Lecture 27 Flashcards
What is artherosclerosis?
This is a disease of the intima which reduces the size of the lumen and causes a blockage of the arteries
What is a hypertrophy?
This is an increase in the wall thickness
Does atherosclerosis expand inwards or outwards?
inwards
After the initial intima injury, what happens in regards to remodelling?
During atherosclerosis, there is insufficient outward remodelling and the lumen decreases. Then there is remodelling of the media (atrophy, loss of smooth muscle cells) to accomodate plaque and preserve the lumen diameter
What is atrophy?
A decrease in the size of a body part
What is restenosis?
This is when you deal with atherosclerosis surgically
Atherosclerosis is defines to certain areas in the body. What are these parts?
- coronary arteries
- carotid/cerebral arteries
- limb arteries
- renal arteries
Atherosclerosis in the coronary arteries leads to what?
coronary heart disease
Atherosclerosis in the cerebral (carotid) arteries leads to what?
transient ischemic attack or stroke
Atherosclerosis in the limb arteries leads to what?
peripheral artery disease
Atherosclerosis in the renal arteries leads to what?
hypertension or kidney failure
What is an aneurysm?
This is a bulge in the artery
How long does atherosclerosis take to develop?
decades
What is the first step in the development of atherosclerosis? What are some of the risk factors of this?
An initial injury of the endothelium. Risk factors include: - hypercholesterolemia (most important) - hypertension - high triglycerides - inflammation
What is meant by a risk factor for an injury of the endothelium?
These are situations that if they are present they are increasing your risk of developing initial injury of endothelium
What are the two types of cholesterol? Which is the good one?
HDL and LDL
HDL is the good one
What are high risk levels for HDL and LDL and what are normal levels?
HDL: normal is more than 1.6 mmol/L, high risk is less than 1.0mmol/L
LDL: normal is less than 2.6 mmol/L, more than 4.1 mmol/L is high risk
Why is LDL bad and why is HDL good?
LDL stick to the artery walls which leads to plaque formation and the HDL carried LDL away from the artery walls
What is the next step after the initial injury to the endothelium in the process of atherosclerosis?
There is the formation of the fatty streak
Describe the formation of a fatty streak (part one)
LDL can migrate through the epithelial cells into the intima. If the influx exceeds the elimination pool, they can’t be cleared by the HDL so there is a build up of LDL in the intima. This forms an LDL pool in the vessel wall
After the build up of the LDL pool what happens (during the formation of a fatty streak)?
The LDL is sitting in the subendothelial intima. If there are lots of radical species present (eg. during inflammation), then LDL becomes oxidised (oxLDL).
What is the problem with having oxLDL during the formation of a fatty streak?
oxLDL triggers a response that attracts __________ by expression of __________ ____________ molecules. This leads to __________ secretion which attracts _____________. The endothelium are being damaged which opens more to let _______ in, and this leads to _______ attraction. __________ enter the intima.
oxLDL triggers a response that attracts monocytes by expression of leucocyte adhesion molecules. This leads to chemokine secretion which attracts monocytes. The endothelium are being damaged which opens more to more LDL in, and this leads to monocyte attraction. Monocytes enter the intima.
What happens after the monocytes enter the intima during the formation of the fatty streak?
Monocytes turn into macrophages to take up the excessive oxLDL which kills them and then they turn into foam cells. Foam cells can attract more monocytes if the LDL is not removed and this causes a fatty streak
What is the relevance of fatty streaks in terms of DEATH?
In general it is not directly clinical significant or life threatening. Many just disappear and only some progress to atherosclerosis plaques
What is the next stage after formation of a fatty streak in terms of atherosclerosis?
formation of plaque
Describe the formation of plaque
Once you have foam cells in the intima, it the situation doesn’t improve, the smooth muscle cells migrate from the media into the intima and are triggered to grow. This triggers the formation of the ECM which consists of elastin and collagen
What happens after the synthesis of ECM in the formation of plaque?
Microphages trigger the formation of collagen and elastin in the intima and they also develop calcium crystals. This is part of an inflammatory response. This forms a cap around the lipid core to isolate the core to prevent it from clotting
What happens after the formation of the fibrous cap around the lipid core during the formation of plaque?
The plaque is the core of the fibrous cap and this is made of collagen, elastin, calcium. If the fatty streaks grow, you get a core when it needs to be protected from getting to the lumen. This is good for the short terms but if it not fixed, it could affect blood flow. If there is a lesion in the endothelium, there is a blood clot which impacts blood flow
What happens after the formation of plaque in the process of atherosclerosis?
Activation of plaque
Describe the activation of plaque during the process of atherosclerosis
If there are lesions and fissures (eruption of the plaque) in the endothelium, there could be a formation of a thrombus (blood clot) on the plaque. This is because the factors in the blood are triggered by the lipid core to form a blood clot. If that sits in a blood vessel, it impedes blood flow. If it gets too lose, it becomes an embolism.
What is an arterial/venous thrombosis?
This is the formation of a thrombus within an artery or a vein
What is the arterial/venous embolism?
Interruption of blood flow due to an embolus (free-moving thrombus), potentially causing infarction of almost any organ/part in body. The vascular system goes from large to small vessels so could block an artery
During the formation of a fibrous cap:
a. monocytes turn into macrophages and take up the excessive oxLDL particles.
b. smooth muscle cells migrate into the media.
c. the clinical risk for an arterial thrombus is very high.
d. calcium crystals are formed in the intima.
d. calcium crystals are formed in the intima.
Atherosclerosis is a ________ phenomenon but where does it occur?
local
it occurs in specific types of arteries - normally in the elastic arteries such as the aorta, carotid arteries, iliac arteries, large-medium sized muscular arteries but not usually in small arteries
What are the risk factors of Atherosclerosis?
hypertension, smoking, diabetes, hyperlipidemia
Atherosclerosis is a local phenomenon but the risk factors are what?
systemic
It is a combination of the systemic risk factors and the local factors that cause Atherosclerosis, true or false?
true
Why is Atherosclerosis more common in the elastic arteries?
Atherosclerosis is abnormalities of blood vessel wall, it is a vascular repair response. It can also be related to abnormalities of the constituents of the blood (coagulation and platelet activation). It is also due to abnormalities in blood flow, particularly in relation to shear stress
What is shear stress? What senses it?
Force resulting from friction of flowing blood on luminal surface
The endothelial cells are a mechano-sensing element which means that they can sense the shear stress
What happens when there is a normal amount of shear stress?
NO production which ________ vessels, there is a decrease expression of _________ response mediators, _______ molecules (which means that there is less attraction of ________), vasoconstrictors and _________ which means that there is less risk of ______________
NO production which dilates vessels, there is a decrease expression of inflammatory response mediators, adhesion molecules (which means that there is less attraction of monocytes), vasoconstrictors and oxidants which means that there is less risk of oxLDL
What happens if there is low shear stress (due to low blood flow) or turbulent shear stress?
Reduced _________ production, enhanced ___________ adhesion, ____________ activation, _________ ________ Cell proliferation, ________ activity, ___________
These are all involved in the formation of the fatty streak
Reduced NO production, enhanced monocyte adhesion, platelet activation, Smooth Muscle Cell proliferation, oxidant activity, vasoconstriction
These are all involved in the formation of the fatty streak
When there is nice shear stress, what do the endothelial cells look like?
They are nicely aligned
When there is turbulent shear stress, what do the endothelial cells look like?
they are not aligned and there is longer interaction time between blood constituents and endothelium
When there is turbulent shear stress, what do the endothelial cells look like?
they are not aligned
Local areas with low shear stress and altered flow directions during cardiac cycles have higher risk of atherosclerosis. What are examples of them?
Arteries with turbulent and pulsatile flow
Elastic arteries (Aorta, carotid arteries, iliac arteries)
Large-medium sized muscular arteries (coronary + femoral)
Why is the carotid artery susceptible to plaque formation?
Lower blood pressures because the head above the heart. There is also turbulent blood flow in the “fork”.
Why are the coronary arteries susceptible to plaque formation?
They have the high(est) blood pressures from aorta
Ageing and Hypertension (Reflections)
They are part of the heart and the heart contracts whcih means that it’s part of the compressive systolic force. There is turbulent flow, constant compressive systolic force which makes it susceptible to plaque formation
How can we prevent atherosclerosis?
take statin which lowers the LDL or take things that absorb cholesterol
Once you have atherosclerosis, what can you do about it?
You can go into the vascular system and move up to the heart and inject a contrast dye. This means that you can see the blockage. You can put a stent in to keep the lumen open. You could also do angioplasty (ballooning of the vessel) but this could lead to a rupture. Stenting and angioplasty work but if people don’t adjust their lifestyle, it can also lead to restenosis. There could be remodelling and you could end up at the original situation
What is an endarterectomy?
This is the removal of atheromatous plaque material. This only works for some vessels. If it is in the heart, instead you normally get a bypass using an artifical artery or vein
What are aortic aneurysms?
They can result from atherosclerosis. This is the dilatation of the aorta which can occur in the Ascending, arch, descending, infrarenal, juxtarenal, suprarenal part of the aorta. If it ruptures, you die. Repair them with stents
Coronary arteries have a high risk of developing atherosclerosis BECAUSE coronary arteries have a relative high blood pressure and continuously turbulent flow.
A. Both statements are correct and causally related.
