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asthma-pathogenesis-230531144001-56d3d3c9.pptx
- 1. Asthma - Pathogenesis Dr.MDRAIHAN MD(PATHOLOGY)
- 2. What is Asthma? •Heterogenous disease • Chronic airway inflammation • Expiratory airflow obstruction • Symptoms • Wheezing • Shortness of breath • Chest tightness • cough
- 3. Major subtypes • AtopicAsthma •Type 1 hypersensitivity • Childhood • Environmental allergens • Positive family history • High total serum IgE levels • Serum radioallergosorbent tests • NonAtopic asthma • No evidence of sensitization • Less common family history • Associated with • Viral respiratory infections • Air pollutants • Cold
- 4. Major subtypes • Occupationalasthma • Fumes • Dusts • Chemicals • Even minute quantities are sufficient • Repeated exposure • Drug – Induced asthma • Aspirin sensitive asthma • NSAIDs • Associated with utricaria Inhibition of COX Arachidonic acid not metobolised Less Prostaglandin E2
- 5. Pathogenesis • Th2 responses,IgE and Inflammation • Genetic susceptibility • Environmental factors
- 6. Th2 responses, IgEand Inflammation Th2 cells IL -4 Ig E production IL – 5 Eosinophil recruitment IL – 13 Endobronchial Secretions Th 17 IL – 17 Neutrophil recruitment
- 7.
- 8. Early Phase Bronchoconstriction Increased mucusproduction Vasodilation Vascular permeability
- 9. Late Phase Recruitment ofLeucocytes - Eosinophils - Neutrophils - More T cells
- 10. Mediators Definite Leucotrienes C4, D4 &E4 Acetylcholi ne IL -5 Galectin 10 Minor role Histamine Prostagland in D2 PAF Others IL – 4 IL – 13 TNF
- 11. Genetic susceptibility • Chromosome5q • Gene cluster encoding for IL3, IL4, IL5, IL9, IL13 & IL4 receptor • Class II HLAalleles • Genes encoding • IL33 • Thymic stromal lymphoprotein
- 12.
- 13. Exaggerated response Airway Inflammation AirwayDysfunction Airway remodelling
- 14. Normal vs AsthmaticAirway
- 15. Gross • Hyperinflated lungs •Occlusion of bronchi by thick, tenacious mucus plugs
- 16. Microscopy • Airway wallthickening • Eosinophilic inflammation • Goblet cell hyperplasia • Muscle hypertrophy • Sub basement membrane fibrosis • Increased vascularity • Increased size of submucosal glands
- 17. BAL Wash findings Curschmannspirals Charcot leyden crystals
- 18. References • Robbins andCotran pathologic basis of disease • Autopsy pathology –Amanual and atlas,Andrew J. Connolly • Comprehensive Cytology, Marluce Bibbo