Laboratory Investigation of Cardiac Disease Flashcards
- List 5 biochemical tests used in clinical medicine?
- Screening ( subclinical conditions that are not recognisable in clinical findings)
- Diagnosis (abnormal vs normal)
- Monitoring ( course of disease)
- Clinical management (treatment/response)
- Prognosis (risk stratification - classification into group depending on risk levels)
- What is a biomarker?
A substance which allows identification of the disease and measure of treatment effectiveness
- What are two analytical characteristics of an ideal biomarker?
- Measurable by cost-effective method and simple to perform.
- Rapid turnaround time with sufficient precision & accuracy.
- What are five clinical characteristics of an ideal biomarker?
- Early detection of disease and the ability to improve patient outcome
- Sensitivity vs specificity
- Validated decision limits
- Selection of therapy
- Risk stratification and Prognostic value (information about overall likely outcome of disease).
- Cardiovascular disease is an umbrella term for other lil diseases- give some examples of what diseases these would be?
• coronary heart disease (CHD), cerebrovascular disease, peripheral arterial disease, rheumatic and congenital heart diseases, venous thromboembolism and lymphatic disease.
- What % of deaths are caused by cardiovascular disease?
1/4
- Fill in the blank”
Every * minutes , someone dies from cardiovascular disease”
8
- What is the total healthcare cost of cardiovascular disease?
9 Billion
- Coronary heart diseases causes the most deaths in men and women , how?
Myocardial Infarction
Heart failure
- How does an atheromatous plaque develop?
- Foam Cells ( macrophages) localise to fatty deposits on blood vessels wall and infiltrate
- Lipids accumulate forming lipid cores , –> surface defects, thrombosis and sometimes haemorrhage
- What % of the age groups below have a risk of getting significant coronary atherosclerosis (build-up of plaques):
<20 year olds
20-29 year olds
30-39 year olds
20% in <20 year olds,
50% in 20-29 year olds and
up to 65% in 30-39 year olds.
- Describe the initiation of Atherosclerosis?
LDL penetrates the endothelium–>oxidative modification—> releases pro inflammatory lipids–> surface now expresses adhesion molecules –>surface monocytes adhere to–>Monocytes then enter the intima and respond to the cytokines–>M-CSF -> monocytes = macrophages–>upregulate expression of surface receptors–> release of proinflammatory mediators–> Receptors mediate the uptake of oxidised LDL–>cholesterol accumulation in the cell which then develops into a foam cell.
- What does M-CSF stand for?
macrophage colony stimulating factor - cytokine
- What is the main consequence of Coronary Thrombosis?
Ischaemia (decreased blood flow due to plaque build-up in the coronary arteries) can become necrosis (dead tissue). This can cause myocardial infarction.
- Explain the whole process of atherosclerosis in simple terms?
- Irritant (LDL, Toxins)
- Irritant disrupts endothelium
- Cholesterol build up (fatty streak) in damaged wall
- LDL oxidised
- Sends signals which cause monocytes to arrive
- M-CSF converts monocytes to macrophages
- Macrophages try to engulf LDL, become foam cells and die, release cytokines
- Smooth muscle cells form fibrous cap around plaque and release calcium (makes plaque hard)
- How can a plaque rupture lead to myocardial infarction?
o A plaque with a fibrous cap (muscle cells, foam cells, collagen/elastin etc) causes angina.
o When the cap ruptures and LDL is released, it causes acute coronary syndromes.
o A blood clot forms around the cap rupture, this blocks the artery and causes heart attack.
- Why is it important to define the type of ischaemic heart disease?
oIt is important to differentiate between stable angina and acute myocardial infarction because this determines the treatment, prognosis and management needed.
- What are some causes of chest pain?
o Broken ribs, collapsed lungs or ‘pulled’ muscles.
o Nerve infection (shingles) or other infections.
o Pericarditis (inflammation of the pericardium) or blood clot in the lungs (PE).
o Heart burn (hernia) or angina or myocardial infarction.
o Areas of radiation pain: neck, jaw, upper abdomen, shoulders or arms.
- What kind of assessments would you do for a patient with Ischaemia heart disease?
Medical history, Risk factors, Presenting signs/symptoms, ECG, Imaging/Scans and Biomarkers.
- What can biochemical markers of cardiac damage contribute to?
o Rule in/out an acute MI o Confirm an old MI o Help to define therapy and monitor success of therapy o Diagnosis of heart failure o Risk stratification of death
- What does irreversible myocardial injury require?
Irreversible injury typically requires 30 minutes of ischaemia.
22.How long does it take after damage for 80% of cardiac cells to die ? How about 100% of cells?
o High risk that 80% of cardiac cells die within 3 hours and almost 100% by 6 hours.
- During myocardial injury you may have cellular content leak out through membrane . What does this depend on?
Size
Solubility
- Why is the concentration gradient of cellular compartments inside to outside the myocardial cells important?
high gradient improves detection of early damage
25, What are some markers of myocardial damage’?
o After Mi, there is a 7-36 h peak in heart muscles specific markers troponin-T and troponin-I.
o Creatine kinase (Increase of 90% MIs, but less specific as also released from skeletal muscle).
o Heart specific isoforms of creatine phosphokinase (CPK-MB).
o Myoglobin raised early but less specific for heart damage.
- For the serum protein CREATINE KINASE :
- How long does it take to elevate for the 1st time after infarction
- How long does it take for its peak elevation??
- What is the duration of elevation?
- 4-6 hours
- 18-36 hours
- 3 days
- For the serum protein MYOGLOBIN :
- How long does it take to elevate for the 1st time after infarction
- How long does it take for its peak elevation??
- What is the duration of elevation?
- 2-3 hours
- 6-9 hours
- 1 day
- For the serum protein TROPONIN I & T :
- How long does it take to elevate for the 1st time after infarction
- How long does it take for its peak elevation??
- What is the duration of elevation?
- 4-6 Hours
- 24-36 hours
- duration depends on extent of damage
- What is the troponin complex a component of?
o The troponin complex is a component of the thin filaments in striated muscle complexed to actin.
- How are troponin different to each other?
different proteins, structurally unrelated
- What are the three types of troponin and what is their function?):
Troponin T (tropomyosin binding), Troponin I (inhibits actomyosin ATPase), Troponin C (calcium binding).
- Fill in the blank “ Cardiac troponin T and I differ significantly from troponin **”
- CHECK THIS -
T
- CHECK THIS-
- DOESN’T MAKE SENSE-
- Which muscle would we find Troponin I?
Skeletal Muscle
- What are 3 clinical advantages of cardiac troponin?
An index of cardiac damage
Blood levels related to severity of cardiac damage
Predicts major adverse cardiac events such as myocardial infarction
- What type of test do we use to detect troponin?
ELISA
Enzyme linked immunosorbent assay
- Explain how an ELISA tests work?
- Immobilised Capture antibody
- Add patient sample
- Detecting antibody
- Any “Troponin” in the patient sample will bind with capture antibodies and detecting antibodies- now immobilised
- Well is washed
- Signal is added that binds with detecting antibody-so we can see how much troponin in the sample
- What is heart failure?
o A complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.
- How many people in the UK are living with heart failure?
920,000 people living with heart failure in the UK
- What is the prevalence of heart failure?
1-2% of men and women
- What is the prognosis for heart failure?
1 year survival
50%
- What are some major causes of heart failure?
- Coronary Artery Disease
- Chronic Hypertension
- Cardiomyopathy
- Heart Valve Disease
- Arrhythmias- AF,VT
- Infective endocarditis
- Pulmonary Hypertension- PE, COPD
- Alcohol and Drugs (e.g. cocaine).
- What are some signs and symptoms of congestive heart failure?
- Shortness of breath
- Lack of energy
- Swelling of legs and feet
- Chronic lack of energy
- Swollen or tender abdomen with loss of appetite
- Cough with frothy sputum
- Increased urination at night
- -Difficulty to sleep at night because of breathing problems
- Confusion/impaired memory
- Are the signs and symptoms for cardiac heart failure very quick and easy to spot and then diagnose cardiac heart failure?
o Sensitivity and specificity of signs and symptoms of heart failure is relatively poor.
- What is the clinical utilisation of cardiac biomarker testing in heart failure ?
oInitial evaluation of heart failure.
oScreening for cardiac dysfunction
oGuiding management of heart failure.
oThe assessment of prognosis and survival
- What types of peptides are markers of cardiac overload?
Natriuretic Peptides
- What are the names of the ABC markers?
-ANP
-BNP
-CNP
(A,B,C natriuretic peptide..)
- Name the source for the following natriuretic peptides:
- ANP
- BNP
- CNP
- ANP = ATRIUM
- BNP = VENTRICLE
- CNP= ENDOTHELIAL
- What form are all peptides synthesised as?
HMW Precursor
- What are the main effects of the following peptides:
-ANP
-BNP
-CNP
??
ANP + BNP :
- Natriuretic (sodium excretion in the urine)
- Vasorelaxant
- RAAS inhibition (decreases sodium reabsorption)
CNP:
- Vasorelaxant
- CNS effects
- What is the stimulus that causes the secretion of ANP and BNP?
ANP:
-Atrial Stretch
BNP:
=Ventricular dilation
- What kind of function do these peptides (A,B,C) have . Endocrine, autocrine or paracrine
ANP:
-Endocrine
BNP:
-Endocrine
CNP:
-Paracrine
- How do we measure the patient plasma for natriuretic peptides?
o Assays available for the active peptides and the N-terminal precursor forms of BNP.
- What are some advantages of measuring for the N -terminal precursor forms of BNP?
- Longer half-life so higher plasma concentrations
* Less sensitive to rapid fluctuations
- Why would we measure for plasma BNP- What can it tell us?
o Assessment of severity and monitoring the response to a treatment in congestive heart failure
o Screening for mild heart failure
o Prognostic outcome/risk stratification
o Higher proBNP: Higher probability/risk of heart failure.
- What values of BNP and NT-proBNP would indicate a high probability of HF?
BNP >500 pg/ml
NT-proBNP >1800 pg/ml
56.What values of BNP and NT-proBNP would indicate an intermediate probability of HF?
BNP 100-400 pg/ml
NT-proBNP 300-1800 pg/ml
- What values of BNP and NT-proBNP would indicate an low probability of HF?
BNP <100 pg/ml
NT-proBNP <300 pg/ml
- If troponin I increases hours after cardiac damage, what is it a sign off?
MI
