Digestive Diseases and Sciences

, Volume 41, Issue 9, pp 1864–1870 | Cite as

Total parenteral nutrition impairs bile flow and alters bile composition in newborn piglet

  • Donald R. Duerksen
  • John E. van Aerde
  • George Chan
  • Alan B. R. Thomson
  • Laurence J. Jewell
  • Michael T. Clandinin
Growth, Development, And Nutrition

Abstract

Cholestatic liver disease complicates total parenteral nutrition (TPN) in premature neonates. We investigated TPN-induced liver disease in the newborn piglet, hypothesizing that: (1) TPN impairs bile flow by reducing the bile acid-dependent (BADF) and the bile acid-independent component of bile flow (BAIF); and (2) TPN changes bile composition. For three weeks, eight piglets received TPN and nine piglets were fed milk. Basal bile flow was measured and bile composition analyzed for bile acids, cholesterol (C), phospholipids (PL), and PL fatty acids. Bile flow was also measured after stimulation with 20, 50, and 100 µmol/kg taurocholic acid (TCA). Liver histology and bilirubin content were examined. Basal bile flow was reduced from 11.6±1.2 µl/g liver/10 min in orally fed animals to 1.6±0.4 µl/g liver/10 min in the TPN group. The stimulated bile flow in the TPN group did not respond to TCA and was lower than in the orally fed animals at each TCA dose. Both BADF and BAIF were significantly lower in the TPN group. Bile acid secretion was less than 50% of control values and total C and PL secretions were less than 5% of control. Liver and serum bilirubin were elevated in the TPN group. The newborn piglet is a valid model to study TPN-induced cholestasis, characterized by decreased bile acid secretion, impaired BADF and BAIF, and reduced bile flow stimulation after intravenous TCA.

Key words

total parenteral nutrition cholestasis bile acids bile flow 

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References

  1. 1.
    Quigley EMM, Marsh MN, Shaffer JL, Markin RS: Hepatobiliary complications of total parenteral nutrition. Gastroenterology 104:286–301, 1993PubMedGoogle Scholar
  2. 2.
    Beale EF, Nelson RM, Bucciarelli RL, Donnelly WH, Eitzman DV: Intrahepatic cholestasis associated with parenteral nutrition in premature infants. Pediatrics 64:342–347, 1979PubMedGoogle Scholar
  3. 3.
    Truskett PG, Shi ECP, Rose M, Sharp PA, Ham JM: Model of TPN-associated hepatobiliary dysfunction in the young pig. Br J Surg 74:639–642, 1987PubMedGoogle Scholar
  4. 4.
    Omland E, Mathisen O: Mechanism of ursodeoxycholic acidand canrenoate-induced biliary bicarbonate secretion and the effect on glucose- and amino acid-induced cholestasis. Scand J Gastroenterol 26:513–522, 1991PubMedGoogle Scholar
  5. 5.
    Lirussi F, Vaja S, Murphy GM, Dowling RH: Cholestasis of total parenteral nutrition: Bile acid and bile lipid metabolism in parenterally nourished rats. Gastroenterology 96:493–502, 1989PubMedGoogle Scholar
  6. 6.
    Belli DC, Fournier LA, Lepage G, et al: Total parenteral nutrition-associated cholestasis in rats: Comparison of different amino acid mixtures. JPEN 11:67–73, 1987Google Scholar
  7. 7.
    Das JB, Ghosh S, Cosentino CM, Ansari GG: Hepatic organic anion transport kinetics and bile flow during short-term total parenteral nutrition in the rabbit. Proc Soc Exp Biol Med 195:274–278, 1990PubMedGoogle Scholar
  8. 8.
    Gleghorn EE, Merritt RJ, Henton DH, Neustein HM, Landing B, Sinatra FR: A subacute rabbit model for hepatobiliary dysfunction during total parenteral nutrition. J Pediatr Gastroenterol Nutr 9:246–255, 1989PubMedGoogle Scholar
  9. 9.
    Zahavi I, Shaffer EA, Gall DG: Total parenteral nutrition-associated cholestasis: Acute studies in infant and adult rabbits. J Pediatr Gastroenterol Nutr 4:622–627, 1985PubMedGoogle Scholar
  10. 10.
    Doty JE, Pitt HA, Porter-Fink V, DenBesten L: The effect of intravenous fat and total parenteral nutrition on biliary physiology. JPEN 8:263–268, 1984Google Scholar
  11. 11.
    Hata S, Kamata S, Nezu R, Takagi Y, Okada A: A newborn rabbit model for total parenteral nutrition: Effects of nutritional components on cholestasis. JPEN 13:265–271, 1989Google Scholar
  12. 12.
    Miller ER, Ullrey DE: The pig as a model for human nutrition. Annu Rev Nutr 7:361–382, 1987PubMedGoogle Scholar
  13. 13.
    Innis SM: The colostrum-deprived piglet as a model for study of infant lipid nutrition. J Nutr 123:386–390, 1993PubMedGoogle Scholar
  14. 14.
    Moughan PJ, Birtles MJ, Cranwell PD, Smith WC, Pedraza M: The piglet as a model animal for studying aspects of digestion and absorption in milk-fed human infants. World Rev Nutr Diet 67:40–113, 1992PubMedGoogle Scholar
  15. 15.
    Wykes LJ, Ball RO, Pencharz PB: Development and validation of a total parenteral nutrition model in the neonatal piglet. J Nutr 123:1248–1259, 1993PubMedGoogle Scholar
  16. 16.
    Shulman RJ: The piglet can be used to study the effect of parenteral and enteral nutrition on body composition. J Nutr 123:395–398, 1993PubMedGoogle Scholar
  17. 17.
    Cohen IT, Meunier KM, Lipman RD, Ellis NG: Spectrum of hepatic, splenic and pulmonary histopathology in the hyperalimented neonatal piglet.In Swine in Biomedical Research. ME Tumbleson (ed). New York, Plenum Press, 1986, pp 1253–1263Google Scholar
  18. 18.
    Shulman RJ, Fiorotto ML, Hwai-Ping S: Liver composition and histology in growing infant miniature pigs given different total parenteral nutrition fuel mixes. JPEN 2:275–279, 1987Google Scholar
  19. 19.
    Cohen IT, Meunier KM, Hirsch MP: The effects of entral stimulation on gallbladder bile during total parenteral nutrition in the neonatal piglet. J Pediatr Surg 25:163–167, 1990PubMedGoogle Scholar
  20. 20.
    National Research Council: Nutrient Requirements of Swine. Washington, DC, National Academic Press, 1988Google Scholar
  21. 21.
    Ross FW, Mayer D, Haindl H: Bile acids.In Method of Enzymatic analysis. HU Bermeyer (ed). Orlando, Florida, Academic Press, 1974, pp 1886–1889Google Scholar
  22. 22.
    Folch J, Lees M, Sloane SG: A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509, 1956Google Scholar
  23. 23.
    Rudel LL, Morris MD: The determination of cholesterol in lipid extracts withO-phthaldehyde. J Lipid Res 14:364–366, 1973PubMedGoogle Scholar
  24. 24.
    Hargreaves KM, Clandinin MT: Phosphatidylethanolamine methyltransferase evidence for influence of diet fat on selectivity of substrate for methylation in rat brain synaptic plasma membranes. Biochim Biophys Acta 918:97–105, 1987PubMedGoogle Scholar
  25. 25.
    Lightner DA: Chemistry.In Bilirubin. KP Heirwegh, SB Brown (eds). Boca Raton, Florida, CRC Press, 1982, p 36Google Scholar
  26. 26.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951PubMedGoogle Scholar
  27. 27.
    Gimmon Z, Kelley RE, Simko V, Fischer JE: Total parenteral nutrition solution increases bile lithogenicity in rat. J Surg Res 32:256–263, 1982PubMedGoogle Scholar
  28. 28.
    Borum PR: Use of the colostrum-deprived piglet to evaluate parenteral feeding formulas. J Nutr 123:391–394, 1993PubMedGoogle Scholar
  29. 29.
    Putet G: Energy.In Nutritional Needs of The Preterm Infant: Scientific Basis and Practical Guidelines. RC Tsang, A Lucas, R Uauy, S Zlotkin, (eds). Baltimore, Williams & Wilkins, 1993, pp 15–28Google Scholar
  30. 30.
    Simon FR: Physiology and pathophysiology of bile secretion.In Principles and Practice of Gastroenterology and Hepatology. T Gitnick, (ed). Norwalk, Connecticut, Appleton & Lange, 1994, pp 723–730Google Scholar
  31. 31.
    Hardison WG, Aster JT: Micellar theory of biliary cholesterol secretion. Am J Physiol 222:61–67, 1972PubMedGoogle Scholar
  32. 32.
    Carey MC, Canalone M: Enterohepatic circulation.In The Liver: Biology and Pathobiology. IM Arias (ed). New York, Raven Press, 1988, pp 573–616Google Scholar
  33. 33.
    Innis SM: Hepatic transport of bile salt and bile composition following TPN with and without lipid emulsion in the rat. Am J Clin Nutr 41:1283–1288, 1985PubMedGoogle Scholar
  34. 34.
    Shaffer EA: Abnormalities in gallbladder function in cholesterol gallstone disease: Bile and blood, mucosa and muscle. The list lengthens. Gastroenterology 102:1808–1812, 1992PubMedGoogle Scholar
  35. 35.
    Berr F, Holl J, Jungst D, Fischer S: Dietary N-3 polyunsaturated fatty acids decrease biliary cholesterol saturation in gall-stone disease. Hepatology 16:960–967, 1992PubMedGoogle Scholar
  36. 36.
    Hardison WGM, Norman JC: Effect of bile salt and secretion upon bile flow from the isolated perfused pig liver. Gastroenterology 53:412–417, 1967Google Scholar
  37. 37.
    Boyer JL, Klatskin G: Canalicular bile flow and bile secretory pressure: Evidence for a non-bile salt dependent fraction in the isolated perfused rat liver. Gastroenterology 59:853–859, 1970PubMedGoogle Scholar
  38. 38.
    Haber BA, Lake AM: Cholestatic jaundice in the newborn. Clin Perinatol 17:483–506, 1990PubMedGoogle Scholar
  39. 39.
    Howard D, Thompson DF: Taurine: an essential amino acid to prevent cholestasis in neonates? Ann Pharmacother 26:1390–1392, 1992PubMedGoogle Scholar
  40. 40.
    Duerksen D, Chan G, Thomson ABR, Clandinin MT, Van Aerde J: Intravenous lipid emulsions with fatty acid compositions similar to milk reduce incidence of neonatal cholestasis induced by total parenteral nutrition. Gastroenterology (suppl) 104:A1036, 1993Google Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Donald R. Duerksen
    • 1
    • 2
    • 3
  • John E. van Aerde
    • 1
    • 2
    • 3
  • George Chan
    • 1
    • 2
    • 3
  • Alan B. R. Thomson
    • 1
    • 2
    • 3
  • Laurence J. Jewell
    • 1
    • 2
    • 3
  • Michael T. Clandinin
    • 1
    • 2
    • 3
  1. 1.From the Department of Pediatrics, Nutrition and Metabolism Research Group, Perinatal Research CentreUniversity of AlbertaEdmontonCanada
  2. 2.Department of Medicine, Nutrition and Metabolism Research Group, Perinatal Research CentreUniversity of AlbertaEdmontonCanada
  3. 3.Department of Pathology, Nutrition and Metabolism Research Group, Perinatal Research CentreUniversity of AlbertaEdmontonCanada

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