Alkaline Phosphatase Isoenzyme
Order Code: ALPI
Epic Lab Code: LAB2552
Order Form: A-1a Miscellaneous Request or Epic Req
Commercial Mail-out Laboratory
01250 PFP
356-3527
Specimen(s):
Serum
Collection Medium:
Red top tube
Minimum:
1 mL of serum divided into TWO tubes each containing 0.5 mL
Specimen Instructions:
Patient's age and sex are required.
Testing Schedule:
Alkaline Phosphatase: Monday through Sunday; Continuously
Alkaline Phosphatase Isoenzymes: Monday through Friday
Turn Around Time:
4 days upon receipt at reference laboratory
Reference Range:
ALKALINE PHOSPHATASE Males Females 4 years: 149-369 U/L 4 years: 169-372 U/L 5 years: 179-416 U/L 5 years: 162-355 U/L 6 years: 179-417 U/L 6 years: 169-370 U/L 7 years: 172-405 U/L 7 years: 183-402 U/L 8 years: 169-401 U/L 8 years: 199-440 U/L 9 years: 175-411 U/L 9 years: 212-468 U/L 10 years: 191-435 U/L 10 years: 215-476 U/L 11 years: 185-507 U/L 11 years: 178-526 U/L 12 years: 185-562 U/L 12 years: 133-485 U/L 13 years: 182-587 U/L 13 years: 120-449 U/L 14 years: 166-571 U/L 14 years: 153-362 U/L 15 years: 138-511 U/L 15 years: 75-274 U/L 16 years: 102-417 U/L 16 years: 61-264 U/L 17 years: 69-311 U/L 17-23 years: 52-144 U/L 18 years: 52-222 U/L 24-45 years: 37-98 U/L > or =19 years: 45-115 U/L 46-50 years: 39-100 U/L 51-55 years: 41-108 U/L 56-60 years: 46-118 U/L 61-65 years: 50-130 U/L > or =66 years: 55-142 U/L Reference values have not been established for patients that are <4 years of age. ALKALINE PHOSPHATASE ISOENZYMES Liver 1% Liver 1 0-6 years: 5.1-49.0% 0-6 years: 7.0-112.7 IU/L 7-9 years: 3.0-45.0% 7-9 years: 7.4-109.1 IU/L 10-13 years: 2.9-46.3% 10-13 years: 7.8-87.6 IU/L 14-15 years: 7.8-48.9% 14-15 years: 10.3-75.6 IU/L 16-18 years: 14.9-50.5% 16-18 years: 13.7-78.5 IU/L > or =19 years: 27.8-76.3% > or =19 years: 16.2-70.2 IU/L Liver 2% Liver 2 0-6 years: 2.9-13.7% 0-6 years: 3.0-41.5 IU/L 7-9 years: 3.7-12.5% 7-9 years: 4.0-35.6 IU/L 10-13 years: 2.9-22.3% 10-13 years: 3.3-37.8 IU/L 14-15 years: 2.2-19.8% 14-15 years: 2.2-32.1 IU/L 16-18 years: 1.9-12.5% 16-18 years: 1.4-19.7 IU/L > or =19 years: 0.0-8.0% > or =19 years: 0.0-5.8 IU/L Bone % Bone 0-6 years: 41.5-82.7% 0-6 years: 43.5-208.1 IU/L 7-9 years: 39.9-85.8% 7-9 years: 41.0-258.3 IU/L 10-13 years: 31.8-91.1% 10-13 years: 39.4-346.1 IU/L 14-15 years: 30.6-85.4% 14-15 years: 36.4-320.5 IU/L 16-18 years: 38.9-72.6% 16-18 years: 32.7-214.6 IU/L > or =19 years: 19.1-67.7% > or =19 years: 12.1-42.7 IU/L Intestine % Intestine 0-6 years: 0.0-18.4% 0-6 years: 0.0-37.7 IU/L 7-9 years: 0.0-18.3% 7-9 years: 0.0-45.6 IU/L 10-13 years: 0.0-11.8% 10-13 years: 0.0-40.0 IU/L 14-15 years: 0.0-8.2% 14-15 years: 0.0-26.4 IU/L 16-18 years: 0.0-8.7% 16-18 years: 0.0-12.7 IU/L > or =19 years: 0.0-20.6% > or =19 years: 0.0-11.0 IU/L Placental Not present
Interpretive Data:
Total Alkaline Phosphatase (ALP)
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, and 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's disease, as a result 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 (L1) is increased in some non-malignant 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 (L2) 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's disease) increase the bone isoenzyme. Paget's 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 (carcinoplacental antigen) and Regan isoenzyme can be elevated in cancer patients.
Comments:
Useful for: 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 also is elevated in disorders of the skeletal system that involve osteoblast hyperactivity and bone remodeling, such as Paget's disease rickets and osteomalacia, fractures, and malignant tumors. Moderate elevation of ALP may be seen in other disorders such as Hodgkin's disease, congestive heart failure, ulcerative colitis, regional enteritis, and intra-abdominal bacterial infections.
Test Limitations:
Bone Specific Alkaline Phosphatase and 5'nucleotidase may be useful in identifying disorders of bone and liver, respectively.
Methodology:
Total Alkaline Phosphatase (ALP)
ALP cleaves p-nitrophenyl phosphate in the presence of magnesium ion to yield phosphate and p-nitrophenol. The rate of p-nitrophenol formation is directly proportional to the ALP activity and is determined photometrically at 450 nm.

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 in order 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.
CPT Code:
84075, 84080