The alkaline phosphatases (ALP) are a group of enzymes with similar catalytic activity. They may be found in high concentration in a number of tissues throughout the body. Different tissues contain different isoenzymes or isoforms and this may allow identification of the source of ALP in some cases. The tissues which contain highest levels of ALP are liver, bone, placenta, and intestine. As a liver function test ALP particularly reflects pathology of the biliary system, therefore known as a cholestatic enzyme.

Physiological rises in ALP (source in brackets)

• Any period of growth, especially infants and during adolescence (bone)
• During Pregnancy, especially during the third trimester (placenta)

Pathological rises in ALP due to Bone disease

• Paget’s disease
• Bone malignancy (primary or secondary)
• Hyperparathyroidism
• Vitamin D deficiency
• Healing fracture
• Chronic renal failure.

ALP is a marker of bone formation due to osteoblast activity.

Pathological rises in ALP due to Liver disease (hepatic)

• Cholestasis, including inflammation of the biliary tree
• Hepatocellular damage – less significant and delayed compared to the rise in ALT
• Hepatic space occupying lesion, including primary or secondary malignancies
• Drugs, especially alcohol and anti-convulsants (less frequently than GGT)

Other causes of ALP elevation

• Ectopic production by malignancies – the Regan isoenzyme
• Transient hyperphosphatasaemia of infancy
• Hyperthyroidism
• Congestive cardiac failure.

Physiology: There are 4 genes in the ALP gene family: intestinal ( found on chromosome 2); placental (2); germ cell (2) and non-tissue specific (1). The tissue non-specific isoenzyme includes the common serum forms of ALP from bone and liver.
Intestine and placenta are "true" isoenzymes, ie from different genes. Liver and bone ALP are isoforms of the tissue non-specific isoenzyme, differing due to post-translational glycation. In adult plasma bone and liver ALP are found at similar concentrations. In children bone ALP is usually the predominant form in the circulation. Bone ALP is an ectozyme of osteoblasts bound to outer cell membrane by linkage to phosphotidyl inositol, some of which is released into the circulation.

Pathology: Circulating levels of bone ALP are raised in conditions of increased bone deposition, ie increased osteoblast activity. This occurs during bone growth, (eg puberty), with various diseases and some drugs (eg cyclosporin treatment). Low levels occur with decreased bone deposition eg systemic steroid treatment. Serum concentrations of bone ALP parallel growth velocity and may be used to monitor the response to Growth Hormone treatment in children. Placental ALP is found in the circulation during pregnancy and is identified by a marked stability to heating. This type of ALP is also occasionally produced by malignancies.

Measurement: In most cases the source of the ALP is not in doubt. Comparison with GGT is generally informative with simultaneous rises occurring when liver is the source and ALP alone with bone sources. Qualitative identification may be performed by several techniques of which electrophoresis with is a satisfactory method. Results from this method will indicate the predominant form present in the plasma and will indicate the presence of any abnormal forms. The method however is not quantitative. It is not possible to perform fractionation at total ALP concentrations of les than 150 U/L.