CARDIAC ENZYMES AND PROTEINS الفريق الطبي األكاديمي. Done By :- Obadah Abubaker & Yousef Qandeel

Size: px

Start display at page:

Download "CARDIAC ENZYMES AND PROTEINS الفريق الطبي األكاديمي. Done By :- Obadah Abubaker & Yousef Qandeel"

Giles Berry
5 years ago
Views:

1 CARDIAC ENZYMES AND PROTEINS الفريق الطبي األكاديمي Done By :- Obadah Abubaker & Yousef Qandeel لكية الطب البرشي البلقاء التطبيقية / املركز /

Cardiac enzymes and cardiac proteins In this lecture, we are going to talk about different types of cardiac biomarkers and how these biomarkers are used for diagnosis and.

2 Cardiac enzymes and cardiac proteins In this lecture, we are going to talk about different types of cardiac biomarkers and how these biomarkers are used for diagnosis and. ف يال طالعة prognosis of myocardial infarction (0-4:40min) Sometimes myocardial infarction cannot be detected by ECG so it is important to do enzymatic test in order to confirm the diagnoses or to follow up the diagnosis of myocardial infarction. It is very important that the biomarker must be sensitive and specific. Sensitive: the biomarker must be found in large amount in order to be measured and to avoid false positives or false negatives of that biomarker. Specific: it is found in a specific tissue and not found in other tissues. Page 1

3 So these two parameters (sensitive and specific) are very important for a biomarker to be used. It is very important to take different samples at different times to follow up the myocardial infarction, the time course of that biomarker if it is increased or decreased and that will tell you about the condition of infarction. ببساطة بقلك مهم جدا نوخذ عينات متعددة بأوقات متتابعة بحيث نالحظ ونتابع حالة ال.biomarker من خالل تركيز ال myocardial infarction (4:40-5:54min) The ideal marker for myocardial infarction must satisfy in addition to specificity and sensitivity it must help in early diagnosis (that mean you have to look for some biomarkers that will appear in the blood at the onset of the infarction not after one or two days because in that case it will be missed so the marker must appear in the circulation as soon as the infarction happened. Page 2

4 The biomarker is used for prognosis to follow up the infarction and it also must be selected in order to test if re-infarction is happened or not. (5:54-9:50min) The most two biomarkers that are used nowadays and if you go to hospitals and see those patients who are suspected of myocardial infarction or who have myocardial infarction blood tests are taken to assay or to determine two important things : troponin and CK, sometimes myoglobin is determined and we will tell you why. الفقرة السابقة بس بتقلك عن اهم ال biomarkers اللي لو راح حدى عالمستشفى وكان مشكوك او معه myocardial infarction رح يفحصوا دمه بحيث يشوفوا تراكيز ال cardiac biomarkers واهم شيئين همه ال troponin and CK ولقدام سيتم التفصيل اما هذه فكرة عامة عن الموضوع. So we have two important things which are the CK and it is isoenzyme and the second thing is troponin. Page 3

5 CK: creatine kinase that will phosphorylate creatine to creatine phosphate. Troponin: it is a protein found in cardiac muscle as well as skeletal muscle it is associated with actin and myosin in the muscle and there we are are 3 types of troponin (troponin I, troponin T, troponin C), interested here for myocardial infarction in troponin I. الزبدة انه النوع اللي بهمنا من ال troponin بموضوع ال myocardial infarction هو ال. troponin I CK-MB: is an isoenzyme of the CK and we will explain this in moments. Myoglobin: it is a protein which is found not only in cardiac muscle but in all types of muscles and because of this myoglobin is not specific for cardiac muscle but the advantage of myoglobin : it appears early after the onset of the infarction. - CK is not much specific as troponin but it helps - The CK-MB is more specific than the total CK as you will see Page 4

6 (10:05-15:15min) Page 5

7 Creatine kinase is an enzyme that is found in muscles including cardiac muscle, it is a dimer (it is composed of 2 subunit one subunit is called M and the second subunit is called B) because it is composed of 2 subunits there must be 3 isoenzymes (three forms of creatine kinase enzyme) for this enzyme : One form is composed of two B subunits (BB),one form is composed of two M subunits (MM) and one form is a heterodimer which is composed of one M subunit and one B subunit(mb),, and what concerns us is MB, because the MB isoenzyme is specific for cardiac muscle (found mainly in cardiac muscle). BB mostly in brain, MM mostly in muscles other than cardiac muscles. النوع اللي بهمنا أكثر شيء في ال myocardial infarction هو ال CK-MB So if you want to diagnose myocardial infarction you must ask to analyze blood sample from the patient and determine the total CK, then determine how much of this total is CK-MB, then determine the RI which means how much you have of CK-MB out of the total CK multiply by hundred, if the ratio that percentage of the RI is less than 3 then there is no infarction, if it is above 3 then there is an infarction. MB is the isoenzyme that is found mainly in cardiac tissue, so after ischemia, there is no more oxygen for the heart demand and anaerobic glycolysis will take place, pyruvate will convert to lactate after that we will have acidosis, lysozymes will be activated and that will lead to necrosis of the cardiac tissue, after this process CK total will leak to the blood circulation including the CK- MB, so you take blood sample and analyze for total CK and for the CK-MB and compare it to the normal physiological values. الفقرة السابقة مشروحة في هذه الفترة لمن لم تتضح له الفكرة كما يجب (14:04-15:05min) Page 6

8 (15:18-19:18min) Now we want to see the time course of this enzyme (CK) and its isoenzyme (CK- MB) with the onset of the infarction, now the y axis represent the values of each of the parameter that we are going to talk about, and the x axis represent time, how many hours from the onset of infarction, now we will concentrate on two curves (Total CK curve, CK-MB curve) As you see,total CK start to rise 4 hours to 8 hours from the onset of the infarction as well as the CK-MB, after 20 to24 hours both curves will peak, in 48 to 72 hours it will go back to the normal value, if any re infarction happened after this time, that will be in 4 hours and in another 24 hours it will reach the peak, it is not much specific as you will see but relatively specific specially CK-MB, from these values, knowing the total CK and CK-MB you could calculate RI (ratio) RI : how much CK-MB is found per total CK multiply by 100 If RI > (3-5) -positive or infarction- Page 7

9 Troponin I (19:30-24:00) Troponin is a protein that is associated with actin and myosin and as we said it has 3 types of troponin (T & I & C) it was found that troponin I is the most specific type that will be detected in MI Troponin I is the subunit of the troponin complex that binds actin and inhibits actomyosin ATPase activity in the absence of calcium Three isoforms of troponin I have been described, one cardiac (ctni), and two skeletal muscle (slow twitch, stni, and fast twitch, ftni). Each of the three TnI isoforms is encoded by different genes located on different chromosomes. If we look at the figure above we can see that troponin I like CK- MB can be detected after 4-8 hours after MI symptoms onset and it will reach its peak after hours which will stay for 5-7 days until it go back to normal Now unlike CK-MB in a healthy people we can t detect any ctni so once we detect it that indicates that there is an infarction. Page 8

10 ctni has been shown to be a very sensitive and specific marker for acute MI. But in case of reinfarction after 24 hours CK-MB level will rise CK-MB important in case of reinfarction (because ctni level stays elevated for long time so we can t detect reinfarction depending on it) ctni very sensitive and important marker to confirm the diagnosis of MI Nowadays a test is done routinely for people who are suspected for MI by taking a blood sample, add it on a strip and detecting ctni if it s exist or not (appears as fragments on the strip) and it s done in 1 minute, but it s important to determine the absolute value of the ctni because it will tell you the size of the infarction. Due to long duration of increase of ctni following onset of chest pain, it could replace LD-2 isoenzyme for the detection of late presenting AMI patients. Additionally, recent studies demonstrate that ctni is more sensitive than the LD1/LD2 ratio. ctni has proved to be a diagnostic and prognostic marker for myocardial damage with high diagnostic sensitivity and specificity. So it s the most important biomarker for MI Myoglobin (24:00-24:35) One of earliest markers, which is very sensitive but, lacks specificity. Its diagnostic value is primarily due to its early appearance. Page 9

Case (24:35-29:15) This table shows multiple tests for a patient to know if he has MI or not and we usually make many tests to follow up with the situation and know the size of the infarction.

11 Case (24:35-29:15) This table shows multiple tests for a patient to know if he has MI or not and we usually make many tests to follow up with the situation and know the size of the infarction. After few days from the treatment we take blood sample to know if the treatment worked or not ( if the biomarkers values stays high that mean that there was no response to the treatment) Old biomarkers (29:15-34:00) These biomarkers were used in about 20 years ago and they are not used anymore Aspartate aminotransferase : which is a transaminase enzyme it s found in many tissues not only the heart but it s level increase in MI Lactate dehydrogenase : this enzyme as we know will be very active in case of ischemia which will convert pyruvate to lactate and increase acidity LDH is composed of 2 types of subunits (4 subunits in total) LDH as we ll see in the next table has 5 isoenzymes and the important ones are LDH1 and LDH2 Nowadays we use more specific biomarkers than these ones Page 10

12 CARDIAC ENZYMES AND PROTEINS Lactate dehydrogenaserises in 12 to 24 hours following MI, Peaks in 2 to 3 days Gradually disappearing in 5 to 14 days Tissue distribution of LDH Page 11

13 This is the electrophoresis of LDH enzyme. Normally LD1 is less than LD2 but in case of MI LD1 level becomes more than LD2 so the ratio between LD1 and LD2 will help to diagnose and to see if there is reinfarction or not Page 12

Biomarkers of myocardial infarction. Dr. Mamoun Ahram Cardiovascular system, 2013

Biomarkers of myocardial infarction Dr. Mamoun Ahram Cardiovascular system, 2013 References This lecture Hand-outs Acute Myocardial Infarction A rapid development of myocardial necrosis caused by prolonged