ANGELES UNIVERSITY FOUNDATION MEDICAL CENTER
Center for Anatomic Pathology and
Laboratory Medicine
Creatine Kinase, Lactate Dehydrogenase
And Aldolase
Submitted By:
Frances Dei Del Rosario, Medical Technology Intern
Submitted To:
Ms. Diana Ocampo Icban, RMT
Submitted at:
February 2, 2015
Creatine Kinase
Creatine Kinase catalyzes the transfer of phosphate group between creatine
phosphate and adenosine diphosphate. This reaction occurs prominently in
muscle tissue, allowing for storage of phosphate band as creatine phosphate.
It is a dimeric molecule, composed of two monomers called M and B.
It is found in small amounts throughout the body, but high concentrations
are found in the muscle and brain. Every contraction cycle of muscle results
in creatine phosphate use.
Creatine + ATP
Creatine Phosphate + ADP
CK is widely distributed in the body tissues; there are high concentrations
found in the skeletal muscle, heart muscle and brain tissue. Because of its
high concentrations in muscle tissues, it is frequently elevated in cases of
skeletal and cardiac muscle disorders. CK is also considered as an indicator
for acute myocardial infarction and muscle dystrophy.
CK has three izoenzymes:
1) CK-BB (brain type) / CK-1
2) CK-MB (hybrid type) / CK-2
3) CK-MM (muscle type) / CK-3
Isoenzyme
CK-MM
Tissue
Heart
Skeletal Muscle
CK-MB
Heart
Skeletal Muscle
CK-BB
Brain
Bladder
Lung
Prostate
Condition
Myocardial Infarction
Skeletal Muscle Disorder
Muscular dystrophy
Myocardial Infarction
Myocardial Injury
Ischemia
Inflammatory
Heart
Disease
CNS shock
Anoxic encephalopathy
Seizure
Diagnostic Significance:
CK-MB is found mainly in myocardial tissue- it is used as a
serodiagnostic test for AMI
Following AMI CK-MB levels rises within 4-8 hours, peaks at 12-24 hours
and normalizes within 48-72 hours
Total CK is markedly elevated after trauma to skeletal muscle.
Highest elevation of total CK is seen in Duchennes muscular dystrophy
Assay Enzyme Activity:
1) Forward/ Direct Method
> Also known as Tanzer-Gilbarg Assay
> optimal pH: 9.0; absorbance: 340 nm
Creatine + ATP
Creatine PO4 + ADP
ADP + phosphoenolpyruvate
Pyruvate + NADH
Pyruvate + ATP
Lactate + NAD
2) Reverse/ Indirect Method
> Oliver-Rosalki Method
> commonly performed method in the clinical laboratory,
proceeds two to six times faster than the forward reaction
> optimal pH: 6.9; absorbance: 340nm
Creatine PO4 + ADP
ATP + glucose
Glucose-6-PO4 + NADP
Reference Range:
Total CK:
Creatine + ATP
ADP + glucose-6-PO4
6-phosphogluconate + NADPH
Male: 15 160 U/L
Female: 15-130 U/L
CK-MB: <6% of total CK
CK relative Index:
-
Expression of percentage that is attributed to CK-MB
This is computed to know possible release of CK-MB from non cardiac
tissues when total CK is high
CKI = CK-MB ug/L or IU/L
Total CK IU/L
x100
Lactate Dehydrogenase
LDH is an enzyme that catalyses the interconversion of lactic and pyruvic
acid.
LDH is widely distributed in the body. It is highly concentrated or high
activities are found in the liver, skeletal muscle, kidney and erythrocytes.
Because of its wide distribution in the body, it is elevated in a variety of
disorders.
Since LDH is also found in the erythrocytes, highest levels of it are found in
cases of pernicious anemia and hemolytic disorders. AMI also shows slight
elevations in LDH. In AMI LDH rises within 12-24 hours, reaches its peak level
at 48-72 hours and may remain elevated for 10 days.
Because a lot of disorders are associated with LDH, its findings are
considered almost nonspecific. Findings are more clinically significant when it
is separated into its isoenzymes. LDH can be separated into five major
fractions:
-
LDH-1
LDH-2
LDH-3
LDH-4
LDH-5
ISOENZYME
LDH-1
LDH-2
LDH-3
/
/
/
/
/
HHHH
HHHM
HHMM
HMMM
MMMM
TISSUE
Heart
Red blood cell
Heart
Red blood cell
Lung
Pancreas
LDH-4
Liver
LDH-5
Skeletal muscle
DISORDER
Myocardial infarction
Haemolytic anemia
Megaloblastic anemia
Acute renal infarct
Pulmonary embolism
Acute pancreatitis
Carcinoma
Hepatic injury or
inflammation
Skeletal muscle injury
Diagnostic Significance:
LD-1 > LD-2 is known as the flipped pattern and seen in myocardial
infarction and haemolytic anemia
LD-2, LD-3, LD-4 are LD cancer markers; acure leukemia , germ cell
tumors and lung cancers
Highest serum levels are seen in pernicious anemia and hemolytic
anemia
In AMI LDH rises within 12-24 hours, reaches its peak level at 48-72
hours and may remain elevated for 10 days.
Assay Enzyme Actvity:
-
Interconversion of lactic and pyruvic acids using the coenzyme NAD+
1)
-
Forward/Direct reaction
Optimal pH: 8.3 8.9
Not affected by product inhibition
Wacker Method
Lactate + NAD
Pyruvate + NADH
2) Reverse/Indirect reaction
- Optimal pH: 7.1 7.4
- Three times faster however more susceptible to substrate exhaustion
and loss of linearity
- Wrobleuski La Due
- Preferred method for fry slide technology
Pyruvate + NADH
Lactate + NAD
Reference Range:
Forward reaction: 100-225 U/L
Reverse reaction: 80-280 U/L
Aldolase
Aldolase is an enzyme responsible for breaking down glucose products into
energy, specifically converting fructose 1,6-bisphosphate into the triose
phosphates dihydroxyacetone phosphate (DHAP) and glyceraldehydes 3phosphate.
An aldolase blood test is used to help identify damaged structures to organs
such as liver, muscle, kidney, or heart. There are three isoenzymes of
aldolase:
-
Aldolase A
Aldolase B
Aldolase C
Aldolase A is expressed in muscle, erythrocytes, and the brain; aldolase B is
expressed in the liver, kidneys, and enterocytes; aldolase C is expressed in
the brain.
Diagnostic Significance:
Measurement of aldolase A can also help differentiate between muscle
versus neurological myopathy. If aldolase A is elevated, the primary cause of
myopathy may be related to an inflammatory state of the muscle. If Aldolase
A is not elevated, the pathology may be related to a secondary cause. An
example is a patient with a history of multiple sclerosis who presents with
muscle weakness and has normal aldolase A levels.
Aldolase B levels are elevated in liver disease or heart disease (myocardial
infarction). This particular marker is not widely used because other blood
tests are more specific for liver and heart-related diseases (LFTs and Cardiac
enzymes).
Reference Range:
Age 0-2 years: < 16 U/L (approximation)
Age 3-16 years: < 8 U/L (approximation)
Age 17 years and older: < 7.5 U/L
Reference:
Clinical Chemistry, A fundamental Textbook by Donald Calbreath
Clinical Chemistry Techniques, Principles, Correlations 6th edition by
Michael Bishop, et al
Henrys Clinical Diagnosis and Management by Laboratory Methods
22nd Edition
Clinical Chemistry Review Handbook for Medical Technologists
revised 2014 by Maria Teresa Rodriguez
