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Flashcards in Atheroma Deck (26):
1

Define atheroma

A chronic lesion in the intima that occurs in the arteries, producing narrowing of the lumen and weakening of the vessel wall. 

2

Define atherosclerosis

Hardening of the arteries characteries by intimal lesions (atheromas) that protrude into the vessel lumen. 

3

Define arteriosclerosis

Hardening of the arteries and arterioles which results in thickening of the vessel wall and loss of elasticity

4

State 5 risk factors for atherosclerosis

Modifiable: 
Hyperlipidaemia (LDLs, cholesterol): increases risk of lesion development
Hypertension
Smoking
Diabetes Mellitus: induces high cholesterol

Non-modifiable:
Aging: progressive disease, doesn't manifest til 40+
Male: premenopausal women protected by oestrogen
Family history
Genetic abnormalities e.g. familial hypercholesterolemia

Risk factors have a multiplicative effect

5

Name 5 risk markers for atherosclerosis

Obesity

Low HDLs

Sedentary lifestyle

Alcohol

High carbohydrate intake

Low oestrogen post-menopause

Hypothyroidism

6

Describe the cellular events leading to the formation of athersclerotic lesions

Endothelial injury causes increased vascular permeability and activates endothelium to release cytokines, chemokines and express adhesion molecules. 

Increased vascular permability allows lipids to leak into the intima  where they are oxidised by free radicals and enzymes

Monocytes adhere to the endothelium, and migrate to the intima where they digest lipids and are transformed into foam cells. Activated macrophages release cytokines that recruit T-cells and APCs. T-cells release cytokines and promote a chronic inflammatory state

Damage to the endothelum exposes collagen and vWF which activates platelets, promoting thrombosis. 

Factors released from activated platelets, macrophages and endothelial cells recruit smooth muscle cells from the intima and circulation, which proliferate and produce ECM.

Smooth muscle cells also take up oxidised lipids to become foam cells. There is also intracellular calcification which is deposited as cells degenerate

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7

What is an atheroma?

An intimal lesion (atherosclerotic plaque) that consists of a lipid core (mostly cholesterol) and an accumulation of inflammatory cells, vascular smooth muscle cells and ECM covered by a white fibrous cap made of smooth muscle cells and collagen. 

Often undergo calcification

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8

What are the 5 common arteries involved in atherosclerosis?

Abdominal aorta

Coronoary arteries

Legs (poplitieal)

Internal carotid

Cerebral arteries

9

How does blood flow affect the development of atheroma?

Plaques tend to occur at opening of vessels, branch points and along the posterior wall of the aorta. 

Flow is more turbulent in these areas, and they are therefore more susceptible to endothelial damage. 

10

What is a fatty streak?

Deposition of foam cells, ECM and proliferating smooth muscle in the intima. Early lesion which can later develop into a mature atheroma. 

 

11

What is the composition of atherosclerotic plaques?

Cells: Smooth muscle cells, macrophages, T-cells

ECM: collage, slastin, proteoglycans

Lipid: intracellular and extracellular cholesterol and LDLs

12

State four things that can damage the endothelium (favours atheroma formation)

Haemodynamic disturbance: hypertension, turbulent flow

Infection

Inflammation: complement, cytokines,

Lipid products

Toxins: bacterial products, smoking

13

What are the consequences of atherosclerotic disease?

Ischemia: small vessels can become occluded, compromising tissue perfusion

Thrombosis: rupture, ulceration or erosion of the atheromatous plaque can result in thromosis which can partially or completely occlude the lumen

Haemorrhage into a plaque due to a rupture of the fibrous cap, causing it to expand and occlude the vessel

Atheroembolism: plaque can rupture and release debris into the bloodstream

Aneurysm formation: atherosclerosis induces pressure/ischemic atrophy of the media and there is loss of elastic tissue, causing weakness of the vessel wall. 

14

What are the possible complications of an aortic aneurysm?

Rupture

thrombus

emboli

pressure on structures (e.g. vertebrae)

fistulas to the GI tract

15

What factors affect plaque stability?

Intrinsic factors: Plaque structure and composition

Extrinsic factors: Blood pressure, Platelet reactivity

The compositon of plaques is dynamic and this can affect stability, those with large areas of foam cells or thin fibrous caps are more likely to rupture

Rupture of a plaque means it was unable to withstand the vascular shear forces of blood flow. 

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16

How can the circadian pattern of onset of acute MI be explained?

Blood pressure is an extrinsic factor that affects stability of atheromatous plaques. Adrenergic stimulation can increase systemic blood pressure or induce local vasoconstriction which increases the stress on the plaque. 

Adrenergic stimulation is involved in standing from a horizontal/seated position causing a sudden increase in blood pressure. 

17

What determines the effect of atheroma on distal tissue?

Effects of atheroma on the tissue supplied distally is determined by:

size of the lumen

stability of the plaque

degree of degeneration of the underlying wall

natural history of the plaque

type of blood supply

18

What is an aneurysm?

Localised abnormal dilation of a blood vessel or the heart

True aneurysm involves an intact, attenuated arterial wall or a thinned ventricular wall of the heart. 

Occur when the structure or function of the connective tissue in the vascular wall is compromised

19

What are the two most common disorders that predispose to aortic aneurysms?

athersclerosis (abdominal aorta) and hypertension (ascending aorta)

 

Other conditions; trauma, vasculitis

20

How do abdominal aortic aneurysms develop?

Atherosclerotic plaque in the intima compresses the underlying media and compromoses the blood supply from the vascular lumen to the arterial wall. 

Lack of nutrients and waste removal causes atrophy and necrosis that results in weakening and thinning of the arterial wall. This causes it to dilate in response to the high pressure of the blood running through it as the structure cannot be maintained. 

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21

What is endothlial dysfuntion?

Altered phenot type of the endothelial cells that impairs vasoreactivity or induces a thrombogenic surface

22

What are the symptoms of peripheral vascular disease?

Intermittent claudication (muscle cramp normally in the calf, during exercise which resolves with rest)

Pain at rest (unremitting pain in the foot)

Ischaemic limb (ulceration or gangrene)

Cold limbs with dry skin and lack of hair

Diminished/absent pulses

23

What are the effects of atherosclerotic plaques in the mesenteric arteries?

Chronic bowel ischemia 

Can result in mesenteric angina (pain following a meal)

or ischemic colitis (necrosis of the bowel tissue causing diarrhoea)

24

What are the effects of atherosclorotic plaques in the cerebral arteries

Vascular dementia - occurs due to small emboli lodging in the vessels causing cellular damage. Presents as a stepwise decline with each new emboli (not progressive)

TIA: neurological symptoms due to ischemia (dizzyness, parasthesia)

Cerebrovascular accident: affects vision, cognition, motor function

25

What is the effects of atherosclerosis on the heart?

Myocardial ischemia (90% caused by atherosclerotic plaques in the coronary arteries). 

Can result in MI, angina, heart failure or sudden cardiac death

 

Obstruction of 75% of the lumen is required to cause symptoms (angina) beause compensatory vasodilation is no longer sufficient to meet increases in myocardial demand. 

26

Name four effects of atheroma

Plaque rupture: leading to thrombus formation and/or emboli which causes occlusion

Bleeding into atheroma: causes occlusion

Chronic narrowing of the lumen: reduces blood flow, causes chronis ischemia

Weakening of vessel wall: aneurysm

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