The patient's medical history involved a resected colorectal carcinoma at the age of 60, with no evidence of metastatic disease. Liver function was normal at the time of surgery. Three years later, the female patient was found to have serum bilirubin levels of 20 ?mol/L. The serum levels for aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were 23 U/L and 820 U/L, respectively.
Interpretation of the Laboratory Tests
High serum levels of ALP can indicate the presence of disease in the liver, bone, intestinal tract, and/or parathyroid, but the most common use for this assay is to detect disease of the hepatobiliary tract (Tietz, 1999, p 676). This is because the liver will respond to any obstruction in the biliary tree by producing more ALP, and these levels can be especially high if the blockage is extrahepatic (> 3 times the upper limit of the normal range). The normal range for women between the ages of 61 and 65 is 50-130 U/L, which is the age of the patient at the time of the most recent test. The patient's serum ALP levels are therefore 6-fold higher than the upper limit of the normal range. This level of ALP is consistent with a number of diseases and conditions, including extrahepatic obstructions like stones or a tumor of the pancreas head, or osteogenic bone cancer. The patient's ALP levels are not consistent with Paget's disease, because this condition tends to produce serum levels reaching 10 to 25 times the normal upper limit (Tietz, 1999, p. 677). The presence of disease affecting hepatocytes is unlikely given how high the ALP levels are, but this possibility can't be eliminated using this test alone. The sources of serum ALP can also be discriminated to some extent through laboratory testing, because different ALP isoenzymes are produced by the liver, bone, and placenta. This test can help discriminate between liver or bone diseases, including malignancies, or ectopic expression of the placental form (Regan isoenzyme) by other malignancies.
Assuming the bilirubin assay results are for total bilirubin, then the patients serum levels are slightly elevated (17%). The upper limit of the normal range for adult females is 17.1 ?mol/L (Tietz, 1999, p. 1170), so a serum level of 20 ?mol/L in an adult female would represent mild hyperbilirubinemia insufficient to cause the symptoms of jaundice (Tietz, 1999, p. 1158). The evaluation of total bilirubin serum levels is normally performed to assess liver function, but can also be used to evaluate diseases and treatments affecting the various stages of bilirubin production, metabolism, and excretion. In healthy individuals, bilirubin is extracted from senescent red blood cells by the liver, where it is conjugated with glucuronic acid for excretion in the bile (Tietz, 1999, p. 1135). Hemolysis or ineffective erythropoiesis represent prehepatic causes of hyperbilirubinemia, producing unconjugated bilirubin, otherwise any number of intrahepatic or post-hepatic diseases and conditions that affect liver or biliary function can elevate conjugated bilirubin serum levels as well (Jones, 2001). Together with the high serum levels of ALP, the mild hyperbilirubinemia could indicate a problem with the hepatobiliary system, but is otherwise not very useful diagnostically.
The patient's serum levels of AST (23 U/L) are well within the normal range for this enzyme (8-43 U/L; Jones, 2005). This test is typically used to assess liver function and represents one of two markers that can indicate the presence of liver disease. The other enzyme frequently used to assess liver function is alanine aminotransferase (ALT), which is a more specific and longer lasting marker for diseases affecting the cellular integrity of hepatocytes. In mild hepatocellular disease, the cytosolic forms of ALT and AST are released and the ALT/AST ratio is typically close to, or above, unity (Tietz, 1999, p. 653). If the liver disease is severe enough to cause hepatocyte necrosis, then the ALT/AST ratio is depressed due to the additional release of the mitochondrial isoenzyme of AST. Both AST and ALT can become elevated before clinical signs or symptoms of disease have manifested, and are therefore a preferred method for assessing hepatocyte health. In contrast to ALT, which is specific to hepatocytes, AST is also stored at high concentrations in the heart, skeletal muscle, and kidneys, and is therefore less liver-specific than ALT. The fact that…