Session 7 - Atheroma Flashcards
Atheroma
What is atheroma?
Accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
What is atherosclerosis?
Thickening and hardening of arterial walls as a consequence of atheroma
What is arteriosclerosis?
Thickening of artery walls due to hypertension or diabetes mellitus
What are the different types of atheroma macroscopically?
The fatty streak
The simple plaque
The complicated plaque
Features of fatty streak atheroma
lipid deposits in intima
yellow, slightly raised
Features of the simple plaque
white, raised, irregular outline, widely distributed, enlarge and coalesce
Features of the complicated plaque
Thrombosis
Heamorrhage into plaque
Calcification
Aneurysm formation
Common sites of atheroma?
Aorta - especially abdominal Coronary arteries Carotid arteries Cerebral arteries Leg arteries
What are the early microscopic features of atheroma?
proliferation of smooth muscle cells
accumulation of foam cells (macrophages with lipid)
extracellular lipid
What are the later microscopic features of atheroma?
fibrosis
necrosis
cholesterol clefts
maybe inflammatory cells
disruption of internal elastic lamina -> media
ingrowth of blood vessels
plaque fissuring (blood pressure shearing force)
Clinical effects of atheroma?
Ischaemic heart disease
-> death
-> MI
-> angina pectoris
-> arrhytmias -> VF -> death
-> cardiac failure
Cerebral ischaemia
-> transient ischaemic attack (mini stroke)
-> cerebral infarction (stroke) -> Rx carotid endarterectomy
-> multi-infarct dementia (tiny infarcts)
Mesenteric ischaemia
-> ischaemic colitis ( atheroma in superior mesenteric artery)
-> malabsorption
-> intestinal infarction
Peripheral vascular disease
-> intermittent claudication
-> leriche syndrome -> iliac arteries, pain in buttocks
-> ischaemic rest pain
-> gangrene
Main cause of atheroma?
Hyperlipidaemia - high plasma cholesterol (LDL)
Signs of familial hyperlipidaemia?
corneal arcus
tendon xanthomas
xanthelasma
Pathogenesis of atheroma?
Endothelial injury due to: raised LDL toxins (cigarette smoke) hypertension haemodynamic stress
What does endothelial injury cause?
platelet adhesion, PDGF release, smooth muscle cell proliferation and migration -> matrix material
insudation of lipid, LDL oxidation
migration of monocytes into intima -> foam cells secrete cytokines -> further SMC stimulation, and recruitment of other inflammatory cells
Prevention of atheroma?
no smoking reduced fat treat hypertension less alcohol regular exercise
What cells are involved in atheroma? (6)
endothelial cells platelets smooth muscle cells (SMC) macrophages (foam cells) Lymphocytes Neutrophils
What do endothelial cells do?
Haemostasis
have altered permeability to lipoproteins
secretion of collagen
stimulate SMC
What do platelets do?
Haemostasis
stimulate SMC via PDGF
What do smooth muscle cells do?
take up LDLs and other lipid to form foam cells
synthesise collagen and proteoglycans
What do macrophages do?
oxidise LDLs
Take up lipids to become foam cells
secrete proteases (modify matrix)
stimulate proliferation and migration of SMC
What do lymphocytes do?
TNF may affect lipoprotein metabolism
stimulate proliferation and migration of SMC
What do neutrophils do?
secrete proteases leading to continued local damage and inflammation
What pathogens are associated with atheroma?
Chlamydia pneumoniae
Helicobacter pylori
Cytomegalovirus
Risk factors for atheroma? (13)
Age Gender Hyperlipidaemia Cigarette smoking Hypertension Diabetes mellitus Alcohol Infection Lack of exercise Obesity Soft water Oral contraceptives Stress and personality type
