Creatine kinase

Overview
Creatine kinase (CK), also known as phosphocreatine kinase or creatine phosphokinase (CPK) is an enzyme expressed by various tissue types. It catalyses the conversion of creatine to phosphocreatine, consuming adenosine triphosphate (ATP) and generating adenosine diphosphate (ADP).

In tissues that consume ATP rapidly, especially skeletal muscle, but also brain and smooth muscle, phosphocreatine serves as an energy reservoir for the rapid regeneration of ATP. Thus Creatine Kinase is an important enzyme in such tissues.

Clinically, creatine kinase is assayed in blood tests as a marker of myocardial infarction (heart attack), rhabdomyolysis (severe muscle breakdown), muscular dystrophy and in acute renal failure.

There are three different isoenzymes that come from three distinct locations in the body:
 * BB: Brain, prostate, gastrointestinal, breast, ovary, lung
 * MM: Skeletal muscle
 * MB: Heart

Types
In most of the cell, the CK enzyme consists of two subunits, which can be either B (brain type) or M (muscle type). There are, therefore, three different isoenzymes: CK-MM, CK-BB and CK-MB. The genes for these subunits are located on different chromosomes: B on 14q32 and M on 19q13. In addition to those, there are two mitochondrial creatine kinases, the ubiquitous and sarcomeric form.

Isoenzyme patterns differ in tissues. CK-BB occurs mainly in tissues, and its levels do rarely have any significance in bloodstream. Skeletal muscle expresses CK-MM (98%) and low levels of CK-MB (1%). The myocardium (heart muscle), in contrast, expresses CK-MM at 70% and CK-MB at 25-30%. CK-BB is expressed in all tissues at low levels and has little clinical relevance.

The mitochondrial creatine kinase (CKm), which produces ATP from ADP by converting creatine phosphate to creatine, is present between the two membranes of the mitochondrion. Apart from the mitochondrial form, there are three forms present in the cytosol—CKa (in times of acute need, produces ATP in the cytosol at the cost of creatine phosphate), CKc (maintains critical concentration of creatine and creatine phosphate in the cytosol by coupling their phosphorylation and dephosphorylation respectively with ATP and ADP) and CKg (which couples direct phosphorylation of creatine to the glycolytic pathway (see glycolysis).

Laboratory testing
CK is often determined routinely in emergency patients. In addition, it is determined specifically in patients with chest pain and acute renal failure is suspected. Normal values are usually between 25 and 200 U/L. This test is not specific for the type of CK that is elevated.

Elevation of CK is an indication of damage to muscle. It is therefore indicative of injury, rhabdomyolysis, myocardial infarction, muscular dystrophy, myositis, myocarditis, malignant hyperthermia and neuroleptic malignant syndrome. It is also seen in McLeod syndrome and hypothyroidism. The use of statin medications, which are commonly used to decrease serum cholesterol levels, may be associated with elevation of the CPK level in about 1% of the patients taking these medications, and with actual muscle damage in a much smaller proportion.

Lowered CK can be an indication of alcoholic liver disease and rheumatoid arthritis.

Isoenzyme determination has been used extensively as an indication for myocardial damage in heart attacks. Troponin measurement has largely replaced this in many hospitals, although some centers still rely on CK-MB.

Differential Diagnosis of Increased Total CK

 * Alcoholism
 * Arterial embolism
 * Bacterial myositis
 * Becker's Muscular Dystrophy
 * Crush injury or trauma
 * Duchenne's Muscular Dystrophy
 * Hyperthermia
 * Hyperthyroidism
 * Hypothyroidism
 * Intramuscular injections
 * Leyden-Moebius Muscular Dystrophy
 * Liver, pancreas and gastrointestinal diseases
 * Muscular spasm
 * Myasthenia Gravis
 * Myositis
 * Neurogenic muscular atrophy
 * Pancreatic cancer
 * Polymyositis
 * Pregnancy and labor
 * Rhabdomyolysis
 * Seizure
 * Surgery
 * Thyrotoxicosis
 * Vigorous exercise
 * Viral myositis

Differential Diagnosis of Increased Total CK and CK-MB Ratio

 * Cardiac contusion
 * Cardiogenic shock
 * Heart surgery
 * Myocardial Infarction
 * Perimyocarditis
 * Right ventricular failure