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Clinical Presentations -
Alkaline Phosphatase
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Written by Dr Sebastian Zeki
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Alkaline Phosphatase
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Raised
ALP levels
Alkaline phosphatase
Cholestasis causes
Extra hepatic
Duct: stones/parasites
Wall:
stricture/cholangitis/PSC/choled
ochal 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/liv
er transplantation/benign
post op cholestasis
Cholangiopathies-
PBC/idiopathic adult
ductopenia. Sclerosing
cholangitis
Intrahepatic
Liver Bloods- Cholestasis
Measurement
of
alkaline phosphatase
Measure 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 acids
Present in cell membranes of kidneys, pancreas, liver, spleen, heart, brain, and seminal vesicles
Measurement 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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