Flashcards in MoD S7 - Atheroma Deck (45)
Atheroma is the accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
The thickening and hardening of the arterial walls as a consequence of atheroma
The thickening of the walls of arteries and arterioles as a result of hypertension or diabetes mellitus
What are the 3 macroscopic features of atheroma?
How do these features reflect atheromatous progression?
Constitute a spectrum of progression from the fatty streak to complicated plaque as atheroma worsens
What is the fatty streak?
Lipid deposits in the intima
Appear as a slightly raised yellow streak along the intima
Relationship to atheroma somewhat debated as it is found in regions of the body not prone to atheroma and in populations where atheroma isn't as prevalent
What are the key features of a simple atheromatous plaque?
A raised yellow/white area of the vessel
Progressively enlarge and coalesce
What are some complications that can occur as a result of atheromatous plaques being present in an artery?
Haemorrhage into the plague:
- Unstable plaque disrupted by blood flow at high pressure allowing haemorrhage into the vessel wall
- As atheroma becomes more extensive in the tunica media the elastic tissue is affected and number of elastic fibres is reduced, aneurysm forms via stretching of the vessel wall
What sites in the vasculature are particularly affected by atheroma?
What about other sites in the vasculature?
Why are these sites in particular vulnerable?
Other sites in the body are less likely to develop plaques
Not known why these sites are particularly effected
What are the early microscopic changes seen in someone developing atheroma?
Proliferation of smooth muscle cells
Accumulation of foam cells (macrophages and smooth muscle cells with cytoplasmic lipid accumulation)
Extracellular lipid in the wall of the artery
Abnormalities in the composition of the extracellular matrix
What are the later microscopic changes seen in someone with atheroma?
Fibrosis (dense fibrotic caps on plaques)
- Cholesterol crystallises and forms needle shaped crystals, these are dissolved in histological preparation and we see the 'cleft' left behind
- Widely varies, may influence stability, likelihood of thrombosis and aneurysm formation
Disruption of internal elastic lamina
Damage extends to media
Ingrowth of blood vessels into the plaque (new 'leaky' capillaries, may contribute to haemorrhage into plaque)
Plaque fissuring (due to sheering forces of blood against an unstable plaque)
What are some of the primary effects of atheroma?
Ischaemic heart disease
Peripheral vascular disease
Abdominal aortic aneurysm (AAA)
List some of the conditions that may be a result of ischaemic heart disease due to atheroma
What are some of the conditions that may be a result of cerebral ischaemia due to atheroma?
Transient ischaemia attach
Multi-infarct dementia (multiple small infarcts that affect cognitive function leading to dementia)
What are some of the conditions that result from mesenteric ischaemia due to atheroma?
Ischaemic colitis (chronic, leads to abdominal pain/bleeding)
What are some of the conditions that result from peripheral vascular disease due to atheroma?
Intermittent claudication (pain in calves on walking)
Leriche syndrome (pain in buttocks, impotence due to atheroma of the iliac artery)
Ischaemic rest pain
What are some of the risk factors for atheroma?
Lack of exercise
What are the gender differences in risk of atheroma developing?
Affects men more than women
Women relatively pretected before menopause, assumed hormonal basis
Why is hyperlipidaemia associated with atheroma?
High plasma cholesterol associated with atheroma
LDL most significant
HDL is protective
How is hypertension related to atheroma?
There is a strong link between high BP and Ischaemic heart disease
Endothelial damage may be caused by high BP
How is diabetes mellitus related to atheroma?
Diabetes mellitus doubles ischaemic heart disease risk
Also associated with cerebrovascular and peripheral vascular disease
May also be related to hyperlipidaemia and hypertension, raising risk of atheroma further
At what level of alcohol consumption does risk of atheroma increase?
>5 units per day increases risk of IHD and atheroma
Smaller amounts may be protective
Give 3 examples of infection that may increase risk of atheroma
This association is mostly theoretical at this point, no conclusive evidence
How is cigarette smoking related to atheroma?
Powerful risk factor for IHD
Risk falls after giving up
Mode of action uncertain:
- May work via the coagulation system
- May cause reduced prostacyclin
- Hence causing increased platelet aggregation
- This may lead to atherogenesis (We're not sure)
What are some genetic factors that may predispose to atheroma development?
Variations in apolipoprotein metabolism
(E.g. Familial hyperlipidaemia)
Variations in apolipoprotein receptors
How is apolipoprotein E related to atheroma development?
Genetic variations in Apo E are associated with changes in LDL levels
Polymorphisms of the genes involved lead to at least 6 phenotypes
These phenotypes can be used as risk markers for atheroma
What is familial hyperlipidaemia?
What are some of the associated physical signs?
Genetically determined abnormalities of lipoproteins
These lead to early development of atheroma
Associated physical signs include:
- Corneal Arcus (ring around the cornea)
- Tendon xanthomas (cholesterol rich lipid deposition in tendons)
- Xanthelasma (raised deposits of fat around the eyes/eyelids)
What are the 4 theories of atheroma pathogenesis?
How are they all related?
Reaction to injury hypothesis
Can be collected to form the 'Unified theory'
Describe the Thrombogenic theory and Insudation theory of atheroma pathogenesis
- Plaques formed by repeated thrombi sticking to the arterial wall
- Then somehow becoming associated with lipid
- A cap then forms over the thrombus
- This is repeated over and over as the plaques grow
- Some method of endothelial injury
- This leads to inflammation
- This increases the permeability of the vessel wall to lipids allowing lipids into the vessel wall from the plasma
Describe the Reaction to injury hypothesis of atheroma pathogenesis
Plaques form in response to endothelial injury
Hyperlipidaemia leads to the endothelial damage
Injury increases permeability and allows platelet adhesion
Monocytes penetrate into endothelium and become foam cells
Smooth muscle cells proliferate and migrate
Later suggested that:
- Endothelial injury was so subtle as to be undetectable visually
- Oxidised LDL may be what is damaging the endothelium