CREATINE KINASE (CK), CK ISOENZYMES, AND ISOFORMS CK (adenosine triphosphate creatine ^-phosphotransferase) is an intracellular enzyme involved in the transfer of high-energy phosphate groups from ATP to creatine. Although found in small quantities in many tissues, CK is present in large concentrations in cardiac and skeletal muscle as well as brain. The enzyme is a dimer composed of two subunits, each of which may be either the M (muscle) type or the B (brain) type, thus creating three distinct dimers, or isoenzymes: cK-BB, predominantly found in brain tissue; CK-MM, the predominant isoenzyme in skeletal muscle (although CK-MB is also found there in small amounts); and CK-MB, accounting for 14 to 42 percent of the total enzyme activity present in cardiac muscle (the predominant enzyme remaining CK-MM).
The quantitative and temporal patterns of appearance and disappearance of CK and its isoenzymes in the blood occur in a reproducible manner but can vary considerably depending on the amount of CK released from cells, the amount of perfusion of damaged tissues, and the rate of clearance by the reticuloendothelial system. CK levels usually become abnormally high within 4 to 8 h after coronary artery occlusion (onset of symptoms), peak between 12 and 24 h, and return to normal between 3 and 4 days (Fig 45..-.2). Reports of the sensitivity of total CK vary from 93 to 100 percent, whereas the specificity is lower, ranging from 57 to 86
percent. Owing to the presence of CK in other tissues, many conditions other than AMI may cause an elevated total CK level, thus limiting this marker's usefulness.
FIG. 45-2. Multiple marker curve.
Soon after MI, the CK-MB isoenzyme curve parallels the total CK curve, with levels detectable 4 to 8 h after onset of symptoms ( Fig 45-2). CK-MB may peak slightly earlier than total CK, and it is cleared more rapidly, usually within 48 h (versus 72 to 96 h). Using CK-MB and the ratio of MB to total CK, most studies report both sensitivity and specificity to be greater than 95 percent. Cutoff values vary between techniques, laboratories and populations, but CK-MB values in healthy controls may be up to 5 U/L and up to 5 percent of total CK. Until recently, CK-MB had been almost universally adopted as the "gold standard" for diagnosis of MI. Although specificity is generally improved over total CK, 37 conditions other than MI have been associated with elevated CK-MB levels ( I.a.bJ.e...,45:2). Fortunately, most of these conditions can be easily differentiated from MI on clinical grounds. Ihe relatively rapid return of elevated MB levels to normal is another potential disadvantage because of the possibility of missing the diagnosis in patients presenting later in the course of MI. However, this rapid clearance may be used to a different advantage because it enables the identification of infarct extension and reinfarction.
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