CK-MB

Sample

1. The test is done in the serum (clotted blood 3-5 ml) of the patient.
2. It also helps in quantifying myocardial muscle damage.
3. The sample is stable for 4 to 8 hours at room temperature.
   1. 1 to 2 days at 4 °C.
   2. One month at -20 °C.

Purpose of the test (Indications) for CK-MB:

1. To diagnose myocardial muscle injury (MI).
2. It is an early marker of acute myocardial infarction. This is considered an early gold standard diagnostic tool.
3. It Detects reinfarction or extension of myocardial damage after 72 hours.
4. It is needed for reperfusion after thrombolytic therapy.
5. This may replace troponins when advised within 24 hours of the onset of symptoms.

Precautions for CK-MB

1. Avoid intramuscular injection with cardiac disease. I/M may raise the CK-MB level.
2. Strenuous exercise and recent surgery may increase the CK-MB level.
3. Early pregnancy may produce a decreased level of CK-MB.
4. Drugs that may increase the level are alcohol, ampicillin, amphotericin B, aspirin, anesthetics, decadron, furosemide (Lasix), lidocaine, morphine, propanol, lithium, captopril, clofibrate, colchicine, and statins.

Definition of CK-MB

1. CK-MB is an isoenzyme of Creatinine kinase.
2. It is present in the cardiac muscles, skeletal muscles, and brain.
3. CK-BB is found in the brain and nervous tissue; it is also found in the serum of newborn babies and malignancies showing embryonic tissue differentiation.
4. The more rapid rise in CK-MB and fall back of the CK-MB marker of myocardial infarction.

Pathophysiology of CK-MB

1. CK, creatine kinase; adenosine triphosphate:
   1. Creatine N-phosphotransferase is a dimeric enzyme with 82 kDa weight.
   2. It will catalyze the reversible phosphorylation of creatine by adenosine triphosphate (ATP).
2. When muscle contracts, then ATP is converted into ADP (adenosine diphosphate).
3. CK catalyzes the conversion of ATP to ADP using phosphocreatine (creatine phosphate) as the phosphorylation reservoir.

4. Creatinine kinase comprises two polypeptide chains, B and M, making up three forms. These are the cytosolic enzymes.
5. Distinct genes encode the M and B subunits.
6. CK has isoenzymes:
   1. CK-1 =BB (CK-BB) = It is found predominantly in the brain and lungs.
   2. CK-2 =MB (CK-MB) = It is found predominantly in the cardiac muscles.
      1. CK-MB is found mainly in the cardiac muscle, 25% to 30% of total myocardial CPK.
      2. Skeletal muscle contains a small fraction of CK-MB, 3% to 5%.
   3. CK-3 =MM (CK-MM) =  It is found in the skeletal muscles.

Distribution of the creatinine kinase isoenzymes:

Tissue where CK is found	CK-BB	CK-MB	CK-MM
Location in the body	Brain and lungs	Cardiac muscles	Skeletal muscles
Skeletal muscles (red fibers)	<1%	3%	97%
Skeletal muscles (white)	<1%	1%	99%
Brain	100%	0	0
Heart	<1%	22%	78%
Smooth muscle GIT	96%	1%	3%
Smooth muscle urinary bladder	92%	6%	2%

CK-MB significance:

1. CK-MB is a cardiac marker released into the blood circulation when damage (necrosis) to the cardiac muscles occurs.
2. CK-MB release into the blood circulation is detected within 6 to 18 hours of the onset of acute myocardial infarction.
3. Because of the protein degradation mechanism that eliminates CK-MB from the blood circulation. Because of this short window, the CK-MB peak level may be missed.

CK-MB role in the diagnosis of Acute Myocardial Infarction:

1. It is specific for diagnosing cardiac muscle damage in the first few hours of Myocardial Infarction (MI).
2. CK-MB is high in cardiac muscle and low in skeletal muscle, which is <3%.
3. Around 10% of people have normal CK, while CK-MB is raised in myocardial infarction.
4. This may be raised in skeletal muscle injury but not in injury due to injections and exercise.
5. CK-Mb is not raised in the pulmonary embolism unless there is a heart muscle injury.
   1. In Duchenne’s muscular dystrophy, in the early stages, CK-MB is raised.
   2. CK-MB may be increased in patients with gangrene or severe ischemia of the limbs.
6. If there is a persistent increase in CK-MB greater than 30 to 40% of the total CK indicates malignancy.
7. CK-MB can be reported as:
   1. % of the total CPK = CK-MB/Total CPK.
   2. It can measure directly by immunoassay.
8. CK-MB relative index:
   1. This is done to avoid skeletal muscle injury with myocardial muscle damage.
   2. Calculation:
      1. CPK-MB/total CPK
         1. If CPK-MB = 3.0 ng/mL
            1. Relative index = ≥2.5
            2. This is highly suggestive of myocardial injury.
         2. If CPK-MB = >3.0 ng/mL
            1. Relative index = <2.5
            2. Not diagnostic for myocardial injury.

CK-MB when begins to rise and interpretations:

1. CK-MB begins to rise 3 to 6 hours after the onset of Acute Myocardial infarction (AMI).
2. The peak is between 12 to 24 hours.
3. It returns to normal in 24 to 48 hours.

4. There is a rough correlation between the level of CK-MB and myocardial muscle damage.
   1. CK-MB after 72 hours of the AMI, 2/3 of the patients show an increase in CK-MB.

False-negative CK-MB results may be caused by:

1. Poor sample timing, like only one sample in 24 hours.
   1. Sample <4 hours before the onset of AMI.
   2. Sample after >72 hours of AMI.
2. A small infarct may not increase CK-MB level noticeably.
3. Take the blood sample on admission or onset of acute chest pain immediately.
   1. Then repeat the sample at 6, 12, 18, and 24 hours afterward.
   2. Some of the hospitals repeat 3 samples, and some take 4 samples.
      1. 3 samples, take an immediate sample, and then at 12 and 24 hours.
      2. 4 samples, take an immediate sample, and then at 8, 16, and 24 hours.
   3. There is controversy about whether total CK or CK-MB level rises in the case of ischemia only.
   4. If you take LDH (isoenzyme) and CK-MB at the same time. The diagnostic specificity will increase.
      1. If an LDH blood sample is taken at 24 and 48 hours, while a CK-MB sample is taken immediately at 12 and 24 hours.
      2. In that case specificity of AMI reaches 95% or more.
   5. It reaches a peak in 12 to 24 hours.
4. In one of the references:
   1. CK  raised level in the first sample was 18%
   2. In the first 12 hours sample was 50%.
   3. In 24 hours sample was 4%.
   4. CK has not raised the level was 18%.
5. Troponin is a more specific cardiac marker than CK-MB.

Disadvantages of CK-MB:

1. Diagnosis can not be based on one sample value.
2. Rapid return to normal CK-MB makes it a poor marker >72 hours after symptoms.
3. CK-MB and total CK are decreased after cardiac surgery.
4. A diagnosis of AMI can not be made until >12  to 24 hours after cardiac surgery.
5. CK-MB and total CK can be increased in chronic disease and exercise.
   1. If CK-MB >20% or persists >48 to 72 hours considered atypical CK-MB.

Normal CK-MB

Source 1

• Normal  = 5 to 25 IU/L
  • Or it is 3 to 5% of Total CK.
• Single estimation is not reliable.
• Multiple samples are estimated for CK-MB.

Source 2

• CK – MB = 0 to 10 U/L
• CK – MB  = 0 to 9 µg/L
• CK – MB by Immunoassay = <10 µg/L
• CK – MB On electrophoresis = <4 to 6%

Source 3

• CK-MB = 0 to 3 ng/mL
  • Or o to 3 µg/L.

CK-MB and other cardiac enzymes:

Enzyme	Start to rise hours	Peak (hours)	Days to normal
CK-MB	4	18	2
Total CPK	4  to 6	24	3  to  4
Troponin T	4  to  6	10  to  24	10
Troponin I	4  to  6	10  to  24	4
LDH	24	72	8 – 9
SGOT	8	24  to  48	4

CK-MB may be raised in:

1. Acute myocardial infarction.
2. Cardiac aneurysmal surgery.
3. Myocarditis.
4. Ventricular arrhythmias.
5. Duchenne’s muscular dystrophy.
6. Patients with gangrene or severe ischemia of the limbs.
7. Acute myositis of various types.
8. Athletes who are long race runners.
9. Idiopathic myoglobinemia.
10. Reye’s syndrome.
11. Rocky-spotted mountain fever.

CK-MB level is normal in:

1. one study shows that CK-MB level is normal in:
   1. Myocarditis.
   2. Pericarditis.
   3. Subacute bacterial endocarditis.
   4. This is normal in patients undergoing defibrillation cardiac resuscitation unless there is cardiac muscle injury.
   5. If there is no muscular injury, then the CK-MB level is normal in angioplasty and coronary angiography.

• Please see more details in CK.

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