title: Review article: hyperammonaemic and catabolic consequences of upper gastrointestinal bleeding in cirrhosis.
abstract: BACKGROUND
  Upper gastrointestinal (UGI) bleeding in patients with cirrhosis of the liver induces hyperammonaemia and leads to a catabolic cascade that precipitates life-threatening complications. The haemoglobin molecule is unique because it lacks the essential amino acid isoleucine and contains high amounts of leucine and valine. UGI bleed therefore presents the gut with protein of very low biologic value, which may be the stimulus to induce net catabolism.
  
  
  OBJECTIVE
  To describe the hyperammonaemic and catabolic consequences of UGI bleeding in cirrhosis.
  
  
  METHODS
  A semi-structured literature search was performed using PubMed and article references.
  
  
  RESULTS
  It has recently been proven that ('simulation of ') a UGI bleed in patients with cirrhosis leads to impaired protein synthesis that can be restored by intravenous infusion of isoleucine. This may have therapeutic implications for the function of rapidly dividing cells and short half-life proteins such as clotting factors. Renal and small bowel ammoniagenesis were shown to be the most prominent causes for the hyperammonaemia that resulted from a UGI bleed. This provides an explanation for the therapeutic failure of the current clinical therapies that are aimed at large bowel-derived ammonia production. Isoleucine infusion did not diminish renal ammoniagenesis.
  
  
  CONCLUSIONS
  New pharmacological therapies to diminish postbleeding hyperammonaemia should target the altered inter-organ ammonia metabolism and promote ammonia excretion and/or increase the excretion of precursors of ammoniagenesis, e.g. l-ornithine-phenylacetate.
authors.affiliation: Department of Surgery, Maastricht University Medical Centre and Nutrition & Toxicology Research Institute Maastricht (NUTRIM), Maastricht, The Netherlands. steven.oldedamink@ah.unimaas.nl
authors.forename: S W M
authors.initials: SW
authors.lastname: Olde Damink
authors.forename: C H C
authors.initials: CH
authors.lastname: Dejong
authors.forename: R
authors.initials: R
authors.lastname: Jalan
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000378:metabolism* / Q000627:therapeutic use; D006471:Gastrointestinal Hemorrhage / Q000150:complications* / Q000209:etiology; D006801:Humans; D022124:Hyperammonemia / Q000188:drug therapy / Q000209:etiology*; D007532:Isoleucine / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000150:complications*
chemical_list: D000597:Amino Acids, Branched-Chain; D007532:Isoleucine