Hepatocytes are therefore unlikely to be affected in this patient by whatever is causing these symptoms.
The 6-fold increase in ALP levels over the upper limit of the normal range for a female between 61 and 65 years of age suggests the presence of disease in a number of different organs and tissues, but the normal AST levels eliminate hepatocytes as a possible source. The combination of high ALP levels and mild hyperbilirubinemia, in the absence of high AST levels, is consistent with a diagnosis of cholestatic disease. Given the patient's gender and age, a diagnosis of primary biliary cirrhosis is certainly possible (Tietz, 1999, p. 1162), but given her history of colorectal cancer, other possibilities need to be explored as well. These include tumor masses blocking the flow of bile, bone malignancies, and other malignancies producing placental ALP ectopically.
Additional tests are required to obtain a definitive diagnosis. First, the possibility of drug toxicity or a history of alcoholism affecting liver function should be assessed (Walmsley, Watkinson, and Cain, 1999, p. 151). If these factors are eliminated then the most instructive laboratory tests would be serum levels for ?-glutamyl transferase (GGT) or 5'-nucleotidase (NTP), because these biliary tract enzymes can help to discriminate between several possible sources of elevated ALP (Tietz, 1999, p. 1168).
GGT is present in all tissues except muscle, but at particularly high concentrations in the kidney (Tietz, 1999, p. 687). Despite the wide distribution throughout the body and being concentrated in the kidneys, elevated serum levels are almost always diagnostic of any form of liver disease. In cases of hepatic or posthepatic biliary obstruction the serum levels may rise 5- to 30-fold above the normal range, and is therefore more sensitive than ALP and NTP, and more specific than ALP.
Although NTP is present in many different tissues throughout the body, it is generally considered to be specific for hepatobiliary disease. In contrast to ALP though, NTP is only slightly elevated by some cases of bone malignancy, but always tracks with ALP when the hepatobiliary system is affected (Tietz, 1999, p. 685). If NPT levels in this patient were found to be similar to ALP levels, then it would be diagnostic for hepatobiliary disease.
If the GGT or NTP serum levels turn out to be significantly elevated, then the cancer history of the patient should trigger an ultrasound and/or CT scan of the biliary tree in an effort to locate any tumor masses that could be obstructing bile flow (Tietz, 1999, p. 1168). Screening for hepatitis should also be performed, because chemotherapy can sometimes trigger reactivation of the virus (Kusumoto, Tanaka, Mizokami, and Ueda, 2009).
Should the above tests for GGT or NTP turn out to be negative, then this would suggest the source of ALP is not the hepatobiliary system, but a bone or other malignancy (Tietz, 1999, p. 1168). In this situation, determining the ALP isoenzyme responsible for the elevated serum levels would be diagnostically useful. This test would help discriminate between liver, bone, and ectopic ALP production by malignancies. Given the gender of the patient and history of cancer, screening for breast cancer is also warranted.
Other tests that should be run given the age of the patient include determination of plasma calcium, phosphate, and vitamin D levels, and running parathyroid hormone studies (Walmsley, Watkinson, and Cain, 1999, pp. 157-158). Blood calcium and phosphate levels could be indicative of bone involvement. Vitamin D deficiency often results in elevated serum ALP levels, and is typically one of the first symptoms detected. Secondary hyperparathyroidism can also cause elevated serum levels of ALP.
Burtis, C.A. And Ashwood, E.R. eds., 1999. Tietz textbook of clinical chemistry. Philidelphia: W.B. Saunders.
Jones, G., 2001. Bilirubin. SydPath: The Institute of Laboratory Medicine. [online] Available at: [Accessed 5 March 2011].
Jones, G., 2005. AST. SydPath: The Institute of Laboratory Medicine. [online] Available at: [Accessed 5 March 2011].
Kusumoto, S., Tanaka, Y., Mizokami, M., and Ueda, R. 2009. Reactivation of hepatitis B virus following systemic chemotherapy for malignant lymphoma. International Journal…