Hepatic role cirrhosis

Hepatocellutar Disease. Most forms of acute or chronic hepatocellular disease, including acute viral hepatitis and cirrhosis with jaundice, are associated with decreased levels of Hp, possibly caused in part by altered estrogen metabolism. Increased red cell breakdown secondary to erythrocyte membrane lipid alterations may also play a role, although this has never been documented with turnover studies. In contrast, biliary obstruction is also associated with significant lipid alterations but with increased Hp levels, in the absence of severe hepatocellular disease. 

The citric acid cycle is the final common pathway for the aerobic oxidation of carbohydrate, lipid, and protein because glucose, fatty acids, and most amino acids are metabolized to acetyl-CoA or intermediates of the cycle. It also has a central role in gluconeogenesis, lipogenesis, and interconversion of amino acids. Many of these processes occur in most tissues, but the hver is the only tissue in which all occur to a significant extent. The repercussions are therefore profound when, for example, large numbers of hepatic cells are damaged as in acute hepatitis or replaced by connective tissue (as in cirrhosis). Very few, if any, genetic abnormalities of citric acid cycle enzymes have been reported such ab-normahties would be incompatible with life or normal development. 

Iron overload is known to be toxic and potentially fatal. The major pathological effects of hepatic iron overload are fibrosis and cirrhosis, and hepatocellular carcinoma (Bonkovsky, 1991). The role of free radicals in the pathology of hepatic iron overload has been the subject of a detailed review recently (Bacon and Britton, 1990). 

One of the most unusual mechanisms claimed for milk thistle involves an increase in RNA polymerase I activity in nonmalignant hepatocytes but not in hepatoma or other malignant cell lines. By increasing this enzyme s activity, enhanced protein synthesis and cellular regeneration may occur in diseased but not malignant cells. Milk thistle may have a role in hepatic fibrosis. In an animal model of cirrhosis, it reduced collagen accumulation, and in an in vitro model it reduced expression of the profibrogenic cytokine TGF-13. 

Hepato toxicity Liver, bile duct, and gall bladder. The liver is particularly susceptible to xenobiotics due to its large blood supply and its role in metabolism Steatosis (lipid accumulation in hepatocytes) Chemical hepatitis (inflammation of the liver) Hepatic necrosis (death of the hepatocytes) Hepatic cancer (cancer of the liver) Hepatic cirrhosis (chronic fibrosis) Hypersensitivity (immune reaction resulting in hepatic necrosis)... 

Lieber, C.S. Hepatic and metabolic effects of ethanol pathogenesis and prevention. Ann. Med. 1994 26 325-330 Ethanol metabolism, cirrhosis and alcoholism. Clin. Chim. Acta 1997 257 59-84 Role of oxidative stress and antioxidant therapy in alcoholic and non-alcoholic liver diseases. Adv. Pharmacol. 1997 38 601-628... 

Wanless, LR., Wong, F., Blendis, L.M., Greig, R, Heathcote, E.J., Levy, G. Hepatic and portal vein thrombosis in cirrhosis possible role in development of parenchymal extinction and portal hypertension. Hepatology 1995 21 1238-1247... 

Wanless, I.R., Liu, J.J., Butany, J. Role of thrombosis in the pathogenesis of congestive hepatic fibrosis (cardiac cirrhosis). Hepatology 1995 21 1232-1237... 

Secondary hyperaldosteronism plays a major role in the pathogenesis of edema in patients with cirrhosis. Therefore these patients should initially be treated with spironolactone in the absence of impaired GFR and hyperkalemia. Thiazides may then be added for patients with a creatinine clearance >50 mL/min. For those patients who remain diuretic resistant, a loop diuretic may replace the thiazide. Patients with impaired GFR (creatinine clearance of <30 mL/min) generally will require a loop diuretic, with addition of a thiazide in those who do not achieve adequate diuresis. Care should be taken to avoid hypokalemia, which may precipitate hepatic encephalopathy by increasing ammoniagenesis (Fig. 49-8). ... 

Consistent wdth a major role of the liver in maintaining normal somatomedin levels in the circulation, low levels of somatomedin-A activity have been found in unextracted plasma of patients with cirrhosis of the liver and chronic hepatitis (S14, T5). Significant correlations were seen between somatomedin-A and albumin, cholinesterase, and other indicators of liver function (T5). The decrease measured in this RRA appears to be due to low levels of both somatomedins and binding protein, since Zapf et al. (Z5) have shown an 89% decrease in immunoreactive IGF-I, a 74% decrease in total IGF by protein binding assay (which preferentially measures IGF-II), and a 57% decrease in specific binding of somatomedin tracer to stripped serum, in patients with cirrhosis. 

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