Atherosclerosis COPY Flashcards
What is an atheroma?
Accumulation of intracellular and extracellular lipid in the intima and media of the large and medium arteries
What is atherosclerosis?
Thickening and hardening of arterial walls due to an atheroma
What is arteriosclerosis?
Thickening and hardening of walls of arteries and arterioles as a result of hypertension/diabetes mellitus
3 stages of atherosclerosis
Fatty streak
Simple plaque
Complicated plaque
Fatty streak
Lipid deposits in intima
Yellow
Raised
The simple plaque
Yellow/white Raised Irregular outline Widely distributed Enlarge and coalesce
Complicated plaque
Thrombosis
Haemorrhage into plaque
Calcification
Aneurysm formation
Common sites for atherosclerosis
Aorta (ABDOMINAL) Coronary arteries Carotid arteries Cerebral arteries Leg arteries
Normal arterial structure
Intima Internal elastic lamina Media (muscular) External elastic lamina Adventitia
What happens early on in atherosclerosis?
Proliferation of smooth muscle cells and foam cells
Extracellular lipid
Later changes in atherosclerosis
Fibrosis
necrosis
cholesterol clefts (holes)
+- inflammatory cells
Later vessel changes atherosclerosis
Internal elastic lamina disrupted
damage to media
ingrowth of BV
Plaque fissuring
Clinical effects of atherosclerosis
Ischaemic heart disease Cerebral Ischaemia Mesenteric ischaemia Peripheral vascular disease Aortic aneurysm
Ischaemic heart disease can lead to…
MI, death, angina pectoris, arrythmias, cardiac failure
Cerebral ischaemia can lead to
Transient ischaemic attack (mini stroke)
Cerebral infarct (stroke)
Multi infarct dementia
Mesenteric ischaemia can lead to…
Ischaemic colitis
Malabsorption
Intestinal infarction
Peripheral vascular disease can lead to…
Intermittent claudication (calf pain on exercise)
Leriche syndrome
Ischaemic rest pain
gangrene
What is leriche syndrome?
Pain in buttocks
Impotence
(from ischaemia of iliac arteries)
Risk factors atherosclerosis
Age Gender Hyperlipidaemia (LDL high) Smoking Hypertension Diabetes mellitus Alcohol Infection Oral contraceptive
Gender for atherosclerosis
Men affected more than women until menopause
Oestrogen is protective
Apo E and atheroscelrosis
Genetic variations in Apo E = changes in LDL levels
caused by polymorphisms of genes (can be used as risk markers)
Physical signs of familial hyperlipidaemia
Corneal arcus
Tendon Xanthoma (nodules)
Xanthalasma (yellow fatty eye deposits)
Problems with smoking
Risk factor for ischaemic heart disease
activates coagulation
reduced prostaglandins
increased aggregation of platelets
Why is hypertension a risk for IHD?
Endothelilal damage from raised pressure?
Diabetes mellitus risks
Increase risk of IHD
Cerebrovascular and peripheral vascular disease
(no protective effect for premenopausal women if have diabetes)
Alcohol risk of IHD
Greater than 5 units per day = increased risk
Smaller amounts protective
Infections causing atherosclerosis
Chlamydia pneumoniae
Helicobacter pylori
Cytomegalovirus
Broad risk factors Atherosclerosis
Lack of exercise
Obesity
Stress/personality
Genetic predisposition
What can cause genetic predisposition for atherosclerosis?
Variations in apolipoprotein metabolism
Variation in apolipoprotein receptors
Theories of atherosclerosis
Thrombogenic
Insudation
Monoclonal
Reaction to injury
Thrombogenic theory (1852 Rokitansky)
plaques are formed by repeated thrombi
Lipid derived from thrombi
Overlying fibrous cap
Insudation theory (1856 Virchow)
Endothelial injury
inflammation
increased permeability to lipid from plasma
Reaction to injury hypothesis (1972 Ross and Glomset)
Endothelial injury
hypercholesterolaemia = endothelial damage
injury increases permeability allows platelet adhesion
monocytes penetrate
smooth muscle cells proliferate
Reaction to injury (1986 Ross)
Endothelial injury is subtle (undetectable visibly)
Oxidised LDL may cause damage to endothelium
Monoclonal hypothesis (Benditt and Benditt)
Smooth muscle cell proliferation = crucial
monoclonal plaques - benign tumours?
viral causes
Process of atherosclerosis
Thrombosis
Lipid accumulation
Production of intercellular matrix
Interactions between cell types
Cells involved in atherosclerosis
Endothelial cells Platelets Smooth muscle cells Macrophages Lymphocytes & Neutrophils
Endothelial cells roll in atehrosclerosis
Haemostasis
Altered permeability to lipoproteins
Produce collagen
Stimulate proliferation and migration of SMC (EGF)
Platelet role in atherosclerosis
Haemostasis
Stimulate proliferation and migration of SMC (PDGF)
Smooth muscle cells role in atherosclerosis
Take up LDL and lipid
Become foam cells
Synthesise collagen and proteoglycans
Macrophages role in atherosclerosis
Oxidise LDL
Become foam cells (engulf lipid)
Secrete proteases = modify matrix
Stimulate proliferation and migration of SMC
Lymphocytes role in atherosclerosis
Produce TNF
Affect lipoprotein metabolism
Stimulate proliferation and migration of SMC
Neutrophils role in atherosclerosis
Secrete proteases = local damage and inflammation
Unified hypothesis
Endothelial damage
Effects of injury
SMC stimulated and produce matrix
Why does endothetlial damage occur?
Raised LDL
Toxins (smoking)
Hypertension
haemodynamic stress
What does endothelial injury cause?
Platelet adhesion
PDGF release = SMC proliferation and migration Accumulation of lipid LDL oxidation (lipid uptake by macrophages and SMC)
Migration of monocytes to intima
What do foam cells do?
Secrete cytokines =
further SMC stimulation
recruitment of other inflammatory cells
Prevention of atherosclerosis
No smoking Treat hypertension/diabetes mellitus Not too much alcohol Regular exercise/weight control Lipid lowering drugs
