Pathophysiology Of Chronic Liver Disease

The pathophysiology of advanced liver disease results in two cardinal pathophysiological abnormalities: hepatocellular failure and portal hypertension. In acute liver failure, portal hypertension is seldom a clinical problem while in cirrhosis, an increased portal pressure may give rise to complications while hepatocellular function is preserved. The importance of these two factors is recognized in the Child-Turcotte-Pugh classification, a prognostic tool in patients with cirrhosis.(Table 9.7)

Portal Hypertension

Portal pressure rises as a result of both a high hepatic vascular resistance and an increased portal venous inflow. The anatomical site of the increased vascular resistance in the liver will vary with different etiologies of cirrhosis15, the hepatic sinusoids being the critical site for alcoholic cirrhosis. A functional component to this resistance may also be present, as transformed stellate cells in the sinusoids may respond to vasoconstrictive stimuli, such as endothelin. Once a critical level of portal hypertension is reached (hepatic venous pressure gradient of 10-12 mmHg, defined by the pressure gradient between the portal vein and the hepatic vein), portal-systemic collaterals form in an attempt to decompress the portal system. Portal hypertension is sustained by the development of increased portal venous inflow.

This increase in portal flow is part of a generalized hemodynamic abnormality of both acute and chronic liver failure consisting of a hyperdynamic circulation. The mechanisms which contribute to the arteriolar vasodilatation are under investigation, but an increased production of nitric oxide in the vascular endothelium and hence low systemic vascular resistance may explain the levels of circulating cytokines (such as TNFa) that are present in patients with both acute and chronic liver disease. The hyperdynamic state has repercussions on other organs, such as lung and kidneys, which pose specific problems in the management of the patient before, during and after liver transplantation.(Fig. 9.2)

Hepatocellular Failure

The "intact hepatocyte" theory of hepatocellular failure postulates that a critical number of viable hepatocytes is needed to maintain liver function. The "sick hepatocyte" theory suggests a generalized malfunction of individual cells. There

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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