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Flow chart for pathophysiology for asthma

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Pathophysiology of Asthma Flowchart
Here is the flowchart, and below is a structured walkthrough of each step:

Pathophysiology of Asthma

1. Triggers

Allergens, exercise, stress, respiratory infections, cold air, pollutants (diesel fumes, ozone, nitrates).

2. Sensitization Phase

  • Antigen presented by dendritic cells → Th2 cell activation
  • Th2 cells release IL-4, IL-5, IL-13
  • B-cells stimulated → IgE synthesis
  • IgE binds to mast cells and basophils (sensitization complete)

3. Early Phase Reaction (0–30 min)

Re-exposure to antigen → IgE-mediated mast cell degranulation:
  • Preformed mediators: Histamine, chemotactic factors, heparin, proteolytic enzymes
  • Secondary mediators: Leukotrienes (LTC4, LTD4), prostaglandins, PAF
Immediate effects:
  • Smooth muscle bronchoconstriction
  • Mucus hypersecretion
  • ↑ Vascular permeability → mucosal edema

4. Late Phase Reaction (2–8 hrs)

Recruitment of inflammatory cells:
  • Eosinophils, neutrophils, mononuclear cells, basophils
These release:
  • Cytokines: IL-3 to IL-6, TNF-α, IFN-γ
  • Arachidonic acid metabolites
  • Major basic protein (MBP) from eosinophils → epithelial damage
  • Activation of epithelial and endothelial cells amplifying the response

5. Three Mechanisms of Airflow Obstruction

MechanismCause
BronchoconstrictionSmooth muscle contraction
Mucosal edemaVascular leak + inflammatory infiltrate
Mucus plug formationGoblet cell hypersecretion

6. Airway Hyperresponsiveness

  • Chronic inflammation lowers the threshold for bronchoconstriction
  • Even mild stimuli trigger exaggerated responses

7. Chronic Inflammation → Airway Remodeling (if untreated)

  • Goblet cell hyperplasia
  • Smooth muscle hypertrophy
  • Subepithelial fibrosis
  • Basement membrane thickening
  • Angiogenesis
  • Leads to irreversible airflow limitation

8. Clinical Manifestations

  • Wheezing, dyspnea, chest tightness, cough
  • ↓ FEV₁, ↓ FEV₁/FVC ratio (< 0.75 in adults)
  • Reversible with bronchodilators (unlike COPD)
Reference diagram from textbook (normal vs. asthmatic bronchus):
Normal vs Asthmatic Bronchus
Sources: Lippincott Illustrated Reviews: Pharmacology; Swanson's Family Medicine Review
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