Hyperammonemia in Hepatic Encephalopathy

A. R. Jayakumar, Michael D Norenberg

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The precise mechanism underlying the neurotoxicity of Hepatic Encephalopathy (HE) is remains unclear. The dominant view has been that gut-derived nitrogenous toxins are not extracted by the diseased liver and thereby enter the brain. Among the various toxins proposed, the case for ammonia is most compelling. Events that lead to increased levels of blood or brain ammonia have been shown to worsen HE, whereas reducing blood ammonia levels alleviates HE. Clinical, pathological, and biochemical changes observed in HE can be reproduced by increasing blood or brain ammonia levels in experimental animals, while exposure of cultured astrocytes to ammonium salts reproduces the morphological and biochemical findings observed in HE. However, factors other than ammonia have recently been proposed to be involved in the development of HE, including cytokines and other blood and brain immune factors. Moreover, recent studies have questioned the critical role of ammonia in the pathogenesis of HE since blood ammonia levels do not always correlate with the level/severity of encephalopathy. This review summarizes the vital role of ammonia in the pathogenesis of HE in humans, as well as in experimental models of acute and chronic liver failure. It further emphasizes recent advances in the molecular mechanisms involved in the progression of neurological complications that occur in acute and chronic liver failure.

Original languageEnglish (US)
JournalJournal of Clinical and Experimental Hepatology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Hyperammonemia
Hepatic Encephalopathy
Ammonia
End Stage Liver Disease
Acute Liver Failure
Brain
Immunologic Factors
Brain Diseases
Ammonium Compounds
Astrocytes
Liver Diseases
Theoretical Models
Salts
Cytokines

Keywords

  • ammonia
  • hepatic encephalopathy
  • inflammation
  • matricellular proteins
  • TDP-43 and tau proteinopathies

ASJC Scopus subject areas

  • Hepatology

Cite this

Hyperammonemia in Hepatic Encephalopathy. / Jayakumar, A. R.; Norenberg, Michael D.

In: Journal of Clinical and Experimental Hepatology, 01.01.2018.

Research output: Contribution to journalArticle

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