Enzymes, Cardiac Markers, Hepatic Tests

• clinically useful enzymes: tissue sources

• preanalytical variables affecting enzyme activities

• isoenzymes

• myocardial markers and diagnosis of myocardial injury

• hepatic function, choice of tests, interpretation of results

Clinically Useful Enzymes

• LDH: heart, liver, muscle, RBC, neural tissue, leukocytes, tumor cells

• AST: liver, heart, muscle

• ALT: liver

• CK: muscle, heart, neural tissue

• ALP: liver, bone, intestine, placenta

• GGT: liver, pancreas, kidney

Preanalytical Variables

• IN THE PATIENT- age, sex, food, exercise, trauma

• IN THE SAMPLE

• Hemolysis -inc in Total LDH & LDH 1/II

• EDTA: inhibition of ALP

CK Isoenzymes

• Dimer: M & B monomers

• CK- 1: BB; neural & mesenchymal tissue

• CK- 2: MB; muscle (<1%); heart (<40%)

• CK- 3: MM; heart (60 - 80%) muscle (>99%)

CK Isoforms

• CKMM-3 & CKMB-2 (tissue isoforms of CK) after tissue release are converted by carboxypeptidases in blood to:

- CKMM-2 & CKMM-1, and- CKMB-1

Detection of Myocardial Injury Major Issues

• THE Acute Coronary Syndrome - stable angina- unstable angina- acute myocardial infarction

• Choice of biochemical cardiac marker

Acute Coronary Syndrome: Risk Stratification

• Chest pain

• ECG – ST segment changes

• Troponins

• Other risk factors: CRP, fibrinogen, BNP

Myocardial Markers

• Troponin-I or T

• Myoglobin

• CK- MB

• CK- MB Relative Index

• CK Isoforms

Myocardial Markers

Marker Time to (hr) Length of CK-MB 3-12 48- 72 hr Tn-I 3-12 5 - 10d Tn-T 3-12 5 - 14d Myoglobin 1-4 18 - 24hr CK-isoforms 1-4 1 - 4d

Myocardial Markers:References

• Donnelly, R, Millar-Craig, MW: Cardiac troponins: IT upgrade for the heart. Lancet 1998;351:537-9

• Apple,FS & Wu,A: Myocardial infarction redefined: role of cardiac troponin testing. Clin Chem 2001; 47:377-8

• Sabatine, MS et al: Multimarker approach to risk stratification in non-ST elevation ACS. Circulation 2002; 105:1760-3