In alpha-1 antitrypsin deficiency, panacinar emphysema affecting the lower lobes develops because:

• A Reactive oxygen species from cigarette smoke directly oxidize alveolar epithelial cells
• B Complement-mediated lysis of pneumocytes via MAC deposition
• C IL-17-driven neutrophil recruitment causing alveolar flooding
• D Neutrophil elastase acts unopposed due to absent A1AT, degrading elastin and matrix proteins in the lung ✓

Explanation

A1AT is the main inhibitor of neutrophil elastase. In A1AT deficiency, elastase acts unopposed, degrading elastin and other matrix proteins, causing panacinar emphysema predominantly in lower lobes (greatest blood flow and neutrophil delivery). Cigarette smoke-related emphysema is predominantly centrilobular and upper-lobe; it works partly by oxidative inactivation of A1AT, but in A1AT deficiency the primary mechanism is absent inhibitor protein.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.