Increase and decrease in alkaline phosphatase

In children, alkaline phosphatase is elevated until puberty. Increased alkaline phosphatase activity accompanies rickets of any etiology, Paget's disease, bone changes associated with hyperparathyroidism. The enzyme activity rapidly increases in osteogenic sarcoma, cancer metastases to bone, myeloma, lymphogranulomatosis with bone damage.

The activity of the liver form of phosphatase most often increases due to damage or destruction of hepatocytes (hepatocellular mechanism) or impaired bile transport (cholestatic mechanism). The hepatocellular mechanism of increasing the activity of alkaline phosphatase plays a leading role in viral and autoimmune hepatitis, toxic and drug-induced liver damage. Bile outflow is impaired due to extrahepatic obstruction of the bile ducts (for example, by a stone or during the development of a postoperative stricture), narrowing of the intrahepatic ducts (for example, in primary sclerosing cholangitis), damage to the bile ducts (for example, in primary biliary cirrhosis of the liver ) or impaired bile transport at the level of small bile ducts (with the use of a number of drugs, such as chlorpromazine). In some cases, the activity of alkaline phosphatase increases due to the simultaneous action of both injury mechanisms.

Increased activity of alkaline phosphatase in liver damage occurs due to its release from hepatocytes. Activity of alkaline phosphatase in viral hepatitis, in contrast to aminotransferases, remains normal or increases slightly. Increased activity of alkaline phosphatase is also detected in icteric patients with liver cirrhosis (in a third of cases).

Approximately half of patients with infectious mononucleosis also show an increase in alkaline phosphatase activity during the first week of the disease. A significant increase in alkaline phosphatase activity is observed in cholestasis. Extrahepatic bile duct obstruction is accompanied by a sharp increase in enzyme activity.

Increased alkaline phosphatase activity is observed in 90% of patients with primary liver cancer and liver metastases. Its activity increases sharply in cases of alcohol poisoning due to alcoholism. It may increase when taking drugs that have a hepatotoxic effect (tetracycline, paracetamol, mercaptopurine, salicylates, etc.). Cholestatic jaundice and, accordingly, increased alkaline phosphatase activity are possible in women taking oral contraceptives containing estrogens and progesterone. According to various authors, only approximately 65% of hospitalized patients have high alkaline phosphatase activity due to liver disease.

Very high enzyme activity is observed in women with preeclampsia, which is associated with placental damage. Reduced alkaline phosphatase activity in pregnant women may indicate insufficient placental development.

In addition to the above reasons, increased alkaline phosphatase activity is detected in the following diseases and conditions: increased metabolism in bone tissue (during fracture healing), primary and secondary hyperparathyroidism, osteomalacia, renal rickets, cytomegalovirus infection (CMV infection) in children, sepsis, ulcerative colitis, regional ileitis, intestinal bacterial infections, thyrotoxicosis. This is due to the fact that alkaline phosphatase is produced not only in the liver, but also in other organs - bones, intestines.

The series of values represent factors by which the upper reference limit value for alkaline phosphatase is multiplied.

An increase in the level of this hepatocyte enzyme suggests the presence of cholestasis. However, alkaline phosphatase consists of several isoenzymes and is found in various tissues, particularly bone.

Alkaline phosphatase levels increase by 4-fold or more within 1 to 2 days of onset of biliary obstruction, regardless of the degree of obstruction. The enzyme level may remain elevated for several days after the obstruction has been relieved, since the half-life of alkaline phosphatase is approximately 7 days. Enzyme levels increase by 3-fold in a variety of liver disorders, including hepatitis, cirrhosis, liver masses, and infiltrative lesions. Isolated elevations of the enzyme (i.e., when other liver function tests are normal) are common with focal liver disease (eg, abscess, tumor) or with partial or intermittent biliary tract obstruction. Isolated elevations also occur in the absence of liver or biliary tract disease, such as malignancies without liver involvement (eg, bronchogenic carcinoma, Hodgkin's lymphoma, renal cell carcinoma), after ingestion of fatty foods (the enzyme is formed in the small intestine), during pregnancy (in the placenta), in children and adolescents during growth (due to bone growth), and in chronic renal failure (in the intestine and bone tissue). Alkaline phosphatase fractionation is technically difficult. Increases in enzymes more specific to the liver, namely 5'-nucleotidase or gamma-glutamyl transpeptidase (GGT), allow differentiation between a hepatic and extrahepatic source of alkaline phosphatase. Isolated elevations in asymptomatic alkaline phosphatase in the elderly are usually associated with skeletal pathology (eg, Paget's disease) and do not require further investigation.

A decrease in alkaline phosphatase activity is observed in hypothyroidism, scurvy, severe anemia, kwashiorkor, and hypophosphatemia.

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