KHAIRUL AMRAN HS221/5 MEDICAL LAB TECH UITM THE CURRENT CARDIAC MARKERS CHARACTERISTICS, COMPARISON BETWEEN MORMAL

LEVEL WITH AMI AND THEIR CLINICAL UTILITIES.

Enzymes/markers and isoenzymes Sources Physiologic Function Comparison of level in normal and AMI / Diagnostic window Total CK Normal : Male : 38-174U/L Female : 26-140U/L In AMI: Rise : 6-8hr Peak : 24-36hr Normal : 3-4days CK-MB (isoenzyme) Normal CK-MB mass:< 10 g/L Electrophoresis : (<4%-6%) In AMI: Rise : 4-6hr Peak : 12-24hr Normal : >48hr Specificity/sensitivity Clinical Utility

Creatinine Kinase 1. Total CK 2. CK-MB 3. CK-BB 4. CK-MM

Found is skeletal muscle, cardiac muscle, brain and other tissue. CK is composed of two subunits, CK-M (muscle type) and CK-B (brain Rephosphorylation of type), which ADP, forming ATP in are combined muscle contraction into three distinct isoenzymes: CK-MM (1), CK-MB (2), and CK-BB(3). These isoenzymes can be separated and measured by electrophoresis.

Total CK Specificity is low, the analysis of CK-MB isoenzymes is the most valuable tool for diagnosing AMI. CK-MB (CK-2) Specificity is higher than total CK,or other isoenzyme (CK-BB /1). It because the CK-MB is appear in cardiac muscle in high percentage than appears in skeletal muscle and brain. So, in case of high value of CK-MB, damage to heart tissue is highly suspected because brain and skeletal tissue contain insignificant trace amount of CKMB. Eventhough the CK-MM contain high percentage of CK from heart, it also contain a higher percentage of CK from the skeletal muscle. So the high value of CKMM are not specific for myocardium damage. The values must be interpreted with caution, since there is overlap between cardiac and skeletal muscle tissue source of the isoenzymes.

Total CK Limited since it increased in various disease. CK isoenzyme is more useful.

Ratio of CK isoenzymes in serum : CK-BB : 0 trace CK-MB : <6% CK-MM : >94%

CK-MB (isoenzyme) Mass assay of CK-MB isoenzyme is the current gold standard for early diagnosis of AMI.

KHAIRUL AMRAN HS221/5 MEDICAL LAB TECH UITM

Percentage of CK isoenzymes in different tissue (sources) : CK-BB Brain : 100% Skeletal : 0% Cardiac : 0% CK-MB isoform/ isoenzymes : 1. CK-MB1. 2. CK-MB 2 CK-MB Brain : 0% Skeletal : 0-4% Cardiac : 2040% CK-MM Brain : 0% Skeletal : 96100% Cardiac : 6080% Nonspecific early marker to rule in/out AMI. Advantage from other: turn positive sooner than troponin (very early). When it positive, it maybe come from heart or other skeletal muscle, so it is not specific for heart damage. Follow up with other markers should be done.

CK-MB isoforms and ratio Normal : 0.5-1.0 U/L (both) <1.5 isoform ratio In AMI: Rise : 2-6hr Peak : 6-12hr Normal : 24-36hr

CK-MB isoforms The CK isoform assay developed improve the sensitivity of biochemical diagnosis of AMI. CKMB isoforms are more specific to cardiac tissue injury than CK-MM, since CK-MB is more specific to cardiac tissue. Increased ratio is highly sensitive and specific indicator of early stage AMI.

CK-MB isoform (ratio) Early marker of AMI, more specific than myoglobin.

After AMI, CK-MB2 rapidly rises above CK-MB1, producing an increased ratio.

The serum level for both are approximately equal, producing an CK-MB2 : CKMB1 ratio of about 1.0.

Normal: <100g/L Myoglobin - oxygenbinding protein pigment Found in skeletal muscle, primarily cardiac muscle and red-skeletal muscle. storage and transport of oxygen. When muscle damaged, it released to blood stream. In AMI: Rise : 2-3hr Peak : 6-9hr Normal : 24-36hr

Use in conjunction with troponin to diagnose heart attack. Most useful when combined with electrocardiogram (ECG)

KHAIRUL AMRAN HS221/5 MEDICAL LAB TECH UITM

Both cTnI and cTnT are highly specific for myocardial injury because they only rises in bloodstream when cardiac injury (if not, they only present as a little amount in blood). cTnT 84% sensitivity for myocardial infarction 8 hours after onset of symptoms and 81% specificity. Low specificity for unstable angina -22%. cTnI 90% sensitivity for myocardial infarction 8 hours after onset of symptoms and 95% specificity. Low specificity for unstable angina36%. cTnI is more than specific than cTnT because it only measured cardiac troponin while cTnT involve other tissue.

cTnI Normal : <3.1 g/L Rise : 4-8hr Peak : 14-18hr Normal : 5-9days Found in skeletal and heart muscle fibers. Troponin Troponin T (TnT) Troponin I (TnI) Troponin C (TnC) TnT and TnI only found in heart. These cardiac-specific troponin called cTnT and cTnI. Certain amount of cTnT also comes from regenerating skeletal muscle. Troponin (T,I,C) are responsible to regulate muscular contraction; bound to tropomyosin and actin. cTnT Normal : 0.0-0.1 g/L

To diagnose myocardial injury. Potential usage in angina patients. Potential to diagnose AMI in patient who also have skeletal muscle abnormality.

In AMI: Rise : 4-8hr Peak : 14-18hr Normal : >14days

Test results are usually considered normal if the results are:

Troponin I : less than 10 g/L Troponin T : 00.1 g/L

KHAIRUL AMRAN HS221/5 MEDICAL LAB TECH UITM

Many body tissues, especially the heart, liver, kidney, skeletal muscle, brain, blood cells, and lungs. The sources of LDH are according to their isoenzymes : Lactate Dehydrogenase (LDH) LDH-1 (HHHH) : Heart,red cells, kidney LDH-2 (HHHM) : Same as in LDH1, except LDH 2 is lesser in kidney. LDH-3 (HHMM) Lungs, other tisue LDH-4 (HMMM) WBC, lymph node, muscle, liver (less) LDH-5 (MMMM) Liver, skeletal muscle Cellular respiration, the conversion of glucose (sugar) from food is converted to energy.

Because the LDH can be found in many tissue, it is not specific to cardiac tissue damage. From total LDH, LDH 2 make up the greatest percentage. LDH is most often The LDH-1 isoenzyme level is more measured to check for sensitive and specific than the tissue damage. But tne total LDH. Normally, the level of total LDH cannot LDH-2 is higher than LDH-1. If LDH- provide an information 1 level higher than LDH-2, it is the location of the called as "flipped LDH pattern" and damage/tissue injury. strongly indicative of a heart attack Thus the LDH occured. The flipped LDH usually isoenzymes should be appears within 12-24 hours after done to pinpoint the attack. In about 80% of cases, exact location of the flipped LDH is present within 48 damage. hours of the incident. A normal LDH-1/LDH-2 ratio is considered reliable evidence that a heart attack is not occurred.

LDH Normal : 105 250 IU/L In AMI: Rise : 6-12hr Peak : 24-48hr Duration : 6-8days This pattern is a useful tool for a delayed diagnosis of heart attack.

KHAIRUL AMRAN HS221/5 MEDICAL LAB TECH UITM