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LEARNING OBJECTIVES

  1. Identify the laboratory tests useful in the evaluation of liver function, and the pathophysiology that results in the generation of these abnormal test results.

  2. Understand the clinical laboratory evaluation of the patient for viral hepatitis.

  3. Associate specific disorders of the liver with the laboratory test results expected for those clinical diagnoses.

INTRODUCTION

Laboratory evaluation of the hepatobiliary system centers on measurements of (1) hepatocyte plasma membrane integrity, (2) measurements of the detoxifying and excretory functions of the hepatobiliary system, and (3) measurements of the synthetic capacity of hepatocytes.

PLASMA MEMBRANE INTEGRITY AND DISORDERS PREDOMINANTLY ASSOCIATED WITH ELEVATED CONCENTRATIONS OF LIVER-DERIVED ENZYMES IN THE BLOOD

With hepatocyte or biliary tract disease, many cellular enzymes are released that enter the circulation. Enzymes indicative of hepatocyte disease are alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Alkaline phosphatase (ALP) elevations relate to biliary tract disease (Table 16–1). Note that ALP is also derived from other sources such as bone.

TABLE 16–1Enzymes Indicative of Liver Plasma Membrane Integrity

Enzyme concentrations are usually measured by determining the enzyme activity in serum or plasma. Such measurements are reported as units per liter or international units per liter, where the unit is an activity measurement (e.g., the rate of appearance of product or disappearance of substrate per unit time).

Normally, the healthy plasma membrane and various organelles contain (e.g., “hold”) enzymes within the cell. An elevated enzyme level in the blood suggests organ dysfunction because of a functional or anatomic disruption in the plasma membrane. One way to assess the degree of elevation of an enzyme is to calculate the ratio of the patient's enzyme concentration relative to the upper limit of the reference interval. For example, if the upper limit of the reference interval for ALT were 40 U/L and the patient's ALT was 120 U/L, the patient's ALT would be said to be “three times above the upper limit of normal.”

Enzymes indicative of hepatocyte disease are alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Alkaline phosphatase (ALP) elevations relate to biliary tract disease.

While not specific for hepatocytes, elevations of ALT and AST are characteristic of hepatocellular disease. The major sources of ALT include the liver and the kidney. Lesser amounts are released from skeletal and cardiac muscle. AST is also found in these organs. ALT is exclusively localized in the cell cytoplasm. AST is located in the cytoplasm and mitochondria. However, AST derived from the cytoplasm and mitochondria cannot be distinguished through currently available clinical laboratory testing. ALT ...

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