Splanchnic and leg exchange of amino acids and ammonia in acute liver failure.
OBJECTIVE
In patients with acute liver failure, hyperammonemia is associated with cerebral herniation. We examined the splanchnic and leg exchange of amino acids, urea, and ammonia in such patients.


METHODS
Bedside liver vein catheterization was used in 22 patients after development of hepatic encephalopathy grades III-IV. Femoral venous blood was sampled in 7 of these patients.


RESULTS
Arterial amino acid concentration (8.1 +/- 4.1 mmol/L) was increased 4-fold above normal. Glutamine (2.4 +/- 1.8 mmol/L) and alanine (0.57 +/- 0.35 mmol/L) were by far the predominant amino acids exchanged in the splanchnic and leg circulation. In the splanchnic circulation, there was a net uptake of glutamine (241 +/- 353 micromol/min) and ammonia and alanine were released in an almost 1:1 stoichiometry (r(2) = 0.47; P < 0.001). In the leg, ammonia and alanine were removed and glutamine released. The leg ammonia concentration difference was correlated to that of glutamine (r(2) = 0.80; P = 0.008) and alanine (r(2) = 0.67; P = 0.03).


CONCLUSIONS
Splanchnic metabolism of glutamine in combination with decreased hepatic function was responsible for the splanchnic release of ammonia and alanine. These processes were reversed in skeletal muscle. Stimulation of skeletal muscle metabolism of ammonia could be a important target for future treatment of patients with acute liver failure.
Clemmesen
J O
JO
Department of Hepatology, Rigshospitalet, University of Copenhagen, Denmark. otto@dadlnet.dk
Kondrup
J
J
Ott
P
P
D000328:Adult; D000409:Alanine / Q000097:blood; D000596:Amino Acids / Q000097:blood*; D000641:Ammonia / Q000097:blood*; D001806:Blood Urea Nitrogen; D002956:Citrulline / Q000097:blood; D005260:Female; D005263:Femoral Artery / Q000502:physiology; D005268:Femoral Vein / Q000502:physiology; D005355:Fibrosis / Q000378:metabolism / Q000503:physiopathology; D005973:Glutamine / Q000097:blood; D006801:Humans; D007866:Leg / Q000098:blood supply; D017114:Liver Failure, Acute / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011392:Proline / Q000097:blood; D013152:Splanchnic Circulation / Q000502:physiology*; D014508:Urea / Q000097:blood
D000596:Amino Acids; D005973:Glutamine; D002956:Citrulline; D000641:Ammonia; D014508:Urea; D011392:Proline; D000409:Alanine