What causes hepatic encephalopathy (HE)?
This complication may occur with hepatic failure or with portal or hepatic circulatory dysfunction, as caused by acute or chronic hepatitis, hepatic necrosis, cirrhosis, or portocaval anastomosis.
There are multiple theories about the pathogenesis of HE.
Ammonia is thought to play an important role in the pathogenesis of HE. Patients with HE have been shown to have increased diffusion of ammonia through the blood–brain barrier. In the brain, cytoplasmic enzymes in the astrocyte medicate ammonia detoxification.
Overloading of this system with excess ammonia generates free radicals in the mitochondria, causing cellular swelling and astrocytic dysfunction.
Another important potential factor are nonpharmacologic ligands interacting with the gamma-aminobutyric acid (GABA) receptor. These ligands are normally occurring substances proposed to accumulate in brain tissue in HE.
In addition, ammonia also plays a role in the affinity of GABA receptors to GABA itself.
Reduction in the serum concentration of ammonia, or addition of centrally acting GABA antagonists, may temporarily improve hepatic encephalopathy, although correction of the precipitating causes of hepatic dysfunction is necessary for ultimate recovery.