الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Hepatic encephalopathy is defined as a range of neurological and psychiatric disorders that complicates liver disease. Hepatic coma occurs secondary to diversion of portal blood into the systemic circulatory system through portosystemic collaterals. Hepatic encephalopathy is a disorder that results from neurotoxic substance accumulation in the brain such as ammonia and GABA.
Ammonia is produced in the gastrointestinal tract by bacterial action on amines, amino acids, purines, and urea. The Krebs-Henseleit cycle detoxifies ammonia in the liver by converting it to urea. Ammonia is also consumed in the conversion of glutamate to glutamine
Two factors contribute to the cirrhosis-related hyperammonemia. First, the mass of functioning hepatocytes is decreasing, resulting in fewer opportunities to detoxify ammonia through the above processes. Second, portosystemic shunting shifts blood containing ammonia from the liver to the systemic circulation.
It is believed that GABA and endogenous benzodiazepines may pass an extrapermeable blood-brain barrier. Binding of GABA and benzodiazepines to GABA’s supersensitive neuronal receptor complex enabled the influx of chloride ions into post-synaptic neurons, resulting in inhibitory postsynaptic potential. Ammonia, which rises in HE, has been shown to excite a glutamate-related neurotoxicity, which can in turn alter the system of receptors (GABA)A receptor
Endozepines are endogenous compounds that act on the benzodiazepine receptor (BZD) found in the central nervous system (CNS). Endozepines act as positive allosteric modulators of GABAA receptors and mimic pharmacological activity of exogenous benzodiazepines.
Endozepine-4, an endogenous ligand for the benzodiazepine detection site of the GABAA receptor, can play a significant role in HE pathogenesis and can be useful for monitoring patients with hepatic coma. Hyperammonemia is associated with increased GABA production through the neuronal cycle of tricarboxylic acid (indirect pathway).