1. THE RESPIRATORY SYSTEM Chen Maohuai Dept. of Pathology, Shantou University Medical College

2. Section 3 Contents Section 3 Contents 1. Chronic obstructive pulmonary diseases –(1) chronic bronchitis and chronic bronchiolitis –(2) emphysema –(3) bronchiectasis

3. Contents Contents –(4) silicosis –(5) chronic cor pulmonale (pulmonary heart disease) 2. Pulmonary infections –(1) lobar pneumonia

4. Contents Contents –(2) lobular pneumonia (bronchopneumonia) –(3) interstitial pneumonia (A) viral pneumonia (A) viral pneumonia (B) mycoplasmal pneumonia (B) mycoplasmal pneumonia 3. Nasopharyngeal carcinoma and lung cancer

5. 一． Chronic bronchitis Defined clinically as persistent cough with sputum production for at least 3 months in at least 2 consecutive years.

6. （一） Pathogenesis Two sets of factors are important in the genesis of chronic bronchitis: –1. Chronic irritation by inhaled substances: atmospheric pollution, tobacco smoking.

7. Pathogenesis Pathogenesis –2. Microbiologic infections. They are a secondary factor that maintain and promote the injury initiated by smoking.

8. Pathogenesis Pathogenesis –Both sexes and all ages may be affected, but chronic bronchitis is most frequent in middle-aged men. Four to ten times more common in heavy smokers.

9. （二） Morphology Grossly ： –1. Hyperemia and edema of mucous membranes of the lung. –2. Mucinous secretions or casts filling airways.

10. Morphology Histologic feature: –1. Increase in size of the mucous glands. The ratio of the thickness of the mucous gland layer to the thickness of the wall (Reid index) is increased (normally <0.4).

11. Morphology Morphology –2. A marked increase in goblet cells. Bronchial/bronchiolar mucous plugging, inflammation, and fibrosis. –3. Squamous metaplasia/dysplsia of bronchial epithelium.

12. （三） Clinical course 1. Persistent cough productive of copious sputum, dyspnea, hypercapnia, hypoxemia. 2. Emphysema. 3. Cor pulmonale with cardiac failure. 4. Bronchiectasis

13. 二． Emphysema Defined morphologically as the abnormal enlargement of air spaces distal to the terminal bronchioles, with destruction of their walls.

14. Emphysema Emphysema Emphysema is further classified according to the anatomic distribution of the lesion within the acinus: –(1) Centriacinar emphysema –(2) Panacinar emphysema

15. Emphysema Emphysema the two types above are the common forms of emphysema. –(3) Paraseptal emphysema –(4) Irregular emphysema

16. ( 一 ) Pathogenesis 1. Repeated bronchitis, chronic irritation 2. Alpha1-antitrypsin deficiency

17. Pathogenesis Pathogenesis –Destruction of alveolar walls in emphysema stems from an imbalance between proteases and their inhibitors (antiprotease) in the lung. –The genetic deficiency of the enzyme alpha1-antitrypsin (  1 -AT), Tobacco smoking contributes to emphysema.

18. ( 二 ) Morphology Grossly, with diffuse forms, lungs can become voluminous and pillowy.

19. 图 9-6 肺气肿

20. Morphology Morphology Microscopically, air spaces are enlarged, walls thinned, and septal capillaries compressed and bloodless. Rupture of walls may produce honeycombing.

21. 图 9-7 肺气肿图

22. （三） Clinical course （三） Clinical course 1. The manifestations do not appear in early stage(until at least one-third of the functioning pulmonary parenchyma is incapacitated).

23. Clinical course Clinical course 2. Progressive dyspnea with prolonged expiration, weight loss, barrel-chest. 3. Cor pulmonale and congestive heart failure, pneumothorax, respiratory failure.

24. 图 9-8 肺气肿患者 （采自希巴）

25. 三． Bronchiectasis Represents a chronic necrotizing infection of bronchi and bronchioles leading to or associated with abnormal permanent dilatation of these airways.

26. ( 一 ) Morphology The most severe change are seen in distal airways of lower lobes, with dilatations of varying shapes(clindrical, fusiform, or saccular).

27. 图 9-9 支气管扩张模式图 图 9-10 支气管扩张（采自希巴）

28. Morphology Morphology Histololgy shows a spectrum of mild to necrotizing acute and chronic inflammation of the airways. Fibrosis develops in chronic cases. Extension of bronchial infection may lead to abscess formation.

29. ( 二 ) Clinical features Cough, fever, and abundant purulent sputum. Complications: cor pulmonale, metastatic abscesses, and systemic amyloidosis.

30. 四． Silicosis Prolonged inhalation of silica particles produces a chronic, nodular, dense pulmonary fibrosis.

31. （一） Sources of silica exposure mining (gold, tin, copper, coal) and quarrying. mining (gold, tin, copper, coal) and quarrying. sandblasting. sandblasting. metal grinding. metal grinding. manufacture of ceramics. manufacture of ceramics.

32. （二） Pathogenesis Silicosis involves promotion of persistent inflammation and fibrosis by the interaction of silica particles and lung macrophages.

33. Pathogenesis Pathogenesis Ingested silica leads to macrophage activation and release of oxidants, cytokines, and growth factors that ultimately cause fibroblast proliferation and collagen deposition. Ingested silica leads to macrophage activation and release of oxidants, cytokines, and growth factors that ultimately cause fibroblast proliferation and collagen deposition.

34. Pathogenesis Pathogenesis Injury also may be perpetuated by direct toxic effects on the macrophage, causing cell death and release of the silica- restarting the injury cycle. Injury also may be perpetuated by direct toxic effects on the macrophage, causing cell death and release of the silica- restarting the injury cycle.

35. （三） Morphology Distinct collagenous nodules start as small lesions in the upper lung, but grow larger and more diffuse as the disease progresses.

36. Morphology Morphology Coalescence of lesions forms large areas of dense scar. Calcification or concomitant blackening by coal dust is often present.

37. Morphology Morphology Microscopically, hyalinized whorls of collagen are seen with scant inflammation. Polarized light often shows birefringent silica particles within nodules.

38. 细胞性矽结节

39. （四） Clinical course 1. Development of shortness of breath until late in the course. 2. Silicosis with tuberculosis of lung. 3. Cor pulmonale, emphysema, pueumothorax

40. 五． Chronic cor pulmonale (pulmonary heart disease)

41. Chronic cor pulmonale Chronic cor pulmonale Definition: Right ventricular hypertrophy or dilatation secondary to pulmonary hypertension caused by disorders affecting lung structure or function.

42. Chronic cor pulmonale Chronic cor pulmonale Excluded is Right ventricular (RV) enlargement due to congenital heart disease or LV pathology.

43. Chronic cor pulmonale Etiology:obstruction of the pulmonary arteries or arterioles or compression or obliteration of septal capillaries.

44. ( 一 ) Morphology RV hypertrophy to 1 cm or more thickness. The wall of right ventricular become thickening over 0.5 cm.

45. Morphology Morphology RV dilatation may lead to tricuspid regurgitation. The left side of the heart is essentially normal.

46. ( 二 ) Clinical features Chronic cor pulmonale is responsible for 10% to 30% of hospital admissions for cardiac decompensation. However, cardiac symptoms may be masked by those of underlying lung disease.

47. Section 2. Pulmonary infections

48. 一． lobar pneumonia Definition: lobar pneumonia is a widespread fibrinosuppurative consolidation of large areas and even whole lobes of the lung by acute bacterial infection.

49. lobar pneumonia This pattern of acute bacterial infection involves a large portion of or an entire lobe of lung. This pattern of acute bacterial infection involves a large portion of or an entire lobe of lung.

50. ( 一 ) Etiology: A. Most lobar pneumonias are caused by pneumococci, which enter the lungs via the airways. B. Other organisms: klebsiella peumoniae, staphylococci, streptococci.

51. Etiology Pneumonia can result whenever the defense mechanisms are impaired or whenever the resistence of the host in general in lowered e.g. accumulation of secretions. Pneumonia can result whenever the defense mechanisms are impaired or whenever the resistence of the host in general in lowered e.g. accumulation of secretions.

52. Etiology Etiology Mainly between 30-50 years old adult males previously healthy.

53. ( 二 ) Morphology The following sequence of stages is "classic" but infrequently seen because of antibiotic therapy. Four stages of the inflammatory response include congestion, red hepatization, gray hepatization and resolution.

54. Morphology Morphology 1. Congestion – Predominates in the first 24 hours. – The lung is heavy, boggy and red. – Vascular engorgement, intra- alveolar fluid with few neutrophils. – Often presence of numerous bacteria.

55. Morphology 2. Red hepatization (consolidation) –Describes lung tissue with confluent acute exudation containing neutrophils and red cells, giving a red, firm, liver- like gross appearance.

56. 图 9-15 红色肝样变期

58. Morphology Morphology 3. Grey hepatization –Follows, as the red cells disintegrate and the remaining fibrinosuppurative exudate persists, giving a gray-brown gross appearance.

59. 图 9-16 灰色肝样变期

60. 图 9-17 实变期 灰色肝样变期镜下改变

61. Morphology Morphology 4. Resolution –The favorable final stage in which consolidated exudate undergoes enzymatic digestion and cellular degradation and clearance. Normal structure is restored.

62. ( 三 ) Complications 1. Abscess formation 2. Empyema(spread of infection to pleural cavity)

63. Complications Complications 3. Carnification: organization of exudate into fibrotic scar tissue (incomplete resolution). 4. Bacteremia, septicemia and sepsis, with infection of other organs.

64. 图 9-19 肺肉质变

65. （四） Clinical course （四） Clinical course 1. The major symptoms: malaise, fever, and cough productive of sputum. Pleuritic pain and pleural friction rub. 2. The characteristic radiologic appearance: radiopaque well- circumscribed lobe.

66. 二． lobular pneumonia (bronchopneumonia) This pattern of bacterial pneumonia is marked by patchy exudative consolidation of acute suppurative inflammation in lung parenchyma, caused most commonly by staphylococci, streptococci, pneumococci, and coliform bacteria.

67. lobular pneumonia lobular pneumonia It tends to occur in the more vulnerable two extremes of life --infancy and old age, particularly in those already suffering from some serious disorder.

68. ( 一 ) Morphology Grossly, the lungs show dispersed, elevated, focal areas of palpable consolidation and suppuration.

69. 图 9-20 小叶性肺炎 ( 大体改变 )

70. Morphology Morphology Histologic features consist of an acute (neutrophilic) suppurative exudate filling air spaces and airways, usually about bronchi and bronchioles.

71. 小叶性肺炎 ( 镜下改变 )

72. Morphology Morphology Resolution of the exudate usually restores normal lung structure, but organization may occur and result in fibrous scarring in some cases, or aggressive disease may produce abscesses.

73. （二） Clinical course 1. The major symptoms: fever, and cough productive of sputum. Abscess formation. Empyema. 2. The characteristic radiologic appearance: focal opacities.

74. 三． Interstitial pneumonia (viral and mycoplasmal pneumonia)

75. Interstitial pneumonia Interstitial pneumonia Infections by viruses (e.g., influenza A or B, respiratory syncytial virus, adenovirus, rhinovirus, herpes simplex, cytomegalovirus) or mycoplasma pneumoniae.

76. Interstitial pneumonia Interstitial pneumonia Clinical and pathologic patterns: ranging from relatively mild upper respiratory tract involvements (e.g., the common cold) to severe lower respiratory tract disease.

77. ( 一 ) Morphology Grossly, patchy or lobar areas of congestion without the consolidation of bacterial pneumonias(hence the term "atypical" pneumonia).

78. Morphology Morphology 1. A predominance of interstitial with widened, edematous alveolar walls containing a mononuclear inflammatory cell infiltrate.

79. Morphology Morphology 2. The formation of hyaline membranes, reflecting diffuse alveolar damage. 3. Frequent superimposed bacterial infection.

80. 图 9-21 病毒 肺炎（间质 性肺炎）

82. Morphology Morphology 4. Certain viruses cause necrosis of bronchial or alveolar epithelium in severe infections (herpes simplex, adenovirus, varicella).

83. Morphology Morphology 5. Characteristic cytopathic changes are seen with some, e.g., cytomegaly and nuclear inclusions in the cytomegalovirus infection. 5. Characteristic cytopathic changes are seen with some, e.g., cytomegaly and nuclear inclusions in the cytomegalovirus infection.

84. 图 9-22 病毒性肺炎（病毒包含体）

85. （二） Clinical course 1. The major manifestations: fever, headache, muscle aches. 2. Low mortality rate(<1%) in the sporadic form and greater mortality in epidemic form.

86. Section 3 Carcinoma of the respiratory system

87. 一． Carcinoma of the lung It is the most common cause of cancer death in both men and women. It is the bronchogenic carcinoma It is the bronchogenic carcinoma

88. ( 一 ) Pathogenesis 1. Tobacco smoking 2. Other etiologic factors: include exposure to radiation, asbestos, air pollution and miscellaneous occupational inhaled substances.

89. 图 9-24 支气管粘膜上 皮癌变模式图

90. （二） Histologic types 1. Squamous cell carcinoma –(1) The closest correlation with smoking. –(2) Most arise in or near the hilus of the lung.

91. 图 9-25 中央型肺癌

92. Histologic types Histologic types –(3) The tumors are more common in males and the most common form of bronchogenic carcinoma.

93. Histologic types Histologic types –(4) They vary from well- differentiated keratinizing neoplasms to anaplastic tumors with only focal differentiation.

94. 图 9-26 肺鳞状细胞癌

95. Histologic types 2. Adenocarcinoma –(1) The most common lung cancer in women and is often associated with nonsmokers. –(2) It frequently presents as a peripheral mass.

96. 图 9-27 周围型模式图

97. Histologic types –(3) Gland formation, usually with mucin production. –(4) Two subsets: bronchial derived and bronchioloalveolar adenocarcinoma.

98. 图 9-28 肺细支气 管肺泡癌

99. Histologic types Histologic types 3. Small cell carcinoma –(1) The most malignant of lung cancers and usually presents as a central or hilar tumor. –(2) It is strongly associated with cigarette smoking.

100. Histologic types Histologic types –(3) Small, "oat"-like cells with little cytoplasm in nests or clusters, without squamous or glandular organization. –(4) The cancer cells may exhibit neurosecretory granules (APUDomas).

101. 图 9-29 小细胞癌

102. Histologic types Histologic types 4. Large cell carcinoma –Probably represents poorly differentiated squamous cell carcinomas or adenocarcinomas.

103. ( 三 ) Clinical features: (1) Commonly occur after 40 years old man, male is more frequently than female. (2) The major complaints: cough, weight loss, chest pain, and dyspnea.

104. Clinical features Clinical features (2) Overall 5-year survival is approximately 9%. (3) Paraneoplastic syndromes (hormones or hormone-like factors).

105. Clinical features (4) Small cell carcinoma has almost always metastasized by the time of diagnosis, but is sensitive to radiation and chemotherapy.

106. （四） Early diagnosis 1. Frequently radioscopic examination of the chest. 2.Cytologic examination of sputum or FNA. 3.Bronchial washings or brushings.

107. 二． Nasopharyngeal carcinoma ( NPC )

108. ( 一 ) Etiology: 1. Heredity 2. Infection with EBV.

110. Etiology Etiology 3.Age: NPC are particularly common in parts of Africa, where they are the most common childhood cancer. In contrast, in southern China, they are the most common cancer in adults but rarely occur in children.

111. ( 二 ) Morphology 1. Keratinizing squamous cell carcinomas (WHO-1) 2. Nonkeratinizing squamous cell carcinomas (WHO-2) 3. Undifferentiated carcinomas (WHO-3) (lymphoepithelioma)

112. 图 9-30 鼻咽泡状核细胞

113. ( 三 ) Clinical features 1. Tend to grow silently until they have become unresectable and have often spread to cervical nodes or distant sites.

114. Clinical features Clinical features 2. Radiotherapy is the standard modality of treatment, the undifferentiated carcinoma is the most radiosensitive, and the keratinizing the least radiosensitive.

115. Thanks