Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content +++ CIRRHOSIS ++ Cirrhosis is a diffuse injury to the liver characterized by fibrosis and a conversion of the normal hepatic architecture into structurally abnormal nodules. The end result is destruction of hepatocytes and their replacement by fibrous tissue. The resulting resistance to blood flow results in portal hypertension and the development of varices and ascites. Hepatocyte loss and intrahepatic shunting of blood result in diminished metabolic and synthetic function, which leads to hepatic encephalopathy (HE) and coagulopathy. Cirrhosis has many causes (Table 21–1). In the United States, excessive alcohol intake and chronic viral hepatitis (types B and C) are the most common causes. Cirrhosis results in elevation of portal blood pressure because of fibrotic changes within the hepatic sinusoids, changes in the levels of vasodilatory and vasoconstrictor mediators, and an increase in blood flow to the splanchnic vasculature. The pathophysiologic abnormalities that cause it result in the commonly encountered problems of ascites, portal hypertension and esophageal varices, HE, and coagulation disorders. Portal hypertension is noted by elevated pressure gradient between the portal and central venous pressure and is characterized by hypervolemia, increased cardiac index, hypotension, and decreased systemic vascular resistance. Ascites is the pathologic accumulation of fluid within the peritoneal cavity. It is one of the earliest and most common presentations of cirrhosis. The development of ascites is related to systemic arterial vasodilation mediated by nitric oxide that leads to the activation of the baroreceptors in the kidney and an activation of the renin–angiotensin–aldosterone system, activation of the sympathetic nervous system, and release of antidiuretic hormone in response to the arterial hypotension. These changes cause sodium and water retention. ++Table Graphic Jump LocationTABLE 21–1Etiology of CirrhosisView Table|Favorite Table|Download (.pdf) TABLE 21–1 Etiology of Cirrhosis Chronic alcohol consumption Chronic viral hepatitis (types B and C) Metabolic liver disease Hemochromatosis Wilson’s disease α1-antitrypsin deficiency Nonalcoholic steatohepatitis (“fatty liver”) Immunologic disease Autoimmune hepatitis Primary biliary cirrhosis Vascular disease Budd–Chiari Cardiac failure Drugs Isoniazid, methyldopa, amiodarone, amoxicillin-clavulanate, nitrofurantoin, diclofenac, methotrexate, nevirapine, propylthiouracil, valproate +++ PORTAL HYPERTENSION AND VARICES ++ The most important sequelae of portal hypertension are the development of varices and alternative routes of blood flow resulting in acute variceal bleeding. Portal hypertension is defined by the presence of a gradient of greater than 5 mm Hg (0.7 kPa) between the portal and central venous pressures. Progression to bleeding can be predicted by Child-Pugh score, size of varices, and the presence of red wale markings on the varices. First variceal hemorrhage occurs at an annual rate of about 15% and carries a mortality of 7% to 15%. +++ HEPATIC ENCEPHALOPATHY ++ Hepatic encephalopathy (HE) is a metabolically induced functional disturbance of the brain that is potentially reversible. The symptoms of HE are thought to result from an accumulation of gut-derived nitrogenous substances in the systemic circulation as a consequence of shunting ... GET ACCESS TO THIS RESOURCE Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth Get Free Access Through Your Institution Contact your institution's library to ask if they subscribe to McGraw-Hill Medical Products. Access My Subscription GET ACCESS TO THIS RESOURCE Subscription Options Pay Per View Timed Access to all of AccessPharmacy 24 Hour $34.95 (USD) Buy Now 48 Hour $54.95 (USD) Buy Now Best Value AccessPharmacy Full Site: One-Year Individual Subscription $595 USD Buy Now View All Subscription Options