Chronic alcohol consumption profoundly affects the function of several vital organs—particularly the liver—and the nervous, gastrointestinal, cardiovascular, and immune systems. Since ethanol has low potency, it requires concentrations thousands of times higher than other misused drugs (eg, cocaine, opiates, amphetamines) to produce its intoxicating effects. As a result, ethanol is consumed in quantities that are unusually large for a pharmacologically active drug. The tissue damage caused by chronic alcohol ingestion results from a combination of the direct effects of ethanol and acetaldehyde, and the metabolic consequences of processing a heavy load of a metabolically active substance. Specific mechanisms implicated in tissue damage include increased oxidative stress coupled with depletion of glutathione, damage to mitochondria, growth factor dysregulation, and potentiation of cytokine-induced injury.
Chronic consumption of large amounts of alcohol is associated with an increased risk of death. Deaths linked to alcohol consumption are caused by liver disease, cancer, accidents, and suicide.
A. Liver and Gastrointestinal Tract
Liver disease is the most common medical complication of alcohol abuse; an estimated 15–30% of chronic heavy drinkers eventually develop severe liver disease. Alcoholic fatty liver, a reversible condition, may progress to alcoholic hepatitis and finally to cirrhosis and liver failure. In the United States, chronic alcohol abuse is the leading cause of liver cirrhosis and of the need for liver transplantation. The risk of developing liver disease is related both to the average amount of daily consumption and to the duration of alcohol abuse. Women appear to be more susceptible to alcohol hepatotoxicity than men. Concurrent infection with hepatitis B or C virus increases the risk of severe liver disease. Cirrhosis contributes to elevated portal blood pressure and esophageal and gastric venous varices. These varices may rupture and result in massive bleeding.
What Can Drunken Worms, Flies, and Mice Tell Us about Alcohol?