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A character that is objectively measured and evaluated as an indicator of normal biological processes, pathological processes, or pharmacological responses to a therapeutic intervention.
biomarker
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What makes it hard to interpret biomarkers?
there is overlap between normal and abnormal, making it difficult to make a set "cut off" point (extreme numbers are easy to interpret but numbers close to the reference interval can lead to many false negatives and positives)
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How can a discrimination threshold using cardiac biomarkers be generated?
2 populations (diseased and healthy animals) are studied, and the parameter intercept b/w the two is sed as the discrimination limit
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What does the diagnostic cut off mean?
the overlap point b/w normal and diseased populations
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What are leakage markers, ad what is the most useful one?
leak out of diseases myocardium- Troponin I
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What is the main functional biomarker?
BNP (+/- ANP)
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What are the potential diagnostic benefits of using cardiac biomarkers? (10)
early detection of abnormalities, easy to use, earlier management, avoidance of unnecessary treatments, diagnosis of diseases usually difficult to recognize, equivocal results of other tests, monitoring effects of cardiotoxic drugs, prognostic information, anesthetic risk assessment, screening tool at reasonable cost
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List 3 sources of cardiac troponin I.
cell membrane, cytosolically dissolved, structurally bound (majority- this is why release is biphasic)
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What is the major source of circulating troponin in the body?
myocardium
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What disease processes can damage the myocardium and cause leakage of troponinI?
primary myocardial disease, drugs, neoplasms, inflammation, infections, wall stress (pulmonary embolism), hypoxia/ischemia reperfusion, cytokines, trauma, neurohormones, toxins/metabolites
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Troponin biomarks are _________ specific but not _________ specific.
organ; disease
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TnI has a _______ half life; therefore,...
short; if it is circulating, there must be ongoing damage.
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Why is release of TnI biphasic in nature?
structurally bound, so mild release early after injury then a larger release later after degradation kicks in
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What is the diagnostic cut off for cardiac TnI?
0.20 ng/mL (serum)
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What does the I in cardiac troponin I stand for?
cTnI= inhibitory; regulates muscle contraction
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What does the T in cardiac troponin T stand for?
cTnT= structural protein that binds troponin-tropomyosin complex to the actin filament
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What are specific clinical indications for analyzing circulating cTnI? (5)
myocardial infarction/ ischemic heart disease, suspect myocarditis, arrhythmia of unknown origin, chemotherapy with doxorubicin, ionophore toxicity
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Is cTnI a good screening tool for dogs with DCM?
NO- many dogs with late stage CHF have no elevation in troponin
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Can cTnI be used as a screening tool for CHF clinical and symptomatic disease?
No-too much overlap b/c asymptomatic and clinical disease
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cTnI is increased in many dogs and cats with cardiac disease indicating ongoing... (3)
myocardial ischemia, necrosis, or acute degeneration.
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How can you use cTnI as a biomarker of heart disease?
serial analyses for prognostication (not a good screening test, cannot replace echo)
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What are the effects of natriuretic peptides? (5)
natriuresis, diuresis, balanced vasodilation, inhibition of neurohormonal activation, prevention of myocardial fibrosis
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How is ANP synthesized and stored?
ANP is synthesized in the atrial muscle and stored in granules (ready to go)--> acute or chronic atrial stretch, sudden changes in HR--> release of ANP [acute changes can be monitored using ANP analysis]
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What is the major source of circulating natriuretic peptides in the body?
myocardium
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What makes ANP diagnostically inferior to BNP?
such a short half-life...may be gone before you even get your sample to the lab
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Why do we used NTproBNP as a diagnostic indicator instead of BNP?
BNP is produced in the myocardium in atrium in normal animals, in ventricle in pathology; made with NTproBNP then cleaved to BNP; BNP is unstable; NTproBNP is much more stable, both are released in equimolar ratios and is therefore an accurate marker of BNP release
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How can you get a false elevation of NTproBNP (absence of cardiac disease)?
renal insufficiency
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What are the 2 major triggers for BNP release?
pathologic hypertrophy and wall stress
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Why is NTproBNP better for detecting chronic changes?
BNP not stored in granules (unlike ANP), so it takes hours to say to see an elevation
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What is NTproBNP a diagnostic tool for? (4)
screening for HCM, staging of heart failure, to determine is respiratory distress is due to lung or heart, justification for echo
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BNP has a high ________; therefore, ...
NPV; if it comes back negative, you are almost certain the cat doesn't have HCM; if it comes back positive, you must proceed to echo to rule it in.
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What is the diagnostic screening cut off for NTproBNP for feline HCM?
100 pmol/L
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If NTproBNPa good screening test for DCM in dogs?
No- too many false negative and positives (use 24hr EKG and echo to diagnose)
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How does the IDEXX felineNTproBNP snap test work?
valve over 200pmol/L comes up positive [negative--> rule out CHF; positive--> move forward with echo]
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