Biochemistry Enzymes and Biomarkers Flashcards
Enzymes are:
- Intracellular catalysts
2. Measured by activity (U/L) or concentration (ng/L)
Serum enzyme activity is a marker of
Tissue function or dysfunction
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
Clinical important enzymes:
- Liver enzymes
- Creatine kinase (CK)
- Amylase
LFT looks at
Bilirubin ALk Phosphatase (cholestasis measurement) ALT – hepatocullar function Total Protein Albumin Globulin
Tranaminases types
ALT and AST (intracellular enzymes)
ALT location
Largely confined to hepatic cytoplasm
Use routinely to test liver function
AST location**
o Hepatic cytoplasm and mitochondria
o Skeletal and cardiac muscle (will rise post MI)
o Red blood cells (haemolysis causes increased0
Causes of increased transaminase
>10 x ULN (>400 U/L)
- Acute hepatitis and liver necrosis
- Paracetamol poisoning
- Major crush injuries (AST)
- Severe hypoxia
Increased Transaminase
5-10 x ULN (200-400 U/L)
- Chronic hepatitis
- Following surgery or liver trauma
- Myocardial infarction (AST)
- Skeletal muscle disease (AST)
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)
Haemolysis can cause
increased in AST
Necrosis of the liver cells e.g. fatty liver disease LF shows
– AST rises more than ALT
• Non-alcohol fatty liver disease
Tests of cholestasis:
Alkaline Bone phosphatase (ALP)
• Bone (osteoblasts) – can be seen in late childhood with finishing growing
• Liver (biliary tree and cell surface)
Minor Sources of ALP
- Intestine (some patients, postprandial)
- Placenta (third trimester, variable)
- Rare cancers (e.g. germ cell)
Causes of increased alkaline phosphatase
Physiological
- Pregnancy (third trimester) – usually use bile acids as test of choice for cholestasis
- Childhood – germ cell tumours
Causes of increased alkaline phosphatase:
Pathological
Often >5 x ULN
- Cholestasis (intra – and extra hepatic)
- Cirrhosis
- Paget’s disease of bone (metabolic)
- Osteomalacia, rickets
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
Pregnancy (late) disease:
- HeLLPs syndrome
* Obstetric Cholestasis
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.
Gamma glytamyl trnasferase (γGT)
Source – very sensitive
Liver
Kidney
Pancreas
Seminal vesicles
γGT increased in
Cholestasis and hepatocellular damage
Also due to enzyme induction – alcohol, phenobarbitone, phenytoin, oestrogen
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.
γGT in alcohol abuse elevation due to
Enzyme induction
Structural damage – cholestasis e.g. alcoholic cirrhosis
