Alcohol Metabolism and Effects on the Liver

Alcohol Review

• Absorption is passive diffusion, following a concentration gradient.
• Distribution is proportional to water content in tissues.
• Metabolism: 90-98% oxidation in the liver.
• Excretion: small amounts in breath and urine.
• Alcohol metabolism is zero-order kinetics due to limited liver capacity to convert NADH to NAD+.
• Two inhibitors of alcohol metabolism are fomepizole and disulfiram, with specific mechanisms of action and clinical uses.
• Heavy alcohol use can cause hypoglycemia, ketonemia, lactic acidosis, and hyperuricemia.
• Alcohol's effects on the central nervous system (CNS) are characterized by depression, reduced anxiety, and disinhibition, with disturbed balance between excitatory and inhibitory influences.

Alcohol's Effects on the Liver

• Initial effect is reversible fat deposition in hepatocytes.
• Prolonged exposure can lead to hepatic steatosis (fatty liver), alcoholic hepatitis, and cirrhosis (irreversible).
• Cirrhosis is characterized by fibrosis, liver dysfunction, and impaired circulation.
• Women are more susceptible to liver damage.

Alcohol Impact on Other Systems

• Gastrointestinal tract: can cause acute and chronic gastritis.
• Hematopoietic system: anemia, thrombocytopenia, immune depression possible.
• Cardiovascular system: cardiomyopathy, hypertension, hypothermia.
• Facial features (FAS): individuals with FAS often have facial abnormalities and growth deficits, alongside central nervous system abnormalities.

Gender Differences in Alcohol Metabolism

• Women are more vulnerable than men to alcohol's effects.
• Women achieve higher blood alcohol concentrations due to factors like lower gastric ADH (alcohol dehydrogenase) and a smaller volume of distribution, leading to faster development of alcohol-related liver diseases.

Alcohol Use Disorder (AUD)

• A major substance use disorder, characterized by behavioral and physical symptoms (withdrawal, tolerance, craving).
• Average onset age is 21, with 14% of adults currently affected and 29% over a lifetime.
• Associated with a threefold increase in early mortality. 30% of adults are considered at-risk drinkers.
• Management often includes benzodiazepines for withdrawal, disulfiram, naltrexone, and acamprosate for relapse prevention.

Pharmacodynamic Interactions

• Alcohol interacts with warfarin and acetaminophen through CYP2E1 modulation.
• Acute alcohol exposure inhibits CYP2E1, amplifying warfarin's anticoagulant effect.
• Chronic alcohol use induces CYP2E1, reducing warfarin's action.
• For acetaminophen, alcohol's metabolism via CYP2E1 increases production of hepatotoxic metabolite NAPQI; chronic use exacerbates damage, and acute exposure may increase toxicity.

Explore the intricate processes of alcohol absorption, distribution, metabolism, and excretion. This quiz delves into the effects of alcohol on the liver, detailing the consequences of prolonged exposure and the mechanisms of inhibitors that affect metabolism. Test your knowledge on how alcohol impacts both liver function and the central nervous system.