Clinical Chemistry - Creatine Kinase

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Clinical Chemistry

Cardiac-related tests

Creatine Kinase

Author: Larry Bernstein, M.D. (see Reviewers page)
Revised: 15 March 2011, last major update June 2010
Copyright: (c) 2008-2011, PathologyOutlines.com, Inc.

Definition

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● 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

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● 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

Physiology

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● 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)

Acute myocardial infarction

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● 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:

(a) troponin I >= 0.4 ng/mL (0.4 μg/L) in any specimen

(b) doubling of myoglobin between 2 sequential specimens with any detectable TnI at least by the second of the 2 specimens, or

(c) 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:

(a) If total CK < 80 IU/L, don’t do CK-MB

(b) Do CK-MB (reference range is 0-4.9 ng/mL) if total CK is between 80-500 IU/L

Test methodology

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● Continuous Spectrophotometric Rate Determination

● Temperature: 30 degrees C, pH: 7.4

● Wavelength: A340nm, Light path: 1 cm

CK-MB Mass Assay

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● 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

● References: Abbott, Beckman-Coulter

Test indications

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● 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

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● 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

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● 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

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● Wikipedia

End of Clinical Chemistry > Cardiac related tests > Creatine Kinase

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