Clinical Chemistry of Myocardial Infarction

Question 0

Define diagnostic enzymology?

Answer 0

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

Question 1

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

Answer 1

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)

Question 2

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

Answer 2

pp. 9

Question 3

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

Answer 3

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

Question 4

What are the 3 enzymes increased after MI?

Answer 4

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

Question 5

Define Isoenzymes?

Answer 5

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

Question 6

What is the diagnostic value of Isoenzymes?

Answer 6

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.

Question 7

What enzyme catalyzes the following reaction?

creatine + ATP creatine-phosphate + ADP

Answer 7

creatine kinase

Question 8

T/F CK is a tetramer just like hemoglobin.

Answer 8

F. CK is a dimer.

Question 9

What are the subunits of CK?

Answer 9

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

Question 10

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

Answer 10

Composition Name Tissue origin

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

Question 11

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

Answer 11

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

NOTE: CK2 elevation is specific to myocyte necrosis.

Question 12

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

Answer 12

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

Question 13

What would be used to diagnose re-infraction?

Answer 13

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

Question 14

What reaction is catalyzed by lactate dehydrogenase (LDH)?

Answer 14

Lactate + NAD pyruvate +NADH

Question 15

T/F LDH is a tetramer just like hemoglobin.

Answer 15

T.

Question 16

What are the subunits of LDH?

Answer 16

• 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.

Question 17

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

Answer 17

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

Question 18

What does an increase in LDH5 indicate?

Answer 18

Liver congestion

SK mm dystrophy

Question 19

How is LDH used to diagnose MI?

Answer 19

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

Question 20

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

Answer 20

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

Question 21

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

Answer 21

Troponin

Question 22

What are the subunits of Troponin?

Answer 22

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

Question 23

Which type of troponins are specific to the heart?

Answer 23

cTn-T and cTn-I

Question 24

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

Answer 24

Due to alternative splicing: Tn-T1 Tn-T2

Question 25

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

Answer 25

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

Question 26

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

Answer 26

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

Question 27

Why are cardiac troponin levels sensitive markers for MI?

Answer 27

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).

Question 28

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

Answer 28

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

Question 29

What is used to detect small infractions?

Answer 29

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

Question 30

Why can't we use myoglobin to detect infractions?

Answer 30

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.

Question 31

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

Answer 31

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

Question 32

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

Answer 32

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

Question 33

What enzymes are used as therapeutic agents in MI?

Answer 33

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

Question 34

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

Answer 34

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