cardiac enzymes

Cardiac Enzymes

Appear Early
Accurate
Easily Detected
Has to be specific

EC 2.7.3.2

What is the E.C. number for Creatine Kinase?

The transfer of a phosphate group between creatine phosphate and adenosine diphosphate

What chemical reaction does Creatine Kinase (CK) catalyze?

Creatinine Phosphate

Creatine + ATP --> _ + ADP

It is involved in the energy storage of tissues, specifically muscles

What is the primary physiological role of Creatine Kinase?

No. It is not specific because,
it is found in many locations, including major sources like skeletal muscle and brain, and minor sources like the bladder, liver, and GIT.

Is total Creatine Kinase a specific marker for cardiac arrest?

What co-factor is required for Creatine Kinase activity

Magnesium.

molecular structure of Creatine Kinase

It is a dimeric molecule composed of two subunit types:
B (Brain Type)
M (Muscle Type)

Acute Myocardial Infarction (AMI)
Duchenne disorder

Creatine Kinase is a sensitive indicator for which two specific clinical conditions

Skeletal Muscle, Heart Muscle, and Brain

Where are the "Major" sources of Creatine Kinase found in the body?

CK1 (CK-BB)
CK2 (CK-MB)
CK3 (CK-MM)

What are the three isoenzymes of Creatine Kinase and their alternative names

Brain, intestine, and smooth muscle

Where is CK1 (CK-BB) primarily found?

CK2 (CK-MB)

Which CK isoenzyme is known as the "Hybrid" type?

it has high specificity to cardiac tissue and is utilized as a serodiagnostic test for myocardial infarction.

Why is CK2 (CK-MB) clinically significant

Rise: 4-8 hours after AMI
Peak: 12-24 hours
Normalize: 48-72 hours

What is the timeline for CK-MB levels during an Acute Myocardial Infarction (AMI)

Heart: ~30%
Skeletal Muscle: ~1%

What is the percentage distribution of CK2 (CK-MB) in the Heart vs. Skeletal Muscle?

It is found in striated, cardiac, and skeletal muscles. It is the slowest migrating isoenzyme

Where is CK3 (CK-MM) found, and how fast does it migrate compared to others?

Heart: ~70%
Skeletal Muscle: 94% - 100%

What is the percentage distribution of CK3 (CK-MM) in the Heart vs. Skeletal Muscle

pH 9

What is the optimal pH for the Tanzer-Gilbarg Assay (Forward method)?

340 nm.

At what wavelength is the Tanzer-Gilbarg Assay read?

The Oliver-Rosalki method

Which CK determination method is considered "Reverse or Indirect"?

It is faster and has lesser interference.

Why is the Oliver-Rosalki method the most commonly used?

pH 6.8.

What is the optimal pH for the Oliver-Rosalki method?

It is rapidly inactivated, especially if sulfhydryl groups are oxidized

Why is CK activity in serum considered unstable?

Sulfhydryl compounds, such as N-acetylcysteine.

What can be added to the assay to reverse the inactivation of CK?

Red cell lysis releases Adenylate Kinase (AK), which hydrolyzes ADP and interferes with the assay (particularly if > 320 mg/L)

How does hemolysis interfere with CK assays?

Adenosine monophosphate (AMP)

What is added to the reverse method to inhibit Adenylate Kinase (AK)?

Light and pH

Besides hemolysis, what other environmental factors is CK sensitive to?

Physically well-trained individuals tend to have higher total CK

How does physical training affect Total CK levels?

Bedridden patients tend to have lower CK activity

How does being bedridden affect CK activity?

46 - 171 U/L.

What is the reference range for Total CK in males?

34 - 145 U/L

What is the reference range for Total CK in females?

Because of increased muscle mass

Why do males generally have higher Total CK values than females?

Less than 5% (<5%)

What is the normal ratio of CK-MB to Total CK?

Mitochondrial CK.

What does CK-MI stand for?

Atypical forms of CK.

What is "Macro CK"?

Lactate Dehydrogenase (LDH)

It catalyzes the interconversion of lactic and pyruvic acids

Nicotinamide adenine dinucleotide (NAD). It is classified as a hydrogen-transfer enzyme.

What coenzyme is required by LDH for its activity?

molecular structure of LDH.

It is a tetrameric molecule consisting of four subunits. These subunits come in two forms: H (Heart) and M (Muscle)

LD-1: 14-26%
LD-2: 29-39% (The most abundant in normal serum)
LD-3: 20-26%
LD-4: 8-16%
LD-5: 6-16%

List the 5 primary LDH isoenzymes and their normal percentage ranges in total LD

What is the significance of the "Flipped Pattern" in LDH levels?

A flipped pattern occurs when LD1 > LD2. In a healthy state, LD2 is usually higher than LD1

this reversal is often a clinical marker for conditions like myocardial infarction (heart attack) or hemolytic anemia

LD6

Alcohol Dehydrogenase. It converts methanol to ethylene glycol.

What does an increase in LD6 usually signify clinically?

It reflects liver injury. It is specifically increased in cases of hepatotoxicity and obstructive jaundice

Where is LD CCCC found, and why is it not considered diagnostically significant?

It is found in spermatozoa and semen. It is not diagnostically significant because it is not found in the serum.

LD-1: H4
LD-2: H3M1
LD-3: H2M2
LD-4: H1M3
LD-5: M4

Match the LDH isoenzyme to its subunit composition (H and M)
LD-1:
LD-2:
LD-3:
LD-4:
LD-5:

LD-1 is the fastest/most anodic, while LD-5 is the slowest/closest to the point of application

n LDH electrophoresis, which isoenzyme migrates the fastest toward the anode (+ve)?

Heart
Red blood cells

Which tissues contain the highest concentrations of LD-1 and LD-2?

Myocardial infarction
Hemolytic anemia
Megaloblastic anemia
Acute renal infarct
Hemolyzed specimen

What clinical disorders are associated with elevations in LD-1 and LD-2?

Lung
Lymphocytes
Spleen
Pancreas

Which tissues are primary sources for LD-3?

Pulmonary embolism
Extensive pulmonary pneumonia
Lymphocytosis
Acute pancreatitis
Carcinoma

What disorders are associated with an elevation of LD-3?

• Tissue: Liver
  Disorder: Hepatic injury or inflammation

What is the primary tissue source and clinical disorder for LD-4?

• Tissue: Skeletal muscle
  Disorder: Skeletal muscle injury

What is the primary tissue source and clinical disorder for LD-5?

Wacker method

Forward/direct reaction (Lactate ->Pyruvate)

optimal pH 8.3-8.9

not affected by product inhibition.

Wrobleuski-LaDue Method

Reverse/indirect reaction (Pyruvate -> Lactate)

optimal pH 7.1-7.4

3x faster with shorter reaction time

uses smaller volume

susceptible to substrate exhaustion

Temperature: Read at 37°C.
Wavelength: 340 nm.
Reference Range: 125 - 220 U/L.

What are the shared testing conditions for both LD determination methods (Wacker and Wrobleuski-LaDue)

125 - 220 U/L

Reference Range for Wrobleuski -Laude Method

• Must be processed within 24 hours after collection.
  Levels increase temporarily after blood transfusion.
  LD is used to differentiate transudates from exudates.

What are the key storage and processing requirements for LD

LD levels in Tenfold increase. Significant for checking drug toxicity.

Hepatic carcinoma and toxic hepatitis

Twofold increase in LD5:

Viral hepatitis and cirrhosis.

Aspartate Aminotransferase

What does AST stand for?

EC 2.6.1.1

What is the enzyme classification (EC number) of AST?

SGOT (Serum Glutamic Oxaloacetic Transaminase)

What is another name for AST?

Cytoplasmic AST (predominant in serum)
Mitochondrial AST

What isoenzymes does AST have?

Cytoplasmic AST

Which AST isoenzyme is predominant in serum?

Cardiac tissue
Liver
Skeletal muscle

What are the major tissue sources of AST?

Myocardial infarction (MI)
Hepatocellular disorders
Skeletal muscle involvement

Elevated AST is significant in which conditions?

5-37 U/L

What is the reference range for AST?

Pyridoxal phosphate (PLP), which functions as a coenzyme

What is the cofactor for AST?

No. AST is also found in the liver and skeletal muscles

Is AST specific to the heart? Why or why not?

Hepatocellular disorders

In which condition is AST found at the highest concentration

Up to 100× normal

How much can AST increase in viral hepatitis?

Moderately increased only

How does AST change in cirrhosis?

For monitoring therapy

: How is AST used in patients taking potentially hepatotoxic drugs

When AST is >3× the upper limit of normal

When should hepatotoxic drug therapy be stopped based on AST levels?

Karmen method

What is the traditional method used to measure AST?

pH 7.3-7.8

What is the optimal pH for AST activity measurement

Pyridoxal-5-phosphate (P-5-P) and malate dehydrogenase (MDH)

AST measurement involves a coupled reaction with which enzymes?

37°C

At what temperature is the AST reaction measured?

Decrease in absorbance at 340 nm (continuous monitoring)

What spectrophotometric change is monitored in AST assays?

Hemolysis

What pre-analytical factor can interfere with AST results?

Stable at refrigerator temperature

How stable is AST in serum?

2-3 hours

When is Troponin T detectable after onset of AMI?

Up to 10 days

How long can Troponin T remain elevated in blood?

Troponin T

Which is more sensitive: Troponin T or CK-MB?

After ~4 hours

When does Troponin I increase after AMI?

no

Does Troponin C have diagnostic value?

myoglobin

Assists oxygen transport in cardiac and skeletal muscles

Rises rapidly (within 1 hour

myoglobin

Nonspecific

also increases in skeletal muscle injury, muscular dystrophy, and renal failure

What is the main limitation of myoglobin as a cardiac marker?

Troponin

Which marker indicates cardiac cell necrosis

They are detected in blood only when cardiac injury is present

Why are troponins considered specific markers for heart damage?

1-4 hours

When does myoglobin rise after myocardial infarction (MI)?