Creatine Kinase and Myocardial Infarction Flashcards
What is a myocardial infarct
The death of heart muscle cells
Why do the heart muscle cells die
Due to a lack of oxygen
Why may there be a lack of oxygen
Blockage of the cardiac arteries- atherosclerosis. Atherosclerotic plaques made up of lipid, connective tissue, macrophages, bulge into the lumen of coronary artery. During exertion, the plaque may rupture and lead to occlusion of the artery. Cells become hypoxic or anoxic.
Why do cells die without oxygen
Active exclusion of some things such as Na+ ions, which required a protein pump in the plasma membrane. The pumps are a type of enzyme called ATPases. They use energy from the hydrolysis of ATP t pump ions, and ATP is generated via glycolysis, TCA cycle and oxidative phosphorylation. End point requires atmospheric oxygen as an electron acceptor. No oxygen = no ATP, pumps don’t work, ion balance is lost and cells die.
What happens when cells die
The cell contents are released, so proteins that should be held within the cell against their concentration gradients appear in the serum. This is why CK and LDH can be used as indicators of cell death
In what tissues is creatine kinase normally found
Although it is present in all cells at low levels, it is found in high concentrations in metabolically very active cells such as the brain, heart and skeletal muscle.
How can CK activity in the serum be detected
Blood sample from patient
Coupled assay
Creatine phosphate + ADP — Creatine + ADP
D-glucose + ATP — ADP + G6P
G6P + NADP+ — 6-PG + NADPH (detectable by UV absorption) + H+
There is a direct relationship between UV absorbance of NADPH and the activity of creatine kinase
Describe the structure of creatine kinase
It is made from two subunits of monomers ( it is a dimer)
The two monomers are coded for by different genes.
The two monomer isoforms are B and M, which have approximately the same molecular weight, but differ in isometric points. ( 5.2 for B and 6.7 for M).
These monomers associate and bind to each other in the cytoplasm to form active dimers.
What active dimer is found in the brain
BB
What active dimer is found in skeletal muscle
MM
What active dimer is found exclusively in the heart
MB - this needs to be detected in the serum to diagnose myocardial infarction
How are levels of CK BM isoform related to the amount of cell death
The amount of CK in the serum is directly proportional to the amount of cell death in the heart. This is because each myocyte can be considered to be of approximately equal volume ( they have an equal likelihood of dying independent of their size). This means that as each cell dies, a quantum of CK is released into the serum.
How do we determine whether the MB isoform is present in the serum
Isoelectric focusing- pH gradient in an electric field. The pH gradient is formed by ampholyte molecules under the influence of an electric field.
Acidic at the anode
Basic at the cathode
At the isoelectric point (neutral) the protein no longer moves in the electric field
As it moved towards anode, it gains protons and so becomes less negatively charged
As it moves towards the cathode it loses protons and becomes less positively charged
What other tests could we use to detect CK
Manufacture specific antibodies that bind to MB isoform of CK- commercial kits are now available.
Tests are never used in isolation, need to consider context, and do other tests, this test is used to determine size of infarct and how long ago it occurred by measuring changes in CK levels.
How do levels of CK in serum change
Peak after 1,5 days, decrease in conc until 5 days. Best to measure between 0.5 and 1.5 days.
