L27 Flashcards
what is atherOsclerosis :
hardening of the arteries, narrowing or blocking the vessel lumen
in atherOsclerosis, after initial intima injury, what happens to the media
remodelling of media (atrophy, loss of
SMC’s) occurs to accommodate plaque and preserve lumen diameter
hypertrophy of vascular walls can cause growth….
inward and outward
what is inward vascular remoderling called
atherOsclerosis
which is the most common/most clinically relevant form of vascular remodeling because of hypertension
atherOsclerosis
what is aneurysm
when vessel wall mass increases but wall thickness decreases
Aneurysms = bulge in a artery – life threating if burst
what is restenosis
an atherOsclerosis vessel PTCA
after you have clinically dealt with it
Atherosclerosis in the body is defined to specific areas
what are the different names for Atherosclerosis over the body
theres 4
Coronary arteries = coronary artery disease
Cerebral (carotid) arteries = transient ischemic attack (TIA), or stroke
Limb arteries = peripheral artery disease
Renal arteries = hypertension, or kidney failure
where do Aneurysms usually occur
usually happen in large arteries
Process of Atherosclerosis is because of…
Endothelial Dysfunction
in atherosclerosis, what are the risk factors which could cause the Initial injury of endothelium
Hypercholesterolemia (most important)
Hypertension
High triglycerides (FFA)
Inflammation
what are the 2 different types of cholesterole (that we learn about) and which is the good and bad one
Low-density lipoprotein (LDL)
- This is the one that sticks to the artery walls and causes the plaques to form
High-density lipoprotein (HDL)
- This is the con that carries LDL away (the good one)
why is Low-density lipoprotein (LDL) bad
it sticks to the artery walls and causes the plaques to form
what is the desirable levels of HDL and what is a high risk level for atherosclerosis
normal > 1.6 mmol/L
high risk < 1mmol/L
what is the optimal levels of LDL and what is a high risk level for atherosclerosis
optimal <2.6mmol/L
high risk > 4.1mmol/L
why do you need to measure for specific types of cholesterol and not just the total
total is misleading because as long as the different types of cholesterol are in balance with each other, therefore if they are both elevated then you are ok it it just if they become imbalanced that you have a problem
as you get older cholesterol levels get higher
what ages should you be checking your cholesterol levels to make sure they are still in ballance to try and prevent atherosclerosis
35-56
men have slightly higher levels
after the initial injury of the intima what is the first steep in the process of atherosclerosis formation
formation of a fatty steak
what is the first steep in fatty streak formation
LDL circulating in the body is able to migrate between the endothelial cells into the intima . If the influx of LDL exceeds the elimination pool and are not eliminated by the HDL then there is a buildup of LDL within the intima. You then get an LDL pool within the intima
what happens to LDL in the presents of reactive oxygen species or radicals (inflammatory factors)
LDL gets oxidised which is bad
LDL on its own aren’t that bad, but once they become oxidised then they are really bad as they do lots of things
oxidised LDL (oxLDL) causes many things to happen
in terms of formation of fatty streak what d they do
Ox LDL attracts monocytes by expression of leucocyte adhesion molecules on the endothelium.
If there is a lot of Oxidation then it could release cytokines which further damage the endothelium making gaps to let more LDL in. It will also leads to monocytes
what happens in fatty streak formation when monocytes enter the intima
Once monocytes are in the intima they become macrophages which uptake the oxidised LDL (this is an immune response) they interalise oxLDL, causing them to die and become foam cells.
These then attack more monocytes which will then form a fatty streak. Fome cell also activate T cells
(T cell = immune response)
describe the formation of a fatty streak
Influx of LDL exceeds eliminating capacity – extracellular LDL pool
LDL migrate to subendothelial intima
LDL oxidized by radicals - oxLDL
oxLDL- expression leucocyte adhesion molecules - chemokine secretion to attract monocytes
Monocytes enter the intima
Monocytes turn into Macrophages to take up the excessive oxLDL
Macrophages internalize oxLDL
Dead macrophages - Foam cells
Foam cells attract more monocytes and form a fatty streak
Foam cells also activate T-cell immune response
faty streaks are formed by oxidized LDL deposition ->
inflammation, macrophages -> foam cells
how clinically significant is this
In general not directly clinical significant or life threatening risk factor
Many just disappear and only some progress to atherosclerotic plaques
how do fatty streaks disappear
If you start exercising, losing weight and start eating healthy these will disappear
when does fatty streak formation occur
This occurs during the first decade of the disease
in the process of atherosclerosis
initial injury –> formation of fatty streak –>?
what happens next
formation of a plaque
what causes the formation of a plaque
in the last steep of fatty streak formation foam cells trigger an immune response (T Cell activation)
Smooth muscle cells (SMCs)
migrate from media into the
intima, and are triggered to grow
Macrophages, foam cell and smooth muscle cells within the intama then trigger the formation of extracellular matrix. This is a immune response (t cells) which trigger the formation of collagen, eleaston (ECM) and calcium crystals (inflammatory response because of c-reactive protein)
what does the inflammatory response in plaque formation cause
This forms a fibrous cap around the lipid core which isolates and stiffens the lipid core to stop the blood from clotting.
what causes the inflammatory response in plaque formation
immune response causes smooth muscle cells to migrate into the intima
in the intima a combo nation of Macrophages, foam cell and smooth muscle cells trigger the formation of extracellular matrix. This is a immune response (t cells) which trigger the formation of collagen, eleaston (ECM) and calcium crystals (inflammatory response because of c-reactive protein)
what is a plaque
The plaque is the lipid core and the fibrous cap (cologen, elestin and Ca).
fatty streaks are harmless but if they keep growing then the body needs to do a repair response (plaque formation)
why is this
to stop blood clotting from happening.
what is the concequences of plaque formation
However if it keeps growing then it can block the vessel causing changes in blood flow which has concequences
If thing get worse again then the plaque could move and form a thrombus and then an embolus
are plaques a clinical problem
Plaques are not a major clinical problem as long as they don’t grow into the leman or form a thrombus
what causes activation of a plaque
for whatever reason they become lesioned or fissured (small tear) in the endothelium and you get a blood cloth formation on the plaque
where can plaque activation occur
This can occur in the arteries and the veins
what are the 2 things that can happen when a plaque becomes activated
It can remain attached to the lipid core or it can move away from it but it will still be attached to the vessel wall
thrombosis
when it becomes detached from the wall it is a embolism
Typically in peripheral arteries disease where are thrombosis formed
in the legs in the veins around the valves
what is the difference between a thrombosis and an embolism
When the thrombus disattaches from the wall it becomes an embolism
The embolus will eventually get stuck somewhere causing blockage of blood flow. This is life threatening
the process of atherosclerosis is what kind of response
a vascular repair response to arterial trauma
it is a defense mechanism in the body that develops over years
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
a. happens before
b. they are already in the media they migrate into the intima
c. no its not
D is correct
atherosclerosis is a local phenomenon
where does it usually happen
Aorta, carotid arteries, iliac arteries
Large-medium sized muscular arteries (coronary + femoral)
Seldom in small arteries
what are the risk factors for atherosclerosis
Atherosclerosis is local but risk factors are systemic
eg hypertension, smoking, diabetes, hyperlipidemia and can be genetic
Systemic factors act in concert with local factors
what are some local abnormalities that cause atherosclerosis
Abnormalities of blood vessel wall: vascular repair response
Abnormalities of blood constituents: coagulation, platelet activation
these cause abnormalities of blood flow: shear stress! (mechanical and physical characteristics)
what is shear stress and what is it detected by
Force resulting from friction of flowing blood on luminal surface
Endothelial mechano-sensing element
describe normal shear stress
NO production, decrease expression of inflammatory
response mediators, adhesion molecules, vasoconstrictors
and oxidants
Less oxidence means that there is less risk of the formation of oxLDLs, decrease in adhesions molecules means that there is less attraction of monocytes
describe low or turbulent shear stress
Reduced NO production, enhanced monocyte adhesion, platelet activation, SMC proliferation, oxidant activity, vasoconstriction
describe low shear stress
low shear stress = low blood flow = Prolonged interaction time between blood constitutions and the endothelium making it more lily to get activation of monocytes and adhesions
Low = shear stress is not aligning the endothelial cells
what is the relationship between low shear stress and turbulent shear stress
Local areas with low shear stress and altered flow directions during cardiac cycles (making it turbulent)
why do elestic arteries develop atherosclerosis
Local areas with low shear stress and altered flow directions during
cardiac cycles have higher risk of atherosclerosis (more pulsatile = more risk)
eg arteries with turbulent and pulsatile flow
Elastic (Aorta, carotid arteries, iliac arteries)
Large-medium sized muscular arteries (coronary + femoral)
what are some reasons for turbulent shear stress
Branches, Bifurcations, Stenosis = Turbulence
describe the carotid arteries in terms of atherosclerosis
Particularly susceptible to plaque formation
has lower blood pressures because the head above the heart
get turbulent blood flow in the “fork” (Bifurcations) and therefore plaque build up
describe the coronary arteries in terms of atherosclerosis
Highest blood pressures from aorta
Ageing and Hypertension (Reflections)
Turbulent flow because of constant compressive systolic force means they are susceptible to plaque build up
describe how the face of atherosclerosis has changed
the traditional stereotypical face of atherosclerosis is a Smoking overweight Caucasian midlife male
now it is a Asian, south Asian, Central and South America, younger women
Obesity because of high consumption of sugar/fructose diets in addition to high fat diets
causing people to have low HDL cholesterol, and high triglycerides
what are statins
HMG-CoA reductase inhibitors, lowers LDL
LDL lowering drugs
what are some examples of statins
Cholesterol absorption inhibitors: block absorption cholesterol in intestine
Inclisiran: interferring RNA lowers LDL levels, only twice a year required.
Bempedoic acid: upstream target of statins
PPARalpha agonists to target triglycerides; anti-inflammatory therapies
what is angiography
Angiography = use of contrast dye and X-ray to see blockages in the vasculature
what is an angioplasty
ballooning
they shove a balloon in the vessel to open it back up to let blood through
Can cause rupture of plaque which can be dangerous
what is stenting
this is when they place a stent in the vessel to open it back up. they can now be drug-eluting (things like NO) to further increase dilation of the vessel
when would precautions like angioplasty and stenting be used
If people don’t adjust their lifestyle
causes restenosis (it will just happen again and you will return to the original situation)
what is a endarterectomy
surgical removal of atheromatous plaque material
mostly used for peripheral artery disease
when would a bypass be used
Coronary artery disease
what does a bypass involve
an artificial, artery or vein
This means that the blockage stays and you make a new artery so that the heart can be perfussed again
what are aortic aneurysms caused by
Aorta dilatation (atherosclerosis – age)
where can aortic aneurysms happen
Ascending, arch, descending, infrarenal, juxtarenal, suprarenal
why are aortic aneurysms so bad
Rupture is almost certain death
Symptoms are rare and non-specific
need to be repaired with stents
You can not know that this is occurring and they are usually discovered by accident. They will then either leave it and monitor it or they can do open heart surgery and replace parts of it
Coronary arteries have a high risk of developing atherosclerosis
BECAUSE
coronary arteries have a relative high blood pressure and continuously
turbulent flow.
both statements are true and causally related
