Cardio - Biochemical Markers

Front 1

What is cTnI?

Back 1

Highly sensitive and specific indicator of myocardial cell necrosis (leakage marker)

Front 2

What does Troponin I do? What is the homology to skeletal TnI?

Back 2

cTnI - inhibits cardiomyocyte contractions - prevents actin-myosin interaction until cTnC is bound by intracellular Ca++
40% is dissimilar so it is SPECIFIC to the heart

Front 3

What does Troponin T do? What is the homology to skeletal TnT?

Back 3

Binds the troponin-tropomyosin complex to the actin filament
distinct skeletal and cardiac forms

Front 4

What is the function of Troponin-C? Is it specific for the heart?

Back 4

Binds intracellular calcium
Non-specific - no practical value

Front 5

What are 4 things that can effect cTn levels?

Back 5

1. release from myocytes
2. leakage into general circulation
3. degradation by serum proteases
3. clearance by kidney, liver, RES

Front 6

Can cTn samples from different analyzers be compared? What is important when evaluating cTn on a specific analyzer?

Back 6

No - propietary information of different analyzers makes them vary as much as 100x
Need reference values for that particular analyzer for dogs or cats

Front 7

Why would background troponin be elevated (not from cardiac disease)?

Back 7

age, stenous exercise, non-cardiogenic disease

Front 8

Which is a more sensitive indicator of cardiac disease cTnI or cTnT? Why?

Back 8

cTnI, because they are elevated earlier and more readily than cTnT

Front 9

What is the difference in cTn levels in cats with HCM w/o CHF and cats w/ CHF?

Back 9

HCM cats have elevated cTn levels
MORE elevated w/ CHF

Front 10

What is the main problem w/ cTn levels as a biomarker?

Back 10

Not specific - could be primary heart failure OR a result of systemic disease

Front 11

What is lactate dehydrogenase? Is it specific for myocardial damage?

Back 11

enzyme that interconverts pyruvate and lactate in glycolysis
NO - poor specificity - no longer recommended

Front 12

What is myoglobin? Is it a useful biomarker for veterinary species?

Back 12

Heme protein associated w/ striated muscle
No - used in human medicine for MI, low specificity and half life make it less useful for veterinary species

Front 13

What does CK-MB do? Why is it not a useful biomaker for veterinary species?

Back 13

Catalyst for transfer of Ph from ATP to creatine to make creatine phosphate
Rapid clearance, lack of species-specific assays make it less useful for veterinary species

Front 14

Where is ANP produced?

Back 14

atria

Front 15

Describe the synthesis of ANP.

Back 15

1. pre-proANP
2. cleavage to pro-ANP - stored in atrial myocyte granules
3. cleaved to inactive NT-proANP and active C-terminal ANP

Front 16

True or False. Canine ANP is very different from Human ANP.

Back 16

False. they are very similar in structure

Front 17

True or False. All BNPs are the same in all species and can be analyzed using the same machines.

Back 17

False. There is variability in length, structure, and action of BNP. Species specific analyzers are needed.

Front 18

Where is BNP produced normally and pathologically?

Back 18

Normal - atria w/ little ventricle production
Volume/Pressure overload - Ventricular myocytes become the major source of BNP

Front 19

Which is a better biomarker BNP or NT-proBNP?

Back 19

NT-proBNP
1. higher serum concentrations
2. longer half-life

Front 20

What is ANP a marker for and why?

Back 20

Acute atrial distention.
Release of ANP is proportional to degree of atrial stretch or increased HR

Front 21

What stimulates ANP release?

Back 21

atrial stretch and dilation

Front 22

What is the effect of ANP?

Back 22

Overall works to reduce volume by
natriuresis, diuresis, balanced vasodilation, counteract RAAS and SNS, inhibits vasopressin release, modulates cardiomyocyte hypertrophy and fibrosis

Front 23

Where is BNP production controlled? What stimulates its release?

Back 23

At level of gene expression - transcription
Increased in response to ventricular dysfunction and hypertrophy - not as reliant on hemodynamic state

Front 24

Are the enzymes for BNP and ANP assays species specific?

Back 24

ANP - no, they are universal
BNP - yes they are highly species specific

Front 25

What disease states are associated with increased NP levels?

Back 25

Volume overload states - CHF, ventricular hypertrophy, decreased renal clearance, tachycardia, hypoxia

Front 26

What is ANP an indicator for? What can it tell you?

Back 26

acute congestion
Can be used to assess disease severity in chronic valvular disease

Front 27

What is NT-proBNP used for?

Back 27

detection of cardiomyopathy, correlated with degree of LV dysfunction, increasing heart size and worsening CHF class

Front 28

What is the primary endothelin isoform secreted by the endothelial cells and cardiomyocytes?

Back 28

ET-1

Front 29

Describe the synthesis of ETs.

Back 29

1. pre-proET cleaved by endopeptidases
2. Forms inactive pro-ET = big ET
3. Big ET converted to active ET by endothelin-converting enzyme

Front 30

What is the activity of ET-1?

Back 30

1. vasoconstriction
2. mediation of adrenergic and RAAS activation - maintain vascular tone and BP

Front 31

At what level is ET regulated? What stimulates release?

Back 31

Gene expression
Stimulated by pulsatile vessel stretch, low shear stress, hypoxia, ATII, Epi, cytokines and growth factor

Front 32

How quickly is ET-1 released after stimulation?

Back 32

w/in minutes of activation

Front 33

What has a higher concentration of ET-1 plasma or tissue? Why?

Back 33

Tissue, short half-life in plasma

Front 34

What form of ET-1 is useful in plasma? Why?

Back 34

Big ET-1, because it is cleared more gradually

Front 35

In what disease states is ET-1 elevated?

Back 35

CHF and pulmonary hypertension

Front 36

Where is TNF-a produced?

Back 36

Produced in activated macrophages and failing myocardium

Front 37

When is TNF-a increased? What is it an indicator of?

Back 37

Chronic CHF, indicates disease progression

Front 38

What is NO? How does it change?

Back 38

antagonist of ET and ATII (vasodilator)
impaired endothelial release and enhanced myocardial release in CHF - causes endothelial dysfunction (impaired vasodilation) reduced contractile function, and cardiomyocyte loss

Front 39

What is adrenomedullin? Under what conditions is it increase?

Back 39

Vasodilatory, natriuretic peptide
Increased in congestive states and pulmonary hypertension