1. Diseases of Respiratory System Lecture 2 Dr. Faten Ghazal Prof. of Pathology, Ain Shams University  Bronchial Asthma  Chronic Bronchitis  Bronchiectasis

2. How can we classify diffuse pulmonary diseases? 2 Broad Categories: 1.Obstructive (increased resistance to air flow due to partial or complete obstruction) 2.Restrictive (reduced expansion of lung parenchyma)

3. LUNG DISEASES Diffuse pulmonary diseases can be classified into 2 categories Obstructive Disease It is ch.ch. by increased resistance to airflow due to partial or complete obstruction. The major obstructive diseases after excluding tumors & inhalation of foreign body are: 1.Bronchial Asthma 1.Bronchial Asthma (anatomic airway narrowing) 2.Emphysema 2.Emphysema (loss of elastic recoil) 3.Chronic bronchitis (both 2&3 are called COPD) 4.Bronchiectasis 5.Cystitis fibrosis 6.Bronchiolitis Restrictive Disease It is ch.ch. by reduced expansion of lung parenchyma with decreased total lung capacity. The restrictive diseases occur in 2 conditions: acute chronic pneumoconiosis 1.Acute and chronic interstitial lung diseases e.g. acute respiratory distress syndrome and chronic diseases as pneumoconiosis, sarcoidosis & idiopathic pulmonary fibrosis. pleural diseases 2.Extra pulmonary disorders e.g. obesity, poliomyelitis, pleural diseases and kyphoscoliosis.

4. (objectives) By the end of this lecture you will be able to: (objectives)  Define bronchial asthma and differentiate between its extrinsic & intrinsic types.  Explain the of each type  Explain the pathogenesis of each type  Describe the bronchial asthma  Describe the pathological features of bronchial asthma  Define chronic bronchitis list.  Define chronic bronchitis and list its possible types.  Describe the pathologic features of chronic bronchitis.  Compare & contrast simple chronic bronchitis and extrinsic bronchial asthma.  Compare & contrast the pathologic features of simple chronic bronchitis and extrinsic bronchial asthma.  Define bronchiectasis and state its clinical manifestation.  List with bronchiectasis  List the most frequent conditions associated (predisposing factors) with bronchiectasis  Describe the pathologic characteristics of bronchiectasis.  Enumerate the of bronchiectasis  Enumerate the complications of bronchiectasis

5. Bronchial Asthma episodic paroxysmal reversible Asthma is chronic inflammatory disorder of airways (bronchi) characterized by episodic (occurring at irregular intervals), paroxysmal (sudden attacks) reversible bronchoconstriction (bronchospasm) resulting from hyper reactivity of the tracheo- bronchial tree to various stimuli. What is the type of disease ?What is the type of disease ? Which part of respiratory tract ?Which part of respiratory tract ? What are the characteristics of the disease?What are the characteristics of the disease? What is the cause of the disease?What is the cause of the disease?

6. Bronchial Asthma Clinically: it is characterized by attacks of: expiratory dyspnea, cough and wheezing (a soft whistling sound during expiration).

7. Are there different types for bronchial asthma? 1.Extrinsic Asthma 2.Intrinsic Asthma

8. Intrinsic Asthma: non immune mediated susceptible person 1.It is a non immune mediated disease triggered by a number of stimuli in a susceptible person e.g. respiratory tract infection, chemical irritant or drugs. adult life 2.Usually in adult life no 3.Usually no family history 4.Normal 4.Normal serum levels of IgE who has extrinsic asthma asthmatic attackexposed to factors implicated in intrinsic asthma. A person who has extrinsic asthma is also susceptible to develop asthmatic attack when exposed to factors implicated in intrinsic asthma. Bronchial Asthma Extrinsic Asthma: type I IgE mediated hypersensitivity 1.Typically initiated by type I IgE mediated hypersensitivity reaction on exposure to an extrinsic antigen. first 2 decades 2.Starts in the first 2 decades of life 3.Family history Serum levelIgE eosinophils 4. Serum level of IgE & eosinophils

9. Exaggerated bronchoconstrictor response to various stimuli (Airway Hyper responsiveness) The basis for this hyperreactivity is persistent chronic bronchial inflammation What causes the bronchial inflammation? Bronchial Asthma Aetiology

10. Explain the pathogenesis for each type of bronchial asthma; the extrinsic and the intrinsic type

11. Second Exposure to Antigen Primary Exposure to Antigen T-helper activation Mast cells IgE forming B cellsEosinophils YYY Y YYY Y Mediators Increased vascular permeabilityIncreased vascular permeability BronchospasmBronchospasm +Mucus production+Mucus production Recruit other inflammatory cellsRecruit other inflammatory cells Early phase within30-60min. Mediators Epithelial damageEpithelial damage Exaggeration of the initial responseExaggeration of the initial response Recruit other inflammatory cells including neutrophilsRecruit other inflammatory cells including neutrophils Late phase 4-8 hours later Pathogenesis of Extrinsic Asthma Type I Hypersensitivity Reaction

12. It lowers the threshold of subepithelial vagal receptors stimulation to irritants & damaged epithelial cells also liberate chemical mediators Activation of antigen specific T cells & liberation of mediators that promotes eosinophilic infiltration Pathogenesis of Intrinsic Asthma Viral Infection of respiratory tract Inhaled air pollutants as SO2,ozone,NO2, or drugs both normalasthmatic Hyper reactivity of both normal & asthmatic subjects Bronchial Spasm asthmatics Bronchial Spasm which is much more severe & sustained in asthmatics (susceptible ones) Initiating stimuli

13. Thus, the eosinophil has emerged as a key player in both subtypes of bronchial asthma Bronchial Asthma Recent studies have demonstrated that there is a considerable overlap in their pathogenesis but still the basic mechanism of susceptibility remains largely unknown.

14. Describe the Pathological Features of Bronchial Asthma

15. Hypertrophy & hyperplasia of smooth muscle layer Thick mucus plug thick tenacious mucus plugs. over distended The most striking gross finding is occlusion of bronchi and bronchioles by thick tenacious mucus plugs. During the attacks, the lungs are over distended because of over inflation. Small areas of collapse (atelectasis) may be seen. Pathological Features of Bronchial Asthma

16. In bronchial asthma the hypertrophied & hyperplastic smooth muscle layer contracts (bronchospasm) with increased mucus secretion resulting in narrowing of the bronchial lumen.

17. Bronchial Asthma Thick mucus plug occluding the bronchi

18. Bronchial Asthma Cast of bronchial tree formed of inspissated mucus

19. Normal Bronchus

20. Normal Bronchiole

21. Mucus plug collagen Smooth muscle (++) Mucous glands (++) in submucosa Bronchus in Bronchial Asthma

22. Bronchial Asthma Mast cells, eosinophils & collagen

23. Microscopic: Patchy necrosismucus plug(MP)Patchy necrosis of the epithelial cells, mucus plug in the lumen (MP) increased collagenThere is increased collagen immediately beneath the basement membrane. oedema,hyperaemia dense inflammatory infiltrate eosinophils.There is oedema, hyperaemia & dense inflammatory infiltrate (mast cells, basophils, M, L) in the mucosa and submucosa with prominent eosinophils. Hyperplasia hypertrophy (SM) Hyperplasia & hypertrophy of the smooth muscles (SM) submucosal mucous glandshyperplastic (MG)The submucosal mucous glands are hyperplastic (MG) (SM) (MG) (MP) Bronchial Asthma Patchy necrosis& hyperplasia of epithelium collagen

24. Clinical Course of Bronchial Asthma: Severe dyspnea, wheeze then coughSevere dyspnea, wheeze then cough Difficulty in air entrance then more difficulty in getting air outDifficulty in air entrance then more difficulty in getting air out Progressive hyperinflation of the lungs (trapped air distal to constricted bronchi that are full of mucus)Progressive hyperinflation of the lungs (trapped air distal to constricted bronchi that are full of mucus) It lasts for 1 hour or more which is relieved spontaneously or by bronchodilators & corticosteroids

25. Chronic Bronchitis

26. How can we define chronic bronchitis? Persistent productive cough for at least 3 consecutive months in at least 2 consecutive years. 3m x 2y Persistent productive cough (production of sputum) for at least 3 consecutive months in at least 2 consecutive years. 3m x 2y

27. Chronic bronchitis can occur in several forms: 1.Simple chronic bronchitis no obstruction 1.Simple chronic bronchitis: Productive cough but no obstruction 2.Chronic mucopurulent bronchitis secondary infection 2.Chronic mucopurulent bronchitis: mucopurulent sputum due to secondary infection 3.Chronic asthmatic bronchitis bronchial asthma 3.Chronic asthmatic bronchitis: Chronic bronchitis associated with bronchial asthma 4.Chronic obstructive bronchitis evidence of associated emphysema. 4.Chronic obstructive bronchitis: chronic bronchitis with evidence of associated emphysema.

28. Explain the pathogenesis of chronic bronchitis

29. Pathogenesis of Chronic Bronchitis Continuous exposure to irritants as smoking or air pollutants Chronic airway obstruction Irritation Irritation of both large and small bronchi Hypertrophy & hyperplasia of mucous glands Metaplastic formation of goblet cells in surface epithelium Inflammation and fibrosis in bronchial wall Mucous hyper-secretion Narrowing of bronchi & bronchioles

30. Chronic Bronchitis Chronic nonspecific inflammatory cell infiltration

31. Chronic Bronchitis Mucous glands Microscopically: The diagnostic feature of chronic bronchitis is: Hyperplasia of mucous glands Reid index (n=0.4)