Diseases of the Respiratory System Lu hua

1. Diseases of the Respiratory SystemLu hua Dept. of Pathology Three Gorges University Medical College

2. Emphysema

3. Definition Emphysema is a condition of the lung characterized by abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls and without obvious fibrosis.

4. In contrast, the enlargement of airspaces unaccompanied by destruction is termed "overinflation“. Interstitial emphysema--is characterized by the entrance of air into the connective tissue stroma of the lung, mediastinum, or subcutaneous tissue . (rib fracture , penetrating injury of chest, coughing plus some bronchiolar obstruction, etc.) Compensatory emphysema-- the distention of airspaces that occurs in the remaining lung parenchyma that follows surgical removal of a diseased lung or lobe. senile emphysema--For the elastic force of older pulmonary tissue change to weakened, it make pulmonary residual volume increased and cause lung expansion. Obstructive Overinflation--Obstructive overinflation refers to the condition in which the lung expands because air is trapped within it. A common cause is subtotal obstruction by a tumor or foreign object.

5. Types of true emphysema: four major types • Centriacinar (Centrilobular ) emphysema • The central or proximal parts of the acini, formed by respiratory bronchioles, are affected, whereas distal alveoli are spared. • Distal Acinar (Paraseptal) Emphysema • The proximal portion of the acinus is normal, but the distal part is predominantly involved. • Panacinar (Panlobular) Emphysema • The acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind alveoli • Irregular Emphysema (Airspace Enlargement with Fibrosis)

6. Irregular emphysema, so named because the acinus is irregularly involved, is almost invariably associated with scarring. Thus, it may be the most common form of emphysema because careful search of most lungs at autopsy shows one or more scars from a healed inflammatory process. In most instances, these foci of irregular emphysema are often asymptomatic, clinically insignificant and only an accidental autopsy finding.

7. Distal Acinar (Paraseptal) Emphysema Centriacinar (Centrilobular ) emphysema

8. Pathogenesis: synergy of many factors • Two main factors: • Bronchial obstruction • The protease-antiprotease theory

9. 1.Mild chronic inflammation throughout the airways, parenchyma, and pulmonary vasculature Damage of elastic fiber in the wall of bronchiole and alveolar wall. Blood supply of the alveolar interval reduce Stenosis of bronchiole Damage of alveolar interval , it make alveolar interval disappeared Incomplete obstruction of bronchiole Dilatation of airspaces distal to the terminal bronchiole Alveolar fusion to form the bulla

10. Inadequate ventilation • Less perfusion • Narrowed bronchiole • Destruction of alveolar walls

11. 2.The protease-antiprotease theory The most plausible hypothesis to account for the destruction of alveolar walls is the protease-antiprotease mechanism, aided and abetted by oxidant-antioxidant imbalance. The protease-antiprotease theory holds that alveolar wall destruction results from an imbalance between proteases (mainly elastase) and antiproteases in the lung.

12. The protease-antiprotease imbalance and oxidant-antioxidant imbalance are additive in their effects and contribute to tissue damage. α1-antitrypsin (α1-AT) deficiency can be either congenital or "functional" as a result of oxidative inactivation. (IL-8, interleukin 8; LTB4, leukotriene B4; TNF, tumor necrosis factor.)

13. Morphology • Enlargement • Overinflation • Brim blunt circle • Grey • Low elasticity

14. Centriacinar emphysema. Central areas show marked emphysematous damage (E), surrounded by relatively spared alveolar spaces

15. Panacinar emphysema involving the entire pulmonary architecture.

16. 镜下： Thin and stretched alveolar walls Spurs of broken septa Distended alveoli and alveolar duct Inflammatory changes are usually absent.

18. Clinical features: The clinical manifestations of emphysema do not appear until at least one third of the functioning pulmonary parenchyma is damaged. Dyspnea----it is usually the first symptom; it begins insidiously but is steadily progressive. Cough and expectoration----these are extremely variable and depend on the extent of the associated bronchitis. Weight loss— it is common and can be so severe as to suggest a hidden malignant tumor. Barrel-chested

19. Such patients may overventilate and remain well oxygenated and therefore are somewhat ingloriously designated as pink puffers (PP type). Patients with chronic bronchitis more often have a history of recurrent infection, abundant purulent sputum, hypercapnia, and severe hypoxemia, prompting the equally inglorious designation of blue bloaters (BB type).

21. Death in most patients is due to • Respiratory acidosis and coma • Right-sided heart failure • Massive collapse of the lungs secondary to pneumothorax.

22. Bronchial Asthma

23. Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or in the early morning. These symptoms are usually associated with widespread but variable bronchoconstriction and airflow limitation that is at least partly reversible, either spontaneously or with treatment. It is thought that inflammation causes an increase in airway responsiveness (bronchospasm) to a variety of stimuli.

24. Etiopathogenesis and types: • Typically, asthma is categorized into three types: • Extrinsic (atopic, allergic) asthma —initiated by a type I hypersensitivity reaction induced by exposure to an extrinsic antigen • Intrinsic (idiosyncratic, non-atopic) asthma —initiated by diverse, nonimmune mechanisms, including ingestion of aspirin; pulmonary infections, especially viral; cold; inhaled irritants; stress; and exercise • Mixed type —many patients do not clearly fit into either of the above two categories and have mixed features of both.

25. Morphology features: Grossly; Overdistended --the lungs are overdistended because of overinflation, and there may be small areas of atelectasis. Mucous plugs --The most striking macroscopic finding is occlusion of bronchi and bronchioles by thick, tenacious mucous plugs.

26. Hyperinflated lungs of a patient who died with status asthmaticus.

27. Mucous plugs

29. Basement membrane Infiltration of eosnophils

30. Smooth muscle thickening

31. Mucous plugs

32. The bronchial lumen filled with mucus at the left Submucosa is widened by smooth muscle hypertrophy, edema, and inflammation (mainly eosinophils). mucus bronchial cartilage smooth muscle

33. At high magnification, the numerous eosinophils are prominent from their bright red cytoplasmic granules in this case of bronchial asthma

34. Charcot-Leyden Crystals The sputum usually contains numerous eosinophils and diamond-shaped crystals (it formed by the fusion of the eosinophilic particles derived from eosinophils).

36. The Spectrum of COPD