Atherosclerosis Flashcards
What does atheroma / atherosclerosis involve?
The formation of focal elevated lesions (plaques) in intima of large and medium sized arteries
What is atheroma?
Atheromatous plaques narrow the lumen causing ischaemia
What is atherosclerosis?
Age related change in muscular arteries
What happens in atherosclerosis?
Smooth muscle hypertrophy
Reduplication of internal elastic laminae
Intimal fibrosis
Decrease in vessel diameter
Pathology of atheroma
Fatty streak
Yellow linear elevation of intimal lining
Comprises masses of lipid laden macrophages
Two step process in the development of atheromatous plaques
- Injury to the endothelial lining of the artery
2. Chronic inflammatory and healing response of the vascular wall to agent causing injury
Pathogenesis of atherosclerosis
- Endothelial injury and dysfunction of endothelial cells
- Accumulation of LDL (lipoproteins) in vessel wall
- Monocyte adhesion to endothelium - migration into the intima and transformation to foamy macrophages
- Platelet adhesion
- Factor release from activated platelets and macrophages results in smooth muscle recruitment
- Smooth muscle cell proliferation, extracellular matrix and T cell recruitment
- Lipid accumulation (extracellular and in foamy macrophages)
Causes of endothelial injury
Haemodynamic disturbances (turbulent flow) Hypercholesteraemia
What happens in injured endothelial cells are functionally altered?
Enhanced expression of cell adhesion molecules
High permeability for LDL
Increased thrombogenicity
A fully developed atheromatous plaque consists of…..
Central lipid core with fibrous tissue cap, covered by arterial endothelium, rich in cellular lipids/debris derived from macrophages (died in plaque)
Collagens
Inflammatory cells
Pathology of complicated atheroma
Established atheromatous plaque
Haemorrhage into plaque which if heals leads to calcification
Plaque rupturing/fissuring
Thrombosis
What % of stenosis of a vessel lumen can result in a critical reduction of blood flow in a distal arterial bed resulting in reversible tissue ischaemia?
> 50 - 75%
What would a stenosed atheromatous coronary artery result in?
Stable angina
What would very severe stenosis of a coronary artery result in?
Ischaemic pain at rest - i.e. unstable angina
What would ileal, femoral or popliteal artery stenosis result in?
Intermittent claudication (peripheral artery disease)
What does long standing tissue ischaemia result in?
Atrophy of affected organ
Major complication of acute atherothrombotic occlusion
Rupture of the plaque
What does rupture of a atherothrombotic plaque result in?
Exposes highly thrombogenic plaque contents (collagen, lipid, debris) to blood stream - activation of coagulation cascade and thrombotic occlusion in very short time
What does total occlusion of an artery result in?
Irreversible ischaemia - necrosis
What would total occlusion of a coronary artery result in?
MI
What would total occlusion of a carotid or a cerebral artery result in?
Stroke
What would the total occlusion of e.g. ileal, femoral or popliteal artery result in?
Lower limb gangrene
What does embolic occlusion of small vessels lead to?
Small infarcts in organs
Pathology of ruptured AAA
Media beneath atheromatous plaques gradually weakned (lipid related inflammatory activity in plaque)
Leads to dilatation of great vessel
Slow but progressive
Sudden rupture leads to massive retroperitoneal haemorrhage
Who are AAA seen in?
Elderly
What size of aneurysms in diameter are at high risk of rupture?
> 5cm
Contents of atheromatous plaque
Thin fibrous cap
Large lipid core
Prominent inflammation
Preventative measures of atheroma
Stop smoking Control BP Weight loss Regular exercise Dietary modifications
Secondary prevention of atheroma
Cholesterol lowering drugs
Aspirin
What does aspirin do?
Inhibits platelet aggregation to decrease risk of thrombosis on established atheromatous plaques
Most important risk factor for atheroma
Hypercholesterolaemia
Why is hypercholesterolaemia the most important risk factor for atheroma?
Causes plaque formation and growth in the absence of other risk factors
Risk factors for atheroma
Hypercholesterolaemia Smoking HTN DM Male Elderly Obesity Sedentary lifestyle Low socio economic status Low birthweight
Signs of major hyperlipidaemia
Biochemical - LDL, HDL, total cholesterol, triglycerides
Corneal arcus
Tendon xanthomata
Xanthelasmata
What is corneal arcus?
White rim formed around the iris
What is xanthelasmata?
Yellowish deposit of fat under the skin, usually on or around the eyelids
Where do you see tendon xanthomata?
Knuckles
Achilles
What is normal blood flow?
Laminar
Two types of abnormal blood flow
Stasis
Turbulence
What is stasis?
Stagnation of blood flow
What is turbulence?
Forceful, unpredicted flow
Examples of defects in blood flow
Thromboembolism Atheroma Hyperviscosity Spasm External compression Vasculitis Vascular steel syndrome
Definition of vasculitis
Inflammation of blood vessel wall
Definition of vascular steel syndrome
Vascular network within a network steals blood from another vascular network in the same organ
Pathogenesis of thrombosis - virchows triad
- Endothelial injury
- Stasis or turbulent blood flow (i.e. abnormal blood flow)
- Hypercoagulability of the blood
Possible outcomes of thrombus
Resolution
Organisaion / recanalization
Death
Propagation (leading to embolism)
What do the factors of virchows triad cause?
Thrombus
Examples of changes in blood constitutents in virchows triad
Hyperviscosity
Post traumatic / post surgical hypercoagulablity
Examples of changes in blood flow in virchows triad
Post op stasis
Atheromatous plaque or aneurysm causing turbulent flow
Relationship between atheroma and thrombosis
Arterial thrombosis is most commonly superimposed on atheroma
Thrombus vs clot
Thrombus - solidifies within vascular system
Clot - solidifies outside vascular system
What is a post morteom clot?
Solidifying of blood after death
Definition of embolism
The movement of abnormal material in the bloodstream and its impaction in a vessel, blocking its lumen
Types of embolus
Systemic / arterial thromboembolus Venous thromboembolous Fat Gas Tumour Trophoblast Septic material Amniotic fluid Bone marrow Foreign bodies
Sources of arterial thromboembolus
Mural thrombosis
Aortic aneurysms
Atheromatous plaques
Valvular vegetations
Where do venous thromboembolus originate and where do they go?
Originate from deep venous thrombosis (lower limbs)
Travel to pulmonary arterial circulation (may occlude main pulmonary artery, bifurcation (saddle embolus) or smaller arteries
What is the most common form of thromboembolic disease?
Venous thromboembolus
What do multiple pulmonary emboli result in?
Pulmonary HTN
Right ventricular failure
When would you get a fat embolus?
After major fractures
Syndrome of fat embolism
Brain
Kidneys
Skin
When would you get a gas embolus?
Decompression sickness (e.g. a diver)
Head and neck wounds
Surgery
CV lines
Risk factors for DVT and pulmonary thromboembolism
Cardiac failure Severe trauma / burns Post op / post partum Nephrotic syndrome Disseminated malignancy Oral contraceptive Increased age Bed rest / immobilisation Obesity PMH of DVT
Prophylaxis for surgical patients at risk
TEDs
s/c heparin
What risk stratification score is used to calculate a persons 10 year CVS risk score?
QRISK2
What statin is used for primary prevention?
Atorvastatin 20mg
What statin is used for secondary prevention?
Atorvastatin 80mg
Diagnostic criteria for orthostatic hypotension
Drop in SBP of at least 20mmHg and/or drop in DBP of at least 10mmHg after 3 mins of standing
When should statins be stopped?
Pregnancy
When an oral macrolide antibiotic is started
