A 45-year-old male smoker with severe early-onset emphysema is found to have a serum alpha-1 antitrypsin (AAT) level of 20 mg/dL (normal >100 mg/dL) and a Pi*ZZ genotype. The mechanism of emphysema in AAT deficiency is:
- A Oxidative inactivation of alveolar macrophages by cigarette smoke compounds
- B Unopposed neutrophil elastase activity digesting alveolar walls due to absent serine protease inhibitor ✓
- C Excessive mucus production occluding small airways and trapping air distal to obstruction
- D AAT protein aggregation in hepatocytes causing inflammatory cytokine release that damages lung parenchyma
Explanation
Alpha-1 antitrypsin (AAT, SERPINA1) is the principal serine protease inhibitor protecting lung tissue from neutrophil elastase released during inflammation. In the Pi*ZZ genotype, misfolded Z-AAT protein aggregates within hepatocytes (causing liver disease) and insufficient functional AAT reaches the lung. Unopposed neutrophil elastase degrades elastin and collagen of alveolar walls, particularly in the lower lobes (panacinar emphysema pattern). Smoking exacerbates this by both recruiting neutrophils and directly oxidizing AAT's active methionine, reducing its inhibitory capacity. The protease-antiprotease imbalance is the central mechanism.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.