What is the ammonia hypothesis of encephalopathy pathogenesis in cirrhosis?

Updated: Jul 30, 2018
  • Author: David C Wolf, MD, FACP, FACG, AGAF, FAASLD; Chief Editor: BS Anand, MD  more...
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Ammonia is produced in the GI tract by bacterial degradation of amines, amino acids, purines, and urea. Normally, ammonia is detoxified in the liver by conversion to urea and glutamine. In liver disease or portosystemic shunting, portal blood ammonia is not converted efficiently to urea. Increased levels of ammonia may enter the systemic circulation because of portosystemic shunting.

Ammonia has multiple neurotoxic effects, including alteration of the transit of amino acids, water, and electrolytes across the neuronal membrane. Ammonia also can inhibit the generation of excitatory and inhibitory postsynaptic potentials. Therapeutic strategies to reduce serum ammonia levels tend to improve hepatic encephalopathy. However, approximately 10% of patients with significant encephalopathy have normal serum ammonia levels. Furthermore, many patients with cirrhosis have elevated ammonia levels without evidence of encephalopathy.

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