Week 6 - Atherosclerosis Flashcards
What is atherosclerosis?
The thickening and hardening of arterial walls as a consequence of atheroma
What is an atheroma?
The accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
What is arteriosclerosis?
The thickening of the walls or arteries and arterioles, usually as a result of hypertension or diabetes mellitus
What is the unifying hypothesis for the formation of atherosclerotic lesions?
Chronic endothelial injury, due to:
- Raised LDL
- Toxins
- Hypertension
- Haemodynamic stress
Endothelial dysfunction, leads to:
- Platelet adhesion and platelet-derived growth factor release
- Acute inflammation and chronic inflammation brings macrophages and lymphocytes in
- Smooth muscle cell proliferation and migration
- Insudation (accumulation) of lipid in wall
- Migration of monocytes into intima
- LDL oxidation
Macrophages and smooth muscle cells engulf lipid to form foam cells
- The foam cells secrete cytokines, causing further smooth muscle stimulation and recruitment of other inflammatory cells
- There is collagen and matrix deposition, extracellular lipid deposition and neovascularisation
What are the macroscopic features of atherosclerosis?
- Fatty streak (lipid deposits in intima, yellows slightly raised)
- Simple plaque (raised yellow/white, irregular outline, widely distributed)
The simple plaque gradually enlarges and coalesces to form: - Complicated plaque
What are some of the complications that can cause a simple plaque to become a complicated plaque?
- Thrombosis
- Haemorrhage into plaque
- Calcification
- Aneurysm formation
What are the microscopic features of atherosclerosis?
Early changes: - Proliferation of smooth muscle cells - Accumulation of foam cells - Extracellular lipid Later changes: - Fibrosis - Necrosis - Cholesterol clefts - +/- inflammatory cells - Disruption of internal elastic lamina - Damage extends into media - Ingrowth of blood vessels - Plaque fissuring (disruption of the plaque roof due to movement underneath)
Where are the common sites for atherosclerosis?
- Aorta (especially abdominal)
- Coronary arteries
- Carotid arteries
- Cerebral arteries
- Leg arteries
What is the effect of ischaemic heart disease?
Causes sudden death Can lead to: - Myocardial infarction - Angina pectoris - Arrhythmias - Cardiac failure
What is the effect of cerebral ischaemia?
- Transient ischaemic attack
- Cerebral infarction (stroke)
- Multi-infarct dementia
What are the effects of mesenteric ischaemia?
- Ischaemic colitis
- Malabsorption
- Intestinal infarction
What are the effects of peripheral vascular disease?
- Intermittent claudication (pain in calf due to ischaemia)
- Leriche syndrome
- Ischaemic rest pain
- Gangrene
What is an abdominal aortic aneurysm and what are its effects?
An atheroma in the abdominal aorta
- Can damage elasticity
- It may rupture, which will cause a massive bleed
- May affect the kidneys
What is the epidemiology of coronary heart disease?
- Age: slowly progressive throughout adult life
- Gender: women protected by oestrogen before menopause
- Hyperlipidaemia: high plasma cholesterol associated with atheroma
- Cigarette smoking: risk falls after giving up
- Hypertension
- Diabetes mellitus (doubles risk)
- Alcohol consumption: drinking more than 5 units per day is associated with increased risk of CHD, often associated with other risk factors
- Infection: chlamydia pneumoniae, helicobacter pylori, cytomegalovirus
- Lack of exercise
- Obesity
- Soft water
- Oral contraceptives
- Stress
- Personality type
- Genetic predisposition
How can you prevent atherosclerosis?
- No smoking
- Reduce fat intake
- Treat hypertension
- Don’t drink too much alcohol
- Regular exercise/weight control
What interventions are there for atherosclerosis?
- Stop smoking
- Modify diet
- Treat hypertension
- Treat diabetes
- Lipid lowering drugs
What are the processes involved in an atheroma?
- Thrombosis
- Lipid accumulation
- Production of intracellular matrix
- Interactions between cell types
What cells are involved in an atheroma?
- Endothelial cells
- Platelets
- Smooth muscle cells
- Macrophages
- Lymphocytes
- Neutrophils
What is the role of endothelial cells in an atheroma?
- Key role in haemostasis
- Altered permeability to lipoproteins
- Secretion of collagen
- Stimulation of proliferation and migration of smooth muscle cells
What is the role of platelets in an atheroma?
- Key role in haemostasis
- Stimulate proliferation and migration of smooth muscle cells
What is the role of smooth muscle cells in an atheroma?
- Take up LDL and other lipid to become foam cells
- Synthesise collagen and proteoglycans
What is the role of macrophages in an atheroma?
- Oxidise LDL
- Take up lipids to become foam cells
- Secrete proteases which modify matrix
- Stimulate proliferation and migration of smooth muscle cells
What is the role of lymphocytes in an atheroma?
- Tissue necrosis factor may affect lipoprotein metabolism
- Stimulate migration and proliferation of smooth muscle cells
What is the role of neutrophils in an atheroma?
- Secrete proteases leading to continued local damage and inflammation
In atherogenesis, what is the insudation theory?
- Endothelial injury
- Inflammation
- Increased permeability to lipid from plasma
In atherogenesis, what is the reaction to injury hypothesis?
- Plaques form in response to endothelial injury
- Hypercholesterolaemia leads to endothelial damage in experimental animals
- Injury increases permeability and allows platelet adhesion
- Monocytes penetrate endothelium
- Smooth muscle cells proliferate and migrate
- LDL, especially oxidised, may damage endothelium
In atherogenesis, what is the monoclonal hypothesis?
- Crucial role for smooth muscle proliferation
- Each plaque is monoclonal
- Might represent abnormal growth control
- Is each plaque a benign tumour?
What is familial hyperlipidaemia?
Genetically determined abnormalities of lipoproteins
- Leads to early development of atheroma
- Associated physical signs: arcus, tendon xanthomas, xanthelasma
