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 chemicals 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 indicator for certain medical conditions, diseases and syndromes.[citation needed]
If the cause for alkaline phosphatase elevation 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").[clarification needed]
It is essential to use age-specific normal reference values, as healthy infants and children usually have levels that would be considered elevated in adults.[4] Additionally, ALP levels are "not well defined" as of 2020, and can vary by sex and by racial group.[5] Latinos tend to have higher normal levels, followed by those of African heritage, Europeans, and Asians or Pacific Islanders tend to have the lowest baseline ALP levels (all groups assuming body mass index within normal weight range).[5] Men tend to have slightly higher normal ALP levels than women,[5] except during pregnancy.
Other unlisted musculoskeletal conditions may also cause elevated alkaline phosphatase.
Obesity
Elevated levels of the alkaline phosphatase enzyme are reported among 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 nature of the relationship between alkaline phosphatase and obesity is still being investigated.[8]
Kidney
Elevated serum levels of alkaline phosphatase has been associated with chronic kidney disease (CKD).[9] 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.[10]
Elevated alkaline phosphatase in patients with cancer normally spans[clarification needed] throughout the bones or liver. Metastases that exist in the lung, breast, prostate, colon, thyroid, and further organs can also enter the liver or bone.[12] Cancers that are already present in certain organs and tissues can produce alkaline phosphatase elevations if metastasis is not present. In experiential studies, isoenzymes, which are distinct forms of alkaline phosphatase generated by these tumors, can raise the total volume of alkaline phosphatase in the blood. The Regan isoenzyme [clarification needed][13] is one of the best studied[clarification needed] 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 gonadal and urologic cancers.[citation needed]
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 diseases such as Paget disease, liver diseases such as hepatitis, blood disorders, or other conditions.[20]
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.[21] It is possible to distinguish between the different forms (isoenzymes) of ALP produced by different types of body tissues, in order to identify the cause of elevated ALP; this can facilitate choosing a treatment course.
Normally, children and adolescents have higher alkaline phosphatase levels than adults, due to accelerated bone growth. ALP is especially high during the pubertal growth spurt.[22]
Treatments
The following are the most common treatments of elevated alkaline phosphatase.[23]
Treatment of the underlying condition
Once doctors identify the cause of elevated ALP and diagnose a treatment, the levels of alkaline phosphatase fluctuates back to normal
Removal of medication. Drugs can be associated with increased levels of alkaline phosphatase, including:
^Pruessner HT (March 1998). "Detecting celiac disease in your patients". Am Fam Physician. 57 (5): 1023–34, 1039–41. PMID9518950.
^Cremers J, Drent M, Driessen A, Nieman F, Wijnen P, Baughman R, Koek G (January 2012). "Liver-test abnormalities in sarcoidosis". Eur J Gastroenterol Hepatol. 24 (1): 17–24. doi:10.1097/MEG.0b013e32834c7b71. PMID22008629.
^Pareek SS (January 1979). "Liver involvement in secondary syphilis". Dig Dis Sci. 24 (1): 41–3. doi:10.1007/BF01297236. PMID428289.
^Matsushita M, Harajiri S, Tabata S, Yukimasa N, Muramoto Y, Komoda T (April 2013). "[Alkaline phosphatase activity in blood group B or O secretors is fluctuated by the dinner intake of previous night]". Rinsho Byori (in Japanese). 61 (4): 307–12. PMID23855186.
