In alpha-1-antitrypsin deficiency causing emphysema, the pathogenic mechanism is primarily:

• A Uninhibited neutrophil elastase degrading alveolar walls predominantly in the upper lobes
• B Macrophage-derived matrix metalloproteinase 9 acting unopposed in centriacinar distribution
• C Uninhibited neutrophil elastase degrading alveolar wall collagen and elastin in the lower lobes ✓
• D Mucus plugging of small airways causing air trapping and alveolar wall destruction

Explanation

Alpha-1-antitrypsin (A1AT) is the principal serum inhibitor of neutrophil elastase. In A1AT deficiency, unopposed elastase (and other serine proteases) from neutrophils and macrophages in the lower lung fields (where blood flow is greatest) progressively destroys alveolar walls, producing panacinar emphysema predominating in the lower lobes. This contrasts with smoking-related centriacinar emphysema, which predominates in upper lobes from macrophage protease activity at alveolar duct-acinar junctions. Mucus plugging is the mechanism of chronic bronchitis, not emphysema.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.