Atherosclerosis Flashcards

1
Q

Atherosclerosis

A

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

It’s also the thickening and hardening of arterial walls as a consequence of this build up of lipid

The thickening of the walls due to this lipid of arteries and arterioles usually is as a result of hypertension or diabetes mellitus (increased cholesterol and fat levels)

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2
Q

ATS macroscopic features

A

Fatty streak - Lipid deposits in intima
Yellow, slightly raised
Relationship to atherosclerosis somewhat debatable

Simple plaque - It’s raised and is yellow/white
It has an irregular outline
And is widely distributed
If there is enough then groups can enlarge and coalesce

Complicated plaque - Thrombosis forms when groups of simple plaques coalesce
This can lead to a haemorrhage into plaque
Which calcifies and an aneurysm forms

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3
Q

ATS - common sites

A

Aorta

Coronary arteries

Carotid arteries

Cerebral arteries

Leg arteries

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4
Q

Normal arterial structure

A

Endothelium

Sub endothelial connective tissue

Internal elastic lamina

Muscular media

External elastic lamina

Adventitia

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5
Q

ATS - microscopic features

A

Early changes -
proliferation of smooth muscle cells
accumulation of foam cells
formation and build up of extracellular lipid

Later changes - 
	fibrosis
	necrosis
	cholesterol clefts
	\+/- inflammatory cells
	disruption of internal elastic lamina
	damage extends into media
	ingrowth of blood vessels
	plaque fissuring
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6
Q

ATS - clinical effects

A

Ischaemic heart disease, which can lead to - sudden death - heart stops

MI - large part of the heart cant get blood therefore dies via necrosis

angina pectoris - chest pains due to part of the heart being blocked

arrhythmias - abnormal (not sinus) rhythm due to lack of blood/dying parts of the heart

cardiac failure - heart cant pump enough blood to meet the bodies needs

Cerebral ischaemia - transient ischaemic attack - blood flow to part of the brain is temporarily blocked - could be due to a blood clot, narrowing of vessels - etc

cerebral infarction

multi-infarct dementia - loss of congitve functions due to lack of blood to the brain

Mesenteric ischaemia - ischaemic colitis - blood supply to bowel is compromised, therefore not enough blood for tissues in cell

malabsorption - occurs due to lack of oxygen to tissues of bowel

intestinal infarction - bowel starts to die due to lack of oxygen

Peripheral vascular disease - intermittent claudication - pain in legs after mild excursion, relieved after rest

Leriche syndrome - build up of plaque in your 2 iliac arteries

ischaemic rest pain - pain in feet when elevated

gangrene - tissue death due to lack of blood supply

Abdominal Aortic aneurysm - Weakening of aortic vessel walls, due to presence of ATS (causes damage to the elastic lamina therefore when stretched there is less recoil therefore abnormal dilation, which can lead to rupture)

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7
Q

ATS pathogenesis

A

Age - slowly progressive throughout adult life, risk factors operate over years

Gender - women protected relatively before menopause, presumed hormonal basis - after menopause they are at more risk

Hyperlipidaemia - high plasma cholesterol associated with atherosclerosis , increased LDL count is most significant, high HDL count is seen as protective

Cigarette smoking - Powerful risk factor for IHD, Risk falls after giving up, Mode of action for ATS is uncertain? - does it affect the coagulation system? reduce PGI2? Or increase platelet aggregation?

Hypertension - Strong link between IHD and high systolic/diastolic blood pressure, Mechanism uncertain? - endothelial damage caused by raised pressure?

Diabetes mellitus - DM doubles IHD risk, the protective effect in premenopausal women lost, DM is also associated with high risk of cerebrovascular and peripheral vascular disease, may be related to hyperlipidaemia and hypertension

Alcohol - >5 units /day associated with increased risk of IHD, Alcohol consumption often associated with other risk factors eg smoking and high BP but still an independent risk factor
Smaller amounts of alcohol have indicated a protective function

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8
Q

ATS - lipid metabolism

A

Lipid in the blood is carried on lipoproteins

Lipoproteins carry cholesterol and triglycerides (TG)

These lipoproteins contain a hydrophobic lipid core and a hydrophilic outer layer of phospholipid and apolipoprotein (A-E) - they come in different forms -

Chylomicrons - transport lipid from intestine to liver
LDL - rich in cholesterol, carry cholesterol to non liver cells
VLDL - carry cholesterol and TG from the liver, TG removed leaving LDL
HDL - carrry cholesterol from periphery back to liver

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9
Q

ATS and apolipoprotein E

A

Genetic variations in Apo E are associated with changes in LDL levels

Polymorphisms of the genes involved lead to at least 6 Apo E phenotypes

Polymorphisms can be used as risk markers for atherosclerosis

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10
Q

Familial hyperlipidaemia

A

Genetically determined abnormalities of lipoproteins

Lead to early development of atherosclerosis

Associated physical signs
arcus - blue/grey circle around the cornea of the eye
tendon xanthomas - build up of lipid underneath the skin causing a yellow patch
xanthelasma - an xanthoma but around the eye

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11
Q

Risk factors for ATS

A

Lack of exercise

Obesity

Oral contraceptives

Stress and personality type?

Genetic Predisposition - Familial predisposition well known
Possibly due to
variations in apolipoprotein metabolism
variations in apolipoprotein receptors

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12
Q

Processes and roles of cells in ATS

A
Processes that occur in ATS - 
Thrombosis 
Lipid accumulation 
Production of intercellular matrix 
Interactions between cell types

The role of Endothelial Cells in ATS - Key role in haemostasis
In ATS they have altered permeability to lipoproteins
In ATS they have increased production of collagen
And stimulation of proliferation and migration of smooth muscle cells occurs to the site of the plaque build up in the intima of the vessel

Role of Platelets - Key role in haemostasis
Stimulate proliferation and migration of smooth muscle cells (PDGF)

Role of Smooth Muscle Cells - Take up LDL and other lipid to become foam cells
Synthesise collagen and proteoglycans

Role of Macrophages - Oxidise LDL
Take up lipids to become foam cells
Secrete proteases which modify matrix
Stimulate proliferation and migration of smooth muscle cells

Role of Lymphocytes - TNF may affect lipoprotein metabolism
Stimulate proliferation and migration of smooth muscle cells

Role of Neutrophils - Secrete proteases leading to continued local damage and inflammation

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13
Q

ATS - a unifying hypothesis

A
Endothelial injury occurs in blood vessels due to -
	raised LDL
	‘toxins’ eg cigarette smoke
	hypertension
	haemodynamic stress

This endothelial injury causes
platelet adhesion, PDGF release, smooth muscle cell proliferation and migration
accumulation of lipid, LDL oxidation, uptake of lipid by Smooth muscle cells and macrophages
migration of monocytes from the blood into intima

The smooth muscles cells that have been stimulated produce matrix material - such as collagen (this holds all the cells, lipids and inflammatory mediators in one place - forms the fibrous cap)
Foam cells that have formed secrete cytokines causing
further SMC stimulation
recruitment of other inflammatory cells
Once this fibrous cap gets too big it ruptures causing a bleed - which could lead to thrombosis and occulsion of the vessel

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14
Q

ATS - prevention and intervention

A
Prevention:
No smoking 
Reduce fat intake 
Treat hypertension 
Not too much alcohol 
Regular exercise/weight control
BUT some people will still develop atherosclerosis!
Atherosclerosis - Intervention: 
Stop smoking 
Modify diet 
Treat hypertension 
Treat diabetes 
Lipid lowering drugs
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