Interorgan ammonia trafficking in liver disease.
Patients with liver disease have reduced urea synthesis capacity resulting in reduced capacity to detoxify ammonia in the liver. The contribution of the gut to the hyperammonemic state observed during liver failure is mainly due to portacaval shunting and not the result of changes in the metabolism of ammonia in the gut. Small intestinal synthesis of ammonia is related to amino acid breakdown, predominantly glutamine, whereas large bowel ammonia production is caused by bacterial breakdown of amino acids and urea. The kidneys produce ammonia but adapt to liver failure in experimental portacaval shunting by reducing ammonia release into the systemic circulation. The kidneys have the ability to switch from net ammonia production to net ammonia excretion. Data from recent studies in patients with cirrhosis of the liver show that the kidneys have a major role in post upper gastrointestinal bleeding hyperammonemia. During hyperammonemia muscle takes up ammonia and plays a major role in (temporarily) detoxifying ammonia to glutamine. Net uptake of ammonia by the brain occurs in patients and experimental animals with acute and chronic liver failure. Insight will be given in recent developments on ammonia lowering therapies which are based on the information of interorgan ammonia trafficking.
Olde Damink
Steven W M
SW
Department of Surgery, Maastricht University Medical Center, PO Box 5800, Maastricht, AZ, 6202 The Netherlands. steven.oldedamink@ah.unimaas.nl
Jalan
Rajiv
R
Dejong
Cornelius H C
CH
D000596:Amino Acids / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D022124:Hyperammonemia / Q000378:metabolism* / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D008102:Liver Circulation / Q000502:physiology*; D008107:Liver Diseases / Q000150:complications* / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000378:metabolism
D000596:Amino Acids; D005973:Glutamine; D000641:Ammonia