diseases Flashcards
1- what is thrombosis?
- formation of a solid mass from the constituents of blood within the vascular system during life
- due disruption of Virchow’s Triad (endothelial injury, statis/ turbulent blood flow, hypercoagulability of blood)
1- where do you find a clot?
outside the body’s arteries + veins (? unconfirmed)
1- what are the symptoms for thrombosis?
ischaemia (insufficient blood flow to an organ, especially heart muscle)
1- what is the cause of thrombosis?
- pathogenesis: atheromatous coronary artery, turbulent blood flow, loss of intimate cells; denuded plaque; collagen exposed (platelets adhere and become activated)
- fibrin meshwork, RBCs all trapped = alternating bands (bands of Zahn (dark/light)
- further turbulence + platelet deposition
- propagation
- consequences
1- what are the three poles of Virchow’s triade?
- changes in blood vessel wall (atheroma)
- changes in the blood constituents (hyperviscosity/ hypercoagulability due to pregnancy or trauma)
- changes in the pattern of blood flow (stasis due to bed rest or travel/ turbulent)
1- what are the possible consequences of thrombosis?
depend on site/ extent/ collateral circulation (could be DVT, ischaemic limb disease, MI)
1- what are the possible outcomes of thrombosis?
- resolution
- organisation/ recanalisation
- propagation = embolism
- death
2- what is an embolism?
movement of abnormal detached intravascular solid/ liquid/ gaseous mass in the bloodstream, blocking the lumen of a vessel
2- where do most emboli come from?
they are mostly dislodged thrombi (thromboembolism)
2- what factors cause an embolism?
depends on the type of embolism
2- what is a systemic/ arterial thromboembolus? what are it’s consequences?
travels to wide variety of sites (lower limbs most common/ brain), consequences depend on vulnerability of affected tissues to ischaemia, calibre of occluded vessel, collateral circulation but usually:
- infarction occurs (ex: mural thrombus / aortic aneurysms / atheromatous plaques / valvular vegetations
2- what is a venous thromboembolus? where can it travel? what are it’s consequences?
originate from deep venous thrombosis (lower limbs); most common form of thromboembolic disease; can travel to the pulmonary arterial circulation; depending on size, may occlude main pulmonary artery / bifurcation / smaller arteries; often multiple; can cause silent issues / pulmonary infarction / right heart failure / sudden death
2- when can fat be an embolism? what organs can be affected?
- after major fractures
- syndrome of fat embolism in the brain/ kidneys/ skin affected
2- when can gas be an embolism?
- decompression sickness
- N2 forms as bubbles which lodge in capillaries
2- when can air be an embolism? how do you manage this?
- head and neck wounds, surgery
- cv catheters
2- when can tumours be similar to an embolism?
in metasasis
2- where can a trophoblast act as embolism?
can lodge in the lungs of pregnant women
2- when can septic material be an embolism?
in infective endocarditis
2- when can amniotic fluid be an embolism?
rare obstetric condition where amniotic fluid gets in mother’s bloodstream- common cause of collapse + death in childbirth
2- when can bone marrow be a embolism?
fractures (due to CPR)
2- when can foreign bodies form an embolism?
intravascular cannula tipis/ sutures
3- what is atherosclerosis/ atheroma
- formation of focal elevated lesions (plaques) in the intima of large and medium sized arteries
3- what can be the outcome of atherosclerosis/ atheroma?
- in coronary arteries this can lead to narrowed lumens and result in coronary ischaemia (reduced blood supply to the heart)
3- what can be the outcome of coronary ischaemia?
- angina
- myocardial infarctions (atheroma complicated by thromboembolism)
3- how is arteriosclerosis different from atherosclerosis?
arteriosclerosis is an age related change in muscular arteries (smooth muscle hypertrophy + reduplication of internal elastic laminae leads to intimal fibrosis and the vessel diameter decreases); cause of cardiac/ cerebral/ colonic/ renal ischaemia in the elderly
3- what is the pathogenesis of atherosclerosis/ atheroma?
- endothelial injury + dysfunction
- accumulation of lipoprotein (LDL) in vessel wall
- monocyte adhesion to endothelium
- migration into intima and transformation to foamy macrophages platelet adhesion
- factor release from activated platelet + macrophages -> recruits smooth muscle cells
- smooth muscle cells proliferation and produce an extracellular matrix + recruit T cells
- lipid accumulation (extracellular and in foamy macrophages) = necrotic core
- fibrous cap
3- what happens if the atherosclerosis/ atheroma ruptures?
exposure of highly thrombotic plaque contents (collagen/ lipid/ debris) to blood stream; activation of coagulation cascade and thrombotic occlusion in very short time
3- what are the signs for atherosclerosis/ atheroma?
- hyperlipidaemia
- corneal arcus (white ring around the iris)
- tendon axanthomata (swelling on the knuckles/ achilles)
- xanthelasmata; fat deposits around the eye
3- what are the complications of atherosclerosis/ atheroma?
- stenosis of 50-75% -> reversible tissue ischaemia -> angina
- very severe stenosis -> ischaemic pain at rest -> unstable agina
- peripheral lower limb stenosis -> intermittent claudication
- longstanding tissue ischaemia -> atrophy of tissue (wasting away)
- acute occlusion -> necrosis / infarction of tissues; myocardial infarction/ cerebral infection/ lower limb gangrene
- aneurysm
3- what are the risk factors for atherosclerosis/ atheroma?
- hypercholesterolaemia (most important risk factor as it causes plaque formation an d growth in absence of the others (LDL cholesterol) (comes from a mutation whereby you lack cell membrane receptors for LDL results in elevated plasma levels)
- smoking
- hypertension
- diabetes mellitus
- male
- elderly
- obesity/ sedentary lifestyle/ low birthweight/ low socio-economic status (all these are less common)
3- what causes endothelial injury?
- haemodynamic disturbances (turbulent flow)
- hypercholesterolaemia (increasing local production of reactive oxygen species which directly impairs endothelial cell function; function alters and they express cell adhesion molecules/ increase permeability for LDL and increase thrombogenicity)
3- what are the different layers of the artery wall? (from inside to outside)
endothelium, tunica intima, integral elastic lamina, tunica media, external elastic lamina, tunica adventitia/ external
3- how does the growth of atherosclerosis mainly take place in beginning? (1st & 2nd decade)
- growth mainly by lipid accumulation
- foam cells
- fatty streaks; yellow linear elevation of intimal lining (lipid-laden macrophages); may disappear/ no clinical significance
3- how does the growth of atherosclerosis take place at a later stage? (3rd decade)
- growth mainly by lipid accumulation
- intermediate lesions
- atheroma
3- how does the growth of atherosclerosis take place at en even LATER stage? (4th decade)
- smooth muscle & collagen / thrombosis & haematoma
- fibrous plaque; central lipid core; collagens provide structural strength (produced by smooth muscle cells); inflammatory cells reside in the cap (dead macrophages + new)
- complicated lesion/ rupture = haemorrhage into plaque (calcification); plaque aggregation forming a thrombus; rupture forming embolism
4- how does a stable ischaemic heart disease occur?
arises as a result of a mismatch between myocardial blood oxygen supply and demand
4- how can an angina attack be triggered?
any stress which increases cardiac work and myocardial oxygen demand (anything which increases heart rate/ stroke/ volume/ BP) most common: - exertion - cold weather - emotional stress - heavy meal
4- what is angina pectoris?
discomfort in chest and/ or adjacent areas (medial edge upper arm) associated with myocardial ischaemia but without myocardial necrosis
4- what is the usual sight for angina?
retrosternal
4- what is the usual character for angina?
tight band (pressure/ heavy)
4- what are the usual radiation sites for angina?
neck, jaw and arms
4- is angina stable?
yes until a spontaneous plaque rupture (thrombosis then occurs, causing a degree of occlusion causing acute coronary symptoms)
4- how is angina relieved?
GTN / rest
4- what is the cardiovascular differential diagnosis of the symptoms of angina?
aortic dissection/ pericarditis
4- what is the respiratory differential diagnosis of the symptoms of angina?
pneumonia/ pleurisy/ peripheral pulmonary embolism (pleuritic)
4- what is the musculoskeletal differential diagnosis of the symptoms of angina?
cervical disease/ costochondritis/ muscle spasm or strain
4- how do you rank angina using the Canadian classification of angina severity?
1= symptoms only on significant exertion, normal physical activity does not cause angina 2= slight limitation of ordinary activity, symptoms on walking 2 blocks or > 1 flight of stairs 3= marked limitation, symptoms on walking only 1-2 blocks or 1 flight of stairs 4= symptoms on any activity (getting washed/ dressed)
4- what are the typical symptoms of angina?
chest pain on exertion, normal at rest, fatigue, near syncope
4- what symptoms make angina unlikely?
- sharp/ stabbing pain (pleuritic/ pericardial)
- associated with body movements/ respiration/ very localised/ patient able to pinpoint site
- begins after exercise
- lasts for hours
4- what are the signs to look for when confirming angina diagnosis?
- tar stains
- centripedal obesity
- xanthalasma (lipid formation around eyes)
- hypertension
- abdominal aortic aneurysm
- arterial bruit
- absent or reduced peripheral pulses
- diabetic retinopathy/ hypertensive retinopathy on fundoscopy
4- what are typical signs of exacerbation of angina?
- pallor of anaemia
- tachycardia
- tremor
- ejection systolic murmur
- plateau pulse of aortic stenosis
- pansystolic murmur of mitral regurgitation
- heart failure
- basal crackles
- elevated JVP
- peripheral oedema
4- what are the risk factors for coronary artery disease?
- age
- gender
- family history
- genetic factors
- smoking
- lifestyle (exercise/ diet)
- diabetes mellitus
- hypertension
- hyperlipidaemia
4- what are the common causes of stable ischaemic heart disease?
- obstructive coronary atherosclerosis
- pathological increases myocardial oxygen demand
4- what could cause obstructive coronary atherosclerosis (cause of ischaemic heart disease)?
- coronary artery spasm (uncommon)
- coronary inflammation / arteritis (very rare)
- reduced oxygen transport (anaemia)
4- what could cause pathological increase in myocardial oxygen demand?
- permanent hypertension
- significant aortic stenosis
- hypertrophic cardiomyopathy or thyrotoxicosis
4- what would you want to investigate in bloods?
- FBC
- lipid profile
- fasting glucose
- electrolytes
- liver + thyroid tests
4- why would you go for a CXR when diagnosing ischaemic heart disease?
helps to show the causes of chest pain and can show pulmonary oedema
4- what would you expect to find on an ECG?
normal in over 50%, Q-waves can be present (prior MI), lateral ST-segment depression (evidence of left ventricular hypertrophy)
4- why would you do a exercise tolerance test (ETT)?
often can confirm angina; relies on ability to walk for long enough to produce sufficient CV stress; typical symptoms and ST segment depression for positive test; negative doesn’t exclude coronary atheroma but if negative at high workload then prognosis is good
4- why would you do a myocardial perfusion imaging?
superior to ETT in detection of CAD: localisation of ischaemia and assessing size of area affected; expensive; involves radioactivity, if available, used if ETT not possible/ equivocal; radionuclide tracer injected IV at peak stress on one occasion, at rest on another, comparison of images.
- normal myocardium will take up tracer
- ischaemia will cause trader to be passed down the body (=seen) at rest, but not after stress
- infarction will cause tracer to be passed down the body (=seen) at rest and after stress
4- when and why would you go for computed tomography (CT) coronary angiography?
done if:
-early or strongly positive ETT (suggests multi-vessel issues)
- diagnosis not cleared after non-invasiveness tests
- occupation or lifestyle with risk (drivers)
gives a definition of:
- coronary anatomy with sites
- coronary distribution
- nature of atheromatous disease
- helps decide whether medication alone is ok or whether percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) is needed
4- how do you perform a CT coronary angiogram?
- local anaesthetic
- arterial cannula inserted into femoral/ radial artery
- catheter passed to aortic root and introduced into ostium (opening) or coronary arteries
- radio-opaque contrast injected down coronary arteries and visualised on X-ray
4- how do drugs help stable ischaemic heart disease?
drugs help correct the imbalance by:
- decreasing myocardial oxygen demand (by reducing cardiac workload/ reducing heart rate/ reducing myocardial contractility/ reducing afterload)
- increasing the supply of oxygen (to ischaemic myocardium)
4- give examples of rate-limiters used for management of stable ischaemic heart disease
beta-blockers
ivabradine
calcium channel blockers
4- give examples of vasodilators used for management of stable ischaemic heart disease?
- calcium channel blockers
- nitrates (oral/ sublingual)
- potassium channel-openers
- anti-platelets (aspirin 75mg/ clopidogrel/ igagrelor)
- statins (HMG CoA reductase inhibitors/ fibrates; if total cholesterol above 3,5mmol/l)
- ace-inhibitors
4- give examples of beta-blockers (for relief of symptoms)
- CCBs (for relief of symptoms)
- ivabridine (for relief of symptoms)
- nitrates (for relief of symptoms)
- nicorandil (for relief of symptoms)
- aspirin (stopping disease progression)
- statins (stopping disease progression)
- ACEi (stopping disease progression)
- GTN used for immediate relief (sublingual) but no effect on mortality
general measures: address risk factors = BP/ diabetes mellitus/ cholesterol/ lifestyle
4- what two procedures can happen as an outcome of stable ischaemic heart disease?
- PCI/PTCA (requires aspirin + clopidogrel)
- CABG (long saphenous vein = conduit)
4- give examples of beta-blockers?
bisoprolol and atenolol
4- which nervous system do B blocker block? what effects do they have?
- sympathetic system
- decrease heart rate, decrease force of contraction, decrease systolic wall tension, decrease cardiac output, decrease velocity of contraction, decrease blood pressure, protect cardiomyocytes from oxygen free radicals formed during ischaemic episodes -> increase exercise threshold at which angina occurs (move the balance point of demand for oxygen closer to the supply; sudden cessation of beta-blocker therapy can cause myocardial infarction (rebound phenomena)
4- what are the contraindications for B blockers?
asthma, peripheral vascular disease, Raynaud’s Syndrome, heart failure (depend on sympathetic drive), bradycardia, heart block
4- what are the adverse drug reactions from B blockers?
tiredness, fatigue, lethargy, impotence, bradycardia, bronchospasm
4- what possible drug-drug interactions are there with B blockers?
- hypotension (anti-hypertensives)
- bradycardia (rate-limiting drugs)
- cardiac failure (negative inotropic agents)
- defective when used with NSAIDs
- exaggerate + mask hypoglycaemic actions of insulin
4- how do calcium channel blockers work?
by preventing L-type calcium influx into myocytes and smooth muscle lining arteries/ arterioles
4- what does rate-limiting mean?
reduce heart rate / reduce force of contraction
4- give examples of rate-limiting calcium channel blockers
diltiazem, verapamil
4- what does vasodilating mean?
reduce vascular tone and so produce vasodilation, reducing afterload (reducing myocardial work load)
4- give examples of vasodilating calcium channel blockers
nifedipine, amlodipine
4- what are the contraindications for vasodilating claim channel blockers?
never use nifedipine immediate release (fast acting vasodilators can precipitate MI/ stroke)
4- what possible joint adverse drug reactions are there to vasodilating calcium channel blockers?
ankle oedema (does not respond to diuretics)/ headache, flushing, palpitation
4- what nitrovasodilators exist?
- glyceryle trinitrate (GTN)
- isosorbide mononitrate
- isordbide dinitrate
4- how is GTN taken? why is it taken? how often can it be used?
- sublingual/ buccal/ transdermal (to avoid first pass metabolism
- GTN used for rapid treatment of angina pain
- can be used frequently and prophylactically
4- how is isosorbide mononitrate taken?
sustained release formation/ tablets; commonly given once a day sustained release formulation for prophylaxis
4- how is isosorbide dinitrate taken?
sustained formulation/ tablets; commonly given once a day sustained release formulation for prophylaxis
4- why are IV nitrates used?
mainstay in the treatment of unstable angina here they are used in combination with heparin
4- how do IV heparin work?
work by relaxing almost all smooth mdcl by releasing nitrous oxide which stimulates the release of cGMP which produces smooth muscle relaxation; reduce preload (reducing venous return) and afterload (arteriolar dilatation) so reduce myocardial oxygen consumption/ also direction of blood flow to ischaemic areas of the myocardium; no evidence that nitrates reduce mortality
4- what problem is associated with the consumption of nitrates?
tolerance can develop rapidly; the problem can be overcome by giving asymmetric doses of nitrate 8am/2pm; sustained release formulation incorporates a nitrate-free period
4- what potential adverse drug reactions are there with nitrate intake?
headache/ hypotension (GTN syncope)
