Creatine kinase (CK), Creatine phosphokinase (CPK)

Creatine kinase

Sample for Creatine kinase

1. It is done on serum (clotted blood 3 to 5 ml).
   1. The plasma may also be used.
2. The sample is stable for 4 to 8 hours at room temperature.
   1. 1 to 2 days stable at  4 °C. (in another reference, the stability at 4 °C for 8 to 12 hours).
3. One month stable at -20 °C.
4. CK-MB level in case of AMI:
   1. In the case of AMI, get multiple samples of CK-MB at 6, 12, 18, and 24 hours.
   2. Some people recommend 4 samples, one immediately, then at 8, 16, and 24 hours.
   3. While some recommend 3 samples, immediately, 12 hours, and 24 hours.

Precautions

1. Avoid excessive physical therapy.
2. There is no need for special preparation of the patient.
3. Avoid the hemolyzed sample.
4. Citrate and fluoride inhibit CK activity.
5. Protect from light.
6. Store in airtight tubes.
7. Please do not take the sample immediately after the I/M injection. Either wait for at least one hour or take the sample before the injection.
8. Trauma to the muscles makes the result unreliable for a few days.

Purpose of the test (Indications)

1. To find cardiac muscular injury (myocardial infarction).
2. To support the possibility of neurologic or skeletal muscle diseases (Muscular dystrophy).
3. This test is specific for muscular and cardiac muscle injury.
4. CK-MB isoenzymes level helps quantify the degree of myocardial infarction and the timing of onset of infarction.
   1. This enzyme is also used to determine the effectiveness of thrombolytic therapy used for myocardial infarction.

Pathophysiology

1. CPK (creatine phosphate) is the incorrect name, and actually, this is Creatine kinase.
   1. CK is also known as Creatine phosphokinase (CPK).
   2. CK gives a reversible phosphorylation reaction.
      

      creatine kinase (CPK)

Creatine kinase facts sheet:

1. Creatine Kinase (CK) is found predominantly in the heart muscles, Skeletal muscles, and brain.
   1. Concentration in the brain is low.
   2. It is elevated in 90% to 93% in patients with acute myocardial infarction (AMI).
   3. In AMI, it behaves like AST (SGOT).
   4. This is also elevated in myocarditis and some patients with tachyarrhythmias, mostly ventricular type, without any known reason.
   5. In the case of acute liver cell injury where AST (SGOT) is raised, but CK is normal.
2. CK level rises within 6 hours after the injury.
   1. If the injury is transient, the peak level is 18 hours and then returns to normal in 2 to 3 days.
   2. CK values are usually raised in muscular dystrophy, muscular trauma, myositis after the surgery, postpartum, and after exercise (moderate to severe).
   3. This is also raised in delirium, convulsions, and tremens.
   4. CK level is abnormal after 24 to 48 hours in most of the persons after heavy drinking of alcohol and in patients with delirium and tremens. But CK level is normal in chronic alcoholics.
   5. CK level is usually raised after the I/M injections.
   6. CK level is raised in case of meningitis, encephalitis, uremic coma, hepatic coma, cerebrovascular accidents, and epilepsy (seizures of epilepsy).
   7. CK is raised in 19% to 47% of uremia cases.

Isoenzymes of CPK are:

1. CK-BB = CK 1 = This is the fast-moving component.
   1. This is found mainly in the Brain and the lesser amount found in the urinary bladder, stomach, and prostate.
   2. These enzymes are present in the cytosol and the myofibrillar structure of the cells.
2. CK-MB = CK 2 = This is found in cardiac and skeletal muscles. The cardiac muscle has 30%, and the skeletal muscle has 1% MB.
3. CK-MM =  CK 3 = This is found in the Skeletal and cardiac muscle.
   1. Skeletal muscle is 99% MM, and cardiac is 70%.
      

      Isoenzymes of CPK

      

      CK isoenzymes and their presence in different organs

      

      CK – distribution in various organs

4. CK activity in the serum depends upon various physiologic variants like muscle mass.
   1. It is lower in the female as a comparison to males.
   2. Depends on the ethnic group, like more black American females than white males. 
5. CK-MB is raised in myocardial infarction.
   1. It does not arise in the case of angina, congestive heart failure, or pulmonary embolism.
   2. The mild rise may be seen in unstable angina, indicating a risk for occlusive attack.
   3. There may be a rise in shock, myopathies, malignant hyperthermia, or myocarditis.
   4. A small amount of CK-MB is present in the skeletal muscles, so there may be a mild rise in the injury to skeletal muscles.
   5. CK-MB level does not rise in angina, pulmonary embolism, or congestive heart failure.
6. CK-MB is advised that 12, 24 hours of admission reflect myocardial infarction’s timing, quantity, and resolution.
   CK and CK-MB level rise pattern:

   Enzyme	Starts to rise in hours	Peak level/hours	Returns to normal/days
   Total CK	4 to 6	24	3 to 4
   CK-MB	2 to 4	18	2

7. CK-BB is raised in the brain injury (also in the lung injury).
8. CK-MM is raised in the muscular injury.
   1. CK-MM isoenzyme makes up almost all the circulatory total CK in the healthy person.
   2. CK-MM depends on the muscle mass; large muscular people may have a high normal range.

Clinical significance of creatine kinase

1. Muscular diseases: This is significantly elevated in muscular disorders, especially muscular dystrophy (Duchenne type), where it is 50 times the normal upper limit.
   1. This may be raised before the clinical disease is apparent.
   2. CK activity decreases with the increasing age of the patient.
   3. Patients with Duchenne disease carriers female, 50 to 80, haves 3 to 6 times raised the CK levels in their blood.
   4. Markedly raised level of CK is seen in viral myositis, polymyositis, and muscle diseases.
   5. The level is normal in neurogenic muscular diseases like myasthenia gravis, multiple sclerosis, poliomyelitis, and Parkinson’s disease.
      1. CK-MM is 7 to 12 times increased than the normal value.
2. Myocardial infarction
   1. CK-MB is normal initially in MI and begins to rise:
      1. After 2 to 4 hours after the infarction.
      2. The peak is between 12 to 24 hours.
      3. Return to normal within 48 hours.
      4. 10 to 25 times the normal value.
         

         CK curve in AMI

   2. Nowadays, a more specific test than CK- MB is Troponin-T.
      1. CK-MB is a diagnostic of MI.
      2. If there is negative CK-MB for > 48 hours, it is clear that the patient had no MI attack.
      3. The CK-MB level is helpful to quantify the level of muscle damage in MI.
      4. CK-MB/total CK ratio improves the specificity of CK-MB for myocardial infarction.
         1. If it is >5% is suggestive of the cardiac source (cardiac muscle damage).

3. Liver diseases
   1. As the liver has a negligible amount of CK, there is no marked increase of CK in liver diseases.
   2. In cirrhosis, CK is normal.
4. Central nervous system diseases 
   1. There is an increase in the CK level in cerebrovascular diseases and cerebral ischemia.
   2. There is a noticeable increase in CK-3 (CK-MM).
   3. There is no CK-1 (CK-BB) increase.
5. Thyroid diseases
   1. In hypothyroid 60% of the cases (in another reference 80%), there is 5 to 50 times elevation than the normal range.
   2. In hyperthyroidism, the CK activity is low to the lower level of normal.

The main isoenzyme is CK-3 (CK-MM).

Drawbacks of CK level:

1. As CK depends upon the muscle mass, so its level will be low in person with less muscle mass.
2. CK level after AMI is short when the CK level is raised.
3. False raised level after I/M injection.

Normal

Source 1

• 0 to 250 U/L
• Adult male = 55 to 170 units /L
  •  Female = 30 to 135 units /L
• Above 90 years
  • Male  = 21 to 203 U/L
  •  Female = 22 to 99 U/L
• Newborn = 68 to 580 U/L (2 to 3 times of adult value).
• Isoenzymes:
  • CK-MM (CK-3) =94 to 100 %
  • CK-MB (CK-2)= 0 to 6 %
  • CK-BB (CK-1) = 0 %

Source 2

Age	Male  U/L	Female U/L
At 37 °C
20 to 60 years	52 to 200	35 to 165
Adult	38 to 174	26 to 140
>90 years	21 to 203	22 to 99
AT 30 °C
20 to 59 years	25 to 80	20 to 75
60 to 69 years	20 to 110	61 to 81
70 to 90	22 to 90	19 to 76
Adult	15 to 105	10 to 80
At 25 °C
Adult	10 to 65	7 to 55

• To convert to SI unit x 0.017 = µKat/L

Raised level of total Creatine kinase (CK):

1. Increased CK/CPK seen in:
   1. Acute myocardial infarction.
   2. Severe myocarditis.
   3. After open-heart surgery.
   4. Acute cerebrovascular accidents.
   5. Progressive muscular dystrophy.
   6. Dermatomyositis and Polymyositis.
   7. Electric shock.
   8. Malignant hyperthermia.
   9. Reye’s syndrome.
   10. Last week of pregnancy and during childbirth.
   11. Hypothyroidism.
   12. Acute psychosis.
   13. Neoplasm of the prostate, GI Tract, and Urinary bladder.
2. CK is increased in:
   1. The only raised level of CK is seen in the injury of the heart muscles, skeletal muscles, and brain.
   2. CK-MM is raised in muscular injuries.
   3. CK-MB is raised in myocardial infarction of damage.
   4. CK-BB is raised in brain injury.

Raised level of CK-MB:

1. Acute myocardial infarction.
2. Cardiac surgery (e.g., an aneurysm ).
3. cardiac defibrillation.
4. Myocarditis.
5. cardiac ischemia.
6. ventricular arrhythmias

Raised level of CK-MM:

1. Muscular dystrophy.
2. Rhabdomyolysis.
3. Myositis.
4. Recent injury.
5. Intramuscular injection.
6. Trauma and crushing injuries.
7. Hypothyroidism.
8. shock.

Raised level of CK-BB:

1. Brain Injury.
2. Brain cancers.
3. Cerebrovascular accidents.
4. Subarachnoid hemorrhage.
5. Shock.
6. Seizure.
7. Adenocarcinoma, especially lung and breast.
8. Pulmonary infarction.

• Normal values are found in myasthenia gravis and multiple sclerosis.

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