A 65-year-old lifelong smoker undergoes pulmonary function testing showing an FEV1/FVC ratio of 0.58, irreversible after bronchodilator. CT scan reveals hyperinflation and enlarged air spaces distal to the terminal bronchiole with destruction of alveolar walls but no fibrosis. The primary enzymatic mechanism underlying this lesion is:

• A Increased elastase activity relative to alpha-1 antitrypsin ✓
• B Excessive collagen deposition by fibroblasts
• C Hypersensitivity reaction causing eosinophilic infiltration
• D Mucus gland hypertrophy with airway obstruction

Explanation

Emphysema results from an imbalance between proteases and antiproteases, where neutrophil elastase and matrix metalloproteinases released by macrophages and neutrophils (recruited by cigarette smoke) overwhelm the protective alpha-1 antitrypsin. This leads to permanent destruction of alveolar walls, enlargement of air spaces, and loss of elastic recoil. The obstruction is irreversible, differentiating it from asthma where remodeling is partially reversible.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.