Interorgan ammonia and amino acid metabolism in metabolically stable patients with cirrhosis and a TIPSS.
Ammonia is central to the pathogenesis of hepatic encephalopathy. This study was designed to determine the quantitative dynamics of ammonia metabolism in patients with cirrhosis and previous treatment with a transjugular intrahepatic portosystemic stent shunt (TIPSS). We studied 24 patients with cirrhosis who underwent TIPSS portography. Blood was sampled and blood flows were measured across portal drained viscera, leg, kidney, and liver, and arteriovenous differences across the spleen and the inferior and superior mesenteric veins. The highest amount of ammonia was produced by the portal drained viscera. The kidneys also produced ammonia in amounts that equaled total hepatosplanchnic area production. Skeletal muscle removed more ammonia than the cirrhotic liver. The amount of nitrogen that was taken up by muscle in the form of ammonia was less than the glutamine that was released. The portal drained viscera consumed glutamine and produced ammonia, alanine, and citrulline. Urea was released in the splenic and superior mesenteric vein, contributing to whole-body ureagenesis in these cirrhotic patients. In conclusion, hyperammonemia in metabolically stable, overnight-fasted patients with cirrhosis of the liver and a TIPSS results from portosystemic shunting and renal ammonia production. Skeletal muscle removes more ammonia from the circulation than the cirrhotic liver. Muscle releases excessive amounts of the nontoxic nitrogen carrier glutamine, which can lead to ammonia production in the portal drained viscera (PDV) and kidneys. Urinary ammonia excretion and urea synthesis appear to be the only way to remove ammonia from the body.
Olde Damink
Steven W M
SW
Liver Unit and Department of Radiology, Royal Infirmary of Edinburgh, Scotland.
Jalan
Rajiv
R
Redhead
Doris N
DN
Hayes
Peter C
PC
Deutz
Nicolaas E P
NE
Soeters
Peter B
PB
D000596:Amino Acids / Q000378:metabolism*; D000641:Ammonia / Q000378:metabolism*; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000378:metabolism / Q000601:surgery; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D019168:Portasystemic Shunt, Transjugular Intrahepatic; D013152:Splanchnic Circulation / Q000502:physiology
D000596:Amino Acids; D000641:Ammonia