10 - Atherosclerosis Flashcards
What is the definition of atherosclerosis?
- Accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
- Leads to necrotic atheroma in middle and plaque can calcify
What part of the aorta is atherosclerosis most likely to occur in?
Abdominal rather than thoracic
What is arteriosclerosis?
Thickening and hardening of the arteries as a consequence of atherosclerosis
What is arteriolosclerosis?
Hardening and thickening of the arterioles, mainly affects the kidey. Little or no connection with atherosclerosis, linked to diabetes or sever hypertension
What is Monckeburg’s disease?
Uncommon disease where there is calcification of the media of the large arteries
What is an atheroma and what does it consist of?
Necrotic core of atherosclerotic plaque, consists of dead cells, debris and cholesterol crystals
What is an atherosclerotic plaque?
- Lesion of atherosclerosis containing:
What are the proccesses involved in plaque formation?
1. Chronic endothelial insult
- Lipid droplets, mainly from LDL’s, cross from damaged endothelium and accumulate in intima. Monocytes attracted
- Lipids oxidised and macrophages ingest them to become foam cells
- Crowds of foam cells cause endothelium to bulge and smooth muscle cells migrate into lesion from media and start to proliferate = fatty streak
- Plaque continues to grow as foam and smooth muscle cells proliferate. Muscle cells take up some lipid and foam secrete cytokines
- Smooth muscle cells lay on top of plaque beneath endothelium and reenforced by collagen and elastin to form fibrous cap
- As endothelium stretches over plaque gaps appear between cells and platelets adhere to gaps
- Cells in centre of plaque undergo necrosis and released cholesterol so cholesterol crystals
- Small blood vessels grow into plaque from adventitia and plaque can undergo calcification
What can cause chronic endothelial insult?
- Hyperlipidaemia
- Smoking
- Hypertension
- Haemodynamic factors
What are the macroscopic appearances of atherosclerosis?
1. Fatty streak: flat and no disturbance to blood. yellow and form in childhoold
2. Simple plaque: white/yellow and impinge on lumen
3. Complicated plaque: Thrombosis and haemorraghe into plaque
What does atherosclerosis look like microscopically?
- Fatty streak: foam cells, extracellular lipid, smooth muscle cells (flat and yellow)
- Plaque: Fibrosis, necrosis, cholesterol clefts, distruption of elastic lamina, extension into media and ingrowth of vessels from adventitia, inflammatory cells (raised)
Where are the most common sites of athersclerosis?
- Effects mainly seen in heart, brain, kidneys, legs or bowel
How can plaques become complicated?
- Ulceration: fibrous cap eroded and plaque exposed to blood so thrombogenic
- Thrombosis on plaque: may occlude lumen
- Spasm at site of plaque: vasoconstrictors released from thrombi
- Embolisation
- Calcification: stiffening artery
- Haemmoraghe: break plaque open or occlude
- Aneurysm formation
- Rupture of atherosclerotic artery: weakend media mainly in cerebral arteries with hypertension
Why might a atherosclerotic plaque lead to an aneurysm?
- Local dilatations due to elastic tissue destroyed by plaque which weakens walls
- May rupture or thrombus occur within them that embolises
What conditions can plaques lead to ?
- Heart: MI, chronic ischemic heart disease, arrythmias, cardiac failure, sudden cardiac death
- Brain: TIA, cerebral infarction (stroke), multiinfarct dementia
- Kidneys: hypertension, renal failure
- Legs: peripheral vascular disease, gangrene
- Bowel: ischemic colitis, malabsorption, bowel infarction
ALL DUE TO NARROWING OF VESSELS OR EMBOLISMS FROM PLAQUE
What are two diseases only of the arteries?
- Aneurysms
- Atherosclerosis
What is dilatation of the veins called?
- Varices
What are the different types of aneurysms?
- Saccular: mainly in aorta, generally lined or filled by thrombus and protect aneurysm from bursting
- Fusiform: is spindle shaped
- Dissecting: Only really in aorta and major branches. Form in couple of minutes and fatal.
What causes dissecting artery?
- Inner layer of arterial walls tears open
- Blood enters the tear and separates media into two layers
- As the tears fills with blood lumen of artery can be occluded
- Blood can push back into lumem by secondary tear
What are some non-modifiable risk factors for atherosclerosis?
- Age
- Gender: males till menopause as oestrogen protective
- Genetic predisposition: clustering of risk factors like high cholesterol, diabetes, apolipoprotein E genotype associated with high HDL
What is familial hyperlipidaemia/hypercholesterolaemia?
- Recessive
- Defects in LDL receptor so decreased hepatic uptake of LDL so high circulating LDL
- MI before age of 20 and high risk of atherosclerosis
What are some modifiable risk factors associated with atherosclerosis?
- Hyperlipidaemia
- Hypertension (pressure damages walls)
- Smoking (inflammation of cells walls so oxidation of lipids)
- Geography (lower incidence in south america, asia and africa)
- Obesity (hypertension, reduced LDL, diabetes)
- Infection
What are some possible risk factors of atherosclerosis that haven’t already been named?
- Lack of excercise
- Obesity
- OC pill
- Soft water
- Stress
What are the different theories of the pathogenesis of atherosclerosis?
- Thromogenic
- Insudation
- Monoclonal
- Reaction to injury
What is the response to injury hypothesis for atherosclerosis formation?
- Chronic inflammatory response of arterial wall initiated by injury to endothelium
- Lesion progression due to interaction between modified lipoproteins, macrophages, T-lymphocytes and cells of arterial wall
What is the insudation hypothesis?
What is the thromogenic/encrustation hypothesis?
- Plaques formed as repeated thrombi overlying a thrombi fibrous cap
- Lipid core derived from thrombi
What is the monoclonal hypothesis of atherosclerosis?
- Some plaques monoclonal, from same smooth muscle
- Is each plaque a benign neoplastic growth induced by cholesterol or virus?
- Unlikely as some areas of normal arteries not clonal
What are the processes and cells involved in atherosclerosis?
How can you prevent atherosclerosis?
START IN CHILDHOOD
- stop smoking
- control hypertension
- control weight and regular exerise
- decrease LDL and increase HDL
- Hhigh fibre diet and low fat diet
- Treat diabeted
- Antioxidants like vitamin E
- Sensible alcohol intake to prevent hyperlipidaemia
What are some intervention strategies of atherosclerosis?
- Lipid lowering drugs, e.g aspirin, statins
- Thrombolysis, angioplasty, stents, CABG
What do each of the cells involved in atherosclerosis do?
ALL STIMULATE PROLIFERATION AND MIGRATION OF SMC
- Endothelial: haemostasis, produce collagen
- Platelets: haemostasis
- SMC: take up LDL to become foams, synthesis collagen and proteoglycans
- Macrophages: oxidise LDL, foam cells, secrete proteases to modify matrix
- Lymphocyes: TNF affect lipoprotein metabolism
- Neutrophils: secrete proteases causing inflammation
How does aspirin work as an anti-coagulant?
Prevents synthesis of thromboxane A2 so platelets cannot clot
What is this under a 27 year old patients armpit and what defect is causing this?
- Xanthoma
- Hyperlipidaemia due to familial hypercholesterolaemia from faulty LDL receptor
- Will have lots of foam cells under microscope
What are the two types of calcification in the body and how does it appear under the microscope?
Really blue under the microscope
This shows a bowel with a red infarct, what could be the cause of this?
- Atherosclerosis
- Thrombo-embolism
- Twisting on mesentry so torsion
- Abdominal adhesions
- Coagulation problems
Why would someone with this have a low blood pressure and high heart rate?
Septic shock as may be rupture so lots of commensals in the bowel have got into the systemic circulation
What is the difference between a TIA and a stroke, and what is the most likely cause of a stroke?
- Timing
- Often due to atherosclerotic plaque in carotid arteries
What is a watershed infarct?
- Wedge shaped infarct due to being on the border of two blood supplies and being the furthest away
- Often seen in strokes when this occurs at border between anterior and posterior comparment for example
