Basic Science applied to medicine

1. Education is what remains after one has forgotten what one has learned in school.
-Albert Einstein
DEFINITION
● A biomarker is a substance used as an indicator of a biologic state
● Morrow and de lomos criteria for biomarkers
○ Accurate repeated measurements at reasonable cost
○ Must provide additional information
○ Should aid treatment
IDEAL BIOMARKER
● High cardiac specificity
● Pharmacokinetics of cardiac biomarker
● Easy diagnosis
● Marker should play a designed role in the treatmentand management of clinical subject
BIOMARKERS
● Markers of myocardial necrosis
○ Creatine kinase – MB
○ Myoglobin
○ Cardiac troponins
● Markers of myocardial ischemia
○ Ischemia Modified Albumin (IMA)
○ Heart-type fatty acid binding protein (H-FABP )
● Markers of hemodynamic stress
○ ANP
○ BNP
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by Dr. Eashan Srivastava

2. Education is what remains after one has forgotten what one has learned in school.
-Albert Einstein
○ ProBNP
● Markers of inflammation
○ Hs-CRP
○ Homocysteine
○ MPO
1. CREATINE KINASE AND CK-MB
a. Were commonly used prior to troponin
b. Little relevance now
c. Detection of early reinfarction
d. CK basics
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by Dr. Eashan Srivastava

3. Education is what remains after one has forgotten what one has learned in school.
-Albert Einstein
i. Enzyme CK (formerly creatine phosphokinase)
ii. Dimers of M and B chains
iii. 3 combinations - MM, MB, and BB
iv. Found in cytosol
v. Found in heart and skeletal muscle
e. Total CK
i. Non specific for cardiac damage
ii. >2x increase required for diagnosis
iii. Individuals with lower muscle mass, may have low baseline total CK
f. CK-MB fraction
i. Less sensitive and specific than Troponin
ii. CK linked to IgG - Can confound diagnosis
iii. >20% - Significant
iv. Begins to rise - 4-6 hours
v. Return to baseline - 36 to 48 hours
vi. Uses
1. Prognosis
a. Correlation between infarct size and CK-MB
2. Reinfarction
a. cTn elevated for 10-14 days
3. After myocardial revascularization
a. Still used by some to detect MI after revascularization
2. Troponin
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by Dr. Eashan Srivastava

4. Education is what remains after one has forgotten what one has learned in school.
-Albert Einstein
a. Diagnosis
i. Higher sensitivity and specificity compared with CK-MB and other
markers
ii. Sensitivity = More troponin is found in the heart per gram of myocardium
iii. Specificity = Not found in other tissues
b. Prognosis
i. Troponin measurements have prognostic value
3. MYOGLOBIN
a. Heme protein
b. Rapidly released from damaged tissue because of its small size
c. T50 = 9 minutes
d. Highly sensitive cardiac troponin (cTn) assays is elevated prior to elevations in
myoglobin
4. COPEPTIN
a. C-terminal portion of the arginine vasopressin precursor peptide
b. Used along with cTn assays to allow some patients to be sent home earlier
5. HEART-TYPE FATTY ACID BINDING PROTEIN
a. Similarly to myoglobin in its kinetics and release
b. More specific than myoglobin
c. Raised < 2 hours of symptoms
d. Sensitivity - Poor
6. LACTATE DEHYDROGENASE
a. Consists of M (muscle) and H (heart) subunits
b. 5 isoenzymes
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by Dr. Eashan Srivastava

5. Education is what remains after one has forgotten what one has learned in school.
-Albert Einstein
c. The heart primarily contains LD1 and some LD2
d. Rises approximately 10 hours after the onset of MI
e. Peaks at 24 to 48 hours
f. Elevated for six to eight days
IMA
● A novel marker of ischemia
● Produced when circulating serum albumin contacts ischemic tissues
● Measured by the albumin cobalt binding (ACB)
● Mechanism- due to structural change in the amino terminal end of albumin
● IMA levels rise within 6 hours
● remain elevated for 12 hours
● Drawbacks
○ IMA levels raised in non- cardiac ischemia
○ Modification to n- terminal end may also be induced by extracellular hypoxia,
acidosis etc.
- Created with love
by Dr. Eashan Srivastava