Wilson disease (hepatolenticular degeneration) involves copper accumulation due to mutation in ATP7B. In the liver, excess copper primarily accumulates within which organelle BEFORE causing hepatocyte injury?

• A Nucleus (forming copper-binding metallothionein-nuclear complexes)
• B Mitochondria (causing mitochondrial swelling and impaired ATP synthesis)
• C Lysosomes (as lysosomal storage deposit) ✓
• D Endoplasmic reticulum (disrupting protein folding and causing ER stress)

Explanation

In Wilson disease, defective ATP7B fails to incorporate copper into ceruloplasmin and fails to excrete copper into bile. Excess hepatocellular copper is initially sequestered in lysosomes (as hepatic copper storage, detectable by rhodanine or orcein stains on liver biopsy). When lysosomal storage capacity is exceeded, free copper accumulates in the cytosol and nucleus, causing oxidative damage to mitochondria (characteristic mitochondrial pleomorphism on EM — most specific finding), lipid peroxidation, and eventually hepatocyte death, cirrhosis, and ultimately copper spillover to brain (basal ganglia), eyes (Kayser-Fleischer rings), kidneys, and RBCs (Coombs-negative hemolytic anemia).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.