Normal, High, and Low Alkaline Phosphatase

Alkaline Phosphatase (ALP) exists in all the tissues of human body. However, the highest concentrations of Alkaline Phosphatase are found in the liver, bone, and biliary tract epithelium. This type of phosphatase enzyme is named “Alkaline” since its activity elevates in an alkaline environment (pH between 9 and 10). Alkaline Phosphatase test is used to diagnose minor liver and bone disorders.


Alkaline Phosphatase is found in Kupffer cells which are located in the Liver. Kupffer cells are macrophages that breakdown old Red Blood Cells into reusable Globin chains, Iron, and bilirubin which is conjugated glucuronic acid later. Kupffer cell line the walls of the biliary collecting system and Alkaline Phosphatase is excreted into the bile along with the conjugated bilirubin. Hepetic Tumors and Hepatitis are Liver conditions that are associated with slightly high Alkaline Phosphatase levels. However, the Alkaline Phosphatase is mainly used to diagnose other Liver diseases including Cirrhosis and Metastatic Liver Tumer


Bone is the most frequent extrahepatic source of ALP; new bone growth is associated with elevated ALP levels. Pathologic new bone growth occurs with osteoblastic metastatic (e.g., breast, prostate) tumors. Paget disease, healing fractures, rheumatoid arthritis, hyperparathyroidism, and normal-growing bones are sources of elevated ALP levels as well.


Isoenzymes of ALP are also used to distinguish between liver and bone diseases. These isoenzymes are most easily differentiated by the heat stability test and electrophoresis. The isoenzyme of liver origin (ALP1) is heat stable; the isoenzyme of bone origin (ALP2) is inactivated by heat. The detection of isoenzymes can help differentiate the source of the pathologic condition associated with the elevated total ALP. ALP1 would be expected to be high when liver disease is the source of the elevated total ALP. ALP2 would be expected to be high when bone disease is the source of the elevated total ALP. Another way to separate the source of elevated ALP is to simultaneously test for 5′-nucleotidase. This later enzyme is made predominantly in the liver. If total ALP and 5′-nucleotidase are concomitantly elevated, the disease is in the liver. If 5′-nucleotidase is normal, the bone is the most probable source.




Causes of False Alkaline Phosphatase Indications

  • Recent ingestion of a meal can increase the ALP level.
  • Age: Young children with rapid bone growth have increased ALP levels. This is most magnified during the growth spurt. Females and males differ in age of growth spurt.
  • Drugs that may cause high ALP levels include Albumin which is made from the placental tissue, Allopurinol, Antibiotics, Azathioprine, colchicine, fluorides, indomethacin, isoniazid (INH), methotrexate, methyldopa, nicotinic acid, phenothiazine, probenecid, tetracycline, and verapamil.
  • Drugs that may cause low levels include arsenicals, cyanides, fluorides, nitrofurantoin, oxalates, and zinc salts.




Normal Alkaline Phosphatase Levels

Children normally have higher Alkaline Phosphatase levels than adults because their bones are growing. ALP levels also increase rabidly during the “growth spurt,” which occurs at different ages in males and females. The following are the ranges of Normal Alkaline Phosphatase Levels for each age group:


Children younger than 2 years: 85 to 235 units/L.

Between 2 and 8 years: 65 to 210 units/L.

Between 9 and 15 years: 60 to 300 units/L.

Between 16 and 21 years: 30-300 units/L.

Adults: 30 to 120 units/L.




Causes of High Alkaline Phosphatase Levels

  • Alkaline Phosphatase is found in the liver and biliary epithelium and it is normally excreted into the bile. Obstruction will cause elevations in ALP levels in the blood which is caused by Primary Cirrhosis, Intrahepatic or Extrahepatic Biliary Obstruction, or Primary or Metastatic Liver Tumor.
  • ALP comes from the bone, which is the reason why High Alkaline Phosphatase Levels are associated with Metastatic Tumor to the Bone, Healing Fracture, Hyperparathyroidism, Osteomalacia, Paget Disease, Rheumatoid Arthritis, and Rickets.
  • Intestinal Ischemia or Infarction.
  • Myocardial Infarction.
  • Sarcoidosis.




Causes of Low Alkaline PhosphataseLevels

  • Hypophosphatemia: There is insufficient phosphate to make ALP.
  • Hypophosphatasia.
  • Malnutrition.
  • Milk-alkali syndrome.
  • Pernicious anemia.
  • Scurvy (vitamin C deficiency).