Atherosclerosis - Pathophysiology

biology and Medicine videos please make sure to subscribe join the foring group for the latest videos please visit Facebook Aran in this video we're going to talk about arthrosclerosis which is hardening of the arteries actually it's in the narrowing of the arteries due to plaque formation a pla in this case is basically a waxy substance made of predominantly lipids and atherosclerosis is different to arteriosclerosis arteriosclerosis is just hardening of the arteries now arthrosclerosis is a common cause of heart attacks so if here I'm drawing the heart we have blood vessels called these coronary arteries that

supply the heart with oxygen so let's take a look at two different scenarios here are vessels and here are cardiac muscle cells normally the vessels the blood vessels are carrying blood full of oxygen to the cardiac muscle cells thus allowing the ciac muscle cells to function normally which means the heart will function normally however if we look at an authos if we look at an atherosclerosis scenario there is a plaque formation blood can't be delivered properly to the heart or there is reduced like blood flow to the heart and as a consequence the cardiac muscle

cells are deprived of oxygen symptoms of atherosclerosis in the coronary arteries uh include vomiting anxiety angina which is pain in the in the chest area coughing and feeling faint so again if the atherosclerosis in the coronary artery here is so severe it can actually block everything it can block the blood supply all together and we get es schea of the cardiac muscle cells and so as a consequence the the these cells will die and you get a heart attack or heart failure so arthrosclerosis formation of the coronary arteries can lead to myocardial esea but there

can also be oscuros formation in the cored arteries this can cause symptoms such as weakness dvia headache facial numbness and paralysis and this is because the cored arteries is the blood supply to your brain so if you don't get any blood to your brain you get stroke as well as these symptoms um alos scerotic plot can cause peripheral vascular disease now periphal vascular disease is the reduced circulation of blood to a body part other than the brain or heart so you know for example the liver or or uh something else like your reproductive organs and

this is bad in every respect uh in peral vascular disease you can have uh hair loss erectile dysfunction and weakening of the associated area another important site where atherosclerosis can occur is the Ral arteries this can cause a reduction in appetite swelling of the hands and um and most importantly it can trigger renin release which will significantly increase the blood pressure okay so there were some common sites where althos scerotic PLS can occur but let's see how severe and aortic plot can become so here is the increase in severity the first blood vessel here is

normal with normal blood flow as we can see a pla can form within the layer of the blood vessel firstly will be growing downwards so pushing sort of the vessel down when more plot forms the pla become begins growing upwards so it will actually narrow the blood vessel if the pla keeps growing severity increases and the blood vessel really begins to narrow the massive PL at the end can actually then rupture forming a thrombus forming a clot which will stop or impede blood flow when an Arctic plock ruptures it is serious now that we get

the overall picture let's look at the mechanism of plot formation in a bit more detail so let us Zoom first into this blood vessel and look at its different layers and what they contain so here is our endothelial cells and here is the Lumen where we have red blood cells and also lipoproteins such as ldls which are low density lipoproteins surrounding the endothelium we have the Tunica Ina and then the chuna media in the Chun media we have smooth muscle cells that are important in contraction of vessels surrounding the media we have the adventia which

is essentially connective tissue there are a few theories of how atherosclerosis begins one Theory be uh suggests that there is endothelial dysfunction and when there is high amounts of circulating ldls because there are high con concentrations or high circulating low density lapo proteins low ldls these ldls can deposit in the chuna intima and then become oxidized oxidized LDL activates endothelial cells causing the endothelial cells to express receptors uh for white blood cells on their surface so to summarize here I wrote increase in ldls deposits in chuna intima and becomes oxidized which will activate endothelial cells

so here I'm drawing the same layers of the blood vessel and we can see there is accumulation of O um o oxidized ldls which will activate endothelial cells which will begin expressing adhesion mod molecules for white blood cells adhesion of white blood cells adhesion of blood Lucy to activated endothelial uh cells will allow um monocytes and t- helper cells to move into the Tunica Ina layer of the blood vessel when monocytes move into the Tunica intima they will become macrofagos and macrofagos will then take up these oxidized ldls and then become foam cells the foam

cells are key in atherosclerosis foam cells do many things one of which is it promotes migration of smooth muscle cells SMC from the Tunica Media into the Tunica intima and also promotes smooth muscle cell proliferation an increase in smooth muscle cell proliferation heightens or increases synthesis of collagen which can lead to hardening of the author's chloric plot during this whole process foam cells will also die releasing its lipid content this drives the growth of the plock as the plock grows it builds in pressure which can cause rupturing of the plaque itself which is where things

can become serious so here again we have the Tunica intima and tuna media of the blood vessel here are the smooth muscle cells which have accumulated in the Tunica inal layer um as well as collagen foam cells are here and they die together with other cells in the area so here we have dead foam cells with lipid contents spilt out the growth of the plaque is this area here now the pla can then rupture which can lead to thrombosis thrombosis is when the plaque ruptures and where coagulation happens to stop uh to stop the plot

from spilling its content into the Lumen this forms a thrombus a clot which can impede blood flow and cause serious complications so okay that was re that was that was a bit of detail of how AOS scerotic pla forms and how it ruptures but let us go a step further and look at it in a bit more detail and and a I guess a a better diagram maybe so here is we have the endothelial cell the chuna intima layer and then we have the chuna media layer containing smooth muscle cells and here is our Lumen

the inside of the blood V vessel we can where we can find red blood cells and we can find circulating low density lipoproteins um this black dot here of the LDL is called a is is is the protein part anyway let's just say we have dysfun a dysfunctional endothelial cells dysfunctional endothelial cells here this allows the you know a lot of ldls to basically move into the tuna intimal layer when it moves into into malayer the dysfunctional endothelial cells release reactive oxygen species and other enzymes such as metalloproteases which will oxidize the LDL so when

the LDL is oxidized it cannot actually leave the Tunica intima it's trapped okay the dysfunctional endothelium and the O subsequently oxidized LDL uh triggers the endothelial cells to remember Express uh adhesion molecules for white blood cells so here we have a monite circulating around it attaches to these receptors and then it will move in when it moves into the tunic Ina when monocytes move into tissues they become macres so here we have a maccrage three the maccrage has a receptor a scavenger receptor that will basically eat up that will take in this o oxidized LDL

the maccrage engulfs this oxidized LDL and then it will become a foam cell now foam cells they're basically macres containing lipids and they have many many functions one of which is that it will release chemokines to attract more macrofagos foam cells can also do step four here I'm drawing it can release uh igf1 which is basically a growth factor and this growth factor will cause smooth muscle cells to migrate and cause smooth muscle cell proliferation in the Tunica intima so here we have the smooth muscle cells in the chuna media layer and they will migrate

into the chuna intimal layer and they will proliferate and here because we have a lot of a smooth muscle cells step five they make more collagen fo foam cells in Step six can also die and they will die releasing their lipid contents including DNA materials this DNA material will actually attract nutrifil because it's sort of very it's it's actually inflammatory in this respect foam cells can also release pro-inflammatory cyto kindes and reactive oxygen species and um and this together with neutrophils will increase inflammation in the area and this area is actually now the plaque cuz

it's got foam cells it's got dead dead foam cells it's got collagen it's got smooth muscle cells it's got all this stuff and this makes up the pla another interesting thing that occurs is uh we there is an increase in blood supply to the layer of the chuna intima to the vessel so it's if you didn't know vessel blood vessels have its own vessel Supply and this vessels these vessels are known as V vas of zorm anyways these te te- cells also have a role uh in atherosclerosis so these te- cells they can Bine onto

adhesion receptors which are expressed on endothelial cells they then enter the area they enter the pla area they can be activated by macrofagos and they can begin releasing other substances such as interfer and Gamma interfer and Gamma essentially promotes inflammation and it activates endothelial cells to attract more wide blood cells than everything else so this plaque essentially will just keep growing it will cause in it causes foam cells to die it's it's there's increase in lipid content there's inflammation and then all this as it grows it can rupture and this is when thrombosis occurs rupturing

and when it ruptures a thrombus can form a clot can form and a clot forms when there's heaps of platelets heaps of clotting factors that all aggregate to the area and all this can impede blood flow uh so that was a video on authos sclerosis I hope you enjoyed it thank you