Flashcards in Biochemistry Enzymes and Biomarkers Deck (63)
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Enzymes are:
1. Intracellular catalysts
2. Measured by activity (U/L) or concentration (ng/L)
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Serum enzyme activity is a marker of
Tissue function or dysfunction
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Isoenzymes:
Enzymes of similar catalytic activity but structural differences, pattern may be helpful to localize origin, e.g. CK, ALP
e.g. alkaline phosphatase isoenzymes
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Clinical important enzymes:
• Liver enzymes
• Creatine kinase (CK)
• Amylase
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LFT looks at
Bilirubin
ALk Phosphatase (cholestasis measurement)
ALT – hepatocullar function
Total Protein
Albumin
Globulin
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Tranaminases types
ALT and AST (intracellular enzymes)
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ALT location
Largely confined to hepatic cytoplasm
Use routinely to test liver function
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AST location**
o Hepatic cytoplasm and mitochondria
o Skeletal and cardiac muscle (will rise post MI)
o Red blood cells (haemolysis causes increased0
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Causes of increased transaminase
>10 x ULN (>400 U/L)
• Acute hepatitis and liver necrosis
• Paracetamol poisoning
• Major crush injuries (AST)
• Severe hypoxia
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Increased Transaminase
5-10 x ULN (200-400 U/L)
• Chronic hepatitis
• Following surgery or liver trauma
• Myocardial infarction (AST)
• Skeletal muscle disease (AST)
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Increased Transaminase Usually <5x ULN (40-200 U/L) – upper limit of normal
• Other liver disease (e.g. drug induced)
• Pancreatitis
• Haemolysis (in vivo and in vitro) (AST)
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Haemolysis can cause
increased in AST
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Necrosis of the liver cells e.g. fatty liver disease LF shows
– AST rises more than ALT
• Non-alcohol fatty liver disease
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Tests of cholestasis:
Alkaline Bone phosphatase (ALP)
• Bone (osteoblasts) – can be seen in late childhood with finishing growing
• Liver (biliary tree and cell surface)
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Minor Sources of ALP
• Intestine (some patients, postprandial)
• Placenta (third trimester, variable)
• Rare cancers (e.g. germ cell)
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Causes of increased alkaline phosphatase
Physiological
• Pregnancy (third trimester) – usually use bile acids as test of choice for cholestasis
• Childhood – germ cell tumours
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Causes of increased alkaline phosphatase:
Pathological
Often >5 x ULN
• Cholestasis (intra – and extra hepatic)
• Cirrhosis
• Paget’s disease of bone (metabolic)
• Osteomalacia, rickets
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ALP - Usually <5 x ULN
Seen in
• Hepatitis
• Infiltrative liver disease
• IBD – ascending cholangitis
• Hepatic space-occupying lesions –obstruction drainage
• Bone tumours (primary and secondary) – Mets very common
• Renal bone disease (RARE)
• Primary hyperparathyroidism (longstanding)
• Healing fractures
• Osteomyelitis
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Pregnancy (late) disease:
• HeLLPs syndrome
• Obstetric Cholestasis
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Tests of cholestasis:
Not in liver function tests as very sensitive e.g. ptients with autumn virus (subclinical disease will cause a rise in γGT.
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Gamma glytamyl trnasferase (γGT)
Source – very sensitive
Liver
Kidney
Pancreas
Seminal vesicles
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γGT increased in
Cholestasis and hepatocellular damage
Also due to enzyme induction – alcohol, phenobarbitone, phenytoin, oestrogen
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γGT clinical uses
Detection of alcohol – via hyper-lipid detection – not extremely specific
Identification of the source of ALP (.e. Liver or Bone) – of γGT is normal then ALP likely to be coming from bone.
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γGT in alcohol abuse elevation due to
Enzyme induction
Structural damage – cholestasis e.g. alcoholic cirrhosis
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γGT is elevated in
50-66% of subjects consuming >80g/day
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γGT sensitivity in alcoholics
54-85%
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Predictive value of a positive test for the diagnosis of alcoholism is approximately
20% (if prevalence is 1%)
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AST/ALT elevated and normal alkaline phosphatase means that
Approx. 90% have hepatitis
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AST/ALT normal and elevated alkaline phosphatase means that
Approx. 90% have obstructive jaundice
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