Hepatic encephalopathy, ammonia, glutamate, glutamine and oxidative stress.
This review addresses recent and not so recent works that emphasize on the mechanisms by which liver damage can induce encephalopathy. Hepatic encephalopathy constitutes an intriguing complication in severe liver acute and chronic disease, whose pathophysiology is still not completely understood. In this pathology, alterations in normal brain function are associated with morphological and functional impairments of astrocytes and neurons. A wide spectrum of psychoneurological symptoms has been described and the anatomical substratum is usually associated with brain edema and intracranial hypertension, as well as with changes in the function of brain cells. An increase in blood ammonia, toxic to the brain, depends on the activity of the enzyme glutamine synthetase, the glutamine/glutamate cycle and the brain capacity to eliminate toxic substances. When the concentration of the excitotoxic neurotransmitter glutamate is increased, it acts as a toxic agent, especially when its specific transporters are altered and its uptake is decreased. Glutamine has also been recently considered a toxic substance when its concentration is high, and consequently contributes to brain edema. Finally, the formation of reactive oxygen species, basically produced by mitochondria, influence with their toxic action on membrane lipids, proteins and DNA. In conclusion we suggest that at least these four elements are involved directly in the mechanism of hepatic encephalopathy.
Lemberg
Abraham
A
Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina. allef2002@yahoo.com
Fernández
Maria Alejandra
MA
D000641:Ammonia / Q000097:blood*; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress
D005973:Glutamine; D018698:Glutamic Acid; D000641:Ammonia