In alcoholic liver disease, which mechanism most directly explains the development of macrovesicular steatosis?

• A Direct toxic effect of acetaldehyde causing mitochondrial cristae dissolution
• B Upregulation of PPAR-alpha increasing fatty acid uptake into hepatocytes
• C Kupffer cell activation releasing TNF-alpha which inhibits VLDL secretion
• D Increased NADH:NAD+ ratio from alcohol oxidation inhibiting fatty acid oxidation and gluconeogenesis, promoting lipid accumulation ✓

Explanation

Alcohol metabolism by alcohol dehydrogenase and acetaldehyde dehydrogenase generates excess NADH, raising the NADH:NAD+ ratio. This elevated ratio inhibits beta-oxidation of fatty acids (requires NAD+) and gluconeogenesis, while promoting fatty acid synthesis and esterification. Excess fatty acids are esterified to triglycerides and accumulate as macrovesicular lipid droplets in hepatocytes.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.