Pathogenesis of asthma

1. Pathogenesis Of
Bronchial Asthma

2. Pathology
Mucosa-Activated Eosinophils, T lymphocytes, mast
cells.
Thickening Basement membrane-Subepithelial
collagen deposition.
Lumen has
1. Epithelial cells(Desquamation).
2.Mucous plug(Mucous glycoproteins-Goblet cells;
Plasma proteins- leaky bronchial vessels).
Vasodilation, blood vessels.
Narrowed, erythematous and edematous.

3. Airway
Inflammation
Airway
Hyperresponsiveness
Airway Remodelling

4. Cells
Mast Cells-Initiation. Sensitivity by binding specific IgE.
Macrophage-Activated by IgE.
Dendritic cells-Major Antigen Presenting Cells.
Eosinophils-Characteristic of Asthma. Basic Proteins and
ROS AHR. Growth Factors Remodelling and
exacerbations.
Neutrophils-Severe Asthma and during exacerbations.
T lymphocytes-Recruitment and survival of Eosinophils.
Maintenance of Mast cells. TH2 predominant. IL-5, IL-4 and
IL-13.
Structural cells-Epithelial cells(TSLP, IL-25 & IL-33),
Fibroblasts and Airway smooth muscle cells.

5. • Leukotrienes C4, D4, E4.
• Acetyl Choline.Proved
• Histamine.
• Prostaglandin D2.
• Platelet-Activating Factor.
Minor
• Chemokines(Eotaxin, CCL17, CCL22).
• Reactive oxygen species.
• Nitric Oxide.
• Transcription Factors(NF-kB, activator protein-1,
GATA-3 and nuclear factor of activated T cells).
Suspects
“Mediator Soup”

7. Effects Of Inflammation
 Airway Epithelium-Loss of Barrier, Enzymes & Relaxant Factor; exposed
Sensory Nerves.
 Fibrosis-Basement Membrane Thickening Sub epithelial Type 3 & 5
collagen deposition. TGF-β. Severe patients within airway wall.
 Airway Smooth Muscle- Responsiveness to constriction. Response to β
agonist. PDGF/Endothelin-1 Hypertrophy and Hyperplasia.
 Vascular Response- Mucosal blood flow. Angiogenesis(VEGF).
Microvascular leak.
 Mucous Hypersecretion-IL-13. Hyperplasia of Submucosal glands and
Goblet cells.
 Neural Regulation-Neurotrophins. Substance P. Hyperalgesia. Reflex
cholinergic contraction.
 Airway Remodelling.
 Airway Hyperresponsiveness-Excessive Bronchoconstriction. Direct and
Indirect.

8. Summary

9. References
Harrison’s Principles of Internal Medicine, 19E.
Robbins & Cotran Pathologic Basis Of Disease, 9E.

10. Thank You