朱 荣 上海医学院病理学系 东一号楼 207 室 zhurongss@fudan

1. Diseases of Respiratory System 朱 荣 上海医学院病理学系 东一号楼207室　 zhurongss@fudan.edu.cn

2. ANATOMY and FUNCTION • Upper respiratory tract — nose, pharynx, larynx • Lower respiratory tract — trachea & bronchi  Right bronchus diverging at a lesser angle, foreign material more frequently aspirated  Lobar, segmental, lobular • Terminal airwaysand alveoli — respiratory bronchiole alveolar sac alveolus

4. Bronchus 1. Mucosa ciliated column cell，goblet cell, basal cell, stem cell, small granule cell (neurosecretory granules) 2. Submucosal glands — serous and mucus 3. Wall — smooth muscle, contractile — elastic fibers, provide flexibility — cartilage plate, for support BronchioleΦ < 1mm 1. Mucosa — ciliated epithelial cell — Clara cell (non-ciliated secretary cell) 2. Wall — smooth muscle — no gland — no cartilage

5. Terminal airwayand alveolus • Unit of gas exchange the ultimate site of gas exchange — respiratory bronchioles, alveolar ducts, alveolar sac, alveoli • Alveolar type I cell — 95% of the surface — gas permeable • Alveolar type II cell — 5% of the surface — producing surfactant, lowering the surface tension, involved in the repair of alveolar epithelium

8. Remarks 1. Respiratory system is communicating with external environment, so it is susceptible to the diseases. 2. All blood from the body will pass through the lung and the biological pathogens and embolus can be trapped in the lung.

9. 3. The lung is closely related to the heart, not only by their location but also by the pulmonary circulation. 4. The diseases specific to the lung (e.g damage to the wall of bronchial tree, obstruction of bronchioles and disintegration of alveolar/ capillary membrane)

10. Pulmonary Infections Pulmonary Host Defense Mechanisms Nasal hair and Turbinates Interference from resident flora Mucociliary apparatus and cough Immunoglobulin (IgG, IgM, IgA) Complement production Cytokines (IL-1, TNF) Alveolar macrophages Polymorphonuclear leukocytes Cell-mediated immunity

11. Pneumonia can result whenever these defense mechanisms are impaired or the resistance of the host is lowered: Defects in innate immunity and immunodeficiency Cell-mediated immune defects Exogenous aspects of lifestyle interfere: cigarette smoke, alcohol --From the nasopharynx all the way into the alveolar airspaces Pulmonary infections in the form of pneumonia are responsible for one-sixth of all deaths in the USA.

12. I. Pneumonia 肺 炎 Pneumonia can be very broadly defined as any infection in the lung Classification: It is best to classify pneumonias either by the specific etiologic agent ( Air containing hazardous dusts, chemicals and microorganisms ) or, if no pathogen can be isolated, by the clinical setting in which infection occurs.

13. The Pneumonia Syndromes Pneumonia can arise in seven distinct clinical settings: Community-Acquired Acute Pneumonia Community-Acquired Atypical Pneumonia Nosocomial Pneumonia Aspiration Pneumonia Chronic Pneumonia Necrotizing Pneumonia and Lung Abscess Pneumonia in the Immunocompromised Host

14. Acute, fulminant or chronic Histologic spectrum  Fibrinopurulent alveolar exudates — acute bacterial pneumonias  Mononuclear interstitial infiltrates — viral and other atypical pneumonias  Granulomas and cavitation — chronic pneumonias

15. Anatomic and radiographic patterns: Acute bacterial pneumonias  Lobar pneumonia Consolidation of a large portion of a lobe or of an entire lobe  Lobular pneumonia (Bronchopneumonia) Scattered solid foci in the same or several lobes; an initial infection of the bronchi and bronchioles with extension into the adjacent alveoli.

16. Remarks 1. The anatomic distinction between lobar pneumonia and bronchopneumonia is blurry: Many organisms present with either of the two patterns of distribution. Confluent bronchopneumonia can be hard to distinguish radiologically from lobar pneumonia. 2. The onset is usually abrupt, with high fever, shaking chills, pleuritic chest pain, and a productive mucopurulent cough.

17. A. Lobar pneumonia Conception Contiguous airspaces of part or all of a lobe are homogeneously filled with an exudate that can be visualized on radiographs as a lobar or segmental consolidation. — A disease of acute exudative inflammation

18. Pathogenesis — Healthy adults — Host defenses depressed — Heavy contamination by virulent pathogens — Normal inhabitants of the oropharynx and nasopharynx Pneumococcus (95%)

19. Pathology and clinical features A rather clear cut 4 staged battle in the affected lung in a period about 7~8 days A complete and unsloppy recovery Four stages: Congestion Red hepatization Gray hepatization Resolution

20. I Congestion (1~2d) Gross — Heavy, red, boggy LM — Vascular congestion — Proteinaceous fluid containing numerous pneumococci filling the alveoli — Scattered neutrophils

21.  Clinical features — Abrupt onset of high fever, shaking chills — pink frothy sputum — Moist rale — Chest radiograph: dim, uniform shadow

22. II Red hepatization (3~4d) Gross — A liver-like consistency, granular — A fibrinous or fibrinopurulent exudate of pleura

23.  LM — Intra-alveolar hemorrhage —Massive neutrophils — Fibrin packing within alveolar spaces — Numerous pneumococci detected

24.  Clinical feature — Rusty sputum （hemosiderin from red cell degradation) — Dyspnea, cyanosis, chest pain — Chest radiograph: a solid appearance extending to entire lobes or segments — Pulmonary consolidation(实化)

25. III Gray hepatization (4~6d) “A turning point”  Gross — Dry, gray, firm, granular

26.  LM — Red cells lysed —Fibrinous exudate and neutrophils within alveoli — No pneumococci detected Clinical features same as red hepatization purulent sputum hypoxia improved

27. IV Resolution  Gross — Pleural resolved or organized fibrous thickening or permanent adhesions  LM — Exudates within alveoli enzymatically digested Either resorbed and ingested by macrophages or expectorated Clinical features Recovery

28. Remarks 1.In the era before antibiotics, lobar pneumonia evolved through four stages. 2. Early antibiotic therapy alters or halts this typical progression. The anatomic changes seen at autopsy may not conform to the classic stages.

29. Complications Not common; Death rate: 3 ~ 5 % Carnification (肺肉化, organizing pneumonia） Pulmonary abscess and pyothorax  Septicemia  Toxic pneumonia Organized by fibroblasts growing into it. Organization of the intra-alveolar exudate may convert areas of the lung into solid fibrous tissue.

30. Carnification

31. B. Lobular pneumonia (Bronchopneumonia)  Resulting from an initial infection of the bronchi and bronchioles with extension into the adjacent alveoli  A purulent inflammation  A patchy distribution of inflammation that generally involves more than one lobe  Most frequently bilateral and basal  Much more prevalent at the extremes of age

32. Pathogenesis  Organisms: Relatively avirulent Pneumococcus, staphylococcus, and streptococcus, etc. “Opportunistic infection”  Often a secondary disease — Terminally ill patients, infants and taking immunosuppressive drugs, etc. — Aspiration pneumonia  A common cause of death “ terminal pneumonia ”

33. Pathology and clinical features Gross — In the lower and posterior portions — lesions：Ф1cm, up to 3-4cm, gray to yellow  Confluence of foci the appearance of a lobar consolidation  Surrounding areas of consolidation is hyperemic and edematous  Scattered irregular foci of pneumonia are centered on terminal bronchioles and respiratory bronchioles

34. Lobular pneumonia

35.  LM — Focal suppurative exudate filling the bronchi, bronchioles and adjacent alveolar spaces Clinical features Onset delitescence Cough Mucosal fluid sputum Bubble X-ray: foci of solid

36. Lobular pneumonia

37. Complications — Common — Poor in prognosis — “ terminal pneumonia ”  Abscess formation  Empyema  Solid fibrous tissue  Meningitis, arthritis, and infective endocarditis  Respiratory insufficient  Cardiac insufficient

38. Comparison between lobar and lobular pneumonia lobar lobular Onset Primary Secondary A definite disease entity Not a definite entity Age Healthy adults Often infants and the elderly Bact Mostly pneumococcus Often commensals Prog A complete recovery Poor in prognosis, “terminal pneumonia” Path LM Fibrinou-purulent Purulent Gross Lower or middle lobe Bilateral and basal Liver-like Patchy distribution

39. C. Interstitial pneumonia Atypical pneumonia — Modest sputum production — No physical findings of consolidation — White cell count moderately elevated  Mononuclear inflammatory infiltration in pulmonary interstitium and alveolar septa ( the thickened alveolar walls)

40. Pathogenesis Mycoplasma — the most common cause Viruses, chlamydiae and rickettsiae, etc.  A primarily upper respiratory tract infection with coryza, pharyngitis, laryngitis and tracheobronchitis  Mycoplasma: Children & young adults Sporadically or as local epidemic Viral infections — at any age

41. Pathology Gross — Patchy, whole lobes bilaterally or unilaterally — Red-yellow, congested and subcrepitant(捻发音)

42. LM Inflammatory reaction is largely confined within the walls of the alveoli — Septa widened and edematous A mononuclear inflammatory infiltrate (lymphocytes, histiocytes, plasma cells) — Alveolar spaces are free of cellular exudate — Diffuse alveolar damage with hyaline membranes in severe cases — A mixed histological picture with secondary infection (bacterial infection)

43. Normal

44. Cytomegalovirus Infections Inclusions in the plasma

45. Clinical course Extremely varied — A severe upper respiratory tract infection — Chest radiographs Transient, ill-defined patches mainly in the lower lobes — Physical findings characteristically minimal — Identifying the causative agent can be difficult Prognosis — Good, Complete recovery — Most serious infections complicated by bacterial superinfection and poor in prognosis

46. Severe acute respiratory syndrome (SARS) First identified in November 2002 in China

47. SARS coronavirus • Laboratory diagnostic criteria — Serological test of anti-SARS CoV • Clinical features Fulminant, fever, contagious Rapidly progressing to severe respiratory syndrome • Pathological feature Severe atypical pneumonia

48. coronavirus The SARS-Cov appears to have been first transmitted to humans through contact with wild masked palm civets

49. Early stage: edema Fluid including fibrin exudate Swell and consolidation

50. The lungs of patients dying of SARS usually demonstrate diffuse alveolar damage Hyaline membrane Respiratory distress