Elevated alkaline phosphatase

Elevated alkaline phosphatase occurs when levels of alkaline phosphatase (ALP) exceed the reference range. This group of enzymes has a low substrate specificity and catalyzes the hydrolysis of phosphate esters in a basic environment. The major function of alkaline phosphatase is transporting across cell membranes.[1] Alkaline phosphatases are present in many human tissues, including bone, intestine, kidney, liver, placenta and white blood cells.[2] Damage to these tissues causes the release of ALP into the bloodstream. Elevated levels can be detected through a blood test. Elevated alkaline phosphate is associated with certain medical conditions[3] or syndromes (e.g., hyperphosphatasia with mental retardation syndrome, HPMRS). It serves as a significant indication for certain medical conditions, diseases and syndromes.

Elevated alkaline phosphatase
Micrograph showing changes that may be associated with an elevated alkaline phosphatase (cholestasis and feathery degeneration). Liver biopsy. H&E stain.
SpecialtyPathology

If the reason for alkaline phosphatase is unknown, isoenzyme studies using electrophoresis can confirm the source of the ALP. Heat stability also distinguishes bone and liver isoenzymes ("bone burns, liver lasts").

Cause

Liver

Bones

Other unlisted musculoskeletal conditions may also cause elevated alkaline phosphatase.

Obesity

Elevated levels of the alkaline phosphatase enzyme are reported with those who have obesity. A study reported there were higher serum levels of alkaline phosphatase in obese than in the non obese. With elevated alkaline phosphatase levels there is an increase in disproportionate intracellular fat depots and thereby releasing itself into the bloodstream. The relationship between alkaline phosphatase and obesity is still being tested.[5]

Kidney

Elevated serum levels of alkaline phosphatase has been associated with Chronic Kidney Disease (CKD). Studies have shown that elevated levels may predict mortality independent of bone metabolism factors and liver function tests in CKD. Elevated levels are also associated with diabetes, hypertension, and cardiovascular disease; it was found that elevated levels are associated with elevated serum C-reactive protein (CRP), which could reflect an inflammatory and atherogenic milieu, possibly an alternative cause for elevated serum alkaline phosphatase.[6]

Cancer

Elevated alkaline phosphatase in patients with cancer normally spans throughout the bones or liver. Metastases that exist in the lung, breast, prostate, colon, thyroid, and further organs can penetrate in the liver or bone.[8] Yet, cancers that are already present in certain organs and tissues can produce alkaline phosphatase elevations if metastasis is not present. Isoenzymes, which are certain forms of alkaline phosphatase generated by these tumors, enlarges the total volume of alkaline phosphatase levels on experiential studies. The Regan isoenzyme[9] is one of the best studies of these isoenzymes that is linked to several human cancers. Basically, the Regan isozenzyme is an alkaline phosphatase that is located in the placenta and associated with the gonadal and urologic cancers.

Diagnosis

An alkaline phosphatase isoenzyme test can be done to check for elevated ALP levels. Tissues that contain high levels of ALP include the liver, bile ducts, and bones. Normal levels of ALP range from (44 to 147) U/L (units per liter) and significantly elevated levels may be an indication of conditions such as various types of cancer, bone disease such as Paget disease, liver disease such as hepatitis, blood disorders, or other conditions.[10]

Elevated alkaline phosphatase is most commonly caused by liver disease or bone disorders. Testing for ALP primarily consists of obtaining a blood sample from a patient along with several other tests for the disorder in question that may be associated with the increase in ALP in the blood serum.[11] It is possible to distinguish between the different forms (isoenzymes) of ALP produced by different types of tissues in the body, in order to pinpoint what's causing the increase of ALP, in order to treat the patient for either liver disease or bone disorder. A more rapid way for testing ALP concentration is by using p-nitrophenyl phosphate as substrate.[12] The required volume of serum is 5 mm3. for each testing. The sample is first incubated for 30 min. at 38 °C, in a buffered solution in the presence of p-nitrophenyl phosphate. By the action of ALP, phosphate groups are removed from the substrate and para- nitrophenol is liberated giving off a yellow color in solution which can be measured spectrophotometrically.[13]

Normally, children and adolescents have higher Alkaline Phosphatase levels than adults due to an increase in bone growth. ALP is especially high during a period of growth spurt which occurs are different ages in boys and girls.[14]

Other

Treatments

The following are the most common treatments of elevated alkaline phosphatase.[21]

  • Treatment of the underlying condition
    • Once doctors identifies the cause of elevated ALP and diagnose a treatment, the levels of alkaline phosphatase fluctuates back to normal
  • Removal of medication – that is associated with increased levels of alkaline phosphatase
  • Dietary changes
    • Include foods rich in vitamin D
  • Lifestyle change
    • Healthy diet in association with physical exercise
    • Exposure to sunlight which increases the production of vitamin D

References
  1. Celik, Handan; Tosun, Midraci; Cetinkaya, Mehmet Bilge; Bektab, Ahmet; Malatyalýodlu, Erdal (2009-08-01). "Markedly elevated serum alkaline phosphatase level in an uncomplicated pregnancy". The Journal of Maternal-Fetal & Neonatal Medicine. 22 (8): 705–707. doi:10.1080/14767050802702323. ISSN 1476-4954. PMID 19544151.
  2. Kaplan, Marshall M. (1972). "Alkaline Phosphatase". New England Journal of Medicine. 286 (4): 200–202. doi:10.1056/nejm197201272860407. PMID 4550137.
  3. Li-Fern H, Rajasoorya C (February 1999). "The elevated serum alkaline phosphatase—the chase that led to two endocrinopathies and one possible unifying diagnosis". Eur. J. Endocrinol. 140 (2): 143–7. doi:10.1530/eje.0.1400143. PMID 10069658.
  4. Gennari L, Di Stefano M, Merlotti D, et al. (October 2005). "Prevalence of Paget's disease of bone in Italy". J. Bone Miner. Res. 20 (10): 1845–50. doi:10.1359/JBMR.050518. PMID 16160742.
  5. Khan, Abdul Rehman; Awan, Fazli Rabbi; Najam, SyedaSadia; Islam, Mehboob; Siddique, Tehmina; Zain, Maryam (2015). "Elevated serum level of human alkaline phosphatase in obesity". Journal of Pakistan Medical Association. 65 (11): 1182–1185. Retrieved 2016-05-19.
  6. Damera, Sriharsha; Raphael, Kalani L.; Baird, Bradley C.; Cheung, Alfred K.; Greene, Tom; Beddhu, Srinivasan (2011-01-02). "Serum alkaline phosphatase levels associate with elevated serum C-reactive protein in chronic kidney disease". Kidney International. 79 (2): 228–233. doi:10.1038/ki.2010.356. PMC 5260661. PMID 20881941.
  7. Damera, Sriharsha (September 2010). "Serum alkaline phosphatase levels associate with elevated serum C-reactive protein in chronic kidney disease". International Society of Nephrology.
  8. Christensen, Stephen. "Elevated Alkaline Phosphatase & Cancer |". LIVESTRONG.COM. Retrieved 2016-05-10.
  9. Fishman, W. H. (1980-01-01). "Immunology and biochemistry of the Regan isoenzyme". The Prostate. 1 (4): 399–410. doi:10.1002/pros.2990010403. ISSN 0270-4137. PMID 7024957.
  10. "ALP – blood test". MedlinePlus. Retrieved 2016-05-10.
  11. Majeska, Robert (April 10, 1982). "The Effect of 1,25(OH)zD3 on Alkaline Phosphatase in Osteoblastic Osteosarcoma Cell". The Journal of Biological Chemistry.
  12. BESSEY, O. A.; LOWKY, O. H.; BROCK, M. J. (1946-01-01). "A method for the rapid determination of alkaline phosphatase with 5 mm3 of serum". Journal of Biological Chemistry. 164. ISSN 0021-9258.
  13. BESSEY, O. A.; LOWKY, O. H.; BROCK, M. J. (1946-01-01). "A method for the rapid determination of alkaline phosphatase with five cubic millimeters of serum". Journal of Biological Chemistry. 164. ISSN 0021-9258.
  14. "Transient hyperphosphatasemia of infancy and early childhood". www.uptodate.com. Retrieved 2017-05-08.
  15. Cappello, Maria; Randazzo, Claudia; Bravatà, Ivana; Licata, Anna; Peralta, Sergio; Craxì, Antonio; Almasio, Piero Luigi (2014). "Liver Function Test Abnormalities in Patients with Inflammatory Bowel Diseases: A Hospital-based Survey". Clinical Medicine Insights: Gastroenterology. 7: 25–31. doi:10.4137/CGast.S13125. ISSN 1179-5522. PMC 4069044. PMID 24966712.
  16. Lange PH, Millan JL, Stigbrand T, Vessella RL, Ruoslahti E, Fishman WH (August 1982). "Placental alkaline phosphatase as a tumor marker for seminoma". Cancer Res. 42 (8): 3244–7. PMID 7093962.
  17. L Tibi; A W Patrick; P Leslie; A D Toft; A F Smith (1989-07-01). "Alkaline phosphatase isoenzymes in plasma in hyperthyroidism". Clinchem.org. Retrieved 2014-07-03.
  18. Pruessner, Harold T, “Detecting Celiac Disease in your Patients” American Family Physician: 57 (5), March 1, 1998 pp1023-1034.
  19. Eur J Gastroenterol Hepatol. 2012 Jan;24(1):17–24. doi: 10.1097/MEG.0b013e32834c7b71. Liver-test abnormalities in sarcoidosis. Cremers J, Drent M, Driessen A, Nieman F, Wijnen P, Baughman R, Koek G.
  20. Pareek, S. S., “Liver involvement in secondary syphilis” Digestive Diseases and Sciences: 24 (1), January 1979 pp 41–43.
  21. "Elevated Alkaline Phosphatase – Levels, Causes and Treatment". healthh.com. Retrieved 2016-05-19.
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