S6) Atherosclerosis Flashcards
What is an atheroma?
Atheroma is the accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
What is atherosclerosis?
Atherosclerosis is the thickening and hardening of arterial walls as a consequence of an atheroma
What is arteriosclerosis?
Arteriosclerosis is the thickening and hardening of arteries and arterioles due to conditions such as hypertension and diabetes mellitus
Identify three macroscopic features of atherosclerosis
- The fatty streak
- The simple plaque
- The complicated plaque
Describe the appearance of the fatty streak
- Lipid deposits in intima
- Yellow, slightly raised
Describe the appearance of the simple plaque
- Raised yellow/white
- Irregular outline
- Widely distributed
- Enlarged and coalesce
Describe the appearance of the complicated plaque
- Thrombosis
- Haemorrhage into plaque
- Calcification
- Aneurysm formation
Identify five common sites for atherosclerosis
- Aorta (especially abdominal)
- Coronary arteries
- Carotid arteries
- Cerebral arteries
- Leg arteries
Describe normal arterial structure
Describe the microscopic appearance of the early changes in atherosclerosis
- Proliferation of smooth muscle cells
- Accumulation of foam cells
- Extracellular lipid deposition
Describe the microscopic appearance of the later changes in atherosclerosis
- Fibrosis & necrosis
- Cholesterol clefts
- Disruption of internal elastic lamina
- Ingrowth of blood vessels
- Plaque fissuring (could lead to thrombosis)
Identify 5 clinical effects of atherosclerosis
- Ischaemic Heart Disease
- Cerebral ischaemia
- Mesenteric ischaemia
- Peripheral vascular disease
- Abdominal Aortic Aneurysm
Identify 5 complications of Ischaemic Heart Disease due to severe atherosclerosis in the heart
- Sudden death
- Myocardial infarction
- Angina pectoris
- Arrhythmias
- Cardiac failure
Identify 3 complications of cerebral ischaemia due to severe atherosclerosis in the brain
- Transient ischaemic attack
- Cerebral infarction (stroke)
- Multi-infarct dementia
Identify 3 complications of mesenteric ischemia due to severe atherosclerosis in the colon
- Ischaemic colitis
- Malabsorption
- Intestinal infarction
Identify 3 complications of peripheral vascular disease due to severe atherosclerosis in the peripheries
- Intermittent claudication
- Ischaemic rest pain
- Gangrene
What are the possible reasons for the genetic predisposition to atherosclerosis?
- Variations in apolipoprotein metabolism
- Variations in apolipoprotein receptors
Identify four theories / hypotheses explaining the pathogenesis of atherosclerosis
- Thrombogenic theory
- Insudation theory
- Monoclonal hypothesis
- Reaction to injury hypothesis
How does the thrombogenic / encrustation hypothesis explain the possible mechanisms of atherogenesis?
- Plaques formed by repeated thrombi
- Lipid derived from thrombi
- Overlying fibrous cap
How does the insudation hypothesis explain the possible mechanisms of atherogenesis?
- Endothelial injury
- Inflammation
- Increased permeability to lipid from plasma
How does the monoclonal hypothesis explain the possible mechanisms of atherogenesis?
- Crucial role for smooth muscle proliferation
- Each plaque is monoclonal
- Might represent abnormal growth control
How does the reaction to injury hypothesis explain the possible mechanisms of atherogenesis?
- Endothelial injury may be very subtle and be undetectable visually
- LDL, especially oxidised, may damage endothelium
Identify the four processes involved in atherogenesis
- Thrombosis
- Lipid accumulation
- Production of intercellular matrix
- Interaction between cell types
Identify the six cells involved in atherogenesis
- Endothelial cells
- Platelets
- Smooth muscle cells
- Macrophages
- Lymphocytes
- Neutrophils
Describe the role of endothelial cells in atherogenesis
- Altered permeability to lipoproteins
- Production of collagen
- Stimulation of proliferation and migration of smooth muscle cells
Describe the role of platelets in atherogenesis
Stimulate proliferation and migration of smooth muscle cells (PDGF)
Describe the role of smooth muscle cells in atherogenesis
- Take up LDL and other lipid to become foam cells
- Synthesis collagen and proteoglycans
Describe the role of macrophages in atherogenesis
- Oxidise LDL
- Take up lipids to become foam cells
- Secrete proteases which modify matrix
- Stimulate proliferation and migration of smooth muscle cells
Describe the role of lymphocytes in atherogenesis
- TNF may affect lipoprotein metabolism
- Stimulate proliferation and migration of smooth muscle cells
Describe the role of neutrophils in atherogenesis
Secrete proteases leading to continued local damage and inflammation
Outline the Unifying Hypothesis 1
Endothelial injury occurs due to:
- Raised LDL
- Toxins e.g. cigarette smoke
- Hypertension
- Haemodynamic stress
Outline the Unifying Hypothesis 2
Endothelial injury causes:
- Platelet adhesion, PDGF release, SMC proliferation and migration
- Insudation of lipid, LDL oxidation, uptake of lipid by SMC and macrophages
- Migration of monocytes into intima
Outline the Unifying Hypothesis 3
- Stimulated SMC produce matrix material
- Foam cells secrete cytokines causing further SMC stimulation and the recruitment of other inflammatory cells
Identify 10 risk factors for atherosclerosis
- Diabetes Mellitus
- Infection
- Smoking
- Hypertension
- Hyperlipidaemia
- Gender
- Age
- Familial hyperlipidaemia
- Alcohol consumption
- Apolipoproteins E genotype
Mnemonic: DISHH GAFAA
Discuss the epidemiology of atherosclerosis in light of Diabetes Mellitus
- DM also associated with high risk of IHD, cerebrovascular and peripheral vascular disease
- DM is related to hyperlipidaemia and hypertension
Which infections increase the likelihood of atherosclerosis?
- Chlamydia pneumoniae
- Helicobacter pylori
- Cytomegalovirus
Discuss the epidemiology of atherosclerosis, in light of smoking
- Powerful risk factor for IHD
- Mode of action uncertain – coagulation system, reduced PGI2, increased platelet aggregation
Discuss the epidemiology of atherosclerosis, in light of hypertension
- Strong link with IHD
- Mechanism uncertain – endothelial damage caused by raised pressure
Discuss the epidemiology of atherosclerosis, in light of hyperlipidaemia
High plasma cholesterol associated with atherosclerosis:
- LDL most significant
- HDL is protective
Discuss the epidemiology of atherosclerosis, in light of gender
Women protected relatively before menopause (resumed hormonal basis)
Discuss the epidemiology of atherosclerosis, in light of age
- Slowly progressive throughout adult life
- Risk factors operate over years
Discuss the epidemiology of atherosclerosis, in light of familial hyperlipidaemia
Genetically determined abnormalities of lipoproteins leads to early development of atherosclerosis
Discuss the epidemiology of atherosclerosis, in light of alcohol consumption
- >5 units /day associated with increased risk of IHD
- Often associated with other risk factors e.g. smoking and high BP
Discuss the epidemiology of atherosclerosis, in light of apolipoproteins E genotype
- 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 and can be used as risk markers for atherosclerosis
How can atherosclerosis be prevented?
- Sensible alcohol intake
- Regular exercise and control of weight
- Reduce fat intake
- Treat hypertension
- No smoking
Identify the steps that can be taken for disease intervention in atherosclerosis
- Stop smoking
- Treat hypertension
- Treat diabetes mellitus
- Lipid lowering drugs where needed
What is a transient ischaemic attack?
- A TIA (aka “mini stroke”) is a brief episode of neurological dysfunction caused by a temporary disruption in cerebral blood flow (ischaemia without infarction)
- It presents with sudden symptoms similar to a stroke e.g. speech and visual disturbance, and numbness or weakness in the face, arms and legs
What is a stroke?
A stroke is a rapid onset of cerebral deficit (usually focal) lasting more than 24 hours or leading to death, with no cause apparent other than a vascular one
What is an ischaemic stroke?
An ischaemic stroke is a stroke secondary to a reduction or cessation of blood flow to a localised area of brain due to arterial occlusion or hypoperfusion
Describe four causes of an ischaemic stroke
- Embolisation from a distant source
- In situ thrombus on an atherosclerotic plaque
- Inflammation of blood vessels (infectious/non-infectious vasculitis)
- Hypoperfusion i.e. severe hypotension
Where might the embolus have come from in an ischaemic stroke?
- Cardiac mural thrombi (MI & AF)
- Thromboemboli from carotid arteries, aortic arch or vertebral arteries
- Calcific material / vegetations from heart valves
- Fragments of atrial myxoma
What is a haemorrhagic stroke?
A haemorrhagic stroke is a stroke secondary to bursting of a blood vessel, often seen in hypertension
What is a berry aneurysm?
- A berry aneurysm is a common form of intracranial aneurysm which is congenital or secondary to blood vessel injury (not atherosclerosis)
- They commonly occur within the circle of Willis and the adjacent arteries and thus, blood accumulates in the subarachnoid space
