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home - Liver - Clinical Presentations - Alkaline Phosphatase Written by Dr Sebastian Zeki

Alkaline Phosphatase

Raised ALP levels Alkaline phosphatase Cholestasis causes Extra hepatic Duct: stones/parasites Wall: stricture/cholangitis/PSC/choledochal cysts Outside: porta hepatis/pancreatic head/pancreatitis either acute or chronic Familial and congenital-PFIC 1,2 and 3-MRPL-ABCG5/8-BRIC (FIC1 gene)-Cholestasis at pregnancy-Choledochal cysts/caroli's disease-Congenital biliary atresia-Dubin Johnson (MRP2 gene) Hepatocellular-ETOH related-Viral hepatitis-Cirrhosis-Medication:-Wilson's-Hereditary haemochromatosis Infiltrative-Granulomatous-Cancer-Amyloidosis Infective-viral/bacterial/fungal/HIV Miscellaneous-post operative sepsis/TPN/pregnancy/liver transplantation/benign post op cholestasis Cholangiopathies-PBC/idiopathic adult ductopenia. Sclerosing cholangitis Intrahepatic Liver Bloods- Cholestasis Measurement of alkaline phosphataseMeasure release of p-nitrophenol or phosphate from p-nitrophenylphosphate under specified conditions.It is expressed as international units (IU/L) (= activity of alkaline phosphatase that releases 1 mmol of chromogen or Pi/min).Polyacrylamide gel slab separation is the best way to seperate liver, bone intestinal, and placental isoenzymes. Gamma-glutamyl transpeptidase (GGT)Catalyzes transfer of GG group from GG peptides (eg glutathione) to other peptides and to L-amino acidsPresent in cell membranes of kidneys, pancreas, liver, spleen, heart, brain, and seminal vesiclesMeasurement done spectrophotometrically using liberated product of enzyme on substrate gamma-L-glutamyl-r-nitroanalide Clinical significance —Present in the serum of healthy individuals (NR 0 30 IU/L (0 to 0.5 mkat/L))Major role is to source alkaline phosphatase as GGT not elevated in bone disease.Isolated GGT elevation may reflect alcohol abuse or alcoholic liver disease Causs of isolated or disproportionate eleva-tion:Partial bile duct obstruction eg. gallstones or tumour.Early in the course of cholestatic liver diseases eg PSC and PBC.Infiltrative diseases eg amyloidosis, sarcoidosis, hepatic abscesses, tuberculosis, and metastatic carcinoma.Extrahepatic diseases such as myeloid metaplasia, peritonitis, diabetes mellitus, subacute thyroiditis, and uncomplicated gastric ulcer (thought to be related to hepatic dysfunction despite the absence of overt liver disease).Extrahepatic tumours, including osteosarco-mas, lung, gastric, head and neck, renal cell carcinoma, ovarian, uterine cancer, and Hodgkin lymphoma, that secrete alkaline phosphatase (often a form known as the Regan isoenzyme) or cause leakage of hepatic alkaline phosphatase into serum by an unknown mechanism.Certain drugs eg phenytoin.Infants and young children occasionally display marked transient elevation of serum alkaline phosphatase activity in the absence of detectable liver or bone disease. Primarily derived from three sources: liver, bone, and the intestinal tract in some patients Clinical significance Alk phos higher in men than women in 15-50 age group.In children- it is related to rate of bone growth- can get transient elevation in the absence of bone or liver disease.Enzyme activity in the serum may double late in normal pregnancy, primarily because of influx from the placenta. Causes of low alkaline phosphatase level Hypothyroidism. Pernicious anaemia. Zinc deficiency. Congenital hypophosphataemia. Acute haemolytic anaemia.Wilson's. Rule out physiological cause:pregnancy, post prandial increase (1.5-2X ULN). Ensure it is not of bony origin with GGT AMA +ve. Undilated ducts Liver biopsy Dilated-ducts ERCP AMA -ve, USS normal >50% increased <50% increased Liver biopsy Observe Check AMA and RUQ USS Written by Dr Sebastian Zeki

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