Document Detail


Mechanisms of hyperammonemia.
MedLine Citation:
PMID:  12241009     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hyperammonemia is mainly found in hepatic encephalopathy and in genetic defects of the urea cycle or other pathways of the intermediary metabolism. Clinically a difference has to be made between chronic moderate hyperammonemia and acutely increased concentrations. Pathogenetic mechanisms of ammonia toxicity to the brain are partly unraveled. In some animal models confounding variables, such as the reduced intake of food and amino acid imbalance due to liver insufficiency, do not allow to establish unequivocal causal relationships between the ammonia concentration and measured effects. In chronic moderate hyperammonemia an increased flux through the serotonin pathway is a key factor. It is caused by an increased transport of large neutral amino acids (including tryptophan) through the blood-brain barrier, accentuated by the imbalance of plasma amino acids in hepatic insufficiency. It is stimulated by D- or L-glutamine. Evidence is presented showing that a functioning gamma-glutamyl cycle (glutathione formation) is a prerequisite. In acute hyperammonemia involvement of NMDA receptors, glutamate, NO and cGMP plays an additional role. In hyperammonemic crises the increased cerebral blood flow leads to brain edema; factors discussed here are increased osmolytes in astrocytes and serotoninergic activity. Recent data indicate that axonal development is affected by ammonia and can be normalized in vitro by creatine supplementation in developing mixed brain cell aggregate cultures, thus reviving the old hypothesis of the impact of hyperammonemia on energy metabolism in the developing brain that could cause mental retardation.
Authors:
Claude Bachmann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Clinical chemistry and laboratory medicine : CCLM / FESCC     Volume:  40     ISSN:  1434-6621     ISO Abbreviation:  Clin. Chem. Lab. Med.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-09-20     Completed Date:  2003-07-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9806306     Medline TA:  Clin Chem Lab Med     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  653-62     Citation Subset:  IM    
Affiliation:
Laboratoire Central de Chimie Clinique, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. Claude.Bachmann@chuv.hospvd.ch
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / metabolism
Ammonia / metabolism
Animals
Brain / blood supply,  metabolism,  pathology
Hepatic Encephalopathy
Humans
Hyperammonemia / complications,  etiology*
Chemical
Reg. No./Substance:
0/Amino Acids; 7664-41-7/Ammonia

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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