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4.17: Bone Disease, Alkaline Phosphatase Isoenzymes

  • Page ID
    122358
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    A “bone profile” (calcium, inorganic phosphate, and alkaline phosphatase) has been performed on a hospital patient who is being treated for pneumonia. The alkaline phosphatase result is 375 U/L (upper limit of normal for an adult is approximately 100 U/L). The calcium and inorganic phosphorus results are within accepted normal ranges. The patient’s physician would like the laboratory to determine the source of the elevated alkaline phosphatase.

    QUESTIONS

    1. What would be the best procedure(s) to perform to differentiate the source of the elevated alkaline phosphatase?
    2. This laboratory uses polyacrylamide gel electrophoresis to determine the source of increased alkaline phosphatase. However, since it is Friday afternoon, the electrophoresis will not be performed until the following week. Since it is presumed that the serum alkaline phosphatase is elevated because of some tissue disease, an alternative approach is to measure some other analyte that would reflect liver or bone dysfunction. What other commonly available tests might be used to establish the source of the alkaline phosphatase?
    3. The laboratory performs a hepatic profile consisting of AST, ALT, gama-glutamyl transferase, and total bilirubin. The results for all these analytes are within the accepted normal range. If the results of these tests are within the reference range, one assumes, with 95% confidence, that bone is the source of the increased serum alkaline phosphatase activity. If the enzymes are significantly elevated (>3 times upper limit), liver is assumed to be the source. Therefore, the most likely source of the increased serum alkaline phosphatase is presumed to be bone.

      The results of the hepatic profile are communicated to the physician who remains concerned about the source of the elevated alkaline phosphatase. Some information about the patient is requested, and the laboratory is told that the patient is a 14 year old male who was brought into the hospital three days ago for a severe upper respiratory tract infection. How does this additional information help resolve the problem of the elevated alkaline phosphatase activity?

    Questions to Consider

    1. Which tissue sources contribute the majority of the alkaline phosphatase activity found in serum?
    2. What procedures are available to measure alkaline phosphatase isoenzymes?
    3. Are there sensitive tests to determine whether liver is the source of elevated serum alkaline phosphatase?
    4. Since calcium concentration, the marker for bone disease, is normal, does this rule out bone disease?
    5. Are there any non-disease states that can cause an elevation in bone alkaline phosphatase activity?
    Answer
    1. The best procedure for estimating the source of alkaline phosphatase isoenzymes is polyacrylamide gel electrophoresis.
    2. Since good alkaline phosphatase isoenzyme procedures are costly, the approach used here is reasonable. The enzymes gammaglutamyl transferase, AST, and ALT are quick and inexpensive ways to rule out liver as the source of an increased alkaline phosphatase (Chapter 27). Large elevations (2-3 times the upper limit of the reference ranges) of these enzymes, especially gamma glutamyl transferase, 5' nucleotidase, would strongly suggest that liver is the source of the elevated alkaline phosphatase. Relatively normal enzyme activities would point to bone as the source of the elevated alkaline phosphatase.
    3. This additional information clearly supports the previous laboratory data. Both the physician and laboratory agree that the source of the elevated alkaline phosphatase is normal bone growth activity in this actively growing patient. The reference range for serum alkaline phosphatase for pre-adult males and females can be 2-3 times higher than the adult values (See Method Alkaline Phosphatase in CD-ROM).

    Answers to Questions to Consider

    1. The most usual tissue sources of alkaline phosphatase found in serum are liver, bone, and intestine (See Method Alkaline Phosphatase on CD-ROM).
    2. The most commonly used methods for estimating the amounts of individual alkaline phosphatase isoenzymes are heat or chemical inactivation, and physical separation by polyacrylamide gel electrophoresis (See Method Alkaline Phosphatase on CD-ROM).
    3. Gamma glutamyl transferase, 5' nucleotidase, and the transaminases, ALT and AST, are all used as markers of liver dysfunction (Chapter 27). Because the transaminases are relatively non-specific for liver function, many laboratories use gamma glutamyl transferase or 5' nucleotidase, which are more specific for the liver and are not present in bone, to help differentiate between bone and liver disease. An elevation in serum alkaline phosphatase accompanied by normal levels of gamma glutamyl transferase or 5' nucleotidase would strongly suggest bone as the source of the alkaline phosphatase.
    4. No. Such bone disease as osteoporosis, osteotitis fibrosa, and vitamin D resistant rickets can be associated with normal serum calcium levels (Chapter 28).
    5. Increases in bone alkaline phosphatase activity can be seen in patients mending broken bones, patients being treated with lithium, and in pre-pubital, growing children (See Chapter 28 and Method Alkaline Phosphatase in CD-ROM).

    This page titled 4.17: Bone Disease, Alkaline Phosphatase Isoenzymes is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by Lawrence Kaplan & Amadeo Pesce.

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