Week 7: Atherosclerosis

Question 1

What is atherosclerosis?

Answer 1

a fibrofatty lesion in the tunica intima of large and medium sized arteries. This develops ‘plaque’ like substances.

Question 2

What are the 3 things that atherosclerotic plaque can lead to on the atrial wall?

Answer 2

Decrease Lumen diameter –> decreases blood flow Weaken vessel wall Plaque thrombus/emboli formation

Question 3

What is the number 1 cause for atherosclerosis?

Answer 3

Dyslipidaemia –> as the plaque has a high lipid composition

Question 4

Differentiate between the two lipoproteins, and which one causes atherosclerosis?

Answer 4

 If there is an imbalance, anytime LDL increases and HDL decreases, there is a greater risk of atherosclerosis

Question 5

What are the 3 major stages of atherosclerosis?

Answer 5

1. Fatty streak formation 2. Plaque progression 3. Plaque disruption

Question 6

Describe the process of ‘fatty streak’

Answer 6

Endothelial dysfunction –> LDLs leak into tunica intima at rate which cannot be managed by macrophages. (INSUDATION) LDLs become trapped and are ‘modified’. Endothelium responds by expressing leukocyte adhesion molecules which grab onto passing monocytes and migrates them in. These monocytes are then converted into macrophages which try to engulf the modified LDLs. Macrophages become engorged with modified LDLs creating foam cells. You get accumulation of foam cells within the intima which gives rise to fatty streak If endothelial disruption persists the risk factors remain and inflammatory processes increase

Question 7

How does the endothelium respond to increase LDLs being trapped in the tunica intima?

Answer 7

 The endothelium will respond by expressing leukocyte adhesion molecules, which will grab onto passing monocytes migrating them into the vessel wall  These monocytes are then converted into macrophages, which try to protect the tunica intima by eating up all the modified LDL molecules (via scavenger receptors)

Question 8

Describe the plaque progression stage

Answer 8

 The next stage is characterised by the migration of the smooth muscle cells from the tunica media to the tunica intima  This stage occurs if the foam cells are not taking up enough modified LDLs to prevent the destruction to the Tunica Intima, so the SMCs are called in to help  When these SMCs migrate towards the tunica intima they begin to synthesise connective tissue, most importantly collagen and proteoglycans  This facilitates the formation of an appropriate ‘cap’ between the lipid core and fragile endothelial cells so that the endothelial dysfunction is minimised in an attempt to regain homeostasis (also prevents the exposure of the contents to the blood)  If the risk factors and endothelial dysfunction and dyslipidaemia remains, the plaque progression the necrotic core continues to develop (meaning lipid content within tunica intima is extremely high)  This process may remain silent, or may progress to form stable (resistant to rupture) or unstable plaque (vulnerable to rupture)

Question 9

What are the 2 types of plaque?

Answer 9

1. Stable plaque - Usually will have a good thick fibrous cap, that is full of collagen and elastin, sequesters the contents from the blood stream - With a small lipid core - These tend to narrow causing stenosis or narrowing of the arteries (these are easy to find with angiography) which can be treated with a stent 2. Vulnerable plaque (unstable) - This plaque is very vulnerable to rupture which would expose the inner content to the blood stream - This type of plaque usually is associated with a large necrotic core (high lipid content), and quite a thin fibrous cap - These have a large number of macrophages - These also have a progressive blood supply towards the plaque regions (neovascularisation) - As the newly developed blood vessels formed through neovascularisation are newly formed, they break quite easily. As a result of this intraplaque haemorrhage is common

Question 10

What happens if plaque disruption occurs

Answer 10

 If disruption or erosion of the plaques fibrous cap occurs, it causes thrombosis  Once the plaque opens up, exposing its content to the blood it starts the clotting process immediately as blood coagulant factors contact the blood (which is produced by the apoptotic macrophages and SMCs)  The body fights back, and if the patient has good anti-thrombotic mechanisms this wont necessarily develop into a clot  This can occlude the lumen partially or completely, resulting in the development of symptoms

Question 11

How could a necrotic core formation lead to a life threatening situation?

Answer 11

Eventually reduces arterial lumen space, also weakens the arterial wall –> can eventually lead to a rupture

Question 12

What are the organs which are most often affected by atherosclerotic plaque?

Answer 12

Heart, brain, kidneys, arms and legs

Question 13

How does tobacco smoking increase atherosclerotic plaque formation?

Answer 13

Toxins promote every step of the process

Question 14

How does diabetes increase atherosclerotic plaque?

Answer 14

dyslipidaemia and increase glycolated produced

Question 15

What strategies will reduce circulating LDL and enhance HDL further leading to lower risk of atherosclerosis?

Answer 15

Stop smoking Healthy diet Exercise lose weight control diabetes decrease obesity

Question 16

What are a few methods to stabilise vulnerable plaque?

Answer 16

Decrease LDLs, increase HDLs, decrease angiotensin 2, decrease blood pressure

Question 17

What are some routine diagnostic tests employed to assess risk of atherosclerosis?

Answer 17

Test LDL and HDL levels Look at blood sugars Cardiac stress test –> put them on treadmill to see if they get chest pain when exercising. More occluded blood vessel more likely to get symptoms. Can use stent or bypass to treat

Question 18

What are the non-modifiable and modifiable risks for atherosclerosis

Answer 18