Nicotinamide adenine dinucleotide (NAD) plays a key role in fatty acid oxidation and levels of NAD are decreased in the hepatocytes of alcoholics secondary to the metabolism of alcohol. Fat, therefore, accumulates and leads to alcoholic steatohepatitis.
One major route for alcohol (ethanol) metabolism is the alcohol dehydrogenase-mediated conversion of ethanol to acetaldehyde. In the reaction, NAD is reduced to NADH, therefore cytoplasmic levels of NAD decrease. Eventually, the acetaldehyde formed can be converted to acetic acid in the mitochondria by aldehyde dehydrogenase.
Woods et al. outline the presentation and treatment of alcoholic liver disease. Classically, patients present with anorexia, weight loss, fatigue, fever, leukocytosis, jaundice and tender hepatomegaly. A serologic workup may reveal leukocytosis or leukopenia, anemia, a prolonged prothrombin time and elevated liver enzymes. Treatment involves abstinence from alcohol, nutritional supplementation and corticosteroids.
Stickel and Seitz discuss severe alcoholic steatohepatitis and state that jaundice and signs of liver failure can form as a result of alcohol abuse. The diagnosis of alcoholic liver disease is established by elevated liver transaminases (though can be normal levels with chronic "burned out" liver disease), neutrophil counts, serum bilirubin, and impaired coagulation in light of a history of excessive alcohol consumption.
Image A displays a liver biopsy of steatohepatitis involving fat-filled hepatocytes. Illustration A depicts the metabolism of ethanol to acetaldehyde. Note the role of NAD. Illustration B depicts beta-oxidation of fats demonstrating the role of NAD.
Answer 1: The alcohol dehydrogenase reaction leads to a decrease, not increase, in cytoplasmic NAD levels.
Answer 3: The decrease in cytoplasmic NAD levels lead to a decrease, not increase, in fatty acid oxidation.
Answer 4: In alcoholic steatohepatitis, there is decreased synthesis/exportation of lipoproteins.
Answer 5: Increased fat uptake is not the main cause of fat accumulation in hepatocytes.
Stickel F, Seitz HK. Alcoholic steatohepatitis. Best Pract Res Clin Gastroenterol. 2010 Oct;24(5)
PMID:20955970 (Link to Abstract)
Woods SE, Hitchcock M, Meyer A. Alcoholic hepatitis. Am Fam Physician. 1993 Apr;47(5):1171-8.
PMID:8465712 (Link to Abstract)
USMLE World Step 1 QBank Question #370. Copyright © USMLEWorld, LLC 2012