Atheroma Flashcards
What is an atheroma?
An accumulation of intracellular and extracellular lipid in the intima and media or large and medium sized arteries
Where do atheromas happen?
On the inside of the arteries, and spreads through the wall
Where is the fat deposited in an atheroma?
Can be on outside and inside wall
What is atherosclerosis?
The thickening and hardening of arterial walls as a consequence of atheoma
What is arteriosclerosis?
The thickening of walls of arteries and arterioles, usually as a result of hypertension or diabetes mellitus
What are the three macroscopic stages of an atheroma?
The fatty streak
The simple plaque
The complicated plaque
What causes the fatty streak?
Lipid deposits in the intima
How does the fatty streak appear macroscopically?
Yellow and slightly raised
What is the relationship between the fatty streak and atheroma?
Somewhat debatable- generally regarded as the precursor, but some people disagree
Why do some people dispute that the fatty streak is the precursor to atheroma?
Fatty streak may be seen in populations that don’t progress to atherosclerosis.
Some discussion about anatomical position of fatty streak compared to atherosclerosis
How does the simple plaque appear macroscopically?
Raised yellow/white, with an irregular outline
What happens as simple plaques develop?
They enlarge and coalesce, eventually becoming complicated
What occurs when a complicated plaque has formed?
Thrombosis
Why do complicated plaques lead to thrombosis?
Because the plaque has an irregular surface, which disrupts flow
What can happen to a complicated plaque?
It may rupture
Can be haemorrhage into plaque
Calcification
Aneurysm formation
What happens when a complicated plaque ruptures?
It releases substances that cause thrombosis
What are the common sites of atheroma?
Aorta, especially abdominal Coronary arteries Carotid arteries Cerebral arteries Leg arteries
What do early changes in atheroma include?
Proliferation of smooth muscle cells
Accumulation of foam cells and extracellular lipid, either in or between cells
The matrix of the cell may be substantially changed from normal
What do later changes in atheroma include?
Fibrosis
Necrosis
May be inflammatory cells
Cholesterol clefts
What are cholesterol clefts?
Where cholesterol crystals are laid down, there are needle shaped crystals of cholesterol that are soluble, so when solvents are used they are dissolved, leaving clefts
What is the eventual result of atheroma?
Disruption of the internal elastic lamina, with damage that extends into the media.
Ingrowth of blood vessels
Plaque fissuring
Why is there an ingrowth of blood vessels in atheroma?
Because whenever there is damage/inflammation, there is always a vascular response
What is plaque fissuring?
When the inside can move relative to the outside
What is the problem with plaque fissuring?
It allows for the release of materials that cause thrombosis
What are the clinical effects of atheroma?
Ischaemic heart disease
Cerebral ischaemia
Mesenteric ischaemia
Peripheral vascular disease
What is ischaemic heart disease?
The process of atheroma reducing flow of blood with or without thrombotic occlusion of arteries
What can ischaemic heart disease lead to?
Sudden death Myocardial infarction Angina pectoris Arrhythmias Cardiac failure
Why does ischaemic heart disease cause cardiac failure?
Causes scarring of the heart so it can’t function properly
What may be seen in cardiac failure caused by ischaemic heart disease?
Swollen arteries, scarring
What is cerebral ischaemia a result of?
Atherosclerosis in cerebral or carotid vessels
What can cerebral ischaemia lead to?
Transient ischaemic attack Cerebral infarction (stroke) Multi-infarct dementia Can undergo secondary haemorrhages Abdominal aortic aneurysm
When may someone undergo secondary cerebral haemorrhages?
Where dying tissues start to degenerate
How does mesenteric ischaemia often present?
Rectal bleeding
Maybe abdominal pain
What can mesenteric ischaemia lead to?
Ischaemic colitis
Malabsorption
Intestinal infarction
What is an acute intestinal infarction more likely to be caused by?
Thrombus or embolus
Where are intenstinal infarctions most common?
In superior mesenteric artery
What is peripheral vascular disease?
Atherosclerosis affecting vessels supplying the legs
What can peripheral vascular disease lead to?
Intermittent claudication
Leriche syndrome
Ischaemic rest pain
Gangrene
What is intermittent claudication?
Pain in legs because of reduced blood supply
What happens to claudication distance as time goes on?
It gets shorter
What is meant by claudication distance?
How long can walk for before gets too painful
What is Leriche syndrome?
Buttock claudication
What is Leriche syndrome often associated with?
Impotence
What is ischaemic rest pain?
When muscles hurt even when not exercising
What causes gangrene?
No oxygen supply to tissue
Why is gangrene problematic when amputating?
Needs to heal, but that increases oxygen demand, causing further gangrene, so need amputation stump in good, healthy tissue
How can the clinical affect of peripheral vascular disease be delayed?
The development of a collateral channel
What are the risk factors for atheroma?
Age Gender Hyperlipidaemia Cigarette smoking Hypertension Diabetes mellitus Alcohol Infection Lack of exercise Obesity Soft water Oral contraceptive Stress and personality type
How does age affect the risk of atheroma?
The older you are, the more likely you are to have it, until you get to right at the top of the age range (because people living that long are likely not to have atheroma, or they wouldn’t have lived that long)
Why does risk of atheroma increase with age?
Because risk factors operative over years, building up
How does gender affect the risk of atheroma?
Men are at a high risk than women, until the menopause where women catch up
How is hyperlipidaemia associated with atheroma?
High plasma cholesterol associated with atheroma
How do the different types of cholesterol impact on the risk of atheroma?
LDL most significant risk of the types
HDL protecting
What happens to the risk of atheroma after giving up smoking?
It falls
Why does cigarette smoking increase the risk of atheroma?
Mode of action uncertain, but possible causes are-
Changes to coagulation system
Reduced PGI2
Increased platelet aggregation
What is strongly linked to high systolic/diastolic BP?
IHD
Why does hypertension cause IHD?
Mechanism uncertain, but could be due to endothelial damage caused by raised pressure
By how much does diabetes mellitus increase the risk of atheroma?
Doubles it
Why does diabetes mellitus increase the risk of atheroma?
Protective effect in premenopausal women lost
Could be related to hyperlipidaemia and hypertension
What else is diabetes mellitus associated with high risk of?
Cerebrovascular and peripheral vascular disease
How much alcohol is associated with high risk of atheroma?
> 5 units a day
What other risk factors is alcohol associated with?
Smoking
High BP
What effect can small amount of alcohol have on risk of atheroma?
Can be protecting
How is lipid carried in the blood?
On lipoproteins
What do lipoproteins carry?
Cholesterol and triglycerides
What do lipoproteins consist of?
Hydrophobic lipid core
Hydrophilic outer layer of phospholipid and apolipoprotein (A-E)
What do chylomicrons do?
Transport lipid from intestine to liver
What do VLDL do?
Carry cholesterol and TG from liver, and TG is removed leaving LDL
What is LDL rich in?
Cholesterol
What do LDLs do?
Carry cholesterol to non-liver cells
What do HDLs do?
Carry cholesterol from periphery back to liver
What are genetic variations in ApoE associated with?
Changes in LDL levels
What do polymorphisms of genes involved in lipid metabolism lead to?
At least 6 ApoE phenotypes
How can polymorphisms of genes involved in lipid metabolisms be used?
As risk markers for atheromas
What is familial hyperlipidaemia?
Genetically determined abnormalities of lipoproteins
What does familial hyperlipidaemia lead to?
Early development of atheroma
What are the associated physical signs of familial hyperlipidaemia?
Arcus
Tendon xanthomas
Xanthelasma
What is a corneal arcus?
A ring around the iris due to lipid
What is an xanthalasma?
A small accumulate of fat in skin and subcutaneous tissue
What could genetic predisposition to atheroma be due to?
Variations in apolipoprotein metabolism
Variations in apolipoprotein receptors
What are the theories of pathogenesis of atheroma?
Thrombogenic theroy
Insudation theory
Reaction to injury hypothesis
Monoclonal hypothesis
What is thrombogenic theory?
Plaques formed by repeated thrombi. Lipid derived from
thrombi. Overlying fibrous cap.
What is insudation theory?
Endothelial injury. Inflammation. Increased
permeability to lipid from plasma
What is the reaction to injury hypothesis?
Plaques form in response to endothelial injury.
Hypercholesterolemia leads to endothelial damage in experimental animals.
Injury increases permeability and allows platelet adhesion. Monocytes penetrate
endothelium. Smooth muscle cells proliferate and migrate.
Amended to say that endothelial injury may be very
subtle and undetectable visually and that LDL, especially oxidised, may damage
endothelium
What is the monoclonal hypothesis?
Crucial role for smooth muscle proliferation. Each
plaque is monoclonal. Might represent abnormal growth control. Each plaque
could be benign tumour, or atheroma could have viral aetiology.
What processes are involved in atheroma?
Thrombosis
Lipid accumulation
Production of intercellular matrix
Interactions between cell types
What cells are involved in atheroma?
Endothelial cells Platelets Smooth muscle cells Macrophages Lymphocytes Neutrophils
What is the role of endothelial cells in atheroma?
Key role in haemostasis
Alter their permeability to lipoproteins
Produce collagen
Stimulate proliferation and migration of smooth muscle cells
What is the role of platelets in atheroma?
Key role in haemostasis
Stimulate proliferation and migration of smooth muscle cells
How do platelets stimulate the proliferation and migration of smooth muscle cells?
Using PDGF
What is the role of smooth muscle cells in atheroma?
Take up LDL and other lipids to become foam cells
Synthesis collagen and other proteoglycans
What is the role of macrophages in atheroma?
Oxidise LDL
Secrete proteases
Stimulate proliferation and migration of smooth muscle cells
What do the proteases secreted by macrophages do?
Modify the matrix
What is the role of lymphocytes in atheroma?
TNF may affect lipoprotein metabolism
Stimulate proliferation and migration of smooth muscle cells
What is the role of neutrophils in atheroma?
Secrete proteases leading to continued local damage and inflammation
What is the unified atheroma hypothesis?
Endothelial injury occurs due to- Raised LDL Toxins, e.g. cigarette smoke Hypertension Haemodynamic stress
Endothelial injury causes- Platelet adhesion PDGF release Smooth muscle proliferation and migration Insudation of lipid LDL oxidation Uptake of lipid by smooth muscle cells and macrophages Migration of monocytes into intima
Stimulated smooth muscle cells produce matrix material, and foam cells secrete cytokines, causing further smooth muscle stimulation and recruitment of inflammatory cells
How can atheroma be prevented?
No smoking Reduce fat intake Treat hypertension Reduce alcohol intake Regular exercise Weight control
What interventions can be made to help with atheroma?
Stop smoking Modify diet Treat hypertension Treat diabetes Lipid lowering drugs
