Briefly describe the three major hypotheses that explain the impairment of neurotransmission involved with hepatic encephalopathy

Answer 1

Hepatic encephalopathy (HE) is a syndrome of impaired mental status and abnormal neuromuscular function that results from liver failure. The ammonia hypothesis states that liver disease interferes with ammonia detoxification and shifts ammonia metabolism to skeletal muscle, where it is used in the conversion of glutamate to glutamine. Ammonia levels increase in the blood and the brain because of muscle wasting. The ammonia is detoxified via the conversion of glutamate to glutamine; the depletion of glutamate and accumulation of glutamine in the brain contributes to hepatic encephalopathy. The synergistic neurotoxin hypothesis proposes that neurotoxins, many of which are produced by intestinal bacteria, are involved in hepatic encephalopathy. Hyperammonemia is thought to stimulate glucagon secretion and enhance gluconeogenesis from amino acids. The resulting hyperglycemia stimulates hyperinsulinemia, enhancing the uptake of branched-chain amino acids (BCAA) by muscle and lowering the plasma levels of BCAA relative to aromatic amino acids (AAA) that accumulate in the brain. The subsequent rise in tryptophan level leads to the formation of the inhibitory neurotransmitter serotonin, and the raised phenylalanine level leads to the inhibition of dihydroxyphenylalanine (DOPA) production and formation of so-called "false neurotransmitters.". The false neurotransmitter hypothesis suggests that these false transmitters may displace catecholamines from their receptors.