Download Myocardial infarction - Lectures For UG-5

Lecture 5
Infarction
 The process by which necrosis results from ischemia is
called infarction
 Ischemic necrosis of myocardial cells is one of the
commonest cause of death in industrialized countries.
Pathology
 Atherosclerosis
 Narrowing of arterial lumen
 Reduced coronary blood supply
 Clinical manifestations
 Chest pain
Diagnosis
 History
 ECG
 Biomarkers
WHO classification of MI
2/3 these criteria:
Ischemic symptoms
EKG changes.
Increased serum markers.
ECG
CARDIAC PROFILE TEST
 ENZYMES
 Creatinine Kinase –MB(CK-MB)
 Lactate Dehydrogenase(LDH 1 and 2)
 Aspartate Aminotransferase(AST)/Serum Glutamate Oxaloacetate
Transaminase(SGOT)
 Alanine Aminotransferase(ALT)/ Serum Pyruvate
Transaminase(SGPT)
• PROTEINS


Myoglobin
Troponin
 LIPID PROFILE
 CHOLESTEROL
 TRIGLYCERIDE
 HDL
 LDL
AST
found in all tissue, especially the heart, liver, and skeletal
muscles
It catalyzes the transfer of the amino group of aspartic acid to
alpha-ketoglutaric acid to form oxaloacetic acid and glutamic
acid
Reference range: < 35 U/L in male and < 31 in female
Considerations in AST assays
-Serum is the best specimen
-Hemolyzed samples must be avoided
-Muscle trauma like intramuscular injections, exercise, or
surgical operation can significantly increase AST levels
Clinical significance
 Myocardial infarction
 In myocardial infarction, AST levels are usually 4-10
times the upper limit of normal
 These develop within 4-6 hours after the onset of pain
 Peak on the 24th – 36th hour
 Usually normalize on the 4th or 5th day
 Muscular dystrophy
 Hepatocellular disorders
 Skeletal muscle disorders
LACTATE DEHYDROGENASE (LDH)
 Catalyzes the reversible oxidation of lactate to
pyruvate
 Used to indicate AMI
 Is a cytoplasmic enzyme found in most cells of the
body, including the heart
 Not specific for the diagnosis of cardiac disease
Distribution of LD isoenzymes
 LD1 and LD2 (HHHH, HHHM)
 Fast moving fractions and are heat-stable
 Found mostly in the myocardium and erythrocytes
 Also found in the renal cortex
 LD3 (HHMM)
 Found in a number of tissues, predominantly in the white
blood cells and brain
 LD4 and LD5 (HMMM, MMMM)
 Slow moving and are heat labile
 Found mostly in the liver and skeletal muscle
Considerations in LD assays
 Red cells contain 150 times more LDH than serum,
therefore hemolysis must be avoided
 LDH has its poorest stability at 0°C
Clinical Significance
 In myocardial infarction, LD increases 3-12 hours after
the onset of pain
 Peaks at 48-60 hours and remain elevated for 10-14 days
 In MI, LD1 is higher than LD2, thus called “flipped” LD
pattern
flipped LDH
An inversion of the ratio of LD isoenzymes
LD1 and LD2; LD1 is a tetramer of 4 H–heart
subunits, and is the predominant cardiac LD
isoenzyme;
Normally the LD1 peak is less than that of the
LD2, a ratio that is inverted–flipped in 80% of
MIs within the first 48 hrs
DiffDx.
LD flips also occur in renal infarcts, hemolysis,
hypothyroidism, and gastric CA
Increased levels of LD
 Trauma
 Megaloblastic anemia
 Pulmonary infarction
 Granulocyte leukemia
 Hemolytic anemia
 Progressive muscular dystrophy (PMD)
CREATINE KINASE (CK)
 Is a cytosolic enzyme involved in the transfer of energy
in muscle metabolism
 Catalyzes the reversible phosphorylation of creatine by
ATP
 -Is a dimer comprised of two subunits, resulting in
three CK isoenzymes
 The B, or brain form
 The M, or muscle form
isoenzymes
 CK-BB (CK1) isoenzyme
 Is of brain origin and only found in the blood if the blood-brain barrier
has been breached
 CK-MM (CK3) isoenzyme
 Accounts for most of the CK activity in skeletal muscle
 CK-MB (CK2) isoenzyme
 Has the most specificity for cardiac muscle
 It accounts for only 3-20% of total CK activity in the heart
 Is a valuable tool for the diagnosis of AMI because of its relatively high
specificity for cardiac injury
 Established as the benchmark and gold standard for other cardiac
markers
Clinical Significance
 -In myocardial infarction, CK will rise 1-3 hours after




the onset of pain
-Peaks at 18-30 hours and returns to normal on the
third day
-CK is the most specific indicator for myocardial
infarction (MI)
Ratio of CK-MB/ total CK activity (specificity)
CK-MB mass instead of activity (sensitivity)
Raised levels of CK
 Progressive muscular dystrophy
 Polymyositis
 Acute psychosis
 Alcoholic myopathy
 Hypothyroidism
 Malignant hyperthermia
 Acute cerebrovascular disease
 Trichinosis and dermatomyositis
 Exercise and intramuscular injections causes CK
elevations
Normal Value:
 a. Male – 25-90 IU/mL
 b. Female – 10-70 IU/mL
Myoglobin
 Non specific marker
 Frequently elevated in other conditions
 Most useful when not detected
 Can not be used alone for the diagnosis of MI.
Troponins
 Proteins that regulate muscle contraction
 T & I are specific for cardiac muscles
Cardiac troponins:
1. Troponin C: binds with calcium.
2. Troponin T: binds with tropomyosin.
3. Troponin I: inhibits contraction.
Troponin T & I
 Require myocardial necrosis for release from
sarcomere.
 Early rise (4-12 hours after symptom).
 Peak 12-24 hours (sensitivity is 100%).
 Continuous release up to 10-14 days
 Myocardial infarction: elevation of serum troponin T/I
>0.1. (AHA)
 Negative troponin and normal EKG, mortality 1%.
 Negative troponin and ischemic EKG: mortatity 4% at
1 month.
 Troponin and EKG changes complementary.
 Problems with TnI: variability of assays.
 Complement clinical risk factors and EKG changes.