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Anatomy and Vascular Biology of the Cells in the Portal Circulation

  • Chapter
Portal Hypertension

Part of the book series: Clinical Gastroenterology ((CG))

Abstract

Portal hypertension occurring during the natural course of liver cirrhosis is a consequence of the increased intrahepatic resistance to portal flow. For a long time, this phenomenon has been ascribed only to the profound changes of liver tissue angioarchitecture consequent to the progression of the fibrogenic process. However, studies performed during the last decade have demonstrated that there is also an increased vascular tone that could be modulated to a certain extent by pharmacological agents. The aim of this chapter is to provide general information on the anatomy of the portal systems and on the regulation of vascular tone in this specific vascular district and in the splanchnic circulation. Information about the collateral circulation that becomes relevant in the case of portal hypertension is also provided.

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References

  1. Battaglia DM, Wanless IR, Brady AP, Mackenzie RL. Intrahepatic sequestered segment of liver presenting as focal fatty change. Am J Gastroenterol 1995;90:2238–2239.

    PubMed  CAS  Google Scholar 

  2. Madding GF, Kennedy PA. Trauma of the liver. In: Calne RY’s Liver Surgery with Operative Color Illustrations. WB Saunders, Philadelphia, PA, 1982, p. 5.

    Google Scholar 

  3. Douglas BE, Baggenstoss AH, Hollinshead WH. The anatomy of the portal vein and its tributaries. Surg Gynecol Obstet 1979;91:562–576.

    Google Scholar 

  4. Bosch J, Navasa M, Garcia-Pagán JC, De Locy AM, Rodes J. Portal hypertension. Med Clin North Am 1989;73:931–953.

    PubMed  CAS  Google Scholar 

  5. Popper H, Elias H, Petty DE. Vascular pattern of the cirrhotic liver. Am J Clin Pathol 1952;22:717–722.

    PubMed  CAS  Google Scholar 

  6. Vianna A, Hayes PC, Moscoso G, et al. Normal venous circulation of the gastresophageal junction. A route to understanding varices. Gastroenterology 1987;93:876–889.

    PubMed  CAS  Google Scholar 

  7. Crissinger KD, Granger DN. Gastrointestinal blood flow. In: Yamada T, et al., eds. Textbook of Gastroenterology. Lippincott-Williams & Wilkins, Philadelphia, PA, 1999, p. 519.

    Google Scholar 

  8. Granger DN, Kvietys PR, Korthuis R, Premen AJ. Microcirculation of the intestinal mucosa. In: Wood ID, ed. Handbook of Gastrointestinal Physiology. American Physiological Society, 1989, pp. 1405–1474.

    Google Scholar 

  9. Benoit IN, Korthuis RJ, Granger DN, Battarbee HD. Splanchnic hemodynamics in acute and chronic portal hypertension. In: Bonzon A, Blendis LM, eds. Cardiovascular Complications of Liver Disease. CRC, Boca Raton, FL, 1990, p. 179.

    Google Scholar 

  10. Jensen JE, Groszmann RJ. Pathophysiology of portal hypertension. In: Kaplowitz N, ed. Liver and Biliary Diseases. Williams & Wilkins, Baltimore, 1992, pp. 494–503.

    Google Scholar 

  11. Bioulac-Sage P, Lafon ME, Saric J, Balabaud C. Nerves and persinusoidal cells in human liver. J Hepatol 1990;10:105–112.

    Article  PubMed  CAS  Google Scholar 

  12. Wanless IR. Physioanatomic consideration. In: Schiff ER, Sorrel MF, Maddrey WC, ed. Schiff’s Diseases of the Liver, 8th ed., Lippincott-Raven, Philadelphia, PA, 1999, pp. 18,19.

    Google Scholar 

  13. Wisse E, De Zanger RB, Jacobs R, McCuskey RS. Scanning electron microscope observations on the structure of portal veins, sinusoids and central veins in rat liver. Scan Electron Microsc 1983;3:1441–1452.

    Google Scholar 

  14. Nopanitayo W, Grisham JW, Aghajanian JG, Carso JL. Intrahepatic microcirculation: SEM study of the terminal distribution of the hepatic artery. Scan Electron Microsc 1978;11:837–842.

    Google Scholar 

  15. Lautt WW. Relationship between hepatic blood flow and overall metabolism: the hepatic arterial buffer response. Fed Proc 1983;42:1662–1666.

    PubMed  CAS  Google Scholar 

  16. Ezzat WR, Lautt WW. Hepatic arterial pressure-flow autoregulation is adenosine mediated. Am J Physiol 1986;252:H836–H845.

    Google Scholar 

  17. Shikare SV, Baschir K, Abraham P, Tilve GH. Hepatic perfusion index in portal hypertension of cirrhotic and non cirrhotic aetiologies. Nucl Med Comm 1996;17:520–522.

    Article  CAS  Google Scholar 

  18. Rappaport AM. The microcirculatory hepatic unit. Microvasc Res 1973;6:212–218.

    Article  PubMed  CAS  Google Scholar 

  19. Yamamoto K, Sherman T, Phillips MJ, Fisher MM. Three-dimensional observation of the hepatic arterial terminations in the rat, hamster and human liver by scanning electron microscopy of micro vascular casts. Hepatology 1985;5:452–456.

    Article  PubMed  CAS  Google Scholar 

  20. Rappaport AM. Physioanatomic consideration. In: Schiff L, Schiff ER, eds. Diseases of the Liver. JB Lippincott, Philadelphia, PA, 1987, pp. 1–46.

    Google Scholar 

  21. Sherlock S, Doodley J. The portal venous system and portal hypertension. In: Sherlock S, Doodley J, eds. Disease of the Liver and Biliary System, 7th ed. Blackwell Science, Oxford, UK, 1997.

    Google Scholar 

  22. McCuskey RS, Reilly FD. Hepatic microvasculature: dynamic structure and its regulation. Semin Liver Dis 1993;13:1–12.

    PubMed  CAS  Google Scholar 

  23. Ternberg JL, Butcher HR Jr. Blood-flow relation between hepatic artery and portal vein. Science 1965;150:1030,1031.

    Article  PubMed  CAS  Google Scholar 

  24. Itai Y, Moss AA, Goldberg HI. Transient hepatic attenuation difference of lobar or segmental distribution detected by dynamic computed tomography. Radiology 1982;144:835–839.

    PubMed  CAS  Google Scholar 

  25. Kawasaki T, Carmichael FJ, Saldivia V, Roldan L, Orrego H. Relationship between portal venous and hepatic arterial blood flows. Spectrum of response. Am J Physiol 1990;259:1010–1018.

    Google Scholar 

  26. Braet F, Wisse E. Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: areview. Comp Hepatol 2002;1:1–17.

    Article  PubMed  Google Scholar 

  27. De Leeuw AM, Brouwer A, Knook DL. Sinusoidal endothelial cells of the liver: fine structure and function in relation to age. J Electron Microsc Tech 1990;14:218–236.

    Article  PubMed  Google Scholar 

  28. Wisse E, De Zanger RB, Charels K, Van Der Smissen P, McCuskey RS. The liver sieve: considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of Disse. Hepatology 1985;5:683–692.

    Article  PubMed  CAS  Google Scholar 

  29. Oda M, Kazemoto S, Kaneko H, et al. Involvement of Ca++-calmodulin-actomyosin system in the contractility of hepatic sinusoidal endothelial fenestrae. In: Knook DL, Wisse E, eds. Cells of the Hepatic Sinusoid 4. Kupffer Cell Foundation, Leiden, 1993, pp. 174–178.

    Google Scholar 

  30. Yokomori H, Oda M, Ogi M, et al. Hepatic sinusoidal endothelial fenestrae express plasma membrane Ca++pump and Ca++Mg++-ATPase. Liver 2000;20:458–464.

    Article  PubMed  CAS  Google Scholar 

  31. Steffan AM, Gendrault JL, Kim A. Increase in the number of fenestrae in mouse endothelial liver cells by altering the cytoskeleton with cytochalasin B. Hepatology 1987;7:1230–1238.

    Article  PubMed  CAS  Google Scholar 

  32. Wake K. Liver perivascular cells revealed by gold and silver impregnation methods and electron microscopy. In: Motta P, ed. Biopathology of the Liver, an Ultrastructural Approach. Kluwer, Dordrecht, 1988, pp. 23–26.

    Google Scholar 

  33. Pinzani M, Gentilini P. Biology of hepatic stellate cells and their possible relevance in the pathogcncsis of portal hypertension in cirrhosis. Semin Liver Dis 1999;397–410.

    Google Scholar 

  34. Pinzani M, Failli P, Ruocco C, et al. Fat-storing cells as liver-specific pericytes: spatial dynamics of agonist-stimulated intracellular calcium transients. J Clin Invest 1992;90:642–646.

    PubMed  CAS  Google Scholar 

  35. Kawada N, Klein H, Decker K. Eicoesanoid-mediated contractility of hepatic stellate cells. Biochem J 1992;285:367–371.

    PubMed  CAS  Google Scholar 

  36. Lafon ME, Bioulac-Sage P, LeBail N. Nerves and perisinusoidal cells in human liver. In: Wisse E, Knook DL, Decker K, eds. Cells of Hepatic Sinusoid. Kupffer Cell Foundation, Riswijk, 1989, pp. 230–234.

    Google Scholar 

  37. Ueno T, Inuzuka S, Torimura T, et al. Distribution of substance P and vasoactive intestinal peptide in the human liver. Light and electron immunoperoxidase methods of observation. Am J Gastroenterol 1991;138:1233–1242.

    Google Scholar 

  38. Knittel T, Aurisch S, Neubauer K, Eichhorst S, Ramadori G. Cell-type-specific expression of neural cell adhesion molecule (N-CAM) in Ito cells of rat liver. Am J Pathol 1996;149:449–462.

    PubMed  CAS  Google Scholar 

  39. Niki T, Pekny M, Hellemans K, et al. Class VI intermediate filament protein nestin is induced during activation of rat hepatic stellate cells. Hepatology 1999;29:520–527.

    Article  PubMed  CAS  Google Scholar 

  40. Cassiman D, van Pelt J, De Vos R, et al. Synaptosphysin: a novel marker for human and rat hepatic stellate cells. Am J Pathol 1999;155:1831–1839.

    PubMed  CAS  Google Scholar 

  41. Cassiman D, Denef C, Desmet VJ, Roskams T. Human and rat hepatic stellate cells express neurotrophins and neurotrophin receptors. Hepatology 2001;33:148–158.

    Article  PubMed  CAS  Google Scholar 

  42. Sherer TB, Neff PS, Hankins GR, Tuttle JB. Mechanisms of increased NGF production in vascular smooth muscle of the spontaneous hypertensive rat. Exp Cell Res 1998;241:186–193.

    Article  PubMed  CAS  Google Scholar 

  43. Hasan W, Zhang R, Liu M, Wain D, Smith PG. Coordinate expression of NGF and alpha-smooth muscle actin mRNA and protein in cutaneous wound tissue of developing and adult rats. Cell Tissue Res 2000;300:97–109.

    PubMed  CAS  Google Scholar 

  44. Ekataksin W, Kaneda K. Liver microvascular architecture: an insight into the pathophysiology of portal hypertension. Semin Liver Dis 1999;19:359–382.

    Article  PubMed  CAS  Google Scholar 

  45. Zhang JX, Pegoli W Jr, Clemens MG. Endothelin-1 induces direct constriction of hepatic sinusoids. Am J Physiol 1994;266:G624–G632.

    PubMed  CAS  Google Scholar 

  46. Zhang JX, Bauer M, Clemens MG. Vessel-and target cell-specific actions of endothelin-land endothelin-3 in rat liver. Am J Physiol 1995;269:G269–G277.

    PubMed  CAS  Google Scholar 

  47. Thimgan MS, Yee HF Jr. Quantitation of rat hepatic stellate cell contraction: stellate cells’ contribution to sinusoidal tone. Am J Physiol 1999;277:G137–G143.

    PubMed  CAS  Google Scholar 

  48. Yanagisawa M, Masaki T. Endothelin, a novel endothelium-derived peptide. Biochem Pharmacol 1989;38:1877–1883.

    Article  PubMed  CAS  Google Scholar 

  49. Simonson MS, Dunn MJ. Endothelins: a family of regulatory peptides. Hypertension 1991;17:856–863.

    PubMed  CAS  Google Scholar 

  50. Simonson MS. Endothelins: multifunctional renal peptides. Physiol Rev 1993;73:375–411.

    PubMed  CAS  Google Scholar 

  51. Gandhi CR, Stephenson K, Olson MS. Endothelin, a potent peptide agonist in the liver. J Biol Chem 1990;265:17,432–17,435.

    PubMed  CAS  Google Scholar 

  52. Roden M, Vierhapper H, Liener K, Waldhausl W. Endothelin-1-stimulated glucose production in vitro in the isolated perfused rat liver. Metabolism 1992;41:290–295.

    Article  PubMed  CAS  Google Scholar 

  53. Thran-Thi T-A, Kawada N, Decker K. Regulation of endothelin-1 action on the perfused rat liver. FEBS Lett 1993;318:353–357.

    Article  Google Scholar 

  54. Gandhi CR, Behal RH, Harvey SA, Nouchi TA, Olson MS. Hepatic effects of endothelin. Receptor characterization and endothelin-induced signal transduction in hepatocytes. Biochem J 1992;287:897–904.

    PubMed  CAS  Google Scholar 

  55. Serradeil-Le Gal C, Jouneaux C, Sanchez-Bueno A, et al. Endothelin action in rat liver. Receptors, free Ca2+ oscillations, and activation of glycogenolysis. J Clin Invest 1991;87:133–138.

    PubMed  CAS  Google Scholar 

  56. Rieder H, Ramadori G, Meyer zum Buschenfelde KH. Sinusoidal endothelial liver cells in vitro release endothelin: augmentation by transforming growth factor β and Kupffer cell-conditioned media. Klin Wochenschr 1991;69:387–391.

    Article  PubMed  CAS  Google Scholar 

  57. Furoya S, Naruse S, Nakayama T, Nokihara K. Binding of 125I-endothelin-l to fat-storing cells in rat liver revealed by electron microscopic radioautography. Anat Embryol 1992;185:97–100.

    Article  Google Scholar 

  58. Gondo K, Ueno T, Masaharu S, Sakisaka S, Sata M, Tanikawa K. The endothelin-1 binding site in rat liver tissue: light-and electron-microscopic autoradiographic studies. Gastroenterology 1993;104:1745–1749.

    PubMed  CAS  Google Scholar 

  59. Housset CN, Rockey DC, Bissel DM. Endothelin receptors in rat liver: lipocytes as a contractile target for endothelin 1. Proc Natl Acad Sci USA 1993;90:9266–9270.

    Article  PubMed  CAS  Google Scholar 

  60. Pinzani M, Milani S, DeFranco R, et al. Endothelin 1 is overexpressed in human cirrhotic liver and exerts multiple effects on activated hepatic stellate cells. Gastroenterology 1996;110:534–548.

    Article  PubMed  CAS  Google Scholar 

  61. Rockey DC. Fouassier L, Chung JJ, etal. Cellular localization of endothelin-1 and increased production in liver injury in the rat: potential for autocrine and paracrine effects on stellate cells. Hepatology 1998;27:472–480.

    Article  PubMed  CAS  Google Scholar 

  62. Gabriel A, Kuddus RH, Rao AS, Watkins WD, Ghandi CR. Superoxide-induced changes in endothelin (ET) receptors in hepatic stellate cells. J Hepatol 1998;29:614–627.

    Article  PubMed  CAS  Google Scholar 

  63. Shao R, Yan W, Rockey DC. Regulation of endothelin-1 synthesis by endothelin-converting enzyme-1 during wound healing. J Biol Chem 1999;274:3228–3234.

    Article  PubMed  CAS  Google Scholar 

  64. Shao R, Shi Z, Gotwals PJ, Koteliansky VE, George J, Rockey DC. Cell and molecular regulation of endothelin-1 production during hepatic wound healing. Mol Biol Cell 2003;14:2327–2341.

    Article  PubMed  CAS  Google Scholar 

  65. Reinehr RM, Kubitz R, Peters-Regehr T, Bode JG, Haussinger D. Activation of rat hepatic stellate cells in culture is associated with increased sensitivity to endothelin 1. Hepatology 1998;28:1566–1577.

    Article  PubMed  CAS  Google Scholar 

  66. Chi X, Anselmi K, Watkins S, Gandhi CR. Prevention of cultured rat stellate cell transformation and endothelin-B receptor upregulation by retinoic. Br J Pharmacol 2003;139:765–774.

    Article  PubMed  CAS  Google Scholar 

  67. Wang YZ, Pouyssegur J, Dunn MJ. Endothelin stimulates mitogen-activated protein kinase activity in mesangial cells through ET(A). J Am Soc Nephrol 1994;5:1074–1080.

    PubMed  CAS  Google Scholar 

  68. Mallat A., Fouassier F, Preaux AM, et al. Growth inhibitory properties of endothelin-1 in human hepatic myofibroblastic Ito cells: an endothelin B receptor-mediated pathway. J Clin Invest 1995;96:42–49.

    PubMed  CAS  Google Scholar 

  69. Mallat A, Preaux A-M, Serradeil-Le Gal C, et al. Growth inhibitory properties of endothelin-1 in activated human hepatic stellate cells: a cyclic adenosine monophosphate-mediated pathway. J Clin Invest 1996;98:2771–2778.

    PubMed  CAS  Google Scholar 

  70. Reinehr R, Fischer R, Haussinger D. Regulation of endothelin-A receptor sensitivity by cyclic adenosine monophosphate in rat hepatic stellate cells. Hepatology 2002;36:861–873.

    PubMed  CAS  Google Scholar 

  71. Leivas A, Jimenez W, Bruix J, et al. Gene expression of endothelin-1 and ET(A) and ET(B) receptors in human cirrhosis: relationship with hepatic hemodynamics. J Vase Res 1998;35:186–193.

    Article  CAS  Google Scholar 

  72. Gross SS, Wolin MS. Nitric oxide: pathophysiological mechanisms. Annu Rev Physiol 1995;57:737–769.

    Article  PubMed  CAS  Google Scholar 

  73. Mittal MK, Gupta TK, Lee FY, Sieber CC, Groszmann RJ. Nitric oxide modulates hepatic vascular tone in normal rat liver. Am J Physiol 1994;267:G416–G422.

    PubMed  CAS  Google Scholar 

  74. Shah V, Haddad FG, Garcia-Cardena G, et al. Liver sinusoidal endothelial cells are responsible for nitric oxide modulation of resistance in the hepatic sinusoids. J Clin Invest 1997;100:2923–2930.

    PubMed  CAS  Google Scholar 

  75. Rockey DC, Chung JJ. Reduced nitric oxide production by endothelial cells in cirrhotic rat liver: endothelial dysfunction in portal hypertension. Gastroenterology 1998;114:344–351.

    Article  PubMed  CAS  Google Scholar 

  76. Gupta TK, Toruner M, Chung MK, Groszmann RJ. Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats. Hepatology 1998;28:926–931.

    Article  PubMed  CAS  Google Scholar 

  77. Yu Q, Shao R, Qian HS, George SE, Rockey DC. Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension. J Clin Invest 2000;105:741–748.

    Article  PubMed  CAS  Google Scholar 

  78. Kawada N, Kuroki T, Uoya M, Inoue M, Kobayashi K. Smooth muscle α-actin expression in rat hepatic stellate cell is regulated by nitric oxide and cAMP. Biochem Biophy s Res Comm 1996;229:238–242.

    Article  CAS  Google Scholar 

  79. Casini A, Ceni E, Salzano R, et al. Neutrophil-derived superoxide anion induces lipid peroxidation and stimulates collagen synthesis in human hepatic stellate cells. Role of nitric oxide. Hepatology 1997;25:361–367.

    Article  PubMed  CAS  Google Scholar 

  80. Rockey DC, Chung JJ, McKee CM, Noble PW. Stimulation of inducible nitric oxide synthase in rat liver by hyaluronan fragments. Hepatology 1998;27:86–92.

    Article  PubMed  CAS  Google Scholar 

  81. Rockey DC, Chung JJ. Regulation of inducible nitric oxide synthase and nitric oxide during hepatic injury and fibrogenesis. Am J Physiol 1997;273:G124–G130.

    PubMed  CAS  Google Scholar 

  82. Failli P, DeFranco RMS, Caligiuri A, et al. Nitric oxide-generating vasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells. Gastroenterology 2000;119:479–492.

    Article  PubMed  CAS  Google Scholar 

  83. Fiorucci S, Antonelli E, Morelli O, et al. NCX-1000, a NO-releasing derivative of ursodeoxycholic acid, selectively delivers NO to the liver and protects against development of portal hypertension. Proc Natl Acad Sci USA 2001;98:8897–8902.

    Article  PubMed  CAS  Google Scholar 

  84. Gasull X, Bataller R, Gines P, et al. Human myofibroblastic hepatic stellate cells express Ca(2+)-activated K(+) channels that modulate the effects of endothelin-1 and nitric oxide. J Hepatol 2001;35:739–748.

    Article  PubMed  CAS  Google Scholar 

  85. Gorbig MN, Gines P, Bataller R, et al. Atrial natriuretic peptide antagonizes endothelin-induced calcium increase in cultured human hepatic stellate cells. Hepatology 1999;30:501–509.

    Article  PubMed  CAS  Google Scholar 

  86. Tao J, Mallat A, Gallois C, et al. Biological effects of C-type natriuretic peptide in human myofibroblastic hepatic stellate cells. J Biol Chan 1999;274:23,761–23,769.

    Article  CAS  Google Scholar 

  87. Titos E, Claria J, Bataller R, et al. Hepatocyte-derived cy stony 1 leukotrienes modulate vascular tone in experimental cirrhosis. Gastroenterology 2000;119:794–805.

    Article  PubMed  CAS  Google Scholar 

  88. Goulis J, Patch D, Burroughs AK. Bacterial infection in the pathogenesis of variceal bleeding. Lancet 1999;353:139–142.

    Article  PubMed  CAS  Google Scholar 

  89. Wiest R, Tsai M-H, Groszmann R. Octreotide potentiates PKC-dependent vasoconstrictors in portal-hypertensive rats. Gastroenterology 2001;120:975–983.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratorio di Epatologia, Dipartimento di Medicina Interna, Universita di Firenze, Firenze, Italy

    Massimo Pinzani MD, PhD & Francesco Vizzutti MD

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  1. Massimo Pinzani MD, PhD
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  2. Francesco Vizzutti MD
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Editors and Affiliations

  1. Division of Gastroenterology, Virginia Commonwealth Medical Center, Richmond, VA

    Arun J. Sanyal MBBS, MD

  2. GI Research Unit, Mayo Clinic, Rochester, MN

    Vijay H. Shah MD

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Pinzani, M., Vizzutti, F. (2005). Anatomy and Vascular Biology of the Cells in the Portal Circulation. In: Sanyal, A.J., Shah, V.H. (eds) Portal Hypertension. Clinical Gastroenterology. Humana Press. https://doi.org/10.1007/978-1-59259-885-4_2

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  • DOI: https://doi.org/10.1007/978-1-59259-885-4_2

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