Define atherosclerosis
Atherosclerosis is the accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries.
The thickening and hardening of arterial walls as a consequence of atheroma
Define arteriosclerosis
The thickening of the walls of arteries and arterioles usually as a result of hypertension or diabetes mellitus
What are the macroscopic features of atherosclerosis?
Fatty streak
Simple plaque
Complicated plaque
What is a fatty streak?
Lipid deposits in intima
Yellow, slightly raised
Relationship to atherosclerosis somewhat debatable but, seen as precursors for it.
What is a simple plaque?
raised yellow / white
Irregular outline
Widely distribute
Enlarge and coalesce
What is a complicated plaque?
Thrombosis
Haemorrhage into plaque
Calcification - Can see on x-rays
Aneurysm formation - expansion of artery
What are some common sites of atherosclerosis?
- Aorta - particularly abdominal (renal and could go into iliac)
- Coronary arteries
- Carotid arteries
- Cerebral arteries
- Leg arteries
What is normal arterial structure?
- Endothelium
- Sub-endothelial CT
- Internal elastic lamina (closer to heart, more elastic and muscle)
- Muscular media
- External elastic lamina
- Adventitia
Microscopic features of atherosclerosis (early changes)
Early changes:
- Proliferation of smooth muscle cells
- Accumulation of foam cells
- Extracellular lipid
Microscopic features of atherosclerosis (later changes)
Later changes:
- Fibrosis
- Necrosis
- Cholesterol clefts - where cholesterol was
- +/- inflammatory cells
- Disruption of internal elastic lamina
- Damage extends into media
- Ingrowth of blood vessels - leaky, can lead to haemorrhage
- Plaque fissuring
What are the clinical effects of atherosclerosis?
- Ischaemic heart disease
- Sudden death
- Myocardial infarction
- Angina pectoris (chest pain on exertion - goes away when rested)
- Arrhythmias
- Cardiac failure - due to fibrosis.
- Manifest as shortness of breath and pulmonary oedema.
What are the clinical effects of athlerosclerosis in the brain?
Cerebral ischaemia
- Transient ischaemic attach (TIA - mini stroke as resolve in 24hrs)
- Cerebral infarction (stroke) - thrombus in cerebral artery or thromboembolus
- Multi-infarct dementia
Clinical effects of atherosclerosis of the bowel
Mesenteric ischaemia
- Ischaemic colitis
- Malabsorption
- Intestinal infarction
What are the clinical effects of peripheral vascular disease?
- Arms are rare so usually legs
- Intermittent claudication - distance can walk before pain in calf.
- Leriche syndrome (blockage of abdominal aorta as it goes to common iliac arteries.)
- Ischaemic rest pain - when worse
- Gangrene - once tissue has infarcted.
Why do people get athleroscleosis?
- Age - slowly progressive throughout adult life. Risk factors operate over years
- Gender - males more affected than females as women are protected relatively before menopause. There is a presumed hormonal basis
- Hyperlipidaemia
- Cigarette smoking
- Hypertension
- Diabetes mellitus
- Alcohol
- Infection
Why does hyperlipidaemia cause athlerosclerosis?
- High plasma cholesterol associated with athlerosclerosis
- LDL most significant
- HDL protective
Lipid metabolism
- Lipid in the blood is carried on lipoproteins
- Lipoproteins carry cholestrol and triglycerides (TG)
- Hydrophobic lipid core
- Hydrophilic outer later of phospholipid and apolipoprotein (A-E)
- Chylomicrons - Transport lipid from intestine to liver
- LDL - Rich in cholestrol and carries to choletrol to non-liver cells.
- VLDL - Carry cholestrol and TG to liver. TG removed leaving LDL.
- HDL - Carry cholestrol from periphery back to liver
Apolipoprotein E
- Genetic variations in Apo E are associated with changes in LDL levels
- Polymorphisms of the genes involved lead to at least 6 Apo E phenotypes.
- Polymorphisms can be used as risk markers for atherosclerosis
Familial Hyperlipidaemia
Genetically determined abnormalities of lipoproteins
Lead to early development of atherosclerosis
Associated physical signs:
- Arcus (A thin, whitish circle around the iris; normal finding in old people.)
- Tendon xanthoma (deposits of cholestrol)
- xanthelasma (depositions of cholestrol)
How does cigarette smoking cause atherosclerosis?
- Don’t know - effect coagulation system, reduced Prostaglanin I2, Incresed platelet aggregation.
- Powerful risk factor for IHD
- Risk falls after giving up.
Hypertension and atherosclerosis
- Strong link between IHD and high systolic / diastolic BP
- Mechanism uncertain
- Maybe endothelial damage caused by raised pressure.
Atherosclerosis and diabetes Mellitus
- DM doubles IHD risk.
- Protective effect in premenopausal women lost
- DM also associated with high risk of carebrovascular and peripheral vascular disease
- It is maybe related to hylerlipidaemia?
Atherosclerosis - Alcohol Consumption
Over 5 units per day is associated with increased risk of IHD
Alcohol consumption after associated with other risk factors e.g. smoking and high BP but still an independent risk factor.
Smaller amounts of alcohol may be protective.
Atherosclerosis-Infection
- Chlamydia pneumoniae
- Helicobacter pylori
- Cyromegalovirus
All look at but no hard evidence.
