PP 6 Atherosclerosis Flashcards
What blood test is used to aid diagnosis of myocardial infarction?
Troponin I + T
4 hours after MI
When should the troponin test be taken after MI?
4 hours after
Atheroma meaning
Necrotic core of atherosclerotic plaque
Arteriosclerosis meaning
Thickening of walls of arteries or arterioles
What is arteriosclerosis usually due to?
Hypertension
Diabetes mellitus - smooth muscle hypertrophy
What can arteriosclerosis lead to?
Poor tissue perfusion
Inelastic/weak vessels > aneurysm
Increased risk of thrombosis
Atherosclerosis meaning
Accumulation of intracellular and extracellular lipids in intima + media of large + medium sized arteries
What can cause chronic endothelial damage?
Hyperlipidaemia
Hypertension
Smoking - toxins
Haemodynamic stressors
What does endothelial dysfunction lead to?
Platelet adhesion
Smooth muscle cell proliferation and migration
Lipids cross into intima
Monocytes > macrophages
What do foam cells secrete?
What does this cause?
Cytokines
- Further smooth muscle cell stimulation
- Recruitment of other inflammatory cells
What do smooth muscle cells produce?
Matrix material - collagen + elastin
What are the components of an atherosclerotic plaque?
Cells
Lipids
Extracellular matrix
What are the cells in an atherosclerotic plaque?
Endothelial cells
Platelets
Neutrophils
Macrophages
WBCs
SMC
What lipids make up atherosclerotic plaques?
Intracellular - foam cells
Extracellular - pools
What makes up the extracellular matrix in atherosclerotic plaque?
Collagen
Elastin
Proteoglycans
Function of endothelial cells
- Role in haemostasis
- Altered permeability to lipoproteins
- Production of collagen
- Stimulation of proliferation + migration of SMCs
What is the microscopic appearance of a stable/simple atherosclerotic plaque?
Fibrosis
Necrosis
Cholesterol clefts
+/- inflammatory cells
What is the microscopic appearance of an unstable/complicated atherosclerotic plaque?
Disruption of the internal elastic lamina
Damage extends into media
New vessels grow into plaque
Plaque breaks/erodes/ulcers
What is the microscopic appearance of a fatty streak?
Accumulation of foam cells
Extracellular lipid
Proliferation of smooth muscle cells
What is the macroscopic appearance of a stable/simple atherosclerotic plaque?
Raised white/yellow
Irregular outline
Enlarged - widely distributed
What is the macroscopic appearance of an unstable/complicated atherosclerotic plaque?
Yellow + red (haem + thrombosis)
Irregular
Rough + hard - calcified
What is the macroscopic appearance of a fatty streak?
Slightly raised yellow area in intima
Complications of atherosclerosis
Ulceration
Thrombosis
Vasospasm
Embolisation - from thrombus or plaque
Calcification
Haemorrhage
Aneurysm
Rupture of atherosclerotic artery
Vasospasm meaning
Sudden constriction of blood vessel
Effect of calcification on vessels
Stiffens vessel
Reduced elasticity
Effects of arterial narrowing + occlusion
Ischaemia
Infarction
Specific effects dependent on site
What does cerebral ischaemia cause?
Transient ischaemic attack
Stroke - cerebral infarction
Vascular dementia
What differentiates a TIA from a stroke?
TIA - symptoms of stroke <24 hours
What is a TIA?
Transient ischaemic attack
What can an atherosclerotic plaque in carotid arteries cause?
Plaque can embolism > cerebral circulation
Causes TIA or stroke
What does myocardial ischaemia cause?
Sudden death
Myocardial infarction
Angina pectoris
Arrhythmias
Cardia failur
What does acute mesenteric ischameia cause?
Intestinal infarction
What does chronic mesenteric ischaemia cause?
Ischaemic colitis
Malabsorption
What is ischaemic colitis?
Inflammation of colon
What does peripheral vascular disease cause?
Acute limb ischaemia
Intermittent claudication
Ischaemic rest pain
Gangrene
What are the symptoms of limb ischaemia?
6 Ps
Pallor
Pain
Paraesthesia
Perishingly cold
Paralysis
Pulselessness
What is intermittent claudication?
Limping
What can an atherosclerotic plaque in the abdominal aorta cause?
Rupture
Thrombosis + emboli > acute limb ischaemia
Aneurysmal formation
How does gender have an effect on atherosclerosis?
Protective effect in premenopausal women
What three areas can there be defects in lipid metabolism?
Enzyme defects
Receptor defect
Apolipoprotein defects
Enzyme defects in lipid metabolism
Lipoprotein lipase
Receptor defects in lipid metabolism
Example of conditions caused by this
LDL receptor mutations
e.g familial hypercholesteroaemia
Apolipoprotein defects in lipid metabolism
ApoA1 deficiency
ApoA1 variants
ApoE variants
Presentation of familial Hyperlipidaemia
Tendon xanthomas
Xanthlasma
Cornea arcus
What is cornea arus?
White/blue circle around eye
What is the clinical significance of cornea arcus?
Concern in young children
Normal in older people
Sign of high cholesterol
What can familial Hyperlipidaemia lead to?
Early development of atheroscleosis
Prevention + reduction of familial Hyperlipidaemia
Decrease cholesterol + LDLs in diet
Statins - lipid lowering drugs
Low fat + high fibre diet
Aspirin
Effects of cigarette smoking on atherosclerosis
- Risk factor for atherosclerosis and ischaemic heart disease
- dose related
- risk decreases after stopping
Effects of hypertension on atherosclerosis
Link between high BP and IHD
Effects of cigarette on atherosclerosis
- Double IHD risk
- Protective effect in premenopausal women lost
- High risk of cerebrvasular + peripheral vascular disease
Effects of alcohol consumption on atherosclerosis
> 5 units/day = increased risk of IHD
Small amounts can be productive
How can you reduce the atherosclerotic burden?
Statins - decreases cholesterol
Anti-hypertensives - decreases BP
Exercise
Normal BMI
Non-smoker
Alcohol in moderation
Balance diet - decreased diabetes risk
Diabetes medication
CANTOS - targets inflammation
What is an example of a diet which reduces the risk of diabetes?
Mediterranean
Three macroscopic features of atherosclerosis
Fatty streak
Simple plaque
Complicated plaque v
Identify four theories explaining the pathogenesis of atherosclerosis
Thrombogenic theory
Insulation theory
Monoclonal hypothesis
Reaction to injury hypothesis
Modifiable risk factors of atherosclerosis
- smoking
- obesity
- Hyperlipidaemia
- hypertension
Non modifiable risk factors of atherosclerosis
- older age
- male
- post menopausal women
- family history
What is the most important risk factor of atherosclerosis
Hypercholesteroaemia
Where does atherosclerosis commonly affect? (5)
- abdominal aorta
- coronary arteries
- carotid arteries
- cerebral arteries
- arteries in leg
Outline the formation of plaque + what occurs after
- chronic endothelial damage
- accumulation of LDL in tunica intima
- oxidation of LDL
- phagocytosis by macrophage > foam cells
- migration of SMC into tunica media > fatty streak
- plaque growth
- SMC on surface form fibrous cap
- endothelium stretches over plaque + platelets adhere to gaps
- central plaque cells die > Atheroma
- small blood vessels grow into plaque from tunica adventitia
Why does physical activity reduce your risk of atherosclerosis?
Regular physical activity can lower BP + improve cholestrol levels
