Myocardial infarctionLecture 5

InfarctionThe process by which necrosis results from

ischemia is called infarctionIschemic necrosis of myocardial cells is one of

the commonest cause of death in industrialized countries.

Pathology AtherosclerosisNarrowing of arterial lumenReduced coronary blood supplyClinical manifestations

Chest pain

Diagnosis History ECGBiomarkers

WHO classification of MI2/3 these criteria:Ischemic symptomsEKG changes.Increased serum markers.

ECG

CARDIAC PROFILE TESTENZYMES

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 MyoglobinTroponin

LIPID PROFILECHOLESTEROL TRIGLYCERIDEHDLLDL

ASTfound 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 disordersSkeletal muscle disorders

LACTATE DEHYDROGENASE (LDH)

Catalyzes the reversible oxidation of lactate to pyruvate

Used to indicate AMIIs a cytoplasmic enzyme found in most cells

of the body, including the heartNot specific for the diagnosis of cardiac

disease

Distribution of LD isoenzymes

LD1 and LD2 (HHHH, HHHM)Fast moving fractions and are heat-stableFound mostly in the myocardium and erythrocytesAlso 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 labileFound mostly in the liver and skeletal muscle

Considerations in LD assaysRed cells contain 150 times more LDH than

serum, therefore hemolysis must be avoidedLDH has its poorest stability at 0°C

Clinical Significance In myocardial infarction, LD increases 3-12

hours after the onset of painPeaks at 48-60 hours and remain elevated for 10-

14 daysIn MI, LD1 is higher than LD2, thus called

“flipped” LD pattern

flipped LDHAn 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 LDTrauma Megaloblastic anemiaPulmonary infarctionGranulocyte leukemiaHemolytic anemiaProgressive 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 formThe M, or muscle form

isoenzymesCK-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 CKProgressive muscular dystrophyPolymyositis Acute psychosisAlcoholic myopathy HypothyroidismMalignant hyperthermiaAcute cerebrovascular diseaseTrichinosis and dermatomyositisExercise and intramuscular injections causes CK

elevations

Normal Value:a. Male – 25-90 IU/mL b. Female – 10-70 IU/mL

Myoglobin Non specific markerFrequently elevated in other conditions Most useful when not detectedCan not be used alone for the diagnosis of

MI.

TroponinsProteins that regulate muscle contractionT & 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.