24. Lab Investigations of Cardiac Disorders Flashcards
What are the general biochemical tests in clinical medicine?
Screening (subclinical conditions)
Diagnosis (normal vs abnormal values)
Monitoring (course of disease)
Clinical management (treatment/ response)
Prognosis (Risk stratification)
What are the classifications of laboratory tests in cardiac disease?
Markers of risk factors for development of coronary artery disease
Genetic analysis for candidate genes of risk factors
Markers of cardiac tissue damage
Markers of myocardial function/overload
What are cardiac markers?
Located in the myocardium. Released in response to:
- cardiac overload
- cardiac injury
- cardiac failure
Can be measured in blood samples
What can biochemical markers of cardiac dysfunction/damage contribute to?
- Rule in/out an acute MI
- Confirm an old MI
- Help to define therapy
- Monitor success of therapy
- Diagnosis of heart failure
- Risk stratification of death
What are the analytical and clinical characteristics of an ideal cardiac marker?
ANALYTICAL: • Measurable by cost-effective method • Simple to perform • Rapid turnaround time • Sufficient precision & accuracy • Reasonable cost
CLINICAL: • Early detection of disease • Sensitivity vs specificity • Validated decision limits • Selection of therapy • Risk stratification • Prognostic value • Ability to improve patient outcome
Describe the development of an atheromatous plaque
INITIAL LESION:
- Histologically “normal”
- Macrophage infiltration
- Isolated foam cells
FATTY STREAK:
- Mainly intracellular lipid accumulation
INTERMEDIATE LESION:
- Intracellular lipis accumulation
- Small extracellular lipid pools
ATHEROMA:
- Intracellular lipid accumulation
- Core of extracellular lipid
FIBROATHEROMA:
- Single or multiple lipid cores
- Fibrotic/calcific layers
COMPLICATED LESION:
- Surface defect
- Heamotoma-heamorrhage
- Thrombosis
What are the major consequences of coronary thrombosis?
The bloackage can cause ischaemia (restriction of the oxygen supply to the tissue)
- Leads to necrosis (tissue death)
- and ultimately a myocardial infarction
List some chronic ischaemia heart disease
- Stable angina
- Variant angina
- Silent myocardial ischaemia
List some acute ischaemia heart disease
- Unstable angina
- ST-segment elevation MI
- non ST-segment elevation MI
Why is it important to define the type of IHD?
This is because different heart diseases have/need different:
- treatments
- prognosis
- management
What are some causes of chest pain?
- Broken rib
- Collapsed lung
- Nerve infection (shingles)
- “Pulled” muscle
- Infection
- Heart burn (hernia)
- Pericarditis
- Blood clot in the lungs (PE)
- Angina
- Myocardial infarction
How would you assess IHD?
- Medical history
- Risk factors
- Presenting signs and symptoms
- ECG
- Biomarkers
- Imaging/scans
Describe the prognosis of myocardial injury (i.e. relation between time and damage done).
- Irreversible injury typically requires 30 minutes of ischaemia
- High risk that 80% of cardiac cells die within 3 hours and almost 100% by 6 hours
- Cellular content leak out through membrane dependent on size and solubility
- Concentration gradient from inside to outside important (high gradient improves detection of early damage)
Which myocardial cell constituents are released first?
- Ions (such as potassium phosphate) are released first since they are teh smallest, followed by metabolites (such as lactate or adenosine) and then finally, we have macromolecules (such as enzymes or proteins)
What are some markers of myocardial damage?
- > Heart muscle specific markers troponin-T and troponin-I
- > Creatine kinase (increase 90% MIs, but less specific as also released from skeletal muscle)
- Heart specific isoforms of creatine phosphokinase (CPK-MB
- > Myoglobin raised early but less specific for heart damage
Describe troponins
The troponin complex is a component of the thin filaments in striated muscle complexed to actin
There are three types of troponins:
• Troponin T (tropomyosin binding)
• Troponin I (inhibits actomyosin ATPase)
• Troponin C (calcium binding)
The troponins are three different proteins structurally unrelated with each other
Cardiac troponin T and I differ significantly from troponin T and I found in skeletal muscle
What are the 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
How would you detect troponins in the blood?
You would do an ELISA (enzyme linked
immunosorbant assay) test
Briefly describe heart failure in the UK, and list some of the major causes of heart failure.
“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”
Incidence: 920,000 people living with
Heart failure in the UK
•Prevalence: 1- 2 % of men and women
•Poor prognosis: 1 year survival ~ 50%
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 (eg cocaine)
What are some signs and symptoms of congestive heart failure?
- shortness of breath
- swelling of feet and legs
- chronic lack of energy
- difficulty sleeping at night due to breathing problems
- swollen or tender abdomen with loss of appetite
- cough with frothy sputum
- increased urination at night
- confusion and/or impaired memory
What is the clinical utilisation of cardiac biomarker testing in heart failure?
- Initial evaluation of heart failure
- Screening for cardiac dysfunction
- Guiding management of heart failure
- Assessment of prognosis and survival
For the three natriuretic peptides, list source, main effects, secretion stimulus and function
- ANP
- Source(main): Atrium
- Main effects: Natriuretic, Vasorelaxant, RAAS inhibition
- Secretion stimulus: Atrial stretch
- Function: Endocrine
- BNP
- Source(main): Ventricle
- Main effects: Natriuretic, Vasorelaxant, RAAS inhibition
- Secretion stimulus: Ventricular dilatation
- Function: Endocrine
- CNP
- Source(main): Endothelial
- Main effects: Vasorelaxant, CNS effects
- Secretion stimulus:
- Function: Paracrine ?
How would you measure plasma natriuretic peptides?
Assays available for the active peptides and the N-terminal precursor forms of BNP.However, it was found that measuring the BNP precursor forms of the NPs were more clinically useful.
Advantages of N-terminal precursor forms of BNP:
- Longer half-life
- Higher plasma concentrations
- Less sensitive to rapid fluctuations
What conditions can be investigated using BNP?
- Assessment of severity of congestive heart failure
- Screening for mild heart failure
- Monitor response to treatment in congestive heart failure
- Prognostic outcome/risk stratification
