Session 6 - Atheroma formation Flashcards by Matt Quinn

Define atheroma

The accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries

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Define atherosclerosis

The thickening and hardening of arterial walls as a consequence of atheroma

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Define arteriosclerosis

The thickening of the walls of arteries and arterioles usually as a result of hypertesnion or diabetes mellitus

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What are the three types of atheroma?

Fatty streak
Simple plaque
Complicated plaque

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What is a fatty streak atheroma?

What does it look like?

Lipid deposits in intima

Yellow, slightly raised

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What does a simple plaque atheroma look like?

Raised yellow/white
Irregular outline
Widely distributed
Enlarge and coalesce

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What is another name for a complicated plaque?

Thrombosis

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How is complicated plaque caused?

Haemorrhage into plaque with subsequent calcification

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What can a complicated plaque cause?

Aneurysm formation

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Name five common sites of atheroma formation

Aorta
Coronary arteries
Carotid arteries
Cerebral arteries
Leg arteries

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What is this image?

**** Fatty streak atheroma

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What is this an image of?

****Simple plaque

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What is this an image of?

**** Complicated plaque

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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

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What are the early microscopic changes in atheroma?

Proliferation of smooth muscle cells
Accumulation of foam cells
Extracellular lipid

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What are later micrscopic changes involved in atheroma?

Fibrosis
Necrosis
Cholesterol clefts
Change in number of inflammatory cells

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What are the clinical effects of atheroma formation?

Ischaemic heart disease
Cerebral ischaemia
Mesenteric ischaemia
Peripheral vascular disease

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What five conditions are associated with ischaemic heart disease?

Sudden death
MI
Angina pectoris
Arrhythmias
Cardiac failure

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What are three effects of cerebral ischaemia?

Transient ischaemic attack
Cerebral infarction ( stroke)
Multi-infarct dementia

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What are three effects of mesenteric ischaemia?

Ischaemic colitis
Malabsorption
Intestinal infarction

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What are the four effects of peripheral vascular disease?

Intermittent claudication
Leriche syndrome
Iscaemic rest pain
Gangrene

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Give eight risk factors for atheroma formation

Age
Gender
Hyperlipidaemia
Cigarette smoking
Hypertension
Diabetes mellitus
Alcohol 
Infection

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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

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How does gender effect your risk of atheroma formation?

Women protected before menopause due to hormones

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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

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 ```