Skip to main content
SpringerLink
Log in

Causation and Consequences of Cholestasis: An Overview

  • Chapter
Jaundice

Part of the book series: Hepatology ((H,volume 2))

Abstract

“Intrahepatic cholestasis” was coined in 1952 to describe the morphologic findings in the liver when clinical and laboratory features pointed to biliary obstruction and none was found (1). That the condition could be caused by drugs was recognized more than a decade earlier (2). It was originally called intrahepatic obstructive jaundice and many proposals have been made about the mechanism by which the phenomenon is produced.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. POPPER H, SCHAFFNER F: Laboratory diagnosis of liver disease. Coordinated use of histological and biochemical observations. JAMA 150: 1367–1372, 1952.

    Article  CAS  Google Scholar 

  2. HANGER FM, GUTMAN AB: Postarsphenamine jaundice apparently due to obstruction of intrahepatic biliary tract. JAMA 115: 263–271, 1940.

    Article  Google Scholar 

  3. RÖSSLE R: Die cholangiolitische Zirrhose. In Entzütndungen der Leber, vol. 5, no. 1, of Handbuch der speziellen pathologischen Anatomie und Histologie. Ed. F Henke, O Lubarsch. Berlin, Springer, 1939, pp 448–452.

    Google Scholar 

  4. WATSON CJ, HOFFBAUER FW: Problem of prolonged hepatitis with particular reference to cholangiolitic type and to development of cholangiolitic cirrhosis of liver. Ann Intern Med 25: 195–227, 1946.

    PubMed  CAS  Google Scholar 

  5. POPPER H, SZATO PB: Intrahepatic cholestasis (“cholangio-litis”). Gastroenterology 31: 683–699, 1956.

    PubMed  CAS  Google Scholar 

  6. WACHSTEIN M, MEISEL E: Histochemistry of hepatic phosphatase at a physiologic pH. With special reference to the demonstration of bile canaliculi. Am J Clin Pathol 27: 13–23, 1957.

    PubMed  CAS  Google Scholar 

  7. ROUILLER C: Les canalicules biliares. Etude au microscope electronique. Acta Anat (Basel) 26: 94–109, 1956.

    Article  CAS  Google Scholar 

  8. SCHAFFNER F, POPPER H: Morphologic studies of cholestasis. Gastroenterology 37: 565–573, 1959.

    PubMed  CAS  Google Scholar 

  9. STEINER JW, JEZEQUEL AM, PHILLIPS MJ, et al: Some aspects of the ultrastructural pathology of the liver. In Progress in Liver Diseases, vol. 2. Ed. H. Popper, F. Schaffner. New York, Grune and Stratton, 1965. pp. 303–372.

    Google Scholar 

  10. ZAKI FG: Ultrastructure of hepatic cholestasis. Medicine 45: 537–545, 1966.

    Article  PubMed  CAS  Google Scholar 

  11. SCHATZKI P: The passage of radioactive lanthanum from the biliary to the vascular system. An electron microscopic and radioactive tracer study. Z Zellforsch 119: 451–459, 1971.

    Article  PubMed  CAS  Google Scholar 

  12. DEWOLF-PEEERS C, DEVOS R, DESMET V: Histochemical evidence of a cholestatic period in neonatal rats. Pediatr Res 5: 704–709, 1971.

    Article  Google Scholar 

  13. TOULOUKIAN RJ, DOWNING SE: Cholestasis associated with long-term parenteral hyperalimentation. Arch Surg 106: 58–62, 1973.

    Article  PubMed  CAS  Google Scholar 

  14. LEVINE G, FAVARA BE, MIERAU G, BAILEY WC: Jaundice, liver ultrastructure, and congenital pyloric stenosis. Arch Pathol 95: 267–270, 1973.

    PubMed  CAS  Google Scholar 

  15. RAGER R, FINEGOLD MJ: Cholestasis in low birth weight prematures: is parenteral alimentation the cause? Am J Pathol 74: 6a–7a, 1974.

    Google Scholar 

  16. WILLS EJ, EPSTEIN ME: Subcellular changes in surface adenosine triphosphatase activity of human liver in extrahepatic obstructive jaundice. Am J Pathol 49605–635, 1966.

    PubMed  CAS  Google Scholar 

  17. DESMET VJ: Morphologic and histochemical aspects of cholestasis. In Progress in Liver Diseases, vol. 4. Ed. H. Popper, F. Schaffner. New York, Grune and Stratton, 1972. pp. 97–132.

    Google Scholar 

  18. STEINER JW, CARRUTHERS JS: Studies on the fine structure of the terminal branches of the biliary tree. II. Observations of pathologically altered bile canaliculi. Am J Pathol 39 41–63, 1961.

    PubMed  CAS  Google Scholar 

  19. HAMPTON JC: Electron microscopic study of extrahepatic biliary obstruction in the mouse. Lab Invest 10: 502–513, 1961.

    PubMed  CAS  Google Scholar 

  20. POPPER H: Cholestasis. Ann Rev Med 19: 39–56, 1968.

    Article  PubMed  CAS  Google Scholar 

  21. DUBIN IN, PETERSON LH: An explanation for the centrolobular localization of intrahepatic bile stasis in acute liver diseases. Am J Med Sci 236: 45–52, 1958.

    Article  PubMed  CAS  Google Scholar 

  22. SCHAFFNER F, KNIFEEN JC: Electron microscopy as related to hepatotoxicity. Ann NY Acad Sci 104: 847–857, 1963.

    Google Scholar 

  23. SCHAFFNER F, JAVITT NB: Morphologic changes in hamster liver during intrahepatic cholestasis induced by taurolithocholate. Lab Invest 15: 1783–1792, 1966.

    PubMed  CAS  Google Scholar 

  24. JAVITT NB, EMERMAN S: Effect of sodium tarolithocholate on bile flow and bile acid excretion. J Clin Invest 47: 1002–1014, 1968.

    Article  PubMed  CAS  Google Scholar 

  25. HUTTRER F, KLION FM, WENGRAF A, et al: Hepatocellular adaptation and injury. Structural and biochemical changes following dieldrin and methyl butter yellow. Lab Invest 20: 455–464, 1969.

    Google Scholar 

  26. BOYD GS, PERCY-ROBB IW: Enzymatic regulation of bile acid synthesis. Am J Med 51: 580–587, 1971.

    Article  PubMed  CAS  Google Scholar 

  27. SCHAFFNER F, POPPER H: Hypothesis: cholestasis is the result of hypoactive hypertrophic smooth endoplasmic reticulum in the hepatocyte. Lancet 2: 355–359, 1969.

    Article  PubMed  CAS  Google Scholar 

  28. MAKINO I, SJOVALL J, NORMAN A, et al: Excretion of 3ß-hydroxy-5-cholanoic and 3hydroxy-5cholanoic acids in urine of infants with biliary atresia. FEBS Letters15: 161–164, 1971.

    Article  PubMed  CAS  Google Scholar 

  29. BACK P: Identification and quantitative determination of urinary bile acids excreted in cholestasis. Clin Chilli Acta 44: 199–207, 1973.

    Article  CAS  Google Scholar 

  30. HUTTERER F, BACCHIN PG, RAISFELD IH, et al: Alteration of microsomal biotransformation in the liver in cholestasis. Proc Soc Exp Biol Med 133: 702–706, 1970.

    PubMed  CAS  Google Scholar 

  31. FISHER MM, MAGNUSSON R, MIYAI K: Bile acid metabolism in mammals. I. Bile acid-induced intrahepatic cholestasis. Lab Invest 25: 88–91, 1971.

    PubMed  CAS  Google Scholar 

  32. HUTTERER F, DENK H, BACCHIN PG, et al: Mechanism of cholestasis. I. Effect of bile acids on microsomal cytochrome P-450 dependent biotransformation system in vitro. Life Sci 9: 877–887, 1970.

    Article  CAS  Google Scholar 

  33. GREIM H, TRULZSCH D, ROBOZ J, et al: Mechanism of cholestasis. 5. Bile acids in normal rat livers and in those after bile duct ligation. Gastroenterology 63: 837–845, 1972.

    PubMed  CAS  Google Scholar 

  34. GREIM H, TRULZSCH D, CZYGAN P, et al: Mechanism of cholestasis. 6. Bile acids in human livers with or without biliary obstruction. Gastroenterology 63: 846–850, 1972.

    PubMed  CAS  Google Scholar 

  35. SCHAFFNER F, BACCHIN PG, HUTTERER F, et al: Mechanism of cholestasis. 4. Structural and biochemical changes in the liver and serum in rats after bile duct ligation. Gastroenterology 60: 888–897, 1971.

    PubMed  CAS  Google Scholar 

  36. DENK H, GREIM H, HUTTERER F, et al: Turnover of hepatic cytochrome P-450 in experimental cholestasis. Exp Mol Pathol 19: 241–247, 1973.

    Article  PubMed  CAS  Google Scholar 

  37. MACKINNON AM, SIMON FR: Reduced synthesis of hepatic microsomal cytochrome P-450 in the bile duct ligated rat. Biochem Biophys Res Commun 56: 437–443, 1974.

    Article  PubMed  CAS  Google Scholar 

  38. POPPER H, SCHAFFNER F: Pathophysiology of cholestasis. Hum Pathol 1: 1–24, 1970.

    Article  PubMed  CAS  Google Scholar 

  39. SCHERSTEN T: Metabolic differences between hepatitis and cholestasis in human liver. In Progress in Liver Diseases, vol. 4. Ed. H. Popper, F. Schaffner. New York, Grune and Stratton, 1972. pp. 133–150.

    Google Scholar 

  40. SEIDEL D, ALAUPOVIC P, FURMAN RH: A lipoprotein characterizing obstructive jaundice. I. Method for quantitative separation and identification of lipoproteins in jaundiced subjects. J Clin Invest 48: 1211–1223, 1969.

    Article  PubMed  CAS  Google Scholar 

  41. HARRY DS, DINI M, McINTYRE N: Effect of cholesterol feeding and biliary obstruction on hepatic cholesterol biosynthesis in the rat. Biochim Biophys Acta 296: 209–220, 1973.

    Article  PubMed  CAS  Google Scholar 

  42. KATTERMAN R, CREUTZFELDT W: The effect of experimental cholestasis on the negative feedback regulation of cholesterol in rat liver. Scand J Gastroenterol 5: 337–342, 1970.

    Google Scholar 

  43. WEIS JH, DIETSCHY JM: Presence of an intact cholesterol feedback mechanism in the liver in biliary stasis. Gastroenterology 61; 77–84, 1971.

    PubMed  CAS  Google Scholar 

  44. CARRUTHERS JS, STEINER JW: Experimental extrahepatic biliary obstruction: fine structural changes of liver cell mitochondria. Gastroenterology 42: 419–430, 1962.

    PubMed  CAS  Google Scholar 

  45. KILLENBERG PG, HOPPEL CL: Inhibition of rat liver mitochondrial oxidative phosphorylation by sulfobromophthalein. Mol Pharmacol 10: 108–118, 1974.

    PubMed  CAS  Google Scholar 

  46. OZAWA K, TAKASAN H, KITAMURA O, et al: Alteration in liver mitochondrial metabolism in a patient with biliary obstruction due to liver carcinoma. Am J Surg 126: 653–657, 1973.

    Article  PubMed  CAS  Google Scholar 

  47. LEE MJ, WHITEHOUSE MW: Inhibition of electron transport and coupled phosphorylation in liver mitochondria by cholanic (bile) acids and their conjugates. Biochim Biophys Acta 100: 317–328, 1965.

    Article  PubMed  CAS  Google Scholar 

  48. WITZLEBEN CL: Hepatic ultrastructural effects of cholic acid overload. Exp Mol Pathol 16: 47–53, 1972.

    Article  PubMed  CAS  Google Scholar 

  49. KYAI K, PRICE VM, FISHER MM: Bile acid metabolism in mammals. Ultrastructural studies on the intrahepatic cholestasis induced by lithocholic and chenodeoxycholic acids in the rat. Lab Invest 24: 292–302, 1971.

    Google Scholar 

  50. BOYCE W, WITZLEBEN CL: Bilirubin as a cholestatic agent. II.Effect of variable doses of bilirubin on the severity of mangane sebilirubin cholestasis. Am J Pathol 72: 427–431, 1973.

    PubMed  CAS  Google Scholar 

  51. FULOP M, KATZ S, LAWRENCE C: Extreme hyperbilirubinemia. Arch Int Med 127: 254–258, 1971.

    Article  CAS  Google Scholar 

  52. MULDER GJ: The rate limiting step in the biliary elimination of some substrates of uridine diphosphate glucuronyl transferase in the rat. Biochem Pharmacol 22: 1751–1763, 1973.

    Article  PubMed  CAS  Google Scholar 

  53. ALPERT S, MOSHER M, SHANSKE A et al: Multiplicity of hepatic excretory mechanisms for organic anions. J Gen Physiol 53: 238–247, 1969.

    Article  PubMed  CAS  Google Scholar 

  54. SIMON FR, ARIAS IM: Alteration of bile canalicular enzymes in cholestasis. A possible cause of bile secretory failure. J Clin Invest 52: 765–775, 1973.

    Article  PubMed  CAS  Google Scholar 

  55. ESSNER E, NOVIKOFF A, MASEK B: Adenosinetriphosphatase activities in the plasma membrane of liver cells as revealed by electron microscopy. J Biochem Biophys Cytol 4: 711–716, 1958.

    Article  CAS  Google Scholar 

  56. SANDSTROM B: The functional significance of bile canalicular nucleoside phosphatase activity. Histochemie 25: 9–14, 1971.

    Article  PubMed  CAS  Google Scholar 

  57. HOLZNER J: Fermenthistochemische Untersuchungen au Leberbiopsien. Verh Dtsch Ged Pathol 44: 233–237, 1960.

    CAS  Google Scholar 

  58. ERLINGER S, DHUMEAUX D: Mechanisms and control of secretion of bile water and electrolytes. Gastroenterology 66: 281–304, 1974.

    PubMed  CAS  Google Scholar 

  59. DUMONT M, ERLINGER S: Influence of hydrocortisone on bile formation in the rat. Biol Gastroenterol (Paris) 6: 197–203, 1973.

    CAS  Google Scholar 

  60. SPERBER I: Biliary secretion of organic anions and its influence on bile flow. In The Biliary System. A Symposium of the NATO Advanced Study Institute. Ed. W. Taylor, Philadelphia, F.A. Davis, 1965. pp. 457–467.

    Google Scholar 

  61. SIMON FR, ARIAS IM: Alterations in liver plasma membranes and their possible role in cholestasis. Gastroenterology62: 342–345, 1972.

    PubMed  CAS  Google Scholar 

  62. JAVITT NB: The cholestatic syndrome -1971. Am J Med 51: 637–641, 1971.

    Article  PubMed  CAS  Google Scholar 

  63. HERNDON JH Jr: Pathophysiology of pruritus associated with elevated bile acids in serum. Arch Intern Med 130: 632–637, 1972.

    Article  Google Scholar 

  64. MIYAI K, MAYR W, RICHARDSON A: Freeze fracture study of bile canalicular changes induced by lithocholic acid. Lab Invest 30: 384, 1974.

    Google Scholar 

  65. COOPER AD, JONES AL, KOLDINGER RE, et al: Selective biliary obstruction: a model for the study of lipid metabolism in cholestasis. Gastroenterology 66: 574–585, 1974.

    PubMed  CAS  Google Scholar 

  66. CLAUDE A: Growth and differentiation of cytoplasmic membranes in the course of lipoprotein granule synthesis in the hepatic cell. I.Elaboration of elements of the Golgi complex. J Cell Biol 47: 745–766, 1970.

    Article  PubMed  CAS  Google Scholar 

  67. STEIN O, BAR-ON H, STEIN Y: Lipoproteins and the liver. In Progress in Liver Diseases, vol. 4. Ed. H. Popper, F. Schaffner. New York, Grune and Stratton, 1972. pp. 45–62.

    Google Scholar 

  68. REYES H, LEVI AJ, GATMAITAN Z, et al: Studies of Y and Z, two hepatic cytoplasmic anion-binding proteins: effect of drugs, chemicals, hormones, and cholestasis. J Clin Invest 50: 2242–2252, 1971.

    Article  PubMed  CAS  Google Scholar 

  69. ’STEINER JW, CARRUTHERS JS: Experimental extrahepatic biliary obstruction. Some aspects of the fine sturctural changes of bile ductules and pre-ductules (Ducts of Hering). Am J Pathol 40: 253–270, 1962.

    PubMed  CAS  Google Scholar 

  70. SASAKI H, SCHAFFNER F, POPPER H: Bile ductules in cholestasis. Morphologic evidence for secretion and absorption in man. Lab Invest 16: 84–95, 1967.

    PubMed  CAS  Google Scholar 

  71. SCHAFFNER F, POPPER H: Electron microscopic studies of normal and proliferated bile ductules. Am J Pathol 38: 393–410, 1961.

    PubMed  CAS  Google Scholar 

  72. STEINER JW, CARRUTHERS JS, KALIFAT SR: The ductular cell reaction of rat liver in extrahepatic cholestasis. I. Proliferated biliary epithelial cells. Exp Md. Pathol 1; 162–185, 1962.

    Article  CAS  Google Scholar 

  73. GUZELIAN P, BOYER JL: Glucose reabsorption from bile. Evidence for a biliohepatic circulation. J Clin Invest 53: 526–535, 1974.

    Article  PubMed  CAS  Google Scholar 

  74. SCHAFFNER F, SCHARNBECK HH, HUTTERER F, et al: Mechanism of cholestasis. VII: naphthylisothiocyanate induced jaundice. Lab Invest 28: 321–331, 1973.

    PubMed  CAS  Google Scholar 

  75. KLION FM, SCHAFFNER F: Electron microscopic observations in primary biliary cirrhosis. Arch Pathol (Chicago) 81: 152–161, 1966.

    PubMed  CAS  Google Scholar 

  76. HUNT R, LEVEILLE G, SAUBERLICH H: Dietary bile acids and lipid metabolism. Effects of lithocholic acid in mammalian species. Proc Soc Exp Biol Med 115: 277–280, 1964.

    PubMed  CAS  Google Scholar 

  77. PALMER RH, HRUBAN Z: Production of bile duct hyperplasia and gallstones by lithocholic acid. J Clin Invest 45: 1255–1267, 1966.

    Article  PubMed  CAS  Google Scholar 

  78. BIAVA C: Studies on cholestasis. The fine structure and morphogenesis of hepatocellular and canalicular bile pigment. Lab Invest 13: 1099–1123, 1964.

    PubMed  CAS  Google Scholar 

  79. HOLLANDER M, SCHAFFNER F: Electron microscopic studies in biliary atresia. I. Bile ductular proliferation. Am J Pis Child 116: 49–56, 1968.

    CAS  Google Scholar 

  80. GERBER MA, ORR W, DENK H, et al: Hepatocellular hyalin in cholestasis and cirrhosis: its diagnostic significance. Gastroenterology 64: 89–98, 1973.

    PubMed  CAS  Google Scholar 

  81. JAVITT NB, MORRISSEY KP, SIEGEL E, et al: Cholestatic syndromes in infancy: diagnostic value of serum bile acid pattern and cholestyramine administration. Pediatr. Res 7: 119–125, 1973.

    Article  PubMed  CAS  Google Scholar 

  82. SHARP HL, MIRKIN BL: Effect of phenobarbital on hyperbilirubinemia, bile acid metabolism and microsomal enzyme activity in chronic intrahepatic cholestasis of childhood. J Pediatr 81; 116–126, 1972.

    Article  PubMed  CAS  Google Scholar 

  83. BRAUN W, WOCKEL W, GIERTLER U, et al: Phenobarbital behandlung der benignen rezidivierenden intrahepatischen Cholestase. Schweiz Med Wochensc 102: 1769–1772, 1972.

    CAS  Google Scholar 

  84. STIEHL A, THALER MM, ADMIRAND WH: Effects of phenobarbital on bile salt metabolism in cholestasis due to bile duct hypoplasia. Pediatrics 51: 992–997, 1973.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Stratton Laboratory for Liver Diseases, Mount Sinai School of Medicine, The City University of New York, New York, N.Y., 10029, USA

    Fenton Schaffner & Hans Popper

Authors
  1. Fenton Schaffner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hans Popper
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. McGill University, Montreal, Quebec, Canada

    Carl A. Goresky M.D. (Professor of Medicine) (Professor of Medicine)

  2. University of Toronto, Toronto, Ontario, Canada

    Murray M. Fisher M.D. (Associate Professor of Medicine and Pathology) (Associate Professor of Medicine and Pathology)

Rights and permissions

Reprints and permissions

Copyright information

© 1975 Plenum Press, New York

About this chapter

Cite this chapter

Schaffner, F., Popper, H. (1975). Causation and Consequences of Cholestasis: An Overview. In: Goresky, C.A., Fisher, M.M. (eds) Jaundice. Hepatology, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-2649-6_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-2649-6_20

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-2651-9

  • Online ISBN: 978-1-4684-2649-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation