Liver biopsy from a 30-year-old nonsmoker with progressive breathlessness and mild transaminase elevation shows periodic acid-Schiff positive, diastase-resistant eosinophilic globules within periportal hepatocytes. The underlying defect is:

• A Defective lysosomal degradation of glycoproteins in Kupffer cells
• B Accumulation of misfolded alpha-1 antitrypsin within hepatocyte endoplasmic reticulum ✓
• C Retention of copper-bound metallothionein in periseptal hepatocytes
• D Deposition of polymerized fibrinogen in the space of Disse

Explanation

The PiZZ variant of alpha-1 antitrypsin (Glu342Lys in SERPINA1) causes misfolding so the protein polymerizes and cannot exit the hepatocyte endoplasmic reticulum, forming PAS positive, diastase-resistant globules in periportal hepatocytes. Low circulating enzyme permits panacinar emphysema of the lower lobes. Copper accumulation occurs in Wilson disease but stains with rhodanine, not PAS.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.