CARDIAC ENZYMES

AND PROTEINS الفريق الطبي األكاديمي

لكــية الطب البرشي

البلقاء التطبيقية / املركز

6102/6166أ حياها و من

Done By :- Obadah Abubaker & Yousef Qandeel

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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

prognosis of myocardial infarction ف يال طالعة .

(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.

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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 .

ال حالة ببساطة بقلك مهم جدا نوخذ عينات متعددة بأوقات متتابعة بحيث نالحظ ونتابع

myocardial infarction من خالل تركيز الbiomarker .

(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.

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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 .

اللي لو راح حدى عالمستشفى وكان biomarkersالفقرة السابقة بس بتقلك عن اهم ال

ال رح يفحصوا دمه بحيث يشوفوا تراكيز myocardial infarctionمعه اومشكوك

cardiac biomarkers واهم شيئين همه الtroponin 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.

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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

are 3 types of troponin (troponin I, troponin T, troponin C) , we are

interested here for myocardial infarction in troponin I .

هو myocardial infarctionبموضوع ال troponinالنوع اللي بهمنا من ال الزبدة انه

troponin I .ال

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

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(10:05-15:15min)

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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 .

CK-MBهو ال myocardial infarctionالنوع اللي بهمنا أكثر شيء في ال

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 .

(15:05min-14:04) الفقرة السابقة مشروحة في هذه الفترة لمن لم تتضح له الفكرة كما يجب

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(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-

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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 14-36 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.

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• 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.

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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

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• 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

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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