The pathogenesis of emphysema in alpha-1 antitrypsin (AAT) deficiency involves loss of protection against which protease, leading to alveolar wall destruction?

• A Neutrophil elastase ✓
• B Matrix metalloproteinase-9 (MMP-9)
• C Cathepsin G
• D Plasminogen activator

Explanation

Alpha-1 antitrypsin (AAT) is the primary inhibitor of neutrophil elastase in the lung. In AAT deficiency (PiZZ phenotype), uninhibited neutrophil elastase (a serine protease) degrades elastin and other extracellular matrix proteins in alveolar walls, causing panacinar emphysema predominantly in the lower lobes. This protease-antiprotease imbalance is the central mechanism; smoking worsens it by both recruiting more neutrophils and oxidatively inactivating residual AAT.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.