Role of Toxins and Synergism in Hepatic Encephalopathy
The foremost hypothesis of pathogenesis of hepatic encephalopathy recognizes that in hepatic failure, toxins with coma-inducing potential accumulate and depress neuronal function by affecting fundamental neurophysiologic processes such as postsynaptic inhibition and excitation, and fundamental metabolic processes such as mitochondrial electron transfer and microsomal Na+, K+-ATPase activity. While accumulating, the toxins interact synergistically with each other and with various augmenting endogenous metabolic abnormalities to intensify their cellular effects. Specific toxins that both accumulate with hepatic failure and induce encephalopathy and coma in experimental animals are ammonia, methanethiol, fatty acids, and phenols (Figure 1). By interacting synergistically, they have neurological effects that are out of proportion to their individual abnormalities. Of these toxins, ammonia is the most important and has the most cumulative evidence for its role as an etiologic factor. However, the relative importance of each toxin may vary with the pathologic process.
KeywordsSulfide Phenol Arginine Glutamine Neurol
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