1. PULMONARY PATHOLOGY Prof Frank Carey

2. General Approach r Understanding mechanisms of disease r Emphasizing the role of the pathologist in diagnosis

3. Functional Classification of Lung Disease Distinctive clinical and physiological features define: r Obstructive lung disease r Restrictive lung disease

4. Airway Narrowing/Obstruction r Muscle spasm r Mucosal oedema (inflammatory or otherwise r Airway collapse due to loss of support r (Localised obstruction due to tumour or foreign body)

5. Main Categories of Obstructive Disease r Asthma r Chronic obstructive pulmonary disease (COPD/COAD/COLD)

6. Chronic Obstructive Disease r Chronic bronchitis r Emphysema Symptomatic patients often have both

7. Chronic Bronchitis Cough productive of sputum on most days for 3 months of at least 2 successive years r An epidemiological definition r Does not imply airway inflammation

8. Chronic Bronchitis r Chronic irritationdefensive increase in mucus production with increase in numbers of epithelial cells (esp goblet cells) r Poor relation to functional obstruction r Role in sputum production and increased tendency to infection

9. Chronic Bronchitis r Non-reversible obstruction r In some patients there may be a reversible (“asthmatic”) component

10. Normal vs. Chronic Bronchitis

11. Small airways in Chronic Bronchitis r More important than traditionally realised r Goblet cell metaplasia, macrophage accumulation and fibrosis around bronchioles may generate functional obstruction

12. Emphysema r Increase beyond the normal in the size of the airspaces distal to the terminal bronchiole r Without fibrosis The gas-exchanging compartment of the lung

13. Emphysema (types) r Centriacinar (centrilobular) r Panacinar r Others (e.g. localised around scars in the lung)

14. Emphysema r Difficult to diagnose in life (apart from in extremis) r Radiology (CT) can show changes in lung density r Correlation with function known from autopsy studies

15. Emphysema r “Dilatation” is due to loss of alveolar walls (tissue destruction) r Appears as “holes” in the lung tissue

16. Normal lung

17. Centriacinar emphysema

18. Panacinar emphysema 1

19. Panacinar emphysema 2

20. Emphysema How do these changes relate to functional deficit? r Poorly at macroscopic level r Better with microscopic measurement

21. Normal

22. Early emphysema

23. Emphysema Impairs Respiratory Function r Diminished alveolar surface area for gas exchange r Loss of elastic recoil and support of small airways leading to tendency to collapse with obstruction

24. Loss of surface area (emphysema)

25. Loss of support on bronchiolar walls

26. As disease advances…. Pa O 2 leads to: r Dyspnoea and increased respiratory rate r Pulmonary vasoconstriction (and pulmonary hypertension)

28. Epidemiology of COPD r Smoking r Atmospheric pollution r Genetic factors

29. Pathophysiology of Emphysema High rate of emphysema in the rare genetic condition of  1 antitrypsin deficiency r THE PROTEASE/ANTIPROTEASE HYPOTHESIS

30. Elastic Tissue r Sensitive to damage by elastases (enzymes produced by neutrophils and macrophages)   1 antitrypsin acts as an anti-elastase Imbalance in either arm of this system predisposes to destruction of elastic alveolar walls (emphysema)

31. Tobacco smoke….. r Increases nos. of neutrophils and macrophages in lung r Slows transit of these cells r Promotes neutrophil degranulation  Inhibits  1 antitrypsin

32. Bronchial Asthma A chronic inflammatory disorder characterised by hyperreactive airways leading to episodic reversible bronchoconstriction

33. Asthma r Extrinsic - response to inhaled antigen r Intrinsic - non-immune mechanisms (cold, exercise, aspirin)

34. Immunological Mechanisms Type  hypersensitivity - allergen binds to IgE on surface of mast cells r Degranulation (histamine) l muscle spasm l inflammatory cell influx (eosinophils) l mucosal inflammation/oedema r Inflammatory infiltrate tends to chronicity

35. Pathology r Narrowed oedematous airways r Mucus plugs r Inflammatory cells (lymphocytes, plasma cells, eosinophils) r Epithelial cell damage

37. Mucosal oedema

38. Mucus plugs

39. Mucus plug/inflammation

40. Inflammation

41. Inflammation/epithelial damage