Biochemical InvestigationsIn Heart DisaesesBiochemical InvestigationsIn Heart Disaeses
OverviewOverview
•Myocardial infarction•Myocardial infarction
•Time-course of plasma enzyme changes•Time-course of plasma enzyme changes
•Creatine kinase (CK)•Creatine kinase (CK)
•Lactate dehydrogenase (LDH)•Lactate dehydrogenase (LDH)
•Aspartate aminotransferase (AST)•Aspartate aminotransferase (AST)
•Myoglobin•Myoglobin
•Cardiac troponins I and T•Cardiac troponins I and T
Acute Coronary Syndromes
Similar pathophysiology
Similar presentation andearly management rules
STEMI requiresevaluation for acutereperfusion intervention
Unstable Angina
Non-ST-SegmentElevation MI(NSTEMI)
ST-SegmentElevation MI(STEMI)
The increased levels of troponins although not associated by ECG changesindicates increased risk of subsequent cardiac events
What is Myocardial Infarction?
Myocardial ischemia results from the reduction of coronaryblood flow to an extent that leads to insufficiency ofoxygen supply to myocardial tissue
When this ischemia is prolonged & irreversible, myocardialcell death & necrosis occurs ---this is defined as:
myocardial infarction
is the death & necrosis of myocardial cells
as a result of coronary prolonged & irreversibleischemia
Previously:
WHO criteria for the diagnosis of myocardialinfarction ( at least 2/3):
1.Typical history of chest pain
2.Presence of ECG changes
3.Rise of biochemical markers
With the advent of troponins, which is moresensitive biochemical marker, newdefinition:
Types of Biochemical Markers
1- Cardiac Enzymes (isoenzymes):
Total CK
CK-MB activity
CK-MB mass
Aspartate aminotransferase (AST)
Lactate dehydrogenase (LDH)
2- Cardiac proteins:
Myoglobin
Troponins
Cardiac Enzymes
Total CK (sum of CK-MM, CK-MB & CK-BB)
non specific to cardiac tissue (available in skeletal ms.)
CK-MB (CK-2) activity
more specific than total CK
BUT: less specific than troponin I (available in sk. Ms)
appears in blood: within 4-6 hours of onset of attack
peak: 12 - 24 hours
returns to normal: within 2 - 3 days (no long stay in blood)
Advantages: - useful for early diagnosis of MI
- useful for diagnosis reinfarction
Disadvantages: not used for delayed admission (more than 2 days)
not 100% specific (elevated in sk.ms damage)
Cardiac Proteins
Myoglobin
cytosolic protein
- not specific for cardiac tissue (also in sk.ms. & renal tissue)
- appears in blood EARLIER than other markers (within 1-4 hours)
So, with high sensitivity
- BUT: Returns to normal in 24 hours
So, not for delayed admission cases (after one day of onset
of attack)
Cardiac Troponins
Protein complex located on the thin filament of striated muscles
consists of 3 subunits: cTn T, cTnI & cTn C
with different structures & functions
cTnI & cTnT are used are biomarkers for MI diagnosis
Cardiac troponins (cTn) are different from skeletal muscle tropnins
So, more specific for MI diagnosis
cTnI:
100 % cardiac specific
With greater sensitivity for diagnosing minor damage of MI
Appears in blood within 6 hours after onset of infarction
peak: around 24 hours
Disappears from blood after about one week (stays longer)
So, useful for diagnosis of delayed admission cases
Prognostic marker (relation between level in blood & extent ofcardiac damage)
Lactate dehydrogenase (LDH)
LDH is a tetramer, each chain may be one of twotypes (H,M) where LDH1 is (H4) while LD5 is (M4)
LD1 & LD2 predominates in heart and red cells
LDH increases later than CK-Mb and Ck
Reaches a max. level in 48 h
Remains elevated for 5-6 days after the MI
A non-specific marker of tissue injury:
* High levels are found in liver, lung,
kidney and other diseases
AST is somewhat heart-specific than ALT
A non-specific marker of MI
It appears in liver and other diseases
Aspartate aminotransferase(AST)
Plasma enzymes follow a pattern of activities after a MI
The initial lag phase lasts for about 3 hours
Enzymes rise rapidly to peak levels in 18-36 hours
The levels return to normal based on enzyme half-life
Rapid rise and fall indicates diagnostic value.
Time-course of enzymechanges
• Blood samples collected at:* Baseline (upon admission)* Between 12 to 24 hours after the onset of symptoms
Time-Course of Changes
Enzyme
Detectable
(hours)
Peak value
(hours)
Duration
(days)
CK-MB
3-10
12-24
1.5-3
Total CK
5-12
18-30
2-5
AST
6-12
20-30
2-6
LDH
(heart specific)
8-16
30-48
5-14
Cardiactroponins
4-6
12-24
Up to 10
