Porth's Essentials of Pathophysiology, 4e

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Disorders of Hepatobiliary and Exocrine Pancreas Function

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Unrelieved obstruction leads to biliary tract fibrosis and ultimately to end-stage biliary cirrhosis. Pruritus is the most common presenting symptom in persons with cholestasis, probably related to an elevation in plasma bile acids. Skin xanthomas (focal accumulations of cholesterol) may occur as the result of hyperlipidemia and impaired excretion of choles- terol. A characteristic laboratory finding is elevated levels of serum ALP. Other manifestations of reduced bile flow relate to intestinal absorption, including nutritional deficiencies of the fat-soluble vitamins A, D, E, and K. Tests of Hepatobiliary Function The history and physical examination, in most instances, provide clues about liver function. Diagnostic tests help to evaluate liver function and the extent of liver damage. Laboratory tests commonly are used to assess liver func- tion and confirm the diagnosis of liver disease. Liver function tests, including serum levels of liver enzymes, are used to assess injury to liver cells, the liver’s ability to synthesize proteins, and the excretory functions of the liver. 5,6 Elevated serum enzyme test results usually indicate liver injury earlier than other indicators of liver function. The key enzymes are alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which are present in liver cells. ALT is liver specific, whereas AST is derived from organs other than the liver. In most cases of liver damage, there are parallel rises in ALT and AST. The most dramatic rise is seen in cases of acute hepa- tocellular injury, as occurs with viral hepatitis, autoim- mune hepatitis, hypoxic or ischemic injury, acute toxic injury, or Reye syndrome. The liver’s synthetic capacity is reflected in measures of serum protein levels (albumin) and prothrombin time (i.e., synthesis of coagulation fac- tors). Deficiencies of fibrinogen and coagulation factors (II, VII, IX, and X) may occur. Serum bilirubin, γ -glutamyltransferase (GGT), and ALP measure hepatic excretory function. 6 Alkaline phos- phatase is present in the membranes between liver cells and the bile duct and is released by disorders affecting the bile duct. γ -glutamyltransferase, which is thought to function in the transport of amino acids and peptides into liver cells, is a sensitive indicator of hepatobiliary disease but not used much clinically as it has limited use in specific disease diagnosis. Ultrasonography provides information about the size, composition, and blood flow of the liver. It is used predominately in detecting stones in the gallbladder or biliary tree. Computed tomography (CT) scanning and magnetic resonance imaging (MRI) provide informa- tion similar to that obtained by ultrasonography, but offer greater detail regarding composition, and blood and/or bile flow through the liver. Selective angiog- raphy of the celiac, superior mesenteric, or hepatic artery may be used to visualize the hepatic or portal circulation. A liver biopsy affords a means of examining liver tissue without surgery. There are several methods for

obtaining liver tissue: percutaneous liver biopsy, which uses a suction, cutting, or spring-loaded cutting needle; laparoscopic liver biopsy; and fine needle biopsy, which is performed under ultrasonographic or CT guidance. 7 The type of method used is based on the number of specimens needed and the amount of tissue required for evaluation. Laparoscopic liver biopsy provides the means for examining abdominal masses and staging liver cancers.

SUMMARY CONCEPTS

Disorders of Hepatic and Biliary Function The structures of the hepatobiliary system are subject to many of the same pathologic conditions that affect other body systems. This section focuses on alterations in liver function due to viral and autoimmune hepatitis; intrahe- patic biliary disorders; drug- and alcohol-induced liver disease; nonalcoholic fatty liver disease; the hepatic syn- dromes of cirrhosis, portal hypertension, and liver fail- ure; and cancer of the liver. ■■ The liver, which is the largest and most versatile organ in the body, is located between the gastrointestinal tract and the systemic circulation. Venous blood from the intestine flows through the liver before it is returned to the heart, allowing nutrients to be removed for processing and storage, and bacteria and other foreign matter to be removed before the blood is returned to the systemic circulation. ■■ The main functions of the liver include synthesis of plasma proteins, maintenance of blood glucose levels, regulation of circulating lipoprotein levels, and vitamin and mineral storage.The liver also plays an essential role in the metabolism and elimination of harmful toxins and drugs, conversion of ammonia to urea, and removal of bilirubin, a product of hemoglobin breakdown, from the blood. ■■ Serum liver enzymes, especially alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are used to assess injury to liver cells; plasma proteins (e.g., serum albumin) and blood clotting factors (prothrombin time) provide information related to the liver’s synthetic capacity; and serum bilirubin, serum γ -glutamyltransferase (GGT), and alkaline phosphatase (ALP) are used as measures of hepatic excretory function.