Test Id : ALKI

Patient's age and sex are required.

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL, divided

Collection Instructions: Centrifuge and aliquot serum into 2 tubes, each containing 0.5 mL

0.5 mL divided into 2 tubes each containing 0.25 mL

Diagnosis and treatment of liver, bone, intestinal, and parathyroid diseases

Determining the tissue source of increased alkaline phosphatase (ALP) activity in serum

Differentiating between liver and bone sources of elevated ALP

Alkaline phosphatase (ALP) is present in a number of tissues including liver, bone, intestine, and placenta. The activity of ALP found in serum is a composite of isoenzymes from those sites and, in some circumstances, placental or Regan isoenzymes. Serum ALP is of interest in the diagnosis of 2 main groups of conditions: hepatobiliary disease and bone disease associated with increased osteoblastic activity.

A rise in ALP activity occurs with all forms of cholestasis, particularly with obstructive jaundice. The response of the liver to any form of biliary tree obstruction is to synthesize more ALP. The main site of new enzyme synthesis is the hepatocytes adjacent to the biliary canaliculi.

ALP is also elevated in disorders of the skeletal system that involve osteoblast hyperactivity and bone remodeling, such as Paget disease, rickets, osteomalacia, fractures, and malignant tumors.

Moderate elevation of ALP may be seen in other disorders such as Hodgkin disease, congestive heart failure, ulcerative colitis, regional enteritis, and intra-abdominal bacterial infections.

ALKALINE PHOSPHATASE

Males

0-14 days: 83-248 U/L

15 days-<1 year: 122-469 U/L

1-<10 years: 142-335 U/L

10-<13 years: 129-417 U/L

13-<15 years: 116-468 U/L

15-<17 years: 82-331 U/L

17-<19 years: 55-149 U/L

> or =19 years: 40-129 U/L

Females

0-14 days: 83-248 U/L

15 days-<1 year: 122-469 U/L

1-<10 years: 142-335 U/L

10-<13 years: 129-417 U/L

13-<15 years: 57-254 U/L

15-<17 years: 50-117 U/L

> or =17 years: 35-104 U/L

ALKALINE PHOSPHATASE ISOENZYMES

Liver 1%

0-6 years: 5.1-49.0%

7-9 years: 3.0-45.0%

10-13 years: 2.9-46.3%

14-15 years: 7.8-48.9%

16-18 years: 14.9-50.5%

> or =19 years: 27.8-76.3%

Liver 1

0-6 years: 7.0-112.7 IU/L

7-9 years: 7.4-109.1 IU/L

10-13 years: 7.8-87.6 IU/L

14-15 years: 10.3-75.6 IU/L

16-18 years: 13.7-78.5 IU/L

> or =19 years: 16.2-70.2 IU/L

Liver 2%

0-6 years: 2.9-13.7%

7-9 years: 3.7-12.5%

10-13 years: 2.9-22.3%

14-15 years: 2.2-19.8%

16-18 years: 1.9-12.5%

> or =19 years: 0.0-8.0%

Liver 2

0-6 years: 3.0-41.5 IU/L

7-9 years: 4.0-35.6 IU/L

10-13 years: 3.3-37.8 IU/L

14-15 years: 2.2-32.1 IU/L

16-18 years: 1.4-19.7 IU/L

> or =19 years: 0.0-5.8 IU/L

Bone %

0-6 years: 41.5-82.7%

7-9 years: 39.9-85.8%

10-13 years: 31.8-91.1%

14-15 years: 30.6-85.4%

16-18 years: 38.9-72.6%

> or =19 years: 19.1-67.7%

Bone

0-6 years: 43.5-208.1 IU/L

7-9 years: 41.0-258.3 IU/L

10-13 years: 39.4-346.1 IU/L

14-15 years: 36.4-320.5 IU/L

16-18 years: 32.7-214.6 IU/L

> or =19 years: 12.1-42.7 IU/L

Intestine %

0-6 years: 0.0-18.4%

7-9 years: 0.0-18.3%

10-13 years: 0.0-11.8%

14-15 years: 0.0-8.2%

16-18 years: 0.0-8.7%

> or =19 years: 0.0-20.6%

Intestine

0-6 years: 0.0-37.7 IU/L

7-9 years: 0.0-45.6 IU/L

10-13 years: 0.0-40.0 IU/L

14-15 years: 0.0-26.4 IU/L

16-18 years: 0.0-12.7 IU/L

> or =19 years: 0.0-11.0 IU/L

Placental

Not present

Total Alkaline Phosphatase:

Alkaline phosphatase (ALP) elevations tend to be more marked (more than 3-fold) in extrahepatic biliary obstructions (eg, by stone or cancer of the head of the pancreas) than in intrahepatic obstructions: the more complete the obstruction, the greater the elevation. With obstruction, serum ALP activities may reach 10 to 12 times the upper limit of normal, returning to normal upon surgical removal of the obstruction. The ALP response to cholestatic liver disease is similar to the response of gamma-glutamyltransferase (GGT) but more blunted. If both GGT and ALP are elevated, a liver source of the ALP is likely.

Among bone diseases, the highest level of ALP activity is encountered in Paget disease, because of the action of the osteoblastic cells as they try to rebuild bone that is being resorbed by the uncontrolled activity of osteoclasts. Values from 10 to 25 times the upper limit of normal are not unusual. Only moderate rises are observed in osteomalacia, while levels are generally normal in osteoporosis. In rickets, levels 2 to 4 times normal may be observed. Primary and secondary hyperparathyroidism are associated with slight to moderate elevations of ALP; the existence and degree of elevation reflects the presence and extent of skeletal involvement. Very high enzyme levels are present in patients with osteogenic bone cancer. A considerable rise in ALP is seen in children following accelerated bone growth.

ALP increases of 2 to 3 times normal may be observed in women in the third trimester of pregnancy, although the reference interval is very wide, and levels may not exceed the upper limit of normal in some cases. In pregnancy, the additional enzyme is of placental origin.

ALP Isoenzymes:

Liver ALP isoenzyme is associated with biliary epithelium and is elevated in cholestatic processes. Various liver diseases (primary or secondary cancer, biliary obstruction) increase the liver isoenzyme.

Liver 1 is increased in some nonmalignant diseases (such as cholestasis, cirrhosis, viral hepatitis, and in various biliary and hepatic pathologies). It is also increased in malignancies with hepatic metastasis, in cancer of the lungs and digestive tract, and in lymphoma.

An increase of liver 2 may occur in cholestasis and biliary diseases (eg, cirrhosis, viral hepatitis) and in malignancies (eg, breast, liver, lung, prostate, digestive tract) with liver metastasis.

Osteoblastic bone tumors and hyperactivity of osteoblasts involved in bone remodeling (eg, Paget disease) increase the bone isoenzyme. Paget disease leads to a striking, solitary elevation of bone ALP.

The intestinal isoenzyme may be increased in patients with cirrhosis and in individuals who are blood group O or B secretors.

The placental (carcino-placental antigen) and Regan isoenzyme can be elevated in cancer patients.

No significant cautionary statements

1. Rifai N, Horvath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics 6th ed. Elsevier; 2018

2. Lowe D, Sanvictores T, John S. Alkaline phosphatase. In: StatPearls [Internet]. StatPearls Publishing; 2021. Updated August 11, 2021. Accessed November 10, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK459201

3. Teitelbaum JE, Laskowski A, Barrows FP: Benign transient hyperphosphatasemia in infants and children: a prospective cohort. J Pediatr Endocrinol Metab. 2011;24(5-6):351-353

4. Jassam NJ, Horner J, Marzo-Ortega H, et al: Transient rise in alkaline phosphatase activity in adults. BMJ Case Rep. 2009;2009: bcr09.2009.2250

5. Verma J, Gorard DA: Persistently elevated alkaline phosphatase. BMJ Case Reports. 2012 Aug;24;2012:bcr2012006768

6. Sharma U, Pal D, Prasad R: Alkaline phosphatase: An overview. Indian J Clin Biochem. 2014 Jul;29(3):269-278

Total Alkaline Phosphatase:

In the presence of magnesium and zinc ions, p-nitrophenyl phosphate is cleaved by phosphatases into phosphate and p-nitrophenol. The p-nitrophenol released is directly proportional to the catalytic alkaline phosphatase (ALP) activity. It is determined by measuring the increase in absorbance.(Package insert: Alkaline Phosphatase reagent. Roche Diagnostics; 02/2012)

ALP Isoenzymes:

Serum samples are electrophoresed through alkaline buffered (pH 9.1) agarose gels. Almost all ALP isoenzymes can be separated by electrophoresis according to their charge difference. However, because the electrophoretic mobilities of the liver and bone isoenzymes are quite similar, a modification is required for separation. The Sebia system utilizes differences between liver and bone isoenzyme sialation to achieve separation. Each sample is applied to the agarose gel in duplicate. One sample is passed through wheat germ lectin (wheat germ agglutin:WGA) and is deposited anodally from the point of sample application. The bone isoenzyme, which is rich in sialic acids, reacts with WGA and precipitates adjacent to the lectin application point. The separated isoenzymes are visualized using a specific chromogenic substrate, 5-bromo-4-chloro-3-indolyl phosphate/nitro blue tetrazolium in aminomethyl propanol (AMP) buffer, pH 10.0. The dried gels are read on a densitometer for the quantification of tissue isoforms.(Package insert: Sebia Hydragel 7 and 15 ISO-PAL. Sebia; 01/2017)

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This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

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