fig_num,image_path,image_caption,golden_corpus,positive_corpus
Figure 9.1,pulmonary/images/Figure 9.1.jpg,Figure 9.1: Severe pleural effusion leading to displacement of the mediastinum and heart to the right. This patient’s condition is critical because of the threat to cardiac output.,"Exudative effusion is caused by increased capillary permeability, such as that caused by the inflammatory process. Relate this back to your understanding of exudative pleurisy (figure 9.1). As larger molecules can exit the leaky capillaries, exudative effusion has a higher specific gravity, higher protein concentration, and likely a higher cell count.","{'0def0019-efda-4bf8-be84-5b336770125a': 'In our description of pleurisy we eluded to our next pleural disorder,\xa0pleural effusion. The normally small amount of pleural fluid is sufficient to lubricate the movement of the lungs and is not detectable on x-ray without specialized radiography. Pleural effusion is the abnormal accumulation of fluid in the pleural space and is easily detectable. As with the formation of\xa0fluid accumulation in any part of the body, a normal fluid level in the pleural space is dependent on a balanced rate of formation and reabsorption. In pleural effusion, this balance is lost.', '902fd1dd-cadc-4a50-8f63-14d5cccf816f': 'Initially it was thought that pleural fluid was formed by hydrostatic pressure in capillaries in the parietal membrane pushing fluid into the pleural space, and the fluid was then absorbed by capillaries in the visceral membrane. However, there is mounting evidence to show that reabsorption is actually performed by the lymph vessels in the parietal membrane. The low hydrostatic pressure and large capacity of these vessels helps maintain the normal, small volume of pleural fluid. Pleural effusion can be caused by:', 'efd6567f-5f5c-4501-bbea-0cacb9da552d': 'For example, pleural effusion in cardiac pulmonary edema occurs as fluid leaks across the visceral pleura from the lung.', 'd24c3129-0e09-4597-aba0-f501519a0c12': 'Two broad classifications exist, transudate and exudate, so let us\xa0compare them now (summary in table 9.1).', '15308720-28b8-4057-8aba-0d06e11d901b': 'Transudative effusion occurs when there is a disturbance in the Starling’s forces influencing fluid movement across the capillary. As such transudate can be caused by an increase in hydrostatic force pushing fluid out of the capillary, such as in congestive heart failure, or a decrease in the plasma oncotic pressure retaining fluid in the capillary, such as in kidney or liver disease. This results in a transudate with low specific gravity, protein concentration, and cell count.', '7cff022c-a76f-4a82-b17e-f78a5fdd876d': 'Exudative effusion is caused by increased capillary permeability, such as that caused by the inflammatory process. Relate this back to your understanding of exudative pleurisy (figure 9.1). As larger molecules can exit the leaky capillaries, exudative effusion has a higher specific gravity, higher protein concentration, and likely a higher cell count.', '1e0b031d-9c50-4863-b745-92487d68f087': 'Table 9.1:\xa0Comparison of transudative and exudative pleural effusions.', 'd28a84a9-71ac-4502-8ece-95fa5e2224ec': 'The manifestation of pleural effusion varies with the quantity of fluid accumulation and the time line. Symptoms may in fact be absent when the effusion is small. In the case of exudative pleurisy, an initial rub pain may disappear as exudate accumulates and separates the rubbing pleural surfaces.', 'd575ecdb-955c-4b19-916f-a59a4460db7f': 'As the effusion volume increases the patient is likely to experience dyspnea and physical exam will\xa0more likely include dullness to percussion and absence of breath sounds as the effusion forms a fluid pillow around the lung.', '2b911b0a-c25c-424a-9007-658fd882bfdd': 'As the severity of the effusion increases the patient will be severely short of breath, and the risk of the effusion pushing mediastinal structures to the contralateral side becomes significant and urgent (figure 9.1) as even mild displacement of the mediastinum can reduce cardiac output and produce hypotension. More significant displacement can become life threatening.', '6a213ac2-3232-4642-b5ea-84dc3b2e1882': 'As we have already mentioned, the pleural fluid’s composition can provide a great deal of information about the underlying mechanism. We have already mentioned the ability to distinguish between an exudate and a transudate by analysis of the fluid. But gross inspection of the fluid can be revealing before lab tests are ready.', '39e4babc-3e32-4837-a9aa-93149918524f': 'Fluid drawn through thoracentesis that appears clear and straw colored (figure 9.2) is likely to be transudate. The clarity of the fluid relates to a low protein content reflecting intact capillaries, and you should be looking for disturbances in Starling’s forces. Lab results can confirm the integrity of the capillary beds. Clinically the pleural fluid’s protein content and lactate dehydrogenase concentration are used and are expressed as a ratio with the patient’s plasma concentrations. Light’s criteria set diagnostic thresholds for these ratios to determine transudative or exudative effusions.', 'c7344b21-2aa5-4a33-9e99-55431504c570': 'The higher protein of exudative effusion gives the fluid a more turbid or cloudy appearance, and high protein content may even give the fluid a foamy head (figure 9.2). Further lab analysis of the composition and cell content of the exudate can help determine the underlying cause of the leak.\xa0For example, presence of polymorphonuclear leukocytes is highly suggestive of pyrogenic infection, whereas predominance of lymphocytes is indicative of TB or malignancy.', 'fc06e3ad-477c-4c24-8714-7e8253b62da5': 'Presence of lysed red blood cells will give the fluid a red turbid appearance (figure 9.2) and is indicative of trauma or malignancy, and again will require further investigation. If a malignancy has penetrated the lymphatics, such as the thoracic duct, the resultant chylous exudate will have a milky appearance.', '55dda68d-a0fb-4804-8f51-27432e0a7d33': 'A purulent fluid (figure 9.2) is indicative of infection within the pleural space and culturing the fluid will allow the pathogen to be determined. When pleural fluid is grossly purulent or contains pyogenic organisms we refer to this as pleural empyema. The most common route of entry for organisms is from underlying\xa0pneumonia or lung abscess, or through penetrative surgery or chest wound. The patient usually presents with fever and other manifestations of bacterial infection.'}"
Figure 9.2,pulmonary/images/Figure 9.2.jpg,Figure 9.2: Appearance of pleural fluid and diagnosis.,"Fluid drawn through thoracentesis that appears clear and straw colored (figure 9.2) is likely to be transudate. The clarity of the fluid relates to a low protein content reflecting intact capillaries, and you should be looking for disturbances in Starling’s forces. Lab results can confirm the integrity of the capillary beds. Clinically the pleural fluid’s protein content and lactate dehydrogenase concentration are used and are expressed as a ratio with the patient’s plasma concentrations. Light’s criteria set diagnostic thresholds for these ratios to determine transudative or exudative effusions.","{'0def0019-efda-4bf8-be84-5b336770125a': 'In our description of pleurisy we eluded to our next pleural disorder,\xa0pleural effusion. The normally small amount of pleural fluid is sufficient to lubricate the movement of the lungs and is not detectable on x-ray without specialized radiography. Pleural effusion is the abnormal accumulation of fluid in the pleural space and is easily detectable. As with the formation of\xa0fluid accumulation in any part of the body, a normal fluid level in the pleural space is dependent on a balanced rate of formation and reabsorption. In pleural effusion, this balance is lost.', '902fd1dd-cadc-4a50-8f63-14d5cccf816f': 'Initially it was thought that pleural fluid was formed by hydrostatic pressure in capillaries in the parietal membrane pushing fluid into the pleural space, and the fluid was then absorbed by capillaries in the visceral membrane. However, there is mounting evidence to show that reabsorption is actually performed by the lymph vessels in the parietal membrane. The low hydrostatic pressure and large capacity of these vessels helps maintain the normal, small volume of pleural fluid. Pleural effusion can be caused by:', 'efd6567f-5f5c-4501-bbea-0cacb9da552d': 'For example, pleural effusion in cardiac pulmonary edema occurs as fluid leaks across the visceral pleura from the lung.', 'd24c3129-0e09-4597-aba0-f501519a0c12': 'Two broad classifications exist, transudate and exudate, so let us\xa0compare them now (summary in table 9.1).', '15308720-28b8-4057-8aba-0d06e11d901b': 'Transudative effusion occurs when there is a disturbance in the Starling’s forces influencing fluid movement across the capillary. As such transudate can be caused by an increase in hydrostatic force pushing fluid out of the capillary, such as in congestive heart failure, or a decrease in the plasma oncotic pressure retaining fluid in the capillary, such as in kidney or liver disease. This results in a transudate with low specific gravity, protein concentration, and cell count.', '7cff022c-a76f-4a82-b17e-f78a5fdd876d': 'Exudative effusion is caused by increased capillary permeability, such as that caused by the inflammatory process. Relate this back to your understanding of exudative pleurisy (figure 9.1). As larger molecules can exit the leaky capillaries, exudative effusion has a higher specific gravity, higher protein concentration, and likely a higher cell count.', '1e0b031d-9c50-4863-b745-92487d68f087': 'Table 9.1:\xa0Comparison of transudative and exudative pleural effusions.', 'd28a84a9-71ac-4502-8ece-95fa5e2224ec': 'The manifestation of pleural effusion varies with the quantity of fluid accumulation and the time line. Symptoms may in fact be absent when the effusion is small. In the case of exudative pleurisy, an initial rub pain may disappear as exudate accumulates and separates the rubbing pleural surfaces.', 'd575ecdb-955c-4b19-916f-a59a4460db7f': 'As the effusion volume increases the patient is likely to experience dyspnea and physical exam will\xa0more likely include dullness to percussion and absence of breath sounds as the effusion forms a fluid pillow around the lung.', '2b911b0a-c25c-424a-9007-658fd882bfdd': 'As the severity of the effusion increases the patient will be severely short of breath, and the risk of the effusion pushing mediastinal structures to the contralateral side becomes significant and urgent (figure 9.1) as even mild displacement of the mediastinum can reduce cardiac output and produce hypotension. More significant displacement can become life threatening.', '6a213ac2-3232-4642-b5ea-84dc3b2e1882': 'As we have already mentioned, the pleural fluid’s composition can provide a great deal of information about the underlying mechanism. We have already mentioned the ability to distinguish between an exudate and a transudate by analysis of the fluid. But gross inspection of the fluid can be revealing before lab tests are ready.', '39e4babc-3e32-4837-a9aa-93149918524f': 'Fluid drawn through thoracentesis that appears clear and straw colored (figure 9.2) is likely to be transudate. The clarity of the fluid relates to a low protein content reflecting intact capillaries, and you should be looking for disturbances in Starling’s forces. Lab results can confirm the integrity of the capillary beds. Clinically the pleural fluid’s protein content and lactate dehydrogenase concentration are used and are expressed as a ratio with the patient’s plasma concentrations. Light’s criteria set diagnostic thresholds for these ratios to determine transudative or exudative effusions.', 'c7344b21-2aa5-4a33-9e99-55431504c570': 'The higher protein of exudative effusion gives the fluid a more turbid or cloudy appearance, and high protein content may even give the fluid a foamy head (figure 9.2). Further lab analysis of the composition and cell content of the exudate can help determine the underlying cause of the leak.\xa0For example, presence of polymorphonuclear leukocytes is highly suggestive of pyrogenic infection, whereas predominance of lymphocytes is indicative of TB or malignancy.', 'fc06e3ad-477c-4c24-8714-7e8253b62da5': 'Presence of lysed red blood cells will give the fluid a red turbid appearance (figure 9.2) and is indicative of trauma or malignancy, and again will require further investigation. If a malignancy has penetrated the lymphatics, such as the thoracic duct, the resultant chylous exudate will have a milky appearance.', '55dda68d-a0fb-4804-8f51-27432e0a7d33': 'A purulent fluid (figure 9.2) is indicative of infection within the pleural space and culturing the fluid will allow the pathogen to be determined. When pleural fluid is grossly purulent or contains pyogenic organisms we refer to this as pleural empyema. The most common route of entry for organisms is from underlying\xa0pneumonia or lung abscess, or through penetrative surgery or chest wound. The patient usually presents with fever and other manifestations of bacterial infection.'}"
Figure 9.3,pulmonary/images/Figure 9.3.jpg,"Figure 9.3: A tall, thin body morph (right) is more prone to a spontaneous pneumothorax.","Spontaneous pneumothorax occurs in the absence of accidental or intentional trauma. When it occurs in otherwise healthy individuals it is usually the fault of anatomy and occurs mostly in tall, thin individuals with a long and narrow chest. If you compare the two body morphs in figure 9.3, the tall, thin torso has a lot of lung mass hanging below a relatively small apical section of pleural membrane compared to the other torso.","{'c7166aaa-f88c-45d5-8fb8-aea658aa589c': 'Normally the negative pressure inside the pleural space opposes the lung’s recoil and holds the lung surface to the interior of the thorax. If the pleural membranes are disrupted this subatmospheric or negative pressure is lost and the lung can recoil, or collapse. This is a\xa0pneumothorax.', 'c2586289-886f-4131-85d6-2457ba18e76c': 'The causal events of losing the negative pleural pressure divide pneumothoraces into one of two categories:\xa0spontaneous or traumatic. (A third category exists, artificial pneumothorax, which was\xa0intentionally induced as part of procedures that are very rarely used today.)', '38f879f0-5ff6-43f0-95ec-fc890ff997cc': 'Spontaneous pneumothorax occurs in the absence of accidental or intentional trauma. When it occurs in otherwise healthy individuals it is usually the fault of anatomy and occurs mostly\xa0in tall, thin individuals with a long and narrow chest. If you compare the\xa0two body morphs in figure 9.3, the tall, thin torso has a lot of lung mass hanging below a relatively small apical section of pleural membrane compared to the other torso.', 'df047406-e161-4f2b-b683-a315a1315378': 'The proportionately greater weight of lung per unit surface area at the apex increases the risk that bulla form (figure 9.4), then rupture\xa0causing loss of pleural\xa0membrane adhesion.', '0fe5da22-93a8-4711-8d35-5624a9f89b5f': 'The most common cause of spontaneous pneumothorax in pulmonary patients is a ruptured bleb or bulla. These thin-walled, air-filled cavities are found near the pleural surface, particularly in cases of emphysema. In the past, TB was thought to be the most common cause of pneumothorax as its destructive path encroached on the pleural space.', 'e8f8516a-c8ad-4295-b55f-73cb46039a26': 'Traumatic pneumothorax is often a consequence of chest injury that involves laceration of the pleura. This might be due to a broken rib or penetrative wound to the chest that allows air to enter the pleural space and equilibrate with the atmosphere. The injury might not be malicious though as some procedures might inadvertently or unavoidably perforate the pleura, such as\xa0thoracentesis, pleural biopsy, lung biopsy, or subclavian vein puncture. Trauma from within the lung may also occur. Similar to the mechanism of a rupturing bleb, if excessive airway pressures are used during mechanical ventilation there is the risk that airspaces are disrupted and barotrauma involves the visceral pleura.', 'fab6752f-0cd2-4f94-b1d6-360dba928893': 'is often a consequence of chest injury that involves laceration of the pleura. This might be due to a broken rib or penetrative wound to the chest that allows air to enter the pleural space and equilibrate with the atmosphere. The injury might not be malicious though as some procedures might inadvertently or unavoidably perforate the pleura, such as', 'e45fe667-2ec7-4033-8c5e-04c092a2b507': ', pleural biopsy, lung biopsy, or subclavian vein puncture. Trauma from within the lung may also occur. Similar to the mechanism of a rupturing bleb, if excessive airway pressures are used during mechanical ventilation there is the risk that airspaces are disrupted and barotrauma involves the visceral pleura.', 'a204c5c6-7a42-4146-a852-8691884ffd56': 'The pneumothorax is readily identified with translucency on the affected side. The pathophysiology of a pneumothorax (figure 9.5) leads to hypoxia and hypercapnia in the affected lung through changes in perfusion and ventilation. Perfusion to the affected side is markedly reduced as the vasoconstrictive response to local hypoxia and the loss of radial traction to vessels profoundly increases vascular resistance. Consequently, perfusion shifts to the contralateral and unaffected lung. Similarly ventilation to the collapsed lung is minimal as airspaces are collapsed and airway resistance is very high, but the chemoreceptive reflexes increase ventilation to the unaffected lung where resistance is normal. Because perfusion and ventilation are shifted to the normal lung, V/Q mismatching may be compensated to some degree and severe hypoxemia may be avoided. When pneumothorax occurs patients usually describe a rapid onset of dyspnea and initial sudden sharp pain. The pain often then transitions into a dull ache.', '40ccba21-8fb6-4af3-aba0-bff1653d3e37': 'Tension pneumothorax may arise if the disruption to the pleural is such that the injury acts like a valve. During inspiration when thoracic pressure falls air enters the airways\xa0and also the thoracic cavity via the injury. During expiration when the thoracic pressure increases, the wound closes, stopping the air that entered the thoracic cavity from leaving. So with each inspiration more air enters while little or none leaves during the subsequent expiration. The accumulating volume can begin to push the heart and mediastinum to the contralateral side. This may severely affect cardiac output and rapidly become life threatening.', 'c8ef4a3e-bc72-41a2-832a-f0993ef52345': 'These CT scans in figure 9.6 shows a spontaneous pneumothorax (left panel) and a tension pneumothorax (right panel) with significant shift of the mediastinum over the contralateral hemithorax. So now you should be able to distinguish between the causes and mechanisms of these pleural disorders and determine their effects on pulmonary and cardiac function.', '34b024cb-5165-4749-a052-0d8070d763e3': 'Husain, Aliya N. “Chapter 15: The Lung.” In Robbins and Cotran Pathologic Basis of Disease, 9th ed., edited by Vinay Kumar, Abul K. Abbas, and John C. Aster. Philadelphia: Saunders, an imprint of Elsevier Inc., 2015.', 'a8850dcf-5c61-474b-b4f7-bdb65edf15a6': 'West, John B. “Chapter 5: Restrictive Diseases.” In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008.', '69f961c0-969d-40e6-8ade-b643ff59d2c7': 'The lung is no different from\xa0any other organ in that it is susceptible to disorders of the immune system. One might argue that it is surprising that the lung does not\xa0encounter more problems, given the lung’s exposure to the environment and the myriad\xa0antigens it encounters. Before we start looking at a few specific disorders, let us\xa0quickly review the four mechanisms through which the immune system might disrupt lung tissue.', '1a94ccb8-a877-481c-afba-6bd5bbb2d630': 'A type 1 reaction, or immediate hypersensitivity\xa0(table\xa08.1), is a result of overexpression of IgE (table\xa08.1). When an antigen binds to the overexpressed IgE on the surface of mast cells, the cell releases histamine and leukotrienes that in turn induce an inappropriate or exaggerated inflammatory response. Allergic asthma is an example of a type 1 reaction.'}"
Figure 9.4,pulmonary/images/Figure 9.4.jpg,Figure 9.4: Rupturing bulla and blebs can lead to spontaneous pneumothorax.,"The proportionately greater weight of lung per unit surface area at the apex increases the risk that bulla form (figure 9.4), then rupture causing loss of pleural membrane adhesion.","{'c7166aaa-f88c-45d5-8fb8-aea658aa589c': 'Normally the negative pressure inside the pleural space opposes the lung’s recoil and holds the lung surface to the interior of the thorax. If the pleural membranes are disrupted this subatmospheric or negative pressure is lost and the lung can recoil, or collapse. This is a\xa0pneumothorax.', 'c2586289-886f-4131-85d6-2457ba18e76c': 'The causal events of losing the negative pleural pressure divide pneumothoraces into one of two categories:\xa0spontaneous or traumatic. (A third category exists, artificial pneumothorax, which was\xa0intentionally induced as part of procedures that are very rarely used today.)', '38f879f0-5ff6-43f0-95ec-fc890ff997cc': 'Spontaneous pneumothorax occurs in the absence of accidental or intentional trauma. When it occurs in otherwise healthy individuals it is usually the fault of anatomy and occurs mostly\xa0in tall, thin individuals with a long and narrow chest. If you compare the\xa0two body morphs in figure 9.3, the tall, thin torso has a lot of lung mass hanging below a relatively small apical section of pleural membrane compared to the other torso.', 'df047406-e161-4f2b-b683-a315a1315378': 'The proportionately greater weight of lung per unit surface area at the apex increases the risk that bulla form (figure 9.4), then rupture\xa0causing loss of pleural\xa0membrane adhesion.', '0fe5da22-93a8-4711-8d35-5624a9f89b5f': 'The most common cause of spontaneous pneumothorax in pulmonary patients is a ruptured bleb or bulla. These thin-walled, air-filled cavities are found near the pleural surface, particularly in cases of emphysema. In the past, TB was thought to be the most common cause of pneumothorax as its destructive path encroached on the pleural space.', 'e8f8516a-c8ad-4295-b55f-73cb46039a26': 'Traumatic pneumothorax is often a consequence of chest injury that involves laceration of the pleura. This might be due to a broken rib or penetrative wound to the chest that allows air to enter the pleural space and equilibrate with the atmosphere. The injury might not be malicious though as some procedures might inadvertently or unavoidably perforate the pleura, such as\xa0thoracentesis, pleural biopsy, lung biopsy, or subclavian vein puncture. Trauma from within the lung may also occur. Similar to the mechanism of a rupturing bleb, if excessive airway pressures are used during mechanical ventilation there is the risk that airspaces are disrupted and barotrauma involves the visceral pleura.', 'fab6752f-0cd2-4f94-b1d6-360dba928893': 'is often a consequence of chest injury that involves laceration of the pleura. This might be due to a broken rib or penetrative wound to the chest that allows air to enter the pleural space and equilibrate with the atmosphere. The injury might not be malicious though as some procedures might inadvertently or unavoidably perforate the pleura, such as', 'e45fe667-2ec7-4033-8c5e-04c092a2b507': ', pleural biopsy, lung biopsy, or subclavian vein puncture. Trauma from within the lung may also occur. Similar to the mechanism of a rupturing bleb, if excessive airway pressures are used during mechanical ventilation there is the risk that airspaces are disrupted and barotrauma involves the visceral pleura.', 'a204c5c6-7a42-4146-a852-8691884ffd56': 'The pneumothorax is readily identified with translucency on the affected side. The pathophysiology of a pneumothorax (figure 9.5) leads to hypoxia and hypercapnia in the affected lung through changes in perfusion and ventilation. Perfusion to the affected side is markedly reduced as the vasoconstrictive response to local hypoxia and the loss of radial traction to vessels profoundly increases vascular resistance. Consequently, perfusion shifts to the contralateral and unaffected lung. Similarly ventilation to the collapsed lung is minimal as airspaces are collapsed and airway resistance is very high, but the chemoreceptive reflexes increase ventilation to the unaffected lung where resistance is normal. Because perfusion and ventilation are shifted to the normal lung, V/Q mismatching may be compensated to some degree and severe hypoxemia may be avoided. When pneumothorax occurs patients usually describe a rapid onset of dyspnea and initial sudden sharp pain. The pain often then transitions into a dull ache.', '40ccba21-8fb6-4af3-aba0-bff1653d3e37': 'Tension pneumothorax may arise if the disruption to the pleural is such that the injury acts like a valve. During inspiration when thoracic pressure falls air enters the airways\xa0and also the thoracic cavity via the injury. During expiration when the thoracic pressure increases, the wound closes, stopping the air that entered the thoracic cavity from leaving. So with each inspiration more air enters while little or none leaves during the subsequent expiration. The accumulating volume can begin to push the heart and mediastinum to the contralateral side. This may severely affect cardiac output and rapidly become life threatening.', 'c8ef4a3e-bc72-41a2-832a-f0993ef52345': 'These CT scans in figure 9.6 shows a spontaneous pneumothorax (left panel) and a tension pneumothorax (right panel) with significant shift of the mediastinum over the contralateral hemithorax. So now you should be able to distinguish between the causes and mechanisms of these pleural disorders and determine their effects on pulmonary and cardiac function.', '34b024cb-5165-4749-a052-0d8070d763e3': 'Husain, Aliya N. “Chapter 15: The Lung.” In Robbins and Cotran Pathologic Basis of Disease, 9th ed., edited by Vinay Kumar, Abul K. Abbas, and John C. Aster. Philadelphia: Saunders, an imprint of Elsevier Inc., 2015.', 'a8850dcf-5c61-474b-b4f7-bdb65edf15a6': 'West, John B. “Chapter 5: Restrictive Diseases.” In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008.', '69f961c0-969d-40e6-8ade-b643ff59d2c7': 'The lung is no different from\xa0any other organ in that it is susceptible to disorders of the immune system. One might argue that it is surprising that the lung does not\xa0encounter more problems, given the lung’s exposure to the environment and the myriad\xa0antigens it encounters. Before we start looking at a few specific disorders, let us\xa0quickly review the four mechanisms through which the immune system might disrupt lung tissue.', '1a94ccb8-a877-481c-afba-6bd5bbb2d630': 'A type 1 reaction, or immediate hypersensitivity\xa0(table\xa08.1), is a result of overexpression of IgE (table\xa08.1). When an antigen binds to the overexpressed IgE on the surface of mast cells, the cell releases histamine and leukotrienes that in turn induce an inappropriate or exaggerated inflammatory response. Allergic asthma is an example of a type 1 reaction.'}"
Figure 9.5,pulmonary/images/Figure 9.5.jpg,Figure 9.5: Pathophysiology of a pneumothorax,"The pneumothorax is readily identified with translucency on the affected side. The pathophysiology of a pneumothorax (figure 9.5) leads to hypoxia and hypercapnia in the affected lung through changes in perfusion and ventilation. Perfusion to the affected side is markedly reduced as the vasoconstrictive response to local hypoxia and the loss of radial traction to vessels profoundly increases vascular resistance. Consequently, perfusion shifts to the contralateral and unaffected lung. Similarly ventilation to the collapsed lung is minimal as airspaces are collapsed and airway resistance is very high, but the chemoreceptive reflexes increase ventilation to the unaffected lung where resistance is normal. Because perfusion and ventilation are shifted to the normal lung, V/Q mismatching may be compensated to some degree and severe hypoxemia may be avoided. When pneumothorax occurs patients usually describe a rapid onset of dyspnea and initial sudden sharp pain. The pain often then transitions into a dull ache.","{'c7166aaa-f88c-45d5-8fb8-aea658aa589c': 'Normally the negative pressure inside the pleural space opposes the lung’s recoil and holds the lung surface to the interior of the thorax. If the pleural membranes are disrupted this subatmospheric or negative pressure is lost and the lung can recoil, or collapse. This is a\xa0pneumothorax.', 'c2586289-886f-4131-85d6-2457ba18e76c': 'The causal events of losing the negative pleural pressure divide pneumothoraces into one of two categories:\xa0spontaneous or traumatic. (A third category exists, artificial pneumothorax, which was\xa0intentionally induced as part of procedures that are very rarely used today.)', '38f879f0-5ff6-43f0-95ec-fc890ff997cc': 'Spontaneous pneumothorax occurs in the absence of accidental or intentional trauma. When it occurs in otherwise healthy individuals it is usually the fault of anatomy and occurs mostly\xa0in tall, thin individuals with a long and narrow chest. If you compare the\xa0two body morphs in figure 9.3, the tall, thin torso has a lot of lung mass hanging below a relatively small apical section of pleural membrane compared to the other torso.', 'df047406-e161-4f2b-b683-a315a1315378': 'The proportionately greater weight of lung per unit surface area at the apex increases the risk that bulla form (figure 9.4), then rupture\xa0causing loss of pleural\xa0membrane adhesion.', '0fe5da22-93a8-4711-8d35-5624a9f89b5f': 'The most common cause of spontaneous pneumothorax in pulmonary patients is a ruptured bleb or bulla. These thin-walled, air-filled cavities are found near the pleural surface, particularly in cases of emphysema. In the past, TB was thought to be the most common cause of pneumothorax as its destructive path encroached on the pleural space.', 'e8f8516a-c8ad-4295-b55f-73cb46039a26': 'Traumatic pneumothorax is often a consequence of chest injury that involves laceration of the pleura. This might be due to a broken rib or penetrative wound to the chest that allows air to enter the pleural space and equilibrate with the atmosphere. The injury might not be malicious though as some procedures might inadvertently or unavoidably perforate the pleura, such as\xa0thoracentesis, pleural biopsy, lung biopsy, or subclavian vein puncture. Trauma from within the lung may also occur. Similar to the mechanism of a rupturing bleb, if excessive airway pressures are used during mechanical ventilation there is the risk that airspaces are disrupted and barotrauma involves the visceral pleura.', 'fab6752f-0cd2-4f94-b1d6-360dba928893': 'is often a consequence of chest injury that involves laceration of the pleura. This might be due to a broken rib or penetrative wound to the chest that allows air to enter the pleural space and equilibrate with the atmosphere. The injury might not be malicious though as some procedures might inadvertently or unavoidably perforate the pleura, such as', 'e45fe667-2ec7-4033-8c5e-04c092a2b507': ', pleural biopsy, lung biopsy, or subclavian vein puncture. Trauma from within the lung may also occur. Similar to the mechanism of a rupturing bleb, if excessive airway pressures are used during mechanical ventilation there is the risk that airspaces are disrupted and barotrauma involves the visceral pleura.', 'a204c5c6-7a42-4146-a852-8691884ffd56': 'The pneumothorax is readily identified with translucency on the affected side. The pathophysiology of a pneumothorax (figure 9.5) leads to hypoxia and hypercapnia in the affected lung through changes in perfusion and ventilation. Perfusion to the affected side is markedly reduced as the vasoconstrictive response to local hypoxia and the loss of radial traction to vessels profoundly increases vascular resistance. Consequently, perfusion shifts to the contralateral and unaffected lung. Similarly ventilation to the collapsed lung is minimal as airspaces are collapsed and airway resistance is very high, but the chemoreceptive reflexes increase ventilation to the unaffected lung where resistance is normal. Because perfusion and ventilation are shifted to the normal lung, V/Q mismatching may be compensated to some degree and severe hypoxemia may be avoided. When pneumothorax occurs patients usually describe a rapid onset of dyspnea and initial sudden sharp pain. The pain often then transitions into a dull ache.', '40ccba21-8fb6-4af3-aba0-bff1653d3e37': 'Tension pneumothorax may arise if the disruption to the pleural is such that the injury acts like a valve. During inspiration when thoracic pressure falls air enters the airways\xa0and also the thoracic cavity via the injury. During expiration when the thoracic pressure increases, the wound closes, stopping the air that entered the thoracic cavity from leaving. So with each inspiration more air enters while little or none leaves during the subsequent expiration. The accumulating volume can begin to push the heart and mediastinum to the contralateral side. This may severely affect cardiac output and rapidly become life threatening.', 'c8ef4a3e-bc72-41a2-832a-f0993ef52345': 'These CT scans in figure 9.6 shows a spontaneous pneumothorax (left panel) and a tension pneumothorax (right panel) with significant shift of the mediastinum over the contralateral hemithorax. So now you should be able to distinguish between the causes and mechanisms of these pleural disorders and determine their effects on pulmonary and cardiac function.', '34b024cb-5165-4749-a052-0d8070d763e3': 'Husain, Aliya N. “Chapter 15: The Lung.” In Robbins and Cotran Pathologic Basis of Disease, 9th ed., edited by Vinay Kumar, Abul K. Abbas, and John C. Aster. Philadelphia: Saunders, an imprint of Elsevier Inc., 2015.', 'a8850dcf-5c61-474b-b4f7-bdb65edf15a6': 'West, John B. “Chapter 5: Restrictive Diseases.” In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008.', '69f961c0-969d-40e6-8ade-b643ff59d2c7': 'The lung is no different from\xa0any other organ in that it is susceptible to disorders of the immune system. One might argue that it is surprising that the lung does not\xa0encounter more problems, given the lung’s exposure to the environment and the myriad\xa0antigens it encounters. Before we start looking at a few specific disorders, let us\xa0quickly review the four mechanisms through which the immune system might disrupt lung tissue.', '1a94ccb8-a877-481c-afba-6bd5bbb2d630': 'A type 1 reaction, or immediate hypersensitivity\xa0(table\xa08.1), is a result of overexpression of IgE (table\xa08.1). When an antigen binds to the overexpressed IgE on the surface of mast cells, the cell releases histamine and leukotrienes that in turn induce an inappropriate or exaggerated inflammatory response. Allergic asthma is an example of a type 1 reaction.'}"
Figure 9.6,pulmonary/images/Figure 9.6.jpg,Figure 9.6: CT comparison of an uncomplicated pneumothorax and a tension pneumothorax.,These CT scans in figure 9.6 shows a spontaneous pneumothorax (left panel) and a tension pneumothorax (right panel) with significant shift of the mediastinum over the contralateral hemithorax. So now you should be able to distinguish between the causes and mechanisms of these pleural disorders and determine their effects on pulmonary and cardiac function.,"{'c7166aaa-f88c-45d5-8fb8-aea658aa589c': 'Normally the negative pressure inside the pleural space opposes the lung’s recoil and holds the lung surface to the interior of the thorax. If the pleural membranes are disrupted this subatmospheric or negative pressure is lost and the lung can recoil, or collapse. This is a\xa0pneumothorax.', 'c2586289-886f-4131-85d6-2457ba18e76c': 'The causal events of losing the negative pleural pressure divide pneumothoraces into one of two categories:\xa0spontaneous or traumatic. (A third category exists, artificial pneumothorax, which was\xa0intentionally induced as part of procedures that are very rarely used today.)', '38f879f0-5ff6-43f0-95ec-fc890ff997cc': 'Spontaneous pneumothorax occurs in the absence of accidental or intentional trauma. When it occurs in otherwise healthy individuals it is usually the fault of anatomy and occurs mostly\xa0in tall, thin individuals with a long and narrow chest. If you compare the\xa0two body morphs in figure 9.3, the tall, thin torso has a lot of lung mass hanging below a relatively small apical section of pleural membrane compared to the other torso.', 'df047406-e161-4f2b-b683-a315a1315378': 'The proportionately greater weight of lung per unit surface area at the apex increases the risk that bulla form (figure 9.4), then rupture\xa0causing loss of pleural\xa0membrane adhesion.', '0fe5da22-93a8-4711-8d35-5624a9f89b5f': 'The most common cause of spontaneous pneumothorax in pulmonary patients is a ruptured bleb or bulla. These thin-walled, air-filled cavities are found near the pleural surface, particularly in cases of emphysema. In the past, TB was thought to be the most common cause of pneumothorax as its destructive path encroached on the pleural space.', 'e8f8516a-c8ad-4295-b55f-73cb46039a26': 'Traumatic pneumothorax is often a consequence of chest injury that involves laceration of the pleura. This might be due to a broken rib or penetrative wound to the chest that allows air to enter the pleural space and equilibrate with the atmosphere. The injury might not be malicious though as some procedures might inadvertently or unavoidably perforate the pleura, such as\xa0thoracentesis, pleural biopsy, lung biopsy, or subclavian vein puncture. Trauma from within the lung may also occur. Similar to the mechanism of a rupturing bleb, if excessive airway pressures are used during mechanical ventilation there is the risk that airspaces are disrupted and barotrauma involves the visceral pleura.', 'fab6752f-0cd2-4f94-b1d6-360dba928893': 'is often a consequence of chest injury that involves laceration of the pleura. This might be due to a broken rib or penetrative wound to the chest that allows air to enter the pleural space and equilibrate with the atmosphere. The injury might not be malicious though as some procedures might inadvertently or unavoidably perforate the pleura, such as', 'e45fe667-2ec7-4033-8c5e-04c092a2b507': ', pleural biopsy, lung biopsy, or subclavian vein puncture. Trauma from within the lung may also occur. Similar to the mechanism of a rupturing bleb, if excessive airway pressures are used during mechanical ventilation there is the risk that airspaces are disrupted and barotrauma involves the visceral pleura.', 'a204c5c6-7a42-4146-a852-8691884ffd56': 'The pneumothorax is readily identified with translucency on the affected side. The pathophysiology of a pneumothorax (figure 9.5) leads to hypoxia and hypercapnia in the affected lung through changes in perfusion and ventilation. Perfusion to the affected side is markedly reduced as the vasoconstrictive response to local hypoxia and the loss of radial traction to vessels profoundly increases vascular resistance. Consequently, perfusion shifts to the contralateral and unaffected lung. Similarly ventilation to the collapsed lung is minimal as airspaces are collapsed and airway resistance is very high, but the chemoreceptive reflexes increase ventilation to the unaffected lung where resistance is normal. Because perfusion and ventilation are shifted to the normal lung, V/Q mismatching may be compensated to some degree and severe hypoxemia may be avoided. When pneumothorax occurs patients usually describe a rapid onset of dyspnea and initial sudden sharp pain. The pain often then transitions into a dull ache.', '40ccba21-8fb6-4af3-aba0-bff1653d3e37': 'Tension pneumothorax may arise if the disruption to the pleural is such that the injury acts like a valve. During inspiration when thoracic pressure falls air enters the airways\xa0and also the thoracic cavity via the injury. During expiration when the thoracic pressure increases, the wound closes, stopping the air that entered the thoracic cavity from leaving. So with each inspiration more air enters while little or none leaves during the subsequent expiration. The accumulating volume can begin to push the heart and mediastinum to the contralateral side. This may severely affect cardiac output and rapidly become life threatening.', 'c8ef4a3e-bc72-41a2-832a-f0993ef52345': 'These CT scans in figure 9.6 shows a spontaneous pneumothorax (left panel) and a tension pneumothorax (right panel) with significant shift of the mediastinum over the contralateral hemithorax. So now you should be able to distinguish between the causes and mechanisms of these pleural disorders and determine their effects on pulmonary and cardiac function.', '34b024cb-5165-4749-a052-0d8070d763e3': 'Husain, Aliya N. “Chapter 15: The Lung.” In Robbins and Cotran Pathologic Basis of Disease, 9th ed., edited by Vinay Kumar, Abul K. Abbas, and John C. Aster. Philadelphia: Saunders, an imprint of Elsevier Inc., 2015.', 'a8850dcf-5c61-474b-b4f7-bdb65edf15a6': 'West, John B. “Chapter 5: Restrictive Diseases.” In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008.', '69f961c0-969d-40e6-8ade-b643ff59d2c7': 'The lung is no different from\xa0any other organ in that it is susceptible to disorders of the immune system. One might argue that it is surprising that the lung does not\xa0encounter more problems, given the lung’s exposure to the environment and the myriad\xa0antigens it encounters. Before we start looking at a few specific disorders, let us\xa0quickly review the four mechanisms through which the immune system might disrupt lung tissue.', '1a94ccb8-a877-481c-afba-6bd5bbb2d630': 'A type 1 reaction, or immediate hypersensitivity\xa0(table\xa08.1), is a result of overexpression of IgE (table\xa08.1). When an antigen binds to the overexpressed IgE on the surface of mast cells, the cell releases histamine and leukotrienes that in turn induce an inappropriate or exaggerated inflammatory response. Allergic asthma is an example of a type 1 reaction.'}"
Figure 8.2,pulmonary/images/Figure 8.2.jpg,Figure 8.2: Chronic phase of hypersensitivity pneumonitis with established fibrosis.,"In the acute phase, lymphocytes and macrophages infiltrate the alveolar walls and loose granulomas can form. The presence of multi-nucleated giant cells (figure 8.2), are helpful in diagnosis, but more typical is a dramatic rise in lymphocyte count in BAL fluid, particularly CD8+ cells.","{'513c66e1-b30f-47a0-804e-ced6ad9b3808': 'In the acute phase, lymphocytes and macrophages infiltrate the alveolar walls and loose granulomas can form. The presence of multi-nucleated giant cells (figure 8.2), are helpful in diagnosis, but more typical is a dramatic rise in lymphocyte count in BAL fluid, particularly CD8+ cells.', 'da5f7d98-82bc-43e0-a76b-cdd2a83989b1': 'In the subacute phase\xa0there is evidence of interstitial thickening and the onset of fibrosis can be seen. Involvement of the bronchioles is seen with evidence of chronic bronchiolitis.\xa0The chronic form is marked by significant fibrosis (figure 8.3), to the extent it is indistinguishable from pulmonary fibrosis with distinctive fibrotic patterns and all the hallmarks of restrictive lung disease.'}"
Figure 8.3,pulmonary/images/Figure 8.3.jpg,Figure 8.3: Patchy airspace consolidation associated with Goodpasture’s syndrome.,"In the subacute phase there is evidence of interstitial thickening and the onset of fibrosis can be seen. Involvement of the bronchioles is seen with evidence of chronic bronchiolitis. The chronic form is marked by significant fibrosis (figure 8.3), to the extent it is indistinguishable from pulmonary fibrosis with distinctive fibrotic patterns and all the hallmarks of restrictive lung disease.","{'513c66e1-b30f-47a0-804e-ced6ad9b3808': 'In the acute phase, lymphocytes and macrophages infiltrate the alveolar walls and loose granulomas can form. The presence of multi-nucleated giant cells (figure 8.2), are helpful in diagnosis, but more typical is a dramatic rise in lymphocyte count in BAL fluid, particularly CD8+ cells.', 'da5f7d98-82bc-43e0-a76b-cdd2a83989b1': 'In the subacute phase\xa0there is evidence of interstitial thickening and the onset of fibrosis can be seen. Involvement of the bronchioles is seen with evidence of chronic bronchiolitis.\xa0The chronic form is marked by significant fibrosis (figure 8.3), to the extent it is indistinguishable from pulmonary fibrosis with distinctive fibrotic patterns and all the hallmarks of restrictive lung disease.'}"
Figure 8.4,pulmonary/images/Figure 8.4.jpg,Figure 8.4: Progression of diffuse fibrosis in chronic SLE.,"The chronic form can progress insidiously with no symptoms or physical findings, and so it frequently it goes unrecognized until later stages of the disease. The later stages are marked with the appearance of progressive fibrosis. This is evident in the chest x-rays in figure 8.4 showing the appearance of diffuse fibrosis over a twenty-month period in a young SLE patient. The fibrosis produces reduced lung volumes and basilar atelectasis may also occur. The increased recoil of the lung can also produce an elevated and weakened diaphragm. There may also be pleural involvement with effusions arising that are normally bilateral and small.","{'a963a7f7-ee87-4a98-b028-be212f62d59d': 'The chronic form can progress insidiously with no symptoms or physical findings, and so it frequently it goes unrecognized until later stages of the disease. The later stages are marked with the appearance of progressive fibrosis. This is evident in the\xa0chest x-rays in figure 8.4\xa0showing the appearance of diffuse fibrosis over a twenty-month period in a young SLE patient. The fibrosis produces reduced\xa0lung volumes and basilar atelectasis may also occur. The increased recoil of the lung can also produce an elevated and weakened diaphragm. There may also be pleural involvement with effusions arising that are normally bilateral and small.'}"
Figure 8.5,pulmonary/images/Figure 8.5.jpg,Figure 8.5: Pleural effusion in a rheumatoid patient.,"Up to 50 percent of rheumatoid patients show pulmonary or pleural manifestations, with pleural involvement being more common and most frequently manifested as pleural effusion (figure 8.5). The effusate tends to have low glucose, and this finding is useful for diagnosis. Pleural and pulmonary manifestations of rheumatoid disease are more common in male patients.","{'c48b9516-2cb6-4fe5-92f6-604b85200655': 'More famous for its effect on the joints, rheumatoid disease can also affect the lungs and pleura. Rheumatoid factors that generate rheumatoid disease continue to be investigated, but\xa0in brief, they are antibodies generated against gamma globulins. Pleural and pulmonary lesions are probably the result of local immune complex–mediated reactions associated with high levels of circulating rheumatoid factors.', '04d7b4aa-886a-4536-98ed-070284e4bd95': 'Up to 50 percent\xa0of rheumatoid patients show pulmonary or pleural manifestations, with pleural involvement being more common and\xa0most frequently manifested as pleural effusion (figure 8.5). The effusate tends to have low glucose, and this finding is useful for diagnosis. Pleural and pulmonary manifestations of rheumatoid disease are more common in male patients.', 'ede6027d-fb5a-4e30-9117-95507266dd44': 'Pulmonary involvement shows as either diffuse or nodular lesions (figure 8.6). The diffuse lesions are\xa0similar to those seen in idiopathic pulmonary fibrosis. The nodular lesions are variable in size and number and usually do not\xa0cause symptoms. They are known as necrobiotic nodules and are capable of cavitating. Bronchiolitis obliterans organizing pneumonia and bronchiectasis have also been seen in rheumatoid disease.', '42a08419-43ef-4114-bb9f-0f12c3b4dfa6': 'It should be noted here that some drugs used to treat difficult rheumatoid arthritis, such as gold preparations, methotrexate, and penicillamine, are toxic to the lung and can produce their own pulmonary lesions.'}"
Figure 8.6,pulmonary/images/Figure 8.6.jpg,Figure 8.6: A nodular lesion (arrow) associated with rheumatoid disease.,Pulmonary involvement shows as either diffuse or nodular lesions (figure 8.6). The diffuse lesions are similar to those seen in idiopathic pulmonary fibrosis. The nodular lesions are variable in size and number and usually do not cause symptoms. They are known as necrobiotic nodules and are capable of cavitating. Bronchiolitis obliterans organizing pneumonia and bronchiectasis have also been seen in rheumatoid disease.,"{'c48b9516-2cb6-4fe5-92f6-604b85200655': 'More famous for its effect on the joints, rheumatoid disease can also affect the lungs and pleura. Rheumatoid factors that generate rheumatoid disease continue to be investigated, but\xa0in brief, they are antibodies generated against gamma globulins. Pleural and pulmonary lesions are probably the result of local immune complex–mediated reactions associated with high levels of circulating rheumatoid factors.', '04d7b4aa-886a-4536-98ed-070284e4bd95': 'Up to 50 percent\xa0of rheumatoid patients show pulmonary or pleural manifestations, with pleural involvement being more common and\xa0most frequently manifested as pleural effusion (figure 8.5). The effusate tends to have low glucose, and this finding is useful for diagnosis. Pleural and pulmonary manifestations of rheumatoid disease are more common in male patients.', 'ede6027d-fb5a-4e30-9117-95507266dd44': 'Pulmonary involvement shows as either diffuse or nodular lesions (figure 8.6). The diffuse lesions are\xa0similar to those seen in idiopathic pulmonary fibrosis. The nodular lesions are variable in size and number and usually do not\xa0cause symptoms. They are known as necrobiotic nodules and are capable of cavitating. Bronchiolitis obliterans organizing pneumonia and bronchiectasis have also been seen in rheumatoid disease.', '42a08419-43ef-4114-bb9f-0f12c3b4dfa6': 'It should be noted here that some drugs used to treat difficult rheumatoid arthritis, such as gold preparations, methotrexate, and penicillamine, are toxic to the lung and can produce their own pulmonary lesions.'}"
Figure 8.7,pulmonary/images/Figure 8.7.jpg,Figure 8.7: Fine reticular fibrosis in lower lung fields (upper CT image) progressing to honeycombing (lower CT image).,"The radiographic findings are similar to pulmonary fibrosis with the early stage of the disease showing fine reticular patterning that progresses to honeycombing in the late stage of the disease (figure 8.7). These changes are mostly found in the lower lung fields. As you might expect, the disease has restrictive characteristics along with diffusion abnormalities that produce hypoxemia during exercise.","{'cb8e1a9f-2a82-4a89-b17c-a1610c12363b': 'Also known as scleroderma, progressive systemic sclerosis primarily affects the blood vessels and connective tissue and likely has an autoimmune mechanism. The result is dysregulation of fibroblasts and uncontrolled collagen formation. The disease can affect many organs and tissues, and pulmonary manifestations are common.', '1c381b39-cda0-46b1-83e7-0ef197c5085c': 'The most common pulmonary findings are interstitial fibrosis, bronchiolar dilation, and pleural fibrosis, as well as the vascular changes that are seen in other organs. These changes produce dyspnea, cough, and basilar rales. The vascular changes can produce pulmonary hypertension that may lead to cor pulmonale.', '46f49161-5bd8-4b1a-bce3-e07a1097b217': 'The radiographic findings\xa0are similar to pulmonary fibrosis with the early stage of the disease showing fine reticular patterning that progresses to honeycombing in the late stage of the disease (figure 8.7). These changes are mostly found in the lower lung fields. As you might expect, the disease has restrictive characteristics along with diffusion abnormalities that produce hypoxemia during\xa0exercise.'}"
Figure 8.1,pulmonary/images/Figure 8.1.jpg,"Figure 8.1: Acute phase of hypersensitivity pneumonitis. Note presence of giant cells in the alveolar septum on the center, right-hand side of field of view.","Table 8.1: Types of immune mechanisms involved in lung tissue injury. Includes Immune mechanism – type 1 by Kindred Grey from Internet archive (CC BY 4.0), Immune mechanism – type 2 by Kindred Grey from Internet archive (CC BY 4.0), Immune mechanism – type 3 by Kindred Grey from Internet archive (CC BY 4.0), and Immune mechanism – type 4 by Kindred Grey from Internet archive (CC BY 4.0).Figure 8.1: Acute phase of hypersensitivity pneumonitis. Mutleysmith. 2012. CC BY-SA 3.0. From WikimediaCommons.","{'c95fa1fa-f9e3-450e-b56a-ad2feb79761c': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapters 13–14.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '46cbc4df-cf41-4ebf-99e9-0d40ac274b65': 'Table 8.1:\xa0Types of immune mechanisms involved in lung tissue injury. Includes Immune mechanism – type 1 by Kindred Grey from Internet archive (CC BY 4.0), Immune mechanism – type 2 by Kindred Grey from Internet archive (CC BY 4.0), Immune mechanism – type 3 by Kindred Grey from Internet archive (CC BY 4.0), and Immune mechanism – type 4 by Kindred Grey from Internet archive (CC BY 4.0).Figure 8.1: Acute phase of hypersensitivity pneumonitis. Mutleysmith. 2012. CC BY-SA 3.0. From WikimediaCommons.', '135b6718-449f-4a77-b8d5-731b7a7b5b9c': 'About 90 percent\xa0of PEs are caused by deep vein thrombi, but at least one of three main predisposing factors (Virchow’s triad)\xa0are present in a case of PE:', '682f75a3-5287-4893-b258-f8c47679450f': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapter 21.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '99ef9463-cb8b-4725-b750-3a5bfddf0607': 'West, John B. “Chapter 6: Vascular Diseases.” In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008.', 'cc05c711-e485-49f6-b7d0-98f4edb46105': 'Four major types of bronchogenic carcinoma can be distinguished by histology, epidemiology, clinical features, and prognosis. They are:', 'd412e5db-7af7-4ded-98bd-d3838d618392': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapter 20.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '5b90a401-f907-458e-acb6-06e6ef81186f': 'Table 6.1: Summary of forms of lung cancer. Includes Squamous Cell Carcinoma Lung 40x by Calicut\xa0Medical\xa0College\xa0from WikimediaCommons (CC BY-SA 4.0), Papillary adenocarcinoma of the lung — intermed mag by Nephron from WikimediaCommons (CC BY-SA 3.0), Large cell carcinoma of the lung by The Armed Forces Institute of Pathology (AFIP) from WikimediaCommons (Public domain), and Lung small cell carcinoma (1) by core needle biopsy by KGH from WikimediaCommons (CC BY-SA 3.0).', '56cdcda8-5410-4a9a-b9e0-4b3903d27c1a': 'There are about two hundred thousand cases of ARDS in the United States\xa0each year. Each case starts with an initial insult to the lung parenchyma and there are numerous examples of this instigating event, but the most common of these (and therefore worth remembering) are sepsis, pulmonary aspiration, and thoracic trauma. The insult can arrive from the airway, such as in pulmonary aspiration or smoke inhalation, or can arrive from the bloodstream, as in a fat embolism or blood-born pathogen.', '01bbc814-2276-4901-bc9f-9f07e914f0f3': 'Regardless of the insult’s route or indeed form, the ensuing pathological events are similar and lead to the same alteration of the lungs. What is initiated is a defensive inflammatory response, and what results is vascular endothelial and alveolar epithelial damage and a leaky alveolar capillary membrane.', 'a657cac1-87c9-4a34-a8b2-a3d673f6934b': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapter 27.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '5351bcef-c613-420f-a998-817912cb0590': 'West, John B. “Chapter 8: Respiratory Failure.” In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008.', '2bf2097e-c952-4e61-bdc7-c018fed73a0c': 'Before we start taking about diseases affecting the lung interstitium, let us\xa0remind ourselves of what it is.', '5a2ecb16-7483-4ecc-9625-a5985a2879c5': 'The interstitial tissue, sometimes referred to as parenchyma, surrounds\xa0the alveolar and capillary structures and contributes to the mechanical behavior of the lungs. The interstitium is extremely thin between the alveoli and capillaries, and forms the basement membrane through which gas exchange occurs. On the parenchymal\xa0side of the capillaries the interstitium is more substantial and is more involved in fluid exchange. There is also substantial amounts of interstitial tissue in the spaces around major vessels and airways, and it also makes up the interlobular septa.', '99cfc116-0672-4e5d-a968-44f58a5d1a46': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapters 12–15.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '643821d1-ed82-48c7-93e1-ebc504ed1987': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapter 3.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '85c596d0-c0f5-467f-b2ce-39e772dc507b': 'Table 3.1: Comparison of typical and atypical pneumonia. Includes Case 1 by Bell, D., Hacking, C., et al. from https://doi.org/10.53347/rID-68496\xa0(CC BY-NC-SA 3.0), Acute pneumonia – i — low mag by Nephron from WikimediaCommons (CC BY-SA 3.0), Case 2 by Paks, M., Knipe, H., et al. from https://doi.org/10.53347/rID-27535 (CC BY-NC-SA 3.0), and image 1 by Dr Patsy Lill from University of South Carolina School of Medicine’s\xa0Microbiologybook.org (Fair use).', 'b3d33b15-a961-4fcf-90af-d04139c33ca5': 'Table 3.2: Comparison of bronchopneumonia and lobar pneumonia. Includes Bronchopneumonia by Kindred Grey from Internet archive (CC BY 4.0), Lobar pneumonia by Kindred Grey from Internet archive (CC BY 4.0), X-ray of bronchopneumonia by Franquet T., Chung J.H. from WikimediaCommons (CC BY 4.0), Case 3 by Paks, M., Knipe, H., et al. from https://doi.org/10.53347/rID-26886\xa0(CC BY-NC-SA 3.0).', '7d48f651-5ec9-4c8c-8c1d-f8ac28654b61': 'As with most URIs the common\xa0cold is caused by a viral infection, and although there are several different viral candidates for causing a common cold, the pathophysiological mechanism and symptoms are the same regardless of the type. This is because it is the innate immune response, rather than the direct infection, that is responsible for most of the symptoms.', 'c9d5fd5e-55d3-44b1-94eb-4c180bbf3596': 'Thomas, Micah, and Paul A. Bomar. Upper Respiratory Tract Infection. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK532961, CC BY 4.0.', 'fc7ec5d0-c678-4556-971c-1fdf56177f67': 'There are numerous underlying mechanisms of asthma (figure 1.1), and they may not be exclusive or independent within the same patient.', '5257cee7-51ab-414b-b5ce-f379a71ee95f': 'We will also look at how exercise and certain pharmacological agents can produce asthma.', 'fbf759df-934f-4ba5-9987-deb818c57280': 'Allergenic asthma: Most allergic asthma is caused by the presence of an excessive amount of IgE (the hallmark antibody of an allergy). Formation of an immune complex between the antigen and the overexpressed IgE results in binding to surface receptors on mast cells and basophilic granulocytes,\xa0of which there are plenty in the lung. The IgE receptor binding results in the release of a cocktail of proinflammatory and airway-active substances. Some of these, including histamine and cytokines that attract eosinophils and neutrophils, are stored in vesicles of mast cells shown in figure 1.2. Others are produced on demand, including leukotrienes, and are derivatives of arachidonic acid (we will return to this later).', 'cbb9aaad-105e-4a3e-ac67-3afc2bac6e48': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapters 8–11.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '2fae69a4-a520-4df1-b51b-916b71d658bf': 'West, John B. “Chapter 4: Obstructive Diseases.” In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008.'}"
Figure 7.1,pulmonary/images/Figure 7.1.jpg,Figure 7.1: Pathophysiology of pulmonary embolism.,"With larger emboli that occlude larger vessels there will not only be a larger impact on gas exchange, but also a more increase in pulmonary vascular resistance. The extreme  (and thankfully rare) case is a “saddle” embolus that is large enough to straddle the bifurcation of the pulmonary trunk, obstruct the left and right pulmonary arteries, and lead to immediate hemodynamic collapse. In lesser cases, pulmonary hypertension will overwhelm the thin myocardium of the right ventricle, and as pulmonary arterial pressure approaches right ventricle pressure then cardiac output will fall. This will exaggerate the hypoxemia and cause the pulmonary vasculature to perform its normal vasoconstrictive response to low oxygen tensions that in turn worsens the pulmonary hypertension (summarized in figure 7.1).","{'6a3a9432-5ad0-4334-a824-8d3ad6ddd2f8': 'The pathophysiology and clinical severity of PE depend on the number and size of the emboli, so clinical manifestations can be highly variable. In fact, PE is suspected to be much more common than previously thought because of improved detection techniques revealing more small and asymptomatic cases.', '4d0d3628-5138-4854-a44d-ba58dcd8838c': 'Small emboli that can travel\xa0further into the vasculature may cause occlusion of relatively small areas of the lung, but with these areas receiving no perfusion and still being ventilated V/Q becomes inappropriately high. Not being able to pass the occlusion, blood will be diverted to other areas of the lung, and consequently cause them to be overperfused, lowering V/Q.', 'd640376a-ecdb-4c83-8343-613efd368b53': 'Depending on the size and number of emboli, these V/Q mismatches can produce\xa0a widening alveolar–arterial PO2\xa0difference and lead to hypoxemia.', '6a590143-e548-4a81-9811-77266509fd09': 'With larger emboli that occlude larger vessels there will not only be a larger impact on gas exchange, but also a more increase in pulmonary vascular resistance. The extreme \xa0(and thankfully rare) case\xa0is a “saddle” embolus that is large enough to\xa0straddle the bifurcation of the pulmonary trunk, obstruct the left and right pulmonary arteries, and lead to immediate\xa0hemodynamic collapse.\xa0In lesser cases,\xa0pulmonary hypertension will overwhelm the thin myocardium of the right ventricle, and as pulmonary arterial pressure approaches right ventricle pressure then cardiac output will fall. This will exaggerate the hypoxemia and cause the pulmonary vasculature to perform its normal vasoconstrictive response to low oxygen tensions that in turn worsens the pulmonary hypertension (summarized in figure 7.1).', 'b6c06c73-33d6-4676-a8a9-9d5c8ec1bf3d': 'Pulmonary infarction, however, is rare, occurring in only 10 percent\xa0of PE cases. The lung tissue is supplied by the bronchial circulation so can usually survive the embolism in the pulmonary circulation unless there is preexisting cardiac disease.'}"
Figure 6.1,pulmonary/images/Figure 6.1.jpg,Figure 6.1: Potential radiographic findings in lung cancer.,"Chest x-ray is usually only capable of detecting advanced cancer stages, and therefore is not the best screening tool. Low-dose CT screening can be used to detect early stages of disease before symptoms arise and is advised for patients between fifty to eighty years old with a twenty-pack-per-year smoking history or who have quit smoking in the past fifteen years. Once the disease is established, however, the x-ray’s findings can either be direct detection of a mass, or a secondary consequence of the mass; therefore they are quite variable (figure 6.1).","{'d34dcb43-d5bb-43a5-a675-20a43c43d204': 'The signs and symptoms can be variable and diverse depending on the location, type, size, and rapidity of growth. Patients may even be asymptomatic when the lesion is found on chest x-ray or with bronchoscope.', '51c38948-4396-4f5a-b997-bb40f22f0dc6': 'The most common symptom is cough, but unfortunately the patient, likely being a smoker, may be accustomed to cough and not think anything of it. Bloody sputum occurs in only about half of patients and is a frequent cause for them seeking medical advice, and severe hemoptysis is uncommon.', '6ff06d00-15aa-4d3a-9574-871ab4f18cb5': 'Chest pain is fairly common and ranges from a mild ache or feeling of heaviness, to severe and unremitting. Pain does not necessarily indicate pleural or chest wall involvement, although significant steady pain is more indicative of this complication.', '4edb3231-5a6a-4444-9c9b-b8e352550942': 'Dyspnea may arise as the tumor obstructs a major airway or causes a large pleural effusion, but it can also be due to underlying bronchopulmonary disease.', 'e4bfe82d-3803-4ffe-919f-997f2394bc42': 'Physical exam is likely to be normal in the early stages of the disease, but as the cancer progresses the exam usually reveals signs associated with either bronchial obstruction or a consequence of metastasis. Bronchial obstruction can lead to wheeze or other modified breath sounds, atelectasis, down-stream pneumonia, or pleural effusion. Paraneoplastic syndromes associated with the cancer can cause disruption to other systems and lead to characteristic weight loss, muscle wasting, and digital clubbing.', '92f391cb-397f-42ca-8027-6aeabc48b471': 'Chest x-ray is usually only capable of detecting advanced cancer stages, and therefore is not the best screening tool. Low-dose CT screening can be used to detect early stages of disease before symptoms arise and is advised for patients\xa0between fifty to eighty years old with a twenty-pack-per-year smoking history or who have quit smoking in the past fifteen\xa0years.\xa0Once the disease is established, however, the x-ray’s findings can either be direct detection of a mass, or a\xa0secondary consequence of the mass; therefore they are quite variable (figure 6.1).'}"
Figure 5.2,pulmonary/images/Figure 5.2.jpg,Figure 5.2: Pathophysiological events of ARDS. ROS = reactive oxygen species.,The process is summarized in figure 5.2.,{'b002921a-3855-45f1-bd5a-3d96e9e69018': 'The process is summarized in figure 5.2.'}
Figure 5.3,pulmonary/images/Figure 5.3.jpg,Figure 5.3: Alveolar wall edema and onset of hyaline membrane formation during the exudative phase of ARDS. The debris inside the airspace is the result of the inflammatory response and the beginning of a hyaline membrane made of “cellular debris.”,"1. Exudative: The first six to seven days comprise the exudative phase that begins with edema appearing in the interstitial walls seen here by the widened alveolar septum. Cellular debris can also be seen in the airspaces, and this can continue with the formation of the hyaline membranes that coat the alveolar surface (figure 5.3).","{'81fd3fe0-f6b1-4b2f-8f8b-91243a4d8699': '1.\xa0Exudative: The first six to seven\xa0days comprise the exudative phase that begins with edema appearing in the interstitial walls seen here by the widened alveolar septum. Cellular debris can also be seen in the airspaces, and this can continue with the formation\xa0of the hyaline membranes that coat the alveolar surface (figure 5.3).', 'd97bee38-539e-41c2-88f9-d40dec596de6': '2.\xa0Proliferative: In the early proliferative stage,\xa0there is increased cell infiltration and squamous metaplasia with proliferation of type II cells (figure 5.4), and these mitotic type II cells have a “hob-nail”\xa0like appearance over a time line of weeks. The infiltrating cells include fibroblasts that begin laying down collagen.', 'b43019e3-eb73-4f55-8900-49b4367dafee': '3.\xa0Fibrotic: Without resolution the patient may enter the third stage, fibrotic stage, that occurs over months (figure 5.5). This\xa0stage occurs much later and is a consequence of unresolved chronic inflammation. Diffuse fibrosis permanently obliterates normal lung architecture and may form cysts.'}"
Figure 5.4,pulmonary/images/Figure 5.4.jpg,Figure 5.4: Proliferation of type II cells and infiltration of fibroblasts in the proliferative phase of ARDS. A clear amount of debris in the airspace can be seen and forms a hyaline membrane that will impede gas exchange.,"2. Proliferative: In the early proliferative stage, there is increased cell infiltration and squamous metaplasia with proliferation of type II cells (figure 5.4), and these mitotic type II cells have a “hob-nail” like appearance over a time line of weeks. The infiltrating cells include fibroblasts that begin laying down collagen.","{'81fd3fe0-f6b1-4b2f-8f8b-91243a4d8699': '1.\xa0Exudative: The first six to seven\xa0days comprise the exudative phase that begins with edema appearing in the interstitial walls seen here by the widened alveolar septum. Cellular debris can also be seen in the airspaces, and this can continue with the formation\xa0of the hyaline membranes that coat the alveolar surface (figure 5.3).', 'd97bee38-539e-41c2-88f9-d40dec596de6': '2.\xa0Proliferative: In the early proliferative stage,\xa0there is increased cell infiltration and squamous metaplasia with proliferation of type II cells (figure 5.4), and these mitotic type II cells have a “hob-nail”\xa0like appearance over a time line of weeks. The infiltrating cells include fibroblasts that begin laying down collagen.', 'b43019e3-eb73-4f55-8900-49b4367dafee': '3.\xa0Fibrotic: Without resolution the patient may enter the third stage, fibrotic stage, that occurs over months (figure 5.5). This\xa0stage occurs much later and is a consequence of unresolved chronic inflammation. Diffuse fibrosis permanently obliterates normal lung architecture and may form cysts.'}"
Figure 5.5,pulmonary/images/Figure 5.5.jpg,Figure 5.5: Fibrotic stage of ARDS.,"3. Fibrotic: Without resolution the patient may enter the third stage, fibrotic stage, that occurs over months (figure 5.5). This stage occurs much later and is a consequence of unresolved chronic inflammation. Diffuse fibrosis permanently obliterates normal lung architecture and may form cysts.","{'81fd3fe0-f6b1-4b2f-8f8b-91243a4d8699': '1.\xa0Exudative: The first six to seven\xa0days comprise the exudative phase that begins with edema appearing in the interstitial walls seen here by the widened alveolar septum. Cellular debris can also be seen in the airspaces, and this can continue with the formation\xa0of the hyaline membranes that coat the alveolar surface (figure 5.3).', 'd97bee38-539e-41c2-88f9-d40dec596de6': '2.\xa0Proliferative: In the early proliferative stage,\xa0there is increased cell infiltration and squamous metaplasia with proliferation of type II cells (figure 5.4), and these mitotic type II cells have a “hob-nail”\xa0like appearance over a time line of weeks. The infiltrating cells include fibroblasts that begin laying down collagen.', 'b43019e3-eb73-4f55-8900-49b4367dafee': '3.\xa0Fibrotic: Without resolution the patient may enter the third stage, fibrotic stage, that occurs over months (figure 5.5). This\xa0stage occurs much later and is a consequence of unresolved chronic inflammation. Diffuse fibrosis permanently obliterates normal lung architecture and may form cysts.'}"
Figure 5.7,pulmonary/images/Figure 5.7.jpg,Figure 5.7: Diffuse bilateral densities associated with ARDS.,"Radiographic findings are an essential part of diagnosing the ARDS patient and will show diffuse bilateral interstitial and airspace densities caused by the edema (figure 5.7). Normal heart and vessel size and absence of pleural effusion distinguish ARDS from cardiogenic pulmonary edema. Although the x-ray gives the appearance of diffuse edema, high-resolution CT often shows that the process is heterogeneous and patchy. This heterogeneity is reflected by remnant patchy fibrosis if the patient recovers; however, the mortality rate for ARDS is around 50 percent.","{'4d0fb6e4-a76c-4d8b-a501-8e8dd45920f3': 'The onset of dyspnea usually occurs within one to two\xa0days after the initial injury, and as tachypnea arises, this symptom progressively worsens. Cough is common and may produce blood-tinged sputum. Findings on chest exam may be surprisingly scant, but some bronchial breath sounds and crackles may be heard.', '899da8e7-7c71-4f23-9158-a61a1da39096': 'As cyanosis becomes apparent, minute ventilation and dyspnea continue to increase\xa0and the patient will likely become distressed.', 'ce745529-8ee6-4ec7-8b21-bd5fce8cf006': 'A high ventilatory rate driven by the hypoxemia can produce hypocapnia and a respiratory alkalosis. The arterial pH can be complicated by the underlying disorder, and it is not uncommon for a mixed acid–base disorder to occur with concurrent respiratory alkalosis and metabolic acidosis. At the onset of respiratory failure arterial CO2\xa0will rise and produce a respiratory acidosis.', 'f8616bb2-6c63-4fc9-bf8a-9bcd12f1a732': 'Radiographic findings are an essential part of diagnosing the ARDS patient and will show diffuse bilateral interstitial and airspace densities caused by the edema (figure 5.7). Normal heart and vessel size and absence of pleural effusion distinguish ARDS from cardiogenic pulmonary edema. Although the x-ray gives the appearance of diffuse edema, high-resolution CT often shows that the process is heterogeneous and patchy. This heterogeneity is reflected by remnant patchy fibrosis if the patient recovers; however, the mortality rate for ARDS is around 50 percent.', 'b66d19ed-4bac-409b-900e-56e1916f41a5': 'So now you should have a clear understanding that after an initial insult to the lung an exaggerated and perpetual inflammatory response leads to the destruction of the alveolar–capillary interface. The resulting edema and hyaline membrane formation produces severe hypoxemia and a critically ill patient.'}"
Figure 4.1,pulmonary/images/Figure 4.1.jpg,Figure 4.1: Basic mechanism of interstitial lung disease.,"Now we will look at the generalized mechanism of interstitial lung disease (figure 4.1). It is worth noting that the numerous conditions that the term ILD encompasses have subtle differences in mechanism and manifestations, and these differences are what we will deal with elsewhere.","{'485f64ad-fa63-4fbf-8b74-59c779f369f8': 'Now we will look at the generalized mechanism of interstitial lung disease (figure 4.1). It is\xa0worth noting that the numerous conditions that the term ILD encompasses have subtle differences in mechanism and manifestations, and these differences are what we will deal with elsewhere.', '6288be73-5e03-483d-8f33-eb75f593ae7e': 'Generally though, ILD\xa0starts with an initial insult to the lung (#1, figure 4.1); the type of insult is a major contributor to the different ILD conditions. (It probably will not be what is depicted in figure 4.1, but if it was, it might lead to the inflammatory condition of tiefitis.)', '0d6d0d01-0c63-4bba-ae16-38598ec0bebd': 'There is then a response by neutrophils and alveolar macrophages (#2, figure 4.1). The macrophage response seems particularly important to the development of ILD. Release of cytokines (#3, figure 4.1) attracts other inflammatory cells, and the arrival of polymorphonuclear leukocytes and lymphocytes play an important role in disease instigation. These cells release cytokines, enzymes, and toxic oxygen radicals that damage and destroy local tissue. Released growth factors, such as TGF-Beta, instigate\xa0the transition of mesenchymal cells to fibroblasts.', '0930cfa0-06e6-4970-8ec3-ce8ab0031868': 'It is worth noting at this point that some forms of ILD are caused by an exaggerated immune reaction—either through an allergic-like response, or a direct immune disorder.', 'b95bc8bc-346f-4fba-875a-8acf17538a8e': 'The destruction of tissue and activity of a growing number of fibroblasts results in the inflamed interstitium becoming fibrosed with excess connective tissue, particularly collagen (#4, figure 4.1).'}"
Figure 4.1,pulmonary/images/Figure 4.1.jpg,Figure 4.1: Basic mechanism of interstitial lung disease.,"Now we will look at the generalized mechanism of interstitial lung disease (figure 4.1). It is worth noting that the numerous conditions that the term ILD encompasses have subtle differences in mechanism and manifestations, and these differences are what we will deal with elsewhere.","{'485f64ad-fa63-4fbf-8b74-59c779f369f8': 'Now we will look at the generalized mechanism of interstitial lung disease (figure 4.1). It is\xa0worth noting that the numerous conditions that the term ILD encompasses have subtle differences in mechanism and manifestations, and these differences are what we will deal with elsewhere.', '6288be73-5e03-483d-8f33-eb75f593ae7e': 'Generally though, ILD\xa0starts with an initial insult to the lung (#1, figure 4.1); the type of insult is a major contributor to the different ILD conditions. (It probably will not be what is depicted in figure 4.1, but if it was, it might lead to the inflammatory condition of tiefitis.)', '0d6d0d01-0c63-4bba-ae16-38598ec0bebd': 'There is then a response by neutrophils and alveolar macrophages (#2, figure 4.1). The macrophage response seems particularly important to the development of ILD. Release of cytokines (#3, figure 4.1) attracts other inflammatory cells, and the arrival of polymorphonuclear leukocytes and lymphocytes play an important role in disease instigation. These cells release cytokines, enzymes, and toxic oxygen radicals that damage and destroy local tissue. Released growth factors, such as TGF-Beta, instigate\xa0the transition of mesenchymal cells to fibroblasts.', '0930cfa0-06e6-4970-8ec3-ce8ab0031868': 'It is worth noting at this point that some forms of ILD are caused by an exaggerated immune reaction—either through an allergic-like response, or a direct immune disorder.', 'b95bc8bc-346f-4fba-875a-8acf17538a8e': 'The destruction of tissue and activity of a growing number of fibroblasts results in the inflamed interstitium becoming fibrosed with excess connective tissue, particularly collagen (#4, figure 4.1).'}"
Figure 4.1,pulmonary/images/Figure 4.1.jpg,Figure 4.1: Basic mechanism of interstitial lung disease.,"Now we will look at the generalized mechanism of interstitial lung disease (figure 4.1). It is worth noting that the numerous conditions that the term ILD encompasses have subtle differences in mechanism and manifestations, and these differences are what we will deal with elsewhere.","{'485f64ad-fa63-4fbf-8b74-59c779f369f8': 'Now we will look at the generalized mechanism of interstitial lung disease (figure 4.1). It is\xa0worth noting that the numerous conditions that the term ILD encompasses have subtle differences in mechanism and manifestations, and these differences are what we will deal with elsewhere.', '6288be73-5e03-483d-8f33-eb75f593ae7e': 'Generally though, ILD\xa0starts with an initial insult to the lung (#1, figure 4.1); the type of insult is a major contributor to the different ILD conditions. (It probably will not be what is depicted in figure 4.1, but if it was, it might lead to the inflammatory condition of tiefitis.)', '0d6d0d01-0c63-4bba-ae16-38598ec0bebd': 'There is then a response by neutrophils and alveolar macrophages (#2, figure 4.1). The macrophage response seems particularly important to the development of ILD. Release of cytokines (#3, figure 4.1) attracts other inflammatory cells, and the arrival of polymorphonuclear leukocytes and lymphocytes play an important role in disease instigation. These cells release cytokines, enzymes, and toxic oxygen radicals that damage and destroy local tissue. Released growth factors, such as TGF-Beta, instigate\xa0the transition of mesenchymal cells to fibroblasts.', '0930cfa0-06e6-4970-8ec3-ce8ab0031868': 'It is worth noting at this point that some forms of ILD are caused by an exaggerated immune reaction—either through an allergic-like response, or a direct immune disorder.', 'b95bc8bc-346f-4fba-875a-8acf17538a8e': 'The destruction of tissue and activity of a growing number of fibroblasts results in the inflamed interstitium becoming fibrosed with excess connective tissue, particularly collagen (#4, figure 4.1).'}"
Figure 4.2,pulmonary/images/Figure 4.2.jpg,"Figure 4.2: Changes in pulmonary histology (A, B) and gross anatomy (C) with interstitial lung disease.","The action of fibroblasts laying down connective tissue, combined with the destruction of alveolar and capillary structures, leads to a widening of airspaces with thick collagenous and infiltrated walls (figure 4.2A and 4.2B), which are a functionally significant departure from the ideal structure for gas exchange.","{'0c71ff29-d3ba-42a8-8fce-844052080d90': 'These changes in structure dramatically change the functional and mechanical properties of the tissue. The changes also tend to follow a characteristic pattern, although, as you might imagine, different conditions have subtle differences in pattern.', '2f7dba2a-3d57-4504-8aab-3a738a53efd2': 'The action of fibroblasts laying down connective tissue, combined with the destruction of alveolar and capillary structures, leads to a widening of airspaces with thick collagenous and infiltrated walls (figure 4.2A and 4.2B), which are a functionally significant departure from the ideal structure for gas exchange.', '6ca2500b-8328-4fa4-8dff-737e70c8af8d': 'The thickened basement membrane poses\xa0a significant obstacle to the transfer of gases, and the dense connective tissue stiffens the lung and thereby reduces its compliance. Combined with loss of capillary beds and airspace surface area,\xa0gas exchange is reduced.', 'caac64f9-dba5-4e86-981f-0c9bc3eb92d9': 'At the end of the disease the lung takes on a characteristic honeycomb appearance, and “ground glass\xa0opacities”\xa0are a hallmark sign on CT images (figure 4.2C). These morphological changes lead to pathophysiological consequences that are shared by most forms of the disease, as all cause varying degrees of\xa0interstitial inflammation and connective tissue deposition.'}"
Figure 4.3,pulmonary/images/Figure 4.3.jpg,Figure 4.3: Pathophysiological consequences of ILD.,"The first major issue is the reduced diffusion capacity of the involved areas, and all ILD patients demonstrate a reduced transfer factor, or DLCO (figure 4.3).","{'3c042458-99fe-4f55-985d-09fb29fe1eae': 'The first major issue is the reduced diffusion capacity of the involved areas, and all ILD patients demonstrate a reduced transfer factor, or DLCO (figure 4.3).', '34939227-a8c9-4d82-8cdf-b7a470753c69': 'Because of the heterogenous distribution of the disease, and the involvement of the pulmonary circulation, severe V/Q abnormalities arise throughout the lung. This and the reduced diffusion capacity result in hypoxemia. In the chronic disease state this may lead to cor pulmonale (figure 4.3).', '5f0a5066-7816-41f8-bb4b-d3e9611df59f': 'The reduction in lung compliance leads to a reduced lung volume. This is easily detected with spirometry as shown by the inner plot of the flow-volume loop in figure 4.3. Because\xa0FEV1\xa0and FVC are both reduced, the ratio frequently remains the same or may even rise; as such FEV1/FVC is a poor indicator of restrictive disease.', 'f1ec629d-7d66-4592-a222-c5466b6cea6d': 'The reduced lung volume and compliance results in a characteristic rapid, shallow breathing pattern as the patient tries to maintain alveolar ventilation (figure 4.3). However, while avoiding unnecessary increases in the work of breathing by not trying to over-expand the noncompliant lung, the rapid shallow breathing proportionally increases dead space ventilation.', 'c60ff515-57cc-465c-890f-8733b6745c07': 'The reduction in tidal volume, combined with a raised hypoxic drive to breathe, results in the cardinal symptom of ILD, which is dyspnea (figure 4.3).'}"
Figure 4.4,pulmonary/images/Figure 4.4.jpg,Figure 4.4: Classifications of ILD.,"Our major subcategory is idiopathic interstitial pneumonia (figure 4.4), or IIP, and this is divided again into six more useful categories that can be distinguished by history, time line, and histological changes. We will deal with these categories in this section, but it might be noted that usual interstitial pneumonia, still frequently called idiopathic pulmonary fibrosis, is the only one that remains untreatable, and early differentiation from the other forms is critical (figure 4.4).","{'ed9376b6-c726-4557-947d-0005c1a4e3cf': 'Our major subcategory is idiopathic interstitial pneumonia (figure 4.4), or IIP, and this is divided again into six\xa0more useful categories that can be distinguished by history, time line, and histological changes. We will deal with these categories in this section, but it might be noted that usual interstitial pneumonia, still frequently called idiopathic pulmonary fibrosis, is the only one that remains untreatable, and early differentiation from the other forms is critical (figure 4.4).', '08ab9220-0913-4a7d-8109-9a3caba0c7a8': 'Interstitial lung diseases can also be induced by numerous different environmental causes that produce nuanced conditions that are distinguishable by environmental and social history (figure 4.4) as well as specific histological features.', '27ff98b6-20f0-436a-8d91-d312ab01dd09': 'The characteristics of usual interstitial pneumonia have been covered in the “Basis of ILD”\xa0section, so let us\xa0start looking at the pathophysiological and clinical features of the other broader disease categories.'}"
Figure 4.5,pulmonary/images/Figure 4.5.jpg,Figure 4.5: Smoker’s macrophages occupying an airspace.,"The histological hallmark is accumulation of numerous smoker’s macrophages in the airspaces (figure 4.5) or the first- and second-order respiratory bronchioles. These macrophages have a characteristic brown pigmentation. In desquamative interstitial pneumonia the airspaces are the primary site of involvement, whereas a respiratory bronchiolitis–associated ILD sees more involvement of the bronchioles (as the name suggests). The alveolar septum may be thickened with infiltrate and there may be mild peribronchilor or alveolar fibrosis, but this does not result in a honeycomb pattern seen in usual interstitial pneumonia.","{'50787a16-ae6e-4bba-a29d-10236766ba20': 'We can deal with the first two together as both share common characteristics and are potentially the same disease occurring in different anatomical locations. Desquamative interstitial pneumonia and respiratory bronchiolitis–associated ILD are both smoking related and are relatively uncommon.', '91e53081-b90c-49bc-a7fb-9984fb280b67': 'The histological hallmark is accumulation of numerous smoker’s macrophages in the airspaces (figure 4.5) or the first- and second-order respiratory bronchioles. These macrophages have a characteristic brown pigmentation. In desquamative interstitial pneumonia the airspaces are the primary site of involvement, whereas a\xa0respiratory bronchiolitis–associated ILD sees more involvement of the bronchioles (as the name suggests). The alveolar septum may be thickened with infiltrate and there may be mild peribronchilor or alveolar fibrosis, but this does not result in a honeycomb pattern seen in usual interstitial pneumonia.', '59bb848d-4092-487d-adf4-e5a25c7cadcf': 'These ILDs\xa0are more prevalent in men, and are usually found in the fifth decade of life and after thirty-pack years. They are marked by the gradual and insidious onset of dyspnea, but lung reductions are usually minimal with both forms. The response to corticosteroid therapy and smoking cessation is good in about 80 percent\xa0of patients who remain stable or improve.'}"
Figure 4.7,pulmonary/images/Figure 4.7.jpg,Figure 4.7: Diffuse alveolar damage.,"The start is marked by a brief exudative phase with fluid entering the airspaces, but the following organizing or proliferative phase is what is usually seen by the time a biopsy is taken and where the similarities to ARDS are seen. The alveolar septa are thickened due to the interstitial edema and the septa may collapse or appose each other (figure 4.7). There is marked infiltration of the interstitial and airspaces by inflammatory cells, and type II cells proliferate. The destruction of the alveolar structure leaves a sludgy hyaline membrane of debris. Thrombi in small arteries may also be apparent.","{'17bb1651-8d8a-4b45-afc2-efd30c082a87': 'While the development of most interstitial lung diseases is slow and insidious, the hallmark of diffuse alveolar damage is rapid, occurring in a matter of days and often in previously healthy individuals. The manifestation of the disease is similar to acute respiratory distress syndrome, and in fact it has been suggested that DAD is a form of\xa0ARDS.', 'c57682e2-8ace-4639-8dc6-8b0d318ccbd1': 'The start is marked by a brief exudative phase with fluid entering the airspaces, but the following organizing or proliferative phase is what is usually seen by the time a biopsy is taken and where the similarities to ARDS are seen. The alveolar septa are thickened due to the interstitial edema and the septa may collapse or appose each other (figure 4.7). There is marked infiltration of the interstitial and airspaces by inflammatory cells, and type II cells proliferate. The destruction of the alveolar structure leaves a sludgy hyaline membrane of debris. Thrombi in small arteries may also be apparent.', '686812e2-4e59-41f6-b99c-c0510409912e': 'Should the patient survive (about 50 percent\xa0do not) the healing phase can show recovery of the alveolar structure with varying degrees of fibrosis. Many patients return to normal lung function, but a few show a progressive fibrotic process that resembles idiopathic pulmonary fibrosis.', '85e07c4e-5535-4942-9ac3-4df19764c6c7': 'Without biopsy, DAD is usually differentiated from other forms of interstitial disease by its rapid onset, but this can be confused with acute exacerbations of other diseases. However, the uniform pattern of damage in real DAD is representative of a single time line.'}"
Figure 4.8,pulmonary/images/Figure 4.8.jpg,Figure 4.8: Extremes of nonspecific interstitial pneumonia.,"Our next disease is at least courteous enough to only have one name, nonspecific interstitial pneumonia (NSIP), but irritatingly, it has three groups that are determined by the degree of either interstitial inflammation or fibrosis. Group 1 is primarily inflammation, group 2 involves inflammation and fibrosis, and group 3 is primarily fibrosis. The differences in groups are most clearly seen looking at the extremes—group 1 shows the puffy alveolar septa infiltrated with lymphocytes (left panel, figure 4.8), whereas group 3 shows a matrix of fibrosis that can be distinguished from usual interstitial pneumonia by the absence of fibroblastic foci and a homogenous onset and distribution (right panel, figure 4.8). As its name suggests, the distinguishing feature of nonspecific interstitial pneumonia is the lack of features that determine it to be something else. If that sounds a bit wishy-washy, take solace in the fact that even experts argue over its classification.","{'4f4b5176-7c16-47a4-b394-6d43d48321aa': 'Our next disease is at least courteous enough to only have one name, nonspecific interstitial pneumonia (NSIP), but irritatingly, it has three groups that are determined by the degree of either interstitial inflammation or\xa0fibrosis. Group 1 is primarily inflammation, group 2 involves inflammation and fibrosis, and group 3 is primarily fibrosis. The differences in groups are most clearly seen looking at the extremes—group 1 shows\xa0the puffy alveolar septa infiltrated with lymphocytes (left panel, figure 4.8), whereas group 3\xa0shows a matrix of fibrosis that can be distinguished from usual interstitial pneumonia by the absence of fibroblastic foci and a homogenous onset and distribution (right panel, figure 4.8). As its name suggests, the distinguishing feature of nonspecific interstitial pneumonia is the lack of features that determine it to be something else. If that sounds a bit wishy-washy, take solace in the fact that even experts argue over its classification.', 'f2b66fec-7e69-4784-9992-536c85ba1f51': 'The presence of lymphocytes in biopsy and bronchoalveolar lavage fluid suggests the involvement of the immune system in the pathogenesis of nonspecific interstitial pneumonia. This is supported by the occurrence of NSIP in immune diseases such as HIV infection\xa0and several connective tissue disorders including polymyositis, rheumatoid arthritis, and systemic sclerosis. Our understanding of the pathological mechanisms is still evolving.'}"
Figure 4.10,pulmonary/images/Figure 4.10.jpg,Figure 4.10: Silicotic nodule in the parenchyma of the lung.,"The pattern of collagen deposition is distinct, with silicotic nodules forming with concentric fibers producing a whirled pattern (figure 4.10). These nodules are distributed throughout the lung but are more common in the upper lobes and perihilar area (figure 4.11). They tend to be surrounded by distorted lung tissue that may show emphysematous changes. Ongoing disease coalescence of the nodules produces irregular masses of noncaseating granulomas. This progressive massive fibrosis can be helped with concurrent TB or atypical mycobacterial disease where caseating granulomas may also be present. Likewise silicosis may impair the macrophage response to TB. It causes contraction of the upper lobes and may lead to emphysema in the lower lobes, sometimes with large bullous changes. The pathophysiology of silicosis is summarized in figure 4.12.","{'32228d49-8d1c-4271-8ef0-75cbf93cb15f': 'Silicosis is related to exposure to silica that occurs frequently in occupations such as stone cutting, foundry work, and mining. Cutting or breaking stone can produce crystalline silica, and when less than 5 microns in diameter, it becomes respirable. When particle size is between 1 and 3\xa0microns, it can reach the alveoli.', 'b52f3881-27ab-47c1-bb26-ec221d70d180': 'The formation of silicosis can be acute with heavy brief exposure (often seen in sandblasters), or chronic and insidious with more prolonged lighter exposures. The process is initiated with alveolar macrophages engulfing the crystals. In response they release cytokines to attract lymphocytes, neutrophils, and fibroblasts—and a familiar story of tissue destruction and laying down of collagen begins. (You might note at this point that engulfing silica in vitro has been shown to damage macrophages,\xa0causing them to release their intracellular enzymes, which may contribute to the destructive mechanism in vivo.)', 'f072a2a0-20f4-4d5a-9f7a-84901c47f894': 'The pattern of collagen deposition is distinct, with silicotic nodules forming with concentric fibers producing a whirled pattern (figure 4.10). These nodules are distributed throughout the lung but are more common in the upper lobes and perihilar area (figure 4.11). They tend to be surrounded by distorted lung tissue that may show emphysematous changes. Ongoing disease coalescence of the nodules produces irregular masses of noncaseating granulomas. This progressive massive fibrosis can be helped with concurrent TB or atypical mycobacterial disease where caseating granulomas may also be present. Likewise silicosis may impair the macrophage response to TB. It causes contraction of the upper lobes and may lead to emphysema\xa0in the lower lobes, sometimes with large bullous changes. The pathophysiology of silicosis is summarized in figure 4.12.', 'db3a7449-a665-414c-9338-2d9268f62327': 'After an insidious, asymptomatic beginning, the main symptom of silicosis is dyspnea, with or without cough (cough is likely generated by concurrent smoking). The dyspnea is progressive but other symptoms that occur are often due to secondary, superimposed infection making repeated bacteriological studies important.', 'c2584430-2397-44fb-b8f1-d1715a340a30': 'The pathophysiology of silicosis is summarized in figure 4.12.'}"
Figure 4.12,pulmonary/images/Figure 4.12.jpg,Figure 4.12: The pathophysiology of silicosis.,The pathophysiology of silicosis is summarized in figure 4.12.,"{'32228d49-8d1c-4271-8ef0-75cbf93cb15f': 'Silicosis is related to exposure to silica that occurs frequently in occupations such as stone cutting, foundry work, and mining. Cutting or breaking stone can produce crystalline silica, and when less than 5 microns in diameter, it becomes respirable. When particle size is between 1 and 3\xa0microns, it can reach the alveoli.', 'b52f3881-27ab-47c1-bb26-ec221d70d180': 'The formation of silicosis can be acute with heavy brief exposure (often seen in sandblasters), or chronic and insidious with more prolonged lighter exposures. The process is initiated with alveolar macrophages engulfing the crystals. In response they release cytokines to attract lymphocytes, neutrophils, and fibroblasts—and a familiar story of tissue destruction and laying down of collagen begins. (You might note at this point that engulfing silica in vitro has been shown to damage macrophages,\xa0causing them to release their intracellular enzymes, which may contribute to the destructive mechanism in vivo.)', 'f072a2a0-20f4-4d5a-9f7a-84901c47f894': 'The pattern of collagen deposition is distinct, with silicotic nodules forming with concentric fibers producing a whirled pattern (figure 4.10). These nodules are distributed throughout the lung but are more common in the upper lobes and perihilar area (figure 4.11). They tend to be surrounded by distorted lung tissue that may show emphysematous changes. Ongoing disease coalescence of the nodules produces irregular masses of noncaseating granulomas. This progressive massive fibrosis can be helped with concurrent TB or atypical mycobacterial disease where caseating granulomas may also be present. Likewise silicosis may impair the macrophage response to TB. It causes contraction of the upper lobes and may lead to emphysema\xa0in the lower lobes, sometimes with large bullous changes. The pathophysiology of silicosis is summarized in figure 4.12.', 'db3a7449-a665-414c-9338-2d9268f62327': 'After an insidious, asymptomatic beginning, the main symptom of silicosis is dyspnea, with or without cough (cough is likely generated by concurrent smoking). The dyspnea is progressive but other symptoms that occur are often due to secondary, superimposed infection making repeated bacteriological studies important.', 'c2584430-2397-44fb-b8f1-d1715a340a30': 'The pathophysiology of silicosis is summarized in figure 4.12.'}"
Figure 4.13,pulmonary/images/Figure 4.13.jpg,Figure 4.13: Pathophysiology of asbestosis.,"The disease course (summarized in figure 4.13) is similar to that described for silicosis. Asbestos fibers arrive in the alveoli and macrophages initiate an inflammatory response. Note that the arrival of neutrophilic leukocytes and their release of cytokines and oxygen radicals seem to play a significant role. Short fibers can be phagocytized and removed, but larger fibers persist in the airway and perpetuate the inflammatory reaction, promoting fibrosis.","{'2ab10898-0cbd-4b8b-a680-b16e2a09947a': 'There are a number of pulmonary manifestations arising from exposure to asbestos. Previously used in the construction and manufacturing industries, the occurrence of related illness led to legislation to restrict its use. However, demolition or renovation of asbestos-containing buildings can still lead to air-born asbestos exposure. The pulmonary manifestations include pulmonary fibrosis, bronchogenic carcinoma, pleural effusion, pleural fibrosis, and mesothelioma. We will deal with the pulmonary fibrosis\xa0here and what is known as asbestosis.', '9164de85-0de6-4f9f-a42d-86c789adf3cc': 'The disease course (summarized in figure 4.13) is similar to that described for silicosis.\xa0Asbestos fibers arrive in the alveoli and macrophages initiate an inflammatory response. Note that the arrival of neutrophilic leukocytes and their release of cytokines and oxygen radicals seem to play a significant role. Short fibers can be phagocytized and removed, but larger fibers persist in the airway and\xa0perpetuate the inflammatory reaction, promoting fibrosis.', '20b818f5-a04d-473e-a4cf-a17b43be300c': 'Histologically, these fibers can been seen as asbestos bodies, or ferruginous bodies, as they are coated with iron-containing protein (figure 4.14).', '7d14e285-f52b-478d-a30d-2ae3074fbc5a': 'Fibrosis ensues, but in contrast to silicosis, asbestos-related fibrosis is nonnodular and mostly involves\xa0the lower lung fields and frequently includes pleural thickening.', '60ca387f-32f1-45fc-9f1e-42ea6f6a1e59': 'The extent of fibrosis is highly variable, from thickened alveolar septum to complete destruction of the alveolar spaces. In the advanced disease honeycomb lung can be observed with CT. Radiography of later-stage disease shows reticular interstitial markings in the lower lung fields (left panel, figure 4.15). Pleural changes are also more common. Rounded atelectasis may occur after a pleural effusion has been reabsorbed and caused a section of the airway to become trapped. A rounded atelectasis is indicated by the arrow in figure 4.15, and care should be taken not to mistake this for a neoplasm. Abestosis\xa0is a risk factor for the development of\xa0mesothelioma and should be considered for patients working in “at-risk”\xa0environments or occupations.'}"
Figure 4.14,pulmonary/images/Figure 4.14.jpg,Figure 4.14: Ferruginous bodies associated with asbestosis.,"Histologically, these fibers can been seen as asbestos bodies, or ferruginous bodies, as they are coated with iron-containing protein (figure 4.14).","{'2ab10898-0cbd-4b8b-a680-b16e2a09947a': 'There are a number of pulmonary manifestations arising from exposure to asbestos. Previously used in the construction and manufacturing industries, the occurrence of related illness led to legislation to restrict its use. However, demolition or renovation of asbestos-containing buildings can still lead to air-born asbestos exposure. The pulmonary manifestations include pulmonary fibrosis, bronchogenic carcinoma, pleural effusion, pleural fibrosis, and mesothelioma. We will deal with the pulmonary fibrosis\xa0here and what is known as asbestosis.', '9164de85-0de6-4f9f-a42d-86c789adf3cc': 'The disease course (summarized in figure 4.13) is similar to that described for silicosis.\xa0Asbestos fibers arrive in the alveoli and macrophages initiate an inflammatory response. Note that the arrival of neutrophilic leukocytes and their release of cytokines and oxygen radicals seem to play a significant role. Short fibers can be phagocytized and removed, but larger fibers persist in the airway and\xa0perpetuate the inflammatory reaction, promoting fibrosis.', '20b818f5-a04d-473e-a4cf-a17b43be300c': 'Histologically, these fibers can been seen as asbestos bodies, or ferruginous bodies, as they are coated with iron-containing protein (figure 4.14).', '7d14e285-f52b-478d-a30d-2ae3074fbc5a': 'Fibrosis ensues, but in contrast to silicosis, asbestos-related fibrosis is nonnodular and mostly involves\xa0the lower lung fields and frequently includes pleural thickening.', '60ca387f-32f1-45fc-9f1e-42ea6f6a1e59': 'The extent of fibrosis is highly variable, from thickened alveolar septum to complete destruction of the alveolar spaces. In the advanced disease honeycomb lung can be observed with CT. Radiography of later-stage disease shows reticular interstitial markings in the lower lung fields (left panel, figure 4.15). Pleural changes are also more common. Rounded atelectasis may occur after a pleural effusion has been reabsorbed and caused a section of the airway to become trapped. A rounded atelectasis is indicated by the arrow in figure 4.15, and care should be taken not to mistake this for a neoplasm. Abestosis\xa0is a risk factor for the development of\xa0mesothelioma and should be considered for patients working in “at-risk”\xa0environments or occupations.'}"
Figure 4.15,pulmonary/images/Figure 4.15.jpg,Figure 4.15: Radiographic findings in asbestosis.,"The extent of fibrosis is highly variable, from thickened alveolar septum to complete destruction of the alveolar spaces. In the advanced disease honeycomb lung can be observed with CT. Radiography of later-stage disease shows reticular interstitial markings in the lower lung fields (left panel, figure 4.15). Pleural changes are also more common. Rounded atelectasis may occur after a pleural effusion has been reabsorbed and caused a section of the airway to become trapped. A rounded atelectasis is indicated by the arrow in figure 4.15, and care should be taken not to mistake this for a neoplasm. Abestosis is a risk factor for the development of mesothelioma and should be considered for patients working in “at-risk” environments or occupations.","{'2ab10898-0cbd-4b8b-a680-b16e2a09947a': 'There are a number of pulmonary manifestations arising from exposure to asbestos. Previously used in the construction and manufacturing industries, the occurrence of related illness led to legislation to restrict its use. However, demolition or renovation of asbestos-containing buildings can still lead to air-born asbestos exposure. The pulmonary manifestations include pulmonary fibrosis, bronchogenic carcinoma, pleural effusion, pleural fibrosis, and mesothelioma. We will deal with the pulmonary fibrosis\xa0here and what is known as asbestosis.', '9164de85-0de6-4f9f-a42d-86c789adf3cc': 'The disease course (summarized in figure 4.13) is similar to that described for silicosis.\xa0Asbestos fibers arrive in the alveoli and macrophages initiate an inflammatory response. Note that the arrival of neutrophilic leukocytes and their release of cytokines and oxygen radicals seem to play a significant role. Short fibers can be phagocytized and removed, but larger fibers persist in the airway and\xa0perpetuate the inflammatory reaction, promoting fibrosis.', '20b818f5-a04d-473e-a4cf-a17b43be300c': 'Histologically, these fibers can been seen as asbestos bodies, or ferruginous bodies, as they are coated with iron-containing protein (figure 4.14).', '7d14e285-f52b-478d-a30d-2ae3074fbc5a': 'Fibrosis ensues, but in contrast to silicosis, asbestos-related fibrosis is nonnodular and mostly involves\xa0the lower lung fields and frequently includes pleural thickening.', '60ca387f-32f1-45fc-9f1e-42ea6f6a1e59': 'The extent of fibrosis is highly variable, from thickened alveolar septum to complete destruction of the alveolar spaces. In the advanced disease honeycomb lung can be observed with CT. Radiography of later-stage disease shows reticular interstitial markings in the lower lung fields (left panel, figure 4.15). Pleural changes are also more common. Rounded atelectasis may occur after a pleural effusion has been reabsorbed and caused a section of the airway to become trapped. A rounded atelectasis is indicated by the arrow in figure 4.15, and care should be taken not to mistake this for a neoplasm. Abestosis\xa0is a risk factor for the development of\xa0mesothelioma and should be considered for patients working in “at-risk”\xa0environments or occupations.'}"
Figure 4.16,pulmonary/images/Figure 4.16.jpg,Figure 4.16: Example of coal macules in simple CWP showing fibrosis and coal macules.,"Again we see the process start with phagocytosis of the coal dust by macrophages after the mucocillary escalator is overwhelmed. The macrophages launch their inflammatory process, and tissue damage is caused by the resultant cytokine bloom and oxygen radical and enzyme release. Fibroblasts form reticulin networks, but there is no significant collagen deposition. Aggregates of reticulin fibers, macrophages, and dust form coal macules (figure 4.16). The coal macules appear as black spots in lung sections and give rise to the condition’s nickname of “black lung.”","{'57b439a5-0b86-4157-85f8-33afd87605ff': 'CWP arises after prolonged exposure to coal dust. While drilling through rock the miner may be susceptible to silicosis, but prolonged and heavy exposure to aerosolized carbon (that is not\xa0usually fibrogenic in lesser exposures) can result in its own distinct condition. Even then it can take ten to twelve years of underground exposure to develop.', '830ca7d1-c3ed-4807-978c-783dda3ba844': 'Again we see the process start with phagocytosis of the coal dust by macrophages after the mucocillary escalator is overwhelmed. The macrophages launch their inflammatory process, and tissue damage is caused by the resultant cytokine bloom and oxygen radical and enzyme release. Fibroblasts form reticulin networks, but there is no significant collagen deposition. Aggregates of reticulin fibers, macrophages, and dust form coal macules (figure 4.16). The coal macules appear as black spots in lung sections\xa0and give rise to the condition’s nickname of “black lung.”', '486e98a7-1b80-4b9d-8880-2ac7031ec1ac': 'The coal macules are associated with dilation of the respiratory bronchioles that can manifest as focal centrilobar emphysema (figure 4.16). This is referred to as simple CWP, whereas the less common, complicated form involves progressive\xa0massive fibrosis, usually in the upper lobes, as in silicosis. However, in CWP these lesions are black and relatively homogenous, where as in silicosis they are a conglomeration of intersecting nodules. Figure 4.17\xa0shows a large black fibrotic lesion destroying the perihilar lung parenchyma.', '5e78f8d0-ca02-4c2d-8811-44c02d710618': 'Clinical manifestations are often complicated by concurrent cigarette smoking that may alone explain the frequency of chronic bronchitis in CWP patients. The simple form can be asymptomatic, but the complicated form produces dyspnea and\xa0signs of respiratory failures, pulmonary hypertension, and cor pulmonale.'}"
Figure 4.17,pulmonary/images/Figure 4.17.jpg,Figure 4.17: Large perihilar lesion in complicated CWP.,"The coal macules are associated with dilation of the respiratory bronchioles that can manifest as focal centrilobar emphysema (figure 4.16). This is referred to as simple CWP, whereas the less common, complicated form involves progressive massive fibrosis, usually in the upper lobes, as in silicosis. However, in CWP these lesions are black and relatively homogenous, where as in silicosis they are a conglomeration of intersecting nodules. Figure 4.17 shows a large black fibrotic lesion destroying the perihilar lung parenchyma.","{'57b439a5-0b86-4157-85f8-33afd87605ff': 'CWP arises after prolonged exposure to coal dust. While drilling through rock the miner may be susceptible to silicosis, but prolonged and heavy exposure to aerosolized carbon (that is not\xa0usually fibrogenic in lesser exposures) can result in its own distinct condition. Even then it can take ten to twelve years of underground exposure to develop.', '830ca7d1-c3ed-4807-978c-783dda3ba844': 'Again we see the process start with phagocytosis of the coal dust by macrophages after the mucocillary escalator is overwhelmed. The macrophages launch their inflammatory process, and tissue damage is caused by the resultant cytokine bloom and oxygen radical and enzyme release. Fibroblasts form reticulin networks, but there is no significant collagen deposition. Aggregates of reticulin fibers, macrophages, and dust form coal macules (figure 4.16). The coal macules appear as black spots in lung sections\xa0and give rise to the condition’s nickname of “black lung.”', '486e98a7-1b80-4b9d-8880-2ac7031ec1ac': 'The coal macules are associated with dilation of the respiratory bronchioles that can manifest as focal centrilobar emphysema (figure 4.16). This is referred to as simple CWP, whereas the less common, complicated form involves progressive\xa0massive fibrosis, usually in the upper lobes, as in silicosis. However, in CWP these lesions are black and relatively homogenous, where as in silicosis they are a conglomeration of intersecting nodules. Figure 4.17\xa0shows a large black fibrotic lesion destroying the perihilar lung parenchyma.', '5e78f8d0-ca02-4c2d-8811-44c02d710618': 'Clinical manifestations are often complicated by concurrent cigarette smoking that may alone explain the frequency of chronic bronchitis in CWP patients. The simple form can be asymptomatic, but the complicated form produces dyspnea and\xa0signs of respiratory failures, pulmonary hypertension, and cor pulmonale.'}"
Figure 4.18,pulmonary/images/Figure 4.18.jpg,Figure 4.18: Pathophysiology of berylliosis.,"Now we return to our pattern: the abundant CD4+ cells release proinflammatory cytokines and granulomatous fibrosis occurs (figure 4.18). The granulomas (figure 4.19) are indistinguishable from those caused by sarcoidosis (which are also caused by CD4+ cells), and many CBD patients may be misdiagnosed as sarcoidosis cases, so appropriate history taking is paramount. Usually CBD involves greater interstitial inflammation, but the most definitive diagnosis comes from the beryllium lymphocyte proliferation test. The test involves exposing lymphocytes from the patient’s blood or BAL fluid to different concentrations of beryllium and assaying their proliferation.","{'18d67239-f8dd-44ba-a54a-bd7b25e8113a': 'The last occupational disorder we will look at is berylliosis, or chronic beryllium disease (CBD), that occurs after exposure to beryllium, a metal used in manufacturing. Here the start to our story is a little different. Beryllium arrives in the airway and there is a hypersensitization of T cells. On subsequent exposures the T cells proliferate—the bronchoalveolar lavage (BAL) fluid of berylliosis patients is rich in sensitized CD4+ cells.', 'a71e1a5a-4ba3-4599-97ec-a55e8d32aa1e': 'Now we return to our pattern:\xa0the abundant CD4+ cells release proinflammatory cytokines and granulomatous fibrosis occurs (figure 4.18). The granulomas (figure 4.19) are indistinguishable from those caused by sarcoidosis (which are also caused by CD4+ cells), and many CBD patients may be misdiagnosed as sarcoidosis cases, so appropriate history taking is paramount. Usually CBD involves greater interstitial inflammation, but the most definitive diagnosis comes from the beryllium lymphocyte proliferation test. The test involves exposing lymphocytes from the patient’s blood or BAL fluid to different concentrations of beryllium and assaying their proliferation.', '793e99c6-587d-4319-b0be-1b2bd3dbae63': 'Susceptibility to becoming hypersensitized appears to have a significant genetic component. Why the process continues after exposure has stopped is unclear, but possibilities include a fundamental T cell disorder, or the fact that the insoluble beryllium causes apoptosis of macrophages, leading\xa0them to release a previously phagocytized beryllium load.', 'be30c734-8a28-4d0d-9a91-b90bf3f61f50': 'As the disease progresses, radiographic findings show that the granuoles can become more organized to produce fibrous nodules that may begin to impact lung function. The immune system involvement can produce hilar lymphadenopathy, and common later signs include interstital fibrosis and pleural thickening.'}"
Figure 3.1,pulmonary/images/Figure 3.1.jpg,Figure 3.1: Pathophysiology of acute bronchitis.,"Acute bronchitis often originates from a migrating upper airway infection, and hence the usual candidates for a URI are the pathogens associated with acute bronchitis, and most are viral but can include mycoplasma infection. Acute bronchitis can be caused by bacteria, but it is usually an opportunistic secondary infection by resident bacteria taking advantage of a weakened airway. Regardless of the pathogen, let us look at the sequence of pathophysiological events in acute bronchitis (figure 3.1).","{'e61c8ba1-f3e6-4190-862a-754314aecd49': 'Acute bronchitis often originates from a migrating upper airway infection, and hence the usual\xa0candidates for a URI are the pathogens associated with acute bronchitis, and most are viral\xa0but can include mycoplasma infection. Acute bronchitis can be caused by bacteria, but it is usually an opportunistic secondary infection by resident bacteria taking advantage of a weakened airway. Regardless of the pathogen, let us\xa0look at the sequence of pathophysiological events in acute bronchitis (figure 3.1).', '21f621b2-758a-44b4-b393-a22b8bf3f997': 'First the bronchial mucus membranes become inflamed. Taking a careful history\xa0can help you distinguish infectious causes from other instigators of airway inflammation, such as physical or chemical insults or an allergic response.\xa0The inflammation will initially produce a dry cough, but within two to three\xa0days bronchial secretions will be established,\xa0the cough will become productive, and rales can be heard over the site of the infection, which constitutes the clinical diagnosis.', '6038d957-953a-4829-b401-c34b0d6d4459': 'The inflamed airways may also become hyperreactive, and this may compound any concurrent allergic response or existing asthma resulting in bronchospasm and wheeze. See figure 3.1 for a summary.'}"
Figure 3.2,pulmonary/images/Figure 3.2.jpg,Figure 3.2: Histological and radiographic findings for an RSV infection. The left panel shows syncytial giant cells (circled). The right panel shows an x-ray of a child with RSV where densities folow bronchi and a flattened diaphragm.,"Infection starts in the nasopharynx and then progresses to the epithelium of the bronchioles that appears particularly susceptible to RSV infection. Immune cells are called to the area, but the predominant feature of the infection is the sloughing of the bronchiolar epithelium and the appearance of syncytial giant cells in the airway lumen, as seen in the insert of the histology slide in figure 3.2. With anatomically smaller bronchioles, infants are susceptible to this epithelial sludge blocking the airway. The hallmark of the infection reflects the obstructive nature of the disease with hyperinflation.","{'1de3847d-9228-4391-8a1e-61fb82d789a5': 'Penetrating deeper into the airway a pathogen can cause acute infectious bronchiolitis. By far the most common culprit is respiratory syncytial virus (RSV). This is the most common cause of lower airway infection in children under one year old and is estimated to cause more infant deaths than any other pathogen with the exception of malaria. While it can affect adults,\xa0it usually occurs only in the elderly and immunosuppressed patients.', '97215dbd-07f2-492e-a63c-bbcefb6af430': 'Infection starts in the nasopharynx and then progresses to the epithelium of the bronchioles that appears particularly susceptible to RSV infection. Immune cells are called to the area, but the predominant feature of the infection is the sloughing of the bronchiolar epithelium and the appearance of syncytial giant cells in the airway lumen, as seen in the insert of the histology slide in figure 3.2. With anatomically smaller bronchioles, infants are susceptible to this epithelial sludge blocking the airway. The hallmark of the infection reflects the obstructive nature of the disease with hyperinflation.', 'bd8e5ef5-b7b4-44f2-a158-2026b0e84aba': 'The young patient will likely present with a recent history of cough and hallmarks of shortness of breath such as use of accessory muscles. A scattered wheeze is likely, and in severe cases the child develops an expiratory grunt.', 'ee55f954-65e9-4b0a-b623-926f13541b01': 'Unresolved the RSV can spread to type 1 and 2 pneumocytes through cell-to-cell transmission. There is a high incidence of apnea associated with RSV infection, presumably due to the virus activating defensive reflexes associated with the larynx.'}"
Figure 3.3,pulmonary/images/Figure 3.3.jpg,"Figure 3.3: Neutrophils, bacteria, and exudate occupy airspaces in a typical pneumonia.","The pathogen arrives in the alveolar space causing activation of alveolar macrophages and recruitment of neutrophils from the bloodstream. These first responder cells release cytokines to attract more neutrophils and hyperpermeabilize the vasculature. Consequently the airspace becomes congested with pathogens, neutrophils, and exudate and incapable of being ventilated (figure 3.3). This produces V/Q mismatching in the effected area and the potential for the establishing of intrapulmonary shunts.","{'fba594d9-9875-4ed1-bfdf-0b867f9bafbe': 'Now we will look at the consequences of infection of the terminal airways and what is\xa0referred to as pneumonia. Although pneumonia can result from infection by one of any number of pathogens, we will first look at a generalized pathophysiological mechanism.', 'ecb4cda9-73d9-465b-a415-9e0b6f0a0216': 'The pathogen arrives in the alveolar space causing activation of alveolar macrophages and recruitment of neutrophils from the bloodstream. These first responder cells release cytokines to attract more neutrophils and hyperpermeabilize the vasculature. Consequently the airspace becomes congested with pathogens, neutrophils, and exudate and incapable\xa0of being ventilated (figure 3.3). This produces V/Q mismatching in the effected area and the potential for the establishing of\xa0intrapulmonary shunts.', '86998207-255c-4311-928a-b83dfc103fff': 'The infection may not be retained by the airway structure and can penetrate the pleural space, in which case an effusion is likely.', '505daa00-9d90-4d25-8a91-46ff01fb9606': 'The pneumonia-causing pathogen can often be found in blood analysis but the patient remains asymptomatic, but if the infection becomes more established significant signs and symptoms of bacteremia arise.', 'ac6216e8-fbc9-4370-bd3e-fa476d4658c9': 'An infection may lead to necrotized tissue and formation of an abscess in the lung. The prevalence of this is mostly dependent on the pathogen; for example, a tuberculosis infection is famous for causing walled-off abscesses (or granuloma) that try to contain the mycobacterium. These processes are summarized in figure 3.4.'}"
Figure 3.4,pulmonary/images/Figure 3.4.jpg,Figure 3.4: General pathophysiology of pneumonia.,"An infection may lead to necrotized tissue and formation of an abscess in the lung. The prevalence of this is mostly dependent on the pathogen; for example, a tuberculosis infection is famous for causing walled-off abscesses (or granuloma) that try to contain the mycobacterium. These processes are summarized in figure 3.4.","{'fba594d9-9875-4ed1-bfdf-0b867f9bafbe': 'Now we will look at the consequences of infection of the terminal airways and what is\xa0referred to as pneumonia. Although pneumonia can result from infection by one of any number of pathogens, we will first look at a generalized pathophysiological mechanism.', 'ecb4cda9-73d9-465b-a415-9e0b6f0a0216': 'The pathogen arrives in the alveolar space causing activation of alveolar macrophages and recruitment of neutrophils from the bloodstream. These first responder cells release cytokines to attract more neutrophils and hyperpermeabilize the vasculature. Consequently the airspace becomes congested with pathogens, neutrophils, and exudate and incapable\xa0of being ventilated (figure 3.3). This produces V/Q mismatching in the effected area and the potential for the establishing of\xa0intrapulmonary shunts.', '86998207-255c-4311-928a-b83dfc103fff': 'The infection may not be retained by the airway structure and can penetrate the pleural space, in which case an effusion is likely.', '505daa00-9d90-4d25-8a91-46ff01fb9606': 'The pneumonia-causing pathogen can often be found in blood analysis but the patient remains asymptomatic, but if the infection becomes more established significant signs and symptoms of bacteremia arise.', 'ac6216e8-fbc9-4370-bd3e-fa476d4658c9': 'An infection may lead to necrotized tissue and formation of an abscess in the lung. The prevalence of this is mostly dependent on the pathogen; for example, a tuberculosis infection is famous for causing walled-off abscesses (or granuloma) that try to contain the mycobacterium. These processes are summarized in figure 3.4.'}"
Figure 2.2,pulmonary/images/Figure 2.2.jpg,Figure 2.2: Pathophysiology of the common cold.,"Looking at the sequence of events involved in “getting a cold” (figure 2.2), we start with delivery of the pathogen to the upper airway and inoculation. The most common modes of delivery are hand-to-nose or hand-to-mouth contact or inhalation of aerosolized nasal fluid produced from a sneeze of an infected person. The causal virus is rarely found in saliva, so infection is spread from snot not spit.","{'93234398-69a1-4864-9f54-5418cb35f91b': 'Looking at the sequence of events involved in “getting a cold”\xa0(figure 2.2), we start with delivery of the pathogen to the upper airway and inoculation. The most common modes of delivery are hand-to-nose or hand-to-mouth contact or inhalation of aerosolized nasal fluid produced from a sneeze of an infected person. The causal virus is rarely found in saliva, so infection is spread from snot not spit.', 'd37b6aa6-f48f-4625-b3a4-2ecdb13824d4': 'Once in the upper airway, and if the pathogen can breach the innate defenses here (mucus and the mucociliary escalator), the virus attaches to, and then enters, the epithelial cells. In response, the invaded epithelial cells release cytokines to instigate an immune response. The primary cytokine released in this scenario is IL-8, which\xa0causes the attraction and accumulation of polymorphonuclear cells (PMN).', 'c2e4bd97-d89a-432b-bfb7-ebacb05d761c': 'It is the substantial increase in PMN cells that is responsible for most of the symptoms of a common cold—runny nose, postnasal drip, and other signs of epithelial inflammation.', '88424554-821d-4fd4-a30b-408bce446a9b': 'By far the most common cause of the common cold is the rhinovirus, followed by coronavirus and influenza, then less frequently by parainfluenza respiratory syncytial virus (RSV), and then rarely by adenovirus or enterovirus (table 2.1).', '3569c1e2-50a7-4653-83e2-246fef266886': 'Table 2.1: The viral pathogens.', 'e77d6cb6-3b21-4d89-afcf-f5d3ac3b7693': 'Seasonal differences (table 2.1) in the prevalence of these pathogens might help you identify the causal agent, but as the viral infections are self-limiting it is more important to ensure there is no bacterial involvement.', '9beb875c-6f9f-4efd-ba79-b48cb3ecb649': 'A viral infection can progress and cause more specific conditions than a cold, and these are identified by their location.'}"
Figure 2.3,pulmonary/images/Figure 2.3.jpg,Figure 2.3: An x-ray of the upper airway of a child suffering from tracheal croup. The arrow points to a narrowing of the trachea that produces a characteristic “steeple” sign as the constriction looks like the pointed steeple of a church building.,"Involvement of the larynx and subglottic airway will produce croup. There are numerous causes of croup and subclassifications depending on the region involved. Viral croup, like other forms, involves inflammation of the larynx that causes the airway to narrow. Edematous airway walls form an upper airway obstruction that produces stridor. Stridor is a crow-like airway sound, and the phase of breathing that it appears in can be helpful in determining the site of obstruction. Stridor during inspiration is indicative of airway collapse above the vocal cords (i.e., extrathoracic), and expiratory stridor suggests a tracheal or bronchial obstruction (i.e., intrathoracic). The constriction of the airway can be seen on x-ray when severe and the narrowing produces a characteristic “steeple” sign in the trachea (see figure 2.3).","{'52964135-ef76-4376-b7cf-88a0dbf15328': 'Involvement of the larynx and subglottic airway will produce croup. There are numerous causes of croup\xa0and subclassifications depending on the region involved. Viral croup, like other forms, involves inflammation of the larynx that causes the airway to narrow. Edematous airway walls form an upper airway obstruction that produces stridor. Stridor is a crow-like airway sound, and the phase of breathing that it appears in can be helpful in determining the site of obstruction. Stridor during inspiration is indicative of airway collapse above the vocal cords (i.e., extrathoracic), and expiratory stridor suggests a tracheal or bronchial obstruction (i.e., intrathoracic). The constriction of the airway can be seen on x-ray when severe and the narrowing produces a characteristic “steeple”\xa0sign in the trachea (see figure 2.3).'}"
Figure 2.4,pulmonary/images/Figure 2.4.jpg,Figure 2.4: Typical signs of “strep throat.”,"In terms of the upper airway it is the leading cause of tonsillopharyngitis in both adults and children. A sore throat may be accompanied by fever, headache, and vomiting. Inflamed tonsils and uvula may be coated in exudates, and palatal petechiae (figure 2.4) may be be present as well as a scarlatiniform rash. Symptoms resolve in three to five days, but antibiotic therapy should be used to reduce the risk of complications that include peritonsillar cellulitis, otitis media, sinusitis, and even acute rheumatic fever.","{'ebfbe95b-bedd-4fac-ac1f-5c74fd78055d': 'The pathogenic mechanisms of Group A Streptococcus are poorly understood—partly because of the numerous and complex ways it interacts with its human host. Its coat protects it from phagocytosis, antibody binding, and opsonization. It is capable of releasing a cocktail of cell-lysing toxins as well as pyrogenic exotoxins that:', '22b5f3a0-0ae4-4e40-ad22-f6114b7ea720': 'In terms of the upper airway it is the leading cause of tonsillopharyngitis in both adults and children. A sore throat may be accompanied by fever, headache, and vomiting. Inflamed tonsils and uvula\xa0may be coated in exudates, and palatal petechiae (figure 2.4) may be be present as well as\xa0a scarlatiniform rash. Symptoms resolve in three to five\xa0days, but antibiotic therapy should be used to reduce the risk of complications that include peritonsillar cellulitis, otitis media, sinusitis, and even acute rheumatic fever.'}"
Figure 2.5,pulmonary/images/Figure 2.5.jpg,Figure 2.5: Clinical signs of C. diphtheriae: pseudomembrane exudate (left) and bull neck (right).,"After inoculation, C. diphtheriae releases diphtheria exotoxin and enters the cell by exploiting a membrane receptor. Once inside, the exotoxin inactivates elongation factor 2, halting protein production and causing cell death. Occurrence of diphtheria is now rare in developed countries because of vaccination programs, but infection produces sore throat, swelling of cervical lymph glands, and low-grade fever. Most cases are tonsillopharyngeal where a pseudomembrane and exudate (figure 2.5) is produced that can spread to other areas. In severe cases the spread can lead to the bull neck of diphtheria (figure 2.5) as swelling and pseudomembranes accumulate and swallowing can become difficult. If the infection becomes systemic, cardiac, neural, and renal issues may arise, including myocarditis, local neuropathies, and in severe cases renal failure.","{'eb7578ba-a236-4c00-a201-cbae2fe28bd9': 'After inoculation, C. diphtheriae releases diphtheria exotoxin and enters the cell by exploiting a membrane receptor. Once inside, the exotoxin inactivates elongation factor 2, halting protein production and causing cell death. Occurrence of diphtheria is now rare in developed countries because of vaccination programs, but infection produces sore throat, swelling of cervical lymph glands, and low-grade fever. Most cases are tonsillopharyngeal where a pseudomembrane and exudate (figure 2.5) is produced that can spread to other areas. In severe cases the spread can lead to the bull neck of diphtheria (figure 2.5) as swelling and pseudomembranes accumulate and swallowing can become difficult. If the infection becomes systemic, cardiac, neural, and renal issues may arise, including myocarditis, local neuropathies, and in severe cases renal failure.'}"
Figure 1.1,pulmonary/images/Figure 1.1.jpg,Figure 1.1: Forms and prevalence of asthma.,"There are numerous underlying mechanisms of asthma (figure 1.1), and they may not be exclusive or independent within the same patient.","{'c95fa1fa-f9e3-450e-b56a-ad2feb79761c': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapters 13–14.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '46cbc4df-cf41-4ebf-99e9-0d40ac274b65': 'Table 8.1:\xa0Types of immune mechanisms involved in lung tissue injury. Includes Immune mechanism – type 1 by Kindred Grey from Internet archive (CC BY 4.0), Immune mechanism – type 2 by Kindred Grey from Internet archive (CC BY 4.0), Immune mechanism – type 3 by Kindred Grey from Internet archive (CC BY 4.0), and Immune mechanism – type 4 by Kindred Grey from Internet archive (CC BY 4.0).Figure 8.1: Acute phase of hypersensitivity pneumonitis. Mutleysmith. 2012. CC BY-SA 3.0. From WikimediaCommons.', '135b6718-449f-4a77-b8d5-731b7a7b5b9c': 'About 90 percent\xa0of PEs are caused by deep vein thrombi, but at least one of three main predisposing factors (Virchow’s triad)\xa0are present in a case of PE:', '682f75a3-5287-4893-b258-f8c47679450f': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapter 21.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '99ef9463-cb8b-4725-b750-3a5bfddf0607': 'West, John B. “Chapter 6: Vascular Diseases.” In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008.', 'cc05c711-e485-49f6-b7d0-98f4edb46105': 'Four major types of bronchogenic carcinoma can be distinguished by histology, epidemiology, clinical features, and prognosis. They are:', 'd412e5db-7af7-4ded-98bd-d3838d618392': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapter 20.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '5b90a401-f907-458e-acb6-06e6ef81186f': 'Table 6.1: Summary of forms of lung cancer. Includes Squamous Cell Carcinoma Lung 40x by Calicut\xa0Medical\xa0College\xa0from WikimediaCommons (CC BY-SA 4.0), Papillary adenocarcinoma of the lung — intermed mag by Nephron from WikimediaCommons (CC BY-SA 3.0), Large cell carcinoma of the lung by The Armed Forces Institute of Pathology (AFIP) from WikimediaCommons (Public domain), and Lung small cell carcinoma (1) by core needle biopsy by KGH from WikimediaCommons (CC BY-SA 3.0).', '56cdcda8-5410-4a9a-b9e0-4b3903d27c1a': 'There are about two hundred thousand cases of ARDS in the United States\xa0each year. Each case starts with an initial insult to the lung parenchyma and there are numerous examples of this instigating event, but the most common of these (and therefore worth remembering) are sepsis, pulmonary aspiration, and thoracic trauma. The insult can arrive from the airway, such as in pulmonary aspiration or smoke inhalation, or can arrive from the bloodstream, as in a fat embolism or blood-born pathogen.', '01bbc814-2276-4901-bc9f-9f07e914f0f3': 'Regardless of the insult’s route or indeed form, the ensuing pathological events are similar and lead to the same alteration of the lungs. What is initiated is a defensive inflammatory response, and what results is vascular endothelial and alveolar epithelial damage and a leaky alveolar capillary membrane.', 'a657cac1-87c9-4a34-a8b2-a3d673f6934b': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapter 27.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '5351bcef-c613-420f-a998-817912cb0590': 'West, John B. “Chapter 8: Respiratory Failure.” In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008.', '2bf2097e-c952-4e61-bdc7-c018fed73a0c': 'Before we start taking about diseases affecting the lung interstitium, let us\xa0remind ourselves of what it is.', '5a2ecb16-7483-4ecc-9625-a5985a2879c5': 'The interstitial tissue, sometimes referred to as parenchyma, surrounds\xa0the alveolar and capillary structures and contributes to the mechanical behavior of the lungs. The interstitium is extremely thin between the alveoli and capillaries, and forms the basement membrane through which gas exchange occurs. On the parenchymal\xa0side of the capillaries the interstitium is more substantial and is more involved in fluid exchange. There is also substantial amounts of interstitial tissue in the spaces around major vessels and airways, and it also makes up the interlobular septa.', '99cfc116-0672-4e5d-a968-44f58a5d1a46': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapters 12–15.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '643821d1-ed82-48c7-93e1-ebc504ed1987': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapter 3.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '85c596d0-c0f5-467f-b2ce-39e772dc507b': 'Table 3.1: Comparison of typical and atypical pneumonia. Includes Case 1 by Bell, D., Hacking, C., et al. from https://doi.org/10.53347/rID-68496\xa0(CC BY-NC-SA 3.0), Acute pneumonia – i — low mag by Nephron from WikimediaCommons (CC BY-SA 3.0), Case 2 by Paks, M., Knipe, H., et al. from https://doi.org/10.53347/rID-27535 (CC BY-NC-SA 3.0), and image 1 by Dr Patsy Lill from University of South Carolina School of Medicine’s\xa0Microbiologybook.org (Fair use).', 'b3d33b15-a961-4fcf-90af-d04139c33ca5': 'Table 3.2: Comparison of bronchopneumonia and lobar pneumonia. Includes Bronchopneumonia by Kindred Grey from Internet archive (CC BY 4.0), Lobar pneumonia by Kindred Grey from Internet archive (CC BY 4.0), X-ray of bronchopneumonia by Franquet T., Chung J.H. from WikimediaCommons (CC BY 4.0), Case 3 by Paks, M., Knipe, H., et al. from https://doi.org/10.53347/rID-26886\xa0(CC BY-NC-SA 3.0).', '7d48f651-5ec9-4c8c-8c1d-f8ac28654b61': 'As with most URIs the common\xa0cold is caused by a viral infection, and although there are several different viral candidates for causing a common cold, the pathophysiological mechanism and symptoms are the same regardless of the type. This is because it is the innate immune response, rather than the direct infection, that is responsible for most of the symptoms.', 'c9d5fd5e-55d3-44b1-94eb-4c180bbf3596': 'Thomas, Micah, and Paul A. Bomar. Upper Respiratory Tract Infection. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK532961, CC BY 4.0.', 'fc7ec5d0-c678-4556-971c-1fdf56177f67': 'There are numerous underlying mechanisms of asthma (figure 1.1), and they may not be exclusive or independent within the same patient.', '5257cee7-51ab-414b-b5ce-f379a71ee95f': 'We will also look at how exercise and certain pharmacological agents can produce asthma.', 'fbf759df-934f-4ba5-9987-deb818c57280': 'Allergenic asthma: Most allergic asthma is caused by the presence of an excessive amount of IgE (the hallmark antibody of an allergy). Formation of an immune complex between the antigen and the overexpressed IgE results in binding to surface receptors on mast cells and basophilic granulocytes,\xa0of which there are plenty in the lung. The IgE receptor binding results in the release of a cocktail of proinflammatory and airway-active substances. Some of these, including histamine and cytokines that attract eosinophils and neutrophils, are stored in vesicles of mast cells shown in figure 1.2. Others are produced on demand, including leukotrienes, and are derivatives of arachidonic acid (we will return to this later).', 'cbb9aaad-105e-4a3e-ac67-3afc2bac6e48': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapters 8–11.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '2fae69a4-a520-4df1-b51b-916b71d658bf': 'West, John B. “Chapter 4: Obstructive Diseases.” In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008.'}"
Figure 1.2,pulmonary/images/Figure 1.2.jpg,Figure 1.2: Example of a mast cell loaded with secretory granules.,"Allergenic asthma: Most allergic asthma is caused by the presence of an excessive amount of IgE (the hallmark antibody of an allergy). Formation of an immune complex between the antigen and the overexpressed IgE results in binding to surface receptors on mast cells and basophilic granulocytes, of which there are plenty in the lung. The IgE receptor binding results in the release of a cocktail of proinflammatory and airway-active substances. Some of these, including histamine and cytokines that attract eosinophils and neutrophils, are stored in vesicles of mast cells shown in figure 1.2. Others are produced on demand, including leukotrienes, and are derivatives of arachidonic acid (we will return to this later).","{'c95fa1fa-f9e3-450e-b56a-ad2feb79761c': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapters 13–14.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '46cbc4df-cf41-4ebf-99e9-0d40ac274b65': 'Table 8.1:\xa0Types of immune mechanisms involved in lung tissue injury. Includes Immune mechanism – type 1 by Kindred Grey from Internet archive (CC BY 4.0), Immune mechanism – type 2 by Kindred Grey from Internet archive (CC BY 4.0), Immune mechanism – type 3 by Kindred Grey from Internet archive (CC BY 4.0), and Immune mechanism – type 4 by Kindred Grey from Internet archive (CC BY 4.0).Figure 8.1: Acute phase of hypersensitivity pneumonitis. Mutleysmith. 2012. CC BY-SA 3.0. From WikimediaCommons.', '135b6718-449f-4a77-b8d5-731b7a7b5b9c': 'About 90 percent\xa0of PEs are caused by deep vein thrombi, but at least one of three main predisposing factors (Virchow’s triad)\xa0are present in a case of PE:', '682f75a3-5287-4893-b258-f8c47679450f': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapter 21.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '99ef9463-cb8b-4725-b750-3a5bfddf0607': 'West, John B. “Chapter 6: Vascular Diseases.” In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008.', 'cc05c711-e485-49f6-b7d0-98f4edb46105': 'Four major types of bronchogenic carcinoma can be distinguished by histology, epidemiology, clinical features, and prognosis. They are:', 'd412e5db-7af7-4ded-98bd-d3838d618392': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapter 20.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '5b90a401-f907-458e-acb6-06e6ef81186f': 'Table 6.1: Summary of forms of lung cancer. Includes Squamous Cell Carcinoma Lung 40x by Calicut\xa0Medical\xa0College\xa0from WikimediaCommons (CC BY-SA 4.0), Papillary adenocarcinoma of the lung — intermed mag by Nephron from WikimediaCommons (CC BY-SA 3.0), Large cell carcinoma of the lung by The Armed Forces Institute of Pathology (AFIP) from WikimediaCommons (Public domain), and Lung small cell carcinoma (1) by core needle biopsy by KGH from WikimediaCommons (CC BY-SA 3.0).', '56cdcda8-5410-4a9a-b9e0-4b3903d27c1a': 'There are about two hundred thousand cases of ARDS in the United States\xa0each year. Each case starts with an initial insult to the lung parenchyma and there are numerous examples of this instigating event, but the most common of these (and therefore worth remembering) are sepsis, pulmonary aspiration, and thoracic trauma. The insult can arrive from the airway, such as in pulmonary aspiration or smoke inhalation, or can arrive from the bloodstream, as in a fat embolism or blood-born pathogen.', '01bbc814-2276-4901-bc9f-9f07e914f0f3': 'Regardless of the insult’s route or indeed form, the ensuing pathological events are similar and lead to the same alteration of the lungs. What is initiated is a defensive inflammatory response, and what results is vascular endothelial and alveolar epithelial damage and a leaky alveolar capillary membrane.', 'a657cac1-87c9-4a34-a8b2-a3d673f6934b': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapter 27.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '5351bcef-c613-420f-a998-817912cb0590': 'West, John B. “Chapter 8: Respiratory Failure.” In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008.', '2bf2097e-c952-4e61-bdc7-c018fed73a0c': 'Before we start taking about diseases affecting the lung interstitium, let us\xa0remind ourselves of what it is.', '5a2ecb16-7483-4ecc-9625-a5985a2879c5': 'The interstitial tissue, sometimes referred to as parenchyma, surrounds\xa0the alveolar and capillary structures and contributes to the mechanical behavior of the lungs. The interstitium is extremely thin between the alveoli and capillaries, and forms the basement membrane through which gas exchange occurs. On the parenchymal\xa0side of the capillaries the interstitium is more substantial and is more involved in fluid exchange. There is also substantial amounts of interstitial tissue in the spaces around major vessels and airways, and it also makes up the interlobular septa.', '99cfc116-0672-4e5d-a968-44f58a5d1a46': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapters 12–15.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '643821d1-ed82-48c7-93e1-ebc504ed1987': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapter 3.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '85c596d0-c0f5-467f-b2ce-39e772dc507b': 'Table 3.1: Comparison of typical and atypical pneumonia. Includes Case 1 by Bell, D., Hacking, C., et al. from https://doi.org/10.53347/rID-68496\xa0(CC BY-NC-SA 3.0), Acute pneumonia – i — low mag by Nephron from WikimediaCommons (CC BY-SA 3.0), Case 2 by Paks, M., Knipe, H., et al. from https://doi.org/10.53347/rID-27535 (CC BY-NC-SA 3.0), and image 1 by Dr Patsy Lill from University of South Carolina School of Medicine’s\xa0Microbiologybook.org (Fair use).', 'b3d33b15-a961-4fcf-90af-d04139c33ca5': 'Table 3.2: Comparison of bronchopneumonia and lobar pneumonia. Includes Bronchopneumonia by Kindred Grey from Internet archive (CC BY 4.0), Lobar pneumonia by Kindred Grey from Internet archive (CC BY 4.0), X-ray of bronchopneumonia by Franquet T., Chung J.H. from WikimediaCommons (CC BY 4.0), Case 3 by Paks, M., Knipe, H., et al. from https://doi.org/10.53347/rID-26886\xa0(CC BY-NC-SA 3.0).', '7d48f651-5ec9-4c8c-8c1d-f8ac28654b61': 'As with most URIs the common\xa0cold is caused by a viral infection, and although there are several different viral candidates for causing a common cold, the pathophysiological mechanism and symptoms are the same regardless of the type. This is because it is the innate immune response, rather than the direct infection, that is responsible for most of the symptoms.', 'c9d5fd5e-55d3-44b1-94eb-4c180bbf3596': 'Thomas, Micah, and Paul A. Bomar. Upper Respiratory Tract Infection. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK532961, CC BY 4.0.', 'fc7ec5d0-c678-4556-971c-1fdf56177f67': 'There are numerous underlying mechanisms of asthma (figure 1.1), and they may not be exclusive or independent within the same patient.', '5257cee7-51ab-414b-b5ce-f379a71ee95f': 'We will also look at how exercise and certain pharmacological agents can produce asthma.', 'fbf759df-934f-4ba5-9987-deb818c57280': 'Allergenic asthma: Most allergic asthma is caused by the presence of an excessive amount of IgE (the hallmark antibody of an allergy). Formation of an immune complex between the antigen and the overexpressed IgE results in binding to surface receptors on mast cells and basophilic granulocytes,\xa0of which there are plenty in the lung. The IgE receptor binding results in the release of a cocktail of proinflammatory and airway-active substances. Some of these, including histamine and cytokines that attract eosinophils and neutrophils, are stored in vesicles of mast cells shown in figure 1.2. Others are produced on demand, including leukotrienes, and are derivatives of arachidonic acid (we will return to this later).', 'cbb9aaad-105e-4a3e-ac67-3afc2bac6e48': 'Farzan, Sattar, with Doris L. Hunsinger and Mary L. Phillips. “Chapters 8–11.” In A Concise Handbook of Respiratory Diseases. Reston, VA: Reston Publishing Company, 1978.', '2fae69a4-a520-4df1-b51b-916b71d658bf': 'West, John B. “Chapter 4: Obstructive Diseases.” In Pulmonary Pathophysiology: The Essentials, 7th ed. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2008.'}"
Figure 1.3,pulmonary/images/Figure 1.3.jpg,Figure 1.3: Vagal reflex of irritant airway receptors and the onset of asthma.,"Cholinergic asthma: Because it is open to the external environment, the airway has defensive, vagal reflexes (figure 1.3). An inappropriate exaggeration of some of these may lead to asthma. The basic reflex arch that ends with a cholinergic response begins with stimulation of airway irritant receptors in the epithelium. An afferent signal to the brainstem instigates an efferent signal to cause airway smooth muscle contraction and mucus secretion by glandular cells. The reflex also stimulates mast cells to release their cocktail, which includes histamine.","{'9403cfd2-ebde-42f9-a224-89717149c0c8': 'The results of this cocktail’s release are the hallmarks of asthma:', '63c4f3fd-ee46-4636-86bd-254ef135edf6': 'The timeline\xa0from the exposure to the antigen to asthmatic response is not straightforward. A response may occur within minutes (“early response”), or\xa0hours later (“late response”). Some patients show only an early response, some only a late one, and some show both in a “dual”\xa0response. The late response may correspond to the arrival of leucocytes in response to the initial release of cytokines. It may also be due to a\xa0mild stimulus arriving later in an airway that was sensitized earlier.', '5ae6e870-08ae-4364-8f65-65722fd3bbf1': 'Cholinergic asthma:\xa0Because\xa0it is open to the external environment, the airway has defensive, vagal reflexes (figure 1.3). An inappropriate exaggeration of some of these may lead to asthma. The basic reflex arch that ends with a cholinergic response begins with stimulation of airway irritant receptors in the epithelium. An afferent signal to the brainstem instigates an efferent signal to cause airway smooth muscle contraction and mucus secretion by glandular cells. The reflex also stimulates mast cells to release their cocktail, which includes histamine.', '302d3114-64ae-41b8-8183-aca19772daa3': 'The released histamine stimulates the airway receptors, setting up the potential for a positive feedback loop and perpetuating the cycle of bronchoconstriction and secretion. The histamine also\xa0stimulates bronchoconstriction through its direct action on the smooth muscle as well as sensitizing the smooth muscle to further vagal stimulation. These processes are summarized in figure 1.3.', '3fd37337-9e1e-405b-a12d-12309bb29ada': 'The cholinergic response may help produce an asthmatic response to another stimulus that normally would not have produced\xa0one\xa0(i.e., it may play a part in the hypersensitivity of the asthmatic airways). Likewise, the presence of an infection, particularly a viral infection,\xa0may place the airway in a proinflammatory state.', '8a63cccf-ca7b-410b-a20c-45c4d45b3743': 'Neural airway control may also contribute to the high prevalence of nocturnal asthma, as during rest when the airways are predominantly under parasympathetic control. But other factors\xa0(summarized in figure 1.4) may contribute:', '7fb4e653-c7a8-4681-b61d-029242e94098': 'Exercise-induced asthma: Although exercise is associated with increased airway caliber, it can also induce asthma. Increased airway flow to meet the increased metabolic demand of exercise results in loss of fluid and heat from airway surfaces. This leaves the peribronchial fluid in a hypertonic state and causes excitation of the irritant airway receptors, which\xa0leads to release of the mast cells’ cocktail.', '65f28ac8-49a8-498c-b6bb-2bfa734c1f6e': 'Exercise-induced asthma is more prevalent in cold (i.e. dry air) where water loss will be higher, so occurs more in sports such as cross-country skiing than swimming in a warm humid environment. Bronchoconstriction usually occurs when exercise stops—when the protective effect of sympathetic activity to the airway smooth muscles ceases.', 'a09ded15-2746-415c-a59c-bbbda3c9bb0e': 'Drug-induced asthma: There are several pharmaceutical and food products that can promote asthma, including tartrazine (a yellow food coloring) and sulfides used as food preservatives. Additionally,\xa010 to 20 percent\xa0of asthmatics are sensitive to aspirin.', '210444a3-7639-4c7d-a3c6-2ccacaada374': 'Recall that some of the on-demand components of the mast cell’s cocktail were derived from arachidonic acid.\xa0There are two pertinent pathways in which arachidonic acid is used:\xa0the lipoxygenase pathway and the cyclooxygenase pathway (figure 1.5). The first leads to the production of leukotrienes, which are potent bronchoconstrictors. The second leads to the production of prostaglandins and thromboxane. Normally the distribution of arachidonic acid down these pathways is balanced to meet demand. However, NSAIDS such as aspirin are COX 2 inhibitors and block the cyclooxygenase route, leaving more substrate for the lipoxygenase pathway and production of leukotrienes (figure 1.5) with their bronchoconstrictive effect.', '6455b9cb-3f00-467a-9e70-4d28360886e5': 'Environmental/occupational asthma: As the airway is open to the environment, it is susceptible to inhaled substances that can cause sensitization; there are over two hundred\xa0substances known to cause asthma, both organic and inorganic. Some common ones are listed below.', '047df8a3-3958-4a52-a01f-7b69cc7475ff': 'Table 1.1: Some of the most common environmental causes of asthma. Taking a\xa0pulmonary history should include asking about potential environmental exposures.', '5b3bd0da-eb35-4624-b0a3-d90f9074bb62': 'Determining whether airway hypersensitivity is due to environmental factors is complicated by\xa0widely varying latency periods. Short latency periods can be as brief as twenty-four\xa0hours and are associated with vapor or smoke exposure that does not cause an immunological response. Longer latency periods that may last years are more commonly associated with an immunological response to large particles that act like antigens.', 'e0159ef2-2eec-4bae-836c-8c9b1b80a7dc': 'The situation is further confused by occupation-related responses, which often cause the airway to become more sensitive to some of the other causes of asthma covered here. This\xa0makes\xa0the role of an environmental factor more difficult to determine.'}"
Figure 1.4,pulmonary/images/Figure 1.4.jpg,Figure 1.4: Factors promoting asthma at night.,"Neural airway control may also contribute to the high prevalence of nocturnal asthma, as during rest when the airways are predominantly under parasympathetic control. But other factors (summarized in figure 1.4) may contribute:","{'9403cfd2-ebde-42f9-a224-89717149c0c8': 'The results of this cocktail’s release are the hallmarks of asthma:', '63c4f3fd-ee46-4636-86bd-254ef135edf6': 'The timeline\xa0from the exposure to the antigen to asthmatic response is not straightforward. A response may occur within minutes (“early response”), or\xa0hours later (“late response”). Some patients show only an early response, some only a late one, and some show both in a “dual”\xa0response. The late response may correspond to the arrival of leucocytes in response to the initial release of cytokines. It may also be due to a\xa0mild stimulus arriving later in an airway that was sensitized earlier.', '5ae6e870-08ae-4364-8f65-65722fd3bbf1': 'Cholinergic asthma:\xa0Because\xa0it is open to the external environment, the airway has defensive, vagal reflexes (figure 1.3). An inappropriate exaggeration of some of these may lead to asthma. The basic reflex arch that ends with a cholinergic response begins with stimulation of airway irritant receptors in the epithelium. An afferent signal to the brainstem instigates an efferent signal to cause airway smooth muscle contraction and mucus secretion by glandular cells. The reflex also stimulates mast cells to release their cocktail, which includes histamine.', '302d3114-64ae-41b8-8183-aca19772daa3': 'The released histamine stimulates the airway receptors, setting up the potential for a positive feedback loop and perpetuating the cycle of bronchoconstriction and secretion. The histamine also\xa0stimulates bronchoconstriction through its direct action on the smooth muscle as well as sensitizing the smooth muscle to further vagal stimulation. These processes are summarized in figure 1.3.', '3fd37337-9e1e-405b-a12d-12309bb29ada': 'The cholinergic response may help produce an asthmatic response to another stimulus that normally would not have produced\xa0one\xa0(i.e., it may play a part in the hypersensitivity of the asthmatic airways). Likewise, the presence of an infection, particularly a viral infection,\xa0may place the airway in a proinflammatory state.', '8a63cccf-ca7b-410b-a20c-45c4d45b3743': 'Neural airway control may also contribute to the high prevalence of nocturnal asthma, as during rest when the airways are predominantly under parasympathetic control. But other factors\xa0(summarized in figure 1.4) may contribute:', '7fb4e653-c7a8-4681-b61d-029242e94098': 'Exercise-induced asthma: Although exercise is associated with increased airway caliber, it can also induce asthma. Increased airway flow to meet the increased metabolic demand of exercise results in loss of fluid and heat from airway surfaces. This leaves the peribronchial fluid in a hypertonic state and causes excitation of the irritant airway receptors, which\xa0leads to release of the mast cells’ cocktail.', '65f28ac8-49a8-498c-b6bb-2bfa734c1f6e': 'Exercise-induced asthma is more prevalent in cold (i.e. dry air) where water loss will be higher, so occurs more in sports such as cross-country skiing than swimming in a warm humid environment. Bronchoconstriction usually occurs when exercise stops—when the protective effect of sympathetic activity to the airway smooth muscles ceases.', 'a09ded15-2746-415c-a59c-bbbda3c9bb0e': 'Drug-induced asthma: There are several pharmaceutical and food products that can promote asthma, including tartrazine (a yellow food coloring) and sulfides used as food preservatives. Additionally,\xa010 to 20 percent\xa0of asthmatics are sensitive to aspirin.', '210444a3-7639-4c7d-a3c6-2ccacaada374': 'Recall that some of the on-demand components of the mast cell’s cocktail were derived from arachidonic acid.\xa0There are two pertinent pathways in which arachidonic acid is used:\xa0the lipoxygenase pathway and the cyclooxygenase pathway (figure 1.5). The first leads to the production of leukotrienes, which are potent bronchoconstrictors. The second leads to the production of prostaglandins and thromboxane. Normally the distribution of arachidonic acid down these pathways is balanced to meet demand. However, NSAIDS such as aspirin are COX 2 inhibitors and block the cyclooxygenase route, leaving more substrate for the lipoxygenase pathway and production of leukotrienes (figure 1.5) with their bronchoconstrictive effect.', '6455b9cb-3f00-467a-9e70-4d28360886e5': 'Environmental/occupational asthma: As the airway is open to the environment, it is susceptible to inhaled substances that can cause sensitization; there are over two hundred\xa0substances known to cause asthma, both organic and inorganic. Some common ones are listed below.', '047df8a3-3958-4a52-a01f-7b69cc7475ff': 'Table 1.1: Some of the most common environmental causes of asthma. Taking a\xa0pulmonary history should include asking about potential environmental exposures.', '5b3bd0da-eb35-4624-b0a3-d90f9074bb62': 'Determining whether airway hypersensitivity is due to environmental factors is complicated by\xa0widely varying latency periods. Short latency periods can be as brief as twenty-four\xa0hours and are associated with vapor or smoke exposure that does not cause an immunological response. Longer latency periods that may last years are more commonly associated with an immunological response to large particles that act like antigens.', 'e0159ef2-2eec-4bae-836c-8c9b1b80a7dc': 'The situation is further confused by occupation-related responses, which often cause the airway to become more sensitive to some of the other causes of asthma covered here. This\xa0makes\xa0the role of an environmental factor more difficult to determine.'}"
Figure 1.5,pulmonary/images/Figure 1.5.jpg,"Figure 1.5: NSAIDS, including aspirin, shift metabolism of arachidonic acid toward bronchoconstrictive leukotrienes.","Recall that some of the on-demand components of the mast cell’s cocktail were derived from arachidonic acid. There are two pertinent pathways in which arachidonic acid is used: the lipoxygenase pathway and the cyclooxygenase pathway (figure 1.5). The first leads to the production of leukotrienes, which are potent bronchoconstrictors. The second leads to the production of prostaglandins and thromboxane. Normally the distribution of arachidonic acid down these pathways is balanced to meet demand. However, NSAIDS such as aspirin are COX 2 inhibitors and block the cyclooxygenase route, leaving more substrate for the lipoxygenase pathway and production of leukotrienes (figure 1.5) with their bronchoconstrictive effect.","{'9403cfd2-ebde-42f9-a224-89717149c0c8': 'The results of this cocktail’s release are the hallmarks of asthma:', '63c4f3fd-ee46-4636-86bd-254ef135edf6': 'The timeline\xa0from the exposure to the antigen to asthmatic response is not straightforward. A response may occur within minutes (“early response”), or\xa0hours later (“late response”). Some patients show only an early response, some only a late one, and some show both in a “dual”\xa0response. The late response may correspond to the arrival of leucocytes in response to the initial release of cytokines. It may also be due to a\xa0mild stimulus arriving later in an airway that was sensitized earlier.', '5ae6e870-08ae-4364-8f65-65722fd3bbf1': 'Cholinergic asthma:\xa0Because\xa0it is open to the external environment, the airway has defensive, vagal reflexes (figure 1.3). An inappropriate exaggeration of some of these may lead to asthma. The basic reflex arch that ends with a cholinergic response begins with stimulation of airway irritant receptors in the epithelium. An afferent signal to the brainstem instigates an efferent signal to cause airway smooth muscle contraction and mucus secretion by glandular cells. The reflex also stimulates mast cells to release their cocktail, which includes histamine.', '302d3114-64ae-41b8-8183-aca19772daa3': 'The released histamine stimulates the airway receptors, setting up the potential for a positive feedback loop and perpetuating the cycle of bronchoconstriction and secretion. The histamine also\xa0stimulates bronchoconstriction through its direct action on the smooth muscle as well as sensitizing the smooth muscle to further vagal stimulation. These processes are summarized in figure 1.3.', '3fd37337-9e1e-405b-a12d-12309bb29ada': 'The cholinergic response may help produce an asthmatic response to another stimulus that normally would not have produced\xa0one\xa0(i.e., it may play a part in the hypersensitivity of the asthmatic airways). Likewise, the presence of an infection, particularly a viral infection,\xa0may place the airway in a proinflammatory state.', '8a63cccf-ca7b-410b-a20c-45c4d45b3743': 'Neural airway control may also contribute to the high prevalence of nocturnal asthma, as during rest when the airways are predominantly under parasympathetic control. But other factors\xa0(summarized in figure 1.4) may contribute:', '7fb4e653-c7a8-4681-b61d-029242e94098': 'Exercise-induced asthma: Although exercise is associated with increased airway caliber, it can also induce asthma. Increased airway flow to meet the increased metabolic demand of exercise results in loss of fluid and heat from airway surfaces. This leaves the peribronchial fluid in a hypertonic state and causes excitation of the irritant airway receptors, which\xa0leads to release of the mast cells’ cocktail.', '65f28ac8-49a8-498c-b6bb-2bfa734c1f6e': 'Exercise-induced asthma is more prevalent in cold (i.e. dry air) where water loss will be higher, so occurs more in sports such as cross-country skiing than swimming in a warm humid environment. Bronchoconstriction usually occurs when exercise stops—when the protective effect of sympathetic activity to the airway smooth muscles ceases.', 'a09ded15-2746-415c-a59c-bbbda3c9bb0e': 'Drug-induced asthma: There are several pharmaceutical and food products that can promote asthma, including tartrazine (a yellow food coloring) and sulfides used as food preservatives. Additionally,\xa010 to 20 percent\xa0of asthmatics are sensitive to aspirin.', '210444a3-7639-4c7d-a3c6-2ccacaada374': 'Recall that some of the on-demand components of the mast cell’s cocktail were derived from arachidonic acid.\xa0There are two pertinent pathways in which arachidonic acid is used:\xa0the lipoxygenase pathway and the cyclooxygenase pathway (figure 1.5). The first leads to the production of leukotrienes, which are potent bronchoconstrictors. The second leads to the production of prostaglandins and thromboxane. Normally the distribution of arachidonic acid down these pathways is balanced to meet demand. However, NSAIDS such as aspirin are COX 2 inhibitors and block the cyclooxygenase route, leaving more substrate for the lipoxygenase pathway and production of leukotrienes (figure 1.5) with their bronchoconstrictive effect.', '6455b9cb-3f00-467a-9e70-4d28360886e5': 'Environmental/occupational asthma: As the airway is open to the environment, it is susceptible to inhaled substances that can cause sensitization; there are over two hundred\xa0substances known to cause asthma, both organic and inorganic. Some common ones are listed below.', '047df8a3-3958-4a52-a01f-7b69cc7475ff': 'Table 1.1: Some of the most common environmental causes of asthma. Taking a\xa0pulmonary history should include asking about potential environmental exposures.', '5b3bd0da-eb35-4624-b0a3-d90f9074bb62': 'Determining whether airway hypersensitivity is due to environmental factors is complicated by\xa0widely varying latency periods. Short latency periods can be as brief as twenty-four\xa0hours and are associated with vapor or smoke exposure that does not cause an immunological response. Longer latency periods that may last years are more commonly associated with an immunological response to large particles that act like antigens.', 'e0159ef2-2eec-4bae-836c-8c9b1b80a7dc': 'The situation is further confused by occupation-related responses, which often cause the airway to become more sensitive to some of the other causes of asthma covered here. This\xa0makes\xa0the role of an environmental factor more difficult to determine.'}"
Figure 1.6,pulmonary/images/Figure 1.6.jpg,"Figure 1.6: Illustrations of normal (A), mildly asthmatic (B), and severely asthmatic (C) airways.","With numerous and maybe concurrent mechanisms, what does asthma look like in the airway? The normal lumen of the airway has a relatively lower resistance, as depicted in panel A of figure 1.6, but in mild asthma the lumen is narrowed (thereby raising resistance to airflow) through swelling of the airway wall, contraction of airway smooth muscle, and blockage (or plugging) of the airway by increased mucus secretion (figure 1.6B). This worsens in more severe asthma until the lumen can be extremely narrow (figure 1.6C) or even completely blocked.","{'097ec5df-dd0e-408e-a729-5850a903e263': 'With numerous and maybe concurrent mechanisms, what does asthma look like in the airway?\xa0The normal lumen of the airway has a relatively lower resistance, as depicted in panel A of figure 1.6, but in mild asthma the lumen is narrowed (thereby raising resistance to airflow) through swelling of the airway wall, contraction of airway smooth muscle, and blockage (or plugging) of the airway by increased mucus secretion (figure 1.6B). This worsens in more severe asthma until the lumen can be extremely narrow (figure 1.6C) or even completely blocked.', 'c47f79de-4ee0-4513-8306-9f155e88c752': 'Other characteristics of asthma include the presence of eosinophillic that infiltrate into the airway walls. The eosinophil enzymes also leave a telltale sign: Charcot–Leyden crystals, as shown in the circled area\xa0of figure 1.7A.', '65a1b979-d155-41e2-9cca-a8018cbe9cb8': 'The sputum of the asthmatic may also contain Curshman’s spirals (figure 1.7B), which\xa0are casts of small bronchioles consisting of mucus and shed epithelial cells. However, Curshman’s spirals are not exclusive to asthma.', '92854127-014f-41fd-a517-c1814b0aafbb': 'With persistent asthma the airway undergoes remodeling (figure 1.8), with thickening of the airway wall and basement membrane, enlarged submucosal glands, and hypertrophy and hyperplasia of airway smooth muscle.'}"
Figure 1.7,pulmonary/images/Figure 1.7.jpg,"Figure 1.7: Histological signs of asthma: A = Charcot–Leyden crystals, B = Curshman’s spirals.","Other characteristics of asthma include the presence of eosinophillic that infiltrate into the airway walls. The eosinophil enzymes also leave a telltale sign: Charcot–Leyden crystals, as shown in the circled area of figure 1.7A.","{'097ec5df-dd0e-408e-a729-5850a903e263': 'With numerous and maybe concurrent mechanisms, what does asthma look like in the airway?\xa0The normal lumen of the airway has a relatively lower resistance, as depicted in panel A of figure 1.6, but in mild asthma the lumen is narrowed (thereby raising resistance to airflow) through swelling of the airway wall, contraction of airway smooth muscle, and blockage (or plugging) of the airway by increased mucus secretion (figure 1.6B). This worsens in more severe asthma until the lumen can be extremely narrow (figure 1.6C) or even completely blocked.', 'c47f79de-4ee0-4513-8306-9f155e88c752': 'Other characteristics of asthma include the presence of eosinophillic that infiltrate into the airway walls. The eosinophil enzymes also leave a telltale sign: Charcot–Leyden crystals, as shown in the circled area\xa0of figure 1.7A.', '65a1b979-d155-41e2-9cca-a8018cbe9cb8': 'The sputum of the asthmatic may also contain Curshman’s spirals (figure 1.7B), which\xa0are casts of small bronchioles consisting of mucus and shed epithelial cells. However, Curshman’s spirals are not exclusive to asthma.', '92854127-014f-41fd-a517-c1814b0aafbb': 'With persistent asthma the airway undergoes remodeling (figure 1.8), with thickening of the airway wall and basement membrane, enlarged submucosal glands, and hypertrophy and hyperplasia of airway smooth muscle.'}"
Figure 1.8,pulmonary/images/Figure 1.8.jpg,"Figure 1.8: Components of airway remodeling in persistent asthma. The epithelium in asthma shows mucous hyperplasia and hypersecretion (gray), and significant basement membrane thickening. Smooth muscle volume is also increased in asthma.","With persistent asthma the airway undergoes remodeling (figure 1.8), with thickening of the airway wall and basement membrane, enlarged submucosal glands, and hypertrophy and hyperplasia of airway smooth muscle.","{'097ec5df-dd0e-408e-a729-5850a903e263': 'With numerous and maybe concurrent mechanisms, what does asthma look like in the airway?\xa0The normal lumen of the airway has a relatively lower resistance, as depicted in panel A of figure 1.6, but in mild asthma the lumen is narrowed (thereby raising resistance to airflow) through swelling of the airway wall, contraction of airway smooth muscle, and blockage (or plugging) of the airway by increased mucus secretion (figure 1.6B). This worsens in more severe asthma until the lumen can be extremely narrow (figure 1.6C) or even completely blocked.', 'c47f79de-4ee0-4513-8306-9f155e88c752': 'Other characteristics of asthma include the presence of eosinophillic that infiltrate into the airway walls. The eosinophil enzymes also leave a telltale sign: Charcot–Leyden crystals, as shown in the circled area\xa0of figure 1.7A.', '65a1b979-d155-41e2-9cca-a8018cbe9cb8': 'The sputum of the asthmatic may also contain Curshman’s spirals (figure 1.7B), which\xa0are casts of small bronchioles consisting of mucus and shed epithelial cells. However, Curshman’s spirals are not exclusive to asthma.', '92854127-014f-41fd-a517-c1814b0aafbb': 'With persistent asthma the airway undergoes remodeling (figure 1.8), with thickening of the airway wall and basement membrane, enlarged submucosal glands, and hypertrophy and hyperplasia of airway smooth muscle.'}"
Figure 1.9,pulmonary/images/Figure 1.9.jpg,Figure 1.9: The progression of an asthma “attack.”,"The characteristic signs of asthma progress and vary with declining FEV1 (summarized in figure 1.9). Most attacks start with mild wheezing and coughing, which progress with the severity of attack. The location and form of sensations vary between patients, but most asthmatics complain of chest tightness. This sensation is more commonly reported by asthmatics than other pulmonary patients, so it is a useful diagnostic sign.","{'4580d001-127d-4038-bcb0-87a588b04fb0': 'One useful diagnostic element\xa0of asthma is its episodic or acute behavior. However, as patients may\xa0be asymptomatic between attacks, the severity of asthma can be difficult to determine without performing bronchial challenge tests.', '9749b941-584e-42d8-944a-ef58e9aff4ed': 'The characteristic signs of asthma progress and vary with declining FEV1 (summarized in figure 1.9). Most attacks start with mild wheezing and coughing, which progress with the severity of attack. The location and form of sensations vary between patients, but most asthmatics complain of chest tightness. This sensation is more commonly reported by asthmatics than other pulmonary patients, so it is a useful diagnostic sign.', '48ac981b-61b0-4a77-b2f4-33fd1bcebd77': 'As airway resistance increases, the accessory muscles are deployed to maintain sufficient airflow through the narrowing airways, and the patient experiences an increased effort to breathe.\xa0Increased expiratory efforts produce dynamic airway collapse and lead to hyperinflation. Further decreases in airway caliber result in insufficient alveolar ventilation and deranged blood gases. The sensation reported at this point is air hunger.\xa0Once the patient is severely\xa0bronchoconstricted, delivery of inhaled therapies is much more difficult, and mechanical ventilation to support the respiratory muscles becomes complicated.\xa0Other signs present during a severe attack are raised heart (tachycardia) and breathing\xa0(tachypnea) rates as well as a paradoxical pulse (i.e., a rise in blood pressure during expiration).', '663afe60-899e-40ce-a85c-3fca6c6c6eb1': 'The typical chest x-ray of an\xa0asthmatic (figure 1.10) shows hyperlucent lung fields, evidence of hyperinflation and peribronchial infiltrate, and perhaps areas of atelectasis. However, the chest x-ray is not particularly effective at distinguishing asthma from some other obstructive disorders.'}"
Figure 1.10,pulmonary/images/Figure 1.10.jpg,Figure 1.10: Typical chest x-ray of an asthmatic patient showing hyperlucent fields and hyperinflation. Notice the flattened diaphragm and the number of ribs that are visible; more than six anterior ribs or ten posterior ribs being visible is indicative of hyperinflation.,"The typical chest x-ray of an asthmatic (figure 1.10) shows hyperlucent lung fields, evidence of hyperinflation and peribronchial infiltrate, and perhaps areas of atelectasis. However, the chest x-ray is not particularly effective at distinguishing asthma from some other obstructive disorders.","{'4580d001-127d-4038-bcb0-87a588b04fb0': 'One useful diagnostic element\xa0of asthma is its episodic or acute behavior. However, as patients may\xa0be asymptomatic between attacks, the severity of asthma can be difficult to determine without performing bronchial challenge tests.', '9749b941-584e-42d8-944a-ef58e9aff4ed': 'The characteristic signs of asthma progress and vary with declining FEV1 (summarized in figure 1.9). Most attacks start with mild wheezing and coughing, which progress with the severity of attack. The location and form of sensations vary between patients, but most asthmatics complain of chest tightness. This sensation is more commonly reported by asthmatics than other pulmonary patients, so it is a useful diagnostic sign.', '48ac981b-61b0-4a77-b2f4-33fd1bcebd77': 'As airway resistance increases, the accessory muscles are deployed to maintain sufficient airflow through the narrowing airways, and the patient experiences an increased effort to breathe.\xa0Increased expiratory efforts produce dynamic airway collapse and lead to hyperinflation. Further decreases in airway caliber result in insufficient alveolar ventilation and deranged blood gases. The sensation reported at this point is air hunger.\xa0Once the patient is severely\xa0bronchoconstricted, delivery of inhaled therapies is much more difficult, and mechanical ventilation to support the respiratory muscles becomes complicated.\xa0Other signs present during a severe attack are raised heart (tachycardia) and breathing\xa0(tachypnea) rates as well as a paradoxical pulse (i.e., a rise in blood pressure during expiration).', '663afe60-899e-40ce-a85c-3fca6c6c6eb1': 'The typical chest x-ray of an\xa0asthmatic (figure 1.10) shows hyperlucent lung fields, evidence of hyperinflation and peribronchial infiltrate, and perhaps areas of atelectasis. However, the chest x-ray is not particularly effective at distinguishing asthma from some other obstructive disorders.'}"
Figure 1.11,pulmonary/images/Figure 1.11.jpg,Figure 1.11: Pathophysiology of chronic bronchitis.,"Chronic bronchitis arises from chronic exposure to bronchial irritants, the most common of which is tobacco smoke. These irritants initiate the release of cytokines from airway epithelial cells and macrophages that result in a cascade of responses (summarized in figure 1.11).","{'c7b77aef-bf23-437e-9c38-10f3e5de0d04': 'Chronic bronchitis is clinically defined as a persistent and productive cough that lasts for at least three\xa0months per\xa0year for two consecutive years.', '416a3eeb-8aba-4a5b-b5d7-0ca3490bffeb': 'Chronic bronchitis arises from\xa0chronic exposure to bronchial irritants, the most common of which is tobacco smoke. These irritants initiate the release of cytokines from airway epithelial cells and macrophages that result in a cascade of responses (summarized in figure 1.11).', 'ba022a1a-fb87-493e-bdf6-facc52b46271': 'Neutrophils, lymphocytes, and macrophages are attracted to the irritated airway, and their presence is maintained through increased expression of cell adhesion molecules on the airway walls. These immune cells lead to acute airway wall inflammation that narrows the airway, and if chronic, can lead to tissue damage. The cytokines released by these cells also sensitize airway irritant receptors, which exacerbates the response to future irritant exposure.', 'b5129469-dd40-4ea7-9332-cf7ed356411a': 'Mucus production increases, and the glands themselves may also release cytokines that further exacerbate the inflammatory response. The mucus also contributes to airway narrowing, and mucus plugs may form that completely block bronchioles.', '25da24f2-ae7b-400c-9da9-c66259b49f04': 'Mesenchymal cells transition into fibroblasts as part of the inflammatory response, and their chronic presence leads to the deposition of fibrotic tissue.', '4f1e1d33-20b5-47bb-a322-14f0cda5f106': 'Collectively these responses to the irritants result in a narrowed airway that is (1) hypersensitive, (2) fibrosed, and (3) blocked by excessive secretions.', '54cd4ac6-6907-4268-9406-ca5c0f5c7c9d': 'Continued exposure to irritants leads to other chronic changes beyond\xa0fibrosis. With excessive stimulation, the size and number of mucus glands increases. The size of mucosal glands is used as a diagnostic test, and the Reid index describes what proportion of the submucosa is spanned by a gland—in the normal airway a normal gland spans less than 40 percent\xa0of the submucosa’s depth, but in chronic bronchitis this exceeds 50 percent\xa0(figure 1.12).', 'ad01645b-127f-4836-9e86-73e40913b9dd': 'In conjunction with an increased mucus production capacity, the airway has a reduced mucus clearance capability with airway remodeling, including squamous metaplasia replacing normal ciliated columnar epithelium (figure 1.13). The mucus escalator is also\xa0compromised by a decline in function of the remaining cilia with exposure to cigarette smoke.', 'd7cd9b07-d0a5-4899-bcc0-30d05cabb18e': 'These changes result in an airway that produces more mucus and is less capable of removing it. The static mucus not only causes airway plugging, but can also promote infections that lead to episodic and characteristic exacerbation of COPD symptoms.'}"
Figure 1.12,pulmonary/images/Figure 1.12.jpg,Figure 1.12: The Reid index compares the width of mucus glands to the width of the submucosal layer of airways.,"Continued exposure to irritants leads to other chronic changes beyond fibrosis. With excessive stimulation, the size and number of mucus glands increases. The size of mucosal glands is used as a diagnostic test, and the Reid index describes what proportion of the submucosa is spanned by a gland—in the normal airway a normal gland spans less than 40 percent of the submucosa’s depth, but in chronic bronchitis this exceeds 50 percent (figure 1.12).","{'c7b77aef-bf23-437e-9c38-10f3e5de0d04': 'Chronic bronchitis is clinically defined as a persistent and productive cough that lasts for at least three\xa0months per\xa0year for two consecutive years.', '416a3eeb-8aba-4a5b-b5d7-0ca3490bffeb': 'Chronic bronchitis arises from\xa0chronic exposure to bronchial irritants, the most common of which is tobacco smoke. These irritants initiate the release of cytokines from airway epithelial cells and macrophages that result in a cascade of responses (summarized in figure 1.11).', 'ba022a1a-fb87-493e-bdf6-facc52b46271': 'Neutrophils, lymphocytes, and macrophages are attracted to the irritated airway, and their presence is maintained through increased expression of cell adhesion molecules on the airway walls. These immune cells lead to acute airway wall inflammation that narrows the airway, and if chronic, can lead to tissue damage. The cytokines released by these cells also sensitize airway irritant receptors, which exacerbates the response to future irritant exposure.', 'b5129469-dd40-4ea7-9332-cf7ed356411a': 'Mucus production increases, and the glands themselves may also release cytokines that further exacerbate the inflammatory response. The mucus also contributes to airway narrowing, and mucus plugs may form that completely block bronchioles.', '25da24f2-ae7b-400c-9da9-c66259b49f04': 'Mesenchymal cells transition into fibroblasts as part of the inflammatory response, and their chronic presence leads to the deposition of fibrotic tissue.', '4f1e1d33-20b5-47bb-a322-14f0cda5f106': 'Collectively these responses to the irritants result in a narrowed airway that is (1) hypersensitive, (2) fibrosed, and (3) blocked by excessive secretions.', '54cd4ac6-6907-4268-9406-ca5c0f5c7c9d': 'Continued exposure to irritants leads to other chronic changes beyond\xa0fibrosis. With excessive stimulation, the size and number of mucus glands increases. The size of mucosal glands is used as a diagnostic test, and the Reid index describes what proportion of the submucosa is spanned by a gland—in the normal airway a normal gland spans less than 40 percent\xa0of the submucosa’s depth, but in chronic bronchitis this exceeds 50 percent\xa0(figure 1.12).', 'ad01645b-127f-4836-9e86-73e40913b9dd': 'In conjunction with an increased mucus production capacity, the airway has a reduced mucus clearance capability with airway remodeling, including squamous metaplasia replacing normal ciliated columnar epithelium (figure 1.13). The mucus escalator is also\xa0compromised by a decline in function of the remaining cilia with exposure to cigarette smoke.', 'd7cd9b07-d0a5-4899-bcc0-30d05cabb18e': 'These changes result in an airway that produces more mucus and is less capable of removing it. The static mucus not only causes airway plugging, but can also promote infections that lead to episodic and characteristic exacerbation of COPD symptoms.'}"
Figure 1.13,pulmonary/images/Figure 1.13.jpg,Figure 1.13: Prolonged irritant exposure can lead to airway remodeling with loss of normal ciliated epithelium.,"In conjunction with an increased mucus production capacity, the airway has a reduced mucus clearance capability with airway remodeling, including squamous metaplasia replacing normal ciliated columnar epithelium (figure 1.13). The mucus escalator is also compromised by a decline in function of the remaining cilia with exposure to cigarette smoke.","{'c7b77aef-bf23-437e-9c38-10f3e5de0d04': 'Chronic bronchitis is clinically defined as a persistent and productive cough that lasts for at least three\xa0months per\xa0year for two consecutive years.', '416a3eeb-8aba-4a5b-b5d7-0ca3490bffeb': 'Chronic bronchitis arises from\xa0chronic exposure to bronchial irritants, the most common of which is tobacco smoke. These irritants initiate the release of cytokines from airway epithelial cells and macrophages that result in a cascade of responses (summarized in figure 1.11).', 'ba022a1a-fb87-493e-bdf6-facc52b46271': 'Neutrophils, lymphocytes, and macrophages are attracted to the irritated airway, and their presence is maintained through increased expression of cell adhesion molecules on the airway walls. These immune cells lead to acute airway wall inflammation that narrows the airway, and if chronic, can lead to tissue damage. The cytokines released by these cells also sensitize airway irritant receptors, which exacerbates the response to future irritant exposure.', 'b5129469-dd40-4ea7-9332-cf7ed356411a': 'Mucus production increases, and the glands themselves may also release cytokines that further exacerbate the inflammatory response. The mucus also contributes to airway narrowing, and mucus plugs may form that completely block bronchioles.', '25da24f2-ae7b-400c-9da9-c66259b49f04': 'Mesenchymal cells transition into fibroblasts as part of the inflammatory response, and their chronic presence leads to the deposition of fibrotic tissue.', '4f1e1d33-20b5-47bb-a322-14f0cda5f106': 'Collectively these responses to the irritants result in a narrowed airway that is (1) hypersensitive, (2) fibrosed, and (3) blocked by excessive secretions.', '54cd4ac6-6907-4268-9406-ca5c0f5c7c9d': 'Continued exposure to irritants leads to other chronic changes beyond\xa0fibrosis. With excessive stimulation, the size and number of mucus glands increases. The size of mucosal glands is used as a diagnostic test, and the Reid index describes what proportion of the submucosa is spanned by a gland—in the normal airway a normal gland spans less than 40 percent\xa0of the submucosa’s depth, but in chronic bronchitis this exceeds 50 percent\xa0(figure 1.12).', 'ad01645b-127f-4836-9e86-73e40913b9dd': 'In conjunction with an increased mucus production capacity, the airway has a reduced mucus clearance capability with airway remodeling, including squamous metaplasia replacing normal ciliated columnar epithelium (figure 1.13). The mucus escalator is also\xa0compromised by a decline in function of the remaining cilia with exposure to cigarette smoke.', 'd7cd9b07-d0a5-4899-bcc0-30d05cabb18e': 'These changes result in an airway that produces more mucus and is less capable of removing it. The static mucus not only causes airway plugging, but can also promote infections that lead to episodic and characteristic exacerbation of COPD symptoms.'}"
Figure 1.14,pulmonary/images/Figure 1.14.jpg,Figure 1.14: The pathophysiological and clinical events as chronic bronchitis progresses.,The signs and symptoms of chronic bronchitis depend on the level of airway obstruction and the consequent decline in lung function (summarized in figure 1.14).,"{'d0fdcfa1-6dc9-494a-b681-9e5ac098fbed': 'The signs and symptoms of chronic bronchitis depend on the level of airway obstruction and the consequent decline in lung function (summarized in figure 1.14).', '2954d908-e93e-4674-b0c9-0975d6cf9fb2': 'As with many pulmonary diseases, the onset can be insidious. Small airway damage may be present but undetectable with normal spirometry, while the patient becomes accustomed to and tolerates a persistent productive cough. However, with continued irritant exposure, this initial simple bronchitis progresses.', '08a74477-a8f1-4b48-ab90-84cbe7259665': 'Secretions continue to worsen and peribronchiolar fibrosis marks the onset of obstructive bronchitis that is reflected by significant expiratory airflow limitation. At this point the patient may have tolerated years of productive cough\xa0and experienced frequent chest infections related to poor mucus clearance. COPDers are particularly susceptible to Haemophilus influenza and Streptococcus pneumoniae. The sputum is abundant and capable of plugging significant numbers of airways and may be blood tinged; COPD is the most common cause of hemoptysis. Airways may demonstrate hyperreactivity and mimic\xa0an asthmatic response.', '27931927-1824-4817-a27b-c32536ca3786': 'The onset of dyspnea is insidious and is usually first experienced during exertion—leading the patient to avoid exercise, which in turn leads to deconditioning and a worsening of the symptom. Lung sounds include wheezes and rales, the rales often clearing after cough.', '2d83191b-b693-4cca-b87f-54e3eaed3a93': 'With worsening airway flow limitation expiration becomes prolonged and may be incomplete due to airway collapse that leads to characteristic hyperinflation.', '0fa93e3c-8ee7-41c9-9d8d-e1eb7473e407': 'Mucus plugging and airway closure leads to areas of V/Q abnormalities through the lung, and localized areas of hypoxia can lead to pulmonary vasoconstriction. When significant regions of the lung are vasoconstricted, pulmonary vascular resistance can rise enough to induce right-sided heart failure.', 'e05298ae-d73f-4d8e-ac5c-1a8da3dd5ecf': 'With continued progression of the disease, blood gases become deranged as insufficient alveolar ventilation is achieved. As the disease approaches its end stage, the patient experiences dyspnea at rest until respiratory failure occurs and the patient is hypoxemic and hypercarbic.'}"
Figure 1.15,pulmonary/images/Figure 1.15.jpg,Figure 1.15: Histological comparison of normal (left) and emphysematous (right) lung tissue.,"Emphysema, a possible second component to COPD, involves permanent enlargement of airspaces distal to the terminal bronchioles and destruction of alveolar walls, as is evident in figure 1.15.","{'3f0a580f-86e2-435d-b0e4-caa5108fb91d': 'Emphysema, a possible second component to COPD, involves permanent enlargement of airspaces distal to the terminal bronchioles and destruction of alveolar walls, as is evident in figure 1.15.', '92d7a511-da4d-461c-abdb-666c0aea2745': 'The pattern of airspace destruction varies with underlying cause and revolves around the acinus (figure 1.16), the functional unit of the lung comprised of the terminal airways and the alveoli that collectively make up the respiratory zone of the lung. In its broadest classification, emphysema can take on either a centriacinar or panacinar distribution (figure 1.16). In centriacinar emphysema, the respiratory duct is affected while the distal alveoli are mostly unaffected. This is more commonly found in the upper lung fields and associated with smoking and the concurrent presence of chronic bronchitis.', '693063c9-85f7-4633-8cb5-7d1b00c1cbcf': 'This pathology slide in figure 1.15\xa0illustrates this pattern of tissue destruction with isolated areas of damage, surrounded by relatively normal alveolar structure.', 'a390d983-31fe-4f9e-a25a-8c31c79eb96b': 'Panacinar emphysema, as the name suggests, involves the entire acinus (figure 1.16), and the alveolar structure is more involved creating large airspaces that occur throughout the lung. This is evident in the pathology slide in figure 1.16\xa0that shows much more uniform damage than the centriacinar example. Panacinar emphysema is much less common and is the pattern of destruction associated with alpha-1 antitrypsin deficiency, which we will deal with in a moment.', 'e21ed96a-346e-493e-986c-6f00e6c6eb04': 'So having seen the morphology of emphysema, we will look at how this damage occurs.'}"
Figure 1.16,pulmonary/images/Figure 1.16.jpg,Figure 1.16: Characteristic patterns of emphysema.,"The pattern of airspace destruction varies with underlying cause and revolves around the acinus (figure 1.16), the functional unit of the lung comprised of the terminal airways and the alveoli that collectively make up the respiratory zone of the lung. In its broadest classification, emphysema can take on either a centriacinar or panacinar distribution (figure 1.16). In centriacinar emphysema, the respiratory duct is affected while the distal alveoli are mostly unaffected. This is more commonly found in the upper lung fields and associated with smoking and the concurrent presence of chronic bronchitis.","{'3f0a580f-86e2-435d-b0e4-caa5108fb91d': 'Emphysema, a possible second component to COPD, involves permanent enlargement of airspaces distal to the terminal bronchioles and destruction of alveolar walls, as is evident in figure 1.15.', '92d7a511-da4d-461c-abdb-666c0aea2745': 'The pattern of airspace destruction varies with underlying cause and revolves around the acinus (figure 1.16), the functional unit of the lung comprised of the terminal airways and the alveoli that collectively make up the respiratory zone of the lung. In its broadest classification, emphysema can take on either a centriacinar or panacinar distribution (figure 1.16). In centriacinar emphysema, the respiratory duct is affected while the distal alveoli are mostly unaffected. This is more commonly found in the upper lung fields and associated with smoking and the concurrent presence of chronic bronchitis.', '693063c9-85f7-4633-8cb5-7d1b00c1cbcf': 'This pathology slide in figure 1.15\xa0illustrates this pattern of tissue destruction with isolated areas of damage, surrounded by relatively normal alveolar structure.', 'a390d983-31fe-4f9e-a25a-8c31c79eb96b': 'Panacinar emphysema, as the name suggests, involves the entire acinus (figure 1.16), and the alveolar structure is more involved creating large airspaces that occur throughout the lung. This is evident in the pathology slide in figure 1.16\xa0that shows much more uniform damage than the centriacinar example. Panacinar emphysema is much less common and is the pattern of destruction associated with alpha-1 antitrypsin deficiency, which we will deal with in a moment.', 'e21ed96a-346e-493e-986c-6f00e6c6eb04': 'So having seen the morphology of emphysema, we will look at how this damage occurs.', 'b097a932-7fa1-4947-8e11-bafa3186560d': 'The normal structure of alveoli and respiratory ducts consists of type 1 and type 2 pneumocytes with elastic fibers that contribute to the structure’s mechanical behavior. Emphysema involves the loss of these parenchymal fibers.', '0fa0b53b-3f87-4efd-b6a0-387c8245a5ae': 'The presence of irritants, such as cigarette smoke, causes oxidization and the dysfunction of antiprotease enzymes. Without their inhibitory action, the activity of proteases increases and causes the destruction of local tissue. One of these proteases is elastase, whose elevated activity leads to irreparable loss of parenchymal fibers.', '459fd924-7a3d-4a28-81ac-df7382c9d225': 'Elastase is also released by neutrophils and macrophages that arrive in response to the inflammatory cascade caused by the inhaled smoke. This causes further destruction of elastin fibers.', 'dc111024-3189-4be2-ad9d-918c626fa685': 'The pathogenesis of emphysema (figure 1.17) might be summarized as an imbalance between the activities of antiproteases and proteases. Antiproteases are suppressed, and proteases are elevated.', '881ad255-a783-48fa-994c-2231712d0f30': 'The emphysema in about 1 percent\xa0of COPD patients is caused by a genetic lack of alpha-1 anti-trypsin. Even without tobacco use, these patients have an antiprotease/protease imbalance that results in loss of elastin and collagen and produces the panacinar emphysema shown previously (figure 1.16). If an alpha1-anti-trypsin patient does smoke, this imbalance is worsened and emphysema may develop by their late twenties.', '0e44cc30-7e48-4ce3-b0b4-d2e00966239a': 'The loss of the elastic tissue and alveolar structure produces several pathophysiological changes in lung mechanics and function that result in typical clinical signs.'}"
Figure 1.17,pulmonary/images/Figure 1.17.jpg,Figure 1.17: Pathological process of emphysema.,"The pathogenesis of emphysema (figure 1.17) might be summarized as an imbalance between the activities of antiproteases and proteases. Antiproteases are suppressed, and proteases are elevated.","{'b097a932-7fa1-4947-8e11-bafa3186560d': 'The normal structure of alveoli and respiratory ducts consists of type 1 and type 2 pneumocytes with elastic fibers that contribute to the structure’s mechanical behavior. Emphysema involves the loss of these parenchymal fibers.', '0fa0b53b-3f87-4efd-b6a0-387c8245a5ae': 'The presence of irritants, such as cigarette smoke, causes oxidization and the dysfunction of antiprotease enzymes. Without their inhibitory action, the activity of proteases increases and causes the destruction of local tissue. One of these proteases is elastase, whose elevated activity leads to irreparable loss of parenchymal fibers.', '459fd924-7a3d-4a28-81ac-df7382c9d225': 'Elastase is also released by neutrophils and macrophages that arrive in response to the inflammatory cascade caused by the inhaled smoke. This causes further destruction of elastin fibers.', 'dc111024-3189-4be2-ad9d-918c626fa685': 'The pathogenesis of emphysema (figure 1.17) might be summarized as an imbalance between the activities of antiproteases and proteases. Antiproteases are suppressed, and proteases are elevated.', '881ad255-a783-48fa-994c-2231712d0f30': 'The emphysema in about 1 percent\xa0of COPD patients is caused by a genetic lack of alpha-1 anti-trypsin. Even without tobacco use, these patients have an antiprotease/protease imbalance that results in loss of elastin and collagen and produces the panacinar emphysema shown previously (figure 1.16). If an alpha1-anti-trypsin patient does smoke, this imbalance is worsened and emphysema may develop by their late twenties.', '0e44cc30-7e48-4ce3-b0b4-d2e00966239a': 'The loss of the elastic tissue and alveolar structure produces several pathophysiological changes in lung mechanics and function that result in typical clinical signs.'}"
Figure 1.16,pulmonary/images/Figure 1.16.jpg,Figure 1.16: Characteristic patterns of emphysema.,"The pattern of airspace destruction varies with underlying cause and revolves around the acinus (figure 1.16), the functional unit of the lung comprised of the terminal airways and the alveoli that collectively make up the respiratory zone of the lung. In its broadest classification, emphysema can take on either a centriacinar or panacinar distribution (figure 1.16). In centriacinar emphysema, the respiratory duct is affected while the distal alveoli are mostly unaffected. This is more commonly found in the upper lung fields and associated with smoking and the concurrent presence of chronic bronchitis.","{'3f0a580f-86e2-435d-b0e4-caa5108fb91d': 'Emphysema, a possible second component to COPD, involves permanent enlargement of airspaces distal to the terminal bronchioles and destruction of alveolar walls, as is evident in figure 1.15.', '92d7a511-da4d-461c-abdb-666c0aea2745': 'The pattern of airspace destruction varies with underlying cause and revolves around the acinus (figure 1.16), the functional unit of the lung comprised of the terminal airways and the alveoli that collectively make up the respiratory zone of the lung. In its broadest classification, emphysema can take on either a centriacinar or panacinar distribution (figure 1.16). In centriacinar emphysema, the respiratory duct is affected while the distal alveoli are mostly unaffected. This is more commonly found in the upper lung fields and associated with smoking and the concurrent presence of chronic bronchitis.', '693063c9-85f7-4633-8cb5-7d1b00c1cbcf': 'This pathology slide in figure 1.15\xa0illustrates this pattern of tissue destruction with isolated areas of damage, surrounded by relatively normal alveolar structure.', 'a390d983-31fe-4f9e-a25a-8c31c79eb96b': 'Panacinar emphysema, as the name suggests, involves the entire acinus (figure 1.16), and the alveolar structure is more involved creating large airspaces that occur throughout the lung. This is evident in the pathology slide in figure 1.16\xa0that shows much more uniform damage than the centriacinar example. Panacinar emphysema is much less common and is the pattern of destruction associated with alpha-1 antitrypsin deficiency, which we will deal with in a moment.', 'e21ed96a-346e-493e-986c-6f00e6c6eb04': 'So having seen the morphology of emphysema, we will look at how this damage occurs.', 'b097a932-7fa1-4947-8e11-bafa3186560d': 'The normal structure of alveoli and respiratory ducts consists of type 1 and type 2 pneumocytes with elastic fibers that contribute to the structure’s mechanical behavior. Emphysema involves the loss of these parenchymal fibers.', '0fa0b53b-3f87-4efd-b6a0-387c8245a5ae': 'The presence of irritants, such as cigarette smoke, causes oxidization and the dysfunction of antiprotease enzymes. Without their inhibitory action, the activity of proteases increases and causes the destruction of local tissue. One of these proteases is elastase, whose elevated activity leads to irreparable loss of parenchymal fibers.', '459fd924-7a3d-4a28-81ac-df7382c9d225': 'Elastase is also released by neutrophils and macrophages that arrive in response to the inflammatory cascade caused by the inhaled smoke. This causes further destruction of elastin fibers.', 'dc111024-3189-4be2-ad9d-918c626fa685': 'The pathogenesis of emphysema (figure 1.17) might be summarized as an imbalance between the activities of antiproteases and proteases. Antiproteases are suppressed, and proteases are elevated.', '881ad255-a783-48fa-994c-2231712d0f30': 'The emphysema in about 1 percent\xa0of COPD patients is caused by a genetic lack of alpha-1 anti-trypsin. Even without tobacco use, these patients have an antiprotease/protease imbalance that results in loss of elastin and collagen and produces the panacinar emphysema shown previously (figure 1.16). If an alpha1-anti-trypsin patient does smoke, this imbalance is worsened and emphysema may develop by their late twenties.', '0e44cc30-7e48-4ce3-b0b4-d2e00966239a': 'The loss of the elastic tissue and alveolar structure produces several pathophysiological changes in lung mechanics and function that result in typical clinical signs.'}"
Figure 1.18,pulmonary/images/Figure 1.18.jpg,Figure 1.18: The pathophysiological events that lead to the clinical signs of emphysema.,"Lung recoil is the opposing force to the chest wall’s tendency to spring outward. The loss of elastin reduces lung recoil and the chest wall can move outward, producing a characteristic “barrel-chest” (figure 1.18).","{'7d8c96ce-9924-4387-94a1-80d055ee2d40': 'Lung recoil is the opposing force to the chest wall’s tendency to spring outward. The loss of elastin reduces lung recoil and the chest wall can move outward, producing a characteristic “barrel-chest”\xa0(figure 1.18).', '87a017cc-f379-4643-98f9-aa8f53dbf94b': 'The lack of recoil also means that passive expiration\xa0is ineffective and active expiration must\xa0be employed. The positive pleural pressure associated with active expiration enhances dynamic airway collapse that leads to gas trapping and characteristic hyperinflation (figure 1.18). To prevent this, the emphysema patient may adopt pursed lip breathing to maintain airway pressure during expiration that props open the airways.', '5742c7ee-8ee9-444a-9662-df0710c7f307': 'The hyperinflation and nonuniform tissue damage can lead to a heterogenous distribution of ventilation and V/Q abnormalities that diminish gas exchange. Gas exchange will also be diminished by the enlargement of airspaces, reducing available surface area (figure 1.18).', '871edbd3-de1f-4969-ac90-c77d04e4fc7d': 'The deterioration of gas exchange and lung mechanics worsens as more lung becomes involved, and the stage of the disease, and any concurrent chronic bronchitis, is classified by the level of airway flow limitation\xa0(e.g.,\xa0FEV1/FVC).', '048065e5-22d3-4ca8-acae-021631ba02ca': 'It might also be worth noting here that COPD can produce or be associated with a number of comorbidities;\xa0we have already mentioned hypertension, but pulmonary artery disease, coronary heart disease, heart failure, lung cancer, and malnutrition may\xa0contribute to a low quality of life that is typically associated with COPD. This in\xa0turn may contribute to the high incidence of anxiety disorders and depression experienced by COPD patients.'}"
Figure 1.19,pulmonary/images/Figure 1.19.jpg,Figure 1.19: The impact of ion currents in normal and CF cells on fluid layer and cilia.,"Control of the airway fluid relies on the action of ion channels in the apical membranes of epithelial cells, and there are two channels to focus on: CFTR and ENaC. The CFTR channels let chloride out of the cell, while the ENaC lets sodium in (top panel, figure 1.19).","{'436e0f88-184e-4ef8-83a7-8ff24e16d8aa': 'Control of the airway fluid relies on the action of ion channels in the apical membranes of epithelial cells, and there are two channels to focus on:\xa0CFTR and ENaC. The CFTR channels let chloride out of the cell, while the ENaC lets sodium in (top panel, figure 1.19).', '92c3a7db-46c2-4254-a908-437e66526269': 'This exchange helps maintain a healthy fluid layer in the airway, but fails in CF because of a nonfunctioning CFTR channel (right\xa0panel, figure 1.19).', 'db961fb6-7ee8-42ad-9b6a-50252109c9f1': 'There are numerous mutations that are known to produce a dysfunctional CFTR channel, but 70 percent\xa0of CF cases are due to the delta-F-508 mutation (so named as the mutation leads to a deletion of phenylalanine at position 508 of the CFTR protein). This is a Mendelian recessive trait, and CF occurrence is 1 in 2,500 live births.', 'db063a96-38f8-483f-b708-339a80edfada': 'So what are the consequences of CFTR dysfunction? Chloride ends up being trapped inside the cell (bottom panel, figure 1.19), and this leads to a greater influx of sodium through the ENaC down its electrochemical gradient, leaving a higher concentration of salt inside the cells that pulls water in from the airway lumen. The low fluid volume in the airway results in:', 'a720ab5f-669c-4f95-9082-c5872f7f154a': 'This combination severely impacts mucus clearance (thicker, heavier mucus with compromised cillary escalator). The defective CFTR channel therefore results in mucus retention and airway obstruction. This in turn leads to reduced alveolar ventilation and repeated infections. The two most common culprits for infection in CF are Staphylococcus aureus and Pseudomonsa aeruginosa. Normal functional CFTR appears to suppress P. aeruginosa, perhaps explaining its prevalence in cystic fibrosis where it can be found in the sputum of almost all CF patients.'}"
Figure 1.19,pulmonary/images/Figure 1.19.jpg,Figure 1.19: The impact of ion currents in normal and CF cells on fluid layer and cilia.,"Control of the airway fluid relies on the action of ion channels in the apical membranes of epithelial cells, and there are two channels to focus on: CFTR and ENaC. The CFTR channels let chloride out of the cell, while the ENaC lets sodium in (top panel, figure 1.19).","{'436e0f88-184e-4ef8-83a7-8ff24e16d8aa': 'Control of the airway fluid relies on the action of ion channels in the apical membranes of epithelial cells, and there are two channels to focus on:\xa0CFTR and ENaC. The CFTR channels let chloride out of the cell, while the ENaC lets sodium in (top panel, figure 1.19).', '92c3a7db-46c2-4254-a908-437e66526269': 'This exchange helps maintain a healthy fluid layer in the airway, but fails in CF because of a nonfunctioning CFTR channel (right\xa0panel, figure 1.19).', 'db961fb6-7ee8-42ad-9b6a-50252109c9f1': 'There are numerous mutations that are known to produce a dysfunctional CFTR channel, but 70 percent\xa0of CF cases are due to the delta-F-508 mutation (so named as the mutation leads to a deletion of phenylalanine at position 508 of the CFTR protein). This is a Mendelian recessive trait, and CF occurrence is 1 in 2,500 live births.', 'db063a96-38f8-483f-b708-339a80edfada': 'So what are the consequences of CFTR dysfunction? Chloride ends up being trapped inside the cell (bottom panel, figure 1.19), and this leads to a greater influx of sodium through the ENaC down its electrochemical gradient, leaving a higher concentration of salt inside the cells that pulls water in from the airway lumen. The low fluid volume in the airway results in:', 'a720ab5f-669c-4f95-9082-c5872f7f154a': 'This combination severely impacts mucus clearance (thicker, heavier mucus with compromised cillary escalator). The defective CFTR channel therefore results in mucus retention and airway obstruction. This in turn leads to reduced alveolar ventilation and repeated infections. The two most common culprits for infection in CF are Staphylococcus aureus and Pseudomonsa aeruginosa. Normal functional CFTR appears to suppress P. aeruginosa, perhaps explaining its prevalence in cystic fibrosis where it can be found in the sputum of almost all CF patients.'}"
Figure 1.20,pulmonary/images/Figure 1.20.jpg,Figure 1.20: Pulmonary consequences of CF.,"The consequences of repeated infection are a mixture of serious conditions and pathologies including atelectasis, pneumonia, bronchiectasis, and other structural abnormalities of the airways (figure 1.20).","{'abc7971b-13c4-4067-9a5a-7665cfa7f8e2': 'The consequences of repeated infection are a mixture of serious conditions and pathologies including atelectasis, pneumonia, bronchiectasis, and other structural abnormalities of the airways (figure 1.20).', '0d167435-239a-41d7-9361-89ba1424b20c': 'The findings of CF obviously include the results of other effected organs, such as the pancreas. But nowadays these are more easily addressed, and it is pulmonary involvement that still proves critical. The onset of pulmonary involvement is variable and may be weeks or years after birth.'}"
Figure 1.21,pulmonary/images/Figure 1.21.jpg,Figure 1.21: Clinical signs of the pulmonary progression of CF.,"Findings progress with progressive airway damage (figure 1.21), but start with cough that may be dry at first but transitions to productive to expel the copious, viscous mucus. With poor mucus clearance, the patient experiences repeated infections that exacerbate symptoms at each stage of the disease.","{'1dd450c4-c78b-4e97-aae4-77b0aeec4455': 'Findings progress with progressive airway damage (figure 1.21), but start with cough that may be dry at first but transitions to productive to expel the copious, viscous mucus. With poor mucus clearance, the patient experiences repeated infections that exacerbate symptoms at each stage of the disease.', '6d6d09c5-8305-4eb8-9cb4-2713e9900058': 'CF patients usually have an abnormal sinus x-ray and evidence of chronic sinusitis as well as a high occurrence of nasal polyps.', '8f15251e-c619-47d8-b829-86276075121b': 'With increasing and irreversible airway damage, the patients begins to experience dyspnea, and the damage may lead to hemoptysis, spontaneous pneumothorax, and a barrel chested appearance.\xa0Signs of prolonged pulmonary dysfunction appear as the disease progresses, such as finger clubbing, cyanosis, and cor pulmonale (right-sided heart failure caused by lung disease).\xa0As the patient approaches respiratory failure the accessory muscles are deployed. Patients succumb to the respiratory failure or an overwhelming infection.', '65d7b0a8-11a4-4885-af6f-25d2bf1e9767': 'Because\xa0CF also affects sweat gland function, the sweat test remains a standard diagnostic with a chloride level greater than 60 mEq/L being indicative of CF. This test is more reliable in children than adults, who may have developed other conditions that affect the composition of sweat.', '9f26e820-60de-49c3-bf18-3b819e96857d': 'Chest x-rays show (figure 1.22) signs of hyperinflation associated with gas trapping and the hallmarks of any other complications that the CF has induced. These are viewed more clearly with the common use of high-resolution computed tomography (HRCT)(figure 1.23) to determine the type and extent of damage that may include bronchiectasis and mucus impactions.', 'b23a55bf-50a0-48a9-930e-2c99087daa92': 'Spirometry detects the airway obstruction and hyperinflation that produce a low vital capacity and high residual volume.'}"
Figure 1.22,pulmonary/images/Figure 1.22.jpg,Figure 1.22: Typical chest x-ray findings of CF.,Chest x-rays show (figure 1.22) signs of hyperinflation associated with gas trapping and the hallmarks of any other complications that the CF has induced. These are viewed more clearly with the common use of high-resolution computed tomography (HRCT)(figure 1.23) to determine the type and extent of damage that may include bronchiectasis and mucus impactions.,"{'1dd450c4-c78b-4e97-aae4-77b0aeec4455': 'Findings progress with progressive airway damage (figure 1.21), but start with cough that may be dry at first but transitions to productive to expel the copious, viscous mucus. With poor mucus clearance, the patient experiences repeated infections that exacerbate symptoms at each stage of the disease.', '6d6d09c5-8305-4eb8-9cb4-2713e9900058': 'CF patients usually have an abnormal sinus x-ray and evidence of chronic sinusitis as well as a high occurrence of nasal polyps.', '8f15251e-c619-47d8-b829-86276075121b': 'With increasing and irreversible airway damage, the patients begins to experience dyspnea, and the damage may lead to hemoptysis, spontaneous pneumothorax, and a barrel chested appearance.\xa0Signs of prolonged pulmonary dysfunction appear as the disease progresses, such as finger clubbing, cyanosis, and cor pulmonale (right-sided heart failure caused by lung disease).\xa0As the patient approaches respiratory failure the accessory muscles are deployed. Patients succumb to the respiratory failure or an overwhelming infection.', '65d7b0a8-11a4-4885-af6f-25d2bf1e9767': 'Because\xa0CF also affects sweat gland function, the sweat test remains a standard diagnostic with a chloride level greater than 60 mEq/L being indicative of CF. This test is more reliable in children than adults, who may have developed other conditions that affect the composition of sweat.', '9f26e820-60de-49c3-bf18-3b819e96857d': 'Chest x-rays show (figure 1.22) signs of hyperinflation associated with gas trapping and the hallmarks of any other complications that the CF has induced. These are viewed more clearly with the common use of high-resolution computed tomography (HRCT)(figure 1.23) to determine the type and extent of damage that may include bronchiectasis and mucus impactions.', 'b23a55bf-50a0-48a9-930e-2c99087daa92': 'Spirometry detects the airway obstruction and hyperinflation that produce a low vital capacity and high residual volume.'}"
Figure 1.24,pulmonary/images/Figure 1.24.jpg,Figure 1.24: Pathophysiology of bronchiectasis.,"A bronchiectasis starts with a section of airway wall becoming inflamed (figure 1.24), disrupting and weakening its structure. This weakening leads to a permanent dilation of the airway that impairs the clearance of secretion. Because the airway is inflamed, the amount of secretion may be significant and it begins to accumulate.","{'63e29543-59b0-4f8e-a93b-d4dd2a24df97': 'This section will address bronchiectasis, a form of airway obstruction that is often a manifestation of chronic airway inflammation. Bronchiectasis involves a permanent dilation of a bronchi or bronchiole—think of bronchiectasis as the airway equivalent of an aneurysm.', '5087adaa-b775-4acc-b424-fac0e5a412c4': 'A bronchiectasis starts with a section of airway wall becoming inflamed (figure 1.24), disrupting and weakening its structure. This weakening leads to a permanent dilation of the airway that impairs the clearance of secretion. Because the airway is inflamed, the amount of secretion may be significant and it begins to accumulate.', '72b427b6-7cf6-41a2-a298-ee8f69387133': 'The stagnant secretion promotes a secondary infection that leads to further inflammation, wall disruption, and dilation. Thus the airway has entered a vicious cycle that causes the dilation and retention of mucus to perpetuate (figure 1.24).', '3b0e3f15-bb01-4e8b-9eb4-5a773362a5ae': 'The establishing of a bronchiectasis has an initial\xa0phase leading to persistent inflammation, desquamation (which worsens the mucus clearance), and the ulceration. In what is probably a familiar story, the continued inflammation leads to fibrosis in the chronic phase of development, and this can lead to airway destruction and perhaps the condition of bronchiolitis obliterans.'}"
Figure 1.25,pulmonary/images/Figure 1.25.jpg,Figure 1.25: Instigating factors for bronchiectasis.,There are some common culprits for initiating bronchiectasis (figure 1.25). Most start with either a decline in mucus clearance and the associated inflammation or damage to the airway wall.,"{'f428b662-610b-4f62-8621-6d3f4a454180': 'There are some common culprits for initiating bronchiectasis (figure 1.25). Most start with either a decline in mucus clearance and the associated inflammation or damage to the airway wall.', '1eadf609-f7b9-4fd9-a3d2-599321b3bb81': 'About 50 percent\xa0of bronchiectasis cases are associated with cystic fibrosis where the genetic condition causes production of copious, thick mucus that is difficult to clear and often results in infection (commonly caused by Staphylococcus aureus).', '21b1bf7f-bbf0-4bb6-92c1-c5a3b2272546': 'Conditions causing cillary dyskinesia, as seen in Kartagener’s syndrome, also disrupt\xa0the mucocillary escalator.'}"
Figure 1.26,pulmonary/images/Figure 1.26.jpg,Figure 1.26: Histological and gross changes associated with severe bronchiectasis.,"The outcomes of bronchiectasis are seen in the histology slide in figure 1.26, with the affected airway lumen filled with mucus and pus, and the airway walls exhibiting fibroglandular tissue and infiltration by inflammatory cells (outer red circle).","{'04f9aefe-9a2e-4d2a-87d6-5f8b1b94232f': 'The outcomes of bronchiectasis\xa0are seen in the\xa0histology slide in figure 1.26, with the affected airway lumen filled with mucus and pus, and the airway walls exhibiting fibroglandular tissue and infiltration by inflammatory cells (outer red circle).', 'aa4b374a-8833-4dd4-8069-844da9e21e7a': 'The gross view (right panel, figure 1.26) shows severely dilated bronchi and noticeable\xa0thickening of their walls.', 'ee2a56dd-bf2a-4bec-846d-e142501aa5a8': 'There are different forms of bronchiectasis; these are classified by their shape (figure 1.27).', '6fbaaa0c-eb4e-4a4f-af24-e98089ffce9c': 'A bronchiectasis can be cylindrical, varicose (also known as fusiform), or cystic (also known as saccular). The\xa0shape is relevant to their effect on the efficacy of coughing; cylindrical form has\xa0very little effect on cough’s ability to clear mucus, whereas varicose and cystic forms tend to disproportionately collapse during cough and reduce its effectiveness at moving mucus up the airway.', '9b95f1a0-8db6-4189-993e-9db465dcd585': 'As shown\xa0in figure 1.28 an x-ray shows the presence of bronchiectasis, but it\xa0can be difficult to ascertain the form. High resolution CT (figure 1.28) is better at determining the form and has all but replaced the much more invasive bronchography, which\xa0involves instillation of radiopaque medium into the tracheobronchial tree.', '40cf67f9-f2f5-4f16-9935-fbb7f928762f': 'Where the bronchiectasis occurs in the lung is somewhat dependent on the cause. The segmental and subsegmental bronchi are the airway types most commonly affected, and the basilar segments of the lower lobes are the most frequent region in the lung. The second most common locations are the right middle lobe and lingual segments, while bronchiectasis caused by primary tuberculosis (TB)\xa0and other infections tend to occur in the upper lung fields where the infection is located (see figure 1.29).', 'd5c4f82c-5276-4294-802a-0338ebfbb119': 'So, how does bronchiectasis present, and what are the results of diagnostic tests?'}"
Figure 1.27,pulmonary/images/Figure 1.27.jpg,Figure 1.27: Forms of bronchiectasis.,There are different forms of bronchiectasis; these are classified by their shape (figure 1.27).,"{'04f9aefe-9a2e-4d2a-87d6-5f8b1b94232f': 'The outcomes of bronchiectasis\xa0are seen in the\xa0histology slide in figure 1.26, with the affected airway lumen filled with mucus and pus, and the airway walls exhibiting fibroglandular tissue and infiltration by inflammatory cells (outer red circle).', 'aa4b374a-8833-4dd4-8069-844da9e21e7a': 'The gross view (right panel, figure 1.26) shows severely dilated bronchi and noticeable\xa0thickening of their walls.', 'ee2a56dd-bf2a-4bec-846d-e142501aa5a8': 'There are different forms of bronchiectasis; these are classified by their shape (figure 1.27).', '6fbaaa0c-eb4e-4a4f-af24-e98089ffce9c': 'A bronchiectasis can be cylindrical, varicose (also known as fusiform), or cystic (also known as saccular). The\xa0shape is relevant to their effect on the efficacy of coughing; cylindrical form has\xa0very little effect on cough’s ability to clear mucus, whereas varicose and cystic forms tend to disproportionately collapse during cough and reduce its effectiveness at moving mucus up the airway.', '9b95f1a0-8db6-4189-993e-9db465dcd585': 'As shown\xa0in figure 1.28 an x-ray shows the presence of bronchiectasis, but it\xa0can be difficult to ascertain the form. High resolution CT (figure 1.28) is better at determining the form and has all but replaced the much more invasive bronchography, which\xa0involves instillation of radiopaque medium into the tracheobronchial tree.', '40cf67f9-f2f5-4f16-9935-fbb7f928762f': 'Where the bronchiectasis occurs in the lung is somewhat dependent on the cause. The segmental and subsegmental bronchi are the airway types most commonly affected, and the basilar segments of the lower lobes are the most frequent region in the lung. The second most common locations are the right middle lobe and lingual segments, while bronchiectasis caused by primary tuberculosis (TB)\xa0and other infections tend to occur in the upper lung fields where the infection is located (see figure 1.29).', 'd5c4f82c-5276-4294-802a-0338ebfbb119': 'So, how does bronchiectasis present, and what are the results of diagnostic tests?'}"
Figure 1.28,pulmonary/images/Figure 1.28.jpg,Figure 1.28: Chest x-ray and CT of severe bronchiectasis. In the x-ray there are clear markings in the right lung that follow the path of affected bronchi. The distinctly widened airways on the right of the CT are consistent with severe bronchiectasis.,"As shown in figure 1.28 an x-ray shows the presence of bronchiectasis, but it can be difficult to ascertain the form. High resolution CT (figure 1.28) is better at determining the form and has all but replaced the much more invasive bronchography, which involves instillation of radiopaque medium into the tracheobronchial tree.","{'04f9aefe-9a2e-4d2a-87d6-5f8b1b94232f': 'The outcomes of bronchiectasis\xa0are seen in the\xa0histology slide in figure 1.26, with the affected airway lumen filled with mucus and pus, and the airway walls exhibiting fibroglandular tissue and infiltration by inflammatory cells (outer red circle).', 'aa4b374a-8833-4dd4-8069-844da9e21e7a': 'The gross view (right panel, figure 1.26) shows severely dilated bronchi and noticeable\xa0thickening of their walls.', 'ee2a56dd-bf2a-4bec-846d-e142501aa5a8': 'There are different forms of bronchiectasis; these are classified by their shape (figure 1.27).', '6fbaaa0c-eb4e-4a4f-af24-e98089ffce9c': 'A bronchiectasis can be cylindrical, varicose (also known as fusiform), or cystic (also known as saccular). The\xa0shape is relevant to their effect on the efficacy of coughing; cylindrical form has\xa0very little effect on cough’s ability to clear mucus, whereas varicose and cystic forms tend to disproportionately collapse during cough and reduce its effectiveness at moving mucus up the airway.', '9b95f1a0-8db6-4189-993e-9db465dcd585': 'As shown\xa0in figure 1.28 an x-ray shows the presence of bronchiectasis, but it\xa0can be difficult to ascertain the form. High resolution CT (figure 1.28) is better at determining the form and has all but replaced the much more invasive bronchography, which\xa0involves instillation of radiopaque medium into the tracheobronchial tree.', '40cf67f9-f2f5-4f16-9935-fbb7f928762f': 'Where the bronchiectasis occurs in the lung is somewhat dependent on the cause. The segmental and subsegmental bronchi are the airway types most commonly affected, and the basilar segments of the lower lobes are the most frequent region in the lung. The second most common locations are the right middle lobe and lingual segments, while bronchiectasis caused by primary tuberculosis (TB)\xa0and other infections tend to occur in the upper lung fields where the infection is located (see figure 1.29).', 'd5c4f82c-5276-4294-802a-0338ebfbb119': 'So, how does bronchiectasis present, and what are the results of diagnostic tests?'}"
Figure 1.29,pulmonary/images/Figure 1.29.jpg,Figure 1.29: Common locations of the segmental and subsegmental broncho affected by bronchiectasis.,"Where the bronchiectasis occurs in the lung is somewhat dependent on the cause. The segmental and subsegmental bronchi are the airway types most commonly affected, and the basilar segments of the lower lobes are the most frequent region in the lung. The second most common locations are the right middle lobe and lingual segments, while bronchiectasis caused by primary tuberculosis (TB) and other infections tend to occur in the upper lung fields where the infection is located (see figure 1.29).","{'04f9aefe-9a2e-4d2a-87d6-5f8b1b94232f': 'The outcomes of bronchiectasis\xa0are seen in the\xa0histology slide in figure 1.26, with the affected airway lumen filled with mucus and pus, and the airway walls exhibiting fibroglandular tissue and infiltration by inflammatory cells (outer red circle).', 'aa4b374a-8833-4dd4-8069-844da9e21e7a': 'The gross view (right panel, figure 1.26) shows severely dilated bronchi and noticeable\xa0thickening of their walls.', 'ee2a56dd-bf2a-4bec-846d-e142501aa5a8': 'There are different forms of bronchiectasis; these are classified by their shape (figure 1.27).', '6fbaaa0c-eb4e-4a4f-af24-e98089ffce9c': 'A bronchiectasis can be cylindrical, varicose (also known as fusiform), or cystic (also known as saccular). The\xa0shape is relevant to their effect on the efficacy of coughing; cylindrical form has\xa0very little effect on cough’s ability to clear mucus, whereas varicose and cystic forms tend to disproportionately collapse during cough and reduce its effectiveness at moving mucus up the airway.', '9b95f1a0-8db6-4189-993e-9db465dcd585': 'As shown\xa0in figure 1.28 an x-ray shows the presence of bronchiectasis, but it\xa0can be difficult to ascertain the form. High resolution CT (figure 1.28) is better at determining the form and has all but replaced the much more invasive bronchography, which\xa0involves instillation of radiopaque medium into the tracheobronchial tree.', '40cf67f9-f2f5-4f16-9935-fbb7f928762f': 'Where the bronchiectasis occurs in the lung is somewhat dependent on the cause. The segmental and subsegmental bronchi are the airway types most commonly affected, and the basilar segments of the lower lobes are the most frequent region in the lung. The second most common locations are the right middle lobe and lingual segments, while bronchiectasis caused by primary tuberculosis (TB)\xa0and other infections tend to occur in the upper lung fields where the infection is located (see figure 1.29).', 'd5c4f82c-5276-4294-802a-0338ebfbb119': 'So, how does bronchiectasis present, and what are the results of diagnostic tests?'}"