Atherosclerosis and associated diseases Flashcards
Distinguish arteriosclerosis and atherosclerosis
Arteriosclerosis - narrowing/hardening of arteries as result of aging: prolif. of SMC, loss of elasticity, intimal fibrosis
Atherosclerosis - narrowing of arteries as result of formation of atheromatous plaques
Outline stages of atheroma development
- Fatty streak in intima- lipid laden macrophages/foamy cells, no clinical sig.
- Early plaque - round smooth plaque in intima formed by foamy cells
- Fully developed plaque - large, confluent plaques. May be calcified. Features:
- lipid core: dead macros, crystallised lipid
- Foamy cell rim around core: soft and highly thrombo
- Fibrous cap - consists of SMC’s proliferated from epithelium, collagen and inflammatory cells.
Features of complicated plaque
Haemorrhage into plaque - causes swelling, narrowing of artery
Fissuring of plaque and thrombosis
Describe the 2 biggest risk factors for atherosclerosis
Hypercholesterolaemia - mutation causing decrease in LDL receptors, heterozygous = major risk factor, cholesterol >8mmol. Homozygous = extreme risk, ultra high LDL cholesterol, death in infancy/childhood from atherosclerosis
Hyperlipidaemia - inherited or secondary. Causes elevated LDL/HDL/Total
Investigation: biochemistry, corneal arcus, tendon xanthomata, xanthalesma - fatty lumps around eyes
List other major risk factors for atherosclerosis
Hypertension, Smoking, Diabetes, Poor diet, Male, Age
Lesser risk factors
Obesity, lack of exercise
Describe the role of hypercholesterolaemia in plaque development
responsible for injury, hypercholesterolaemia causes pro-inflammatory state and productino of ROs.
ROs react with cholesterol that accumulates in intima, forming lipoproteins that cannot be digested by Macros. These cause foamy cell formation and death in plaques.
Outline development of atheromatous plaque
initial injury - turbulent flow or result of hypercholesterolaemia.
injury causes expression of ICAMs and VCAMs which adhere to monocytes and platelets.
Platelets cause clotting above injury.
Mono’s diff. become macros, phag. lipids and become foamy cells., accumulate in injury forming streak/early plaque.
inflammatory response to injury - platelets release PDGF
foamy macros are toxic to epithelial cells, release cytokines and growth factors.
Migration of SMC’s and T cells into intima. Proliferation of SMC’s and production of ECM - collagen, elastin.
Formation of fibrous cap.
Plaque maintained in pro-inflamm. state
Describe micro-thrombi
small thrombi that form on denuded areas of plaque by same mechanisms as plaque.
Complications of non-complicated atheromatous plaques
angina on exertion - 50-70% stenosis
angina at rest - >70%
Intermittent claudication if stenosis in lower limb arteries
Thrombus formation.
Atrophy of distal organs due to long term ischemia eg. kidneys in renal artery stenosis
Disease resulting from complicated plaque
Thrombus formation causing MI, irreversible ischaemia.
Aortic rupture
thrombo-embolism,
Which plaques are most vulnerable to rupture
thin walled, highly inflammed, large lipid core
List possible damage caused by irreversible ischamia
MI
massive stroke (carotid/cerebral)
Gangrene/tissue necrosis
List possible effects of Thrombo-embolism
Stroke, infarcs in distant tissues, MI
outline aortic rupture as result of stenosis
thinning of aorta wall due to inflamm. eventual rupture, massive peritoneal bleed, likely death.
Outline treatment of angina
Treat symptoms - CCB and B blocker to reduce contractility and cardiac demand. GTN for vasodilation and ivabridine.
Treat underlying causes - HT, hyperlipidemia
Prevention of disease - ACEI to prevent further vascular damage. Statin to lower lipid.
Antiplatelets - aspirin, clopidegrol
treatment of NSTEMI
For symptoms - MONA - morphine, O2, Nitrates, Aspirin/Clopidegrol
- then: Beta blocker, LMWH.
Subsequent management:
- ACEi and long term beta blocker to reduce heart O2 demand
- Anti platelet to prevent subsequent thrombosis
- Statin to reduce lipid levels
Advise changes in lifestyle!
treatment of STEMI
Symptoms: MOA - Morphine, Oxygen, antiplatelet (aspirin+clopidegrol)
Then PCI + anti-platelet if immediately available, or thrombolysis and transfer for subsequent PCI if required.
Subsequent management:
- ACEi and long term beta blocker to reduce heart O2 demand
- Anti platelet to prevent subsequent thrombosis
- Statin to reduce lipid levels
Advise changes in lifestyle!
Treatment of Heart failure
Diuretic - Furosemide + TLD
ACE Inhibitor or Angiotensin receptor blocker
Beta blocker - Bisoprolol
– or if intolerant Ivabradine – inhibits signaling from SA
Digoxin
Warfarin
Treatment of stroke
Establish whether ischemic or haemorrhagic
Ischemic:
Thrombolyse if within 4.5 hours + Antiplatelet - (aspirin/clopidegrol)
Manual clot retrieval if ultra dense clot + thrombolysis
hemicraniotomy may be required if massive cerebral oedema.
subsequent management: antiplatelet and warfarin/ribaroxiban for 3 months
Treatment of underlying risk factors.
Treatment of claudication, critical limb ischemia and acute critical limb ischemia
Preventative - underlying factors
Anti-thrombotics: LMWH, clopidegrol
ACEi for HT
Statin to lower cholesterol
curative - PTA
For acute critical limb ischemia:
Thrombolysis and angioplasty or embolectomy.
Amputation may be required if tissue is necrotic
Describe treatment for DVT, PE and massive PE
DVT and PE: LMWH (deltaparin, fondiparinux) until INR is >2, then warfarin
Massive PE - Thrombolysis or surgical embolectomy. then LMWH (deltaparin, fondiparinux) until INR is >2, then warfarin
Treatment of mitral stenosis
Diuretics to reduce preload and afterload
Reduce dietary Na
Surgical - ballooning/valvotomy or valve replacement in severe disease
Treatment of mitral regurg
If acute - diuretic, possible GTN.
If chronic - valve replacement
If AF is present treat accordingly (Beta blocker, digoxin, anticoag.)
