Clinical Biochemistry: Laboratory Investigation of Cardiac Disease Flashcards
What are the different types of biochemical tests in clinical medicine? State what each of these tests are used for
- Screening - Used to look for subclinical conditions, these are conditions that relate to a disease but aren’t severe enough to show symptoms
- Diagnosis - normal vs abnormal values
- Monitoring - Used to look at course of disease over time
- Clinical management - Used to guide treatment/response to a disease
- Prognosis - Used to calculate chnaces of future occurance (risk stratification)
What marker/s would be looked at when screening a person who may be at risk of developing ardiovascular disease?
- Cholesterol levels - LDL/HDL levels
What are some of the analytical characteristics of an ideal biomarker?
- Measurable by cost-effective method
- Simple to perform
- Rapid turnaround time for results
- Sufficient precision & accuracy
What are some of the clinical characteristics of an ideal biomarker?
- Early detection of disease
- Sensitivity vs specificity
- Validated decision limits
- Selection of therapy
- Risk stratification
- Prognostic value
- Ability to improve patient outcome
What is cardiovascular disease?
- Umbrella term for a number of linked pathologies including:
- Coronary heart disease (CHD)
- Cerebrovascular disease
- Peripheral arterial disease
- Rheumatic and congenital heart diseases
- Deep vein thrombosis
- Lymphatic disease
Myocardial infarction occurs as a result of atherosclerosis causing occlusion in a coronary vessel. Briefly explain how an atheromatous plaque is formed
- Endothelial cell dysfunction - due endothelial cell activation, inflammatory response and macrophage infiltration into vessel wall which absorb LDL and form foam cells
- Formation of fatty streaks - occurs due to intracellular lipd accumulation (LDL release from necrotic foam cells)
- Formation of intermdiate lesion - again due to intracellular lipid accumulation which eventually leads to formation of small extracellular lipid pools
- Atheroma formation - Further intracellular lipid accumulation leads to lipid core of atheroma being formed
- Fibroatheroma - Atheroma may develop multiple lipid cores which calicfy and harden due to calcium rlease from foam cells
- Complication lesion formation - Atheroma breaks through endothelium into lumen which causes thrombosis
Explain the process of athersclerosis in more detail
- Low level inflammatory processes cause the arterial endothelial cells to become activated
- These inflammatory processes cause LDL to infiltrate into intima layer of vessel wall
- Once in intima layer LDL particles become oxidised
- Oxidised LDL particles cause activated endothelial cells to produce cytokines and adhesion molecules
- Circulating monocytes bind to the endothelial cells in prescence of adhesion molecules
- Monocytes infiltrate into intima layer of vessel wall and differentiate into macrophages
- Scavenger receptors on macrophages bind oxidsed LDL and cause macrophages to absorb it which causes them to become foam cells
- Foam cells release growth factors causing activation and migration of smooth muscle cells to intima layer
- Activated smooth muscle cells produce collagen/elastin which forms extracellular matrix on the top of the intimia layer
- Cells underneath extracellular matrix, e.g. foam cells, undergo necrosis and release oxidised LDL into intima
- This released LDL accumulates to form lipid core
- Foam cells release calcium to form calcium deposists around lipd core of plaque
- Lipid core of plaque can eventually grow too large and rupture, this exposes sub-endothelium which leads to thrombosis
Atherosclerosis may lead to cornoary thrombosis, what are the consequences of coronary thrombosis?
- Ischaemia - thrombosis leads to blockage of a coronary artery meaning a part of the heart won’t receive sufficient oxygen
- Necrosis - Ischaemia will eventually lead to cardiomyocytes in that area of the heart experiencing cell death
- Myocardial infarction - Necrosis will lead to myocadrial infarction
What is the major difference between the way angina and a myocardial infarction are produced?
- In angina the atherosclerotic plaque does’t rupture which means although the artery is oartially blocked blood is still bale to flow through it
- In myocardial infarction the athersclerotic plaque ruptures leading to thrombosis which causes the complete blockage of the artery
Myocardial infarction and stable angina are both types of ischemic heart disease (IHD), why is it important to define the types of ischemic heart disease?
- It’s important especially when distinguishing between nagina and myocardial infarction because although the sympotoms are similar, e.g chest pain, the treatment, prognosis and management of each disease is very different
What are some causes of chest pain?
- Broken rib
- Collapsed lung
- Heart burn (hernia)
- Pulmonary embolism
- Angina
- Myocardial infarction
What are some of the different things that are looked at/used in the assessment of ischemic heart disease?
- Medical history
- Risk factors
- Presenting signs and symptoms
- ECG
- Cardiac biomarkers
- Imaging/scans
Why are cardiac biomarkers useful in the assessment of ischaemic heart disease?
- 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
How long must ischaemia last for before the myocardial injury it causes becomes irreversible?
- Irreversible injury typically requires 30 minutes of ischaemia
- High risk that 80% of cardiac cells die within 3 hours of ischaemia
- Almost 100% of cardiac cells in the area experiencing ischaemia die after 6 hours
What happens to the cardiac cells as a result of ischaemia?
- Cellular content leak out through membrane dependent on size and solubility - ions will leak out first, then proteins and enzymes
Why is the concentration gradient between the inside and outside of a cardiac cell important in detecting myocardial damage?
- High concentration gradient between insie and outside cardaic cells improves detection of early damage
What are some biochemical markers of myocardial damage?
- Troponin-T and Troponin-I - Heart muscle specific markers
- Creatine kinase - serum level increases in 90% of MIs, but less specific as also released from skeletal muscle
- Creatine kinase myocardial band (CPK-MB) - Heart specific isoforms of creatine phosphokinase
- Myoglobin - Raised in early stages of myocardial damage but less specific for heart damage
How many hours after a myocardial infarction do cardic biomarkers reach their peak levels within the blood?
- Usually after 7-36 hours
Troponin is a protein complex that is made up of 3 different subunits, what are these 3 subuntis and what are their functions?
- Troponin T - tropomyosin binding
- Troponin I - inhibits actomyosin ATPase
- Troponin C - calcium binding
Why can cardiac troponin T and troponin I be used as biochemical markers for myocardial injury?
- Cardiac troponin T and I differ significantly from troponin T and I found in skeletal muscle
- This means if you find increrased levels of cardiac Troponin T and I in the blood you know it’s due to cardiac muscle injury and not due to skeletal muscle injury
What are some of the advantages of using cardiac troponins as biochemical markers of myocardiac injury?
- Provide an index of cardiac damage
- Blood levels related to severity of cardiac damage
- Can predict major adverse cardiac events such as myocardial infarction
How can the serum levels of cardiac troponins be used to indicate the type of myocardial injury that a payient is experiencing?
- If cardiac troponin levels are shown to be massively increased then it indicates a myocardial infarction may have occured
- If cardiac troponin levels are shown to have increased by quite a lot it indicates that a minor myocardial injury may have occured
- If cardiac troponin levels haven’t increased at all but the patient is still experiencing symptoms of cardiac injury, e.g. shortness of breath, then it indicates that the patient may have myocarditis (inflammation of cardiac muscle)
How are Troponin T and I levels measured within the blood?
- The ELISA test is used - enzyme linked immunosorbant assay
What is heart failure?
- Condition that occurs when the heart is unable to pump sufficiently to maintain blood flow to meet the body’s needs
What are some of the major causes of heart failure?
- Coronary Artery Disease
- Chronic Hypertension
- Cardiomyopathy
- Heart Valve Disease
- Arrhythmias- AF,VT
- Alcohol and Drugs (e.g. cocaine)
What are some of the symptoms of heart failure?
- Shortness of breath
- Swelling of feet/legs
- Chronic lack of energy
- Persistant cough
- Confusion
Why are biochemical markers particularly useful in diagnosing heart failure?
- Because the sensitivity and specificity of signs and symptoms of heart failure is relatively poor so it can eaily be misdiagnosed as another condition based purely on the symptoms
What biochemical markers are used to diagnose heart failure?
- Natriuretic peptides which are markers of cardiac overload
What are the names of the natriuretic peptides used to diagnose heart failure?
- Atrial natriuretic peptide (ANP)
- Ventricular (Brain) natriuretic peptide (BNP)
- C-type natriuretic peptide (CNP)
Where are each of the natriuretic peptides released from?
- ANP - Atrium
- BNP - Ventricle
- CNP - Endothelial cells
State the main effects of each of the different types of natriuretic pepyide
- ANP - Natriuretic, Vasorelaxant, RAAS inhibition
- BNP - Natriuretic, Vasorelaxant, RAAS inhibition
- CNP - Vasorelaxant, CNS effects
What are the stimuli for the release of each of these natriuretic peptides?
- ANP - Atrial stretch
- BNP - Ventricular dilatation
- CNP - Sheer stress
How are the serum levels of natriuretic peptides measured?
- Assays available for the active peptides and for the N-terminal precursor forms of BNP
What are the advantages of measuring the N-terminal precursor forms of BNP when diagnosing heart failure?
- Longer half-life
- Higher plasma concentrations
- Less sensitive to rapid fluctuations
