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Pathogenesis

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Ethanol is broken down mainly by oxidation by alcohol dehydrogenase - ADH - resulting in the generation of H+ ions, an increase in the NADH:NAD ratio, and a resultant change in the redox state of the liver.

The net result is that H+ replaces fatty acids as a fuel with the generation of triglycerides and a fatty liver. The NADH:NAD redox changes inhibit the oxidation of fatty acids via the citric acid cycle so that they accumulate and contribute to the increased production of triglycerides.

Lipoprotein synthesis is also increased so that some of the accumulated triglycerides are transported into the circulation producing hyperlipidaemia.

Some of the H+ is used to convert pyruvate to lactate. Hyperlacticacidaemia leads to renal acidosis, uriacidaemia and gout. Reduction of pyruvate to glucose produces hypoglycaemia.

Some alcohol is also metabolised by a microsomal ethanol oxidising system - MEOS - which is inducible by MEOS. This is important:

  • in producing tolerance - more of the alcohol is metabolised via MEOS in chronic alcohol abuse
  • in the enhanced metabolism of drugs such as paracetamol and hormones such as testosterone - this contributes to the toxic effects of the former, and possibly, to infertility and feminisation in the latter

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