Creatine Kinase

Creatine Kinase (CK) is found predominantly in the heart muscle, skeletal muscle, and brain. Serum Creatine Kinase levels are elevated when these muscle or nerve cells are injured. Creatine Kinase levels can rise within 6 hours after damage. If damage is not persistent, the levels peak at 18 hours after injury and return to normal in 2 to 3 day.


To test specifically for myocardial muscle injury, electrophoresis is performed to detect the three Creatine Kinase isoenzymes: CK-BB (CK1), CK-MB (CK2), and CK-MM (CK3). The CK-MB isoenzyme portion appears to be specific for myocardial cells. CK-MB levels rise 3 to 6 hours after infarction occurs. If there is no further myocardial damage, the level peaks at 12 to 24 hours and returns to normal 12 to 48 hours after infarction. CK-MB levels do not usually rise with transient chest pain caused by angina, pulmonary embolism, or congestive heart failure. One can expect to see a rise in CK-MB in patients with shock, malignant hyperthermia, myopathies, or myocarditis. Mild elevation of CK-MB (below the threshold of positive) can occur in patients with unstable angina and will signify an increased risk for an occlusive event. Very small amounts of CK-MB also exist in skeletal muscle. Severe injury to, or diseases of the skeletal muscle can also raise the CK-MB isoenzyme above normal.
The CK-MB isoenzyme level is helpful in both quantifying the degree of Myocardial Infarction (MI) and timing the onset of infarction. The CK-MB isoenzyme is often used to determine appropriateness of thrombolytic therapy, which is used for MI. High CK-MB levels would suggest that significant infarction has already occurred, thereby precluding the benefit of thrombolytic therapy.
Because the CK-BB isoenzyme is found predominantly in the brain and lung, injury to either of these organs (e.g., cerebrovascular accident, pulmonary infarction) will be associated with elevated levels of this isoenzyme.


The CK-MM isoenzyme normally makes up almost all of the circulatory total Creatine Kinase enzymes in healthy people. When the total Creatine Kinase level is elevated as a result of increases in CK-MM, injury to or disease of the skeletal muscle is present. Examples of this include myopathies, vigorous exercise, multiple intramuscular (IM) injections, electroconvulsive therapy, cardioversion, chronic alcoholism, or surgery. Because Creatine Kinase is made only in the skeletal muscle, the normal value of total Creatine Kinase (and therefore CK-MM) varies according to a person’s muscle mass. Large muscular people may normally have a Creatine Kinase level in the high range of normal. Likewise, people of small stature or those with low muscle mass will be expected to have low Creatine Kinase levels. This is important because high normal Creatine Kinase levels in these patients can mask a MI.


Each isoenzyme has been found to have isoforms. The CK-MM isoforms MM1 and MM3 are most useful for cardiac disease. An MM3/MM1 ratio of greater than 1 suggests acute myocardial injury. A CK-MB ratio of MB2/MB1 greater than 1 also indicates acute myocardial injury.


CK is the main cardiac enzyme studied in patients with heart disease. Because its blood clearance and metabolism are well known, its frequent determination (on admission and at 12 hours and 24 hours) can accurately reflect timing, quantity, and resolution of an MI. Lactic dehydrogenase (LDH) and aspartate aminotransferase (AST) are also enzymes that were at one time used to confirm an MI.


New blood assays for cardiac markers have promised to rapidly and accurately detect acute MI (AMI) in the emergency room. One of these assays is troponin. A new assay is ischemia-induced albumin.




Normal Creatine Kinase  Levels

Total CK

Adult/elderly (values are higher after exercise.).

Male: 55-170 units/L or 55-170 units/L (SI units).

Female: 30-135 units/L or 30-135 units/L (SI units).

Newborn: 68-580 units/L (SI units)



CK-MM: 100%.
CK-MB: 0%.
CK-BB: 0%.




Causes of Creatine Kinase False Indications

  •  Intramuscular (IM) injections can cause elevated Creatine Kinase levels.
  • Strenuous Exercise and recent surgery may cause increased Creatine Kinase levels.
  • Early pregnancy may cause decreased Creatine Kinase levels.
  • Muscle mass is related to a patient’s normal Creatine Kinase level.
  • Drugs that may cause increased levels include Alcohol, Amphotericin B, Ampicillin, some Anesthetics, Anticoagulants, Aspirin, Captopril, Clofibrate, Colchicine, Dexamethasone (Decadron), Furosemide (Lasix), Lithium, Lidocaine, Morphine, Propranolol, Statins, and Succinylcholine.




Causes of High Total Creatine Kinase

Diseases or injury affecting the heart muscle, skeletal muscle, and brain.



Causes of High CK-BB Isoenzyme Levels

  • Electroconvulsive Therapy.
  • Adenocarcinoma (especially in the Breast and Lung): The pathophysiology of this observation is not known.
  • Pulmonary infarction: The lung tissue has small amounts of CK-BB. With cellular injury of this organ, the contents of the cell, including Creatine Kinase, spill out into the bloodstream, causing elevated CK-BB isoenzyme levels.


High CK-BB Isoenzyme Levels are usually caused by diseases that affect the Central Nervous System (CNS). These diseases include:

  • Brain Injury.
  • Brain Cancer.
  • Cerebrovascular Accident (Stroke).
  • Subarachnoid Hemorrhage
  • Seizures.
  • Shock.
  • Reye Syndrome.




Causes of High CK-MB Isoenzyme Levels

Any disease or injury to the Myocardium causes CK-MB to spill out of the damaged cells and into the bloodstream, producing elevated CK-MB isoenzyme levels. Situations that cause High CK-MB Isoenzyme Levels to be spilled in the blood stream include:

  • Acute Myocardial Infarction (AMI).
  • Cardiac Aneurysm Surgery.
  • Cardiac Defibrillation.
  • Myocarditis.
  • Ventricular Arrhythmias.
  • Cardiac Ischemia.




Increased Levels of CK-MM Isoenzyme

Diseases that affect skeletal muscle cause CK-MM to spill out of the damaged cells and into the bloodstream, producing High CK-MM Isoenzyme Levels. These disease include:

  • Rhabdomyolysis.
  • Muscular dystrophy.
  • Myositis.


Also injuries that affect skeletal muscle cause CK-MM to spill out of the damaged cells and into the bloodstream, producing High CK-MM Isoenzyme Levels. These injuries can be caused by:

  • Recent Surgery.
  • Electromyography.
  • IM Injections.
  • Trauma.
  • Crush Injuries.

Anoxic injury from lack of blood supply or repetitive muscular motion can cause injury to skeletal muscle. This causes CK-MM to spill out of the damaged cells and into the bloodstream, producing elevated CK-MM isoenzyme levels. Anoxic injury can be a result of:

  • Delirium Tremens.
  • Malignant Hyperthermia.
  • Recent Convulsions.
  • Electroconvulsive Therapy.
  • Shock.


Hypokalemia and Hypothyroidism have a metabolic effect on skeletal muscle. Muscle injury results. This causes CK-MM to spill out of the damaged cells and into the bloodstream, producing elevated CK-MM isoenzyme levels.