SpringerLink
Log in

Liver Metabolic Zonation and Hepatic Microcirculation in Carbon Tetrachloride-Induced Experimental Cirrhosis

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The exact cause of the hepatic failure in livercirrhosis is currently unclear, and two main theorieshave been proposed: the first is based on the alteredhepatocyte function (sick hepatocyte hypothesis); the second on the abnormal hepatic architecture(intact hepatocyte hypothesis). Moreover, themicrocirculation, a fundamental component in liverstructure, shows dramatic changes in cirrhosis thatwould heavily influence the development of thedisease. In order to determine the importance of themicrovascular alterations on liver morphofunctionalfeatures in experimentally induced cirrhosis, theirrelationships with structural, ultrastructural, andhistoenzymological hepatocyte modifications wereinvestigated. Experimental cirrhosis was induced withcontrolled intragastric CCl4 administration.Scanning electron microscopy of the vascular corrosion casttechnique, associated with light microscopy,transmission electron microscopy, and histoenzymologytechniques were employed. The results demonstrated acharacteristic micronodular cirrhosis in all the liversstudied; the microcirculation displayed the presence ofnewly formed perinodular plexus. Inside the nodule,areas with two or more hepatocyte-thick laminae were present. Moreover, a rearrangement of thehepatocyte quantitative ultrastructure without realpathological changes and a loss of normal metaboliclobular zonation were noted in the liver parenchyma.These findings support the concept that theprogressive modifications of the microcirculation duringexperimental CCl4 cirrhosis modify not onlythe normal blood flow direction, but also the normalhepatic metabolic gradient with a loss of the normal hepatocyticzonation.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Gross JB Jr, Reichen J, Zeltner TB, Zimmermann A: The evolution of changes in quantitative liver function tests in a rat model of biliary cirrhosis: Correlation with morfometric measurement of hepatocyte mass. Hepatology 7:457–463, 1987

    Google Scholar 

  2. Reichen J, Hoilien C, Le M, Jones RH: Decreased uptake of taurocholate and ouabain by hepatocytes isolated from cirrhotic rat liver. Hepatology 7:67–70, 1987

    Google Scholar 

  3. Pessayre D, Lebrec D, Descatoire V, Peignoux M, Benhamou JP: Mechanism for reduced drag clearance in patients with cirrhosis. Gastroenterology 74:566–571, 1978

    Google Scholar 

  4. Wood AJJ, Villeneuve JP, Branch RA, Rogers LW, Shand DJ: Intact hepatocyte theory of impaired drug metabolism in experimental cirrhosis in the rat. Gastroenterology 76:1358–1362, 1979

    Google Scholar 

  5. Vaubourdolle M, Gufflet V, Guechot J, Ballet F, Jaillon P, Giboudeau J, Poupon R: Evidence of the intact hepatocyte theory in alcoholic cirrhosis. Scand J Gastroenterol 24:467–474, 1989

    Google Scholar 

  6. Schaffner F, Popper H: Capillarization of hepatic sinusoids in man. Gastroenterology 44:239–242, 1963

    Google Scholar 

  7. Martinez-Hernandez M, Martinez J: The role of capillarization in hepatic failure: Studies in carbon tetracloride induced cirrhosis. Hepatology 14:864–874, 1991

    Google Scholar 

  8. Conn OH, Atterbury CE: Cirrhosis. In Disease of the Liver, 7 ed., L Schiff, ER Schiff (eds). Philadelphia, Lippincott, 1993, pp 875–934

    Google Scholar 

  9. Rappaport AM, Macphee PJ, Fisher PJ, Fischer MM, Phillips MJ: The scarring of the liver acini (cirrhosis). Tridimensional and microcirculatory considerations. Virchows Arch (A) 402:107–137, 1983

    Google Scholar 

  10. Gaudio E, Pannarale L, Ripani M, Onori P, Riggio O: The hepatic microcirculation in experimental cirrhosis a scanning electron microscopy study of microcorrosion cast. Scanning Microsc 5:495–503, 1991

    Google Scholar 

  11. Gaudio E, Pannarale L, Onori P, Riggio O: A scanning electron microscopic study of liver microcirculation disarrangement in experimental rat cirrhosis. Hepatology 17:477–485, 1993

    Google Scholar 

  12. Rappaport AM: Hepatic blood flow. In Liver and Biliary Tract Physiology I. International Review of Physiology, Vol. 21. NB Javit (ed). Baltimore, University Park Press, 1980, pp 1–63

    Google Scholar 

  13. Gumucio JJ, Miller DL: Functional implications of liver cell heterogenety. Gastroenterology 80:393–403, 1981

    Google Scholar 

  14. Gumucio JJ, Miller DL: Zonal hepatic function: solute-hepatocyte interactions within the liver acinus. In H Popper, F Schaffner (eds) Progresses in Liver Disease, Vol VII. New York, Grune & Stratton, 1982, pp 17–30

    Google Scholar 

  15. Sokal EM, Trivedi P, Cheeseman P, Portmann B, Mowat AP: The application of quantitative cytochemistry to study the acinar distribution of enzimatic activities in human liver biopsy sections. J Hepatol 9:42–48, 1989

    Google Scholar 

  16. Kats N, Jungermann K: Metabolic heterogeneity of the liver. In Hepatic Transport and Bile Secretion: Physiology and Pathophysiology. N Tavoloni, PD Berk (eds). New York, Raven Press, 1993, pp 55–70

    Google Scholar 

  17. Sokal EM, Trivedi P, Portmann B, Mowat AP: Adaptative changes of metabolic zonation during the development of cirrhosis in growing rats. Gastroenterology 99:785–792, 1990

    Google Scholar 

  18. Sokal EM, Mostin J, Buts JP: Liver metabolic zonation in rat biliary cirrhosis: Distribution is reverse of that in toxic cirrhosis. Hepatology 5:904–908, 1992

    Google Scholar 

  19. Sokal EM, Collette E, Buts JP: Persistence of a liver metabolic zonation in extra-hepatic biliary atresia cirrhotic livers. Pediatr Res 30:286–289, 1991

    Google Scholar 

  20. Loud AV: A quantitative stereological description of the ultrastructure of normal rat liver parenchymal cells. J Cell Biol 37:27–46, 1968

    Google Scholar 

  21. Weibel ER, Staubli W, Gnagi IR, Hess FA: Correlated morphometric and biochemical studies on the liver cell. J Cell Biol 12:68–91, 1969

    Google Scholar 

  22. Proctor E, Chatamra K: Standardized micronodular cirrhosis in the rat. Eur Surg Res 16:182–186, 1984

    Google Scholar 

  23. Ariosto F, Riggio O, Cantafora A, Colucci S, Gaudio E, Mechelli C, Merli M, Seri S, Capocaccia L: Carbon tetrachloride-induced experimental cirrhosis in the rat: A reappraisal of the model. Eur Surg Res 21:280–286, 1989

    Google Scholar 

  24. Carpino F, Gaudio E, Marinozzi G, Melis M, Motta PM: A scanning and transmission electron microscopic study of experimental extrahepatic cholestasis in the rat. J Submicrosc Cytol 13:581–598, 1981

    Google Scholar 

  25. Alvaro D, Angelico M, Cantafora A, Gaudio E, Gandin C, Santini MT, Masella R, Capocaccia L: Improvement of estradiol 17β-D-glucuronide cholestasis by intravenous administration of dimethylethanolamide in the rat. Hepatology 13:1158–1172, 1991

    Google Scholar 

  26. Jones AL, Schmucker DL: Current concepts of liver structure as related to function. Gastroenterology 73:833–851, 1977

    Google Scholar 

  27. Jones AL, Schmucker DL, Mooney JS, Adler RD, Ockner R: A quantitative analysis of hepatic ultrastructure in rat during enhanced bile secretion. Anat Rec 192:277–288, 1978

    Google Scholar 

  28. Jones AL, Schmucker DL, Mooney JS, Ockner RK, Adler RD: Alterations in hepatic pericanalicular citoplasm during enhanced bile secretory activity. J Lab Invest 40:512–517, 1979

    Google Scholar 

  29. Hodde KC, Miodonski A, Bakker C, Veltman WAM. SEM of microcorrosion casts with special attention on arterio-venous differences and application to the rat cochlea. Scanning Electron Microsc 2:477–484, 1977

    Google Scholar 

  30. Miodonski AJ, Jasinski A: SEM study of microcorrosion casts of the vascular bed in the skin of the spotted salamander. Cell Tissue Res 196:153–162, 1979

    Google Scholar 

  31. Lametschwandtner A, Lametschwandtner U, Weiger T: Scanning electron microscopy of vascular corrosion casts. Technique and applications: updated review. Scanning Microsc 4:889–941, 1990

    Google Scholar 

  32. Pannarale L, Onori P, Ripani M, Gaudio E: Retinal microcirculation as revealed by SEM corrosion casts in the rat. Eur J Ophthalmol 1:96–102, 1991

    Google Scholar 

  33. Miodonski AJ, Jasinski A: SEM study of microcorrosion casts of the vascular bed in the skin of the spotted salamander. Cell Tissue Res 196:153–162, 1979

    Google Scholar 

  34. Krahenbuhl S, Weber FL Jr, Brass EP: Decreased hepatic glicogen content and accellerated response to starvation in rats with carbon tetrachloride-induced cirrhosis. Hepatology 14:1189–1195, 1991

    Google Scholar 

  35. Sherman IA, Pappas SC, Fisher MM: Hepatic microvascular changes associated with development of liver fibrosis and cirrhosis. Am J Physiol 258:H460, 1990

    Google Scholar 

  36. Mitra SK: The terminal distribution of the hepatic artery with special reference to arterio-portal anastomosis. J Anat 100:651–663, 1977

    Google Scholar 

  37. Kirk AP, Jain S, Pocock S, Thomas HC, Sherlock S: Late results of the Royal Free Hospital prospective controlled trial of prednisolone therapy in hepatitis B surface antigen negative chronic active hepatitis. Gut 21:78–83, 1980

    Google Scholar 

  38. Kershenobich D, Vargas F, Garcia-Tsao G, Tamayo RP, Gent M, Rojkind M: Colchicine in the treatment of cirrhosis of the liver. N Engl J Med 318:1709–1784, 1988

    Google Scholar 

  39. Hanauske-Abel HM: Liver selective fibrosuppression: A new approach in therapy of liver fibrosis. J Hepatol 13(suppl 3):S8–S16, 1991

    Google Scholar 

  40. Li J, Kim CI, Leo MA, Mack KM, Rojkind M, Lieber CS: Polyunsaturated lecithin prevents acetaldehyde-mediated hepatic collagen accumulation by stimulating collagenase activity in cultured lypocytes. Hepatology 15:373–381, 1992

    Google Scholar 

  41. Friedman SL: The cellular basis of hepatic fibrosis. Mechanism and treatment strategies. N Engl J Med 328:1828–1835, 1993

    Google Scholar 

  42. Grace ND: The side-to-side portacaval shunt revisited. N Engl J Med 330:208–209, 1994

    Google Scholar 

  43. Rössle M, Haag K, Ochs A, Sellinger M, Noldge G, Perarnau JM, Berger E, Blum U, Gabelmann A, Hauenstein K, Langer M, Gerok W: The transjugular intrahepatic portosystemic stent-shunt procedure for variceal bleeding. N Engl J Med 330:165–171, 1994

    Google Scholar 

Download references

Authors
  1. Eugenio Gaudio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paolo Onori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonio Franchitto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roberta Sferra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Oliviero Riggio
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gaudio, E., Onori, P., Franchitto, A. et al. Liver Metabolic Zonation and Hepatic Microcirculation in Carbon Tetrachloride-Induced Experimental Cirrhosis. Dig Dis Sci 42, 167–177 (1997). https://doi.org/10.1023/A:1018813911469

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018813911469

Search

Navigation