Pathogenesis of Portal Hypertension and Esophageal Varices

Abd Allah, Safaa Khalaf; Galal, Ghada Moustafa; Nazir, Mariam Amir

doi:10.21608/smj.2018.39061

Pathogenesis of Portal Hypertension and Esophageal Varices

Document Type : Original Article

Authors

¹ Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Sohag University

² Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Sohag University.

10.21608/smj.2018.39061

Abstract

Esophageal varices are the major complication of portal hypertension. It is detected in about 50% of cirrhosis patients. Portal hypertensionis associated with both increased portal inflow and increased intrahepatic vascular resistance. Intrahepatic vascular resistance is caused by the architectural distortion of the liver resulting from fibrosis and by increased sinusoidal tone. Portal venous inflow results from a combination of ahyperdynamic circulatory state and increased plasma volume. In response to the increased portal pressure, collateral circulation develops by the opening of preexisting vascular channels. Esophagogastric varices are the most important collateral vessels: they tend to increase in size with the increase of portal pressure and rupture when wall tension exceeds a critical value.

References

1- D’Amico G, Luca A, Morabito A, Miraglia R, D'Amico M (2005): Uncovered transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis. Gastroenterology 129: 1282-93.

2- Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W (2007): Practice Guidelines Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophagealvarices and variceal hemorrhage in cirrhosis. Hepatology 3: 922-38.

3- Mathur SK (2008): Cirrhosis and portal hypertension. In: Haribhakti S, ed. Clinical GI surgery e a reference book for surgeons. 1st ed. Ahmedabad: Haribhakti Education Foundation 835-56.

4- De Franchis R(2010): Revising consensus in portal hypertension: Report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. Journal of Hepatology 53: 762-8.

5- Graham DY, Smith JL (1981): The course of patients after variceal hemorrhage. Gastroenterology 80:800-809.

6- Burroughs AK, Sanchez A, Bass NM, et al (1983): Can endoscopic sclerotherapy influence significantly the course of cirrhotics who survive variceal bleeding? (Abstr.) Gut 24:A972.

7- Schalm SW, van BuurenHR(1985): Prevention of recurrent variceal bleeding: Nonsurgical procedures. ClinGastroenterol 14:209- 232.

8- Atucha NM, Shah V, Garcia-Cardena G, Sessa WE, Groszmann RJ (1996): Role of endothelium in the abnormal response of mesenteric vessels in rats with portal hypertension and liver cirrhosis. Gastroenterology 111: 1627-32.

9- Gupta TK, Toruner M, Chung MK, Groszmann RJ (1998): Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats. Hepatology 28: 926-31.

10- Harrison DG (1997): Cellular and molecular mechanisms of endothelial cell dysfunction. Journal of Clinical Investigation 100: 2153–2157.

11- Gupta T K, Toruner M, Chung M K, and Groszmann R J(1998): Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats. Hepatology 28: 926–931.

12- Zafra C, Abraldes J G, Turnes J et al. (2004): Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis. Gastroenterology 126: 749–755.

13- Abraldes J G, Albillos A,.Banares R et al. (2009): Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology 136: 1651–1658.

14- Bosch J, Berzigotti A, Garcia-Pagan JC, et al (2008): The management of portal hypertension: rational basis, available treatments and future options. J Hepatol 48: S68-S92

15- Wiest R, Groszmann RJ (1999): Nitric oxide and portal hypertension: its role in the regulation of intrahepatic and splanchnic vascular resistance. Seminars in Liver Disease 19:411–426.

16- Loureiro-Silva MR, Iwakiri Y, Abraldes JG, Haq O , Groszmann RJ (2006):Increased phosphodiesterase- 5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers. J Hepatol 44: 886-93.

17- Shah V, Garcia-Cardena G, Sessa WC, Groszmann R.J (1998): The hepatic circulation in health and disease: report of a single-topic symposium. Hepatology 27: 279-88.

18- Pannen BHJ, K¨ohler N, Hole B, Bauer M, Clemens MG, Geiger KK (1998): Protective role of endogenous carbon monoxide in hepatic microcirculatory dysfunction after hemorrhagic shock in rats. Journal of Clinical Investigation 102: 1220-8.

19- Tarquini R, Masini E, La Villa G, Barletta G, Novelli M, Mastroianni R, Romanelli RG, Vizzutti F, Santosuosso U, Laffi G (2009): Increased plasma carbon monoxide in patients with viral cirrhosis and hyperdynamic circulation. Am J of Gastroenterolology 104: 891-7.

20- Thalheimer U, Bellis L, Puoti C, et al (2011). Should we routinely measure portal pressure in patients with cirrhosis, using hepatic venous pressure gradient (HVPG) as a guide for prophylaxis and therapy of bleeding and rebleeding? Eur J Intern Med 22: 5-7

21- Bosch J, Abraldes JC, Fernàndez M, et al. (2010): Hepatic endothelial dysfunction and abnormal angiogenesis: new targets in the treatment of portal hypertension. J Hepatol 53: 558-67

22- Vorobioff J, Bredfeldt JE, Groszmann RJ (1984): Increased blood flow through the portal system in cirrhotic rats. Gastroenterology 87: 1120-6.

23- Iwakiri Y, Groszmann RJ (2006): The hyperdynamic circulation of chronic liver disease: from the patient to the molecule. Hepatology 43: 121-31.

24- Bosch J, Garcia-Pagan JC (2000): Complications of cirrhosis. I. Portal hypertension,” Journal of Hepatology 32: 141-56.

25- Gatta A, Bolognesi M, Merkel C (2008): Vasoactive factors and hemodynamicmechanisms in the pathophysiology of portalhypertension in cirrhosis. Mol Aspects Med 29: 119-129.

26- Sherwin R, Joshi P, Hendler R, Felig P, Conn HO (1974):Hyperglucagonemiain Laennec’s cirrhosis. The role of portal-systemicshunting. N Engl J Med 290: 239-242.

27- Benoit JN, Womack WA, Hernandez L, Granger DN (1985): Forward“and „backward“ flow mechanisms of portal hypertension.Relative contributions in the rat model of portalvein stenosis. Gastroenterology 89: 1092-1096.

28- Vallance P, Moncada S (1991). Hyperdynamic circulation in cirrhosis: a role for nitric oxide? Lancet 337: 776-778.

29- Bosch J, Pizcueta P, Feu F, Fernández M, García-Pagán JC (1992).Pathophysiology of portal hypertension. GastroenterolClin North Am 21: 1-14.

30- Sogni P, Moreau R, Gadano A, Lebrec D (1995). The role of nitric oxide in the hyperdynamic circulatory syndrome associated with portal hypertension. J Hepatol23: 218-224.

31- Sacerdoti D, Abraham NG, Oyekan AO, Yang L, Gatta A, McGiff JC (2004): Role of the hemeoxygenases in abnormalities of the mesenteric circulation in cirrhotic rats. J Pharmacol Exp Ther 308: 636-643

32- Blendis L, Wong F (2001): The hyperdynamic circulation in cirrhosis: an overview. Pharmacol Ther 89: 221-231.

33- Menon KV, Kamath PS (2001): Regional and systemic hemodynamic disturbances in cirrhosis. [viii.]. Clin Liver Dis 5: 617-27.

34- Sanyal J, Bosch A, Blei, Arroyo V (2008): Portal hypertension and its complications. Gastroenterology 134: 1715-28.

35- Widrich WC, Srinivasan M, Semine MC, Robbins AH (1984). Collateral pathways of the left gastric vein in portal hypertension. Am JRoentgenol 142: 375–82.

36- Bengmark S, Borjesson B, Hoevels J, Joelsson B, Lunderquist A, Owman T (1979). Obliteration of esophageal varices by PTP. Ann Surg 190: 549–54.

37- Hashizume M, Kitano S, Sugimachi K, Sueishi K (1988). Three dimensional view of the vascular structure of the lower esophagus in clinical portal hypertension. Hepatology 8: 1482–7.

38- Hassab MA, Younis MT and el-Kilany MS (1968): Gastroesophagealdecongesion and splenectomy in the treatment of esophageal varices secondary to bilharizeal cirrhosis; anatomical and experimental studies. Surgery 63:731-7.

39- Kitano S, Terblanche J, Kahn D and Bornman PC (1986): Venous anatomy of the lower oesophagus in portal hypertension: practical implications. Br J Surg 73:525-31.