Zhejiang University School of Medicine. Basic PATHOLOGY ZHOU REN. Prof., M.D., Ph.D.

Transcription

1 Zhejiang University School of Medicine Basic PATHOLOGY 周 韧 ZHOU REN Prof., M.D., Ph.D. Department of Pathology & Patho-physiology Institute of Pathology & Forensic Medicine Zhejiang University Judicial Evidence & Evaluation Center

2

3 Respiratory Diseases

4 Review of the architecture of the respiratory system

5

6

7

8

9

10 PULMONARY DUCT PULMONARY ACINUS Bronchus Bronchioles Respiratory bronchioles oles Alveolar duct Alveolar cyst Alveolus Acute bronchitis Emphysema Chronic bronchitis Asthma Bronchiectasis Bronchiolar pneumonia Lobular pneumonia Squamous cell carcinoma Adenocarcinoma Bronchioloalveolar carcinoma Pulmonary tuberculosis

11 Pneumonia

12 Pneumonia can be very broadly Defined as any infection in the lung. Pathologically, it may be defined as any inflammation of lung.

13 Classification of pneumonia

14 1. Etiological classification: bacterial pneumonia viral pneumonia fungal pneumonia etc.

15 2. Anatomical classification: lobar pneumonia lobular pneumonia interstitial pneumonia.

16

17 Clinically, etiological classification is more beneficial to the treatment; but the etiological classification usually can not be made readily.

18 The anatomical classification may give a great help to the etiological diagnosis sometimes. > 90%: caused by Streptococcus pneumoniae (pneumococcus) ; interstitial pneumonia are caused by virus or mycoplasm.

19 Bacterial Pneumonia Lobar pneumonia Def. In lobar pneumonia the contiguous air spaces of part or all of a lobe are homogenously filled with an exudates that can be visualized on radiographs as a lobar or segmental consolidation and is thus sometimes referred to as air space pneumonia.

20 The disease which is often seen in previously healthy young adults has a sudden onset and is accompanied by chills, fever, cough with pink-foam sputa and chest-ache.

21

22 Etiology and pathogenesis >90% S. pneumonia enter the lungs via the airways Occasionally other organisms (Klebsiella pneumoniae, staphylococci, streptococci, Haemophilus influenzae).

23 Lobar pneumonia is initiated in periphery acinus, from there the exudative fluid containing etiologic agent flows into the adjacent air passage to infect adjacent lobules until a segment or entire lobe is infected.

24 Morphology For purposes of description, it is convenient to divide the process into four phases:

25 (1) Congestion (2) Red hepatizatio (consolidation) (3) Gray hepatization (4) Resolution

26 1. Congestion stage (1 st -2 nd days) The affected lobe is heavy, red and boggy. A frothy blood-stained fluid can be squeezed from the cut surface.

27 Histologically, there is vascular congestion with proteinaceous fluid, scattered neutrophils, and many bacteria in the alveoli. Clinically, the onset is sudden with fever and rigors.

28

29 2. Red hepatization stage (2 nd -4 th day) Liver-like in consistency Septal capillaries are congested markedly Alveolar spaces are packed with many red cells, and several neutrophils, fibrin. The pleura usually demonstrates a fibrinous or fibrinopurulent exudates.

30

31

32 3. Gray hepatization stage (4 th 8 th day) More solid in consistency Pleural surface is covered with a confluent fibrinous exudates. The cut surface is dry and granular but of a grayish-white color.

33 Histologically, congestion of septal capillaries lightens. The fibrinous exudate persists within the alveoli and a fibrin net forms. There are many neutrophils but is relatively depleted of red cells in the alveoli.

34

35

36

37 4. Resolution stage (8 th -9 th day) With the elimination of bacteria, the inflammation subsides. Since there is no tissue destruction the lung return to normal apart from the pleura.

38 X 光肺叶密度增高 肺叶实变

39

40 Complications: 1. Carnification: Organization of intraalveolar fibrinous exudates instead of resorption may convert areas of the lung into solid fibrous tissue.

41 2. Tissue destruction and necrosis may lead to abscess formation.

42 3. Suppurative material may accumulate in the pleural cavity, producing purulent pleurisy and empyema.

43 4. Septicemia or pyemia: Bacteremic dissemination may lead to meningitis, arthritis, or infective endocarditis. 5. Infective shock: Failure of terminal circulation and appearance of toxic symptoms.

44 Bronchopneumonia Conception: Defined as an acute purulent inflammation characterized by diffuse patchy pneumonic consolidation often with bronchiolitis in its center.

45 It is a threat chiefly to the vulnerable infants, the aged, and those suffering from chronic debilitating illness or immuno-suppression.

46 Children: Whooping cough and measles are important antecedents Adult: influenza, chronic bronchitis, alcoholism, malnutrition, and carcinomatosis are all predisposing conditions.

47 Clinically, bronchopneumonia may appears as a complication of a disease.

48 Hypostatic pneumonia The patient with pulmonary edema from cardiac failure or heavy uremia, et al, is particularly vulnerable, who are necessary to keep themselves in bed in prolonged time. Aspiration pneumonia The patient in coma or apoplexy, heavy anesthesia and so on is particularly vulnerable.

49 Etiology Almost any organism may cause bronchopneumonia, frequent offenders are staphylococci, streptococci, haemophilus influenza, proteus species etc.

50 Morphology Foci of inflammatory consolidation with a center of bronchiolitis are distributed in patches through one or several lobes, most frequently bilateral and basal.

51 Well-developed lesions up to 3 or 4 cm (usually cm) in diameter are slightly elevated, dry, granular, gray-red to yellow and demarcated distinctly.

52

53 The lung substance immediately surrounding areas of consolidation is usually hyperemic and edematous, but the large intervening areas are generally normal.

54 Histologically, the reaction consists of a suppurative exudates that fills the bronchi,bronchioles, and adjacent alveolar spaces. Hyperemia, edema and inflammatary infiltration can be seen in the walls of bronchioles.

55

56

57

58 Complication The same complication, as in lobar pneumonia.

59 Viral pneumonia and mycoplasmal pneumonia They both belong to interstitial pneumonia

60 Def. an inflammatory process involving the interstitial tissue of the lungs.

61 Etiology and pathogenesis The common agents are viruses and mycoplasma.

62 Attachment of the organisms to the respiratory epithelium is followed by necrosis of the cells and an inflammatory response. Then, the inflammation extends to the interstitial tissue including peribronchial connective tissue and interalveolar septa.

63 Morphology Macroscopically: red-blue, congested, and subcrepitant. Because much of the reaction is interstitial, little inflammatory exudates escapes on sectioning of the lung, although there may be slight oozing of red, frothy fluid.

64 Histologically, the inflammatory process is largely confined within the walls of the alveoli. The septa are widened and edematous; they usually contain a mononuclear infiltrate of lymphocytes, histiocytes and occasionally plasma cells.

65

66

67

68 In virus infection, inclusion bodies may be formed within cytoplasm or nucleus of the epithelial cells of bronchioles and alveoli. In severe cases alveolar damage with hyaline membranes may develop.

69 A TRY

70 Chronic obstructive pulmonary disease (COPD) chronic bronchitis emphysema bronchial asthma bronchiectasis

71 Chronic bronchitis Def. A persistent productive cough for at least three consecutive months in at least two consecutive years.

72 Etiology and Pathogenesis

73 smoking, air pollution (SO 2, NO 2 ) hypersecretion of bronchial mucous gland hypertrophy of mucous gland, Goblet cell metaplasia of bronchial epithelium directly or through neurohumoral pathways chronic bronchitis loss of ciliated epithelium retention of secretion microbial infection proliferation of bacteria

74 Morphology

75 Grossly 1mucosal lining of the larger airways is usually hyperemic and swollen by edema fluid; 2it is covered by a layer of mucinous or mucopurulent secretions. The smaller bronchi and bronchioles may also be filled with similar secretions.

76 3. 病理变化 部位 主要特征眼观 : 早期 进展

77 镜检 : (1) 腺体肥大, 分泌亢进后期腺体萎缩, 分泌耗竭 (2) 气管粘膜上皮细胞的损伤 (3) 支气管壁的病变 Histologically: Hypertrophy of mucous gland and goblet cell metaplasia of bronchial wall.

78 1the diagnostic feature : enlargement of the mucus-secreting glands. Reid index: the ratio of the thickness of the submucosal gland layer to that of the bronchial wall. Normal : 1:3 Chronic bronchitis : usually exceeds 1:2.

79 粘液腺肥大 增生 ; 浆液腺发生粘液化生 粘液分泌亢进 上皮鳞化 粘液腺增生肥大

80 2Increased number of goblet cells in the lining epithelium with concomitant loss of ciliated epithelial cells. 3squamous metaplasia of lining epithelium followed by dysplastic changes.

81 4 Mucosal and submucosal lining of bronchi are hyperemic and swollen. inflammatory infiltration (lymphocytes, plasmacytes, sometimes admixed with neutrophils).

82 支气管粘膜慢性炎伴上皮鳞状化生

83 Complications 1. Emphysema 2. cor pulmonals 3. Bronchiectasis 4. Bronchopneumonia 5. bronchogenic carcinoma of lung

84 Emphysema Def. characterized by abnormal permanent enlargement of the air space distal to the terminal bronchiole accompanied by destruction of their walls.

85

86 Etiology 1. Alveolar wall destruction and air space enlargement invokes excess protease or elastase activity unopposed by appropriate antiprotease regulation

87 1Increase either the number of PMN and MP in the lung 2Increase release of protease from PMN and MP 3 oxidants in cigarette smoke and O 2 - radicals secreted by PMN & MP inhibit the active of α 1 -AT and decrease net anti-elastase activity in smokers Antiprotease α 1 -antitrypsin inhibition Smoking Protease : elastase collagenase α 1 -antitrypsin Deficiency PiMM/PiZZ (Chr14) Destruction of elastin and collagen of the lung Emphysema

88 2. Obstruction of the bronchioles. Air enter into the alveoli distal to the obstructed bronchiole through Kohn s pore (interalveolar pore), and air is trapped during expiration because the pore is closed. Emphysema is ended.

89 ( 四 ) 病因与发病机理 (1) 病因 (2) 发病的二个基本环节 细支气管阻塞和狭窄 小气道及肺泡支撑组织的破坏

90

91 Classification and Morphology Alveolar emphysema: centriacinar emphysema panacinar emphysema periacinar emphysema Interstitial emphysema: Others: paracicatrical emphysema bullae lung senile emphysema compensatory emphysema

92 Diagram of the fundamental unit of the lung centriarclinal and panacinar emphysema.

93 Morphology The lesions of centriacinar emphysema are more common and severe in the upper lobes particularly in the apical segments.

94 腺泡中央型肺气肿

95 Panacinar emphysema: pale, voluminous lungs

96 全腺泡型肺气肿

97 Microscopic features: 1. Thinning and destruction of alveolar walls. 2. Adjacent alveoli become confluent, creating large air spaces. 3. Capillaries in alveolar septa decreased.

98 Terminal and respiratory bronchioles may be deformed because of the loss of septa.

99

100

101

102 Bullous emphysema

103

104 囊泡型肺气肿 ( 大泡直径 3cm)

105

106 Conditions related to emphysema. There are several conditions in which enlargement of air spaces is not accompanied by destruction; this is more correctly called overinflation.

107 Compensatory emphysema Senile emphysema

108 Interstitial emphysema designates the entrance of air into the connective tissue of the lung, mediastinum and subcutaneous tissue.

109 This may occur spontaneously with a sudden increase in intraalveolar pressure (as with vomiting or violent coughing) that cause a tear, with dissection of air into the interstitium.

110

111

112 Complications: 1. Cor pulmonale 2. Pneumothorax 3. Respiratory failure

113 Bronchiectasis Def. Permanent dilatation of bronchi and bronchiole due to destruction of the muscle and elastic supporting tissue. The characteristic symptom: cough and expectoration of copious amounts of purulent sputum.

114 Etiology and pathogenesis

115 Bronchial obstruction (tumor, enlarged lymph node, foreign body) loss of ciliated epithelium infection retention of secretion cough rise of intrabronchial pressure during respiration bronchial dilatation congenital or hereditory conditions Weakening and loss of elastic tissue,muscle and cartilage of bronchus

116 Morphology Grossly: usually affects the lower lobes bilaterally, particularly those air passages that are most vertical.

117 The airways may be dilated as much as 4 times their usually diameter and can be followed nearly to the pleural surfaces. (By contrast, in normal lungs the bronchioles cannot be followed by ordinary gross examination beyond a point 2 to 3 cm from the plural surface.)

118 Patterns of dilatation: cystic cylindrical

119

120

121

122 Histologically, 1there is an intense acute and chronic inflammatory exudates within the wall of the bronchi and bronchioles and desquamation of lining epithelium leaving extensive areas of ulcerated epithelium.

123 2there may be squamous metaplasia of the lining epithelium. 3In some instances, the necrosis destroys the bronchial or bronchiolar walls and forms a lung abscess. 4When healing occurs, granulation tissue forms the base of ulcer.

124 Clinicopathological correlation 1. Postural coughing with large quantity of pus. 2. hemoptysis due to erosion of the vessel in granulation tissue.

125 Complications 1. lung abscess 2. Pyemia--metastatic abscesses 3. Pulmonary fibrosis and cor pulmonale.