What is alkaline phosphatase

Alkaline phosphatase (ALP) is an enzyme found in several tissues throughout your body. The highest concentrations of alkaline phosphatase are present in the cells that comprise bone and the liver. Elevated levels of alkaline phosphatase in the blood are most commonly caused by liver disease or bone disorders. Alkaline phosphatase (ALP) occurs in osteoblasts, hepatocytes, leukocytes, the kidneys, spleen, placenta, prostate, and the small intestine. The liver-bone-kidney type is particularly important.

In the liver, alkaline phosphatase is found on the edges of cells that join to form bile ducts, tiny tubes that drain bile from the liver to the bowels, where it is needed to help digest fat in the diet.

Alkaline phosphatase in bone is produced by special cells called osteoblasts that are involved in the formation of bone. Each of the various tissue types produces distinct forms of alkaline phosphatase called isoenzymes. Alkaline phosphatase in serum consists of 4 structural genotypes:

• the liver-bone-kidney type,
• the intestinal type,
• the placental type, and
• the variant from the germ cells.

Alkaline phosphatase isoenzyme test may be used to diagnose or monitor:

• Bone disease
• Liver, gallbladder, or bile duct disease
• Pain in the abdomen
• Parathyroid gland disease
• Vitamin D deficiency

It may also be done to check liver function and to see how medicines you take may affect your liver.

Increases in serum alkaline phosphatase (ALP) activity commonly originate from 1 or both of 2 sources: liver and bone. Consequently, serum alkaline phosphatase measurements are of particular interest in the investigation of 2 groups of conditions: hepatobiliary disease and bone disease associated with increased osteoblastic activity.

Alkaline phosphatase blood levels can be greatly increased, for example, in cases where one or more bile ducts are blocked (obstructive jaundice). This can occur as a result of inflammation of the gallbladder (cholecystitis) or gallstones. Smaller increases of blood alkaline phosphatase are seen in liver cancer and cirrhosis, with use of drugs toxic to the liver, and in hepatitis.

Any condition causing excessive bone formation, including bone disorders such as Paget’s disease, hyperparathyroidism, rickets and osteomalacia, as well as with fractures and malignant tumors, can cause increased alkaline phosphatase levels.

Children and adolescents typically have higher blood alkaline phosphatase levels caused by increased osteoblast activity because their bones are still growing. As a result, the alkaline phosphatase test must be interpreted with different reference (normal) values for children and for adults.

It is possible to distinguish between the different forms (isoenzymes) of alkaline phosphatase produced by different types of tissues in the body. If it is not apparent from clinical signs and symptoms whether the source of a high alkaline phosphatase test result is from liver or bone disease, then a test may be performed to determine which isoenzyme is increased in the blood.

Who is at risk for liver disease and/or damage?

Some of those who are at risk of liver disease include the following:

• People who have been exposed to hepatitis viruses
• Heavy drinkers
• People who take medication that can be toxic to the liver or who are exposed to other liver toxins
• Those who are obese, have metabolic syndrome or insulin resistance
• Those who suffer from congestive heart failure
• People with an inherited disorder affecting the liver such as Wilson disease or hemachromatosis

Alkaline phosphatase blood test

The alkaline phosphatase test is used to help detect liver disease or bone disorders.

• In conditions affecting the liver, damaged liver cells release increased amounts of alkaline phosphatase into the blood. This test is often used to detect blocked bile ducts because alkaline phosphatase is especially high in the edges of cells that join to form bile ducts. If one or more of them are obstructed, for example by a tumor, then blood levels of alkaline phosphatase will often be high.
• Any condition that affects bone growth or causes increased activity of bone cells can affect alkaline phosphatase levels in the blood. An alkaline phosphatase test may be used, for example, to detect cancers that have spread to the bones or to help diagnose Paget’s disease, a condition that causes malformed bones. This test may also sometimes be used to monitor treatment of Paget’s disease or other bone conditions, such as vitamin D deficiency.

If alkaline phosphatase results are increased but it is not clear whether this is due to liver or bone disease, tests for alkaline phosphatase isoenzyme may be done to determine the cause. A gamma-glutamyl transferase (GGT) test and/or a test for 5′-nucleotidase may also be done to differentiate between liver and bone disease. Gamma-glutamyl transferase (GGT) and 5′-nucleotidase levels are increased in liver disease but not in bone disorders.

When is alkaline phosphatase test ordered?

An alkaline phosphatase test may be ordered as part of routine laboratory testing, often with a group of other tests called a liver panel. It is also usually ordered along with several other tests when a person has symptoms of a liver or bone disorder.

Signs and symptoms of liver involvement may include:

• Weakness, fatigue
• Loss of appetite
• Nausea, vomiting
• Abdominal swelling and/or pain
• Jaundice
• Dark urine, light-colored stool
• Itching (pruritus)

Some examples of the signs and symptoms suggesting a bone disorder include:

• Bone and/or joint pain
• Increased frequency of fractures
• Deformed bones

Other conditions for which the alkaline phosphatase test may be done:

• Alcoholic liver disease (hepatitis/cirrhosis)
• Alcoholism
• Biliary stricture
• Gallstones
• Giant cell (temporal, cranial) arteritis
• Multiple endocrine neoplasia (MEN) II
• Pancreatitis
• Renal cell carcinoma

Alkaline phosphatase normal levels

Males

• Age 0-14 days: 83-248 U/L
• Age 15 days to 1 year: 122-469 U/L
• Age 1 to 10 years: 142-335 U/L
• Age 10 to 13 years: 129-417 U/L
• Age  13 to 15 years: 116-468 U/L
• Age 15 to 17 years: 82-331 U/L
• Age 17 to 19 years: 55-149 U/L
• Age 19 years and over: 40-129 U/L

Females

• Age 0-14 days: 83-248 U/L
• Age 15 days to 1 year: 122-469 U/L
• Age 1 to 10 years: 142-335 U/L
• Age 10 to 13 years: 129-417 U/L
• Age 13 to 15 years: 57-254 U/L
• Age 15 to 17 years: 50-117 U/L
• Age 17 years and over: 35-104 U/L

What does abnormal alkaline phosphatase test result mean?

Higher-than-normal alkaline phosphatase levels:

• Biliary obstruction or a blockage in the bile duct
• Cirrhosis
• Hepatitis
• Mononucleosis, which can sometimes cause swelling in the liver
• Bone disease
• Eating a fatty meal if you have blood type O or B
• Healing fracture
• Hepatitis
• Hyperparathyroidism
• Leukemia
• Liver disease
• Lymphoma
• Osteoblastic bone tumors
• Osteomalacia
• Paget disease
• Rickets
• Sarcoidosis

Lower-than-normal levels of alkaline phosphatase:

• Hypophosphatasia
• Malnutrition
• Protein deficiency
• Wilson disease

Levels that are only slightly higher than normal may not be a problem unless there are other signs of a disease or medical problem.

Alkaline phosphatase high

High alkaline phosphatase usually means that either the liver has been damaged or a condition causing increased bone cell activity is present.

Serum alkaline phosphatase was the first enzyme to be used for the investigation of liver disease. The response of the liver to any form of biliary tree obstruction induces the synthesis of alkaline phosphatase by hepatocytes. The newly formed coenzyme is released from the cell membrane by the action of bile salts and enters the circulation to increase the enzyme activity in serum. Increase tends to be more notable (greater than 4-fold the upper reference value) in extrahepatic obstruction (e.g., by gallstone, by cancer of the head of the pancreas) than in intrahepatic obstruction, and is greater the more complete the obstruction. Serum enzyme activities may reach 10 to 12 times the upper reference value and usually return to baseline on surgical removal of the obstruction. A similar increase is seen in patients with advanced primary liver cancer or widespread secondary hepatic metastases. Alkaline phosphatase increase (greater than 2-fold the upper reference value) can predict transplant-free survival rates of patients with primary biliary cirrhosis.

Liver diseases that principally affect parenchymal cells, such as infectious hepatitis, typically show only moderately (less than 3-fold) increased or even normal serum alkaline phosphatase activities. Increases may also be seen as a consequence of a reaction to drug therapy, and alanine aminotransferase (ALT)/alkaline phosphatase-based criteria to discriminate the type of liver injury in drug-induced hepatic toxicity have been recommended. Intestinal alkaline phosphatase isoenzyme, an asialoglycoprotein normally cleared by the hepatic asialoglycoprotein receptors, is often increased in patients with liver cirrhosis.

If other liver tests such as bilirubin, aspartate aminotransferase (AST), or alanine aminotransferase (ALT) are also high, usually the increased alkaline phosphatase is coming from the liver. If gamma-glutamyl transferase (GGT) or 5′-nucleotidase is also increased, then the high alkaline phosphatase is likely due to liver disease. If either of these two tests is normal, then the high alkaline phosphatase is likely due to a bone condition. Likewise, if calcium and/or phosphorus measurements are abnormal, usually the alkaline phosphatase is coming from bone.

If it is not clear from signs and symptoms or from other routine tests whether the high alkaline phosphatase is from liver or bone, then a test for alkaline phosphatase isoenzymes may be necessary to distinguish between bone and liver alkaline phosphatase.

Pregnancy can increase alkaline phosphatase levels. Temporary elevations are also seen with healing fractures.

Children and adolescents normally have higher alkaline phosphatase levels than adults because their bones are growing, and alkaline phosphatase is often very high during a growth spurt, which occurs at different ages in boys and girls.

Some drugs may affect alkaline phosphatase levels. For example, oral contraceptives may decrease levels while anti-epileptics may increase levels.

Alkaline phosphatase in liver disease

Alkaline phosphatase results are usually evaluated along with other tests for liver disease. There are other commonly used liver tests that measure other enzymes found in liver cells, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). A test for bilirubin, a substance produced by the breakdown of red blood cells and removed from the body by the liver, may also be performed. Sometimes these tests (along with albumin and total protein testing) are run together as a liver panel. Other tests that may be performed individually or as part of a liver panel to detect or monitor liver disease include gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), and prothrombin time (PT).

In some forms of liver disease, such as hepatitis, alkaline phosphatase (ALP) is usually much less elevated than aspartate aminotransferase (AST) and alanine aminotransferase (ALT). When the bile ducts are blocked (usually by gallstones, scars from previous gallstones or surgery, or by cancers), alkaline phosphatase and bilirubin may be increased much more than AST or ALT. Alkaline phosphatase may also be increased in liver cancer.

Alkaline phosphatase in bone disease

In some bone diseases, such as Paget’s disease, where bones become enlarged and deformed, or in certain cancers that spread to bone, alkaline phosphatase may be increased.

If a person is being successfully treated for Paget’s disease, then alkaline phosphatase levels will decrease or return to normal over time. If someone with bone or liver cancer responds to treatment, alkaline phosphatase levels should decrease.

Depending on the cause of the bone disease, your condition may be diagnosed and/or monitored using other tests such as calcium, phosphorus, parathyroid hormone [PTH], vitamin D, or bone markers (a group of tests used to measure bone formation and bone resorption).

Moderately elevated alkaline phosphatase

Moderately elevated alkaline phosphatase may result from other conditions, such as Hodgkin’s lymphoma, congestive heart failure, ulcerative colitis, and certain bacterial infections.

Alkaline phosphatase low

• Low levels of alkaline phosphatase may be seen temporarily after blood transfusions or heart bypass surgery.
• A deficiency in zinc may cause decreased levels.
• A rare genetic disorder of bone metabolism called hypophosphatasia can cause severe, protracted low levels of alkaline phosphatase.
• Malnutrition or protein deficiency as well as Wilson disease could also be possible causes for lowered alkaline phosphatase.