Effects of Alcohol on Liver Function

Central to the effects of ethanol is the liver, in which 60-90% of ethanol metabolism occurs. Ethanol displaces many of the substrates usually metabolized in the liver. Metabolism of ethanol by ADH in the liver generates reducing equivalents. ALDH also generates NADH with conversion of acetaldehyde to acetate. The NADH/NAD+ ratio is increased, with a corresponding increase in the lactate/pyruvate ratio. If lactic acidosis combines with a /3-hydroxy-butyrate predominant ketoacidosis, the blood pH can fall to 7.1 and hypoglycemia may occur. Severe ketoacidosis and hypoglycemia can cause permanent brain damage. However, in general the prognosis of alcohol-induced acidosis is good. Lactic acid also reduces the renal capacity for urate excretion. Hyperuricemia is exacerbated by alcohol-induced ketosis and acetate-mediated purine generation. Hyperuricemia explains, at least in part, the clinical observation that alcohol misuse can precipitate gout.

The excess NADH promotes fatty acid synthesis and inhibits lipid oxidation in the mitochondria, resulting in fat accumulation. Fatty changes are usually asymptomatic but can be seen on ultrasound or computed tomography scanning, and they are associated with abnormal liver toxicity tests (e.g., raised activities of serum 7-glutamyl transferase, aspartate aminotransferase, and alanine transaminases).

Progression to alcoholic hepatitis involves invasion of the liver by neutrophils with hepatocyte necrosis. Giant mitochondria are visible and dense cytoplasmic lesions (Mallory bodies) are seen. Alcoholic hepatitis can be asymptomatic but usually presents with abdominal pain, fever, and jaundice, or, depending on the severity of disease, patients may have encephalopathy, ascites, and ankle oedema.

Continued alcohol consumption may lead to cirrhosis. However, not all alcoholics progress to cirrhosis. The reason for this is unclear. It has been suggested that genetic factors and differences in immune response may play a role.

In alcoholic cirrhosis there is fibrocollagenous deposition, with scarring and disruption of surrounding hepatic architecture. There is ongoing necrosis with concurrent regeneration. Alcoholic cirrhosis is classically said to be micronodular, but often a mixed pattern is present. The underlying pathological mechanisms are complex and are the subject of debate. Induction of the MEOS and oxidation of ethanol by catalase result in free radical production. Glutathione (a free radical scavenger) is reduced in alcoholics, impairing the ability to dispose of free radicals. Mitochondrial damage occurs, limiting their capacity to oxidize fatty acids. Peroxisomal oxidation of fatty acids further increases free radical production. These changes eventually result in hepatocyte necrosis, and inflammation and fibrosis ensue. Acetaldehyde also contributes by promoting collagen synthesis and fibrosis.

Alcohol No More

Alcohol No More

Do you love a drink from time to time? A lot of us do, often when socializing with acquaintances and loved ones. Drinking may be beneficial or harmful, depending upon your age and health status, and, naturally, how much you drink.

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