskeletal System** Bones: Aging is accompanied by the loss of bone tissue. The haversian systems in compact bone undergo slow erosion, lacunae are enlarged, canals become widened, and the endosteal cortex converts to spongy bone. The endosteal surface gradually erodes until the rate of loss exceeds the rate of deposition. Bone remodeling cycle takes longer to complete because bone cells slow in the rate of resorption and deposition of bone tissue. The rate of mineralization also slows down. The number of bone cells also decreases because the bone marrow becomes fatty and unable to provide an adequate supply of precursor cells. Because bones become less dense, they become more prone to fractures. Although bone degeneration is inevitable, it is variable if steps are taken before the mid-twenties -around this time our bones break down faster than they rebuild. Bone density increases when our bones are stressed, so physical activity is important. Vitamins and good diet also help build up bone mass. ```{=html} <!-- --> ``` Joints: Cartilage becomes more rigid, fragile, and susceptible to fibrillation. Loss of elasticity and resiliency is attributed to more cross-linking of collagen to elastin, decrease in water content, and decreasing concentrations of glycosaminoglycans. Joints are also more prone to fracture due to the loss of bone mass. ```{=html} <!-- --> ``` Muscles: Decrease in the range of motion of the joint is related to the change of ligaments and muscles. As the body ages, muscle bulk and strength declines especially after the age of 70. As much as 30% of skeletal muscle are lost by age 80. Muscle fibers, RNA synthesis and mitochondrial volume loss may all be contributors to muscle decline. Other factors that could contribute to muscle loss of the aged are: change in activity level, reduced nerve supply to muscle, cardiovascular disease, and nutritional deficiencies. In women, menopause will cause muscle mass to decrease significantly, especially in the first three post-menopausal years. ### **Nervous System** One of the effects of aging on the nervous system is the loss of neurons. By the age of 30, the brain begins to lose thousands of neurons each day. The cerebral cortex can lose as much as 45% of its cells and the brain can weigh 7% less than in the prime of our lives. Associated with the loss of neurons comes a decreased capacity to send nerve impulses to and from the brain. Because of this the processing of information slows down. In addition the voluntary motor movement\'s slow down, reflex time increases, and conduction velocity decreases. Parkinson\'s disease is the most common movement disorder of the nervous system. As we age there are some degenerative changes along with some disease\'s involving the sense organ\'s that can alter vision, touch, smell, and taste. Loss of hearing is also associated with aging. It is usually the result of changes in important structures of the inner ear. #### Dementia Dementia (from Latin de- \"apart, away\" + mens (genitive mentis) \"mind\") is the progressive decline in cognitive function due to damage or disease in the brain beyond what might be expected from normal aging. Particularly affected areas may be memory, attention, language and problem solving, although particularly in the later stages of the condition, affected persons may be disoriented in time (not knowing what day, week, month or year it is), place (not knowing where they are) and person (not knowing who they are). Symptoms of dementia can be classified as either reversible or irreversible depending upon the etiology of the disease. Less than 10% of all dementias are reversible. Dementia is a non-specific term that encompasses many disease processes, just as fever is attributable to many etiologies. #### Alzheimers disease Alzheimer\'s disease (AD) is a neurodegenerative disease characterized by progressive cognitive deterioration together with declining activities of daily living and neuropsychiatric symptoms or behavioral changes. It is the most common cause of dementia. The most striking early symptom is short term memory loss (amnesia), which usually manifests as minor forgetfulness that becomes steadily more pronounced with illness progression, with relative preservation of older memories. As the disorder progresses, cognitive (intellectual) impairment extends to the domains of language (aphasia), skilled movements (apraxia), recognition (agnosia), and those functions (such as decision-making and planning) closely related to the frontal and temporal lobes of the brain as they become disconnected from the limbic system, reflecting extension of the underlying pathological process. This consists principally of neuronal loss or atrophy, together with an inflammatory response to the deposition of amyloid plaques and neurofibrillary tangles. Genetic factors are known to be important, and autosomal dominant mutations in three different genes (presenilin 1, presenilin 2, and amyloid precursor protein) have been identified that account for a small number of cases of familial, early-onset AD. For late onset AD (LOAD), only one susceptibility gene has so far been identified: the epsilon 4 allele of the apolipoprotein E gene. Age of onset itself has a heritability of around 50%. ### **Digestive System** The changes associated with aging of the digestive system include loss of strength and tone of muscular tissue and supporting muscular tissue, decreased secretory mechanisms, decreased motility of the digestive organs, along with changes in neurosensory feedback regarding enzyme and hormone release, and diminished response to internal sensations and pain. In the upper GI tract common changes include periodontal disease, difficulty in swallowing, reduced sensitivity to mouth irritations and sores, loss of taste, gastritis, and peptic ulcer disease. Changes that may appear in the small intestine include, appendicitis, duodenal ulcers, malabsorption, and maldigestion. Other pathologies that increase in occurrence with age are acute pancreatitis, jaundice, and gallbladder problems. Large intestinal changes such as hemorrhoids and constipation may also occur. Cancer of the rectum are quite common. ### **Urinary System** As we get older kidney function diminishes. By the age of 70, the filtering mechanism is only about half as effective as it was at age 40. Because water balance is altered and the sensation of thirst diminishes with age, older people are more susceptible to dehydration. This causes more urinary tract infections in the elderly. other problems may include nocturia (excessive urination at night), increased frequency of urination, polyuria (excessive urine production), dysuria (painful urination), incontinence, and hematuria (blood in the urine). Some kidney diseases that are common as we age include acute and chronic kidney inflammations and renal calculi (kidney stones). The prostate gland is often implicated in various disorders of the urinary tract. Prostate cancer is the most common cancer in elderly males. Because the prostate gland encircles part of the urethra, an enlarged prostate gland may cause difficulty in urination ### **Respiratory Systems** With the advancing of age, the airways and tissue of the respiratory tract become less elastic and more rigid. The walls of the alveoli break down, so there is less total respiratory surface available for gas exchange. This decreases the lung capacity by as much as 30% by the age of 70. Therefore, elderly people are more susceptible to pneumonia, bronchitis, emphysema, and other pulmonary disorders. For a more complete discussion of the respiratory system please visit Chapter 12 The Respiratory System. #### Lung cancer right\|framed\|Correlation between lung cancer and smoking tobacco. Lung cancer is a cancer of the lungs characterized by the presence of malignant tumors. Most commonly it is bronchogenic carcinoma (about 90%). Lung cancer is one of the most lethal forms of cancer worldwide, causing up to 3 million deaths annually. Only one in ten patients diagnosed with this disease will survive the next five years. Although lung cancer was previously an illness that affected predominately men, lung cancer rate for women has been increasing in the last few decades. This has been attributed to the rising ratio of female to male smokers. More women die of lung cancer than any other cancer, including breast cancer, ovarian cancer and uterine cancers combined. Current research indicates that the factor with the greatest impact on risk of lung cancer is long-term exposure to inhaled carcinogens. The most common means of such exposure is tobacco smoke. #### Vision Changes in vision begin at an early age. The cornea becomes thicker and less curved. The anterior chamber decreases in size and volume. The lens becomes thicker and more opaque, and also increases rigidity and loses elasticity. The ciliary muscles atrophy and the pupil constricts. There is also a reduction of rods and nerve cells of the retina. #### Hearing Approximately one third of people over the age of 65 have hearing loss. The ability to distinguish between high and low frequency diminishes with age. Loss of hearing for sounds of high-frequency (presbycusis) is the most common, although the ability to distinguish sound localization also decreases. It is believed that the hearing loss isn\'t so much an age change as it is due to the accumulation of noise damage. #### Taste and Smell Sensitivity to odors and taste decline with age. The sense of smell begins to degenerate with the loss of olfactory sensory neurons and loss of cells from the olfactory bulb. The decline in taste sensation is more gradual than that of smell. The elderly have trouble differentiating between flavors. The number of fungiform papillae of the tongue decline by 50% by the age of 50. Taste could also be affected by the loss of salivary gland secretions, notably amylase. This loss of taste and smell can have a significant effect on an elder\'s health. With the reduced ability to taste and smell, it is difficult to adjust food intake as they can no longer rely on their taste receptors to tell them if something is too salty, or too sweet. This can also cause the problem in that they might not be able to detect if something is spoiled, making them at a higher risk for food poisoning. ### **Cellular Aging** As people age, oxygen intake decreases as well as the basal metabolic rate. The decrease in the metabolic rate, delayed shivering response, sedentary lifestyle, decreased vasoconstrictor response, diminished sweating, and poor nutrition are reasons why the elderly cannot maintain body temperature. There is also a decrease in total body water (TBW). In newborns, TBW is 75% to 80%. TBW continues to decline in childhood to 60% to 65%, to less than 60% in adults. ### **Organism Aging** Aging is generally characterized by the declining ability to respond to stress, increasing homeostatic imbalance and increased risk of disease. Because of this, death is the ultimate consequence of aging. Differences in maximum life span between species correspond to different \"rates of aging\". For example, inherited differences in the rate of aging make a mouse elderly at 3 years and a human elderly at 90 years. These genetic differences affect a variety of physiological processes, probably including the efficiency of DNA repair, antioxidant enzymes, and rates of free radical production. ## Life Expectancy <http://www.senescence.info/definitions.html> ## Stages of Grief- Death and Dying We go through several stages of grief as we near death, receive catastrophic news, or go through some type of life-altering experience. There are five defined stages according to Elisabeth Kübler-Ross. She states, however, that these steps don\'t always come in order, and are not always experienced all together by everyone. She does claim that a person will always experience at least two of the stages. The stages are: **Denial**- This isn\'t happening, there must have been some mistake. **Anger**- Why me? It\'s not fair, how could you do this to me?!? (aimed toward some other \"responsible\" party) **Bargaining**- Just give me 2 more years\...let me live to see\_\_\_\_\_\_\_\_. **Depression**- extreme sadness, lack of motivation or desire to fight anymore **Acceptance**- I\'m ok with this. ## Sidenotes: Aubrey de Grey Aubrey David Nicholas Jasper de Grey, Ph.D., (born 20 April 1963 in London, England) is a controversial biomedical gerontologist who lives in the city of Cambridge, UK. He is working to expedite the development of a cure for human aging, a medical goal he refers to as engineered negligible senescence. To this end, he has identified what he concludes are the seven areas of the aging process that need to be addressed medically before this can be done. He has been interviewed in recent years in many news sources, including CBS 60 Minutes, BBC, the New York Times, Fortune Magazine, and Popular Science. His main activities at present are as chairman and chief science officer of the Methuselah Foundation and editor-in-chief of the academic journal Rejuvenation Research. Here are the seven biological causes of senescence and possible solutions: 1. Cell loss or atrophy. Cell depletion can be partly corrected by therapies involving exercise and growth factors. But stem cell therapy is almost certainly required for any more than just partial replacement of lost cells. This research would involve a large number of details, but is occurring on many fronts. 2. Nuclear mutations and epimutations. A mutation in a functional gene of a cell can cause that cell to malfunction or to produce a malfunctioning product. Because of the sheer number of cells Dr. de Grey believes that redundancy takes care of this problem, although cells that have mutated to produce toxic products might have to be disabled. In Dr. de Grey\'s opinion, the effect of mutations and epimutations that really matters is cancer, since if even one cell turns into a cancer cell it might spread and become deadly. This is to be corrected by whole-body interdiction of lengthening telomeres, or any other cure for cancer, if any is ever found. 3. Mutant mitochondria. Because of the highly oxidative environment in mitochondria and their lack of the sophisticated repair systems found in the cell nucleus, mitochondrial mutations are believed to a be a major cause of progressive cellular degeneration. This is to be corrected by moving the DNA for mitochondria completely within the cellular nucleus, where it is better protected. In humans all but 13 proteins are already protected in this way. It has been experimentally shown the operation is feasible. 4. Cellular senescence. Cellular senescence might be corrected by forcing senescent cells to destroy themselves, a process called apoptosis. Cell killing with suicide genes or vaccines was suggested for making the cells do apoptosis. Healthy cells would multiply to replace them. 5. Extracellular cross-links. These are chemical bonds between structures that are part of the body, but not within a cell. In senescent people many of these become brittle and weak. The proposal is to further develop small-molecular drugs and enzymes to break links caused by sugar-bonding (glycation), and other common forms of chemical linking. 6. Junk outside cells. Junk outside cells might be removed by enhanced phagocytosis (the normal process used by the immune system), and small drugs able to break chemical beta-bonds. The large junk in this class can be removed surgically. Junk here means useless things accumulated by a body, but which cannot be digested or removed by its processes, such as the amyloid plaques characteristic of Alzheimer\'s disease. The oft-mentioned \'toxins\' that people claim cause many diseases would probably also fit under this class. 7. Junk inside cells. Junk inside cells might be removed by adding new enzymes to the cell\'s natural digestion organ, the lysosome. These enzymes would be taken from bacteria, molds and other organisms that are known to completely digest animal bodies. Dr. de Grey\'s research proposals are highly controversial, with many critics arguing the highly complicated biomedical phenomena involved contain too many unknowns for intervention to be considered remotely foreseeable. ## Discoveries In Growth And Development - **Medieval times** In this time the thought was once children emerged form infancy, they were regarded as miniature already formed adults. - **Religious influence of parenting 16th Century** Puritan belief harsh restrictive parenting practices were recommended as the most efficient means of taming the depraved child. - **John Locke\'s 17th Century** Tabula Rosa = Blank slate in this the thought was that children are to begin with nothing at all and all kinds of experiences can shape their characters. This is seen as a negative vision of the development of children because children do contribute to his or her own development. - **Jean Jacques Rousseau 18th Century** Noble savages = endowed with a sense of right or wrong. Children have built in moral sense 1st concept of stage, 2nd maturation of growth refers to genetically determined naturally unfolding course. He saw development as a discontinuous stagewise process mapped cut by nature. - **Charles Darwin the forefather of Scientific Child Study 1859-1936, 19th century** The famous theory of evolution, *the survival of the fittest*, and *natural selection*. - **G. Stanley Hall regarded as the founder of the child study movement 1846-1924** One of the most influential American psychologists of the early twentieth century. The Normative Approach = normative period measures of large numbers of individuals and age related averages are computed to represent typical development. - **The mental testing movement early 20th Century** French psychologist Alfred Binet and Colleague Theodore Simon were the first to come up with a successful intelligence test IQ at Stanford University. - **Sigmund Freud 1856-1939** Theory *\'psychosexual theory*, ID, Ego, and Superego. - **Erik Erikson 1902-1994** Theory *psychosocial theory* - **John Watson 1978-1958** Behaviorism and Social Learning Theory - **Ivan Pavlov** Classical conditioning - **B.F. Skinner** Operant Conditioning - **Albert Bandura** Social learning theory - **Jean Piaget\'s** Cognitive-developmental theory ## Review Questions Answers for these questions can be found here 1\. Growth is the most rapid in : A\) puberty : B\) childhood : C\) infancy : D\) adulthood : E\) Growth is always the same 2\. This hormone stimulates puberty : A\) GnRH : B\) LH : C\) FSH : D\) TSH 3\. Compared to girls\' early growth spurt, growth \_\_\_\_\_\_\_\_\_\_in boys and \_\_\_\_\_\_\_\_\_\_ : A\) is quicker, lasts longer : B\) accelerates more slowly, lasts longer : C\) is slower, shorter : D\) None of the above 4\. This quality symbolizes adulthood in most cultures : A\) stability : B\) method/tact : C\) endurance : D\) objectivity : E\) all of the above 5\. Susie has a very hard time keeping friends, according to Maslow, this could be because : A\) as a child she had a supportive family : B\) she likes to help solve the problems of others : C\) as a teenager her self-esteem was low : D\) as a baby she wasn't breastfed : E\) as a child she lived in an environment that never made her feel safe 6\. According to Maslow, in order for me to reach my full potential of self-actualization I must first : A\) feel safe : B\) gain self-esteem : C\) have friendship : D\) have food : E\) all of the above 7\. Humans are one of the \_\_\_\_\_\_\_\_\_ developing species in the animal kingdom : A\) slowest : B\) quickest : C\) average : D\) none of the above 8\. Jenny thinks that she might be going through menopause, a symptom of this is : A\) bleeding : B\) frequent urination : C\) itchiness : D\) none of the above : E\) all of the above 9\. It is estimated that 52 million people will be afflicted with this by 2010 : A\) Progeria : B\) osteoporosis : C\) Alzheimer's : D\) dementia 10\. This is the leading cause of death for both men and women : A\) progeria : B\) cancer : C\) congestive heart failure : D\) osteoporosis : E\) heart attack ## Glossary Alzheimer\'s disease: The most common form of dementia. It is a progressive condition that destroys brain cells, resulting in the loss of intellectual abilities ```{=html} <!-- --> ``` Apoptosis: The process of regulated cell death ```{=html} <!-- --> ``` Appositional bone growth: The growth in diameter of bones around the diaphysis occurs by deposition of bone beneath the periosteum. ```{=html} <!-- --> ``` Bilirubin: A chemical breakdown product of hemoglobin. ```{=html} <!-- --> ``` canaliculi: small channels or canals in bone. ```{=html} <!-- --> ``` Deciduous teeth: The first set of teeth in the growth development of humans and many other animals. (milk teeth, baby teeth, or primary teeth) ```{=html} <!-- --> ``` Dementia: The progressive decline in cognitive function due to damage or disease in the brain beyond what might be expected from normal aging. ```{=html} <!-- --> ``` Epiphyseal Plate: The cartilage in growing long bones that allows lengthwise growth. The plate ossifies at the end of puberty. ```{=html} <!-- --> ``` Haversian system: The basic structural unit of compact bone which includes a central canal, lamellae, lacunae, osteocytes, and canaliculi. ```{=html} <!-- --> ``` Intramembranous ossification: The type of bone formation responsible for the development of flat bones, especially those found in the skull. In intramembranous ossification mesenchymal cells develop into bone without first going through a cartilage stage. ```{=html} <!-- --> ``` lacunae: spaces between bone lamellae. ```{=html} <!-- --> ``` lamellae: concentric layers of bone matrix. ```{=html} <!-- --> ``` Menopause: The permanent cessation of menstrual cycles. ```{=html} <!-- --> ``` Menarche:The first menstrual bleeding, usually occurs at about 12.7 years of age. ```{=html} <!-- --> ``` Mongolian spots: are common among darker-skinned races, such as Asian, East Indian, and African. They are flat, pigmented lesions with unclear borders and irregular shape. They appear commonly at the base of the spine, on the buttocks and back. They may also can appear as high as the shoulders and elsewhere. Mongolian spots are benign skin markings and are not associated with any conditions or illnesses. ```{=html} <!-- --> ``` Necrosis:A form of cell death that results from acute cellular injury. ```{=html} <!-- --> ``` Osteoporosis: A condition that is characterized by a decrease in bone mass and density, causing bones to become fragile. ```{=html} <!-- --> ``` Puberty: The process of physical changes by which a child\'s body becomes an adult body capable of reproduction ```{=html} <!-- --> ``` Pyloric Stenosis: Narrowing of the pyloric sphincter that reduces or eliminates the passage of food from the stomach to the small intestine, often causing projectile vomiting in infants. ```{=html} <!-- --> ``` Trabeculae: spongy bones that make plates or bars instead of concentric layers. ## References - Methuselahmouse.org - Van De Graaff (2002) *Human Anatomy 6th ed.* McGraw-Hill Higher Education - Windmaier, P.W. Raff, H. Strang, T.S. (2004) *Vander, Sherman, & Luciano\'s Human Physiology, the Mechanisms of Body Function 9th ed.* Mcgraw-Hill - Starr & McMillan (2001) *Human Biology 6th ed.* Thomson-Brooks/cole. - McCance, Kathryn L., Heuther, Sue E. (1994) *Pathophysiology: the biological basis for diseases in adults and children.* Mosby-Year Book, Inc.
# Human Physiology/Appendix 1: answers to review questions This appendix does not provide answers to the review questions posted at the end of each chapter; it is a collection of questions provided at the end of each chapter. ## Homeostasis 1\. Meaning of Homeostasis: : A\) contributor and provider : B\) expanding : C\) same or constant : D\) receiver 2\. What is the normal pH value for body fluid? : A\) 7.15-7.2556 : B\) 7.35-7.45 : C\) 7.55- 7.65 : D\) 7.00-7.35 : E\) 6.5-7.5 3\. An example of the urinary system working with the respiratory system to regulate blood pH would be : A\) When you hold your breath the kidneys will remove CO2 from your blood : B\) If you exercise a lot your urine will become more acidic : C\) If you develop emphysema the kidneys will remove fewer bicarbonate ions from circulation : D\) If you hyperventilate the kidneys will counteract the alkalinity by adding hydrogen ions into the blood stream : E\) None of the above-the urinary system never works with the respiratory system 4\. The urge to breathe comes in direct response to: : A\) How long it has been since you last took a breath : B\) The oxygen concentration of your surrounding environment : C\) The buildup of nitrogen within your blood stream : D\) The pH of your blood : E\) The buildup of blood pressure that occurs when you don\'t breathe 5\. In response to a bacterial infection my body\'s thermostat is raised. I start to shiver and produce more body heat. When my body temperature reaches 101 degrees, I stop shivering and my body temperature stops going up. This is an example of: : A\) Negative feedback : B\) A malfunctioning control system : C\) Positive feedback : D\) A negative impact 6\. Which of the follow is an example of a positive feedback? : A\) Shivering to warm up in a cold winter storm : B\) A cruise control set on your car applies more gas when going up a hill : C\) You sweat on a hot summer\'s day and the blood vessels in your skin vasodilate : D\) You get cut and platelets form a clot. This in turn activates the fibrin clotting system and more blood forms clots 7\. Where is the body\'s \"thermostat\" found? : A\) Within the nervous system, in the Hypothalamus : B\) Within the integumentary system, in the skin : C\) Within the brain, in the corpus callosum : D\) Within the Urinary system, in the kidneys 8\. What system has little to contribute to the homeostasis of the organism? : A\) Urinary System : B\) Reproductive System : C\) Respiratory System : D\) Nervous System ## Cell physiology 1\. List 2 functions of the cell membrane: : **Separates internal metabolic events from the external environment.** : **Controls the movement of materials into and out of the cell.** Questions 2 - 6 Match the following organelles with their function: 2\. Mitochondria **C** 3\. Vacuoles **D** 4\. Cilia **A** 5\. Smooth ER **B** 6\. Golgi Apparatus **E** 7\. The diffusion of H2O across a semi permeable or selectively permeable membrane is termed : A. Active transport : B. Diffusion : C. Osmosis : D. Endocytosis 8\. Oxygen enters a cell via? : a\. Diffusion : b\. Filtration : c\. Osmosis : d\. Active transport 9\. The term used to describe, \"cell eating\" is? : a\. Exocytosis : b\. Phagocytosis : c\. Pinocytosis : d\. Diffusion 10\. Which of the following requires energy? : a\. Diffusion : b\. Osmosis : c\. Active transport : d\. Facilitated diffusion 11\. Protein synthesis occurs at the : a\. Mitochondria : b\. Lysosomes : c\. Within the nucleus : d\. Ribosomes 12\. Which of the following is not found in the cell membrane? : a\. Cholesterol : b\. Phospholipids : c\. Proteins : d\. Galactose : e\. Nucleic Acids 13\. What is a cell? : a\. The largest living units within our bodies. : b\. Enzymes that \"eat\" bacteria : c\. Microscopic fundamental units of all living things. : d\. All of the above. ## Integumentary System 1\. Name all of the parts of the integumentary system. : The integumentary system consists of the skin, the subcutaneous tissue below the skin, hair, nails, and assorted glands. 2\. Name the cells that produce melanin and describe its function. : Melanocytes : These are cells located in the bottom layer of the skin\'s epidermis and in the middle layer of the eye, the uvea. Through a process called : melanogenesis, these cells produce melanin, a pigment in the skin, eyes, and hair. 3\. Name and describe the importance of the cutaneous senses. : The cutaneous senses are touch, pressure, heat, cold and pain. Their purpose is to provide the central nervous system with information about the external environment and its effect on the skin. 4\. Explain how sweating helps maintain normal body temperature. : Eccrine sweat glands are coiled tubular glands derived from the outer layer of skin but extending into the inner layer. The sweat glands are : controlled by sympathetic cholinergic nerves which are controlled by a centre in the hypothalamus. The hypothalamus senses core : temperature directly, and also has input from temperature receptors in the skin and modifies the sweat output, along with other thermoregulatory processes. 5\. Explain where on the body hair has important functions, and describe these functions. : Hair on the scalp provides insulation from cold for the head. : The hair of eyelashes and eyebrows helps keep dust and perspiration out of the eyes. : Hair in our nostrils helps keep dust out of the nasal cavities. : Any other hair on our bodies no longer serves a function, but is an evolutionary remnant. 6\. What is a melanoma? : a\. The outermost layer of skin : b\. A type of nail disease : c\. A malignant tumor that originates in melanocytes : d\. The lower most layer of skin ## The Nervous System 1\. The junction between one neuron and the next, or between a neuron and an effector is called: : A ) A synapse : B ) A dendrite : C ) A neuotransmitter : D ) A ventricle : E ) None of the above 2\. A fast excitatory synapses follows this order: : A ) (1) neurotransmitter released (2) diffused across the synaptic cleft to a receptor protein (3) binding of the transmitter opens pores in the ion channels and positive ions move in. : B ) (1) neurotransmitter released (2) diffused across the synaptic cleft to a receptor protein (3) binding of the transmitter opens pores in the ion channels and negative ions move in. : C ) (1) neurotransmitter released (2) diffused across the synaptic cleft to a receptor amino acid (3) binding of the transmitter opens pores in the ion channels and positive ions move in. : D ) (1) diffused across the synaptic cleft to a receptor protein (2) neurotransmitter released (3) binding of the transmitter opens pores in the ion channels and positive ions move in. : E ) None of the above 3\. Resting potential is : A ) excess positive ions accumulate inside the plasma membrane : B ) excess negative ions accumulate inside the plasma membrane : C ) excess positive ions accumulate outside the plasma membrane : D ) both b & c : E ) both a & c 4\. Sensory neurons have: : A ) A short dendrite and a long axon : B ) A short dendrite and a short axon : C ) A long dendrite and a short axon : D ) A long dendrite and a long axon : E ) Their axons and dendrites may be either long or short 5\. \_\_\_\_\_\_\_\_blocks Acetylcholine receptor sites causing muscle relaxation. : A ) Novocain : B ) curare : C ) Nicotine : D ) Nerve gases 6\. Transmission across a synapse is dependent on the release of \_\_\_\_\_\_\_? : A ) neurotransmitters : B ) synaptic vesicle : C ) neurons : D ) receptor proteins 7\. Motor neurons take messages : A ) from the muscle fiber to the central nervous system : B ) away from the central nervous system to the central nervous system : C ) that are classified : D ) away from the central nervous system to muscle fiber 8\. The medulla oblongata helps to regulate which of the following: : A ) Breathing : B ) Heartbeat : C ) Sneezing : D ) Vomiting : E ) All of the above 9\. The nervous systems main components are what? : A ) The Synapses and Sprinal cord : B ) The neurons and the synapses : C ) The brain and the neurons : D )The brain and the spinal cord 10\. Explain what LTP does to enhance communication between two neurons, on the postsynaptic end. - More receptors, such as AMPA receptors, are added and existing ones are sensitized via phosphorylation. Dendritic spine number and surface area is increased as well. 11\. Explain what LTP does to communication between two neurons, on the presynaptic end. - If the retrograde messenger theory is correct, presynaptic cells participate in the enhancement by increasing the probability of synaptic vesicle release. (Please remember the retrograde messenger is theoretical, I just thought it should be included here) ## Senses ### Critical Thinking: Vision 1\. Explain why you are normally unaware of your blind spot. :\*Since your eyes are looking from different angles, they see each other\'s blind spot and your brain combines the two images. 2\. Stare at a bright light for 10 seconds and then stare at a white sheet of paper. What do you observe and why? :\*You should observe a negative afterimage. This happens when the rod/cone (mostly cone) cells in your eye adapt to the stimulus and lose their sensitivity, leaving you with the negative of the color that was adapted to. 3\. What is it that makes things \"disappear\" when you are staring at them at night, and how do you make them reappear? :\*There are no rods in the fovea, so little light is picked up when you stare directly at the object. To make it reappear, just don\'t look right at it. 4\. Name what rods are sensitive to and also what cones are sensitive to. :\*Rods are more sensitive to lower light levels, but lack color-seeing ability. Cones work in brighter light and perceive color (blue, green, red). 5\. Explain how Deadly Nightshade works :\*Normally, the parasympathetic nervous system constricts the pupil as needed with acetylcholine. The atropine in nightshade is a competitive agonist on the same receptor as the one that accepts acetylcholine. Basically: the atropine takes up all of the places for acetylcholine to bind, and the pupils dilate. ### Critical Thinking: Hearing 1\. Explain how the pitch of sound is coded. How is the loudness of sound coded? 2\. What do the three semicircular canals in the inner ear enable us to do? How do they accomplish this? :\*Each of the three fluid filled canals is on a different plane. Movement is detected on these planes when the fluid inside moves around, vibrating cilia on the cupula which sends it on to the brain. 3\. What does the eustachian tube do? What does the eustachian tube have to do with a middle ear infection? :\*The eustachian tube is to keep pressure in the middle ear the same as atmospheric pressure. If the tube is blocked, the gases in the ear will diffuse back into the surrounding tissues and a vacuum will be made. Eventually, this will pull fluid in and if it becomes infected\... You have an ear infection. 4\. What is the advantage of having a oval window? Sound transducted from air to a more dense medium (endolymph, in scala media where the organ of cortis is placed) would be partially reflected and greatly weakened if not for the ossicular bones that transfer the vibration from membrana tymphani trough malleus, incus and stapes to the foramen ovale where it puts the liquids of cochlea in motion. This motion is then transfered trough membrana vestibularis to membrana basilaris, which in turn puts the haircells in motion. This leads to a bending of the stereocills, fastened to membrana tectori, and as a result; a depolarization of the afferent sensory fibre receptor of n. cochlearis through release of glutamate. The loss of energy in transduction is partially re-gained by the size of membr. tympani compared to the size of foramen ovale and the rotation of the ossicular bones. ### Review Questions 1\. Located under the hardest bone in the body, these control not only hearing but also a sense of gravity and motion: : A\) The incus and the stapes : B\) The pinna and the ear drum : C\) the vestibular nerve and the semi circular canals : D\) The eustachian tube and the stapes 2\. The retina does the following; : A\) allows vision in light and dark, using cones and rods : B\) Gives depth perception using binocular vision : C\) Contains the ciliary muscles that control the shape of the lens : D\) Protects and supports the shape of the eye 3\. This is the reason that we stop feeling the clothes that we are wearing : A\) Merkel's Discs are somewhat rigid in structure, and the fact that they are not encapsulated, causes them to have a sustained response : B\) Meissner's corpuscle are rapidly adapting or phasic, the action potentials generated quickly decrease and eventually cease : C\) Ruffini corpuscles is a class of slowly adapting mechanoreceptor : D\) Pacinian corpuscles allow sodium ions to influx in, creating a receptor potential 4\. When eating a piece of candy, I will use the following to sense that it is sweet : A\) Fungiform papillae : B\) Filiform papillae : C\) Foliate papillae : D\) Circumvallate papillae : E\) All of the above 5\. If I have a cold, food may not taste as good to me because : A\) The nerve fibrils are not functioning properly : B\) My food will taste the same; taste and smell have nothing in common : C\) Papilla become blocked by mucus and are unable to function : D\) Olfaction, taste and trigeminal receptors together contribute to the flavor of my food 6\. Walking from a well lit room into a dark room would cause the following to occur : A\) The sclera in the eye to open and eventually allow me to see in the dark : B\) The extraocular muscles in the eye to open and eventually allow me to see in the dark : C\) The cones in the eye to open and eventually allow me to see in the dark : D\) the rods in the eye to open and eventually allow me to see in the dark 7\. Hair cells in the ear : A\) Are the actual sensory receptors that will fire off action potentials when they are disturbed : B\) Show a graded response, instead of the spikes typical of other neurons : C\) "Rub" against the overhanging tectorial membrane : D\) All of the above 8\. Eyesight decreases with age because : A\) Older eyes receive much less light at the retina : B\) There are numerous eye diseases that can affect an older eye : C\) The extent to which the pupil dilates decreases with age : D\) all of the above 9\. Teens walking off of a roller coaster in Magic Mountain seem to have vertigo because : A\) The fluid in the auricle has not stopped moving causing conflicts with the information coming from your vision : B\) the fluid in the cochlea has not stopped moving causing conflicts with the information coming from your vision : C\) The fluid in the tympanic membrane has not stopped moving causing conflicts with the information coming from your vision : D\) The fluid in the stirrup has not stopped moving causing conflicts with the information coming from your vision 10\. These receptors react to foods treated with monosodium glutamate : A\) Salt : B\) Sour : C\) Bitter : D\) Sweet : E\) Umami ## The Muscular System 1\. Smooth Muscle is : A\) Voluntary and Spindle Shaped : B\) Voluntary and Striated : C\) Involuntary and Spindle Shaped : D\) Involuntary and Striated 2\. Skeletal Muscle is : A\) Voluntary and Spindle Shaped : B)Voluntary and Striated : C\) Involuntary and Spindle Shaped : D\) Involuntary and Striated 3\. Cardiac Muscle is : A\) Voluntary and Spindle Shaped : B\) Voluntary and Striated : C\) Involuntary and Spindle Shaped : D\) Involuntary and Striated 4\. Which type of muscle cell is multinucleated? : A\) Cardiac : B\) Smooth : C\) Skeletal : D\) All of the Above 5\. What is an example of a smooth muscle? : A\) Masseter (Face) : B\) Bladder : C\) Heart : D\) Pronator Teres (Forearm) : E\) Rectus Abdominis (belly) 6\. Each myosin filament is surrounded by \_\_\_\_ actin filaments. : A\) Two : B\) Four : C\) Six : D\) Eight : E\) Seven 7\. The muscular system is controled by what system? : A\) The cardiovascular system : B\) The integumentary System : C\) The Nervous system : D\) None of the above 8\. How many types of muscle are there? : A\) Two : B\) Three (cardiac, smooth and skeletal) : C\) Four : D\) Five ## Blood Physiology 1\. Taking aspirin every day can reduce the risk of heart disease because: : A\) it is a powerful vasodilator : B\) it blocks pain receptors in heart tissue : C\) it stops ventricular fibrillation : D\) it loosens plaque on arterial walls **:E) it prevents platelet clumping** 2\. A hematocrit measures percentage of: : A\) White blood cells : B\) Plasma : C\) Platelets **:D) Red blood cells** 3\. Fred\'s blood type is O- and Ginger\'s is B+. Fred and Ginger have a son who is AB+. What do you conclude? : A\) If they have a second child Ginger needs to have RhoGam shot : B\) There is no risk to a second child, unless it has a negative blood type : C\) If the child needs a blood transfusion Fred could provide it safely, but not Ginger **:D) Fred is not the boy's father** 4\. Which blood component plays the largest role in maintaining the osmotic pressure of blood? **:A) albumin** : B\) carbon dioxide : C\) white blood cells : D\) fibrinogen : E\) globulins 5\. If you hold your breath for one minute : A\) The kidneys will increase sodium ion reabsorption **:B) Hydrogen-ion concentration in the blood will increase** : C\) Your heart rate will greatly slow : D\) Hemoglobin will bind to oxygen more strongly 6\. Most of the carbon dioxide produced by tissues is transported to the lungs as: : A\) Small gas bubbles in the plasma : B\) Gas bound to hemoglobin in the red blood cells **:C) Bicarbonate ions in the plasma** : D\) Gas bound to white blood cells and albumin : E\) Gas transported through the lymphatic system 7\. To prevent blood loss after a tissue injury, blood vessels first : A\) Form a platelet plug : B\) Form a clot : C\) Initiate the coagulation cascade **:D) Constrict and form barriers** 8\. You take a blood sample from a male cyclist at the end of a long race. The hematocrit is 60%. The most likely conclusion is: : A\) This is within normal range for most adult males : B\) This cyclist is anemic : C\) This low of a hematocrit could indicate liver damage or leukemia **:D) The cyclist is dehydrated** : E\) The cyclist has been taking pharmaceutical erythropoietin 9\. In a normal blood sample, which of the following cells will be the most abundant? **:A) Neutrophils** : B\) Basophils : C\) Eosinophils : D\) Monocytes : E\) Lymphocytes 10\. A bag of donated blood does not clot because : A\) There is not enough oxygen : B\) It cannot dry out : C\) It is kept refrigerated : D\) There is no free calcium : E\) All of the above ## The cardiovascular system 1\. This conducts electricity like nerves : A\) Epicardium : B\) Pericardium : C\) Myocardium : D\) Subvalaular Apparatus : E\) None of these, only nerves conduct electricity 2\. This carries the most blood at any given time in the body : A\) Veins : B\) Capillary Beds : C\) Veins : D\) Aorta : E\) Vena Cava 3\. The following contract together to pump blood : A\) Right atrium with the right ventricle and left atrium with the left ventricle : B\) Right atrium with left atrium and right ventricles with left ventricle : C\) Tricuspid valve and mitral valve : D\) Aorta and pulmonary artery : E\) Aorta, pulmonary artery and pulmonary vein 4\. This is the pacemaker of the heart : A\) AV node : B\) Purkinje fibers : C\) AV Bundle : D\) SA node : E\) None of these, a pacemaker is surgically inserted 5\. When reading an EKG, this letter shows the depolarization from the AV node down to the AV bundle : A\) S : B\) P : C\) U : D\) T : E\) Q 6\. The T wave in an EKG shows : A\) Resting potential : B\) Atrial depolarization : C\) SA node excitation : D\) Ventricle repolarization : E\) Purkinje Excitation 7\. Blood pressure is the measure of : A\) Pressure exerted by the blood on the walls of the blood vessels : B\) Pressure exerted by the blood on the arteries : C\) Pressure exerted by the blood on the veins : D\) Pressure exerted by the blood on the aorta 8\. Systolic Pressure is : A\) An average of 120 mm Hg : B\) Lowers steadily during ventricle systole : C\) The highest when blood is being pumped out of the left ventricle into the aorta : D\) An average of 80 mm Hg : E\) Both A and C : F\) Both B and D 9\. The heart has how many chambers? : A\) One : B\) Two : C\) Three : D\) Four (two ventricles and two atria) : E\) Five 10\. End diastolic volume in human : A)120mL : b)50mL : c)70mL : d)100mL ## The Immune System 1-When neutrophils and macrophages squeeze out of capillaries to fight off infection it is called: : A\) phagocytosis : B\) hemolysis : C\) interleukin : D\) diapedesis : E\) folliculitis 2-During a great battle between your WBC\'s and an aggressive microbe, an inflammatory response has been initiated. Reddness and edema has kicked in what else does the body do to protect itself? : A\) Histamine cause vasodilation : B\) Hypothalmus raises the thermostat : C\) Neutrophils engulf and destroy the microbe : D\) Living and dead WBC and bacteria accumulate : E\) All of the above 3-Specificity and memory are associated with which body defense mechanism? : A\) inflammatory response : B\) phagocytosis by macrophages and neutrophils : C\) interferon : D\) T cell and B cell responses : E\) anatomical barriers in the body 4-An additional chemical defense found in tears and saliva? : A\) T lymphocytes : B\) saline : C\) lysozyme : D\) EFC 5-Which of the following does complement protein perform : A\) They cause antibody release : B\) T cell development : C\) The release if histamine : D\) Promotes tissue repair : E\) Mast cell degranulation 6-Which substance induces fever? : A\) Pyrogen : B\) Pus : C\) Monocytes : D\) Edema : E\) Interferon 7-Major function(s) of the lymphatic system is/are? : A\) provide route for return of extracellular fluid : B\) act as drain off for inflammatory response : C\) render surveillance, recognition , and protection against foreign materials via lymphocytes, phagocytes, and antibodies. : D\) a and c : E\) all of the above 8-An antigen is: : A\) a chemical messenger that is released by virus infected cells : B\) a lymphocyte responsible for cell-mediated immunity : C\) something that coats the inside of lungs, causing infection : D\) a protein or other molecule that is recognized as non-self : E\) a thick yellow-white fluid 9-A foreign substance, usually a protein, that stimulates the immune system to react, such as by producing antibodies is a \_\_\_\_\_\_\_\_\_\_\_\_\_\_. : A\) allergen : B\) antigen : C\) histamine : D\) mast cell : E\) interferon 10-When a macrophage ingests an invading bacteria and takes the antigen to a lymph node, what happens next? : A\) the macrophage will present it to the first B-cell it encounters, and the B-cell will in turn change its surface receptors to match the antigen : B\) a B-cell will only become activated if it already has a match for the antigen : C\) a matching B-cell will become activated into a cytotoxic T-cell : D\) the cells of the lymph node will release histamine : E\) the lymph node will increase production of neutrophils 11-What is the most common portal of entry for diseases, into the body? : A\) Respiratory system : B\) Endocrine system : C\) Hematacrit system : D\) Any opening into the body. 12-This gland shrinks in size during adulthood, and has hormones that function in maturation of T-lymphocytes: : A\) lymph nodes : B\) thymus : C\) spleen : D\) GALT : E\) tonsils 13-Which of the following is not a mechanical factor to protect the skin and mucous membranes from infection? : A\) Layers of cells : B\) Tears : C\) Saliva : D\) Lysozyme : E\) None of the above 14-Where is the site of maturation for a B cell? : A\) thymus : B\) bone marrow : C\) pancreas : D\) cortex 15-Nonspecific resistance is : A\) The body\'s ability to ward off diseases. : B\) The body\'s defenses against any kind of pathogen. : C\) The body\'s defense against a particular pathogen. : D\) The lack of resistance. : E\) None of the above. 16-What is an Antibody? : A\) An antimicrobial substance applied to a living tissue to prevent infection. : B\) Programmed cell death : C\) A protein generated by the immune system in response to a foreign substance. : D\) A chemical involved in inflammation. ## The Urinary System 1\. While reading a blood test I notice a high level of creatinine, I could assume from this that : A\) There is a possibility of a UTI : B\) There is a possibility of diabetes : C\) **There is a possibility of kidney failure** : D\) There is nothing wrong, this is normal 2\. Direct control of water excretion in the kidneys is controlled by : A\) **Anti-diuretic hormone** : B\) The medulla oblongata : C\) Blood plasma : D\) Sodium amounts in the blood : E\) Cells 3\. Nephrons : A\) Eliminate wastes from the body : B\) Regulate blood volume and pressure : C\) Control levels of electrolytes and metabolites : D\) Regulate blood pH : E\) **All of the above** 4\. If I am dehydrated, my body will increase : A\) ATP : B\) **CDP** : C\) Diluted urine : D\) ADH 5\. Which part of the nephron removes water, ions and nutrients from the blood? : A ) vasa recta : B ) loop of henle : C ) proximal convoluted tubule : D ) peritubular capillaries : E ) **glomerulus** 6.Kidneys have a direct effect on which of the following : A ) Blood pressure : B ) How much water a person excretes : C ) Total blood volume : D ) pH : E ) **all of the above** 7\. Why do substances in the glomerulus enter the Bowman\'s capsule? : A ) the magnetic charge of the Bowman\'s capsule attracts the substances : B ) the substances are actively transported into the Bowman\'s capsule : C ) **blood pressure of the glomerulus is so great that most substances in blood move into capsule** : D ) little green men force it in with their ray guns 8\. What happens in tubular excretion? : A ) urine bonds are formed between the wastes : B ) wastes are diffused from the tubule : C ) **wastes move into the distal convoluted tubule from the blood** : D ) blood pressure forces wastes away from the kidney 9\. The countercurrent exchange system includes\_\_\_\_\_\_\_\_\_and\_\_\_\_\_\_\_\_\_. : A ) **glomerulus and macula densa** : B ) proximal convoluted tubule and distal convoluted tubule : C ) loop of Henle and collecting tubule : D ) afferent arteriole and efferent arteriole : E ) ureters and bladder 10\. The function of the loop of the nephron in the process of urine formation is: : A ) **reabsorption of water** : B ) production of filtrate : C ) reabsorption of solutes : D ) secretion of solutes ## The respiratory system 1\. This is total lung capacity :\*A) Vital capacity :B) Tidal volume :C) Expiratory reserve volume :D) Inspiratory reserve volume 2. Involuntary breathing is caused by the : A\) Pituitary gland :B) Exocrine gland :C) Cerebral cortex :\*D) Medulla oblongata :E) Endocrine gland 3. Carbon monoxide is dangerous because :\*A) It binds strongly to hemoglobin, making it unavailable to oxygen :B) It binds strongly to plasma, making it unavailable to carbon dioxide :C) It raises the blood's pH level, causing a person to hyperventilate :D) Carbon monoxide is not harmfull, we have it in our bodies normally 4. Clubbing of the fingers could be a sign of :A) A viral infection :B) An upper respiratory infection :\*C) Chronic Obstructive Pulmonary Disease :D) Nothing, it's inherited 5. The need to breathe is caused by :\*A) A decrease in blood pH :B) An increase in blood pH :C) A decrease in blood oxygen levels :D) A decrease in carbon dioxide levels 6. A person more susceptible to Chronic Obstructive Pulmonary Disease would be :A) A long time smoker :B) A long time fireman :C) A child whose parents smoke :D) A farmer that deals with pesticides :\*E) All of the above 7\. The exchange of gases between the blood within the capillaries and tissue fluid surrounding the body\'s cells is called? :A) external respiration :B) cell metabolism :C) cellular respiration :\*D) internal respiration 8. The medulla oblongata and pons regulate and measure what? : A\) The pH level of your blood : B\) Your body temperature : C\) The amount of O2 in your blood : D\) The amount of air in your lungs 9\. About how many alveoli are there in the lungs? : A\) 300 million : B\) 300 billion : C\) 300 trillion : D\) 300 thousand : E\) None of the above 10. In relation to atmospheric pressure, intrapleural pressure is: :A) more pressurized :\*B) less pressurized :C) about the same 11\. Hemoglobin gives up oxygen when the environment is more \_\_\_\_\_\_\_. :\*A)Acidic :B)Alkaline :C)Icey :D)Open 12. The sac that surrounds your lungs is called what? :A) Diaphragm :\*B) Visceral Pleura :C) Pulmonary Thorax :D) None of the above 13. In what cellular organelle is the oxygen actually consumed and carbon dioxide produced? : A\) Nucleus : B\) Cytoplasm : C\) Microfilaments : D\) Mitochondria 14\. Which of these are protective reflexes? : A\) Hiccuping : B\) Sobbing : C\) Sneezing : D\) Itching 15\. Where does gas exchange take place? : A\) Bronchioles : B\) Conchae : C\) Pulmonary Capillaries : D\) Roots of the Lungs 16\. When you hyperventilate you release large amounts of CO2 and drop your O2 levels. As a result you loose the urge to breathe and may pass out. This is called what? :A) Chronic Obstructive Pulmonary Disease :B) Asthma :\*C) Shallow water black out :D) Pulmonary Fibrosis 17. Acidosis is when you blood pH is below ? :A) 7.05 :B) 7.15 :C) 7.25 :\*D) 7.35 18. When we exhale deeply some air is still left in the lungs, this air left is called? :A) Tidal Volume :B) Vital Capacity :C) Expiratory reserve Volume :\*D) Residual Volume ## The gastrointestinal system 1\. This is released in the duodenum in response to acidic chyme : A\) Cholecystokinin : B\) Gastrin : C\) Secretin : D\) Peptide 2\. In the GI tract, this layer is responsible for absorption and secretions : A\) Mucosa : B\) Sub mucosa : C\) Muscularis : D\) Serosa 3\. This digestive enzyme is produced in the salivary glands and the pancreas : A\) Maltase : B\) Amylase : C\) Pepsin : D\) Nuclease : E\) Lipase 4\. This keeps the chyme in the stomach until it reaches the right consistency to pass into the small intestine : A\) Esophageal sphincter : B\) Intrinsic sphincter : C\) Cardiac sphincter : D\) pyloric sphincter 5\. The site where most of the chemical and mechanical digestion is carried out : A\) Pylorus : B\) Fundus : C\) Stomach : D\) Large intestine : E\) Small intestine 6\. Parietal cells secret : A\) Serotonin : B\) Mucus : C\) Pepsinogen : D\) Hydrochloric Acid : E\) Gastrin 7\. The cells at the base of fundic or oxyntic glands : A\) Chief cells : B\) G cells : C\) Argentaffin cells : D\) Goblet cells : E\) Parietal cells 8\. The movement and the flow of chemicals into the stomach is controlled by : A\) Nervous system : B\) Pancreas : C\) Various digestive system hormones : D\) Liver : E\) Both the nervous system and various digestive system hormones 9\. The function of the Ileum is : A\) Absorb nutrients : B\) Absorb vitamin B12 and bile salts : C\) To introduce bile and pancreatic juices : D\) Absorb alcohol and aspirin 10\. The liver does this : A\) Glycogen storage : B\) Plasma protein synthesis : C\) Bile production : D\) Drug detoxification : E\) All of the above 11\. How many layers is the G.I tract composed of? : A)Two : B)Three : C)Four (mucosa, submucosa, muscularis, serosa) : D)Five 12\. Name the 7 accessory organs. :\*Salivary glands, parotid gland, submandibular gland, sublingual gland, tongue, teeth, liver, gallbladder, pancreas, vermiform appendix ## Nutrition 1\. Nonessential amino acids : A\) are stored in the body : B\) are only needed occasionally : C\) can be produced in the body : D\) can be taken in supplements 2\. Micronutrients include : A\) minerals and vitamins : B\) lipids and fatty acids : C\) amino acids and proteins : D\) vitamins and minerals 3\. The body requires amino acids to : A\) produce new red blood cells : B\) produce new protein : C\) replace damaged red blood cells : D\) replace damaged protein : E\) A and C : F\) B and D 4\. The function of lipids : A\) store energy : B\) organ protection : C\) temperature regulator : D\) emulsifiers : E\) all of the above 5\. This vitamin is a vital component of the reproductive process and lowers the risk of getting cancer : A\) B12 : B\) Folic Acid : C\) Niacin : D\) Thiamine : E\) Retinol 6\. This vitamin is needed to make red blood cells : A\) B1 : B\) B2 : C\) B6 : D\) B12 7\. This participates in the synthesis of hemoglobin and melanin : A\) Copper : B\) Chloride : C\) Calcium : D\) Iron : E\) Iodine 8\. I go to visit my grandmother and see that she has multiple bruises- from this I may assume that : A\) she has a vitamin A deficiency : B\) she is old and just clumsy : C\) she has a vitamin K deficiency : D\) she has scurvy : E\) she has rickets 9\. As a pirate I may get scurvy because : A\) I am not getting enough vegetables on the ship : B\) I am not getting enough fruit on the ship : C\) I am eating too much fish on the ship : D\) I am getting too much sun on the ship : E\) I am drinking too much rum on the ship 10\. I am taking anticoagulant medication and it doesn't seem to be working, this could be because : A\) I have too much vitamin A : B\) I have too much B12 : C\) I have too much sodium : D\) I have too much vitamin E : E\) I have too much vitamin K 11\. Which of these are fat soluable? : A\) Vitamin K : B\) Vitamin E : C\) Vitamin D : D\) Vitamin A : e\) All of the above ## The Endocrine System 1\. My child just fell and was hurt, the anxious feeling that I feel is caused by : A\) glucagon : B\) insulin : C\) epinephrine ANS=C : D\) adrenocorticotropic : E\) None of these 2\. All of Bob's life he has had to take insulin shots, this is caused because : A\) his beta cells don't function correctly ANS= A : B\) his alpha cells don't function correctly : C\) his DA hormone isn't functioning correctly : D\) his GHRH hormone isn't functioning correctly 3\. The reason iodine is in salt is : A\) to prevent diabetes : B\) to prevent simple goiters : C\) to prevent addison's disease : D\) to prevent cushing syndrome 4\. All hormones react to a negative feedback except : A\) progesterone : B\) estrogen : C\) prolactin : D\) oxytocin : E\) none of these ANS =E 5\. If I have a high blood calcium level it may be due to : A\) calcitonin : B\) parathyroid : C\) glucocorticoids : D\) glucagon 6\. Hormones that are lipids that are synthesized from cholesterol : A\) protien : B\) amino acid-derived : C\) polypeptide : D\) steroids ANS =D : E\) eicosanoids 7\. This type of hormone must bind to a receptor protein on the plasma membrane of the cell : A\) water soluble : B\) lipid soluble ANS=E : C\) steroid : D\) polypeptide : E\) a and d : F\) b and c 8\. Endocrine glands release hormones in response to : A\) Hormones from other endocrine glands ANS =C : B\) Chemical characteristics of the blood : C\) Neural stimulation : D\) All of the above 9\. The anterior pituitary secretes : A\) oxytocin : B\) endorphins : C\) ADH ANS C : D\) TRH 10\. Chief cells produce : A\) epinephrine : B\) glucagon : C\) insulin ANS A : D\) mineralocoticoids : E\) parathyroid hormone 11\. Name the eight major endocrine glands. ; PITUITARY GLAND FOLLICIL STIMULATING HORMONE,LUTEINIZING STIMULATING HORMONE,THYROID STIMULATING HORMONE ,ADRENOCORTICORTITROPIC HORMONE ,PROLACTIN, GROWTH HORMONE ------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------- -- -- THYROID GLAND PRODUCES THYROXIN &CALCITON PARATHYROID GLAND PRODUCES PARATHYROID HORMONE ADRENAL GLAND PRODUCES ALDOSTERONE ,CORTISOL ,ADRENALINE \[EPINEPHRINE\] PINEAL GLAND MELATONIN ---------------- --------------------------------------- -- -- PANCREAS PRODUCES INSULIN AND GLUCAGON TESTES/OVARIES TESTOSTERONE ,OESTROGEN &PROGESTERONE \*Pituitary gland, thyroid gland, parathyroid gland, pancreas, testes/ovaries, adrenal gland, pineal gland 12\. Name the four major groups hormones can be chemically classified into. ; STEROIDS TESTOSTERONE,ESTROGEN ---------- ----------------------- -- -- \*Amino acid-derived, polypeptides/proteins, steroids, eicosanoids, glycoprotein, amines ## The male reproductive system 1\. This is needed to make immature sperm mature : A\) FHS : B\) LH : C\) FSH : D\) HL 2\. These become engorged with blood in an erection : A\) corpora cavernosa : B\) fibrous envelope : C\) septum pectiniforme : D\) integument : E\) dorsal veins 3\. The difference between male and female sperm : A\) female sperm have a larger head : B\) male sperm are lighter : C\) female sperm are faster : D\) male sperm are weaker : E\) A and B : F\) C and D 4\. The entire process of sperm formation takes about : A\) 5-6 weeks : B\) 7-8 weeks : C\) 3-4 weeks : D\) 9-10 weeks 5\. Hyper Activation occurs when : A\) the sperm are introduced into the urethra : B\) the sperm are ejaculated into the vaginal canal : C\) the sperm begin to interact with the fertilizing layer of an egg cell : D\) the sperm reach the cervix 6\. It takes sperm \_\_\_\_\_\_\_\_\_\_\_ weeks to travel through the epididymis : A\) 6-8 : B\) 1-3 : C\) 2-4 : D\) 4-6 7\. While singing in the choir, Ben suddenly notices his voice is constantly cracking. This is caused by : A\) androgens : B\) LH : C\) FSH : D\) Ben's inability to sing 8\. In sexual homology, the glans penis in the male is equal to \_\_\_\_\_\_\_\_\_\_\_\_\_ in the female : A\) clitoral hood : B\) clitoris : C\) clitoral glans : D\) clitoral crura 9\. In sexual homology, the \_\_\_\_\_\_\_\_\_\_\_ in the male is equal to the fallopian tubes in the female : A\) testis : B\) appendix testis : C\) vas deferens : D\) seminal vesicle : E\) efferent ducts 10\. Joe has a bulge in the groin area that seems to get worse when he lifts things. This most likely is : A\) epididymitis : B\) testicular cancer : C\) varicocele : D\) hydrocele : E\) inguinal hernia ## The female reproductive system 1\. In homology, the \_\_\_\_\_\_\_\_\_\_ in the female is equal to the penis in the male : A\) labia majora : B\) clitoral hood : C\) clitoris : D\) labia minora : E\) none of the above 2\. This contains some of the strongest muscles in the human body : A\) uterus : B\) clitoris : C\) cervix : D\) labia majora 3\. This protects the vaginal and urethral openings : A\) labia majora : B\) labia minora : C\) clitoris : D\) urethra 4\. Sally has noticed that her cervical mucus has changed and now resembles egg whites- from this Sally could assume : A\) her period will begin soon : B\) nothing, this is a normal occurrence : C\) she has a yeast infection : D\) she is ovulating 5\. Debbie recently went to the OBGYN and was diagnosed with PCOD (polycystic ovary syndrome) because of this she has : A\) nothing, its normal in women : B\) antisperm antibodies : C\) an overproduction of LH : D\) leaking of milk from her mammary glands : E\) problems becoming pregnant 6\. Angie went to the doctor because she has had pain in her leg recently- this could be caused by : A\) ovulation pain : B\) her period that will be starting tomorrow : C\) premenstrual syndrome : D\) a blood clot resulting from her birth control pill 7\. Sue recently started her period and has noticed that they are very heavy and painful, and that they are inconsistent in their timing. One explanation could be : A\) endometriosis : B\) ovarian cancer : C\) candidiasis : D\) toxic shock syndrome : E\) amenorrhea 8\. Mary is getting married and is not ready to become a mother- she chooses this birth control because of its high effectiveness : A\) natural family planning : B\) a diaphragm : C\) contraceptive injections : D\) a spermicide foam 9\. The release of LH in woman causes : A\) menstration : B\) ovulation : C\) increase of endometrial lining : D\) decrease of endometrial lining : E\) nothing LH only does something in the male reproductive system 10\. When the ovaries stop producing estrogen, this occurs : A\) ovulation : B\) implantation : C\) premenstrual syndrome : D\) menopause 11\. Infertility affects what percentage of couples? : A\) 5% : B\) 10% : C\) 15% : D\) 20% 12\. What is the only 100% effective form of birth control? : A\) Tubal ligation : B\) IUD : C\) Natural family planning : D\) Abstinence ## Pregnancy and birth 1\. Is at this stage that an egg implants in the uterine lining : A\) morula : B\) zygote : C\) blastocyst : D\) embryoblast 2\. Which part of the embryoblast will become the central nervous system in development : A\) ectoderm : B\) mesoderm : C\) endoderm 3\. This hormone is only produced in the human body when a woman is pregnant : A\) estrogen : B\) HCG : C\) progesterone : D\) FSH : E\) LH 4\. By this week of pregnancy, the beginnings of all major organs have formed : A\) 4 : B\) 7 : C\) 5 : D\) 6 : E\) 8 5\. Stem cells are found in the embryoblast and use of them is very controversial, another place to find stem cells that are usable to treat leukemia and other disorders is the : A\) morula : B\) chorion : C\) amnion : D\) amniotic fluid : E\) umbilical cord 6\. The cervix dilates on an average of \_\_\_\_\_\_ per hour in the active phase of labor : A\) 2 mm : B\) 2 cm : C\) 1mm : D\) 1 cm 7\. The contractions of the uterus are stimulated by the release of : A\) oytocin : B\) FSH : C\) LH : D\) prolactin : E\) estrogen 8\. A sign of pre-labor is : A\) irregular contractions : B\) pain in the front only : C\) loss of the mucus plug : D\) contractions stop during rest 9\. This is the most common complication of pregnancy : A\) preclampcia : B\) miscarriage : C\) smoking : D\) Rh factor : E\) teratogens 10\. Sue decides to breastfeed because she has been told that colostrum contains : A\) high protein : B\) low fat : C\) immunoglobulins : D\) all of the above : E\) none of the above 11\. What is the first milk, after birth, called? : A\) thrush : B\) mastitis : C\) colostrum : D\) milk let down ## Genetics and inheritance 1\. DNA is found on : A\) mitochondria : B\) ribosomes : C\) chromosomes : D\) cytoplasm 2\. Even though each cell has identical copies of all of the same genes, different cells \_\_\_\_\_\_\_\_\_\_ or \_\_\_\_\_\_\_\_\_\_\_ different genes : A\) express, repress : B\) genotype, phenotype : C\) dominate, recessive 3\. In diploid organisms, a dominant allele on one chromosome will : A\) show the expression of a recessive allele : B\) mask the expression of a recessive allele : C\) show that there are dominant alleles on both chromosomes : D\) none of the above 4\. Transcription occurs in the : A\) cytoplasm : B\) gogli apparatus : C\) mitochondria : D\) nucleus 5\. This is the start codon and is found at the beginning of each mRNA : A\) AGU : B\) GAU : C\) UAG : D\) GUA : E\) AUG 6\. Sara was born with cystic fibrosis, from this we could assume that : A\) all of her siblings also have cystic fibrosis : B\) only her dad is a carrier : C\) only her mom is a carrier : D\) both of her parents are carriers 7\. Jesse was born with a flattened face, almond eyes and less muscle tone; it could be assumed that he has : A\) a chromosome abnormality on chromosome 21 : B\) a chromosome abnormality on chromosome 19 : C\) a chromosome abnormality on chromosome 20 : D\) a chromosome abnormality on chromosome 22 : E\) No chromosome abnormality, these are his inherited traits 8\. The most common inherited disease is : A\) hemochromatosis : B\) cystic fibrosis : C\) sickle cell anemia : D\) hemophilia : E\) all of the above 9\. Being a carrier of sickle cell anemia means that the person will : A\) also be a carrier of hemophilia : B\) be resistant to malaria : C\) have children that all have sickle cell anemia : D\) have children that all have malaria : E\) none of the above 10\. Hemophilia is : A\) a Y linked disease : B\) an XY linked disease : C\) an X linked disease ## Development: birth through death 1\. Growth is the most rapid in : A\) puberty : B\) childhood : C\) infancy : D\) adulthood : E\) Growth is always the same 2\. This hormone stimulates puberty : A\) GnRH : B\) LH : C\) FSH : D\) TSH 3\. Compared to girls\' early growth spurt, growth \_\_\_\_\_\_\_\_\_\_in boys and \_\_\_\_\_\_\_\_\_\_ : A\) is quicker, lasts longer : B\) accelerates more slowly, lasts longer : C\) is slower, shorter : D\) None of the above 4\. This quality symbolizes adulthood in most cultures : A\) stability : B\) method/tact : C\) endurance : D\) objectivity : E\) all of the above 5\. Susie has a very hard time keeping friends, according to Maslow, this could be because : A\) as a child she had a supportive family : B\) she likes to help solve the problems of others : C\) as a teenager her self-esteem was low : D\) as a baby she wasn't breastfed : E\) as a child she lived in an environment that never made her feel safe 6\. According to Maslow, in order for me to reach my full potential of self-actualization I must first : A\) feel safe : B\) gain self-esteem : C\) have friendship : D\) have food : E\) all of the above 7\. Humans are one of the \_\_\_\_\_\_\_\_\_ developing species in the animal kingdom : A\) slowest : B\) quickest : C\) average : D\) none of the above 8\. Jenny thinks that she might be going through menopause, a symptom of this is : A\) bleeding : B\) frequent urination : C\) itchiness : D\) none of the above : E\) all of the above 9\. It is estimated that 52 million people will be afflicted with this by 2010 : A\) Progeria : B\) osteoporosis : C\) Alzheimer's : D\) dementia 10\. This is the leading cause of death for both men and women : A\) progeria : B\) cancer : C\) congestive heart failure : D\) osteoporosis : E\) heart attack
# Wikijunior:Big Cats/Complete Edition # INTRODUCTION # Foreword \ # Meet The Cats \ = GREAT CATS = # Lions \ = Tigers = \ = Leopards = \ = Jaguars = \ = Snow Leopards = \ = Clouded Leopards = \ = Marbled Cats = \ = SWIFT CATS = # Cheetahs \ = SMALL NEW WORLD CATS = # Pumas \ = Lynx and bobcats = \ = Ocelots = \ = Margays = \ = Jaguarundis = \ = Rusty-spotted cats = \ = SMALL OLD WORLD CATS = # Caracals \ = Servals = \ = Manuls = \ = Wild cats = \ = Sand cats = \ = HYBRIDS = # Tigons and Ligers \ = MORE TOPICS = # How do cats raise their young? \ = Fossil History = \ = In Danger of Extinction = \ = Keeping Cats = \ # Cat Classification # Glossary
# Wikijunior:Big Cats/Marbled cat \_\_NOTOC\_\_ ![](Lydekker_-_Marbled_Cat.JPG "Lydekker_-_Marbled_Cat.JPG"){width="250"} The **marbled cat** is the big cat that isn\'t big at all, only slightly larger than a domestic cat. Scientists place it in the same closely related group as the lion, tiger and leopard, the *Subfamily Pantherinae*, and even though it\'s much smaller than the clouded leopard it has the same long fangs and a very similar fur pattern. Scientific examination of their blood (blood serum analysis) suggests that they are similar in form to the forest ancestors of the big cats some ten million years ago. However, they may have also decreased in size more recently due to competition with other big cats. ## Where do marbled cats live? !Places where marbled cats live are colored blue. The marbled cat may be found in the forests of the Malay peninsula, Sumatra, Borneo and some neighboring small islands. ## What do marbled cats look like? Marbled cats look similar to clouded leopards but they are smaller, have shorter faces more like a domestic cat, and have a fuzzier tail. Its beautiful, striking coat is pale brown, with irregular slightly darker brown blotches sharply outlined in dark brown or black. Its long cylindrical tail is full from rump to tip and carries its body pattern. ## What do marbled cats eat, and how do they catch their prey? Marbled cats spend a great deal of time in the trees and it is likely that they catch much of their prey there, hunting birds, squirrels, rodents, frogs and reptiles. They have been seen hunting on the ground on the island of Borneo, and this may be a local habit. Not much is known about their habits because they are rare in the wild and there are no specimens currently kept in zoos. ## Fun facts - Marbled cats make sounds similar to a domestic cat, but they purr rarely and their meow is somewhat like a twittering bird call. - The longest a marbled cat lived in captivity was 12 years. ## For more information - Wikipedia: Marbled cat Cheetahs de:Wikijunior Großkatzen/ Marmorkatze
# Wikijunior:Big Cats/Cheetah \_\_NOTOC\_\_ !Two cheetahs together.{width="250"} **Cheetahs** are built for speed, with a whip-like spine, long legs, and a long tail that acts as a rudder for sudden turns. They are the world\'s fastest land animal (but the world's fastest animal is a bird called a peregrine falcon). The cheetah can chase its prey for 274 meters (almost a sixth of a mile) at the speed of 114 kilometers (almost 71 miles per hour) per hour. Both the male and the female of the species are referred to as \"cheetahs,\" unlike in the case of many other animals. Cheetahs can generally live up to seven years. ## Where do cheetahs live? !Places where cheetahs live are colored green. Today, most cheetahs are found in sub-Saharan Africa, though a few are still seen in Iran. In the past, they used to be found throughout northern India and Iran. They prefer to live in semi-deserts, savanna, prairies, and thick brush. As they rely upon speed to hunt, they avoid dense forests. Conservation efforts are required in order to avoid the cheetah becoming an entry on the endangered species list. In India, the forests in which many cheetahs live are not secured and they can leave the forests and travel into cities or villages. In the last two or three years, cheetahs have been found in these urban areas. ## What do cheetahs look like? !Cheetahs used as hunters, Persia, early 1560s Cheetahs are rather dog-like, medium-sized spotted cats with long legs and slender, but muscular, bodies. They have a white belly, and a dark stripe that looks like a tear on both sides of their faces. In contrast to leopards, which have palmette shaped spots, cheetahs have round dark spots on their fur. Adult cheetahs weigh from 40 to 65 kilograms (90 to 140 pounds), and are around 112 to 135 centimeters (four to five feet) in length. Cheetahs are built to do what they do: *run*! Their long tail provides them with balance. They have a big chest, a narrow waist, and powerful muscles in their hind legs. They have small heads and muzzles; large nostrils for increased oxygen intake; and small, round ears. All of this makes the cheetah very sleek and aerodynamic when it runs. ## What do they eat, and how do they catch their prey? Cheetahs mostly eat mammals like gazelles, impala, gnu calves, and hares, which are all about the same size as, or smaller than an adult cheetah. Cheetahs stalk their prey until they are within about thirty meters, and then give chase. The chase is usually over in less than a minute, and if the cheetah doesn\'t catch its prey quickly, it will often give up rather than waste energy. This is because cheetahs use a lot of energy when chasing prey at such high speed. They are very fast runners due to the build of their legs and about half of the chases are successful. Cheetahs must eat their catch quickly or risk losing their food to other stronger predators. They will not usually fight with a larger animal over food as risking an injury would mean certain starvation. Cheetahs are well-adapted to living in arid environments. In the Kalahari desert, they have been estimated to travel an average of 82 kilometers (51 miles) between drinks of water. They have been seen getting their water from the blood or urine of their prey or by eating Tsamma melons. ## Fun facts See how much you know about the world\'s fastest land mammal: - After running at full speed, a cheetah must rest at least 15 minutes before running again. - Cheetahs do not roar, but they make a number of very un-catlike sounds, many of which resemble bird chirps. - Cheetah sounds include purrs, bleats, barks, growls, hisses and chirps but the chirp can be heard at a distance of a mile away (more than 1.5 kilometers)! - Cheetahs were called leopards before leopards were! Earlier the word for Cheetah was \"leopard\", and the word for leopard was simply \"pard\". Cheetahs were called leo-pards then as a mix between \"leo\", Latin for lion, and \"pard\", then the name of leopards. - Apart from pumas, cheetahs are the only big cats that purr. - Many cheetah cubs are killed by a lack of food or their natural enemies: lions, leopards, and hyenas. An old African legend says the tear stain marks on the cheetah\'s face are from the mother weeping for her lost cubs. - Cheetahs do not usually eat the skin or bones of their prey. - Hyenas, leopards, and lions steal the cheetah\'s prey after the cheetah has killed it. ## For more information - Wikipedia: Cheetah Pumas ca:Viquijúnior:Grans felins/Guepard de:Wikijunior Großkatzen/ Gepard fr:Wikijunior:Les félins/Les guépards it:Wikijunior_Grandi_felini/Ghepardo
# Wikijunior:Big Cats/Rusty spotted cat \_\_NOTOC\_\_ **Rusty spotted cats** are the smallest members of the cat family. ## Where do rusty spotted cats live? !The range of the rusty-spotted cat appears in green Rusty spotted cats live in southern India and Sri Lanka. Those living in India mostly live in tropical dry forests and dry grasslands, but in Sri Lanka rainforests are the preferred habitat. This may be due to competition with the Leopard Cat, which occupies the rainforests of the mainland, but does not live in Sri Lanka. ## What do rusty spotted cats look like? They are the smallest cats, with small, round ears, a body about 40 cm in length, plus a relatively short 20 cm tail. The color of the fur is gray, with rusty spots all over the back and the flanks. It is rather similar to its close relative the Leopard Cat. They weigh from three to four pounds. ## What do rusty spotted cats eat, and how do they catch their prey? Rusty spotted cats hunt at night, looking for rodents, birds and lizards. They are known to make a meal of domestic poultry when the opportunity arises.They are popular as pets to control mice and rats ## For more information - Wikipedia: Rusty-spotted cat Caracals de:Wikijunior Großkatzen/ Rostkatze
# Wikijunior:Big Cats/Sand cat \_\_NOTOC\_\_ !A sand cat **Sand cats** are the other extreme cat, taking the desert heat the way the snow leopard takes the icy cold. ## Where do sand cats live? As its name implies, the sand cat is commonly found in sandy desert areas in the arid countries of Northern Africa, Arabia, and parts of Central Asia and Pakistan. ## What do sand cats look like? The sand cat's body is well adapted to desert life - its thick, medium length fur insulates it against the extreme cold of the desert nights and its feet and pads are covered with long hair which protects them from the heat of the desert during the day and gives it extra support needed in moving across the soft, shifting sands. The large triangular ears are very sensitive to sound. ## What do sand cats eat, and how do they catch their prey? The sand cat hunts at night, spending the hottest part of the day sleeping under rough scrubby vegetation or a shallow burrow dug into the sand. At sunset the cat will become active, moving away from its den in search of prey. Its diet is known to include small rodents such as gerbil and jerboas, insects, reptiles, including venomous desert snakes and birds but they occasionally catch larger prey. They can do this due to their great hearing and eyesight. ## Fun facts See how much you know about the sand cat: - Sand cats have a low-pitched meow, but can also bark to communicate at long distances. - Most sand cats never drink water due to them getting all their moisture from their prey. - This cat also tends to chase its tail when it gets bored or nervous. - They eat jerboa. ## For more information - Wikipedia: Sand cat Ligers de:Wikijunior Großkatzen/ Sandkatze
# Wikijunior:Big Cats/Tigards The tigard is a rare feline species that comes from a male tiger and a female leopard. When people tried to cross the tiger and the female leopard the cubs that were born died. There have only been two attempts for crossing this two species: In the year 1900 Carl Hagenbeck crossed this two species but he failed and the cubs died when they were born, the cubs had many rosettes, some spots and a few stripes. In the year 1951 the book \'Mammalian Hybrids\' reported that a male tiger and two female leopards from India had cubs but the cubs were born premature and they had the size of a small mouse or a walnut.
# Wikijunior:Big Cats/In danger of extinction \_\_NOTOC\_\_ ## Extinction is Forever !A photo of an extinct Bali tiger Some big cats throughout history have become extinct because they were replaced with newer species better suited to the environment. The Sabretooth (*Smilodon fatalis*) is one example of a large Ice-Age predator that died out because the large prey it needed retreated with the glaciers. Pumas and jaguars now roam where the mighty Sabertooth once ruled. Natural extinction is part of the grand drama of life on Earth. However, many more cat species are in danger of dying out due to unnatural extinction, the killing of an entire species by man for reasons having nothing to do with fitness for survival. These species are not replaced with newer ones, their death merely leaves a hole in the fabric of life on Earth. ## Predation Many big cats have been killed because they either compete with humans for the same prey animals or because they occasionally attack human-raised livestock. Some big cats that become too weak to hunt their own natural prey find domestic livestock much simpler to acquire. Other big cats develop a taste for livestock out of sheer opportunity. There are times when control of individual predators, through moving or killing, appear to be justified. However there is a much more dangerous approach to predator control where an entire population or even an entire species is classified as a \"pest\" and open to *extermination*. Extermination is an attempt to kill every last individual of a population or species. There were times when pumas were targeted for extermination in large areas of the American west. Bobcats and jaguars have also been targets of extermination. These days most governments in the world agree that extermination is not a good way to control cats, but sometimes local peoples ignore laws designed to protect species from extermination. ## Sport Hunting The majority of people in western countries no longer give big game hunters the same respect they once held in the writings of Ernest Hemmingway. The cheetah, which was once abundant in India, was hunted to complete extinction there. The Mughal emperor Akbar killed nearly 1000 cheetahs during his lifetime when the number of cheetahs was already declining. The Asian lion met with the same fate. Most outdoorsmen no longer seek trophies for their mantles and entrance halls. However, a number of people still consider locating, outwitting, and defeating large predators to be the ultimate test of courage and a satisfying form of enjoying the out of doors. This practice is losing popularity, though. In all fairness, it should be said that sport hunters support laws and practices that benefit wildlife. In the United States, wildlife populations have increased within the past century. This is largely due to funds generated via an excise tax on hunting equipment known as the Pittman-Robertson Act. In addition, sportsmen contribute hundreds of millions of dollars each year to wildlife conservation through sporting organizations that benefit all wildlife. ## Poaching People who defy existing laws to kill predators for money, animal parts, or personal reasons are called poachers. As outlaws, many poachers are dangerous people who are willing to protect their livelihood through violent means. Famous conservation leaders George Adamson and Diane Fossey were killed by poachers who saw them as a threat. Stopping poaching is very difficult because most big cat habitat is remote land that is difficult to patrol and exists in some of the world\'s poorest countries without many law enforcement resources. The most effective way to curb poaching is to reduce the demand for the products they provide. ## Folk Medicines A number of people believe, without any scientific evidence, that folk medicines made from parts of big cats can treat or even cure certain illnesses and conditions. Belief in sympathetic magic, that like-causes-like, leads people to seek the attributes they most admire about big cats by using parts of their bodies. People seeking courage, strength, or a greater capacity for physical intimacy attempt to acquire those things through eating, drinking, applying or wearing parts of the animals that are supposed to possess those traits. For nearly everything supposedly treatable with feline folk medicines, there are effective, safe and proven remedies available in modern medicine. ## The Fur Trade The soft, warm, boldly patterned *pelts* (skins with fur) of big cats were long considered the ultimate expression of fashion and extravagance. Even today, most fashion items made with real fur come from carnivores such as bobcats and mink. Those legal for sale are produced from animals raised on fur farms rather than taken from the wild. The vast majority of natural leopard, ocelot, lynx and jaguar furs are banned on the international market by laws protecting endangered species. ## Habitat Loss !Habitat loss is the silent killer Habitat loss is the silent killer. An animal\'s habitat is an area where it can live, and for most large predators that means cover, adequate prey, freedom of movement, and water. Due to their predatory lifestyle, most big cats require large areas of land without many manmade barriers where they can hunt and raise young unmolested. Uncontrolled development of wild areas, including such wasteful practices as slash-and-burn agriculture, reduce the number of places where big cats can survive and thrive. To some degree protected areas known as Parks and Wildlife Sanctuaries help preserve endangered species habitat. However in many poor countries there is not adequate law enforcement to prevent poaching or illegal development of land inside park boundaries. In addition, animals need more land than the human race can afford to protect in parks. More enlightened use of habitat by man can increase the number of big cats and preserve their genetic diversity. For instance, a timber plantation can provide both high quality wood and habitat for predators and their prey. Using *sustainable management* techniques, land can provide a never-ending source of quality wood products while continuing to preserve wildlife. ## It Is Up To You As someone interested in big cats, you can make your love of big cats known through the way you vote, your lifestyle, and your charitable giving. Governments can only do so much to help stop extinction. For big cats to be saved, they must be saved by all of us working together. Learn what you can do about the challenges facing your favorite animals, and get involved. Always remember: \"We appreciate what we understand and save what we appreciate.\" Cats de:Wikijunior Großkatzen/ Die Gefahr des Aussterbens
# Wikijunior:Big Cats/Classification Scientists classify all living things into different groups. This helps to see what some animals have in common and how related some animals are. It is like building a family tree for living things. They classify cats as well. All cats are in the family Felidae. In English, a Puma may be called a cougar in one place or a mountain lion somewhere else. Animals also have different names in other languages like Russian, Greek and Spanish. To prevent confusion, scientists agree on a single Latin name for each animal. Some early humans did draw pictures of mammoths, mastodons, and European cave lions, but any common names for these extinct animals are forgotten. That\'s why many fossil big cats have an odd scientific name like *Miraconyx inexpectatus* instead of a short, graceful name like *Cheetah*. Below is a list of the classification of the cats in this book. Kingdom: Animalia (Animals) : Phylum: Chordata (Animals with spinal cords) : Subphylum: Vertebrata (Vertebrates) : Class: Mammalia (Mammals) : Order: Carnivora (most Carnivorous Mammals) : Family: Felidae (Cats) : Subfamily **Acinonychinae** : Genus *Acinonyx* : Cheetah, *Acinonyx jubatus* : Subfamily **Felinae** : Genus *Caracal* : Caracal, *Caracal caracal* : Genus *Felis* : Wild Cat, *Felis silvestris* (of which the domestic cat is a subspecies) : Sand Cat, *Felis margarita* : Genus *Herpailurus* : Jaguarundi, *Herpailurus yaguarondi* : Genus *Leopardus* : Ocelot, *Leopardus pardalis* : Margay, *Leopardus wiedii* : Genus *Leptailurus* : Serval, *Leptailurus serval* : Genus *Lynx* : Eurasian Lynx, *Lynx lynx* : Iberian Lynx, *Lynx pardinus* : Canadian Lynx, *Lynx canadensis* : Bobcat, *Lynx rufus* : Genus *Otocolobus* : Pallas Cat, *Otocolobus manul* : Genus *Prionailurus* : Rusty-spotted Cat, *Prionailurus rubiginosus* : Genus *Puma* : Puma, *Puma concolor* : Subfamily **Pantherinae** : Genus *Neofelis* : Clouded Leopard, *Neofelis nebulosa* : Genus *Panthera* : Lion, *Panthera leo* : Tiger, *Panthera tigris* : Leopard, *Panthera pardus* : Jaguar, *Panthera onca* : Liger, *Panthera × leogris* (hybrid) : Tigon, *Panthera × tigreo* (hybrid) : Genus *Pardofelis* : Marbled Cat, *Pardofelis marmorata* : Genus *Uncia* : Snow Leopard, *Uncia uncia* ## For more information Felidae Next Topic: Glossary of Terms
# Non-Programmer's Tutorial for Python 3/Front matter All example Python source code in this tutorial is granted to the public domain. Therefore you may modify it and relicense it under any license you please. Since you are expected to learn programming, the Creative Commons Attribution-ShareAlike license would require you to keep all programs that are derived from the source code in this tutorial under that license. Since the Python source code is granted to the public domain, that requirement is waived. This tutorial is more or less a conversion of Non-Programmer\'s Tutorial for Python 2.6. Older versions and some versions in Korean, Spanish, Italian and Greek are available from <http://jjc.freeshell.org/easytut/> The *Non-Programmers\' Tutorial For Python 3* is a tutorial designed to be an introduction to the Python programming language. Originally, this guide is for someone with no programming experience. However, it does take a few shortcuts here and there. If you\'re confused at some point, try one of the other Python tutorials linked below. Be sure to come back to improve this Wikibook though! ;-) If you have programmed in other languages I recommend the Python Tutorial for Programmers written by Guido van Rossum. If you have any questions or comments please use the discussion pages or see Authors page for author contact information. I welcome questions and comments about this tutorial. I will try to answer any questions you have as best I can. Thanks go to James A. Brown for writing most of the Windows install info. Thanks also to Elizabeth Cogliati for complaining enough :) about the original tutorial (that is almost unusable for a non-programmer), for proofreading, and for many ideas and comments on it. Thanks to Joe Oppegaard for writing almost all the exercises. Thanks to everyone I have missed. ### Other resources - Python Home Page - Python 3 Documentation - Official Python tutorial - A Byte of Python by Swaroop C H - Another free beginners Python tutorial (Python Land) - Porting to Python 3: An in-depth guide ca:Python 3 per a no programadors/Prefaci id:Panduan Python 3 untuk Non-Pemrogram/Pendahuluan
# Non-Programmer's Tutorial for Python 3/Intro ### First things first So, you\'ve never programmed before. As we go through this tutorial, I will attempt to teach you how to program. There really is only one way to learn to program. **You** must read *code* and write *code* (as computer programs are often called). I\'m going to show you lots of code. You should type in code that I show you to see what happens. Play around with it and make changes. The worst that can happen is that it won\'t work. When I type in code it will be formatted like this: ``` python # Python is easy to learn print("Hello, World!") ``` That\'s so it is easy to distinguish from the other text. If you\'re reading this on the Web, you\'ll notice the code is in color \-- that\'s just to make it stand out, and to make the different parts of the code stand out from each other. The code you enter will probably not be colored, or the colors may be different, but it won\'t affect the code as long as you enter it the same way as it\'s printed here. If the computer prints something out it will be formatted like this: `Hello, World!` (Note that printed text goes to your screen, and does not involve paper. Before computers had screens, the output of computer programs would be printed on paper.) Note that this is a Python 3 tutorial, which means that most of the examples will not work in Python 2.7 and before. As well, all but a small number of the extra Python 2.7 libraries (third-party libraries) have been converted to Python 3. Most likely you will want to learn Python 3, but if you are learning Python for a specific package or set of modules that are only written in Python 2.7, you may want to consider learning from the Non-Programmer\'s Tutorial for Python 2.6. However, the differences between Python 2 and 3 are not particularly large, so if you learn one, you should be able to read programs written for the other without much difficulty. There will often be a mixture of the text you type (which is shown in **bold**) and the text the program prints to the screen, which would look like this: `Halt!`\ `Who Goes there? `**`Josh`**\ `You may pass, Josh` (Some of the tutorial has not been converted to this format. Since this is a wiki, you can convert it when you find it.) I will also introduce you to the terminology of programming - for example, that programming is often referred to as *coding* or *hacking*. This will not only help you understand what programmers are talking about, but also help the learning process. Now, on to more important things. In order to program in Python you need the Python 3 software. If you don\'t already have the Python software go to www.python.org/download and get the proper version for your platform. Download it, read the instructions and get it installed. ### Installing Python For Python programming you need a working Python installation and a text editor. Python comes with its own editor, *IDLE*, which is quite nice and totally sufficient for the beginning. As you get more into programming, you will probably switch to some other editor like `nano`, `emacs`, `vi` or another. The Python download page is <http://www.python.org/download>. The most recent version is Python 3.11.5 (as of October 2023); **Python 2.7 and older versions will not work with this tutorial.** There are various different installation files for different computer platforms available on the download site. Here are some specific instructions for the most common operating systems: #### Linux, BSD, and Unix users You are probably lucky and Python is already installed on your machine. To test it type `python3` on a command line. If you see something like what is shown in the following section, you are set. IDLE may need to be installed separately, from its own package such as `idle3` or as part of `python-tools`. If you have to install Python, first try to use the operating system\'s package manager or go to the repository where your packages are available and get Python 3. Python 3.0 was released in December 2008; all distributions should have Python 3 available, so you may not need to compile it from scratch. Ubuntu and Fedora do have Python 3 binary packages available, but they are not yet the default, so they need to be installed specially. Roughly, here are the steps to compile Python from source code in Unix (If these totally don\'t make sense, you may want to read another introduction to \*nix, such as Introduction to Linux): - Download the .tgz file (use your Web browser to get the gzipped tar file from <https://www.python.org/ftp/python/3.7.4/Python-3.7.4.tgz>) - Uncompress the tar file (put in the correct path to where you downloaded it): `$ tar -xvzf ~/Download/Python-3.7.4.tgz`\ *`... list of files as they are uncompressed`* - Change to the directory and tell the computer to compile and install the program `$ cd Python-3.7/`\ `$ ./configure --prefix=$HOME/python3_install`\ *`... lots of output. Watch for error messages here ...`*\ `$ make`\ *`... even more output. Hopefully no error messages ...`*\ `$ make install` - Add Python 3 to your path. You can test it first by specifying the full path. You should add \$HOME/python3_install/bin to your PATH bash variable. `$ ~/python3_install/bin/python3`\ `Python 3.7.4 (... size and date information ...)`\ `[GCC 9.1.0] on linux`\ `Type "help", "copyright", "credits" or "license" for more information.`\ `>>>''` The above commands will install Python 3 to your home directory, which is probably what you want, but if you skip the `--prefix=$HOME/python3_install`, it will install it to `/usr/local`. If you want to use the IDLE graphical code editor, you need to make sure that the `tk` and `tcl` libraries, together with their development files, are installed on the system. You will get a warning during the `make` phase if these are not available. #### Mac users Starting from Mac OS X Tiger (10.4), versions of Python 2 shipped with the operating system by default, but you will need to also install Python 3 unless Mac OS starts including Python 3 (check the version by starting `python3` in a command line terminal). Also IDLE (the Python editor) might be missing in the standard installation. If you want to (re-)install Python, get the Mac OS installer from the Python download site. #### Windows users Download the appropriate Windows installer (the x86 MSI installer, if you do not have a 64-bit AMD or Intel chip). Start the installer by double-clicking it and follow the prompts. See <https://docs.python.org/3/using/windows.html#installing-python> for more information. ##### Configuring your PATH environment variable The PATH environment variable is a list of folders, separated by semicolons, in which Windows will look for a program whenever you try to execute one by typing its name at a Command Prompt. You can see the current value of your PATH by typing this command at a Command Prompt: `echo %PATH%` The easiest way to permanently change environment variables is to bring up the built-in environment variable editor in Windows. How you get to this editor is slightly different on different versions of Windows. **On Windows 8** or **Windows 10**: Press the Windows key and type *Control Panel* to locate the Windows Control Panel. Once you\'ve opened the Control Panel, select View by: Large Icons, then click on *System*. In the window that pops up, click the *Advanced System Settings* link, then click the *Environment Variables\...* button. **On Windows 7** or **Vista**: Click the Start button in the lower-left corner of the screen, move your mouse over *Computer*, right-click, and select *Properties* from the pop-up menu. Click the *Advanced System Settings* link, then click the *Environment Variables\...* button. Once you\'ve brought up the environment variable editor, you\'ll do the same thing regardless of which version of Windows you\'re running. Under *System Variables* in the bottom half of the editor, find a variable called `PATH`. If there is is one, select it and click *Edit\...*. Assuming your Python root is `C:\Python37`, add these two folders to your path (and make sure you get the semicolons right; there should be a semicolon between each folder in the list): `C:\Python37`\ `C:\Python37\Scripts` Note: If you want to double-click and start your Python programs from a Windows folder and not have the console window disappear, you can add the following code to the bottom of each script: ``` python #stops console from exiting end_prog = "" while end_prog != "q": end_prog = input("type q to quit") ``` ### Interactive Mode Go into IDLE (also called the Python GUI). You should see a window that has some text like this: Python 3.0 (r30:67503, Dec 29 2008, 21:31:07) [GCC 4.3.2 20081105 (Red Hat 4.3.2-7)] on linux2 Type "copyright", "credits" or "license()" for more information. **************************************************************** Personal firewall software may warn about the connection IDLE makes to its subprocess using this computer's internal loopback interface. This connection is not visible on any external interface and no data is sent to or received from the Internet. **************************************************************** IDLE 3.0 >>> The `>>>` is Python\'s way of telling you that you are in interactive mode. In interactive mode what you type is immediately run. Try typing `1+1` in. Python will respond with `2`. Interactive mode allows you to test out and see what Python will do. If you ever feel you need to play with new Python statements, go into interactive mode and try them out. ### Creating and Running Programs Go into IDLE if you are not already. In the menu at the top, select *File* then *New File*. In the new window that appears, type the following: ``` python print("Hello, World!") ``` Now save the program: select *File* from the menu, then *Save*. Save it as \"`hello.py`\" (you can save it in any folder you want). Now that it is saved it can be run. Next run the program by going to *Run* then *Run Module* (or if you have an older version of IDLE use *Edit* then *Run script*). This will output `Hello, World!` on the *\*Python Shell\** window. For a more in-depth introduction to IDLE, a longer tutorial with screenshots can be found at <http://hkn.eecs.berkeley.edu/~dyoo/python/idle_intro/index.html>. #### Program file names It is very useful to stick to some rules regarding the file names of Python programs. Otherwise some things *might* go wrong unexpectedly. These don\'t matter as much for programs, but you can have weird problems if you don\'t follow them for module names (modules will be discussed later). 1. Always save the program with the extension `.py`. Do not put another dot anywhere else in the file name. 2. Only use standard characters for file names: letters, numbers, dash (`-`) and underscore (`_`). 3. White space (\"\") should not be used at all (use underscores instead). 4. Do not use anything other than a letter (particularly no numbers!) at the beginning of a file name. 5. Do not use \"non-English\" characters (such as `å`, `ɓ`, `ç`, `ð`, `é`, `õ`, `ü`) in your file names---or, even better, do not use them at all when programming. 6. Do not use module names for file names (such as `print.py`, `math.py`, `list.py`) ### Using Python from the command line If you don\'t want to use Python from the command line, you don\'t have to, just use IDLE. To get into interactive mode just type `python3` without any arguments. To run a program, create it with a text editor (Emacs has a good Python mode) and then run it with `python3 `*`program_name`*. #### Running Python Programs in \*nix If you are using Unix (such as Linux, Mac OS, or BSD), if you make the program executable with chmod, and have as the first line: ``` python #!/usr/bin/env python3 ``` you can run the python program with `./hello.py` like any other command. ### Where to get help At some point in your Python career you will probably get stuck and have no clue about how to solve the problem you are supposed to work on. This tutorial only covers the basics of Python programming, but there is a lot of further information available. #### Python documentation First of all, Python is very well documented. There might even be copies of these documents on your computer that came with your Python installation: - The official Python 3 Tutorial by Guido van Rossum is often a good starting point for general questions. - For questions about standard modules (you will learn what these are later), the Python 3 Library Reference is the place to look. - If you really want to get to know something about the details of the language, the Python 3 Reference Manual is comprehensive but quite complex for beginners. #### Python user community There are a lot of other Python users out there, and usually they are nice and willing to help you. This very active user community is organised mostly through mailing lists and a newsgroup: - The tutor mailing list is for folks who want to ask questions regarding how to learn computer programming with the Python language. - The python-help mailing list is python.org\'s help desk. You can ask a group of knowledgeable volunteers questions about all your Python problems. - The Python newsgroup comp.lang.python (Google groups archive) is the place for general Python discussions, questions and the central meeting point of the community. - Python wiki has a list of local user groups, you can join the group mailing list and ask questions. You can also participate in the user group meetings. - LearnPython subreddit is another location where beginner level questions can be asked. In order not to reinvent the wheel and discuss the same questions again and again, people will appreciate very much if you *do a web search for a solution to your problem before contacting these lists!* ###### Using python online If you don\'t want to download python, or you are using a computer that you cannot download programs on, such as a chromebook, you can use one of the many available online python editors. ca:Python 3 per a no programadors/Introducció id:Panduan Python 3 untuk Non-Pemrogram/Pengantar
# Non-Programmer's Tutorial for Python 3/Hello, World ### What you should know Once you\'ve read and mastered this chapter, you should know how to edit programs in a text editor or IDLE, save them to the hard disk, and run them once they have been saved. ### Printing Programming tutorials since the beginning of time have started with a little program called \"Hello, World!\"[^1] So here it is: ``` python print("Hello, World!") ``` If you are using the command line to run programs then type it in with a text editor, save it as `hello.py` and run it with `python3 hello.py` Otherwise go into IDLE, create a new window, and create the program as in section Creating and Running Programs. When you run this program, the output will look as follows: `Hello, World!` Now I\'m not going to tell you this every time, but when I show you a program, I recommend that you type it yourself and run it (as opposed to copy/pasting it). I tend to learn and internalize the learning material better when I type it in, and you will probably too! Now here is a more complicated program: ``` python print("Jack and Jill went up a hill") print("to fetch a pail of water;") print("Jack fell down, and broke his crown,") print("and Jill came tumbling after.") print("hello python.") print("hello python 3.") print("this is not c++ language") ``` When you run this program it prints out: `Jack and Jill went up a hill`\ `to fetch a pail of water;`\ `Jack fell down, and broke his crown,`\ `and Jill came tumbling after.` When the computer runs this program it first sees the line: ``` python print("Jack and Jill went up a hill") ``` so the computer prints: `Jack and Jill went up a hill` Then the computer goes down to the next line and sees: ``` python print("to fetch a pail of water;") ``` So the computer prints to the screen: `to fetch a pail of water;` The computer keeps looking at each line, follows the command and then goes on to the next line. The computer keeps running commands until it reaches the end of the program. #### Terminology Now is probably a good time to give you a bit of an explanation of what is happening - and a little bit of programming terminology. What we were doing above was using a *function* called `print`. The function\'s name - `print` - is followed by parentheses containing zero or more *arguments*. So in this example ``` python print("Hello, World!") ``` there is one *argument*, which is `"Hello, World!"`. Note that this argument is a group of characters enclosed in double quotes (\"\"). This is commonly referred to as a *string of characters*, or *string*, for short. Another example of a string is `"Jack and Jill went up a hill"`. The combination of a function and parentheses with the arguments is a *function call*. A function and its arguments are one type of *statement* that python has, so ``` python print("Hello, World!") ``` is an example of a statement. Basically, you can think of a statement as a single line in a program. That\'s probably more than enough terminology for now. #### \\n in Printing `\n`, or newline in printing makes the strings after the \\n in a new line, it is also an escape character, here is an example: ``` python print("Hello, World!\nWhat should I do?") ``` Here is the output: `Hello, World!`\ `What should I do?` It can be used to put a bunch of strings that are supposed to be on different lines into 1 print statement instead of making multiple print statements The print statement also sort of uses `\n` even if you do not use it for example: ``` python print("Hello, World!") ``` is actually ``` python print("Hello, World!\n") ``` Well, there is a difference if you do it manually, but python actually adds a newline \"behind the scenes\" at the end of the string ### Expressions Here is another program: ``` python print("2 + 2 is", 2 + 2) print("3 * 4 is", 3 * 4) print("100 - 1 is", 100 - 1) print("(33 + 2) / 5 + 11.5 is", (33 + 2) / 5 + 11.5) ``` And here is the *output* when the program is run: `2 + 2 is 4`\ `3 * 4 is 12`\ `100 - 1 is 99`\ `(33 + 2) / 5 + 11.5 is 18.5` As you can see, Python can turn your thousand-dollar computer into a five-dollar calculator. #### Arithmetic expressions In this example, the print function is followed by two arguments, with each of the arguments separated by a comma. So with the first line of the program ``` python print("2 + 2 is", 2 + 2) ``` The first argument is the string `"2 + 2 is"` and the second argument is the *arithmetic expression* `2 + 2`, which is one kind of *expression*. What is important to note is that a string is printed as is (without the enclosing double quotes), but an *expression* is *evaluated*, or converted to its actual value. Python has seven basic operations for numbers: Operation Symbol Example ------------------------ -------- ------------------------------- Power (exponentiation) `**` `5 ** 2 == 25` Multiplication `*` `2 * 3 == 6` Division `/` `14 / 3 == 4.666666666666667` Integer Division `//` `14 // 3 == 4` Remainder (modulo) `%` `14 % 3 == 2` Addition `+` `1 + 2 == 3` Subtraction `-` `4 - 3 == 1` Notice that there are two ways to do division, one that returns the repeating decimal, and the other that can get the remainder and the whole number. The order of operations is the same as in math: - parentheses `()` - exponents `**` - multiplication `*`, division `/`, integer division `//`, and remainder `%` - addition `+` and subtraction `-` So use parentheses to structure your formulas when needed. ### Commenting in Python Often in programming, you are doing something complicated and may not in the future remember what you did. When this happens the program should probably be commented. A *comment* is a note to you and other programmers explaining what is happening. For example: ``` python # Not quite PI, but a credible simulation print(22 / 7) ``` Which outputs `3.14285714286` Notice that the comment starts with a hash: `#`. Comments are used to communicate with others who read the program and your future self to make clear what is complicated. Note that any text can follow comment and that when the program is run, the text after the `#` through to the end of that line is ignored. The `#` does not have to be at the beginning of a new line: ``` python # Output PI on the screen print(22 / 7) # Well, just a good approximation ``` ### Examples Each chapter (eventually) will contain examples of the programming features introduced in the chapter. You should at least look over them and see if you understand them. If you don\'t, you may want to type them in and see what happens. Mess around with them, change them and see what happens. **Denmark.py** ``` python print("Something's rotten in the state of Denmark.") print(" -- Shakespeare") ``` Output: `Something's rotten in the state of Denmark.`\ `                -- Shakespeare` **School.py** ``` python # This is not quite true outside of USA # and is based on my dim memories of my younger years print("Firstish Grade") print("1 + 1 =", 1 + 1) print("2 + 4 =", 2 + 4) print("5 - 2 =", 5 - 2) print() print("Thirdish Grade") print("243 - 23 =", 243 - 23) print("12 * 4 =", 12 * 4) print("12 / 3 =", 12 / 3) print("13 / 3 =", 13 // 3, "R", 13 % 3) print() print("Junior High") print("123.56 - 62.12 =", 123.56 - 62.12) print("(4 + 3) * 2 =", (4 + 3) * 2) print("4 + 3 * 2 =", 4 + 3 * 2) print("3 ** 2 =", 3 ** 2) ``` Output: `Firstish Grade`\ `1 + 1 = 2`\ `2 + 4 = 6`\ `5 - 2 = 3`\ \ `Thirdish Grade`\ `243 - 23 = 220`\ `12 * 4 = 48`\ `12 / 3 = 4`\ `13 / 3 = 4 R 1`\ \ `Junior High`\ `123.56 - 62.12 = 61.44`\ `(4 + 3) * 2 = 14`\ `4 + 3 * 2 = 10`\ `3 ** 2 = 9` ### Exercises 1. Write a program that prints your full name and your birthday as separate strings. 2. Write a program that shows the use of all 7 arithmetic operations. ------------------------------------------------------------------------ #### Footnotes ```{=html} <references/> ``` ca:Python 3 per a no programadors/Hola, món [^1]: Here is a great list of the famous \"Hello, world!\" program in many programming languages. Just so you know how simple Python can be\...
# Non-Programmer's Tutorial for Python 3/Who Goes There? ### Input and Variables Now I feel it is time for a really complicated program. Here it is: ``` python print("Halt!") user_input = input("Who goes there? ") print("You may pass,", user_input) ``` When **I** ran it, here is what **my** screen showed: `Halt!`\ `Who goes there? `**`Josh`**\ `You may pass, Josh` *Note: After running the code by pressing F5, the python shell will only give output:* `Halt!`\ `Who goes there?` *You need to enter your name in the python shell, and then press enter for the rest of the output.* Of course when you run the program your screen will look different because of the `input()` statement. When you ran the program you probably noticed (you did run the program, right?) how you had to type in your name and then press Enter. Then the program printed out some more text and also your name. This is an example of *input*. The program reaches a certain point and then waits for the user to input some data that the program can use later. Of course, getting information from the user would be useless if we didn\'t have anywhere to put that information and this is where variables come in. In the previous program `user_input` is a *variable*. Variables are like a box that can store some piece of data. Here is a program to show examples of variables: ``` python a = 123.4 b23 = 'Spam' first_name = "Bill" b = 432 c = a + b print("a + b is",c) print("first_name is",first_name) print("Sorted Parts, After Midnight or",b23) ``` And here is the output: `a + b is 555.4`\ `first_name is Bill`\ `Sorted Parts, After Midnight or Spam` Variables store data. The variables in the above program are `a`, `b23`, `first_name`, `b`, and `c`. The two basic types are *strings* and *numbers*. Strings are a sequence of letters, numbers and other characters. In this example `b23` and `first_name` are variables that are storing strings. `Spam`, `Bill`, `a + b is`, `first_name is`, and `Sorted Parts, After Midnight or` are the strings in this program. The characters are surrounded by `"` or `'`. The other type of variables are numbers. Remember that variables are used to store a value, they do not use quotation marks (\" and \'). If you want to use an actual *value*, you *must* use quotation marks. ``` python value1 == Pim value2 == "Pim" ``` Both look the same, but in the first one Python checks if the value stored in the variable `value1` is the same as the value stored in the *variable* `Pim`. In the second one, Python checks if the string (the actual letters `P`,`i`, and `m`) are the same as in `value2` (continue this tutorial for more explanation about strings and about the `==`). ### Assignment Okay, so we have these boxes called variables and also data that can go into the variable. The computer will see a line like `first_name = "Bill"` and it reads it as \"Put the string `Bill` into the box (or variable) `first_name`\". Later on it sees the statement `c = a + b` and it reads it as \"put the sum of `a + b` or `123.4 + 432` which equals `555.4` into `c`\". The right hand side of the statement (`a + b`) is *evaluated* and the result is stored in the variable on the left hand side (`c`). This is called *assignment*, and you should not confuse the assignment equal sign (`=`) with \"equality\" in a mathematical sense here (that\'s what `==` will be used for later). Here is another example of variable usage: ``` python a = 1 print(a) a = a + 1 print(a) a = a * 2 print(a) ``` And of course here is the output: `1`\ `2`\ `4` Even if the same variable appears on both sides of the equals sign (e.g., spam = spam), the computer still reads it as, \"First find out the data to store and then find out where the data goes.\" One more program before I end this chapter: ``` python number = float(input("Type in a number: ")) integer = int(input("Type in an integer: ")) text = input("Type in a string: ") print("number =", number) print("number is a", type(number)) print("number * 2 =", number * 2) print("integer =", integer) print("integer is a", type(integer)) print("integer * 2 =", integer * 2) print("text =", text) print("text is a", type(text)) print("text * 2 =", text * 2) ``` The output I got was: `Type in a number: `**`12.34`**\ `Type in an integer: `**`-3`**\ `Type in a string: `**`Hello`**\ `number = 12.34`\ `number is a <class 'float'>`\ `number * 2 = 24.68`\ `integer = -3`\ `integer is a <class 'int'>`\ `integer * 2 = -6`\ `text = Hello`\ `text is a <class 'str'>`\ `text * 2 = HelloHello` Notice that `number` was created with `float(input())` ,`int(input())` returns an integer, a number with no decimal point, while `text` created with `input()` returns a string(can be written as `str(input())`, too). When you want the user to type in a decimal use `float(input())`, if you want the user to type in an integer use `int(input())`, but if you want the user to type in a string use `input()`. The second half of the program uses the `type()` function which tells what kind a variable is. Numbers are of type `int` or `float`, which are short for *integer* and *floating point* (mostly used for decimal numbers), respectively. Text strings are of type `str`, short for *string*. Integers and floats can be worked on by mathematical functions, strings cannot. Notice how when python multiplies a number by an integer the expected thing happens. However when a string is multiplied by an integer the result is that multiple copies of the string are produced (i.e., `text * 2 = HelloHello`). Operations with strings do different things than operations with numbers. As well, some operations only work with numbers (both integers and floating point numbers) and will give an error if a string is used. Here are some interactive mode examples to show that some more. >>> print("This" + " " + "is" + " joined.") This is joined. >>> print("Ha, " * 5) Ha, Ha, Ha, Ha, Ha, >>> print("Ha, " * 5 + "ha!") Ha, Ha, Ha, Ha, Ha, ha! >>> print(3 - 1) 2 >>> print("3" - "1") Traceback (most recent call last): File "<stdin>", line 1, in <module> TypeError: unsupported operand type(s) for -: 'str' and 'str' >>> Here is the list of some string operations: Operation Symbol Example --------------- -------- ------------------------------------------- Repetition `*` `"i" * 5 == "iiiii"` Concatenation `+` `"Hello, " + "World!" == "Hello, World!"` ### Examples **Rate_times.py** ``` python # This program calculates rate and distance problems print("Input a rate and a distance") rate = float(input("Rate: ")) distance = float(input("Distance: ")) time=(distance/ rate) print("Time:", time) ``` Sample runs: `Input a rate and a distance`\ `Rate: `**`5`**\ `Distance: `**`10`**\ `Time: 2.0` `Input a rate and a distance`\ `Rate: `**`3.52`**\ `Distance: `**`45.6`**\ `Time: 12.9545454545` **Area.py** ``` python # This program calculates the perimeter and area of a rectangle print("Calculate information about a rectangle") length = float(input("Length: ")) width = float(input("Width: ")) Perimeter=(2 * length + 2 * width) print("Area:", length * width) print("Perimeter:",Perimeter) ``` Sample runs: `Calculate information about a rectangle`\ `Length: `**`4`**\ `Width: `**`3`**\ `Area: 12.0`\ `Perimeter: 14.0` `Calculate information about a rectangle`\ `Length: `**`2.53`**\ `Width: `**`5.2`**\ `Area: 13.156`\ `Perimeter: 15.46` **Temperature.py** ``` python # This program converts Fahrenheit to Celsius fahr_temp = float(input("Fahrenheit temperature: ")) celc_temp = (fahr_temp - 32.0) *( 5.0 / 9.0) print("Celsius temperature:", celc_temp) ``` Sample runs: `Fahrenheit temperature: `**`32`**\ `Celsius temperature: 0.0` `Fahrenheit temperature: `**`-40`**\ `Celsius temperature: -40.0` `Fahrenheit temperature: `**`212`**\ `Celsius temperature: 100.0` `Fahrenheit temperature: `**`98.6`**\ `Celsius temperature: 37.0` ### Exercises Write a program that gets 2 string variables and 2 number variables from the user, concatenates (joins them together with no spaces) and displays the strings, then multiplies the two numbers on a new line. ca:Python 3 per a no programadors/Qui hi ha?
# Non-Programmer's Tutorial for Python 3/Count to 10 ### While loops Presenting our first *control structure*. Ordinarily the computer starts with the first line and then goes down from there. Control structures change the order that statements are executed or decide if a certain statement will be run. Here\'s the source for a program that uses the while control structure: ``` python a = 0 # FIRST, set the initial value of the variable a to 0(zero). while a < 10: # While the value of the variable a is less than 10 do the following: a = a + 1 # Increase the value of the variable a by 1, as in: a = a + 1! print(a) # Print to screen what the present value of the variable a is. # REPEAT! until the value of the variable a is equal to 9!? See note. # NOTE: # The value of the variable a will increase by 1 # with each repeat, or loop of the 'while statement BLOCK'. # e.g. a = 1 then a = 2 then a = 3 etc. until a = 9 then... # the code will finish adding 1 to a (now a = 10), printing the # result, and then exiting the 'while statement BLOCK'. # -- # While a < 10: | # a = a + 1 |<--[ The while statement BLOCK ] # print (a) | # -- ``` And here is the extremely exciting output: `1`\ `2`\ `3`\ `4`\ `5`\ `6`\ `7`\ `8`\ `9`\ `10` (And you thought it couldn\'t get any worse after turning your computer into a five-dollar calculator?) So what does the program do? First it sees the line `a = 0` and sets `a` to zero. Then it sees `while a < 10:` and so the computer checks to see if `a < 10`. The first time the computer sees this statement, `a` is zero, so it is less than 10. In other words, as long as `a` is less than ten, the computer will run the tabbed in statements. This eventually makes `a` equal to ten (by adding one to `a` again and again) and the `while a < 10` is not true any longer. Reaching that point, the program will stop running the indented lines. Always remember to put a colon \"**:**\" at the end of the `while` statement line! Here is another example of the use of `while`: ``` python a = 1 s = 0 print('Enter Numbers to add to the sum.') print('Enter 0 to quit.') while a != 0: print('Current Sum:', s) a = float(input('Number? ')) s = s + a print('Total Sum =', s) ``` `Enter Numbers to add to the sum.`\ `Enter 0 to quit.`\ `Current Sum: 0`\ `Number? `**`200`**\ `Current Sum: 200.0`\ `Number? `**`-15.25`**\ `Current Sum: 184.75`\ `Number? `**`-151.85`**\ `Current Sum: 32.9`\ `Number? `**`10.00`**\ `Current Sum: 42.9`\ `Number? `**`0`**\ `Total Sum = 42.9` Notice how `print('Total Sum =', s)` is only run at the end. The `while` statement only affects the lines that are indented with whitespace. The `!=` means does not equal so `while a != 0:` means as long as `a` is not zero run the tabbed statements that follow. Note that `a` is a floating point number, and not all floating point numbers can be accurately represented, so using `!=` on them can sometimes not work. Try typing in 1.1 in interactive mode. #### Infinite loops or Never Ending Loop Now that we have while loops, it is possible to have programs that run forever. An easy way to do this is to write a program like this: ``` python while 1 == 1: print("Help, I'm stuck in a loop.") ``` The \"`==`\" operator is used to test equality of the expressions on the two sides of the operator, just as \"`<`\" was used for \"less than\" before (you will get a complete list of all comparison operators in the next chapter). This program will output `Help, I'm stuck in a loop.` until the heat death of the universe or you stop it, because 1 will forever be equal to 1. The way to stop it is to hit the Control (or *Ctrl*) button and *C* (the letter) at the same time. This will kill the program. (Note: sometimes you will have to hit enter after the Control-C.) On some systems, nothing will stop it, short of killing the process\--so avoid! ### Examples #### Fibonacci sequence **Fibonacci-method1.py** ``` python # This program calculates the Fibonacci sequence a = 0 b = 1 count = 0 max_count = 20 while count < max_count: count = count + 1 print(a, end=" ") # Notice the magic end=" " in the print function arguments # that keeps it from creating a new line. old_a = a # we need to keep track of a since we change it. a = b b = old_a + b print() # gets a new (empty) line. ``` Output: `0 1 1 2 3 5 8 13 21 34 55 89 144 233 377 610 987 1597 2584 4181` Note that the output is on a single line because of the extra argument `end=" "` in the `print` arguments. **Fibonacci-method2.py** ``` python # Simplified and faster method to calculate the Fibonacci sequence a = 0 b = 1 count = 0 max_count = 10 while count < max_count: count = count + 1 print(a, b, end=" ") # Notice the magic end=" " a = a + b b = a + b print() # gets a new (empty) line. ``` Output: `0 1 1 2 3 5 8 13 21 34 55 89 144 233 377 610 987 1597 2584 4181` **Fibonacci-method3.py** ``` python a = 0 b = 1 count = 0 maxcount = 20 #once loop is started we stay in it while count < maxcount: count += 1 olda = a a = a + b b = olda print(olda,end=" ") print() ``` Output: `0 1 1 2 3 5 8 13 21 34 55 89 144 233 377 610 987 1597 2584 4181` #### Enter password **Password.py** ``` python # Waits until a password has been entered. Use Control-C to break out without # the password #Note that this must not be the password so that the # while loop runs at least once. password = str() # note that != means not equal while password != "unicorn": password = input("Password: ") print("Welcome in") ``` Sample run: `Password: `**`auo`**\ `Password: `**`y22`**\ `Password: `**`password`**\ `Password: `**`open sesame`**\ `Password: `**`unicorn`**\ `Welcome in` ### Exercises Write a program that asks the user for a Login Name and password. Then when they type \"lock\", they need to type in their name and password to unlock the program. ca:Python 3 per a no programadors/Comptar fins a 10
# Non-Programmer's Tutorial for Python 3/Decisions ### If statement As always, I believe I should start each chapter with a warm-up typing exercise, so here is a short program to compute the absolute value of an integer: ``` python n = int(input("Number? ")) if n < 0: print("The absolute value of", n, "is", -n) else: print("The absolute value of", n, "is", n) ``` Here is the output from the two times that I ran this program: `Number? `**`-34`**\ `The absolute value of -34 is 34` `Number? `**`1`**\ `The absolute value of 1 is 1` So what does the computer do when it sees this piece of code? First it prompts the user for a number with the statement \"`n = int(input("Number? "))`\". Next it reads the line \"`if n < 0:`\". If `n` is less than zero Python runs the line \"`print("The absolute value of", n, "is", -n)`\". Otherwise it runs the line \"`print("The absolute value of", n, "is", n)`\". More formally Python looks at whether the *expression* `n < 0` is true or false. An `if` statement is followed by an indented *block* of statements that are run when the expression is true. Optionally after the `if` statement is an `else` statement and another indented *block* of statements. This second block of statements is run if the expression is false. There are a number of different tests that an expression can have. Here is a table of all of them: operator function ---------- -------------------------- `<` less than `<=` less than or equal to `>` greater than `>=` greater than or equal to `==` equal `!=` not equal Another feature of the `if` command is the `elif` statement. It stands for else if and means if the original `if` statement is false but the `elif` part is true, then do the `elif` part. And if neither the `if` or `elif` expressions are true, then do what\'s in the `else` block. Here\'s an example: ``` python a = 0 while a < 10: a = a + 1 if a > 5: print(a, ">", 5) elif a <= 3: print(a, "<=", 3) else: print("Neither test was true") ``` and the output: `1 <= 3`\ `2 <= 3`\ `3 <= 3`\ `Neither test was true`\ `Neither test was true`\ `6 > 5`\ `7 > 5`\ `8 > 5`\ `9 > 5`\ `10 > 5` Notice how the `elif a <= 3` is only tested when the `if` statement fails to be true. There can be more than one `elif` expression, allowing multiple tests to be done in a single `if` statement. ### Examples ``` python # This Program Demonstrates the use of the == operator # using numbers print(5 == 6) # Using variables x = 5 y = 8 print(x == y) ``` And the output `False`\ `False` **high_low.py** ``` python # Plays the guessing game higher or lower # This should actually be something that is semi random like the # last digits of the time or something else, but that will have to # wait till a later chapter. (Extra Credit, modify it to be random # after the Modules chapter) number = 7 guess = -1 print("Guess the number!") while guess != number: guess = int(input("Is it... ")) if guess == number: print("Hooray! You guessed it right!") elif guess < number: print("It's bigger...") elif guess > number: print("It's not so big.") ``` Sample run: `Guess the number!`\ `Is it... `**`2`**\ `It's bigger...`\ `Is it... `**`5`**\ `It's bigger...`\ `Is it... `**`10`**\ `It's not so big.`\ `Is it... `**`7`**\ `Hooray! You guessed it right!` **even.py** ``` python # Asks for a number. # Prints if it is even or odd number = float(input("Tell me a number: ")) if number % 2 == 0: print(int(number), "is even.") elif number % 2 == 1: print(int(number), "is odd.") else: print(number, "is very strange.") ``` Sample runs: `Tell me a number: `**`3`**\ `3 is odd.` `Tell me a number: `**`2`**\ `2 is even.` `Tell me a number: `**`3.4895`**\ `3.4895 is very strange.` **average1.py** ``` python # keeps asking for numbers until 0 is entered. # Prints the average value. count = 0 sum = 0.0 number = 1 # set to something that will not exit the while loop immediately. print("Enter 0 to exit the loop") while number != 0: number = float(input("Enter a number: ")) if number != 0: count = count + 1 sum = sum + number if number == 0: print("The average was:", sum / count) ``` **average2.py** ``` python # keeps asking for numbers until count numbers have been entered. # Prints the average value. #Notice that we use an integer to keep track of how many numbers, # but floating point numbers for the input of each number sum = 0.0 print("This program will take several numbers then average them") count = int(input("How many numbers would you like to average: ")) current_count = 0 while current_count < count: current_count = current_count + 1 print("Number", current_count) number = float(input("Enter a number: ")) sum = sum + number print("The average was:", sum / count) ``` Sample runs: `This program will take several numbers then average them`\ `How many numbers would you like to average: `**`2`**\ `Number 1`\ `Enter a number: `**`3`**\ `Number 2`\ `Enter a number: `**`5`**\ `The average was: 4.0` `This program will take several numbers then average them`\ `How many numbers would you like to average: `**`3`**\ `Number 1`\ `Enter a number: `**`1`**\ `Number 2`\ `Enter a number: `**`4`**\ `Number 3`\ `Enter a number: `**`3`**\ `The average was: 2.66666666667` ### Exercises Write a program that asks the user their name, if they enter your name say \"That is a nice name\", if they enter \"John Cleese\" or \"Michael Palin\", tell them how you feel about them ;), otherwise tell them \"You have a nice name.\" Modify the higher or lower program from this section to keep track of how many times the user has entered the wrong number. If it is more than 3 times, print \"That must have been complicated.\" at the end, otherwise print \"Good job!\" Write a program that asks for two numbers. If the sum of the numbers is greater than 100, print \"That is a big number.\"
# Non-Programmer's Tutorial for Python 3/Debugging ### What is debugging? : \"As soon as we started programming, we found to our surprise that it wasn\'t as easy to get programs right as we had thought. Debugging had to be discovered. I can remember the exact instant when I realized that a large part of my life from then on was going to be spent in finding mistakes in my own programs.\" --- *Maurice Wilkes discovers debugging*, 1949 By now if you have been messing around with the programs you have probably found that sometimes the program does something you didn\'t want it to do. This is fairly common. Debugging is the process of figuring out what the computer is doing and then getting it to do what you want it to do. This can be tricky. I once spent nearly a week tracking down and fixing a bug that was caused by someone putting an `x` where a `y` should have been. This chapter will be more abstract than previous chapters. ### What should the program do? The first thing to do (this sounds obvious) is to figure out what the program should be doing if it is running correctly. Come up with some test cases and see what happens. For example, let\'s say I have a program to compute the perimeter of a rectangle (the sum of the length of all the edges). I have the following test cases: height width perimeter -------- ------- ----------- 3 4 14 2 3 10 4 4 16 2 2 8 5 1 12 I now run my program on all of the test cases and see if the program does what I expect it to do. If it doesn\'t then I need to find out what the computer is doing. More commonly some of the test cases will work and some will not. If that is the case you should try and figure out what the working ones have in common. For example here is the output for a perimeter program (you get to see the code in a minute): `Height: `**`3`**\ `Width: `**`4`**\ `perimeter = 15` `Height: `**`2`**\ `Width: `**`3`**\ `perimeter = 11` `Height: `**`4`**\ `Width: `**`4`**\ `perimeter = 16` `Height: `**`2`**\ `Width: `**`2`**\ `perimeter = 8` `Height: `**`5`**\ `Width: `**`1`**\ `perimeter = 8` Notice that it didn\'t work for the first two inputs, it worked for the next two and it didn\'t work on the last one. Try and figure out what is in common with the working ones. Once you have some idea what the problem is finding the cause is easier. With your own programs you should try more test cases if you need them. ### What does the program do? The next thing to do is to look at the source code. One of the most important things to do while programming is reading source code. The primary way to do this is code walkthroughs. A code walkthrough starts at the first line, and works its way down until the program is done. `while` loops and `if` statements mean that some lines may never be run and some lines are run many times. At each line you figure out what Python has done. Lets start with the simple perimeter program. Don\'t type it in, you are going to read it, not run it. The source code is: ``` python height = int(input("Height: ")) width = int(input("Width: ")) print("perimeter =", width + height + width + width) ``` *Question:* What is the first line Python runs? : *Answer:* The first line is always run first. In this case it is: `height = int(input("Height: "))` What does that line do? : Prints `Height:`, waits for the user to type a string in, and then converts the string to an integer variable height. What is the next line that runs? : In general, it is the next line down which is: `width = int(input("Width: "))` What does that line do? : Prints `Width:`, waits for the user to type a number in, and puts what the user types in the variable width. What is the next line that runs? : When the next line is not indented more or less than the current line, it is the line right afterwards, so it is: `print("perimeter = ", width + height + width + width)` (It may also run a function in the current line, but that\'s a future chapter.) What does that line do? : First it prints `perimeter =`, then it prints the sum of the values contained within the variables, `width` and `height`, from `width + height + width + width`. Does `width + height + width + width` calculate the perimeter properly? : Let\'s see, perimeter of a rectangle is the bottom (width) plus the left side (height) plus the top (width) plus the right side (huh?). The last item should be the right side\'s length, or the height. Do you understand why some of the times the perimeter was calculated \"correctly\"? : It was calculated correctly when the width and the height were equal. The next program we will do a code walkthrough for is a program that is supposed to print out 5 dots on the screen. However, this is what the program is outputting: `. . . . ` And here is the program: ``` python number = 5 while number > 1: print(".",end=" ") number = number - 1 print() ``` This program will be more complex to walkthrough since it now has indented portions (or control structures). Let us begin. What is the first line to be run? : The first line of the file: `number = 5` What does it do? : Puts the number 5 in the variable number. What is the next line? : The next line is: `while number > 1:` What does it do? : Well, `while` statements in general look at their expression, and if it is true they do the next indented block of code, otherwise they skip the next indented block of code. So what does it do right now? : If `number > 1` is true then the next two lines will be run. So is `number > 1`? : The last value put into `number` was `5` and `5 > 1` so yes. So what is the next line? : Since the `while` was true the next line is: `print(".",end=" ")` What does that line do? : Prints one dot and since the extra argument `end=" "` exists the next printed text will not be on a different screen line. What is the next line? : `number = number - 1` since that is following line and there are no indent changes. What does it do? : It calculates `number - 1`, which is the current value of `number` (or 5) subtracts 1 from it, and makes that the new value of number. So basically it changes `number`\'s value from 5 to 4. What is the next line? : Well, the indent level decreases so we have to look at what type of control structure it is. It is a `while` loop, so we have to go back to the `while` clause which is `while number > 1:` What does it do? : It looks at the value of number, which is 4, and compares it to 1 and since `4 > 1` the while loop continues. What is the next line? : Since the while loop was true, the next line is: `print(".",end=" ")` What does it do? : It prints a second dot on the line, ending by a space. What is the next line? : No indent change so it is: `number = number - 1` And what does it do? : It takes the current value of number (4), subtracts 1 from it, which gives it 3 and then finally makes 3 the new value of number. What is the next line? : Since there is an indent change caused by the end of the while loop, the next line is: `while number > 1:` What does it do? : It compares the current value of number (3) to 1. `3 > 1` so the while loop continues. What is the next line? : Since the while loop condition was true the next line is: `print(".",end=" ")` And it does what? : A third dot is printed on the line. What is the next line? : It is: `number = number - 1` What does it do? : It takes the current value of number (3) subtracts from it 1 and makes the 2 the new value of number. What is the next line? : Back up to the start of the while loop: `while number > 1:` What does it do? : It compares the current value of number (2) to 1. Since `2 > 1` the while loop continues. What is the next line? : Since the while loop is continuing: `print(".",end=" ")` What does it do? : It discovers the meaning of life, the universe and everything. I\'m joking. (I had to make sure you were awake.) The line prints a fourth dot on the screen. What is the next line? : It\'s: `number = number - 1` What does it do? : Takes the current value of number (2) subtracts 1 and makes 1 the new value of number. What is the next line? : Back up to the while loop: `while number > 1:` What does the line do? : It compares the current value of number (1) to 1. Since `1 > 1` is false (one is not greater than one), the while loop exits. What is the next line? : Since the while loop condition was false the next line is the line after the while loop exits, or: `print()` What does that line do? : Makes the screen go to the next line. Why doesn\'t the program print 5 dots? : The loop exits 1 dot too soon. How can we fix that? : Make the loop exit 1 dot later. And how do we do that? : There are several ways. One way would be to change the while loop to: `while number > 0:` Another way would be to change the conditional to: `number >= 1` There are a couple others. ### How do I fix my program? You need to figure out what the program is doing. You need to figure out what the program should do. Figure out what the difference between the two is. Debugging is a skill that has to be practiced to be learned. If you can\'t figure it out after an hour, take a break, talk to someone about the problem or contemplate the lint in your navel. Come back in a while and you will probably have new ideas about the problem. Good luck.
# Non-Programmer's Tutorial for Python 3/Defining Functions ### Creating Functions To start off this chapter I am going to give you an example of what you could do but shouldn\'t (so don\'t type it in): ``` python a = 23 b = -23 if a < 0: a = -a if b < 0: b = -b if a == b: print("The absolute values of", a, "and", b, "are equal.") else: print("The absolute values of", a, "and", b, "are different.") ``` with the output being: `The absolute values of 23 and 23 are equal.` The program seems a little repetitive. Programmers hate to repeat things \-- that\'s what computers are for, after all! (Note also that finding the absolute value changed the value of the variable, which is why it is printing out 23, and not -23 in the output.) Fortunately Python allows you to create functions to remove duplication. Here is the rewritten example: ``` python a = 23 b = -23 def absolute_value(n): if n < 0: n = -n return n if absolute_value(a) == absolute_value(b): print("The absolute values of", a, "and", b, "are equal.") else: print("The absolute values of", a, "and", b, "are different.") ``` with the output being: `The absolute values of 23 and -23 are equal.` The key feature of this program is the `def` statement. `def` (short for define) starts a function definition. `def` is followed by the name of the function `absolute_value`. Next comes a \'(\' followed by the parameter `n` (`n` is passed from the program into the function when the function is called). The statements after the \':\' are executed when the function is used. The statements continue until either the indented statements end or a `return` is encountered. The `return` statement returns a value back to the place where the function was called. We already have encountered a function in our very first program, the `print` function. Now we can make new functions. Notice how the values of `a` and `b` are not changed. Functions can be used to repeat tasks that don\'t return values. Here are some examples: ``` python def hello(): print("Hello") def area(width, height): return width * height def print_welcome(name): print("Welcome", name) hello() hello() print_welcome("Fred") w = 4 h = 5 print("width =", w, " height =", h, " area =", area(w, h)) ``` with output being: `Hello`\ `Hello`\ `Welcome Fred`\ `width = 4  height = 5  area = 20` That example shows some more stuff that you can do with functions. Notice that you can use no arguments or two or more. Notice also when a function doesn\'t need to send back a value, a return is optional. ### Variables in functions When eliminating repeated code, you often have variables in the repeated code. In Python, these are dealt with in a special way. So far all variables we have seen are global variables. Functions have a special type of variable called local variables. These variables only exist while the function is running. When a local variable has the same name as another variable (such as a global variable), the local variable hides the other. Sound confusing? Well, these next examples (which are a bit contrived) should help clear things up. ``` python a = 4 def print_func(): a = 17 print("in print_func a =", a) print_func() print("a = ", a) ``` When run, we will receive an output of: `in print_func a = 17`\ `a = 4` Variable assignments inside a function do not override global variables, they exist only inside the function. Even though `a` was assigned a new value inside the function, this newly assigned value was only relevant to `print_func`, when the function finishes running, and the `a`\'s values is printed again, we see the originally assigned values. Here is another more complex example. ``` python a_var = 10 b_var = 15 e_var = 25 def a_func(a_var): print("in a_func a_var =", a_var) b_var = 100 + a_var d_var = 2 * a_var print("in a_func b_var =", b_var) print("in a_func d_var =", d_var) print("in a_func e_var =", e_var) return b_var + 10 c_var = a_func(b_var) print("a_var =", a_var) print("b_var =", b_var) print("c_var =", c_var) print("d_var =", d_var) ``` output: `in a_func a_var =  15`\ `in a_func b_var =  115`\ `in a_func d_var =  30`\ `in a_func e_var =  25`\ `a_var =  10`\ `b_var =  15`\ `c_var =  125`\ `d_var = `\ \ `Traceback (most recent call last):`\ ` File "C:\def2.py", line 19, in ``<module>`{=html}\ `   print("d_var = ", d_var)`\ `NameError: name 'd_var' is not defined` In this example the variables `a_var`, `b_var`, and `d_var` are all local variables when they are inside the function `a_func`. After the statement `return b_var + 10` is run, they all cease to exist. The variable `a_var` is automatically a local variable since it is a parameter name. The variables `b_var` and `d_var` are local variables since they appear on the left of an equals sign in the function in the statements `b_var = 100 + a_var` and `d_var = 2 * a_var` . Inside of the function `a_var` has no value assigned to it. When the function is called with `c_var = a_func(b_var)`, 15 is assigned to `a_var` since at that point in time `b_var` is 15, making the call to the function `a_func(15)`. This ends up setting `a_var` to 15 when it is inside of `a_func`. As you can see, once the function finishes running, the local variables `a_var` and `b_var` that had hidden the global variables of the same name are gone. Then the statement `print("a_var = ", a_var)` prints the value `10` rather than the value `15` since the local variable that hid the global variable is gone. Another thing to notice is the `NameError` that happens at the end. This appears since the variable `d_var` no longer exists since `a_func` finished. All the local variables are deleted when the function exits. If you want to get something from a function, then you will have to use `return something`. One last thing to notice is that the value of `e_var` remains unchanged inside `a_func` since it is not a parameter and it never appears on the left of an equals sign inside of the function `a_func`. When a global variable is accessed inside a function it is the global variable from the outside. Functions allow local variables that exist only inside the function and can hide other variables that are outside the function. ### Examples **temperature2.py** ``` python #! /usr/bin/python #-*-coding: utf-8 -*- # converts temperature to Fahrenheit or Celsius def print_options(): print("Options:") print(" 'p' print options") print(" 'c' convert from Celsius") print(" 'f' convert from Fahrenheit") print(" 'q' quit the program") def celsius_to_fahrenheit(c_temp): return 9.0 / 5.0 * c_temp + 32 def fahrenheit_to_celsius(f_temp): return (f_temp - 32.0) * 5.0 / 9.0 choice = "p" while choice != "q": if choice == "c": c_temp = float(input("Celsius temperature: ")) print("Fahrenheit:", celsius_to_fahrenheit(c_temp)) choice = input("option: ") elif choice == "f": f_temp = float(input("Fahrenheit temperature: ")) print("Celsius:", fahrenheit_to_celsius(f_temp)) choice = input("option: ") else: choice = "p" #Alternatively choice != "q": so that print #when anything unexpected inputed print_options() choice = input("option: ") ``` Sample Run: `Options:`\ ` 'p' print options`\ ` 'c' convert from celsius`\ ` 'f' convert from fahrenheit`\ ` 'q' quit the program`\ `option: `**`c`**\ `Celsius temperature: `**`30`**` `\ `Fahrenheit: 86.0`\ `option: `**`f`**\ `Fahrenheit temperature: `**`60`**\ `Celsius: 15.5555555556`\ `option: `**`q`** **area2.py** ``` python #! /usr/bin/python #-*-coding: utf-8 -*- # calculates a given rectangle area def hello(): print('Hello!') def area(width, height): return width * height def print_welcome(name): print('Welcome,', name) def positive_input(prompt): number = float(input(prompt)) while number <= 0: print('Must be a positive number') number = float(input(prompt)) return number name = input('Your Name: ') hello() print_welcome(name) print() print('To find the area of a rectangle,') print('enter the width and height below.') print() w = positive_input('Width: ') h = positive_input('Height: ') print('Width =', w, ' Height =', h, ' so Area =', area(w, h)) ``` Sample Run: `Your Name: `**`Josh`**\ `Hello!`\ `Welcome, Josh`\ \ `To find the area of a rectangle,`\ `enter the width and height below.`\ \ `Width: `**`-4`**\ `Must be a positive number`\ `Width: `**`4`**\ `Height: `**`3`**\ `Width = 4  Height = 3  so Area = 12` ### Exercises Rewrite the area2.py program from the Examples above to have a separate function for the area of a square, the area of a rectangle, and the area of a circle (`3.14 * radius**2`). This program should include a menu interface.
# Non-Programmer's Tutorial for Python 3/Advanced Functions Example *Note: Some people find this section useful, and some find it confusing. If you find it confusing, feel free to skip it and continue with the next section.* To show more advanced ways of using functions, we\'ll now do a walk through for the following program: ``` python def mult(a, b): if b == 0: return 0 rest = mult(a, b - 1) value = a + rest return value result = mult(3, 2) print("3 * 2 = ", result) ``` Basically this program creates a positive integer multiplication function (that is far slower than the built in multiplication function) and then demonstrates this function with a use of the function. This program demonstrates the use of recursion, that is a form of iteration (repetition) in which there is a function that repeatedly calls itself until an exit condition is satisfied. It uses repeated additions to give the same result as multiplication: e.g. 3 + 3 (addition) gives the same result as 3 \* 2 (multiplication). *Question:* What is the first thing the program does? : *Answer:* The first thing done is the function `mult` is defined with the lines: ``` python def mult(a, b): if b == 0: return 0 rest = mult(a, b - 1) value = a + rest return value ``` : This creates a function that takes two parameters and returns a value when it is done. Later this function can be run. What happens next? : The next line after the function, `result = mult(3, 2)` is run. What does this line do? : This line will assign the return value of `mult(3, 2)` to the variable `result`. And what does `mult(3, 2)` return? : We need to do a walkthrough of the `mult` function to find out. What happens next? : The variable `a` gets the value 3 assigned to it and the variable `b` gets the value 2 assigned to it. And then? : The line `if b == 0:` is run. Since `b` has the value 2 this is false so the line `return 0` is skipped. And what then? : The line `rest = mult(a, b - 1)` is run. This line sets the local variable `rest` to the value of `mult(a, b - 1)`. The value of `a` is 3 and the value of `b` is 2 so the function call is `mult(3,1)` So what is the value of `mult(3, 1)` ? : We will need to run the function `mult` with the parameters 3 and 1. So what happens next? : The local variables in the *new* run of the function are set so that `a` has the value 3 and `b` has the value 1. Since these are local values these do not affect the previous values of `a` and `b`. And then? : Since `b` has the value 1 the if statement is false, so the next line becomes `rest = mult(a, b - 1)`. What does this line do? : This line will assign the value of `mult(3, 0)` to rest. So what is that value? : We will have to run the function one more time to find that out. This time `a` has the value 3 and `b` has the value 0. So what happens next? : The first line in the function to run is `if b == 0:`. `b` has the value 0 so the next line to run is `return 0` And what does the line `return 0` do? : This line returns the value 0 out of the function. So? : So now we know that `mult(3, 0)` has the value 0. Now we know what the line `rest = mult(a, b - 1)` did since we have run the function `mult` with the parameters 3 and 0. We have finished running `mult(3, 0)` and are now back to running `mult(3, 1)`. The variable `rest` gets assigned the value 0. What line is run next? : The line `value = a + rest` is run next. In this run of the function, `a = 3` and `rest = 0` so now `value = 3`. What happens next? : The line `return value` is run. This returns 3 from the function. This also exits from the run of the function `mult(3, 1)`. After `return` is called, we go back to running `mult(3, 2)`. Where were we in `mult(3, 2)`? : We had the variables `a = 3` and `b = 2` and were examining the line `rest = mult(a, b - 1)`. So what happens now? : The variable `rest` get 3 assigned to it. The next line `value = a + rest` sets `value` to `3 + 3` or 6. So now what happens? : The next line runs, this returns 6 from the function. We are now back to running the line `result = mult(3, 2)` which can now assign the value 6 to the variable `result`. What happens next? : The next line after the function, `print("3 * 2 = ", result)` is run. And what does this do? : It prints `3 * 2 =` and the value of `result` which is 6. The complete line printed is `3 * 2 = 6`. What is happening overall? : Basically we used two facts to calculate the multiple of the two numbers. The first is that any number times 0 is 0 (`x * 0 = 0`). The second is that a number times another number is equal to the first number plus the first number times one less than the second number (`x * y = x + x * (y - 1)`). So what happens is `3 * 2` is first converted into `3 + 3 * 1`. Then `3 * 1` is converted into `3 + 3 * 0`. Then we know that any number times 0 is 0 so `3 * 0` is 0. Then we can calculate that `3 + 3 * 0` is `3 + 0` which is `3`. Now we know what `3 * 1` is so we can calculate that `3 + 3 * 1` is `3 + 3` which is `6`. This is how the whole thing works: `mult(3, 2)`\ `3 + mult(3, 1)`\ `3 + 3 + mult(3, 0)`\ `3 + 3 + 0`\ `3 + 3`\ `6` #### Recursion Programming constructs solving a problem by solving a smaller version of the same problem are called *recursive*. In the examples in this chapter, recursion is realized by defining a function calling itself. This facilitates implementing solutions to programming tasks as it may be sufficient to consider the next step of a problem instead of the whole problem at once. It is also useful as it allows to express some mathematical concepts with straightforward, easy to read code. Any problem that can be solved with recursion could be re-implemented with loops. Using the latter usually results in better performance. However equivalent implementations using loops are usually harder to get done correctly. Probably the most intuitive definition of *recursion* is: Recursion : If you still don\'t get it, see *recursion*. Try walking through the factorial example if the multiplication example did not make sense. ### Examples **factorial.py** ``` python #defines a function that calculates the factorial def factorial(n): if n == 0: return 1 if n<0: return "Error, negative numbers do not have factorial values!!" return n * factorial(n - 1) print("2! =", factorial(2)) print("3! =", factorial(3)) print("4! =", factorial(4)) print("5! =", factorial(5)) print("-3! =", factorial(-3)) ``` Output: `2! = 2`\ `3! = 6`\ `4! = 24`\ `5! = 120`\ `-3! = Error, negative values do not have factorial values!!` **countdown.py** ``` python def count_down(n): print(n) if n > 0: return count_down(n-1) count_down(5) ``` Output: `5`\ `4`\ `3`\ `2`\ `1`\ `0`
# Non-Programmer's Tutorial for Python 3/Lists ### Variables with more than one value You have already seen ordinary variables that store a single value. However other variable types can hold more than one value. These are called containers because they can contain more than one object. The simplest type is called a list. Here is an example of a list being used: ``` python which_one = int(input("What month (1-12)? ")) months = ['January', 'February', 'March', 'April', 'May', 'June', 'July', 'August', 'September', 'October', 'November', 'December'] if 1 <= which_one <= 12: print("The month is", months[which_one - 1]) ``` and an output example: `What month (1-12)? `**`3`**\ `The month is March` In this example the `months` is a list. `months` is defined with the lines `months = ['January', 'February', 'March', 'April', 'May', 'June', 'July',` and `'August', 'September', 'October', 'November', 'December']` (note that a `\` could also be used to split a long line, but that is not necessary in this case because Python is intelligent enough to recognize that everything within brackets belongs together). The `[` and `]` start and end the list with commas (`,`) separating the list items. The list is used in `months[which_one - 1]`. A list consists of items that are numbered starting at 0. In other words if you wanted January you would use `months[0]`. Give a list a number and it will return the value that is stored at that location. The statement `if 1 <= which_one <= 12:` will only be true if `which_one` is between one and twelve inclusive (in other words it is what you would expect if you have seen that in algebra). Lists can be thought of as a series of boxes. Each box has a different value. For example, the boxes created by `demolist = ['life', 42, 'the universe', 6, 'and', 9]` would look like this: box number 0 1 2 3 4 5 ------------ ---------- ---- ------------------ --- --------- --- demolist \"life\" 42 \"the universe\" 6 \"and\" 9 Each box is referenced by its number so the statement `demolist[0]` would get `'life'`, `demolist[1]` would get `42` and so on up to `demolist[5]` getting `9`. ### More features of lists The next example is just to show a lot of other stuff lists can do (for once I don\'t expect you to type it in, but you should probably play around with lists in interactive mode until you are comfortable with them.). Here goes: ``` python demolist = ["life", 42, "the universe", 6, "and", 9] print("demolist = ",demolist) demolist.append("everything") print("after 'everything' was appended demolist is now:") print(demolist) print("len(demolist) =", len(demolist)) print("demolist.index(42) =", demolist.index(42)) print("demolist[1] =", demolist[1]) # Next we will loop through the list for c in range(len(demolist)): print("demolist[", c, "] =", demolist[c]) del demolist[2] print("After 'the universe' was removed demolist is now:") print(demolist) if "life" in demolist: print("'life' was found in demolist") else: print("'life' was not found in demolist") if "amoeba" in demolist: print("'amoeba' was found in demolist") if "amoeba" not in demolist: print("'amoeba' was not found in demolist") another_list = [42,7,0,123] another_list.sort() print("The sorted another_list is", another_list) ``` The output is: `demolist =  ['life', 42, 'the universe', 6, 'and', 9]`\ `after 'everything' was appended demolist is now:`\ `['life', 42, 'the universe', 6, 'and', 9, 'everything']`\ `len(demolist) = 7`\ `demolist.index(42) = 1`\ `demolist[1] = 42`\ `demolist[ 0 ] = life`\ `demolist[ 1 ] = 42`\ `demolist[ 2 ] = the universe`\ `demolist[ 3 ] = 6`\ `demolist[ 4 ] = and`\ `demolist[ 5 ] = 9`\ `demolist[ 6 ] = everything`\ `After 'the universe' was removed demolist is now:`\ `['life', 42, 6, 'and', 9, 'everything']`\ `'life' was found in demolist`\ `'amoeba' was not found in demolist`\ `The sorted another_list is [0, 7, 42, 123]` This example uses a whole bunch of new functions. Notice that you can just `print` a whole list. Next the `append` function is used to add a new item to the end of the list. `len` returns how many items are in a list. The valid indexes (as in numbers that can be used inside of the `[]`) of a list range from 0 to `len - 1`. The `index` function tells where the first location of an item is located in a list. Notice how `demolist.index(42)` returns 1, and when `demolist[1]` is run it returns 42. To get help on all the functions a list provides for you, type `help(list)` in the interactive Python interpreter. The line `# Next we will loop through the list` is a just a reminder to the programmer (also called a *comment*). Python ignores everything that is written after a `#` on the current line. Next the lines: ``` python for c in range(len(demolist)): print('demolist[', c, '] =', demolist[c]) ``` create a variable `c`, which starts at 0 and is incremented until it reaches the last index of the list. Meanwhile the `print` statement prints out each element of the list. A much better way to do the above is: ``` python for c, x in enumerate(demolist): print("demolist[", c, "] =", x) ``` The `del` command can be used to remove a given element in a list. The next few lines use the `in` operator to test if an element is in or is not in a list. The `sort` function sorts the list. This is useful if you need a list in order from smallest number to largest or alphabetical. Note that this rearranges the list. In summary, for a list, the following operations occur: example explanation ---------------------------- --------------------------------------------------------------------------------------------------------- `demolist[2]` accesses the element at index 2 `demolist[2] = 3` sets the element at index 2 to be 3 `del demolist[2]` removes the element at index 2 `len(demolist)` returns the length of `demolist` `"value" in demolist` is *True* if `"value"` is an element in `demolist` `"value" not in demolist` is *True* if `"value"` is not an element in `demolist` `another_list.sort()` sorts `another_list`. Note that the list must be all numbers or all strings to be sorted. `demolist.index("value")` returns the index of the first place that `"value"` occurs `demolist.append("value")` adds an element `"value"` at the end of the list `demolist.remove("value")` removes the first occurrence of value from `demolist` (same as `del demolist[demolist.index("value")]`) This next example uses these features in a more useful way: ``` python menu_item = 0 namelist = [] while menu_item != 9: print("--------------------") print("1. Print the list") print("2. Add a name to the list") print("3. Remove a name from the list") print("4. Change an item in the list") print("9. Quit") menu_item = int(input("Pick an item from the menu: ")) if menu_item == 1: current = 0 if len(namelist) > 0: while current < len(namelist): print(current, ".", namelist[current]) current = current + 1 else: print("List is empty") elif menu_item == 2: name = input("Type in a name to add: ") namelist.append(name) elif menu_item == 3: del_name = input("What name would you like to remove: ") if del_name in namelist: # namelist.remove(del_name) would work just as fine item_number = namelist.index(del_name) del namelist[item_number] # The code above only removes the first occurrence of # the name. The code below from Gerald removes all. # while del_name in namelist: # item_number = namelist.index(del_name) # del namelist[item_number] else: print(del_name, "was not found") elif menu_item == 4: old_name = input("What name would you like to change: ") if old_name in namelist: item_number = namelist.index(old_name) new_name = input("What is the new name: ") namelist[item_number] = new_name else: print(old_name, "was not found") print("Goodbye") ``` And here is part of the output: `--------------------`\ `1. Print the list`\ `2. Add a name to the list`\ `3. Remove a name from the list`\ `4. Change an item in the list`\ `9. Quit`\ \ `Pick an item from the menu: `**`2`**\ `Type in a name to add: `**`Jack`**\ \ `Pick an item from the menu: `**`2`**\ `Type in a name to add: `**`Jill`**\ \ `Pick an item from the menu: `**`1`**\ `0 . Jack`\ `1 . Jill`\ \ `Pick an item from the menu: `**`3`**\ `What name would you like to remove: `**`Jack`**\ \ `Pick an item from the menu: `**`4`**\ `What name would you like to change: `**`Jill`**\ `What is the new name: `**`Jill Peters`**\ \ `Pick an item from the menu: `**`1`**\ `0 . Jill Peters`\ \ `Pick an item from the menu: `**`9`**\ `Goodbye` That was a long program. Let\'s take a look at the source code. The line `namelist = []` makes the variable `namelist` a list with no items (or elements). The next important line is `while menu_item != 9:`. This line starts a loop that allows the menu system for this program. The next few lines display a menu and decide which part of the program to run. The section ``` python current = 0 if len(namelist) > 0: while current < len(namelist): print(current, ".", namelist[current]) current = current + 1 else: print("List is empty") ``` goes through the list and prints each name. `len(namelist)` tells how many items are in the list. If `len` returns `0`, then the list is empty. Then, a few lines later, the statement `namelist.append(name)` appears. It uses the `append` function to add an item to the end of the list. Jump down another two lines, and notice this section of code: ``` python item_number = namelist.index(del_name) del namelist[item_number] ``` Here the `index` function is used to find the index value that will be used later to remove the item. `del namelist[item_number]` is used to remove an element of the list. The next section ``` python old_name = input("What name would you like to change: ") if old_name in namelist: item_number = namelist.index(old_name) new_name = input("What is the new name: ") namelist[item_number] = new_name else: print(old_name, "was not found") ``` uses `index` to find the `item_number` and then puts `new_name` where the `old_name` was. Congratulations, with lists under your belt, you now know enough of the language that you could do any computations that a computer can do (this is technically known as Turing-Completeness). Of course, there are still many features that are used to make your life easier. ### Examples **test.py** ``` python ## This program runs a test of knowledge # First get the test questions # Later this will be modified to use file io. def get_questions(): # notice how the data is stored as a list of lists return [["What color is the daytime sky on a clear day? ", "blue"], ["What is the answer to life, the universe and everything? ", "42"], ["What is a three letter word for mouse trap? ", "cat"]] # This will test a single question # it takes a single question in # it returns True if the user typed the correct answer, otherwise False def check_question(question_and_answer): # extract the question and the answer from the list # This function takes a list with two elements, a question and an answer. question = question_and_answer[0] answer = question_and_answer[1] # give the question to the user given_answer = input(question) # compare the user's answer to the tester's answer if answer == given_answer: print("Correct") return True else: print("Incorrect, correct was:", answer) return False # This will run through all the questions def run_test(questions): if len(questions) == 0: print("No questions were given.") # the return exits the function return index = 0 right = 0 while index < len(questions): # Check the question #Note that this is extracting a question and answer list from the list of lists. if check_question(questions[index]): right = right + 1 # go to the next question index = index + 1 # notice the order of the computation, first multiply, then divide print("You got", right * 100 / len(questions),\ "% right out of", len(questions)) # now let's get the questions from the get_questions function, and # send the returned list of lists as an argument to the run_test function. run_test(get_questions()) ``` The values `True` and `False` point to 1 and 0, respectively. They are often used in sanity checks, loop conditions etc. You will learn more about this a little bit later (chapter Boolean Expressions). Please note that get_questions() is essentially a list because even though it\'s technically a function, returning a list of lists is the only thing it does. Sample Output: `What color is the daytime sky on a clear day? `**`green`**\ `Incorrect, correct was: blue`\ `What is the answer to life, the universe and everything? `**`42`**\ `Correct`\ `What is a three letter word for mouse trap? `**`cat`**\ `Correct`\ `You got 66 % right out of 3` ### Exercises Expand the test.py program so it has a menu giving the option of taking the test, viewing the list of questions and answers, and an option to quit. Also, add a new question to ask, \"What noise does a truly advanced machine make?\" with the answer of \"ping\".
# Non-Programmer's Tutorial for Python 3/For Loops With a for loop, we can repeat a piece of code. Let\'s look at an example: ``` python one_to_ten = range(1, 11) for count in one_to_ten: print(count) ``` The output of this code looks as follows: `1`\ `2`\ `3`\ `4`\ `5`\ `6`\ `7`\ `8`\ `9`\ `10` The output looks awfully familiar but the program code looks different. The first line uses the `range` function. The `range` function uses two arguments like this `range(start, finish)`. `start` is the first number that is produced. `finish` is one larger than the last number. Note that this program could have been done in a shorter way: ``` python for count in range(1, 11): print(count) ``` The range function returns an iterable. This can be converted into a list with the `list` function. which will then be the dominant number. Here are some examples to show what happens with the `range` command: `>>> `**`range(1, 10)`**\ `range(1, 10)`\ `>>> `**`list(range(1, 10))`**\ `[1, 2, 3, 4, 5, 6, 7, 8, 9]`\ `>>> `**`list(range(-32, -20))`**\ `[-32, -31, -30, -29, -28, -27, -26, -25, -24, -23, -22, -21]`\ `>>> `**`list(range(5,21))`**\ `[5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20]`\ `>>> `**`list(range(5))`**\ `[0, 1, 2, 3, 4]`\ `>>> `**`list(range(21, 5))`**\ `[]` The next line `for count in one_to_ten:` uses the `for` control structure. A `for` control structure looks like `for variable in list:`. `list` is gone through starting with the first element of the list and going to the last. As `for` goes through each element in a list it puts each into `variable`. That allows `variable` to be used in each successive time the `for` loop is run through. Here is another example (you don\'t have to type this) to demonstrate: ``` python demolist = ['life', 42, 'the universe', 6, 'and', 7, 'everything'] for item in demolist: print("The current item is:",item) ``` The output is: `The current item is: life`\ `The current item is: 42`\ `The current item is: the universe`\ `The current item is: 6`\ `The current item is: and`\ `The current item is: 7`\ `The current item is: everything` Notice how the `for` loop goes through and sets item to each element in the list. So, what is `for` good for? The first use is to go through all the elements of a list and do something with each of them. Here\'s a quick way to add up all the elements: ``` python list = [2, 4, 6, 8] sum = 0 for num in list: sum = sum + num print("The sum is:", sum) ``` with the output simply being: `The sum is: 20` Or you could write a program to find out if there are any duplicates in a list like this program does: ``` python list = [4, 5, 7, 8, 9, 1, 0, 7, 10] list.sort() prev = None for item in list: if prev == item: print("Duplicate of", prev, "found") prev = item ``` and for good measure: `Duplicate of 7 found` Okay, so how does it work? Here is a special debugging version to help you understand (you don\'t need to type this in): ``` python l = [4, 5, 7, 8, 9, 1, 0, 7, 10] print("l = [4, 5, 7, 8, 9, 1, 0, 7, 10]", "\t\tl:", l) l.sort() print("l.sort()", "\t\tl:", l) prev = l[0] print("prev = l[0]", "\t\tprev:", prev) del l[0] print("del l[0]", "\t\tl:", l) for item in l: if prev == item: print("Duplicate of", prev, "found") print("if prev == item:", "\t\tprev:", prev, "\titem:", item) prev = item print("prev = item", "\t\tprev:", prev, "\titem:", item) ``` with the output being: `l = [4, 5, 7, 8, 9, 1, 0, 7, 10]        l: [4, 5, 7, 8, 9, 1, 0, 7, 10]`\ `l.sort()                l: [0, 1, 4, 5, 7, 7, 8, 9, 10]`\ `prev = l[0]             prev: 0`\ `del l[0]                l: [1, 4, 5, 7, 7, 8, 9, 10]`\ `if prev == item:        prev: 0         item: 1`\ `prev = item             prev: 1         item: 1`\ `if prev == item:        prev: 1         item: 4`\ `prev = item             prev: 4         item: 4`\ `if prev == item:        prev: 4         item: 5`\ `prev = item             prev: 5         item: 5`\ `if prev == item:        prev: 5         item: 7`\ `prev = item             prev: 7         item: 7`\ `Duplicate of 7 found`\ `if prev == item:        prev: 7         item: 7`\ `prev = item             prev: 7         item: 7`\ `if prev == item:        prev: 7         item: 8`\ `prev = item             prev: 8         item: 8`\ `if prev == item:        prev: 8         item: 9`\ `prev = item             prev: 9         item: 9`\ `if prev == item:        prev: 9         item: 10`\ `prev = item             prev: 10        item: 10` The reason I put so many `print` statements in the code was so that you can see what is happening in each line. (By the way, if you can\'t figure out why a program is not working, try putting in lots of print statements in places where you want to know what is happening.) First the program starts with a boring old list. Next the program sorts the list. This is so that any duplicates get put next to each other. The program then initializes a `prev`(ious) variable. Next the first element of the list is deleted so that the first item is not incorrectly thought to be a duplicate. Next a `for` loop is gone into. Each item of the list is checked to see if it is the same as the previous. If it is a duplicate was found. The value of `prev` is then changed so that the next time the `for` loop is run through `prev` is the previous item to the current. Sure enough, the 7 is found to be a duplicate. (Notice how `\t` is used to print a tab.) The other way to use `for` loops is to do something a certain number of times. Here is some code to print out the first 9 numbers of the Fibonacci series: ``` python a = 1 b = 1 for c in range(1, 10): print(a, end=" ") n = a + b a = b b = n ``` with the surprising output: `1 1 2 3 5 8 13 21 34` Everything that can be done with `for` loops can also be done with `while` loops but `for` loops give an easy way to go through all the elements in a list or to do something a certain number of times.
# Non-Programmer's Tutorial for Python 3/Boolean Expressions Here is a little example of boolean expressions (you don\'t have to type it in): ``` python a = 6 b = 7 c = 42 print(1, a == 6) print(2, a == 7) print(3, a == 6 and b == 7) print(4, a == 7 and b == 7) print(5, not a == 7 and b == 7) print(6, a == 7 or b == 7) print(7, a == 7 or b == 6) print(8, not (a == 7 and b == 6)) print(9, not a == 7 and b == 6) ``` With the output being: `1 True`\ `2 False`\ `3 True`\ `4 False`\ `5 True`\ `6 True`\ `7 False`\ `8 True`\ `9 False` What is going on? The program consists of a bunch of funny looking `print` statements. Each `print` statement prints a number and an expression. The number is to help keep track of which statement I am dealing with. Notice how each expression ends up being either `False` or `True`. In Python false can also be written as 0 and true as 1. The lines: ``` python print(1, a == 6) print(2, a == 7) ``` print out a `True` and a `False` respectively just as expected since the first is true and the second is false. The third print, `print(3, a == 6 and b == 7)`, is a little different. The operator `and` means if both the statement before and the statement after are true then the whole expression is true otherwise the whole expression is false. The next line, `print(4, a == 7 and b == 7)`, shows how if part of an `and` expression is false, the whole thing is false. The behavior of `and` can be summarized as follows: expression result ------------------- -------- true `and` true true true `and` false false false `and` true false false `and` false false Notice that if the first expression is false Python does not check the second expression since it knows the whole expression is false. Try running `False and print("Hi")` and compare this to running `True and print("Hi")` The technical term for this is short-circuit evaluation The next line, `print(5, not a == 7 and b == 7)`, uses the `not` operator. `not` just gives the opposite of the expression. (The expression could be rewritten as `print(5, a != 7 and b == 7)`). Here is the table: expression result ------------- -------- `not` true false `not` false true The two following lines, `print(6, a == 7 or b == 7)` and `print(7, a == 7 or b == 6)`, use the `or` operator. The `or` operator returns true if the first expression is true, or if the second expression is true or both are true. If neither are true it returns false. Here\'s the table: expression result ------------------ -------- true `or` true true true `or` false true false `or` true true false `or` false false Notice that if the first expression is true Python doesn\'t check the second expression since it knows the whole expression is true. This works since `or` is true if at least one half of the expression is true. The first part is true so the second part could be either false or true, but the whole expression is still true. The next two lines, `print(8, not (a == 7 and b == 6))` and `print(9, not a == 7 and b == 6)`, show that parentheses can be used to group expressions and force one part to be evaluated first. Notice that the parentheses changed the expression from false to true. This occurred since the parentheses forced the `not` to apply to the whole expression instead of just the `a == 7` portion. Here is an example of using a boolean expression: ``` python list = ["Life", "The Universe", "Everything", "Jack", "Jill", "Life", "Jill"] # make a copy of the list. See the More on Lists chapter to explain what [:] means. copy = list[:] # sort the copy copy.sort() prev = copy[0] del copy[0] count = 0 # go through the list searching for a match while count < len(copy) and copy[count] != prev: prev = copy[count] count = count + 1 # If a match was not found then count can't be < len # since the while loop continues while count is < len # and no match is found if count < len(copy): print("First Match:", prev) ``` And here is the output: `First Match: Jill` This program works by continuing to check for match `while count < len(copy) and copy[count] is not equal to prev`. When either `count` is greater than the last index of `copy` or a match has been found the `and` is no longer true so the loop exits. The `if` simply checks to make sure that the `while` exited because a match was found. The other \"trick\" of `and` is used in this example. If you look at the table for `and` notice that the third entry is \"false and false\". If `count >= len(copy)` (in other words `count < len(copy)` is false) then `copy[count]` is never looked at. This is because Python knows that if the first is false then they can\'t both be true. This is known as a short circuit and is useful if the second half of the `and` will cause an error if something is wrong. I used the first expression (`count < len(copy)`) to check and see if `count` was a valid index for `copy`. (If you don\'t believe me remove the matches \"Jill\" and \"Life\", check that it still works and then reverse the order of `count < len(copy) and copy[count] != prev` to `copy[count] != prev and count < len(copy)`.) Boolean expressions can be used when you need to check two or more different things at once. ### A note on Boolean Operators A common mistake for people new to programming is a misunderstanding of the way that boolean operators works, which stems from the way the python interpreter reads these expressions. For example, after initially learning about \"and \" and \"or\" statements, one might assume that the expression `x == ('a' or 'b')` would check to see if the variable `x` was equivalent to one of the strings `'a'` or `'b'`. This is not so. To see what I\'m talking about, start an interactive session with the interpreter and enter the following expressions: `>>> 'a' == ('a' or 'b')`\ `>>> 'b' == ('a' or 'b')`\ `>>> 'a' == ('a' and 'b')`\ `>>> 'b' == ('a' and 'b')` And this will be the unintuitive result: `>>>`**`'a' == ('a' or 'b')`**\ `True`\ `>>>`**`'b' == ('a' or 'b')`**\ `False`\ `>>>`**`'a' == ('a' and 'b')`**\ `False `\ `>>>`**`'b' == ('a' and 'b')`**\ `True` At this point, the `and` and `or` operators seem to be broken. It doesn\'t make sense that, for the first two expressions, `'a'` is equivalent to `'a'` or `'b'` while `'b'` is not. Furthermore, it doesn\'t make any sense that \'b\' is equivalent to `'a'` and `'b'`. After examining what the interpreter does with boolean operators, these results do in fact exactly what you are asking of them, it\'s just not the same as what you think you are asking. When the Python interpreter looks at an `or` expression, it takes the first statement and checks to see if it is true. If the first statement is true, then Python returns that object\'s value without checking the second statement. This is because for an `or` expression, the whole thing is true if one of the values is true; the program does not need to bother with the second statement. On the other hand, if the first value is evaluated as false Python checks the second half and returns that value. That second half determines the truth value of the whole expression since the first half was false. This \"laziness\" on the part of the interpreter is called \"short circuiting\" and is a common way of evaluating boolean expressions in many programming languages. Similarly, for an `and` expression, Python uses a short circuit technique to speed truth value evaluation. If the first statement is false then the whole thing must be false, so it returns that value. Otherwise if the first value is true it checks the second and returns that value. One thing to note at this point is that the boolean expression returns a value indicating `True` or `False`, but that Python considers a number of different things to have a truth value assigned to them. To check the truth value of any given object `x`, you can use the function `bool(x)` to see its truth value. Below is a table with examples of the truth values of various objects: True False ------------------------- --------------------- True False 1 0 Numbers other than zero The string \'None\' Nonempty strings Empty strings Nonempty lists Empty lists Nonempty dictionaries Empty dictionaries Now it is possible to understand the perplexing results we were getting when we tested those boolean expressions before. Let\'s take a look at what the interpreter \"sees\" as it goes through that code: **First case:** `>>>`**`'a' == ('a' or 'b')`**`  # Look at parentheses first, so evaluate expression "('a' or 'b')"`\ `                           # 'a' is a nonempty string, so the first value is True`\ `                           # Return that first value: 'a'`\ `>>>`**`'a' == 'a'`**`          # the string 'a' is equivalent to the string 'a', so expression is True`\ `True` **Second case:** `>>>`**`'b' == ('a' or 'b')`**`  # Look at parentheses first, so evaluate expression "('a' or 'b')"`\ `                           # 'a' is a nonempty string, so the first value is True`\ `                           # Return that first value: 'a'`\ `>>>`**`'b' == 'a'`**`          # the string 'b' is not equivalent to the string 'a', so expression is False`\ `False ` **Third case:** `>>>`**`'a' == ('a' and 'b')`**` # Look at parentheses first, so evaluate expression "('a' and 'b')"`\ `                           # 'a' is a nonempty string, so the first value is True, examine second value`\ `                           # 'b' is a nonempty string, so second value is True`\ `                           # Return that second value as result of whole expression: 'b'`\ `>>>`**`'a' == 'b'`**`          # the string 'a' is not equivalent to the string 'b', so expression is False`\ `False` **Fourth case:** `>>>`**`'b' == ('a' and 'b')`**` # Look at parentheses first, so evaluate expression "('a' and 'b')"`\ `                           # 'a' is a nonempty string, so the first value is True, examine second value`\ `                           # 'b' is a nonempty string, so second value is True`\ `                           # Return that second value as result of whole expression: 'b'`\ `>>>`**`'b' == 'b'`**`          # the string 'b' is equivalent to the string 'b', so expression is True`\ `True ` So Python was really doing its job when it gave those apparently bogus results. As mentioned previously, the important thing is to recognize what value your boolean expression will return when it is evaluated, because it isn\'t always obvious. Going back to those initial expressions, this is how you would write them out so they behaved in a way that you want: `>>>`**`'a' == 'a' or 'a' == 'b'`**\ `True`\ `>>>`**`'b' == 'a' or 'b' == 'b'`**\ `True`\ `>>>`**`'a' == 'a' and 'a' == 'b'`**\ `False`\ `>>>`**`'b' == 'a' and 'b' == 'b'`**\ `False` When these comparisons are evaluated they return truth values in terms of True or False, not strings, so we get the proper results. ### Examples **password1.py** ``` python ## This program asks a user for a name and a password. # It then checks them to make sure that the user is allowed in. name = input("What is your name? ") password = input("What is the password? ") if name == "Josh" and password == "Friday": print("Welcome Josh") elif name == "Fred" and password == "Rock": print("Welcome Fred") else: print("I don't know you.") ``` Sample runs `What is your name? `**`Josh`**\ `What is the password? `**`Friday`**\ `Welcome Josh` `What is your name? `**`Bill`**\ `What is the password? `**`Money`**\ `I don't know you.` ### Exercises Write a program that has a user guess your name, but they only get 3 chances to do so until the program quits.
# Non-Programmer's Tutorial for Python 3/Dictionaries This chapter is about dictionaries. Dictionaries have keys and values. The keys are used to find the values. Here is an example of a dictionary in use: ``` python def print_menu(): print('1. Print Phone Numbers') print('2. Add a Phone Number') print('3. Remove a Phone Number') print('4. Lookup a Phone Number') print('5. Quit') print() numbers = {} menu_choice = 0 print_menu() while menu_choice != 5: menu_choice = int(input("Type in a number (1-5): ")) if menu_choice == 1: print("Telephone Numbers:") for x in numbers.keys(): print("Name: ", x, "\tNumber:", numbers[x]) print() elif menu_choice == 2: print("Add Name and Number") name = input("Name: ") phone = input("Number: ") numbers[name] = phone elif menu_choice == 3: print("Remove Name and Number") name = input("Name: ") if name in numbers: del numbers[name] else: print(name, "was not found") elif menu_choice == 4: print("Lookup Number") name = input("Name: ") if name in numbers: print("The number is", numbers[name]) else: print(name, "was not found") elif menu_choice != 5: print_menu() ``` And here is my output: `1. Print Phone Numbers`\ `2. Add a Phone Number`\ `3. Remove a Phone Number`\ `4. Lookup a Phone Number`\ `5. Quit`\ \ `Type in a number (1-5): `**`2`**\ `Add Name and Number`\ `Name: `**`Joe`**\ `Number: `**`545-4464`**\ `Type in a number (1-5): `**`2`**\ `Add Name and Number`\ `Name: `**`Jill`**\ `Number: `**`979-4654`**\ `Type in a number (1-5): `**`2`**\ `Add Name and Number`\ `Name: `**`Fred`**\ `Number: `**`132-9874`**\ `Type in a number (1-5): `**`1`**\ `Telephone Numbers:`\ `Name: Jill     Number: 979-4654`\ `Name: Joe      Number: 545-4464`\ `Name: Fred     Number: 132-9874`\ \ `Type in a number (1-5): `**`4`**\ `Lookup Number`\ `Name: `**`Joe`**\ `The number is 545-4464`\ `Type in a number (1-5): `**`3`**\ `Remove Name and Number`\ `Name: `**`Fred`**\ `Type in a number (1-5): `**`1`**\ `Telephone Numbers:`\ `Name: Jill     Number: 979-4654`\ `Name: Joe      Number: 545-4464`\ \ `Type in a number (1-5): `**`5`** This program is similar to the name list earlier in the chapter on lists. Here\'s how the program works. First the function `print_menu` is defined. `print_menu` just prints a menu that is later used twice in the program. Next comes the funny looking line `numbers = {}`. All that this line does is to tell Python that `numbers` is a dictionary. The next few lines just make the menu work. The lines ``` python for x in numbers.keys(): print("Name:", x, "\tNumber:", numbers[x]) ``` go through the dictionary and print all the information. The function `numbers.keys()` returns a list that is then used by the `for` loop. The list returned by `keys()` is not in any particular order so if you want it in alphabetic order it must be sorted. Similar to lists the statement `numbers[x]` is used to access a specific member of the dictionary. Of course in this case `x` is a string. Next the line `numbers[name] = phone` adds a name and phone number to the dictionary. If `name` had already been in the dictionary `phone` would replace whatever was there before. Next the lines ``` python if name in numbers: del numbers[name] ``` see if a name is in the dictionary and remove it if it is. The operator `name in numbers` returns true if `name` is in `numbers` but otherwise returns false. The line `del numbers[name]` removes the key `name` and the value associated with that key. The lines ``` python if name in numbers: print("The number is", numbers[name]) ``` check to see if the dictionary has a certain key and if it does prints out the number associated with it. Lastly if the menu choice is invalid it reprints the menu for your viewing pleasure. A recap: Dictionaries have keys and values. Keys can be strings or numbers. Keys point to values. Values can be any type of variable (including lists or even dictionaries (those dictionaries or lists of course can contain dictionaries or lists themselves (scary right? :-) ))). Here is an example of using a list in a dictionary: ``` python max_points = [25, 25, 50, 25, 100] assignments = ['hw ch 1', 'hw ch 2', 'quiz ', 'hw ch 3', 'test'] students = {'#Max': max_points} def print_menu(): print("1. Add student") print("2. Remove student") print("3. Print grades") print("4. Record grade") print("5. Print Menu") print("6. Exit") def print_all_grades(): print('\t', end=' ') for i in range(len(assignments)): print(assignments[i], '\t', end=' ') print() keys = list(students.keys()) keys.sort() for x in keys: print(x, '\t', end=' ') grades = students[x] print_grades(grades) def print_grades(grades): for i in range(len(grades)): print(grades[i], '\t', end=' ') print() print_menu() menu_choice = 0 while menu_choice != 6: print() menu_choice = int(input("Menu Choice (1-6): ")) if menu_choice == 1: name = input("Student to add: ") students[name] = [0] * len(max_points) elif menu_choice == 2: name = input("Student to remove: ") if name in students: del students[name] else: print("Student:", name, "not found") elif menu_choice == 3: print_all_grades() elif menu_choice == 4: print("Record Grade") name = input("Student: ") if name in students: grades = students[name] print("Type in the number of the grade to record") print("Type a 0 (zero) to exit") for i in range(len(assignments)): print(i + 1, assignments[i], '\t', end=' ') print() print_grades(grades) which = 1234 while which != -1: which = int(input("Change which Grade: ")) which -= 1 #same as which = which - 1 if 0 <= which < len(grades): grade = int(input("Grade: ")) grades[which] = grade elif which != -1: print("Invalid Grade Number") else: print("Student not found") elif menu_choice != 6: print_menu() ``` and here is a sample output: `1. Add student`\ `2. Remove student`\ `3. Print grades`\ `4. Record grade`\ `5. Print Menu`\ `6. Exit`\ \ `Menu Choice (1-6): `**`3`**\ `       hw ch 1         hw ch 2         quiz            hw ch 3         test `\ `#Max    25              25              50              25              100 `\ \ `Menu Choice (1-6): `**`5`**\ `1. Add student`\ `2. Remove student`\ `3. Print grades`\ `4. Record grade`\ `5. Print Menu`\ `6. Exit`\ \ `Menu Choice (1-6): `**`1`**\ `Student to add: `**`Bill`**\ \ `Menu Choice (1-6): `**`4`**\ `Record Grade`\ `Student: `**`Bill`**\ `Type in the number of the grade to record`\ `Type a 0 (zero) to exit`\ `1   hw ch 1     2   hw ch 2     3   quiz        4   hw ch 3     5   test `\ `0               0               0               0               0 `\ `Change which Grade: `**`1`**\ `Grade: `**`25`**\ `Change which Grade: `**`2`**\ `Grade: `**`24`**\ `Change which Grade: `**`3`**\ `Grade: `**`45`**\ `Change which Grade: `**`4`**\ `Grade: `**`23`**\ `Change which Grade: `**`5`**\ `Grade: `**`95`**\ `Change which Grade: `**`0`**\ \ `Menu Choice (1-6): `**`3`**\ `       hw ch 1         hw ch 2         quiz            hw ch 3         test `\ `#Max    25              25              50              25              100`\ `Bill    25              24              45              23              95 `\ \ `Menu Choice (1-6): `**`6`** Heres how the program works. Basically the variable `students` is a dictionary with the keys being the name of the students and the values being their grades. The first two lines just create two lists. The next line `students = {'#Max': max_points}` creates a new dictionary with the key {`#Max`} and the value is set to be `[25, 25, 50, 25, 100]` (since thats what `max_points` was when the assignment is made) (I use the key `#Max` since `#` is sorted ahead of any alphabetic characters). Next `print_menu` is defined. Next the `print_all_grades` function is defined in the lines: ``` python def print_all_grades(): print('\t',end=" ") for i in range(len(assignments)): print(assignments[i], '\t',end=" ") print() keys = list(students.keys()) keys.sort() for x in keys: print(x, '\t',end=' ') grades = students[x] print_grades(grades) ``` Notice how first the keys are gotten out of the `students` dictionary with the `keys` function in the line `keys = list(students.keys())`. `keys` is an iterable, and it is converted to list so all the functions for lists can be used on it. Next the keys are sorted in the line `keys.sort()`. `for` is used to go through all the keys. The grades are stored as a list inside the dictionary so the assignment `grades = students[x]` gives `grades` the list that is stored at the key `x`. The function `print_grades` just prints a list and is defined a few lines later. The later lines of the program implement the various options of the menu. The line `students[name] = [0] * len(max_points)` adds a student to the key of their name. The notation `[0] * len(max_points)` just creates a list of 0\'s that is the same length as the `max_points` list. The remove student entry just deletes a student similar to the telephone book example. The record grades choice is a little more complex. The grades are retrieved in the line `grades = students[name]` gets a reference to the grades of the student `name`. A grade is then recorded in the line `grades[which] = grade`. You may notice that `grades` is never put back into the students dictionary (as in no `students[name] = grades`). The reason for the missing statement is that `grades` is actually another name for `students[name]` and so changing `grades` changes `student[name]`. Dictionaries provide an easy way to link keys to values. This can be used to easily keep track of data that is attached to various keys.
# Non-Programmer's Tutorial for Python 3/Using Modules Here\'s this chapter\'s typing exercise (name it cal.py (`import` actually looks for a file named calendar.py and reads it in. If the file is named calendar.py and it sees a \"import calendar\" it tries to read in itself which works poorly at best.)): ``` python import calendar year = int(input("Type in the year number: ")) calendar.prcal(year) ``` And here is part of the output I got: `Type in the year number: 2001`\ \ `                                 2001                                  `\ \ `       January                  February                    March      `\ \ `Mo Tu We Th Fr Sa Su      Mo Tu We Th Fr Sa Su      Mo Tu We Th Fr Sa Su`\ `1  2  3  4  5  6  7                1  2  3  4                1  2  3  4     `\ `8  9 10 11 12 13 14       5  6  7  8  9 10 11       5  6  7  8  9 10 11`\ `15 16 17 18 19 20 21      12 13 14 15 16 17 18      12 13 14 15 16 17 18     `\ `22 23 24 25 26 27 28      19 20 21 22 23 24 25      19 20 21 22 23 24 25     `\ `29 30 31                  26 27 28                  26 27 28 29 30 31        ` (I skipped some of the output, but I think you get the idea.) So what does the program do? The first line `import calendar` uses a new command `import`. The command `import` loads a module (in this case the `calendar` module). To see the commands available in the standard modules either look in the library reference for python (if you downloaded it) or go to <http://docs.python.org/3/library/>. If you look at the documentation for the calendar module, it lists a function called `prcal` that prints a calendar for a year. The line `calendar.prcal(year)` uses this function. In summary to use a module `import` it and then use `module_name.function` for functions in the module. Another way to write the program is: ``` python from calendar import prcal year = int(input("Type in the year number: ")) prcal(year) ``` This version imports a specific function from a module. Here is another program that uses the Python Library (name it something like clock.py) (press Ctrl and the \'c\' key at the same time to terminate the program): ``` python from time import time, ctime prev_time = "" while True: the_time = ctime(time()) if prev_time != the_time: print("The time is:", ctime(time())) prev_time = the_time ``` With some output being: `The time is: Sun Aug 20 13:40:04 2000`\ `The time is: Sun Aug 20 13:40:05 2000`\ `The time is: Sun Aug 20 13:40:06 2000`\ `The time is: Sun Aug 20 13:40:07 2000`\ \ `Traceback (innermost last):`\ ` File "clock.py", line 5, in ?`\ `    the_time = ctime(time())`\ \ `KeyboardInterrupt` The output is infinite of course so I cancelled it (or the output at least continues until Ctrl+C is pressed). The program just does an infinite loop (`True` is always true, so `while True:` goes forever) and each time checks to see if the time has changed and prints it if it has. Notice how multiple names after the import statement are used in the line `from time import time, ctime`. The Python Library contains many useful functions. These functions give your programs more abilities and many of them can simplify programming in Python. ### Exercises Rewrite the `high_low.py` program from section Decisions to use an random integer between 0 and 99 instead of the hard-coded 7. Use the Python documentation to find an appropriate module and function to do this. ## Other modules Sometimes you want to use a python module that does not come with the Python installation. You can also import those, but you have to have them installed on your computer. ### Creating your own module When python reads the import command, it first checks files in your directory, then site-packages or pre installed modules. To make your own module, just create a .py file in the current directory and use the command: ``` python3 import module ``` This will try to import the file module.py from your current directory and if not found, from site-packages and prepackaged modules. Changing module to the name of the .py file you created will import that file. However, when it imports the module, it will basically start the file as a program, so any code on there will be run. You want to group all code into functions. ====The \_\_name\_\_ == \_\_main\_\_ trick==== In python, the variable `__name__` will give you the current name of the program. If a module you import prints the `__name__` variable, then it will print the name of the module. If the current file prints the `__name__` variable, it will print `__main__`, to show it is the main program. If an if statement checks the name variable and runs code if the program is main, it can bypass the unintentional run problem created when a module is imported. Say for example you have a file, which runs some code. It also has a function you want to use in another program. However, you only want the function, not to run the code. By setting up the code below, it will only run the code if it is the file that was clicked on or started, not if it was imported. ``` python3 if __name__ == '__main__': pass ``` In this instance, if the file is run but not imported, it will run the pass command. You can replace the pass command with the code you want to be run when not imported. Just remember to indent the code. ### The pip module The pip module is a module that comes with the python installation and acts as a module downloader/manager. You can download other modules from the internet with pip. The pip module is not used in the python interpreter, but is run through the command line. To use it, open up your command line interpreter (for Windows it is Command Prompt, for Mac/Linux it is Terminal) and type in the following code: ``` bash py3 -m pip install module ``` or the alternate code ``` bash pip install module ``` This will try to download and install module from the user-submitted python modules database. Module can be changed to the name of the module.
# Non-Programmer's Tutorial for Python 3/More on Lists We have already seen lists and how they can be used. Now that you have some more background I will go into more detail about lists. First we will look at more ways to get at the elements in a list and then we will talk about copying them. Here are some examples of using indexing to access a single element of a list: `>>> `**`some_numbers = ['zero', 'one', 'two', 'three', 'four', 'five']`**\ `>>> `**`some_numbers[0]`**\ `'zero'`\ `>>> `**`some_numbers[4]`**\ `'four'`\ `>>> `**`some_numbers[5]`**\ `'five'` All those examples should look familiar to you. If you want the first item in the list just look at index 0. The second item is index 1 and so on through the list. However what if you want the last item in the list? One way could be to use the `len()` function like `some_numbers[len(some_numbers) - 1]`. This way works since the `len()` function always returns the last index plus one. The second from the last would then be `some_numbers[len(some_numbers) - 2]`. There is an easier way to do this. In Python the last item is always index -1. The second to the last is index -2 and so on. Here are some more examples: `>>> `**`some_numbers[len(some_numbers) - 1]`**\ `'five'`\ `>>> `**`some_numbers[len(some_numbers) - 2]`**\ `'four'`\ `>>> `**`some_numbers[-1]`**\ `'five'`\ `>>> `**`some_numbers[-2]`**\ `'four'`\ `>>> `**`some_numbers[-6]`**\ `'zero'` Thus any item in the list can be indexed in two ways: from the front and from the back. Another useful way to get into parts of lists is using slicing. Here is another example to give you an idea what they can be used for: `>>> `**`things = [0, 'Fred', 2, 'S.P.A.M.', 'Stocking', 42, "Jack", "Jill"]`**\ `>>> `**`things[0]`**\ `0`\ `>>> `**`things[7]`**\ `'Jill'`\ `>>> `**`things[0:8]`**\ `[0, 'Fred', 2, 'S.P.A.M.', 'Stocking', 42, 'Jack', 'Jill']`\ `>>> `**`things[2:4]`**\ `[2, 'S.P.A.M.']`\ `>>> `**`things[4:7]`**\ `['Stocking', 42, 'Jack']`\ `>>> `**`things[1:5]`**\ `['Fred', 2, 'S.P.A.M.', 'Stocking']` Slicing is used to return part of a list. The slicing operator is in the form `things[first_index:last_index]`. Slicing cuts the list before the `first_index` and before the `last_index` and returns the parts in between. You can use both types of indexing: `>>> `**`things[-4:-2]`**\ `['Stocking', 42]`\ `>>> `**`things[-4]`**\ `'Stocking'`\ `>>> `**`things[-4:6]`**\ `['Stocking', 42]` Another trick with slicing is the unspecified index. If the first index is not specified the beginning of the list is assumed. If the last index is not specified the whole rest of the list is assumed. Here are some examples: `>>> `**`things[:2]`**\ `[0, 'Fred']`\ `>>> `**`things[-2:]`**\ `['Jack', 'Jill']`\ `>>> `**`things[:3]`**\ `[0, 'Fred', 2]`\ `>>> `**`things[:-5]`**\ `[0, 'Fred', 2]` Here is a (HTML inspired) program example (copy and paste in the poem definition if you want): ``` python poem = ["<B>", "Jack", "and", "Jill", "</B>", "went", "up", "the", "hill", "to", "<B>", "fetch", "a", "pail", "of", "</B>", "water.", "Jack", "fell", "<B>", "down", "and", "broke", "</B>", "his", "crown", "and", "<B>", "Jill", "came", "</B>", "tumbling", "after"] def get_bold(text): true = 1 false = 0 ## is_bold tells whether or not we are currently looking at ## a bold section of text. is_bold = false ## start_block is the index of the start of either an unbolded ## segment of text or a bolded segment. start_block = 0 for index in range(len(text)): ## Handle a starting of bold text if text[index] == "<B>": if is_bold: print("Error: Extra Bold") ## print "Not Bold:", text[start_block:index] is_bold = true start_block = index + 1 ## Handle end of bold text ## Remember that the last number in a slice is the index ## after the last index used. if text[index] == "</B>": if not is_bold: print("Error: Extra Close Bold") print("Bold [", start_block, ":", index, "]", text[start_block:index]) is_bold = false start_block = index + 1 get_bold(poem) ``` with the output being: `Bold [ 1 : 4 ] ['Jack', 'and', 'Jill']`\ `Bold [ 11 : 15 ] ['fetch', 'a', 'pail', 'of']`\ `Bold [ 20 : 23 ] ['down', 'and', 'broke']`\ `Bold [ 28 : 30 ] ['Jill', 'came']` The `get_bold()` function takes in a list that is broken into words and tokens. The tokens that it looks for are `<B>` which starts the bold text and `</B>` which ends bold text. The function `get_bold()` goes through and searches for the start and end tokens. The next feature of lists is copying them. If you try something simple like: `>>> `**`a = [1, 2, 3]`**\ `>>> `**`b = a`**\ `>>> `**`print(b)`**\ `[1, 2, 3]`\ `>>> `**`b[1] = 10`**\ `>>> `**`print(b)`**\ `[1, 10, 3]`\ `>>> `**`print(a)`**\ `[1, 10, 3]` This probably looks surprising since a modification to `b` resulted in `a` being changed as well. What happened is that the statement `b = a` makes `b` a *reference* to `a`. This means that `b` can be thought of as another name for `a`. Hence any modification to `b` changes `a` as well. However some assignments don\'t create two names for one list: `>>> `**`a = [1, 2, 3]`**\ `>>> `**`b = a * 2`**\ `>>> `**`print(a)`**\ `[1, 2, 3]`\ `>>> `**`print(b)`**\ `[1, 2, 3, 1, 2, 3]`\ `>>> `**`a[1] = 10`**\ `>>> `**`print(a)`**\ `[1, 10, 3]`\ `>>> `**`print(b)`**\ `[1, 2, 3, 1, 2, 3]` In this case `b` is not a reference to `a` since the expression `a * 2` creates a new list. Then the statement `b = a * 2` gives `b` a reference to `a * 2` rather than a reference to `a`. All assignment operations create a reference. When you pass a list as an argument to a function you create a reference as well. Most of the time you don\'t have to worry about creating references rather than copies. However when you need to make modifications to one list without changing another name of the list you have to make sure that you have actually created a copy. There are several ways to make a copy of a list. The simplest that works most of the time is the slice operator since it always makes a new list even if it is a slice of a whole list: `>>> `**`a = [1, 2, 3]`**\ `>>> `**`b = a[:]`**\ `>>> `**`b[1] = 10`**\ `>>> `**`print(a)`**\ `[1, 2, 3]`\ `>>> `**`print(b)`**\ `[1, 10, 3]` Taking the slice `[:]` creates a new copy of the list. However it only copies the outer list. Any sublist inside is still a references to the sublist in the original list. Therefore, when the list contains lists, the inner lists have to be copied as well. You could do that manually but Python already contains a module to do it. You use the `deepcopy` function of the `copy` module: `>>> `**`import copy`**\ `>>> `**`a = [[1, 2, 3], [4, 5, 6]]`**\ `>>> `**`b = a[:]`**\ `>>> `**`c = copy.deepcopy(a)`**\ `>>> `**`b[0][1] = 10`**\ `>>> `**`c[1][1] = 12`**\ `>>> `**`print(a)`**\ `[[1, 10, 3], [4, 5, 6]]`\ `>>> `**`print(b)`**\ `[[1, 10, 3], [4, 5, 6]]`\ `>>> `**`print(c)`**\ `[[1, 2, 3], [4, 12, 6]]` First of all notice that `a` is a list of lists. Then notice that when `b[0][1] = 10` is run both `a` and `b` are changed, but `c` is not. This happens because the inner arrays are still references when the slice operator is used. However with `deepcopy` `c` was fully copied. So, should I worry about references every time I use a function or `=`? The good news is that you only have to worry about references when using dictionaries and lists. Numbers and strings create references when assigned but every operation on numbers and strings that modifies them creates a new copy so you can never modify them unexpectedly. You do have to think about references when you are modifying a list or a dictionary. By now you are probably wondering why are references used at all? The basic reason is speed. It is much faster to make a reference to a thousand element list than to copy all the elements. The other reason is that it allows you to have a function to modify the inputted list or dictionary. Just remember about references if you ever have some weird problem with data being changed when it shouldn\'t be.
# Non-Programmer's Tutorial for Python 3/Revenge of the Strings And now presenting a cool trick that can be done with strings: ``` python def shout(string): for character in string: print("Gimme an " + character) print("'" + character + "'") shout("Lose") def middle(string): print("The middle character is:", string[len(string) // 2]) middle("abcdefg") middle("The Python Programming Language") middle("Atlanta") ``` And the output is: `Gimme an L`\ `'L'`\ `Gimme an o`\ `'o'`\ `Gimme an s`\ `'s'`\ `Gimme an e`\ `'e'`\ `The middle character is: d`\ `The middle character is: r`\ `The middle character is: a` What these programs demonstrate is that strings are similar to lists in several ways. The `shout()` function shows that `for` loops can be used with strings just as they can be used with lists. The `middle` procedure shows that that strings can also use the `len()` function and array indexes and slices. Most list features work on strings as well. The next feature demonstrates some string specific features: ``` python def to_upper(string): ## Converts a string to upper case upper_case = "" for character in string: if 'a' <= character <= 'z': location = ord(character) - ord('a') new_ascii = location + ord('A') character = chr(new_ascii) upper_case = upper_case + character return upper_case print(to_upper("This is Text")) ``` with the output being: `THIS IS TEXT` This works because the computer represents the characters of a string as numbers from 0 to 1,114,111. For example \'A\' is 65, \'B\' is 66 and א is 1488. The values are the unicode value. Python has a function called `ord()` (short for ordinal) that returns a character as a number. There is also a corresponding function called `chr()` that converts a number into a character. With this in mind the program should start to be clear. The first detail is the line: `if 'a' <= character <= 'z':` which checks to see if a letter is lower case. If it is then the next lines are used. First it is converted into a location so that a = 0, b = 1, c = 2 and so on with the line: `location = ord(character) - ord('a')`. Next the new value is found with `new_ascii = location + ord('A')`. This value is converted back to a character that is now upper case. Note that if you really need the upper case of a letter, you should use `u=var.upper()` which will work with other languages as well. Now for some interactive typing exercise: `>>> `**`# Integer to String`**\ `>>> `**`2`**\ `2`\ `>>> `**`repr(2)`**\ `'2'`\ `>>> `**`-123`**\ `-123`\ `>>> `**`repr(-123)`**\ `'-123'`\ `>>> `**`# String to Integer`**\ `>>> `**`"23"`**\ `'23'`\ `>>> `**`int("23")`**\ `23`\ `>>> `**`"23" * 2`**\ `'2323'`\ `>>> `**`int("23") * 2`**\ `46`\ `>>> `**`# Float to String`**\ `>>> `**`1.23`**\ `1.23`\ `>>> `**`repr(1.23)`**\ `'1.23'`\ `>>> `**`# Float to Integer`**\ `>>> `**`1.23`**\ `1.23`\ `>>> `**`int(1.23)`**\ `1`\ `>>> `**`int(-1.23)`**\ `-1`\ `>>> `**`# String to Float`**\ `>>> `**`float("1.23")`**\ `1.23`\ `>>> `**`"1.23"`**` `\ `'1.23'`\ `>>> `**`float("123")`**\ `123.0` If you haven\'t guessed already the function `repr()` can convert an integer to a string and the function `int()` can convert a string to an integer. The function `float()` can convert a string to a float. The `repr()` function returns a printable representation of something. Here are some examples of this: `>>> `**`repr(1)`**\ `'1'`\ `>>> `**`repr(234.14)`**\ `'234.14'`\ `>>> `**`repr([4, 42, 10])`**\ `'[4, 42, 10]'` The `int()` function tries to convert a string (or a float) into an integer. There is also a similar function called `float()` that will convert an integer or a string into a float. Another function that Python has is the `eval()` function. The `eval()` function takes a string and returns data of the type that python thinks it found. For example: `>>> `**`v = eval('123')`**\ `>>> `**`print(v, type(v))`**\ `123 <type 'int'>`\ `>>> `**`v = eval('645.123')`**\ `>>> `**`print(v, type(v))`**\ `645.123 <type 'float'>`\ `>>> `**`v = eval('[1, 2, 3]')`**\ `>>> `**`print(v, type(v))`**\ `[1, 2, 3] <type 'list'>` If you use the `eval()` function you should check that it returns the type that you expect. One useful string function is the `split()` method. Here\'s an example: `>>> `**`"This is a bunch of words".split()`**\ `['This', 'is', 'a', 'bunch', 'of', 'words']`\ `>>> `**`text = "First batch, second batch, third, fourth"`**\ `>>> `**`text.split(",")`**\ `['First batch', ' second batch', ' third', ' fourth']` Notice how `split()` converts a string into a list of strings. The string is split by whitespace by default or by the optional argument (in this case a comma). You can also add another argument that tells `split()` how many times the separator will be used to split the text. For example: `>>> `**`list = text.split(",")`**\ `>>> `**`len(list)`**\ `4`\ `>>> `**`list[-1]`**\ `' fourth'`\ `>>> `**`list = text.split(",", 2)`**\ `>>> `**`len(list)`**\ `3`\ `>>> `**`list[-1]`**\ `' third, fourth'` ### Slicing strings (and lists) Strings can be cut into pieces --- in the same way as it was shown for lists in the previous chapter --- by using the *slicing* \"operator\" `[]`. The slicing operator works in the same way as before: text\[first_index:last_index\] (in very rare cases there can be another colon and a third argument, as in the example shown below). In order not to get confused by the index numbers, it is easiest to see them as *clipping places*, possibilities to cut a string into parts. Here is an example, which shows the clipping places (in yellow) and their index numbers (red and blue) for a simple text string: `<tt>`{=html} -------- ---- ----- --- --- --- --- --- ------ --- ---- --- ---- --- ----- ---- 0 1 2 \... -2 -1 ↓ ↓ ↓ ↓ ↓ ↓ ↓ text = \" S T R I N G \" ↑ ↑ \[: :\] -------- ---- ----- --- --- --- --- --- ------ --- ---- --- ---- --- ----- ---- `</tt>`{=html} Note that the red indexes are counted from the beginning of the string and the blue ones from the end of the string backwards. (Note that there is no blue -0, which could seem to be logical at the end of the string. Because `-0 == 0`, -0 means \"beginning of the string\" as well.) Now we are ready to use the indexes for slicing operations: `<tt>`{=html} -------------- --- ------------ text\[1:4\] → \"TRI\" text\[:5\] → \"STRIN\" text\[:-1\] → \"STRIN\" text\[-4:\] → \"RING\" text\[2\] → \"R\" text\[:\] → \"STRING\" text\[::-1\] → \"GNIRTS\" -------------- --- ------------ `</tt>`{=html} `text[1:4]` gives us all of the `text` string between clipping places 1 and 4, \"`TRI`\". If you omit one of the \[first_index:last_index\] arguments, you get the beginning or end of the string as default: `text[:5]` gives \"`STRIN`\". For both `first_index` and `last_index` we can use both the red and the blue numbering schema: `text[:-1]` gives the same as `text[:5]`, because the index -1 is at the same place as 5 in this case. If we do not use an argument containing a colon, the number is treated in a different way: `text[2]` gives us one character following the second clipping point, \"`R`\". The special slicing operation `text[:]` means \"from the beginning to the end\" and produces a copy of the entire string (or list, as shown in the previous chapter). Last but not least, the slicing operation can have a second colon and a third argument, which is interpreted as the \"step size\": `text[::-1]` is `text` from beginning to the end, with a step size of -1. -1 means \"every character, but in the other direction\". \"`STRING`\" backwards is \"`GNIRTS`\" (test a step length of 2, if you have not got the point here). All these slicing operations work with lists as well. In that sense strings are just a special case of lists, where the list elements are single characters. Just remember the concept of *clipping places*, and the indexes for slicing things will get a lot less confusing. ### Examples ``` python # This program requires an excellent understanding of decimal numbers. def to_string(in_int): """Converts an integer to a string""" out_str = "" prefix = "" if in_int < 0: prefix = "-" in_int = -in_int while in_int // 10 != 0: out_str = str(in_int % 10) + out_str in_int = in_int // 10 out_str = str(in_int % 10) + out_str return prefix + out_str def to_int(in_str): """Converts a string to an integer""" out_num = 0 if in_str[0] == "-": multiplier = -1 in_str = in_str[1:] else: multiplier = 1 for c in in_str: out_num = out_num * 10 + int(c) return out_num * multiplier print(to_string(2)) print(to_string(23445)) print(to_string(-23445)) print(to_int("14234")) print(to_int("12345")) print(to_int("-3512")) ``` The output is: `2`\ `23445`\ `-23445`\ `14234`\ `12345`\ `-3512`
# Non-Programmer's Tutorial for Python 3/File IO ### File I/O Here is a simple example of file I/O (input/output): ``` python # Write a file with open("test.txt", "wt") as out_file: out_file.write("This Text is going to out file\nLook at it and see!") # Read a file with open("test.txt", "rt") as in_file: text = in_file.read() print(text) ``` The output and the contents of the file `test.txt` are: `This Text is going to out file`\ `Look at it and see!` Notice that it wrote a file called `test.txt` in the directory that you ran the program from. The `\n` in the string tells Python to put a *n*ewline where it is. An overview of file I/O is: - Get a file object with the `open` function - Read or write to the file object (depending on how it was opened) - If you did not use `with` to open the file, you\'d have to close it manually The first step is to get a file object. The way to do this is to use the `open` function. The format is `file_object = open(filename, mode)` where `file_object` is the variable to put the file object, `filename` is a string with the filename, and `mode` is `"rt"` to *r*ead a file as *t*ext or `"wt"` to *w*rite a file as *t*ext (and a few others we will skip here). Next the file objects functions can be called. The two most common functions are `read` and `write`. The `write` function adds a string to the end of the file. The `read` function reads the next thing in the file and returns it as a string. If no argument is given it will return the whole file (as done in the example). Now here is a new version of the phone numbers program that we made earlier: ``` python def print_numbers(numbers): print("Telephone Numbers:") for k, v in numbers.items(): print("Name:", k, "\tNumber:", v) print() def add_number(numbers, name, number): numbers[name] = number def lookup_number(numbers, name): if name in numbers: return "The number is " + numbers[name] else: return name + " was not found" def remove_number(numbers, name): if name in numbers: del numbers[name] else: print(name," was not found") def load_numbers(numbers, filename): in_file = open(filename, "rt") while True: in_line = in_file.readline() if not in_line: break in_line = in_line[:-1] name, number = in_line.split(",") numbers[name] = number in_file.close() def save_numbers(numbers, filename): out_file = open(filename, "wt") for k, v in numbers.items(): out_file.write(k + "," + v + "\n") out_file.close() def print_menu(): print('1. Print Phone Numbers') print('2. Add a Phone Number') print('3. Remove a Phone Number') print('4. Lookup a Phone Number') print('5. Load numbers') print('6. Save numbers') print('7. Quit') print() phone_list = {} menu_choice = 0 print_menu() while True: menu_choice = int(input("Type in a number (1-7): ")) if menu_choice == 1: print_numbers(phone_list) elif menu_choice == 2: print("Add Name and Number") name = input("Name: ") phone = input("Number: ") add_number(phone_list, name, phone) elif menu_choice == 3: print("Remove Name and Number") name = input("Name: ") remove_number(phone_list, name) elif menu_choice == 4: print("Lookup Number") name = input("Name: ") print(lookup_number(phone_list, name)) elif menu_choice == 5: filename = input("Filename to load: ") load_numbers(phone_list, filename) elif menu_choice == 6: filename = input("Filename to save: ") save_numbers(phone_list, filename) elif menu_choice == 7: break else: print_menu() print("Goodbye") ``` Notice that it now includes saving and loading files. Here is some output of my running it twice: `1. Print Phone Numbers`\ `2. Add a Phone Number`\ `3. Remove a Phone Number`\ `4. Lookup a Phone Number`\ `5. Load numbers`\ `6. Save numbers`\ `7. Quit`\ \ `Type in a number (1-7): `**`2`**\ `Add Name and Number`\ `Name: `**`Jill`**\ `Number: `**`1234`**\ `Type in a number (1-7): `**`2`**\ `Add Name and Number`\ `Name: `**`Fred`**\ `Number: `**`4321`**\ `Type in a number (1-7): `**`1`**\ `Telephone Numbers:`\ `Name: Jill     Number: 1234`\ `Name: Fred     Number: 4321`\ \ `Type in a number (1-7): `**`6`**\ `Filename to save: `**`numbers.txt`**\ `Type in a number (1-7): `**`7`**\ `Goodbye` `1. Print Phone Numbers`\ `2. Add a Phone Number`\ `3. Remove a Phone Number`\ `4. Lookup a Phone Number`\ `5. Load numbers`\ `6. Save numbers`\ `7. Quit`\ \ `Type in a number (1-7): `**`5`**\ `Filename to load: `**`numbers.txt`**\ `Type in a number (1-7): `**`1`**\ `Telephone Numbers:`\ `Name: Jill     Number: 1234`\ `Name: Fred     Number: 4321`\ \ `Type in a number (1-7): `**`7`**\ `Goodbye` The new portions of this program are: ``` python def load_numbers(numbers, filename): in_file = open(filename, "rt") while True: in_line = in_file.readline() if not in_line: break in_line = in_line[:-1] name, number = in_line.split(",") numbers[name] = number in_file.close() def save_numbers(numbers, filename): out_file = open(filename, "wt") for k, v in numbers.items(): out_file.write(k + "," + v + "\n") out_file.close() ``` First we will look at the save portion of the program. First it creates a file object with the command `open(filename, "wt")`. Next it goes through and creates a line for each of the phone numbers with the command `out_file.write(k + "," + v + "\n")`. This writes out a line that contains the name, a comma, the number and follows it by a newline. The loading portion is a little more complicated. It starts by getting a file object. Then it uses a `while True:` loop to keep looping until a `break` statement is encountered. Next it gets a line with the line `in_line = in_file.readline()`. The `readline` function will return an empty string when the end of the file is reached. The `if` statement checks for this and `break`s out of the `while` loop when that happens. Of course if the `readline` function did not return the newline at the end of the line there would be no way to tell if an empty string was an empty line or the end of the file so the newline is left in what `readline` returns. Hence we have to get rid of the newline. The line `in_line = in_line[:-1]` does this for us by dropping the last character. Next the line `name, number = in_line.split(",")` splits the line at the comma into a name and a number. This is then added to the `numbers` dictionary. ### Advanced use of .txt files You might be saying to yourself, \"Well I know how to read and write to a textfile, but what if I want to print the file without opening out another program?\" There are a few different ways to accomplish this. The easiest way does open another program, but everything is taken care of in the Python code, and doesn\'t require the user to specify a file to be printed. This method involves invoking the subprocess of another program. Remember the file we wrote output to in the above program? Let\'s use that file. Keep in mind, in order to prevent some errors, this program uses concepts from the Next chapter. Please feel free to revisit this example after the next chapter. ``` Python import subprocess def main(): try: print("This small program invokes the print function in the Notepad application") #Lets print the file we created in the program above subprocess.call(['notepad','/p','numbers.txt']) except WindowsError: print("The called subprocess does not exist, or cannot be called.") main() ``` The `subprocess.call` takes three arguments. The first argument in the context of this example, should be the name of the program which you would like to invoke the printing subprocess from. The second argument should be the specific subprocess within that program. For simplicity, just understand that in this program, `'/p'` is the subprocess used to access your printer through the specified application. The last argument should be the name of the file you want to send to the printing subprocess. In this case, it is the same file used earlier in this chapter. ### Exercises Now modify the grades program from section Dictionaries so that is uses file I/O to keep a record of the students.
# Non-Programmer's Tutorial for Python 3/Dealing with the imperfect ### \...or how to handle errors ### closing files with with We use the \"with\" statement to open and close files.[^1][^2] ``` python with open("in_test.txt", "rt") as in_file: with open("out_test.txt", "wt") as out_file: text = in_file.read() data = parse(text) results = encode(data) out_file.write(results) print( "All done." ) ``` If some sort of error happens anywhere in this code (one of the files is inaccessible, the parse() function chokes on corrupt data, etc.) the \"with\" statements guarantee that all the files will eventually be properly closed. Closing a file just means that the file is \"cleaned up\" and \"released\" by our program so that it can be used in another program. ### catching errors with try So you now have the perfect program, it runs flawlessly, except for one detail, it will crash on invalid user input. Have no fear, for Python has a special control structure for you. It\'s called `try` and it tries to do something. Here is an example of a program with a problem: ``` python print("Type Control C or -1 to exit") number = 1 while number != -1: number = int(input("Enter a number: ")) print("You entered:", number) ``` Notice how when you enter `@#&` it outputs something like: `Traceback (most recent call last):`\ ` File "try_less.py", line 4, in ``<module>`{=html}\ `   number = int(input("Enter a number: "))`\ `ValueError: invalid literal for int() with base 10: '\\@#&'` As you can see the `int()` function is unhappy with the number `@#&` (as well it should be). The last line shows what the problem is; Python found a `ValueError`. How can our program deal with this? What we do is first: put the place where errors may occur in a `try` block, and second: tell Python how we want `ValueError`s handled. The following program does this: ``` python print("Type Control C or -1 to exit") number = 1 while number != -1: try: number = int(input("Enter a number: ")) print("You entered:", number) except ValueError: print("That was not a number.") ``` Now when we run the new program and give it `@#&` it tells us \"That was not a number.\" and continues with what it was doing before. When your program keeps having some error that you know how to handle, put code in a `try` block, and put the way to handle the error in the `except` block. ### Exercises Update at least the phone numbers program (in section Dictionaries) so it doesn\'t crash if a user doesn\'t enter any data at the menu. `{{Solution|title=Solution|text= <syntaxhighlight lang="python"> def print_menu(): print('1. Print Phone Numbers') print('2. Add a Phone Number') print('3. Remove a Phone Number') print('4. Lookup a Phone Number') print('5. Quit') print() numbers = {} menu_choice = 0 print_menu() while menu_choice != 5: try: menu_choice = int(input("Type in a number (1-5): ")) if menu_choice == 1: print("Telephone Numbers:") for x in numbers.keys(): print("Name: ", x, "\tNumber:", numbers[x]) print() elif menu_choice == 2: print("Add Name and Number") name = input("Name: ") phone = input("Number: ") numbers[name] = phone elif menu_choice == 3: print("Remove Name and Number") name = input("Name: ") if name in numbers: del numbers[name] else: print(name, "was not found") elif menu_choice == 4: print("Lookup Number") name = input("Name: ") if name in numbers: print("The number is", numbers[name]) else: print(name, "was not found") elif menu_choice != 5: print_menu() except ValueError: print("That was not a number.")</syntaxhighlight> }}`{=mediawiki} [^1]: \"The \'with\' statement\" [^2]: \'The Python \"with\" Statement by Example\'
# Non-Programmer's Tutorial for Python 3/Recursion ## Recursion In Python, a recursive function is a function which calls itself. ### Introduction to recursion So far, in Python, we have seen functions which call other functions. However, it is possible for a function to call itself. Let\'s look at a simple example. ``` python # Program by Mitchell Aikens # No Copyright # 2010 num = 0 def main(): counter(num) def counter(num): print(num) num += 1 counter(num) main() ``` If you were to run this program in IDLE, it would run forever. The only way to stop the loop would be to interrupt the execution by pressing Ctrl + C on your keyboard. This is an example of an infinite recursion. (Some users have reported a glitch in the current IDLE system causing the exception raised by Ctrl + C to start looping as well. If this happens, press Ctrl + F6, and the IDLE shell should restart.) It is arguable that recursion is just another way to accomplish the same thing as a while loop. In some cases, this is absolutely correct. Though, there are other uses for Recursion that are very valid, where `while` loops or `for` loops may not be optimal. Recursion can be controlled, just like loops. Lets look at an example of a controlled loop. ``` python # Program by Mitchell Aikens # No copyright # 2012 def main(): loopnum = int(input("How many times would you like to loop?\n")) counter = 1 recurr(loopnum,counter) def recurr(loopnum,counter): if loopnum > 0: print("This is loop iteration",counter) recurr(loopnum - 1,counter + 1) else: print("The loop is complete.") main() ``` The above uses arguments/parameters to control the number of recursions. Simply use what you already know about functions and follow the flow of the program. It is simple to figure out. If you are having trouble, please refer back to Non-Programmer\'s Tutorial for Python 3/Advanced Functions Example. ## Practical Applications of Recursion Often, recursion is studied at an advanced computer science level. Recursion is usually used to solve complex problems that can be broken down into smaller, identical problems. Recursion isn\'t required to solve a problem. Problems that can be solved with recursion, most likely can be solved with loops. Also, a loop may be more efficient than a recursive function. Recursive functions require more memory, and resources than loops, making them less efficient in a lot of cases. This usage requirement is sometimes referred to as `<i>`{=html}overhead`</i>`{=html}. You might be thinking, \"Well why bother with recursion. I\'ll just use a loop. I already know how to loop and this is a lot more work.\" This thought is understandable, but not entirely ideal. When solving complex problems, a recursive function is sometimes easier, faster, and simpler to build and code. Think of these two \"rules\": - If I can solve the problem now, without recursion, the function simply returns a value. - If I cannot solve the problem now without recursion, the function reduces the problem to something smaller and similar, and calls itself to solve the problem. Let\'s apply this using a common mathematical concept, factorials. If you are unfamiliar with factorials in mathematics, please refer to the following reading. Factorials The factorial of a number `<i>`{=html}n`</i>`{=html}, is denoted as `<i>`{=html}n!`</i>`{=html}. Here are some basic rules of factorials. If n = 0 then n! = 1 If n \> 0 then n! = 1 x 2 x 3 x \... x n For example, let\'s look at the factorial of the number 9. 9! = 1 x 2 x 3 x 4 x 5 x 6 x 7 x 8 x 9 Let\'s look at a program which calculates the factorial of any number entered by the user, by method of recursion. ``` python3 def main(): num = int(input("Please enter a non-negative integer.\n")) fact = factorial(num) print("The factorial of",num,"is",fact) def factorial(num): if num == 0: return 1 else: return num * factorial(num - 1) main() ``` Recursion is also useful in an advanced topic called generators. To generate the series 1,2,1,3,1,2,1,4,1,2\... we would need this code: ``` python def crazy(min_): yield min_ g=crazy(min_+1) while True: yield next(g) yield min_ i=crazy(1) ``` to get the next element you would call next(i)
# Non-Programmer's Tutorial for Python 3/Intro to Object Oriented Programming in Python 3 ## Object Oriented Programming Up until now, the programming you have been doing has been procedural. However, a lot of programs today are Object Oriented. Knowing both types, and knowing the difference, is very important. Many important languages in computer science such as C++ and Java, often use OOP methods. Beginners, and non-programmers often find the concept of OOP confusing, and complicated. This is normal. Don\'t be put off if you struggle or do not understand. There are plenty of other resources you can use to help overcome any issues you may have, if this chapter does not help you. This chapter will be broken up into different lessons. Each lesson will explain OOP in a different way, just to make sure OOP is covered as thoroughly as possible, because `<b>`{=html}IT IS VERY IMPORTANT.`</b>`{=html} Before the lessons, there is an introduction which explains key concepts, terms, and other important areas of OOP, required to understand each lesson. ## Introduction Think of a procedure as a function. A function has a specific purpose. That purpose may be gathering input, performing mathematical calculations, displaying data, or manipulating data to, from, or in, a file. Typically, procedures use data which is separate from code for manipulation. This data is often passed between procedures. When a program becomes much larger and complex, this can cause problems. For example, you have designed a program which stores information about a product in variables. When a customer requests information on a product, these variables are passed to different functions for different purposes. Later on, as more data is stored on these products, you decide to store the information in a list or dictionary. In order for your program to function, you must now edit each function that accepted variables, to now accept and manipulate a list or dictionary. Imagine the time that would take for a program that was hundreds of megabytes, and hundreds of files in size! It would drive you insane! not to mention, errors in your code, are almost guaranteed, just because of the large volume of work and possibilities to make a typo or other error. This is less than optimal. Procedural programming is centered on procedures or functions. But, OOP is centered on creating Objects. Remember how a procedural program has separated data and code? Remember how that huge program was hundreds of files and would take FOREVER to edit? Well, think of an `<i>`{=html}object`</i>`{=html} as a sort of \"combination\" of those files and data into one \"being\". In a technical sense, an Object is an entity which contains data, AND procedures (code, functions, etc.). `<b>`{=html}Data inside an object is called a `<i>`{=html}data attribute`</i>`{=html}`</b>`{=html}.\ `<b>`{=html}Functions, or procedures inside the object are called `<i>`{=html}methods`</i>`{=html}`</b>`{=html}.\ Think of `<b>`{=html}data attributes`</b>`{=html} as variables.\ Think of `<b>`{=html}methods`</b>`{=html} as functions or procedures.\ Let\'s look at a simple, everyday example. The light and light switch in your bedroom. The data attributes would be as follows. - light_on (True or False) - switch_position (Up or Down) - electricity_flow (True or False) The methods would be as follows. - move_switch - change_electricity_flow The data attributes may or may not be visible. For example, you cannot directly see the electricity flowing to the light. You only know there is electricity, because the light is on. However, you can see the position of the switch (switch_position), and you can see if the light is on or off (light_on). Some methods are `<i>`{=html}private`</i>`{=html}. This means that you cannot directly change them. For example, unless you cut the wires in your light fixture (please don\'t do that, and for the sake of this example, assume that you don\'t know the wires exist), you cannot change the flow of electricity directly. You also cannot directly change if the light is on or off (and no, you can\'t unscrew the bulb! work with me here!). However, you can indirectly change these attributes by using the `<i>`{=html}methods`</i>`{=html} in the object. If you don\'t pay your bill, the `change_electricity_flow` method will change the value of the `electricity_flow` attribute to FALSE. If you flip the switch, the `move_switch` method changes the value of the `light_on` attribute. By now you\'re probably thinking, \"What does this have to do with Python?\" or, \"I understand, but how do I code an Object?\" Well, we are almost to that point! One more concept must be explained before we can dive into code. In Python, an object\'s data attributes and methods are specified by a `<b>`{=html}class`</b>`{=html}. Think of a class as a blueprint to an object. For example, your home - the object that you live in - you can also call it your pad, bungalow, crib, or whatever, was built based on a set of blueprints; these blueprints would be considered the class used to design your home, pad, crib, ahem, you get the idea. Again, a class tells us how to make an object. In technical terms, and this is important here, a class defines the data attributes and methods inside an object. To create a class, we code a `<i>`{=html}class definition`</i>`{=html}. A class definition is a group of statements which define an object\'s data attributes and methods. `<big>`{=html}`<b>`{=html}Lesson One`</b>`{=html}`</big>`{=html} Below is a Procedural program that performs simple math on a single number, entered by a user. ``` python # Program by Mitchell Aikens # No Copyright # 2012 # Procedure 1 def main(): try: # Get a number to maniuplate num = float(input("Please enter a number to manipulate.\n")) # Store the result of the value, after it has been manipulated # by Procedure 2 addednum = addfive(num) # Store the result of the value, after it has been manipulated # by Procedure 3 multipliednum = multiply(addednum) # Send the value to Procedure 4 display(multipliednum) # Deal with exceptions from non-numeric user entry except ValueError: print("You must enter a valid number.\n") # Reset the value of num, to clear non-numeric data. num = 0 # Call main, again. main() # Procedure 2 def addfive(num): return num + 5 # Procedure 3 def multiply(addednum): return addednum * 2.452 # Procedure 4 def display(multi): # Display the final value print("The final value is ",multi) # Call Procedure 1 main() ``` If we were to enter a value of \"5\", the output would be as shown below. `Please enter a number to manipulate.`\ `5`\ `The final value is  24.52` If we were to enter a value of \"g\", and then correct the input and enter a value of \"8\", the output would be as shown below. `Please enter a number to manipulate.`\ `g`\ `You must enter a valid number.`\ \ `Please enter a number to manipulate.`\ `8`\ `The final value is  31.875999999999998` Below, is a Class, and a program which uses that class. This Object Oriented Program does the same thing as the procedural program above. Let\'s cover some important OOP coding concepts before we dive into the Class and program. To create a class, we use the `class` keyword. After the keyword, you type the name you want to name your class. It is common practice that the name of your class uses CapWords convention. If I wanted to create a class named dirtysocks, the code would be: ``` python class DirtySocks ``` The Class is shown first. The program which uses the class is second. ``` python # Filename: oopexample.py # Mitchell Aikens # No Copyright # 2012 # OOP Demonstration - Class class NumChange: def __init__(self): self.__number = 0 def addfive(self,num): self.__number = num return self.__number + 5 def multiply(self,added): self.__added = added return self.__added * 2.452 ``` The program which uses the class above, is below. ``` python # Filename: oopexampleprog.py # Mitchell Aikens # No Copyright # 2012 # OOP Demonstration - Program import oopexample maths = oopexample.NumChange() def main(): num = float(input("Please enter a number.\n")) added = maths.addfive(num) multip = maths.multiply(added) print("The manipulated value is ",multip) main() ``` After looking at that program, you are probably a bit lost. That\'s OK. Let\'s start off by dissecting the class. The class is named \"NumChange\" There are three methods to this class: - \_\_init\_\_ - addfive - multiply These three methods each have a similar code. ``` python def __init__(self): def addfive(self,num): def multiply(self,added): ``` Notice how each method has a parameter named \"self\". This parameter must be present in each method of the class. This parameter doesn\'t HAVE TO be called \"self\", but it is standard practice, which means you should probably stick with it. This parameter is required in each method because when a method executes, it has to know which object\'s attributes to operate on. Even though there is only one Object, we still need to make sure the interpreter knows that we want to use the data attributes in that class. So we play it safe\...and use the \"self\" parameter. Let\'s look at the first method. ``` python def __init__(self): ``` Most Classes in Python have an `__init__` which executes automatically when an instance of a class is created in memory. (When we reference a class, an `<i>`{=html}instance`</i>`{=html} \[or object\] of that class is created.) This method is commonly referred to as the `<i>`{=html}initializer method`</i>`{=html}. When the method executes, the \"self\" parameter is automatically assigned to the object. This method is called the initializer method because is \"initializes\" the data attributes. ↵Under the \_\_init\_\_ method, we set the value of the `number` attribute to 0 initially. We reference the object attribute using dot notation. ``` python def __init__(self): self.__number = 0 ``` The `self.__number = 0` line simply means \"\"the value of the attribute \"number\", in the object, is 0\"\". Let\'s look at the next method. ``` python def addfive(self,num): self.__number = num return self.__number + 5 ``` This method is named \"addfive\". It accepts a parameter called \"num\", from the program using the class. The method then assigns the value of that parameter to the \"number\" attribute inside the object. The method then returns the value of \"number\", with 5 added to it, to the statement which called the method. Let\'s look at the third method. ``` python def multiply(self,added): self.__added = added return self.__added * 2.453 ``` This method is named \"multiply\". It accepts a parameter named \"added\". It assigns the value of the parameter to the \"added\" attribute, and returns the value of the \"added\" attribute multiplied by 2.452, to the statement which called the method. Notice how the name of each method begins with two underscores? Let\'s explain that. Earlier we mentioned that an object operates on data attributes inside itself using methods. Ideally, these data attributes should be able to be manipulated ONLY BY METHODS IN THE OBJECT. It is possible to have outside code manipulate data attributes. To \"hide\" attributes, so only methods in the object can manipulate them, you use two underscores before the object name, as we have been demonstrating. Omitting those two underscores in the attribute name, allows for the possibility of manipulation from code outside the object. Let\'s look at the program which uses the class we just dissected. Notice the first line of non comment code. ``` python import oopexample ``` This line of code imports the class, which we have saved in a separate file (module). Classes do not have to be in a separate file, but it is almost always the case, and thus is good practice to get used to importing the module now. The next line: ``` python maths = oopexample.NumChange() ``` This line creates an instance of the NumChange class, stored in the module named \"oopexample\", and stores the instance in the variable named \"maths\". The syntax is: `<i>`{=html}`modulename.Classname()``</i>`{=html} Next we define the main function. Then, we get a number from the user. The next line `added = maths.addfive(num)` sends the value of the \"num\" variable to the method named \"addfive\", which is part of the class we stored an instance of in the variable named \"maths\", and stores the returned value in the variable named \"added\". The next line `multip = maths.multiply(added)` sends the value of the variable \"added\", to the method named \"multiply\", which is part of the class we stored an instance of in the variable named \"maths\", and stores the returned value in the variable named \"multip\". The next line prints \"The manipulated value is `<value of multip>`{=html}\". The last line calls the main function which executes the steps outlined above.
# Non-Programmer's Tutorial for Python 3/Intro to Imported Libraries and other Functions ## Intro to Imported Libraries and other Functions In this chapter, we will cover some functions from various imported libraries that are commonly asked about, or used in Python. This chapter is not required to fully understand basics of Python. This chapter is meant to show further capability of Python, which can be utilized with what you already know about the language. ### math : The math library has many functions that are useful for programs that need to perform mathematical operations, that cannot be accomplished using the built in operators. ```{=html} <!-- --> ``` : This section assumes you have math training up to and including Trigonometry. The following list shows all the functions in the math library: - math.ceil - math.copysign - math.fabs - math.factorial - math.floor - math.fmod (Not the most ideal for its purpose. Will not be explained.) - math.frexp (Outside the scope of this tutorial. Will not be explained.) - math.fsum - math.isfinite - math.isinf - math.isnan - math.ldexp - math.modf (Outside the realm of this tutorial. Will not be explained.) - math.trunc (Outside the realm of this tutorial. Will not be explained.) - math.exp - math.expm1 - math.log - math.log1p - math.log10 - math.pow - math.sqrt - math.acos - math.asin - math.atan - math.atan2 - math.cos - math.hypot - math.sin - math.tan - math.degrees - math.radians - math.acosh - math.asinh - math.atanh - math.cosh - math.sinh - math.tanh - math.erf - math.erfc - math.gamma - math.lgamma - math.pi - math.e : Of course, we won\'t cover every one of these functions. But we will cover a good chunk of them. Let\'s start off by covering the two constants in the math library. `math.pi` is the mathematical constant \"π\", to available precision on your computer. `math.e` is the mathematical constant \"e\", to available precision on your computer. Here is an example of both constants when entered in interactive mode in the Python shell. `>>> import math`\ `>>> math.e`\ `<span style="color:blue;">`{=html}`2.718281828459045``</span>`{=html}\ `>>> math.pi`\ `<span style="color:blue;">`{=html}`3.141592653589793``</span>`{=html} These constants can be stored in a variable just like any other number. Below is an example of such, and shows simple operations on those variables. `>>> conste = math.e`\ `>>> (conste + 5 / 2) * 2.21`\ `<span style="color:blue;">`{=html}`11.532402840894488``</span>`{=html}\ `>>> constpi = math.pi`\ `>>> (((7 /2.1) % constpi) * 2)`\ `<span style="color:blue;">`{=html}`0.38348135948707984``</span>`{=html}\ `>>>` Now, let\'s look at the functions. Let\'s start at the top of the list, and work our way down. Some of the functions will be skipped. At this point in the tutorial, you should be able to look at each of these examples to follow, and easily figure out what the example does. A simple sentence or two about what the function does will be provided. Below is an example of every `math` module function, and how it is used. (Excluding functions noted above as not to be explained) `>>> import math`\ `>>> math.ceil(4.5) ** Rounds the number up to the nearest non decimal number **`\ `5`\ `>>> math.ceil(4.1)`\ `<span style="color:blue;">`{=html}`5``</span>`{=html}\ `>>> math.copysign(4, -.4)  ** Returns the number ``x`` with the sign of ``y`` in the context of ``(x,y)`\ `<span style="color:blue;">`{=html}`-4.0``</span>`{=html}\ `>>> math.copysign(-4, 4)`\ `<span style="color:blue;">`{=html}`4.0``</span>`{=html}\ `>>> math.fabs(-44)  ** Return the absolute value of the number, as a float **`\ `<span style="color:blue;">`{=html}`44.0``</span>`{=html}\ `>>> math.factorial(4)  **  Returns the factorial of a number **`\ `<span style="color:blue;">`{=html}`24``</span>`{=html}\ `>>> math.floor(4.3)  ** Rounds the number down to the nearest non decimal number. **`\ `<span style="color:blue;">`{=html}`4``</span>`{=html}\ `>>> math.floor(4.99999)`\ `<span style="color:blue;">`{=html}`4``</span>`{=html}\ `>>> math.fsum([.1,.2,5,45.2,-.054,.4]) **  Returns the sum of all the numbers in the brackets. Not always precise **`\ `<span style="color:blue;">`{=html}`50.846000000000004``</span>`{=html}\ `>>> math.isfinite(3) ** Returns ``True`` if the value is neither an infinity nor a NaN. Returns ``False`` otherwise. **`\ `<span style="color:blue;">`{=html}`True``</span>`{=html}
# Non-Programmer's Tutorial for Python 3/The End So here we are at the end, or maybe the beginning. This tutorial is on Wikibooks, so feel free to make improvements to it. If you want to learn more about Python, The Python Tutorial by Guido van Rossum has more topics that you can learn about. If you have been following this tutorial, you should be able to understand a fair amount of it. The Python Programming wikibook can be worth looking at, too. Hopefully this book covers everything you have needed to get started programming. Thanks to everyone who has sent me emails about it. I enjoyed reading them, even when I have not always been the best replier. Happy programming, may it change your life and the world. ### External Resources Here are few other books which cover Python 3: - A Byte of Python by Swaroop C H - DataCamp Interactive Python 3 Tutorial - Online - Hands-on Python Tutorial by Dr. Andrew N. Harrington - Introduction to Object Oriented Programming in Python by Dr. Francesco Lelli - Subject:Python programming language lists other Wikibooks related to Python.
# Blended Learning in K-12/Introduction |previous=BEGINNING |next=Definition|What is "Blended Learning"?}} ``` ## Introduction While teachers have always used a variety of teaching methods and media, blended learning includes the recent availability of digital learning technologies and Internet-based tools that facilitate communication, interaction, and collaborative learning. Neither e-learning nor the traditional classroom are ideal for all types of learning. Blended learning offers the opportunity to incorporate the \'best of both worlds\' to improve teaching and learning, to take \"advantage of the strengths of both learning environments and be more successful in avoiding their weaknesses.\" (Node, 2003) Evidence from a study conducted by Alfred P. Rovai and Hope M. Jordan \"suggest that blended courses produce a stronger sense of community among students than either traditional or fully online courses\" (Rovai and Jordan, 2004). The subheadings in this chapter will provide more information about blended learning, beginning with What is \"Blended Learning\"?. This section will discuss what prominent authors in the field are saying about what blended learning really is. While most authorities in the field agree on blended learning\'s usefulness, each author has a slightly different opinion about what makes a class \"blended\". Quotes will be used from these researchers, explaining their definitions in detail. Blended learning has taken many forms since it was first created several years ago. As blended learning evolved, its name and meaning also changed. It has been called hybrid learning, mixed mode learning, and several other names. The second subheading in Chapter One, The many names of Blended Learning, will discuss the countless names of blended learning, review each meaning, and look at how it has evolved into the term we know today. Finally, Chapter One will examine Why is Blended Learning Important?. Research from many educational areas will be used to show the merits of using blended learning instead of just traditional or e-learning environments.
# Blended Learning in K-12/Definition |previous=Introduction |next=The many names of Blended Learning}} ``` Dr. Margaret Driscoll identifies four different concepts in defining blended learning **The first defines blended learning as meaning \"to combine or mix modes of Web-based technology (e.g., live virtual classroom, self-paced instruction, collaborative learning, streaming video, audio, and text) to accomplish an educational goal.\"** (Driscoll, 2002) Other authors also define blended learning according to Driscoll's first. For example in the introduction to \"Building Effective Blended Learning Programs\", Harry Singh (2003) indicates blended learning models "combine various delivery modes. Anecdotal evidence indicates that blended learning not only offers more choices but also is more effective.\" Dr. Driscoll's **second definition describes blended learning as meaning \"to combine various pedagogical approaches (e.g., constructivism, behaviorism, cognitivism) to produce an optimal learning outcome with or without instructional technology.\"** (Driscoll, 2002) As Charles Graham points out in his introduction to the article "Blended Learning Systems: Definition, Current Trends, and Future Directions", both of these first two concepts "suffer from the problem that they define BL so broadly that there encompass virtually all learning systems." (Bonk & Graham, 2004) The **third definition from Dr. Driscoll (2002) defines blended learning as meaning \"to combine any form of instructional technology (e.g., videotape, CD-ROM, Web-based training, film) with face-to-face instructor-led training.\"** (Driscoll, 2002) Most authors echo this definition such as Gary Harriman, who indicated in his article, "What is Blended Learning" (2004), that "blended learning combines online with face-to-face learning. The goal of blended learning is to provide the most efficient and effective instruction experience by combining delivery modalities.\" (GrayHarriman, 2004) In addition, Judith Smith in her article, "Blended Learning: An Old Friend Gets a New Name", defined blended learning "as a method of educating at a distance that uses technology (high-tech, such as television and the Internet or low-tech, such as voice mail or conference calls) combined with traditional (or, stand-up) education or training.\" (Smith, 2001) Simply put the Rochester Institute of Technology reported in the "Blended Learning Pilot Project: Final Report for the Academic Year 2003--2004" that \"blended learning aims to join the best of classroom teaching and learning with the best of online teaching and learning.\" (Rochester Institute, 2004) New South Wales Department of Education and Training (2005) echoes the above authors in the article, \"Blended Learning" by stating \"blended learning is learning which combines online and face-to-face approaches.\" (NSW, 2005) Richard Voos (2003) also repeats this definition that blended learning is a combination of face-to-face and online media while he goes on to state that blended learning also results in \"seat time\" being "significantly reduced". (Voos, 2003) Carla Garnham and Robert Kaleta (2002) identified blended learning or hybrid courses as joining the best features of "in-class teaching with the best features of online learning to promote active independent learning and reduce class seat time.\" (Garnham and Kaleta, 2002) Alfred Rovai and Hope Jordan (Aug 2004) in the article \"Blended Learning and Sense of Community: A Comparative Analysis with Traditional and Fully Online Graduate Courses\" indicate \"a blended course can lie anywhere between the continuum anchored at opposite ends by fully face-to-face and fully online learning environments.\" (Rovai and Jordan, 2004) "According to Colis and Moonen (2001) blended learning is a hybrid of traditional face-to-face and online learning so that instruction occurs both in the classroom and online, and where the online component becomes a natural extension of traditional classroom learning.\" (Rovai and Jordan, 2004) e-Learning Centre\'s Library defines blended learning as \"a learning solution created through a mixture of face-to-face, live e-learning, self-paced learning as well through a mix of media -- 'the magic is in the mix!' or 'the beauty is in the blend!' \" (e-Learning Centre, 2005) The Australian National Training Authority's (2003) "Definitions of Key Terms Used in e-learning" provides a definition of blended learning from Flexible Learning Advisory Group (2004) as "learning methods that combine e-learning with other forms of flexible learning and more traditional forms of learning. " **The fourth concept from Dr. Driscoll defines blended learning as meaning \"to mix or combine instructional technology with actual job tasks in order to create a harmonious effect of learning and working.\"** (Driscoll, 2002) This fourth definition gives an indication as to the popularity of blended learning as part of corporate training. \"Blended Learning is the latest buzzword in corporate training. Mixing e-learning with other types of training delivery.\" (Bersin, 2003) There are other authors who have defined blended learning by combining Driscoll's first and third concept. The Royer Center for Learning and Academic Technologies (2004) defines blended learning as intermingling "multiple learning strategies or methods with a variety of media. In contemporary terms, learning strategies and media typically include aspects of face-to-face instruction and online (or distance) learning, in combination with a rich variety of learning strategies or dimensions.\" (Royer, 2004) From "The Node\'s Guide to Blended Learning: Getting the Most out of Your Classroom and the Internet" (2001), the Node Learning Technologies Network defines blended learning as learning that uses "multiple strategies, methods and delivery systems" including the "integration of multiple strategies, methods and delivery systems". \"Good teachers have always used a mix of strategies, methods and media to reach their objectives--that's not new. What is new is that today's Internet-based tools can facilitate communication, interaction, and collaborative learning in ways that were not possible before. What's also new is the relative accessibility of digital learning technologies and the ease with which instructors can blend them with classroom resources\" (Node, 2003). Purnima Valiathan (2002) in \"Blended Learning Models" also combined the Driscoll's first and third concepts of blended learning in stating that the term blended learning is "used to describe a solution that combines several different delivery methods, such as collaboration software, Web-based courses, EPSS, and knowledge management practices ... to describe learning that mixes various event-based activities, including face-to-face classrooms, live e-learning, and self-paced learning.\" (Valiathan, 2002) In defining "blended learning", a few authors concentrate on the word blended. As defined in The Concise Oxford Dictionary, 8th edition, to blend means to "form a harmonious compound, become one". (Concise Oxford Dictionary 8th edition,1990) As Peter Isackson (2002) emphasizes, the definition of blended learning needs to focus on the \"blending\" of the methods and strategies and not just the \"tossing\" together of the different modalities. Isackson (2002) uses the analogy of good blending \"like a good Scotch whiskey\"; Royer Center (2004) offers additional analogies of blending as \"compared to gourmet coffees, wines, hybrid vehicles, and even gasoline. Each blend offers a variety of choices that form an appealing whole.\" (Royer, 2004) In connection with these analogies the Royer Center (2004) goes on to explain that blended learning can have a variety of flavors and thus "there is no single approach for 'how to blend' ", just as there exist different recipes for one type of food dish. "Successful blended learning, like a successful recipe, mingles a range of complementary ingredients in order to support the unique purpose of each learning event.\" (Royer, 2004) Thus, as Isackson (2004) points out, "much of what people claim to offer today as \"blended learning\" isn\'t so much blended (like a good Scotch whisky) but \"tossed\" (like a salad)." There is the need to "distinguish between blended learning \-- where there is a real input/output strategy and a dynamic structure \-- and \"tossed learning\" where the form of input alternates.\" (Isackson, 2002) As reported in "The Node\'s Guide to Blended Learning: Getting the Most out of Your Classroom and the Internet", \"blended learning can be many things--there is no prescription and no recipe.\" (Node, 2003) Finally, as there are a number of concepts for defining blended learning, Martin Oliver and Keith Trigwell (2005) in their article, \"Can \'blended learning\' Be Redeemed\", are critical of using the term at all. Oliver and Trigwell (2005) argue that the term 'blended learning' is "ill-defined and inconsistently used. Whilst its popularity is increasing, its clarity is not." Oliver and Trigwell (2005) state that definitions of blended learning lack "an analysis from the perspective of the learner.\" Oliver and Trigwell (2005) suggest the need for a \"shift away from manipulating the blend as seen by the teacher, to an in-depth analysis of the variation in the experience of the learning of the student in the blended learning context.Along the same line as Oliver and Trigwell\'s (2005) criticism of the use of the term \"blended learning\", Don Morrison (2003) writes, \"Personally, I'm much more comfortable talking about the strategic use of learning delivery channels than 'blended learning'. Every enterprise has learning delivery channels---it\'s a question of identifying them and deciding which to use when.\" He continues by saying, \"I have heard blended learning dismissed as the Emperor\'s New Clothes on the basis that all learning---from infancy, through the classroom, and into the enterprise---is blended learning.\" (Morrison, 2003)