Bronchial Asthma

Bronchial Asthma

Episodic & reversible airway disease
Primarily targets the bronchi & its subdivisions & nonrespiratory bronchioles
Extrinsic Asthma
1. Pathogenesis
  1. Type 1 HSR with exposure to extrinsic allergen
  2. Initial sensitization to an inhaled allergen
    1. Stimulate induction of CD4 TH2 >> release IL-4 & IL-5
      1. IL4 stimulates isotype switching to IgE production
      2. IL 5 stimulates production and activation of eosinophils
  3. Inhaled Antigens cross link IgE antibodies on mast cells on mucosal surfaces
    1. Release of histamine & other performed mediators
    2. Function of Mediators : stimulate BRONCHOCONSTRICTION, Mucus Production, Influx of Leukocytes
  4. Late phase reaction ( 4-8 h)
    1. Eotaxin is produced
      1. Chemotactic and activator for eosinophils
    2. Eosinophils release major basic protein and cationic protein
      1. Damage epithelial cells and produce airway constriction
  5. Other mediators involved:
    1. (1) Leukotrienes LTC-D-E4 causes prolonged bronchoconstriction.
    2. (2) Acetylcholine causes airway muscle contraction.
  6. Histologic Changes in Bronchi
    1. (1) Thickening of the basement membrane
    2. (2) Edema and a mixed inflammatory infiltrate
    3. (3) Hypertrophy of submucosal glands
    4. (4) Hypertrophy/hyperplasia of smooth muscle cells
  7. Histologic Changes in Bronchioles
    1. (1) Formation of spiral-shaped mucus plugs
      1. (a) Contain shed epithelial cells called Curschmann spirals
      2. (b) Pathologic effect of MBP and cationic protein
    2. (2) Crystalline granules in eosinophils coalesce to form Charcot-Leyden crystals.
    3. (3) Patchy loss of epithelial cells, goblet cell metaplasia
    4. (4) Thick basement membrane
    5. (5) Smooth muscle cell hypertrophy and hyperplasia
2. Clinical Findings
  1. Episodic expiratory wheezing
  2. Nocturnal cough
  3. Increased anteroposterior diameter << air trapping & increased residual volume
3. Lab Findings:
  1. Initially develop respiratory alkalosis; normal pH or respiratory acidosis indicates need for intubation
  2. FEV1 is best measure of severity
  3. Eosinophilia, positive skin tests for allergens
Intrinsic Asthma
1. Nonimmune
2. Causes
  1. Virus induced respiratory infection ex. rhinovirus, parainfluenza, respiratory syncytial viruses
  2. Air Pollutant
  3. Aspirin or NSAID sensitivity
    1. COX inhibition leaves lipoxygenase pathway open for productionn of leukotrienes
  4. Stress, exercise, cigarette smoke

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	Created by Farah Mansour about 8 years ago