Chemistry
Cardiac related
Creatine kinase

Author: Larry Bernstein, M.D. (see Authors page)

Revised: 2 February 2016, last major update January 2010

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Creatine kinase [title] cardiac
Definition / General
  • Muscle related enzyme released into blood after muscle cell death
  • Serum levels are used to diagnosis acute myocardial infarction, rhabdomyolysis, muscular dystrophy and acute renal failure
Terminology
  • Also known as CK, creatine phosphokinase (CPK), phospho-creative kinase, EC 2.7.3.2
  • "Creatinine kinase" is an incorrect term
  • Creatinine is a break-down product of creatine phosphate in muscle produced at a fairly constant rate, and used to calculate creatinine clearance and glomerular filtration rate
Pathophysiology
  • Present in heart, brain, skeletal and intestinal smooth muscle (acts as energy reservoir for rapid rebuffering and regeneration of ATP), but in different concentrations and with different ratios of the M (muscle) and B (brain) dimeric units
  • CK from brain almost never crosses the blood-brain barrier
  • There are three different isoenzymes: CK-MM, CK-BB and CK-MB
  • Skeletal muscle expresses CK-MM (98%) and low levels of CK-MB (1% in type 1 fibers, 2 - 6% in type 2 fibers, higher amounts during skeletal muscle regeneration)
  • Myocardium expresses CK-MM (70%) and CK-MB (25 - 30%, higher in right heart than left heart)
  • Creatine kinase catalyses the conversion of creatine to phosphocreatine, consuming adenosine triphosphate (ATP) and generating adenosine diphosphate (ADP)
Diagrams / Tables
Interpretation
Acute myocardial infarction
  • Markers are ordered as a panel, because different markers have different time frames for detection
  • American College of Cardiology / American Heart Association recommend results within 30 - 60 minutes of admission, which precludes prolonged serial measures of serum levels of markers
  • Suggested point of care multimarker algorithm to detect acute MI:
    • Troponin I >= 0.4 ng/mL (0.4 μg/L) in any specimen
    • Doubling of myoglobin between 2 sequential specimens with any detectable TnI at least by the second of the 2 specimens, or
    • Myoglobin (doubling) and CK-MB concentrations increasing by 50% or more in 2 or 3 specimens (Am J Clin Pathol 2008;129:788)
  • Algorithm for CK-MB testing:
    • If total CK < 80 IU/L, don’t do CK-MB
    • Do CK-MB (reference range is 0 - 4.9 ng/mL) if total CK is between 80 - 500 IU/L
    • Do CK-MB (no reference range) and CK-MB% (reference range 0.0 - 1.0%) if total CK > 500 IU/L
Laboratory
Test methodology
  • Continuous Spectrophotometric Rate Determination
  • Temperature: 30 degrees C, pH: 7.4
  • Wavelength: A340nm
  • Light path: 1 cm

CK-MB Mass Assay
  • An immunometric assay using a monoclonal antibody, in which CK-MB is considered an antigen
  • Test can be reported in < 1 hour using various automatic platforms
  • Qualitative level is usually reported with relative index / relative percent (CK-MB / total CK)
  • Values suggestive of acute MI are 5 ng/ml or greater and relative index of 2% or greater (Abbot Point of Care - Creatine, BeckmanCoulter)

Test indications
  • CK levels were historically used in emergency room patients to test for myocardial infarction (now often replaced by troponin), rhabdomyolysis, muscular dystrophy, myositis, myocarditis, malignant hyperthermia, neuroleptic malignant syndrome
  • Levels are determined specifically in patients with chest pain and cardinal features of chest pain
  • Activity is estimated in the course of acute ischemic heart disease to diagnose acute myocardial infarction (AMI) and to estimate infarct size
  • CK-MB activity is normal in 25 - 50% of patients with MI at time of admission (Emerg Med Clin North Am 2001;19:321), rises some 4 - 6 hours after the onset of chest pain, peaks within 12 - 24 hours, and returns to baseline levels within 36 - 48 hours
    • These times may be shorted considerably by thrombolytic therapy

Test limitations
  • High serum levels indicate injury to muscle, including rhabdomyolysis, myocardial infarction, muscular dystrophy, myositis, myocarditis, malignant hyperthermia and neuroleptic malignant syndrome
  • Also seen in hypothyroidism
  • The use of statin medications, commonly used to decrease serum cholesterol levels, may be associated with elevation of the CPK level in 1% of the patients taking these medications, and with actual muscle damage in a much smaller proportion
  • CK-MB and CK-BB are quite labile
    • Specimens should be frozen if the assay cannot be performed within 24 hours

Reference ranges
  • Normal values are usually between 25 and 200 U/L, may be lower in women
  • High values for CK-MB: need to be interpreted in the context of chest pain and ECG findings or other muscle damages
  • Patients whose CK does not decline 50% or more within 48 hours of peak have increased risk of reinfarction or death (Clin Chem 1989;35:414)
Additional References