Skip to main content
SpringerLink
Log in
Book cover

Surgical Procedures on the Cirrhotic Patient pp 1–18Cite as

Pathophysiology of Cirrhosis and Portal Hypertension

  • Chapter
  • First Online:

Abstract

Several pathophysiologic changes occur in the patient with liver cirrhosis that should be considered when surgery is planned. This chapter discusses the intrahepatic environment in cirrhosis and the series of events leading to progressive fibrosis and eventually distortion of hepatic lobular architecture. This occurs through a series of interaction between a host of liver cells and cytokines leading to activation of stellate cells, the key player in formation of the fibrous matrix. Once this process advances into later stages, the patient is at risk for portal hypertension and the associated complications including variceal bleeding, ascites, and hepatorenal syndrome. Portal hypertension develops due to both intrahepatic changes (increased resistance) and extrahepatic changes in the form of systemic vasodilation and the concomitant circulatory and hormonal changes. Understanding the basis of these pathophysiologic changes is crucial for appropriate perioperative management of the cirrhotic patient.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   139.99
Price excludes VAT (USA)
  • Durable hardcover 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

Learn about institutional subscriptions

References

  1. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008;371:838–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ramadori G, Moriconi F, Malik I, Dudas J. Physiology and pathophysiology of liver inflammation, damage and repair. J Physiol Pharmacol. 2008;59:107–17.

    PubMed  Google Scholar 

  3. Wallace K, Burt AD, Wright MC. Liver fibrosis. Biochem J. 2008;411:1–18.

    Article  CAS  PubMed  Google Scholar 

  4. Park YN, Yang CP, Fernandez GJ, Cubukcu O, Thung SN, Theise ND. Neoangiogenesis and sinusoidal “capillarization” in dysplastic nodules of the liver. Am J Surg Pathol. 1998;22:656–62.

    Article  CAS  PubMed  Google Scholar 

  5. Xu B, Broome U, Uzunel M, Nava S, Ge X, Kumagai-Braesch M, et al. Capillarization of hepatic sinusoid by liver endothelial cell-reactive autoantibodies in patients with cirrhosis and chronic hepatitis. Am J Pathol. 2003;163:1275–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhou WC, Zhang QB, Qiao L. Pathogenesis of liver cirrhosis. World J Gastroenterol. Baishideng Publishing Group Inc. 2014;20:7312–24.

    Article  CAS  Google Scholar 

  7. Del Carmen Garcíade León M, Montfort I, Tello Montes E, López Vancell R, Olivos García A, González Canto A, et al. Hepatocyte production of modulators of extracellular liver matrix in normal and cirrhotic rat liver. Exp Mol Pathol. 2006;80:97–108.

    Article  CAS  Google Scholar 

  8. Ali MA, Koura BA, el Mashad N, Zaghloul MH. The Bcl-2 and TGF-beta1 levels in patients with chronic hepatitis C, liver cirrhosis and hepatocellular carcinoma. Egyptian J Immunol. 2004;11:83–90.

    Google Scholar 

  9. Yokomori H, Oda M, Yoshimura K, Hibi T. Recent advances in liver sinusoidal endothelial ultrastructure and fine structure immunocytochemistry. Micron. 2012;43:129–34.

    Article  CAS  PubMed  Google Scholar 

  10. Marvie P, Lisbonne M, L’helgoualc'h A, Rauch M, Turlin B, Preisser L, et al. Interleukin-33 overexpression is associated with liver fibrosis in mice and humans. J Cell Mol Med. 2010;14:1726–39.

    Article  CAS  PubMed  Google Scholar 

  11. Bouwens L, Baekeland M, De ZR, Wisse E. Quantitation, tissue distribution and proliferation kinetics of Kupffer cells in normal rat liver. Hepatology. 1986;6:718–22.

    Article  CAS  PubMed  Google Scholar 

  12. Kolios G, Valatas V, Kouroumalis E. Role of Kupffer cells in the pathogenesis of liver disease. World J Gastroenterol. 2006;12:7413–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Fausto N, Laird AD, Webber EM. Role of growth regeneration factors and cytokines in hepatic. FASEB J. 1995;9:1527–36.

    CAS  PubMed  Google Scholar 

  14. MacPhee PJ, Schmidt EE, Groom AC. Evidence for Kupffer cell migration along liver sinusoids, from high-resolution in vivo microscopy. Am J Physiol. 1992;263:G17–23.

    CAS  PubMed  Google Scholar 

  15. Bayón LG, Izquierdo MA, Sirovich I, Van Rooijen N, Beelen RHJ, Meijer S. Role of Kupffer cells in arresting circulating tumor cells and controlling metastatic growth in the liver. Hepatology. 1996;23:1224–31.

    Article  PubMed  Google Scholar 

  16. Elsharkawy AM, Oakley F, Mann DA. The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis. Apoptosis. 2005;10:927–39.

    Article  CAS  PubMed  Google Scholar 

  17. Safadi R, Friedman SL. Hepatic fibrosis-role of hepatic stellate cell activation. Med Gen Med. 2002;4:27.

    Article  Google Scholar 

  18. Gressner AM, Weiskirchen R. Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets. J Cell Mol Med. 2006;10:76–99.

    Article  CAS  PubMed  Google Scholar 

  19. Rockey DC, Friedman SL. Hepatic fibrosis and cirrhosis. Zakim and Boyer’s hepatology, 6th edn. Elsevier Saunders, Philadelphia. 2012:64-85.2012:64–85.

    Google Scholar 

  20. Bataller R, Schwabe RF, Choi YH, Yang L, Paik YH, Lindquist J, et al. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J Clin Invest. 2003;112:1383–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fletcher LM, Powell LW. Hemochromatosis and alcoholic liver disease. Alcohol. 2003;30:131–6.

    Article  CAS  PubMed  Google Scholar 

  22. Canbay A, Taimr P, Torok N, Higuchi H, Friedman S, Gores GJ. Apoptotic body engulfment by a human stellate cell line is profibrogenic. Lab Invest. 2003;83:655–63.

    Article  CAS  PubMed  Google Scholar 

  23. Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Hicklin DJ, et al. Vascular endothelial growth factor and receptor interaction is a prerequisite for murine hepatic fibrogenesis. Gut. 2003;52:1347–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pinzani M, Milani S, Herbst H, DeFranco R, Grappone C, Gentilini A, et al. Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis. Am J Pathol. 1996;148:785–800.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Mazzocca A, Sciammetta SC, Carloni V, Cosmi L, Annunziato F, Harada T, et al. Binding of hepatitis C virus envelope protein E2 to CD81 up-regulates matrix metalloproteinase-2 in human hepatic stellate cells. J Biol Chem. 2005;280:11329–39.

    Article  CAS  PubMed  Google Scholar 

  26. Ohata M, Lin M, Satre M, Tsukamoto H. Diminished retinoic acid signaling in hepatic stellate cells in cholestatic liver fibrosis. Am J Physiol. 1997;272:G589–96.

    CAS  PubMed  Google Scholar 

  27. Eng FJ, Friedman SL, Fibrogenesis I. New insights into hepatic stellate cell activation: the simple becomes complex. Am J Physiol Gastrointest Liver Physiol. 2000;279:G7–11.

    CAS  PubMed  Google Scholar 

  28. Kinnman N, Hultcrantz R, Barbu V, Rey C, Wendum D, Poupon R, et al. PDGF-mediated chemoattraction of hepatic stellate cells by bile duct segments in cholestatic liver injury. Lab Invest. 2000;80:697–707.

    Article  CAS  PubMed  Google Scholar 

  29. Mann DA, Smart DE. Transcriptional regulation of hepatic stellate cell activation. Gut. 2002;50:891–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rockey D. The cellular pathogenesis of portal hypertension: Stellate cell contractility, endothelin, and nitric oxide. Hepatology. 1997;25:2–5.

    Article  CAS  PubMed  Google Scholar 

  31. Schuppan D, Ruehl M, Somasundaram R, Hahn EG. Matrix as a modulator of hepatic fibrogenesis. Semin Liver Dis. 2001;21:351–72.

    Article  CAS  PubMed  Google Scholar 

  32. Wells RG, Kruglov E, Dranoff JA. Autocrine release of TGF-beta by portal fibroblasts regulates cell growth. FEBS Lett. 2004;559:107–10.

    Article  CAS  PubMed  Google Scholar 

  33. Leu JI, Crissey MAS, Taub R. Massive hepatic apoptosis associated with TGF- β 1 activation after Fas ligand treatment of IGF binding protein-1 – deficient mice. J Clin Invest. 2003;111:129–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Liu X, Hu H, Yin JQ. Therapeutic strategies against TGF-β signaling pathway in hepatic fibrosis. Liver Int. 2006;26:8–22.

    Article  PubMed  Google Scholar 

  35. Crespo J, Rivero M, Fábrega E, Cayón A, Amado JA, García-Unzeta MT, et al. Plasma leptin and TNF-alpha levels in chronic hepatitis C patients and their relationship to hepatic fibrosis. Dig Dis Sci. 2002;47:1604–10.

    Article  CAS  PubMed  Google Scholar 

  36. Gressner AM, Weiskirchen R, Breitkopf K, Dooley S. Roles of TGF-beta in hepatic fibrosis. Front Biosci. 2002;7:d793–807.

    Article  CAS  PubMed  Google Scholar 

  37. Czochra P, Klopcic B, Meyer E, Herkel J, Garcia-Lazaro JF, Thieringer F, et al. Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice. J Hepatol. 2006;45:419–28.

    Article  CAS  PubMed  Google Scholar 

  38. Saile B, Eisenbach C, Dudas J, El-Armouche H, Ramadori G. Interferon-gamma acts proapoptotic on hepatic stellate cells (HSC) and abrogates the antiapoptotic effect of interferon-alpha by an HSP70-dependant pathway. Eur J Cell Biol. 2004;83:469–76.

    Article  CAS  PubMed  Google Scholar 

  39. Baroni GS, D’Ambrosio L, Curto P, Casini A, Mancini R, Jezequel AM, et al. Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis. Hepatology. 1996;23:1189–99.

    Article  CAS  PubMed  Google Scholar 

  40. Gieling RG, Wallace K, Han Y-P. Interleukin-1 participates in the progression from liver injury to fibrosis. Am J Physiol Gastrointest Liver Physiol. 2009;296:G1324–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Du W-J, Zhen J-H, Zeng Z-Q, Zheng Z-M, Xu Y, Qin L-Y, et al. Expression of interleukin-17 associated with disease progression and liver fibrosis with hepatitis B virus infection: IL-17 in HBV infection. Diagn Pathol. 2013;8:40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Aleffi S, Petrai I, Bertolani C, Parola M, Colombatto S, Novo E, et al. Upregulation of proinflammatory and proangiogenic cytokines by leptin in human hepatic stellate cells. Hepatology. 2005;42:1339–48.

    Article  CAS  PubMed  Google Scholar 

  43. Iizuka M, Ogawa T, Enomoto M, Motoyama H, Yoshizato K, Ikeda K, et al. Induction of microRNA-214-5p in human and rodent liver fibrosis. Fibrogenesis Tissue Repair. 2012;5:12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Roderburg C, Mollnow T, Bongaerts B, Elfimova N, Cardenas DV, Berger K, et al. Micro-RNA profiling in human serum reveals compartment-specific roles of miR-571 and miR-652 in liver cirrhosis. PLoS One. 2012;7:e32999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bala S, Marcos M, Kodys K, Csak T, Catalano D, Mandrekar P, et al. Up-regulation of microRNA-155 in macrophages contributes to increased tumor necrosis factor {alpha} (TNF{alpha}) production via increased mRNA half-life in alcoholic liver disease. J Biol Chem. 2011;286:1436–44.

    Article  CAS  PubMed  Google Scholar 

  46. Wang B, Li W, Guo K, Xiao Y, Wang Y, Fan J. MiR-181b Promotes hepatic stellate cells proliferation by targeting p27 and is elevated in the serum of cirrhosis patients. Biochem Biophys Res Commun. 2012;421:4–8.

    Article  CAS  PubMed  Google Scholar 

  47. Ogawa T, Enomoto M, Fujii H, Sekiya Y, Yoshizato K, Ikeda K, et al. MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis. Gut. 2012;61:1600–9.

    Article  CAS  PubMed  Google Scholar 

  48. Baltimore D, Boldin MP, O’Connell RM, Rao DS, Taganov KD. MicroRNAs: new regulators of immune cell development and function. Nat Immunol. 2008;9:839–45.

    Article  CAS  PubMed  Google Scholar 

  49. Noetel A, Kwiecinski M, Elfimova N, Huang J, Odenthal M. MicroRNA are central players in anti- and profibrotic gene regulation during liver fibrosis. Front Physiol. 2012;3:49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Venugopal SK, Jiang J, Kim T-H, Li Y, Wang S-S, Torok NJ, et al. Liver fibrosis causes downregulation of miRNA-150 and miRNA-194 in hepatic stellate cells, and their overexpression causes decreased stellate cell activation. Am J Physiol Gastrointest Liver Physiol. 2010;298:G101–6.

    Article  CAS  PubMed  Google Scholar 

  51. Roderburg C, Luedde M, Vargas Cardenas D, Vucur M, Mollnow T, Zimmermann HW, et al. miR-133a mediates TGF-β-dependent derepression of collagen synthesis in hepatic stellate cells during liver fibrosis. J Hepatol. 2013;58:736–42.

    Article  CAS  PubMed  Google Scholar 

  52. Calabro SR, Maczurek AE, Morgan AJ, Tu T, Wen VW, Yee C, et al. Hepatocyte produced matrix metalloproteinases are regulated by CD147 in liver fibrogenesis. PLoS One. 2014;9:e90571.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Barry-Hamilton V, Spangler R, Marshall D, McCauley S, Rodriguez HM, Oyasu M, et al. Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat Med. 2010;16:1009–17.

    Article  CAS  PubMed  Google Scholar 

  54. Oakley F, Trim N, Constandinou CM, Ye W, Gray AM, Frantz G, et al. Hepatocytes express nerve growth factor during liver injury. Am J Pathol. 2003;163:1849–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Preaux AM, D’Ortho MP, Bralet MP, Laperche Y, Mavier P. Apoptosis of human hepatic myofibroblasts promotes activation of matrix metalloproteinase-2. Hepatology. 2002;36:615–22.

    Article  CAS  PubMed  Google Scholar 

  56. Lang A, Schoonhoven R, Tuvia S, Brenner DA, Rippe RA. Nuclear factor kappaB in proliferation, activation, and apoptosis in rat hepatic stellate cells. J Hepatol. 2000;33:49–58.

    Article  CAS  PubMed  Google Scholar 

  57. Issa R, Williams E, Trim N, Kendall T, Arthur MJ, Reichen J, et al. Apoptosis of hepatic stellate cells: involvement in resolution of biliary fibrosis and regulation by soluble growth factors. Gut. 2001;48:548–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sohara N, Znoyko I, Levy MT, Trojanowska M, Reuben A. Reversal of activation of human myofibroblast-like cells by culture on a basement membrane-like substrate. J Hepatol. 2002;37:214–21.

    Article  CAS  PubMed  Google Scholar 

  59. Fallowfield JA, Mizuno M, Kendall TJ, Constandinou CM, Benyon RC, Duffield JS, et al. Scar-associated macrophages are a major source of hepatic matrix metalloproteinase-13 and facilitate the resolution of murine hepatic fibrosis. J Immunol. 2007;178:5288–95.

    Article  CAS  PubMed  Google Scholar 

  60. Duffield JS, Forbes SJ, Constandinou CM, Clay S, Partolina M, Vuthoori S, et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest. 2005;115:56–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Tsuchiya A, Forbes SJ. Macrophage Therapy for Liver Fibrosis and Regeneration. In Gene Therapy and Cell Therapy Through the Liver 2016 (pp. 15-23). Springer Japan.

    Google Scholar 

  62. Berzigotti A, Seijo S, Reverter E, Bosch J. Assessing portal hypertension in liver diseases. Expert Rev Gastroenterol Hepatol. 2013;7:141–55.

    Article  CAS  PubMed  Google Scholar 

  63. García-Pagán JC, Gracia-Sancho J, Bosch J. Functional aspects on the pathophysiology of portal hypertension in cirrhosis. J Hepatol. 2012;57:458–61.

    Article  PubMed  Google Scholar 

  64. Radi R. Peroxynitrite, a stealthy biological oxidant. J Biol Chem. 2013;288:26464–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Morales-Ruiz M, Rodríguez-Vita J, Jiménez W, Ribera J. Pathophysiology of portal hypertension. Pan Vascular Med Second Ed. 2015;18:3631–65.

    Google Scholar 

  66. Rockey DC, Weisiger RA. Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance. Hepatology. 1996;24:233–40.

    Article  CAS  PubMed  Google Scholar 

  67. Taura K, De Minicis S, Seki E, Hatano E, Iwaisako K, Osterreicher CH, et al. Hepatic stellate cells secrete angiopoietin 1 that induces angiogenesis in liver fibrosis. Gastroenterology. 2008;135:1729–38.

    Article  CAS  PubMed  Google Scholar 

  68. Novo E, Cannito S, Zamara E, di Bonzo LV, Caligiuri A, Cravanzola C, et al. Proangiogenic cytokines as hypoxia-dependent factors stimulating migration of human hepatic stellate cells. Am J Pathol. 2007;170:1942–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Dill MT, Rothweiler S, Djonov V, Hlushchuk R, Tornillo L, Terracciano L, et al. Disruption of Notch1 induces vascular remodeling, intussusceptive angiogenesis, and angiosarcomas in livers of mice. Gastroenterology. Elsevier. 2012;142:967–77. e2

    Article  CAS  Google Scholar 

  70. Simonetto DA, Yin YH, Yin M, de Assuncao TM, Kwon JH, Hilscher M, et al. Chronic passive venous congestion drives hepatic fibrogenesis via sinusoidal thrombosis and mechanical forces. Hepatology. 2015;61:648–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Wanless IR, Wong F, Blendis LM, Greig P, Heathcote EJ, Levy G. Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal extinction and portal hypertension. Hepatology. 1995;21:1238–47.

    CAS  PubMed  Google Scholar 

  72. Villa E, Zecchini R, Marietta M, Bernabucci V, Lei B, Vukotic R, et al. Enoxaparin prevents portal vein thrombosis (PVT) and decompensation in advanced cirrhotic patients: final report of a prospective randomized controlled study. Hepatology. 2011;54:418A–9A.

    Google Scholar 

  73. Abraldes JG, Iwakiri Y, Loureiro-Silva M, Haq O, Sessa WC, Groszmann RJ. Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state. Am J Physiol Gastrointest Liver Physiol. 2006;290:G980–7.

    Article  CAS  PubMed  Google Scholar 

  74. Ezkurdia N, Coll M, Raurell I, Rodriguez S, Cuenca S, Gonzalez A, et al. Blockage of the afferent sensitive pathway prevents sympathetic atrophy and hemodynamic alterations in rat portal hypertension. Liver Int. 2012;32:1295–305.

    Article  CAS  PubMed  Google Scholar 

  75. Iwakiri Y. Endothelial dysfunction in the regulation of cirrhosis and portal hypertension. Liver Int. 2012;32:199–213.

    Article  CAS  PubMed  Google Scholar 

  76. Sass DA, Chopra KB. Portal hypertension and variceal hemorrhage. Med Clin North Am. 2009;93:837–53.

    Article  CAS  PubMed  Google Scholar 

  77. Sieber CC, Sumanovski LT, Stumm M, van der Kooij M, Battegay E. In vivo angiogenesis in normal and portal hypertensive rats: role of basic fibroblast growth factor and nitric oxide. J Hepatol. 2001;34:644–50.

    Article  CAS  PubMed  Google Scholar 

  78. Van SC, Ribera J, Geerts A, Pauta M, Tugues S, Casteleyn C, et al. Inhibition of placental growth factor activity reduces the severity of fibrosis, inflammation, and portal hypertension in cirrhotic mice. Hepatology. 2011;53:1629–40.

    Article  CAS  Google Scholar 

  79. Takuma Y, Nouso K, Morimoto Y, Tomokuni J, Sahara A, Toshikuni N, et al. Measurement of spleen stiffness by acoustic radiation force impulse imaging identifies cirrhotic patients with esophageal varices. Gastroenterology. 2013;144:92–101. e2

    Article  PubMed  Google Scholar 

  80. Voros D, Mallas E, Antoniou A, Kafantari E, Kokoris SI, Smyrniotis B, et al. Splenomegaly and left sided portal hypertension. Ann Gastroenterol. 2005;18:341–5.

    Google Scholar 

  81. Ilan Y. Leaky gut and the liver: a role for bacterial translocation in nonalcoholic steatohepatitis. World J Gastroenterol. 2012;18:2609–18.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Fukui H. Gut-liver axis in liver cirrhosis: how to manage leaky gut and endotoxemia. World J Hepatol. 2015;7:425–42.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Messingham KAN, Faunce DE, Kovacs EJ. Alcohol, injury, and cellular immunity. Alcohol. Elsevier. 2002;28:137–49.

    Google Scholar 

  84. Tang Y, Forsyth CB, Keshavarzian A. The role of miRNAs in alcohol-induced endotoxemia, dysfunction of mucosal immunity, and gut leakiness. Alcohol Clin Exp Res. 2014;38:2331–4.

    Article  CAS  PubMed  Google Scholar 

  85. Miller AM, Masrorpour M, Klaus C, Zhang JX. LPS exacerbates endothelin-1 induced activation of cytosolic phospholipase A2 and thromboxane A2 production from Kupffer cells of the prefibrotic rat liver. J Hepatol. 2007;46:276–85.

    Article  CAS  PubMed  Google Scholar 

  86. Bosch J, Groszmann RJ, Shah VH. Evolution in the understanding of the pathophysiological basis of portal hypertension: how changes in paradigm are leading to successful new treatments. J Hepatol. 2015;62:S121–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Rigau J, Bosch J, Bordas JM, Navasa M, Mastai R, Kravetz D, et al. Endoscopic measurement of variceal pressure in cirrhosis: correlation with portal pressure and variceal hemorrhage. Gastroenterology. Wiley. 1989;96:873–80.

    Article  CAS  Google Scholar 

  88. Fernandez M, Vizzutti F, Garcia-Pagan JC, Rodes J, Bosch J. Anti-VEGF receptor-2 monoclonal antibody prevents portal-systemic collateral vessel formation in portal hypertensive mice. Gastroenterology. 2004;126:886–94.

    Article  CAS  PubMed  Google Scholar 

  89. Fernandez M, Mejias M, Garcia-Pras E, Mendez R, Garcia-Pagan JC, Bosch J. Reversal of portal hypertension and hyperdynamic splanchnic circulation by combined vascular endothelial growth factor and platelet-derived growth factor blockade in rats. Hepatology. 2007;46:1208–17.

    Article  CAS  PubMed  Google Scholar 

  90. Escorsell A, Bordas JM, Feu F, Garcia-Pagan JC, Gines A, Bosch J, et al. Endoscopic assessment of variceal volume and wall tension in cirrhotic patients: effects of pharmacological therapy. Gastroenterology. 1997;113:1640–6.

    Article  CAS  PubMed  Google Scholar 

  91. Garcia-Pagán JC, Barrufet M, Cardenas A, Escorsell A. Management of gastric varices. Clin Gastroenterol Hepatol. 2013;12:1–11.

    Google Scholar 

  92. Ryan BM, Stockbrugger RW, Ryan JM. A Pathophysiologic, gastroenterologic, and radiologic approach to the management of gastric varices. Gastroenterology. 2004;126:1175–89.

    Article  PubMed  Google Scholar 

  93. Helmy A, Al Kahtani K, Al FM. Updates in the pathogenesis, diagnosis and management of ectopic varices. Hepatol Int. 2008;2:322–34.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Cubillas R, Rockey DC. Portal hypertensive gastropathy: a review. Liver Int. 2010;30:1094–102.

    Article  CAS  PubMed  Google Scholar 

  95. Gupta R, Sawant P, Parameshwar RV, Lele VR, Kulhalli PM, Mahajani SS. Gastric mucosal blood flow and hepatic perfusion index in patients with portal hypertensive gastropathy. J Gastroenterol Hepatol. 1998;13:921–6.

    Article  CAS  PubMed  Google Scholar 

  96. Perini RF, Camara PRS, Ferraz JGP. Pathogenesis of portal hypertensive gastropathy: translating basic research into clinical practice. Nat Clin Pract Gastroenterol Hepatol. 2009;6:150–8.

    Article  PubMed  Google Scholar 

  97. Mezawa S, Homma H, Ohta H, Masuko E, Doi T, Miyanishi K, et al. Effect of transjugular intrahepatic portosystemic shunt formation on portal hypertensive gastropathy and gastric circulation. Am J Gastroenterol. 2001;96:1155–9.

    Article  CAS  PubMed  Google Scholar 

  98. Patwardhan VR, Cardenas A. Review article: the management of portal hypertensive gastropathy and gastric antral vascular ectasia in cirrhosis. Aliment Pharmacol Ther. 2014;40:354–62.

    Article  CAS  PubMed  Google Scholar 

  99. Kamath PS, Lacerda M, Ahlquist DA, McKusick MA, Andrews JC, Nagorney DA. Gastric mucosal responses to intrahepatic portosystemic shunting in patients with cirrhosis. Gastroenterology. 2000;118:905–11.

    Article  CAS  PubMed  Google Scholar 

  100. Senousy BE, Draganov PV. Evaluation and management of patients with refractory ascites. World J Gastroenterol. 2009;15:67–80.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Cardenas A, Bataller R, Arroyo V. Mechanisms of ascites formation. Clin Liver Dis. 2000;4:447–65.

    Article  CAS  PubMed  Google Scholar 

  102. Arroyo V, Bosch J, Gaya-Beltran J, Kravetz D, Estrada L, Rivera F, et al. Plasma renin activity and urinary sodium excretion as prognostic indicators in nonazotemic cirrhosis with ascites. Ann Intern Med. 1981;94:198–201.

    Article  CAS  PubMed  Google Scholar 

  103. Arroyo V, Guevara M, Ginès P. Hepatorenal syndrome in cirrhosis: pathogenesis and treatment. Gastroenterology. 2002;122:1658–76.

    Article  PubMed  Google Scholar 

  104. Kim MY, Jeong WK, Baik SK. Invasive and non-invasive diagnosis of cirrhosis and portal hypertension. World J Gastroenterol. 2014;20:4300–15.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Groszmann RJ, Wongcharatrawee S. The hepatic venous pressure gradient: anything worth doing should be done right. Hepatology. 2004;39:280–2.

    Article  PubMed  Google Scholar 

  106. Huang JY, Samarasena JB, Tsujino T, Chang KJ. EUS-guided portal pressure gradient measurement with a novel 25-gauge needle device versus standard transjugular approach: a comparison animal study. Gastrointest Endosc. Elsevier. 2016;84:358–62.

    Article  Google Scholar 

  107. Castera L, Pinzani M, Bosch J. Non invasive evaluation of portal hypertension using transient elastography. J Hepatol. 2012;56:696–703.

    Article  PubMed  Google Scholar 

  108. Castera L, Foucher J, Bernard PH. Pitfalls of liver stiffness measurement: a 5-years prospective study of 13,369 examinations. Hepatology. 2010;51:828–35.

    PubMed  Google Scholar 

  109. Guo J, Büning C, Schott E, Kröncke T, Braun J, Sack I, et al. In vivo abdominal magnetic resonance elastography for the assessment of portal hypertension before and after transjugular intrahepatic portosystemic shunt implantation. Invest Radiol. 2015;00:1.

    Google Scholar 

  110. Ronot M, Lambert S, Elkrief L, Doblas S, Rautou PE, Castera L, et al. Assessment of portal hypertension and high-risk oesophageal varices with liver and spleen three-dimensional multifrequency MR elastography in liver cirrhosis. Eur Radiol. 2014;24:1394–402.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gastroenterology Department, Cleveland Clinic Florida, Weston, FL, USA

    Bahaa Eldeen Senousy Ismail MD, MSc

  2. Liver Transplant Department, Cleveland Clinic Florida, Weston, FL, USA

    John M. Rivas MD & Xaralambos B. Zervos DO, MS

Authors
  1. Bahaa Eldeen Senousy Ismail MD, MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John M. Rivas MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xaralambos B. Zervos DO, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xaralambos B. Zervos DO, MS .

Editor information

Editors and Affiliations

  1. Transplantation Center, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, USA

    Bijan Eghtesad

  2. Department of Surgery, University of Chicago, Chicago, Illinois, USA

    John Fung

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Ismail, B.E.S., Rivas, J.M., Zervos, X.B. (2017). Pathophysiology of Cirrhosis and Portal Hypertension. In: Eghtesad, B., Fung, J. (eds) Surgical Procedures on the Cirrhotic Patient. Springer, Cham. https://doi.org/10.1007/978-3-319-52396-5_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-52396-5_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-52394-1

  • Online ISBN: 978-3-319-52396-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation