Abstract
Cholestatic jaundice is the major complication of total parenteral nutrition (TPN). Both the intravenous (IV) route of nutrition and the enteral fast have been implicated as causes of TPN-associated cholestasis (TPN-AC). The purpose of this study was to determine whether TPN-AC is caused by the TPN solution itself or the IV route of administration and enteral fast. Prepubescent rabbits (n = 24) were divided into four groups: CONTROL, fed standard lab chow; TPN, received a standard hyperalimentation solution of dextrose, Aminosyn, and lipids via the jugular vein; ENT, received the same hyperalimentation solution via a duodenostomy tube; and OSM, received a polymeric formula (Osmolite) via a duodenostomy tube. After 14 days on these diets, we measured bile flow, bile acid excretion, sulfobromophthalein (BSP) excretion, plasma amino acid profile, serum liver enzymes, and liver histology. Statistical analysis was by analysis of variance. Hyperalimentation solution significantly depressed hepatobiliary function, whether it was given IV or by gut. Bile flow in both the TPN (36.4 μL/kg/min) and ENT (46.2) groups was significantly less than CONTROL (84.5) or OSM (62.9). Hepatic secretory function, measured by excretion of the cholephilic dye BSP, was depressed in both TPN and ENT (57% and 55% of IV dose excreted in bile over 60 minutes, respectively) compared with CONTROL (84%) or OSM (71%). Serum liver enzymes were normal in all groups. Histological injury similar to TPN-AC in humans (portal inflammation and hepatocyte degeneration) was seen in both groups receiving the hyperalimentation solution. Plasma methionine, the most hepatotoxic amino acid, was elevated in TPN and ENT (64 and 48 μmol/L v 31 for CONTROL) without corresponding elevations in its metabolites, cysteine and taurine. In conclusion, hyperalimentation solution is toxic to the liver. In this model, it produced structural and functional changes in the liver whether it was given intravenously or enterally. This toxicity appears to be caused by free amino acids in the solution, since administration of intact protein (Osmolite) did not cause significant liver damage. Methionine is the probable toxic agent.
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