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BIOCHEMICAL MARKERS OF MYOCARDIAL INJURY

BIOCHEMICAL MARKERS OF MYOCARDIAL INJURY. Goals of Diagnostic tests. Differentiate patients with and without AMI. Laboratory diagnosis of AMI. Estimate extent of myocardial damage. Identify coronary reperfusion. Characteristics of Markers. High concentration in myocardium.

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BIOCHEMICAL MARKERS OF MYOCARDIAL INJURY

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  1. BIOCHEMICAL MARKERS OF MYOCARDIAL INJURY

  2. Goals of Diagnostic tests • Differentiate patients with and without AMI. • Laboratory diagnosis of AMI. • Estimate extent of myocardial damage. • Identify coronary reperfusion.

  3. Characteristics of Markers • High concentration in myocardium. • Not found in other tissues. • Released rapidly and completely. • Released in direct proportion to the damage. • Provide a convenient diagnostic time window

  4. Biochemical markers of MI • Enzymatic: • Creatine Kinase (CK) • Lactate Dehydrogenase (LD) • Asparatate Aminotransferase (AST) • Non-enzymatic: • Myoglobin • Myosin Fragments • Troponins

  5. Creatine kinase (CK) • Creatine Kinase: Structure • Dimer of two subunits B (Brain) and M (Muscle) (MW  40,000). • Synthesized in cytosol of myocytes. • Single subunits are enzymatically inactive. • Isoenzymes: • CK-BB /CK-1 – brain, prostate, gut and lung. • CK-MB /CK-2 – heart (25-40% of CK), skeletal muscle. • CK-MM /CK-3 – skeletal and cardiac muscle.

  6. Creatine Kinase in MI • Rises within 4 to 8 h, peak at 24 h, and return to normal by 36 to 72 hrs. • First CK-2 rises, usually 10-25 times. • Usually CK-2 is < 6% of total CK. • 12 hourly CK-2 adequate and cost effective. • Early detection of reperfusion is not possible with total CK. • CK-2 helps in reperfusion diagnosis. • CK-2 and CK-3 isoforms are early markers of MI.

  7. Lactate Dehydrogenase (LDH) • A tetramer composed of M (muscle) and H (heart) subunits, MW-34,000. • LD1 (H4) Heart, erythrocytes, brain, pancreas and kidney. • LD2 (H3M) Heart. • LD3 (H2M2) Erythrocyte. • LD4 (HM3) Liver. • LD5 (M4) Skeletal muscle.

  8. Lactate Dehydrogenase in MI • Rises within 12-24 h, peak at 48-72 h, and remain elevated for >7 days. • Usually 3-4 fold rise as high as 10 fold 86% patients of AMI  LD activity. • LD-1 has an increased tissue specificity. • Normally LD-2 is > LD-1 (LD-1 / LD-2 is < 0.76). • Ratio > 0.76 suggestive of AMI, value >1.0 improves specificity (Flipped ratio). • Persistent abnormality in LD-1 / LD-2 ratio indicates reinfarction. • Intravascular or extravascular haemolysis  LD-1 and LD-2 levels.

  9. Aspartate Aminotransferase (AST) • Highest concentration in heart, also present in liver, skeletal muscle, kidneys and brain. • Pattern of tissue distribution limits its clinical usefulness. • Elevated in 90% patients of MI • Rises within 6-8 h, peak at 24-48 h, and return to normal by 4-6th day.

  10. Myoglobin • A heme protein abundant in heart and skeletal muscle (MW17,800). • Normal Range: 6-90 ng/ml. • Sensitive but nonspecific marker of AMI. • Detectable 2 h (2-5) after AMI, peaks at 6-12 h, return to normal by 24-36 hrs. •  levels found in 65% patients of AMI. • Also elevate in skeletal muscle injury and renal failure.

  11. Myosin Light Chain • Muscle protein related to Troponin-C and Calmodulin. • Like Troponin T, cell damage  release of MLC. • Start  3-5 hours after Acute Pain. • Remain elevated  2 weeks.

  12. Troponins • Complex of 3 Troponins TrI, TrT and TrC. • Isoforms are product of different genes. • TrI and TrT are highly specific for myocardial injury. • Both  in 6 h and remain high for 7 days with peak times 10 - 24 h (biphasic). • TrT relatively rapid release (early marker of MI). • Due to prolong elevation permit late diagnosis of MI also.

  13. Heart Fatty Acid Binding Proteins • Low molecular mass protein (MW 15,000) abundant in the cytoplasm of myocardial cells. • An important intracellular fatty acid carrier protein. • Initial and peak elevation earlier than CK-2. • Sensitivity, specificity and predictive accuracy of H-FABP are higher than myoglobin for AMI within 6 h of onset of chest pain.

  14. Choice of markers for AMI • Molecular size • Location • Degradation • Specificity • Sensitivity and utility • CK-MB is gold standard

  15. Summary of serum markers after AMI

  16. Characteristics of serum markers • Early Appearance: CK-MB, Troponin & Myoglobin • High specificity: CK-MB, TrI, TrT • Wide diagnostic window: Troponin, LDH, Myosin L.C. • Predicts repurfusion: Myoglobin, CK-MB • Indicator reinfarction: CK-MB AFTER 48 hours of AMI NOT MUCH SIGNIFICANCE ADAPT THE NATURE AND ENJOY THE HEALTHY LIFE

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