Creatine Kinase (CK or CPK) Blood Test – Interpretation of levels and Clinical significance

A Creatine kinase (CK) blood test is a laboratory test to evaluate the amount of creatine kinase in the blood. Creatine kinase (CK) is a dimeric enzyme also called creatine phosphokinase (CPK).

Creatine phosphokinase or creatine kinase is a muscle-specific enzyme and the most sensitive indicator for muscle damage. It has a half-life of almost 2 hours⁽⁶⁾. It’s an important enzyme that catalyzes the phosphorylation process (see below in the diagram). 

What is Creatine Kinase (CK)?

Creatine kinase (CK) a type of protein known as enzyme is predominantly found in skeletal muscle and mitochondrial cytoplasm. It can also be found in the brain, cardiac muscles, and other body tissues. The main role of the Creatine kinase (CK) enzyme is in the transportation and generation of phosphate molecules. 

Creatine kinase (CK) enzyme has two subunits: M and B.

M is for muscle, and B is for the brain.

Creatine kinase is a protein that is metabolized by the process of proteolysis. Proteolysis for CK occurs in lymph nodes or local tissue. 

Creatine kinase (CK) enzyme catalyzes the reversible phosphorylation reaction.

ADP + creatine phosphate → ATP + creatine

Principle of CK blood test procedure

• The Creatine Kinase assay shows the quantity of creatine kinase in human plasma or serum.
• Creatine kinase (CK) enzyme will catalyze the reaction.
• The high-energy phosphate group is transferred from creatine phosphate to ADP.
• ATP is produced.
• This ATP will be used to phosphorylate glucose molecules.
• Glucose-6-phosphate will be formed in the presence of hexokinase.

Then glucose-6-phosphate dehydrogenase enzyme oxidizes Glucose-6-phosphate and reduces nicotinamide adenine dinucleotide phosphate to nicotinamide adenine dinucleotide phosphate reduced form, also called NADPH. 

The formation rate of NADPH is directly proportional to the activity of the Creatine kinase (CK) enzyme in the sample. N-acetyl-L-cysteine (NAC) acts as an enzyme reactivator in all these reactions.

Isoenzymes of Creatine kinase

Creatine kinase (CK) enzyme has three isomeric forms; Creatine kinase-MM (CK-MM), Creatine kinase-MB (CK-MB), and Creatine kinase- BB (CK-BB).⁽⁵⁾

1. CK-BB/CK-1

• Brain tissues are the primary source of Creatine kinase- BB (CK-BB).
• It can also be found in the lungs, prostate, uterus, and thyroid. 

2. CK-MB/CK-2

• CK-MB is highly concentrated in cardiac muscles.
• It is mainly found in type 1 muscle fibers.
• It is more sensitive and specific for detecting myocardial necrosis than total CK enzyme.
• Compared to total CK in skeletal muscles, 1-3% is CKMB, and in cardiac muscles, it is 15-30%⁽⁵⁾.
• CK-MB can also be found in other structures like the prostate, intestine, uterus, and diaphragm.

3. CK-MM/CK-3

• CK-MM is an isoform of the CK enzyme highly concentrated in skeletal muscles.
• That’s why it’s used to diagnose muscular disease. 

Role of CK-MB in Acute Myocardial Infarction

• CK-MB is the most sensitive and specific indicator for diagnosing acute MI.
• After 3-4 hours from the onset of myocardial injury, CK-MB level increases. 
• It will reach its peak in 12-18 hours. 
• It will fall to its baseline within 2-3 days. 
• Because it takes a few hours to elevate, it’s needed to do serial measurements for 24 hours. 

Normal Range 

Normal range for creatine kinase or creatine phosphokinase is:⁽¹⁾

Adult/elderly	• Male: 55 -170 units/L (SI units) • Female: 30 -135 units/L (SI units)
Newborn	• 68-580 units/L (SI units) – this is approximately 2 to 3 times the adult values
Above 90 years	Males = 21 – 203 U/L Females = 22- 99 U/L

Normal Range for isoenzymes of CK or CPK

Creatine kinase-MM (CK-MM) also called CK-3	• 94 -100%
Creatine kinase-MB (CK-MB) also called CK-2	• 0 – 6 %
Creatine kinase- BB (CK-BB)  also called CK-1	• 0%

Note: Creatine kinase (CK) enzyme values may be variable according to the age, race, gender, and physical activity. The value of Creatine kinase (CK) is higher in newborns and black males. There is also variation in the upper limit of creatine kinase enzymes in athletes. 

Types	Composition	Comment
Skeletal Muscle	98% – CK-MM 2% – CK-MB	Elevated in muscle disease
Cardiac Muscle	70-80% – CK-MM 20-30% – CK-MB	Cardiac muscle has highest amount of CK-MB
Brain	CK-BB
Plasma	Mainly CK-MM

Visual Representation for better understanding

Creatine kinase (CPK/CK) isoenzymes subtypes and distribution

Creatine kinase (CPK/CK) isoenzymes subtypes and (distribution in percentages)

Total Creatine kinase (CPK/CK) distribution

Collection of sample (Precautions to be taken)

• The sample is collected in heparinized tubes. 
• Subject is not needed to avoid taking meals. 
• We can draw the sample at any time of the day. 
• It is important to collect the blood sample after or an hour before an intramuscular injection. 
• Storage temperature should be between 4℃ to 24℃ for next 3 days. 

Specifications of CK blood test

Indication	CK blood test is used to evaluate: • Skeletal • Muscle • Heart • Brain
Type of specimen	Serum or plasma
Container used	Heparinized tube is preferred
Quantity	0.6ml of blood should be drawn for test
Specimen storage (Serum and plasma)	• 20 to 25°C for two days (3) • 2 to 8°C for seven days (3, 4)
Precautions	• Store the sample in the proper light and temperature. • Avoid hemolyzed blood sample. • Don’t take a sample just after the IM injection. • Rule out trauma, it may make the test unreliable. • No special preparation is needed.

Clinical Significance of Creatine kinase blood test⁽⁷⁾

• In case of muscular damage, creatine kinase evaluation should be suspected.
• In case of inflammation, damage, or injury to skeletal muscles, necrosis, or heart muscle damage, serum creatine kinase level is elevated. 
• Level of creatine kinase elevates in neuromuscular disorders.
• Serum level of creatine kinase is increased in all types of muscular dystrophy.
• Serum creatine kinase level falls in older ages.
• Serum creatine kinase level increases almost 3 to 6 times in Duchene muscular dystrophy. 
• Levels may also increase after IM (Intramuscular) injection or surgical intervention. 
• Serum creatine kinase level is helpful in making a diagnosis and in the monitoring of muscular diseases like neuromuscular disorders and muscular damage.

What happens if the value of the Creatine kinase (CK) blood test is elevated?

The increased value of the Creatine kinase (CK) blood test is diagnostic for several diseases like:

• Acute myocardial infarction (MI)
• Myopathies
• Rhabdomyolysis
• Muscular dystrophy
• Malignant hyperthermia
• Neuroleptic malignant syndrome
• Paralysis (periodic)
• Drug-induced myopathies
• Renal damage
• Intramuscular injection
• Strenuous exercises

What happens if the value of the Creatine kinase (CK) blood test is below normal?

Creatine kinase value is linked with the amount of muscle in the body. Its value may be below the normal range in the following conditions:

• Lean muscle mass
• In females as compared to males
• Alcoholic liver disease
• Rheumatoid arthritis

Some are confused about the Creatine and Creatinine blood tests – here is a table of comparison between them to help you understand better

Difference between Creatine and Creatinine

Creatine	Creatinine
The Creatine is 2-(carbamimidoyl-methyl amino) acetic acid	Creatinine is 2-amino-1-methyl-5h-imidazole-4-one
The creatine is a linear molecule and amino acid.	Creatinine is a heterocyclic structure and a chemical waste.
It is formed by protein metabolism.	It is formed by creatine metabolism.
It is used as a supplement to increase muscle mass.	It is a waste product of creatine metabolism.
It provides energy to muscles.	It is used along with BUN to determine renal function.
It is produced by the liver, pancreas, and kidneys and is sent to the muscles.	It is produced in the muscles by creatine breakdown.

Frequently asked questions

Reference 

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