6. Atherosclerosis Flashcards
What is the difference between “arteriosclerosis” and “atheroma”?
- arteriosclerosis = thickening of walls of arteries and arterioles, usually as a result of hypertension or diabetes mellitus
- atheroma = thickening and hardening of arterial walls as a consequence of atherosclerosis
What is “atherosclerosis”?
accumulation of intracellular and extracellular lipid in the intima and media of large- and medium-sized arteries
What are the 3 macroscopic stages/features of atherosclerosis?
- fatty streak
- simple plaque
- complicated plaque
What is the difference between fatty streak, simple plaque and complicated plaque?
- fatty streak
- yellow, slightly raised
- lipid deposits in intima - plaque
- raised, yellow/white, irregular outline
- widely distributed, enlarge and coalesce - complicated plaque
- calcification
- haemorrhage into plaque
- thrombosis
- aneurysm formation
What are the common sites of atherosclerosis?
i) aorta - esp. abdominal
ii) coronary arteries (right, left anterior descending and circumflex)
iii) carotid arteries
iv) cerebral arteries
v) leg arteries
Describe the microscopic features of atherosclerosis.
Early changes:
- proliferation of smooth muscle cells
- accumulation of foam cells
- extracellular lipid deposition
Later changes:
- fibrosis
- necrosis
- cholesterol clefts
- +/- inflammatory cells
Later changes:
- disruption of internal elastic lamina
- damage extends into media
- ingrowth of blood vessels
- plaque fissuring
Describe the effects of severe atherosclerosis in ischaemic heart disease.
Can lead to:
- sudden death
- MI
- angina pectoris
- arrhythmias
- cardiac failure
Describe the effects of severe atherosclerosis in cerebral ischaemia.
Can lead to:
- transient ischaemic attach (neurological symptoms similar to stroke but resolve in 24hrs)
- cerebral infarction - stroke (often unilateral neurological probs that don’t resolve)
- multi-infarct dementia (many small cerebral infarcts causing dementia)
Describe the effects of severe atherosclerosis in mesenteric ischaemia.
Can lead to:
- ischaemic colitis (pain and bleeding often at splenic flexure of large bowel due to poor blood supply)
- malabsorption (if small bowel affected)
- intestinal infarction (in mesenteric artery - affects all small bowel)
Describe the effects of severe atherosclerosis in peripheral vascular disease.
Affects blood supply to legs causing:
- intermittent claudication (pain in calves induced by exercise due to reduced arterial supply)
- Leriche syndrome (pain in buttocks and impotence)
- ischaemic rest pain (not enough blood supply even at rest)
- gangrene
Describe the effects of severe atherosclerosis in the abdominal aorta.
Can cause abdominal aortic aneurysm - rupture causes massive intraperitoneal haemorrhage.
Name examples of risk factors for atherosclerosis.
- age - slowly progressive throughout adult life
- gender - post-menopausal women less at risk due to higher oestrogen levels
- hyperlipidaemia - high plasma cholesterol associated with atherosclerosis: LDL most significant whilst HDL protective
- genetics - genetic variations in ApoE associated with changes in LDL levels (6 ApoE phenotypes, polymorphisms can be used as risk markers for atherosclerosis)
- smoking - uncertain mode of action: coagulation system? reduced prostaglandin I2? increased platelet aggregation? Risk falls after giving up. Powerful risk factor for IHD.
- hypertension - uncertain mode of action: endothelial damage caused by raised BP? Strong link between IHD and high BP.
- diabetes mellitus - uncertain MOA: related to hyperlipidaemia and hypertension? Doubles IHD risk, also associated with high risk of cerebrovascular and peripheral vascular disease. Protective effect in premenopausal women lost.
- alcohol consumption - >5 units/day associated with increased risk of IHD. Smaller amounts may be protective.
- infection - e.g. Chlamydia pneumoniae, Helicobacteri pylori, cytomegalovirus
- other: lack of exercise, obesity, soft water, oral contraceptives, stress and personality type?
Which inherited disease is associated with early dev of atherosclerosis? What are the physical signs of this?
familial hyperlipidaemia
i) corneal arcus
ii) tendon xanthomas
iii) xanthelasma
What are the 4 hypotheses for atherosclerosis pathogenesis?
1- thrombogenic theory
2- insudation theory
3- monoclonal hypo.
4. reaction to injury hypo.
Describe the thrombogenic theory.
(Karl Rokitansky 1852)
- plaques formed by repeated thrombi
- lipid derived and released from thrombi
- overlying fibrous cap
