important of creatine kinase enzyme

DIAGNOSIS IMPORTANCE OF CREATINE KINASE

• Introduction• Isomers of creatine kinase• Location of Enzyme• Normal value • When CK level is high in blood• When CK level is low in blood• Diagnostic importance of Creatine

phosphokinase

Introduction

• Enzyme catalysing Creatine and ATP to Phosphocreatine (PCr) and ADP

• Action – This enzyme is associated with the regeneration and storage of high energy phosphate (ATP).

• It catalyzes the following reversible reaction in the body.

Enzyme unstable in serumActivity lost due to sulfhydryl group oxidation at active site.Its molecular weight is approximately 82,000Dimer (each of 41000 Da) B (brain) – chromosome 14 M (muscle) –chromosome 19

Creatine Kinase

skeletal muscleheart musclebrain tissue.

Highest activities are found in

Smaller quantities are found in

kidneythe bladderprostategastrointestinal tractliverpancreasspleenuterusplacentathyroidlung

Indicators of Cardiac Injury

Creatine kinase (CK)

• creatine phosphokinase (CPK)

• catalyze transfer of a PO4 group between creatine PO4 & ADP to form creatine + ATP

• requires magnesium as cofactor

• dimeric with pair of two different monomers M & B

• 3 isozymes: CK1 (BB), CK2 (MB), CK3 (MM)

• M and B subunits antigenically distinct proteins encoded by different genes

• primary tissue sources:

1. Brain, smooth muscle, prostate, thyroid, gut, lung CK-BB

2. Cardiac muscle – MB (20-30%) & MM (70-80%)

3. Skeletal muscle – MB (1-2%) & MM (98-99%)

• relatively small molecular size allows leakage out of ischemic muscle or brain cells

Creatine kinase (CK)

• reference ranges in serum affected by:

1. Amount of lean muscle mass

Thin, sedentary = 30 – 50 U/L

Muscular, exercising regularly = 500 – 1000 U/L

2. Age – in neonates, CK-MB 5-10% of total CK

3. Gender

4. Race – Africans 30% higher than Europeans

5. Muscle activity – direct relationship between intensity of exercise and CK level

Creatine kinase (CK)

• persons exercising periodically & at usual intensity levels with lower CK than those who do not exercise at all

• decrease with severe inactivity

• short-term strenuous exercise 10-100 fold increase

• marathon runners up to 2000 U/L as resting value

Creatine kinase (CK)

CK-MM, which is found in your skeletal muscle and heart.

CK-MB, which is found in the heart and rises when heart muscle is damaged.

CK-BB, which is found mostly in your brain

The three types of CK are called isoenzymes.

• released from damaged muscles: CK, AST, LD, myoglobin

Myoglobin >> CK >> AST and LD

• released during ischemia, injury or inflammation

• also increased in:

1. Chronic myopathies

2. Chronic renal failure

3. Acute respiratory exertion – respiratory muscles with more CK than other muscles

Diagnostic Applications

CM-MM

• Brain trauma or brain surgery

1. Injury to smooth muscles (e.g. intestinal ischemia)

2. Transient increase after cardiac arrest reflect cerebral ischemia

CK-BB

Diagnostic Applications

• primary clinical use: detection of acute MI

Following MI:

Total CK – 98% sensitive but 68-85% specific; peak value 18-30 hrs; duration 2-5 days; level 5-10x normal

CK-MB – rise proportional to extent of infarction; appears in serum within 6 hrs after AMI; peak value 12-24 hrs; duration 1.5-3 days persistence indicates extension or infarction or re-infarctionPost AMI CK-MB

CK-MB increases 4 – 8 hours post AMI

Peaks at 12 - 24 hours post AMI

Returns to normal 48 - 72 hours

CK-MB

Diagnostic Applications

Normal: 24 – 170 U/L (women) 24 – 195 U/L (men)

• Marked elevation (> 5x normal)

1. After trauma from electrocution, crush injury, convulsion, tetany, surgical incision or IM injection

2. Athletic individuals – inc. muscle mass & inc. release during strenuous activity

3. Muscular dystrophies

4. Chronic inflammation of muscle (dermatomyositis or polymyositis)

Total Serum CK

Diagnostic Applications

55 to 170 units/L for men

30 to 135 units/L for women

68 to 580 units/L for newborns

Generally the normal range is:

CK-MM generally rises in response to muscle damage in your heart, brain, or skeleton after a crush injury, seizures, muscular dystrophy, muscle inflammation, or another skeletal muscle disorder.

CK-MB generally rises in response to a heart attack, inflammation of the heart muscle, muscular dystrophy, and other problems related to the heart.

CK-BB tends to rise in response to a brain injury, meningitis, abnormal cell growth, severe shock, stroke, hypothermia, or restricted blood flow to the bowel.

This test may be used to

Diagnose heart attack Evaluate cause of chest pain Determine if or how badly a muscle is

damaged Detect rhabdomyolysis dermatomyositis,

Muscular dystrophy polymyositis, and other muscle diseases

Tell the difference between malignant hyperthermia and postoperative infection.

Acute Renal Failure

LOW LEVEL OF CK IN BLOOD

Having lower-than-normal CK levels in your blood is rare.

Low than normal Level is not abnormality.

Muscle diseases - or renal failure could fall under this genetic abnormality

Brain injury or strokeConvulsionsDelirium tremensDermatomyositis or polymyositisElectric shockHeart attackInflammation of the heart muscle (myocarditis)Lung tissue death (pulmonary infarction)Muscular dystrophiesMyopathyPolymyositis vitamin E-selenium deficiency snake bite poisoningAdditional conditions may give positive test results:HypothyroidismHyperthyroidismPericarditis following a heart attackRhabdomyolysis

High CPK levels may be seen in patients who have:

Cardiac catheterization Intramuscular injections Trauma to muscles Recent surgery Heavy exercise.Drinking too much alcohol

Factors that may affect test results include

Amphotericin B Certain anestheticsStatins FibratesDexamethasone Alcohol Cocaine

Drugs that can increase CPK measurements include

If you have had a heart attack, your doctor may look for high levels of myoglobins or troponins, other proteins that are also found in your heart.

Troponin blood testElectrocardiogram, or ECG, to measure the electrical activity of your heart

What other tests might I have along with this test?

These other tests include:

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