Pathology Outline: Test 3 RESTRICTIVE LUNG DISEASES 1 Restrict ...


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Pathology Outline: Test 3 RESTRICTIVE LUNG DISEASES 1 Restrict ...

  1. 1. Pathology Outline: Test 3<br />RESTRICTIVE LUNG DISEASES 1<br /><ul><li>Restrict lung expansion >> decreased lung volume, increased work of breathing, inadequate ventilation and/or oxygenation.
  2. 2. Intrinsic diseases - interstitial lung disease - involve alveolar tissues >> pulmonary fibrosis, restrictive lung physiology
  3. 3. Extrinsic diseases - extraparenchymal diseases - affect chest wall, pleura, and respiratory muscles.</li></ul>Physiologic Changes in Restrictive Lung Disease <br /><ul><li>Characterized by reduced lung volume >> reduced total lung capacity (TLC)
  4. 4. Decreased measures of forced vital capacity (FVC) and forced expiratory volume (FEV1). Ratio of FEV1/FVC remains normal
  5. 5. Consequence of reduced pulmonary compliance >> attributed to accumulation of parenchymal scar tissue
  6. 6. Impaired gas exchange --- Resting arterial blood gas is normal >> Exercise-induced hypoxemia </li></ul>Idiopathic Pulmonary Fibrosis<br /><ul><li>Chronic, progressive and lethal --- characterized by fibrosis of pulmonary interstitium of unknown etiology.</li></ul>Epidemiology: Affects elderly persons with mean age of 66 years --- more frequent in men.<br />Clinical Manifestations<br /><ul><li>Latency period
  7. 7. May last one decade --- asymptomatic but have histologically-proven IPF >> progresses toward symptomatic IPF.
  8. 8. Early stage
  9. 9. Insidious onset of exertional dyspnea with a dry, nonproductive cough
  10. 10. Auscultation of lungs reveals early inspiratory crackles located in lower posterior lung zones.
  11. 11. Rales have a fine acoustic character reminiscent of sound made by Velcro.
  12. 12. Digital clubbing
  13. 13. Late complications
  14. 14. Respiratory failure with cyanosis, pulmonary hypertension and cor pulmonale
  15. 15. Loud P2 component of 2nd heart sound, fixed split S2, holosystolic tricuspid regurgitation murmur, and pedal edema. </li></ul>Imaging <br /><ul><li>Plain chest radiograph: Bilateral reticular markings (curvilinear opacities) at periphery and bases.
  16. 16. High-resolution computed tomography (HRCT): More accurate
  17. 17. Patchy reticular opacities, predominantly subpleural and bibasilar
  18. 18. Traction bronchiectasis, i.e. secondary involvement of medium-sized airways
  19. 19. Subpleural honeycombing, i.e. small, round translucencies and distortion with basal and peripheral distribution</li></ul>Morphology<br /><ul><li>Gross --- changes primarily in lower lobes
  20. 20. Pleural surfaces are cobblestoned as a result of the retraction of scars along interlobular septa.
  21. 21. Microcysts with intervening dense fibrosis.
  22. 22. Honeycomb --- cystic, dilated bronchioles (mucous and leukocytes) in scarred, fibrotic lung tissue.
  23. 23. Histopathology
  24. 24. Chronic fibrosing interstitial pneumonia associated with a histological pattern of usual interstitial pneumonia (UIP).
  25. 25. Patchy interstitial fibrosis, often in subpleural and/or paraseptal distribution, alternating with areas of normal lung.
  26. 26. Fibrosis is heterogeneous (different ages) with architectural destruction, and dense scarring with honeycombing</li></ul>Disease Course<br /><ul><li>Survival is poor --- mean survival ranging from 2 to 4 years after diagnosis.
  27. 27. Suppressing inflammation prevents progression to pulmonary fibrosis --- However, response to steroids is usually poor </li></ul>Pathogenesis<br /><ul><li>Original hypothesis --- unknown stimuli injure lung resulting in chronic inflammation, fibrogenesis and end-stage fibrotic scar.
  28. 28. Recent studies challenged the concept that inflammation is driving force in development of IPF.
  29. 29. Evident from disappointing effects of anti-inflammatory treatment
  30. 30. Increasing evidence that changes present in IPF result from sequential alveolar epithelial injury and abnormal wound repair.
  31. 31. Injuries induce alveolar epithelial damage resulting in necrosis, fibrin deposition (hyaline membranes) and hemostasis
  32. 32. Secrete growth factors and induce proliferation and differentiation to myofibroblasts that secrete proteins (collagens)
  33. 33. Myofibroblasts --- expression of alpha-smooth muscle actin
  34. 34. Responsible for wound contraction, which takes place during development of pulmonary fibrosis.
  35. 35. Production and secretion of collagen and a variety of cytokines, including profibrotic TGF-beta.
  36. 36. Imbalance of pro- and antifibrotic factors >> deposition of extracellular matrix within alveoli >> pulmonary fibrosis.
  37. 37. TGF-beta1 is known to be fibrogenic and is released from injured type I alveolar epithelial cells.
  38. 38. Favors transformation of fibroblasts into myofibroblasts and deposition of collagen
  39. 39. Down-regulates caveolin-1 (inhibitor of pulmonary fibrosis -- restoring alveolar epithelial repair processes)</li></ul>Pneumoconioses<br /><ul><li>Caused by inhalation of mineral dust, nearly always in occupational settings.
  40. 40. Develop after many years of cumulative exposure; often diagnosed in older individuals, long after onset of exposure. </li></ul>Coal Worker’s Pneumocoiosis<br /><ul><li>Accumulation of coal dust in lungs and tissue's reaction to its presence.
  41. 41. Spectrum of lung findings
  42. 42. Anthracosis
  43. 43. Asymptomatic --- innocuous coal-induced pulmonary lesion
  44. 44. Inhaled carbon particles are engulfed by alveolar macrophages which then accumulate in connective tissue
  45. 45. Accumulation of carbon particles causes no cellular reaction.
  46. 46. Grossly: focal black pigmentation scattered in upper zones of upper and lower lobes.
  47. 47. Simple CWP
  48. 48. Accumulation of carbon-laden macrophages occurs with little or no pulmonary dysfunction.
  49. 49. Characterized by coal macules (1 to 2 mm in diameter) and somewhat larger coal nodules.
  50. 50. Upper lobes and upper zones of lower lobes are heavily involved --- adjacent to respiratory bronchioles
  51. 51. Complicated CWP (progressive massive fibrosis)
  52. 52. Occurs on a background of simple CWP and generally requires many years to develop.
  53. 53. Characterized by intensely blackened scars larger than 2 cm
  54. 54. Center of the lesion is often necrotic, most likely due to local ischemia.
  55. 55. Clinical presentation.
  56. 56. Benign disease that causes little decrement in lung function.
  57. 57. Rarely, progressive massive fibrosis (PMF) develops
  58. 58. Leading to pulmonary dysfunction, respiratory insufficiency, pulmonary hypertension, and cor pulmonale </li></ul>Silicosis <br /><ul><li>Potentially fatal, irreversible, fibrotic pulmonary disease --- develop subsequent to inhalation of large amounts of silica dust.
  59. 59. Decades of exposure >> slowly-progressing, nodular, fibrosing pneumoconiosis.
  60. 60. Pathogenesis.
  61. 61. Crystalline and amorphous forms --- crystalline forms are more fibrogenic (quartz is most commonly implicated)
  62. 62. After inhalation, silica particles are cleared from lung by alveolar macrophages
  63. 63. Generates silicon-based radicals >> production of hydroxyl, hydrogen peroxide, and other oxygen radicals
  64. 64. Become damaged and release mediators -- IL-1, TNF, fibronectin, lipid mediators, and fibrogenic cytokines.
  65. 65. Morphology
  66. 66. Acute silicosis
  67. 67. Follows massive exposure to dust >> stimulates hypersecretion of alveolar surfactant
  68. 68. Alveoli are filled with a lipoproteinaceous material that is eosinophilic, PAS-positive and diastase resistant.
  69. 69. Chronic silicosis
  70. 70. Simple silicosis
  71. 71. Characterized by tiny, hard, palpable, discrete pale to blackened nodules in upper zones of lungs.
  72. 72. Nodule composed of silica surrounded by whorled collagen, macrophages, lymphocytes, fibroblasts
  73. 73. Examination of the nodules by polarized microscopy reveals birefringent silica particles.
  74. 74. Complicated silicosis (progressive massive fibrosis)
  75. 75. Develops when the above described silicotic nodules coalesce forming pulmonary scars >2 cm.
  76. 76. Central softening and cavitation --- due to superimposed tuberculosis or to ischemia.
  77. 77. Fibrotic lesions may also occur in the hilar lymph nodes and pleura.
  78. 78. Thin sheets of calcification occur in lymph nodes --- seen radiographically as eggshell calcification
  79. 79. Clinical manifestations.
  80. 80. Acute silicosis
  81. 81. Causes symptoms weeks to a few years after exposure.
  82. 82. Severe dyspnea, cough, fever, weight loss, pleuritic pain
  83. 83. Chest radiograph suggest a ground-glass appearance, similar to pneumonia or pulmonary edema.
  84. 84. Chronic silicosis
  85. 85. Simple silicosis: may be asymptomatic
  86. 86. Abnormalities detected by x-ray --- Small, rounded opacities in upper lung zones
  87. 87. Chronic cough and exertional dyspnea develop later.
  88. 88. Simple silicosis progresses toward complicated silicosis because of development of severe scarring where
  89. 89. Nodules become confluent, reaching a size of 1.0 cm or greater >> more severe symptoms
  90. 90. Imaging
  91. 91. Chest radiography reveals nodular opacities scattered diffusely throughout lungs more prominent in upper lung fields.
  92. 92. Complicated silicosis manifests as bilateral upper lobe masses, which are formed by the coalescence of nodules.
  93. 93. Pulmonary physiologic changes
  94. 94. Disease progression >> restrictive or mixed pattern of obstruction and restriction
  95. 95. Progressive massive fibrosis causes severe restriction, decreased compliance, and hypoxemia.</li></ul>Asbestos-Related Diseases <br /><ul><li>Caused by inhalation and retention of asbestos fibers.
  96. 96. Occur after high intensity and/or long-term exposure to asbestos.
  97. 97. Types of asbestos fibers.
  98. 98. Chrysotile (serpentine)
  99. 99. Fibers are curly, longer and more flexible
  100. 100. Fibers settle in large airways and are eliminated by ciliary action
  101. 101. Amphiboles
  102. 102. Fibers are characteristically straight, rigid, and needlelike.
  103. 103. Fibers reach small bronchi and alveoli and are most dangerous
  104. 104. Spectrum of asbestos-related diseases.
  105. 105. Benign pleural effusion, pleural plaques, diffuse pleural thickening, asbestosis, mesothelioma, and lung carcinoma.
  106. 106. Asbestosis -- diffuse lung fibrosis due to inhalation of asbestos fibers >> major cause of occupational lung damage
  107. 107. Mesothelioma -- malignant pleural tumor arising from mesothelium lining lungs
  108. 108. Morphology.
  109. 109. Asbestosis
  110. 110. Diffuse pulmonary interstitial fibrosis
  111. 111. Asbestos bodies: golden brown, fusiform or beaded rods with a translucent
  112. 112. Consist of asbestos fibers coated with an iron-containing proteinaceous material.
  113. 113. Arise when macrophages attempt to phagocytose asbestos fibers >> phagocyte ferritin.
  114. 114. ‘Ferruginous bodies’ -- similar to asbestos bodies - mineral filament coated with protein-iron
  115. 115. Fibrous tissue distorts lung architecture, creating enlarged airspaces enclosed within thick fibrous walls.
  116. 116. Affected regions become honeycombed.
  117. 117. Assessing severity of asbestosis
  118. 118. Grade 1 is fibrosis in the wall of a respiratory bronchiole without extension to distant alveoli.
  119. 119. Grades 2 and 3 define more extensive disease
  120. 120. Grade 4 corresponds to honeycombing, i.e. pulmonary fibrosis with spaces larger than alveoli
  121. 121. Begins in lower lobes >> progresses to middle and upper lobes of lungs
  122. 122. Scarring may trap and narrow pulmonary arteries, causing pulmonary hypertension and cor pulmonale.
  123. 123. Pleural plaques
  124. 124. Most common manifestation of asbestos exposure -- asymptomatic and detected on radiographs
  125. 125. Well-circumscribed plaques of dense collagen, often containing calcium.
  126. 126. Develop frequently on anterior and posterolateral aspects of parietal pleura and over domes of diaphragm.
  127. 127. Do not contain asbestos bodies.
  128. 128. Lung carcinomas and mesothelioma: Develop in workers exposed to asbestos.
  129. 129. Clinical manifestations.
  130. 130. Dyspnea is usually first manifestation; at first, it is provoked by exertion, but later it is present even at rest.
  131. 131. Accompanied by a cough associated with production of sputum.
  132. 132. Chest x-rays reveal irregular linear densities, particularly in both lower lobes.
  133. 133. With advancement of pneumoconiosis, a honeycomb pattern develops.
  134. 134. May remain static or progress to respiratory failure, cor pulmonale, and death. </li></ul>Granulomatous Diseases<br />Sarcoidosis <br /><ul><li>Systemic disease of unknown cause characterized by noncaseating granulomas in many tissues and organs.
  135. 135. Etiology and pathogenesis.
  136. 136. Unknown --- evidence suggest that it is a disease of disordered immune regulation.
  137. 137. Immunological abnormalities --- development of a cell-mediated response driven by CD4+ helper T cells.
  138. 138. Systemic immunological abnormalities --- anergy to common skin test antigens such as Candida or PPD.
  139. 139. Evidence of genetic influences --- association with certain HLA genotypes.
  140. 140. Several putative organisms (e.g., mycobacteria, Propionibacterium acnes, and Rickettsia species).
  141. 141. Morphology.
  142. 142. Non-caseating granulomas composed of epithelioid cells, often with Langhans or foreign body-type giant cells.
  143. 143. Enclosed within fibrous rims or may eventually be replaced by hyaline fibrous scars.
  144. 144. Composed of calcium and proteins known as Schaumann bodies and stellate inclusions known as asteroid bodies
  145. 145. May be encountered in other granulomatous diseases (e.g., tuberculosis).
  146. 146. Sites of involvement.
  147. 147. Lungs are common sites of involvement.
  148. 148. Lesions are distributed along lymphatics, around bronchi and blood vessels – also alveolar lesions
  149. 149. Tendency for lesions to heal in lungs, so varying stages of fibrosis and hyalinization are often found.
  150. 150. Lymph nodes: particularly tonsils, hilar and mediastinal nodes >> Enlarged, discrete, and sometimes calcified.
  151. 151. Spleen (granulomas and splenomegaly),
  152. 152. Liver (one third of patients have liver granulomas and hepatomegaly),
  153. 153. Bone marrow, skin (erythema nodosum, macules, papules, and plaques),
  154. 154. Eye (iritis and iridocyclitis)
  155. 155. Muscle (weakness, aches, tenderness, and fatigue).
  156. 156. Hypercalcemia: Epitheloid cells in sarcoidosis granulomas can produce calcitriol (1,25 vitamin D) and cause hypercalcemia,
  157. 157. Hypercalciuria: 3 times more common than hypercalcemia --- result in nephrocalcinosis and renal failure.
  158. 158. Clinical manifestations.
  159. 159. Bilateral hilar lymphadenopathy or lung involvement is visible on chest radiographs is most common.
  160. 160. Eye and skin lesions occur next in frequency.
  161. 161. Peripheral lymphadenopathy, cutaneous lesions, eye involvement, splenomegaly, or hepatomegaly.
  162. 162. Onset of respiratory abnormalities (shortness of breath, cough, chest pain, hemoptysis)
  163. 163. Onset of constitutional signs and symptoms (fever, fatigue, weight loss, anorexia, night sweats).
  164. 164. Disease course.
  165. 165. Unpredictable course characterized by either progressive chronicity or periods of activity interspersed with remissions
  166. 166. Usually recover with minimal or no residual manifestations.</li></ul>Hypersensitivity pneumonitis <br /><ul><li>Immunologically mediated lung disorders caused by intense, prolonged exposure to inhaled organic antigens.
  167. 167. Farmer's lung results from exposure to dusts generated from harvested humid, warm hay
  168. 168. Permits rapid proliferation of the spores of thermophilic actinomycetes.
  169. 169. Pigeon breeder's lung (bird fancier's disease) is provoked by proteins from serum, excreta, or feathers of birds.
  170. 170. Humidifier or air-conditioner lung is caused by thermophilic bacteria in heated water reservoirs.
  171. 171. Categorized as acute, subacute, and chronic progressive -- based on length and intensity of exposure
  172. 172. Epidemiology: Prevalence varies by region, climate, and farming practices --- mean age is 53 years. 
  173. 173. Pathogenesis.
  174. 174. Initially thought to be an immunocomplex-mediated process (type III hypersensitivity)
  175. 175. Complement and immunoglobulins have been demonstrated within vessel walls
  176. 176. Subsequent studies showed that cell-mediated immunity (type IV hypersensitivity) --- noncaseating granulomas
  177. 177. Morphology.
  178. 178. Early stage
  179. 179. Alveolitis with fibrinous exudates and neutrophils within alveolar lumina.
  180. 180. Leads to organization of alveolar exudate by granulation tissue growing and filling alveoli and bronchioles.
  181. 181. Later stage
  182. 182. Non-necrotizing granulomas in lungs >> thickening of alveolar walls by a diffuse lymphocytic infiltrate. 
  183. 183. Hilar lymph nodes are unaffected.
  184. 184. Resolution within 6 months unless is further exposure >> inflammation may progress to an irreversible scarring.
  185. 185. In fatal cases lungs show “honeycombing” with dense fibrosis.
  186. 186. Clinical manifestations.
  187. 187. Acute attacks consist of recurring episodes of fever, dyspnea, cough, and leukocytosis >> 4 to 6 hours after exposure
  188. 188. Infiltrates appear in chest radiograph, and pulmonary function tests show acute restrictive disorder.
  189. 189. If exposure is continuous and protracted >> chronic disease >> respiratory failure, dyspnea, and cyanosis
  190. 190. Laboratory studies.
  191. 191. Leukocytosis and neutrophilia, elevated ESR, and C-reactive protein, and hypergammaglobulinemia
  192. 192. Precipitating antibodies to offending antigen are commonly present --- marker or exposure</li></ul>Pulmonary alveolar proteinosis (PAP) <br /><ul><li>Characterized radiologically by bilateral patchy asymmetric pulmonary opacifications
  193. 193. Characterized histologically by accumulation of acellular surfactant in the intra-alveolar and bronchiolar spaces. </li></ul>Classification: Primary (or acquired), secondary and congenital PAP --- different pathogenesis but similar histologic changes <br />Epidemiology: Rare --- M:F = 4:1. Age of onset varies from 20-50 years old <br />Morphology<br /><ul><li>Characterized by a peculiar granular precipitate within alveoli, causing focal-to-confluent consolidation of large areas of lungs
  194. 194. On section, turbid fluid exudes from these areas >> increase in size and weight of lung.
  195. 195. Alveolar precipitate is periodic acid-Schiff positive and also contains cholesterol clefts.
  196. 196. Immunohistochemical staining reveals abundant accumulation of surfactant protein. </li></ul>Pathogenesis<br /><ul><li>Congenital PAP.
  197. 197. Autosomal Recessive --- Caused by mutations in genes that encode for:
  198. 198. Surfactant proteins B or C (SP-B and SP-C)
  199. 199. Beta chain of receptor for granulocyte–macrophage colony-stimulating factor (GM-CSF).
  200. 200. GM-CSF -- hematologic growth factor which stimulates production of myeloid cells from hematopoietic precursors.
  201. 201. Disruption of gene causes accumulation of abundant surfactant in alveoli
  202. 202. Defect in the catabolism of surfactant by alveolar macrophages.
  203. 203. Pulmonary GM-CSF stimulates production of high levels of PU.1 in alveolar macrophages.
  204. 204. Promotes growth and differentiation of myeloid progenitors required for production of macrophages.
  205. 205. Primary PAP.
  206. 206. Autoimmune disease - Circulating antibodies inhibit GM-CSF activity >> accumulation of proteinaceous fluid in alveoli
  207. 207. Secondary PAP.
  208. 208. Develops with conditions involving functional impairment or reduced numbers of alveolar macrophages.
  209. 209. Hematologic malignancies, particularly chronic myeloid leukemia and lymphomas
  210. 210. Occupational exposures, particularly mineral dusts (silica) and fumes
  211. 211. Infections, including those caused by Nocardia, Mycobacterium tuberculosis, and fungal infections</li></ul>Clinical Manifestations<br /><ul><li>Nonspecific respiratory difficulty of insidious onset, cough, and abundant sputum containing chunks of gelatinous material.
  212. 212. Progressive dyspnea, cyanosis, and respiratory insufficiency may occur, but some patients tend to have a benign course.
  213. 213. Congenital PAP: fatal respiratory disorder that is usually immediately apparent in the newborn.
  214. 214. Develops progressive respiratory distress shortly after birth</li></ul>Prognosis<br /><ul><li>Very good, with achievement of complete remissions in many patients with whole-lung lavage, but relapses may occur.
  215. 215. GM-CSF therapy is effective in 50% of patients
  216. 216. Congenital PAP responds favorably to lung transplantation.</li></ul>RESTRICTIVE LUNG DISEASES 2<br />Pulmonary Surfactant<br /><ul><li>Dipalmitoyl phosphatidylcholine (DPPC), or lecithin, is functionally the primary phospholipid.
  217. 217. Four surfactant proteins (SPs) expressed by respiratory epithelial cells, designated as SP-A, SP-B, SP-C and SP-D.
  218. 218. Surfactant components are synthesized, secreted and recycled by type II pneumocytes in alveolus. </li></ul>Lung Immaturity in Premature Infants <br /><ul><li>Immaturity of the lungs poses one of most common and immediate threats to viability of low-birth-weight infant.
  219. 219. Lining cells of fetal alveoli do not differentiate into type I and type II pneumocytes until late pregnancy.
  220. 220. Composition of lung surfactant changes as fetus matures:
  221. 221. Concentration of lecithin increases rapidly at beginning of 3rd trimester and rises rapidly to reach a peak near term
  222. 222. Most of lecithin in mature lung is dipalmitate -- in immature lung it is less-surface-active alpha-palmitate species
  223. 223. Phosphatidylglycerol starts to increase only at 35 weeks and is found to be predictive of fetal lung maturity
  224. 224. Before 35th week, immature surfactant contains a higher proportion of sphingomyelin than adult surfactant.
  225. 225. Pulmonary surfactant is released into amniotic fluid, which can be sampled by amniocentesis to assess maturity of fetal lung.
  226. 226. Lecithin-to-sphingomyelin ratio (L/S ratio) above 2:1 >> fetus will survive without respiratory distress syndrome.
  227. 227. After 35th week, appearance of phosphatidylglycerol in amniotic fluid is best proof of the maturity of fetal lungs.</li></ul>Hyaline Membrane Disease (HMD) <br /><ul><li>Acute lung disease of premature newborns caused by surfactant deficiency.</li></ul>Epidemiology<br /><ul><li>Associated with prematurity --- related to a relative lack of mature type II epithelial cells of alveolus (type II pneumocytes).
  228. 228. Twice as common in boys as in girls at every gestational age.</li></ul>Pathogenesis<br /><ul><li>Result of anatomic pulmonary immaturity and a deficiency of surfactant.
  229. 229. Absence of surfactant results in poor pulmonary compliance, atelectasis (failure of pulmonary alveoli to expand).
  230. 230. Atelectasis results in perfused but not ventilated alveoli >> decreased gas exchange, severe hypoxia and acidosis.</li></ul>Pathology<br /><ul><li>Gross appearance.
  231. 231. Lungs are heavy, dark and airless
  232. 232. Hepatization --- texture of cut sections of firm, homogeneous, atelectatic tissue is reminiscent of liver.
  233. 233. Microscopic appearance.
  234. 234. Microscopy confirms atelectasis, with air limited to bronchioles.
  235. 235. Interstitial edema --- result of transudation of fluid into the interstitium from capillary leak.
  236. 236. Hyaline membranes are found at boundary of air-filled bronchioles and collapsed alveoli.
  237. 237. Separate from bronchial wall at 36–48 hours and are cleared by alveolar macrophages.
  238. 238. Airways containing hyaline membranes are surrounded by collapsed acini of surfactant-deficient lungs.
  239. 239. Consequence of injury to bronchiolar and alveolar lining.
  240. 240. Physical: shear forces on epithelium at the air-liquid interface >> alveoli collapse.</li></ul>Clinical Presentation<br /><ul><li>First symptom within an hour of birth: increased respiratory effort -- forceful intercostal retraction and use of neck muscles.
  241. 241. Respiratory rate > 100 breaths/min, expiratory grunting (due to partial closure of glottis), nasal flaring and cyanosis.
  242. 242. In severe cases, infant becomes progressively obtunded and flaccid.
  243. 243. Long periods of apnea ensue, and the infant eventually dies of asphyxia.</li></ul>Laboratory Studies<br /><ul><li>Arterial blood gas studies show hypoxemia, hypercapnia, and mixed respiratory and metabolic acidosis.
  244. 244. Respiratory acidosis due alveolar atelectasis (decreased gas exchange >> increased blood carbon dioxide and decreased pH)
  245. 245. Metabolic acidosis results from poor tissue perfusion and anaerobic metabolism (hypoxemia >> production of lactic acid). </li></ul>Imaging<br /><ul><li>Mild to moderate cases of HMD.
  246. 246. Generalized acinar collapse that results from surfactant deficiency.
  247. 247. Chest radiography demonstrates
  248. 248. Decreased lung expansion
  249. 249. Symmetric generalized consolidation of variable severity
  250. 250. Effacement of normal pulmonary vessels
  251. 251. Air bronchograms (air-filled bronchi seen as radiolucent, branching bands within pulmonary densities).
  252. 252. ‘Reticulogranular’ texture of lung opacities
  253. 253. Represents collapsed alveoli, fluid into interstitium from capillary leak, and distention by air of bronchioles
  254. 254. Severe cases of HMD.
  255. 255. Dense bilateral symmetric lung consolidations (white out) completely efface cardiac and diaphragm contours.
  256. 256. Chest radiographs demonstrate granularity that evolved to generalized hazy opacities to clearing</li></ul>Evaluation of Lung Maturity by Amniotic Fluid Analysis <br /><ul><li>Tests of fetal lung maturity -- which measure surfactant obtained by amniocentesis or collected from vagina.
  257. 257. Risk of HMD is low when lecithin/sphingomyelin ratio is > 2, and phosphatidylglycerol is present.</li></ul>Prevention: Giving mother betamethasone or dexamethasone at least 48h before premature delivery induces fetal surfactant production<br />Complications<br /><ul><li>Major complications related to anoxia and acidosis:
  258. 258. Intraventricular cerebral hemorrhage.
  259. 259. Anoxic injury to the periventricular capillaries, venous sludging and thrombosis, and impaired vascular autoregulation.
  260. 260. Persistence of patent ductus arteriosus.
  261. 261. With recovery, pulmonary pressure declines, and high aortic pressure reverses direction of blood flow in ductus
  262. 262. Creating a persistent left-to-right shunt >> Congestive heart failure
  263. 263. Necrotizing enterocolitis.
  264. 264. Ischemia of intestinal mucosa >> bacterial colonization with C. difficile >> lesions, gangrene and perforation of bowel.
  265. 265. Bronchopulmonary dysplasia.
  266. 266. Results from oxygen toxicity --- infants maintained on a positive-pressure respirator with high oxygen tensions
  267. 267. Respiratory distress reflected in hypoxia, acidosis, oxygen dependency, and onset of right-sided heart failure.
  268. 268. Radiographs: change from complete opacification >> spongelike appearance (lucent areas with denser foci).
  269. 269. Microscopic examination: hyperplasia of bronchiolar epithelium and squamous metaplasia in bronchi and bronchioles.
  270. 270. Atelectasis, interstitial edema, and thickening of alveolar basement membranes </li></ul>Evolving Nomenclature <br /><ul><li>‘Hyaline membrane disease’ is now less commonly used in clinical practice
  271. 271. ‘Respiratory distress syndrome’ is used to denote surfactant, but ‘surfactant deficiency disorder’ has been proposed.</li></ul>Risk Factors for Hyaline Membrane Disease <br /><ul><li>Cesarean section
  272. 272. Iatrogenic respiratory distress syndrome (RDS)
  273. 273. Result of: (1) cesarean section as a mode of delivery and (2) birth prior to the onset of labor.
  274. 274. Cesarean section as a mode of delivery
  275. 275. Vaginal birth
  276. 276. Higher catecholamine concentration enhances cardiac performance and mobilized glucose
  277. 277. Stimulates absorption of lung liquid and enhances release of surfactants.
  278. 278. Cesarean section: Larger residual volume of lung fluid, secrete less surfactant >> higher risk for HMD
  279. 279. Maternal diabetes mellitus
  280. 280. Poor glycemic control leads to preterm delivery
  281. 281. Hyperglycemia induces endothelial dysfunction and nitric oxide-depended vasodilatation.
  282. 282. NO is a uterine relaxant -- decreased synthesis of NO in uterus is associated with initiation of labor.</li></ul>Acute Respiratory Distress Syndrome (Synonym: adult respiratory distress syndrome)<br /><ul><li>Initiated by damage to alveolar epithelium and pulmonary capillary endothelium (diffuse alveolar damage)
  283. 283. Followed by increased permeability into lung interstitium and alveolar spaces (noncardiogenic pulmonary edema).
  284. 284. High mortality rate, survivors appear to recover completely but tests of lung function show mild restrictive or diffusion defect.
  285. 285. Hypoxemia from intrapulmonary shunting manifests clinically as cyanosis refractory to oxygen therapy. </li></ul>Pathogenesis of Diffuse Alveolar Damage <br /><ul><li>Type I alveolar pneumocyte and capillary endothelial cell are exceptionally thin >> vulnerable to non-specific damage.
  286. 286. Necrosis of type I alveolar pneumocyte and capillary endothelial cell.
  287. 287. Type I alveolar epithelial cells show cytoplasmic blebbing >> necrosis resulting in denudation of basement membrane
  288. 288. Similar blebbing seen in alveolar capillary endothelium but denudation of basement membrane is seldom observed
  289. 289. Increase in alveolar and pulmonary capillary permeability.
  290. 290. Escape of protein-rich exudates into interstitial and alveoli, loss of alveolar lining film and pulmonary collapse.
  291. 291. Inflammatory cascade.
  292. 292. Activated neutrophils and macrophages follow exudate, and an inflammatory cascade is initiated.
  293. 293. Release of interleukins, tumor necrosis factor, and other inflammatory mediators.
  294. 294. Neutrophils release oxidants, leukotrienes, and various proteases.
  295. 295. Massive cell damage, alveolar denudation, and sloughing of cell debris into lumen of alveolus >> Surfactant depletion
  296. 296. Alveolar collapse.
  297. 297. Surfactant depletion leads to alveolar collapse because of increased surface tension.
  298. 298. As alveoli collapse, closing lung volume decreases and reduced compliance further increasing work of breathing.
  299. 299. Small vessel thrombosis.
  300. 300. In pulmonary capillary, injury to endothelial cells induces platelets to aggregate >> procoagulant cascade
  301. 301. Impairment of oxygen-diffusing capacity.
  302. 302. Widened interstitial space between alveolus and vascular endothelium decreases oxygen-diffusing capacity.  
  303. 303. Respiratory muscle fatigue.
  304. 304. Decrease in lung compliance increases work of breathing and leads to respiratory muscle fatigue.</li></ul>Clinical Presentation<br /><ul><li>Characterized by acute dyspnea and hypoxemia after event (trauma, sepsis, drug overdose, transfusion, or aspiration)
  305. 305. Onset of lung injury >> dyspnea with exertion >> progresses to severe dyspnea at rest, tachypnea, anxiety, agitation
  306. 306. Associated hypotension, peripheral vasoconstriction with cold extremities, cyanosis of lips and nailbeds may occur.</li></ul>Diffuse Alveolar Damage <br /><ul><li>Exudation.
  307. 307. Lasts about 1 week -- lungs are wet, heavy, dark and airless -- cut surface exudes heavily bloodstained watery fluid.
  308. 308. Collapse of alveoli, intense congestion of capillaries, interstitial edema and distension of lymphatics.
  309. 309. At air/tissue interface respiratory movements deposit a fibrin-rich exudate mixed with necrotic epithelial debris
  310. 310. Compact into a thin layer that covers an epithelial basement membrane >> formation of hyaline membranes.
  311. 311. Regeneration.
  312. 312. Healing may be by
  313. 313. Resolution, which involves fibrinolysis and permits the lungs to return to normal
  314. 314. Repair, which involves fibrosis and leaves the lungs permanently scarred.
  315. 315. Stem cell concerned in epithelial regeneration is type II alveolar epithelial cell.
  316. 316. First proliferate and then differentiate into type I cells >> re-epithelializing denuded basement membranes.
  317. 317. Type II cells form simple cuboidal epithelium beneath exudates >> casting hyaline membranes into air space
  318. 318. Atelectatic induration: Regenerating epithelial cells bridge collapsed alveoli so air spaces never re-expand
  319. 319. Repair.
  320. 320. Honeycombing suggests extensive lung fibrosis with alveolar destruction >> Presence of thick-walled, air-filled cysts.
  321. 321. Myofibroblasts contracture -- results in harmful distortion of bronchioloalveolar architecture and shrinkage of lungs.
  322. 322. Fibroblasts proliferate and lay down collagen, leading to development of interstitial fibrosis.
  323. 323. Fibrosis by accretion: incorporation of alveolar collagen into interstitium as basement membrane is formed.
  324. 324. Increase in lung collagen can be detected --- Survivors of ARDS may suffer from debilitating fibrotic lung disease.</li></ul>Etiology of Adult Respiratory Distress Syndrome <br /><ul><li>Entrance to lungs directly via airways, e.g. high oxygen, poisonous gases and metallic fumes.
  325. 325. Penetrate chest wall to damage lungs (e.g. ionizing radiation) or reach lungs via bloodstream, (ingested or injected).
  326. 326. Shock.
  327. 327. State of prolonged hypotension, generally attributable to trauma, hypovolemia, cardiac failure, sepsis or anaphylaxis.
  328. 328. Hypotension leads to inadequate tissue perfusion and multiorgan failure.
  329. 329. Congestive atelectasis or hemorrhagic edema, as described above.
  330. 330. Accumulation of neutrophils in alveolar walls >> damage by production of oxygen radicals and releasing enzymes
  331. 331. Blood transfusion.
  332. 332. Leukocyte antibodies - cause of lung injury > initiate alveolar capillary damage by stimulating granulocyte aggregation
  333. 333. Fat embolism.
  334. 334. Pulmonary fat embolism accompanies bony injury >> progressive hypoxemia, confusion and petechial hemorrhages.
  335. 335. Chemical vasculitis caused by toxic effects of free fatty acids released by action of pulmonary lipase on neutral fats.
  336. 336. Causes necrosis of endothelial and type I cells >> proliferation of type II cells >> progressive fibrosis
  337. 337. Cardiopulmonary bypass.
  338. 338. Entails oxygenation and circulation of blood by extracorporeal devices, permitting major heart surgery.
  339. 339. "Postperfusion lung": showes alveolar damage with degranulation of neutrophils in pulmonary capillaries.
  340. 340. Complement cascade >> Aggregation of neutrophils in lungs >> damage from lysosomal enzymes and radicals.
  341. 341. Oxygen toxicity.
  342. 342. Due to high partial pressure of oxygen for hypoxemia treatment >> intracellular production of active oxygen radicals.
  343. 343. Earliest ultrastructural change is swelling of endothelial cells; cytoplasm becomes grossly edematous and vacuolated.
  344. 344. Swelling and fragmentation of type I epithelial cells follows --- become separated from their basement membrane</li></ul>Prognosis<br /><ul><li>Survivors frequently have significant functional impairment even 1 year after discharge.
  345. 345. Spirometry and lung volumes normalize within 6 months, but diffusing capacity remains diminished at 1 year.
  346. 346. Health-related quality of life is below normal, however, no patient remains oxygen-dependent at 12 months</li></ul>NON INFECTIOUS UPPER RESPIRATORY TRACT DISORDERS<br />  <br />Vocal Cord Nodules and Vocal Cord Polyps<br /><ul><li>Tissue growths that develop on vocal cords --- most often in heavy smokers or those who impose great strain on vocal cords </li></ul>Vocal Cord Nodules (synonym: singer’s nodule)<br /><ul><li>Localized, benign growths on medial surface of true vocal folds that are commonly believed result of phonotrauma.
  347. 347. Smooth, rounded, and sessile --- Bilateral with location at junction of anterior and middle third of vocal cord.
  348. 348. Most often observed in women aged 20-50 years, but are also found commonly in children (Boys>Girls) prone to shouting</li></ul>Vocal Cord Polyps<br /><ul><li>Unilateral with broad spectrum of appearances -- hemorrhagic to edematous, pedunculated to sessile, gelatinous to hyalinized
  349. 349. Pedunculated -- involve free edge of anterior third of vocal cord mucosa.
  350. 350. Result from phonotrauma; however, event that triggers formation is vocal cord bleeding. </li></ul>Histopathology<br /><ul><li>Both covered by squamous epithelium
  351. 351. Core is a loose myxoid connective tissue -- fibrotic or punctuated by numerous vascular channels.
  352. 352. Characteristically change character of voice with progressive hoarseness >> never give rise to cancers. </li></ul>DIagnosis<br /><ul><li>Videostrobolaryngoscopy (or stroboscopy) is most sensitive for detecting laryngeal lesions
  353. 353. Demonstrate subtle differences in appearance, pliability, and mucosal wave characteristics.  
  354. 354. Remains clinical gold standard for assessing properties of glottal phonatory function. </li></ul>Squamous Papilloma of Larynx<br /><ul><li>Most common benign laryngeal tumor -- located on true vocal cords -- form soft, raspberry-like excrescences
  355. 355. Histologically -- slender, finger-like projections supported by fibrovascular cores and covered by stratified squamous epithelium
  356. 356. Arise as multiple tumors, usually in children -- tendency to recur frequently and to spread downward >> trachea, and bronchi.
  357. 357. Known as ‘recurrent respiratory papillomatosis’. </li></ul>Epidemiology<br /><ul><li>Bimodal distribution -- initial peak in childhood (juvenile-onset SP) and a second peak in adulthood (adult-onset SP).
  358. 358. Children: diagnosed at 2–3 years of age, male-to-female ratio is approximately equal
  359. 359. Adult: manifests in age range of 20-40 years. Male-to-female ratio is estimated to be 4:1</li></ul>Clinical Presentation<br /><ul><li>Larynx is most frequently affected site and hoarseness is most common presenting symptom.
  360. 360. Other symptoms include: voice change, foreign body sensation, cough, choking episodes, inspiratory wheezing
  361. 361. Stridor: whistling sound with inspiration resulting from turbulent air flow; indicates obstruction of larynx</li></ul>Etiology: Caused by low-risk human papillomavirus (HPV) types 6 and 11. <br />Pathogenesis<br /><ul><li>Juvenile-onset SP results from peripartum transmission of virus from an infected mother.
  362. 362. Condylomas during pregnancy and vaginal delivery appear to be at greatest risk of infecting their newborn.
  363. 363. Mode of transmission of virus in adults is unknown, but sexual transmission is probable.</li></ul>Laryngeal Carcinoma<br /><ul><li>Malignant tumor of epithelial origin that arises from laryngeal mucosa -- Most common cancer of upper aerodigestive tract. </li></ul>Epidemiology: Most commonly affects men (African Americans > Caucasians) 50 - 60 years old who are smokers and use alcohol<br />Etiology<br /><ul><li>Smoking and alcohol.
  364. 364. Most widely accepted risk factors
  365. 365. Hyperplastic morphological changes of laryngeal mucosa often regress after cessation of smoking.
  366. 366. Other risk factors: Gastroesophageal reflux disease (GERD), HPV infection, nutritional factors, and irradiation. </li></ul>Clinical Presentation<br /><ul><li>Sites of origin.
  367. 367. True vocal cords are most common site, followed by supraglottis, and subglottis.
  368. 368. Anterior portion of true vocal cord is the most common location -- most lesions occurring along free margin
  369. 369. Clinical presentation.
  370. 370. Glottic cancer: Hoarseness is most common symptom, since small irregularities in vocal fold result in voice changes.
  371. 371. Supraglottic cancer: Arises from laryngeal or lingual surface of epiglottis.
  372. 372. Asymptomatic until it manifests as a mass lesion
  373. 373. Odynophagia (painful swallowing), dysphagia (difficulty swallowing), and neck mass >> Hoarseness
  374. 374. Subglottic cancer: Manifest as mass lesion >> airway compromise (inspiratory stridor) or dysphagia >> Hoarseness
  375. 375. Physical findings.
  376. 376. Palpation of neck looking for enlarged lymph nodes is paramount in patient's evaluation.
  377. 377. Patients presenting with hoarseness should undergo a flexible laryngoscope evaluation.
  378. 378. Malignant lesions appear as friable, fungating, ulcerative masses or as subtle changes in mucosal color.
  379. 379. Extremely vulnerable to secondary infection of ulcerating lesion.
  380. 380. With surgery, irradiation, or combination therapy, many patients can be cured, but ~1/3 die of disease.
  381. 381. Usual causes of death are infection of distal respiratory passages or widespread metastases and cachexia.</li></ul>Sequence of Hyperplasia-Dysplasia-Carcinoma <br /><ul><li>The concept of preinvasive stages 
  382. 382. Encompassed within laryngeal squamous epithelium -- not breach basement membrane to reach lamina propria.
  383. 383. Transition from a normal epithelium to squamous cell carcinoma of larynx is a lengthy, multistage process
  384. 384. Progressive accumulation of genetic changes >> selection of a clonal population of transformed epithelial cells.
  385. 385. Histological changes ranges from simple squamous hyperplasia to atypical hyperplasia to carcinoma in situ.
  386. 386. Morphology of preinvasive stages.
  387. 387. Simple squamous hyperplasia: Characterized by a thickening of epithelium. No atypia - mitoses are rare
  388. 388. Atypical hyperplasia: Characteristics of former and, in addition, atypia (enlarged, irregular, hyperchromatic nuclei)
  389. 389. Carcinoma in situ: Atypical changes -- entire thickness of epithelium -- no extension beyond the basement membrane
  390. 390. Potential for malignant transformation.
  391. 391. Likelihood of development of an overt carcinoma is directly proportional to level of atypia.
  392. 392. Simple squamous hyperplasias have almost no potential for malignant transformation. </li></ul>Morphology – Gross Appearance <br /><ul><li>Exophytic lesions.
  393. 393. Mass-forming lesions -- may be nodular, fungating, papillary or verrucous in appearance.
  394. 394. Color varies from red to white, depending on amount of keratinization of epithelial surface.
  395. 395. Feel hard (indurated) due to fibrosis of underlying stroma in response to tumor invasion.
  396. 396. Endophytic lesions: Diffuse enlargement and hardening of mucosa -- infiltrate deeply rather than forming an external mass.  
  397. 397. Ulcerated lesions: Appear as a depressed, irregularly shaped, ulcerated central zone. </li></ul>Morphology – Microscopic Appearance <br /><ul><li>Squamous cell carcinoma.
  398. 398. Form irregular nests and strands of tumor cells separated by varying amounts of fibrous stroma.
  399. 399. Flattened polyhedral, round, or ovoid epithelial cells -- large irregular nuclei, clumped chromatin, varying nucleoli
  400. 400. Keratinization:
  401. 401. Individually, keratinized cells are rounded and have slightly refractile eosinophilic cytoplasm
  402. 402. Easier to recognize when it forms concentrically laminated squamous ‘pearls’.
  403. 403. Intercellular bridging
  404. 404. Represent desmosomal cell junctions -- cell shrinkage results in stretching across intercellular spaces
  405. 405. Histopathologically graded as follows:  
  406. 406. Well-differentiated (grade 1): prominent keratinization throughout
  407. 407. Moderately differentiated (grade 2)
  408. 408. Poorly differentiated (grade 3): require careful scrutiny to identify keratinization or intercellular bridging.
  409. 409. Immunohistochemically
  410. 410. Cytokeratins (densely packed filaments attached to desmosomes) and epithelial membrane antigen
  411. 411. Verrucous carcinoma.
  412. 412. Uncommon, locally aggressive, slow-growing, and well-differentiated SCC which never metastasizes.
  413. 413. Most often in oral cavity, but also involvement in larynx.
  414. 414. Grossly, large, tan or white, exophytic, and warty mass attached by a broad base
  415. 415. Tends to produce prominent surface keratin.
  416. 416. Histologic pattern
  417. 417. Undulating outer densely keratinized layer covering large papillary fronds
  418. 418. Sharply circumscribed deep margin composed of rows of bulbous extremely well-oriented downgrowths.
  419. 419. Stroma is infiltrated by abundance of chronic inflammatory cells.
  420. 420. Well circumscribed and clearly demarcated from adjacent mucosa.
  421. 421. Metastasis is rare, but growth is inexorable if untreated and the tumor can result in the patient's death.
  422. 422. Etiology and clinical presentation is same as laryngeal squamous cell carcinoma. </li></ul>Metastases<br /><ul><li>Cervical lymph nodes: Single most important prognostic factor in squamous cell carcinoma of head and neck.
  423. 423. Distant metastases.
  424. 424. Distant metastases from laryngeal SCC are significantly less frequent than from other human malignancies
  425. 425. Lung metastases are the most commonly found, followed by metastases to bone and liver. </li></ul>Imaging: Neck instrumental investigation is mandatory -- CT scanning and MRI -- accurate in clinical staging <br />Nasopharyngeal Carcinoma<br /><ul><li>Carcinoma arising in nasopharyngeal mucosa that shows microscopic evidence of squamous differentiation</li></ul>Epidemiology<br /><ul><li>Uncommon in U.S., but common among Southeast Asians
  426. 426. Bimodal age distribution: peak in late childhood (10-20 years of age), and a second peak occurs in people aged 50-60 years.
  427. 427. Occurs more frequently in men, with a 2:1 male-to-female ratio. </li></ul>Morphology<br /><ul><li>Gross appearance: Discrete raised nodule or a frankly infiltrative fungating mass.
  428. 428. Common site of origin is lateral wall of nasopharynx (fossa of Rossenmüller - behind opening of Eustachian tube)
  429. 429. Microscopic appearance.
  430. 430. Squamous cell carcinoma
  431. 431. Well-differentiated type -- squamous differentiation, with intercellular bridges and/or keratinization
  432. 432. Nonkeratinizing carcinoma
  433. 433. Poorly differentiated type
  434. 434. Characterized by large tumor cells with indistinct cell borders, round-oval nuclei, large central nucleoli
  435. 435. No intercellular bridges or single keratinized cells can be seen, but tumor cells are of squamous origin. 
  436. 436. Basaloid squamous cell carcinoma
  437. 437. Aggressive variant of SCC -- Composed of both basaloid and SC components
  438. 438. Basaloid component – predominant
  439. 439. Solid tumor nests surrounded by fibrous stroma -- round to ovoid basaloid cells with scanty cytoplasm.
  440. 440. Non-neoplastic lymphoid component
  441. 441. Prototype of lymphoepithelial carcinomas: benign reactive lymphocytes and plasma cells infiltrate tissue</li></ul>Etiology<br /><ul><li>Epstein-Barr virus.
  442. 442. Elevated levels of antibodies (IgA) against Epstein-Barr virus
  443. 443. Presence of Epstein-Barr DNA or RNA in practically all tumor cells
  444. 444. Presence of Epstein-Barr virus in a clonal episomal form >> virus has entered tumor cell before clonal expansion;
  445. 445. Keratinizing SCCs tend to carry lower copy numbers of Epstein-Barr virus compared with nonkeratinizing carcinomas.
  446. 446. Environmental factors.
  447. 447. Ingestion of Cantonese-style salted foods (fish, vegetables) is an important factor among Chinese, and North Africans
  448. 448. Large amounts of nitrites, converted to carcinogenic nitrosamine >> carcinoma of nasal and paranasal sinus cavities
  449. 449. Genetic factors.
  450. 450. HLA locus A and B antigen association in Chinese with nasopharyngeal carcinoma is well established.
  451. 451. HLA B17 and HLA Bw46 are associated with increased risk.</li></ul>Clinical Presentation<br /><ul><li>Painless neck mass representing unilateral or bilateral enlargement of upper cervical lymph nodes (lymph node metastases)
  452. 452. Ear pain, serous otitis media, and ipsilateral hearing loss may occur (due to Eustachian tube obstruction)
  453. 453. Nasal obstruction with rhinorrhea and epistaxis (due to presence of tumor mass in the nasopharynx).
  454. 454. Features of more advanced disease associated with superior extension of tumor
  455. 455. Headaches indicate invasion of the base of skull.
  456. 456. Ophthalmoplegia (paralysis of motor nerves of eye) indicates cavernous sinus invasion with damage of cranial nerves
  457. 457. Palsy of 5th and 6th CNs causes diplopia, facial pain and numbness; palsy of 3rd CN causes ptosis </li></ul>Laboratory Studies<br /><ul><li>Positive serology against Epstein-Barr virus is found in close to 100% of nonkeratinizing squamous cell carcinoma types
  458. 458. IgA against viral capsid antigen and IgG/IgA against early antigens -- most extensively used diagnostic tool
  459. 459. Test for elevated levels of circulating Epstein-Barr virus DNA or RNA by quantitative PCR in the plasma or serum </li></ul>Pathogenesis<br /><ul><li>Epstein-Barr virus infection -- early event in multistep carcinogenesis of nasopharyngeal carcinoma
  460. 460. Leads to increased expression of EBNA1, LMP1, LMP2, and EBERs in epithelial cells.
  461. 461. EBNA1 is important in replication and maintenance of viral genome during cell division.
  462. 462. LMP1 acts as an oncogenic factor: it upregulates several cellular proteins that inhibit apoptosis
  463. 463. Activation of transcription factors, cellular adhesion molecules, and cytokines.
  464. 464. LMP2 prevents reactivation of the virus by blocking phosphorylation by tyrosine kinases.
  465. 465. EBERs do not encode proteins, but they may be important for oncogenesis and resistance to apoptosis.
  466. 466. Inactivation of the p16 tumor suppressor gene by homozygous deletion -- most common molecular alteration
  467. 467. Cyclin-dependent kinase (CDK) inhibitor - inactivates CKD4 enzyme that phosphorylates and activates Rb protein
  468. 468. Rendering retinoblastoma protein inactive >> removes inhibition provided by Rb protein (cell cycle)</li></ul>Tumor Spread<br /><ul><li>Highly malignant behavior, with extensive loco-regional infiltration, early lymphatic spread, and hematogenous dissemination.
  469. 469. Most common sites of hematogenous deposits are, in descending order of frequency, bone, liver, and lung.
  470. 470. Natural history of disease is short, with most metastases diagnosed within 18 months after appearance of first symptoms</li></ul>Imaging<br /><ul><li>CT scanning and MRI of head and neck used to determine tumor extent, base of skull erosion, and cervical lymphadenopathy. </li></ul>Prognosis<br /><ul><li>Nasopharyngeal carcinomas with no distant metastasis are typically treated with nonsurgical means
  471. 471. Surgery is usually reserved for tumors that fail to regress after irradiation.
  472. 472. Because of the high doses of radiotherapy used in this disease, these late toxicities can be significant. </li></ul>ASTHMA 1<br />  <br /><ul><li>Chronic lung disease caused by increased responsiveness of airways > bronchiolar smooth muscle contraction/bronchospasm
  473. 473. Obstruction to air flow – maximal in expiration – and a high pitched wheeze
  474. 474. Paroxysms of wheezing, dyspnea, and cough.
  475. 475. Status asthmaticus: episodes severe, prolonged and unresponsive to therapy >> acute ventilator failure and even death.</li></ul>Etiology<br /><ul><li>Atopic asthma.
  476. 476. Commonest form of asthma
  477. 477. Atopy: genetic -- immediate hypersensitivity reactions (IgE) in response to common environmental proteins.
  478. 478. Allergens -- have protease activity
  479. 479. Usually begins in childhood and is paroxysmal (attack starting suddenly and lasting a few hours or days).
  480. 480. Tends to become less severe as child grows older and often ceases during adolescence.
  481. 481. Patients commonly suffer from other atopic diseases, particularly allergic rhinitis and atopic dermatitis.
  482. 482. Intrinsic (non-allergic) asthma.
  483. 483. Negative skin test to common inhalant allergens and normal serum concentrations of IgE.
  484. 484. Onset in adult life (> 40yo), chronic with exacerbations and remissions less evident and tends to worsen with age
  485. 485. Hyperreactive airways that constrict in response to a variety of nonspecific stimuli.
  486. 486. Aspirin, cold air, exercise, perfumes, cleaning agents, fumes, smoke, and upper respiratory infections
  487. 487. Possible virus-induced inflammation of respiratory mucosa lowers threshold of receptors to irritants.
  488. 488. Tends to be less responsive to treatment than atopic asthma.
  489. 489. Increased incidence of nasal polyps.</li></ul>Genetic Considerations<br /><ul><li>Polygenic disease.
  490. 490. Multifactorial disorder of airways brought about by complex interaction between genetic and environmental factors.
  491. 491. Association of asthma and atopy with polymorphisms of genes on chromosome 5q (contains IL genes)
  492. 492. IL influence T cell development and recruitment of eosinophils, mast cells, neutrophils to site
  493. 493. Novel genes that have been associated with asthma
  494. 494. ADAM33 encodes disintegrin matrix metalloproteinase 33 and is associated with airway remodeling events.
  495. 495. DPP-10 is associated with brochial hyperresponsiveness and IgE.
  496. 496. SPINK5 is another gene that is associated with airway remodeling.
  497. 497. Role of CD14 polymorphisms
  498. 498. Receptor for endotoxin -- maps on chromosome 5q -- expressed by monocytes, macrophages and neutrophils
  499. 499. Play a role in the polarisation of T lymphocytes into Th1 and Th2 subsets
  500. 500. Influence cytokines >> IgE production
  501. 501. Polymorphism in promotor for CD14 (TT genotype)
  502. 502. Associated with reduced levels of IgE and risk for asthma/atopy with low (household) endotoxin exposure
  503. 503. Associated with increased levels of IgE and risk for asthma/atopy with high endotoxin exposure (>> Th2)
  504. 504. Differences may relate to influence of endotoxin levels on regulation of Th1 versus Th2 responses.
  505. 505. Hygiene hypothesis
  506. 506. Lack of early childhood exposure to infectious agents and parasites increases susceptibility to allergic disease
  507. 507. Global microbial burden in early life could deviate immune responses away from allergic responses.
  508. 508. Suspect polymorphisms in CD14 could be protective against allergies in people with high levels of exposure</li></ul>Morphology<br /><ul><li>Sputum: Viscous and yellow (due to myeloperoxidase within eosinophils)
  509. 509. Charcot-Leyden crystals.
  510. 510. Slender, dipyramidal crystals -- hallmark of eosinophilic leukocyte infiltration
  511. 511. Composed of lysolecithin acylhydrolase -- eosinophil proteins involved in antiparasitic and immune functions
  512. 512. Damage respiratory epithelium and increase vascular permeability.
  513. 513. Curschmann spiral: Corkscrew-shaped twist of condensed mucus -- represent casts of small bronchioles
  514. 514. Creola bodies: Compact clumps of columnar epithelial cells shed from bronchial mucosa
  515. 515. Lungs - Gross appearance.
  516. 516. Lungs are greatly distended (overinflation); fail to retract as normal lungs do when opening pleural cavities.
  517. 517. Small areas of atelectasis seen as dark, airless, firm areas, depressed below level of surrounding lung.
  518. 518. Occlusion of bronchi and bronchioles by thick, tenacious mucus plugs.
  519. 519. Air can pass the plugs only on inspiration.
  520. 520. Lungs – Microscopic appearance.
  521. 521. Bronchial plugging by mucus from increased amounts of mucus
  522. 522. Bronchial lumen is compromised by accumulation of mucus
  523. 523. Numerous eosinophils are present admixed with desquamated epithelial cells.
  524. 524. Excessive mucus is produced by hyperplastic goblet cells and enlarged submucosal mucinous glands
  525. 525. Airway mucus is abnormal, reflecting interactions between
  526. 526. Inflammatory cells infiltrating bronchial wall
  527. 527. Hyperplasia of mucosal goblet cells and submucosal mucinous glands in bronchial wall
  528. 528. Pathologic changes in blood vessels in the bronchial wall.
  529. 529. Albumin and DNA are increased, reflecting increased vascular permeability and inflammatory cells.
  530. 530. Increases in plasma-derived proteins, cytokines, and chemokines, reflecting complex inflammation
  531. 531. Bronchial eosinophilic infiltration and inflammatory edema
  532. 532. In status asthmaticus, infiltration by eosinophils, T lymphocytes and mast cells.
  533. 533. Inflammatory infiltration accompanied by marked congestion and edema of bronchial wall.
  534. 534. Loss of ciliated cells contributes to impaired bronchial clearance.
  535. 535. Shedding of epithelial cells
  536. 536. Separation of mucosal cells leaving an intact basal cell layer resting on basement membrane
  537. 537. May be due to eosinophil granules, release of TNF by macrophages, proteases or oxygen radicals.
  538. 538. Remaining epithelium has "fragile" appearance, ciliated cells are swollen, vacuolized and show loss of cilia.
  539. 539. Moderately severe to severe asthmatic patients.
  540. 540. Consequences -- denudation of nerves and bronchial hyperreactivity >> smooth muscle contraction
  541. 541. Thickening of epithelial basement membrane
  542. 542. Thickening is confined to deepest layer, produced by myofibroblasts rather than epithelium.
  543. 543. Bronchial muscle hypertrophy
  544. 544. Increase in amount of bronchial muscle -- reflects sustained muscular contraction
  545. 545. Most apparent in small bronchi
  546. 546. Attributable to smooth muscle cell hyperplasia as well as hypertrophy </li></ul>Clinical Manifestations<br /><ul><li>Typical asthma attack.
  547. 547. Begins with a feeling of tightness in chest and nonproductive cough.
  548. 548. Both inspiratory and expiratory wheezes appear, respiratory rate increases, and patient becomes dyspneic.
  549. 549. Ends with severe coughing and expectoration of thick mucus
  550. 550. Physical examination findings.
  551. 551. Hyperexpansion of thorax (especially in children)
  552. 552. Use of accessory muscles
  553. 553. Hyperresonance to percussion
  554. 554. Diminished breath sounds
  555. 555. Sounds of wheezing during normal breathing or a prolonged phase of forced exhalation (typical of airflow obstruction)
  556. 556. Increased nasal secretion, mucosal swelling and nasal polyps.
  557. 557. Clinical classification of severity.
  558. 558. Mild episode
  559. 559. Characterized by an increased respiratory rate; HR is less than 100/min.
  560. 560. Accessory muscles of respiration are not used. Pulsus paradoxus is not present.
  561. 561. Moderate wheezing, often end expiratory. Oxygen saturation of hemoglobin with room air is > 95%.
  562. 562. Moderately severe episode
  563. 563. Respiratory rate is increased; HR is 100-120/min.
  564. 564. Accessory muscles of respiration are used, and suprasternal retractions are present.
  565. 565. Loud expiratory wheezing can be heard. Oxygen saturation of hemoglobin with room air is 91-95%.
  566. 566. Severe episode
  567. 567. Respiratory rate is often greater than 30/min; HR is more than 120/min.  
  568. 568. Accessory muscles of respiration are usually used, and suprasternal retractions are commonly present.
  569. 569. Loud biphasic (expiratory and inspiratory) wheezing can be heard.
  570. 570. Pulsus paradoxus is often present (pulse becomes weaker with inhalation and stronger with exhalation)
  571. 571. Inspiratory diminution in arterial pressure exceeds 10 mm Hg
  572. 572. Oxygen saturation of hemoglobin with room air is less than 91%.
  573. 573. Status asthmaticus.
  574. 574. Severe bronchoconstriction that does not respond to drugs that usually abort acute attack.
  575. 575. Begins with mild symptoms of dyspnea >> as airway obstruction worsens, respiratory distress may all be observed. 
  576. 576. Abnormally prolonged expiratory phase with audible wheezing. Vital signs show tachycardia and hypertension.
  577. 577. Airflow obstruction might be so extreme as to cause severe cyanosis and even death.
  578. 578. Hypoxemia and hypercapnia develop >> seizures and coma (late signs of respiratory compromise). </li></ul>Imaging: Chest radiography findings are normal or may indicate hyperinflation. <br />Laboratory Studies – non-specific<br /><ul><li>Blood eosinophilia supports diagnosis
  579. 579. Elevated total serum IgE levels observed in allergic patients</li></ul>Arterial Blood Gases<br /><ul><li>Important to determine severity of asthma attack. 4 stages of blood gas progression in status asthmaticus are as follows:
  580. 580. First stage: characterized by hyperventilation with a normal partial pressure of oxygen (PO2).
  581. 581. Second stage: characterized by hyperventilation accompanied by hypoxemia (low PO2) and normal PCO2.
  582. 582. Third stage: hypoxemic (low PO2) but not hyperventilating because of respiratory muscle fatigue. Normal PCO2
  583. 583. Last stage: characterized by a low PO2 and a high PCO2, which occurs with respiratory muscle insufficiency. </li></ul>Pulmonary Function Testing (Spirometry) <br /><ul><li>Primary test to establish asthma diagnosis -- include measurements before and after inhalation of a short-acting bronchodilator
  584. 584. Measures forced vital capacity (FVC), maximal amount of air expired from point of maximal inhalation, and FEV1.
  585. 585. Reduced ratio of FEV1 to FVC, when compared with predicted values, demonstrates the presence of airway obstruction.
  586. 586. Reversibility is demonstrated by increase of 12% and 200 mL after administration of a short-acting bronchodilator. </li></ul>Allergy Skin Test<br /><ul><li>Useful adjunct in individuals with atopy -- Results help guide indoor allergen mitigation.
  587. 587. Two methods: allergy skin tests and blood radioallergosorbent tests (RAST). </li></ul>Loading, Please Wait ... <br />ASTHMA 2<br /> <br />Asthma and Chronic Obstructive Pulmonary Disease <br /><ul><li>Adults with asthma may have an increased risk of developing COPD
  588. 588. Coexisting signs of asthma (reversibility, atopy), chronic bronchitis (sputum) and emphysema (hyperinflation).
  589. 589. Factors such as smoking and repeated episodes of acute bronchitis may facilitate evolution of asthma into COPD.
  590. 590. Coexisting asthma and COPD >> most severe disease based on degree of airflow limitation. </li></ul>Pathogenesis<br /><ul><li>Atopic asthma -- genetic predisposition to type I hypersensitivity (atopy) and exposure to environmental triggers.
  591. 591. Th2 reactions -- bronchial inflammation in which type 2 helper T (Th2) cells (type of CD4 helper T cell) are prominent.
  592. 592. Preceded by IgE-mediated sensitization to common aeroallergens.
  593. 593. Formation of IgE Abs -- inhaled aeroallergens are engulfed by dendritic cells lining airway.
  594. 594. Dendritic cells migrate to lymph nodes >> present antigen to T-cells
  595. 595. Stimulated T-cells (Th2) secrete cytokines >> promote inflammation and stimulate B cells to produce IgE
  596. 596. Early allergic response
  597. 597. IgE antibodies bind to receptors on surface of mast cells, basophils, dendritic cells, and lymphocytes
  598. 598. Activation >> release of proinflammatory cytokines and mediators >> Leukocyte recruitment
  599. 599. Bronchoconstriction, increased mucus production, and vasodilation with increased vascular permeability.
  600. 600. Late allergic response
  601. 601. Activated mast cells and T cells >> Cytokines >> Infiltration of inflammatory cells
  602. 602. Epithelial cells >> cytokines
  603. 603. Eotaxin -- produced by airway epithelial cells, potent chemoattractant and activator of eosinophils.
  604. 604. Protein of eosinophils causes epithelial damage and more airway constriction.
  605. 605. "Suspects" -- subclassified by clinical efficacy of pharmacologic intervention with antagonists of mediators.
  606. 606. Mediators with role in bronchospasm clearly supported by efficacy of pharmacologic intervention:
  607. 607. Leukotrienes C4, D4, and E4: also cause increased vascular permeability and mucus secretion
  608. 608. Acetylcholine: causse airway smooth muscle constriction by directly stimulating muscarinic receptor
  609. 609. Agents present with potent asthma-like effects -- lack of efficacy of potent antagonists or synthesis inhibitors:
  610. 610. Histamine:potent bronchoconstrictor
  611. 611. Prostaglandin D2: elicits bronchoconstriction and vasodilatation
  612. 612. Platelet-activating factor: aggregation and release of histamine and serotonin from granules
  613. 613. Suspects for whom specific antagonists or inhibitors are not available:
  614. 614. Cytokines (IL-1, TNF, IL-6), chemokines (eotaxin), neuropeptides, NO, bradykinin, and endothelins
  615. 615. Repeated allergen exposure and immune reactions >> structural changes in bronchial wall ("airway remodeling")
  616. 616. Hypertrophy and hyperplasia of bronchial smooth muscle, epithelial injury, increased airway vascularity,
  617. 617. Increased subepithelial mucus gland hypertrophy/hyperplasia, and deposition of subepithelial collagen.
  618. 618. Infections with respiratory pathogens can exacerbate chronic changes >> serious worsening of clinical manifestations </li></ul>Phenotypes<br /><ul><li>Allergic asthma
  619. 619. Most common form -- usually seen in children – usually substantial or complete remission of symptoms by age 20
  620. 620. Strongly correlated with skin-test reactivity.
  621. 621. Infectious asthma
  622. 622. Precipitating factor is a viral respiratory tract infection
  623. 623. In children under 2 years, respiratory syncytial virus is the usual agent;
  624. 624. In older children, rhinovirus, influenza, and parainfluenza are common inciting organisms.
  625. 625. Inflammatory response to viral infection >> trigger episode of bronchoconstriction and bronchial hyperreactivity
  626. 626. Exercise-induced asthma
  627. 627. Exercise >> bronchospasm -- related to magnitude of heat or water loss from airway epithelium.
  628. 628. More rapid ventilation and colder and drier air breathed, more likely an attack of asthma.
  629. 629. Consequence of mediator release or vascular congestion secondary to rewarming of airways after exertion.
  630. 630. Occupational asthma
  631. 631. 3 distinct sub-phenotypes, defined by underlying mechanism.
  632. 632. Non-immunologically mediated: response to irritant chemicals >> reactive airways dysfunction syndrome
  633. 633. Immunologically mediated: inflammatory response is IgE-mediated
  634. 634. Response to low molecular-weight triggers >> immunologically-mediated, but IgE involvement is variable.
  635. 635. Therapy: avoidance of asthma trigger
  636. 636. Aspirin-induced asthma
  637. 637. Classic triad of aspirin intolerance, sinusitis with nasal polyps, and asthma.
  638. 638. Ingestion of aspirin/NSAIDs will result in an acute asthma attack accompanied by rhinitis and conjunctival injection
  639. 639. Severe and poorly responsive to corticosteroids
  640. 640. Mechanism: shunt of AA metabolism from prostanoid production >> leukotriene production and bronchoconstriction
  641. 641. Mutations in leukotriene pathway identified
  642. 642. Air pollution
  643. 643. Usually in episodes associated with temperature inversions -- associated with bronchospasm
  644. 644. SO2, oxides of nitrogen, and ozone are commonly implicated environmental pollutants.
  645. 645. Emotional factors: Psychological stress >> bronchospasm due to vagal efferent stimulation.</li></ul>Bronchiectasis <br /><ul><li>Abnormal and permanent dilatation of conducting bronchi or airways, most often secondary to an infectious process.
  646. 646. Involved bronchi are dilated, inflamed, and easily collapsible >> airflow obstruction and impaired clearance of secretions.  </li></ul>Epidemiology: Uncommon in U.S. - more common in females and most commonly presents in their 60s and 70s.<br />Pathogenesis<br /><ul><li>Bronchial obstruction leads to impaired normal clearing mechanisms >> pooling of secretions distal to obstruction
  647. 647. Infection and inflammation of the airway >> necrosis and destruction of surrounding tissue.
  648. 648. Fibrosis causes bronchi to dilate, leading to dilatation of affected bronchi >> vicious cycle of recurrent infections </li></ul>Etiology<br /><ul><li>Categorized as idiopathic, postinfectious, or due to an underlying anatomic or systemic disease
  649. 649. Most patients have no history of lung injury prior to the onset (idiopathic bronchiectasis).
  650. 650. Patients with known history of lung diseases (postinfecitous bronchiectasis) >> pneumonia, childhood infections, TB. 
  651. 651. Minimal or silent infections caused by nontuberculous mycobacteria, Mycobacterium avium complex (MAC).
  652. 652. Congenital causes: associated with defects of mucociliary clearance >> first-line defense against pathogenic microorganisms
  653. 653. Cystic fibrosis
  654. 654. Autosomal recessive defects in gene for cystic fibrosis transmembrane conductance regulator (CFTR),
  655. 655. CFTR encodes for a protein that functions as a chloride channel.
  656. 656. Mutations result in decreased secretion of chloride and increased reabsorption of sodium and water
  657. 657. Electrolytic abnormalities result in viscid secretions in respiratory tract, pancreas, GI, sweat glands.
  658. 658. Secretions difficult to clear >> Lung disease results from clogging of airways
  659. 659. Resulting chronic bronchial infection, especially with Pseudomonas aeruginosa.
  660. 660. Primary ciliary dyskinesia
  661. 661. Autosomal recessive -- characterized by abnormal ciliary motion and impaired mucociliary clearance.
  662. 662. Gene mutations in DNAI1 and DNAH5, which encode for components of outer dynein arm complex.
  663. 663. Leads to recurrent or persistent respiratory infections, sinusitis, otitis media, and male infertility.
  664. 664. Kartagener syndrome: bronchiectasis, sinusitis and situs inversus.
  665. 665. Young syndrome: bronchiectasis, rhinosinusitis and congenital epididymis obstruction (reduced fertility)
  666. 666. Alpha1-antitrypsin deficiency
  667. 667. Autosomal recessive disorder caused by defective production of AAT >> decreased serum AAT levels.
  668. 668. Causes panacinar emphysema and bronchiectasis (with chronic cough and sputum expectoration)
  669. 669. Infectious factors.
  670. 670. Lung injury prior to onset of bronchiectasis
  671. 671. Lung damage occurring after pneumonia, pertussis, measles, or tuberculosis as a cause of bronchiectasis
  672. 672. Microbiological profile in bronchiectasis
  673. 673. Main pathogen isolated is Haemophilus influenzae followed by Pseudomonas aeruginosa.
  674. 674. Others: Moxarella catarrhalis, Streptococcus pneumoniae, Aspergillus and Mycobacterium avium complex
  675. 675. Pseudomonas aeruginosa
  676. 676. Not a primary cause of bronchiectasis, but is associated with increased clinical severity of disease.
  677. 677. MAC
  678. 678. Seen in thin elderly women (>60 yo), have never smoked and have no underlying pulmonary disease.
  679. 679. Bronchiectasis caused by MAC is most often located in right middle lobe and lingula.
  680. 680. Also known as Lady Windermere syndrome
  681. 681. Staphylococsu aureus: relatively uncommon -- repeated isolation should lead to consideration of undiagnosed CF.
  682. 682. Immunodeficiency states.
  683. 683. Congenital immunodeficiency conditions involve B-lymphocyte functions, specifically hypogammaglobulinemia.
  684. 684. IgG subclass deficiency; X-linked agammaglobulinemia; or selective IgA, IgM, or IgE deficiency.
  685. 685. Present in childhood with repeated sinus or pulmonary infections
  686. 686. Acquired immunodeficiency, ie. HIV disease, with resultant AIDS
  687. 687. Bronchiectasis secondary to bronchial damage from repeated infections in immunosuppressed patients
  688. 688. Bronchial obstruction.
  689. 689. Right-middle lobe syndrome results from tuberculous lymphadenitis of middle lobe bronchopulmonary lymph nodes.
  690. 690. Proximal stenosis of right middle lobe bronchus leads to bronchiextasis of more distal segments or divisions.
  691. 691. Foreign Body Aspiration: Altered mental state and unchewed food >> postobstructive pneumonia >> focal bronchiectasis.
  692. 692. Allergic bronchopulmonary aspergillosis.
  693. 693. Not an infection but represents an immune reaction to Aspergillus that results in airway damage and bronchiectasis.
  694. 694. Characterized by bronchospasm, bronchiectasis, and immunologic evidence
  695. 695. Viscid secretions containing hyphae of Aspergillus species
  696. 696. Rheumatologic/autoimmune diseases.
  697. 697. Particularly rheumatoid arthritis, SLE and inflammatory bowel disease
  698. 698. May be due to increased susceptibility to infections in these patients.</li></ul>Clinical Presentation<br /><ul><li>Dominant symptom is a chronic cough with sputum production.
  699. 699. Paroxysms of cough frequent when patient rises in morning (changes in position >> drainage secretions into bronchi)
  700. 700. Sputum described as mucoid, mucopurulent, thick, tenacious, or viscous (viscid).
  701. 701. Dyspnea and wheezing, Pleuritic chest pain, Hemoptysis (erosive airway damage caused by an acute infection).
  702. 702. Auscultatory findings are nonspecific. Most commonly, crackles, rhonchi, and wheezing may be heard upon auscultation.
  703. 703. Rhinosinusitis with visible abnormalities on CT scanning of their nose and sinuses.
  704. 704. Chronic fatigue and clubbing </li></ul>Complication<br /><ul><li>Recurrent pneumonia, abscess, empyema, abscess, obstructive respiratory insufficiency and pulmonary hypertension.
  705. 705. Sinusitis and life-threatening hemoptysis are frequent complications as well.
  706. 706. Obstructive respiratory insufficiency can lead to marked hypoxia, manifested by dyspnea and cyanosis.
  707. 707. Cor pulmonale, brain abscesses, and amyloidosis are less frequent complications</li></ul>Classification<br /><ul><li>Cylindrical bronchiectasis
  708. 708. Bronchi have uniform, thick straight walls and are mildly increased in diameter
  709. 709. Bronchi do not taper and the number of bronchial subdivisions is reduced.
  710. 710. Have a tram track appearance when viewed in a sagittal section or a signet ring appearance in a coronal section.
  711. 711. Varicose bronchiectasis
  712. 712. Bronchi are irregular in shape and size; with alternating areas of constriction and dilatation
  713. 713. Do not taper as they extend peripherally.
  714. 714. Terminations are irregular and bulbous -- give beaded appearance of saphenous varicosities or a string of pearls.
  715. 715. Saccular (cystic) bronchiectasis
  716. 716. Most severe form
  717. 717. Bronchi are dilated and balloon into cysts or “saccules,” -- honeycomb or “cluster of grapes” appearance.
  718. 718. Saccules formed when diseased bronchi are destroyed/fibrosed; inflammation extends and pull bronchi</li></ul>Gross Morphology<br /><ul><li>Involves bronchi of medium size (>2 mm diameter).  
  719. 719. Bronchiectasis caused by childhood infections and aspirations affects lower lobes bilaterally (air passages that are vertical)
  720. 720. Upper lobes are more frequently affected in patients with cystic fibrosis and tuberculosis.
  721. 721. Middle lobes are more frequently affected in patients with MAC, cystic fibrosis and allergic bronchopulmonary aspergillosis.
  722. 722. Bronchiectasis is more diffuse in patients with cystic fibrosis and those with immunodeficiency states.
  723. 723. When tumors or aspiration of foreign bodies lead to bronchiectasis, involvement may be sharply localized to a single segment
  724. 724. Airways are dilated – appear as cysts filled with mucopurulent secretions.
  725. 725. Focal destruction of bronchial wall, increased mucus secretion and retention, and peribronchial fibrosis occur
  726. 726. Surrounding lung shows volume loss, fibrosis, emphysema, and nodular inflammatory foci.
  727. 727. Generalized bronchiectasis: widespread dilation of bronchi and may be congenital or result from bacterial infection.
  728. 728. Inherited conditions: cystic fibrosis, primary ciliary dyskinesia, hypogammaglobulinemia, and IgG deficiencies </li></ul>Histopathology<br /><ul><li>Intense acute and chronic inflammatory exudation within walls of bronchi and bronchioles
  729. 729. Associated with desquamation of lining epithelium and extensive areas of necrotizing ulceration.
  730. 730. May be squamous metaplasia of remaining epithelium.
  731. 731. Mixed flora cultured from ectatic bronchi, including staph, strep, pneumococci, enteric, anaerobic and microaerophilic bacteria,
  732. 732. Particularly in children: Haemophilus influenzae and Pseudomonas aeruginosa. </li></ul> Diagnosis of Bronchiectasis <br /><ul><li>High-resolution CT scanning (HCRT) is able to detect airway abnormalities
  733. 733. Criteria are internal diameter of bronchus wider than its adjacent artery and failure of the bronchi to taper.
  734. 734. Bronchial wall thickening appears to indicate airway inflammation and may have prognostic implications. </li></ul>Pulmonary Function<br /><ul><li>Spirometry often shows a limitation of airflow, with:
  735. 735. Reduced ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC)
  736. 736. Normal or slightly reduced FVC - may indicate that airways are blocked by mucus, collapse with forced exhalation
  737. 737. Reduced FEV1.
  738. 738. Airway hyperresponsiveness demonstrated
  739. 739. Improvement in FEV1 after the administration of a beta-adrenergic
  740. 740. Markedly reduced FEV1 after histamine or methacholine challenge.</li></ul>Loading, Please Wait ... <br />OBSTRUCTIVE PULMONARY DISEASE<br /> <br />Chronic Obstructive Pulmonary Disease <br /><ul><li>Chronic bronchitis, emphysema, asthma, and bronchiectasis
  741. 741. Obstruction to air flow in the lungs.
  742. 742. Forced expiratory volume is decreased.
  743. 743. FEV1 (in 1 sec): maximum volume that can forcibly blow out in first second after full inspiration, measured in liters.
  744. 744. Air flow can be reduced by increasing resistance to air flow or reducing outflow pressure.
  745. 745. Narrowed airways produce increased resistance, whereas loss of elastic recoil results in diminished pressure. </li></ul>Epidemiology: Men are more likely to have COPD than women -- predominantly in individuals older than 40 years. <br />Chronic bronchitis<br /><ul><li>Affects majority of patients with COPD
  746. 746. Presence of a chronic productive cough for 3 months during each of 2 consecutive years
  747. 747. Airflow limitation in chronic bronchitis is due to narrowing of airway caliber and increase in airway resistance. </li></ul>Differential with Acute Bronchitis <br /><ul><li>Most frequently in children younger than 5 years in association with viral respiratory tract infection
  748. 748. Caused by infections with influenza, parainfluenza, adenovirus, rhinovirus, and respiratory syncytial virus.
  749. 749. Mucosa is acutely inflamed, with acute inflammatory cells and copious secretion of mucus.
  750. 750. Symptoms include cough that produces phlegm that last for no more than 3 weeks.
  751. 751. Repeated viral infections may damage airway lining and lead to bacterial infections of the lower respiratory tract
  752. 752. Most common bacterial pathogen that causes lower respiratory tract infections is Streptococcus pneumoniae.
  753. 753. Also, infections with Mycoplasma, Chlamydia pneumoniae, Moraxella catarrhalis, and H. influenzae </li></ul>Epidemiology: More prevalent in people older than 50 years, and affects males more than females<br />Pathogenesis<br /><ul><li>Smoking
  754. 754. Impairs ciliary movement, inhibits alveolar macrophages, hypertrophy and hyperplasia of mucus-secreting glands.
  755. 755. Retained secretions predispose for infection -- increased risk for bacterial infections H. influenzae and S. pneumoniae
  756. 756. Increase airway resistance via vagally mediated smooth muscle constriction.
  757. 757. Air pollution: In particular traffic-related air pollution in urban areas
  758. 758. Occupational exposures.
  759. 759. Agents includes coal, manufactured vitreous fibers, oil mist, cement, silica, silicates, osmium, vanadium, welding fumes, organic dusts, engine exhausts, fire smoke, and secondhand cigarette smoke.</li></ul>Clinical Presentation<br /><ul><li>Symptoms.
  760. 760. Cardinal symptom -- persistent cough productive of sputum
  761. 761. Dyspnea on exertion develops.
  762. 762. Hypercapnia, hypoxemia, and mild cyanosis ("blue bloaters").
  763. 763. Long-standing severe chronic bronchitis commonly leads to cor pulmonale with cardiac failure.
  764. 764. Physical examination findings.
  765. 765. Sputum is mucoid and white >> may become purulent
  766. 766. Accumulates in bronchi during sleep and causes severe obstruction of airways until it is coughed up in morning.
  767. 767. Bacteriological examination of sputum -- Haemophilus influenzae, and Streptococcus pneumoniae are most frequent</li></ul>Morphology<br /><ul><li>Gross appearance.
  768. 768. Bronchi, especially in lower lobes, are found to be filled with a mixture of mucus and pus.
  769. 769. Underlying mucous membrane is seen to be a dusky red.
  770. 770. Microscopic structure of normal bronchus.
  771. 771. Intrapulmonary bronchi are lined by pseudostratified columnar ciliated bronchial epithelium
  772. 772. Supported by a thin layer of lamina propria composed of fine connective tissue and a few lymphocytes.
  773. 773. A thin layer of smooth muscle surrounds lamina propria and separates it from submucosa.
  774. 774. Submucosa contains numerous seromucous bronchial glands.
  775. 775. Bronchial epithelium displays three types of epithelial cells: (a) ciliated columnar, (b) goblet, and (c) basal cells.
  776. 776. Chronic bronchitis – Microscopic appearance.
  777. 777. Increase in size of bronchial mucus-secreting apparatus.
  778. 778. Two types of cells line the mucous glands: pale mucous cells (which are more common) and serous cells.
  779. 779. Hyperplasia and hypertrophy of mucous cells and an increased ratio of mucous to serous cells.
  780. 780. Thus, both the individual acini and the glands enlarge.
  781. 781. Chronic inflammation of bronchial wall with predominantly lymphocytic infiltration.
  782. 782. Reid index.
  783. 783. Correlate severity and duration of chronic bronchitis with size of bronchial glands.
  784. 784. Measure ratio of thickness of gland layer to thickness of wall. Normal value of 0.4.</li></ul>Emphysema <br /><ul><li>Abnormal, permanent enlargement of air spaces distal to bronchioles, with destruction of walls without fibrosis.
  785. 785. Airflow limitation in emphysema is due to loss of elastic recoil.
  786. 786. Vesicular emphysema.
  787. 787. Affects spaces that normally contain air, i.e., lungs.
  788. 788. Chronic lung disease characterized by irreversible enlargement of airspaces distal to terminal bronchioles
  789. 789. Destruction of their walls but without fibrosis.
  790. 790. Primary degenerative disease with a poor prognosis -- destruction of gas-exchanging air spaces is irreversible.
  791. 791. Interstitial (surgical) emphysema.
  792. 792. Ingress of air into normally airless interstitial planes of lung and subcutaneous tissues (Subcutaneous emphysema)
  793. 793. Complication of surgical procedures and trauma.
  794. 794. Collection of gases outside of normal air passages and inside connective interstitial tissues due to rupture of alveoli.
  795. 795. Subcutaneous emphysema usually occurs on chest, neck and face >> travel from chest cavity along fascia.
  796. 796. Characteristic crackling feel to touch, a sensation that is known as subcutaneous crepitation.
  797. 797. Most common causes: lead to pneumothorax and air spread to subcutaneous tissue of neck and face.
  798. 798. Spontaneous rupture of pulmonary blebs
  799. 799. Stab wounds to the chest
  800. 800. Blunt trauma with a fractured rib which punctures the lung. </li></ul>Epidemiology<br /><ul><li>Higher among males than females, among smokers and former smokers than nonsmokers, among those over 40 years old </li></ul>Types<br /><ul><li>Classified according to its anatomic distribution within the pulmonary lobule.
  801. 801. Centriacinar (centrilobular) emphysema.
  802. 802. Central/proximal parts of acini, formed by respiratory bronchioles, are affected, whereas distal alveoli are spared.
  803. 803. Most severe in upper zones of lung, upper lobe, and superior segment of the lower lobe.
  804. 804. Far more common than Panacinar emphysema
  805. 805. The walls of the emphysematous spaces often contain large amounts of black pigment.
  806. 806. Occurs predominantly in heavy smokers, often in association with chronic bronchitis.
  807. 807. Bronchi and bronchioles proximal to the emphysematous spaces are inflamed and narrowed.
  808. 808. Panacinar (panlobular) emphysema.
  809. 809. Acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind alveoli.
  810. 810. More commonly in the lower zones and in the anterior margins of the lung, and it is usually most severe at the bases
  811. 811. Associated with alpha-1-antitrypsin (alpha1-AT) deficiency.
  812. 812. Distal acinar (paraseptal) emphysema.
  813. 813. Proximal portion of the acinus is normal, and the distal part is predominantly involved.
  814. 814. More striking adjacent to the pleura, along the lobular connective tissue septa, and at the margins of the lobules.
  815. 815. Occurs adjacent to areas of fibrosis, scarring, or atelectasis and is usually more severe in the upper half of the lungs.
  816. 816. Characteristic findings are of multiple, continuous, enlarged airspaces, sometimes forming cystlike structures (bullae).
  817. 817. This type of emphysema probably underlies many of the cases of spontaneous pneumothorax in young adults.
  818. 818. Bullous emphysema.
  819. 819. Exceptionally large air spaces, within uppermost portions of lungs that develop secondary to damaged alveoli.
  820. 820. A bulla is an emphysematous space that is more than 1cm in diameter.
  821. 821. Seen in association with centriacinar emphysema and paraseptal emphysema.
  822. 822. Occurs when an abnormal air space ruptures, leaking air into pleural space and causing the affected lung to collapse.
  823. 823. Often seen in young men in association with large, progressive upper-lobe bullae
  824. 824. Paracicatricial (irregular) emphysema.
  825. 825. Emphysematous destruction occurs adjacent to pulmonary scars
  826. 826. Scars consequent to granulomatous inflammation (TB), healed pulmonary infarcts, pneumonia, or pneumoconiosis</li></ul>Morphology<br /><ul><li>Gross morphologic changes.
  827. 827. Begins as areas of destruction (holes in lung) just visible to the naked eye.
  828. 828. Areas of emphysematous destruction are traversed by fine strands -- represent vasculature that once supplied area
  829. 829. Increase in lung volume with progression of emphysema -- correlates with the degree of emphysematous destruction.
  830. 830. Microscopic changes in emphysema.
  831. 831. Early emphysematous changes can only be detected microscopically;
  832. 832. Include loss of alveolar walls, resulting in fewer alveolar attachments to bronchioles.
  833. 833. More severe changes characterized by complete loss of most of wall of air spaces, bronchiolar as well as alveolar.  </li></ul>Pathogenesis<br /><ul><li>Destruction of alveolar walls due to protease-antiprotease mechanism, aided by imbalance of oxidants and antioxidants.
  834. 834. Results when elastolytic activity increases or antielastolytic activity is reduced.
  835. 835. Deficiency of antiprotease anzyme alpha-1 antitrypsin (AAT) -- enhanced tendency to develop pulmonary emphysema
  836. 836. AAT is a major inhibitor of proteases (particularly elastase) secreted by neutrophils during inflammation
  837. 837. Increases in leukocytes (neutrophils and macrophages) or release of granules >> increases pulmonary proteolytic activity.
  838. 838. With low levels of serum AAT, elastic tissue destruction is unchecked and emphysema results.
  839. 839. Emphysema results from the destructive effect of high protease activity in subjects with low antiprotease activity.
  840. 840. In smokers, neutrophils and macrophages accumulate in alveoli
  841. 841. Activate transcription of genes that encode TNF and chemokines >> attract and activate neutrophils.
  842. 842. Accumulated neutrophils are activated and release their granules, resulting in tissue damage.
  843. 843. Smoking enhances elastase activity in macrophages
  844. 844. Oxidant-antioxidant imbalance
  845. 845. Loss of elastic tissue in walls of alveoli that surround respiratory bronchioles causes bronchioles to collapse during expiration.
  846. 846. Leads to functional airflow obstruction despite the absence of mechanical obstruction.
  847. 847. Several changes are seen: narrow the bronchiolar lumen and contribute to airway obstruction
  848. 848. Goblet cell metaplasia with mucus plugging of the lumen
  849. 849. Inflammatory infiltration of the walls with neutrophils, macrophages, B cells, CD4 and CD8+ T cells
  850. 850. Thickening of the bronchiolar wall due to smooth muscle hypertrophy and peribronchial fibrosis.</li></ul>Clinical Course<br /><ul><li>Clinical manifestations of emphysema do not appear until at least 1/3 of functioning pulmonary parenchyma is damaged.
  851. 851. Dyspnea
  852. 852. First symptom; it begins insidiously but is steadily progressive. Minimal non-productive cough.
  853. 853. Tachypneic, with prolonged expiratory phase, sits in a hunched-over position, and breathes through pursed lips.
  854. 854. Weight loss
  855. 855. Due to loss of muscle with or without loss of fat mass -- preferentially in the lower extremities.
  856. 856. Increased proinflammatory mediators such as TNFalpha >> responsible for pulmonary cachexia and wasting process
  857. 857. Physical examination findings
  858. 858. Hyperinflation (barrel chest), wheezing, decreased breath sounds, hyperresonance, prolonged expiration.
  859. 859. In advanced disease, signs of right heart failure (decompensated cor pulmonale)
  860. 860. Cyanosis, elevated jugular venous pressure, and peripheral edema can be observed.</li></ul>Laboratory Studies<br /><ul><li>ABG analysis: Mild-to-moderate hypoxemia without hypercapnia progresses to severe hypoxemia and hypercapnia
  861. 861. Hematocrit value: Chronic hypoxemia may lead to polycythemia. Values > 52% in men and > 47% in women
  862. 862. Bicarbonate value.
  863. 863. Respiratory alkalosis is a clinical disturbance due to alveolar hyperventilation >> decreased PaCO2.
  864. 864. Increases ratio of bicarbonate concentration to PCO2 and increases pH level beyond normal range of 7.35-7.45
  865. 865. Alpha1-antitrypsin level.
  866. 866. Serum levels below protective threshold of 11 mmol/L. Most common severe variant is the Z allele</li></ul>Imaging<br /><ul><li>Chest radiography.
  867. 867. Hyperinflation of lungs, flattening domes of hemidiaphragms, attenuation or absence of pulmonary vasculature, loss of vascular branching pattern, widened retrosternal space, large focal lucencies (bullae), bronchial wall thickening.
  868. 868. Attenuation of vascular shadows accompanied by hyperlucency of the lungs are signs of emphysema.
  869. 869. With complicating pulmonary hypertension, the hilar vascular shadows are prominent;
  870. 870. With right ventricular enlargement, opacity in the lower retrosternal air space may occur. 
  871. 871. CT scanning and HRCT are even better for assessment</li></ul>Pulmonary Function Tests<br /><ul><li>Necessary for diagnosis of obstructive airway disease and for assessments of its severity.
  872. 872. Spirometry is helpful for assessing responses to treatment and disease progression.
  873. 873. Decrease of forced expiratory volume in 1 second (FEV1) is the key to diagnosis.
  874. 874. Increase in total lung capacity, functional residual capacity, and residual volume. The vital capacity is decreased.</li></ul>Clinical Phenotypes<br /><ul><li>Pink puffer.
  875. 875. Emphysema is the primary underlying pathology.
  876. 876. Results from destruction of airways distal to terminal bronchiole, includes gradual destruction of capillary bed
  877. 877. Less surface area for gas exchange -- but less ventilation-perfusion mismatch than blue bloaters.  
  878. 878. Compensate by hyperventilation ("puffer" part) -- less hypoxemia (compared to blue bloaters) with "reddish"
  879. 879. Develop muscle wasting and weight loss.  
  880. 880. Blue bloater.
  881. 881. Primary underlying lung pathology is chronic bronchitis.
  882. 882. Caused by excessive mucus production with airway obstruction
  883. 883. Resulting from hyperplasia of mucus-producing glands, goblet cell metaplasia, and chronic inflammation.  
  884. 884. Pulmonary capillary bed is undamaged.
  885. 885. Body responds to the increased obstruction by decreasing ventilation and increasing cardiac output.
  886. 886. Marked ventilation-to-perfusion mismatch leading to hypoxemia and polycythemia.  
  887. 887. Increased CO2 retention (hypercapnia). 
  888. 888. Because of increasing obstruction, their residual lung volume gradually increases (the "bloating" part). 
  889. 889. Hypoxemic/cyanotic with worse hypoxemia than pink puffers >> manifests as bluish lips and faces--the "blue" part.
  890. 890. Pulmonary Hypertension
  891. 891. Hypoxemia produces constriction of pulmonary arterioles and thus a rise in pulmonary artery pressure.
  892. 892. Increased afterload on the right ventricle causes hypertrophy and ultimately, right-sided heart failure (cor pulmonale)
  893. 893. Causes dilatation and thickening of the wall of main pulmonary artery. </li></ul>Progression of Disease<br /><ul><li>Inexorable decline in respiratory function and progressive dyspnea, for which no treatment is adequate.
  894. 894. Development of cor pulmonale and eventually congestive heart failure, related to secondary pulmonary vascular hypertension,
  895. 895. Death due to respiratory acidosis and coma, right heart failure, and massive collapse of lungs secondary to pneumothorax.
  896. 896. Treatment options include bronchodilators, steroids, bullectomy, and lung volume reduction surgery and lung transplantation. </li></ul>Loading, Please Wait ... <br />DISORDERS OF PLEURA, DIAPHRAGM AND CHEST WALL<br /> <br />Disorders of Pleura<br />Pleural Effusions <br /><ul><li>Accumulation of excess fluid in the pleural cavity
  897. 897. Detected radiologically as obliteration of costophrenic angle, to a massive accumulation that shifts mediastinum and trachea
  898. 898. Pleural fluid accumulates when pleural fluid formation exceeds pleural fluid absorption.
  899. 899. May develop when there is excess pleural fluid formation or decreased fluid removal by the lymphatics.
  900. 900. Accumulation of pleural fluid occurs in the following settings:
  901. 901. Increased hydrostatic pressure, as in congestive heart failure
  902. 902. Increased vascular permeability, as in pneumonia
  903. 903. Decreased osmotic pressure, as in nephrotic syndrome
  904. 904. Increased intrapleural negative pressure, as in atelectasis
  905. 905. Decreased lymphatic drainage, as in mediastinal carcinomatosis
  906. 906. Non-inflammatory pleural effusions (transudative).
  907. 907. Noninflammatory collections of serous fluid within the pleural cavities are called hydrothorax
  908. 908. Fluid is clear and straw colored.
  909. 909. Most common cause is cardiac failure, usually accompanied by pulmonary congestion and edema.
  910. 910. Also found in renal failure and cirrhosis of the liver.
  911. 911. There are two special forms of non-inflammatory pleural effusions:
  912. 912. Hemothorax: escape of blood into the pleural cavity
  913. 913. Fatal complication of a ruptured aortic aneurysm or blunt or penetrating chest trauma.
  914. 914. Identifiable by the large clots that accompany the fluid component of the blood.
  915. 915. Associated with hypotension or shock and respiratory distress.
  916. 916. Patients are tachycardic, tachypneic, PE reveals diminished breath sounds and dull percussion
  917. 917. Chylothorax: presence of lymphatic fluid (chyle) in the pleural space secondary to leakage
  918. 918. Chyle is milky white because it contains finely emulsified fats.
  919. 919. Most common cause is trauma, but it also may result from tumors in mediastinum (lymphoma).
  920. 920. Inflammatory pleural effusions (pleuritis) -- (exudative)
  921. 921. Etiology
  922. 922. Inflammation of pleura may result from extension of any pulmonary infection to the visceral pleura, rheumatoid arthritis, disseminated lupus erythematosus, collagen vascular disease, or pulmonary infarction
  923. 923. Sharp, stabbing chest pain on inspiration. Associated with pleural effusion (exudates)
  924. 924. Serous, serofibrinous and fibrinous pleuritis.
  925. 925. Fibrinous exudations generally reflect a later, more severe exudative reaction
  926. 926. Grossly, a grayish-white fibrinous membrane covers the inflamed pleura which lacks its normal luster.
  927. 927. There is frequently a small amount of fluid serous exudate that is cloudy in appearance.
  928. 928. Purulent pleuritis (Empyema)
  929. 929. Results from infectious seeding of pleural space by contiguous, lymphatic or hematogenous dissemination
  930. 930. Characterized by loculated, yellow-green, creamy pus composed of neutrophils admixed with leukocytes.
  931. 931. Hemorrhagic pleuritis.
  932. 932. Found especially in neoplastic involvement of the pleural cavity (such as pleural metastases).
  933. 933. Lung carcinoma, breast carcinoma, and lymphoma.
  934. 934. Most patients complain of dyspnea, which is frequently out of proportion to the size of the effusion.
  935. 935. Pleural fluid is a sanguineous exudate which must be differentiated from hemothorax.
  936. 936. Diagnosis of pleuritis. 
  937. 937. First step is to determine whether the effusion is a transudate or an exudate.
  938. 938. Distinguished by measuring the lactate dehydrogenase (LDH) and protein levels in the pleural fluid.
  939. 939. Exudative pleural effusions meet at least one of following criteria, whereas transudative pleural effusions meet none:
  940. 940. Pleural fluid protein/serum protein >0.5
  941. 941. Pleural fluid LDH/serum LDH >0.6
  942. 942. Pleural fluid LDH more than two-thirds normal upper limit for serum
  943. 943. If exudative pleural effusion is determined, the following tests on the pleural fluid should be obtained:
  944. 944. Description of the fluid, glucose level, differential cell count, microbiologic studies, and cytology.</li></ul>Pneumothorax <br /><ul><li>Presence of air or gas in pleural cavity between the visceral and parietal pleura.
  945. 945. Air can enter intrapleural space through a communication from chest wall or through lung parenchyma across visceral pleura.
  946. 946. Classification: may be spontaneous, traumatic, iatrogenous or therapeutic.
  947. 947. Primary spontaneous pneumothorax.
  948. 948. Epidemiology: Occurs more frequently in men between 18 and 40 years of age.
  949. 949. Pathogenesis: Occur from rupture of blebs and bullae.
  950. 950. Risk factors
  951. 951. Heavily associated with smoking,
  952. 952. Physical height -- typical patients tend to have a tall and thin body habitus. 
  953. 953. Familial forms
  954. 954. Marfan syndrome is an autosomal dominant disease caused by mutations in the gene encoding fibrillin 1.
  955. 955. Ehlers-Danlos syndrome, especially vascular subtype (type IV)
  956. 956. Birt-Hogg-Dubé syndrome -- associated with pulmonary cysts and renal cancer. Mutations in folliculin gene.
  957. 957. Secondary spontaneous pneumothorax.
  958. 958. Epidemiology: COPD is a common cause of secondary spontaneous pneumothorax
  959. 959. Pathogenesis. Air enters the pleural space via distended, damaged, or compromised alveoli.
  960. 960. Etiology: emphysema in particular and COPD in general, asthma, CF, interstitial lung disease, TB, lung carcinoma
  961. 961. Clinical relevance: may present with more serious clinical symptoms and sequelae due to comorbidity.
  962. 962. Traumatic pneumothorax.
  963. 963. Iatrogenic pneumothorax.
  964. 964. Leading causes include transthoracic needle aspiration, subclavicular needle stick, thoracentesis, transbronchial biopsy, pleural biopsy and positive pressure ventilation.
  965. 965. Therapeutic pneumothorax: designed to create pulmonary parenchymal collapse and has been used to treat lung tuberculosis.
  966. 966. Pneumomediastinum.
  967. 967. Condition in which air is present in the mediastinum.
  968. 968. Etiology: alveolar rupture with dissection of air into the mediastinum, esophageal perforation, and bowel rupture
  969. 969. Diagnosis: confirmed via chest radiograph showing a radiolucent outline around heart and mediastinum or via CT
  970. 970. Clinical presentation
  971. 971. Causes compression, collapse, and atelectasis of the lung and may be responsible for marked respiratory distress.
  972. 972. Acute onset of chest pain and shortness of breath are the predominant symptoms.
  973. 973. Primary spontaneous pneumothorax usually causes limited symptoms
  974. 974. Symptoms of secondary spontaneous pneumothorax tend to be more severe,
  975. 975. Hypoxia, cyanosis and tachycardia are usually present. Hypercapnia may cause confusion and coma.
  976. 976. Physical examination: absent breath sounds, hyperresonance on percussion and decreased tactile fremitus.
  977. 977. Tension pneumothorax.
  978. 978. Secondary to blunt or penetrating injury of the lung which results in a one-way valve being created.
  979. 979. Air leaks from the lung out into the pleural space and is unable to escape, resulting in increased intrapleural pressure.
  980. 980. Increases to the point where it interferes with venous return
  981. 981. Clinical presentation: respiratory distress with tachypnea, tachycardia, cyanosis, hypotension and confusion.
  982. 982. Affected side of chest may