Atherosclerosis

Question 1

What are the stages of Atherosclerosis?

Answer 1

The 3 layers of the artery allow the blood vessels to form a tube and in the lumen, the middle hollow part of the tube, is where the blood will flow.

• The endothelial cells will detect blood flow.
• Blood is made up of many components; RBC (which circulate and carry oxygen or CO2), WBC and immune cells etc.
• As we age the endothelial cell layer will become damaged. The triggers for this may be because of high levels of circulating ‘ bad fat’ e.g. LDLs, smoking, too much free radicals in the blood etc.
• As overtime the endothelial cells become damaged, this will allow the endothelial cells to become leaky. So normally the endothelial cells will serve as a barrier preventing excessive exchange between blood and the blood vessel wall. But overtime they become damaged and leaky and they start to let too much through from the blood into the artery wall.
• One of the things that will pass through when they become leaky is LDL. So once LDL is crossed the endothelial cell layer will sit of the basement membrane and start to accumulate where it will become oxidised and this oxidation is a trigger for the endothelial cells to start expressing markers that will bind to and attract the immune cells across as well to the basement membrane.
• Here they will start to gobble up the oxidised LDL but at the same time theres lots of cell death occurring, hence they’ll start to gobble up fragments of cells as well. This will ultimately result in the immune cells becoming foam-cells.
• This change into foam-cells is the trigger for smooth muscle cells to start to migrate and proliferate. The smooth muscle cells will form a fibrous cap, to block the blood from seeing the contents of this plaque. So it will keep the oxidised LDL, cell debris and foam cells away from the blood. This cap will form and when it’s nice and big it will be known as a stable plaque and very unlikely to rupture.
• Overtime this cap will start to thin because of smooth muscle cell death, proliferation will stop, the migration would slow down etc. This will then lead to a switch from being a stable plaque to an unstable plaque.
• This unstable plaque can rupture, hence the fibrous cap will break. This will then expose the contents of the plaque to the blood. This will then trigger a cascade of events and will eventually block the blood vessels because of clotting.
• This is really bad because if it happens in the artery it can starve the brain and/or the heart of oxygen hence leading to a heart attack or stroke as a result of plaque rupture.

Question 2

How many layers is the artery wall made up of?

Answer 2

3:

• Inner layer made up of endothelial cells and basement membrane.
• Middle layer made up of smooth muscle cells and elastic components that allow the blood vessels in the artery to stretch and recoil in response changes in blood flow and blood pressure
• Outermost layer

Question 3

What is Haemostasis?

Answer 3

“Arrest of blood loss from damaged blood vessels”

• Normally when you damage a blood vessel, you get bleeding and the whole point of bleeding is that it will activate a series of events that will allow the blood vessel to stop leaking and stop losing blood which is known as haemostasis.

1. Damage of blood vessel
2. Bleeding occurs
3. Theres a wound
4. Vasoconstriction occurs
5. Platelet activation and adhesion
6. Coagulation (formation of a haemostat plug)
7. Fibrinolysis (Once the bleeding stops, you’ll resolve the coagulation)

Question 4

What is thrombosis?

Answer 4

Pathological formation of clot in vasculature in the absence of bleeding.

• In atherosclerotic induced coagulation cascade, theres no bleeding, hence thrombosis.

Question 5

What drugs are used for haemostasis and thrombosis?

Answer 5

• Thrombosis prevention - extensively/largely used
• Drugs affect haemostasis and thrombosis by affecting these stages:
  1. Platelet adhesion and activation
  2. Blood coagulation (fibrin formation)
  3. Fibrin removal (fibrinolysis)