Cardiac markers.pptx

Cardiac markers

1. Cardiac markers

2. Introduction Acute myocardial infarction occur when there is sudden block in blood flow in one or more of the coronary arteries and this cuts off blood supply to a part of the heart muscle, causing necrosis Cause – atherosclerotic plaque rupture and thrombus formation Diagnostic criteria WHO guidelines, requires atleast 2 criterias : history of chest pain Evolutionary changes on the ECG Elevation of cardiac markers

3. Heart failure is defined as the pathological condition in which an abnormality of cardiac function is responsible for failure of the heart to pump blood at a rate necessary for the requirements of the metabolizing tissues

4. After myocardial infarction, a number of intracellular proteins are released from damaged cells. They have diagnostic Importance and are called cardiac markers They are laboratory test most useful in the detection of AMI or minor myocardial injury when individuals have non diagnostic ECG tracings

5. Protein markers includes Enzymes Creatine kinase (CK) Lactate dehydrogenase (LDH) Aspartate aminotransferase (AST) Non-enzymes Myoglobin (Mb) Cardiac troponin T and I ( cTnT and cTnI ) Differ in Location within myocyte Release after damage Clearance from serum

6. Creatine Kinase (CK) Catalyzes the formation of phosphocreatine from creatine and ATP Both cytosolic and mitochondrial isoenzymes have been identified. T he cytosolic form of the enzymes is dimer composed of two subunits (M and B) and thus has three isoenzymes CK-2 or CK-MB isoenzyme is specific for the heart.

7. Normal value (CK) – 10 to 100U/L CK-MB – upto 6U/L Increased activity Sharp but transient rise in total CK activity following MI. The degree of increase varies with the extent of tissue damage. CK is 1 st enzyme to appear in serum in higher concentration after MI and probably 1 st to retun to normal levels if there is no further coronary damage Also increase in some cases of coronary insufficiency without MI CK-MB starts to increase within 4 hrs after AMI and reaches maximum within 24 hrs. maximum rise may range from 10U to 40U depending on the severity of the infarct CK-MB is more specific and sensitive test for AMI than total CK

8. Lactate Dehydrogenase (LDH) LDH is reversibly catalyzes the oxidation of lactate to pyruvate Reference values Total LDH = 125 – 290U/L LDH 1 = 20 to 30% of LDH = 100U/L LDH 2 = 30 to 40% of LDH = 115U/L LDH 3 = 17 to 23% of LDH = 65U/L LDH 4 = 3 to 13% of LDH = 40U/L LDH 5 = 4 to 12% of LDH = 35U/L

9. Total LDH become elevated at 12 to 18 hrs after onset of symptoms and peak at 48 to 72 hrs and returns within normal level after 6 to 10 days LDH 1 rise within 10 to 12 hrs. Peak at 72 to 144 hrs and returns normal after 10 days LDH 1 /LDH 2 ratio becomes greater than 1 The combination of an elevated CK-MB and Flipped LDH ratio in a patient suspected of having a MI makes the diagnosis certain.

10. Serum Aspartate A minotransferase (AST) AST is found in practically every tissue of the body, including red blood cells. It is in particularly high concentration in cardiac muscle and liver, intermediate in skeletal muscle and kidney. Reference value Serum AST = 6 to 25U/L

11. AST begins to rise about 6 to 12 hrs after MI and usually reaches its maximum in about 24 to 48hrs and returns normal within 4 to 6 days The increase in activity is not as great as for CK, nor does it rises as early after the infarct. Less specific indication

12. Myoglobin (Mb) It is an oxygen binding protein of cardiac and skeletal muscle Increase in serum myoglobin occur after trauma to either skeletal or cardiac muscle, as in crush injuries or AMI The major advantage offered by myoglobin as a serum marker for myocardial injury is that it is released early from damaged cells

13. It rise as early as 1 hr after the occurrence of an AMI with peak activity in the range of 4 to 12 hrs This peak suggests that serum myoglobin reflects the early course of myocardial necrosis It is cleared rapidly and thus has a substantially reduced clinical sensitivity after 12 hrs The role of Mb in the detection of AMI is within the first 0 to 4 hrs, the time period in which CK-2 and cardiac troponin are still within their normal values Serum Mb has not used extensively for routine analysis of AMI because it is non specific, since it is rised in any form of muscle damage Even minor injury to skeletal muscle may result in an elevated concentration of serum Mb which may lead to the misdiagnosis of AMI

14. Cardiac troponin ( cTn ) Troponin is a complex of three protein subunits Troponin C Troponin I Troponin T Troponin subunits exist in number of isoforms . They are varies between cardiac muscle and slow and fast twitch skeletal muscle The heart isofrom of troponin C is identical to the slow twitch skeletal isoform and so not useful cardiac marker.

15. Cardiac specific: troponin T ( cTnT ) and troponinI ( cTnI ) isoforms have been identified Cardiac specific troponin forms are currently the most sensitive and specific cardiac markers of AMI available. The initial rise in cardiac troponins ( cTnI and cTnT ) after MI occurs at about the same time as CK and CK-MB, but the rise continues for longer than for most of the enzyme, possibly because of later release of insoluble troponin from the infarcted muscle.

16. In AMI serum cTnT and cTnI values become elevated at 4 to 8 hrs after onset of the symptoms. Thus the initial rise of both cTnT and cTnI are similar to those of CK-2 after AMI Secondly, cTnT and cTnI remain elevated upto 5 to 10 days. The long time interval of cardiac troponin increase means it can replace the LDH assay in the detection of late presenting AMI individuals Thirdly, the very low to undetectable, cardiac troponin values in serum from individuals without cardiac disease permits the use of cTnT and cTnI to offer better risk assessment than use of CK-2 Cardiac specificity of troponin T and I eliminates a false diagnosis of AMI in patients with increase CK-2 concentrations after skeletal muscle injuries Furthermore cTnT has been an excellent marker of myocardial injury in the presence of sepsis, drug induced toxicities, chronic dieseases , malignancies, haematological disorders and noncardiac surgery

17. C-Reactive Protein (CRP) Acute phase protein become elevated in inflammatory disease In practice measurements of proteins such as CRP are useful in monitoring of the progress of the inflammation or its response to treatment Levels of CRP in plasma usually rises dramatically after MI

18. Normal level 0.05mg/l to 0.20 mg/l The increase begins with 6 to 12 hrs of the infarction and the level may reach 200 times of normal Increased risk is associated with Aging Smoking Having symptomatic angina Having had previous AMIs

19. Homocysteine Amino acid formed during bio-synthetic pathway of cysteine from methione Causes of hyperhomocysteinaemia Mutation of cystathionine β - synthase Deficiency of : Vitamin B 6 Vitamin B 12 Folic acid

20. Normal value = <15µmol/l in plasma People with elevated homocysteine have an unusually high risk for coronary heart disease and arteriosclerosis It appears to damage cells lining blood vessels and to increase growth of vascular smooth muscle Mildly increased homocysteine causes dysfunction of the vascular endothelium