Abstract
Liver failure is usually associated with serious disturbances of consciousness. These episodes are accompanied by electroencephalographic changes of a diffuse sort with an increase in amount and amplitude of slower frequencies and a diminution of faster frequencies. Some investigators have reported what they considered to be characteristic neurologic signs(1) and electroencephalographic patterns (2-3) in liver disease, but these have not been observed uniformly(4). Observations of increased ammonia content of blood in liver failure(5-6), caused by inability of the liver to remove or “detoxify” ammonia from the portal blood because of shunt or deficiency of the urea synthesizing system have led to an hypothesis for the mechanism of ammonia-genie coma(7). The liver, however, does far more than detoxify substances. It has been pointed out recently that some metabolites essential to brain are probably synthesized in the liver and that liver failure may lead to serious deficiency of these substances(8). Among these may be the precursor material for serotonin, which appears to play a significant role in brain metabolism (9-11). Parenteral injection of moderate amounts of serotonin causes no change in the brain content of this intermediate, but administration of small amounts of a precursor substance, 5 hydroxytryptophane, (5HTP), does cause a large increase of serotonin in brain (12-13) together with symptoms similar to those seen after a block in serotonin metabolism in brain (14) caused by lysergic acid diethylamide. Although the synthesis of 5 HTP in liver preparations has not been demonstrated, other hydroxylations of a similar nature have occurred in that organ. Indirect evidence for failure of supply of the serotonin precursor comes from observations that urinary excretion of 5 hydroxyindole acetic acid, (5HIAA), a major terminal metabolite of serotonin, is diminished in liver disease(15).
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