Biochemical Biochemical Investigations In Investigations In Heart Disaeses Heart Disaeses
Biochemical Biochemical Investigations In Investigations In Heart Disaeses Heart Disaeses
OverviewOverview•Myocardial infarctionMyocardial infarction•Time-course of plasma enzyme Time-course of plasma enzyme changeschanges•Creatine kinase (CK)Creatine kinase (CK)•Lactate dehydrogenase (LDH)Lactate dehydrogenase (LDH)•Aspartate aminotransferase Aspartate aminotransferase (AST)(AST)•MyoglobinMyoglobin•Cardiac troponins I and TCardiac troponins I and T
Acute Coronary Syndromes
Similar pathophysiology
Similar presentation and early management rules
STEMI requires evaluation for acute reperfusion intervention
Unstable Angina
Non-ST-Segment Elevation MI (NSTEMI)
ST-Segment Elevation MI (STEMI)The increased levels of troponins although not associated
by ECG changes indicates increased risk of subsequent cardiac events
What is Myocardial Infarction? Myocardial ischemia results from the reduction of coronary
blood flow to an extent that leads to insufficiency of oxygen supply to myocardial tissue
When this ischemia is prolonged & irreversible, myocardial cell death & necrosis occurs ---this is defined as:
myocardial infarction
is the death & necrosis of myocardial cells
as a result of coronary prolonged & irreversible ischemia
Previously:
WHO criteria for the diagnosis of myocardial infarction ( at least 2/3):
1.Typical history of chest pain2.Presence of ECG changes3.Rise of biochemical markers With the advent of troponins, which is
more sensitive biochemical marker, new definition:
Types of Biochemical Markers1- 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 of cardiac
damage)
Lactate dehydrogenase (LDH)
LDH is a tetramer, each chain may be one of two types (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 enzyme changes
• 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
Cardiac troponins
4-6 12-24 Up to 10