astma 2006-en

By – Dr. SAMIA FATIMA

1. Eosinophils 2. Mast cells 3. T-lymphocytes 4. Neutrophils 5. Basophils

Acute inflammation

Chronic inflammation

Remodeling of airways

Symptoms of bronchoconstriction

Exacerbationnonspecific hyperreactivity

Ongoing obstruction of airways

Pathogenesis of asthma

1.Early phase Inhaled Antigen

Sensitised mast cells on the mucosal surface bronchoconstriction

Histamine bronchoconstriction, increased vascular permeability.

prostaglandin D 2 bronchoconstriction, vasodilatation.

Leucotriene C4,D4, E4 Increased vascular permeability, mucus secretion and bronchoconstriction.

Direct subepithelial parasympathetic stimulation bronchoconstriction.

2.Late phase starts 4 to 8 hours later Mast cell release additional cytokine Influx of leukocytes(neutrophil,eosinophil) Eosinophils are particularly important-

exert a variety of effect

MAST CELLS release histamine,cysteinyl-leukotrienes,cytokines,chemokines, growth factors and neutrophins

causes bronchoconstriction

MACROPHAGES AND DENDRITIC CELLs release cytokines,IL-10. dendritic cells are the antigen presenting cells

EOSINOPHILS release of basic proteins and oxygen derived free

radicals causes airway hyperresponsiveness

NEUTROPHILS increased numbers of activated neutrophils are found in sputum and airways of patients with severe asthma.

T Lymphocytes Th2 cells release IL-5 eosinophilic inflammation IL-4,13 increased IgE formation

PRIMARY MEDIATORS

1.Th2 cells > IL 4,5 > IgE production & Mast cell recruitment

2.Histamine - bronchconstriction by direct and cholinergic reflex actions

3.ECF and NCF

Secondary mediators LT C4, D4, and E4. prolonged bronchospasm increased vascular permeability increased mucus secretion. Prostaglandins (D2) Bronchospasm Vasodilation PAF platelet aggregation granule secretion.

i. Inflammatory cell infiltration of the airwaysii. Increased thickness of the bronchial

smooth muscleiii. Partial or full loss of the respiratory

epitheliumiv. Subepithelial fibrosisv. Hypertrophy and hyperplasia of the

submucosal glands and goblet cellsvi. Partial or full occlusion of the airway lumen

by mucous plugsvii. Enlarged mucous glands and blood vessels

Acute bronchoconstriction

Swelling of bronchial wall

Chronic production of mucous

Remodeling of airways walls