Obstructive Pulmonary Diseases

1. Obstructive Pulmonary Diseases

2. Obstructive Pulmonary Diseases

3. Chronic Obstructive Pulmonary Diseases

4. COPD is defined as a disease state characterized by the presence of airflow obstruction due to • Chronic bronchitis • Bronchiectasis • Emphysema • Asthma • The airflow obstruction generally is progressive, may be accompanied by airway hyperreactivity, and may be partially reversible.

5. The term “chronic obstructive pulmonary disease” (COPD) refers to a group of conditions; • They are accompanied by chronic or recurrent obstruction to air flow within the lung, • They share a major symptom: dyspnea.

6. Pathophysiology • Pathological changes in COPD occur in: • the large (central) airways, • the small (peripheral) bronchioles, • the lung parenchyma. • The increased number of activated polymorphonuclear leukocytes and macrophages release elastases lung destruction • Increased oxidative stress free radicals (released by phagocytes, and polymorphonuclear leukocytes) apoptosis or necrosis of exposed cells

7. Factors in COPD • Smoking • Air pollution and COPD • Other factors • Airway hyperresponsiveness • Alpha1-antitrypsin (a 1-AT) deficiency

8. SMOKING • The primary cause of COPD is exposure to tobacco smoke. • Chronic bronchitis is primarily a disease of cigarette smokers: 90% of cases occur in smokers. • Chronic bronchitis occurs in less than 5% of nonsmokers, 10% to 15% of moderate smokers, and more than 25% of heavy smokers.

9. Smoke • The primary cause of COPD • Clinically significant COPD • chronic bronchitis • emphysema • Almost 4000 chemicals, 43 carcinogens • Neoplastic and Non-neoplastic diseases

10. Neoplastic diseases (cancers): Lung Bladder Stomach Pancreas Oral cavity Larynx Cervix Non-neoplastic diseases: Lung diseases Gastritis Atherosclerosis Ischemic heart disease Hypertension Bürger’s disease

11. Pathophysiology of COPD in smokers • Smokers have greater numbers of neutrophils and macrophages in their alveoli • Smoking • Stimulates release of elastase from neutrophils • Enhances elastolytic protease(s) activity in macrophages • Inhibition of antielastase activity • oxidants in cigarette smoke • oxygen free radicals secreted by neutrophils inhibit a1-AT.

12. AIR POLLUTION • The use of solid fuels for cooking and heating may result in high levels of indoor air pollution and the development of COPD • sulfur dioxide • nitrogen dioxide

13. OTHER FACTORS IN COPD • Airway hyperresponsiveness • Smokers with airway hyperresponsiveness are at increased risk of developing COPD with an accelerated decline in lung function • a1-antitrypsin deficiency • a1-antitrypsin deficiency is the only known genetic risk factor for developing COPD (panacinar emphysema) and accounts for less than 1% of all cases (a1-antitrypsin is a protease inhibitor produced by the liver that acts predominantly by inhibiting neutrophil elastase in the lungs)

14. Chronic Bronchitis • Bronchiectasis • Emphysema • Asthma

15. Chronic Bronchitis Chronic bronchitis is four to ten times more common in heavy smokers irrespective of age, sex, and occupation. When persistent for years, it may • (1) lead to cor pulmonale and heart failure, • (2) cause atypical metaplasia and dysplasia of the respiratory epithelium (cancerous transformation).

16. Clinical observations: Chronic bronchitis • Productive cough • Acute & Chronic inflammation of mucosa • Secondary Pulmonary Infections (Haemophilus influenzae and Streptococcus pneumoniae) • Inflammation retention infection obstructioninflammation.......(circulus viciosus). • Acute respiratory failure in patients with advanced chronic bronchitis

17. Pathology: Chronic bronchitis • Mucous gland enlargement is the histologic hallmark of chronic bronchitis • Increased ratio of mucous cells to serous ones • Excess mucus in airways • Increase in the number of goblet cells (hyperplasia) • Lack of cilia • Thickening of the bronchial wall • Mucous gland enlargement and edema (which leads to encroachment on the bronchial lumen) • Increased smooth muscle (which may indicate bronchial hyperreactivity) • Squamous metaplasia of the bronchial epithelium (epithelial damage from tobacco smoke)

18. Histology • Earliest features of chronic bronchitis are • hypersecretion of mucus in the large airways, • hypertrophy of the submucosal glands in the trachea and bronchi. • As chronic bronchitis persists, • marked increase in goblet cells of small airways (small bronchi and bronchioles) • excessive mucus production that contributes to airway obstruction.

19. Chronic Bronchitis: Histology

20. Bronchiectasis • Bronchiectasis is a chronic necrotizing infection of the bronchi and bronchioles leading to or associated with abnormal dilation of these airways. • It is manifested clinically by • cough, • fever, • the expectoration of copious amounts of foul-smelling, purulent sputum. • To be considered bronchiectasis, the dilation should be permanent; • reversible bronchial dilation often accompanies viral and bacterial pneumonia

21. Etiology: Bronchial obstruction Localized (to the obstructed lung segment): • tumor • foreign bodies • mucous impaction • Diffuse (obstructive airway diseases): • asthma • chronic bronchitis

22. Pathogenesis • Smoking irritation of mucosa • Mucus hypersecretion  Obstruction, Cough • Atelectasis • Metaplasia  loss of ciliated epithelium • Retention of secretion • Secondary infection • Recurrent Inflammation and Fibrosis • Destruction of bronchial wall • Dilated bronchus filled with pus

23. The dilatation ("-ectasis") results from • recurrent inflammations, and • contraction of scar surrounding the bronchus.

24. Gross Pathology • Generalized bronchiectasis is usually bilateral and is most common in the lower lobes • The left more commonly involved than the right • Bronchi are dilated and have white or yellow thickened walls • Bronchial lumens frequently contain thick, mucopurulent secretions

25. Gross Pathology On gross examination, bronchial dilation is saccular, cylindrical or varicose (they may produce cystic pattern): • Saccular bronchiectasis: bronchi are severely dilated and end blindly in dilated sacs, with collapse and fibrosis of the distal lung parenchyma. • Cylindrical bronchiectasisshows uniform, moderate dilation. • It is a milder disease than saccular bronchiectasis and leads to fewer clinical symptoms. • Varicose bronchiectasis: bronchi resemble varicose veins when visualized by radiologic bronchography, with irregular dilations and constrictions. • Bronchiolar obliteration is not as severe, and parenchymal abnormalities are variable.

26. Bronchiectasis

27. Bronchiectasis

28. Pleural adhesions

29. Microscopy • Severe inflammation of bronchi and bronchioles • Destruction of all components of the bronchial wall • Collapse of distal lung parenchyma, the damaged bronchi dilate • Hypersecretion of mucus • Abnormalities of the surface epithelium • squamous metaplasia • increased goblet cells • Lymphoid follicles are often seen in the bronchial walls • Scarred and often obliterated bronchi and bronchioles (distal ones) • The bronchial arteries increase in size to supply the inflamed bronchial wall and fibrous tissue

30. In the full-blown, active case: Intense acute and chronic inflammatory exudation within the walls of the bronchi and bronchioles, A vicious circle pool of mucus is liable to further infection, which leads to progressive destruction of the bronchial walls  more mucus  new infection ....... Desquamation of the lining epithelium and extensive areas of ulceration (necrosis), Pseudostratification of the columnar cells or squamous metaplasia of the remaining epithelium, Necrosis(destroys the bronchial or bronchiolar walls and forms a lung abscess), In chronic cases: Fibrosis of the bronchial and bronchiolar walls.

31. Bronchiectasis intense acute and chronic inflammatory exudation desquamation of the lining epithelium

32. Bronchiectasis Necrosis (destroys the bronchial or bronchiolar walls and forms a lung abscess).

33. Complications • amyloidosis • meningitis • brain abscesses • cor pulmonale • pneumonia • empyema • septicemia

34. Emphysema • Emphysema is a chronic lung disease characterized by enlargement of airspaces distal to the terminal bronchioles, with destruction of their walls but without fibrosis. • Loss of elasticity of the lung with some destruction of the alveoli. • 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. • Emphysema causes obstruction to air flow.

35. Classification of Emphysema • (1) Centrilobular(centriacinar) • (2) Panacinar (panlobular) • (3) Localised (paraseptal) • (4) Senile • Of these, the first two are the most important clinically

36. 1.Centrilobular emphysema • Most frequent • Usually associated with cigarette smoking (often in association with chronic bronchitis) • Destruction of the cluster of terminal bronchioles near the end of the bronchiolar tree in the central part of the pulmonary lobule • Dilated respiratory bronchioles form enlarged airspaces that are separated from each other and from the lobular septa by normal alveolar ducts and alveoli • Distal structures also may be involved • Bronchioles proximal to the emphysematous spaces are inflamed and narrowed • Centrilobular emphysema is most severe in the upper zones of the lung, the upper lobe, and the superior segment of the lower lobe

37. The walls of the emphysematous spaces often contain large amounts of black pigment. • Inflammation around bronchi and bronchioles and in the septa is common. • Focal dust emphysema, a disease of coal miners, resembles centrilobular emphysema but differs in that the enlarged spaces are smaller and more regular and inflammation of the bronchioles is not apparent.

38. Smokers lungNormal Lung

39. Smokers lung – Emphysema

40. Centrilobular Emphysema

41. Severe Centrilobular Emphysema

42. Microscopy

43. 2. Panacinar (Panlobular) Emphysema • The acinus is uniformly involved, with destruction of the alveolar septa from the center to the periphery of the acinus (entire alveolus distal to the terminal bronchiole) • In the final stage, panacinar emphysema leaves behind a lacy network of supporting tissue (cotton-candy lung) • This variant occurs in several situations

44. Diffuse panacinar emphysema is typically associated with a 1-AT deficiency [a congenital disease caused by a1-protease inhibitor ("antitrypsin") deficiency] • It is also often found in cigarette smokers in association with centrilobular emphysema • In such cases, the panacinar pattern tends to occur in the lower zones of the lung, whereas centrilobular emphysema is seen in the upper regions

45. Grossly, cut surface of the lung shows diffuse enlargement of airspaces in the affected parenchyma. • Often the enlarged spaces are traversed by delicate, spider-web-like strands representing the residual alveolar walls. • As in centrilobular emphysema, fibrosis is not seen.

46. Panacinar (Panlobular) Emphysema

47. 3. Localised (Paraseptal) Emphysema • Characterized by destruction of alveoli and resulting emphysema in only one or at most a few locations • The remainder of the lungs is normal • The lesion is usually found at the apex of an upper lobe, although it may occur anywhere in the pulmonary parenchyma, such as in a subpleural location. • Progression of localized emphysema can result in a large area of destruction, termed a bulla, which ranges in size from as small as 2 cm to a large lesion (Bullous Emphysema). • Although it is of no clinical significance itself, rupture of an area of localized emphysema produces spontaneous pneumothorax (sudden death).

48. Bullous Emphysema

49. Bullous Emphysema

50. 4. Senile emphysema • This form of emphysema is usually associated with "old age“ • It may occur anywhere in the pulmonary parenchyma