asthma-pathogenesis

asthma-pathogenesis

Asthma: Pathogenesis
Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Ciara Hanly Yonglin Mai (􏰁􏰃􏰄) Naushad Hirani* * MD at time of publication
Genetic factors
(i.e. HLA gene mutations, defects in bronchial airway epithelium)
Environmental factors
(i.e. excess hygiene, fewer siblings, antibiotics within the first two years)
Asthma:
Defined as airway hyper-responsiveness causing variable and reversible airflow obstruction
Atopy:
predisposition to allergic hyper-sensitivity in airways
First exposure to triggers*
sensitizes helper T cells
Stimulation of B-cells to produce IgE, which binds to mast cell surfaces
Activated Helper-T cells & IgE-sensitized mast cells now line the airways
Triggers of airway hyper- responsiveness include:
Upper respiratory tract infections (URTIs)
Allergens (pollen, animal dander, dust, mold, etc)
Air pollution, cigarette smoke, other chemicals
Drugs (aspirin, NSAIDs, Beta- blockers)
Cold air
Exercise
Early response (0-2 hrs)
Delayed response (3-4 hrs)
Allergens cross-link IgEs on mast cells
Activated mast cells & helper T cells release cytokines
Mast cells release histamines, leukotrienes, and other inflammatory mediators
Induce maturation of granular WBCs like eosinophils
Eosinophils migrate into:
Vascular permeabilityà edema of airway mucosa
Goblet cell hyperplasia à­ mucus secretion
Bronchial smooth muscle contraction
Airway obstruction
Second exposure to triggers
Asthma Airways Bronchiole constriction
Eyes Conjunctivitis Nose Rhinitis
Note: Delayed response presents within 3-4 hrs, peaks within 6-8 hrs, and resolves within 24 hrs
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published Dec 17, 2012, updated Aug 19, 2021 on www.thecalgaryguide.com