Abstract
BACKGROUND—Hyperammonaemia is a pathogenetic factor for hepatic encephalopathy that may be augmented after a transjugular intrahepatic portosystemic shunt (TIPS). Experimental data suggest that hyperammonaemia may be caused to a large extent by metabolism of small intestinal enterocytes rather than colonic bacteria. AIMS—To evaluate if ammonia release and glutamine metabolism by small intestinal mucosa contribute to hyperammonaemia in vivo in patients with liver cirrhosis. METHODS—Using TIPS to examine mesenteric venous blood, we measured mesenteric venous-arterial concentration differences in ammonia and glutamine in patients with liver cirrhosis before, during, and after enteral (n=8) or parenteral (n=8) isonitrogenous infusion of a glutamine containing amino acid solution. RESULTS—During enteral nutrient infusion, ammonia release increased rapidly compared with the post-absorptive state (65 (58-73) v 107 (95-119) µmol/l after 15 min; mean (95% confidence interval)) in contrast with parenteral infusion (50 (41-59) v 62 (47-77) µmol/l). This resulted in a higher portal ammonia load (29 (21-36) v 14 (8-21) mmol/l/240 minutes) and a higher degree of systemic hyperammonaemia (14 (11-17) v 9 (6-12) mmol/l/240 minutes) during enteral than parenteral infusion. The mesenteric venous-arterial concentration difference in glutamine changed from net uptake to release at the end of the enteral infusion period (−100 (−58 to −141) v 31 (−47-110) µmol/l) with no change during parenteral nutrition. CONCLUSIONS—These data suggest that small intestinal metabolism contributes to post-feeding hyperammonaemia in patients with cirrhosis. When artificial nutrition is required, parenteral nutrition may be superior to enteral nutrition in patients with portosystemic shunting because of the lower degree of systemic hyperammonaemia. Keywords: hepatic encephalopathy; intestinal metabolism; ammonia; glutamine; enteral nutrition; parenteral nutrition
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Figure 1 .
Experimental design of the infusion protocol. Infusions were performed from 0 to 120 minutes.
Figure 2 .
Enteral amino acid infusion. Ammonia (A) and glutamine (B) concentrations before, during (0-120 minutes), and after enteral infusion. Arterial and superior mesenteric venous (SMV) concentrations are mean (SEM).
Figure 3 .
Parenteral amino acid infusion. Ammonia (A) and glutamine (B) concentrations before, during (0-120 minutes), and after parenteral infusion. Arterial and superior mesenteric venous (SMV) concentrations are mean (SEM).
Figure 4 .
Degree of systemic hyperammonaemia and systemic availability of glutamine following enteral (E) or parenteral (P) amino acid infusion. Values are calculated as area under the curve of increments in arterial substrate concentrations above baseline from 0 to 240 minutes. Error bars indicate SEM. *p<0.05, enteral v parenteral.
Figure 5 .
Concentration differences between the superior mesenteric vein (SMV) and artery during enteral or parenteral infusion of amino acids (0-120 minutes). Values are mean (SEM) for ammonia (A) and glutamine (B).
Figure 6 .
Intestinal exchange of ammonia (A) and glutamine (B) before and during the last 60 minutes of enteral or parenteral amino acid infusion, as calculated by the area under the curve method. Error bars indicate SEM. **p<0.01, ***p<0.001, before v during infusion.
Figure 7 .
Portal ammonia load and portal availability of glutamine following enteral (E) or parenteral (P) amino acid infusion. Values are calculated as area under the curve of increments in mesenteric venous substrate concentrations above baseline from 0 to 240 minutes. Error bars indicate SEM. *p<0.05, **p<0.01, enteral v parenteral.
Selected References
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