MBC - Creatine Kinase Flashcards
What is a myocardial infarct?
Death of heart muscle cell
Why cells die?
Lack of oxygen
Why lack of oxygen?
Block in cardiac arteries - Atherosclerosis
Why do cells need oxygen, if not why die?
- Active transport of Na+ ions w/ protein pump; ATPase
- ATPase use ATP as energy to pump ions
- ATP generation requires oxidative phosphorylation
- less oxygen —> less ATP —> pump don’t function —> ion balance lost —> cell die
What happens when cell die?
Cell contents are released (protein normally in cells appear in serum)
Including creatine kinase, so can be used as indicator of cell death
Where is Creatine kinase (CK) normally?
In all cells in low levels, though is high conc. in metabolically very reactive tissue (brain, heart, skeletal muscle)
How is CK detected?
By detecting NADPH in 3 step reaction;
- Creatine phosphate + ADP ——CK——> creatine + ATP
- Glucose + ATP ————> ADP + G6P
- G6P + NADP+ ——G6P dehydrogenase——> NADPH + 6-PG + H+
How is CK specifically related to the death of cardiac muscle fibre?
CK is a dimer (made of 2 monomers) only cardiac muscles express both genes B&M
How can CK BM isoform assess cardiac cell death?
Levels of CK BM isoform are directly proportional to amount of cell death
- each myocyte is approximately equal volume so release a certain amount of CK
How are dimers formed? (For CK)
Monomers coded by different genes generate two isoforms “B” & “M” which bind together in the cytoplasm
What dimer go where? Isoforms B & M
BB - Brain only express B gene
MM - Skeletal muscle cell only express M gene (useful in diagnosis of damage in muscular dystrophies)
All + BM - Cardiac muscles
Why is only measuring CK activity in serum not good enough for diagnostics for myocardial infarction?
Because activities could come from either brain, skeletal or heart - MUST be BM
How can you distinguish between isoforms?
Electrophoresis/ column chromatography- separate by charge/ molecular weight
Not ideal in casualty department as too slow
Other ways of discriminate protein?
Artificial manufacture of antibody against desired protein - eg against BM
Test given along with others (particularly determine how big the infarct is, and see changes in level to see how long ago it happened)
What is the time course of CK after infarction?
Refer to note (start increase in 3-6 hours and peak between 15-16 hours)
