Flashcards in Session 6 - Atheroma formation Deck (70):
The accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
The thickening and hardening of arterial walls as a consequence of atheroma
The thickening of the walls of arteries and arterioles usually as a result of hypertesnion or diabetes mellitus
What are the three types of atheroma?
What is a fatty streak atheroma?
What does it look like?
Lipid deposits in intima
Yellow, slightly raised
What does a simple plaque atheroma look like?
Enlarge and coalesce
What is another name for a complicated plaque?
How is complicated plaque caused?
Haemorrhage into plaque with subsequent calcification
What can a complicated plaque cause?
Name five common sites of atheroma formation
What is this image?
************ Fatty streak atheroma
What is this an image of?
What is this an image of?
************ Complicated plaque
Give structure of normal artery
Sub endothelial ct
Internal elastic lamina
External elastic lamina
Even sexy idiots make ellen angry
What are the early microscopic changes in atheroma?
Proliferation of smooth muscle cells
Accumulation of foam cells
What are later micrscopic changes involved in atheroma?
Change in number of inflammatory cells
What are the clinical effects of atheroma formation?
Ischaemic heart disease
Peripheral vascular disease
What five conditions are associated with ischaemic heart disease?
What are three effects of cerebral ischaemia?
Transient ischaemic attack
Cerebral infarction ( stroke)
What are three effects of mesenteric ischaemia?
What are the four effects of peripheral vascular disease?
Iscaemic rest pain
Give eight risk factors for atheroma formation
How does age affect the risk of having an atheroma form?
Slow increase in risk as you age
Risks factors accumulate over the course of your life
How does gender effect your risk of atheroma formation?
Women protected before menopause due to hormones
How does hyperlipidaemia cause atheroma?
High plasma cholesterol associated with atheroma
What are the most significant factors in hyperlipidaemia?
LDL levels are dangerous
High HDL are protective
How are lipids carried in the blood?
What do lipoproteins carry (be specific)
Cholesterol, triglycerides, phospholipids and apolipoprotein, to be precise
What is the structure of a lipoprotein
Hydrophobic lipid core, hydrophillic outer layer of phospholipid and apolipoprotein
Name four different types of lipid
What is the role of chylomicrons?
Transport lipid from intestine to liver
What is the role of LDL's?
Carry cholesterol to non-liver cells
What is the role of VLDL's?
Carry cholesterol and TG from liverr
What is the role of HDL?
Carry cholesterol from adipose tissue to the liver
What apolipoprotein are atheromas linked to?
Polymorphisms of genes involved lead to at least 6 Apo E phenotypes
What can polymorphisms of genes causing increased Apo E be used for?
Risk markers for atherome
What is familial hyperlipidaemia?
Genetically determined abnormalities of lipoproteins which leads to early development of atheroma
What are the associated physical signs of familial lipidaemia?
- Corneal arcus
- Tendon xanthomas
What is cigarette smoking a powerful risk factor for, other than atheroma? (Vascular disease)
Ischaemic Heart Disease
Give three possible modes of action of cigarette smoking causing atheromas
Reduced prostacyclin (PGI2, eicosanoids)
Increased platelet aggregation
What is hypertension linked to? How does it cause damage?
Strong link to IHD? Endothelial damage caused by raised blood pressure
What affect does DM have on IHD risk?
Doubles the chance
What effect does DM have on premenopausal women?
Lose their protected status
What three atheroma related diseases are associated with DM?
IHD, cebrovascular and peripheral vascular disease,.
What two other risk factors is DM related to?
Hyperlipidaemia and hypertension
How many units of alcohol per day must be consumed for their to be increased risk IHD
Why is alcohol so potent a risk factor?
Often associated with other lifestyle related risk factors
What is interesting about alcohol consumption?
Smaller amounts are protective of atheroma
Give five more risk factors of atheroma formation
Lack of exercise
Stress and personality
What two variations in phenotype can account for increased genetic predisposition
Variations in apolipoprotein metabolism
Variations in apolipoprotein receptors
What are the four theories concerning atheroma pathogenesis?
Reaction to injury hypothesis
What is the insudation theory of atheroma formation?
Increased permeability to lipid from plasma
What is the reaction to injury hypothesis?
Plaques form in response to endothelial injury as a result of hypercholesterolaemia
Injury increases permeability and allows platelet adhesion
monocytes penetrate endothelium
Smooth muscle cells proliferate and migrate
How does hypercholesterolaemia damage endothelium?
Oxidised LDL can cause subtle and undetectable injury
What is the monoclonal hypothesis?
Belief that artheroma may have viral aeitology, stemming from the observation that each plaque is monoclonal, and may thus represent abnormal growth control .
What is given a crucial role in the monoclonal hypothesis?
Smooth muscle prolifeation
What are the four processes involved in atheroma formation?
Production of intercellular matrix
Interactions between cell types
What are the six cells involved in atheroma?
Smooth muscle cells
What the four roles of endothelial cells in atheroma formation?
Key role in haemostasis
Altered permeability to lipoprotein
Secretion of collagen
Stimulation of proliferation and migration of smooth muscle cells
What are the two rolls of platelets in atheroma formation?
Key role in haemostasis
Stimulate proliferation and migration of smooth muscle cells (PDGF - platelet derived growth factor)
What are the two roles of smooth muscle cells
Take up LDL and other lipid to become foam cells
Synthesis collagen and proteoglycans
What are the four roles of atheroma formation of macrophages?
take up lipids to become foam cells
Secrete proteases which modify matrix
Stimulation proliferation and migration of smooth muscle cells
How are lymphocytes involved in atheroma formation?
Tumour necrosis factor (TNF) may affect lipoprotein metabolism
Stimulate proliferation and migration of smooth muscle cells
What is the role of neutrophils in atheroma formation?
Secrete proteases leading to continues local damage and inflammation
What are the two steps of the unifying hypothesis?
Results of endothelial injury
What causes endothelial injury under the unifying hypothesis?
What does endothelial injury result in under the unifying hypothesis?
- Platelet adhesion, PDGF release, smooth muscle cells (SMC) proliferation and migration
- Insudation of lipid, LDL oxidation, uptake of lipid by SMC and macrophages
- Migration of monocytes into intima
- Stimulated SMC produce matrix material
- Foam cells secrete cytokines
What does the secretion of cytokines by foam cells cause in atheroma formation?
Further SMC stimulation
Recruitment of other inflammatory cells
What are the five ways of reducing risk of atheroma formation?
Reduce fat intake
Not too much alcohol
Regular exercise/weight control