CHEMPATH: Enzymes and Cardiac Markers Flashcards
Where is ALP found?
- Intestines
- Bone
- Liver
- Placenta
How can you differentiate between liver and bone ALP?
- GGT measurement (if GGT raised with ALP implies ALP is coming from the liver)
- Electrophoresis separation
- Bone-specific ALP immunoassay
What is the clinical approach to unexplained high ALP?
- Look at LFTs - ALT, GGT
- Vitamin D levels - if deficiency then increased bone metabolism can cause increased ALP
- ALP isoenzymes by electrophoresis can also be done
Does reference range vary for ALP according to anything?
Age and sex in childhood, then evens out
When does raised ALP indicate osteoporosis?
Only when a fracture is present
Summarise the pathological and physiological causes of raised ALP.
Physiological
- Pregnancy – 3rd trimester (from placenta)
- Childhood – growth spurts
Pathological:
- <5x upper limit:
- Bone – tumours, fractures, osteomyelitis
- Liver – infiltrative disease, hepatitis (doesn’t go up nearly as much as AST/ALT)
- >5x upper limit:
- Bone – Paget’s disease, osteomalacia
- Liver – cholestasis, cirrhosis
What are ALT and AST invovled in?
Amino acid metabolism
What are the organs linked to raised ALT? List some causes.
What are the organs linked to raised GGT? List some causes.
What are the organs linked to rasied LDH? List some causes.
What are the organs linked to rasied serum amylase? List some causes.
What are the 3 forms of CK?
Three forms (they are dimers containing either M (muscle) and B (brain) subunits):
- CK-MM = skeletal muscles (responsible for almost the entire normal plasma activity)
- CK-MB = cardiac muscle
- CK-BB = brain (activity is minimal even in severe brain damage)
Where is CK found? What conditions?
Statins can also cause myopathy but this is RARE
What medications can commonly cause raised CK? What genetic condition? What physiological factors?
- Medications
- Mostly, w/ simvastatin when co-prescribed other medications involved in CYP3A4 – i.e. clarithromycin
- Can have statin-related myopathy (check levels of CK-MM, should be increased 10-fold)
- Muscle damage due to any cause
- Myopathy (e.g. Duchennes) = >x10 Upper Limit
- Myocardial infarction= >x10 UL
- Severe exercise = 5x UL
- Physiological (Afro-Caribbean) = <5x UL
When should troponin be measured in MI?
- Troponins:
- Rise at 4-6 hours post MI
- Peaks at 12-24 hours
- Remains elevated for 3-10 days
- MEASURE TWICE - measured at 6 hours** and again at **12 hours after the onset of chest pain
After 12-24 hours if there is no rise in troponin, then you have almost certainly not had an MI as troponin at 12-24 hours is 100% sensitive + 98% specific
Name 3 myocardial enzymes and where they are found in the cell.
Troponin (cytosolic and subcellular)- initially, troponins released from free cytosolic pool –> then as contractile bundles break, there will be increased release of troponins
Myoglobin (cytosolic) rises quickly
CK-MB (sub-cellular - mitochondria and nuceli)
Name the enzymes and when they rise in MI.
What are the primary and secondary causes of cardiac injury causing a raised troponin?
How do you distinguish between different types of MI and angina?
What are the two natriuretic peptides? Where do they originate?
- Atrial NP (secreted by atria)
- Brain NP (secreted by ventricles) used for:
- Assess ventricular function
- To exclude heart failure in a clinical setting (highly sensitive)
What units are most enzymes measured in?
- Most assays measure activity rather than mass/volume
- Enzyme activity measured in International Units / Litre
- One IU of enzyme activity = quantity of enzyme that catalyses the reaction of 1 μmol of substrate per minute
- Activity is dependent on assay conditions such as temperature and pH
Reference ranges will differ between laboratories because conditions may vary.
