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Pathogenesis of liver injury in circulatory failure

Lawrence S Friedman, MD
Section Editor
Sanjiv Chopra, MD, MACP
Deputy Editor
Kristen M Robson, MD, MBA, FACG


The liver's complex vascular supply and high metabolic activity make it particularly vulnerable to circulatory disturbances. The severity and characteristics of hepatic injury depend upon the blood vessels that are involved and the degree to which injury is related to passive congestion or diminished perfusion [1].

There are several well-recognized forms of vascular injury to the liver including Budd-Chiari syndrome, sinusoidal obstruction syndrome (hepatic veno-occlusive disease), passive congestion due to heart failure, hepatic infarction, and ischemic hepatitis. This topic review will focus on the pathogenesis of passive congestion and ischemic hepatitis. Discussions on Budd-Chiari syndrome and sinusoidal obstruction syndrome are presented separately. (See "Budd-Chiari syndrome: Epidemiology, clinical manifestations, and diagnosis" and "Diagnosis of hepatic sinusoidal obstruction syndrome (veno-occlusive disease) following hematopoietic cell transplantation".)


The liver receives approximately 25 percent of cardiac output even though it makes up only approximately 2 to 3 percent of total body weight [2,3]. The portal vein provides approximately two-thirds of the blood supply while the hepatic artery provides the rest. Blood flowing through the liver is drained via the right, left, and middle hepatic veins into the inferior vena cava and then into the right side of the heart.

The composition of the portal venous and hepatic arterial blood supply differ. While portal venous blood is rich in basic nutrients (such as glucose, amino acids, and triglycerides) it is relatively deficient in oxygen. In contrast, the hepatic artery supplies oxygen-rich blood (accounting for more than 50 percent of the oxygen delivered to the liver and 100 percent to the major bile ducts) but contains fewer basic nutrients.

Despite its importance in providing oxygenated blood, ligation or occlusion of the hepatic artery in humans can be tolerated without adverse consequences. In most patients, collateral arterial flow combined with portal blood flow can provide adequate circulation [4]. In rare patients, disruption of the hepatic arterial flow can cause focal hepatic infarction.

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Literature review current through: Nov 2017. | This topic last updated: Dec 16, 2015.
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  1. Giallourakis CC, Rosenberg PM, Friedman LS. The liver in heart failure. Clin Liver Dis 2002; 6:947.
  2. Lautt WW, Greenway CV. Conceptual review of the hepatic vascular bed. Hepatology 1987; 7:952.
  4. Mays ET. Lobar dearterialization for exsanguinating wounds of the liver. J Trauma 1972; 12:397.
  5. Rappaport AM. The microcirculatory hepatic unit. Microvasc Res 1973; 6:212.
  6. Ross RM. Hepatic dysfunction secondary to heart failure. Am J Gastroenterol 1981; 76:511.
  7. Fuhrmann V, Kneidinger N, Herkner H, et al. Hypoxic hepatitis: underlying conditions and risk factors for mortality in critically ill patients. Intensive Care Med 2009; 35:1397.
  8. Kleber G, Steudel N, Behrmann C, et al. Hepatic arterial flow volume and reserve in patients with cirrhosis: use of intra-arterial Doppler and adenosine infusion. Gastroenterology 1999; 116:906.
  9. Ceppa EP, Fuh KC, Bulkley GB. Mesenteric hemodynamic response to circulatory shock. Curr Opin Crit Care 2003; 9:127.
  10. Dunn GD, Hayes P, Breen KJ, Schenker S. The liver in congestive heart failure: a review. Am J Med Sci 1973; 265:174.
  11. Rosser BG, Gores GJ. Liver cell necrosis: cellular mechanisms and clinical implications. Gastroenterology 1995; 108:252.
  12. Jones SM, Thurman RG. L-arginine minimizes reperfusion injury in a low-flow, reflow model of liver perfusion. Hepatology 1996; 24:163.
  13. Tacchini L, Radice L, Pogliaghi G, Bernelli-Zazzera A. Differential activation of heat shock and nuclear factor kappaB transcription factors in postischemic reperfused rat liver. Hepatology 1997; 26:186.
  14. Frederiks WM, Fronik GM, Marx F, James J. Influence of nutritional state on ischemic damage in rat liver. Liver 1985; 5:342.
  15. Gasbarrini A, Borle AB, Farghali H, et al. Effect of anoxia on intracellular ATP, Na+i, Ca2+i, Mg2+i, and cytotoxicity in rat hepatocytes. J Biol Chem 1992; 267:6654.
  16. Lemasters JJ, Ji S, Thurman RG. Centrilobular injury following hypoxia in isolated, perfused rat liver. Science 1981; 213:661.
  17. Safran AP, Schaffner F. Chronic passive congestion of the liver in man. Electron microscopic study of cell atrophy and intralobular fibrosis. Am J Pathol 1967; 50:447.
  18. Wanless IR, Liu JJ, Butany J. Role of thrombosis in the pathogenesis of congestive hepatic fibrosis (cardiac cirrhosis). Hepatology 1995; 21:1232.
  19. SHERLOCK S. The liver in heart failure; relation of anatomical, functional, and circulatory changes. Br Heart J 1951; 13:273.
  20. Cohen JA, Kaplan MM. Left-sided heart failure presenting as hepatitis. Gastroenterology 1978; 74:583.
  21. Seeto RK, Fenn B, Rockey DC. Ischemic hepatitis: clinical presentation and pathogenesis. Am J Med 2000; 109:109.
  22. Henrion J, Minette P, Colin L, et al. Hypoxic hepatitis caused by acute exacerbation of chronic respiratory failure: a case-controlled, hemodynamic study of 17 consecutive cases. Hepatology 1999; 29:427.
  23. Henrion J, Schapira M, Luwaert R, et al. Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases. Medicine (Baltimore) 2003; 82:392.
  24. Whelan G, Pierce AK, Schenker S, Combes B. Hepatic function in patients with hypoxaemia due to chronic pulmonary disease. Australas Ann Med 1969; 18:243.
  25. Shorey J, Schenker S, Combes B. Effect of acute hypoxia on hepatic excretory function. Am J Physiol 1969; 216:1441.
  26. Henrion J, Colin L, Schapira M, Heller FR. Hypoxic hepatitis caused by severe hypoxemia from obstructive sleep apnea. J Clin Gastroenterol 1997; 24:245.