Wilson's disease (hepatolenticular degeneration) results from mutation in ATP7B encoding a copper-transporting ATPase. The principal pathological mechanism of copper toxicity in hepatocytes is:

• A Copper directly inhibits glucokinase, impairing glycogen synthesis
• B Copper competitively inhibits iron absorption, causing hemolytic anemia
• C Free copper generates reactive oxygen species via Fenton-like reactions, causing oxidative liver cell injury ✓
• D Copper activates complement cascade leading to immune-mediated hepatocyte destruction

Explanation

In Wilson's disease, defective biliary copper excretion leads to hepatic copper accumulation. Excess free copper (not bound to ceruloplasmin) generates hydroxyl radicals via Fenton-like reactions (Cu+ + H₂O₂ → Cu²+ + OH• + OH⁻), causing oxidative damage to lipids, proteins, and DNA. Hepatocyte injury progresses from steatohepatitis to cirrhosis. Copper also accumulates in brain basal ganglia (neuropsychiatric disease) and Descemet's membrane (Kayser-Fleischer rings).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.