What is Alkaline Phosphatase?
Alkaline Phosphatase (ALP) is a membrane-bound glycoprotein widely found in almost all living tissues, from bacteria to mammals [1, 2]. It is an enzyme that catalyzes the hydrolysis of phosphate monoesters at alkaline pH, namely the cleavage of these compounds into simpler substances [2, 3].
What does Alkaline Phosphatase do?
ALP plays a critical role in many crucial functions: its presence is necessary for DNA synthesis; it participates in the calcification of bones and dragging down the inflammatory response [4]. It is involved in the transport of phosphate out of epithelial cells of the intestine, and it plays an important role in bone calcification [2, 5].
According to the site of tissue expression, four isozymes of ALP are currently defined: intestinal ALP, placental ALP, germ cell ALP and the liver/bone/kidney (L/B/K) or tissue nonspecific alkaline phosphatase, with clear functional differences between them [2, 4].
As an example in clinical medicine, ALP has long been one of the most frequently assayed enzymes in routine clinical testing. Its elevated level is regarded as a diagnostic biomarker for numerous human diseases including liver dysfunction, bone diseases, acute kidney injury and cancers [6].
Causes of Elevated Alkaline Phosphatase Levels
ALP levels can be elevated for many reasons. Liver disease is the most common cause. ALP is an enzyme produced by the liver. A high ALP level does not exclusively mean that the problem is a result of liver disease. ALP is also produced by bone, therefore it may be elevated because of bone disease.
High ALP levels can also reflect a severe whole-body infection called sepsis. In an analysis of hospitalized patients with extremely high ALP levels, sepsis was identified in 10 of them on a list of potential causes [1].
Obstructive biliary diseases and infiltrative liver disease are likewise relatively common causes of elevated ALP. In one retrospective study of adult inpatients in Thailand, such conditions accounted for among the most commonly identified causes of elevated ALP [2].
High Alkaline Phosphatase Levels in Women
ALP values that are increased may be more important for women, who often experience hormonal fluctuations . After menopause, elevated ALP levels can occur as a result of increased bone turnover, and predict an increased risk of osteoporosis [3].
Pregnancy can also result in increased ALP levels. ALP levels in pregnancy rise up to two times the limit of normal level due to placental release and fetal bone growth [4]; in some cases, very high levels of ALP have been associated with adverse pregnancy outcomes [5].
Does High Alkaline Phosphatase influence Pregnancy?
ALP levels increase up to two times the normal level during pregnancy owing to placental release and foetal bone growth. However, extreme elevations in ALP beyond this point during pregnancy might be associated with perinatal complications [4, 5].
Very high ALP levels have, in some instances, been found to be associated with adverse pregnancy outcomes. In a given case of preeclampsia, abnormally raised cross-sectional ALP levels have been linked to the development of intrahepatic cholestasis of pregnancy and preeclampsia in a pregnant woman without a prior history of preeclampsia. Intrahepatic cholestasis of pregnancy is a liver condition that can be associated with preeclampsia. Another study reported that an abnormally raised pregnancy level was associated with a higher incidence of intrauterine growth restriction (IUGR) [7].
But even if ALP levels increase, there is not always trouble – in some cases, women with markedly elevated ALP have had a normal delivery with a healthy baby [5, 6].
Besides, there is the consideration that the extra ALP may have come from another source than the placenta – perhaps from an elevation of bone isozyme [6, 8] or from placental isozyme [9].
In conclusion, while high ALP levels can occur naturally during pregnancy, extremely high levels may be associated with certain complications. However, more research is needed to fully understand the implications of high ALP levels during pregnancy.
Side effects of High Alkaline Phosphatase in Pregnancy
One possible complication is gestational diabetes. In one study of pregnant subjects, 29% of those with extremely high ALP levels had gestational diabetes mellitus [10].
Another risk is developing hypertensive disorders. The same study found that 29% of pregnant women with high ALP levels also suffered from a hypertensive disorder [10].
Enhanced activity of ALP has occasionally been linked to pre-term birth. For example, one report outlined the case of a woman with extremely high ALP levels who went into labour after only 36 weeks of gestation [4].
A case of intrahepatic cholestasis of pregnancy, an inflammation of the liver occurring during pregnancy, has similarly been causally connected with extremely high ALP levels as well [4].
Lastly, high ALP levels could be indicative of placental insufficiency, a condition where the placenta does not function adequately, compromising fetal health [8].