Cardiovascular Flashcards
What is Atherosclerosis?
Plaque rupture leading to thrombus formation, leading to partial/complete arterial blockage by ‘stiff’ ‘paste’.
Principle behind heart attack, stroke and gangrene of the extremities where blood supply to these areas is blocked.
Leading cause of the death in the world.
What is the epidemiology of cardiovascular disease in the UK?
More prevalent in men than in women.
More prevalent is less affluent areas (Yorkshire and the North).
What are the risk factors for Atherosclerosis?
Age – over 50s, post-menopausal, chronic disease
Tobacco Smoking – increases systemic inflammation
High Serum Cholesterol
Obesity – metabolic syndrome increases systemic inflammation, high serum cholesterol due to high fat diet
Diabetes
Hypertension
Family History – genetic component, get put on statins early on
How are atherosclerotic plaques distributed?
Found within peripheral and coronary arteries
Focal distribution along the artery length
Distribution may be governed by haemodynamic factors:
Changes in flow/turbulence (eg at bifurcations) cause the artery to alter endothelial cell function. Wall thickness is also changed leading to neointima.
Altered gene expression in the key cell types is key.
What is neointimal hyperplasia?
Proliferation and migration of vascular smooth muscle cells primarily in the tunica intima, resulting in the thickening of arterial walls and decreased arterial lumen space.
What are the layers of the arterial wall?
The wall of an artery consists of three layers.
The tunica intima is simple squamous epithelium surrounded by a connective tissue basement membrane with elastic fibers.
The tunica media, is primarily smooth muscle and is usually the thickest layer. It not only provides support for the vessel but also changes vessel diameter to regulate blood flow and blood pressure.
The outermost layer, which attaches the vessel to the surrounding tissue, is the tunica externa or tunica adventitia. This layer is connective tissue with varying amounts of elastic and collagenous fibers.
What is the structure of the atherosclerotic plaque?
A complex lesion made up of: Lipid Necrotic core Connective tissue Fibrous “cap” The plaque will either occlude the vessel lumen resulting in a restriction of blood flow (angina), or it may “rupture” (thrombus formation – death).
What is the ‘Response to Injury’ hypothesis?
First suggested in 1856 by Rudolph Virchow and updated by Russell Ross in 1993 and 1999.
Initiated by an injury to the endothelial cells which leads to endothelial dysfunction (inappropriate and abnormal).
Signals sent to circulating leukocytes which then accumulate and migrate into the vessel wall.
Inflammation ensues.
What is good about inflammation? Why do we need it?
Without it we’d be infested with pathogens and parasites, and even if we all lived in sterile conditions, we’d be over-come by tumors and be unable to heal wounds.
What can be bad about inflammation?
Can be inappropriate and harmful!
How can inflammation be harmful in auto-immune diseases?
In auto immune diseases such as Rheumatoid arthritis or allergic inflammatory diseases such as asthma the body’s own inflammatory mechanisms are directed against self or respond inappropriately to harmless stimuli such as pollen or house dust mites.
How can inflammation be harmful in Ischaemia-reperfusion injury?
In Ischaemia-reperfusion injury, tissues that have their blood supply blocked (eg by thrombus in myocardial infarction) are injured. Re-institution of blood flow (by fibrinolysis), necessary to rescue surviving cells, permits inflammatory cells (neutrophils) to enter the injured tissue. Although these neutrophils have an important role in cleaning up dead and injured cells and in wound healing, they can also extend the area of injury beyond that originally cut off from the of blood supply.
How can inflammation be harmful in shock?
In septic or traumatic shock, large numbers of neutrophils are mobilised from bone marrow and are recruited to tissues to fight potential infection. The availability of antibiotics and advance trauma surgical techniques means that the magnitude of the inflammatory response can actually present more of a threat to the patient than the infection or injuries.
How can inflammation be harmful in atherosclerosis?
The response to injury hypothesis says that atherosclerosis occurs due to an inappropriate immune response due initiated by endothelial dysfunction.
Necrotic core – when cells die from necrosis, they release pro-inflammatory mediators which encourage other inflammatory cells to migrate.
What initiates inflammation in the arterial wall in atherogenesis?
LDL - can pass in and out of the arterial wall in excess it accumulates in arterial wall, and undergoes oxidation and glycation. Endothelial dysfunction (Response to Injury hypothesis) Not sure what causes this!
What is the stimulus for adhesion of leukocytes in atherogenesis?
Once inflammation is initiated, chemoattractants (chemicals that attract leukocytes) are released from endothelium and send signals to leukocytes.
Chemoattractants are released from site of injury and a concentration-gradient is produced showing the cells where to go
Name some of the inflammatory cytokine found in plaques?
IL-1 IL-6 IL-8 IFN-g TGF-b MCP-1 – Monocyte chemoattractant protein 1 (C reactive protein)
What is leukocyte adhesion in atherogenesis controlled by?
Once the leukocytes receive the chemoattractant signals, they are recruited to the blood vessel wall.
This is the adhesion cascade.
Initial stages are regulated by selectins, later stages regulated by integrins and chemoattractants.
For every adhesion molecule there is a counter receptor – allowing for sticking together.
What is the first stage of atherosclerosis progression?
Fatty streaks
Earliest lesion of atherosclerosis
Not causative but provide a foundation for the progression
Appear at a very early age (<10 years)
Consist of aggregations of lipid–laden macrophages and T lymphocytes within the intimal layer of the vessel wall
No effect on blood flow.
What is the second stage of atherosclerosis progression?
Intermediate lesions
Composed of layers of :
Lipid laden macrophages (bubbles of lipid - foam cells)
Vascular smooth muscle cells
T lymphocytes
Adhesion and aggregation of platelets to vessel wall
Isolated pools of extracellular lipid
What is the third stage of atherosclerosis progression?
Fibrous plaques or advanced lesions
Impedes blood flow
Prone to rupture
Covered by dense fibrous cap made of ECM proteins including collagen (strength) and elastin (flexibility) laid down by SMC that overlies lipid core and necrotic debris
Highly pro-inflammatory
May be calcified
Contains: smooth muscle cells, macrophages and foam cells and T lymphocytes
What is the fourth stage of atherosclerosis progression?
Plaque rupture
Plaques constantly growing and receding.
Fibrous cap has to be resorbed and redeposited in order to be maintained.
If balance shifted eg in favour of inflammatory conditions (increased enzyme activity – matrix metalloproteinases), the cap becomes weak and the plaque ruptures.
Basement membrane, collagen, and necrotic tissue exposure as well as haemorrhage of vessels within the plaque
Thrombus (clot) formation and vessel occlusion
What is a TCFA?
Thin capped fibroatheroma
A type of vulnerable plaque that is prone to rupture
Can detect plaque rupture by using an ECG
What is the fifth stage of atherosclerosis progression?
Plaque erosion
Second most prevalent cause of coronary thrombosis (more common in MI in females than plaque rupture).
Lesions tend to be small ‘early lesions’
Don’t understand why this happens
Fibrous cap thick may disrupt by collagen triggering thrombosis rather than tissue factor (as in plaque rupture)
A platelet-rich clot may overlie the luminal surface.
There may be a prominent lipid core.
How can plaque erosion be detected?
These lesions are very difficult to detect with any kind of imaging so far. OCT is the best and the presence of luminal thrombus over an intact fibrous cap is indicative. OCT is intravascular tomography processing backscattering using infrared light.
What is PCI?
PCI - Percutaneous Coronary Intervention
Used to treat coronary artery disease
2 million + procedures / year worldwide
More than 90% require stent implantation. Stents made out of stainless steel, cobalt chromium, metals that are cost-effective.
Restenosis was a major limitation, no longer a problem.
What is restenosis?
The body wants to heal the area where the stent has been put in – smooth muscle cell proliferation.
Used to happen after PCI.
But drug eluting stents (with Taxol and Sirolimus) are so good now that restenosis is not a problem. These drugs work by reducing smooth muscle cell proliferation and in turn, this reduces regrowth after placement of the stent.
Name some useful anti-platelet drugs?
Patients will be given anti-platelet therapy before a stent.
Aspirin – irreversible inhibitor of platelet cyclo-oxygenase
Clopidogrel/Ticagrelor – inhibitors of the P2Y12 ADP receptor on platelets
Statins – inhibit HMG CoA reductase, reducing cholesterol synthesis
What is canakinumab?
New anti-inflammatory biologic (antibody) developed in 2017 to target IL-1 which acts as a major cytokine in atherosclerosis.
Major clinical trial showed beneficial results.
What is Colchicine?
A generic anti-inflammatory drug that lowers ischaemic events in patients with recent MI.
Already used for gout and pericarditis.
Given within 30 days of a heart attack.
Why are the letters PQRST used in an ECG?
Original deflections were labelled ABCD
Mathematical convention dating back to Descartes using the second half of the alphabet; N has other meanings in mathematics and O was used for the origin of Cartesian coordinates. Einthoven chose the next letter of the alphabet!
What is an ECG?
Echo-cardiogram is a representation of the electrical events of the cardiac cycle.
Each event has a distinctive wave form.
The study of the waveform can give insight into the patient’s cardiac pathophysiology.
What can you identify using an ECG?
Arrhythmia Myocardial ischemia and infarction Pericarditis Chamber hypertrophy Electrolyte disturbances - hyper/hypokalemia Drug toxicity
What is depolarisation of the heart?
Contraction of any muscle associated with electrical changes is called depolarisation.
The vast majority of the activity that we see on an ECG is depolarization, rather than repolarization.
What are the pacemakers of the heart and their bpm?
SA Node - dominant pacemaker with an intrinsic rate of 60-100 bpm
AV Node - back up pacemaker with an intrinsic rate of 40-60 bpm
Ventricular cells - back up pacemaker with a intrinsic rate of 25-40 bpm
What is a standard calibration of an ECG?
25mm/s
0.1mV/mm
Electrical impulse that travels towards the electrode produces an upward ‘positive’ deflection.
What is the pathway of impulse conduction in the heart?
Sinoatrial node AV node Bundle of His Bundle branches Purkinje fibres
What do the different waves on the ECG represent?
P wave - atrial depolarisation
QRS complex - ventricular depolarisation
T wave - ventricular repolarisation
We do have atrial repolarisation but it gets lost behind the QRS complex.
What is the PR interval?
Atrial depolarisaton
PLUS a delay in AV junction
Delay allows for the atria to contract before the ventricles contract.
What does the ECG paper represent?
Horizontally One small box - 0.04 s One large box - 0.20 s Vertically One large box - 0.5 mV
What are the ECG leads?
They measure the difference in electrical potential between two different points.
Bipolar leads: two different points on the body
Unipolar leads: one point on the body and a virtual reference point with zero electrical potential located in the centre of the heart
What are types of leads are the 12 leads of the ECG?
VERTICAL PLANE 3 standard leads 3 augmented leads HORIZONTAL PLANE 6 precordial leads
What are the characteristics of the P wave?
Always positive in leads I and II Always negative in lead aVR Less than 3 small boxes in duration Less than 2.5 small boxes in amplitude Best seen in lead II
What does the ECG look like for right and left atrial enlargement?
Right atrial enlargement: Tall (>2.5mm) and pointed P waves (P pulmonale)
Left atrial enlargement: Notched/bifid M-shaped P wave in limb leads (P ‘mitrale’)
What do short and long PR intervals suggest?
Short PR interval - Wolff Parkinson’s White syndrome
Accessory pathway allows for early activation of the ventricles
Long PR interval - first degree heart block
What are the characteristics of the ST segment?
ST segment is flat (isoelectric)
Elevation or depression of the ST segment by 1mm or more
“J” junction is the point between QRS and ST segment.
What are the characteristics of T wave?
Normal T wave is asymmetrical, first half having a more gradual slope than the second.
Rarely exceeds 10mm.
Abnormal T waves are symmetrical, tall, peaked, biphasic or inverted.
T waves follow the direction of the QRS deflection.
What is the QT interval?
Total duration of the depolarisation and repolarisation
QT interval decreases when heart rate increases
Should be between 0.35-0.45 s
Should not be more than half of the interval between adjacent R waves (R-R interval)
What is the U wave?
Afterdepolarisations that occur after repolarisation
Small, round, symmetrical and positive in lead II with amplitude <2mm.
U wave direction is the same as T wave.
More prominent at slow heart rates.
How to calculate the heart rate on an ECG for regular rhythms?
Count the number of big boxes between two QRS complexes and divide this by 300 (1500 for smaller boxes).
How to calculate the heart rate on an ECG for irregular rhythms?
ECGs record 10 seconds of rhythm per page
Count the number of beats present on the ECG
Multiple by 6.
What does the QRS axis tell you?
Represents overall direction of the heart’s electrical activity.
Abnormalities hint at ventricular enlargement and conduction blocks.
Normal QRS axis is from -30 to +90
-30 to -90 is referred to as left axis deviation (LAD)
+90 to +180 is referred to as right axis deviation (RAD)
What are the key features of the heart’s contraction?
Involves a two stage electrical generated contraction
Contraction initiated by depolarisation and changes to calcium concentration
Removal of calcium (energy dependent) for relaxation to occur
What is myocardial hypertrophy?
Enlargement of the heart muscle
Hypertrophic response triggered by angiotensin 2, ET-1 and insulin-like growth factor 1, TGF-β.
Can be an adaptive process in pregnancy/athletes
If you exceed stretch capability of sarcomeres then cardiac contraction force diminishes, there’s only so far the heart can stretch before it goes into heart failure.
What effect will different kinds of heart failure have?
Left sided cardiac failure – pulmonary congestion and then overload of right side.
Right sided cardiac failure with venous hypertension and congestion.
Diastolic cardiac failure ~ Stiffer heart
What is fetal embryogenesis of the heart?
The heart comprises a single chamber until the fifth week of gestation, then divided by intra-ventricular and intra-atrial septa from endocardial cushions. The muscular intra-ventricular septum grows upwards from the apex of the heart producing the four chambers and allowing valve development to occur.
What is congenital heart disease?
Results from faulty embryonic development
May complicate up to 1% of all live births.
Misplaced structures or arrest of the progression of normal structure development.
Ventricular and atrial septal defects are the most common.
What can cause congenital heart disease?
Single genes associated = trisomy 21 (Downs), Turner Syndrome (XO) and di-George Syndrome.
Homeobox genes particularly associated
Infections – Rubella
Drugs – Thalidomide, alcohol, Phenytoin, amphetamines, lithium, eostrogenic steroids
Diabetes
What is the tetralogy of Fallot?
Main features:
- Pulmonary stenosis
- Ventricular septal defect
- Dextraposition/over-riding ventricular septal defect
- Right ventricle hypertrophy
Characteristic boot-shape on radiology and macroscopically.
Often associated with other cardiac abnormalities.
As a result of the pulmonary stenosis, right ventricle blood is shunted into the left heart producing cyanosis from birth. Surgical correction usually is performed during the first two years of life, as progressive cardiac debility and risk of cerebral thrombosis increases.
What are the risk factors for ischaemic heart disease?
Systemic hypertension Cigarette smoking Diabetes mellitus Elevated cholesterol Also: obesity, increasing age, male sex, family history, oral contraceptive pill, sedentary life habit, personality features etc
What can cause imperfect blood supply to the heart?
Atherosclerosis Thrombosis Thromboemboli Artery spasm Collateral blood vessels Blood pressure/cardiac output/heart rate Arteritis Anaemia Altered oxygen dissociation curve Carbon monoxide Cyanide Increased demand from hypertension, valvular heart disease, hyperthyroidism, fever, thiamin (B1) deficiency, catecholamine stress.
What are the patterns of infarction?
Subendocardial/patchy infarction OR
Transmural infarction
Size and pattern of the infarction varies. Complications of infarcts differ according to which territory has compromised.
Can date the infarct.
The infarct can affect other areas of the heart - the immediate area may be ischaemic and there may be other areas which were already prone to infarction which will now be affected.
Why is reperfusion of ischaemic myocardium a problem?
Reperfusion of completely infarcted tissue can produce significant haemorrhage - risks of problems downstream. The reperfusion allows oxygen delivery and a further degree of injury as a result of generation of superoxide radicals etc.
What is an aneurysm?
This is a dilation of part of the myocardial wall, usually associated with fibrosis and atrophy of myocytes.
Variable fatty tissue replacement may also occur.
The dilatation of the thin walled sac allows blood stasis and thrombosis.
Risk of subsequent embolism of such material.
What is hypertensive heart disease?
Reflects cardiac enlargement due to hypertension, and in the absence of other cause.
Compensatory hypertrophy of the heart initially with increased myocyte size, squaring of the nuclei and slight increase of the interstitial fibrous tissue.
Initially able to handle the increased workload, eventually the hypertrophy no longer compensates.
Falling amount of oxygen delivery to cardiac myocytes produces further fibrosis and progressive contractile dysfunction.
Often associated with coronary atheroma and ischaemic heart disease – aggravating situation.
What is Cor pulmonale?
Right ventricular hypertrophy and dilatation due to pulmonary hypertension.
May reflect an acute event - causes problems with backstream pressure on the ventricular system.
Classically disproportionate right ventricular hypertrophy as compared with the left.
Progressive features of right side cardiac failure with venous overload, peripheral oedema and progressive hepatic congestion.
What is Acute rheumatic fever?
Group A β-haemolytic streptococcus infection usually in upper respiratory tract.
Peak age of pathology 9-11 years, but can occur in adults. Seen commonly in those who have migrated to the UK and have not have antibiotics in childhood.
Symptoms and features diminish after 3-6 months.
Some patients die acutely and are shown to have granulomatous foci of inflammation (Aschoff body, Anitchkov cells and some giant cells). There may be pericarditis and endocarditis.
Chronically scarring and deformity produces contracture of the valves (particularly the mitral and aortic valve) and chordae tendinae. These may subsequently calcify and distort blood flow allowing localised thrombosis. They also provide ideal settling sites for bacteria within the blood stream, and the development of infective endocarditis.
What are the clinical features of acute rheumatic fever?
Clinical features include:
carditis (cardiomegaly, murmurs, pericarditis and cardiac failure) polyarthritis, chorea, erythema marginatum and subcutaneous nodules.
Minor criteria for diagnosis include:
previous history of rheumatic fever, arthralgia, raised CRP, ESR and white cell count.
Antibodies against group A streptococcal antigens, anti-streptolysin O, anti-DNAse B and anti-hyaluronidase.
What is infective endocarditis?
Infection produces rapidly increasing cardiac valve distortion and disruption with acute cardiac dysfunction.
Apart from the sudden development of cardiac failure and septic problems there are other consequences including generation of infected thromboemboli and damage to the kidneys (focal segmental glomerulonephritis FSGS).
- Protean symptoms
- Fever, anorexia, fatigue
- Progressive splenomegaly, petechiae, clubbing
- Neurological dysfunction due to mitotic emboli and aneurysms
High morbidity and mortality rates.
What causes infective endocarditis?
In adults causes include rheumatic valvular heart, mitral valve prolapse, intravenous drug abuse, prosthetic valves, diabetes, the elderly and pregnancy.
Characteristic organisms include streptococci and staphylococci although fungi and atypical bacteria are also recognised - will destroy the tissue and cause problems.
What is Calcific aortic stenosis?
Nodular calcific deposits in cusps with progressive distortion of valves opening/closure.
Obstruction to left ventricle outflow produces pressure overload and cardiac hypertrophy.
Accelerated in bicuspid aortic valves.
Risk of thrombosis and sudden cardiac death, as well as infective endocarditis.
What is Mitral valve disease?
Degenerative process which makes you prone to regurgitation.
Calcification of the mitral valve annulus is usually asymptomatic and of no significance. It does not usually affect the mobile leaflets.
However, calcification of the valves, following rheumatic valvular disease or previous inflammation/valvitis, is of significance with either mitral stenosis or regurgitant pathology.
What is Mitral valve prolapse?
Degeneration of the mitral valves such that the inner fibrosa layer becomes more loose and fragmentary with accumulation of mucopolysaccharide material.
The valve cusp bow upwards and may not close adequately producing incompetence/regurgitation.
Risk of sudden cardiac death and infective endocarditis.
What is Myocarditis?
Inflammation of the myocardium usually associated with muscle cell necrosis and degeneration.
Can be caused by rheumatic fever or other causes.
Viral myocarditis is the commonest.
Direct viral toxicity with associated cell mediated immunity aggravating cell damage. Healing with scarring, but high risk of sudden death.
Symptoms vary, often in association with an upper respiratory tract infection preceding.
What causes Myocarditis?
Viruses – Coxsackie, Adeno-, Echo, Influenza
Rickettsia – typhus
Bacteria –diphtheria, staphylococcal, streptococcal, borrelia, leptospira
Fungi and Protozoa parasites – toxoplasmosis, cryptococcus
Metazoa - echinococcus
Non-infective:
Hypersensitivity/immune related diseases – rheumatic fever, SLE, scleroderma, drug reaction, rheumatoid arthritis
Radiation
Miscellaneous – sarcoid, uraemia
What is Giant cell myocarditis?
A very rare highly aggressive form of cardiac disease with areas of muscle cell death due to macrophage giant cells. Often fatal.
Early treatment is transplantation but disease can often recur.
What are the main types of Cardiomyopathy?
Various types ~ primary cardiac disease with contractile dysfunction and atypical morphology
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy
Secondary dilated cardiomyopathy
Rare forms
What is dilated cardiomyopathy?
1/3 familial: Most autosomal dominant (AD) but some recessive and X-linked.
Poorly generated contractile force leads to progressive dilation of heart with some diffuse interstitial fibrosis.
May also follow a viral myocarditis or an inflammatory myocarditis/toxic myocarditis
Enlarged, heavy and dilated heart, possibly cardiac weight up to 900 g.
Histology shows variable atrophy and hypertrophy - increased interstitial tissue, occasional inflammatory cells
Clinical progression slowly deteriorating cardiac failure, dysrrhythmias and ultimately death.
What causes secondary dilated cardiomyopathy?
Alcohol Cobalt toxicity Catecholamines Micro-infarction Anthracyclines Cocaine Pregnancy. This may affect up to 1% of females, with an Afro-Caribbean bias. Many recover spontaneously, but one can be left with permanently damaged and dilated heart.
What is Hypertrophic cardiomyopathy?
Muscle gene mutation - prone to cause bigger, thicker heart muscle. Bulge into the chambers affecting the valves.
Related to defects in force degeneration/ energy usage allowing progressive sarcomeric dysfunction.
Compensatory hypertrophy often occurs.
Many mutations recognised involving β-myosin, myosin binding protein C, troponin T, titin etc.
Asymmetric hypertrophy with distortion of a papillary architecture.
Increased fibrosis in tissues.
Ventricular outflow distortion.
Myocyte disarray.
What is Arrhythmogenic right ventricular cardiomyopathy?
A degenerative condition with progressive dilatation of the right ventricle with fibrosis, lymphoid infiltrate and fatty tissue replacement.
Particularly common in parts of Italy
Familial inheritance pattern with genetic linkage chromosome 14,1 and 2.
Sudden cardiac death.
What is Restrictive cardiomyopathy?
This is a group of diseases in which poor dilation of the heart restricts the eventual ability of the heart to take on blood and pass it to the rest of the body.
This can either be amyloid related to the heart (cardiac amyloid) or part of a systemic disorder (amyloidosis AL, AA).
Firm enlarged and heavy heart with diffuse infiltration of the protein into the myocytes, blood vessels and valves.
Progressive deterioration with right and left side failure.
What is Endomyocardial disease?
Endomyocardial fibrosis, particularly in African settings and Löeffler endocarditis.
This is a temporate region disorder with high grade eosinophilia , rash and progress endocarditis leading to cardiac failure.
Characteristically grey-white layer of fibrous tissue extending of the endocardial surfaces of the ventricular cavities.
Stiff and poorly compliant ventricle.
What is Sarcoidosis?
A chronic granulomatous disease with numerous granulomas of non-caseating giant cell type. May involve the heart producing widespread areas of fibrosis and compensatory hypertrophy. It can produce a restrictive disorder. If it involves the conduction system then this may be the prime pathology of the patients with the risk of sudden death.
What is Cardiac myxoma?
Most common cardiac tumour
At least 75% of cardiac tumours with bias towards atria.
Rather jelly like proliferation of myxoid cells with abundant endothelial vascular channels.
Usually produces obstructive symptoms but risk of embolisation.
What is a cardiac sarcoma?
These are rare and can show differentiation towards vascular, fibrous and muscle phenotypes. Almost invariably fatal - days or weeks.
Cannot treat.
What is Atheroma?
A degenerative condition of arteries characterised often by a fibrous and lipid rich plaque with variable inflammation, calcification and a tendency to thrombosis.
Associated with ischaemic heart disease, myocardial infarction, stroke, peripheral vascular disease etc.
What are the pathological stages of atherosclerosis?
Initiation - Endothelial dysfunction and injury around sites of sheer and damage with subsequent lipid accumulation at sites of impaired endothelial barrier.
Local cellular proliferation and incorporation of oxidised lipoproteins occurs. Mural thrombi on surface with subsequent healing and repeat of cycle.
Adaptation - As plaque progresses to 50% of vascular lumen size the vessel can no longer compensate by re-modelling and becomes narrowed. This drives variable cell turnover within the plaque with new matrix surfaces and degradation of matrix. May progress to unstable plaque.
Clinical stage - The plaque continues to encroach upon the lumen and runs the risk of haemorrhage of exposure of tissue HLA-DR antigens which may stimulate T cell accumulation. This drives an inflammatory reaction against part of the plaque contents.
What are the potential complications associated with plaque rupture?
Acute occlusion due to thrombus
Chronic narrowing of vessel lumen with healing of the local thrombus
Aneurysm change
Embolism of thrombus +/- plaque lipid content - can break off and travel to other parts of the body
What are the risk factors for atherosclerosis?
Hypertension Serum cholesterol level Tobacco smoking Diabetes Increasing age Male > female Inactive and stressful life patterns Homocysteine level CRP
What is essential hypertension?
Altered renin-angiotensin system elevates blood pressure by impairing sympathetic output increasing mineralocorticoid secretion and direct vaso-constriction.
In effect the changes to auto-regulation produce an increase in peripheral resistance, that in normality would allow increased blood pressure, diuresis and restoration of normal pressure and volume.
What is Raynaud’s phenomenon?
Intermittent bilateral ischaemia of digits/extremities precipitated by motional cold temperature. Accelerated in cases of scleroderma and SLE. May produce distal atrophy and ulceration.
What is Vasculitis?
An inflammatory and variably necrotic process centred on the blood vessels that may involve arteries, veins or capillaries. Inflammation damaging the walls of the vessels.
What is Giant cell arteritis?
Commonest type of vasculitis.
Focal, chronic and granulomatous inflammation of temporal arteries mostly.
Association with polymyalgia rheumatica.
Can involve large arteries (aortic aneurysm/dissection).
Average age 70+. Female bias.
Feel stiff in the morning, painful head - temporal artery which supplies the scalp.
Can go blind in a couple of hours.
What the pathology behind Giant cell arteritis?
Thickened blood vessel, often palpable.
Granulomatous inflammation involving the full thickness of the wall with macrophages, lymphocytes, plasma cells, neutrophils and occasionally eosinophils.
Giant cells tend to congregate around IEL. Variable necrosis.
Old areas of inflammation show up as focal scars with fragmentation of elastic laminae. Thrombosis may occur.
What is Buerger disease?
An inflammatory disease of medium and small arteries affecting the distal limbs.
Strong association with tobacco smoking.
Cell mediated hypersensitivity to collagen II and III with impaired endothelium.
Distal ischaemic symptoms and necrosis.
What are aneurysms?
These are dilated areas of vasculature suggesting either congenital or acquired weakness of the wall of the vessels. The incidence rises with age.
Described as fusiform, saccular, dissecting and arterio-venous.
Prone to bulging off and travelling downstream or bursting.
What is an Abdominal aortic aneurysm?
> 50% dilatation of aortic diameter
Those greater than 5-6 cm diameter increased risk of aneurysm rupture.
Prevalence rises with age, smoking, high blood pressure
Strong association with atheromatous disease
Familial clustering suggests a genetic component
Local inflammatory changes can be profound and involve ureters and local nerves.
Sudden shocking pain - death within minutes.
What is a berry aneurysm?
This rounded berry-like vascular dilatation is particularly common in the cerebral circulation.
Consequence of long standing hypertension and/or focal area of weakness within the arterial substructure.
What is a Dissecting aneurysm?
This is a haematoma within the arterial wall with blood entering under pressure from the lumenal surface and dissecting along the length of the media.
What are varicose veins?
A varicose vein is an enlarged and torturous vein, principally affecting the superficial leg veins.
Risk factors – age, female (pregnancy related), hereditary, posture, obesity
Progressive incompetence of valves with further back pressure on venous circuit.
Thinning and dilatation of vascular wall in places with patchy calcification.
May produce stasis dermatitis with trophic changes to the skin.
What is Haemangioma?
This is a benign proliferation of blood vessel tissue, which varies in name and substructure depending on the site and age of the patient.
Capillary haemangioma – birth marks, ruby spots
Juvenile haemangioma – strawberry haemangioma
Cavernous haemangioma – port wine stains
Most are of no consequence.
What is a Glomus tumour?
A benign neoplasm involving the glomus body.
Small lesion which is intensely painful.
Composed of vascular channels with proliferation of the glomus cells (neuromyoarterial receptors) mainly affect the hands.
What is Angiosarcoma?
This is a highly aggressive malignant neoplasm of endothelial cells.
Very difficult to control, often fatal.
Commonly skin, soft tissue, breast, bone, live and spleen.
Rapidly enlarging haemorrhagic tumour with rapid dissemination to other organs.
Environmental carcinogens – arsenic and vinyl chloride.
What are the risk factors for deep vein thrombosis?
Venous flow stasis from any cause (eg. cardiac failure, chronic venous insufficiency, post operative immobilisation, prolonged bed rest)
Injury (trauma, surgery, child birth)
Hypercoaguability (OCP), pregnancy, cancer, inherited thrombophilic disorders)
Advanced age
Sickle cell disease
What is an embolism?
The passage of material through the venous or arterial circulations.
Commonest process is thrombo-embolus from a deep vein thrombosis.
Post operative deep vein thrombosis occurs often following surgery or immobilisation following illness.
Pulmonary emboli may be asymptomatic and small.
May produce transient dyspnoea for relatively small emboli.
May produce focal pulmonary infarction with chest pain, haemoptysis and secondary effusion (when lung tissue dies it can be painful).
At a certain size, they can produce cardiovascular collapse and sudden death (saddle embolus).
What are the sources of an embolus?
Atherosclerotic plaques, mural thrombus in heart or vasculature
Infective endocarditis
Sites particularly vulnerable – brain, intestine, distal limbs, kidneys and coronary circulation
What is Angina?
Mismatch of oxygen supply and demand
Blockage of coronary arteries means that heart muscle cannot receive adequate oxygen
Most common cause is ischemic heart disease
What are the risk factors of IHD?
Age Cigarette smoking Family history Diabetes mellitus Hyperlipidemia Hypertension Kidney disease Obesity Physical inactivity Stress
What are some of the exacerbating factors of IHD that affect the supply of blood to the heart?
Anemia Hypoxemia Polycythemia Hypothermia Hypovolaemia Hypervolaemia
What are some of the exacerbating factors of IHD that affect the demand of blood to the heart?
Hypertension Tachyarrhythmia Valvular heart disease Hyperthyroidism Hypertrophic cardiomyopathy
What is the physiology of myocardial ischemia?
Myocardial ischemia occurs when there is an imbalance between the heart’s oxygen demand and supply, usually from an increase in demand (eg exercise) accompanied by limitation of supply:
- Impairment of blood flow by proximal arterial stenosis
- Increased distal resistance eg left ventricular hypertrophy
- Reduced oxygen-carrying capacity of blood eg anemia
What are some of the other types of angina?
Prinzmetal’s angina (coronary spasm)
Microvascular angina – left ventricular hypertrophy, older people, in diabetics
Crescendo angina – no chest pain at rest, but now have an inability to perform physical activity
Unstable angina – critical ischaemia but not quite enough to cause a MI
What are the symptoms for IHD?
Chest pain
Breathlessness
May have other symptoms like fluid retention, palpitation, syncope or pre-syncope.
What aspects should you ask about when a patient complains of pain?
Onset Position (site) Quality (nature / character) Relationship (with exertion, posture, meals, breathing and with other symptoms) Radiation Relieving or aggravating factors Severity Timing Treatment
What are the differential diagnoses for chest pain?
Myocardial ischemia Pericarditis/ myocarditis Pulmonary embolism/ pleurisy Chest infection/ pleurisy Dissection of the aorta Gastro-esophageal (reflux, spasm, ulceration) Musculo-skeletal Psychological
What is the treatment for IHD?
Reassure
Lifestyle - stop smoking, lose weight, more exercise, improve diet
Advice for emergency
Medication - Aspirin, B blocker, statin, GTN
Revascularisation
What are the diagnostic tests that can be used to investigate angina?
Routine bloods, lipids, ECG taken
NICE recommends a CT Coronary Angiography for both typical and atypical presentations of angina (used more as a planning than diagnostic tool).
Exercise testing with an ECG may also be used.
Stress echocardiogram may be used - patient given a stimulant to look at the heart in ischemia (high-skill)
Perfusion MRI
What’s the effect of B-blockers on the heart?
Negatively chronotropic - reduced heart rate
Negatively inotropic - reduced force of contraction
Reduced cardiac output
Reduced oxygen demand
Side-effects: tiredness, nightmares, erectile dysfunction, bradycardia, cold hands and feet
DO NOT give to asthmatics
What’s the effect of nitrates on the heart?
Very good at dilating coronary arteries and arterioles, reducing blood pressure and afterload, reducing venous return and preload.
Most common side effect: headache
What is preload and afterload?
Preload is the initial stretching of the cardiac myocytes (muscle cells) prior to contraction. It is related to ventricular filling.
Afterload is the force or load against which the heart has to contract to eject the blood, the ‘load’ to which the heart must pump against.
What’s the effect of calcium channel blockers on the heart?
Third-line treatment
Coronary arteries dilate
Negatively inotropic - reduced LV contraction
Negatively chronotropic - reduced heart rate
Reduced blood pressure
Reduced afterload
Side effects are flushing, postural hypotension, swollen ankles.
What’s the effect of aspirin?
Aspirin is a derivative of salicylic acid - and is also known as acetylsalicylic acid.
Cyclo-oxygenase inhibitor
↓ prostaglandin synthesis, incl. thromboxane
↓ platelet aggregation, antipyretic, anti-inflammatory, analgesic
Most common side effect: gastric irritation
What’s the effect of ACE inhibitors?
Angiotensin II as part of the renin-angiotensin system causes vasocontriction
ACE inhibitors like ramipril block the angiotensin converting enzymes which convert angiotensin I to angiotensin II.
Given to patients with IHD with high blood pressure or diabetes mellitus.
What’s the treatment for angina?
Aspirin GTN β Blocker – first-line Long acting nitrate – second-line Statin ACE inhibitor
If drugs aren’t successful in managing angina
Revascularisation: PCI / CABG: MDT meeting
Third-line
Ca++ channel blocker
Potassium channel opener
Ivabradine
What is PCI?
Percutaneous Coronary Intervention (PCI, formerly known as angioplasty with stent) is a non-surgical procedure that uses a catheter (a thin flexible tube) to place a small structure called a stent to open up blood vessels in the heart that have been narrowed by atherosclerosis.
What is CABG?
Coronary Artery Bypass Grafting AKA Heart Bypass Surgery
Used when coronary arteries are narrowed or blocked
Blood vessels can be taken from your leg (saphenous vein), inside your chest (internal mammary artery - PREFERRED), or your arm (radial artery) to graft onto the coronary arteries to provide a alternative route around the blockage.
What are the pros and cons of PCI?
Pros Less invasive Convenient Repeatable Acceptable
Cons Risk stent thrombosis Risk restenosis Can’t deal with complex disease Dual antiplatelet therapy
What are the pros and cons of CABG?
Pros
Better prognosis
Deals with complex disease
Cons Invasive Risk of stroke, bleeding Can’t do if frail, co-morbidities One time treatment Length of stay Time for recovery
What are acute coronary syndromes?
Covers a spectrum of acute cardiac conditions from unstable angina to varying degrees of evolving myocardial infarction (MI)
How is unstable angina clinically classified?
Cardiac chest pain at rest
Cardiac chest pain with crescendo pattern
New onset angina
Take history, ECG, troponin levels (no significant rise in unstable angina)
How is STEMI and NSTEMI diagnosed?
ST-elevation MI can usually be diagnosed on ECG at presentation
Non-ST-elevation MI is a retrospective diagnosis made after troponin results and sometimes other investigation results are available.
May also be defined retrospectively as non-Q wave or Q-wave (broader and deeper) MI on the basis of whether new pathological Q waves develop on the ECG.
STEMI and MI with LBBB are more likely to develop pathological Q wave formation.
What are the common symptoms of an MI?
Cardiac chest pain that is:
unremitting
usually severe but may be mild or absent
occuring at rest
associated with sweating, breathlessness, nausea and/or vomiting
one third occur in bed at night
