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CV Week 2 > Clinical Chemistry of Myocardial Infarction > Flashcards

Clinical Chemistry of Myocardial Infarction Flashcards

0
Q

Define diagnostic enzymology?

A

measuring serum/plasma enzyme levels that are tissue specific in order to diagnose a disease.

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1
Q

What kind of proteins are present in the blood? How does this change during disease?

A

1) Proteins at high concentrations, specific to and with a functional role in blood
2) Proteins at low concentrations and with no role in blood (i.e. released to blood as normal cell turnover)
* In disease increased release of intracellular ptn into the blood (ex: heart enzymes in case of MI)

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2
Q

Study table and be able to relate what enzyme is used to diagnose what disease

A

pp. 9

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3
Q

What are the 4 things to consider when using serum enzyme pattern to diagnose MI?

A

1) Tissue specificity
2) Time of appearance
3) Time of disappearance
4) Detection level
5) Availability of specific tests

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4
Q

What are the 3 enzymes increased after MI?

A

1) creatine kinase (CK)
2) lactate dehydrogenase (LDH)
3) alpha-hydorxybutyric acid dehydrogenase (HBDH)

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5
Q

Define Isoenzymes?

A

enzymes that catalyze the same reaction but differ slightly in aa composition, since there are d/f genes coding for them.

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6
Q

What is the diagnostic value of Isoenzymes?

A

D/f organs are more likely to contain specific proportions of isoenzymes. This can be used to identify the specific site of tissue damage. D/f aa in the isoenzymes causes difference in net charge of these subunits and enzyme complex-electrophoretic separation.

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7
Q

What enzyme catalyzes the following reaction?

creatine + ATP creatine-phosphate + ADP

A

creatine kinase

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8
Q

T/F CK is a tetramer just like hemoglobin.

A

F. CK is a dimer.

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9
Q

What are the subunits of CK?

A

1) M (short for muscle)
2) B (short for brain)
NOTE: It was just that they were first discovered in the muscle or brain.

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10
Q

Describe the d/f ways that the subunits of CK can combine.

A

Composition Name Tissue origin

1) BB CK1 brain (bowl)
2) MB CK2 myocardium
3) MM CK3 SK mm and myocardium

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11
Q

What are the CK compositions of SK mm and Cardiac mm?

A

SK mm: CK3 + 0-2% CK2
Cardiac mm: 85% CK3 +15% CK2

NOTE: CK2 elevation is specific to myocyte necrosis.

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12
Q

Discuss the rise of CK2, CK3 and tot. LDH after MI.

A

CK2 (MB) isozyme increase to max. within 1 day of MI, CK3 (MM) lags behind by about 1 day, tot. LDH increases more slowly.

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13
Q

What would be used to diagnose re-infraction?

A

CK2 (MB) b/c it begins to fall after a day, so subsequent elevations are indicative of another event.

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14
Q

What reaction is catalyzed by lactate dehydrogenase (LDH)?

A

Lactate + NAD pyruvate +NADH

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15
Q

T/F LDH is a tetramer just like hemoglobin.

A

T.

16
Q

What are the subunits of LDH?

A
  • 2 kinds of subunits
    1) H (stands for heart)
    2) M (stands for muscle)

NOTE: the 2 subunits can be combined in 5 d/f ways.

17
Q

What are the different types of LDH? Names? Tissue origin?

A

Composition Name Tissue origin
HHHH LDH1 myocardium (more LDH1) & RBC (more LDH2)
MHHH LDH2 myocardium and RBC
MMHH LDH3 brain and kidney
MMMH LDH4 has no specific location
MMMM LDH5 liver and SK mm

18
Q

What does an increase in LDH5 indicate?

A

Liver congestion

SK mm dystrophy

19
Q

How is LDH used to diagnose MI?

A

LDH1/2 (the ration of LDH 1 to LDH 2) is specific of MI.

20
Q

When does CK2 (CK-MB) appear, and peak after MI?

A

Appears 4-8hrs after chest pain and peaks at 24hrs.

21
Q

What are the cardiac ptns used in the diagnosis of MI?

A

Troponin

22
Q

What are the subunits of Troponin?

A

Tn-C (Ca binding)-bind Ca->Tn-I is no longer bound to actin
Tn-I (Inhibitory)-bind to actin covering the myosin binding site
Tn-T (Tropomyosin binding)-anchors complex to tropomyosin

23
Q

Which type of troponins are specific to the heart?

A

cTn-T and cTn-I

24
Q

What are the two isoforms of cardiac Tn-T? What causes Tn-T to have 2 types of isoforms?

A

Due to alternative splicing:
Tn-T1
Tn-T2

25
Q

How does the serum levels of Tn-T2 change after MI?

A

Increase with 4hr of acute MI, and remain high for 14days.

NOTE: the appearance of Tn-T2 in serum is 100% sensitive and 95% specific for detection of MI

26
Q

How is Tn-I used to predict adverse outcomes of angina pectoris or MI?

A

elevated serum levels of the cardiac isoform 4hrs after MI and stays up for 7-10days in 68% of patients.

27
Q

Why are cardiac troponin levels sensitive markers for MI?

A

Normally cardiac troponin levels are so low that they can’t be detected by most blood tests (Tn-I<10ug/L, Tn-T=0-0.1ug/L).

28
Q

T/F Re-infraction can be detected by troponin levels at least for 2 weeks.

A

F. Can’t be detected at least for 2 weeks because it takes up to 14 days for troponin to come back to normal after MI

29
Q

What is used to detect small infractions?

A 
Troponin level
ECG         5-10g cell death
CK           0.2g
CK-MB    0.02
Tn-T        0.003g
30
Q

Why can’t we use myoglobin to detect infractions?

A

Myoglobin is not specific to cardiac mm also found in other types of mm. But it can be used to diagnose extent of mm damage.

31
Q

Draw a table that shows the enzymes used to diagnose MI (when they appear, peak, disappear, use in re-infarction, specificity and sensitivity).

A

After MI: Detection Peak Back to Use in Specificity Sensitivity
normal re-infarction
CK Tot. 8-24hrs 24-36hrs 48-72hrs after 3-4 days low high
CK2(MB) 4-10hrs 24hrs 48hrs after 48hrs high high
LDH1/2 12hrs 24hrs 14days after 2wks low low
cTn-T2 4hrs 14days after 2wks high high
cTn-I 4hrs 7days after 1wk high high

32
Q

What is plasmin? What is the inactive form of plasmin?

A

Plasmin is a protein that is circulating in blood and can dissolve blood clot. The inactive form is plasminogen

33
Q

What enzymes are used as therapeutic agents in MI?

A

Tissue plasminogen activator (t-PA): expressed in E. coli as a recombinant ptn.
Streptokinase: from streptococcus

34
Q

What is the drawback to enzymes used as therapeutic agents in MI?

A

They are removed from circulation very rapidly so high doses must be used.

CV Week 2 (6 decks)

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