Jaundice pp 195-215 | Cite as

Principles of Biliary Secretion

  • Henry O. Wheeler
Part of the Hepatology book series (H, volume 2)


Bile is a transparent, colored, single-phase solution containing substantial quantities of organic as well as inorganic solutes, and produced continuously by the liver with great variations in rate of flow and composition. Although technically an “external” secretion, the great bulk of its constituents is destined for intestinal reabsorption and is returned to the liver via the so-called enterohepatic circulation. Although bile is primarily a digestive fluid the biliary tract also serves as a route of excretion for a variety of substances, and for a few (e.g. bilirubin) it is practically the sole excretory pathway. Heretofore, the study of bile formation has necessitated at least temporary diversion of bile to the exterior by various unphysiological maneuvres, and hence interruption of the enterohepatic circulation. Newer techniques such as those devised by Dowling and his associates (1) for study of the rhesus monkey have permitted the examination of the flow and composition of bile in conscious animals with either mininal or controlled interruption of the enterohepatic circulation. The following remarks will summarize some of our present knowledge of the flow, pressure, composition, regulation and mechanisms of bile formation. For more detailed information particular attention is called to the excellent recent review by Erlinger and Dhumeaux (2).


Bile Acid Bile Flow Enterohepatic Circulation Canalicular Bile Biliary Secretion 
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  1. 1.
    DOWLING RH, MACK E, PICOTT J, et al: Experimental model for study of the enterohepatic circulation of bile in rhesus monkeys. J Lab Clin Med 72: 169–176, 1963.Google Scholar
  2. 2.
    ERLINGER S, DHUMEAUX D: Mechanisms and control of secretion of bile water and electrolytes. Gastroenterology 66: 281–304, 1974.PubMedGoogle Scholar
  3. 3.
    SOBOTKA H: Physiological Chemistry of the Bile. Baltimore, Williams and Wilkins, 1937,Google Scholar
  4. 4.
    CHENDEROVITCH J, PHOCAS E, RAUTUREAU M: Effects of hypertonic solutions on bile formation. Am J Physiol 205: 863–867, 1963.PubMedGoogle Scholar
  5. 5.
    GILMAN A, COWGILL GR: Osmotic relations between blood and body fluids. IV. Pancreatic juice, bile and lymph. Am J Physiol 104: 476–479, 1933.Google Scholar
  6. 6.
    WHEELER HO, RAMOS OL: Determinants of the flow and composition of bile in the unanesthetized dog during constant infusions of sodium taurocholate. J Clin Invest 39: 161–170, 1960.PubMedCrossRefGoogle Scholar
  7. 7.
    PREISIG R, COOPER HL, WHEELER HO: The relationship between taurocholate secretion rate and bile production in the unanesthetized dog during cholinergic blockade and during secretin administration. J Clin Invest 41: 1152–1162, 1962.PubMedCrossRefGoogle Scholar
  8. 8.
    HARDISON WGM, NORMAN JC: Effect of secretin on bile osmolality.J L ab Clin Med 73: 34–41, 1969.PubMedGoogle Scholar
  9. 9.
    THUREBORN E: Human hepatic bile. Composition changes due to altered enterohepatic circulation. Acta chir scand Suppl 303: 1–63, 1962.Google Scholar
  10. 10.
    . HARDWICKE J, RANKIN JG, BAKER KJ et al: The loss of protein in human and canine hepatic bile. Clin Sci 26: 509–517, 1964.PubMedGoogle Scholar
  11. 11.
    ROSENTHAL WS, KUBO K, DOLINSKI M, et al: The passage of serum albumin into bile in man. Am J Dig Pis 10: 271–283, 1965.CrossRefGoogle Scholar
  12. 12.
    RUSSELL IS, FLECK A, BURNETT W: The protein content of human bile. Clin Chim Acta 10: 210–213, 1964.PubMedCrossRefGoogle Scholar
  13. 13.
    FINK S: Studies on hepatic bile obtained from a patient with an external biliary fistula; its composition and changes after diamox administration. N Eng J Med 254: 258–262, 1956.CrossRefGoogle Scholar
  14. 14.
    WAITMAN AM, DYCK WP, JANOWITZ HD: Effect of secretin and acetazolamide on the volume and electrolyte composition of hepatic bile in man. Gastroenterology 56: 286–294, 1969.PubMedGoogle Scholar
  15. 15.
    BARBER-RILEY G: The rate of biliary secretion during flow up vertical cannulas of different bore. Experientia 20: 639–645, 1964.CrossRefGoogle Scholar
  16. 16.
    BARBER-RILEY G: Measurement of the capacity of the biliary tree. In The Biliary System, edited by Taylor W, Oxford, Blackwell, 1965. pp 90–97.Google Scholar
  17. 17.
    BRAUER RW: Hepatic blood supply and the secretion in bile. In The Biliary System, edited by Taylor W, Oxford, Blackwell, 1965. pp. 41–67.Google Scholar
  18. 18.
    BRAUER RW, LEONG GF, HOLLOWAY RJ: Mechanics of bile secretion: The effect of perfusion pressure and temperature on bile flow and bile secretion pressure. Am J Physiol 177: 103–112, 1954.PubMedGoogle Scholar
  19. 19.
    RICHARDS TG, THOMSON JY: The secretion of bile against pressure. Gastroenterology 40: 705–707, 1961.PubMedGoogle Scholar
  20. 20.
    STRASBERG SM, DORN BC, REDINGER RN, et al: Effects of alteration of biliary pressure on bile composition -A method for study: primate biliary physiology V. Gastroenterology 61: 357–362, 1971.PubMedGoogle Scholar
  21. 21.
    MAFFLY RH, LEAF A: The potential of water in mammalian tissues. J Gen Physiol 42: 1257–1275, 1959.PubMedCrossRefGoogle Scholar
  22. 22.
    CURRAN PF, McINTOSH JR: A model system for biological water transport. Nature (Lond) 193: 347–348, 1962.CrossRefGoogle Scholar
  23. 23.
    OGILVIE JT, McINTOSH JR, CURRAN PF: Volume flow in a series membrane system. Biochim Biophys Acta 66: 441–444, 1963.PubMedGoogle Scholar
  24. 24.
    DIAMOND JM, BOSSERT WH: Standing-gradient osmotic flow.J Gen Physiol 50: 2061–2083, 1967.PubMedCrossRefGoogle Scholar
  25. 25.
    TORMEY J McD, DIAMOND JM: The ultrastructural route of fluid transport in rabbit gallbladder.J Gen Physiol50: 2031–2060, 1967.CrossRefGoogle Scholar
  26. 26.
    PATLAK CS, GOLDSTEIN DA, HOFFMAN JF: The flow of solute and solvent across a two-membrane system. J Theor Biol 5: 426–442, 1963.PubMedCrossRefGoogle Scholar
  27. 27.
    KAYE G, WHEELER HO, WHITLOCK RT, et al: Fluid transport in the rabbit gallbladder. A combined physiological and electron microscopic study. J Cell Biol 30: 237–268, 1967.Google Scholar
  28. 28.
    WHITLOCK RT, WHEELER HO: Coupled transport of solute and water across rabbit gallbladder epithelium. J Clin Invest 43: 2249–2265, 1964.PubMedCrossRefGoogle Scholar
  29. 29.
    WHEELER HO: Water and electrolytes in bile. In Handbook of Physiology, Sect 6, Alijnentary Canal, vol 5. Edited by Code CF, Washington, Amer Physiol Soc, 1968. pp 2409–2431.Google Scholar
  30. 30.
    SPERBER I: Secretion of organic anions in the formation of rine and bile.Pharm Rev 11 109–134, 1959.PubMedGoogle Scholar
  31. SPERBER I: Biliary secretion of organic anions and its nfluence on bile flow. In The Biliary System, edited by Taylor W, Oxford, Blackwell, 1965, pp 457–467.Google Scholar
  32. 32.
    SCHANKER LS: Secretion of organic compounds in bile. n Handbook of Physiology, Sect 6, Alimentary Canal,Google Scholar
  33. vol 5. Edited by Code CF, Washington, Amer Physiol Soc, 968. pp 2433-2449.Google Scholar
  34. 33.
    HART LG, SCHANKER LS: The chemical forms in which phenol ed is secreted into the bile of rats. Proc. Soc Exp Biol Med 123: 433–435, 1966.PubMedGoogle Scholar
  35. 34.
    COOK DL, LAWLER CA, CALVIN LD, et al: Mechanisms of bile ormation. Am J Physiol 171: 62–74, 1952.PubMedGoogle Scholar
  36. 35.
    DESPOPOULOS A: Congruence of excretory functions in liver nd kidney: hippurates. Am J Physiol 210: 760–764, 1966.PubMedGoogle Scholar
  37. 36.
    DESPOPOULOS A, SONNENBERG H: Congruence of excretory functions of liver and kidney: sulfonamides. Am J Physiol 212: 1117–1122, 1967.PubMedGoogle Scholar
  38. 37.
    TWISS JR, BERGER WV, GILLETTE L, et al: The biliary excretion of erythromycin (Ilotycin). Surg, Gynec Obstet 102: 355–357, 1956.Google Scholar
  39. 38.
    AYLIFEE GAJ, DAVIES A: Ampicillin levels in human bile. Brit J Pharmacol 24: 189–193, 1965.Google Scholar
  40. 39.
    CHERRICK GR, STEIN SW, LEEVY CM, et al: Indocyanine green: observations on its physical properties, plasma decay and hepatic excretion. J Clin Invest 39: 592–600, 1960.PubMedCrossRefGoogle Scholar
  41. 40.
    WHEELER HO, CRANSTON WI, MELTZER JI: Hepatic uptake and biliary excretion of indocyanine green in the dog. Proc Soc Exp Biol Med 99: 11–14, 1958.PubMedGoogle Scholar
  42. 41.
    JENNER FA, SMYTH DH: The excretion of phlorhizin. J Physiol (Lond) 146: 563–571, 1959.Google Scholar
  43. 42.
    HART LG, SCHANKER LS: Active transport of chlorothiazide into bile. Am J Physiol 211: 643–646, 1966.PubMedGoogle Scholar
  44. 43.
    ALPERT S, MOSHER M, SHANSKE A, et al: Multiplicity of hepatic excretory mechanisms for organic anions. J Gen Physiol 53: 238–247, 1969.PubMedCrossRefGoogle Scholar
  45. 44.
    O’MAILLE ERL, RICHARDS TG, SHORT AH: Acute taurine depletion and maximal rates of hepatic conjugation and secretion of cholic acid in the dog.J Physiol (Lond) 18067–79, 1965.Google Scholar
  46. 45.
    O’MAILLE ERL, RICHARDS TG, SHORT AH: The influence of conjugation of cholic acid on its uptake and secretion: hepatic extraction of taurocholate and cholate in the dog. J Physiol (lond) 189: 337–350, 1967.Google Scholar
  47. 46.
    SCHOENFIELD LJ, FOULK W: Studies of sulfobromophthalein sodium (BSP) metabolism in man. II. The effect of artificially induced fever, norethandrolone (Nilevar) and iopanoic acid (Telepaque). J Clin Invest 43: 1419–1423, 1964.PubMedGoogle Scholar
  48. 47.
    GOETZEE AE, RICHARDS TG, TINDALL VR: Experimental changes in liver function induced by probenecid. Clin Sci 19: 63–78, 1960.PubMedGoogle Scholar
  49. 48.
    WEINER IM, GLASSER JE, LACK L: Renal excretion of bile: taurocholic, glycocholic, and cholic acids. Am J Physiol 207: 964–970, 1964.PubMedGoogle Scholar
  50. 49.
    BARNHART J, RITT D, WARE A, et al: A comparison of the effects of taurocholate and theophylline on BSP excretion in dogs. In The Liver, Quantitative Aspects of Structure and Function. Edited by Paumgartner G, Preisig R, Basel, Karger, 1973. pp. 315–325.Google Scholar
  51. 50.
    BOYER JL, SCHEIG RL, KLATSKIN G: The effect of sodium taurocholate on the hepatic metabolism of sulfobromo-phthalein sodium (BSP). The role of bile flow. J Clin Invest 49: 206–215, 1970.CrossRefGoogle Scholar
  52. 51.
    ERLINGER S, DUMONT M: Influence of canalicular bile flow on sulfobromophthalein transport maximum in bile in the dog. In The Liver. Quantitative Aspects of Structure and Function. Edited by Paumgartner G, Preisig R, Basel, Karger, 1973. pp. 306–314.Google Scholar
  53. 52.
    FORKER EL, GIBSON G: Interaction between sulfobromophthalein (BSP) and taurocholate. In The Liver. Quantitative Aspects of Structure and Function. Edited by Paumgartner G, Preisig R, Basel, Karger, 1973. pp. 326–336.Google Scholar
  54. 53.
    O’MAILLE ERL, RICHARDS TG, SHORT AH: Factors determining the maximal rate of organic anion secretion by the liver and further evidence on the hepatic site of action of the hormone secretin. J Physiol (Lond) 186: 424–438, 1966.Google Scholar
  55. 54.
    RIT DJ, COMBES B: Enhancement of apparent excretory maximum of sulfobromophthalein sodium (BSP) by taurocholate and dehydrocholate. J Clin Invest 46: 1108, 1967 (Abstract).Google Scholar
  56. BERK RN, GOLDBERGER LE, LOEB PM: The role of bile salts in the hepatic excretion of iopanoic acid. Invest Radiol. (in press).Google Scholar
  57. 56.
    DUNN CR, BERK RN: The pharmacokinetics of telepaque metabolism: The relation of blood concentration and bile flow to the rate of hepatic excretion. Am J Roentgenol 114: 758–766, 1972.Google Scholar
  58. 57.
    MOSS AA, AMBERG JR, JONES RS: Relationship of bile salts and bile flow to biliary excretion of iopanoic acid. Invest Radiol 7: 11–15, 1972.PubMedGoogle Scholar
  59. 58.
    SCHANKER LS: Hepatic transport of organic cations. In The Biliary System, edited by Taylor W, Oxford, Blackwell, 1965. pp 469–480.Google Scholar
  60. 59.
    SCHANKER LS, SOLOMON HM: Active transport of quaternary ammonium compounds into bile. Am J Physiol 204: 829–832, 1963.PubMedGoogle Scholar
  61. 60.
    KUPEERBERG HJ, SCHANKER LS: Biliary secretion of ouabain-H3 and its uptake by liver slices in the rat. Am J Physiol 214: 1048–1053, 1968.Google Scholar
  62. 61.
    MEYER-BRUNOT HG, KEBERLE H: Biliary excretion of ferrioxamines of varying liposolubility in perfused rat liver. Am J Physiol 214: 1193–1200, 1968.PubMedGoogle Scholar
  63. 62.
    SPERBER I: Biliary excretion and choleresis. In Proceedings First International Pharmacological Meeting. Oxford, Pergaon Press, 1963. vol 4, pp. 137–143.Google Scholar
  64. 63.
    ERLINGER S, DHUMEAUX D, BERTHELOT P et al: Effect of inhibitors of sodium transport on bile formation in the rabbit. Amer J Physiol 219: 416–422, 1970.PubMedGoogle Scholar
  65. 64.
    FORKER EL: Two sites of bile formation as determined by mannitol and erythritol clearance in the guinea pig. J Clin Invest 46: 1189–1195, 1967.PubMedCrossRefGoogle Scholar
  66. 65.
    FORKER EL, HICKLIN T, SORNSON T: The clearance of mannitol and erythritol in rat bile. Proc Soc Exp Biol Med 126: 115–119, 1967.PubMedGoogle Scholar
  67. 66.
    WHEELER HO, ROSS ED, BRADLEY SE: Canalicular bile production in dogs. Am J Physiol 214: 866–874, 1968.PubMedGoogle Scholar
  68. 67.
    CAHILL GF Jr, ASHMORE J, EARLE AS, et al: Glucose penetration into liver. Am J Physiol 192: 491–496, 1958.Google Scholar
  69. 68.
    SACKS J, BAKSHY S: Insulin and tissue distribution of pentose in nep;rectomized cats. Am J Physiol 189:339–342, 1957.PubMedGoogle Scholar
  70. 69.
    SCHANKER LS, HOGBEN CAM: Biliary excretion of inulin, sucrose, and mannitol: analysis of bile formation. Am J Physiol 200:1087–1090, 1968.Google Scholar
  71. 70.
    FORKER EL: Bile formation in guinea pigs: analysis with inert solutes of graded molecular radius. Am J Physiol 216: 56–62, 1968.Google Scholar
  72. 71.
    FRIEDMAN MHF, SNAPE WJ: Comparative effectiveness of extracts of intestinal mucosa in stimulating the external secretions of the pancreas and the liver. Fed Proc 4: 21–22, 1945.Google Scholar
  73. 72.
    CRIGLER JF, Jr, NAJJAR VA: Congenital familial nonhemolytic jaundice with kernicterus. Pediatrics 10: 169–179, 1952.PubMedGoogle Scholar
  74. 73.
    BERTHELOT P, ERLINGER S, DHUMEAUX D, et al: Mechanism of phenobarbital-induced choleresis in the rat. Am J Physiol 219: 809–813, 1970.PubMedGoogle Scholar
  75. 74.
    BOYER JL: Canalicular bile formation in the isolated perfused rat liver. Am J Physiol 221: 1156–1163, 1971.PubMedGoogle Scholar
  76. 75.
    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, 1970.PubMedGoogle Scholar
  77. 76.
    WHEELER HO, MANCUSI-UNGARO PL: Role of bile ducts during secretin choleresis in dogs. Am J Physiol 210: 1153–1159, 1966.PubMedGoogle Scholar
  78. 77.
    HARDISON WG, NORMAN JC: Electrolyte composition of the secretin fraction of bile from the perfused pig liver. Am J Physiol 2m: 758–763, 1968.Google Scholar
  79. 78.
    JONES RS, GROSSMAN MI: Choleretic effects of secretin and histamine in the dog. Am J Physiol 217: 532–535, 1969.PubMedGoogle Scholar
  80. 79.
    ZATERKA S, GROSSMAN MI: The effect of gastrin and histamine on secretion of bile. Gastroenterology 50: 500–505, 1966.PubMedGoogle Scholar
  81. 80.
    LONDON CD, DIAMOND JM, BROOKS FP: Electrical potential differences in the biliary tree. Biochim Biophys Acta 150: 509–517, 1968.PubMedCrossRefGoogle Scholar
  82. 81.
    FORKER EL: The effect of estrogen on bile formation in the rat. J Clin Invest 48: 654–663, 1969.PubMedCrossRefGoogle Scholar
  83. 82.
    FORKER EL: Hepatocellular uptake of inulin, sucrose and mannitol in rats. Am J Physiol 219: 1568–1573, 1970.PubMedGoogle Scholar
  84. 83.
    SWELL L, ENTENMAN C, LEONG GF, et al: Bile acids and lipid metabolism: IV. Influence of bile acids on biliary and liver organelle phospholipids and cholesterol. Am J Physiol 215: 1390–1396, 1968.Google Scholar
  85. 84.
    NILSSON S, SCHERSTEN T: Importance of bile acids for phospholipid secretion into human hepatic bile. Gastroenterology 57: 525–532, 1969.PubMedGoogle Scholar
  86. 85.
    HARDISON WGM, APTER JT: Micellar theory of biliary cholesterol excretion. Am J Physiol 226: 61–67, 1972.Google Scholar
  87. 86.
    WHEELER HO, KING KK: Biliary excretion of lecithin and cholesterol in the dog. J Clin Invest 51: 1337–1350, 1972.PubMedCrossRefGoogle Scholar
  88. 87.
    DOWLING RH, MACK E, SMALL DM: Biliary lipid secretion and bile composition after acute and chronic interruption of enterohepatic circulation in the rhesus monkey. IV. Primate biliary physiology. J Clin Invest 50: 1917–1926, 1971.Google Scholar
  89. 88.
    NILSSON S, SCHERSTEN T: Influence of bile acids on the synthesis of biliary phospholipids in man. Europ J Clin Invest 1: 109–111, 1970.PubMedCrossRefGoogle Scholar
  90. 89.
    GRUNDY SM, METZGER AL, ADLER RD: Mechanisms of lithogenic bile formation in American Indian women with cholesterol gallstones. J Clin Invest 51: 3026–3043, 1972.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1975

Authors and Affiliations

  • Henry O. Wheeler
    • 1
  1. 1.University HospitalUniversity of California, San Diego School of MedicineSan DiegoUSA

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