Interorgan ammonia metabolism in liver failure.
In the post-absorptive state, ammonia is produced in equal amounts in the small and large bowel. Small intestinal synthesis of ammonia is related to amino acid breakdown, whereas large bowel ammonia production is caused by bacterial breakdown of amino acids and urea. 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. Patients with liver disease have reduced urea synthesis capacity and reduced peri-venous glutamine synthesis capacity, resulting in reduced capacity to detoxify ammonia in the liver. 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, which is beneficial for the hyperammonemic patient. Data in experimental animals suggest that the kidneys could have a major role in post-feeding and post-haemorrhagic 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. Concomitant release of glutamine has been demonstrated in experimental animals, together with large increases of the cerebral cortex ammonia and glutamine concentrations. In this review we will discuss interorgan trafficking of ammonia during acute and chronic liver failure. Interorgan glutamine metabolism is also briefly discussed, since glutamine synthesis from glutamate and ammonia is an important alternative pathway of ammonia detoxification. The main ammonia producing organs are the intestines and the kidneys, whereas the major ammonia consuming organs are the liver and the muscle.
Olde Damink
Steven W M
SW
Department of Surgery, Maastricht University, Maastricht, The Netherlands.
Deutz
Nicolaas E P
NE
Dejong
Cornelis H C
CH
Soeters
Peter B
PB
Jalan
Rajiv
R
D000641:Ammonia / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001158:Arteries; D001921:Brain / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D017093:Liver Failure / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism
D000641:Ammonia