Creatine kinase (CK), is found primarily in skeletal muscle, brain and cardiac tissue. Normally, the majority of creatine kinases are located in myocytes, and elevated creatine kinase in the blood generally indicates that muscle damage is present or is occurring. Elevated creatine kinase (CPK) is an abnormal test result that can be seen in many disorders and is not an independent disease.
Clinically, we often see elevated creatine kinase (CK) alone, but the diagnosis of myocardial infarction has been ruled out by various cardiac tests. At this point, it is necessary for our physicians to consider various aspects and make reasonable and beneficial treatment to avoid delaying the disease and causing misdiagnosis and mistreatment.
If the clinician finds any doubt in the test results during the diagnosis, he/she should contact the laboratory department in time to understand the relevant situation in order to make the correct diagnosis.
I. Biochemical characteristics
Creatine kinase (CK) is systematically named as adenosine triphosphate: creatine phosphotransferase.
The phosphocreatine generated by the action of CK contains high-energy phosphate bonds and is the direct source of energy during muscle contraction, and is most abundant in three types of muscle tissue and brain tissue.
CK is a dimer composed of two different subunits (M and B), so that normal human tissues often contain three isoenzymes, in the order of electrophoretic rate: CK-BB (CK1), CK-MB (CK2) and CK-MM (CK3), respectively.
II. Tissue distribution
CK mainly exists in skeletal muscle, cardiac muscle, brain tissue, in addition to some organs containing smooth muscle such as the gastrointestinal tract, uterus. The content in liver and red blood cells is minimal or absent.
Physiological variation
Age, gender and race all have an effect on CK content.
CK content is closely related to muscle movement, and its amount is related to the total amount of human muscle.
CK-MB is higher in children under 14 years of age than in adults, both in absolute and relative activity, and this physiological difference should be taken into account when diagnosing acute myocarditis in children.
IV. Determination of CK
(A) Specimen collection, processing and storage
In order to reduce the influence of exercise on test results, it is generally recommended to avoid strenuous exercise and sports for 2 days before the test. Patients who arrive at the clinic in the morning in a hurry should rest.
(B) Measurement methods
CK can be measured by colorimetric method, enzyme coupling method, fluorescence method and bioluminescence method, etc.
V. Determination of CK isoenzymes
(A) Specimen collection, processing and storage
Both serum and plasma can be used for CK isoenzyme assay. In 4 ℃ can be stored for several days, -15 ℃ can be stored for 2 weeks, if the plasma should be used EGTA, but not EDTA anticoagulation.
VI. Clinical application
CK and its isoenzymes are currently the most clinically measured enzymes in the world.
CK is often significantly elevated in skeletal muscle, cardiac muscle and brain disorders, and the simultaneous measurement of isoenzymes can also help in the differential diagnosis of diseases.
When we encounter a patient with higher than normal serum CK-MB activity, which accounts for more than 30% of the total CK activity, it is generally not due to myocardial injury and should be analyzed by isoenzyme electrophoresis to determine the cause and make a clear diagnosis.
Seven, the main clinical significance of abnormal serum creatine kinase test.
1. It is mainly used for the early diagnosis of acute myocardial infarction, especially for the diagnosis of myocardial ischemia and subendocardial myocardial infarction with higher sensitivity than other enzymes. It starts to rise in 2-4 hours at acute onset, reaches a peak in 12-48 hours, and can return to normal in 2-4 days. And the degree of increase is basically consistent with the degree of myocardial damage. After thrombolytic treatment for myocardial infarction restores blood flow to the infarcted vessels, CK reaches its peak earlier, so dynamic detection of CK changes can help in disease observation and prognosis estimation.
2, various muscle diseases, such as progressive myotonic dystrophy episodes, viral myocarditis, polymyositis, severe muscle injury (such as extrusion syndrome) or increased levels of serum CK after surgery.
3.The level of serum CK is increased during cerebrovascular disease, acute traumatic brain injury, alcoholism, generalized convulsions, and seizures; the level of CK is also increased during hypothyroidism with mucinous edema and cerebral infarction.
4. Staying up late, excessive fatigue, and strenuous exercise before the physical examination can also increase creatine kinase. Taking drugs can also cause creatine kinase to increase, such as colchicine tablets, Advil, Donepezil hydrochloride tablets, etc.
The CK level test assesses neuromuscular disease in five basic ways.
1. early diagnosis of suspected muscle disease before other symptoms appear.
2. determine whether the cause of muscle weakness is due to the muscle tissue itself or a neurological problem.
3. To distinguish between various types of muscle disease, for example, between muscular dystrophy and congenital muscle disease.
4. To detect “carriers” of neuromuscular diseases, especially Duchenne muscular dystrophy. “Carriers” have a certain genetic defect, they do not show any symptoms themselves, but their offspring may become patients.
Duchenne muscular dystrophy, also known as pseudohypertrophic muscular dystrophy, is a genetic disorder for which there is no effective treatment.
5. To monitor the course of certain diseases with fluctuating changes (mainly inflammatory muscle diseases) or to confirm the acute damage phase of certain metabolic muscle diseases.
Chronic elevation of creatine kinase is called hypercreatine kinaseemia and is occasionally seen in normal subjects. 1980 Rowland called the condition idiopathic hypercreatine kinaseemia in the absence of clinical and histopathological evidence of neuromuscular disease. In cases of hypercreatine kinaseemia with clinical signs of neuromuscular disease, it is usually possible to make a definitive diagnosis after consultation with a variety of relevant tests.
Asymptomatic hypercreatine kinaseemia is defined as follows
1. an incidental finding of elevated serum creatine kinase
2. persistent hypercreatine kinaseemia for at least 3 months
3. asymptomatic or with only mild and non-specific symptoms (occasional mild muscle pain) detected at the time of presentation.
4. no family history of neuromuscular disease
5. lack of clinical manifestations of neuromuscular disease associated with hypercreatine kinaseemia
6. absence of cardiac disease (normal CK-MB and electrocardiogram)
7. absence of other causes of hypercreatine kinaseemia (malignancy, alcohol and drug abuse, systemic metabolic diseases, infections, malignant hyperthermia, thyroid and other diseases)
(malignant hyperthermia, thyroid and parathyroid disorders, blood disorders, pregnancy, drugs, etc.).
In cases of asymptomatic hypercreatinemia, the following tests should be performed to determine the cause
1. neurological examination, especially muscle strength examination.
2. Creatine kinase measurement by family members.
3. Blood lactate test: including basal state, after forearm ischemia, and after exercise.
4. Needle electrode electromyography.
5. muscle biopsy, specimens for routine histology, multiple histochemical staining, immunohistochemical staining for certain antibodies, and electron microscopy.
If the results are still negative after the above mentioned systems, idiopathic hypercreatine kinaseemia (idiopathichyperCKemias) can be considered.
A significant increase in serum creatine kinase in a child may be related to an overload of the digestive system due to an improperly structured diet and excessive intake of high-protein foods. The metabolic function of the child may be improved by physical exercise.
Exercise causes changes in blood chemistry, and vigorous exercise can significantly affect metabolism and the release of intracellular enzymes in the body. For example, serum creatine kinase and transaminase, important indicators for the diagnosis of myocardial infarction and hepatitis, respectively, are significantly elevated in people who do not normally exercise regularly, once they overdo it. After exercise, serum creatine kinase can increase by a factor of 1, while transaminases can remain high by about 40% one hour after exercise stops.