There are various explanations why liver dysfunction or portosystemic shunting might lead to encephalopathy. In healthy subjects,
nitrogen-containing compounds from the
intestine, generated by
gut bacteria from food, are transported by the
portal vein to the liver, where 80–90% are
metabolised through the
urea cycle and/or excreted immediately. This process is impaired in all subtypes of hepatic encephalopathy, either because the
hepatocytes (liver cells) are incapable of metabolising the waste products or because portal venous blood bypasses the liver through
collateral circulation or a medically constructed shunt. Nitrogenous waste products accumulate in the
systemic circulation (hence the older term "portosystemic encephalopathy"). The most important waste product is
ammonia (NH3). This small molecule crosses the
blood–brain barrier and is absorbed and metabolised by the
astrocytes, a population of cells in the brain that constitutes 30% of the
cerebral cortex. Astrocytes use ammonia when synthesising
glutamine from
glutamate. The increased levels of glutamine lead to an increase in osmotic pressure in the astrocytes, which become swollen. There is increased activity of the inhibitory
γ-aminobutyric acid (GABA) system, and the energy supply to other brain cells is decreased. This can be thought of as an example of brain edema of the "cytotoxic" type.
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