T2: Creatine Kinase & Myocardial Infarction Flashcards
Q: In what tissues is CK present at high levels?
A: in metabolically active tissue including brain, heart, skeletal muscle
Q: When and why is CK found in blood?
A: when cells are dying, cell contents is released into blood including creatine kinase (E)
Q: How might you determine CK activity in the serum?
A: detected by a coupled assay which leads to detectable products (P of the substrate of interest are measured)
NADH is measured
Q: Explain how the isomers of CK arise.
Which isomer is produced in the brain, skeletal muscle and cardiac muscle?
A: CK is a protein made by 2 subunits/ monomers making CK a dimer
the 2 monomers are coded for by different genes -> isoforms B and M (have same molecular weight but different isoelectric points
monomers associate and bind to one another in the cytoplasm to produce active dimers
thus if both genes are expressed in a cell the 3 final dimers possible are BB, MM, MB
brain- only B gene -> BB isomer only
skeletal muscle - M gene only -> MM isomer only
cardiac muscle- both genes -> make all 3 dimers including BM
Q: How might one establish a diagnosis of myocardial damage?
A: cardiac muscle- both genes -> make all 3 dimers including BM
can measure serum BM somehow
Q: Does an increase in serum CK activity relate to the size of myocardial damage? Why?
A: CK BM isomer is directly proportional to amount of cell death in heart
because each myocyte can be considered to be approximately of equal volume so as each cell dies it releases a ‘quantum’ of CK into the extracellular fluid and thence into the serum
Q: What is the time course serum CK after a myocardial infarction?
A: diagram, very high peak and just after day one
0 to 2 range of peak then decreases with less steepness
Q: What other markers can be used for diagnosis of myocardial damage?
A: SGOT- serum glutamate oxaloacetate transaminase (in case they don’t go hospital straight away) -> peak day 2 (half of CK height)
LDH- lactate dehydrogenase (not the best, as level doesn’t get particularly high) -> peak day 5 (third of CK height)
cardiac troponin- troponin I and T are specific to cardiac muscle- presence = significant marker- typically appear after 48h and persist for around 5 days
Q: What is a myocardial infarct?
A: death of heart muscle cells
Q: Why do cells die during a myocardial infarct?
A: lack of oxygen
Q: What causes a lack of oxygen in cells during a myocardial infarct?
A: blockage of the cardiac arteries
Q: Why might the three isoenzymes be separated by electrophoresis?
Negatives?
A: different isoelectric points for each dimer
so they would separate on the basis on charge
slow and require expert techniques