Alkaline phosphatase (ALP)

 

  • Alkaline phosphatase (ALP)

 

Overview:

 

Sites

Alkaline phosphatase (ALP) is an enzyme in the cells lining the biliary ducts of the liver. ALP is also present in bone , intestine and placental tissue

 

 

Functions of phosphatase

Alkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation. As the name suggests, alkaline phosphatases are most effective in an alkaline environment.

 

 

Role inside the body

Its role is not fully known but its attachment to cell membrane suggesting an association between ALP activity and membrane transport so its function may be:

  • Facilitate the transferee of metabolites across cell membrane
  • Calcification process in bone synthesis

 

 

ALP Isoenzymes

Four isoenzymes are found liver isoenzyme , bone isoenzyme , Intestinal isoenzyme , Placental isoenzyme.

  • High activity of serum ALP in infant is due to the predominance of BAP bone isoenzyme
  • LAP liver isoenzyme accounts for most of the activity in healthy adults
  • Placental isoenzyme present in second and third trimester so ALP is elevated during normal pregnancy

 

 

Interpretation:

 

Increased ALP level

Physiological increase

  • Age: children usually have much higher ALP levels than adults because rapid bone growth is normal in children.
  • Pregnancy: women in the third trimester of pregnancy have high ALP levels because the placenta produces ALP.
  • Bone healing: normal healing of a bone fracture can raise ALP levels.

 

Pathological increase

 

  • Liver disease
    • Liver disease without jaundice:

That affect the paranchymal cells as fatty liver and liver cirrhosis show only moderate or even normal ALP

  • Liver disease with jaundice
    • Intra-hepatic cholestasis

This is due to suppression of bile flow due to hepatocellular failure as in hepatocellular carcinoma or metastatic neoplasia (cancer that has spread (metastasized) to the liver from another location in the body.).

 

  • Extra-hepatic cholestasis

This is due to suppression of bile flow due to mechanical obstruction as gall bladder stone and pancreatic head cancer

 

Note:  elevation is more marked in case of extra-hepatic than in intra-hepatic and the degree of obstruction is parallel to increased elevation

 

  • Bone disease

High ALP levels can be caused by bone diseases:

  • Paget’s disease
  • osteosarcoma (so it can be used as a tumor marker for bone cancer)
  • Bone metastases of prostatic cancer (High / very high ALP values)
  • Fractured bone(active bone formation occurring as ALP is a byproduct of osteoblast activity)

 

  • Due to drugs
    • That cause cholestasis: as antidepressants and immunosuppressant
    • That cause cell toxicity: as paracitamol and antiepileptic

 

Decreased ALP level

  • Cretinism

Hypothyroidism in infancy leads to failure of physiological and mental growth

  • Congenital hypophsphatesia

The metabolic basis of hypophosphatasia stems from a molecular defect in the gene encoding tissue non-specific alkaline phosphatase (TNSALP). TNSALP is an enzyme found in the outer surface of osteoblast and chondrocyte cell membranes. This enzyme normally hydrolyzes several substances, including inorganic pyrophosphate (PPi). The enzyme defect leads to inorganic pyrophosphate (PPi) accumulates extracellularly and potently inhibits formation of hydroxyapatite (mineralization) causing rickets in infants and children and osteomalacia (soft bones) in adults.

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