Session 6 - Atheroma formation Flashcards
Define atheroma
The accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
Define atherosclerosis
The thickening and hardening of arterial walls as a consequence of atheroma
Define arteriosclerosis
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?
Fatty streak
Simple plaque
Complicated plaque
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?
Raised yellow/white
Irregular outline
Widely distributed
Enlarge and coalesce
What is another name for a complicated plaque?
Thrombosis
How is complicated plaque caused?
Haemorrhage into plaque with subsequent calcification
What can a complicated plaque cause?
Aneurysm formation
Name five common sites of atheroma formation
Aorta Coronary arteries Carotid arteries Cerebral arteries Leg arteries
What is this image?
**** Fatty streak atheroma
What is this an image of?
****Simple plaque
What is this an image of?
**** Complicated plaque
Give structure of normal artery
Endothelium Sub endothelial ct Internal elastic lamina Muscular media External elastic lamina Adventitia
ESIMEA
Even sexy idiots make ellen angry
What are the early microscopic changes in atheroma?
Proliferation of smooth muscle cells
Accumulation of foam cells
Extracellular lipid
What are later micrscopic changes involved in atheroma?
Fibrosis
Necrosis
Cholesterol clefts
Change in number of inflammatory cells
What are the clinical effects of atheroma formation?
Ischaemic heart disease
Cerebral ischaemia
Mesenteric ischaemia
Peripheral vascular disease
What five conditions are associated with ischaemic heart disease?
Sudden death MI Angina pectoris Arrhythmias Cardiac failure
What are three effects of cerebral ischaemia?
Transient ischaemic attack
Cerebral infarction ( stroke)
Multi-infarct dementia
What are three effects of mesenteric ischaemia?
Ischaemic colitis
Malabsorption
Intestinal infarction
What are the four effects of peripheral vascular disease?
Intermittent claudication
Leriche syndrome
Iscaemic rest pain
Gangrene
Give eight risk factors for atheroma formation
Age Gender Hyperlipidaemia Cigarette smoking Hypertension Diabetes mellitus Alcohol Infection
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?
Lipoproteins
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
Chylomicrons
LDL
VLDL
HDL
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?
Apo E
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
- Xanthelasma
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
Coagulation system
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
> 5
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 Obesity Soft water Oral contraceptive 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?
Thrombogenic theory
Insudation theory
Monoclonal hypothesis
Reaction to injury hypothesis
What is the insudation theory of atheroma formation?
Endothelial injury
Inflammation
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?
Thrombosis
Lipid accumulation
Production of intercellular matrix
Interactions between cell types
What are the six cells involved in atheroma?
Endothelial cells Platelets Smooth muscle cells Macrophages Lymphocytes Neutrophils
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?
Oxidise LDL
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?
Endothelial injury
Results of endothelial injury
What causes endothelial injury under the unifying hypothesis?
Raised LDL
Toxins
Hypertension
Haemodynamic stress
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?
No smoking Reduce fat intake Treat hypertension Not too much alcohol Regular exercise/weight control
What are five interventions to halt atheroma formation?
Stop smoking Modify diet Treat hypertension Treat diabetes Lipid lowering drugs