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+Figure 18.1,pulmo2/images/Figure 18.1.jpg,Figure 18.1: Conditions that can produce dyspnea. ARDS: Acute respiratory distress syndrome.,"Dyspnea is also a strong predictor of mortality in most heart and lung diseases. As well as cardiopulmonary conditions, dyspnea is also prevalent in other conditions that affect breathing or metabolism, and (see figure 18.1) it is prevalent during end-stage disease where it is as common as pain and forms a significant problem for end-of-life care. Despite its prevalence there are few options for treating this symptom. Unlike pain, there are no specific drugs to reduce this sensation.","{'ed66933c-0507-4838-8b90-3e3328daf222': 'It might be worth putting dyspnea in a clinical context. Like pain, dyspnea can occur across a number of pathological conditions. It is the cardinal symptom of lung disease, but it is highly prevalent in heart diseases as well—in fact it is a more common sign of myocardial infarction in women than the classical symptom of chest pain that is\xa0more prevalent in men.', '116f070e-6849-4ded-b300-6139c518706b': 'Dyspnea is also a strong predictor of mortality in most heart and lung diseases. As well as cardiopulmonary conditions, dyspnea is also prevalent in other conditions that affect breathing or metabolism, and (see figure 18.1) it is prevalent during end-stage disease where it is as common as pain and forms a significant problem for end-of-life care. Despite its prevalence there are few options for treating this symptom. Unlike pain, there are no specific drugs to reduce this sensation.', 'eaf7bcbf-edca-4466-9a42-b46c6949eff1': 'In this chapter we will have a look at the regions of the nervous system that control breathing and how they interact or override each other.', '5867bf01-6acb-4d92-bac8-5e75bde55544': 'This chapter will describe how the alveolar–arterial PO2 difference is calculated and what assumptions can be made from it.', '4ef36793-42e1-48cb-be98-c099eb0e004a': 'Before you start, a quick reminder that an uppercase A refers to alveolar and lowercase to arterial.', '8f30f95b-215b-436b-9512-3ae10768618b': 'There are other elements that should be considered when dealing with the air-hungry patient. Probably because of its homeostatic importance, the sensation of air hunger is very effective at getting attention and producing fear and anxiety. Recent comparisons of attentive and emotional impacts suggest air hunger is perceived as much more threatening and worrisome than pain at equivalent intensities. (Ironically we routinely ask about patients’ pain, but rarely about their air hunger.)', 'fb7adc11-d772-4195-b5da-be301bfab084': 'This emotional impact of air hunger is reflected in the regions of the brain\xa0that are consistently seen to be activated in recent functional brain imaging studies (see figure 18.5). The amygdala, anterior insula, and anterior cingulate are all persistently seen to activate during air hunger, and all are either associated with the brain’s fear network or generation of emotional responses. The activation of the anterior insula is also interesting as this phylogenically old part of the cortex also responds to other homeostatic imbalances, such as thirst, hunger for food, and pain. Although air hunger itself is unpleasant, it is these emotional components that produce air hunger’s profoundly negative effect on patients’ quality of life and makes end-of-life distressing for both the patient and their loved ones. We will come back to the\xa0impact of emotional responses in a moment.', '4b7a8014-6af3-445b-b4be-e857a0bc111a': 'So there we are—three different forms of dyspnea, with separate neural mechanisms. That said, it is unlikely that a patient will ever walk into your office and tell you they have “dyspnea,”\xa0or pinpoint which form of dyspnea they have. But\xa0taking an interest in the subtleties of your patients’ comments may not be a purely academic exercise either. More likely they are likely to use descriptors like those shown in table 18.1. These descriptors that use more common, everyday language have been related to each form of dyspnea. Knowing which form or forms of dyspnea the patient is experiencing can help in diagnosis as the different causes of dyspnea\xa0(like those listed in figure 18.1)\xa0can produce different levels of each form. For example, chest tightness is much more commonly reported by asthmatics, whereas patients with chronic obstructive pulmonary disease tend to use descriptors more related to effort to breathe\xa0and\xa0air hunger.', '12aa1d7b-d9ba-4fcb-889e-d4973fa700f7': 'Table 18.1: Patient descriptors for the three different forms of dyspnea.', '5a0b5c38-5d23-49af-be59-525bac0623e2': 'While the different forms of dyspnea have been investigated, described, and now explored as their potential as diagnostic tools, the emotional impact of dyspnea is only now receiving more attention. The most immediate complication caused by the emotional component is the potential for a positive feedback loop to form between air hunger and the anxiety it generates.\xa0The anxiety that air hunger produces results in an increased drive to breathe;\xa0in turn this increased drive to breathe causes the air hunger to increase, which leads to more anxiety and so on (figure 18.6).', 'c02eb73c-f5b5-4ccd-8113-3e904d9ae87f': 'Behavioral effects of dyspnea: This cycle can be entered into by different types of patients;\xa0those with cardiopulmonary disease enter the cycle at the point of the air hunger, whereas patients with anxiety disorders can enter the cycle at this point and can experience significant air hunger even with apparently perfectly normal lung and heart function. On a more long-term basis the quality of life of air-hungry patients can be diminished by another positive feedback scenario that can produce “respiratory cripples”\xa0of cardiopulmonary patients. The air hunger produced by the underlying disease worsens during exertion, so makes\xa0exercising uncomfortable. This frequently results in patients avoiding exercise, perhaps starting with taking an elevator instead of the stairs, or driving to the grocery store when previously they might have walked.', '0701b412-5140-4761-96ac-7ad79d1b62d8': 'This reduction in exercise leads to cardiac deconditioning, which in turn makes the air hunger worse and leads to further avoidance of exercise. Along with the progression of the disease, this cycle may leave the patient out-of-breath while simply sitting in a chair.', 'ff30a35d-ec49-4a2b-8402-f685ad7483bb': 'The patient’s quality of life becomes severely diminished as their life is ruled by dyspnea that prevents them from leaving the house, interacting with children or grandchildren, and performing simple activities that used to bring enjoyment, such as gardening, wood-working, walking, and more. This reduced quality of life can potentially lead to depression, and the emotional response to dyspnea may be exacerbated.', '3fa222a8-44f6-40e4-9700-b4c786fbd3df': 'So what can be done to relieve the patient’s air hunger and the associated anxiety? Well, despite its prevalence, the treatment of dyspnea is decades behind the treatment of pain. For too long the approach to treating dyspnea has been to treat the underlying disease with the expectation that the dyspnea will go away.\xa0This is true and a perfect course of action for many conditions, but for many diseases that produce dyspnea we have ineffective cures, such as emphysema, lung cancer, and pulmonary fibrosis. How do we make the 49 percent\xa0of terminally ill patients who suffer with dyspnea at the end of life more comfortable?', '96bf1610-7ea3-41bb-83c4-4fe808ffa128': 'Opioids: A common practice is to use opioids, but the mechanism of how they might work and indeed their overall efficacy has been disputed. There are a number of routes for how\xa0morphine may act, if it indeed does so. Opioids may have a direct inhibitory effect on the central networks that generate air hunger, or\xa0at higher dose concentrations they may reduce air hunger indirectly by causing respiratory depression—that is, they tackle air hunger at what we think to be its source. Alternatively, opioids may reduce the affective or emotional component of dyspnea (i.e., the patient may perceive air hunger, but simply is not\xa0as bothered by it). Recent work from Harvard University suggests that morphine has a direct effect on both the sensory and affective components of air hunger independent of its effect on ventilatory drive.', 'acd95dde-e94e-456d-b79c-aaf7cda0accb': 'Anxiolytics: As the emotional component of air hunger is so strong, the fear and anxiety produced can be treated in the absence of any specific drug to treat the air hunger itself. Use of anxiolytics drugs has also produced mixed results that may be complicated by the patient’s underlying condition, and whether the type of anxiolytic causes ventilatory depression.', '98681128-282c-4676-af4c-e9237fc4b75c': 'Furosemide: Although there is currently no drug that specifically tackles air hunger, there is a growing body of evidence that inhaled furosemide (the loop diuretic) reduces air hunger by sensitizing pulmonary stretch receptors, meaning they fire more for any given lung volume. This amplifies the stretch receptors’ inhibitory effect on air hunger described earlier, by fooling the brain into thinking the lungs are at a greater volume than they really are.', 'd4f7d731-abe8-4b12-9515-b817f4c6a042': 'Nonpharmaceutical alternatives: A nonpharmaceutical alternative is to simply cool the patient’s face with a fan or wet cloth. This facial cooling initiates the “diving reflex”\xa0via the trigeminal nerve. One component of the diving reflex is to reduce ventilatory drive at the brainstem—an ideal response if one is heading underwater.', '2f2f59dd-03fc-41e1-b326-987748de2c35': 'This inhibition of ventilatory drive is likely responsible for the moderate reduction in air hunger seen with facial cooling.', '7276f9ff-0abe-46ec-add8-1d0160bf075e': 'Rehabilitation and desensitization: While dyspnea can be addressed by other methods than those briefly described here, few have been shown to work consistently or effectively. On a more long-term basis, breathing training and pulmonary rehabilitation appear to help patients overcome exacerbations of their disease or even reduce chronic air hunger, but both require patient cooperation and compliance and may have limited effect in severe disease. What can be taken from the literature is that the treatment of dyspnea is in desperate need of more attention. For a symptom that is so common and has such an impact on patients, dyspnea is a clinical issue that is woefully underaddressed.'}"
+Figure 18.2,pulmo2/images/Figure 18.2.jpg,Figure 18.2: Types of dyspnea.,So now let us look at the distinguishable sensations that the term dyspnea encompasses and begin to understand how they differ neurologically (see figure 18.2).,"{'f5d49a8e-7472-47f2-aa2e-2ae15bf3322c': 'So now let us look at the distinguishable sensations that the term dyspnea encompasses and begin to understand how they differ neurologically (see figure 18.2).', '971f0265-da9a-4606-aaea-3f064a1f4859': 'Effort to breathe: The first form of dyspnea is the sensation of work or effort to breathe. The healthy individual is usually unaware of the effort they\xa0are putting into breathing until breathing is significantly increased, such as during exercise when ventilation and work of breathing rises. The sensation of the work or effort to breathe is not particularly uncomfortable. If you jogged down the street now you might become more aware of the effort to breathe, but are not disturbed by it.'}"
+Figure 18.3,pulmo2/images/Figure 18.3.jpg,Figure 18.3: The proposed neural mechanism of air hunger.,"So any signals to the brainstem respiratory networks that increase the drive to breathe are likely to promote air hunger, and these influences may not all be chemical (see figure 18.3). For example, emotions such as anxiety increase the drive to breathe, and this is a pertinent point with clinical ramifications that we will return to.","{'e6fc31fa-4351-4dd2-bccd-ff4a91ad3da8': 'An increase in motor drive is required to activate more tension or movement in any skeletal muscle, including the respiratory muscles. And like other skeletal muscles, such as limb muscles, we believe that the sensation of effort comes from a perception of that increased motor drive. Sensory information from the activated muscles, in our case the respiratory muscles, is thought to generate the sensation of work.', '133ab222-0225-4d54-bcd5-18c6b4070b00': 'Getting laboratory subjects to report work and effort separately is very difficult, so for our purposes right now, we are grouping what might be two sensations together as one.', 'a9e094a8-293b-450f-ba3a-bca93185329f': 'Chest tightness: The next form of dyspnea is primarily reported by asthmatic patients during bronchoconstriction. Similar to the sensation of work and effort, tightness was originally thought to arise from the increase in respiratory muscle activity associated with a rise in resistive work of breathing.\xa0But in 2002 we showed that “tightness”\xa0was unrelated to respiratory effort by removing respiratory muscle activity of bronchoconstricted asthmatics with mechanical ventilation. When we did this, “tightness”\xa0persisted, despite the respiratory muscles being inactive. So what does cause tightness? The next best, but so far unproven, alternative is that inflammation of the airways associated with an asthma attack leads to activation of airway irritant (or rapidly adapting) receptors, the afferent activity from which is perceived centrally as tightness.', '52ae02da-d9e8-4763-989e-d5354904f7ee': 'Air hunger: Air hunger is arguably the most complex and clinically important form. “Air hunger”\xa0is the sensation of suffocation and can be described as a “desperate urge to breathe.”\xa0You may have experienced this sensation at the end of a prolonged breath-hold, and it is the unpleasantness of air hunger that made you resume breathing. “Air hunger”\xa0is a warning signal that ventilation is insufficient and blood gases are becoming deranged; given the immediate importance of maintaining constant blood gases, air hunger is perhaps our most important homeostatic signal, and it has been referred to as the “suffocation alarm.”\xa0The mechanisms underlying air hunger are still unclear, but again, they were once thought to involve the respiratory muscle motor and sensory signals and detection of a disparity between them—that is, the brain perceived that the respiratory muscles were not achieving the work they had been commanded to do. This hypothesis was developed in the sixties and still persists in texts today; however, it is wrong. In two separate labs, one at Harvard University and the other in Australia, pulmonary physiologists completely paralyzed each other to remove all motor activity; when they inhaled carbon dioxide, they still felt air hungry, suggesting the respiratory muscle signals were not essential to generate air hunger. So where does air hunger come from?', '72bffedf-aac4-414b-a6c7-eea6e2e282ec': 'We see air hunger arise when PaCO2 rises, when PaO2 falls, or when arterial pH decreases. These changes are detected by chemoreceptors that reflexly increase the drive to breathe from the brainstem. While we are not usually aware of our reflex breathing drive, we think that once this drive increases to a critical level, a signal is sent upward that is perceived as air hunger.', '1453b6a2-caa4-4494-848f-1a198da08ae0': 'So any signals to the brainstem respiratory networks that increase the drive to breathe are likely to promote air hunger, and these influences may not all be chemical (see figure 18.3). For example, emotions such as anxiety increase the drive to breathe, and this is a pertinent point with clinical ramifications that we will return to.', '7690de05-839f-42ba-a0b7-de654894948f': 'Likewise, any influences that reduce the drive to breathe also have a tendency to reduce air hunger (see figure 18.3). Perhaps the most interesting example of this is the effect of pulmonary stretch receptor activity. Pulmonary stretch receptors are mechanoreceptors in the airways that respond to lung inflation. Although this pulmonary afferent activity is thought to have little effect on the control of breathing in man, it reduces the drive to breathe in other species as part of the Hering–Breuer reflex. What we see in humans is that lung inflation, and presumably an increase in pulmonary stretch receptor firing, profoundly reduces air hunger, even in the absence of any blood gas improvements.', 'a9f22713-e80c-40c9-ac82-38c879c982a5': 'This is easy to demonstrate to yourself by holding your breath; during the breath-hold CO2\xa0will gradually accumulate in your bloodstream and you will feel a gradually increasing urge to breathe that will become increasingly more uncomfortable to a point when it is intolerable and you must begin breathing again. That first big breath you take does not return your arterial CO2\xa0to normal, but despite this you get great relief from air hunger by taking it, probably because that big breath stretched the lung and caused a rapid increase of stretch receptor activity to the brainstem.', 'd3edc83e-0deb-4917-8aeb-ee3ced677ae0': 'So air hunger is really affected by a balance of influences:\xa0those that increase the drive to breathe (such as hypercapnia and hypoxia) promote air hunger, while inhibitory influences on the drive to breathe tend to promote comfort (see figure 18.4).'}"
+Figure 18.4,pulmo2/images/Figure 18.4.jpg,Figure 18.4: Balance of pulmonary stretch receptors and chemoreceptor firing.,"So air hunger is really affected by a balance of influences: those that increase the drive to breathe (such as hypercapnia and hypoxia) promote air hunger, while inhibitory influences on the drive to breathe tend to promote comfort (see figure 18.4).","{'e6fc31fa-4351-4dd2-bccd-ff4a91ad3da8': 'An increase in motor drive is required to activate more tension or movement in any skeletal muscle, including the respiratory muscles. And like other skeletal muscles, such as limb muscles, we believe that the sensation of effort comes from a perception of that increased motor drive. Sensory information from the activated muscles, in our case the respiratory muscles, is thought to generate the sensation of work.', '133ab222-0225-4d54-bcd5-18c6b4070b00': 'Getting laboratory subjects to report work and effort separately is very difficult, so for our purposes right now, we are grouping what might be two sensations together as one.', 'a9e094a8-293b-450f-ba3a-bca93185329f': 'Chest tightness: The next form of dyspnea is primarily reported by asthmatic patients during bronchoconstriction. Similar to the sensation of work and effort, tightness was originally thought to arise from the increase in respiratory muscle activity associated with a rise in resistive work of breathing.\xa0But in 2002 we showed that “tightness”\xa0was unrelated to respiratory effort by removing respiratory muscle activity of bronchoconstricted asthmatics with mechanical ventilation. When we did this, “tightness”\xa0persisted, despite the respiratory muscles being inactive. So what does cause tightness? The next best, but so far unproven, alternative is that inflammation of the airways associated with an asthma attack leads to activation of airway irritant (or rapidly adapting) receptors, the afferent activity from which is perceived centrally as tightness.', '52ae02da-d9e8-4763-989e-d5354904f7ee': 'Air hunger: Air hunger is arguably the most complex and clinically important form. “Air hunger”\xa0is the sensation of suffocation and can be described as a “desperate urge to breathe.”\xa0You may have experienced this sensation at the end of a prolonged breath-hold, and it is the unpleasantness of air hunger that made you resume breathing. “Air hunger”\xa0is a warning signal that ventilation is insufficient and blood gases are becoming deranged; given the immediate importance of maintaining constant blood gases, air hunger is perhaps our most important homeostatic signal, and it has been referred to as the “suffocation alarm.”\xa0The mechanisms underlying air hunger are still unclear, but again, they were once thought to involve the respiratory muscle motor and sensory signals and detection of a disparity between them—that is, the brain perceived that the respiratory muscles were not achieving the work they had been commanded to do. This hypothesis was developed in the sixties and still persists in texts today; however, it is wrong. In two separate labs, one at Harvard University and the other in Australia, pulmonary physiologists completely paralyzed each other to remove all motor activity; when they inhaled carbon dioxide, they still felt air hungry, suggesting the respiratory muscle signals were not essential to generate air hunger. So where does air hunger come from?', '72bffedf-aac4-414b-a6c7-eea6e2e282ec': 'We see air hunger arise when PaCO2 rises, when PaO2 falls, or when arterial pH decreases. These changes are detected by chemoreceptors that reflexly increase the drive to breathe from the brainstem. While we are not usually aware of our reflex breathing drive, we think that once this drive increases to a critical level, a signal is sent upward that is perceived as air hunger.', '1453b6a2-caa4-4494-848f-1a198da08ae0': 'So any signals to the brainstem respiratory networks that increase the drive to breathe are likely to promote air hunger, and these influences may not all be chemical (see figure 18.3). For example, emotions such as anxiety increase the drive to breathe, and this is a pertinent point with clinical ramifications that we will return to.', '7690de05-839f-42ba-a0b7-de654894948f': 'Likewise, any influences that reduce the drive to breathe also have a tendency to reduce air hunger (see figure 18.3). Perhaps the most interesting example of this is the effect of pulmonary stretch receptor activity. Pulmonary stretch receptors are mechanoreceptors in the airways that respond to lung inflation. Although this pulmonary afferent activity is thought to have little effect on the control of breathing in man, it reduces the drive to breathe in other species as part of the Hering–Breuer reflex. What we see in humans is that lung inflation, and presumably an increase in pulmonary stretch receptor firing, profoundly reduces air hunger, even in the absence of any blood gas improvements.', 'a9f22713-e80c-40c9-ac82-38c879c982a5': 'This is easy to demonstrate to yourself by holding your breath; during the breath-hold CO2\xa0will gradually accumulate in your bloodstream and you will feel a gradually increasing urge to breathe that will become increasingly more uncomfortable to a point when it is intolerable and you must begin breathing again. That first big breath you take does not return your arterial CO2\xa0to normal, but despite this you get great relief from air hunger by taking it, probably because that big breath stretched the lung and caused a rapid increase of stretch receptor activity to the brainstem.', 'd3edc83e-0deb-4917-8aeb-ee3ced677ae0': 'So air hunger is really affected by a balance of influences:\xa0those that increase the drive to breathe (such as hypercapnia and hypoxia) promote air hunger, while inhibitory influences on the drive to breathe tend to promote comfort (see figure 18.4).'}"
+Figure 18.5,pulmo2/images/Figure 18.5.jpg,Figure 18.5: Central regions associated with air hunger.,"This emotional impact of air hunger is reflected in the regions of the brain that are consistently seen to be activated in recent functional brain imaging studies (see figure 18.5). The amygdala, anterior insula, and anterior cingulate are all persistently seen to activate during air hunger, and all are either associated with the brain’s fear network or generation of emotional responses. The activation of the anterior insula is also interesting as this phylogenically old part of the cortex also responds to other homeostatic imbalances, such as thirst, hunger for food, and pain. Although air hunger itself is unpleasant, it is these emotional components that produce air hunger’s profoundly negative effect on patients’ quality of life and makes end-of-life distressing for both the patient and their loved ones. We will come back to the impact of emotional responses in a moment.","{'8f30f95b-215b-436b-9512-3ae10768618b': 'There are other elements that should be considered when dealing with the air-hungry patient. Probably because of its homeostatic importance, the sensation of air hunger is very effective at getting attention and producing fear and anxiety. Recent comparisons of attentive and emotional impacts suggest air hunger is perceived as much more threatening and worrisome than pain at equivalent intensities. (Ironically we routinely ask about patients’ pain, but rarely about their air hunger.)', 'fb7adc11-d772-4195-b5da-be301bfab084': 'This emotional impact of air hunger is reflected in the regions of the brain\xa0that are consistently seen to be activated in recent functional brain imaging studies (see figure 18.5). The amygdala, anterior insula, and anterior cingulate are all persistently seen to activate during air hunger, and all are either associated with the brain’s fear network or generation of emotional responses. The activation of the anterior insula is also interesting as this phylogenically old part of the cortex also responds to other homeostatic imbalances, such as thirst, hunger for food, and pain. Although air hunger itself is unpleasant, it is these emotional components that produce air hunger’s profoundly negative effect on patients’ quality of life and makes end-of-life distressing for both the patient and their loved ones. We will come back to the\xa0impact of emotional responses in a moment.', '4b7a8014-6af3-445b-b4be-e857a0bc111a': 'So there we are—three different forms of dyspnea, with separate neural mechanisms. That said, it is unlikely that a patient will ever walk into your office and tell you they have “dyspnea,”\xa0or pinpoint which form of dyspnea they have. But\xa0taking an interest in the subtleties of your patients’ comments may not be a purely academic exercise either. More likely they are likely to use descriptors like those shown in table 18.1. These descriptors that use more common, everyday language have been related to each form of dyspnea. Knowing which form or forms of dyspnea the patient is experiencing can help in diagnosis as the different causes of dyspnea\xa0(like those listed in figure 18.1)\xa0can produce different levels of each form. For example, chest tightness is much more commonly reported by asthmatics, whereas patients with chronic obstructive pulmonary disease tend to use descriptors more related to effort to breathe\xa0and\xa0air hunger.', '12aa1d7b-d9ba-4fcb-889e-d4973fa700f7': 'Table 18.1: Patient descriptors for the three different forms of dyspnea.', '5a0b5c38-5d23-49af-be59-525bac0623e2': 'While the different forms of dyspnea have been investigated, described, and now explored as their potential as diagnostic tools, the emotional impact of dyspnea is only now receiving more attention. The most immediate complication caused by the emotional component is the potential for a positive feedback loop to form between air hunger and the anxiety it generates.\xa0The anxiety that air hunger produces results in an increased drive to breathe;\xa0in turn this increased drive to breathe causes the air hunger to increase, which leads to more anxiety and so on (figure 18.6).', 'c02eb73c-f5b5-4ccd-8113-3e904d9ae87f': 'Behavioral effects of dyspnea: This cycle can be entered into by different types of patients;\xa0those with cardiopulmonary disease enter the cycle at the point of the air hunger, whereas patients with anxiety disorders can enter the cycle at this point and can experience significant air hunger even with apparently perfectly normal lung and heart function. On a more long-term basis the quality of life of air-hungry patients can be diminished by another positive feedback scenario that can produce “respiratory cripples”\xa0of cardiopulmonary patients. The air hunger produced by the underlying disease worsens during exertion, so makes\xa0exercising uncomfortable. This frequently results in patients avoiding exercise, perhaps starting with taking an elevator instead of the stairs, or driving to the grocery store when previously they might have walked.', '0701b412-5140-4761-96ac-7ad79d1b62d8': 'This reduction in exercise leads to cardiac deconditioning, which in turn makes the air hunger worse and leads to further avoidance of exercise. Along with the progression of the disease, this cycle may leave the patient out-of-breath while simply sitting in a chair.', 'ff30a35d-ec49-4a2b-8402-f685ad7483bb': 'The patient’s quality of life becomes severely diminished as their life is ruled by dyspnea that prevents them from leaving the house, interacting with children or grandchildren, and performing simple activities that used to bring enjoyment, such as gardening, wood-working, walking, and more. This reduced quality of life can potentially lead to depression, and the emotional response to dyspnea may be exacerbated.', '3fa222a8-44f6-40e4-9700-b4c786fbd3df': 'So what can be done to relieve the patient’s air hunger and the associated anxiety? Well, despite its prevalence, the treatment of dyspnea is decades behind the treatment of pain. For too long the approach to treating dyspnea has been to treat the underlying disease with the expectation that the dyspnea will go away.\xa0This is true and a perfect course of action for many conditions, but for many diseases that produce dyspnea we have ineffective cures, such as emphysema, lung cancer, and pulmonary fibrosis. How do we make the 49 percent\xa0of terminally ill patients who suffer with dyspnea at the end of life more comfortable?', '96bf1610-7ea3-41bb-83c4-4fe808ffa128': 'Opioids: A common practice is to use opioids, but the mechanism of how they might work and indeed their overall efficacy has been disputed. There are a number of routes for how\xa0morphine may act, if it indeed does so. Opioids may have a direct inhibitory effect on the central networks that generate air hunger, or\xa0at higher dose concentrations they may reduce air hunger indirectly by causing respiratory depression—that is, they tackle air hunger at what we think to be its source. Alternatively, opioids may reduce the affective or emotional component of dyspnea (i.e., the patient may perceive air hunger, but simply is not\xa0as bothered by it). Recent work from Harvard University suggests that morphine has a direct effect on both the sensory and affective components of air hunger independent of its effect on ventilatory drive.', 'acd95dde-e94e-456d-b79c-aaf7cda0accb': 'Anxiolytics: As the emotional component of air hunger is so strong, the fear and anxiety produced can be treated in the absence of any specific drug to treat the air hunger itself. Use of anxiolytics drugs has also produced mixed results that may be complicated by the patient’s underlying condition, and whether the type of anxiolytic causes ventilatory depression.', '98681128-282c-4676-af4c-e9237fc4b75c': 'Furosemide: Although there is currently no drug that specifically tackles air hunger, there is a growing body of evidence that inhaled furosemide (the loop diuretic) reduces air hunger by sensitizing pulmonary stretch receptors, meaning they fire more for any given lung volume. This amplifies the stretch receptors’ inhibitory effect on air hunger described earlier, by fooling the brain into thinking the lungs are at a greater volume than they really are.', 'd4f7d731-abe8-4b12-9515-b817f4c6a042': 'Nonpharmaceutical alternatives: A nonpharmaceutical alternative is to simply cool the patient’s face with a fan or wet cloth. This facial cooling initiates the “diving reflex”\xa0via the trigeminal nerve. One component of the diving reflex is to reduce ventilatory drive at the brainstem—an ideal response if one is heading underwater.', '2f2f59dd-03fc-41e1-b326-987748de2c35': 'This inhibition of ventilatory drive is likely responsible for the moderate reduction in air hunger seen with facial cooling.', '7276f9ff-0abe-46ec-add8-1d0160bf075e': 'Rehabilitation and desensitization: While dyspnea can be addressed by other methods than those briefly described here, few have been shown to work consistently or effectively. On a more long-term basis, breathing training and pulmonary rehabilitation appear to help patients overcome exacerbations of their disease or even reduce chronic air hunger, but both require patient cooperation and compliance and may have limited effect in severe disease. What can be taken from the literature is that the treatment of dyspnea is in desperate need of more attention. For a symptom that is so common and has such an impact on patients, dyspnea is a clinical issue that is woefully underaddressed.'}"
+Figure 18.1,pulmo2/images/Figure 18.1.jpg,Figure 18.1: Conditions that can produce dyspnea. ARDS: Acute respiratory distress syndrome.,"Dyspnea is also a strong predictor of mortality in most heart and lung diseases. As well as cardiopulmonary conditions, dyspnea is also prevalent in other conditions that affect breathing or metabolism, and (see figure 18.1) it is prevalent during end-stage disease where it is as common as pain and forms a significant problem for end-of-life care. Despite its prevalence there are few options for treating this symptom. Unlike pain, there are no specific drugs to reduce this sensation.","{'ed66933c-0507-4838-8b90-3e3328daf222': 'It might be worth putting dyspnea in a clinical context. Like pain, dyspnea can occur across a number of pathological conditions. It is the cardinal symptom of lung disease, but it is highly prevalent in heart diseases as well—in fact it is a more common sign of myocardial infarction in women than the classical symptom of chest pain that is\xa0more prevalent in men.', '116f070e-6849-4ded-b300-6139c518706b': 'Dyspnea is also a strong predictor of mortality in most heart and lung diseases. As well as cardiopulmonary conditions, dyspnea is also prevalent in other conditions that affect breathing or metabolism, and (see figure 18.1) it is prevalent during end-stage disease where it is as common as pain and forms a significant problem for end-of-life care. Despite its prevalence there are few options for treating this symptom. Unlike pain, there are no specific drugs to reduce this sensation.', 'eaf7bcbf-edca-4466-9a42-b46c6949eff1': 'In this chapter we will have a look at the regions of the nervous system that control breathing and how they interact or override each other.', '5867bf01-6acb-4d92-bac8-5e75bde55544': 'This chapter will describe how the alveolar–arterial PO2 difference is calculated and what assumptions can be made from it.', '4ef36793-42e1-48cb-be98-c099eb0e004a': 'Before you start, a quick reminder that an uppercase A refers to alveolar and lowercase to arterial.', '8f30f95b-215b-436b-9512-3ae10768618b': 'There are other elements that should be considered when dealing with the air-hungry patient. Probably because of its homeostatic importance, the sensation of air hunger is very effective at getting attention and producing fear and anxiety. Recent comparisons of attentive and emotional impacts suggest air hunger is perceived as much more threatening and worrisome than pain at equivalent intensities. (Ironically we routinely ask about patients’ pain, but rarely about their air hunger.)', 'fb7adc11-d772-4195-b5da-be301bfab084': 'This emotional impact of air hunger is reflected in the regions of the brain\xa0that are consistently seen to be activated in recent functional brain imaging studies (see figure 18.5). The amygdala, anterior insula, and anterior cingulate are all persistently seen to activate during air hunger, and all are either associated with the brain’s fear network or generation of emotional responses. The activation of the anterior insula is also interesting as this phylogenically old part of the cortex also responds to other homeostatic imbalances, such as thirst, hunger for food, and pain. Although air hunger itself is unpleasant, it is these emotional components that produce air hunger’s profoundly negative effect on patients’ quality of life and makes end-of-life distressing for both the patient and their loved ones. We will come back to the\xa0impact of emotional responses in a moment.', '4b7a8014-6af3-445b-b4be-e857a0bc111a': 'So there we are—three different forms of dyspnea, with separate neural mechanisms. That said, it is unlikely that a patient will ever walk into your office and tell you they have “dyspnea,”\xa0or pinpoint which form of dyspnea they have. But\xa0taking an interest in the subtleties of your patients’ comments may not be a purely academic exercise either. More likely they are likely to use descriptors like those shown in table 18.1. These descriptors that use more common, everyday language have been related to each form of dyspnea. Knowing which form or forms of dyspnea the patient is experiencing can help in diagnosis as the different causes of dyspnea\xa0(like those listed in figure 18.1)\xa0can produce different levels of each form. For example, chest tightness is much more commonly reported by asthmatics, whereas patients with chronic obstructive pulmonary disease tend to use descriptors more related to effort to breathe\xa0and\xa0air hunger.', '12aa1d7b-d9ba-4fcb-889e-d4973fa700f7': 'Table 18.1: Patient descriptors for the three different forms of dyspnea.', '5a0b5c38-5d23-49af-be59-525bac0623e2': 'While the different forms of dyspnea have been investigated, described, and now explored as their potential as diagnostic tools, the emotional impact of dyspnea is only now receiving more attention. The most immediate complication caused by the emotional component is the potential for a positive feedback loop to form between air hunger and the anxiety it generates.\xa0The anxiety that air hunger produces results in an increased drive to breathe;\xa0in turn this increased drive to breathe causes the air hunger to increase, which leads to more anxiety and so on (figure 18.6).', 'c02eb73c-f5b5-4ccd-8113-3e904d9ae87f': 'Behavioral effects of dyspnea: This cycle can be entered into by different types of patients;\xa0those with cardiopulmonary disease enter the cycle at the point of the air hunger, whereas patients with anxiety disorders can enter the cycle at this point and can experience significant air hunger even with apparently perfectly normal lung and heart function. On a more long-term basis the quality of life of air-hungry patients can be diminished by another positive feedback scenario that can produce “respiratory cripples”\xa0of cardiopulmonary patients. The air hunger produced by the underlying disease worsens during exertion, so makes\xa0exercising uncomfortable. This frequently results in patients avoiding exercise, perhaps starting with taking an elevator instead of the stairs, or driving to the grocery store when previously they might have walked.', '0701b412-5140-4761-96ac-7ad79d1b62d8': 'This reduction in exercise leads to cardiac deconditioning, which in turn makes the air hunger worse and leads to further avoidance of exercise. Along with the progression of the disease, this cycle may leave the patient out-of-breath while simply sitting in a chair.', 'ff30a35d-ec49-4a2b-8402-f685ad7483bb': 'The patient’s quality of life becomes severely diminished as their life is ruled by dyspnea that prevents them from leaving the house, interacting with children or grandchildren, and performing simple activities that used to bring enjoyment, such as gardening, wood-working, walking, and more. This reduced quality of life can potentially lead to depression, and the emotional response to dyspnea may be exacerbated.', '3fa222a8-44f6-40e4-9700-b4c786fbd3df': 'So what can be done to relieve the patient’s air hunger and the associated anxiety? Well, despite its prevalence, the treatment of dyspnea is decades behind the treatment of pain. For too long the approach to treating dyspnea has been to treat the underlying disease with the expectation that the dyspnea will go away.\xa0This is true and a perfect course of action for many conditions, but for many diseases that produce dyspnea we have ineffective cures, such as emphysema, lung cancer, and pulmonary fibrosis. How do we make the 49 percent\xa0of terminally ill patients who suffer with dyspnea at the end of life more comfortable?', '96bf1610-7ea3-41bb-83c4-4fe808ffa128': 'Opioids: A common practice is to use opioids, but the mechanism of how they might work and indeed their overall efficacy has been disputed. There are a number of routes for how\xa0morphine may act, if it indeed does so. Opioids may have a direct inhibitory effect on the central networks that generate air hunger, or\xa0at higher dose concentrations they may reduce air hunger indirectly by causing respiratory depression—that is, they tackle air hunger at what we think to be its source. Alternatively, opioids may reduce the affective or emotional component of dyspnea (i.e., the patient may perceive air hunger, but simply is not\xa0as bothered by it). Recent work from Harvard University suggests that morphine has a direct effect on both the sensory and affective components of air hunger independent of its effect on ventilatory drive.', 'acd95dde-e94e-456d-b79c-aaf7cda0accb': 'Anxiolytics: As the emotional component of air hunger is so strong, the fear and anxiety produced can be treated in the absence of any specific drug to treat the air hunger itself. Use of anxiolytics drugs has also produced mixed results that may be complicated by the patient’s underlying condition, and whether the type of anxiolytic causes ventilatory depression.', '98681128-282c-4676-af4c-e9237fc4b75c': 'Furosemide: Although there is currently no drug that specifically tackles air hunger, there is a growing body of evidence that inhaled furosemide (the loop diuretic) reduces air hunger by sensitizing pulmonary stretch receptors, meaning they fire more for any given lung volume. This amplifies the stretch receptors’ inhibitory effect on air hunger described earlier, by fooling the brain into thinking the lungs are at a greater volume than they really are.', 'd4f7d731-abe8-4b12-9515-b817f4c6a042': 'Nonpharmaceutical alternatives: A nonpharmaceutical alternative is to simply cool the patient’s face with a fan or wet cloth. This facial cooling initiates the “diving reflex”\xa0via the trigeminal nerve. One component of the diving reflex is to reduce ventilatory drive at the brainstem—an ideal response if one is heading underwater.', '2f2f59dd-03fc-41e1-b326-987748de2c35': 'This inhibition of ventilatory drive is likely responsible for the moderate reduction in air hunger seen with facial cooling.', '7276f9ff-0abe-46ec-add8-1d0160bf075e': 'Rehabilitation and desensitization: While dyspnea can be addressed by other methods than those briefly described here, few have been shown to work consistently or effectively. On a more long-term basis, breathing training and pulmonary rehabilitation appear to help patients overcome exacerbations of their disease or even reduce chronic air hunger, but both require patient cooperation and compliance and may have limited effect in severe disease. What can be taken from the literature is that the treatment of dyspnea is in desperate need of more attention. For a symptom that is so common and has such an impact on patients, dyspnea is a clinical issue that is woefully underaddressed.'}"
+Figure 18.6,pulmo2/images/Figure 18.6.jpg,"Figure 18.6: The cycle of anxiety causing an increase in the drive to breathe and air hunger, which in turn causes more anxiety. Psychological disorders can produce air hunger if they involve anxiety.","While the different forms of dyspnea have been investigated, described, and now explored as their potential as diagnostic tools, the emotional impact of dyspnea is only now receiving more attention. The most immediate complication caused by the emotional component is the potential for a positive feedback loop to form between air hunger and the anxiety it generates. The anxiety that air hunger produces results in an increased drive to breathe; in turn this increased drive to breathe causes the air hunger to increase, which leads to more anxiety and so on (figure 18.6).","{'8f30f95b-215b-436b-9512-3ae10768618b': 'There are other elements that should be considered when dealing with the air-hungry patient. Probably because of its homeostatic importance, the sensation of air hunger is very effective at getting attention and producing fear and anxiety. Recent comparisons of attentive and emotional impacts suggest air hunger is perceived as much more threatening and worrisome than pain at equivalent intensities. (Ironically we routinely ask about patients’ pain, but rarely about their air hunger.)', 'fb7adc11-d772-4195-b5da-be301bfab084': 'This emotional impact of air hunger is reflected in the regions of the brain\xa0that are consistently seen to be activated in recent functional brain imaging studies (see figure 18.5). The amygdala, anterior insula, and anterior cingulate are all persistently seen to activate during air hunger, and all are either associated with the brain’s fear network or generation of emotional responses. The activation of the anterior insula is also interesting as this phylogenically old part of the cortex also responds to other homeostatic imbalances, such as thirst, hunger for food, and pain. Although air hunger itself is unpleasant, it is these emotional components that produce air hunger’s profoundly negative effect on patients’ quality of life and makes end-of-life distressing for both the patient and their loved ones. We will come back to the\xa0impact of emotional responses in a moment.', '4b7a8014-6af3-445b-b4be-e857a0bc111a': 'So there we are—three different forms of dyspnea, with separate neural mechanisms. That said, it is unlikely that a patient will ever walk into your office and tell you they have “dyspnea,”\xa0or pinpoint which form of dyspnea they have. But\xa0taking an interest in the subtleties of your patients’ comments may not be a purely academic exercise either. More likely they are likely to use descriptors like those shown in table 18.1. These descriptors that use more common, everyday language have been related to each form of dyspnea. Knowing which form or forms of dyspnea the patient is experiencing can help in diagnosis as the different causes of dyspnea\xa0(like those listed in figure 18.1)\xa0can produce different levels of each form. For example, chest tightness is much more commonly reported by asthmatics, whereas patients with chronic obstructive pulmonary disease tend to use descriptors more related to effort to breathe\xa0and\xa0air hunger.', '12aa1d7b-d9ba-4fcb-889e-d4973fa700f7': 'Table 18.1: Patient descriptors for the three different forms of dyspnea.', '5a0b5c38-5d23-49af-be59-525bac0623e2': 'While the different forms of dyspnea have been investigated, described, and now explored as their potential as diagnostic tools, the emotional impact of dyspnea is only now receiving more attention. The most immediate complication caused by the emotional component is the potential for a positive feedback loop to form between air hunger and the anxiety it generates.\xa0The anxiety that air hunger produces results in an increased drive to breathe;\xa0in turn this increased drive to breathe causes the air hunger to increase, which leads to more anxiety and so on (figure 18.6).', 'c02eb73c-f5b5-4ccd-8113-3e904d9ae87f': 'Behavioral effects of dyspnea: This cycle can be entered into by different types of patients;\xa0those with cardiopulmonary disease enter the cycle at the point of the air hunger, whereas patients with anxiety disorders can enter the cycle at this point and can experience significant air hunger even with apparently perfectly normal lung and heart function. On a more long-term basis the quality of life of air-hungry patients can be diminished by another positive feedback scenario that can produce “respiratory cripples”\xa0of cardiopulmonary patients. The air hunger produced by the underlying disease worsens during exertion, so makes\xa0exercising uncomfortable. This frequently results in patients avoiding exercise, perhaps starting with taking an elevator instead of the stairs, or driving to the grocery store when previously they might have walked.', '0701b412-5140-4761-96ac-7ad79d1b62d8': 'This reduction in exercise leads to cardiac deconditioning, which in turn makes the air hunger worse and leads to further avoidance of exercise. Along with the progression of the disease, this cycle may leave the patient out-of-breath while simply sitting in a chair.', 'ff30a35d-ec49-4a2b-8402-f685ad7483bb': 'The patient’s quality of life becomes severely diminished as their life is ruled by dyspnea that prevents them from leaving the house, interacting with children or grandchildren, and performing simple activities that used to bring enjoyment, such as gardening, wood-working, walking, and more. This reduced quality of life can potentially lead to depression, and the emotional response to dyspnea may be exacerbated.', '3fa222a8-44f6-40e4-9700-b4c786fbd3df': 'So what can be done to relieve the patient’s air hunger and the associated anxiety? Well, despite its prevalence, the treatment of dyspnea is decades behind the treatment of pain. For too long the approach to treating dyspnea has been to treat the underlying disease with the expectation that the dyspnea will go away.\xa0This is true and a perfect course of action for many conditions, but for many diseases that produce dyspnea we have ineffective cures, such as emphysema, lung cancer, and pulmonary fibrosis. How do we make the 49 percent\xa0of terminally ill patients who suffer with dyspnea at the end of life more comfortable?', '96bf1610-7ea3-41bb-83c4-4fe808ffa128': 'Opioids: A common practice is to use opioids, but the mechanism of how they might work and indeed their overall efficacy has been disputed. There are a number of routes for how\xa0morphine may act, if it indeed does so. Opioids may have a direct inhibitory effect on the central networks that generate air hunger, or\xa0at higher dose concentrations they may reduce air hunger indirectly by causing respiratory depression—that is, they tackle air hunger at what we think to be its source. Alternatively, opioids may reduce the affective or emotional component of dyspnea (i.e., the patient may perceive air hunger, but simply is not\xa0as bothered by it). Recent work from Harvard University suggests that morphine has a direct effect on both the sensory and affective components of air hunger independent of its effect on ventilatory drive.', 'acd95dde-e94e-456d-b79c-aaf7cda0accb': 'Anxiolytics: As the emotional component of air hunger is so strong, the fear and anxiety produced can be treated in the absence of any specific drug to treat the air hunger itself. Use of anxiolytics drugs has also produced mixed results that may be complicated by the patient’s underlying condition, and whether the type of anxiolytic causes ventilatory depression.', '98681128-282c-4676-af4c-e9237fc4b75c': 'Furosemide: Although there is currently no drug that specifically tackles air hunger, there is a growing body of evidence that inhaled furosemide (the loop diuretic) reduces air hunger by sensitizing pulmonary stretch receptors, meaning they fire more for any given lung volume. This amplifies the stretch receptors’ inhibitory effect on air hunger described earlier, by fooling the brain into thinking the lungs are at a greater volume than they really are.', 'd4f7d731-abe8-4b12-9515-b817f4c6a042': 'Nonpharmaceutical alternatives: A nonpharmaceutical alternative is to simply cool the patient’s face with a fan or wet cloth. This facial cooling initiates the “diving reflex”\xa0via the trigeminal nerve. One component of the diving reflex is to reduce ventilatory drive at the brainstem—an ideal response if one is heading underwater.', '2f2f59dd-03fc-41e1-b326-987748de2c35': 'This inhibition of ventilatory drive is likely responsible for the moderate reduction in air hunger seen with facial cooling.', '7276f9ff-0abe-46ec-add8-1d0160bf075e': 'Rehabilitation and desensitization: While dyspnea can be addressed by other methods than those briefly described here, few have been shown to work consistently or effectively. On a more long-term basis, breathing training and pulmonary rehabilitation appear to help patients overcome exacerbations of their disease or even reduce chronic air hunger, but both require patient cooperation and compliance and may have limited effect in severe disease. What can be taken from the literature is that the treatment of dyspnea is in desperate need of more attention. For a symptom that is so common and has such an impact on patients, dyspnea is a clinical issue that is woefully underaddressed.'}"
+Figure 17.1,pulmo2/images/Figure 17.1.jpg,Figure 17.1: Brainstem respiratory network.,"These DRG (figure 17.1) neurons show ramp-like bursts of activity that cause inspiratory muscle contraction to induce inspiration, then stop, allowing the inspiratory muscles to relax and passive exhalation to begin. This intermittent ramp of activity can be modulated by input from the sensors or other regions of the central nervous system, but it is not spontaneous; rather this activity is initiated by another respiratory pacemaker. It was this pacemaker that eluded physiologists for decades.","{'b610698c-7867-40bf-9f03-839655118614': 'These DRG (figure 17.1) neurons show ramp-like bursts of activity that cause inspiratory muscle contraction to induce inspiration, then stop, allowing the inspiratory muscles to relax and passive exhalation to begin. This intermittent ramp of activity can be modulated by input from the sensors or other regions of the central nervous system, but it is not spontaneous; rather this activity is initiated by another respiratory pacemaker. It was this pacemaker that eluded physiologists for decades.', 'd8b83920-c9e5-4c00-94ef-666420f6e650': 'On the other side of medulla is the ventral respiratory group (figure 17.1), which has been known for a long time to contain circuits that contribute to the control of breathing within its rostral, intermediate, and caudal regions. Within the intermediate region a cluster of neurons called the pre-Bötzinger complex (figure 17.1) with apparently spontaneous activity is currently thought to be the respiratory pacemaker. The pre-bötzinger complex is likely responsible for the activity of the DRG inspiratory neurons to produce the ramping activity.', '5964420c-b5bc-46f6-9eda-53aa0a34e0cc': 'The ventral respiratory group\xa0also contains neurons with inspiratory-related activity and connections to the inspiratory motor neurons. It is better known for its expiratory neurons, however, which\xa0are capable of activating the expiratory muscles when expiration must become active rather than remain passive. During quiet resting breathing, these expiratory neurons remain dormant.', 'c90b1cb4-2cce-4fac-aff5-e33efe169340': 'This medullary circuitry can be influenced by other brainstem centers thought to be responsible for fine-tuning the breathing rhythm.', '54677cd2-0ea5-437f-a884-bdf43ab1c066': 'The Apneustic center in the lower pons (figure 17.1) excites the inspiratory neurons and prolongs the ramp activity they produce; this inevitably produces a prolonged inspiratory period. Higher up in the pons is the Pneumotaxic center (figure 17.1), which\xa0acts as an off switch for inspiratory neurons;\xa0thus it regulates inspiratory volume and indirectly influences the rate of breathing, tending to increase it. This is a very basic overview of the breathing circuitry that is capable of generating inspiration\xa0and active expiration when needed. But these centers take information and direction from other neural influences, including chemoreceptors, receptors in the lung, and higher brain centers.\xa0We will look at the latter two now.'}"
+Figure 17.1,pulmo2/images/Figure 17.1.jpg,Figure 17.1: Brainstem respiratory network.,"These DRG (figure 17.1) neurons show ramp-like bursts of activity that cause inspiratory muscle contraction to induce inspiration, then stop, allowing the inspiratory muscles to relax and passive exhalation to begin. This intermittent ramp of activity can be modulated by input from the sensors or other regions of the central nervous system, but it is not spontaneous; rather this activity is initiated by another respiratory pacemaker. It was this pacemaker that eluded physiologists for decades.","{'b610698c-7867-40bf-9f03-839655118614': 'These DRG (figure 17.1) neurons show ramp-like bursts of activity that cause inspiratory muscle contraction to induce inspiration, then stop, allowing the inspiratory muscles to relax and passive exhalation to begin. This intermittent ramp of activity can be modulated by input from the sensors or other regions of the central nervous system, but it is not spontaneous; rather this activity is initiated by another respiratory pacemaker. It was this pacemaker that eluded physiologists for decades.', 'd8b83920-c9e5-4c00-94ef-666420f6e650': 'On the other side of medulla is the ventral respiratory group (figure 17.1), which has been known for a long time to contain circuits that contribute to the control of breathing within its rostral, intermediate, and caudal regions. Within the intermediate region a cluster of neurons called the pre-Bötzinger complex (figure 17.1) with apparently spontaneous activity is currently thought to be the respiratory pacemaker. The pre-bötzinger complex is likely responsible for the activity of the DRG inspiratory neurons to produce the ramping activity.', '5964420c-b5bc-46f6-9eda-53aa0a34e0cc': 'The ventral respiratory group\xa0also contains neurons with inspiratory-related activity and connections to the inspiratory motor neurons. It is better known for its expiratory neurons, however, which\xa0are capable of activating the expiratory muscles when expiration must become active rather than remain passive. During quiet resting breathing, these expiratory neurons remain dormant.', 'c90b1cb4-2cce-4fac-aff5-e33efe169340': 'This medullary circuitry can be influenced by other brainstem centers thought to be responsible for fine-tuning the breathing rhythm.', '54677cd2-0ea5-437f-a884-bdf43ab1c066': 'The Apneustic center in the lower pons (figure 17.1) excites the inspiratory neurons and prolongs the ramp activity they produce; this inevitably produces a prolonged inspiratory period. Higher up in the pons is the Pneumotaxic center (figure 17.1), which\xa0acts as an off switch for inspiratory neurons;\xa0thus it regulates inspiratory volume and indirectly influences the rate of breathing, tending to increase it. This is a very basic overview of the breathing circuitry that is capable of generating inspiration\xa0and active expiration when needed. But these centers take information and direction from other neural influences, including chemoreceptors, receptors in the lung, and higher brain centers.\xa0We will look at the latter two now.'}"
+Figure 17.2,pulmo2/images/Figure 17.2.jpg,"Figure 17.2: Lung volume and pulmonary stretch receptor firing. The top tracing represents lung volume with two full inflations followed by a sustained inflation. In response to the increases in lung volume, pulmonary stretch receptors depolarize, producing action potentials, which are shown in the lower trace as upward spikes. The increase in action potentials with increased lung volume is seen as more densely clustered spikes. Note how the sustained inflation causes an initial high frequency of action potentials that gradually falls as the receptor adapts to the high lung volume.","Pulmonary stretch receptors are mechanoreceptors found in airway walls and smooth muscle. As their name suggests, they respond to expansion of the lung, and their afferent activity to the brainstem increases with lung volume, as figure 17.2 shows. Upon arrival at the NTS the PSR activity tends to inhibit inspiratory neurons and can stop inspiratory activity completely in other species (the Hering–Breuer reflex). However, their influence on the control of breathing in humans is weak, and while they might not contribute to the control of breathing in man, they likely influence respiratory sensations, such as shortness of breath.","{'131d0e8e-0e90-43eb-bd29-2da7eadc4a8f': 'The brainstem drive to breathe can be modulated from above and from below. The literature about whether these influences increase or decrease the drive to breathe is often confused, perhaps because of the wide range of experiments performed and the different species used. We will have a look at some of the most consistent and clinically pertinent aspects here, starting in the lung and three populations of intrapulmonary neural receptors.', 'b9b6f27e-0866-410e-b07c-8c8539553429': 'Pulmonary stretch receptors\xa0are mechanoreceptors found in airway walls and smooth muscle. As their name suggests, they respond to expansion of the lung, and their afferent activity to the brainstem increases with lung volume, as figure 17.2 shows. Upon arrival at the NTS the PSR activity tends to inhibit inspiratory neurons and can stop inspiratory activity completely in other species (the Hering–Breuer reflex). However, their influence on the control of breathing in humans is weak, and while they might not contribute to the control of breathing in man, they likely influence respiratory sensations, such as shortness of breath.', '9a879c60-0390-4150-b2e0-feb665277246': 'Irritant receptors are found in the airway epithelium and are ideally placed to perform their role of detecting harmful substances entering the lungs, such as noxious gases, particulates, and even cold air. They generally have an inhibitory influence on the drive to breathe, perhaps as an attempt to limit the amount of noxious substance entering the lung. Other components to their defensive strategies are bronchoconstriction and induction of the cough reflex. Their response to inflammatory mediators also suggests they may play a role in asthma.', '0d90f985-2aad-4750-9b34-83804b15cdcf': 'J-receptors, or Juxtacapillary receptors, are found at the junction of the pulmonary capillaries and alveoli. These receptors respond to increases in interstitial pressure so are likely to play a role in the response to pulmonary edema. Their effect on the drive to breathe can be regarded as excitatory as they cause an increase in breathing rate as part of the J-reflex, which includes cardiac components and is intended to prevent over-exercising and cardiopulmonary collapse. As such the J-receptors may also contribute to generating the sensation of shortness of breath.', 'c259f790-0487-49a7-a758-669eee1efafa': 'These\xa0three pulmonary receptor groups are the three that usually appear in textbooks, perhaps because of their clinical pertinence, but perhaps because we know most about these. Others exist, and details can be found in other sources. We will now focus briefly on the influence of higher centers on breathing, and these are generally all positive (i.e., cause an increase in breathing). Cortical influences are numerous and undefined, that collectively they produce what is referred to as the wakeful drive to breath. The extent of cortical influence is best illustrated by sleep, when the higher brain is unconscious and any wakeful drive is removed. During sleep breathing is significantly reduced—enough so that arterial PCO2\xa0is several mmHg higher than during wakefulness. This suggests that cortical influences on breathing are enough to cause a lower PaCO2\xa0than would be determined by chemoreflexes alone.'}"
+Figure 17.3,pulmo2/images/Figure 17.3.jpg,Figure 17.3: Chemoreflex circuit.,"Before getting into the details of the chemoreceptors, let us take a quick overview of the basic circuitry of the chemoreflexes (figure 17.3). There are two sets of sensors in our circuit: the peripheral chemoreceptors that are in the vasculature, and the central chemoreceptors that are found on the surface of the brainstem. The central chemoreceptors are capable of detecting changes in arterial CO2, while the peripheral chemoreceptors respond to changes in CO2, O2, and arterial pH.","{'4b40d226-7425-49f8-b741-e4f66e18c57a': 'It perhaps comes as no surprise that the major influence on the reflex drive to breathe comes from the homeostatic need to match ventilation with metabolic demand and maintain blood O2, CO2, and pH within narrow ranges. The chemoreflexes are therefore capable of\xa0sensing changes in arterial oxygen, carbon dioxide, and pH, modifying the activity of the brainstem respiratory centers and affecting an appropriate change in alveolar ventilation. These reflexes all act as classical negative feedback circuits and are capable of maintaining despite large changes in O2\xa0consumption and CO2\xa0production by metabolizing tissue.', 'ec911790-4994-421d-95fb-f8cb2839638c': 'Before getting into the details of the chemoreceptors, let us take a quick overview of the basic circuitry of the chemoreflexes (figure 17.3). There are two sets of sensors in our circuit:\xa0the peripheral chemoreceptors that are in the vasculature, and the central chemoreceptors that are found on the surface of the brainstem. The central chemoreceptors are capable of detecting changes in arterial CO2, while the peripheral chemoreceptors respond to changes in CO2, O2, and arterial pH.', '621a5b3a-b03b-456f-8755-29de9f879f11': 'Upon excitation by changes in blood gas values, the receptors fire back to the reflex’s controller, the respiratory centers in the brainstem. This results in an increase in reflex ventilatory drive\xa0and a greater motor signal to the respiratory muscles. This produces an increase in alveolar ventilation that corrects the blood gas disturbances and stops the chemoreceptors from firing.', '14e4f4f0-e774-4f43-852e-b59d08bff992': 'With that basic circuit in mind, let us now look more closely at the chemoreceptors and the ventilatory responses they can induce.'}"
+Figure 17.4,pulmo2/images/Figure 17.4.jpg,Figure 17.4: Peripheral chemoreceptors.,"The peripheral chemoreceptors are directly exposed to arterial blood and are capable of responding to changes in CO2, O2, and pH. There are two populations of chemoreceptive cells in the vasculature (see figure 17.4). One population is found in the aortic arch and is referred to as the aortic bodies. These are wired into the brainstem through afferent fibers that project to and join the vagus nerve. The other chemoreceptor is comprised of the carotid bodies, found in the bifurcation of the common carotid arteries. These connect to the brainstem through the carotid sinus and the glossopharyngeal nerves. The carotid bodies are by far the most important in humans, with the aortic bodies contributing very little to any ventilatory response.","{'53bcaa8e-3968-4dd6-af8f-0b7263f68ef2': 'The peripheral chemoreceptors are directly exposed to arterial blood and are capable of responding to changes in CO2, O2, and pH. There are two populations of chemoreceptive cells in the vasculature (see figure 17.4). One population is found in the aortic arch\xa0and is referred\xa0to as the aortic bodies. These are wired into the brainstem through afferent fibers that project to and join the vagus nerve. The other chemoreceptor is comprised of the carotid bodies, found in the bifurcation of the common carotid arteries. These connect to the brainstem through the carotid sinus and the glossopharyngeal nerves. The carotid bodies are by far the most important in humans, with the aortic bodies contributing very little to any ventilatory response.', '105e0bd6-ef24-40ab-8c61-0cb33135cca7': 'Although the carotid bodies play little role in reflex response to CO2, their response to hypercapnia is more rapid than the central chemoreceptors and so they are capable of breath-by-breath regulation and responding to abrupt changes in arterial PCO2. More importantly the peripheral chemoreceptors are entirely responsible for the response to hypoxia. The mechanism as to how these receptors work is unclear, but cells within the carotid bodies have very high metabolic rates and receive a proportionately high blood flow. It is likely that a decline in oxygen interrupts their metabolism and reduces their inhibitory interaction on neurotransmitter-filled neighboring cells, allowing excitation of the carotid sinus nerve.\xa0Their response to a decline in blood oxygen is far from linear. A decline in PO2\xa0below 100 mmHg causes little change in\xa0action potential firing, but the rate of firing rapidly increases at PO2s below 50. This is reflected in the hypoxic ventilatory response illustrated in the graph in figure 17.5.', '7d454584-4e63-4a14-bc6f-e71196169e7b': 'Because of this, the hypoxic ventilatory response normally plays little role in the control of breathing in humans. The hypoxic ventilatory response becomes more significant at altitude when inspired PO2\xa0is low, or more pertinently in lung disease, where alveolar ventilation or gas exchange is compromised.', '439b2a3b-9500-414a-aa44-02adc653c5fd': 'The hypercapnic ventilatory response (figure 17.6) is much more influential on breathing in humans on a normal day-to-day basis. The response is very linear, with a rise in PCO2\xa0producing a proportionate rise in ventilation, driven of course primarily by the central chemoreceptors, but also contributed to by\xa0the afferent activity of the peripheral receptors.', 'b4e8594d-4342-429e-a1d3-29deb926f070': 'The central and peripheral chemoreceptors keep arterial PCO2\xa0within very fine limits, primarily because of CO2‘s effect on pH. Alveolar ventilation rapidly increases with even a moderate rise in arterial CO2, but can completely stop (apnea) if arterial CO2\xa0falls below normal (~40 mmHg). The wakeful drive to breathe tends to keep CO2\xa0a little lower than the set-point of the chemoreceptors—a point illustrated during sleep, when the brainstem has complete control of breathing and PaCO2\xa0is seen to rise a few mmHg.', '64b429be-4d21-4cce-b4be-01fbc2ba73c4': 'The hypercapnic ventilatory response\xa0adapts to chronically elevated arterial CO2, such as in severe lung disease. Here we not only see the CSF increase its buffering capacity with increased bicarbonate, but we also see the chemoreceptors change their set-point. It is not uncommon to see COPD patients with arterial PCO2s above 60.', 'a7b008bd-dbb5-41e3-9c1e-334d7f944f71': 'Finally, the hypoxic and hypercapnic ventilatory responses are not independent, and when they are both present at the same time a potentiation is seen (i.e., the response to hypoxic and hypercapnia is greater than the sum of the two individual responses).', 'f5c85927-3e75-41d5-a3dc-748f9aab2b25': 'The hypoxic ventilatory response we have just looked at was measured at an alveolar PCO2\xa0of 35.8 mmHg. If the same test is performed at higher PCO2s (figure 17.7), then the hypoxic ventilatory response is much greater, as shown by these upwardly shifted lines when alveolar PCO2\xa0is set to 43.7 mmHg and 48.7 mmHg.', '4b57208b-e130-430c-bd66-a47e7bc49def': 'Likewise, the hypercapnic ventilatory response is exaggerated in the presence of hypoxia (see figure 17.8). The hypercapnic ventilatory response we have just looked at was measured at a “normal”\xa0alveolar PO2\xa0of 110 mmHg. If the hypercapnic response is measured in the presence of hypoxia, then the curve shifts upward, as shown by\xa0the upper lines when alveolar PO2 is reduced to 47 mmHg and 37 mmHg. This potentiation likely comes from the peripheral chemoreceptors, whose firing rate is potentiated in the presence of both stimuli. Consequently, when a patient is both hypoxic and hypercapnic, then they are likely to have a very high drive to breathe, and when this occurs they are likely to feel very short of breath—the topic of the last chapter.', 'd1eb2ee4-c45e-4b70-bebb-601f16788991': 'The chemoreflexes modulate breathing to maintain constant arterial blood gases and pH. These reflexes are initiated by central sensors that respond to hypoxia and peripheral sensors that respond to hypercapnia, hypoxia, and changes in arterial pH. Together these sensors can maintain arterial blood gases within narrow ranges despite large changes in oxygen consumption and CO2\xa0production associated with changes in metabolic rate.'}"
+Figure 17.5,pulmo2/images/Figure 17.5.jpg,"Figure 17.5: Hypoxic ventilatory response. BTPS: body temperature and pressure, saturated.","Although the carotid bodies play little role in reflex response to CO2, their response to hypercapnia is more rapid than the central chemoreceptors and so they are capable of breath-by-breath regulation and responding to abrupt changes in arterial PCO2. More importantly the peripheral chemoreceptors are entirely responsible for the response to hypoxia. The mechanism as to how these receptors work is unclear, but cells within the carotid bodies have very high metabolic rates and receive a proportionately high blood flow. It is likely that a decline in oxygen interrupts their metabolism and reduces their inhibitory interaction on neurotransmitter-filled neighboring cells, allowing excitation of the carotid sinus nerve. Their response to a decline in blood oxygen is far from linear. A decline in PO2 below 100 mmHg causes little change in action potential firing, but the rate of firing rapidly increases at PO2s below 50. This is reflected in the hypoxic ventilatory response illustrated in the graph in figure 17.5.","{'53bcaa8e-3968-4dd6-af8f-0b7263f68ef2': 'The peripheral chemoreceptors are directly exposed to arterial blood and are capable of responding to changes in CO2, O2, and pH. There are two populations of chemoreceptive cells in the vasculature (see figure 17.4). One population is found in the aortic arch\xa0and is referred\xa0to as the aortic bodies. These are wired into the brainstem through afferent fibers that project to and join the vagus nerve. The other chemoreceptor is comprised of the carotid bodies, found in the bifurcation of the common carotid arteries. These connect to the brainstem through the carotid sinus and the glossopharyngeal nerves. The carotid bodies are by far the most important in humans, with the aortic bodies contributing very little to any ventilatory response.', '105e0bd6-ef24-40ab-8c61-0cb33135cca7': 'Although the carotid bodies play little role in reflex response to CO2, their response to hypercapnia is more rapid than the central chemoreceptors and so they are capable of breath-by-breath regulation and responding to abrupt changes in arterial PCO2. More importantly the peripheral chemoreceptors are entirely responsible for the response to hypoxia. The mechanism as to how these receptors work is unclear, but cells within the carotid bodies have very high metabolic rates and receive a proportionately high blood flow. It is likely that a decline in oxygen interrupts their metabolism and reduces their inhibitory interaction on neurotransmitter-filled neighboring cells, allowing excitation of the carotid sinus nerve.\xa0Their response to a decline in blood oxygen is far from linear. A decline in PO2\xa0below 100 mmHg causes little change in\xa0action potential firing, but the rate of firing rapidly increases at PO2s below 50. This is reflected in the hypoxic ventilatory response illustrated in the graph in figure 17.5.', '7d454584-4e63-4a14-bc6f-e71196169e7b': 'Because of this, the hypoxic ventilatory response normally plays little role in the control of breathing in humans. The hypoxic ventilatory response becomes more significant at altitude when inspired PO2\xa0is low, or more pertinently in lung disease, where alveolar ventilation or gas exchange is compromised.', '439b2a3b-9500-414a-aa44-02adc653c5fd': 'The hypercapnic ventilatory response (figure 17.6) is much more influential on breathing in humans on a normal day-to-day basis. The response is very linear, with a rise in PCO2\xa0producing a proportionate rise in ventilation, driven of course primarily by the central chemoreceptors, but also contributed to by\xa0the afferent activity of the peripheral receptors.', 'b4e8594d-4342-429e-a1d3-29deb926f070': 'The central and peripheral chemoreceptors keep arterial PCO2\xa0within very fine limits, primarily because of CO2‘s effect on pH. Alveolar ventilation rapidly increases with even a moderate rise in arterial CO2, but can completely stop (apnea) if arterial CO2\xa0falls below normal (~40 mmHg). The wakeful drive to breathe tends to keep CO2\xa0a little lower than the set-point of the chemoreceptors—a point illustrated during sleep, when the brainstem has complete control of breathing and PaCO2\xa0is seen to rise a few mmHg.', '64b429be-4d21-4cce-b4be-01fbc2ba73c4': 'The hypercapnic ventilatory response\xa0adapts to chronically elevated arterial CO2, such as in severe lung disease. Here we not only see the CSF increase its buffering capacity with increased bicarbonate, but we also see the chemoreceptors change their set-point. It is not uncommon to see COPD patients with arterial PCO2s above 60.', 'a7b008bd-dbb5-41e3-9c1e-334d7f944f71': 'Finally, the hypoxic and hypercapnic ventilatory responses are not independent, and when they are both present at the same time a potentiation is seen (i.e., the response to hypoxic and hypercapnia is greater than the sum of the two individual responses).', 'f5c85927-3e75-41d5-a3dc-748f9aab2b25': 'The hypoxic ventilatory response we have just looked at was measured at an alveolar PCO2\xa0of 35.8 mmHg. If the same test is performed at higher PCO2s (figure 17.7), then the hypoxic ventilatory response is much greater, as shown by these upwardly shifted lines when alveolar PCO2\xa0is set to 43.7 mmHg and 48.7 mmHg.', '4b57208b-e130-430c-bd66-a47e7bc49def': 'Likewise, the hypercapnic ventilatory response is exaggerated in the presence of hypoxia (see figure 17.8). The hypercapnic ventilatory response we have just looked at was measured at a “normal”\xa0alveolar PO2\xa0of 110 mmHg. If the hypercapnic response is measured in the presence of hypoxia, then the curve shifts upward, as shown by\xa0the upper lines when alveolar PO2 is reduced to 47 mmHg and 37 mmHg. This potentiation likely comes from the peripheral chemoreceptors, whose firing rate is potentiated in the presence of both stimuli. Consequently, when a patient is both hypoxic and hypercapnic, then they are likely to have a very high drive to breathe, and when this occurs they are likely to feel very short of breath—the topic of the last chapter.', 'd1eb2ee4-c45e-4b70-bebb-601f16788991': 'The chemoreflexes modulate breathing to maintain constant arterial blood gases and pH. These reflexes are initiated by central sensors that respond to hypoxia and peripheral sensors that respond to hypercapnia, hypoxia, and changes in arterial pH. Together these sensors can maintain arterial blood gases within narrow ranges despite large changes in oxygen consumption and CO2\xa0production associated with changes in metabolic rate.'}"
+Figure 17.6,pulmo2/images/Figure 17.6.jpg,Figure 17.6: Hypercapnic ventilatory response.,"The hypercapnic ventilatory response (figure 17.6) is much more influential on breathing in humans on a normal day-to-day basis. The response is very linear, with a rise in PCO2 producing a proportionate rise in ventilation, driven of course primarily by the central chemoreceptors, but also contributed to by the afferent activity of the peripheral receptors.","{'53bcaa8e-3968-4dd6-af8f-0b7263f68ef2': 'The peripheral chemoreceptors are directly exposed to arterial blood and are capable of responding to changes in CO2, O2, and pH. There are two populations of chemoreceptive cells in the vasculature (see figure 17.4). One population is found in the aortic arch\xa0and is referred\xa0to as the aortic bodies. These are wired into the brainstem through afferent fibers that project to and join the vagus nerve. The other chemoreceptor is comprised of the carotid bodies, found in the bifurcation of the common carotid arteries. These connect to the brainstem through the carotid sinus and the glossopharyngeal nerves. The carotid bodies are by far the most important in humans, with the aortic bodies contributing very little to any ventilatory response.', '105e0bd6-ef24-40ab-8c61-0cb33135cca7': 'Although the carotid bodies play little role in reflex response to CO2, their response to hypercapnia is more rapid than the central chemoreceptors and so they are capable of breath-by-breath regulation and responding to abrupt changes in arterial PCO2. More importantly the peripheral chemoreceptors are entirely responsible for the response to hypoxia. The mechanism as to how these receptors work is unclear, but cells within the carotid bodies have very high metabolic rates and receive a proportionately high blood flow. It is likely that a decline in oxygen interrupts their metabolism and reduces their inhibitory interaction on neurotransmitter-filled neighboring cells, allowing excitation of the carotid sinus nerve.\xa0Their response to a decline in blood oxygen is far from linear. A decline in PO2\xa0below 100 mmHg causes little change in\xa0action potential firing, but the rate of firing rapidly increases at PO2s below 50. This is reflected in the hypoxic ventilatory response illustrated in the graph in figure 17.5.', '7d454584-4e63-4a14-bc6f-e71196169e7b': 'Because of this, the hypoxic ventilatory response normally plays little role in the control of breathing in humans. The hypoxic ventilatory response becomes more significant at altitude when inspired PO2\xa0is low, or more pertinently in lung disease, where alveolar ventilation or gas exchange is compromised.', '439b2a3b-9500-414a-aa44-02adc653c5fd': 'The hypercapnic ventilatory response (figure 17.6) is much more influential on breathing in humans on a normal day-to-day basis. The response is very linear, with a rise in PCO2\xa0producing a proportionate rise in ventilation, driven of course primarily by the central chemoreceptors, but also contributed to by\xa0the afferent activity of the peripheral receptors.', 'b4e8594d-4342-429e-a1d3-29deb926f070': 'The central and peripheral chemoreceptors keep arterial PCO2\xa0within very fine limits, primarily because of CO2‘s effect on pH. Alveolar ventilation rapidly increases with even a moderate rise in arterial CO2, but can completely stop (apnea) if arterial CO2\xa0falls below normal (~40 mmHg). The wakeful drive to breathe tends to keep CO2\xa0a little lower than the set-point of the chemoreceptors—a point illustrated during sleep, when the brainstem has complete control of breathing and PaCO2\xa0is seen to rise a few mmHg.', '64b429be-4d21-4cce-b4be-01fbc2ba73c4': 'The hypercapnic ventilatory response\xa0adapts to chronically elevated arterial CO2, such as in severe lung disease. Here we not only see the CSF increase its buffering capacity with increased bicarbonate, but we also see the chemoreceptors change their set-point. It is not uncommon to see COPD patients with arterial PCO2s above 60.', 'a7b008bd-dbb5-41e3-9c1e-334d7f944f71': 'Finally, the hypoxic and hypercapnic ventilatory responses are not independent, and when they are both present at the same time a potentiation is seen (i.e., the response to hypoxic and hypercapnia is greater than the sum of the two individual responses).', 'f5c85927-3e75-41d5-a3dc-748f9aab2b25': 'The hypoxic ventilatory response we have just looked at was measured at an alveolar PCO2\xa0of 35.8 mmHg. If the same test is performed at higher PCO2s (figure 17.7), then the hypoxic ventilatory response is much greater, as shown by these upwardly shifted lines when alveolar PCO2\xa0is set to 43.7 mmHg and 48.7 mmHg.', '4b57208b-e130-430c-bd66-a47e7bc49def': 'Likewise, the hypercapnic ventilatory response is exaggerated in the presence of hypoxia (see figure 17.8). The hypercapnic ventilatory response we have just looked at was measured at a “normal”\xa0alveolar PO2\xa0of 110 mmHg. If the hypercapnic response is measured in the presence of hypoxia, then the curve shifts upward, as shown by\xa0the upper lines when alveolar PO2 is reduced to 47 mmHg and 37 mmHg. This potentiation likely comes from the peripheral chemoreceptors, whose firing rate is potentiated in the presence of both stimuli. Consequently, when a patient is both hypoxic and hypercapnic, then they are likely to have a very high drive to breathe, and when this occurs they are likely to feel very short of breath—the topic of the last chapter.', 'd1eb2ee4-c45e-4b70-bebb-601f16788991': 'The chemoreflexes modulate breathing to maintain constant arterial blood gases and pH. These reflexes are initiated by central sensors that respond to hypoxia and peripheral sensors that respond to hypercapnia, hypoxia, and changes in arterial pH. Together these sensors can maintain arterial blood gases within narrow ranges despite large changes in oxygen consumption and CO2\xa0production associated with changes in metabolic rate.'}"
+Figure 17.7,pulmo2/images/Figure 17.7.jpg,Figure 17.7: Hypoxic ventilatory responses with varying degrees of hypercapnia.,"The hypoxic ventilatory response we have just looked at was measured at an alveolar PCO2 of 35.8 mmHg. If the same test is performed at higher PCO2s (figure 17.7), then the hypoxic ventilatory response is much greater, as shown by these upwardly shifted lines when alveolar PCO2 is set to 43.7 mmHg and 48.7 mmHg.","{'53bcaa8e-3968-4dd6-af8f-0b7263f68ef2': 'The peripheral chemoreceptors are directly exposed to arterial blood and are capable of responding to changes in CO2, O2, and pH. There are two populations of chemoreceptive cells in the vasculature (see figure 17.4). One population is found in the aortic arch\xa0and is referred\xa0to as the aortic bodies. These are wired into the brainstem through afferent fibers that project to and join the vagus nerve. The other chemoreceptor is comprised of the carotid bodies, found in the bifurcation of the common carotid arteries. These connect to the brainstem through the carotid sinus and the glossopharyngeal nerves. The carotid bodies are by far the most important in humans, with the aortic bodies contributing very little to any ventilatory response.', '105e0bd6-ef24-40ab-8c61-0cb33135cca7': 'Although the carotid bodies play little role in reflex response to CO2, their response to hypercapnia is more rapid than the central chemoreceptors and so they are capable of breath-by-breath regulation and responding to abrupt changes in arterial PCO2. More importantly the peripheral chemoreceptors are entirely responsible for the response to hypoxia. The mechanism as to how these receptors work is unclear, but cells within the carotid bodies have very high metabolic rates and receive a proportionately high blood flow. It is likely that a decline in oxygen interrupts their metabolism and reduces their inhibitory interaction on neurotransmitter-filled neighboring cells, allowing excitation of the carotid sinus nerve.\xa0Their response to a decline in blood oxygen is far from linear. A decline in PO2\xa0below 100 mmHg causes little change in\xa0action potential firing, but the rate of firing rapidly increases at PO2s below 50. This is reflected in the hypoxic ventilatory response illustrated in the graph in figure 17.5.', '7d454584-4e63-4a14-bc6f-e71196169e7b': 'Because of this, the hypoxic ventilatory response normally plays little role in the control of breathing in humans. The hypoxic ventilatory response becomes more significant at altitude when inspired PO2\xa0is low, or more pertinently in lung disease, where alveolar ventilation or gas exchange is compromised.', '439b2a3b-9500-414a-aa44-02adc653c5fd': 'The hypercapnic ventilatory response (figure 17.6) is much more influential on breathing in humans on a normal day-to-day basis. The response is very linear, with a rise in PCO2\xa0producing a proportionate rise in ventilation, driven of course primarily by the central chemoreceptors, but also contributed to by\xa0the afferent activity of the peripheral receptors.', 'b4e8594d-4342-429e-a1d3-29deb926f070': 'The central and peripheral chemoreceptors keep arterial PCO2\xa0within very fine limits, primarily because of CO2‘s effect on pH. Alveolar ventilation rapidly increases with even a moderate rise in arterial CO2, but can completely stop (apnea) if arterial CO2\xa0falls below normal (~40 mmHg). The wakeful drive to breathe tends to keep CO2\xa0a little lower than the set-point of the chemoreceptors—a point illustrated during sleep, when the brainstem has complete control of breathing and PaCO2\xa0is seen to rise a few mmHg.', '64b429be-4d21-4cce-b4be-01fbc2ba73c4': 'The hypercapnic ventilatory response\xa0adapts to chronically elevated arterial CO2, such as in severe lung disease. Here we not only see the CSF increase its buffering capacity with increased bicarbonate, but we also see the chemoreceptors change their set-point. It is not uncommon to see COPD patients with arterial PCO2s above 60.', 'a7b008bd-dbb5-41e3-9c1e-334d7f944f71': 'Finally, the hypoxic and hypercapnic ventilatory responses are not independent, and when they are both present at the same time a potentiation is seen (i.e., the response to hypoxic and hypercapnia is greater than the sum of the two individual responses).', 'f5c85927-3e75-41d5-a3dc-748f9aab2b25': 'The hypoxic ventilatory response we have just looked at was measured at an alveolar PCO2\xa0of 35.8 mmHg. If the same test is performed at higher PCO2s (figure 17.7), then the hypoxic ventilatory response is much greater, as shown by these upwardly shifted lines when alveolar PCO2\xa0is set to 43.7 mmHg and 48.7 mmHg.', '4b57208b-e130-430c-bd66-a47e7bc49def': 'Likewise, the hypercapnic ventilatory response is exaggerated in the presence of hypoxia (see figure 17.8). The hypercapnic ventilatory response we have just looked at was measured at a “normal”\xa0alveolar PO2\xa0of 110 mmHg. If the hypercapnic response is measured in the presence of hypoxia, then the curve shifts upward, as shown by\xa0the upper lines when alveolar PO2 is reduced to 47 mmHg and 37 mmHg. This potentiation likely comes from the peripheral chemoreceptors, whose firing rate is potentiated in the presence of both stimuli. Consequently, when a patient is both hypoxic and hypercapnic, then they are likely to have a very high drive to breathe, and when this occurs they are likely to feel very short of breath—the topic of the last chapter.', 'd1eb2ee4-c45e-4b70-bebb-601f16788991': 'The chemoreflexes modulate breathing to maintain constant arterial blood gases and pH. These reflexes are initiated by central sensors that respond to hypoxia and peripheral sensors that respond to hypercapnia, hypoxia, and changes in arterial pH. Together these sensors can maintain arterial blood gases within narrow ranges despite large changes in oxygen consumption and CO2\xa0production associated with changes in metabolic rate.'}"
+Figure 17.8,pulmo2/images/Figure 17.8.jpg,Figure 17.8: Hypercapnic ventilatory responses with varying degrees of hypoxia.,"Likewise, the hypercapnic ventilatory response is exaggerated in the presence of hypoxia (see figure 17.8). The hypercapnic ventilatory response we have just looked at was measured at a “normal” alveolar PO2 of 110 mmHg. If the hypercapnic response is measured in the presence of hypoxia, then the curve shifts upward, as shown by the upper lines when alveolar PO2 is reduced to 47 mmHg and 37 mmHg. This potentiation likely comes from the peripheral chemoreceptors, whose firing rate is potentiated in the presence of both stimuli. Consequently, when a patient is both hypoxic and hypercapnic, then they are likely to have a very high drive to breathe, and when this occurs they are likely to feel very short of breath—the topic of the last chapter.","{'53bcaa8e-3968-4dd6-af8f-0b7263f68ef2': 'The peripheral chemoreceptors are directly exposed to arterial blood and are capable of responding to changes in CO2, O2, and pH. There are two populations of chemoreceptive cells in the vasculature (see figure 17.4). One population is found in the aortic arch\xa0and is referred\xa0to as the aortic bodies. These are wired into the brainstem through afferent fibers that project to and join the vagus nerve. The other chemoreceptor is comprised of the carotid bodies, found in the bifurcation of the common carotid arteries. These connect to the brainstem through the carotid sinus and the glossopharyngeal nerves. The carotid bodies are by far the most important in humans, with the aortic bodies contributing very little to any ventilatory response.', '105e0bd6-ef24-40ab-8c61-0cb33135cca7': 'Although the carotid bodies play little role in reflex response to CO2, their response to hypercapnia is more rapid than the central chemoreceptors and so they are capable of breath-by-breath regulation and responding to abrupt changes in arterial PCO2. More importantly the peripheral chemoreceptors are entirely responsible for the response to hypoxia. The mechanism as to how these receptors work is unclear, but cells within the carotid bodies have very high metabolic rates and receive a proportionately high blood flow. It is likely that a decline in oxygen interrupts their metabolism and reduces their inhibitory interaction on neurotransmitter-filled neighboring cells, allowing excitation of the carotid sinus nerve.\xa0Their response to a decline in blood oxygen is far from linear. A decline in PO2\xa0below 100 mmHg causes little change in\xa0action potential firing, but the rate of firing rapidly increases at PO2s below 50. This is reflected in the hypoxic ventilatory response illustrated in the graph in figure 17.5.', '7d454584-4e63-4a14-bc6f-e71196169e7b': 'Because of this, the hypoxic ventilatory response normally plays little role in the control of breathing in humans. The hypoxic ventilatory response becomes more significant at altitude when inspired PO2\xa0is low, or more pertinently in lung disease, where alveolar ventilation or gas exchange is compromised.', '439b2a3b-9500-414a-aa44-02adc653c5fd': 'The hypercapnic ventilatory response (figure 17.6) is much more influential on breathing in humans on a normal day-to-day basis. The response is very linear, with a rise in PCO2\xa0producing a proportionate rise in ventilation, driven of course primarily by the central chemoreceptors, but also contributed to by\xa0the afferent activity of the peripheral receptors.', 'b4e8594d-4342-429e-a1d3-29deb926f070': 'The central and peripheral chemoreceptors keep arterial PCO2\xa0within very fine limits, primarily because of CO2‘s effect on pH. Alveolar ventilation rapidly increases with even a moderate rise in arterial CO2, but can completely stop (apnea) if arterial CO2\xa0falls below normal (~40 mmHg). The wakeful drive to breathe tends to keep CO2\xa0a little lower than the set-point of the chemoreceptors—a point illustrated during sleep, when the brainstem has complete control of breathing and PaCO2\xa0is seen to rise a few mmHg.', '64b429be-4d21-4cce-b4be-01fbc2ba73c4': 'The hypercapnic ventilatory response\xa0adapts to chronically elevated arterial CO2, such as in severe lung disease. Here we not only see the CSF increase its buffering capacity with increased bicarbonate, but we also see the chemoreceptors change their set-point. It is not uncommon to see COPD patients with arterial PCO2s above 60.', 'a7b008bd-dbb5-41e3-9c1e-334d7f944f71': 'Finally, the hypoxic and hypercapnic ventilatory responses are not independent, and when they are both present at the same time a potentiation is seen (i.e., the response to hypoxic and hypercapnia is greater than the sum of the two individual responses).', 'f5c85927-3e75-41d5-a3dc-748f9aab2b25': 'The hypoxic ventilatory response we have just looked at was measured at an alveolar PCO2\xa0of 35.8 mmHg. If the same test is performed at higher PCO2s (figure 17.7), then the hypoxic ventilatory response is much greater, as shown by these upwardly shifted lines when alveolar PCO2\xa0is set to 43.7 mmHg and 48.7 mmHg.', '4b57208b-e130-430c-bd66-a47e7bc49def': 'Likewise, the hypercapnic ventilatory response is exaggerated in the presence of hypoxia (see figure 17.8). The hypercapnic ventilatory response we have just looked at was measured at a “normal”\xa0alveolar PO2\xa0of 110 mmHg. If the hypercapnic response is measured in the presence of hypoxia, then the curve shifts upward, as shown by\xa0the upper lines when alveolar PO2 is reduced to 47 mmHg and 37 mmHg. This potentiation likely comes from the peripheral chemoreceptors, whose firing rate is potentiated in the presence of both stimuli. Consequently, when a patient is both hypoxic and hypercapnic, then they are likely to have a very high drive to breathe, and when this occurs they are likely to feel very short of breath—the topic of the last chapter.', 'd1eb2ee4-c45e-4b70-bebb-601f16788991': 'The chemoreflexes modulate breathing to maintain constant arterial blood gases and pH. These reflexes are initiated by central sensors that respond to hypoxia and peripheral sensors that respond to hypercapnia, hypoxia, and changes in arterial pH. Together these sensors can maintain arterial blood gases within narrow ranges despite large changes in oxygen consumption and CO2\xa0production associated with changes in metabolic rate.'}"
+Figure 16.1,pulmo2/images/Figure 16.1.jpg,Figure 16.1: Basic structure of hemoglobin.,"The hemoglobin molecule consists of four polypeptide chains, two alpha and two beta (figure 16.1). These proteins comprise the “globin” part of the molecule but are not simply structural as they contain sites that are capable of receiving CO2 and also hydrogen ions—a handy function, as you might imagine. Some anemias, such as sickle cell anemia, involve a conformational change in these proteins and diminish the molecule’s gas carrying ability.","{'709e47ee-7a91-414c-81cc-5c3752c06c47': 'American Thoracic Society Committee on Dyspnea. “An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea.” American Journal of Respiratory and Critical Care Medicine 185, no. 4: 435–52. https://doi.org/10.1164/rccm.201111-2042ST.', 'd5f1a15f-0fcf-40e5-aa89-9237e2b68c6a': 'Banzett, Robert B., Robert W. Lansing, and Andrew P. Binks. “Air Hunger: A Primal Sensation and a Primary Element of Dyspnea.” Comprehensive Physiology 11, no. 2 (April 2021): 1449–83. https://doi.org/10.1002/cphy.c200001.', '114c8441-5da7-4816-9a98-ebe7006695e0': 'Levitsky, Michael G. “Chapter 9: Control of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '73bce2fb-98ad-41f3-8101-4bf9af7e048d': 'West, John B. “Chapter 8: Control of Ventilation—How Gas Exchange Is Regulated.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'b8d4a9c3-0d94-4647-88e2-309c65d3b974': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 8” and “Chapter 9.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'db0a65e0-e669-4647-b737-5a183e68a90c': 'The hemoglobin molecule consists of four polypeptide chains, two alpha and two beta (figure 16.1). These proteins comprise the “globin”\xa0part of the molecule but are not simply structural as they contain sites that are capable of receiving CO2\xa0and also hydrogen ions—a handy function, as you might imagine. Some anemias, such as sickle cell anemia, involve a conformational change in these proteins and diminish\xa0the molecule’s gas carrying ability.', 'b3772caa-6325-41b5-beea-7c431fd6d4b3': 'The heme component of hemoglobin is an iron-containing porphyrin molecule capable of binding with oxygen. Each of the four polypeptide chains contains a heme molecule, meaning that each hemoglobin molecule is capable of transporting four oxygen molecules. It is\xa0also worth noting that binding of oxygen to the heme molecule induces a conformational change that results in oxyhemoglobin having some different behaviors and indeed color to deoxyhemoglobin. We will look at some of these differences in behavior later on.', '305cc335-e478-4f77-85c3-749b48edc277': 'It is\xa0also worth reviewing hemoglobin’s home here as well—the red blood cell (RBC). The red blood cell’s classic biconcave shape provides a large surface area for gas exchange and also means that no hemoglobin molecule inside is very far from the edge of the cell, cutting down on the diffusion distance of gases. The cell is also very flexible, making it capable of squeezing through narrow and twisting capillaries so that its walls and those of the capillary may be in\xa0close contact and again diffusion distances are reduced.', '396c63b3-8995-41de-a103-31ebc88c8ab7': 'Each RBC is capable of holding up to 250 million hemoglobin molecules, so consequently is capable of holding one billion oxygen molecules; as such the RBC fulfills its primary role of oxygen transport well. This oxygen transport system fails in anemias that result in either too few red blood cells\xa0or too little hemoglobin in each cell (or both). Now let us look at the behavior of hemoglobin.', 'b3a2853f-4d49-466c-b233-b1e3ad132937': 'The behavior of hemoglobin is best described by the oxygen saturation curve (figure 16.2), and this is one of the most important curves to understand in medicine. The curve shows the percentage of hemoglobin that has all of its heme molecules bound with oxygen (i.e., are saturated). So for example a 50 percent\xa0saturation would mean that half of the heme sites were occupied by oxygen. The curve shows percentage saturation in relation to oxygen partial pressure, and what should be immediately noticeable is that the higher the partial pressure of oxygen then the greater the saturation. But the relationship is far from linear and its shape offers several important physiological advantages. If it helps understand it, think of this curve as an instruction manual for hemoglobin,\xa0telling how saturated it should be at any PO2. In reality it is an enzyme kinetics curve, describing hemoglobin’s affinity for oxygen over a range of PO2.', '240bd48e-3307-4e02-a6c4-3980b6721979': 'First\xa0let us put the curve in a physiological context. The alveolar PO2\xa0is around 100 mmHg. This means that as blood passes the alveoli and is exposed to this PO2, then oxygen saturation becomes close to 100 percent, about 98 percent. The first important physiological feature of this curve is that PO2\xa0can fall a considerably long way before it has an impact on oxygen saturation. So, taking time to look at the numbers on the graph, let us say, for example, that a patient begins to hypoventilate and alveolar PO2\xa0falls to 70 mmHg; while this is a considerable fall in PO2, the saturation will only fall a few percentage points, and PO2\xa0must\xa0fall to 50 before significant loss of saturation, or desaturation, occurs. Below 50, however, notice how the curve rapidly steepens, and now for a small change in PO2, we get a large desaturation.', '57274494-19e2-4442-a9f6-72dc7f08e65a': 'This steep section of the curve is therefore clinically critical. If your patient’s saturation monitor reads 83 percent\xa0what should spring into your mind is it that such a low saturation puts the patient onto the steep part of the curve. It will now take only a small further decline in alveolar PO2\xa0to have a profound effect on saturation, unlike at the top and flat section of the curve where small changes in alveolar PO2\xa0have very little effect on saturation.', 'ae59bbfa-2b77-438a-a039-3640d3f50564': 'So what is the advantage of having such a steep curve at lower PO2s? Let us look at the physiological situation again. We have\xa0already said that the alveolar PO2\xa0of 100 results in a saturation close to 100 percent (i.e., at the lung the hemoglobin\xa0has a high affinity for oxygen and becomes fully saturated).', '9db43d4c-5e74-4450-aeb0-f34c80abd999': 'At the tissue, however, we want hemoglobin\xa0to lose its affinity for oxygen and release some to the metabolizing cells. At the tissue the local PO2\xa0is much lower, around 40, because of the oxygen consumption by the tissue. At the lower PO2, hemoglobin’s affinity for oxygen falls, and it will lose some of its oxygen to the tissue and saturation will fall. This is ideal, as now our oxygen carrier is capable of releasing oxygen where it is\xa0needed.', '5b86e2bb-12a9-4a32-80fa-554e0dcae3ee': 'If tissue PO2\xa0falls even lower, such as when metabolic rate is high, then more oxygen will be released by hemoglobin as its affinity for oxygen declines with the lower tissue PO2. Therefore the delivery system for oxygen is intrinsically tied to metabolic rate.', '56b865af-bc70-47ec-8696-ba94d1f42869': 'The shape of this curve makes hemoglobin a remarkable molecule—able to grab oxygen at the oxygen-providing lung, but relinquish it to oxygen-demanding tissue and relinquish more when the tissue needs more. There are other factors that fine-tune the amount of oxygen delivered to tissue to match its oxygen demand. This is summarized in figure 16.3.', '4ed813be-9b8e-460b-bafa-7979fda65ba0': 'Levitsky, Michael G. “Chapter 7: Transport of Oxygen and Carbon Dioxide in the Blood.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'd6a16cf9-d059-46b3-b7e2-0261a878af63': 'West, John B. “Chapter 6: Gas Transport by the Blood—How Gases Are Moved to the Peripheral Tissues.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'eebcdd0d-d4a0-48ea-b604-9534d41496ed': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 6.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '279562ba-f525-4412-9982-1e9c07d279bb': 'There are two circulatory networks that normally form shunts. The bronchial circulation, that supplies\xa0the bronchi, empties its venous blood into the pulmonary veins, thereby sending slightly deoxygenated blood back toward the left heart and into the systemic arterial system. Likewise a very small portion of the coronary venous blood is returned to the left ventricle (through the thebesian veins) and thereby bypasses the lung completely before going back in the systemic circulation.', 'e26d0d11-466b-4a31-bc87-c83397920658': 'These two wayward circulations and the imperfect V/Q matching in the lung serve to suppress arterial oxygen saturation.', 'c0f16823-bf43-4645-9269-c51c6ce26d14': 'Levitsky, Michael G. “Chapter 5: Ventilation–Perfusion Relationships.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '4a3745c2-5916-41da-b111-3377965154c7': 'West, John B. “Chapter 5: Ventilation–Perfusion Relationships—How Matching of Gas and Blood Determines Gas Exchange.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '0b3f01fc-f893-4c2a-ba14-78f6613e445c': 'Levitsky, Michael G. “Chapter 3: Alveolar Ventilation.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'ef7d1b93-3a1e-49fe-8e36-f72ffeb5d196': 'Let us\xa0start with a description of the ideal situation, where ventilation to alveoli is matched with the perfusion, then we will see how the lung does not quite achieve this.', '20443118-b1a8-481e-b40b-fabc2cdacdae': 'This is what we would expect if the lung were perfect, with uniform distribution of ventilation and perfusion to all regions and a V/Q of 1 in all regions.', '1266c3d9-2603-4ab5-a23b-c4c09c575487': 'The lung is not a perfect organ, however, and ventilation and perfusion are not equally distributed, and the lung as a whole only achieves an average V/Q of 0.8, which is close to our ideal of 1, but not quite there. Consequently, by the time the blood has passed the alveoli and regrouped in the pulmonary veins, the PO2 of the blood is less than alveolar. This alveolar–arterial PO2 difference is caused by the less-than-perfect matching of V and Q across the lung; but it is\xa0not all the lung’s fault, as venous blood that has been through the bronchial and a small section of the coronary circulation (and therefore is deoxygenated) is mixed into the vessels returning to the left heart, which brings down arterial saturation as well. The mixing-in of bronchial and coronary circulations and the less-than-ideal V/Q in the lung as a whole is the reason why your saturation monitors do not\xa0read 100 percent, but normal oxygen saturation is considered as 96–98 percent.', '736d22e3-bd4e-497c-bf9a-992a06cc406d': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 7.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'c7f4c268-560a-4009-8867-a730d1d4a684': 'Levitsky, Michael G. “Chapter 8: Acid–Base Balance.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '405afb7b-5d31-4d56-b756-36329df0d2fa': 'Levitsky, Michael G. “Chapter 10: Nonrespiratory Functions of the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9cfd8d5d-3721-4961-8c24-8b2bba6b0e82': 'West, John B. “Chapter 4: Blood Flow and Metabolism—How the Pulmonary Circulation Removes Gas from the Lung and Alters Some Metabolites.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '5bbf18cb-720e-433f-a97c-7a9a17affa5c': 'Levitsky, Michael G. “Chapter 4: Blood Flow to the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '58f3e187-02d3-4794-a834-033ae16daf9b': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 5.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '7ee7bd78-ee76-462c-8326-3223973d9968': 'Levitsky, Michael G. “Chapter 6: Diffusion of Gases and Interpretation of Pulmonary Function Tests.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '7098f0e3-8f6c-4a7f-8bb9-019917fbc96e': 'West, John B. “Chapter 3: Diffusion—How Gas Gets Across the Blood–Gas Barrier.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '83eef49d-f1b3-4248-908d-fe1c99a681e8': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 4.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '94a2e555-32f9-4cc7-8f5b-ef7daead5687': 'Before we do that though, we need to be able to calculate the units of measurement we use when describing gas exchange. When referring to gas exchange we are really referring to diffusion of gases down their concentration gradient, but rather than use concentrations, we use partial pressures.', '83d5f78d-9abb-48e8-b071-bef116366b8f': 'Partial pressures describe what proportion of the total pressure is exerted by a particular component of a mixed gas. Let us\xa0look at the specific situation we are interested in to illustrate this description.', 'd82456a7-eec8-4a00-acb8-976db3f8f866': 'Atmospheric pressure at sea level is 760 mmHg. This pressure is generated by the collisions of all the molecules with each other and other objects. At high altitude there are fewer molecules, so fewer collisions, and hence atmospheric pressure is lower.', 'a630d4b8-fca5-42f2-b5b5-7435455e5bc6': 'Now looking at the composition of our atmosphere we know that 79 percent\xa0is nitrogen, 20.9 percent\xa0is oxygen, and some trace gases collectively get us to 100 percent. Now let us\xa0calculate a partial pressure. If 79 percent\xa0of the atmosphere is nitrogen, then 79 percent\xa0of our atmospheric pressure is generated by the collisions by nitrogen molecules. Likewise 20.9 percent\xa0of the atmospheric pressure is due to oxygen, so to calculate the partial pressure of oxygen (PO2) we simply multiply atmospheric pressure (PB) by the percentage of oxygen, which means our atmosphere has a partial pressure of oxygen of 159 mmHg.', 'e125ba2f-6da8-4e10-bea6-e132c5f31f62': 'Although this phenomenon is present in the healthy lung, we will see how it is exacerbated in certain disease states and how this exacerbation can be detected by common pulmonary function tests.', '6443f20b-c2ba-4f2a-912d-b820480b48dc': 'First, let us\xa0look at the forces involved during a normal, passive expiration.', 'b41f13e9-f936-4f36-a5cf-fb0da07ecd91': 'For simplicity, the schematic in figure 6.1 shows one airway and an alveolus within the thoracic cavity. At the onset of passive expiration (driven by the recoil of the expanded lung), the intrapleural pressure is negative (about −8 cm H2O). As it remains negative, intrapleural pressure helps keep the airways open.', 'e3fd9346-74ee-4550-ac3d-c10b889a9616': 'West, John B. “Chapter 7: Mechanics of Breathing—How the Lung Is Supported and Moved.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'f3d82c09-4fa4-4232-b7c2-ca82c3f0e4d6': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 3.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '2abbd8fc-bc45-4021-95f3-7cc764fb7854': 'The first factor we must consider when thinking about airflow is the type of flow that is occurring.', '90b7c113-9453-48ab-af12-da3e977c0466': 'The most efficient form of flow is laminar\xa0(i.e., laminar flow takes the lowest pressure differential for flow to occur). In laminar flow the molecules are moving in an orderly manner, those at the side of the tube moving a little slower due to contact with tube walls\xa0and those in the middle moving fastest (figure 5.1).', '185f8384-ae77-4ecc-8216-cf9651f31397': 'When velocity increases or tube radius decreases then this organization is lost. Collisions between molecules and with the tube wall are now more frequent and movement is more chaotic, and the flow becomes turbulent (figure 5.2). At this point some molecules are at times moving against the pressure gradient due to these collisions. Consequently, to generate the same amount of molecule movement (i.e., flow) from one end of the tube to another, a greater pressure differential is needed when flow becomes turbulent. Turbulent flow is more common in the large airways where velocity and airway radius are high.', '78016837-1b1e-4b72-9459-159a81636088': 'In reality, the vast majority of the airways are branching small tubes, so we see a mixture of the two above—mostly laminar flow but some turbulence generated at the branch (or transitional) points (figure 5.3).', 'd8c9a412-74b3-47d6-9885-10a68f3195dc': 'For our purposes though we are going to look at the factors that affect flow when it is laminar—the dominant form of flow in the majority of airways. These factors are described by Poiselle’s equation. We will now break down Poiselle’s equation in relation to flow of air down airways. Although initially an intimidating equation, there are some things we can generally ignore.', '329ee30f-0280-4186-a272-76cda4611f6d': 'Equation 5.1', 'ccf522d3-ed2e-4e8f-951d-b5f59bf4614f': 'Levitsky, Michael G. “Chapter 2: Mechanics of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '6122ed24-6881-4243-b127-64fd05cdb94a': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 1.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '3265bb73-23ce-4e55-b347-c6a6e3d0f4a2': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 2.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '5b7cdf1c-6e3e-4689-a4b4-001b0e7d0b85': 'Before we get into the details of how we breathe in, let me make sure we are all on the same page by going right back to basics, so bare with me or skip ahead if you are happy with pressure, volume, and flow.', '9e430d7f-a263-41b5-819a-5d6f57a475d3': 'To get air to move into the lungs we need to generate a pressure differential;\xa0that is the pressure inside the lungs must be lower than the pressure outside\xa0(i.e., atmospheric pressure), so that air moves down the pressure gradient into the lungs.', '2a56dfa9-1088-4e0d-8a05-7d0dae7eabe3': 'The low pressure inside the lungs is generated by increasing lung volume; bigger volume means fewer molecules in the same space, and therefore lower pressure (go back and revisit Boyle’s law if needed).', '700a30d9-cdcb-4a22-934d-dbb9221c27e8': 'The basis of inspiration is lowering lung pressure below atmospheric pressure, so that atmospheric pressure pushes air down the airways until pressure equilibrates. So the fundamental first step is, how do we increase lung volume?', 'f0582f89-5080-4d8c-973f-c82797cb93ae': 'To understand the mechanics of breathing we have to deal with two concepts:\xa0first how the action of the respiratory muscles increases thoracic volume, and second\xa0(and more complex) we need to understand the interaction of the lungs and the thoracic wall.', 'cf71568f-25a9-4c48-880c-f5fdda101c9b': 'Let us deal with the respiratory muscles and expansion of the thorax first.', '338eec0f-6210-47e2-815e-4cb6f22fc67a': 'West, John B. “Chapter 2: Ventilation—How Gas Gets to the Alveoli.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '3c8b34ab-c9f8-4728-8aad-518dd91e7284': 'We will see how blood gases are monitored and maintained through neurochemical control of lung expansion and relaxation to achieve the appropriate level of alveolar ventilation. Factors that affect the\xa0degree of gas exchange between the lung and blood will be discussed, along with the coordination of ventilation and perfusion of the lung. Finally, we will see how oxygen and carbon dioxide are transported in the bloodstream to and from tissue and the mechanisms that ensure appropriate delivery and a stable blood gas environment.\xa0Before we begin, however, we will look at the functional anatomy of the lung and how the lung is well designed to perform its primary role and defend itself from the external environment.', 'bb13387c-a557-4bd6-8b04-3e30d6d82916': 'Levitsky, Michael G. “Chapter 1: Function and Structure of the Respiratory System.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9faee6ea-d9bf-4b11-a3d3-8561cb811717': 'West, John B. “Chapter 1: Structure and Function—How the Architecture of the Lung Subserves Its Function.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.'}"
+Figure 16.2,pulmo2/images/Figure 16.2.jpg,Figure 16.2: Hemoglobin saturation curve.,"The behavior of hemoglobin is best described by the oxygen saturation curve (figure 16.2), and this is one of the most important curves to understand in medicine. The curve shows the percentage of hemoglobin that has all of its heme molecules bound with oxygen (i.e., are saturated). So for example a 50 percent saturation would mean that half of the heme sites were occupied by oxygen. The curve shows percentage saturation in relation to oxygen partial pressure, and what should be immediately noticeable is that the higher the partial pressure of oxygen then the greater the saturation. But the relationship is far from linear and its shape offers several important physiological advantages. If it helps understand it, think of this curve as an instruction manual for hemoglobin, telling how saturated it should be at any PO2. In reality it is an enzyme kinetics curve, describing hemoglobin’s affinity for oxygen over a range of PO2.","{'709e47ee-7a91-414c-81cc-5c3752c06c47': 'American Thoracic Society Committee on Dyspnea. “An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea.” American Journal of Respiratory and Critical Care Medicine 185, no. 4: 435–52. https://doi.org/10.1164/rccm.201111-2042ST.', 'd5f1a15f-0fcf-40e5-aa89-9237e2b68c6a': 'Banzett, Robert B., Robert W. Lansing, and Andrew P. Binks. “Air Hunger: A Primal Sensation and a Primary Element of Dyspnea.” Comprehensive Physiology 11, no. 2 (April 2021): 1449–83. https://doi.org/10.1002/cphy.c200001.', '114c8441-5da7-4816-9a98-ebe7006695e0': 'Levitsky, Michael G. “Chapter 9: Control of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '73bce2fb-98ad-41f3-8101-4bf9af7e048d': 'West, John B. “Chapter 8: Control of Ventilation—How Gas Exchange Is Regulated.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'b8d4a9c3-0d94-4647-88e2-309c65d3b974': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 8” and “Chapter 9.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'db0a65e0-e669-4647-b737-5a183e68a90c': 'The hemoglobin molecule consists of four polypeptide chains, two alpha and two beta (figure 16.1). These proteins comprise the “globin”\xa0part of the molecule but are not simply structural as they contain sites that are capable of receiving CO2\xa0and also hydrogen ions—a handy function, as you might imagine. Some anemias, such as sickle cell anemia, involve a conformational change in these proteins and diminish\xa0the molecule’s gas carrying ability.', 'b3772caa-6325-41b5-beea-7c431fd6d4b3': 'The heme component of hemoglobin is an iron-containing porphyrin molecule capable of binding with oxygen. Each of the four polypeptide chains contains a heme molecule, meaning that each hemoglobin molecule is capable of transporting four oxygen molecules. It is\xa0also worth noting that binding of oxygen to the heme molecule induces a conformational change that results in oxyhemoglobin having some different behaviors and indeed color to deoxyhemoglobin. We will look at some of these differences in behavior later on.', '305cc335-e478-4f77-85c3-749b48edc277': 'It is\xa0also worth reviewing hemoglobin’s home here as well—the red blood cell (RBC). The red blood cell’s classic biconcave shape provides a large surface area for gas exchange and also means that no hemoglobin molecule inside is very far from the edge of the cell, cutting down on the diffusion distance of gases. The cell is also very flexible, making it capable of squeezing through narrow and twisting capillaries so that its walls and those of the capillary may be in\xa0close contact and again diffusion distances are reduced.', '396c63b3-8995-41de-a103-31ebc88c8ab7': 'Each RBC is capable of holding up to 250 million hemoglobin molecules, so consequently is capable of holding one billion oxygen molecules; as such the RBC fulfills its primary role of oxygen transport well. This oxygen transport system fails in anemias that result in either too few red blood cells\xa0or too little hemoglobin in each cell (or both). Now let us look at the behavior of hemoglobin.', 'b3a2853f-4d49-466c-b233-b1e3ad132937': 'The behavior of hemoglobin is best described by the oxygen saturation curve (figure 16.2), and this is one of the most important curves to understand in medicine. The curve shows the percentage of hemoglobin that has all of its heme molecules bound with oxygen (i.e., are saturated). So for example a 50 percent\xa0saturation would mean that half of the heme sites were occupied by oxygen. The curve shows percentage saturation in relation to oxygen partial pressure, and what should be immediately noticeable is that the higher the partial pressure of oxygen then the greater the saturation. But the relationship is far from linear and its shape offers several important physiological advantages. If it helps understand it, think of this curve as an instruction manual for hemoglobin,\xa0telling how saturated it should be at any PO2. In reality it is an enzyme kinetics curve, describing hemoglobin’s affinity for oxygen over a range of PO2.', '240bd48e-3307-4e02-a6c4-3980b6721979': 'First\xa0let us put the curve in a physiological context. The alveolar PO2\xa0is around 100 mmHg. This means that as blood passes the alveoli and is exposed to this PO2, then oxygen saturation becomes close to 100 percent, about 98 percent. The first important physiological feature of this curve is that PO2\xa0can fall a considerably long way before it has an impact on oxygen saturation. So, taking time to look at the numbers on the graph, let us say, for example, that a patient begins to hypoventilate and alveolar PO2\xa0falls to 70 mmHg; while this is a considerable fall in PO2, the saturation will only fall a few percentage points, and PO2\xa0must\xa0fall to 50 before significant loss of saturation, or desaturation, occurs. Below 50, however, notice how the curve rapidly steepens, and now for a small change in PO2, we get a large desaturation.', '57274494-19e2-4442-a9f6-72dc7f08e65a': 'This steep section of the curve is therefore clinically critical. If your patient’s saturation monitor reads 83 percent\xa0what should spring into your mind is it that such a low saturation puts the patient onto the steep part of the curve. It will now take only a small further decline in alveolar PO2\xa0to have a profound effect on saturation, unlike at the top and flat section of the curve where small changes in alveolar PO2\xa0have very little effect on saturation.', 'ae59bbfa-2b77-438a-a039-3640d3f50564': 'So what is the advantage of having such a steep curve at lower PO2s? Let us look at the physiological situation again. We have\xa0already said that the alveolar PO2\xa0of 100 results in a saturation close to 100 percent (i.e., at the lung the hemoglobin\xa0has a high affinity for oxygen and becomes fully saturated).', '9db43d4c-5e74-4450-aeb0-f34c80abd999': 'At the tissue, however, we want hemoglobin\xa0to lose its affinity for oxygen and release some to the metabolizing cells. At the tissue the local PO2\xa0is much lower, around 40, because of the oxygen consumption by the tissue. At the lower PO2, hemoglobin’s affinity for oxygen falls, and it will lose some of its oxygen to the tissue and saturation will fall. This is ideal, as now our oxygen carrier is capable of releasing oxygen where it is\xa0needed.', '5b86e2bb-12a9-4a32-80fa-554e0dcae3ee': 'If tissue PO2\xa0falls even lower, such as when metabolic rate is high, then more oxygen will be released by hemoglobin as its affinity for oxygen declines with the lower tissue PO2. Therefore the delivery system for oxygen is intrinsically tied to metabolic rate.', '56b865af-bc70-47ec-8696-ba94d1f42869': 'The shape of this curve makes hemoglobin a remarkable molecule—able to grab oxygen at the oxygen-providing lung, but relinquish it to oxygen-demanding tissue and relinquish more when the tissue needs more. There are other factors that fine-tune the amount of oxygen delivered to tissue to match its oxygen demand. This is summarized in figure 16.3.', '4ed813be-9b8e-460b-bafa-7979fda65ba0': 'Levitsky, Michael G. “Chapter 7: Transport of Oxygen and Carbon Dioxide in the Blood.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'd6a16cf9-d059-46b3-b7e2-0261a878af63': 'West, John B. “Chapter 6: Gas Transport by the Blood—How Gases Are Moved to the Peripheral Tissues.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'eebcdd0d-d4a0-48ea-b604-9534d41496ed': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 6.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '279562ba-f525-4412-9982-1e9c07d279bb': 'There are two circulatory networks that normally form shunts. The bronchial circulation, that supplies\xa0the bronchi, empties its venous blood into the pulmonary veins, thereby sending slightly deoxygenated blood back toward the left heart and into the systemic arterial system. Likewise a very small portion of the coronary venous blood is returned to the left ventricle (through the thebesian veins) and thereby bypasses the lung completely before going back in the systemic circulation.', 'e26d0d11-466b-4a31-bc87-c83397920658': 'These two wayward circulations and the imperfect V/Q matching in the lung serve to suppress arterial oxygen saturation.', 'c0f16823-bf43-4645-9269-c51c6ce26d14': 'Levitsky, Michael G. “Chapter 5: Ventilation–Perfusion Relationships.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '4a3745c2-5916-41da-b111-3377965154c7': 'West, John B. “Chapter 5: Ventilation–Perfusion Relationships—How Matching of Gas and Blood Determines Gas Exchange.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '0b3f01fc-f893-4c2a-ba14-78f6613e445c': 'Levitsky, Michael G. “Chapter 3: Alveolar Ventilation.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'ef7d1b93-3a1e-49fe-8e36-f72ffeb5d196': 'Let us\xa0start with a description of the ideal situation, where ventilation to alveoli is matched with the perfusion, then we will see how the lung does not quite achieve this.', '20443118-b1a8-481e-b40b-fabc2cdacdae': 'This is what we would expect if the lung were perfect, with uniform distribution of ventilation and perfusion to all regions and a V/Q of 1 in all regions.', '1266c3d9-2603-4ab5-a23b-c4c09c575487': 'The lung is not a perfect organ, however, and ventilation and perfusion are not equally distributed, and the lung as a whole only achieves an average V/Q of 0.8, which is close to our ideal of 1, but not quite there. Consequently, by the time the blood has passed the alveoli and regrouped in the pulmonary veins, the PO2 of the blood is less than alveolar. This alveolar–arterial PO2 difference is caused by the less-than-perfect matching of V and Q across the lung; but it is\xa0not all the lung’s fault, as venous blood that has been through the bronchial and a small section of the coronary circulation (and therefore is deoxygenated) is mixed into the vessels returning to the left heart, which brings down arterial saturation as well. The mixing-in of bronchial and coronary circulations and the less-than-ideal V/Q in the lung as a whole is the reason why your saturation monitors do not\xa0read 100 percent, but normal oxygen saturation is considered as 96–98 percent.', '736d22e3-bd4e-497c-bf9a-992a06cc406d': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 7.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'c7f4c268-560a-4009-8867-a730d1d4a684': 'Levitsky, Michael G. “Chapter 8: Acid–Base Balance.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '405afb7b-5d31-4d56-b756-36329df0d2fa': 'Levitsky, Michael G. “Chapter 10: Nonrespiratory Functions of the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9cfd8d5d-3721-4961-8c24-8b2bba6b0e82': 'West, John B. “Chapter 4: Blood Flow and Metabolism—How the Pulmonary Circulation Removes Gas from the Lung and Alters Some Metabolites.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '5bbf18cb-720e-433f-a97c-7a9a17affa5c': 'Levitsky, Michael G. “Chapter 4: Blood Flow to the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '58f3e187-02d3-4794-a834-033ae16daf9b': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 5.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '7ee7bd78-ee76-462c-8326-3223973d9968': 'Levitsky, Michael G. “Chapter 6: Diffusion of Gases and Interpretation of Pulmonary Function Tests.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '7098f0e3-8f6c-4a7f-8bb9-019917fbc96e': 'West, John B. “Chapter 3: Diffusion—How Gas Gets Across the Blood–Gas Barrier.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '83eef49d-f1b3-4248-908d-fe1c99a681e8': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 4.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '94a2e555-32f9-4cc7-8f5b-ef7daead5687': 'Before we do that though, we need to be able to calculate the units of measurement we use when describing gas exchange. When referring to gas exchange we are really referring to diffusion of gases down their concentration gradient, but rather than use concentrations, we use partial pressures.', '83d5f78d-9abb-48e8-b071-bef116366b8f': 'Partial pressures describe what proportion of the total pressure is exerted by a particular component of a mixed gas. Let us\xa0look at the specific situation we are interested in to illustrate this description.', 'd82456a7-eec8-4a00-acb8-976db3f8f866': 'Atmospheric pressure at sea level is 760 mmHg. This pressure is generated by the collisions of all the molecules with each other and other objects. At high altitude there are fewer molecules, so fewer collisions, and hence atmospheric pressure is lower.', 'a630d4b8-fca5-42f2-b5b5-7435455e5bc6': 'Now looking at the composition of our atmosphere we know that 79 percent\xa0is nitrogen, 20.9 percent\xa0is oxygen, and some trace gases collectively get us to 100 percent. Now let us\xa0calculate a partial pressure. If 79 percent\xa0of the atmosphere is nitrogen, then 79 percent\xa0of our atmospheric pressure is generated by the collisions by nitrogen molecules. Likewise 20.9 percent\xa0of the atmospheric pressure is due to oxygen, so to calculate the partial pressure of oxygen (PO2) we simply multiply atmospheric pressure (PB) by the percentage of oxygen, which means our atmosphere has a partial pressure of oxygen of 159 mmHg.', 'e125ba2f-6da8-4e10-bea6-e132c5f31f62': 'Although this phenomenon is present in the healthy lung, we will see how it is exacerbated in certain disease states and how this exacerbation can be detected by common pulmonary function tests.', '6443f20b-c2ba-4f2a-912d-b820480b48dc': 'First, let us\xa0look at the forces involved during a normal, passive expiration.', 'b41f13e9-f936-4f36-a5cf-fb0da07ecd91': 'For simplicity, the schematic in figure 6.1 shows one airway and an alveolus within the thoracic cavity. At the onset of passive expiration (driven by the recoil of the expanded lung), the intrapleural pressure is negative (about −8 cm H2O). As it remains negative, intrapleural pressure helps keep the airways open.', 'e3fd9346-74ee-4550-ac3d-c10b889a9616': 'West, John B. “Chapter 7: Mechanics of Breathing—How the Lung Is Supported and Moved.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'f3d82c09-4fa4-4232-b7c2-ca82c3f0e4d6': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 3.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '2abbd8fc-bc45-4021-95f3-7cc764fb7854': 'The first factor we must consider when thinking about airflow is the type of flow that is occurring.', '90b7c113-9453-48ab-af12-da3e977c0466': 'The most efficient form of flow is laminar\xa0(i.e., laminar flow takes the lowest pressure differential for flow to occur). In laminar flow the molecules are moving in an orderly manner, those at the side of the tube moving a little slower due to contact with tube walls\xa0and those in the middle moving fastest (figure 5.1).', '185f8384-ae77-4ecc-8216-cf9651f31397': 'When velocity increases or tube radius decreases then this organization is lost. Collisions between molecules and with the tube wall are now more frequent and movement is more chaotic, and the flow becomes turbulent (figure 5.2). At this point some molecules are at times moving against the pressure gradient due to these collisions. Consequently, to generate the same amount of molecule movement (i.e., flow) from one end of the tube to another, a greater pressure differential is needed when flow becomes turbulent. Turbulent flow is more common in the large airways where velocity and airway radius are high.', '78016837-1b1e-4b72-9459-159a81636088': 'In reality, the vast majority of the airways are branching small tubes, so we see a mixture of the two above—mostly laminar flow but some turbulence generated at the branch (or transitional) points (figure 5.3).', 'd8c9a412-74b3-47d6-9885-10a68f3195dc': 'For our purposes though we are going to look at the factors that affect flow when it is laminar—the dominant form of flow in the majority of airways. These factors are described by Poiselle’s equation. We will now break down Poiselle’s equation in relation to flow of air down airways. Although initially an intimidating equation, there are some things we can generally ignore.', '329ee30f-0280-4186-a272-76cda4611f6d': 'Equation 5.1', 'ccf522d3-ed2e-4e8f-951d-b5f59bf4614f': 'Levitsky, Michael G. “Chapter 2: Mechanics of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '6122ed24-6881-4243-b127-64fd05cdb94a': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 1.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '3265bb73-23ce-4e55-b347-c6a6e3d0f4a2': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 2.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '5b7cdf1c-6e3e-4689-a4b4-001b0e7d0b85': 'Before we get into the details of how we breathe in, let me make sure we are all on the same page by going right back to basics, so bare with me or skip ahead if you are happy with pressure, volume, and flow.', '9e430d7f-a263-41b5-819a-5d6f57a475d3': 'To get air to move into the lungs we need to generate a pressure differential;\xa0that is the pressure inside the lungs must be lower than the pressure outside\xa0(i.e., atmospheric pressure), so that air moves down the pressure gradient into the lungs.', '2a56dfa9-1088-4e0d-8a05-7d0dae7eabe3': 'The low pressure inside the lungs is generated by increasing lung volume; bigger volume means fewer molecules in the same space, and therefore lower pressure (go back and revisit Boyle’s law if needed).', '700a30d9-cdcb-4a22-934d-dbb9221c27e8': 'The basis of inspiration is lowering lung pressure below atmospheric pressure, so that atmospheric pressure pushes air down the airways until pressure equilibrates. So the fundamental first step is, how do we increase lung volume?', 'f0582f89-5080-4d8c-973f-c82797cb93ae': 'To understand the mechanics of breathing we have to deal with two concepts:\xa0first how the action of the respiratory muscles increases thoracic volume, and second\xa0(and more complex) we need to understand the interaction of the lungs and the thoracic wall.', 'cf71568f-25a9-4c48-880c-f5fdda101c9b': 'Let us deal with the respiratory muscles and expansion of the thorax first.', '338eec0f-6210-47e2-815e-4cb6f22fc67a': 'West, John B. “Chapter 2: Ventilation—How Gas Gets to the Alveoli.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '3c8b34ab-c9f8-4728-8aad-518dd91e7284': 'We will see how blood gases are monitored and maintained through neurochemical control of lung expansion and relaxation to achieve the appropriate level of alveolar ventilation. Factors that affect the\xa0degree of gas exchange between the lung and blood will be discussed, along with the coordination of ventilation and perfusion of the lung. Finally, we will see how oxygen and carbon dioxide are transported in the bloodstream to and from tissue and the mechanisms that ensure appropriate delivery and a stable blood gas environment.\xa0Before we begin, however, we will look at the functional anatomy of the lung and how the lung is well designed to perform its primary role and defend itself from the external environment.', 'bb13387c-a557-4bd6-8b04-3e30d6d82916': 'Levitsky, Michael G. “Chapter 1: Function and Structure of the Respiratory System.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9faee6ea-d9bf-4b11-a3d3-8561cb811717': 'West, John B. “Chapter 1: Structure and Function—How the Architecture of the Lung Subserves Its Function.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.'}"
+Figure 16.3,pulmo2/images/Figure 16.3.jpg,"Figure 16.3: The hemoglobin saturation at the lung (A), at the tissue (B), and at very metabolically active tissue (C).","The shape of this curve makes hemoglobin a remarkable molecule—able to grab oxygen at the oxygen-providing lung, but relinquish it to oxygen-demanding tissue and relinquish more when the tissue needs more. There are other factors that fine-tune the amount of oxygen delivered to tissue to match its oxygen demand. This is summarized in figure 16.3.","{'709e47ee-7a91-414c-81cc-5c3752c06c47': 'American Thoracic Society Committee on Dyspnea. “An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea.” American Journal of Respiratory and Critical Care Medicine 185, no. 4: 435–52. https://doi.org/10.1164/rccm.201111-2042ST.', 'd5f1a15f-0fcf-40e5-aa89-9237e2b68c6a': 'Banzett, Robert B., Robert W. Lansing, and Andrew P. Binks. “Air Hunger: A Primal Sensation and a Primary Element of Dyspnea.” Comprehensive Physiology 11, no. 2 (April 2021): 1449–83. https://doi.org/10.1002/cphy.c200001.', '114c8441-5da7-4816-9a98-ebe7006695e0': 'Levitsky, Michael G. “Chapter 9: Control of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '73bce2fb-98ad-41f3-8101-4bf9af7e048d': 'West, John B. “Chapter 8: Control of Ventilation—How Gas Exchange Is Regulated.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'b8d4a9c3-0d94-4647-88e2-309c65d3b974': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 8” and “Chapter 9.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'db0a65e0-e669-4647-b737-5a183e68a90c': 'The hemoglobin molecule consists of four polypeptide chains, two alpha and two beta (figure 16.1). These proteins comprise the “globin”\xa0part of the molecule but are not simply structural as they contain sites that are capable of receiving CO2\xa0and also hydrogen ions—a handy function, as you might imagine. Some anemias, such as sickle cell anemia, involve a conformational change in these proteins and diminish\xa0the molecule’s gas carrying ability.', 'b3772caa-6325-41b5-beea-7c431fd6d4b3': 'The heme component of hemoglobin is an iron-containing porphyrin molecule capable of binding with oxygen. Each of the four polypeptide chains contains a heme molecule, meaning that each hemoglobin molecule is capable of transporting four oxygen molecules. It is\xa0also worth noting that binding of oxygen to the heme molecule induces a conformational change that results in oxyhemoglobin having some different behaviors and indeed color to deoxyhemoglobin. We will look at some of these differences in behavior later on.', '305cc335-e478-4f77-85c3-749b48edc277': 'It is\xa0also worth reviewing hemoglobin’s home here as well—the red blood cell (RBC). The red blood cell’s classic biconcave shape provides a large surface area for gas exchange and also means that no hemoglobin molecule inside is very far from the edge of the cell, cutting down on the diffusion distance of gases. The cell is also very flexible, making it capable of squeezing through narrow and twisting capillaries so that its walls and those of the capillary may be in\xa0close contact and again diffusion distances are reduced.', '396c63b3-8995-41de-a103-31ebc88c8ab7': 'Each RBC is capable of holding up to 250 million hemoglobin molecules, so consequently is capable of holding one billion oxygen molecules; as such the RBC fulfills its primary role of oxygen transport well. This oxygen transport system fails in anemias that result in either too few red blood cells\xa0or too little hemoglobin in each cell (or both). Now let us look at the behavior of hemoglobin.', 'b3a2853f-4d49-466c-b233-b1e3ad132937': 'The behavior of hemoglobin is best described by the oxygen saturation curve (figure 16.2), and this is one of the most important curves to understand in medicine. The curve shows the percentage of hemoglobin that has all of its heme molecules bound with oxygen (i.e., are saturated). So for example a 50 percent\xa0saturation would mean that half of the heme sites were occupied by oxygen. The curve shows percentage saturation in relation to oxygen partial pressure, and what should be immediately noticeable is that the higher the partial pressure of oxygen then the greater the saturation. But the relationship is far from linear and its shape offers several important physiological advantages. If it helps understand it, think of this curve as an instruction manual for hemoglobin,\xa0telling how saturated it should be at any PO2. In reality it is an enzyme kinetics curve, describing hemoglobin’s affinity for oxygen over a range of PO2.', '240bd48e-3307-4e02-a6c4-3980b6721979': 'First\xa0let us put the curve in a physiological context. The alveolar PO2\xa0is around 100 mmHg. This means that as blood passes the alveoli and is exposed to this PO2, then oxygen saturation becomes close to 100 percent, about 98 percent. The first important physiological feature of this curve is that PO2\xa0can fall a considerably long way before it has an impact on oxygen saturation. So, taking time to look at the numbers on the graph, let us say, for example, that a patient begins to hypoventilate and alveolar PO2\xa0falls to 70 mmHg; while this is a considerable fall in PO2, the saturation will only fall a few percentage points, and PO2\xa0must\xa0fall to 50 before significant loss of saturation, or desaturation, occurs. Below 50, however, notice how the curve rapidly steepens, and now for a small change in PO2, we get a large desaturation.', '57274494-19e2-4442-a9f6-72dc7f08e65a': 'This steep section of the curve is therefore clinically critical. If your patient’s saturation monitor reads 83 percent\xa0what should spring into your mind is it that such a low saturation puts the patient onto the steep part of the curve. It will now take only a small further decline in alveolar PO2\xa0to have a profound effect on saturation, unlike at the top and flat section of the curve where small changes in alveolar PO2\xa0have very little effect on saturation.', 'ae59bbfa-2b77-438a-a039-3640d3f50564': 'So what is the advantage of having such a steep curve at lower PO2s? Let us look at the physiological situation again. We have\xa0already said that the alveolar PO2\xa0of 100 results in a saturation close to 100 percent (i.e., at the lung the hemoglobin\xa0has a high affinity for oxygen and becomes fully saturated).', '9db43d4c-5e74-4450-aeb0-f34c80abd999': 'At the tissue, however, we want hemoglobin\xa0to lose its affinity for oxygen and release some to the metabolizing cells. At the tissue the local PO2\xa0is much lower, around 40, because of the oxygen consumption by the tissue. At the lower PO2, hemoglobin’s affinity for oxygen falls, and it will lose some of its oxygen to the tissue and saturation will fall. This is ideal, as now our oxygen carrier is capable of releasing oxygen where it is\xa0needed.', '5b86e2bb-12a9-4a32-80fa-554e0dcae3ee': 'If tissue PO2\xa0falls even lower, such as when metabolic rate is high, then more oxygen will be released by hemoglobin as its affinity for oxygen declines with the lower tissue PO2. Therefore the delivery system for oxygen is intrinsically tied to metabolic rate.', '56b865af-bc70-47ec-8696-ba94d1f42869': 'The shape of this curve makes hemoglobin a remarkable molecule—able to grab oxygen at the oxygen-providing lung, but relinquish it to oxygen-demanding tissue and relinquish more when the tissue needs more. There are other factors that fine-tune the amount of oxygen delivered to tissue to match its oxygen demand. This is summarized in figure 16.3.', '4ed813be-9b8e-460b-bafa-7979fda65ba0': 'Levitsky, Michael G. “Chapter 7: Transport of Oxygen and Carbon Dioxide in the Blood.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'd6a16cf9-d059-46b3-b7e2-0261a878af63': 'West, John B. “Chapter 6: Gas Transport by the Blood—How Gases Are Moved to the Peripheral Tissues.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'eebcdd0d-d4a0-48ea-b604-9534d41496ed': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 6.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '279562ba-f525-4412-9982-1e9c07d279bb': 'There are two circulatory networks that normally form shunts. The bronchial circulation, that supplies\xa0the bronchi, empties its venous blood into the pulmonary veins, thereby sending slightly deoxygenated blood back toward the left heart and into the systemic arterial system. Likewise a very small portion of the coronary venous blood is returned to the left ventricle (through the thebesian veins) and thereby bypasses the lung completely before going back in the systemic circulation.', 'e26d0d11-466b-4a31-bc87-c83397920658': 'These two wayward circulations and the imperfect V/Q matching in the lung serve to suppress arterial oxygen saturation.', 'c0f16823-bf43-4645-9269-c51c6ce26d14': 'Levitsky, Michael G. “Chapter 5: Ventilation–Perfusion Relationships.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '4a3745c2-5916-41da-b111-3377965154c7': 'West, John B. “Chapter 5: Ventilation–Perfusion Relationships—How Matching of Gas and Blood Determines Gas Exchange.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '0b3f01fc-f893-4c2a-ba14-78f6613e445c': 'Levitsky, Michael G. “Chapter 3: Alveolar Ventilation.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'ef7d1b93-3a1e-49fe-8e36-f72ffeb5d196': 'Let us\xa0start with a description of the ideal situation, where ventilation to alveoli is matched with the perfusion, then we will see how the lung does not quite achieve this.', '20443118-b1a8-481e-b40b-fabc2cdacdae': 'This is what we would expect if the lung were perfect, with uniform distribution of ventilation and perfusion to all regions and a V/Q of 1 in all regions.', '1266c3d9-2603-4ab5-a23b-c4c09c575487': 'The lung is not a perfect organ, however, and ventilation and perfusion are not equally distributed, and the lung as a whole only achieves an average V/Q of 0.8, which is close to our ideal of 1, but not quite there. Consequently, by the time the blood has passed the alveoli and regrouped in the pulmonary veins, the PO2 of the blood is less than alveolar. This alveolar–arterial PO2 difference is caused by the less-than-perfect matching of V and Q across the lung; but it is\xa0not all the lung’s fault, as venous blood that has been through the bronchial and a small section of the coronary circulation (and therefore is deoxygenated) is mixed into the vessels returning to the left heart, which brings down arterial saturation as well. The mixing-in of bronchial and coronary circulations and the less-than-ideal V/Q in the lung as a whole is the reason why your saturation monitors do not\xa0read 100 percent, but normal oxygen saturation is considered as 96–98 percent.', '736d22e3-bd4e-497c-bf9a-992a06cc406d': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 7.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'c7f4c268-560a-4009-8867-a730d1d4a684': 'Levitsky, Michael G. “Chapter 8: Acid–Base Balance.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '405afb7b-5d31-4d56-b756-36329df0d2fa': 'Levitsky, Michael G. “Chapter 10: Nonrespiratory Functions of the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9cfd8d5d-3721-4961-8c24-8b2bba6b0e82': 'West, John B. “Chapter 4: Blood Flow and Metabolism—How the Pulmonary Circulation Removes Gas from the Lung and Alters Some Metabolites.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '5bbf18cb-720e-433f-a97c-7a9a17affa5c': 'Levitsky, Michael G. “Chapter 4: Blood Flow to the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '58f3e187-02d3-4794-a834-033ae16daf9b': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 5.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '7ee7bd78-ee76-462c-8326-3223973d9968': 'Levitsky, Michael G. “Chapter 6: Diffusion of Gases and Interpretation of Pulmonary Function Tests.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '7098f0e3-8f6c-4a7f-8bb9-019917fbc96e': 'West, John B. “Chapter 3: Diffusion—How Gas Gets Across the Blood–Gas Barrier.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '83eef49d-f1b3-4248-908d-fe1c99a681e8': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 4.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '94a2e555-32f9-4cc7-8f5b-ef7daead5687': 'Before we do that though, we need to be able to calculate the units of measurement we use when describing gas exchange. When referring to gas exchange we are really referring to diffusion of gases down their concentration gradient, but rather than use concentrations, we use partial pressures.', '83d5f78d-9abb-48e8-b071-bef116366b8f': 'Partial pressures describe what proportion of the total pressure is exerted by a particular component of a mixed gas. Let us\xa0look at the specific situation we are interested in to illustrate this description.', 'd82456a7-eec8-4a00-acb8-976db3f8f866': 'Atmospheric pressure at sea level is 760 mmHg. This pressure is generated by the collisions of all the molecules with each other and other objects. At high altitude there are fewer molecules, so fewer collisions, and hence atmospheric pressure is lower.', 'a630d4b8-fca5-42f2-b5b5-7435455e5bc6': 'Now looking at the composition of our atmosphere we know that 79 percent\xa0is nitrogen, 20.9 percent\xa0is oxygen, and some trace gases collectively get us to 100 percent. Now let us\xa0calculate a partial pressure. If 79 percent\xa0of the atmosphere is nitrogen, then 79 percent\xa0of our atmospheric pressure is generated by the collisions by nitrogen molecules. Likewise 20.9 percent\xa0of the atmospheric pressure is due to oxygen, so to calculate the partial pressure of oxygen (PO2) we simply multiply atmospheric pressure (PB) by the percentage of oxygen, which means our atmosphere has a partial pressure of oxygen of 159 mmHg.', 'e125ba2f-6da8-4e10-bea6-e132c5f31f62': 'Although this phenomenon is present in the healthy lung, we will see how it is exacerbated in certain disease states and how this exacerbation can be detected by common pulmonary function tests.', '6443f20b-c2ba-4f2a-912d-b820480b48dc': 'First, let us\xa0look at the forces involved during a normal, passive expiration.', 'b41f13e9-f936-4f36-a5cf-fb0da07ecd91': 'For simplicity, the schematic in figure 6.1 shows one airway and an alveolus within the thoracic cavity. At the onset of passive expiration (driven by the recoil of the expanded lung), the intrapleural pressure is negative (about −8 cm H2O). As it remains negative, intrapleural pressure helps keep the airways open.', 'e3fd9346-74ee-4550-ac3d-c10b889a9616': 'West, John B. “Chapter 7: Mechanics of Breathing—How the Lung Is Supported and Moved.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'f3d82c09-4fa4-4232-b7c2-ca82c3f0e4d6': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 3.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '2abbd8fc-bc45-4021-95f3-7cc764fb7854': 'The first factor we must consider when thinking about airflow is the type of flow that is occurring.', '90b7c113-9453-48ab-af12-da3e977c0466': 'The most efficient form of flow is laminar\xa0(i.e., laminar flow takes the lowest pressure differential for flow to occur). In laminar flow the molecules are moving in an orderly manner, those at the side of the tube moving a little slower due to contact with tube walls\xa0and those in the middle moving fastest (figure 5.1).', '185f8384-ae77-4ecc-8216-cf9651f31397': 'When velocity increases or tube radius decreases then this organization is lost. Collisions between molecules and with the tube wall are now more frequent and movement is more chaotic, and the flow becomes turbulent (figure 5.2). At this point some molecules are at times moving against the pressure gradient due to these collisions. Consequently, to generate the same amount of molecule movement (i.e., flow) from one end of the tube to another, a greater pressure differential is needed when flow becomes turbulent. Turbulent flow is more common in the large airways where velocity and airway radius are high.', '78016837-1b1e-4b72-9459-159a81636088': 'In reality, the vast majority of the airways are branching small tubes, so we see a mixture of the two above—mostly laminar flow but some turbulence generated at the branch (or transitional) points (figure 5.3).', 'd8c9a412-74b3-47d6-9885-10a68f3195dc': 'For our purposes though we are going to look at the factors that affect flow when it is laminar—the dominant form of flow in the majority of airways. These factors are described by Poiselle’s equation. We will now break down Poiselle’s equation in relation to flow of air down airways. Although initially an intimidating equation, there are some things we can generally ignore.', '329ee30f-0280-4186-a272-76cda4611f6d': 'Equation 5.1', 'ccf522d3-ed2e-4e8f-951d-b5f59bf4614f': 'Levitsky, Michael G. “Chapter 2: Mechanics of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '6122ed24-6881-4243-b127-64fd05cdb94a': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 1.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '3265bb73-23ce-4e55-b347-c6a6e3d0f4a2': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 2.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '5b7cdf1c-6e3e-4689-a4b4-001b0e7d0b85': 'Before we get into the details of how we breathe in, let me make sure we are all on the same page by going right back to basics, so bare with me or skip ahead if you are happy with pressure, volume, and flow.', '9e430d7f-a263-41b5-819a-5d6f57a475d3': 'To get air to move into the lungs we need to generate a pressure differential;\xa0that is the pressure inside the lungs must be lower than the pressure outside\xa0(i.e., atmospheric pressure), so that air moves down the pressure gradient into the lungs.', '2a56dfa9-1088-4e0d-8a05-7d0dae7eabe3': 'The low pressure inside the lungs is generated by increasing lung volume; bigger volume means fewer molecules in the same space, and therefore lower pressure (go back and revisit Boyle’s law if needed).', '700a30d9-cdcb-4a22-934d-dbb9221c27e8': 'The basis of inspiration is lowering lung pressure below atmospheric pressure, so that atmospheric pressure pushes air down the airways until pressure equilibrates. So the fundamental first step is, how do we increase lung volume?', 'f0582f89-5080-4d8c-973f-c82797cb93ae': 'To understand the mechanics of breathing we have to deal with two concepts:\xa0first how the action of the respiratory muscles increases thoracic volume, and second\xa0(and more complex) we need to understand the interaction of the lungs and the thoracic wall.', 'cf71568f-25a9-4c48-880c-f5fdda101c9b': 'Let us deal with the respiratory muscles and expansion of the thorax first.', '338eec0f-6210-47e2-815e-4cb6f22fc67a': 'West, John B. “Chapter 2: Ventilation—How Gas Gets to the Alveoli.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '3c8b34ab-c9f8-4728-8aad-518dd91e7284': 'We will see how blood gases are monitored and maintained through neurochemical control of lung expansion and relaxation to achieve the appropriate level of alveolar ventilation. Factors that affect the\xa0degree of gas exchange between the lung and blood will be discussed, along with the coordination of ventilation and perfusion of the lung. Finally, we will see how oxygen and carbon dioxide are transported in the bloodstream to and from tissue and the mechanisms that ensure appropriate delivery and a stable blood gas environment.\xa0Before we begin, however, we will look at the functional anatomy of the lung and how the lung is well designed to perform its primary role and defend itself from the external environment.', 'bb13387c-a557-4bd6-8b04-3e30d6d82916': 'Levitsky, Michael G. “Chapter 1: Function and Structure of the Respiratory System.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9faee6ea-d9bf-4b11-a3d3-8561cb811717': 'West, John B. “Chapter 1: Structure and Function—How the Architecture of the Lung Subserves Its Function.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.'}"
+Figure 16.4,pulmo2/images/Figure 16.4.jpg,Figure 16.4: Effect of temperature on the saturation curve.,"Shifts with temperature: Figure 16.4 shows the saturation curve at difference tissue temperatures. The curve we have just looked at was at 38ºC. Notice that as temperature is reduced, the curve shifts to the left, but more importantly (physiologically) when temperature increases then the curve shifts to the right. Let us look at what this means in terms of hemoglobin’s affinity for oxygen (follow the numbers on the graph again). As before, we will assume that our tissue PO2 is 40 mmHg, and at normal temperatures this results in a saturation of about 70 percent.","{'fc79ef8e-374a-45ad-b458-bf2beabb7f8e': 'The metabolic rate of tissue determines its oxygen demand, with more active\xa0tissue requiring hemoglobin to relinquish more oxygen. So there are several other factors, beyond low local PO2, that are associated with active tissue that cause hemoglobin to reduce its affinity for oxygen and therefore release it. Tissue with a high metabolic rate tends to have (1) higher temperature, (2) high PCO2, and (3) lower pH. We can look at the effect of each of these factors on the saturation curve.', '2bb04c75-d144-4a6c-9c8e-4498ac2e1887': 'Shifts with temperature: Figure 16.4\xa0shows the saturation curve at difference tissue temperatures. The curve we have just looked at was at 38ºC. Notice that as temperature is reduced, the curve shifts to the left, but more importantly (physiologically) when temperature increases then the curve shifts to the right. Let us look at what this means in terms of hemoglobin’s affinity for oxygen (follow the numbers on the graph again). As before, we will assume that our tissue PO2\xa0is 40 mmHg, and at normal temperatures this results in a saturation of about 70 percent.', 'da148794-5848-490d-b6cf-40af24935c19': 'Now at the same PO2\xa0but a higher temperature (e.g., 43ºC) the hemoglobin\xa0O2\xa0saturation falls to a little over 50 percent, meaning that more oxygen has been relinquished to the tissue (i.e., an increase in temperature reduces hemoglobin’s affinity for oxygen).', '211cabf9-d406-4501-9908-849d3790c833': 'Shifts with CO2: We see a similar situation with a rise in PCO2, shown in figure 16.5\xa0with the saturation curve at different PCO2s. At a normal arterial PCO2\xa0(40 mmHg) we get the same saturation\xa0curve that we saw previously. But if PCO2 is raised, such as in the locality of highly active tissue (e.g., 80 mmHg), then the curve shifts rightward. Again this means that hemoglobin’s affinity is lowered at equivalent PO2 and more oxygen is released, resulting in a lower saturation.', 'b7dca429-0ab1-4cc0-8453-0f8954dbb0b6': 'Shifts with pH: Finally, the same is true for changes in pH, shown in figure 16.6\xa0with the curve at different pHs. When pH falls, as in active tissue, then the curve shifts rightward from its normal position at normal pH (7.4). Again, this result\xa0describes a lowered affinity for oxygen, so at equivalent levels of PO2 more oxygen is released when the hemoglobin enters a low pH environment (e.g., 7.2 shown on figure 16.6). Obviously pH and PCO2 are related, and their effect on hemoglobin\xa0binding is known as the Bohr effect.', '586eb5e0-d3bf-4f95-8cd4-ded1f58d5fad': 'One last factor that causes this rightward shift is 2,3 diphosphoglycerate, or DPG. DPG is an end product of RBC metabolism, and as it increases inside the cell it reduces hemoglobins, affinity for oxygen. Elevated DPG levels are associated with chronic hypoxia, such as experienced at altitude\xa0or more pertinently in the presence of chronic lung disease. Conversely, DPG levels are lower in stored blood, so transfused blood may have a problem giving up its oxygen.', '1fef71c1-4e58-4c5b-a2dd-2ff64270fa82': 'All these factors mean that hemoglobin will deliver more oxygen to busy tissue.', '3a1b9676-8f37-4ed5-a186-1380b218d734': 'Total oxygen carriage: So far we have discussed oxygen transport in terms of hemoglobin only. But despite its lack of solubility, some oxygen can dissolve into the plasma. Realistically this is a very small amount at physiological partial pressures (i.e. at an alveolar PO2 of 100 mmHg only a fraction of a milliliter of oxygen will dissolve into the blood, as figure 16.7 shows).', '4fb823cf-5ec6-4af0-be80-d21a46d8957e': 'Obviously this amount of oxygen is completely inadequate to support metabolism and illustrates the need for hemoglobin. But this minute amount when added to the O2 combined to the hemoglobin makes up the total O2 content of the blood. When calculating the oxygen content of the blood we must consider both of these compartments—hemoglobin and plasma (figure 16.8).'}"
+Figure 16.5,pulmo2/images/Figure 16.5.jpg,Figure 16.5: Effect of PCO2 on the saturation curve.,"Shifts with CO2: We see a similar situation with a rise in PCO2, shown in figure 16.5 with the saturation curve at different PCO2s. At a normal arterial PCO2 (40 mmHg) we get the same saturation curve that we saw previously. But if PCO2 is raised, such as in the locality of highly active tissue (e.g., 80 mmHg), then the curve shifts rightward. Again this means that hemoglobin’s affinity is lowered at equivalent PO2 and more oxygen is released, resulting in a lower saturation.","{'fc79ef8e-374a-45ad-b458-bf2beabb7f8e': 'The metabolic rate of tissue determines its oxygen demand, with more active\xa0tissue requiring hemoglobin to relinquish more oxygen. So there are several other factors, beyond low local PO2, that are associated with active tissue that cause hemoglobin to reduce its affinity for oxygen and therefore release it. Tissue with a high metabolic rate tends to have (1) higher temperature, (2) high PCO2, and (3) lower pH. We can look at the effect of each of these factors on the saturation curve.', '2bb04c75-d144-4a6c-9c8e-4498ac2e1887': 'Shifts with temperature: Figure 16.4\xa0shows the saturation curve at difference tissue temperatures. The curve we have just looked at was at 38ºC. Notice that as temperature is reduced, the curve shifts to the left, but more importantly (physiologically) when temperature increases then the curve shifts to the right. Let us look at what this means in terms of hemoglobin’s affinity for oxygen (follow the numbers on the graph again). As before, we will assume that our tissue PO2\xa0is 40 mmHg, and at normal temperatures this results in a saturation of about 70 percent.', 'da148794-5848-490d-b6cf-40af24935c19': 'Now at the same PO2\xa0but a higher temperature (e.g., 43ºC) the hemoglobin\xa0O2\xa0saturation falls to a little over 50 percent, meaning that more oxygen has been relinquished to the tissue (i.e., an increase in temperature reduces hemoglobin’s affinity for oxygen).', '211cabf9-d406-4501-9908-849d3790c833': 'Shifts with CO2: We see a similar situation with a rise in PCO2, shown in figure 16.5\xa0with the saturation curve at different PCO2s. At a normal arterial PCO2\xa0(40 mmHg) we get the same saturation\xa0curve that we saw previously. But if PCO2 is raised, such as in the locality of highly active tissue (e.g., 80 mmHg), then the curve shifts rightward. Again this means that hemoglobin’s affinity is lowered at equivalent PO2 and more oxygen is released, resulting in a lower saturation.', 'b7dca429-0ab1-4cc0-8453-0f8954dbb0b6': 'Shifts with pH: Finally, the same is true for changes in pH, shown in figure 16.6\xa0with the curve at different pHs. When pH falls, as in active tissue, then the curve shifts rightward from its normal position at normal pH (7.4). Again, this result\xa0describes a lowered affinity for oxygen, so at equivalent levels of PO2 more oxygen is released when the hemoglobin enters a low pH environment (e.g., 7.2 shown on figure 16.6). Obviously pH and PCO2 are related, and their effect on hemoglobin\xa0binding is known as the Bohr effect.', '586eb5e0-d3bf-4f95-8cd4-ded1f58d5fad': 'One last factor that causes this rightward shift is 2,3 diphosphoglycerate, or DPG. DPG is an end product of RBC metabolism, and as it increases inside the cell it reduces hemoglobins, affinity for oxygen. Elevated DPG levels are associated with chronic hypoxia, such as experienced at altitude\xa0or more pertinently in the presence of chronic lung disease. Conversely, DPG levels are lower in stored blood, so transfused blood may have a problem giving up its oxygen.', '1fef71c1-4e58-4c5b-a2dd-2ff64270fa82': 'All these factors mean that hemoglobin will deliver more oxygen to busy tissue.', '3a1b9676-8f37-4ed5-a186-1380b218d734': 'Total oxygen carriage: So far we have discussed oxygen transport in terms of hemoglobin only. But despite its lack of solubility, some oxygen can dissolve into the plasma. Realistically this is a very small amount at physiological partial pressures (i.e. at an alveolar PO2 of 100 mmHg only a fraction of a milliliter of oxygen will dissolve into the blood, as figure 16.7 shows).', '4fb823cf-5ec6-4af0-be80-d21a46d8957e': 'Obviously this amount of oxygen is completely inadequate to support metabolism and illustrates the need for hemoglobin. But this minute amount when added to the O2 combined to the hemoglobin makes up the total O2 content of the blood. When calculating the oxygen content of the blood we must consider both of these compartments—hemoglobin and plasma (figure 16.8).'}"
+Figure 16.6,pulmo2/images/Figure 16.6.jpg,Figure 16.6: Effect of pH on the saturation curve.,"Shifts with pH: Finally, the same is true for changes in pH, shown in figure 16.6 with the curve at different pHs. When pH falls, as in active tissue, then the curve shifts rightward from its normal position at normal pH (7.4). Again, this result describes a lowered affinity for oxygen, so at equivalent levels of PO2 more oxygen is released when the hemoglobin enters a low pH environment (e.g., 7.2 shown on figure 16.6). Obviously pH and PCO2 are related, and their effect on hemoglobin binding is known as the Bohr effect.","{'fc79ef8e-374a-45ad-b458-bf2beabb7f8e': 'The metabolic rate of tissue determines its oxygen demand, with more active\xa0tissue requiring hemoglobin to relinquish more oxygen. So there are several other factors, beyond low local PO2, that are associated with active tissue that cause hemoglobin to reduce its affinity for oxygen and therefore release it. Tissue with a high metabolic rate tends to have (1) higher temperature, (2) high PCO2, and (3) lower pH. We can look at the effect of each of these factors on the saturation curve.', '2bb04c75-d144-4a6c-9c8e-4498ac2e1887': 'Shifts with temperature: Figure 16.4\xa0shows the saturation curve at difference tissue temperatures. The curve we have just looked at was at 38ºC. Notice that as temperature is reduced, the curve shifts to the left, but more importantly (physiologically) when temperature increases then the curve shifts to the right. Let us look at what this means in terms of hemoglobin’s affinity for oxygen (follow the numbers on the graph again). As before, we will assume that our tissue PO2\xa0is 40 mmHg, and at normal temperatures this results in a saturation of about 70 percent.', 'da148794-5848-490d-b6cf-40af24935c19': 'Now at the same PO2\xa0but a higher temperature (e.g., 43ºC) the hemoglobin\xa0O2\xa0saturation falls to a little over 50 percent, meaning that more oxygen has been relinquished to the tissue (i.e., an increase in temperature reduces hemoglobin’s affinity for oxygen).', '211cabf9-d406-4501-9908-849d3790c833': 'Shifts with CO2: We see a similar situation with a rise in PCO2, shown in figure 16.5\xa0with the saturation curve at different PCO2s. At a normal arterial PCO2\xa0(40 mmHg) we get the same saturation\xa0curve that we saw previously. But if PCO2 is raised, such as in the locality of highly active tissue (e.g., 80 mmHg), then the curve shifts rightward. Again this means that hemoglobin’s affinity is lowered at equivalent PO2 and more oxygen is released, resulting in a lower saturation.', 'b7dca429-0ab1-4cc0-8453-0f8954dbb0b6': 'Shifts with pH: Finally, the same is true for changes in pH, shown in figure 16.6\xa0with the curve at different pHs. When pH falls, as in active tissue, then the curve shifts rightward from its normal position at normal pH (7.4). Again, this result\xa0describes a lowered affinity for oxygen, so at equivalent levels of PO2 more oxygen is released when the hemoglobin enters a low pH environment (e.g., 7.2 shown on figure 16.6). Obviously pH and PCO2 are related, and their effect on hemoglobin\xa0binding is known as the Bohr effect.', '586eb5e0-d3bf-4f95-8cd4-ded1f58d5fad': 'One last factor that causes this rightward shift is 2,3 diphosphoglycerate, or DPG. DPG is an end product of RBC metabolism, and as it increases inside the cell it reduces hemoglobins, affinity for oxygen. Elevated DPG levels are associated with chronic hypoxia, such as experienced at altitude\xa0or more pertinently in the presence of chronic lung disease. Conversely, DPG levels are lower in stored blood, so transfused blood may have a problem giving up its oxygen.', '1fef71c1-4e58-4c5b-a2dd-2ff64270fa82': 'All these factors mean that hemoglobin will deliver more oxygen to busy tissue.', '3a1b9676-8f37-4ed5-a186-1380b218d734': 'Total oxygen carriage: So far we have discussed oxygen transport in terms of hemoglobin only. But despite its lack of solubility, some oxygen can dissolve into the plasma. Realistically this is a very small amount at physiological partial pressures (i.e. at an alveolar PO2 of 100 mmHg only a fraction of a milliliter of oxygen will dissolve into the blood, as figure 16.7 shows).', '4fb823cf-5ec6-4af0-be80-d21a46d8957e': 'Obviously this amount of oxygen is completely inadequate to support metabolism and illustrates the need for hemoglobin. But this minute amount when added to the O2 combined to the hemoglobin makes up the total O2 content of the blood. When calculating the oxygen content of the blood we must consider both of these compartments—hemoglobin and plasma (figure 16.8).'}"
+Figure 16.7,pulmo2/images/Figure 16.7.jpg,Figure 16.7: Oxygen carriage.,"Total oxygen carriage: So far we have discussed oxygen transport in terms of hemoglobin only. But despite its lack of solubility, some oxygen can dissolve into the plasma. Realistically this is a very small amount at physiological partial pressures (i.e. at an alveolar PO2 of 100 mmHg only a fraction of a milliliter of oxygen will dissolve into the blood, as figure 16.7 shows).","{'fc79ef8e-374a-45ad-b458-bf2beabb7f8e': 'The metabolic rate of tissue determines its oxygen demand, with more active\xa0tissue requiring hemoglobin to relinquish more oxygen. So there are several other factors, beyond low local PO2, that are associated with active tissue that cause hemoglobin to reduce its affinity for oxygen and therefore release it. Tissue with a high metabolic rate tends to have (1) higher temperature, (2) high PCO2, and (3) lower pH. We can look at the effect of each of these factors on the saturation curve.', '2bb04c75-d144-4a6c-9c8e-4498ac2e1887': 'Shifts with temperature: Figure 16.4\xa0shows the saturation curve at difference tissue temperatures. The curve we have just looked at was at 38ºC. Notice that as temperature is reduced, the curve shifts to the left, but more importantly (physiologically) when temperature increases then the curve shifts to the right. Let us look at what this means in terms of hemoglobin’s affinity for oxygen (follow the numbers on the graph again). As before, we will assume that our tissue PO2\xa0is 40 mmHg, and at normal temperatures this results in a saturation of about 70 percent.', 'da148794-5848-490d-b6cf-40af24935c19': 'Now at the same PO2\xa0but a higher temperature (e.g., 43ºC) the hemoglobin\xa0O2\xa0saturation falls to a little over 50 percent, meaning that more oxygen has been relinquished to the tissue (i.e., an increase in temperature reduces hemoglobin’s affinity for oxygen).', '211cabf9-d406-4501-9908-849d3790c833': 'Shifts with CO2: We see a similar situation with a rise in PCO2, shown in figure 16.5\xa0with the saturation curve at different PCO2s. At a normal arterial PCO2\xa0(40 mmHg) we get the same saturation\xa0curve that we saw previously. But if PCO2 is raised, such as in the locality of highly active tissue (e.g., 80 mmHg), then the curve shifts rightward. Again this means that hemoglobin’s affinity is lowered at equivalent PO2 and more oxygen is released, resulting in a lower saturation.', 'b7dca429-0ab1-4cc0-8453-0f8954dbb0b6': 'Shifts with pH: Finally, the same is true for changes in pH, shown in figure 16.6\xa0with the curve at different pHs. When pH falls, as in active tissue, then the curve shifts rightward from its normal position at normal pH (7.4). Again, this result\xa0describes a lowered affinity for oxygen, so at equivalent levels of PO2 more oxygen is released when the hemoglobin enters a low pH environment (e.g., 7.2 shown on figure 16.6). Obviously pH and PCO2 are related, and their effect on hemoglobin\xa0binding is known as the Bohr effect.', '586eb5e0-d3bf-4f95-8cd4-ded1f58d5fad': 'One last factor that causes this rightward shift is 2,3 diphosphoglycerate, or DPG. DPG is an end product of RBC metabolism, and as it increases inside the cell it reduces hemoglobins, affinity for oxygen. Elevated DPG levels are associated with chronic hypoxia, such as experienced at altitude\xa0or more pertinently in the presence of chronic lung disease. Conversely, DPG levels are lower in stored blood, so transfused blood may have a problem giving up its oxygen.', '1fef71c1-4e58-4c5b-a2dd-2ff64270fa82': 'All these factors mean that hemoglobin will deliver more oxygen to busy tissue.', '3a1b9676-8f37-4ed5-a186-1380b218d734': 'Total oxygen carriage: So far we have discussed oxygen transport in terms of hemoglobin only. But despite its lack of solubility, some oxygen can dissolve into the plasma. Realistically this is a very small amount at physiological partial pressures (i.e. at an alveolar PO2 of 100 mmHg only a fraction of a milliliter of oxygen will dissolve into the blood, as figure 16.7 shows).', '4fb823cf-5ec6-4af0-be80-d21a46d8957e': 'Obviously this amount of oxygen is completely inadequate to support metabolism and illustrates the need for hemoglobin. But this minute amount when added to the O2 combined to the hemoglobin makes up the total O2 content of the blood. When calculating the oxygen content of the blood we must consider both of these compartments—hemoglobin and plasma (figure 16.8).'}"
+Figure 16.8,pulmo2/images/Figure 16.8.jpg,Figure 16.8: Compartment of blood oxygen content.,Obviously this amount of oxygen is completely inadequate to support metabolism and illustrates the need for hemoglobin. But this minute amount when added to the O2 combined to the hemoglobin makes up the total O2 content of the blood. When calculating the oxygen content of the blood we must consider both of these compartments—hemoglobin and plasma (figure 16.8).,"{'fc79ef8e-374a-45ad-b458-bf2beabb7f8e': 'The metabolic rate of tissue determines its oxygen demand, with more active\xa0tissue requiring hemoglobin to relinquish more oxygen. So there are several other factors, beyond low local PO2, that are associated with active tissue that cause hemoglobin to reduce its affinity for oxygen and therefore release it. Tissue with a high metabolic rate tends to have (1) higher temperature, (2) high PCO2, and (3) lower pH. We can look at the effect of each of these factors on the saturation curve.', '2bb04c75-d144-4a6c-9c8e-4498ac2e1887': 'Shifts with temperature: Figure 16.4\xa0shows the saturation curve at difference tissue temperatures. The curve we have just looked at was at 38ºC. Notice that as temperature is reduced, the curve shifts to the left, but more importantly (physiologically) when temperature increases then the curve shifts to the right. Let us look at what this means in terms of hemoglobin’s affinity for oxygen (follow the numbers on the graph again). As before, we will assume that our tissue PO2\xa0is 40 mmHg, and at normal temperatures this results in a saturation of about 70 percent.', 'da148794-5848-490d-b6cf-40af24935c19': 'Now at the same PO2\xa0but a higher temperature (e.g., 43ºC) the hemoglobin\xa0O2\xa0saturation falls to a little over 50 percent, meaning that more oxygen has been relinquished to the tissue (i.e., an increase in temperature reduces hemoglobin’s affinity for oxygen).', '211cabf9-d406-4501-9908-849d3790c833': 'Shifts with CO2: We see a similar situation with a rise in PCO2, shown in figure 16.5\xa0with the saturation curve at different PCO2s. At a normal arterial PCO2\xa0(40 mmHg) we get the same saturation\xa0curve that we saw previously. But if PCO2 is raised, such as in the locality of highly active tissue (e.g., 80 mmHg), then the curve shifts rightward. Again this means that hemoglobin’s affinity is lowered at equivalent PO2 and more oxygen is released, resulting in a lower saturation.', 'b7dca429-0ab1-4cc0-8453-0f8954dbb0b6': 'Shifts with pH: Finally, the same is true for changes in pH, shown in figure 16.6\xa0with the curve at different pHs. When pH falls, as in active tissue, then the curve shifts rightward from its normal position at normal pH (7.4). Again, this result\xa0describes a lowered affinity for oxygen, so at equivalent levels of PO2 more oxygen is released when the hemoglobin enters a low pH environment (e.g., 7.2 shown on figure 16.6). Obviously pH and PCO2 are related, and their effect on hemoglobin\xa0binding is known as the Bohr effect.', '586eb5e0-d3bf-4f95-8cd4-ded1f58d5fad': 'One last factor that causes this rightward shift is 2,3 diphosphoglycerate, or DPG. DPG is an end product of RBC metabolism, and as it increases inside the cell it reduces hemoglobins, affinity for oxygen. Elevated DPG levels are associated with chronic hypoxia, such as experienced at altitude\xa0or more pertinently in the presence of chronic lung disease. Conversely, DPG levels are lower in stored blood, so transfused blood may have a problem giving up its oxygen.', '1fef71c1-4e58-4c5b-a2dd-2ff64270fa82': 'All these factors mean that hemoglobin will deliver more oxygen to busy tissue.', '3a1b9676-8f37-4ed5-a186-1380b218d734': 'Total oxygen carriage: So far we have discussed oxygen transport in terms of hemoglobin only. But despite its lack of solubility, some oxygen can dissolve into the plasma. Realistically this is a very small amount at physiological partial pressures (i.e. at an alveolar PO2 of 100 mmHg only a fraction of a milliliter of oxygen will dissolve into the blood, as figure 16.7 shows).', '4fb823cf-5ec6-4af0-be80-d21a46d8957e': 'Obviously this amount of oxygen is completely inadequate to support metabolism and illustrates the need for hemoglobin. But this minute amount when added to the O2 combined to the hemoglobin makes up the total O2 content of the blood. When calculating the oxygen content of the blood we must consider both of these compartments—hemoglobin and plasma (figure 16.8).'}"
+Figure 16.9,pulmo2/images/Figure 16.9.jpg,Figure 16.9: Formation of bicarbonate at the tissue.,"The bicarbonate ion is pumped out of the cell, but without intervention this would leave the inside of the cell too positively charged as the negative charge of the bicarbonate is lost. To maintain electroneutrality the bicarbonate is exchanged for a chloride ion; this process is referred to as the chloride shift. The formation of bicarbonate at the tissue is summarized in figure 16.9.","{'ce63434c-8f96-4e2f-8362-b545fcf90d39': 'High concentrations of CO2 at the tissue push this equation right to produce bicarbonate.', 'abd5629c-c673-4e9a-8df0-aa831db05237': 'The bicarbonate ion is pumped out of the cell, but without intervention this would leave the inside of the cell too positively charged as the negative charge of the bicarbonate is lost. To maintain electroneutrality the bicarbonate is exchanged for a chloride ion; this process is referred to as the chloride shift. The formation of bicarbonate at the tissue is summarized in figure 16.9.', 'fc091c03-7cae-437e-a615-41436e19bee0': 'The CO2\xa0now travels through the bloodstream as bicarbonate toward\xa0the lungs. At the lungs the process is basically reversed. The partial pressure of CO2\xa0at the lungs is low;\xa0consequently our equation is driven toward\xa0the left-hand side as CO2\xa0leaves toward\xa0the low alveolar PCO2\xa0(equation 16.6).', '215659fb-025a-4e62-a33c-af3b48508e3a': 'Equation 16.6', '9cab90f6-802a-4357-8093-bbe7a798e746': 'So after accounting for the dissociation constant of carbonic acid and CO2 and water, we can simply replace carbonic acid concentration with concentration of CO2 (equation 12.12).', '73357170-0c41-4678-be54-1f9ce98a2ba6': 'Equation 12.12'}"
+Figure 16.10,pulmo2/images/Figure 16.10.jpg,Figure 16.10: Reformation of CO2 at the lungs.,"All these moves help promote the right-to-left direction of our now infamous equation and the re-forming of CO2. Alveolar ventilation gets rid of the re-formed CO2 to the atmosphere, maintaining the alveolar PCO2 at relatively low levels and the direction of the equation right-to-left. The reformation of CO2 at the lungs is summarized in figure 16.10.","{'70d42d98-ce38-4c12-9f5b-cd34e4fcc912': 'High bicarbonate and low CO2\xa0at the lung force the equation leftward.', 'b186eeeb-b127-4a4e-aa75-ac5446c366c5': 'The high alveolar PO2\xa0also promotes the leftward movement—binding of oxygen to hemoglobin makes hemoglobin a less effective proton binder so it loses the proton and raises the amount of substrate on the right-hand side and thereby promotes reformation of CO2. The Haldane effect is also reversed—as hemoglobin gains oxygen at the lung it loses its affinity for CO2\xa0and releases it into the plasma. This raises plasma PCO2\xa0and promotes diffusion of CO2\xa0into the alveoli for expulsion.', '43f2b04d-f366-4f0b-87d5-ffafb597f78b': 'Likewise the chloride shift is reversed and bicarbonate reenters the cell as chloride is pumped back out.', '9116d612-5ccb-474a-8573-3bf4b72b4eda': 'All these moves\xa0help promote the right-to-left direction of our now infamous equation and the re-forming of CO2. Alveolar ventilation gets rid of the re-formed CO2\xa0to the atmosphere, maintaining the alveolar PCO2\xa0at relatively low levels and the direction of the equation right-to-left. The reformation of CO2\xa0at the lungs is summarized in figure 16.10.'}"
+Figure 16.11,pulmo2/images/Figure 16.11.jpg,Figure 16.11: CO2 dissociation curve.,"So, for want of a better name, we can also draw a CO2 dissociation or saturation curve, as is shown in figure 16.11. The graph shows the CO2 concentration in blood across a wide range of PCO2 and shows the effect of Hb O2 saturation on CO2 carriage. The CO2 dissociation curve is unlike the oxygen saturation curve and is virtually linear (i.e., the higher the PCO2, the higher the CO2 content of the blood); there is no plateau to the curve as we saw with O2 transport. The ramification of this is that the lower the alveolar PCO2, the lower the blood PCO2, and the higher the alveolar PCO2, the higher the blood PCO2. It is a very simple relationship that ends with the obvious statement that the more you breathe, the lower arterial CO2 becomes. It is worth reminding ourselves here that this is not a relationship seen with oxygen that is limited by the capacity of hemoglobin (breathing more does not necessarily result in more oxygen in the bloodstream). The other aspect to note here is the effect of hemoglobin’s oxygen saturation on carbon dioxide carriage. This has clinical ramifications, so we will look at this more closely.","{'d819d8c4-d693-44d1-8d35-4c4d37acecb7': 'So, for want of a better name, we can also draw a CO2\xa0dissociation or saturation curve, as is shown in figure 16.11. The graph shows the CO2\xa0concentration in blood across a wide range of PCO2\xa0and shows the effect of Hb O2\xa0saturation on CO2\xa0carriage. The CO2\xa0dissociation curve is unlike the oxygen saturation curve and is virtually linear (i.e., the higher the PCO2, the higher the CO2\xa0content of the blood); there is no plateau to the curve as we saw with O2\xa0transport. The ramification of this is that the lower the alveolar PCO2, the lower the blood PCO2, and the higher the alveolar PCO2, the higher the blood PCO2. It is\xa0a very simple relationship that ends with the obvious statement that the more you breathe, the lower arterial CO2\xa0becomes. It is worth reminding ourselves here that this is not a relationship seen with oxygen that is limited by the capacity of hemoglobin (breathing more does not necessarily result in more oxygen in the bloodstream). The other aspect to note here is the effect of hemoglobin’s oxygen saturation on carbon dioxide carriage. This has clinical ramifications, so we will look at this more closely.', '1a3609d2-2c4e-42a8-8d0c-313f22cb6f86': 'When deoxygenated, hemoglobin’s structure promotes binding of CO2\xa0and buffering of protons by the polypeptide chains. So when O2\xa0saturation is zero, the CO2\xa0and proton carrying capability of Hb is high. As already mentioned, this means that when Hb is in its deoxygenated form at the tissue, its CO2 carrying ability is increased.', 'b8b21369-d788-4de9-8042-8259b1d039cf': 'When we get to the lung, however, the Hb is exposed to the high alveolar PO2\xa0and oxygen binds to the heme sites and becomes saturated; this causes a conformational change, and the CO2\xa0and proton carrying ability is reduced. So conveniently CO2\xa0release is promoted at the lung.', 'da0e740b-9ae7-4eaa-8b46-ed5cadf7fa9c': 'Although CO2\xa0is highly soluble, very little of it can be transported as dissolved CO2\xa0in plasma because of its effect on pH. The majority is converted to bicarbonate in red blood cells and transported in plasma, while about 25 percent\xa0is transported bound to hemoglobin.'}"
+Figure 15.1,pulmo2/images/Figure 15.1.jpg,"Figure 15.1: Schematic of a pulmonary shunt (anatomical or physiological) showing flow (Q) through the pulmonary capillaries (QC), flow through the shunt (QS), and total flow (QT) returning to the left heart.","Because even a small shunt can have a large effect on arterial PO2, it is critical to determine the size of a shunt should one be suspected. Figure 15.1 shows the lungs with blood passing through as normal (QC), while some bypasses the heart (QS) and is shunted back into the systemic circulation. The size of a shunt (QS) is expressed as the percentage of total blood (QT in figure 15.1) (i.e., QS/QT). We will look now at how this is calculated from oxygen concentration. First, let us see what we know.","{'4ebe9b5f-9a81-497d-b977-d939be39cada': 'Because even a small shunt can have a large effect on arterial PO2, it is critical to determine the size of a shunt should one be suspected. Figure 15.1 shows the lungs with blood passing through as normal (QC), while some bypasses the heart (QS) and is shunted back into the systemic circulation. The size of a shunt (QS) is expressed as the percentage of total blood (QT\xa0in figure 15.1) (i.e., QS/QT). We will look now at how this is calculated from oxygen concentration. First, let us\xa0see what we know.', 'e553ad86-e664-4ecf-bbb2-9dd8e5e5bf63': 'We can measure the oxygen concentration of the venous system (CVO2\xa0in figure 15.2) and can assume that the shunted blood, having performed no gas exchange, will have the same oxygen concentration. We can also measure the oxygen concentration in the arterial system (CaO2\xa0in figure 15.2), and if we assume that all the blood that passed\xa0through the gas exchange capillaries in the lungs equilibrated with the alveolar PO2, we can use the alveolar gas equation to determine the capillary oxygen concentration (CCO2\xa0in figure 15.2).', '4068ac99-f409-4266-b009-a69d11e354ad': 'So know we can use these oxygen concentrations to work out the percentage of shunted blood.', 'f36e6b61-b7bc-468a-86ba-0fcf894754a2': 'Now let us\xa0combine our flow and oxygen concentration and think in terms of absolute oxygen contents in each part of our diagram. (Critical point: The absolute oxygen content is the product of the blood volume and oxygen concentration.)\xa0So now thinking of absolute oxygen contents, let us\xa0generate a first basic equation (equation 15.1) with what we know—the amount of oxygen in our flow going back to the left heart (QT) equals the oxygen from the pulmonary capillaries, plus that from the shunt.', 'affef48c-01e8-43fd-acbd-4ded7294567f': 'Equation 15.1'}"
+Figure 15.2,pulmo2/images/Figure 15.2.jpg,Figure 15.2: Oxygen concentrations used to calculate the size of a pulmonary shunt.,"We can measure the oxygen concentration of the venous system (CVO2 in figure 15.2) and can assume that the shunted blood, having performed no gas exchange, will have the same oxygen concentration. We can also measure the oxygen concentration in the arterial system (CaO2 in figure 15.2), and if we assume that all the blood that passed through the gas exchange capillaries in the lungs equilibrated with the alveolar PO2, we can use the alveolar gas equation to determine the capillary oxygen concentration (CCO2 in figure 15.2).","{'4ebe9b5f-9a81-497d-b977-d939be39cada': 'Because even a small shunt can have a large effect on arterial PO2, it is critical to determine the size of a shunt should one be suspected. Figure 15.1 shows the lungs with blood passing through as normal (QC), while some bypasses the heart (QS) and is shunted back into the systemic circulation. The size of a shunt (QS) is expressed as the percentage of total blood (QT\xa0in figure 15.1) (i.e., QS/QT). We will look now at how this is calculated from oxygen concentration. First, let us\xa0see what we know.', 'e553ad86-e664-4ecf-bbb2-9dd8e5e5bf63': 'We can measure the oxygen concentration of the venous system (CVO2\xa0in figure 15.2) and can assume that the shunted blood, having performed no gas exchange, will have the same oxygen concentration. We can also measure the oxygen concentration in the arterial system (CaO2\xa0in figure 15.2), and if we assume that all the blood that passed\xa0through the gas exchange capillaries in the lungs equilibrated with the alveolar PO2, we can use the alveolar gas equation to determine the capillary oxygen concentration (CCO2\xa0in figure 15.2).', '4068ac99-f409-4266-b009-a69d11e354ad': 'So know we can use these oxygen concentrations to work out the percentage of shunted blood.', 'f36e6b61-b7bc-468a-86ba-0fcf894754a2': 'Now let us\xa0combine our flow and oxygen concentration and think in terms of absolute oxygen contents in each part of our diagram. (Critical point: The absolute oxygen content is the product of the blood volume and oxygen concentration.)\xa0So now thinking of absolute oxygen contents, let us\xa0generate a first basic equation (equation 15.1) with what we know—the amount of oxygen in our flow going back to the left heart (QT) equals the oxygen from the pulmonary capillaries, plus that from the shunt.', 'affef48c-01e8-43fd-acbd-4ded7294567f': 'Equation 15.1'}"
+Figure 15.3,pulmo2/images/Figure 15.3.jpg,Figure 15.3: Elements of the shunt equation and where they exist physiologically.,"Let us build on that and put some values in place. The amount of oxygen arriving back in the arterial side must equal the volume of blood multiplied by the arterial oxygen concentration (QT x CaO2), as shown in figure 15.3. And we know that this amount of O2 must be the sum of that from the capillaries, and that from the shunt.","{'edf017e4-f8e9-4b25-b8fa-9b71a438769e': 'Let us\xa0build on that and put some values in place. The amount of oxygen arriving back in the arterial side must equal the volume of blood multiplied by the arterial oxygen concentration (QT\xa0x CaO2), as shown in figure 15.3. And we know that this amount of O2\xa0must be the sum of that from the capillaries, and that from the shunt.', '9ec0dd8c-8545-409c-9501-82b35955ff9d': 'The amount of oxygen from the shunt is calculated as shunt flow multiplied by the venous oxygen concentration (QS\xa0x CVO2), as shown in figure 15.3.', 'ad5e9778-4a18-4fb1-a97f-baef972211e6': 'The amount of oxygen going through the pulmonary capillaries can be described as the total volume minus the shunt volume (QT−QS) multiplied by the capillary oxygen concentration (figure 15.3).', '94eb27ac-ad53-47da-bbf1-abc30fb76ada': 'Let us\xa0put those terms into our basic equation (equation 15.2).', 'd71780b8-6e76-4c41-910d-38a5d7cd3e17': 'Equation 15.2'}"
+Figure 15.3,pulmo2/images/Figure 15.3.jpg,Figure 15.3: Elements of the shunt equation and where they exist physiologically.,"Let us build on that and put some values in place. The amount of oxygen arriving back in the arterial side must equal the volume of blood multiplied by the arterial oxygen concentration (QT x CaO2), as shown in figure 15.3. And we know that this amount of O2 must be the sum of that from the capillaries, and that from the shunt.","{'edf017e4-f8e9-4b25-b8fa-9b71a438769e': 'Let us\xa0build on that and put some values in place. The amount of oxygen arriving back in the arterial side must equal the volume of blood multiplied by the arterial oxygen concentration (QT\xa0x CaO2), as shown in figure 15.3. And we know that this amount of O2\xa0must be the sum of that from the capillaries, and that from the shunt.', '9ec0dd8c-8545-409c-9501-82b35955ff9d': 'The amount of oxygen from the shunt is calculated as shunt flow multiplied by the venous oxygen concentration (QS\xa0x CVO2), as shown in figure 15.3.', 'ad5e9778-4a18-4fb1-a97f-baef972211e6': 'The amount of oxygen going through the pulmonary capillaries can be described as the total volume minus the shunt volume (QT−QS) multiplied by the capillary oxygen concentration (figure 15.3).', '94eb27ac-ad53-47da-bbf1-abc30fb76ada': 'Let us\xa0put those terms into our basic equation (equation 15.2).', 'd71780b8-6e76-4c41-910d-38a5d7cd3e17': 'Equation 15.2'}"
+Figure 14.1,pulmo2/images/Figure 14.1.jpg,Figure 14.1: The alveolar gas equation.,"Obviously to measure the alveolar–arterial PO2 difference, we need to know both the alveolar and arterial PO2s. The arterial PO2 is routinely measured as part of a blood gas panel, along with arterial PCO2. However, from your understanding of V/Q distribution across the lung, you might appreciate that the measurement of a “typical” alveolar PO2 is difficult, and it must be calculated as an estimate of the whole lung. This is the role of the alveolar gas equation, and we will look at it now, not just because it may appear on your board exams, but primarily because of its clinical importance. As there are several forms of the equation, we will take the easy way out and use the simplest one (figure 14.1), which is accurate for the vast majority of cases you will ever see.","{'3fb6de3d-2dcc-42c8-b6d5-1c6e1447a3c9': 'Obviously to measure the alveolar–arterial PO2 difference, we need to know both the alveolar and arterial PO2s. The arterial PO2 is routinely measured as part of a blood gas panel, along with arterial PCO2. However, from your understanding of V/Q distribution across the lung, you might appreciate that the measurement of a “typical”\xa0alveolar PO2 is difficult, and it must\xa0be calculated as an estimate of the whole lung. This is the role of the alveolar gas equation, and we will\xa0look at it now, not just because it may appear on your board exams, but primarily because of its clinical importance. As there are several forms of the equation, we will take the easy way out and use the simplest one (figure 14.1), which is accurate for the vast majority of cases you will\xa0ever see.'}"
+Figure 14.2,pulmo2/images/Figure 14.2.jpg,Figure 14.2: Alveolar and arterial oxygen tensions in the normal state lead to a normal alveolar–arterial PO2 difference.,"Normal lung: With a well-ventilated and perfused lung (figure 14.2), alveolar PO2 is normal, and when there are no problems with diffusion across the membrane into an adequately perfused blood vessel, arterial PO2 is normal as well. Thus the difference between alveolar and arterial PO2 is minimal and normal, and in reality for a young healthy person is no more than 5–10 mmHg (note, however, this difference increases with age).","{'d8a4e1cb-8727-4554-8087-372ab3bdca8f': 'Normal lung: With a well-ventilated and perfused lung (figure 14.2),\xa0alveolar PO2 is normal, and when there are\xa0no problems with diffusion across the membrane into an adequately perfused blood vessel, arterial PO2 is normal as well. Thus the difference between alveolar and arterial PO2 is minimal and normal, and in reality for a young healthy person is no more than 5–10 mmHg (note, however, this difference increases with age).', 'dfadaa83-f3cc-4495-8e0f-68e356600a1a': 'Hypoventilation: Now let us\xa0look at a case of where the alveolus is inadequately ventilated (figure 14.3): perhaps a patient has been given a high enough dose of opioid for pain relief and it has\xa0caused respiratory depression, so the patient no longer breathes enough to achieve sufficient gas exchange. This will lead to a decline in alveolar PO2\xa0and consequently a fall in arterial PO2 as well. However, because the alveolar and arterial PO2s have both decreased, then the difference between the two of them remains the same. So we see low alveolar PO2, low arterial PO2, but a normal A–a PO2 difference.', 'd84525ab-d131-4bb7-9b3c-544e0c7734e9': 'Impaired diffusion: Now let us\xa0look at a patient with a diffusion abnormality—perhaps some pathological process has caused thickening of the alveolar membranes. Here the alveolus is still\xa0adequately ventilated, so alveolar PO2 remains high or at least the same (figure 14.4). But although blood is passing the ventilated region, the thickened membranes prevent diffusion of oxygen into the blood, and arterial PO2 does not equilibrate and so is lower. As a consequence, the A–a difference increases. So this scenario results in a normal alveolar PO2, a low arterial PO2, and\xa0an increased difference between the two.', '25cefbc3-5776-4459-9216-f5542ac0cc03': 'Inadequate perfusion: Now let us\xa0look at a last scenario where perfusion has been stopped, perhaps by a pulmonary embolus (figure 14.5). Ventilation still reaches the region, but there is no perfusion; this is a form of V/Q mismatch. Alveolar PO2 remains normal because\xa0air still reaches the region, but with no perfusion and therefore no gas exchange arterial PO2 will fall. This, again, results in an increased A–a PO2 difference.', '26823ba2-cc36-4772-85fc-cd9e4662d428': 'So what you should see from the summary in table 14.1 is that all three abnormalities cause a decrease in arterial PO2, so all three patients are likely to present with low arterial saturations. But when blood gases are taken and the alveolar–arterial PO2 difference is calculated, then one or more of our abnormalities could be ruled out. If there is an increased difference, you know it is\xa0not hypoventilation. If there is no\xa0increase in A–a difference,\xa0you know it is\xa0neither a diffusion problem nor a V/Q mismatch.', 'e05798d0-51c0-4eaf-9124-90ebfc0b3dbf': 'To calculate alveolar PO2\xa0we need to account for the water vapor that is added to the inspired air as it enters the airways. This is equivalent to\xa0adding another gas and must be accounted for. Water vapor exerts a pressure of 47 mmHg. Subtracting this from our atmospheric pressure, our total gaseous pressure is 713 mmHg;\xa0multiplying this by our fraction of inspired O2\xa0(FiO2\xa0is merely the percentage (fraction) of oxygen inspired), we see our alveolar PO2\xa0is theoretically 149.7 mmHg (i.e., ~150 mmHg).'}"
+Figure 14.3,pulmo2/images/Figure 14.3.jpg,Figure 14.3: Alveolar and arterial oxygen tensions during hypoventilation result in a normal alveolar–arterial PO2 difference.,"Hypoventilation: Now let us look at a case of where the alveolus is inadequately ventilated (figure 14.3): perhaps a patient has been given a high enough dose of opioid for pain relief and it has caused respiratory depression, so the patient no longer breathes enough to achieve sufficient gas exchange. This will lead to a decline in alveolar PO2 and consequently a fall in arterial PO2 as well. However, because the alveolar and arterial PO2s have both decreased, then the difference between the two of them remains the same. So we see low alveolar PO2, low arterial PO2, but a normal A–a PO2 difference.","{'d8a4e1cb-8727-4554-8087-372ab3bdca8f': 'Normal lung: With a well-ventilated and perfused lung (figure 14.2),\xa0alveolar PO2 is normal, and when there are\xa0no problems with diffusion across the membrane into an adequately perfused blood vessel, arterial PO2 is normal as well. Thus the difference between alveolar and arterial PO2 is minimal and normal, and in reality for a young healthy person is no more than 5–10 mmHg (note, however, this difference increases with age).', 'dfadaa83-f3cc-4495-8e0f-68e356600a1a': 'Hypoventilation: Now let us\xa0look at a case of where the alveolus is inadequately ventilated (figure 14.3): perhaps a patient has been given a high enough dose of opioid for pain relief and it has\xa0caused respiratory depression, so the patient no longer breathes enough to achieve sufficient gas exchange. This will lead to a decline in alveolar PO2\xa0and consequently a fall in arterial PO2 as well. However, because the alveolar and arterial PO2s have both decreased, then the difference between the two of them remains the same. So we see low alveolar PO2, low arterial PO2, but a normal A–a PO2 difference.', 'd84525ab-d131-4bb7-9b3c-544e0c7734e9': 'Impaired diffusion: Now let us\xa0look at a patient with a diffusion abnormality—perhaps some pathological process has caused thickening of the alveolar membranes. Here the alveolus is still\xa0adequately ventilated, so alveolar PO2 remains high or at least the same (figure 14.4). But although blood is passing the ventilated region, the thickened membranes prevent diffusion of oxygen into the blood, and arterial PO2 does not equilibrate and so is lower. As a consequence, the A–a difference increases. So this scenario results in a normal alveolar PO2, a low arterial PO2, and\xa0an increased difference between the two.', '25cefbc3-5776-4459-9216-f5542ac0cc03': 'Inadequate perfusion: Now let us\xa0look at a last scenario where perfusion has been stopped, perhaps by a pulmonary embolus (figure 14.5). Ventilation still reaches the region, but there is no perfusion; this is a form of V/Q mismatch. Alveolar PO2 remains normal because\xa0air still reaches the region, but with no perfusion and therefore no gas exchange arterial PO2 will fall. This, again, results in an increased A–a PO2 difference.', '26823ba2-cc36-4772-85fc-cd9e4662d428': 'So what you should see from the summary in table 14.1 is that all three abnormalities cause a decrease in arterial PO2, so all three patients are likely to present with low arterial saturations. But when blood gases are taken and the alveolar–arterial PO2 difference is calculated, then one or more of our abnormalities could be ruled out. If there is an increased difference, you know it is\xa0not hypoventilation. If there is no\xa0increase in A–a difference,\xa0you know it is\xa0neither a diffusion problem nor a V/Q mismatch.', 'e05798d0-51c0-4eaf-9124-90ebfc0b3dbf': 'To calculate alveolar PO2\xa0we need to account for the water vapor that is added to the inspired air as it enters the airways. This is equivalent to\xa0adding another gas and must be accounted for. Water vapor exerts a pressure of 47 mmHg. Subtracting this from our atmospheric pressure, our total gaseous pressure is 713 mmHg;\xa0multiplying this by our fraction of inspired O2\xa0(FiO2\xa0is merely the percentage (fraction) of oxygen inspired), we see our alveolar PO2\xa0is theoretically 149.7 mmHg (i.e., ~150 mmHg).'}"
+Figure 14.4,pulmo2/images/Figure 14.4.jpg,Figure 14.4: Diffusion abnormalities lead to an increased alveolar–arterial PO2 difference.,"Impaired diffusion: Now let us look at a patient with a diffusion abnormality—perhaps some pathological process has caused thickening of the alveolar membranes. Here the alveolus is still adequately ventilated, so alveolar PO2 remains high or at least the same (figure 14.4). But although blood is passing the ventilated region, the thickened membranes prevent diffusion of oxygen into the blood, and arterial PO2 does not equilibrate and so is lower. As a consequence, the A–a difference increases. So this scenario results in a normal alveolar PO2, a low arterial PO2, and an increased difference between the two.","{'d8a4e1cb-8727-4554-8087-372ab3bdca8f': 'Normal lung: With a well-ventilated and perfused lung (figure 14.2),\xa0alveolar PO2 is normal, and when there are\xa0no problems with diffusion across the membrane into an adequately perfused blood vessel, arterial PO2 is normal as well. Thus the difference between alveolar and arterial PO2 is minimal and normal, and in reality for a young healthy person is no more than 5–10 mmHg (note, however, this difference increases with age).', 'dfadaa83-f3cc-4495-8e0f-68e356600a1a': 'Hypoventilation: Now let us\xa0look at a case of where the alveolus is inadequately ventilated (figure 14.3): perhaps a patient has been given a high enough dose of opioid for pain relief and it has\xa0caused respiratory depression, so the patient no longer breathes enough to achieve sufficient gas exchange. This will lead to a decline in alveolar PO2\xa0and consequently a fall in arterial PO2 as well. However, because the alveolar and arterial PO2s have both decreased, then the difference between the two of them remains the same. So we see low alveolar PO2, low arterial PO2, but a normal A–a PO2 difference.', 'd84525ab-d131-4bb7-9b3c-544e0c7734e9': 'Impaired diffusion: Now let us\xa0look at a patient with a diffusion abnormality—perhaps some pathological process has caused thickening of the alveolar membranes. Here the alveolus is still\xa0adequately ventilated, so alveolar PO2 remains high or at least the same (figure 14.4). But although blood is passing the ventilated region, the thickened membranes prevent diffusion of oxygen into the blood, and arterial PO2 does not equilibrate and so is lower. As a consequence, the A–a difference increases. So this scenario results in a normal alveolar PO2, a low arterial PO2, and\xa0an increased difference between the two.', '25cefbc3-5776-4459-9216-f5542ac0cc03': 'Inadequate perfusion: Now let us\xa0look at a last scenario where perfusion has been stopped, perhaps by a pulmonary embolus (figure 14.5). Ventilation still reaches the region, but there is no perfusion; this is a form of V/Q mismatch. Alveolar PO2 remains normal because\xa0air still reaches the region, but with no perfusion and therefore no gas exchange arterial PO2 will fall. This, again, results in an increased A–a PO2 difference.', '26823ba2-cc36-4772-85fc-cd9e4662d428': 'So what you should see from the summary in table 14.1 is that all three abnormalities cause a decrease in arterial PO2, so all three patients are likely to present with low arterial saturations. But when blood gases are taken and the alveolar–arterial PO2 difference is calculated, then one or more of our abnormalities could be ruled out. If there is an increased difference, you know it is\xa0not hypoventilation. If there is no\xa0increase in A–a difference,\xa0you know it is\xa0neither a diffusion problem nor a V/Q mismatch.', 'e05798d0-51c0-4eaf-9124-90ebfc0b3dbf': 'To calculate alveolar PO2\xa0we need to account for the water vapor that is added to the inspired air as it enters the airways. This is equivalent to\xa0adding another gas and must be accounted for. Water vapor exerts a pressure of 47 mmHg. Subtracting this from our atmospheric pressure, our total gaseous pressure is 713 mmHg;\xa0multiplying this by our fraction of inspired O2\xa0(FiO2\xa0is merely the percentage (fraction) of oxygen inspired), we see our alveolar PO2\xa0is theoretically 149.7 mmHg (i.e., ~150 mmHg).'}"
+Figure 14.5,pulmo2/images/Figure 14.5.jpg,Figure 14.5: Perfusion abnormalities lead to an increased alveolar–arterial PO2 difference.,"Inadequate perfusion: Now let us look at a last scenario where perfusion has been stopped, perhaps by a pulmonary embolus (figure 14.5). Ventilation still reaches the region, but there is no perfusion; this is a form of V/Q mismatch. Alveolar PO2 remains normal because air still reaches the region, but with no perfusion and therefore no gas exchange arterial PO2 will fall. This, again, results in an increased A–a PO2 difference.","{'d8a4e1cb-8727-4554-8087-372ab3bdca8f': 'Normal lung: With a well-ventilated and perfused lung (figure 14.2),\xa0alveolar PO2 is normal, and when there are\xa0no problems with diffusion across the membrane into an adequately perfused blood vessel, arterial PO2 is normal as well. Thus the difference between alveolar and arterial PO2 is minimal and normal, and in reality for a young healthy person is no more than 5–10 mmHg (note, however, this difference increases with age).', 'dfadaa83-f3cc-4495-8e0f-68e356600a1a': 'Hypoventilation: Now let us\xa0look at a case of where the alveolus is inadequately ventilated (figure 14.3): perhaps a patient has been given a high enough dose of opioid for pain relief and it has\xa0caused respiratory depression, so the patient no longer breathes enough to achieve sufficient gas exchange. This will lead to a decline in alveolar PO2\xa0and consequently a fall in arterial PO2 as well. However, because the alveolar and arterial PO2s have both decreased, then the difference between the two of them remains the same. So we see low alveolar PO2, low arterial PO2, but a normal A–a PO2 difference.', 'd84525ab-d131-4bb7-9b3c-544e0c7734e9': 'Impaired diffusion: Now let us\xa0look at a patient with a diffusion abnormality—perhaps some pathological process has caused thickening of the alveolar membranes. Here the alveolus is still\xa0adequately ventilated, so alveolar PO2 remains high or at least the same (figure 14.4). But although blood is passing the ventilated region, the thickened membranes prevent diffusion of oxygen into the blood, and arterial PO2 does not equilibrate and so is lower. As a consequence, the A–a difference increases. So this scenario results in a normal alveolar PO2, a low arterial PO2, and\xa0an increased difference between the two.', '25cefbc3-5776-4459-9216-f5542ac0cc03': 'Inadequate perfusion: Now let us\xa0look at a last scenario where perfusion has been stopped, perhaps by a pulmonary embolus (figure 14.5). Ventilation still reaches the region, but there is no perfusion; this is a form of V/Q mismatch. Alveolar PO2 remains normal because\xa0air still reaches the region, but with no perfusion and therefore no gas exchange arterial PO2 will fall. This, again, results in an increased A–a PO2 difference.', '26823ba2-cc36-4772-85fc-cd9e4662d428': 'So what you should see from the summary in table 14.1 is that all three abnormalities cause a decrease in arterial PO2, so all three patients are likely to present with low arterial saturations. But when blood gases are taken and the alveolar–arterial PO2 difference is calculated, then one or more of our abnormalities could be ruled out. If there is an increased difference, you know it is\xa0not hypoventilation. If there is no\xa0increase in A–a difference,\xa0you know it is\xa0neither a diffusion problem nor a V/Q mismatch.', 'e05798d0-51c0-4eaf-9124-90ebfc0b3dbf': 'To calculate alveolar PO2\xa0we need to account for the water vapor that is added to the inspired air as it enters the airways. This is equivalent to\xa0adding another gas and must be accounted for. Water vapor exerts a pressure of 47 mmHg. Subtracting this from our atmospheric pressure, our total gaseous pressure is 713 mmHg;\xa0multiplying this by our fraction of inspired O2\xa0(FiO2\xa0is merely the percentage (fraction) of oxygen inspired), we see our alveolar PO2\xa0is theoretically 149.7 mmHg (i.e., ~150 mmHg).'}"
+Figure 13.2,pulmo2/images/Figure 13.2.jpg,Figure 13.2: Partial pressures when V/Q = 1.,"When V and Q are matched (V/Q = 1): Atmospheric PO2 is diluted as it descends the airways to give an alveolar PO2 of 100 mmHg, and alveolar PCO2 is 40 mmHg. The blood returning from the tissue has a diminished PO2 of 40 mmHg and a raised PCO2 of 45 mmHg. As this blood passes the alveolus, oxygen moves into the bloodstream down its pressure gradient and CO2 moves into the alveolus down its pressure gradient. As ventilation and perfusion are matched then equilibrium is reached and the blood leaves with arterial gas tensions that are the same as alveolar tensions (figure 13.2).","{'85f0f70d-8677-4678-bea9-07259ce001f8': 'When V and Q are matched (V/Q =\xa01): Atmospheric PO2 is diluted as it descends the airways to give an alveolar PO2 of 100 mmHg, and alveolar PCO2 is 40 mmHg. The blood returning from the tissue has a diminished PO2 of 40 mmHg and a raised PCO2 of 45 mmHg. As this blood passes the alveolus, oxygen moves into the bloodstream down its pressure gradient and CO2 moves into the alveolus down its pressure gradient. As ventilation and perfusion are\xa0matched then equilibrium is reached and the blood leaves with arterial gas tensions that are the same as alveolar tensions (figure 13.2).', 'ae9928fc-ebed-484b-9d0e-f106637f0444': 'When V = 0: Now let us look at another and extreme situation, where ventilation (V) is zero so our V/Q is zero (zero divided by anything is zero).', '2004592f-936b-4a32-8de4-acb4a232cda9': 'This situation is clinically possible\xa0as airways can collapse or become blocked with a mucus plug. Without any ventilation the gas tensions inside the alveolus rapidly equilibrate with the returning venous blood, so alveolar gas tensions end up as a PO2 of 40 mmHg and a PCO2 of 45 mmHg. The venous gas tensions, never having been exposed to a ventilated alveolus, now circulate into the arterial system, and arterial PO2 becomes 40 mmHg and PCO2 becomes 45 mmHg there as well (figure 13.3).', '3daf23a3-a6fa-4dd2-ad9f-81f3a8ecaa97': 'When Q = 0: Now let us go to the other extreme, where perfusion is zero and ventilation is normal (V/Q goes to infinity). Again, this can occur in reality should a pulmonary vessel become blocked by an embolus. In this scenario V/Q becomes infinity—anything divided by zero is infinity. With no perfusion, no gas exchange occurs in this alveolus, and as it is still being ventilated then the alveolar gas tensions equilibrate with the atmosphere (figure 13.4).', '6b17964d-6a5d-4fb4-a079-5ebef1888fa2': 'So going from these extremes of V/Q as zero, passing through the ideal of V/Q of 1 to a V/Q of infinity, we get a range of alveolar gas tensions going from venous gas tensions when V/Q is zero to atmospheric gas tensions when V/Q is infinite.', '3eb035cf-cde4-46d0-9c3b-0f04bc73270a': 'This range of alveolar gas tensions is represented by the ventilation–perfusion line (figure 13.5). This graph takes a minute to come\xa0to grips with, so let us\xa0break it down. The axes of the graph show alveolar PO2 on the X and\xa0alveolar PCO2 on the Y. The plot shows the range of V/Q ratios we have just discussed, ranging from zero when there is perfusion but no ventilation, to infinity when there is ventilation but no perfusion. Looking at figure 13.5 more carefully will confirm our numbers. When ventilation and perfusion are present and V/Q is 1, then our alveolar PO2 is 100 mmHg, and the alveolar PCO2 is 40 mmHg—just as we have seen.', '010a8427-3fa7-44e2-a0c4-21eefc77ebb8': 'If we stop ventilation and go to a V/Q of zero, we again see that the alveolar gas tensions become equal to venous values, with alveolar PO2 at 40 mmHg and PCO2 at 45 mmHg.', '80e28412-7783-4aa2-afe4-4cad6fd00f7a': 'And finally, when we stop perfusion and V/Q becomes infinite, then alveolar PO2 becomes 150 mmHg\xa0and PCO2 becomes zero (i.e., equilibrates with the atmosphere).'}"
+Figure 13.3,pulmo2/images/Figure 13.3.jpg,Figure 13.3: Partial pressures when V/Q = 0.,"This situation is clinically possible as airways can collapse or become blocked with a mucus plug. Without any ventilation the gas tensions inside the alveolus rapidly equilibrate with the returning venous blood, so alveolar gas tensions end up as a PO2 of 40 mmHg and a PCO2 of 45 mmHg. The venous gas tensions, never having been exposed to a ventilated alveolus, now circulate into the arterial system, and arterial PO2 becomes 40 mmHg and PCO2 becomes 45 mmHg there as well (figure 13.3).","{'85f0f70d-8677-4678-bea9-07259ce001f8': 'When V and Q are matched (V/Q =\xa01): Atmospheric PO2 is diluted as it descends the airways to give an alveolar PO2 of 100 mmHg, and alveolar PCO2 is 40 mmHg. The blood returning from the tissue has a diminished PO2 of 40 mmHg and a raised PCO2 of 45 mmHg. As this blood passes the alveolus, oxygen moves into the bloodstream down its pressure gradient and CO2 moves into the alveolus down its pressure gradient. As ventilation and perfusion are\xa0matched then equilibrium is reached and the blood leaves with arterial gas tensions that are the same as alveolar tensions (figure 13.2).', 'ae9928fc-ebed-484b-9d0e-f106637f0444': 'When V = 0: Now let us look at another and extreme situation, where ventilation (V) is zero so our V/Q is zero (zero divided by anything is zero).', '2004592f-936b-4a32-8de4-acb4a232cda9': 'This situation is clinically possible\xa0as airways can collapse or become blocked with a mucus plug. Without any ventilation the gas tensions inside the alveolus rapidly equilibrate with the returning venous blood, so alveolar gas tensions end up as a PO2 of 40 mmHg and a PCO2 of 45 mmHg. The venous gas tensions, never having been exposed to a ventilated alveolus, now circulate into the arterial system, and arterial PO2 becomes 40 mmHg and PCO2 becomes 45 mmHg there as well (figure 13.3).', '3daf23a3-a6fa-4dd2-ad9f-81f3a8ecaa97': 'When Q = 0: Now let us go to the other extreme, where perfusion is zero and ventilation is normal (V/Q goes to infinity). Again, this can occur in reality should a pulmonary vessel become blocked by an embolus. In this scenario V/Q becomes infinity—anything divided by zero is infinity. With no perfusion, no gas exchange occurs in this alveolus, and as it is still being ventilated then the alveolar gas tensions equilibrate with the atmosphere (figure 13.4).', '6b17964d-6a5d-4fb4-a079-5ebef1888fa2': 'So going from these extremes of V/Q as zero, passing through the ideal of V/Q of 1 to a V/Q of infinity, we get a range of alveolar gas tensions going from venous gas tensions when V/Q is zero to atmospheric gas tensions when V/Q is infinite.', '3eb035cf-cde4-46d0-9c3b-0f04bc73270a': 'This range of alveolar gas tensions is represented by the ventilation–perfusion line (figure 13.5). This graph takes a minute to come\xa0to grips with, so let us\xa0break it down. The axes of the graph show alveolar PO2 on the X and\xa0alveolar PCO2 on the Y. The plot shows the range of V/Q ratios we have just discussed, ranging from zero when there is perfusion but no ventilation, to infinity when there is ventilation but no perfusion. Looking at figure 13.5 more carefully will confirm our numbers. When ventilation and perfusion are present and V/Q is 1, then our alveolar PO2 is 100 mmHg, and the alveolar PCO2 is 40 mmHg—just as we have seen.', '010a8427-3fa7-44e2-a0c4-21eefc77ebb8': 'If we stop ventilation and go to a V/Q of zero, we again see that the alveolar gas tensions become equal to venous values, with alveolar PO2 at 40 mmHg and PCO2 at 45 mmHg.', '80e28412-7783-4aa2-afe4-4cad6fd00f7a': 'And finally, when we stop perfusion and V/Q becomes infinite, then alveolar PO2 becomes 150 mmHg\xa0and PCO2 becomes zero (i.e., equilibrates with the atmosphere).'}"
+Figure 13.4,pulmo2/images/Figure 13.4.jpg,Figure 13.4: Partial pressures when V/Q is infinite.,"When Q = 0: Now let us go to the other extreme, where perfusion is zero and ventilation is normal (V/Q goes to infinity). Again, this can occur in reality should a pulmonary vessel become blocked by an embolus. In this scenario V/Q becomes infinity—anything divided by zero is infinity. With no perfusion, no gas exchange occurs in this alveolus, and as it is still being ventilated then the alveolar gas tensions equilibrate with the atmosphere (figure 13.4).","{'85f0f70d-8677-4678-bea9-07259ce001f8': 'When V and Q are matched (V/Q =\xa01): Atmospheric PO2 is diluted as it descends the airways to give an alveolar PO2 of 100 mmHg, and alveolar PCO2 is 40 mmHg. The blood returning from the tissue has a diminished PO2 of 40 mmHg and a raised PCO2 of 45 mmHg. As this blood passes the alveolus, oxygen moves into the bloodstream down its pressure gradient and CO2 moves into the alveolus down its pressure gradient. As ventilation and perfusion are\xa0matched then equilibrium is reached and the blood leaves with arterial gas tensions that are the same as alveolar tensions (figure 13.2).', 'ae9928fc-ebed-484b-9d0e-f106637f0444': 'When V = 0: Now let us look at another and extreme situation, where ventilation (V) is zero so our V/Q is zero (zero divided by anything is zero).', '2004592f-936b-4a32-8de4-acb4a232cda9': 'This situation is clinically possible\xa0as airways can collapse or become blocked with a mucus plug. Without any ventilation the gas tensions inside the alveolus rapidly equilibrate with the returning venous blood, so alveolar gas tensions end up as a PO2 of 40 mmHg and a PCO2 of 45 mmHg. The venous gas tensions, never having been exposed to a ventilated alveolus, now circulate into the arterial system, and arterial PO2 becomes 40 mmHg and PCO2 becomes 45 mmHg there as well (figure 13.3).', '3daf23a3-a6fa-4dd2-ad9f-81f3a8ecaa97': 'When Q = 0: Now let us go to the other extreme, where perfusion is zero and ventilation is normal (V/Q goes to infinity). Again, this can occur in reality should a pulmonary vessel become blocked by an embolus. In this scenario V/Q becomes infinity—anything divided by zero is infinity. With no perfusion, no gas exchange occurs in this alveolus, and as it is still being ventilated then the alveolar gas tensions equilibrate with the atmosphere (figure 13.4).', '6b17964d-6a5d-4fb4-a079-5ebef1888fa2': 'So going from these extremes of V/Q as zero, passing through the ideal of V/Q of 1 to a V/Q of infinity, we get a range of alveolar gas tensions going from venous gas tensions when V/Q is zero to atmospheric gas tensions when V/Q is infinite.', '3eb035cf-cde4-46d0-9c3b-0f04bc73270a': 'This range of alveolar gas tensions is represented by the ventilation–perfusion line (figure 13.5). This graph takes a minute to come\xa0to grips with, so let us\xa0break it down. The axes of the graph show alveolar PO2 on the X and\xa0alveolar PCO2 on the Y. The plot shows the range of V/Q ratios we have just discussed, ranging from zero when there is perfusion but no ventilation, to infinity when there is ventilation but no perfusion. Looking at figure 13.5 more carefully will confirm our numbers. When ventilation and perfusion are present and V/Q is 1, then our alveolar PO2 is 100 mmHg, and the alveolar PCO2 is 40 mmHg—just as we have seen.', '010a8427-3fa7-44e2-a0c4-21eefc77ebb8': 'If we stop ventilation and go to a V/Q of zero, we again see that the alveolar gas tensions become equal to venous values, with alveolar PO2 at 40 mmHg and PCO2 at 45 mmHg.', '80e28412-7783-4aa2-afe4-4cad6fd00f7a': 'And finally, when we stop perfusion and V/Q becomes infinite, then alveolar PO2 becomes 150 mmHg\xa0and PCO2 becomes zero (i.e., equilibrates with the atmosphere).'}"
+Figure 13.5,pulmo2/images/Figure 13.5.jpg,Figure 13.5: Ventilation–perfusion line.,"This range of alveolar gas tensions is represented by the ventilation–perfusion line (figure 13.5). This graph takes a minute to come to grips with, so let us break it down. The axes of the graph show alveolar PO2 on the X and alveolar PCO2 on the Y. The plot shows the range of V/Q ratios we have just discussed, ranging from zero when there is perfusion but no ventilation, to infinity when there is ventilation but no perfusion. Looking at figure 13.5 more carefully will confirm our numbers. When ventilation and perfusion are present and V/Q is 1, then our alveolar PO2 is 100 mmHg, and the alveolar PCO2 is 40 mmHg—just as we have seen.","{'85f0f70d-8677-4678-bea9-07259ce001f8': 'When V and Q are matched (V/Q =\xa01): Atmospheric PO2 is diluted as it descends the airways to give an alveolar PO2 of 100 mmHg, and alveolar PCO2 is 40 mmHg. The blood returning from the tissue has a diminished PO2 of 40 mmHg and a raised PCO2 of 45 mmHg. As this blood passes the alveolus, oxygen moves into the bloodstream down its pressure gradient and CO2 moves into the alveolus down its pressure gradient. As ventilation and perfusion are\xa0matched then equilibrium is reached and the blood leaves with arterial gas tensions that are the same as alveolar tensions (figure 13.2).', 'ae9928fc-ebed-484b-9d0e-f106637f0444': 'When V = 0: Now let us look at another and extreme situation, where ventilation (V) is zero so our V/Q is zero (zero divided by anything is zero).', '2004592f-936b-4a32-8de4-acb4a232cda9': 'This situation is clinically possible\xa0as airways can collapse or become blocked with a mucus plug. Without any ventilation the gas tensions inside the alveolus rapidly equilibrate with the returning venous blood, so alveolar gas tensions end up as a PO2 of 40 mmHg and a PCO2 of 45 mmHg. The venous gas tensions, never having been exposed to a ventilated alveolus, now circulate into the arterial system, and arterial PO2 becomes 40 mmHg and PCO2 becomes 45 mmHg there as well (figure 13.3).', '3daf23a3-a6fa-4dd2-ad9f-81f3a8ecaa97': 'When Q = 0: Now let us go to the other extreme, where perfusion is zero and ventilation is normal (V/Q goes to infinity). Again, this can occur in reality should a pulmonary vessel become blocked by an embolus. In this scenario V/Q becomes infinity—anything divided by zero is infinity. With no perfusion, no gas exchange occurs in this alveolus, and as it is still being ventilated then the alveolar gas tensions equilibrate with the atmosphere (figure 13.4).', '6b17964d-6a5d-4fb4-a079-5ebef1888fa2': 'So going from these extremes of V/Q as zero, passing through the ideal of V/Q of 1 to a V/Q of infinity, we get a range of alveolar gas tensions going from venous gas tensions when V/Q is zero to atmospheric gas tensions when V/Q is infinite.', '3eb035cf-cde4-46d0-9c3b-0f04bc73270a': 'This range of alveolar gas tensions is represented by the ventilation–perfusion line (figure 13.5). This graph takes a minute to come\xa0to grips with, so let us\xa0break it down. The axes of the graph show alveolar PO2 on the X and\xa0alveolar PCO2 on the Y. The plot shows the range of V/Q ratios we have just discussed, ranging from zero when there is perfusion but no ventilation, to infinity when there is ventilation but no perfusion. Looking at figure 13.5 more carefully will confirm our numbers. When ventilation and perfusion are present and V/Q is 1, then our alveolar PO2 is 100 mmHg, and the alveolar PCO2 is 40 mmHg—just as we have seen.', '010a8427-3fa7-44e2-a0c4-21eefc77ebb8': 'If we stop ventilation and go to a V/Q of zero, we again see that the alveolar gas tensions become equal to venous values, with alveolar PO2 at 40 mmHg and PCO2 at 45 mmHg.', '80e28412-7783-4aa2-afe4-4cad6fd00f7a': 'And finally, when we stop perfusion and V/Q becomes infinite, then alveolar PO2 becomes 150 mmHg\xa0and PCO2 becomes zero (i.e., equilibrates with the atmosphere).'}"
+Figure 13.6,pulmo2/images/Figure 13.6.jpg,"Figure 13.6: Ventilation, perfusion, and V/Q distributions.","As you should understand, ventilation increases down the lung so is greatest at the base, and perfusion follows the same pattern—all due to the effects of gravity. But the increase in ventilation down the lung structure is not equal to the increase in perfusion, as can be seen in figure 13.6. You can see here that perfusion is higher than ventilation at the base; it falls off much more rapidly as the lung is ascended, so it ends up being lower than ventilation at the apex.","{'c8a75611-c00c-4f33-9054-51f0832f74fe': 'As you should understand, ventilation increases down the lung so is greatest at the base, and perfusion follows the same pattern—all due to the effects of gravity. But the increase in ventilation down the lung structure is not equal to the increase in perfusion, as can be seen in figure 13.6. You can see here that perfusion is higher than ventilation at the base; it\xa0falls off much more rapidly as the lung is ascended, so it ends up being lower than ventilation at the apex.', '2255125b-cca4-4f0c-9fc5-f6bcab3bd4c8': 'This means there is a range of ventilation–perfusion ratios up the height of the lung (figure 13.6, maroon\xa0plot). At the base perfusion is higher than ventilation, so V/Q is less than 1, while toward\xa0the apex V/Q rises and becomes greater than\xa01. At about the level of the third rib, V/Q is perfect (yay!) as ventilation and perfusion are matched, seen here at\xa0the points the lines cross. This range of V/Q results in the previously mentioned whole lung average of 0.8.'}"
+Figure 13.7,pulmo2/images/Figure 13.7.jpg,Figure 13.7: V/Q and alveolar gas distribution.,"As you should appreciate from understanding the ventilation–perfusion line, this range of V/Q across the lung results in a range of alveolar gas partial pressures across the lung. The apical alveoli, being relatively overventilated (or underperfused, whichever way you would like to think about it), have a high V/Q and consequently have partial pressures closer to atmospheric partial pressures. On the other extreme, the basal alveoli are relatively underventilated (or overperfused, your choice) and so have a low V/Q, tending toward zero; thus their partial pressures are closer to venous values (figure 13.7).","{'71bbd182-2263-4cb5-b087-6aa5f841cd42': 'As you should appreciate from understanding the ventilation–perfusion line, this range of V/Q across the lung results in a range of alveolar gas partial pressures across the lung. The apical alveoli, being relatively overventilated (or underperfused, whichever way you would\xa0like to think about it), have a high V/Q and consequently have partial pressures closer to atmospheric partial pressures. On the other extreme, the basal alveoli are relatively underventilated (or overperfused, your choice) and so have a low V/Q, tending toward zero; thus their partial pressures are closer to venous values (figure 13.7).'}"
+Figure 13.8,pulmo2/images/Figure 13.8.jpg,Figure 13.8: Consequences of V/Q nonuniformity on arterial PO2.,"The difference in alveolar PO2 from apex to base is as high as 40 mmHg, as is reflected in this figure. The apical alveoli have a high PO2 (shown in figure 13.8 as 132 mmHg), primarily due to their poor perfusion and relatively high ventilation and thus high V/Q. This produces a high diffusion gradient from 132 mmHg in the apical alveoli, to 40 mmHg in the apical blood. Consequently, what blood does go to the apex becomes fully saturated before it heads back toward the left heart.","{'3392289c-1e53-4468-8cc4-bf80c8823b52': 'In between these two extremes is a progressive range, so what we see is that alveolar PO2 declines down the lung while alveolar PCO2 rises. As you might imagine, having a range of alveolar gas tensions down the lung has ramifications for gas exchange and particularly for oxygen saturation. This inequality in V/Q resulting in differences in alveolar PO2 is substantial enough to suppress arterial oxygen saturation—and contribute to your oxygen saturation meter never reading 100 percent. Let us see why.', '3f5defb8-c9c9-4403-bd5c-80eab935516d': 'The difference in alveolar PO2 from apex to base is as high as 40 mmHg, as is reflected in this figure. The apical alveoli have a high PO2\xa0(shown in figure 13.8 as 132 mmHg), primarily due to their poor perfusion and relatively high ventilation and thus high V/Q. This produces a high diffusion gradient from 132 mmHg in the apical alveoli, to 40 mmHg in the apical blood. Consequently, what blood does go to the apex becomes fully saturated before it heads back toward the left heart.', 'f4dbeadd-5730-41ed-9fbe-7bef557b245f': 'Down at the base, however, V/Q is low because of the high perfusion and relatively low ventilation. Consequently the PO2 in basal alveoli tend toward venous values, shown in figure 13.8 as 89 mmHg. This lower alveolar PO2 means a diminished diffusion gradient\xa0(from 89 in the alveoli to 40 mmHg in the blood), and combined with a shift down the hemoglobin saturation curve (more on this\xa0later), this means blood leaving the basal alveoli may not be completely saturated with oxygen.', 'cc40646b-880c-45d8-b6b3-f871e00f52bb': 'When the blood from the apex and base mix on their journey back to the left heart, the outcome is that the combined oxygen saturation is less than 100 percent, about 97 percent. It is worth making perhaps an obvious but critical point here. The blood from the apex is exposed to a substantially higher PO2\xa0and becomes 100 percent\xa0saturated (i.e., it cannot take on any more O2 as it is at its full oxygen carrying capacity). There is no way that it can pick up extra to compensate for the blood coming from basal alveoli, which are not at capacity.', '640a915e-d9b3-432a-a1da-e6e3361d4808': 'The same is not true for CO2 though. Because of its high solubility, CO2 transport does not rely on a transporter protein like hemoglobin; the transfer of CO2 is really dependent on the diffusion gradient present. So at the apex the lower alveolar PCO2 (slightly less than 30 mmHg looking at our V/Q line) generates a larger diffusion gradient with venous blood, and more CO2 is transferred out the blood, meaning that it can compensate for the low diffusion gradient (perhaps only a few mmHg) that occurs between the alveoli and blood at the lung’s base.', '3aeac80e-d966-43bc-aa51-84f9ad55e318': 'As a study exercise it may be worthwhile for you to go back to the ventilation–perfusion line and calculate the diffusion gradients for oxygen and carbon dioxide between the alveoli and venous blood at different heights in the lung. I urge you to come\xa0to grips with this concept as it is highly pertinent to respiratory disease and can explain clinical-related changes in blood gases.', '763cc107-131b-4180-9eb7-abc2a42d3dfc': 'The take-home message, however, is that even the normal lung is not perfect and has an average V/Q ratio of 0.8, rather than the ideal of 1, and this slight matching of ventilation and perfusion contributes to the arterial saturation being slightly less than 100 percent, but has little effect on arterial CO2. If respiratory disease increases the mismatch, this effect on oxygen saturation can become more pronounced, but the lung has a defense mechanism for this.'}"
+Figure 13.9,pulmo2/images/Figure 13.9.jpg,Figure 13.9: Correcting V/Q mismatches.,"Let us look at a common scenario that might occur in a patient with chronic bronchitis. Figure 13.9 represents two regions of the lung. One region becomes blocked by a mucus plug, and ventilation to that region goes to zero.","{'5ba36db2-9526-4010-9983-6e6b3bd379b3': 'In an attempt to maintain V/Q close to 1 and prevent V/Q mismatching, the pulmonary vasculature has an unusual response to hypoxia. While the systemic vasculature responds to local hypoxia with a vasodilation to bring more blood to the area, the pulmonary vasculature constricts in the presence of low oxygen to shunt blood away from hypoxic regions.', '612b5220-0f54-4d23-a7ec-030ebc728c48': 'Let us\xa0look at a common scenario that might occur in a patient with chronic bronchitis. Figure 13.9 represents two regions of the lung. One region becomes blocked by a mucus plug, and ventilation to that region goes to zero.', '4e716cd7-2a3d-4ff9-8152-0575cceb89ae': 'The alveolar partial pressures will rapidly equilibrate to venous pressures, and desaturated blood goes back to the left heart from this region while the local region around this area becomes mildly hypoxic. The pulmonary vasculature responds to the hypoxia by vasoconstricting, reducing the perfusion to the unventilated region and helping to rematch the V/Q ratio in this region (i.e., low ventilation is matched with low perfusion). In common sense terms, there is no point sending pulmonary blood to an unventilated region, so the hypoxia-driven vasoconstriction prevents this from happening.', 'b29ea3de-4ed5-4b0f-a6bd-6dcf00852fdf': 'The distensibility of the pulmonary vasculature means that the blood is shunted to unconstricted vessels (i.e., those supplying ventilated regions). Thus the lung has its own inherent mechanism to optimize V/Q and promote the most effective gas exchange possible.', '4fde109e-5932-4163-af9e-a45beb0d6c49': 'The unusual response of the pulmonary vasculature is demonstrated in figure 13.10, showing how as alveolar PO2 falls (as occurs with a decline in alveolar ventilation) then blood flow falls—and likewise, the more oxygen in the alveolus, the more pulmonary perfusion it receives.', '3be15f81-0c88-4ce4-83c2-19c9b755f4da': 'This effect is driven by a hypoxia-sensitive potassium channel found on the albeit sparse smooth muscle of the pulmonary arterioles. This channel is normally open and allows the exit of potassium, which in turn keeps the inside of the muscle cell polarized. When exposed to hypoxia the channel closes, and the outward potassium current stops, allowing the muscle cell’s membrane potential to rise and consequently depolarize to cause a contraction.', 'a3a54ece-31f1-40de-ac3e-9f1e54b27e27': 'So to summarize, the ratio of ventilation and perfusion changes across the lung, and this affects the alveolar and consequently arterial gas tensions from those regions. While the lung does not reach the ideal V/Q ratio,\xa0it is capable of shunting pulmonary blood flow away from unventilated areas to optimize gas exchange.'}"
+Figure 13.10,pulmo2/images/Figure 13.10.jpg,Figure 13.10: Response of pulmonary vasculature to hypoxia.,"The unusual response of the pulmonary vasculature is demonstrated in figure 13.10, showing how as alveolar PO2 falls (as occurs with a decline in alveolar ventilation) then blood flow falls—and likewise, the more oxygen in the alveolus, the more pulmonary perfusion it receives.","{'5ba36db2-9526-4010-9983-6e6b3bd379b3': 'In an attempt to maintain V/Q close to 1 and prevent V/Q mismatching, the pulmonary vasculature has an unusual response to hypoxia. While the systemic vasculature responds to local hypoxia with a vasodilation to bring more blood to the area, the pulmonary vasculature constricts in the presence of low oxygen to shunt blood away from hypoxic regions.', '612b5220-0f54-4d23-a7ec-030ebc728c48': 'Let us\xa0look at a common scenario that might occur in a patient with chronic bronchitis. Figure 13.9 represents two regions of the lung. One region becomes blocked by a mucus plug, and ventilation to that region goes to zero.', '4e716cd7-2a3d-4ff9-8152-0575cceb89ae': 'The alveolar partial pressures will rapidly equilibrate to venous pressures, and desaturated blood goes back to the left heart from this region while the local region around this area becomes mildly hypoxic. The pulmonary vasculature responds to the hypoxia by vasoconstricting, reducing the perfusion to the unventilated region and helping to rematch the V/Q ratio in this region (i.e., low ventilation is matched with low perfusion). In common sense terms, there is no point sending pulmonary blood to an unventilated region, so the hypoxia-driven vasoconstriction prevents this from happening.', 'b29ea3de-4ed5-4b0f-a6bd-6dcf00852fdf': 'The distensibility of the pulmonary vasculature means that the blood is shunted to unconstricted vessels (i.e., those supplying ventilated regions). Thus the lung has its own inherent mechanism to optimize V/Q and promote the most effective gas exchange possible.', '4fde109e-5932-4163-af9e-a45beb0d6c49': 'The unusual response of the pulmonary vasculature is demonstrated in figure 13.10, showing how as alveolar PO2 falls (as occurs with a decline in alveolar ventilation) then blood flow falls—and likewise, the more oxygen in the alveolus, the more pulmonary perfusion it receives.', '3be15f81-0c88-4ce4-83c2-19c9b755f4da': 'This effect is driven by a hypoxia-sensitive potassium channel found on the albeit sparse smooth muscle of the pulmonary arterioles. This channel is normally open and allows the exit of potassium, which in turn keeps the inside of the muscle cell polarized. When exposed to hypoxia the channel closes, and the outward potassium current stops, allowing the muscle cell’s membrane potential to rise and consequently depolarize to cause a contraction.', 'a3a54ece-31f1-40de-ac3e-9f1e54b27e27': 'So to summarize, the ratio of ventilation and perfusion changes across the lung, and this affects the alveolar and consequently arterial gas tensions from those regions. While the lung does not reach the ideal V/Q ratio,\xa0it is capable of shunting pulmonary blood flow away from unventilated areas to optimize gas exchange.'}"
+Figure 10.1,pulmo2/images/Figure 10.1.jpg,"Figure 10.1: Pulmonary metabolism of arachidonic acid. Blockade of cyclooxygenase by aspirin means more arachidonic acid is available for the production of leukotrienes, which can cause bronchoconstriction.","Arachidonic acid: The lung is also involved in the metabolism of arachidonic acid, which is worth dealing with here as well because not only are the products of this metabolism vasoactive, they can also influence airway smooth muscle and cause bronchoconstriction. In brief, arachidonic acid is produced by the action of a phospholipase on membrane-bound phospholipids. The arachidonic acid can then follow one of two pathways (figure 10.1): to produce leukotrienes, which are involved in the inflammatory response and can cause bronchoconstriction, or to produce prostaglandins and thromboxane through the action of cyclooxygenases. The relevance for us here is that these alternative pathways explain why some asthmatics are sensitive to aspirin and bronchoconstrict when they take aspirin. Aspirin inhibits cyclooxygenase and thus blocks one of these pathways. Consequently there is more substrate, arachidonic acid, available for the alternate pathway and so more leukotrienes are produced, in response to which the hypersensitive airways of the asthmatic bronchoconstrict.","{'f0baf849-e326-4ec8-93bb-514e7233bd5f': 'Because\xa0all cardiac output travels through the pulmonary circulation, it is\xa0ideally suited to host the enzymes needed to perform metabolic functions on blood components.', 'c6e65db3-efe0-4c75-aea2-22ddbed0900a': 'We will deal with only a few here as it is more effective to address each metabolic pathway in context of its function, rather than merely because of the location in which it occurs.', 'a0a2175b-9e8d-44cd-914c-9d802cc9a705': 'ACE: Perhaps the lung’s most well-known metabolic role is to host the angiotensin-converting enzyme (or ACE). This enzyme is responsible for converting angiotensin I (released during periods of hypotension) to angiotensin II, a powerful vasoconstrictor that helps raise blood pressure. The same enzyme also inactivates 80 percent\xa0of circulating bradykinin (a potent vasodilator).', '37f8cdc0-2060-4076-88d8-9f72c303515e': 'Serotonin: Other circulating substances that are controlled by the lung include serotonin, as the lung is the major site for removing serotonin from the circulation. The lung stores the serotonin, rather than breaking it down, and even transfers it to platelets who use serotonin in their hemostatic role.', 'd48f6563-76cf-4d0e-94ea-3da171ab0196': 'Arachidonic acid: The lung is also involved in the metabolism of arachidonic acid, which is worth dealing with here as well because\xa0not only are the products of this metabolism vasoactive, they can also influence airway smooth muscle\xa0and cause bronchoconstriction. In brief, arachidonic acid is produced by the action of a phospholipase on membrane-bound phospholipids. The arachidonic acid can then follow one of two pathways (figure 10.1): to produce leukotrienes, which\xa0are involved in the inflammatory response and can cause bronchoconstriction, or\xa0to produce prostaglandins and thromboxane through the action of cyclooxygenases. The relevance for us here is that these alternative pathways explain why some asthmatics are sensitive to aspirin and bronchoconstrict when they take aspirin. Aspirin inhibits cyclooxygenase\xa0and thus blocks one of these pathways. Consequently there is more substrate, arachidonic acid, available for the alternate pathway and so more leukotrienes are produced, in response to which\xa0the hypersensitive airways of the asthmatic bronchoconstrict.'}"
+Figure 9.1,pulmo2/images/Figure 9.1.jpg,Figure 9.1: The pulmonary circulation. A latex cast of the pulmonary circulation shows the complete and vast penetration of the lung structure by the vasculature.,"The pulmonary circulation takes all cardiac output from the right heart via the pulmonary arteries. Thus, even at rest it has a tremendous blood flow – about 5 liters per minute, just the same as the systemic circulation. This volume enters a vast array of vessels that penetrate all the lung structure – so much so that the complete lung structure is visible from the cast of the pulmonary vasculature in figure 9.1.","{'2d656643-3fd1-43fc-96ee-10525d50b3a7': 'The pulmonary circulation takes all cardiac output from the right heart via the pulmonary arteries. Thus, even at rest it has a tremendous blood flow – about 5 liters per minute, just the same as the systemic circulation. This volume enters a vast array of vessels that penetrate all the lung structure – so much so that the complete lung structure is visible from the cast of the pulmonary vasculature in figure 9.1.', '203cf211-dc4b-4b38-8067-a5e2bc9c8686': 'Main arteries follow a similar branching pattern to the bronchial tree until the terminal bronchioles are reached. This anatomical arrangement allows perfusion to follow the ventilation. Upon reaching the terminal bronchioles the vessels divide into a vast array of capillaries\xa0that wrap around the respiratory ducts and alveoli to form the respiratory zone of the lungs.', '71adf9d0-36ec-43e0-a596-d39992c60ac8': 'The density of the capillary beds is so great that individual capillaries can loose their distinct anatomy as can be seen in this electron micrograph where the capillaries are seen to form more sheet-like structures around where the alveoli would be. A common analogy for this is the capillaries look more like a floor of a parking garage with pillars for support but mainly open space – rather (figure 9.3) than the distinct tubes seen in other circulations.', 'd0577b04-fbad-40d6-a316-b00097d55971': 'The capillary beds converge into small veins after traveling over the alveolar surfaces, and these small veins then collect into four pulmonary veins that lead back to the left heart. This is an unusual example of veins carrying blood with arterial gas pressures.', '4a245151-c7e3-4f86-a18b-ec19ffdc9e6f': 'Despite receiving the same blood volume per minute as the systemic circulation the pulmonary circulation is a low-pressure system. Systolic pressure is normally only 25 mmHg, compared to 120 in the systemic circulation, diastolic is 8, compared to 80 and mean pulmonary artery pressure is only 15. These numbers are well worth remembering.', 'e736cb28-7cdf-4455-993e-4b5f2ffa34ab': 'So how can this one circulation receive so much volume (the complete cardiac output) and yet remain at such low pressure? The first reason is the vast size of the capillary beds. As figure 9.4 suggests, the much higher density of pulmonary capillary beds than that seen in the systemic circulation allows pressure to dissipate much more quickly.', 'b3758842-3c66-487d-ab1b-6fa24991e892': 'The pulmonary arteries show different characteristic to their systemic counterparts as well.\xa0The walls of a pulmonary arterioles are thin\xa0compared to systemic arterioles. They also lack\xa0the smooth muscle layer seen in the systemic arteriole. In fact pulmonary arterioles look much more like systemic veins and they are often mistaken for such in biopsy or dissection. With little smooth muscle it’s clear that these vessels have little role in controlling the distribution of blood flow – a vital role of their systemic counterparts. As the pulmonary circulation receives all cardiac output, all the time, such precise control isn’t required.', '36e1ecec-46eb-4a1f-9188-93fae0ef19ae': 'The thin walls and lack of smooth muscle also make the pulmonary arterioles highly compliant and so they behave much more like veins in their pressure response – extending when pressure increases. This gives the pulmonary arteriole system a rather unique pressure-resistance relationship that we’ll look at in a moment.', 'd733e2c5-3e4a-4418-a68f-e424ee6e64cc': 'This low pressure and compliant system also means that the right heart has much less work to perform to generate its output. In fact the right ventricle has about a tenth of the work of the left heart to move exactly the same blood volume. Hence the structure and work capacity of the right heart is so much smaller than the left – something worth bearing in mind if disease causes changes in the\xa0pulmonary vasculature that in turn causes the\xa0less substantial right heart to work harder and undergo hypertrophy'}"
+Figure 9.3,pulmo2/images/Figure 9.3.jpg,Figure 9.3: Schematic of the pulmonary and systemic circulations – compare capillary densities and pressures.,The density of the capillary beds is so great that individual capillaries can loose their distinct anatomy as can be seen in this electron micrograph where the capillaries are seen to form more sheet-like structures around where the alveoli would be. A common analogy for this is the capillaries look more like a floor of a parking garage with pillars for support but mainly open space – rather (figure 9.3) than the distinct tubes seen in other circulations.,"{'2d656643-3fd1-43fc-96ee-10525d50b3a7': 'The pulmonary circulation takes all cardiac output from the right heart via the pulmonary arteries. Thus, even at rest it has a tremendous blood flow – about 5 liters per minute, just the same as the systemic circulation. This volume enters a vast array of vessels that penetrate all the lung structure – so much so that the complete lung structure is visible from the cast of the pulmonary vasculature in figure 9.1.', '203cf211-dc4b-4b38-8067-a5e2bc9c8686': 'Main arteries follow a similar branching pattern to the bronchial tree until the terminal bronchioles are reached. This anatomical arrangement allows perfusion to follow the ventilation. Upon reaching the terminal bronchioles the vessels divide into a vast array of capillaries\xa0that wrap around the respiratory ducts and alveoli to form the respiratory zone of the lungs.', '71adf9d0-36ec-43e0-a596-d39992c60ac8': 'The density of the capillary beds is so great that individual capillaries can loose their distinct anatomy as can be seen in this electron micrograph where the capillaries are seen to form more sheet-like structures around where the alveoli would be. A common analogy for this is the capillaries look more like a floor of a parking garage with pillars for support but mainly open space – rather (figure 9.3) than the distinct tubes seen in other circulations.', 'd0577b04-fbad-40d6-a316-b00097d55971': 'The capillary beds converge into small veins after traveling over the alveolar surfaces, and these small veins then collect into four pulmonary veins that lead back to the left heart. This is an unusual example of veins carrying blood with arterial gas pressures.', '4a245151-c7e3-4f86-a18b-ec19ffdc9e6f': 'Despite receiving the same blood volume per minute as the systemic circulation the pulmonary circulation is a low-pressure system. Systolic pressure is normally only 25 mmHg, compared to 120 in the systemic circulation, diastolic is 8, compared to 80 and mean pulmonary artery pressure is only 15. These numbers are well worth remembering.', 'e736cb28-7cdf-4455-993e-4b5f2ffa34ab': 'So how can this one circulation receive so much volume (the complete cardiac output) and yet remain at such low pressure? The first reason is the vast size of the capillary beds. As figure 9.4 suggests, the much higher density of pulmonary capillary beds than that seen in the systemic circulation allows pressure to dissipate much more quickly.', 'b3758842-3c66-487d-ab1b-6fa24991e892': 'The pulmonary arteries show different characteristic to their systemic counterparts as well.\xa0The walls of a pulmonary arterioles are thin\xa0compared to systemic arterioles. They also lack\xa0the smooth muscle layer seen in the systemic arteriole. In fact pulmonary arterioles look much more like systemic veins and they are often mistaken for such in biopsy or dissection. With little smooth muscle it’s clear that these vessels have little role in controlling the distribution of blood flow – a vital role of their systemic counterparts. As the pulmonary circulation receives all cardiac output, all the time, such precise control isn’t required.', '36e1ecec-46eb-4a1f-9188-93fae0ef19ae': 'The thin walls and lack of smooth muscle also make the pulmonary arterioles highly compliant and so they behave much more like veins in their pressure response – extending when pressure increases. This gives the pulmonary arteriole system a rather unique pressure-resistance relationship that we’ll look at in a moment.', 'd733e2c5-3e4a-4418-a68f-e424ee6e64cc': 'This low pressure and compliant system also means that the right heart has much less work to perform to generate its output. In fact the right ventricle has about a tenth of the work of the left heart to move exactly the same blood volume. Hence the structure and work capacity of the right heart is so much smaller than the left – something worth bearing in mind if disease causes changes in the\xa0pulmonary vasculature that in turn causes the\xa0less substantial right heart to work harder and undergo hypertrophy'}"
+Figure 9.4,pulmo2/images/Figure 9.4.jpg,Figure 9.4: Pulmonary vascular resistance decreases as pressure increases.,"So how can this one circulation receive so much volume (the complete cardiac output) and yet remain at such low pressure? The first reason is the vast size of the capillary beds. As figure 9.4 suggests, the much higher density of pulmonary capillary beds than that seen in the systemic circulation allows pressure to dissipate much more quickly.","{'2d656643-3fd1-43fc-96ee-10525d50b3a7': 'The pulmonary circulation takes all cardiac output from the right heart via the pulmonary arteries. Thus, even at rest it has a tremendous blood flow – about 5 liters per minute, just the same as the systemic circulation. This volume enters a vast array of vessels that penetrate all the lung structure – so much so that the complete lung structure is visible from the cast of the pulmonary vasculature in figure 9.1.', '203cf211-dc4b-4b38-8067-a5e2bc9c8686': 'Main arteries follow a similar branching pattern to the bronchial tree until the terminal bronchioles are reached. This anatomical arrangement allows perfusion to follow the ventilation. Upon reaching the terminal bronchioles the vessels divide into a vast array of capillaries\xa0that wrap around the respiratory ducts and alveoli to form the respiratory zone of the lungs.', '71adf9d0-36ec-43e0-a596-d39992c60ac8': 'The density of the capillary beds is so great that individual capillaries can loose their distinct anatomy as can be seen in this electron micrograph where the capillaries are seen to form more sheet-like structures around where the alveoli would be. A common analogy for this is the capillaries look more like a floor of a parking garage with pillars for support but mainly open space – rather (figure 9.3) than the distinct tubes seen in other circulations.', 'd0577b04-fbad-40d6-a316-b00097d55971': 'The capillary beds converge into small veins after traveling over the alveolar surfaces, and these small veins then collect into four pulmonary veins that lead back to the left heart. This is an unusual example of veins carrying blood with arterial gas pressures.', '4a245151-c7e3-4f86-a18b-ec19ffdc9e6f': 'Despite receiving the same blood volume per minute as the systemic circulation the pulmonary circulation is a low-pressure system. Systolic pressure is normally only 25 mmHg, compared to 120 in the systemic circulation, diastolic is 8, compared to 80 and mean pulmonary artery pressure is only 15. These numbers are well worth remembering.', 'e736cb28-7cdf-4455-993e-4b5f2ffa34ab': 'So how can this one circulation receive so much volume (the complete cardiac output) and yet remain at such low pressure? The first reason is the vast size of the capillary beds. As figure 9.4 suggests, the much higher density of pulmonary capillary beds than that seen in the systemic circulation allows pressure to dissipate much more quickly.', 'b3758842-3c66-487d-ab1b-6fa24991e892': 'The pulmonary arteries show different characteristic to their systemic counterparts as well.\xa0The walls of a pulmonary arterioles are thin\xa0compared to systemic arterioles. They also lack\xa0the smooth muscle layer seen in the systemic arteriole. In fact pulmonary arterioles look much more like systemic veins and they are often mistaken for such in biopsy or dissection. With little smooth muscle it’s clear that these vessels have little role in controlling the distribution of blood flow – a vital role of their systemic counterparts. As the pulmonary circulation receives all cardiac output, all the time, such precise control isn’t required.', '36e1ecec-46eb-4a1f-9188-93fae0ef19ae': 'The thin walls and lack of smooth muscle also make the pulmonary arterioles highly compliant and so they behave much more like veins in their pressure response – extending when pressure increases. This gives the pulmonary arteriole system a rather unique pressure-resistance relationship that we’ll look at in a moment.', 'd733e2c5-3e4a-4418-a68f-e424ee6e64cc': 'This low pressure and compliant system also means that the right heart has much less work to perform to generate its output. In fact the right ventricle has about a tenth of the work of the left heart to move exactly the same blood volume. Hence the structure and work capacity of the right heart is so much smaller than the left – something worth bearing in mind if disease causes changes in the\xa0pulmonary vasculature that in turn causes the\xa0less substantial right heart to work harder and undergo hypertrophy', '6325a5d6-c907-458f-84da-8cb60a279adc': 'As we have just seen, with little smooth muscle and a compliant wall, the arterioles act more like veins. As pulmonary arterial pressure rises, the resistance of the pulmonary circulation falls, as seen in figure 9.4, and this occurs for\xa0several reasons.', '2bbb86e4-449d-4278-ad09-1990a2d8b684': 'Unlike systemic arterioles there is little autoregulation by the pulmonary arterioles, so the pulmonary arterioles do not actively vasoconstrict when stretched by high pressure. Instead, they passively distend, thereby reducing their resistance with increasing resistance.', 'e559d206-42f3-4699-bd6c-3b0df3ae3c3c': 'A rise in pulmonary pressure not only distends vessels but initiates flow through otherwise unused, or dormant, vessels, particularly those closer to the apex of the lung (we will see why later on). With more vessels recruited, the total cross-sectional area of used vessels increases and total resistance falls.', '3ec59c37-13fa-479f-8c93-87d98c5f6443': 'But there are other and more complex peculiarities of the pulmonary circulation that determine its resistance…'}"
+Figure 9.4,pulmo2/images/Figure 9.4.jpg,Figure 9.4: Pulmonary vascular resistance decreases as pressure increases.,"So how can this one circulation receive so much volume (the complete cardiac output) and yet remain at such low pressure? The first reason is the vast size of the capillary beds. As figure 9.4 suggests, the much higher density of pulmonary capillary beds than that seen in the systemic circulation allows pressure to dissipate much more quickly.","{'2d656643-3fd1-43fc-96ee-10525d50b3a7': 'The pulmonary circulation takes all cardiac output from the right heart via the pulmonary arteries. Thus, even at rest it has a tremendous blood flow – about 5 liters per minute, just the same as the systemic circulation. This volume enters a vast array of vessels that penetrate all the lung structure – so much so that the complete lung structure is visible from the cast of the pulmonary vasculature in figure 9.1.', '203cf211-dc4b-4b38-8067-a5e2bc9c8686': 'Main arteries follow a similar branching pattern to the bronchial tree until the terminal bronchioles are reached. This anatomical arrangement allows perfusion to follow the ventilation. Upon reaching the terminal bronchioles the vessels divide into a vast array of capillaries\xa0that wrap around the respiratory ducts and alveoli to form the respiratory zone of the lungs.', '71adf9d0-36ec-43e0-a596-d39992c60ac8': 'The density of the capillary beds is so great that individual capillaries can loose their distinct anatomy as can be seen in this electron micrograph where the capillaries are seen to form more sheet-like structures around where the alveoli would be. A common analogy for this is the capillaries look more like a floor of a parking garage with pillars for support but mainly open space – rather (figure 9.3) than the distinct tubes seen in other circulations.', 'd0577b04-fbad-40d6-a316-b00097d55971': 'The capillary beds converge into small veins after traveling over the alveolar surfaces, and these small veins then collect into four pulmonary veins that lead back to the left heart. This is an unusual example of veins carrying blood with arterial gas pressures.', '4a245151-c7e3-4f86-a18b-ec19ffdc9e6f': 'Despite receiving the same blood volume per minute as the systemic circulation the pulmonary circulation is a low-pressure system. Systolic pressure is normally only 25 mmHg, compared to 120 in the systemic circulation, diastolic is 8, compared to 80 and mean pulmonary artery pressure is only 15. These numbers are well worth remembering.', 'e736cb28-7cdf-4455-993e-4b5f2ffa34ab': 'So how can this one circulation receive so much volume (the complete cardiac output) and yet remain at such low pressure? The first reason is the vast size of the capillary beds. As figure 9.4 suggests, the much higher density of pulmonary capillary beds than that seen in the systemic circulation allows pressure to dissipate much more quickly.', 'b3758842-3c66-487d-ab1b-6fa24991e892': 'The pulmonary arteries show different characteristic to their systemic counterparts as well.\xa0The walls of a pulmonary arterioles are thin\xa0compared to systemic arterioles. They also lack\xa0the smooth muscle layer seen in the systemic arteriole. In fact pulmonary arterioles look much more like systemic veins and they are often mistaken for such in biopsy or dissection. With little smooth muscle it’s clear that these vessels have little role in controlling the distribution of blood flow – a vital role of their systemic counterparts. As the pulmonary circulation receives all cardiac output, all the time, such precise control isn’t required.', '36e1ecec-46eb-4a1f-9188-93fae0ef19ae': 'The thin walls and lack of smooth muscle also make the pulmonary arterioles highly compliant and so they behave much more like veins in their pressure response – extending when pressure increases. This gives the pulmonary arteriole system a rather unique pressure-resistance relationship that we’ll look at in a moment.', 'd733e2c5-3e4a-4418-a68f-e424ee6e64cc': 'This low pressure and compliant system also means that the right heart has much less work to perform to generate its output. In fact the right ventricle has about a tenth of the work of the left heart to move exactly the same blood volume. Hence the structure and work capacity of the right heart is so much smaller than the left – something worth bearing in mind if disease causes changes in the\xa0pulmonary vasculature that in turn causes the\xa0less substantial right heart to work harder and undergo hypertrophy', '6325a5d6-c907-458f-84da-8cb60a279adc': 'As we have just seen, with little smooth muscle and a compliant wall, the arterioles act more like veins. As pulmonary arterial pressure rises, the resistance of the pulmonary circulation falls, as seen in figure 9.4, and this occurs for\xa0several reasons.', '2bbb86e4-449d-4278-ad09-1990a2d8b684': 'Unlike systemic arterioles there is little autoregulation by the pulmonary arterioles, so the pulmonary arterioles do not actively vasoconstrict when stretched by high pressure. Instead, they passively distend, thereby reducing their resistance with increasing resistance.', 'e559d206-42f3-4699-bd6c-3b0df3ae3c3c': 'A rise in pulmonary pressure not only distends vessels but initiates flow through otherwise unused, or dormant, vessels, particularly those closer to the apex of the lung (we will see why later on). With more vessels recruited, the total cross-sectional area of used vessels increases and total resistance falls.', '3ec59c37-13fa-479f-8c93-87d98c5f6443': 'But there are other and more complex peculiarities of the pulmonary circulation that determine its resistance…'}"
+Figure 9.5,pulmo2/images/Figure 9.5.jpg,Figure 9.5: Pulmonary vessels can be categorized as alveolar or extra-alveolar.,"To explain these phenomena we have to divide the pulmonary circulation into two subdivisions, the alveolar vessels and the extra-alveolar vessels (figure 9.5). These two vessel types behave differently, so we will deal with them separately.","{'18ebdcaa-ba5a-453f-8caa-380515f09552': 'Another unique characteristic of the pulmonary circulation is that it is exposed to the changing pressures in the airways and alveoli. It is also involved in the fiber network that generates radial traction. Consequently pulmonary vessels can be expanded or compressed in a way no other circulation is.', '3f0e9c13-9090-4942-9128-184922b0e4e5': 'To explain these phenomena we have to divide the pulmonary circulation into two subdivisions, the alveolar vessels and the extra-alveolar vessels (figure 9.5). These two vessel types behave differently, so we will deal with them separately.', '30c04fba-638c-4161-875c-e9c874074e28': 'Alveolar vessels: These are primarily the capillaries and small vessels in close contact with the alveoli. Consequently they are exposed to the alveolar pressures. First,\xa0the surface tension within the alveolus that is tending to pull the alveolus closed also pulls on the vessels between alveoli, tending to pull it open as neighboring alveoli pull inward on themselves, and play tug-of-war with the vessel walls in between, extending them and causing a decrease in vascular resistance.', 'a6908a5d-de72-4643-9dbd-7c05bae9db4a': 'Alternatively, when alveolar pressure increases (e.g., at high lung volumes), the raised alveolar pressure can compress the vessels running over its surface, causing an increase in vascular resistance.', '33efc853-5de8-41ff-8faa-0de4b021fdf1': 'Extra-alveolar vessels: By definition these vessels are not in contact with the alveoli, so they are not exposed to the same alveolar forces. These are exposed to the intrapleural forces, however, so as we saw airways opening during inspiration when intra-pleural pressure falls, these extra-alveolar vessels are also pulled open during inspiration by radial traction, and their resistance consequently falls as lung volume increases.', '41d6d59f-fe3d-411a-a0c2-66ac80e86083': 'The summation of these forces (alveolar pressure, surface tension, and radial traction) means that pulmonary vasculature resistance has a complex relationship with lung volume.'}"
+Figure 9.6,pulmo2/images/Figure 9.6.jpg,Figure 9.6: The relationship between lung volume and pulmonary vascular resistance.,"Vascular resistance at low lung volumes: At low lung volumes (figure 9.6, gray zone on the left), you should know that intra-pleural pressure is less negative because the lung recoil is less. With less negative pressure to hold open the extra-alveolar vessels via radial traction, these tend to narrow and vasculature resistance becomes relatively high.","{'79ac47de-cbee-4e67-902e-326cf326ff5a': 'Vascular resistance at low lung volumes: At low lung volumes (figure 9.6, gray zone on the left), you should know that intra-pleural pressure is less negative because the lung recoil is less. With less negative pressure to hold open the extra-alveolar vessels via radial traction,\xa0these tend to narrow and vasculature resistance becomes relatively high.', 'c8eb161e-6df3-439e-b207-ca61bd6a145b': 'Vascular resistance at medium lung volumes: As lung volume increases (figure 9.6, tan zone in the middle), the intrapleural pressure becomes more negative. Radial or parenchymal traction now begins to pull the extra-alveolar vessels open, and as they become wider, vascular resistance falls. Common sense would tell you that this effect would increase with continually larger lung volumes, and one might expect that vascular resistance would continue to decrease as lung volume increased. But this is evidently not the case.', '662a01db-ceb5-4631-8916-57168017e69f': 'Vascular resistance at high lung volumes: With further increases in lung volume (figure 9.6, pink zone on the right), vascular resistance rises. At high lung volumes the alveoli are enlarging, and this causes the capillaries running around them to stretch. As the capillaries stretch, they\xa0narrow—a little like how a piece of latex tubing narrows when it is\xa0stretched. This narrowing of a large number of capillaries overcomes the radial traction effect on the extra-alveolar vessels, and there is a net increase in vascular resistance.', '689ce975-ea30-416b-844d-fd839fcb438f': 'So vascular resistance and lung volume are related with an inverted bell-shaped relationship. Now let us\xa0look at the forces that determine the distribution of blood flow across the lung structure.'}"
+Figure 9.7,pulmo2/images/Figure 9.7.jpg,Figure 9.7: Perfusion distribution up the lung.,"We see a similar distribution of blood flow in the lung as well, as figure 9.7 shows with blood flow being greater at the base of the lung than it is at the apex. Again this is simply due to gravity. Gravity pushes against the blood rising from heart level, hence the base is better perfused than the apex. Because of this, gravity is responsible for matching the level of perfusion and ventilation up the lung; both are high at the bottom, and both are low at the apex. This is advantageous, as well ventilated areas need more perfusion for efficient gas exchange, and likewise there is little point in sending large amounts of pulmonary blood to poorly ventilated areas. The relationship between ventilation and perfusion (known as the V/Q ratio) that gravity establishes is not quite ideal, however, and we will see the ramifications of this less-than-perfect relationship later on. There are also other forces affecting the distribution of perfusion as well, and we can look at them now.","{'ebf14881-b887-46d5-aa4b-57d239510c35': 'You may recall that gravity affected the distribution of ventilation by generating the gradient of intrapleural pressures down the lung—most negative at the apex, less negative at the base.', '3e7ca2e1-e790-4b9f-b380-ae003c217ec6': 'We see a similar distribution of blood flow in the lung as well, as figure 9.7\xa0shows with blood flow being greater at the base of the lung than it is at the apex. Again this is simply due to gravity. Gravity pushes against the blood rising from heart level, hence the base is better perfused than the apex. Because of this, gravity is responsible for matching the level of perfusion and ventilation up the lung; both are high at the bottom, and both are low at the apex. This is advantageous, as well ventilated areas need more perfusion for efficient gas exchange, and likewise there is little point in sending large amounts of pulmonary blood to poorly ventilated areas. The relationship between ventilation and perfusion (known as the V/Q ratio) that gravity establishes is not quite ideal, however, and we will see the ramifications of this less-than-perfect relationship later on. There are also other forces affecting the distribution of perfusion as well, and we can look at them now.'}"
+Figure 8.1,pulmo2/images/Figure 8.1.jpg,Figure 8.1: Diffusion and perfusion limitations.,"If a sufficient diffusion gradient exists across a membrane, then the rate of transfer of gas is primarily dependent on the properties of the membrane (see the left side of the figure 8.1). The transfer of gas in this case is referred to as a diffusion limitation.","{'ea085c56-bcc8-4188-83d6-9514a3d788c6': 'Identifying whether deranged blood gases are due to diffusion or perfusion limitations can help in the diagnosis of an underlying pathological issue, so we will look at them here.', '463fa892-1416-4654-be18-50ff142f7f54': 'If a sufficient diffusion gradient exists across a membrane, then the rate of transfer of gas is primarily dependent on the properties of the membrane (see the left side of the figure 8.1). The transfer of gas in this case is referred to as a diffusion limitation.', '3c95b469-429c-4487-826d-731547875baa': 'If gas starts to accumulate on the other side of the membrane, however, the pressure gradient will dissipate and transfer rates become limited (right side of figure 8.1). This is referred to as a perfusion limitation, as it is indicative of low blood flow that is insufficient to “wash away”\xa0transferred gas, keep blood gas partial pressure low, and maintain the diffusion gradient.', '6c66fe37-5877-45a5-8184-401b37c5900c': 'We can illustrate these diffusion and perfusion limitations with the behavior of two nonphysiological gases transferring from the alveolus to the bloodstream.', '2e41ac57-5da4-462e-a1ea-a28cb636db14': 'Carbon monoxide is well known for its affinity for hemoglobin. When CO passes across the membrane it rapidly binds to hemoglobin and is thus removed from solution. This removal from solution maintains the pressure gradient across the membrane. So with a maintained pressure gradient the major impediment to CO transfer is diffusion across the membrane. Therefore CO transfer is referred to as diffusion limited and dependent on the properties of the membrane. (Consequently CO is used in diffusion limitation testing (DLCO) in pulmonary function labs.)', '79366767-25f0-4533-89cb-10bcd3076920': 'Nitrous oxide, alternatively, does not\xa0bind with hemoglobin at all, so its arterial partial pressure rises rapidly as it stays in solution. So maintaining the pressure gradient is dependent on how quickly the transferred nitrous oxide is washed away by blood flow. Because of this, nitrous oxide is referred to as perfusion limited.', '984378f8-8885-440a-93fe-2ed0658d9617': 'So while our two nonphysiological gases provide good examples of diffusion and perfusion limitations, let us\xa0see how oxygen behaves.', '5112588e-a1a8-4d11-ab6b-ec9e9a12b260': 'The blood partial pressure of CO rises very little along the capillary as it is rapidly binding to hemoglobin (Hb)\xa0(figure 8.2), the pressure gradient is maintained, and the CO is only limited by the membrane; it exhibits diffusion limitation.', 'fcb04a87-d9cf-452a-bfc9-9e25aede1a08': 'The blood partial pressure of nitrous oxide, alternatively, rapidly rises (figure 8.2), and the transfer of NO becomes reliant on the rate of perfusion to maintain the gradient and gas transfer\xa0(i.e., it is\xa0perfusion limited).', '07c87127-f693-453f-bb01-92a16e7f2c7d': 'The results for O2\xa0fall much closer to the perfusion limitation (NO) line than the diffusion limitation line (figure 8.2, O2\xa0normal). Oxygen binds to hemoglobin so the arterial PO2\xa0does\xa0not rise as quickly as nitrous oxide, but the binding of O2\xa0is so much less than carbon monoxide it actually demonstrates more perfusion, rather than diffusion limitation.', '7c077748-f7da-4e48-82c8-e8c12aa90d58': 'The transfer of O2\xa0is also hampered by having to start off at venous partial pressures (40 mmHg), compared to our test gases that start off at zero. Consequently the initial pressure gradient is less. Despite this, the arterial partial pressure of oxygen equilibrates with alveolar pressures within 0.25 seconds (i.e., a third of the distance around the capillary). With the blood still having another 0.5 seconds in the capillary, this provides a large reserve time.', 'a832895e-d2aa-49dd-8fc7-669911a24b06': 'This reserve time is often eaten into in some disease states (figure 8.2, abnormal); if for example a diffusion problem arises, such as thickening of the membrane, then that extra 0.5 seconds, or last 2/3 seconds of the transit time around the alveolus, can still allow alveolar and arterial PO2s to equilibrate. The patient may still show normal oxygen pressures until they exercise, during which the velocity of pulmonary blood flow increases and transit time is reduced; you can see from figure 8.2 if transit time is reduced to 0.5 seconds then arterial PO2\xa0will not equilibrate with alveolar values in the abnormal lung.', '00d5d42c-2cac-4631-a847-74fc82e3cfce': 'While in the normal state the transfer of oxygen is perfusion limited, in lung diseases that affect the surface area or membrane thickness of the gas exchange surface, the transfer of oxygen may become diffusion limited. Being able to measure the transfer of gas into the blood provides a valuable diagnostic tool. This is what we will look at here, not only because of its clinical pertinence, but also because it summarizes some physiological principles.'}"
+Figure 8.2,pulmo2/images/Figure 8.2.jpg,Figure 8.2: Transfer of gases from alveolus to capillary.,"The blood partial pressure of CO rises very little along the capillary as it is rapidly binding to hemoglobin (Hb) (figure 8.2), the pressure gradient is maintained, and the CO is only limited by the membrane; it exhibits diffusion limitation.","{'ea085c56-bcc8-4188-83d6-9514a3d788c6': 'Identifying whether deranged blood gases are due to diffusion or perfusion limitations can help in the diagnosis of an underlying pathological issue, so we will look at them here.', '463fa892-1416-4654-be18-50ff142f7f54': 'If a sufficient diffusion gradient exists across a membrane, then the rate of transfer of gas is primarily dependent on the properties of the membrane (see the left side of the figure 8.1). The transfer of gas in this case is referred to as a diffusion limitation.', '3c95b469-429c-4487-826d-731547875baa': 'If gas starts to accumulate on the other side of the membrane, however, the pressure gradient will dissipate and transfer rates become limited (right side of figure 8.1). This is referred to as a perfusion limitation, as it is indicative of low blood flow that is insufficient to “wash away”\xa0transferred gas, keep blood gas partial pressure low, and maintain the diffusion gradient.', '6c66fe37-5877-45a5-8184-401b37c5900c': 'We can illustrate these diffusion and perfusion limitations with the behavior of two nonphysiological gases transferring from the alveolus to the bloodstream.', '2e41ac57-5da4-462e-a1ea-a28cb636db14': 'Carbon monoxide is well known for its affinity for hemoglobin. When CO passes across the membrane it rapidly binds to hemoglobin and is thus removed from solution. This removal from solution maintains the pressure gradient across the membrane. So with a maintained pressure gradient the major impediment to CO transfer is diffusion across the membrane. Therefore CO transfer is referred to as diffusion limited and dependent on the properties of the membrane. (Consequently CO is used in diffusion limitation testing (DLCO) in pulmonary function labs.)', '79366767-25f0-4533-89cb-10bcd3076920': 'Nitrous oxide, alternatively, does not\xa0bind with hemoglobin at all, so its arterial partial pressure rises rapidly as it stays in solution. So maintaining the pressure gradient is dependent on how quickly the transferred nitrous oxide is washed away by blood flow. Because of this, nitrous oxide is referred to as perfusion limited.', '984378f8-8885-440a-93fe-2ed0658d9617': 'So while our two nonphysiological gases provide good examples of diffusion and perfusion limitations, let us\xa0see how oxygen behaves.', '5112588e-a1a8-4d11-ab6b-ec9e9a12b260': 'The blood partial pressure of CO rises very little along the capillary as it is rapidly binding to hemoglobin (Hb)\xa0(figure 8.2), the pressure gradient is maintained, and the CO is only limited by the membrane; it exhibits diffusion limitation.', 'fcb04a87-d9cf-452a-bfc9-9e25aede1a08': 'The blood partial pressure of nitrous oxide, alternatively, rapidly rises (figure 8.2), and the transfer of NO becomes reliant on the rate of perfusion to maintain the gradient and gas transfer\xa0(i.e., it is\xa0perfusion limited).', '07c87127-f693-453f-bb01-92a16e7f2c7d': 'The results for O2\xa0fall much closer to the perfusion limitation (NO) line than the diffusion limitation line (figure 8.2, O2\xa0normal). Oxygen binds to hemoglobin so the arterial PO2\xa0does\xa0not rise as quickly as nitrous oxide, but the binding of O2\xa0is so much less than carbon monoxide it actually demonstrates more perfusion, rather than diffusion limitation.', '7c077748-f7da-4e48-82c8-e8c12aa90d58': 'The transfer of O2\xa0is also hampered by having to start off at venous partial pressures (40 mmHg), compared to our test gases that start off at zero. Consequently the initial pressure gradient is less. Despite this, the arterial partial pressure of oxygen equilibrates with alveolar pressures within 0.25 seconds (i.e., a third of the distance around the capillary). With the blood still having another 0.5 seconds in the capillary, this provides a large reserve time.', 'a832895e-d2aa-49dd-8fc7-669911a24b06': 'This reserve time is often eaten into in some disease states (figure 8.2, abnormal); if for example a diffusion problem arises, such as thickening of the membrane, then that extra 0.5 seconds, or last 2/3 seconds of the transit time around the alveolus, can still allow alveolar and arterial PO2s to equilibrate. The patient may still show normal oxygen pressures until they exercise, during which the velocity of pulmonary blood flow increases and transit time is reduced; you can see from figure 8.2 if transit time is reduced to 0.5 seconds then arterial PO2\xa0will not equilibrate with alveolar values in the abnormal lung.', '00d5d42c-2cac-4631-a847-74fc82e3cfce': 'While in the normal state the transfer of oxygen is perfusion limited, in lung diseases that affect the surface area or membrane thickness of the gas exchange surface, the transfer of oxygen may become diffusion limited. Being able to measure the transfer of gas into the blood provides a valuable diagnostic tool. This is what we will look at here, not only because of its clinical pertinence, but also because it summarizes some physiological principles.'}"
+Figure 7.1,pulmo2/images/Figure 7.1.jpg,Figure 7.1: Oxygen tensions around the alveolus.,"So how does this value relate to gas exchange in the lung? The venous blood PO2 (PVO2), returning from the systemic tissue where oxygen has been consumed, is 40 mmHg (see figure 7.1). This blood passes the gas exchange surface, and a pressure gradient of 60 mmHg allows oxygen to move into the pulmonary blood. By the time the blood has passed the alveolus, arterial PO2 will have equilibrated with the alveolar PO2 and will also be 100 mmHg. These numbers are well worth committing to memory.","{'58d7a984-0b05-480d-a977-641d70b4ff44': '[latex]P_AO_2 = 20.9\\% \\times (760 - 47) = 149.7\\:mmHg\\:or \\sim 150\\:mmHg[/latex]', 'd78ff3df-9ffa-46b9-b14f-8135c3c1a230': 'If we understand that there will be mixing with air remaining from the previous breath, the real PAO2\xa0is 100 mmHg (however, we will see this varies across the regions of the lung).', '08e5a60b-4262-4849-8300-e592f290d3d6': 'So how does this value relate to gas exchange in the lung? The venous blood PO2\xa0(PVO2), returning from the systemic tissue where oxygen has been consumed, is 40 mmHg (see figure 7.1). This blood passes the gas exchange surface, and a pressure gradient of 60 mmHg allows oxygen to move into the pulmonary blood. By the time the blood has passed\xa0the alveolus, arterial PO2\xa0will have equilibrated with the alveolar PO2\xa0and will also be 100 mmHg. These numbers are well worth committing to memory.', 'ed53b093-27bf-4647-99ec-a32df33bc45a': 'The other critical values we need to address here are the partial pressures of CO2\xa0(see figure 7.2). Venous blood returning from the tissue has a PCO2\xa0of 45 mmHg, compared to alveolar PCO2\xa0that is 40 mmHg. This pressure gradient of 5 mmHg is enough to allow blood to equilibrate with the alveolus, and so arterial PCO2\xa0is 40 mmHg.\xa0Again, these numbers are worth remembering.', '80f14e98-6d0d-46d5-a094-2dd9f1a23aa6': 'A much smaller diffusion gradient is needed for CO2 because CO2\xa0is much more soluble than oxygen, a factor\xa0among\xa0others that is\xa0included in Fick’s law of diffusion.'}"
+Figure 7.2,pulmo2/images/Figure 7.2.jpg,Figure 7.2: Carbon dioxide tensions around the alveolus.,"The other critical values we need to address here are the partial pressures of CO2 (see figure 7.2). Venous blood returning from the tissue has a PCO2 of 45 mmHg, compared to alveolar PCO2 that is 40 mmHg. This pressure gradient of 5 mmHg is enough to allow blood to equilibrate with the alveolus, and so arterial PCO2 is 40 mmHg. Again, these numbers are worth remembering.","{'58d7a984-0b05-480d-a977-641d70b4ff44': '[latex]P_AO_2 = 20.9\\% \\times (760 - 47) = 149.7\\:mmHg\\:or \\sim 150\\:mmHg[/latex]', 'd78ff3df-9ffa-46b9-b14f-8135c3c1a230': 'If we understand that there will be mixing with air remaining from the previous breath, the real PAO2\xa0is 100 mmHg (however, we will see this varies across the regions of the lung).', '08e5a60b-4262-4849-8300-e592f290d3d6': 'So how does this value relate to gas exchange in the lung? The venous blood PO2\xa0(PVO2), returning from the systemic tissue where oxygen has been consumed, is 40 mmHg (see figure 7.1). This blood passes the gas exchange surface, and a pressure gradient of 60 mmHg allows oxygen to move into the pulmonary blood. By the time the blood has passed\xa0the alveolus, arterial PO2\xa0will have equilibrated with the alveolar PO2\xa0and will also be 100 mmHg. These numbers are well worth committing to memory.', 'ed53b093-27bf-4647-99ec-a32df33bc45a': 'The other critical values we need to address here are the partial pressures of CO2\xa0(see figure 7.2). Venous blood returning from the tissue has a PCO2\xa0of 45 mmHg, compared to alveolar PCO2\xa0that is 40 mmHg. This pressure gradient of 5 mmHg is enough to allow blood to equilibrate with the alveolus, and so arterial PCO2\xa0is 40 mmHg.\xa0Again, these numbers are worth remembering.', '80f14e98-6d0d-46d5-a094-2dd9f1a23aa6': 'A much smaller diffusion gradient is needed for CO2 because CO2\xa0is much more soluble than oxygen, a factor\xa0among\xa0others that is\xa0included in Fick’s law of diffusion.'}"
+Figure 7.1,pulmo2/images/Figure 7.1.jpg,Figure 7.1: Oxygen tensions around the alveolus.,"So how does this value relate to gas exchange in the lung? The venous blood PO2 (PVO2), returning from the systemic tissue where oxygen has been consumed, is 40 mmHg (see figure 7.1). This blood passes the gas exchange surface, and a pressure gradient of 60 mmHg allows oxygen to move into the pulmonary blood. By the time the blood has passed the alveolus, arterial PO2 will have equilibrated with the alveolar PO2 and will also be 100 mmHg. These numbers are well worth committing to memory.","{'58d7a984-0b05-480d-a977-641d70b4ff44': '[latex]P_AO_2 = 20.9\\% \\times (760 - 47) = 149.7\\:mmHg\\:or \\sim 150\\:mmHg[/latex]', 'd78ff3df-9ffa-46b9-b14f-8135c3c1a230': 'If we understand that there will be mixing with air remaining from the previous breath, the real PAO2\xa0is 100 mmHg (however, we will see this varies across the regions of the lung).', '08e5a60b-4262-4849-8300-e592f290d3d6': 'So how does this value relate to gas exchange in the lung? The venous blood PO2\xa0(PVO2), returning from the systemic tissue where oxygen has been consumed, is 40 mmHg (see figure 7.1). This blood passes the gas exchange surface, and a pressure gradient of 60 mmHg allows oxygen to move into the pulmonary blood. By the time the blood has passed\xa0the alveolus, arterial PO2\xa0will have equilibrated with the alveolar PO2\xa0and will also be 100 mmHg. These numbers are well worth committing to memory.', 'ed53b093-27bf-4647-99ec-a32df33bc45a': 'The other critical values we need to address here are the partial pressures of CO2\xa0(see figure 7.2). Venous blood returning from the tissue has a PCO2\xa0of 45 mmHg, compared to alveolar PCO2\xa0that is 40 mmHg. This pressure gradient of 5 mmHg is enough to allow blood to equilibrate with the alveolus, and so arterial PCO2\xa0is 40 mmHg.\xa0Again, these numbers are worth remembering.', '80f14e98-6d0d-46d5-a094-2dd9f1a23aa6': 'A much smaller diffusion gradient is needed for CO2 because CO2\xa0is much more soluble than oxygen, a factor\xa0among\xa0others that is\xa0included in Fick’s law of diffusion.'}"
+Figure 7.2,pulmo2/images/Figure 7.2.jpg,Figure 7.2: Carbon dioxide tensions around the alveolus.,"The other critical values we need to address here are the partial pressures of CO2 (see figure 7.2). Venous blood returning from the tissue has a PCO2 of 45 mmHg, compared to alveolar PCO2 that is 40 mmHg. This pressure gradient of 5 mmHg is enough to allow blood to equilibrate with the alveolus, and so arterial PCO2 is 40 mmHg. Again, these numbers are worth remembering.","{'58d7a984-0b05-480d-a977-641d70b4ff44': '[latex]P_AO_2 = 20.9\\% \\times (760 - 47) = 149.7\\:mmHg\\:or \\sim 150\\:mmHg[/latex]', 'd78ff3df-9ffa-46b9-b14f-8135c3c1a230': 'If we understand that there will be mixing with air remaining from the previous breath, the real PAO2\xa0is 100 mmHg (however, we will see this varies across the regions of the lung).', '08e5a60b-4262-4849-8300-e592f290d3d6': 'So how does this value relate to gas exchange in the lung? The venous blood PO2\xa0(PVO2), returning from the systemic tissue where oxygen has been consumed, is 40 mmHg (see figure 7.1). This blood passes the gas exchange surface, and a pressure gradient of 60 mmHg allows oxygen to move into the pulmonary blood. By the time the blood has passed\xa0the alveolus, arterial PO2\xa0will have equilibrated with the alveolar PO2\xa0and will also be 100 mmHg. These numbers are well worth committing to memory.', 'ed53b093-27bf-4647-99ec-a32df33bc45a': 'The other critical values we need to address here are the partial pressures of CO2\xa0(see figure 7.2). Venous blood returning from the tissue has a PCO2\xa0of 45 mmHg, compared to alveolar PCO2\xa0that is 40 mmHg. This pressure gradient of 5 mmHg is enough to allow blood to equilibrate with the alveolus, and so arterial PCO2\xa0is 40 mmHg.\xa0Again, these numbers are worth remembering.', '80f14e98-6d0d-46d5-a094-2dd9f1a23aa6': 'A much smaller diffusion gradient is needed for CO2 because CO2\xa0is much more soluble than oxygen, a factor\xa0among\xa0others that is\xa0included in Fick’s law of diffusion.'}"
+Figure 6.1,pulmo2/images/Figure 6.1.jpg,Figure 6.1: Intrapleural and airway pressures during normal/passive expiration.,"For simplicity, the schematic in figure 6.1 shows one airway and an alveolus within the thoracic cavity. At the onset of passive expiration (driven by the recoil of the expanded lung), the intrapleural pressure is negative (about −8 cm H2O). As it remains negative, intrapleural pressure helps keep the airways open.","{'709e47ee-7a91-414c-81cc-5c3752c06c47': 'American Thoracic Society Committee on Dyspnea. “An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea.” American Journal of Respiratory and Critical Care Medicine 185, no. 4: 435–52. https://doi.org/10.1164/rccm.201111-2042ST.', 'd5f1a15f-0fcf-40e5-aa89-9237e2b68c6a': 'Banzett, Robert B., Robert W. Lansing, and Andrew P. Binks. “Air Hunger: A Primal Sensation and a Primary Element of Dyspnea.” Comprehensive Physiology 11, no. 2 (April 2021): 1449–83. https://doi.org/10.1002/cphy.c200001.', '114c8441-5da7-4816-9a98-ebe7006695e0': 'Levitsky, Michael G. “Chapter 9: Control of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '73bce2fb-98ad-41f3-8101-4bf9af7e048d': 'West, John B. “Chapter 8: Control of Ventilation—How Gas Exchange Is Regulated.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'b8d4a9c3-0d94-4647-88e2-309c65d3b974': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 8” and “Chapter 9.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'db0a65e0-e669-4647-b737-5a183e68a90c': 'The hemoglobin molecule consists of four polypeptide chains, two alpha and two beta (figure 16.1). These proteins comprise the “globin”\xa0part of the molecule but are not simply structural as they contain sites that are capable of receiving CO2\xa0and also hydrogen ions—a handy function, as you might imagine. Some anemias, such as sickle cell anemia, involve a conformational change in these proteins and diminish\xa0the molecule’s gas carrying ability.', 'b3772caa-6325-41b5-beea-7c431fd6d4b3': 'The heme component of hemoglobin is an iron-containing porphyrin molecule capable of binding with oxygen. Each of the four polypeptide chains contains a heme molecule, meaning that each hemoglobin molecule is capable of transporting four oxygen molecules. It is\xa0also worth noting that binding of oxygen to the heme molecule induces a conformational change that results in oxyhemoglobin having some different behaviors and indeed color to deoxyhemoglobin. We will look at some of these differences in behavior later on.', '305cc335-e478-4f77-85c3-749b48edc277': 'It is\xa0also worth reviewing hemoglobin’s home here as well—the red blood cell (RBC). The red blood cell’s classic biconcave shape provides a large surface area for gas exchange and also means that no hemoglobin molecule inside is very far from the edge of the cell, cutting down on the diffusion distance of gases. The cell is also very flexible, making it capable of squeezing through narrow and twisting capillaries so that its walls and those of the capillary may be in\xa0close contact and again diffusion distances are reduced.', '396c63b3-8995-41de-a103-31ebc88c8ab7': 'Each RBC is capable of holding up to 250 million hemoglobin molecules, so consequently is capable of holding one billion oxygen molecules; as such the RBC fulfills its primary role of oxygen transport well. This oxygen transport system fails in anemias that result in either too few red blood cells\xa0or too little hemoglobin in each cell (or both). Now let us look at the behavior of hemoglobin.', 'b3a2853f-4d49-466c-b233-b1e3ad132937': 'The behavior of hemoglobin is best described by the oxygen saturation curve (figure 16.2), and this is one of the most important curves to understand in medicine. The curve shows the percentage of hemoglobin that has all of its heme molecules bound with oxygen (i.e., are saturated). So for example a 50 percent\xa0saturation would mean that half of the heme sites were occupied by oxygen. The curve shows percentage saturation in relation to oxygen partial pressure, and what should be immediately noticeable is that the higher the partial pressure of oxygen then the greater the saturation. But the relationship is far from linear and its shape offers several important physiological advantages. If it helps understand it, think of this curve as an instruction manual for hemoglobin,\xa0telling how saturated it should be at any PO2. In reality it is an enzyme kinetics curve, describing hemoglobin’s affinity for oxygen over a range of PO2.', '240bd48e-3307-4e02-a6c4-3980b6721979': 'First\xa0let us put the curve in a physiological context. The alveolar PO2\xa0is around 100 mmHg. This means that as blood passes the alveoli and is exposed to this PO2, then oxygen saturation becomes close to 100 percent, about 98 percent. The first important physiological feature of this curve is that PO2\xa0can fall a considerably long way before it has an impact on oxygen saturation. So, taking time to look at the numbers on the graph, let us say, for example, that a patient begins to hypoventilate and alveolar PO2\xa0falls to 70 mmHg; while this is a considerable fall in PO2, the saturation will only fall a few percentage points, and PO2\xa0must\xa0fall to 50 before significant loss of saturation, or desaturation, occurs. Below 50, however, notice how the curve rapidly steepens, and now for a small change in PO2, we get a large desaturation.', '57274494-19e2-4442-a9f6-72dc7f08e65a': 'This steep section of the curve is therefore clinically critical. If your patient’s saturation monitor reads 83 percent\xa0what should spring into your mind is it that such a low saturation puts the patient onto the steep part of the curve. It will now take only a small further decline in alveolar PO2\xa0to have a profound effect on saturation, unlike at the top and flat section of the curve where small changes in alveolar PO2\xa0have very little effect on saturation.', 'ae59bbfa-2b77-438a-a039-3640d3f50564': 'So what is the advantage of having such a steep curve at lower PO2s? Let us look at the physiological situation again. We have\xa0already said that the alveolar PO2\xa0of 100 results in a saturation close to 100 percent (i.e., at the lung the hemoglobin\xa0has a high affinity for oxygen and becomes fully saturated).', '9db43d4c-5e74-4450-aeb0-f34c80abd999': 'At the tissue, however, we want hemoglobin\xa0to lose its affinity for oxygen and release some to the metabolizing cells. At the tissue the local PO2\xa0is much lower, around 40, because of the oxygen consumption by the tissue. At the lower PO2, hemoglobin’s affinity for oxygen falls, and it will lose some of its oxygen to the tissue and saturation will fall. This is ideal, as now our oxygen carrier is capable of releasing oxygen where it is\xa0needed.', '5b86e2bb-12a9-4a32-80fa-554e0dcae3ee': 'If tissue PO2\xa0falls even lower, such as when metabolic rate is high, then more oxygen will be released by hemoglobin as its affinity for oxygen declines with the lower tissue PO2. Therefore the delivery system for oxygen is intrinsically tied to metabolic rate.', '56b865af-bc70-47ec-8696-ba94d1f42869': 'The shape of this curve makes hemoglobin a remarkable molecule—able to grab oxygen at the oxygen-providing lung, but relinquish it to oxygen-demanding tissue and relinquish more when the tissue needs more. There are other factors that fine-tune the amount of oxygen delivered to tissue to match its oxygen demand. This is summarized in figure 16.3.', '4ed813be-9b8e-460b-bafa-7979fda65ba0': 'Levitsky, Michael G. “Chapter 7: Transport of Oxygen and Carbon Dioxide in the Blood.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'd6a16cf9-d059-46b3-b7e2-0261a878af63': 'West, John B. “Chapter 6: Gas Transport by the Blood—How Gases Are Moved to the Peripheral Tissues.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'eebcdd0d-d4a0-48ea-b604-9534d41496ed': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 6.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '279562ba-f525-4412-9982-1e9c07d279bb': 'There are two circulatory networks that normally form shunts. The bronchial circulation, that supplies\xa0the bronchi, empties its venous blood into the pulmonary veins, thereby sending slightly deoxygenated blood back toward the left heart and into the systemic arterial system. Likewise a very small portion of the coronary venous blood is returned to the left ventricle (through the thebesian veins) and thereby bypasses the lung completely before going back in the systemic circulation.', 'e26d0d11-466b-4a31-bc87-c83397920658': 'These two wayward circulations and the imperfect V/Q matching in the lung serve to suppress arterial oxygen saturation.', 'c0f16823-bf43-4645-9269-c51c6ce26d14': 'Levitsky, Michael G. “Chapter 5: Ventilation–Perfusion Relationships.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '4a3745c2-5916-41da-b111-3377965154c7': 'West, John B. “Chapter 5: Ventilation–Perfusion Relationships—How Matching of Gas and Blood Determines Gas Exchange.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '0b3f01fc-f893-4c2a-ba14-78f6613e445c': 'Levitsky, Michael G. “Chapter 3: Alveolar Ventilation.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'ef7d1b93-3a1e-49fe-8e36-f72ffeb5d196': 'Let us\xa0start with a description of the ideal situation, where ventilation to alveoli is matched with the perfusion, then we will see how the lung does not quite achieve this.', '20443118-b1a8-481e-b40b-fabc2cdacdae': 'This is what we would expect if the lung were perfect, with uniform distribution of ventilation and perfusion to all regions and a V/Q of 1 in all regions.', '1266c3d9-2603-4ab5-a23b-c4c09c575487': 'The lung is not a perfect organ, however, and ventilation and perfusion are not equally distributed, and the lung as a whole only achieves an average V/Q of 0.8, which is close to our ideal of 1, but not quite there. Consequently, by the time the blood has passed the alveoli and regrouped in the pulmonary veins, the PO2 of the blood is less than alveolar. This alveolar–arterial PO2 difference is caused by the less-than-perfect matching of V and Q across the lung; but it is\xa0not all the lung’s fault, as venous blood that has been through the bronchial and a small section of the coronary circulation (and therefore is deoxygenated) is mixed into the vessels returning to the left heart, which brings down arterial saturation as well. The mixing-in of bronchial and coronary circulations and the less-than-ideal V/Q in the lung as a whole is the reason why your saturation monitors do not\xa0read 100 percent, but normal oxygen saturation is considered as 96–98 percent.', '736d22e3-bd4e-497c-bf9a-992a06cc406d': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 7.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'c7f4c268-560a-4009-8867-a730d1d4a684': 'Levitsky, Michael G. “Chapter 8: Acid–Base Balance.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '405afb7b-5d31-4d56-b756-36329df0d2fa': 'Levitsky, Michael G. “Chapter 10: Nonrespiratory Functions of the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9cfd8d5d-3721-4961-8c24-8b2bba6b0e82': 'West, John B. “Chapter 4: Blood Flow and Metabolism—How the Pulmonary Circulation Removes Gas from the Lung and Alters Some Metabolites.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '5bbf18cb-720e-433f-a97c-7a9a17affa5c': 'Levitsky, Michael G. “Chapter 4: Blood Flow to the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '58f3e187-02d3-4794-a834-033ae16daf9b': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 5.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '7ee7bd78-ee76-462c-8326-3223973d9968': 'Levitsky, Michael G. “Chapter 6: Diffusion of Gases and Interpretation of Pulmonary Function Tests.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '7098f0e3-8f6c-4a7f-8bb9-019917fbc96e': 'West, John B. “Chapter 3: Diffusion—How Gas Gets Across the Blood–Gas Barrier.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '83eef49d-f1b3-4248-908d-fe1c99a681e8': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 4.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '94a2e555-32f9-4cc7-8f5b-ef7daead5687': 'Before we do that though, we need to be able to calculate the units of measurement we use when describing gas exchange. When referring to gas exchange we are really referring to diffusion of gases down their concentration gradient, but rather than use concentrations, we use partial pressures.', '83d5f78d-9abb-48e8-b071-bef116366b8f': 'Partial pressures describe what proportion of the total pressure is exerted by a particular component of a mixed gas. Let us\xa0look at the specific situation we are interested in to illustrate this description.', 'd82456a7-eec8-4a00-acb8-976db3f8f866': 'Atmospheric pressure at sea level is 760 mmHg. This pressure is generated by the collisions of all the molecules with each other and other objects. At high altitude there are fewer molecules, so fewer collisions, and hence atmospheric pressure is lower.', 'a630d4b8-fca5-42f2-b5b5-7435455e5bc6': 'Now looking at the composition of our atmosphere we know that 79 percent\xa0is nitrogen, 20.9 percent\xa0is oxygen, and some trace gases collectively get us to 100 percent. Now let us\xa0calculate a partial pressure. If 79 percent\xa0of the atmosphere is nitrogen, then 79 percent\xa0of our atmospheric pressure is generated by the collisions by nitrogen molecules. Likewise 20.9 percent\xa0of the atmospheric pressure is due to oxygen, so to calculate the partial pressure of oxygen (PO2) we simply multiply atmospheric pressure (PB) by the percentage of oxygen, which means our atmosphere has a partial pressure of oxygen of 159 mmHg.', 'e125ba2f-6da8-4e10-bea6-e132c5f31f62': 'Although this phenomenon is present in the healthy lung, we will see how it is exacerbated in certain disease states and how this exacerbation can be detected by common pulmonary function tests.', '6443f20b-c2ba-4f2a-912d-b820480b48dc': 'First, let us\xa0look at the forces involved during a normal, passive expiration.', 'b41f13e9-f936-4f36-a5cf-fb0da07ecd91': 'For simplicity, the schematic in figure 6.1 shows one airway and an alveolus within the thoracic cavity. At the onset of passive expiration (driven by the recoil of the expanded lung), the intrapleural pressure is negative (about −8 cm H2O). As it remains negative, intrapleural pressure helps keep the airways open.', 'e3fd9346-74ee-4550-ac3d-c10b889a9616': 'West, John B. “Chapter 7: Mechanics of Breathing—How the Lung Is Supported and Moved.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'f3d82c09-4fa4-4232-b7c2-ca82c3f0e4d6': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 3.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '2abbd8fc-bc45-4021-95f3-7cc764fb7854': 'The first factor we must consider when thinking about airflow is the type of flow that is occurring.', '90b7c113-9453-48ab-af12-da3e977c0466': 'The most efficient form of flow is laminar\xa0(i.e., laminar flow takes the lowest pressure differential for flow to occur). In laminar flow the molecules are moving in an orderly manner, those at the side of the tube moving a little slower due to contact with tube walls\xa0and those in the middle moving fastest (figure 5.1).', '185f8384-ae77-4ecc-8216-cf9651f31397': 'When velocity increases or tube radius decreases then this organization is lost. Collisions between molecules and with the tube wall are now more frequent and movement is more chaotic, and the flow becomes turbulent (figure 5.2). At this point some molecules are at times moving against the pressure gradient due to these collisions. Consequently, to generate the same amount of molecule movement (i.e., flow) from one end of the tube to another, a greater pressure differential is needed when flow becomes turbulent. Turbulent flow is more common in the large airways where velocity and airway radius are high.', '78016837-1b1e-4b72-9459-159a81636088': 'In reality, the vast majority of the airways are branching small tubes, so we see a mixture of the two above—mostly laminar flow but some turbulence generated at the branch (or transitional) points (figure 5.3).', 'd8c9a412-74b3-47d6-9885-10a68f3195dc': 'For our purposes though we are going to look at the factors that affect flow when it is laminar—the dominant form of flow in the majority of airways. These factors are described by Poiselle’s equation. We will now break down Poiselle’s equation in relation to flow of air down airways. Although initially an intimidating equation, there are some things we can generally ignore.', '329ee30f-0280-4186-a272-76cda4611f6d': 'Equation 5.1', 'ccf522d3-ed2e-4e8f-951d-b5f59bf4614f': 'Levitsky, Michael G. “Chapter 2: Mechanics of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '6122ed24-6881-4243-b127-64fd05cdb94a': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 1.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '3265bb73-23ce-4e55-b347-c6a6e3d0f4a2': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 2.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '5b7cdf1c-6e3e-4689-a4b4-001b0e7d0b85': 'Before we get into the details of how we breathe in, let me make sure we are all on the same page by going right back to basics, so bare with me or skip ahead if you are happy with pressure, volume, and flow.', '9e430d7f-a263-41b5-819a-5d6f57a475d3': 'To get air to move into the lungs we need to generate a pressure differential;\xa0that is the pressure inside the lungs must be lower than the pressure outside\xa0(i.e., atmospheric pressure), so that air moves down the pressure gradient into the lungs.', '2a56dfa9-1088-4e0d-8a05-7d0dae7eabe3': 'The low pressure inside the lungs is generated by increasing lung volume; bigger volume means fewer molecules in the same space, and therefore lower pressure (go back and revisit Boyle’s law if needed).', '700a30d9-cdcb-4a22-934d-dbb9221c27e8': 'The basis of inspiration is lowering lung pressure below atmospheric pressure, so that atmospheric pressure pushes air down the airways until pressure equilibrates. So the fundamental first step is, how do we increase lung volume?', 'f0582f89-5080-4d8c-973f-c82797cb93ae': 'To understand the mechanics of breathing we have to deal with two concepts:\xa0first how the action of the respiratory muscles increases thoracic volume, and second\xa0(and more complex) we need to understand the interaction of the lungs and the thoracic wall.', 'cf71568f-25a9-4c48-880c-f5fdda101c9b': 'Let us deal with the respiratory muscles and expansion of the thorax first.', '338eec0f-6210-47e2-815e-4cb6f22fc67a': 'West, John B. “Chapter 2: Ventilation—How Gas Gets to the Alveoli.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '3c8b34ab-c9f8-4728-8aad-518dd91e7284': 'We will see how blood gases are monitored and maintained through neurochemical control of lung expansion and relaxation to achieve the appropriate level of alveolar ventilation. Factors that affect the\xa0degree of gas exchange between the lung and blood will be discussed, along with the coordination of ventilation and perfusion of the lung. Finally, we will see how oxygen and carbon dioxide are transported in the bloodstream to and from tissue and the mechanisms that ensure appropriate delivery and a stable blood gas environment.\xa0Before we begin, however, we will look at the functional anatomy of the lung and how the lung is well designed to perform its primary role and defend itself from the external environment.', 'bb13387c-a557-4bd6-8b04-3e30d6d82916': 'Levitsky, Michael G. “Chapter 1: Function and Structure of the Respiratory System.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9faee6ea-d9bf-4b11-a3d3-8561cb811717': 'West, John B. “Chapter 1: Structure and Function—How the Architecture of the Lung Subserves Its Function.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.'}"
+Figure 6.2,pulmo2/images/Figure 6.2.jpg,Figure 6.2: Intrapleural and airway pressures during forced expiration.,"In a forced expiration (see figure 6.2) the intrapleural pressure can become positive (as much as 120 cm H2O), but in this example we will say it is 25 cm H2O. This positive pressure in the pleural cavity comes from the chest wall and diaphragm now “pushing” the pleural membranes together and compressing the lung.","{'b2595d16-3472-4347-8652-8a5041e897ec': 'The elastic forces of the alveolus wall exert an inward force of about +10 cm H2O. This results in a net force of +2 cm H2O in the alveolus, and a gradient between this positive pressure is established between the alveolus and the atmosphere outside the lung. That means that along the airway toward\xa0the mouth there is a gradient of progressively decreasing pressure to zero (shown in maroon).', '4d8eebf9-c2a1-4fc0-af77-1f63bd8d903f': 'Importantly in this example of passive expiration the airway pressure is greater than the pleural pressure along the whole length of the airway toward the mouth. Along with the radial traction provided by the surrounding parenchymal tissue, this favorable transmural pressure gradient helps keep the airway open during expiration.', '85336abb-ae09-42b1-8f3d-90c22ce05bb5': 'Now let us\xa0look at what happens if expiration is forceful, or active, rather than passively relying on lung recoil.', '6141bd45-9a97-4ead-8439-2dddc888dac7': 'In a forced expiration (see figure 6.2) the intrapleural pressure can become positive (as much as 120 cm H2O), but in this example we will say it is\xa025 cm H2O. This positive pressure in the pleural cavity comes from the chest wall and diaphragm now “pushing”\xa0the pleural membranes together and compressing the lung.', '8b63e01d-2e8d-46d0-90ae-dad23f3025c1': 'Again, we have the elastic forces of the alveolus generating an inward force (still +10 cm H2O), and when summed with the now positive intrapleural forces, we end up with an alveolar pressure of +35 cm H2O.', '2aefa857-cbcc-430c-96cb-ba4ef825fd3d': 'Again, a pressure gradient between the alveolus and the atmosphere is established (again shown in maroon), but this time there is a fundamental difference caused by the larger intrapleural pressure.', '8da683bb-c7ee-4f58-b005-bf64671bdced': 'At some point along the airway, as airway pressure is decreasing, the intrapleural pressure exceeds airway pressure (in this example it is 25 cm H2O). At this “choke”\xa0point (arrows pointing toward airway in figure 6.2), the airway can become compressed or even collapse.', '480559ff-b1ff-40db-8773-ae708a2320e6': 'This\xa0effect is somewhat reduced by the radial traction of the parenchyma, but airway compression occurs even in the healthy normal lung, and the greater the effort of expiration (i.e., the more positive the intrapleural pressure), the greater degree airways compress and compression occurs closer to the alveoli (i.e., further up the pressure gradient in the airway).', 'e843288a-9a88-4e3a-b197-33a90f9c8ed9': 'If airways are already narrowed, as in obstructive lung diseases such as asthma, or parenchymal traction is lost, such as in emphysema, dynamic airway compression occurs to a greater extent. In these obstructive diseases the increased airway resistance results in the patient having to forcefully expire to overcome the increased resistance of the narrowed airways. This promotes airway compression and leads to air being trapped behind the choke point, causing hyperinflation (breathing at an elevated lung volume).', 'f1570577-d8ed-42e9-afb5-85e530a4feb6': 'This airway compression or any other increase in airway resistance can be demonstrated by a common pulmonary function test, the flow-volume loop.', 'f471b51b-53e8-4a5c-8be6-104466a4f6cc': 'The intrapleural pressure at the base of the lung may actually become positive at low lung volumes. Now that force that tended to open up alveoli is actually a force that tends to compress alveoli. In our example here the intrapleural reaches 3.5 cm H2O, a force that may lead to airway compression and thereby reduce ventilation to the basal alveoli. This intrapleural pressure will certainly place these alveoli on the very flat\xa0and therefore noncompliant section of the compliance curve and make them difficult to inflate because of the surface tension and small radius effect we have discussed previously.', 'd16ea004-19ec-4b3b-9a78-420bddc6679f': 'Too low a lung volume and compliance falls and work of breathing increases, likewise during breathing at high lung volumes, another contributing reason for\xa0why tidal volume plateaus during exercise.', '451b76e9-589e-4a74-bfc0-49991bb084ef': 'So now let us look at why compliance is low at high and low lung volumes, starting with the cause of low lung compliance at low volumes.', 'b3fcd35a-6d91-4bc7-b257-ff73349fa7b3': 'Low compliance at low volumes—Surface tension: The reason why the lung takes more pressure to inflate at low volumes is surface tension. As mentioned in chapter 1 the alveoli have a thin layer of fluid lining their inner surface. As we saw in the pleural space, this causes surface tension. Unlike the surface tension in the pleural space, in the alveoli surface tension is a disadvantage.', 'ca8faa42-d2ec-4bae-952e-07edccef8f5d': 'Surface tension is generated as water molecules cluster together to reduce their exposure to the gas in the alveolar space. As they gather together they drag the alveolar wall with them, producing a force that tends to pull the alveolar walls inward. The alveolar pressure opposes this force and should prevent the alveolus from collapsing (figure 3.4).', 'da746387-5ed7-484c-bf0b-c88bcb2f1276': 'The relationship between these two opposing forces is described by Laplace’s law that states the outward (alveolar) pressure needed to oppose the inwardly directed tension is proportionate to the tension (obviously), but also inversely related to the radius of the alveolus\xa0(i.e., the smaller the radius, the greater the inwardly acting force).', '3509f1ca-8ecc-4ad2-b9cf-3eff570619b3': 'This explains why compliance is low at low\xa0lung volumes. At low lung volumes the alveoli are smaller and\xa0thus have a smaller radius. Laplace’s law states that with a low radius the pressure needed to overcome the inward force will be greater, explaining why a larger alveolar (outward) pressure is needed to inflate the alveolus from a low starting volume.', '036a0fe8-5632-4d81-bf4b-f27259dbb8ed': 'As lung volume increases, and thus alveolar radius increases, the pressure needed to overcome the inward acting force becomes less and the compliance of the lung increases. This explains why compliance is improved at the normal operating range of lung volumes.', '000e0120-8738-495c-8cd9-a9f3b7a795c5': 'This also explains the hysteresis of the compliance curve. During expiration as alveoli are becoming progressively smaller, the inwardly acting force generated by surface tension becomes progressively greater. This phenomenon consequently assists expiration and contributes to expiration being a passive process.', 'da35cdea-8870-4095-b7fa-9c77d9540a3e': 'Low compliance at high lung volumes—Elastic limit: At high lung volumes the alveolar radius has increased further, suggesting that compliance should be further improved as the effect of surface tension will be much less. But surface tension is not the only factor involved, and the compliance curve flattens here, meaning a greater pressure is needed to achieve a volume change at high lung volumes. The low compliance at high lung volumes is caused by another phenomenon altogether. At high lung volumes expansion of the lung becomes limited by the elastic limit of the lung, a little like trying to further stretched an already stretch elastic band—it is harder to do.', '8484b092-d7eb-44a1-b241-2fecb31ef15e': 'So with surface tension causing problems at low lung volumes\xa0and tissue elastic limit causing problems at high lung volumes, the compliance curve is steepest (i.e., most favorable) in the middle, as mentioned before, which is the operating volume of the lung. These principles are summarized in figure 3.5.', '29a73de0-3529-4d42-9213-a65ad7fce041': 'Improving lung compliance with surfactant: So after that information on how surface tension is a problem for the lung, we now have to look at how it could be so much worse if the lung did not\xa0protect itself.', '4e9740cc-c080-4ddb-8640-dac07d5ffc9a': 'Despite it having an effect, particularly at low lung volumes, the lung actually reduces the effect of alveolar surface tension by releasing “surfactant,”\xa0a molecule that disrupts surface tension. In brief, the surfactant molecule (dipalmitoyl phosphatidylcholine) has a similar structure to the phospholipids that make up cell membranes with a hydrophobic end and a hydrophilic end, allowing it to surround water and repel it\xa0at the same time, thus breaking up the interaction between water molecules. So as surfactant significantly reduces surface tension, it thereby increases lung compliance and the risk of alveolar collapse. It also helps keep the air space dry, as excessive surface tension tends to draw water into the space from the capillaries and interstitial spaces.', 'fdc63085-2513-4355-8ded-f5d0c9698671': 'Surfactant is released onto the alveolar inner surface by Type II alveolar cells (recall Type I cells are those making up the alveolar wall). Type II cells produce surfactant at a high rate\xa0and thus demand a constant and generous blood flow; therefore any condition that disrupts this blood supply will cause surfactant concentrations to decline and therefore put the alveolus at risk of collapse as surface tension is allowed to increase.', '08ca76c6-e7cf-44d2-ac4f-713cf0644d61': 'A good illustration of the effect of surfactant is respiratory distress syndrome of the newborn. The underdeveloped lungs of infants born prematurely (at about twenty-eight\xa0weeks), cannot produce sufficient surfactant. Alveoli rapidly collapse (known as atelectasis), and pulmonary edema develops because of the excessive surface tension in the alveolar walls.'}"
+Figure 6.3,pulmo2/images/Figure 6.3.jpg,Figure 6.3: Typical and normal flow-volume loop. FVC: forved vital capacity.,"Flow-volume loops are briefly discussed in context of the relevant physiology. Figure 6.3 shows a normal flow-volume loop. Note that the volume axis seems to be the wrong way around; this is because expired volume and flow are generally more useful, so the plot has expiratory flow as positive and lung volume orientated for expiration. While breathing on a spirometer, the patient begins to breathe in from residual volume (bottom half of maroon line). As inspiration continues, lung volume increases (moves toward the y-axis) and airflow increases (moves downward). The patient continues inhaling until they are at total lung capacity (or TLC).","{'2d0afc3b-7842-421e-810c-7315aa2dca00': 'Flow-volume loops are briefly discussed in context of the relevant physiology. Figure 6.3 shows a normal flow-volume loop. Note that the volume axis seems to be the wrong way around; this is because expired volume and flow are generally more useful, so the plot has expiratory flow as positive and lung volume orientated for expiration. While breathing on a spirometer, the patient begins to breathe in from residual volume (bottom half of maroon line). As inspiration continues, lung volume increases (moves toward the y-axis) and airflow increases (moves downward). The patient continues inhaling until they are at total lung capacity (or TLC).', '3c648ba2-73e4-47f5-b712-da0d0aea9f7f': 'They then exhale as hard and as fast as they can, forcefully emptying the lung as quickly as possible. During forced exhalation of the first liter or so, expiratory flow rapidly increases until it reaches peak expiratory flow; this is the first clinically pertinent measure. After this point expiratory flow begins an exponential decline; as lung volume continues to decrease, so does the flow rate until flow reaches zero when the lung is emptied (at residual volume).', 'ef8ca426-319c-46e9-8681-ab7bb5b4aa47': 'The rate of this decline in flow rate is also an important clinical measure and brings together a couple of important physiological points:', '76b0deb9-f98e-4fd6-afdf-0e3793be0296': 'Although there are a number of measurements that are calculated from this forced exhalation, two are most commonly reported. First, the total volume that is expelled from the lung is referred to as the forced vital capacity (FVC). The forced expiratory volume that is expelled from the lung in the first second of expiration is referred to as FEV1. The ratio of these two values, known as FEV1/FVC, describes the percentage of lung volume that can be emptied in one second and is a useful indicator of airway resistance. A normal FEV1/FVC is 90 percent\xa0or higher, meaning over 90 percent\xa0of vital capacity can be emptied from the lung within a second. This value is dependent on age, gender, and body size, but commonly used predicted values take\xa0these variables into account when assessing for disease.'}"
+Figure 6.4,pulmo2/images/Figure 6.4.jpg,Figure 6.4: Normal (maroon) and obstructive disease (gray) flow-volume loops.,"The loop produced by a patient with chronic obstructive lung disease, or COPD, looks very different (gray line in figure 6.4). With disease causing airway narrowing, the peak expiratory flow is significantly reduced, and the decay in expiratory flow as lung volume declines is much more pronounced as the narrowed airways can be easier to collapse due to a lower starting radius and/or loss of radial traction.","{'6eae07de-134e-4157-b1f9-2c21589e94f1': 'The loop produced by a patient with chronic obstructive lung disease, or COPD, looks very different (gray\xa0line in figure 6.4). With disease causing airway narrowing, the peak expiratory flow is significantly reduced, and the decay in expiratory flow as lung volume declines is much more pronounced as the narrowed airways can be easier to collapse due to a lower starting radius and/or loss of radial traction.', 'a9447d8a-043e-40ac-9a3d-eaf68ecb640f': 'This means that FEV1\xa0is significantly reduced, but FVC may remain unchanged\xa0(i.e., the lung volume is the same, but it takes longer to empty). An FEV1/FVC significantly less than 90 percent\xa0is indicative of obstructive disease. Notice that the inspiratory loop of the COPD patient appears normal, illustrating the effect of increasingly negative intrapleural pressure, increasing lung volume and radial traction on airway resistance.', 'b1f7270f-a1a0-42ea-840c-1b10afdbc09d': 'Alternatively, diseases that restrict lung expansion (figure 6.5), such as pulmonary fibrosis, demonstrate a reduced lung volume, where FVC is substantially reduced, but FEV1\xa0may not be significantly affected;\xa0in fact it is not uncommon for FEV1/FVC to increase to about normal in restricted diseases, but this is of course due to a decline in FVC rather than a rise in FEV1. Notice also that the inspiratory loop is affected, with volumes being reduced here as well.', 'bfae96d4-8f73-47a3-bc15-1e4a8b89fe16': 'A flow-volume loop is a quick, cheap, and powerful diagnostic measure, but it is highly dependent on the patient performing a forced expiration to encourage\xa0dynamic compression and peak flows\xa0be obtained so that any airway abnormalities can be seen. This is why you may hear a pulmonary function technologist (PFT)\xa0shouting encouragement to a patient as you walk past the lab.'}"
+Figure 6.5,pulmo2/images/Figure 6.5.jpg,Figure 6.5: Normal (maroon) and restrictive (gray) flow-volume loops.,"Alternatively, diseases that restrict lung expansion (figure 6.5), such as pulmonary fibrosis, demonstrate a reduced lung volume, where FVC is substantially reduced, but FEV1 may not be significantly affected; in fact it is not uncommon for FEV1/FVC to increase to about normal in restricted diseases, but this is of course due to a decline in FVC rather than a rise in FEV1. Notice also that the inspiratory loop is affected, with volumes being reduced here as well.","{'6eae07de-134e-4157-b1f9-2c21589e94f1': 'The loop produced by a patient with chronic obstructive lung disease, or COPD, looks very different (gray\xa0line in figure 6.4). With disease causing airway narrowing, the peak expiratory flow is significantly reduced, and the decay in expiratory flow as lung volume declines is much more pronounced as the narrowed airways can be easier to collapse due to a lower starting radius and/or loss of radial traction.', 'a9447d8a-043e-40ac-9a3d-eaf68ecb640f': 'This means that FEV1\xa0is significantly reduced, but FVC may remain unchanged\xa0(i.e., the lung volume is the same, but it takes longer to empty). An FEV1/FVC significantly less than 90 percent\xa0is indicative of obstructive disease. Notice that the inspiratory loop of the COPD patient appears normal, illustrating the effect of increasingly negative intrapleural pressure, increasing lung volume and radial traction on airway resistance.', 'b1f7270f-a1a0-42ea-840c-1b10afdbc09d': 'Alternatively, diseases that restrict lung expansion (figure 6.5), such as pulmonary fibrosis, demonstrate a reduced lung volume, where FVC is substantially reduced, but FEV1\xa0may not be significantly affected;\xa0in fact it is not uncommon for FEV1/FVC to increase to about normal in restricted diseases, but this is of course due to a decline in FVC rather than a rise in FEV1. Notice also that the inspiratory loop is affected, with volumes being reduced here as well.', 'bfae96d4-8f73-47a3-bc15-1e4a8b89fe16': 'A flow-volume loop is a quick, cheap, and powerful diagnostic measure, but it is highly dependent on the patient performing a forced expiration to encourage\xa0dynamic compression and peak flows\xa0be obtained so that any airway abnormalities can be seen. This is why you may hear a pulmonary function technologist (PFT)\xa0shouting encouragement to a patient as you walk past the lab.'}"
+Figure 5.1,pulmo2/images/Figure 5.1.jpg,Figure 5.1: Laminar flow.,"The most efficient form of flow is laminar (i.e., laminar flow takes the lowest pressure differential for flow to occur). In laminar flow the molecules are moving in an orderly manner, those at the side of the tube moving a little slower due to contact with tube walls and those in the middle moving fastest (figure 5.1).","{'709e47ee-7a91-414c-81cc-5c3752c06c47': 'American Thoracic Society Committee on Dyspnea. “An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea.” American Journal of Respiratory and Critical Care Medicine 185, no. 4: 435–52. https://doi.org/10.1164/rccm.201111-2042ST.', 'd5f1a15f-0fcf-40e5-aa89-9237e2b68c6a': 'Banzett, Robert B., Robert W. Lansing, and Andrew P. Binks. “Air Hunger: A Primal Sensation and a Primary Element of Dyspnea.” Comprehensive Physiology 11, no. 2 (April 2021): 1449–83. https://doi.org/10.1002/cphy.c200001.', '114c8441-5da7-4816-9a98-ebe7006695e0': 'Levitsky, Michael G. “Chapter 9: Control of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '73bce2fb-98ad-41f3-8101-4bf9af7e048d': 'West, John B. “Chapter 8: Control of Ventilation—How Gas Exchange Is Regulated.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'b8d4a9c3-0d94-4647-88e2-309c65d3b974': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 8” and “Chapter 9.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'db0a65e0-e669-4647-b737-5a183e68a90c': 'The hemoglobin molecule consists of four polypeptide chains, two alpha and two beta (figure 16.1). These proteins comprise the “globin”\xa0part of the molecule but are not simply structural as they contain sites that are capable of receiving CO2\xa0and also hydrogen ions—a handy function, as you might imagine. Some anemias, such as sickle cell anemia, involve a conformational change in these proteins and diminish\xa0the molecule’s gas carrying ability.', 'b3772caa-6325-41b5-beea-7c431fd6d4b3': 'The heme component of hemoglobin is an iron-containing porphyrin molecule capable of binding with oxygen. Each of the four polypeptide chains contains a heme molecule, meaning that each hemoglobin molecule is capable of transporting four oxygen molecules. It is\xa0also worth noting that binding of oxygen to the heme molecule induces a conformational change that results in oxyhemoglobin having some different behaviors and indeed color to deoxyhemoglobin. We will look at some of these differences in behavior later on.', '305cc335-e478-4f77-85c3-749b48edc277': 'It is\xa0also worth reviewing hemoglobin’s home here as well—the red blood cell (RBC). The red blood cell’s classic biconcave shape provides a large surface area for gas exchange and also means that no hemoglobin molecule inside is very far from the edge of the cell, cutting down on the diffusion distance of gases. The cell is also very flexible, making it capable of squeezing through narrow and twisting capillaries so that its walls and those of the capillary may be in\xa0close contact and again diffusion distances are reduced.', '396c63b3-8995-41de-a103-31ebc88c8ab7': 'Each RBC is capable of holding up to 250 million hemoglobin molecules, so consequently is capable of holding one billion oxygen molecules; as such the RBC fulfills its primary role of oxygen transport well. This oxygen transport system fails in anemias that result in either too few red blood cells\xa0or too little hemoglobin in each cell (or both). Now let us look at the behavior of hemoglobin.', 'b3a2853f-4d49-466c-b233-b1e3ad132937': 'The behavior of hemoglobin is best described by the oxygen saturation curve (figure 16.2), and this is one of the most important curves to understand in medicine. The curve shows the percentage of hemoglobin that has all of its heme molecules bound with oxygen (i.e., are saturated). So for example a 50 percent\xa0saturation would mean that half of the heme sites were occupied by oxygen. The curve shows percentage saturation in relation to oxygen partial pressure, and what should be immediately noticeable is that the higher the partial pressure of oxygen then the greater the saturation. But the relationship is far from linear and its shape offers several important physiological advantages. If it helps understand it, think of this curve as an instruction manual for hemoglobin,\xa0telling how saturated it should be at any PO2. In reality it is an enzyme kinetics curve, describing hemoglobin’s affinity for oxygen over a range of PO2.', '240bd48e-3307-4e02-a6c4-3980b6721979': 'First\xa0let us put the curve in a physiological context. The alveolar PO2\xa0is around 100 mmHg. This means that as blood passes the alveoli and is exposed to this PO2, then oxygen saturation becomes close to 100 percent, about 98 percent. The first important physiological feature of this curve is that PO2\xa0can fall a considerably long way before it has an impact on oxygen saturation. So, taking time to look at the numbers on the graph, let us say, for example, that a patient begins to hypoventilate and alveolar PO2\xa0falls to 70 mmHg; while this is a considerable fall in PO2, the saturation will only fall a few percentage points, and PO2\xa0must\xa0fall to 50 before significant loss of saturation, or desaturation, occurs. Below 50, however, notice how the curve rapidly steepens, and now for a small change in PO2, we get a large desaturation.', '57274494-19e2-4442-a9f6-72dc7f08e65a': 'This steep section of the curve is therefore clinically critical. If your patient’s saturation monitor reads 83 percent\xa0what should spring into your mind is it that such a low saturation puts the patient onto the steep part of the curve. It will now take only a small further decline in alveolar PO2\xa0to have a profound effect on saturation, unlike at the top and flat section of the curve where small changes in alveolar PO2\xa0have very little effect on saturation.', 'ae59bbfa-2b77-438a-a039-3640d3f50564': 'So what is the advantage of having such a steep curve at lower PO2s? Let us look at the physiological situation again. We have\xa0already said that the alveolar PO2\xa0of 100 results in a saturation close to 100 percent (i.e., at the lung the hemoglobin\xa0has a high affinity for oxygen and becomes fully saturated).', '9db43d4c-5e74-4450-aeb0-f34c80abd999': 'At the tissue, however, we want hemoglobin\xa0to lose its affinity for oxygen and release some to the metabolizing cells. At the tissue the local PO2\xa0is much lower, around 40, because of the oxygen consumption by the tissue. At the lower PO2, hemoglobin’s affinity for oxygen falls, and it will lose some of its oxygen to the tissue and saturation will fall. This is ideal, as now our oxygen carrier is capable of releasing oxygen where it is\xa0needed.', '5b86e2bb-12a9-4a32-80fa-554e0dcae3ee': 'If tissue PO2\xa0falls even lower, such as when metabolic rate is high, then more oxygen will be released by hemoglobin as its affinity for oxygen declines with the lower tissue PO2. Therefore the delivery system for oxygen is intrinsically tied to metabolic rate.', '56b865af-bc70-47ec-8696-ba94d1f42869': 'The shape of this curve makes hemoglobin a remarkable molecule—able to grab oxygen at the oxygen-providing lung, but relinquish it to oxygen-demanding tissue and relinquish more when the tissue needs more. There are other factors that fine-tune the amount of oxygen delivered to tissue to match its oxygen demand. This is summarized in figure 16.3.', '4ed813be-9b8e-460b-bafa-7979fda65ba0': 'Levitsky, Michael G. “Chapter 7: Transport of Oxygen and Carbon Dioxide in the Blood.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'd6a16cf9-d059-46b3-b7e2-0261a878af63': 'West, John B. “Chapter 6: Gas Transport by the Blood—How Gases Are Moved to the Peripheral Tissues.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'eebcdd0d-d4a0-48ea-b604-9534d41496ed': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 6.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '279562ba-f525-4412-9982-1e9c07d279bb': 'There are two circulatory networks that normally form shunts. The bronchial circulation, that supplies\xa0the bronchi, empties its venous blood into the pulmonary veins, thereby sending slightly deoxygenated blood back toward the left heart and into the systemic arterial system. Likewise a very small portion of the coronary venous blood is returned to the left ventricle (through the thebesian veins) and thereby bypasses the lung completely before going back in the systemic circulation.', 'e26d0d11-466b-4a31-bc87-c83397920658': 'These two wayward circulations and the imperfect V/Q matching in the lung serve to suppress arterial oxygen saturation.', 'c0f16823-bf43-4645-9269-c51c6ce26d14': 'Levitsky, Michael G. “Chapter 5: Ventilation–Perfusion Relationships.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '4a3745c2-5916-41da-b111-3377965154c7': 'West, John B. “Chapter 5: Ventilation–Perfusion Relationships—How Matching of Gas and Blood Determines Gas Exchange.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '0b3f01fc-f893-4c2a-ba14-78f6613e445c': 'Levitsky, Michael G. “Chapter 3: Alveolar Ventilation.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'ef7d1b93-3a1e-49fe-8e36-f72ffeb5d196': 'Let us\xa0start with a description of the ideal situation, where ventilation to alveoli is matched with the perfusion, then we will see how the lung does not quite achieve this.', '20443118-b1a8-481e-b40b-fabc2cdacdae': 'This is what we would expect if the lung were perfect, with uniform distribution of ventilation and perfusion to all regions and a V/Q of 1 in all regions.', '1266c3d9-2603-4ab5-a23b-c4c09c575487': 'The lung is not a perfect organ, however, and ventilation and perfusion are not equally distributed, and the lung as a whole only achieves an average V/Q of 0.8, which is close to our ideal of 1, but not quite there. Consequently, by the time the blood has passed the alveoli and regrouped in the pulmonary veins, the PO2 of the blood is less than alveolar. This alveolar–arterial PO2 difference is caused by the less-than-perfect matching of V and Q across the lung; but it is\xa0not all the lung’s fault, as venous blood that has been through the bronchial and a small section of the coronary circulation (and therefore is deoxygenated) is mixed into the vessels returning to the left heart, which brings down arterial saturation as well. The mixing-in of bronchial and coronary circulations and the less-than-ideal V/Q in the lung as a whole is the reason why your saturation monitors do not\xa0read 100 percent, but normal oxygen saturation is considered as 96–98 percent.', '736d22e3-bd4e-497c-bf9a-992a06cc406d': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 7.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'c7f4c268-560a-4009-8867-a730d1d4a684': 'Levitsky, Michael G. “Chapter 8: Acid–Base Balance.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '405afb7b-5d31-4d56-b756-36329df0d2fa': 'Levitsky, Michael G. “Chapter 10: Nonrespiratory Functions of the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9cfd8d5d-3721-4961-8c24-8b2bba6b0e82': 'West, John B. “Chapter 4: Blood Flow and Metabolism—How the Pulmonary Circulation Removes Gas from the Lung and Alters Some Metabolites.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '5bbf18cb-720e-433f-a97c-7a9a17affa5c': 'Levitsky, Michael G. “Chapter 4: Blood Flow to the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '58f3e187-02d3-4794-a834-033ae16daf9b': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 5.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '7ee7bd78-ee76-462c-8326-3223973d9968': 'Levitsky, Michael G. “Chapter 6: Diffusion of Gases and Interpretation of Pulmonary Function Tests.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '7098f0e3-8f6c-4a7f-8bb9-019917fbc96e': 'West, John B. “Chapter 3: Diffusion—How Gas Gets Across the Blood–Gas Barrier.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '83eef49d-f1b3-4248-908d-fe1c99a681e8': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 4.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '94a2e555-32f9-4cc7-8f5b-ef7daead5687': 'Before we do that though, we need to be able to calculate the units of measurement we use when describing gas exchange. When referring to gas exchange we are really referring to diffusion of gases down their concentration gradient, but rather than use concentrations, we use partial pressures.', '83d5f78d-9abb-48e8-b071-bef116366b8f': 'Partial pressures describe what proportion of the total pressure is exerted by a particular component of a mixed gas. Let us\xa0look at the specific situation we are interested in to illustrate this description.', 'd82456a7-eec8-4a00-acb8-976db3f8f866': 'Atmospheric pressure at sea level is 760 mmHg. This pressure is generated by the collisions of all the molecules with each other and other objects. At high altitude there are fewer molecules, so fewer collisions, and hence atmospheric pressure is lower.', 'a630d4b8-fca5-42f2-b5b5-7435455e5bc6': 'Now looking at the composition of our atmosphere we know that 79 percent\xa0is nitrogen, 20.9 percent\xa0is oxygen, and some trace gases collectively get us to 100 percent. Now let us\xa0calculate a partial pressure. If 79 percent\xa0of the atmosphere is nitrogen, then 79 percent\xa0of our atmospheric pressure is generated by the collisions by nitrogen molecules. Likewise 20.9 percent\xa0of the atmospheric pressure is due to oxygen, so to calculate the partial pressure of oxygen (PO2) we simply multiply atmospheric pressure (PB) by the percentage of oxygen, which means our atmosphere has a partial pressure of oxygen of 159 mmHg.', 'e125ba2f-6da8-4e10-bea6-e132c5f31f62': 'Although this phenomenon is present in the healthy lung, we will see how it is exacerbated in certain disease states and how this exacerbation can be detected by common pulmonary function tests.', '6443f20b-c2ba-4f2a-912d-b820480b48dc': 'First, let us\xa0look at the forces involved during a normal, passive expiration.', 'b41f13e9-f936-4f36-a5cf-fb0da07ecd91': 'For simplicity, the schematic in figure 6.1 shows one airway and an alveolus within the thoracic cavity. At the onset of passive expiration (driven by the recoil of the expanded lung), the intrapleural pressure is negative (about −8 cm H2O). As it remains negative, intrapleural pressure helps keep the airways open.', 'e3fd9346-74ee-4550-ac3d-c10b889a9616': 'West, John B. “Chapter 7: Mechanics of Breathing—How the Lung Is Supported and Moved.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'f3d82c09-4fa4-4232-b7c2-ca82c3f0e4d6': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 3.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '2abbd8fc-bc45-4021-95f3-7cc764fb7854': 'The first factor we must consider when thinking about airflow is the type of flow that is occurring.', '90b7c113-9453-48ab-af12-da3e977c0466': 'The most efficient form of flow is laminar\xa0(i.e., laminar flow takes the lowest pressure differential for flow to occur). In laminar flow the molecules are moving in an orderly manner, those at the side of the tube moving a little slower due to contact with tube walls\xa0and those in the middle moving fastest (figure 5.1).', '185f8384-ae77-4ecc-8216-cf9651f31397': 'When velocity increases or tube radius decreases then this organization is lost. Collisions between molecules and with the tube wall are now more frequent and movement is more chaotic, and the flow becomes turbulent (figure 5.2). At this point some molecules are at times moving against the pressure gradient due to these collisions. Consequently, to generate the same amount of molecule movement (i.e., flow) from one end of the tube to another, a greater pressure differential is needed when flow becomes turbulent. Turbulent flow is more common in the large airways where velocity and airway radius are high.', '78016837-1b1e-4b72-9459-159a81636088': 'In reality, the vast majority of the airways are branching small tubes, so we see a mixture of the two above—mostly laminar flow but some turbulence generated at the branch (or transitional) points (figure 5.3).', 'd8c9a412-74b3-47d6-9885-10a68f3195dc': 'For our purposes though we are going to look at the factors that affect flow when it is laminar—the dominant form of flow in the majority of airways. These factors are described by Poiselle’s equation. We will now break down Poiselle’s equation in relation to flow of air down airways. Although initially an intimidating equation, there are some things we can generally ignore.', '329ee30f-0280-4186-a272-76cda4611f6d': 'Equation 5.1', 'ccf522d3-ed2e-4e8f-951d-b5f59bf4614f': 'Levitsky, Michael G. “Chapter 2: Mechanics of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '6122ed24-6881-4243-b127-64fd05cdb94a': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 1.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '3265bb73-23ce-4e55-b347-c6a6e3d0f4a2': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 2.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '5b7cdf1c-6e3e-4689-a4b4-001b0e7d0b85': 'Before we get into the details of how we breathe in, let me make sure we are all on the same page by going right back to basics, so bare with me or skip ahead if you are happy with pressure, volume, and flow.', '9e430d7f-a263-41b5-819a-5d6f57a475d3': 'To get air to move into the lungs we need to generate a pressure differential;\xa0that is the pressure inside the lungs must be lower than the pressure outside\xa0(i.e., atmospheric pressure), so that air moves down the pressure gradient into the lungs.', '2a56dfa9-1088-4e0d-8a05-7d0dae7eabe3': 'The low pressure inside the lungs is generated by increasing lung volume; bigger volume means fewer molecules in the same space, and therefore lower pressure (go back and revisit Boyle’s law if needed).', '700a30d9-cdcb-4a22-934d-dbb9221c27e8': 'The basis of inspiration is lowering lung pressure below atmospheric pressure, so that atmospheric pressure pushes air down the airways until pressure equilibrates. So the fundamental first step is, how do we increase lung volume?', 'f0582f89-5080-4d8c-973f-c82797cb93ae': 'To understand the mechanics of breathing we have to deal with two concepts:\xa0first how the action of the respiratory muscles increases thoracic volume, and second\xa0(and more complex) we need to understand the interaction of the lungs and the thoracic wall.', 'cf71568f-25a9-4c48-880c-f5fdda101c9b': 'Let us deal with the respiratory muscles and expansion of the thorax first.', '338eec0f-6210-47e2-815e-4cb6f22fc67a': 'West, John B. “Chapter 2: Ventilation—How Gas Gets to the Alveoli.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '3c8b34ab-c9f8-4728-8aad-518dd91e7284': 'We will see how blood gases are monitored and maintained through neurochemical control of lung expansion and relaxation to achieve the appropriate level of alveolar ventilation. Factors that affect the\xa0degree of gas exchange between the lung and blood will be discussed, along with the coordination of ventilation and perfusion of the lung. Finally, we will see how oxygen and carbon dioxide are transported in the bloodstream to and from tissue and the mechanisms that ensure appropriate delivery and a stable blood gas environment.\xa0Before we begin, however, we will look at the functional anatomy of the lung and how the lung is well designed to perform its primary role and defend itself from the external environment.', 'bb13387c-a557-4bd6-8b04-3e30d6d82916': 'Levitsky, Michael G. “Chapter 1: Function and Structure of the Respiratory System.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9faee6ea-d9bf-4b11-a3d3-8561cb811717': 'West, John B. “Chapter 1: Structure and Function—How the Architecture of the Lung Subserves Its Function.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.'}"
+Figure 5.2,pulmo2/images/Figure 5.2.jpg,Figure 5.2: Turbulent flow.,"When velocity increases or tube radius decreases then this organization is lost. Collisions between molecules and with the tube wall are now more frequent and movement is more chaotic, and the flow becomes turbulent (figure 5.2). At this point some molecules are at times moving against the pressure gradient due to these collisions. Consequently, to generate the same amount of molecule movement (i.e., flow) from one end of the tube to another, a greater pressure differential is needed when flow becomes turbulent. Turbulent flow is more common in the large airways where velocity and airway radius are high.","{'709e47ee-7a91-414c-81cc-5c3752c06c47': 'American Thoracic Society Committee on Dyspnea. “An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea.” American Journal of Respiratory and Critical Care Medicine 185, no. 4: 435–52. https://doi.org/10.1164/rccm.201111-2042ST.', 'd5f1a15f-0fcf-40e5-aa89-9237e2b68c6a': 'Banzett, Robert B., Robert W. Lansing, and Andrew P. Binks. “Air Hunger: A Primal Sensation and a Primary Element of Dyspnea.” Comprehensive Physiology 11, no. 2 (April 2021): 1449–83. https://doi.org/10.1002/cphy.c200001.', '114c8441-5da7-4816-9a98-ebe7006695e0': 'Levitsky, Michael G. “Chapter 9: Control of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '73bce2fb-98ad-41f3-8101-4bf9af7e048d': 'West, John B. “Chapter 8: Control of Ventilation—How Gas Exchange Is Regulated.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'b8d4a9c3-0d94-4647-88e2-309c65d3b974': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 8” and “Chapter 9.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'db0a65e0-e669-4647-b737-5a183e68a90c': 'The hemoglobin molecule consists of four polypeptide chains, two alpha and two beta (figure 16.1). These proteins comprise the “globin”\xa0part of the molecule but are not simply structural as they contain sites that are capable of receiving CO2\xa0and also hydrogen ions—a handy function, as you might imagine. Some anemias, such as sickle cell anemia, involve a conformational change in these proteins and diminish\xa0the molecule’s gas carrying ability.', 'b3772caa-6325-41b5-beea-7c431fd6d4b3': 'The heme component of hemoglobin is an iron-containing porphyrin molecule capable of binding with oxygen. Each of the four polypeptide chains contains a heme molecule, meaning that each hemoglobin molecule is capable of transporting four oxygen molecules. It is\xa0also worth noting that binding of oxygen to the heme molecule induces a conformational change that results in oxyhemoglobin having some different behaviors and indeed color to deoxyhemoglobin. We will look at some of these differences in behavior later on.', '305cc335-e478-4f77-85c3-749b48edc277': 'It is\xa0also worth reviewing hemoglobin’s home here as well—the red blood cell (RBC). The red blood cell’s classic biconcave shape provides a large surface area for gas exchange and also means that no hemoglobin molecule inside is very far from the edge of the cell, cutting down on the diffusion distance of gases. The cell is also very flexible, making it capable of squeezing through narrow and twisting capillaries so that its walls and those of the capillary may be in\xa0close contact and again diffusion distances are reduced.', '396c63b3-8995-41de-a103-31ebc88c8ab7': 'Each RBC is capable of holding up to 250 million hemoglobin molecules, so consequently is capable of holding one billion oxygen molecules; as such the RBC fulfills its primary role of oxygen transport well. This oxygen transport system fails in anemias that result in either too few red blood cells\xa0or too little hemoglobin in each cell (or both). Now let us look at the behavior of hemoglobin.', 'b3a2853f-4d49-466c-b233-b1e3ad132937': 'The behavior of hemoglobin is best described by the oxygen saturation curve (figure 16.2), and this is one of the most important curves to understand in medicine. The curve shows the percentage of hemoglobin that has all of its heme molecules bound with oxygen (i.e., are saturated). So for example a 50 percent\xa0saturation would mean that half of the heme sites were occupied by oxygen. The curve shows percentage saturation in relation to oxygen partial pressure, and what should be immediately noticeable is that the higher the partial pressure of oxygen then the greater the saturation. But the relationship is far from linear and its shape offers several important physiological advantages. If it helps understand it, think of this curve as an instruction manual for hemoglobin,\xa0telling how saturated it should be at any PO2. In reality it is an enzyme kinetics curve, describing hemoglobin’s affinity for oxygen over a range of PO2.', '240bd48e-3307-4e02-a6c4-3980b6721979': 'First\xa0let us put the curve in a physiological context. The alveolar PO2\xa0is around 100 mmHg. This means that as blood passes the alveoli and is exposed to this PO2, then oxygen saturation becomes close to 100 percent, about 98 percent. The first important physiological feature of this curve is that PO2\xa0can fall a considerably long way before it has an impact on oxygen saturation. So, taking time to look at the numbers on the graph, let us say, for example, that a patient begins to hypoventilate and alveolar PO2\xa0falls to 70 mmHg; while this is a considerable fall in PO2, the saturation will only fall a few percentage points, and PO2\xa0must\xa0fall to 50 before significant loss of saturation, or desaturation, occurs. Below 50, however, notice how the curve rapidly steepens, and now for a small change in PO2, we get a large desaturation.', '57274494-19e2-4442-a9f6-72dc7f08e65a': 'This steep section of the curve is therefore clinically critical. If your patient’s saturation monitor reads 83 percent\xa0what should spring into your mind is it that such a low saturation puts the patient onto the steep part of the curve. It will now take only a small further decline in alveolar PO2\xa0to have a profound effect on saturation, unlike at the top and flat section of the curve where small changes in alveolar PO2\xa0have very little effect on saturation.', 'ae59bbfa-2b77-438a-a039-3640d3f50564': 'So what is the advantage of having such a steep curve at lower PO2s? Let us look at the physiological situation again. We have\xa0already said that the alveolar PO2\xa0of 100 results in a saturation close to 100 percent (i.e., at the lung the hemoglobin\xa0has a high affinity for oxygen and becomes fully saturated).', '9db43d4c-5e74-4450-aeb0-f34c80abd999': 'At the tissue, however, we want hemoglobin\xa0to lose its affinity for oxygen and release some to the metabolizing cells. At the tissue the local PO2\xa0is much lower, around 40, because of the oxygen consumption by the tissue. At the lower PO2, hemoglobin’s affinity for oxygen falls, and it will lose some of its oxygen to the tissue and saturation will fall. This is ideal, as now our oxygen carrier is capable of releasing oxygen where it is\xa0needed.', '5b86e2bb-12a9-4a32-80fa-554e0dcae3ee': 'If tissue PO2\xa0falls even lower, such as when metabolic rate is high, then more oxygen will be released by hemoglobin as its affinity for oxygen declines with the lower tissue PO2. Therefore the delivery system for oxygen is intrinsically tied to metabolic rate.', '56b865af-bc70-47ec-8696-ba94d1f42869': 'The shape of this curve makes hemoglobin a remarkable molecule—able to grab oxygen at the oxygen-providing lung, but relinquish it to oxygen-demanding tissue and relinquish more when the tissue needs more. There are other factors that fine-tune the amount of oxygen delivered to tissue to match its oxygen demand. This is summarized in figure 16.3.', '4ed813be-9b8e-460b-bafa-7979fda65ba0': 'Levitsky, Michael G. “Chapter 7: Transport of Oxygen and Carbon Dioxide in the Blood.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'd6a16cf9-d059-46b3-b7e2-0261a878af63': 'West, John B. “Chapter 6: Gas Transport by the Blood—How Gases Are Moved to the Peripheral Tissues.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'eebcdd0d-d4a0-48ea-b604-9534d41496ed': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 6.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '279562ba-f525-4412-9982-1e9c07d279bb': 'There are two circulatory networks that normally form shunts. The bronchial circulation, that supplies\xa0the bronchi, empties its venous blood into the pulmonary veins, thereby sending slightly deoxygenated blood back toward the left heart and into the systemic arterial system. Likewise a very small portion of the coronary venous blood is returned to the left ventricle (through the thebesian veins) and thereby bypasses the lung completely before going back in the systemic circulation.', 'e26d0d11-466b-4a31-bc87-c83397920658': 'These two wayward circulations and the imperfect V/Q matching in the lung serve to suppress arterial oxygen saturation.', 'c0f16823-bf43-4645-9269-c51c6ce26d14': 'Levitsky, Michael G. “Chapter 5: Ventilation–Perfusion Relationships.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '4a3745c2-5916-41da-b111-3377965154c7': 'West, John B. “Chapter 5: Ventilation–Perfusion Relationships—How Matching of Gas and Blood Determines Gas Exchange.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '0b3f01fc-f893-4c2a-ba14-78f6613e445c': 'Levitsky, Michael G. “Chapter 3: Alveolar Ventilation.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'ef7d1b93-3a1e-49fe-8e36-f72ffeb5d196': 'Let us\xa0start with a description of the ideal situation, where ventilation to alveoli is matched with the perfusion, then we will see how the lung does not quite achieve this.', '20443118-b1a8-481e-b40b-fabc2cdacdae': 'This is what we would expect if the lung were perfect, with uniform distribution of ventilation and perfusion to all regions and a V/Q of 1 in all regions.', '1266c3d9-2603-4ab5-a23b-c4c09c575487': 'The lung is not a perfect organ, however, and ventilation and perfusion are not equally distributed, and the lung as a whole only achieves an average V/Q of 0.8, which is close to our ideal of 1, but not quite there. Consequently, by the time the blood has passed the alveoli and regrouped in the pulmonary veins, the PO2 of the blood is less than alveolar. This alveolar–arterial PO2 difference is caused by the less-than-perfect matching of V and Q across the lung; but it is\xa0not all the lung’s fault, as venous blood that has been through the bronchial and a small section of the coronary circulation (and therefore is deoxygenated) is mixed into the vessels returning to the left heart, which brings down arterial saturation as well. The mixing-in of bronchial and coronary circulations and the less-than-ideal V/Q in the lung as a whole is the reason why your saturation monitors do not\xa0read 100 percent, but normal oxygen saturation is considered as 96–98 percent.', '736d22e3-bd4e-497c-bf9a-992a06cc406d': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 7.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'c7f4c268-560a-4009-8867-a730d1d4a684': 'Levitsky, Michael G. “Chapter 8: Acid–Base Balance.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '405afb7b-5d31-4d56-b756-36329df0d2fa': 'Levitsky, Michael G. “Chapter 10: Nonrespiratory Functions of the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9cfd8d5d-3721-4961-8c24-8b2bba6b0e82': 'West, John B. “Chapter 4: Blood Flow and Metabolism—How the Pulmonary Circulation Removes Gas from the Lung and Alters Some Metabolites.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '5bbf18cb-720e-433f-a97c-7a9a17affa5c': 'Levitsky, Michael G. “Chapter 4: Blood Flow to the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '58f3e187-02d3-4794-a834-033ae16daf9b': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 5.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '7ee7bd78-ee76-462c-8326-3223973d9968': 'Levitsky, Michael G. “Chapter 6: Diffusion of Gases and Interpretation of Pulmonary Function Tests.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '7098f0e3-8f6c-4a7f-8bb9-019917fbc96e': 'West, John B. “Chapter 3: Diffusion—How Gas Gets Across the Blood–Gas Barrier.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '83eef49d-f1b3-4248-908d-fe1c99a681e8': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 4.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '94a2e555-32f9-4cc7-8f5b-ef7daead5687': 'Before we do that though, we need to be able to calculate the units of measurement we use when describing gas exchange. When referring to gas exchange we are really referring to diffusion of gases down their concentration gradient, but rather than use concentrations, we use partial pressures.', '83d5f78d-9abb-48e8-b071-bef116366b8f': 'Partial pressures describe what proportion of the total pressure is exerted by a particular component of a mixed gas. Let us\xa0look at the specific situation we are interested in to illustrate this description.', 'd82456a7-eec8-4a00-acb8-976db3f8f866': 'Atmospheric pressure at sea level is 760 mmHg. This pressure is generated by the collisions of all the molecules with each other and other objects. At high altitude there are fewer molecules, so fewer collisions, and hence atmospheric pressure is lower.', 'a630d4b8-fca5-42f2-b5b5-7435455e5bc6': 'Now looking at the composition of our atmosphere we know that 79 percent\xa0is nitrogen, 20.9 percent\xa0is oxygen, and some trace gases collectively get us to 100 percent. Now let us\xa0calculate a partial pressure. If 79 percent\xa0of the atmosphere is nitrogen, then 79 percent\xa0of our atmospheric pressure is generated by the collisions by nitrogen molecules. Likewise 20.9 percent\xa0of the atmospheric pressure is due to oxygen, so to calculate the partial pressure of oxygen (PO2) we simply multiply atmospheric pressure (PB) by the percentage of oxygen, which means our atmosphere has a partial pressure of oxygen of 159 mmHg.', 'e125ba2f-6da8-4e10-bea6-e132c5f31f62': 'Although this phenomenon is present in the healthy lung, we will see how it is exacerbated in certain disease states and how this exacerbation can be detected by common pulmonary function tests.', '6443f20b-c2ba-4f2a-912d-b820480b48dc': 'First, let us\xa0look at the forces involved during a normal, passive expiration.', 'b41f13e9-f936-4f36-a5cf-fb0da07ecd91': 'For simplicity, the schematic in figure 6.1 shows one airway and an alveolus within the thoracic cavity. At the onset of passive expiration (driven by the recoil of the expanded lung), the intrapleural pressure is negative (about −8 cm H2O). As it remains negative, intrapleural pressure helps keep the airways open.', 'e3fd9346-74ee-4550-ac3d-c10b889a9616': 'West, John B. “Chapter 7: Mechanics of Breathing—How the Lung Is Supported and Moved.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'f3d82c09-4fa4-4232-b7c2-ca82c3f0e4d6': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 3.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '2abbd8fc-bc45-4021-95f3-7cc764fb7854': 'The first factor we must consider when thinking about airflow is the type of flow that is occurring.', '90b7c113-9453-48ab-af12-da3e977c0466': 'The most efficient form of flow is laminar\xa0(i.e., laminar flow takes the lowest pressure differential for flow to occur). In laminar flow the molecules are moving in an orderly manner, those at the side of the tube moving a little slower due to contact with tube walls\xa0and those in the middle moving fastest (figure 5.1).', '185f8384-ae77-4ecc-8216-cf9651f31397': 'When velocity increases or tube radius decreases then this organization is lost. Collisions between molecules and with the tube wall are now more frequent and movement is more chaotic, and the flow becomes turbulent (figure 5.2). At this point some molecules are at times moving against the pressure gradient due to these collisions. Consequently, to generate the same amount of molecule movement (i.e., flow) from one end of the tube to another, a greater pressure differential is needed when flow becomes turbulent. Turbulent flow is more common in the large airways where velocity and airway radius are high.', '78016837-1b1e-4b72-9459-159a81636088': 'In reality, the vast majority of the airways are branching small tubes, so we see a mixture of the two above—mostly laminar flow but some turbulence generated at the branch (or transitional) points (figure 5.3).', 'd8c9a412-74b3-47d6-9885-10a68f3195dc': 'For our purposes though we are going to look at the factors that affect flow when it is laminar—the dominant form of flow in the majority of airways. These factors are described by Poiselle’s equation. We will now break down Poiselle’s equation in relation to flow of air down airways. Although initially an intimidating equation, there are some things we can generally ignore.', '329ee30f-0280-4186-a272-76cda4611f6d': 'Equation 5.1', 'ccf522d3-ed2e-4e8f-951d-b5f59bf4614f': 'Levitsky, Michael G. “Chapter 2: Mechanics of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '6122ed24-6881-4243-b127-64fd05cdb94a': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 1.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '3265bb73-23ce-4e55-b347-c6a6e3d0f4a2': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 2.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '5b7cdf1c-6e3e-4689-a4b4-001b0e7d0b85': 'Before we get into the details of how we breathe in, let me make sure we are all on the same page by going right back to basics, so bare with me or skip ahead if you are happy with pressure, volume, and flow.', '9e430d7f-a263-41b5-819a-5d6f57a475d3': 'To get air to move into the lungs we need to generate a pressure differential;\xa0that is the pressure inside the lungs must be lower than the pressure outside\xa0(i.e., atmospheric pressure), so that air moves down the pressure gradient into the lungs.', '2a56dfa9-1088-4e0d-8a05-7d0dae7eabe3': 'The low pressure inside the lungs is generated by increasing lung volume; bigger volume means fewer molecules in the same space, and therefore lower pressure (go back and revisit Boyle’s law if needed).', '700a30d9-cdcb-4a22-934d-dbb9221c27e8': 'The basis of inspiration is lowering lung pressure below atmospheric pressure, so that atmospheric pressure pushes air down the airways until pressure equilibrates. So the fundamental first step is, how do we increase lung volume?', 'f0582f89-5080-4d8c-973f-c82797cb93ae': 'To understand the mechanics of breathing we have to deal with two concepts:\xa0first how the action of the respiratory muscles increases thoracic volume, and second\xa0(and more complex) we need to understand the interaction of the lungs and the thoracic wall.', 'cf71568f-25a9-4c48-880c-f5fdda101c9b': 'Let us deal with the respiratory muscles and expansion of the thorax first.', '338eec0f-6210-47e2-815e-4cb6f22fc67a': 'West, John B. “Chapter 2: Ventilation—How Gas Gets to the Alveoli.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '3c8b34ab-c9f8-4728-8aad-518dd91e7284': 'We will see how blood gases are monitored and maintained through neurochemical control of lung expansion and relaxation to achieve the appropriate level of alveolar ventilation. Factors that affect the\xa0degree of gas exchange between the lung and blood will be discussed, along with the coordination of ventilation and perfusion of the lung. Finally, we will see how oxygen and carbon dioxide are transported in the bloodstream to and from tissue and the mechanisms that ensure appropriate delivery and a stable blood gas environment.\xa0Before we begin, however, we will look at the functional anatomy of the lung and how the lung is well designed to perform its primary role and defend itself from the external environment.', 'bb13387c-a557-4bd6-8b04-3e30d6d82916': 'Levitsky, Michael G. “Chapter 1: Function and Structure of the Respiratory System.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9faee6ea-d9bf-4b11-a3d3-8561cb811717': 'West, John B. “Chapter 1: Structure and Function—How the Architecture of the Lung Subserves Its Function.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.'}"
+Figure 5.3,pulmo2/images/Figure 5.3.jpg,Figure 5.3: Transitional flow.,"In reality, the vast majority of the airways are branching small tubes, so we see a mixture of the two above—mostly laminar flow but some turbulence generated at the branch (or transitional) points (figure 5.3).","{'709e47ee-7a91-414c-81cc-5c3752c06c47': 'American Thoracic Society Committee on Dyspnea. “An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea.” American Journal of Respiratory and Critical Care Medicine 185, no. 4: 435–52. https://doi.org/10.1164/rccm.201111-2042ST.', 'd5f1a15f-0fcf-40e5-aa89-9237e2b68c6a': 'Banzett, Robert B., Robert W. Lansing, and Andrew P. Binks. “Air Hunger: A Primal Sensation and a Primary Element of Dyspnea.” Comprehensive Physiology 11, no. 2 (April 2021): 1449–83. https://doi.org/10.1002/cphy.c200001.', '114c8441-5da7-4816-9a98-ebe7006695e0': 'Levitsky, Michael G. “Chapter 9: Control of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '73bce2fb-98ad-41f3-8101-4bf9af7e048d': 'West, John B. “Chapter 8: Control of Ventilation—How Gas Exchange Is Regulated.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'b8d4a9c3-0d94-4647-88e2-309c65d3b974': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 8” and “Chapter 9.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'db0a65e0-e669-4647-b737-5a183e68a90c': 'The hemoglobin molecule consists of four polypeptide chains, two alpha and two beta (figure 16.1). These proteins comprise the “globin”\xa0part of the molecule but are not simply structural as they contain sites that are capable of receiving CO2\xa0and also hydrogen ions—a handy function, as you might imagine. Some anemias, such as sickle cell anemia, involve a conformational change in these proteins and diminish\xa0the molecule’s gas carrying ability.', 'b3772caa-6325-41b5-beea-7c431fd6d4b3': 'The heme component of hemoglobin is an iron-containing porphyrin molecule capable of binding with oxygen. Each of the four polypeptide chains contains a heme molecule, meaning that each hemoglobin molecule is capable of transporting four oxygen molecules. It is\xa0also worth noting that binding of oxygen to the heme molecule induces a conformational change that results in oxyhemoglobin having some different behaviors and indeed color to deoxyhemoglobin. We will look at some of these differences in behavior later on.', '305cc335-e478-4f77-85c3-749b48edc277': 'It is\xa0also worth reviewing hemoglobin’s home here as well—the red blood cell (RBC). The red blood cell’s classic biconcave shape provides a large surface area for gas exchange and also means that no hemoglobin molecule inside is very far from the edge of the cell, cutting down on the diffusion distance of gases. The cell is also very flexible, making it capable of squeezing through narrow and twisting capillaries so that its walls and those of the capillary may be in\xa0close contact and again diffusion distances are reduced.', '396c63b3-8995-41de-a103-31ebc88c8ab7': 'Each RBC is capable of holding up to 250 million hemoglobin molecules, so consequently is capable of holding one billion oxygen molecules; as such the RBC fulfills its primary role of oxygen transport well. This oxygen transport system fails in anemias that result in either too few red blood cells\xa0or too little hemoglobin in each cell (or both). Now let us look at the behavior of hemoglobin.', 'b3a2853f-4d49-466c-b233-b1e3ad132937': 'The behavior of hemoglobin is best described by the oxygen saturation curve (figure 16.2), and this is one of the most important curves to understand in medicine. The curve shows the percentage of hemoglobin that has all of its heme molecules bound with oxygen (i.e., are saturated). So for example a 50 percent\xa0saturation would mean that half of the heme sites were occupied by oxygen. The curve shows percentage saturation in relation to oxygen partial pressure, and what should be immediately noticeable is that the higher the partial pressure of oxygen then the greater the saturation. But the relationship is far from linear and its shape offers several important physiological advantages. If it helps understand it, think of this curve as an instruction manual for hemoglobin,\xa0telling how saturated it should be at any PO2. In reality it is an enzyme kinetics curve, describing hemoglobin’s affinity for oxygen over a range of PO2.', '240bd48e-3307-4e02-a6c4-3980b6721979': 'First\xa0let us put the curve in a physiological context. The alveolar PO2\xa0is around 100 mmHg. This means that as blood passes the alveoli and is exposed to this PO2, then oxygen saturation becomes close to 100 percent, about 98 percent. The first important physiological feature of this curve is that PO2\xa0can fall a considerably long way before it has an impact on oxygen saturation. So, taking time to look at the numbers on the graph, let us say, for example, that a patient begins to hypoventilate and alveolar PO2\xa0falls to 70 mmHg; while this is a considerable fall in PO2, the saturation will only fall a few percentage points, and PO2\xa0must\xa0fall to 50 before significant loss of saturation, or desaturation, occurs. Below 50, however, notice how the curve rapidly steepens, and now for a small change in PO2, we get a large desaturation.', '57274494-19e2-4442-a9f6-72dc7f08e65a': 'This steep section of the curve is therefore clinically critical. If your patient’s saturation monitor reads 83 percent\xa0what should spring into your mind is it that such a low saturation puts the patient onto the steep part of the curve. It will now take only a small further decline in alveolar PO2\xa0to have a profound effect on saturation, unlike at the top and flat section of the curve where small changes in alveolar PO2\xa0have very little effect on saturation.', 'ae59bbfa-2b77-438a-a039-3640d3f50564': 'So what is the advantage of having such a steep curve at lower PO2s? Let us look at the physiological situation again. We have\xa0already said that the alveolar PO2\xa0of 100 results in a saturation close to 100 percent (i.e., at the lung the hemoglobin\xa0has a high affinity for oxygen and becomes fully saturated).', '9db43d4c-5e74-4450-aeb0-f34c80abd999': 'At the tissue, however, we want hemoglobin\xa0to lose its affinity for oxygen and release some to the metabolizing cells. At the tissue the local PO2\xa0is much lower, around 40, because of the oxygen consumption by the tissue. At the lower PO2, hemoglobin’s affinity for oxygen falls, and it will lose some of its oxygen to the tissue and saturation will fall. This is ideal, as now our oxygen carrier is capable of releasing oxygen where it is\xa0needed.', '5b86e2bb-12a9-4a32-80fa-554e0dcae3ee': 'If tissue PO2\xa0falls even lower, such as when metabolic rate is high, then more oxygen will be released by hemoglobin as its affinity for oxygen declines with the lower tissue PO2. Therefore the delivery system for oxygen is intrinsically tied to metabolic rate.', '56b865af-bc70-47ec-8696-ba94d1f42869': 'The shape of this curve makes hemoglobin a remarkable molecule—able to grab oxygen at the oxygen-providing lung, but relinquish it to oxygen-demanding tissue and relinquish more when the tissue needs more. There are other factors that fine-tune the amount of oxygen delivered to tissue to match its oxygen demand. This is summarized in figure 16.3.', '4ed813be-9b8e-460b-bafa-7979fda65ba0': 'Levitsky, Michael G. “Chapter 7: Transport of Oxygen and Carbon Dioxide in the Blood.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'd6a16cf9-d059-46b3-b7e2-0261a878af63': 'West, John B. “Chapter 6: Gas Transport by the Blood—How Gases Are Moved to the Peripheral Tissues.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'eebcdd0d-d4a0-48ea-b604-9534d41496ed': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 6.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '279562ba-f525-4412-9982-1e9c07d279bb': 'There are two circulatory networks that normally form shunts. The bronchial circulation, that supplies\xa0the bronchi, empties its venous blood into the pulmonary veins, thereby sending slightly deoxygenated blood back toward the left heart and into the systemic arterial system. Likewise a very small portion of the coronary venous blood is returned to the left ventricle (through the thebesian veins) and thereby bypasses the lung completely before going back in the systemic circulation.', 'e26d0d11-466b-4a31-bc87-c83397920658': 'These two wayward circulations and the imperfect V/Q matching in the lung serve to suppress arterial oxygen saturation.', 'c0f16823-bf43-4645-9269-c51c6ce26d14': 'Levitsky, Michael G. “Chapter 5: Ventilation–Perfusion Relationships.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '4a3745c2-5916-41da-b111-3377965154c7': 'West, John B. “Chapter 5: Ventilation–Perfusion Relationships—How Matching of Gas and Blood Determines Gas Exchange.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '0b3f01fc-f893-4c2a-ba14-78f6613e445c': 'Levitsky, Michael G. “Chapter 3: Alveolar Ventilation.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', 'ef7d1b93-3a1e-49fe-8e36-f72ffeb5d196': 'Let us\xa0start with a description of the ideal situation, where ventilation to alveoli is matched with the perfusion, then we will see how the lung does not quite achieve this.', '20443118-b1a8-481e-b40b-fabc2cdacdae': 'This is what we would expect if the lung were perfect, with uniform distribution of ventilation and perfusion to all regions and a V/Q of 1 in all regions.', '1266c3d9-2603-4ab5-a23b-c4c09c575487': 'The lung is not a perfect organ, however, and ventilation and perfusion are not equally distributed, and the lung as a whole only achieves an average V/Q of 0.8, which is close to our ideal of 1, but not quite there. Consequently, by the time the blood has passed the alveoli and regrouped in the pulmonary veins, the PO2 of the blood is less than alveolar. This alveolar–arterial PO2 difference is caused by the less-than-perfect matching of V and Q across the lung; but it is\xa0not all the lung’s fault, as venous blood that has been through the bronchial and a small section of the coronary circulation (and therefore is deoxygenated) is mixed into the vessels returning to the left heart, which brings down arterial saturation as well. The mixing-in of bronchial and coronary circulations and the less-than-ideal V/Q in the lung as a whole is the reason why your saturation monitors do not\xa0read 100 percent, but normal oxygen saturation is considered as 96–98 percent.', '736d22e3-bd4e-497c-bf9a-992a06cc406d': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 7.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', 'c7f4c268-560a-4009-8867-a730d1d4a684': 'Levitsky, Michael G. “Chapter 8: Acid–Base Balance.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '405afb7b-5d31-4d56-b756-36329df0d2fa': 'Levitsky, Michael G. “Chapter 10: Nonrespiratory Functions of the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9cfd8d5d-3721-4961-8c24-8b2bba6b0e82': 'West, John B. “Chapter 4: Blood Flow and Metabolism—How the Pulmonary Circulation Removes Gas from the Lung and Alters Some Metabolites.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '5bbf18cb-720e-433f-a97c-7a9a17affa5c': 'Levitsky, Michael G. “Chapter 4: Blood Flow to the Lung.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '58f3e187-02d3-4794-a834-033ae16daf9b': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 5.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '7ee7bd78-ee76-462c-8326-3223973d9968': 'Levitsky, Michael G. “Chapter 6: Diffusion of Gases and Interpretation of Pulmonary Function Tests.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '7098f0e3-8f6c-4a7f-8bb9-019917fbc96e': 'West, John B. “Chapter 3: Diffusion—How Gas Gets Across the Blood–Gas Barrier.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '83eef49d-f1b3-4248-908d-fe1c99a681e8': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 4.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '94a2e555-32f9-4cc7-8f5b-ef7daead5687': 'Before we do that though, we need to be able to calculate the units of measurement we use when describing gas exchange. When referring to gas exchange we are really referring to diffusion of gases down their concentration gradient, but rather than use concentrations, we use partial pressures.', '83d5f78d-9abb-48e8-b071-bef116366b8f': 'Partial pressures describe what proportion of the total pressure is exerted by a particular component of a mixed gas. Let us\xa0look at the specific situation we are interested in to illustrate this description.', 'd82456a7-eec8-4a00-acb8-976db3f8f866': 'Atmospheric pressure at sea level is 760 mmHg. This pressure is generated by the collisions of all the molecules with each other and other objects. At high altitude there are fewer molecules, so fewer collisions, and hence atmospheric pressure is lower.', 'a630d4b8-fca5-42f2-b5b5-7435455e5bc6': 'Now looking at the composition of our atmosphere we know that 79 percent\xa0is nitrogen, 20.9 percent\xa0is oxygen, and some trace gases collectively get us to 100 percent. Now let us\xa0calculate a partial pressure. If 79 percent\xa0of the atmosphere is nitrogen, then 79 percent\xa0of our atmospheric pressure is generated by the collisions by nitrogen molecules. Likewise 20.9 percent\xa0of the atmospheric pressure is due to oxygen, so to calculate the partial pressure of oxygen (PO2) we simply multiply atmospheric pressure (PB) by the percentage of oxygen, which means our atmosphere has a partial pressure of oxygen of 159 mmHg.', 'e125ba2f-6da8-4e10-bea6-e132c5f31f62': 'Although this phenomenon is present in the healthy lung, we will see how it is exacerbated in certain disease states and how this exacerbation can be detected by common pulmonary function tests.', '6443f20b-c2ba-4f2a-912d-b820480b48dc': 'First, let us\xa0look at the forces involved during a normal, passive expiration.', 'b41f13e9-f936-4f36-a5cf-fb0da07ecd91': 'For simplicity, the schematic in figure 6.1 shows one airway and an alveolus within the thoracic cavity. At the onset of passive expiration (driven by the recoil of the expanded lung), the intrapleural pressure is negative (about −8 cm H2O). As it remains negative, intrapleural pressure helps keep the airways open.', 'e3fd9346-74ee-4550-ac3d-c10b889a9616': 'West, John B. “Chapter 7: Mechanics of Breathing—How the Lung Is Supported and Moved.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', 'f3d82c09-4fa4-4232-b7c2-ca82c3f0e4d6': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 3.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '2abbd8fc-bc45-4021-95f3-7cc764fb7854': 'The first factor we must consider when thinking about airflow is the type of flow that is occurring.', '90b7c113-9453-48ab-af12-da3e977c0466': 'The most efficient form of flow is laminar\xa0(i.e., laminar flow takes the lowest pressure differential for flow to occur). In laminar flow the molecules are moving in an orderly manner, those at the side of the tube moving a little slower due to contact with tube walls\xa0and those in the middle moving fastest (figure 5.1).', '185f8384-ae77-4ecc-8216-cf9651f31397': 'When velocity increases or tube radius decreases then this organization is lost. Collisions between molecules and with the tube wall are now more frequent and movement is more chaotic, and the flow becomes turbulent (figure 5.2). At this point some molecules are at times moving against the pressure gradient due to these collisions. Consequently, to generate the same amount of molecule movement (i.e., flow) from one end of the tube to another, a greater pressure differential is needed when flow becomes turbulent. Turbulent flow is more common in the large airways where velocity and airway radius are high.', '78016837-1b1e-4b72-9459-159a81636088': 'In reality, the vast majority of the airways are branching small tubes, so we see a mixture of the two above—mostly laminar flow but some turbulence generated at the branch (or transitional) points (figure 5.3).', 'd8c9a412-74b3-47d6-9885-10a68f3195dc': 'For our purposes though we are going to look at the factors that affect flow when it is laminar—the dominant form of flow in the majority of airways. These factors are described by Poiselle’s equation. We will now break down Poiselle’s equation in relation to flow of air down airways. Although initially an intimidating equation, there are some things we can generally ignore.', '329ee30f-0280-4186-a272-76cda4611f6d': 'Equation 5.1', 'ccf522d3-ed2e-4e8f-951d-b5f59bf4614f': 'Levitsky, Michael G. “Chapter 2: Mechanics of Breathing.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '6122ed24-6881-4243-b127-64fd05cdb94a': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 1.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '3265bb73-23ce-4e55-b347-c6a6e3d0f4a2': 'Widdicombe, John G., and Andrew S. Davis. “Chapter 2.” In Respiratory Physiology. Baltimore: University Park Press, 1983.', '5b7cdf1c-6e3e-4689-a4b4-001b0e7d0b85': 'Before we get into the details of how we breathe in, let me make sure we are all on the same page by going right back to basics, so bare with me or skip ahead if you are happy with pressure, volume, and flow.', '9e430d7f-a263-41b5-819a-5d6f57a475d3': 'To get air to move into the lungs we need to generate a pressure differential;\xa0that is the pressure inside the lungs must be lower than the pressure outside\xa0(i.e., atmospheric pressure), so that air moves down the pressure gradient into the lungs.', '2a56dfa9-1088-4e0d-8a05-7d0dae7eabe3': 'The low pressure inside the lungs is generated by increasing lung volume; bigger volume means fewer molecules in the same space, and therefore lower pressure (go back and revisit Boyle’s law if needed).', '700a30d9-cdcb-4a22-934d-dbb9221c27e8': 'The basis of inspiration is lowering lung pressure below atmospheric pressure, so that atmospheric pressure pushes air down the airways until pressure equilibrates. So the fundamental first step is, how do we increase lung volume?', 'f0582f89-5080-4d8c-973f-c82797cb93ae': 'To understand the mechanics of breathing we have to deal with two concepts:\xa0first how the action of the respiratory muscles increases thoracic volume, and second\xa0(and more complex) we need to understand the interaction of the lungs and the thoracic wall.', 'cf71568f-25a9-4c48-880c-f5fdda101c9b': 'Let us deal with the respiratory muscles and expansion of the thorax first.', '338eec0f-6210-47e2-815e-4cb6f22fc67a': 'West, John B. “Chapter 2: Ventilation—How Gas Gets to the Alveoli.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.', '3c8b34ab-c9f8-4728-8aad-518dd91e7284': 'We will see how blood gases are monitored and maintained through neurochemical control of lung expansion and relaxation to achieve the appropriate level of alveolar ventilation. Factors that affect the\xa0degree of gas exchange between the lung and blood will be discussed, along with the coordination of ventilation and perfusion of the lung. Finally, we will see how oxygen and carbon dioxide are transported in the bloodstream to and from tissue and the mechanisms that ensure appropriate delivery and a stable blood gas environment.\xa0Before we begin, however, we will look at the functional anatomy of the lung and how the lung is well designed to perform its primary role and defend itself from the external environment.', 'bb13387c-a557-4bd6-8b04-3e30d6d82916': 'Levitsky, Michael G. “Chapter 1: Function and Structure of the Respiratory System.” In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.', '9faee6ea-d9bf-4b11-a3d3-8561cb811717': 'West, John B. “Chapter 1: Structure and Function—How the Architecture of the Lung Subserves Its Function.” In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.'}"
+Figure 5.4,pulmo2/images/Figure 5.4.jpg,Figure 5.4: Airway resistance down the bronchial tree.,"So with radius having such a powerful effect on airway resistance we would expect that the early and larger generations of airways would offer the least resistance to flow, and resistance would increase as we descended deeper into the lung to the smaller and later airway generations. Figure 5.4 shows the opposite is true—that airway resistance decreases as the airway generations are descended. This is because the total cross-sectional area increases with each generation—while the early and large airways are wide, they are few. The lower and smaller airways are much more numerous, and so collectively they have a greater cross-sectional area and therefore offer less resistance.","{'c7af50f6-2c05-47d3-9087-5b1f80d3fccb': 'So with radius having such a powerful effect on airway resistance we would expect that the early and larger generations of airways would offer the least resistance to flow, and resistance would increase as we descended deeper into the lung to the smaller and later airway generations. Figure 5.4\xa0shows the opposite is true—that airway resistance decreases as the airway generations are descended. This is because the total cross-sectional area increases with each generation—while the early and large airways are wide, they are few. The lower and smaller airways are much more numerous, and so collectively they have a greater cross-sectional area and therefore offer less resistance.', 'b1b161a6-1bb8-45d6-88e1-70fe35847671': 'The highest point of resistance is actually the midsize bronchioles. There are a couple of clinically important points to make here:'}"
+Figure 5.5,pulmo2/images/Figure 5.5.jpg,Figure 5.5: Radial traction decreases airway resistance as lung volume increases.,"The airways without cartilaginous support significantly change their radius when the lung expands due to the radial traction. In brief, parenchymal fibers tethered to the alveoli and exterior of the airways allow the airways to be pulled open by the expanding alveoli when lung volume increases (illustrated in figure 5.5).","{'cbb7a36b-87fc-4845-9394-57c7374d4733': 'The airways without cartilaginous support significantly change their radius when the lung expands\xa0due to the radial traction. In brief, parenchymal fibers tethered to the alveoli and exterior of the airways allow the airways to be pulled open by the expanding alveoli when lung volume increases (illustrated in figure 5.5).', '16bcda72-2e9a-413f-ae1d-b5d369159840': 'This increase in airway diameter means that airway resistance falls as lung volume increases. This is demonstrated by figure 5.6; as lung volume increases, then airway resistance falls exponentially.', 'ce71d882-d522-4f75-9d9c-d0057c48fede': 'The inverse is also true, that as lung volume decreases, airway radius declines. This may happen to a sufficient extent to allow small airways to collapse. It is worth noting here that respiratory patients frequently breathe at higher lung volumes. While there are mechanical reasons for this that we will discover in the next chapter, the higher lung volume may at least improve airway conductance (although it carries many other disadvantages).'}"
+Figure 5.6,pulmo2/images/Figure 5.6.jpg,Figure 5.6: Airway resistance and lung volume.,"This increase in airway diameter means that airway resistance falls as lung volume increases. This is demonstrated by figure 5.6; as lung volume increases, then airway resistance falls exponentially.","{'cbb7a36b-87fc-4845-9394-57c7374d4733': 'The airways without cartilaginous support significantly change their radius when the lung expands\xa0due to the radial traction. In brief, parenchymal fibers tethered to the alveoli and exterior of the airways allow the airways to be pulled open by the expanding alveoli when lung volume increases (illustrated in figure 5.5).', '16bcda72-2e9a-413f-ae1d-b5d369159840': 'This increase in airway diameter means that airway resistance falls as lung volume increases. This is demonstrated by figure 5.6; as lung volume increases, then airway resistance falls exponentially.', 'ce71d882-d522-4f75-9d9c-d0057c48fede': 'The inverse is also true, that as lung volume decreases, airway radius declines. This may happen to a sufficient extent to allow small airways to collapse. It is worth noting here that respiratory patients frequently breathe at higher lung volumes. While there are mechanical reasons for this that we will discover in the next chapter, the higher lung volume may at least improve airway conductance (although it carries many other disadvantages).'}"
+Figure 4.1,pulmo2/images/Figure 4.1.jpg,Figure 4.1: The fiber networks of the lung.,"In brief, collagenous and elastic fibers run the length of the large airways and into the lobes forming the axial network. Fibers beneath the pleura and within the septal spaces between the lobes form a peripheral network, and finally thin fibers surrounding the alveoli within the lobes form the septal network. Together these networks form a fibrous “web” of the lung (figure 4.1).","{'be8b78cd-0195-4b08-b835-d711e5910ebf': 'In brief, collagenous and elastic fibers run the length of the large airways and into the lobes forming the axial network. Fibers beneath the pleura and within the septal spaces between the lobes form a peripheral network, and finally thin fibers surrounding the alveoli within the lobes form the septal network. Together these networks form a fibrous “web” of the lung (figure 4.1).', '05b86415-fa0a-4fd9-bcd2-ac5248007ef1': 'Functionally what this means is that movement of one lung structure is transferred to others. As the lung inflates these fibrous connections have a significant impact on lung function and the pulmonary vasculature. Expanding alveoli pull on fibers that are attached to neighboring airways and blood vessels and, indeed, other alveoli.', 'e6b3312f-2269-4d95-a367-9aa35274f3d4': 'The expanding lung volume tends to pull open airways and blood vessels, lowering the resistance of both as inspiration continues, as is illustrated in figure 4.2.', 'e09c9161-fc78-4197-acb5-13e6b2517377': 'Radial traction (sometimes called parenchymal traction) is an important component of the lung’s mechanical behavior, and it means that lung volume has an effect on airway and vascular resistance.', '7fac62a3-dcfc-4f2a-9ed3-f2ad58606fce': 'More important for us now though is the understanding that the lung is highly connected within itself. And it is\xa0a good thing\xa0that it is\xa0these fiber networks transfer changes in pleural pressure from the lung periphery to its center; without the networks, only the alveoli at the periphery of the lung would expand when pleural pressure became negative during inspiration.', 'b86a276d-3ccd-419d-80d8-19a1ed9b8520': 'It also means that the effects of gravity are transferred to the lung as a single unit, and we will look at that now.'}"
+Figure 4.2,pulmo2/images/Figure 4.2.jpg,Figure 4.2: The action of radial traction.,"The expanding lung volume tends to pull open airways and blood vessels, lowering the resistance of both as inspiration continues, as is illustrated in figure 4.2.","{'be8b78cd-0195-4b08-b835-d711e5910ebf': 'In brief, collagenous and elastic fibers run the length of the large airways and into the lobes forming the axial network. Fibers beneath the pleura and within the septal spaces between the lobes form a peripheral network, and finally thin fibers surrounding the alveoli within the lobes form the septal network. Together these networks form a fibrous “web” of the lung (figure 4.1).', '05b86415-fa0a-4fd9-bcd2-ac5248007ef1': 'Functionally what this means is that movement of one lung structure is transferred to others. As the lung inflates these fibrous connections have a significant impact on lung function and the pulmonary vasculature. Expanding alveoli pull on fibers that are attached to neighboring airways and blood vessels and, indeed, other alveoli.', 'e6b3312f-2269-4d95-a367-9aa35274f3d4': 'The expanding lung volume tends to pull open airways and blood vessels, lowering the resistance of both as inspiration continues, as is illustrated in figure 4.2.', 'e09c9161-fc78-4197-acb5-13e6b2517377': 'Radial traction (sometimes called parenchymal traction) is an important component of the lung’s mechanical behavior, and it means that lung volume has an effect on airway and vascular resistance.', '7fac62a3-dcfc-4f2a-9ed3-f2ad58606fce': 'More important for us now though is the understanding that the lung is highly connected within itself. And it is\xa0a good thing\xa0that it is\xa0these fiber networks transfer changes in pleural pressure from the lung periphery to its center; without the networks, only the alveoli at the periphery of the lung would expand when pleural pressure became negative during inspiration.', 'b86a276d-3ccd-419d-80d8-19a1ed9b8520': 'It also means that the effects of gravity are transferred to the lung as a single unit, and we will look at that now.'}"
+Figure 4.3,pulmo2/images/Figure 4.3.jpg,"Figure 4.3: Interaction of lung volume, compliance, and distribution of ventilation.","Simply because of gravity, therefore, we have a distribution of intrapleural pressures. As you know from the previous chapter, intrapleural pressure determines alveolus size (figure 4.3). So at the apex of the lung alveoli tend to be large because of the more negative intrapleural pressure, while at the base, alveoli are less extended because of the less negative intrapleural pressure. If an analogy would help, look at this slinky being held up (figure 4.4). The coils near the top of it are pulled far apart because of the weight of the slinky below the top. As you travel down the slinky the coils are less and less extended as less and less weight below pulls on them. The lung acts just the same; alveoli at the top are extended at rest, while those at the base have a smaller volume.","{'0d6fedce-9752-4d68-81b5-7494c5f5e736': 'Alveoli at the apex (top) of the lung have a substantial amount of lung tissue below them for gravity to act on,\xa0so there is a large force pulling the lung away from the pleural space here and hence at the top of the lung intrapleural pressure is more negative. As we descend down the lung the mass below each point becomes less and less, so the pull on the pleural space declines, and we see intrapleural pressure become less and less negative.', 'd88f06b7-a07c-477f-a356-9b5556a97395': 'Simply because of gravity, therefore, we have a distribution of intrapleural pressures. As you know from the previous chapter, intrapleural pressure determines alveolus size (figure 4.3). So at the apex of the lung alveoli tend to be large because of the more negative intrapleural pressure, while at the base, alveoli are less extended because of the less negative intrapleural pressure.\xa0If an analogy would help, look at this slinky being held up (figure 4.4). The coils near the top of it are pulled far apart because of the weight of the slinky below the top. As you travel down the slinky the coils are less and less extended as less and less weight below pulls on them. The lung acts just the same;\xa0alveoli at the top are extended at rest, while those at the base have a smaller volume.', '9e36424f-a1ab-4191-8732-63f704c81294': 'This has ramifications on where air entering the lung goes and how ventilation is distributed across the lung (more on the implications of this in chapter 13). Alveoli at the apex of the lung are already extended and therefore have limited capacity to take in more air;\xa0their resting volume is also close to the flat part of the compliance curve (figure 4.3), so they are more difficult to inflate. The smaller alveoli at the base of the lung, however, still have a greater capacity for expansion, and the smaller resting volume places them on the steeper section of the compliance curve;\xa0consequently they are easier to inflate, and air takes the path of least resistance.', '18e21582-f8de-47df-b66f-013595cc7781': 'Because of this, the alveoli at the apex of the lung rapidly fill to capacity on inspiration, and the vast majority of inspired air descends toward\xa0the base toward\xa0the more compliant and less extended alveoli. This uneven distribution of ventilation is something we will return to when we address other learning objectives, so it is worth understanding.'}"
+Figure 3.1,pulmo2/images/Figure 3.1.jpg,Figure 3.1: Lung volumes detected by spirometry.,First let us look at lung volumes. This trace from a spirometer (figure 3.1) shows the change in lung volume as a patient breathes normally and then performs some specific maneuvers.,"{'6ba80913-757c-4bf2-9fae-0abce683e342': 'First let us\xa0look at lung volumes. This trace from a spirometer (figure 3.1) shows the change in lung volume as a patient breathes normally and then performs some specific maneuvers.', 'ac8ec9e3-516a-425c-b7ce-a82558e6e9e2': 'Let us\xa0work through the trace from left to right. The initial part of the trace shows resting or “tidal”\xa0breathing. The amount of volume inspired during each breath is referred to as tidal volume.', 'f67812e4-2a8d-4331-bec3-b0fae9916f7f': 'Once a normal expiration is complete, however, the lung is far from empty, and when instructed, this patient (figure 3.1) breathes out as far as they can; this excess that comes out the lung is referred to as the expiratory reserve volume.', 'dc56756d-41ee-4ec8-b969-4573065f4b6b': 'Even at this point, however, some air remains in the lung, and this is referred to as residual volume. Even with maximal efforts, this volume cannot be exhaled, so at no point can the lung be fully emptied. This also means that residual volume can never be measured with a spirometer.', 'f288c178-32e1-4731-8af8-c03a67151b63': 'Our patient (figure 3.1) returns to normal tidal breathing for two breaths before taking a full breath in, filling the lungs as much as they can. This extra volume into the lung after a normal tidal inspiration is referred to as inspiratory reserve volume. Related to\xa0this volume is the inspiratory capacity, which is the volume that can be taken into the lung after a normal expiration; inspiratory capacity is a useful clinical measurement that we will return to when we deal with some disease states.', '8763a675-1a95-47e8-9ccf-01a538f10261': 'Another clinically valuable measurement is vital capacity, which is the volume of air that our patient can move out of the lung after a full inspiration, that is, the total lung capacity, minus the residual volume (remember: residual volume\xa0cannot be expelled). Forced vital capacity is a common measure taken in pulmonary function testing, and this is simply the volume that can be expelled from total lung capacity during a forceful expiration. The importance of this maneuver being forced will be dealt with when we look at airway compression (chapter 6).', 'f9e309dc-7742-4d89-91f5-00041b8b6a6d': 'While the volumes we have just seen measured by spirometry in the pulmonary function lab provide valuable clinical information, we need to now look at some physiological variables that are also critical for our understanding of lung function and disease.'}"
+Figure 3.2,pulmo2/images/Figure 3.2.jpg,Figure 3.2: Changes in breathing tidal volume and respiratory rate with increasing levels of exercise.,"This partially explains why increases in ventilation are initially achieved by increases in tidal volume; as shown in figure 3.2, as tidal volume increases during exercise intensity (represented by oxygen uptake) until it reaches a plateau. Only when this plateau is reached are further increases in minute ventilation achieved by increasing respiratory rate.","{'1c16b300-39ec-49c1-bfc7-5a2dc76d4d07': 'So despite maintaining the same minute ventilation, the second patient’s alveolar minute ventilation is reduced by 1,500 mL, which is significant given that this is the volume of air going to the gas exchange surfaces.', '37c67bfc-e104-4064-89dc-96788fcfaf6a': 'This partially explains why increases in ventilation are initially achieved by increases in tidal volume; as shown in figure 3.2, as tidal volume increases during exercise intensity (represented by oxygen uptake) until it reaches a plateau. Only when this plateau is reached are further increases in minute ventilation\xa0achieved by increasing respiratory rate.', 'f9badee4-82c4-4073-9f76-7490c77f53b7': 'So why not keep increasing tidal volume? At higher lung volumes the elastic limit of the lung is approached, and it\xa0takes more energy (muscular force) to expand, so it is more efficient and the work of breathing is less if the rate of breathing is increased to achieve higher levels of minute ventilation. This brings us to our next topic, lung compliance.'}"
+Figure 3.3,pulmo2/images/Figure 3.3.jpg,Figure 3.3: Lung compliance curve.,"Lung compliance is a description of how easy the lung is to inflate, more specifically, how much volume will change for a given pressure differential. Figure 3.3 shows a typical and normal lung compliance curve. The lower line shows how volume changes as intrapleural pressure becomes more negative (as the chest wall and diaphragm expand the thorax). The upper curve is the compliance of the lung during expiration, and it is clearly different; this is an example of hysteresis, meaning that the relationship depends on direction, and we will see why this exists later.","{'eb090bbf-c764-42ea-a0e8-7f58725e4d00': 'Lung compliance is a description of how easy the lung is to inflate, more specifically, how much volume will change for a given pressure differential. Figure 3.3 shows a typical and normal lung compliance curve. The lower line shows how volume changes as intrapleural pressure becomes more negative (as the chest wall and diaphragm expand the thorax). The upper curve is the compliance of the lung during expiration, and it is clearly different; this is an example of hysteresis, meaning that the relationship depends on direction, and we will see why this exists later.', 'bf688c7a-ae87-4784-bff0-a4fc4b6648af': 'You will notice at low lung volumes the slope of the compliance curve (figure 3.3) is shallower, meaning that it takes a relatively large pressure change to cause an increase in volume. This tells us at low lung volumes the lung is less distensible, or has low compliance.', '4568b50b-5850-4ce8-87d7-3a44de82dbfb': 'If we start to breathe at a higher lung volume, the slope of the curve is steeper, meaning that for a similar change in pressure there is a greater change in volume\xa0(i.e., the lung is more compliant).', '938ef1ff-989b-4d01-8605-5f387607d321': 'If we start breathing at a higher lung volume still, closer to total lung capacity, we see the slope of the compliance curve flatten out again, showing that at the lung volumes the compliance of the lung is low.', '8a48fba0-bb2d-407f-98e1-170502f90531': 'As you might imagine, the normal range for breathing is in the middle range where the slope is steep and the lung compliant. This corresponds to an intrapleural pressure range of −5 to −10 cm H2O, which you should know is the normal range of intrapleural pressures during tidal breathing. This means we normally breathe at a lung volume at which the lung is most compliant and therefore takes less work to inflate.'}"
+Figure 3.3,pulmo2/images/Figure 3.3.jpg,Figure 3.3: Lung compliance curve.,"Lung compliance is a description of how easy the lung is to inflate, more specifically, how much volume will change for a given pressure differential. Figure 3.3 shows a typical and normal lung compliance curve. The lower line shows how volume changes as intrapleural pressure becomes more negative (as the chest wall and diaphragm expand the thorax). The upper curve is the compliance of the lung during expiration, and it is clearly different; this is an example of hysteresis, meaning that the relationship depends on direction, and we will see why this exists later.","{'eb090bbf-c764-42ea-a0e8-7f58725e4d00': 'Lung compliance is a description of how easy the lung is to inflate, more specifically, how much volume will change for a given pressure differential. Figure 3.3 shows a typical and normal lung compliance curve. The lower line shows how volume changes as intrapleural pressure becomes more negative (as the chest wall and diaphragm expand the thorax). The upper curve is the compliance of the lung during expiration, and it is clearly different; this is an example of hysteresis, meaning that the relationship depends on direction, and we will see why this exists later.', 'bf688c7a-ae87-4784-bff0-a4fc4b6648af': 'You will notice at low lung volumes the slope of the compliance curve (figure 3.3) is shallower, meaning that it takes a relatively large pressure change to cause an increase in volume. This tells us at low lung volumes the lung is less distensible, or has low compliance.', '4568b50b-5850-4ce8-87d7-3a44de82dbfb': 'If we start to breathe at a higher lung volume, the slope of the curve is steeper, meaning that for a similar change in pressure there is a greater change in volume\xa0(i.e., the lung is more compliant).', '938ef1ff-989b-4d01-8605-5f387607d321': 'If we start breathing at a higher lung volume still, closer to total lung capacity, we see the slope of the compliance curve flatten out again, showing that at the lung volumes the compliance of the lung is low.', '8a48fba0-bb2d-407f-98e1-170502f90531': 'As you might imagine, the normal range for breathing is in the middle range where the slope is steep and the lung compliant. This corresponds to an intrapleural pressure range of −5 to −10 cm H2O, which you should know is the normal range of intrapleural pressures during tidal breathing. This means we normally breathe at a lung volume at which the lung is most compliant and therefore takes less work to inflate.'}"
+Figure 3.4,pulmo2/images/Figure 3.4.jpg,Figure 3.4: Opposing forces of alveolar pressure and surface tension.,"Surface tension is generated as water molecules cluster together to reduce their exposure to the gas in the alveolar space. As they gather together they drag the alveolar wall with them, producing a force that tends to pull the alveolar walls inward. The alveolar pressure opposes this force and should prevent the alveolus from collapsing (figure 3.4).","{'b2595d16-3472-4347-8652-8a5041e897ec': 'The elastic forces of the alveolus wall exert an inward force of about +10 cm H2O. This results in a net force of +2 cm H2O in the alveolus, and a gradient between this positive pressure is established between the alveolus and the atmosphere outside the lung. That means that along the airway toward\xa0the mouth there is a gradient of progressively decreasing pressure to zero (shown in maroon).', '4d8eebf9-c2a1-4fc0-af77-1f63bd8d903f': 'Importantly in this example of passive expiration the airway pressure is greater than the pleural pressure along the whole length of the airway toward the mouth. Along with the radial traction provided by the surrounding parenchymal tissue, this favorable transmural pressure gradient helps keep the airway open during expiration.', '85336abb-ae09-42b1-8f3d-90c22ce05bb5': 'Now let us\xa0look at what happens if expiration is forceful, or active, rather than passively relying on lung recoil.', '6141bd45-9a97-4ead-8439-2dddc888dac7': 'In a forced expiration (see figure 6.2) the intrapleural pressure can become positive (as much as 120 cm H2O), but in this example we will say it is\xa025 cm H2O. This positive pressure in the pleural cavity comes from the chest wall and diaphragm now “pushing”\xa0the pleural membranes together and compressing the lung.', '8b63e01d-2e8d-46d0-90ae-dad23f3025c1': 'Again, we have the elastic forces of the alveolus generating an inward force (still +10 cm H2O), and when summed with the now positive intrapleural forces, we end up with an alveolar pressure of +35 cm H2O.', '2aefa857-cbcc-430c-96cb-ba4ef825fd3d': 'Again, a pressure gradient between the alveolus and the atmosphere is established (again shown in maroon), but this time there is a fundamental difference caused by the larger intrapleural pressure.', '8da683bb-c7ee-4f58-b005-bf64671bdced': 'At some point along the airway, as airway pressure is decreasing, the intrapleural pressure exceeds airway pressure (in this example it is 25 cm H2O). At this “choke”\xa0point (arrows pointing toward airway in figure 6.2), the airway can become compressed or even collapse.', '480559ff-b1ff-40db-8773-ae708a2320e6': 'This\xa0effect is somewhat reduced by the radial traction of the parenchyma, but airway compression occurs even in the healthy normal lung, and the greater the effort of expiration (i.e., the more positive the intrapleural pressure), the greater degree airways compress and compression occurs closer to the alveoli (i.e., further up the pressure gradient in the airway).', 'e843288a-9a88-4e3a-b197-33a90f9c8ed9': 'If airways are already narrowed, as in obstructive lung diseases such as asthma, or parenchymal traction is lost, such as in emphysema, dynamic airway compression occurs to a greater extent. In these obstructive diseases the increased airway resistance results in the patient having to forcefully expire to overcome the increased resistance of the narrowed airways. This promotes airway compression and leads to air being trapped behind the choke point, causing hyperinflation (breathing at an elevated lung volume).', 'f1570577-d8ed-42e9-afb5-85e530a4feb6': 'This airway compression or any other increase in airway resistance can be demonstrated by a common pulmonary function test, the flow-volume loop.', 'f471b51b-53e8-4a5c-8be6-104466a4f6cc': 'The intrapleural pressure at the base of the lung may actually become positive at low lung volumes. Now that force that tended to open up alveoli is actually a force that tends to compress alveoli. In our example here the intrapleural reaches 3.5 cm H2O, a force that may lead to airway compression and thereby reduce ventilation to the basal alveoli. This intrapleural pressure will certainly place these alveoli on the very flat\xa0and therefore noncompliant section of the compliance curve and make them difficult to inflate because of the surface tension and small radius effect we have discussed previously.', 'd16ea004-19ec-4b3b-9a78-420bddc6679f': 'Too low a lung volume and compliance falls and work of breathing increases, likewise during breathing at high lung volumes, another contributing reason for\xa0why tidal volume plateaus during exercise.', '451b76e9-589e-4a74-bfc0-49991bb084ef': 'So now let us look at why compliance is low at high and low lung volumes, starting with the cause of low lung compliance at low volumes.', 'b3fcd35a-6d91-4bc7-b257-ff73349fa7b3': 'Low compliance at low volumes—Surface tension: The reason why the lung takes more pressure to inflate at low volumes is surface tension. As mentioned in chapter 1 the alveoli have a thin layer of fluid lining their inner surface. As we saw in the pleural space, this causes surface tension. Unlike the surface tension in the pleural space, in the alveoli surface tension is a disadvantage.', 'ca8faa42-d2ec-4bae-952e-07edccef8f5d': 'Surface tension is generated as water molecules cluster together to reduce their exposure to the gas in the alveolar space. As they gather together they drag the alveolar wall with them, producing a force that tends to pull the alveolar walls inward. The alveolar pressure opposes this force and should prevent the alveolus from collapsing (figure 3.4).', 'da746387-5ed7-484c-bf0b-c88bcb2f1276': 'The relationship between these two opposing forces is described by Laplace’s law that states the outward (alveolar) pressure needed to oppose the inwardly directed tension is proportionate to the tension (obviously), but also inversely related to the radius of the alveolus\xa0(i.e., the smaller the radius, the greater the inwardly acting force).', '3509f1ca-8ecc-4ad2-b9cf-3eff570619b3': 'This explains why compliance is low at low\xa0lung volumes. At low lung volumes the alveoli are smaller and\xa0thus have a smaller radius. Laplace’s law states that with a low radius the pressure needed to overcome the inward force will be greater, explaining why a larger alveolar (outward) pressure is needed to inflate the alveolus from a low starting volume.', '036a0fe8-5632-4d81-bf4b-f27259dbb8ed': 'As lung volume increases, and thus alveolar radius increases, the pressure needed to overcome the inward acting force becomes less and the compliance of the lung increases. This explains why compliance is improved at the normal operating range of lung volumes.', '000e0120-8738-495c-8cd9-a9f3b7a795c5': 'This also explains the hysteresis of the compliance curve. During expiration as alveoli are becoming progressively smaller, the inwardly acting force generated by surface tension becomes progressively greater. This phenomenon consequently assists expiration and contributes to expiration being a passive process.', 'da35cdea-8870-4095-b7fa-9c77d9540a3e': 'Low compliance at high lung volumes—Elastic limit: At high lung volumes the alveolar radius has increased further, suggesting that compliance should be further improved as the effect of surface tension will be much less. But surface tension is not the only factor involved, and the compliance curve flattens here, meaning a greater pressure is needed to achieve a volume change at high lung volumes. The low compliance at high lung volumes is caused by another phenomenon altogether. At high lung volumes expansion of the lung becomes limited by the elastic limit of the lung, a little like trying to further stretched an already stretch elastic band—it is harder to do.', '8484b092-d7eb-44a1-b241-2fecb31ef15e': 'So with surface tension causing problems at low lung volumes\xa0and tissue elastic limit causing problems at high lung volumes, the compliance curve is steepest (i.e., most favorable) in the middle, as mentioned before, which is the operating volume of the lung. These principles are summarized in figure 3.5.', '29a73de0-3529-4d42-9213-a65ad7fce041': 'Improving lung compliance with surfactant: So after that information on how surface tension is a problem for the lung, we now have to look at how it could be so much worse if the lung did not\xa0protect itself.', '4e9740cc-c080-4ddb-8640-dac07d5ffc9a': 'Despite it having an effect, particularly at low lung volumes, the lung actually reduces the effect of alveolar surface tension by releasing “surfactant,”\xa0a molecule that disrupts surface tension. In brief, the surfactant molecule (dipalmitoyl phosphatidylcholine) has a similar structure to the phospholipids that make up cell membranes with a hydrophobic end and a hydrophilic end, allowing it to surround water and repel it\xa0at the same time, thus breaking up the interaction between water molecules. So as surfactant significantly reduces surface tension, it thereby increases lung compliance and the risk of alveolar collapse. It also helps keep the air space dry, as excessive surface tension tends to draw water into the space from the capillaries and interstitial spaces.', 'fdc63085-2513-4355-8ded-f5d0c9698671': 'Surfactant is released onto the alveolar inner surface by Type II alveolar cells (recall Type I cells are those making up the alveolar wall). Type II cells produce surfactant at a high rate\xa0and thus demand a constant and generous blood flow; therefore any condition that disrupts this blood supply will cause surfactant concentrations to decline and therefore put the alveolus at risk of collapse as surface tension is allowed to increase.', '08ca76c6-e7cf-44d2-ac4f-713cf0644d61': 'A good illustration of the effect of surfactant is respiratory distress syndrome of the newborn. The underdeveloped lungs of infants born prematurely (at about twenty-eight\xa0weeks), cannot produce sufficient surfactant. Alveoli rapidly collapse (known as atelectasis), and pulmonary edema develops because of the excessive surface tension in the alveolar walls.'}"
+Figure 3.5,pulmo2/images/Figure 3.5.jpg,"Figure 3.5: Summary of lung volumes and compliance. At low volumes alveoli are small and subject to greater surface tension forces that generate an inwardly acting force that requires greater alveolar pressure to achieve inflation. At higher lung volumes surface tension is less effective at generating an inward force, so less pressure is required to cause inflation (the lung is more compliant). At very high lung volumes surface tension poses even less of a problem, but the elastic limits of the lung are being reached, and increases in volume require alveolar pressures to overcome elastic recoil.","So with surface tension causing problems at low lung volumes and tissue elastic limit causing problems at high lung volumes, the compliance curve is steepest (i.e., most favorable) in the middle, as mentioned before, which is the operating volume of the lung. These principles are summarized in figure 3.5.","{'b2595d16-3472-4347-8652-8a5041e897ec': 'The elastic forces of the alveolus wall exert an inward force of about +10 cm H2O. This results in a net force of +2 cm H2O in the alveolus, and a gradient between this positive pressure is established between the alveolus and the atmosphere outside the lung. That means that along the airway toward\xa0the mouth there is a gradient of progressively decreasing pressure to zero (shown in maroon).', '4d8eebf9-c2a1-4fc0-af77-1f63bd8d903f': 'Importantly in this example of passive expiration the airway pressure is greater than the pleural pressure along the whole length of the airway toward the mouth. Along with the radial traction provided by the surrounding parenchymal tissue, this favorable transmural pressure gradient helps keep the airway open during expiration.', '85336abb-ae09-42b1-8f3d-90c22ce05bb5': 'Now let us\xa0look at what happens if expiration is forceful, or active, rather than passively relying on lung recoil.', '6141bd45-9a97-4ead-8439-2dddc888dac7': 'In a forced expiration (see figure 6.2) the intrapleural pressure can become positive (as much as 120 cm H2O), but in this example we will say it is\xa025 cm H2O. This positive pressure in the pleural cavity comes from the chest wall and diaphragm now “pushing”\xa0the pleural membranes together and compressing the lung.', '8b63e01d-2e8d-46d0-90ae-dad23f3025c1': 'Again, we have the elastic forces of the alveolus generating an inward force (still +10 cm H2O), and when summed with the now positive intrapleural forces, we end up with an alveolar pressure of +35 cm H2O.', '2aefa857-cbcc-430c-96cb-ba4ef825fd3d': 'Again, a pressure gradient between the alveolus and the atmosphere is established (again shown in maroon), but this time there is a fundamental difference caused by the larger intrapleural pressure.', '8da683bb-c7ee-4f58-b005-bf64671bdced': 'At some point along the airway, as airway pressure is decreasing, the intrapleural pressure exceeds airway pressure (in this example it is 25 cm H2O). At this “choke”\xa0point (arrows pointing toward airway in figure 6.2), the airway can become compressed or even collapse.', '480559ff-b1ff-40db-8773-ae708a2320e6': 'This\xa0effect is somewhat reduced by the radial traction of the parenchyma, but airway compression occurs even in the healthy normal lung, and the greater the effort of expiration (i.e., the more positive the intrapleural pressure), the greater degree airways compress and compression occurs closer to the alveoli (i.e., further up the pressure gradient in the airway).', 'e843288a-9a88-4e3a-b197-33a90f9c8ed9': 'If airways are already narrowed, as in obstructive lung diseases such as asthma, or parenchymal traction is lost, such as in emphysema, dynamic airway compression occurs to a greater extent. In these obstructive diseases the increased airway resistance results in the patient having to forcefully expire to overcome the increased resistance of the narrowed airways. This promotes airway compression and leads to air being trapped behind the choke point, causing hyperinflation (breathing at an elevated lung volume).', 'f1570577-d8ed-42e9-afb5-85e530a4feb6': 'This airway compression or any other increase in airway resistance can be demonstrated by a common pulmonary function test, the flow-volume loop.', 'f471b51b-53e8-4a5c-8be6-104466a4f6cc': 'The intrapleural pressure at the base of the lung may actually become positive at low lung volumes. Now that force that tended to open up alveoli is actually a force that tends to compress alveoli. In our example here the intrapleural reaches 3.5 cm H2O, a force that may lead to airway compression and thereby reduce ventilation to the basal alveoli. This intrapleural pressure will certainly place these alveoli on the very flat\xa0and therefore noncompliant section of the compliance curve and make them difficult to inflate because of the surface tension and small radius effect we have discussed previously.', 'd16ea004-19ec-4b3b-9a78-420bddc6679f': 'Too low a lung volume and compliance falls and work of breathing increases, likewise during breathing at high lung volumes, another contributing reason for\xa0why tidal volume plateaus during exercise.', '451b76e9-589e-4a74-bfc0-49991bb084ef': 'So now let us look at why compliance is low at high and low lung volumes, starting with the cause of low lung compliance at low volumes.', 'b3fcd35a-6d91-4bc7-b257-ff73349fa7b3': 'Low compliance at low volumes—Surface tension: The reason why the lung takes more pressure to inflate at low volumes is surface tension. As mentioned in chapter 1 the alveoli have a thin layer of fluid lining their inner surface. As we saw in the pleural space, this causes surface tension. Unlike the surface tension in the pleural space, in the alveoli surface tension is a disadvantage.', 'ca8faa42-d2ec-4bae-952e-07edccef8f5d': 'Surface tension is generated as water molecules cluster together to reduce their exposure to the gas in the alveolar space. As they gather together they drag the alveolar wall with them, producing a force that tends to pull the alveolar walls inward. The alveolar pressure opposes this force and should prevent the alveolus from collapsing (figure 3.4).', 'da746387-5ed7-484c-bf0b-c88bcb2f1276': 'The relationship between these two opposing forces is described by Laplace’s law that states the outward (alveolar) pressure needed to oppose the inwardly directed tension is proportionate to the tension (obviously), but also inversely related to the radius of the alveolus\xa0(i.e., the smaller the radius, the greater the inwardly acting force).', '3509f1ca-8ecc-4ad2-b9cf-3eff570619b3': 'This explains why compliance is low at low\xa0lung volumes. At low lung volumes the alveoli are smaller and\xa0thus have a smaller radius. Laplace’s law states that with a low radius the pressure needed to overcome the inward force will be greater, explaining why a larger alveolar (outward) pressure is needed to inflate the alveolus from a low starting volume.', '036a0fe8-5632-4d81-bf4b-f27259dbb8ed': 'As lung volume increases, and thus alveolar radius increases, the pressure needed to overcome the inward acting force becomes less and the compliance of the lung increases. This explains why compliance is improved at the normal operating range of lung volumes.', '000e0120-8738-495c-8cd9-a9f3b7a795c5': 'This also explains the hysteresis of the compliance curve. During expiration as alveoli are becoming progressively smaller, the inwardly acting force generated by surface tension becomes progressively greater. This phenomenon consequently assists expiration and contributes to expiration being a passive process.', 'da35cdea-8870-4095-b7fa-9c77d9540a3e': 'Low compliance at high lung volumes—Elastic limit: At high lung volumes the alveolar radius has increased further, suggesting that compliance should be further improved as the effect of surface tension will be much less. But surface tension is not the only factor involved, and the compliance curve flattens here, meaning a greater pressure is needed to achieve a volume change at high lung volumes. The low compliance at high lung volumes is caused by another phenomenon altogether. At high lung volumes expansion of the lung becomes limited by the elastic limit of the lung, a little like trying to further stretched an already stretch elastic band—it is harder to do.', '8484b092-d7eb-44a1-b241-2fecb31ef15e': 'So with surface tension causing problems at low lung volumes\xa0and tissue elastic limit causing problems at high lung volumes, the compliance curve is steepest (i.e., most favorable) in the middle, as mentioned before, which is the operating volume of the lung. These principles are summarized in figure 3.5.', '29a73de0-3529-4d42-9213-a65ad7fce041': 'Improving lung compliance with surfactant: So after that information on how surface tension is a problem for the lung, we now have to look at how it could be so much worse if the lung did not\xa0protect itself.', '4e9740cc-c080-4ddb-8640-dac07d5ffc9a': 'Despite it having an effect, particularly at low lung volumes, the lung actually reduces the effect of alveolar surface tension by releasing “surfactant,”\xa0a molecule that disrupts surface tension. In brief, the surfactant molecule (dipalmitoyl phosphatidylcholine) has a similar structure to the phospholipids that make up cell membranes with a hydrophobic end and a hydrophilic end, allowing it to surround water and repel it\xa0at the same time, thus breaking up the interaction between water molecules. So as surfactant significantly reduces surface tension, it thereby increases lung compliance and the risk of alveolar collapse. It also helps keep the air space dry, as excessive surface tension tends to draw water into the space from the capillaries and interstitial spaces.', 'fdc63085-2513-4355-8ded-f5d0c9698671': 'Surfactant is released onto the alveolar inner surface by Type II alveolar cells (recall Type I cells are those making up the alveolar wall). Type II cells produce surfactant at a high rate\xa0and thus demand a constant and generous blood flow; therefore any condition that disrupts this blood supply will cause surfactant concentrations to decline and therefore put the alveolus at risk of collapse as surface tension is allowed to increase.', '08ca76c6-e7cf-44d2-ac4f-713cf0644d61': 'A good illustration of the effect of surfactant is respiratory distress syndrome of the newborn. The underdeveloped lungs of infants born prematurely (at about twenty-eight\xa0weeks), cannot produce sufficient surfactant. Alveoli rapidly collapse (known as atelectasis), and pulmonary edema develops because of the excessive surface tension in the alveolar walls.'}"
+Figure 3.2,pulmo2/images/Figure 3.2.jpg,Figure 3.2: Changes in breathing tidal volume and respiratory rate with increasing levels of exercise.,"This partially explains why increases in ventilation are initially achieved by increases in tidal volume; as shown in figure 3.2, as tidal volume increases during exercise intensity (represented by oxygen uptake) until it reaches a plateau. Only when this plateau is reached are further increases in minute ventilation achieved by increasing respiratory rate.","{'1c16b300-39ec-49c1-bfc7-5a2dc76d4d07': 'So despite maintaining the same minute ventilation, the second patient’s alveolar minute ventilation is reduced by 1,500 mL, which is significant given that this is the volume of air going to the gas exchange surfaces.', '37c67bfc-e104-4064-89dc-96788fcfaf6a': 'This partially explains why increases in ventilation are initially achieved by increases in tidal volume; as shown in figure 3.2, as tidal volume increases during exercise intensity (represented by oxygen uptake) until it reaches a plateau. Only when this plateau is reached are further increases in minute ventilation\xa0achieved by increasing respiratory rate.', 'f9badee4-82c4-4073-9f76-7490c77f53b7': 'So why not keep increasing tidal volume? At higher lung volumes the elastic limit of the lung is approached, and it\xa0takes more energy (muscular force) to expand, so it is more efficient and the work of breathing is less if the rate of breathing is increased to achieve higher levels of minute ventilation. This brings us to our next topic, lung compliance.'}"
+Figure 2.1,pulmo2/images/Figure 2.1.jpg,Figure 2.1: The diaphragm.,"The muscle that generates the greatest change in thoracic volume (and thereby the greatest contribution to breathing) is the diaphragm (figure 2.1). Separating the thoracic and abdominal cavities, this sheetlike muscle forms a dome shape in the relaxed state that encroaches into the thorax. This sheet is formed of three sections, the anterior portion originating at the ribs and sternum, and the posterior portion originating on the vertebrae. These are connected by the central portion that is comprised of a tendon sheet.","{'2e10d819-9c0e-4ff8-97ba-e2aa7cfc6a63': 'The muscle that generates the greatest change in thoracic volume (and thereby the greatest contribution to breathing) is the diaphragm (figure 2.1). Separating the thoracic and abdominal cavities, this sheetlike muscle forms a dome shape in the relaxed state that encroaches into the thorax. This sheet is formed of three sections, the anterior portion originating at the ribs and sternum, and the posterior portion originating on the vertebrae. These are connected by the central portion that is comprised of a tendon sheet.', '8b500a6a-6ed6-49c0-a989-611c6fd54a2f': 'It is\xa0worth a quick reminder that while controlling a visceral organ and performing a homeostatic function, the diaphragm and the other respiratory muscles are skeletal muscle and have the force-generation characteristics of such. As well as being under reflex control, it can also be controlled voluntarily (such as during speech).', '6630b073-10dd-4a89-9b32-1f911273bc20': 'Activation of the phrenic nerve stimulates\xa0the diaphragm and generates inspiration. Upon stimulation the contracting diaphragm flattens out, descending toward the abdomen. As it does so the thoracic volume increases, and consequently thoracic pressure falls. When thoracic pressure falls below atmospheric pressure, air moves down the generated pressure gradient and enters the lung. Note that this increase in thoracic volume comes at the expense of the abdominal volume, and abdominal contents can be compressed during inspiration. The diaphragm may descend as much as 10 cm, but a descent of 1 cm is sufficient to provide tidal breathing (figure 2.2).', '9b4271e3-76cb-47d8-9449-ce65ba432fd8': 'When phrenic nerve activity stops, the diaphragm relaxes and returns to its resting dome-like position; this is aided by the recoil of the expanded lung and the decompression of the abdominal contents. The return to the resting position reduces thoracic volume\xa0and increases thoracic pressure above atmospheric pressure\xa0and air exits the lung down the reversed pressure gradient.', '218f33db-878e-4e96-a7ae-8fea0a27b6ff': 'During inspiration the thoracic volume is also increased by the action of the external intercostal muscles. Controlled by the intercostal nerve, contraction of the external intercostals causes the rib cage to rise upward and outward, resulting in an expansion of the thoracic volume in addition to the action of the diaphragm. This action is generated by the oblique positioning of the external intercostals between the ribs,\xa0and the sternum and upper ribs are stabilized\xa0by simultaneous activation of the scalenus muscles.', 'a1515008-08ab-4670-a844-d743bdd8e6e5': 'During periods of high ventilatory need (or drive) other muscles can contribute to expansion of the rib\xa0cage (figure 2.3). These “accessory”\xa0muscles assist the external intercostals and include the sternocleidomastoids, the scalenes, and the pectoralis minor. All of these groups allow for a greater thoracic expansion and thus a greater lung volume. Recognizing that a patient is using these muscles to breath is a useful clinical sign; use of these muscles during rest is highly indicative of a raised respiratory effort to cope with an underlying and probably significant problem.', '26844539-30f0-458f-ba5e-1090747c25a6': 'Expiration is generally simpler. The elastic tissue of the lung has been expanded during inspiration, and a little like letting go of a stretch elastic band, the lungs recoil when the inspiratory muscles relax. This recoil reduces lung volume and\xa0increases lung pressure above atmospheric pressure and air exits the lung. Depending on the final lung volume achieved during inspiration, recoil of the chest wall may\xa0also contribute to expiration.', '519a542a-f7b9-46fe-b36b-95775d34ba1b': 'So during quiet resting breathing, expiration is passive, relying on the expenditure of the stored, potential energy in the elastic lung tissue. However, when ventilation needs to be increased, such as during exercise, this process is too slow, and this passive process needs some active help in order to increase the rate of breathing. Activation of the internal intercostal muscles draws the rib cage downward to reduce thoracic volume. Thoracic volume is further decreased by contraction of muscles surrounding the abdomen; these increase abdominal pressure and help push the diaphragm upward (figure 2.4).'}"
+Figure 2.2,pulmo2/images/Figure 2.2.jpg,Figure 2.2: Diaphragm positional change.,"Activation of the phrenic nerve stimulates the diaphragm and generates inspiration. Upon stimulation the contracting diaphragm flattens out, descending toward the abdomen. As it does so the thoracic volume increases, and consequently thoracic pressure falls. When thoracic pressure falls below atmospheric pressure, air moves down the generated pressure gradient and enters the lung. Note that this increase in thoracic volume comes at the expense of the abdominal volume, and abdominal contents can be compressed during inspiration. The diaphragm may descend as much as 10 cm, but a descent of 1 cm is sufficient to provide tidal breathing (figure 2.2).","{'2e10d819-9c0e-4ff8-97ba-e2aa7cfc6a63': 'The muscle that generates the greatest change in thoracic volume (and thereby the greatest contribution to breathing) is the diaphragm (figure 2.1). Separating the thoracic and abdominal cavities, this sheetlike muscle forms a dome shape in the relaxed state that encroaches into the thorax. This sheet is formed of three sections, the anterior portion originating at the ribs and sternum, and the posterior portion originating on the vertebrae. These are connected by the central portion that is comprised of a tendon sheet.', '8b500a6a-6ed6-49c0-a989-611c6fd54a2f': 'It is\xa0worth a quick reminder that while controlling a visceral organ and performing a homeostatic function, the diaphragm and the other respiratory muscles are skeletal muscle and have the force-generation characteristics of such. As well as being under reflex control, it can also be controlled voluntarily (such as during speech).', '6630b073-10dd-4a89-9b32-1f911273bc20': 'Activation of the phrenic nerve stimulates\xa0the diaphragm and generates inspiration. Upon stimulation the contracting diaphragm flattens out, descending toward the abdomen. As it does so the thoracic volume increases, and consequently thoracic pressure falls. When thoracic pressure falls below atmospheric pressure, air moves down the generated pressure gradient and enters the lung. Note that this increase in thoracic volume comes at the expense of the abdominal volume, and abdominal contents can be compressed during inspiration. The diaphragm may descend as much as 10 cm, but a descent of 1 cm is sufficient to provide tidal breathing (figure 2.2).', '9b4271e3-76cb-47d8-9449-ce65ba432fd8': 'When phrenic nerve activity stops, the diaphragm relaxes and returns to its resting dome-like position; this is aided by the recoil of the expanded lung and the decompression of the abdominal contents. The return to the resting position reduces thoracic volume\xa0and increases thoracic pressure above atmospheric pressure\xa0and air exits the lung down the reversed pressure gradient.', '218f33db-878e-4e96-a7ae-8fea0a27b6ff': 'During inspiration the thoracic volume is also increased by the action of the external intercostal muscles. Controlled by the intercostal nerve, contraction of the external intercostals causes the rib cage to rise upward and outward, resulting in an expansion of the thoracic volume in addition to the action of the diaphragm. This action is generated by the oblique positioning of the external intercostals between the ribs,\xa0and the sternum and upper ribs are stabilized\xa0by simultaneous activation of the scalenus muscles.', 'a1515008-08ab-4670-a844-d743bdd8e6e5': 'During periods of high ventilatory need (or drive) other muscles can contribute to expansion of the rib\xa0cage (figure 2.3). These “accessory”\xa0muscles assist the external intercostals and include the sternocleidomastoids, the scalenes, and the pectoralis minor. All of these groups allow for a greater thoracic expansion and thus a greater lung volume. Recognizing that a patient is using these muscles to breath is a useful clinical sign; use of these muscles during rest is highly indicative of a raised respiratory effort to cope with an underlying and probably significant problem.', '26844539-30f0-458f-ba5e-1090747c25a6': 'Expiration is generally simpler. The elastic tissue of the lung has been expanded during inspiration, and a little like letting go of a stretch elastic band, the lungs recoil when the inspiratory muscles relax. This recoil reduces lung volume and\xa0increases lung pressure above atmospheric pressure and air exits the lung. Depending on the final lung volume achieved during inspiration, recoil of the chest wall may\xa0also contribute to expiration.', '519a542a-f7b9-46fe-b36b-95775d34ba1b': 'So during quiet resting breathing, expiration is passive, relying on the expenditure of the stored, potential energy in the elastic lung tissue. However, when ventilation needs to be increased, such as during exercise, this process is too slow, and this passive process needs some active help in order to increase the rate of breathing. Activation of the internal intercostal muscles draws the rib cage downward to reduce thoracic volume. Thoracic volume is further decreased by contraction of muscles surrounding the abdomen; these increase abdominal pressure and help push the diaphragm upward (figure 2.4).'}"
+Figure 2.3,pulmo2/images/Figure 2.3.jpg,Figure 2.3: Inspiratory muscles of the rib cage.,"During periods of high ventilatory need (or drive) other muscles can contribute to expansion of the rib cage (figure 2.3). These “accessory” muscles assist the external intercostals and include the sternocleidomastoids, the scalenes, and the pectoralis minor. All of these groups allow for a greater thoracic expansion and thus a greater lung volume. Recognizing that a patient is using these muscles to breath is a useful clinical sign; use of these muscles during rest is highly indicative of a raised respiratory effort to cope with an underlying and probably significant problem.","{'2e10d819-9c0e-4ff8-97ba-e2aa7cfc6a63': 'The muscle that generates the greatest change in thoracic volume (and thereby the greatest contribution to breathing) is the diaphragm (figure 2.1). Separating the thoracic and abdominal cavities, this sheetlike muscle forms a dome shape in the relaxed state that encroaches into the thorax. This sheet is formed of three sections, the anterior portion originating at the ribs and sternum, and the posterior portion originating on the vertebrae. These are connected by the central portion that is comprised of a tendon sheet.', '8b500a6a-6ed6-49c0-a989-611c6fd54a2f': 'It is\xa0worth a quick reminder that while controlling a visceral organ and performing a homeostatic function, the diaphragm and the other respiratory muscles are skeletal muscle and have the force-generation characteristics of such. As well as being under reflex control, it can also be controlled voluntarily (such as during speech).', '6630b073-10dd-4a89-9b32-1f911273bc20': 'Activation of the phrenic nerve stimulates\xa0the diaphragm and generates inspiration. Upon stimulation the contracting diaphragm flattens out, descending toward the abdomen. As it does so the thoracic volume increases, and consequently thoracic pressure falls. When thoracic pressure falls below atmospheric pressure, air moves down the generated pressure gradient and enters the lung. Note that this increase in thoracic volume comes at the expense of the abdominal volume, and abdominal contents can be compressed during inspiration. The diaphragm may descend as much as 10 cm, but a descent of 1 cm is sufficient to provide tidal breathing (figure 2.2).', '9b4271e3-76cb-47d8-9449-ce65ba432fd8': 'When phrenic nerve activity stops, the diaphragm relaxes and returns to its resting dome-like position; this is aided by the recoil of the expanded lung and the decompression of the abdominal contents. The return to the resting position reduces thoracic volume\xa0and increases thoracic pressure above atmospheric pressure\xa0and air exits the lung down the reversed pressure gradient.', '218f33db-878e-4e96-a7ae-8fea0a27b6ff': 'During inspiration the thoracic volume is also increased by the action of the external intercostal muscles. Controlled by the intercostal nerve, contraction of the external intercostals causes the rib cage to rise upward and outward, resulting in an expansion of the thoracic volume in addition to the action of the diaphragm. This action is generated by the oblique positioning of the external intercostals between the ribs,\xa0and the sternum and upper ribs are stabilized\xa0by simultaneous activation of the scalenus muscles.', 'a1515008-08ab-4670-a844-d743bdd8e6e5': 'During periods of high ventilatory need (or drive) other muscles can contribute to expansion of the rib\xa0cage (figure 2.3). These “accessory”\xa0muscles assist the external intercostals and include the sternocleidomastoids, the scalenes, and the pectoralis minor. All of these groups allow for a greater thoracic expansion and thus a greater lung volume. Recognizing that a patient is using these muscles to breath is a useful clinical sign; use of these muscles during rest is highly indicative of a raised respiratory effort to cope with an underlying and probably significant problem.', '26844539-30f0-458f-ba5e-1090747c25a6': 'Expiration is generally simpler. The elastic tissue of the lung has been expanded during inspiration, and a little like letting go of a stretch elastic band, the lungs recoil when the inspiratory muscles relax. This recoil reduces lung volume and\xa0increases lung pressure above atmospheric pressure and air exits the lung. Depending on the final lung volume achieved during inspiration, recoil of the chest wall may\xa0also contribute to expiration.', '519a542a-f7b9-46fe-b36b-95775d34ba1b': 'So during quiet resting breathing, expiration is passive, relying on the expenditure of the stored, potential energy in the elastic lung tissue. However, when ventilation needs to be increased, such as during exercise, this process is too slow, and this passive process needs some active help in order to increase the rate of breathing. Activation of the internal intercostal muscles draws the rib cage downward to reduce thoracic volume. Thoracic volume is further decreased by contraction of muscles surrounding the abdomen; these increase abdominal pressure and help push the diaphragm upward (figure 2.4).'}"
+Figure 2.4,pulmo2/images/Figure 2.4.jpg,Figure 2.4: Expiratory muscles.,"So during quiet resting breathing, expiration is passive, relying on the expenditure of the stored, potential energy in the elastic lung tissue. However, when ventilation needs to be increased, such as during exercise, this process is too slow, and this passive process needs some active help in order to increase the rate of breathing. Activation of the internal intercostal muscles draws the rib cage downward to reduce thoracic volume. Thoracic volume is further decreased by contraction of muscles surrounding the abdomen; these increase abdominal pressure and help push the diaphragm upward (figure 2.4).","{'2e10d819-9c0e-4ff8-97ba-e2aa7cfc6a63': 'The muscle that generates the greatest change in thoracic volume (and thereby the greatest contribution to breathing) is the diaphragm (figure 2.1). Separating the thoracic and abdominal cavities, this sheetlike muscle forms a dome shape in the relaxed state that encroaches into the thorax. This sheet is formed of three sections, the anterior portion originating at the ribs and sternum, and the posterior portion originating on the vertebrae. These are connected by the central portion that is comprised of a tendon sheet.', '8b500a6a-6ed6-49c0-a989-611c6fd54a2f': 'It is\xa0worth a quick reminder that while controlling a visceral organ and performing a homeostatic function, the diaphragm and the other respiratory muscles are skeletal muscle and have the force-generation characteristics of such. As well as being under reflex control, it can also be controlled voluntarily (such as during speech).', '6630b073-10dd-4a89-9b32-1f911273bc20': 'Activation of the phrenic nerve stimulates\xa0the diaphragm and generates inspiration. Upon stimulation the contracting diaphragm flattens out, descending toward the abdomen. As it does so the thoracic volume increases, and consequently thoracic pressure falls. When thoracic pressure falls below atmospheric pressure, air moves down the generated pressure gradient and enters the lung. Note that this increase in thoracic volume comes at the expense of the abdominal volume, and abdominal contents can be compressed during inspiration. The diaphragm may descend as much as 10 cm, but a descent of 1 cm is sufficient to provide tidal breathing (figure 2.2).', '9b4271e3-76cb-47d8-9449-ce65ba432fd8': 'When phrenic nerve activity stops, the diaphragm relaxes and returns to its resting dome-like position; this is aided by the recoil of the expanded lung and the decompression of the abdominal contents. The return to the resting position reduces thoracic volume\xa0and increases thoracic pressure above atmospheric pressure\xa0and air exits the lung down the reversed pressure gradient.', '218f33db-878e-4e96-a7ae-8fea0a27b6ff': 'During inspiration the thoracic volume is also increased by the action of the external intercostal muscles. Controlled by the intercostal nerve, contraction of the external intercostals causes the rib cage to rise upward and outward, resulting in an expansion of the thoracic volume in addition to the action of the diaphragm. This action is generated by the oblique positioning of the external intercostals between the ribs,\xa0and the sternum and upper ribs are stabilized\xa0by simultaneous activation of the scalenus muscles.', 'a1515008-08ab-4670-a844-d743bdd8e6e5': 'During periods of high ventilatory need (or drive) other muscles can contribute to expansion of the rib\xa0cage (figure 2.3). These “accessory”\xa0muscles assist the external intercostals and include the sternocleidomastoids, the scalenes, and the pectoralis minor. All of these groups allow for a greater thoracic expansion and thus a greater lung volume. Recognizing that a patient is using these muscles to breath is a useful clinical sign; use of these muscles during rest is highly indicative of a raised respiratory effort to cope with an underlying and probably significant problem.', '26844539-30f0-458f-ba5e-1090747c25a6': 'Expiration is generally simpler. The elastic tissue of the lung has been expanded during inspiration, and a little like letting go of a stretch elastic band, the lungs recoil when the inspiratory muscles relax. This recoil reduces lung volume and\xa0increases lung pressure above atmospheric pressure and air exits the lung. Depending on the final lung volume achieved during inspiration, recoil of the chest wall may\xa0also contribute to expiration.', '519a542a-f7b9-46fe-b36b-95775d34ba1b': 'So during quiet resting breathing, expiration is passive, relying on the expenditure of the stored, potential energy in the elastic lung tissue. However, when ventilation needs to be increased, such as during exercise, this process is too slow, and this passive process needs some active help in order to increase the rate of breathing. Activation of the internal intercostal muscles draws the rib cage downward to reduce thoracic volume. Thoracic volume is further decreased by contraction of muscles surrounding the abdomen; these increase abdominal pressure and help push the diaphragm upward (figure 2.4).'}"
+Figure 2.5,pulmo2/images/Figure 2.5.jpg,Figure 2.5: The pleural membranes and space.,"The inside of the thoracic cavity is lined with a membrane, the parietal pleura. The outside of the lungs are lined with a membrane called the visceral pleura. The space between these membranes, the pleural cavity or pleural space, is filled with pleural fluid (figure 2.5). Normally there is only 5–10 mL of pleural fluid to cover all the lung’s external surface. So the fluid layer and the intra-pleural space is extremely thin. When a thin layer of fluid is trapped between two surfaces it exerts surface tension and holds the two surfaces together; if you’ve ever been doing the washing up and trapped a layer of water between too dinner plates you’ll have noticed its difficult to pry the plates apart. It is similar for the pleural membranes, and it is this surface tension that holds the outside of the lungs to the inside of the thorax. We will deal with surface tension in more detail in a later chapter.","{'b79578ea-4f17-4d85-a425-ccef0537b748': 'Now having dealt with the expansion of the thoracic cage, we should look at the relationship between the thoracic wall and the lungs and how the lungs and the inside of the thorax are adhered to each other so when the thoracic wall moves the lungs follow.', '5fcde448-c4dd-4364-9f75-8234b4d7ccea': 'The inside of the thoracic cavity is lined with a membrane, the parietal pleura. The outside of the lungs are lined with a membrane called the visceral pleura. The space between these membranes, the pleural cavity or pleural space, is filled with pleural fluid (figure 2.5). Normally there is only 5–10 mL\xa0of pleural fluid to cover all the lung’s external surface. So the fluid layer and the intra-pleural space is extremely thin. When a thin layer of fluid is trapped between two surfaces it exerts surface tension and holds the two surfaces together; if you’ve ever been doing the washing up and trapped a layer of water between too dinner plates you’ll have noticed its difficult to pry\xa0the plates apart.\xa0It is similar for the pleural membranes, and it is\xa0this surface tension that holds the outside of the lungs to the inside of the thorax. We will deal with surface tension in more detail in a later chapter.', '9a164c3c-d73e-457a-8d69-06f6aa3c6a12': 'We have mentioned the pressure inside the lungs, but now we have to think about the pressure inside the pleural space—called intra-pleural pressure. Even at normal, resting lung volumes the elastic tissue in the lungs is already somewhat stretched, so the lungs have a tendency to recoil, pulling inward. The chest wall, alternatively, has a tendency to spring outward. These opposing movements are prevented by the surface tension in the pleural space and cause a negative intrapleural pressure, that is below atmospheric pressure.', '4f7752a8-2faa-45cb-ab9f-36a375757362': 'We should now consider what happens to intrapleural and airway pressures during the breathing cycle. First, let us\xa0look at the pressures and volumes before inspiration begins (figure 2.6). The intrapleural pressure is slightly negative (−5 cm H2O) due to the recoil of the lung and outward spring of the chest wall. Before the breath starts lung volume is considered zero and flow is also zero\xa0(i.e., volume has not changed and there is\xa0no movement of air in the airways). Alveolar pressure, the pressure inside the lungs, is also zero, really meaning it is equal to atmospheric pressure.', 'be8d9cc7-fde3-4e7d-91dd-b6426638caed': 'Look at what happens (figure 2.6) when the respiratory muscles are activated to increase thoracic volume and achieve a breath in. As the thoracic wall moves outward and the diaphragm descends, thoracic volume and therefore lung volume increases. More tension is generated in the stretching elastic tissue of the lungs as the lung expands—and just like stretching an elastic band, the recoil force increases, and the stretching lung now pulls back harder on the pleural space. This causes the intrapleural pressure to become even more negative (−8 cm H2O).', '00c543a1-17f7-4f9a-b450-3f05758900fe': 'This increase in lung volume (and referring back to Boyle’s law,\xa0the pressure of a gas tends to decrease as the volume of the container increases)\xa0causes a decrease in pressure in the lung. This is reflected in a decrease in alveolar pressure.', 'fdffa40a-6b58-4b16-8891-34463a849827': 'This drop in alveolar pressure generates a pressure differential between the airways and the atmosphere outside—the atmospheric pressure now being greater than the reduced airway pressure causes the flow of air into the airways and toward the alveoli.', '6f11a9b3-494e-4ff8-8809-20a8917f1621': 'Now let us look at these pressures during expiration. At the end of inspiration the lungs are stretched and the recoil force is high. When the activity of the inspiratory muscles stops, the recoil of the lung is unopposed and the lung recoils (a little like letting go of that stretched elastic band). Therefore, in quiet breathing, the process of breathing out is normally passive\xa0and relies on the potential energy stored in the lungs’ elastic tissue.', 'f733002d-db88-4551-bac3-5e617da255e0': 'As the lung recoils and returns toward\xa0its resting position, the intrapleural pressure becomes less negative and the volume decreases, resulting in a rise in alveolar pressure, as described by Boyle’s law. This rise in alveolar pressure means the pressure gradient is reversed, with pressure inside the lung becoming greater than atmospheric pressure. This reversed pressure differential causes the flow of air from the airways toward the outside—and expiration is achieved.', '72cefa2a-7f84-4d03-a27d-2a7be6d25a22': 'As already mentioned, this is a passive process that relies on lung recoil, and the expiratory muscles remain inactive during quiet breathing. However, when there is a greater ventilatory demand, such as during exercise or lung disease, the respiratory system cannot wait for this passive and relatively slow process to occur, so the expiratory muscles are activated and thoracic volume (and therefore lung volume) is reduced actively much more quickly; this may cause intrapleural pressure to go positive as the thoracic wall actively pushes on the intrapleural space (and the lungs). This positive pleural pressure during active expiration can have significant ramifications in diseased lungs that we will see later on.'}"
+Figure 2.6,pulmo2/images/Figure 2.6.jpg,Figure 2.6: The breathing cycle.,"We should now consider what happens to intrapleural and airway pressures during the breathing cycle. First, let us look at the pressures and volumes before inspiration begins (figure 2.6). The intrapleural pressure is slightly negative (−5 cm H2O) due to the recoil of the lung and outward spring of the chest wall. Before the breath starts lung volume is considered zero and flow is also zero (i.e., volume has not changed and there is no movement of air in the airways). Alveolar pressure, the pressure inside the lungs, is also zero, really meaning it is equal to atmospheric pressure.","{'b79578ea-4f17-4d85-a425-ccef0537b748': 'Now having dealt with the expansion of the thoracic cage, we should look at the relationship between the thoracic wall and the lungs and how the lungs and the inside of the thorax are adhered to each other so when the thoracic wall moves the lungs follow.', '5fcde448-c4dd-4364-9f75-8234b4d7ccea': 'The inside of the thoracic cavity is lined with a membrane, the parietal pleura. The outside of the lungs are lined with a membrane called the visceral pleura. The space between these membranes, the pleural cavity or pleural space, is filled with pleural fluid (figure 2.5). Normally there is only 5–10 mL\xa0of pleural fluid to cover all the lung’s external surface. So the fluid layer and the intra-pleural space is extremely thin. When a thin layer of fluid is trapped between two surfaces it exerts surface tension and holds the two surfaces together; if you’ve ever been doing the washing up and trapped a layer of water between too dinner plates you’ll have noticed its difficult to pry\xa0the plates apart.\xa0It is similar for the pleural membranes, and it is\xa0this surface tension that holds the outside of the lungs to the inside of the thorax. We will deal with surface tension in more detail in a later chapter.', '9a164c3c-d73e-457a-8d69-06f6aa3c6a12': 'We have mentioned the pressure inside the lungs, but now we have to think about the pressure inside the pleural space—called intra-pleural pressure. Even at normal, resting lung volumes the elastic tissue in the lungs is already somewhat stretched, so the lungs have a tendency to recoil, pulling inward. The chest wall, alternatively, has a tendency to spring outward. These opposing movements are prevented by the surface tension in the pleural space and cause a negative intrapleural pressure, that is below atmospheric pressure.', '4f7752a8-2faa-45cb-ab9f-36a375757362': 'We should now consider what happens to intrapleural and airway pressures during the breathing cycle. First, let us\xa0look at the pressures and volumes before inspiration begins (figure 2.6). The intrapleural pressure is slightly negative (−5 cm H2O) due to the recoil of the lung and outward spring of the chest wall. Before the breath starts lung volume is considered zero and flow is also zero\xa0(i.e., volume has not changed and there is\xa0no movement of air in the airways). Alveolar pressure, the pressure inside the lungs, is also zero, really meaning it is equal to atmospheric pressure.', 'be8d9cc7-fde3-4e7d-91dd-b6426638caed': 'Look at what happens (figure 2.6) when the respiratory muscles are activated to increase thoracic volume and achieve a breath in. As the thoracic wall moves outward and the diaphragm descends, thoracic volume and therefore lung volume increases. More tension is generated in the stretching elastic tissue of the lungs as the lung expands—and just like stretching an elastic band, the recoil force increases, and the stretching lung now pulls back harder on the pleural space. This causes the intrapleural pressure to become even more negative (−8 cm H2O).', '00c543a1-17f7-4f9a-b450-3f05758900fe': 'This increase in lung volume (and referring back to Boyle’s law,\xa0the pressure of a gas tends to decrease as the volume of the container increases)\xa0causes a decrease in pressure in the lung. This is reflected in a decrease in alveolar pressure.', 'fdffa40a-6b58-4b16-8891-34463a849827': 'This drop in alveolar pressure generates a pressure differential between the airways and the atmosphere outside—the atmospheric pressure now being greater than the reduced airway pressure causes the flow of air into the airways and toward the alveoli.', '6f11a9b3-494e-4ff8-8809-20a8917f1621': 'Now let us look at these pressures during expiration. At the end of inspiration the lungs are stretched and the recoil force is high. When the activity of the inspiratory muscles stops, the recoil of the lung is unopposed and the lung recoils (a little like letting go of that stretched elastic band). Therefore, in quiet breathing, the process of breathing out is normally passive\xa0and relies on the potential energy stored in the lungs’ elastic tissue.', 'f733002d-db88-4551-bac3-5e617da255e0': 'As the lung recoils and returns toward\xa0its resting position, the intrapleural pressure becomes less negative and the volume decreases, resulting in a rise in alveolar pressure, as described by Boyle’s law. This rise in alveolar pressure means the pressure gradient is reversed, with pressure inside the lung becoming greater than atmospheric pressure. This reversed pressure differential causes the flow of air from the airways toward the outside—and expiration is achieved.', '72cefa2a-7f84-4d03-a27d-2a7be6d25a22': 'As already mentioned, this is a passive process that relies on lung recoil, and the expiratory muscles remain inactive during quiet breathing. However, when there is a greater ventilatory demand, such as during exercise or lung disease, the respiratory system cannot wait for this passive and relatively slow process to occur, so the expiratory muscles are activated and thoracic volume (and therefore lung volume) is reduced actively much more quickly; this may cause intrapleural pressure to go positive as the thoracic wall actively pushes on the intrapleural space (and the lungs). This positive pleural pressure during active expiration can have significant ramifications in diseased lungs that we will see later on.'}"
+Figure 1.2,pulmo2/images/Figure 1.2.jpg,"Figure 1.2: The mucociliary escalator of the airway. The cilia on the apical surface of the pseudostratified epithelium push a layer of mucus (produced by the goblet cells) toward the mouth, carrying pathogens and particulates out of the airway.","As the only internal organ exposed to the external environment, the lung needs special protection from particles or pathogens that could be transported down the airways with inhaled air. The first line of defense is the nasal cavity, which is lined with a ciliated epithelial, dispersed within which are goblet cells producing mucus (figure 1.2). This mucus forms a sticky layer on top of the epithelial surface and traps inhaled particles, bacteria, or other potential pathogens. The mucus is then moved by the cilia back toward the pharynx where it can be coughed or spat out.","{'57f4f53d-d33e-4c7e-873d-33f33788ea22': 'As the only internal organ exposed to the external environment, the lung needs special protection from particles or pathogens that could be transported down the airways with inhaled air.\xa0The first line of defense is the nasal cavity, which is lined with a ciliated epithelial, dispersed\xa0within which are\xa0goblet cells producing mucus (figure 1.2). This mucus forms\xa0a sticky layer on top\xa0of the epithelial surface and\xa0traps inhaled particles, bacteria, or other potential pathogens. The mucus is\xa0then moved by the\xa0cilia back toward the pharynx where it can be coughed or spat out.', 'f288bfbb-d2c9-4f26-bd73-b9cc05195f26': 'The inhaled air also must be warmed and humidified before it reaches the gas exchange surfaces,\xa0otherwise the relatively cold and dry air would cause evaporation of the thin water layer\xa0lining the gas exchange surfaces that\xa0is essential for allowing gases to dissolve and\xa0diffuse\xa0into or out of the pulmonary bloodstream. This warming and humidification is achieved by transfer of heat and water from blood in the highly vascularized nasal cavity (figure 1.3).', '696f5302-3baf-4605-87e5-ffa601be665d': 'The second line of defense (which becomes more important when breathing through the mouth) is the lining of the trachea. Again, this is covered with a ciliated epithelium with mucus-producing goblet cells (figure 1.2). As in the\xa0nasal cavity, particles and potential pathogens are\xa0trapped in the mucus layer and cilia move the mucus up toward\xa0the mouth for expulsion.\xa0The trachea and larynx also contain\xa0sensory nerve endings (rapidly adapting receptors, nicknamed “irritant receptors”) that respond to the arrival of particles on the epithelial surface and initiate the cough reflex and propel the offending particles out of the airway (see more in chapter 17).'}"
+Figure 1.3,pulmo2/images/Figure 1.3.jpg,Figure 1.3: Air conditioning. The highly vascularized nasal cavity helps warm and humidify inhaled air before it proceeds toward the lower airways.,"The inhaled air also must be warmed and humidified before it reaches the gas exchange surfaces, otherwise the relatively cold and dry air would cause evaporation of the thin water layer lining the gas exchange surfaces that is essential for allowing gases to dissolve and diffuse into or out of the pulmonary bloodstream. This warming and humidification is achieved by transfer of heat and water from blood in the highly vascularized nasal cavity (figure 1.3).","{'57f4f53d-d33e-4c7e-873d-33f33788ea22': 'As the only internal organ exposed to the external environment, the lung needs special protection from particles or pathogens that could be transported down the airways with inhaled air.\xa0The first line of defense is the nasal cavity, which is lined with a ciliated epithelial, dispersed\xa0within which are\xa0goblet cells producing mucus (figure 1.2). This mucus forms\xa0a sticky layer on top\xa0of the epithelial surface and\xa0traps inhaled particles, bacteria, or other potential pathogens. The mucus is\xa0then moved by the\xa0cilia back toward the pharynx where it can be coughed or spat out.', 'f288bfbb-d2c9-4f26-bd73-b9cc05195f26': 'The inhaled air also must be warmed and humidified before it reaches the gas exchange surfaces,\xa0otherwise the relatively cold and dry air would cause evaporation of the thin water layer\xa0lining the gas exchange surfaces that\xa0is essential for allowing gases to dissolve and\xa0diffuse\xa0into or out of the pulmonary bloodstream. This warming and humidification is achieved by transfer of heat and water from blood in the highly vascularized nasal cavity (figure 1.3).', '696f5302-3baf-4605-87e5-ffa601be665d': 'The second line of defense (which becomes more important when breathing through the mouth) is the lining of the trachea. Again, this is covered with a ciliated epithelium with mucus-producing goblet cells (figure 1.2). As in the\xa0nasal cavity, particles and potential pathogens are\xa0trapped in the mucus layer and cilia move the mucus up toward\xa0the mouth for expulsion.\xa0The trachea and larynx also contain\xa0sensory nerve endings (rapidly adapting receptors, nicknamed “irritant receptors”) that respond to the arrival of particles on the epithelial surface and initiate the cough reflex and propel the offending particles out of the airway (see more in chapter 17).'}"
+Figure 1.4,pulmo2/images/Figure 1.4.jpg,Figure 1.4: The bronchial tree. The major airways of the conducting zone (anatomical dead space) are labeled.,"The airways, or bronchial tree (figure 1.4), consist of a series of branching tubes that become narrower and shorter but more numerous as they descend into the lung.","{'e9c72af1-ff8b-4aae-b16e-1c90f7d65f86': 'The airways, or bronchial tree (figure 1.4), consist\xa0of a series of branching tubes that become narrower and\xa0shorter\xa0but more numerous\xa0as they descend into the lung.', 'd54cb433-447c-4fc8-a471-77d0133a64ab': 'The trachea bifurcates into the primary bronchi, left and right, transporting air into the left and right lungs, respectively. The primary bronchi consequently divide into lobar (or secondary) bronchi, the number of which correspond to the number of lobes in each lung. The lobar bronchi then divide into segmental (or tertiary) bronchi to supply the segments of each lobe. This bifurcation process continues to the terminal bronchioles. This initial section of the bronchial tree is referred to as the conducting zone as its role is to transfer air to the gas exchange surfaces (figure 1.4). As no gas exchange takes place here, these airways constitute the anatomical dead space and have\xa0a volume of approximately 150 mL.', 'f02e387e-e075-4b37-b9b6-a610e5f32c9b': 'Each terminal bronchiole then divides into numerous respiratory bronchioles, the walls of which may contain some alveoli and are therefore capable of some gas exchange; this is the transition to the respiratory zone of the lung and the onset of gas exchange (figure 1.4). The respiratory zone becomes firmly established when terminal bronchioles divide into alveolar ducts that are fundamentally tubes lined\xa0with alveoli. These alveolar ducts then terminate in alveolar sacs. The portion of lung distal to each terminal bronchiole forms an anatomical unit called the acinus. Although only a few millimeters long, collectively\xa0these acini make\xa0up the respiratory zone and form the vast majority of the lung’s volume.'}"