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so I want to talk to you a little bit about {atherosclerosis},

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and I have already cheated a little bit, and I started drawing,

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I already make a slightly nice drawing, because I want to make sure that

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the important thing is we can actually see them, and that is --it's pretty clear.

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So, in the top left, I have a small vessel,

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and it have the three layers, and in the middle is the lumen,

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and on the outside is the --the outside.

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So, this little white box I've drawn, I've tried to blow it up for you a little bit here,

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so again, over on this side we have the lumen, just to orient you again,

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and this is the outside of a blood vessel.

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So, we know that a blood vessel have three layers and this particular blood vessel is--

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actually, let me lable it, is a middle or large arteries.

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so I'm specifically talking about {large and middle size arteries} here.

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And the reasons that this makes the differece, I'll point out specifically again,

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but there're these green little coils I've drawn here, these little green squigglies,

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and this is a little protein called the {elastin},

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and I specifically want to talk about these arteries, because

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these large and middle arteries that have --in them, in the walls-- elastin,

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are very very susceptible to atherosclerosis, this process.

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And so, I've thought that it makes sense to point out just for you to know exactly

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which vessels are being affected by this process.

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So let's go through and --quckly refresh ourselves, and talk about three layers of the vessel,

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we have the intima, the {tunica intima}.

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And I was writing 'T' for tunica.

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And then --that's the innermost layer.

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The middle layer right here, in red, is the {tunica media},

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and remember that, because it's the middle layer, so media, middle.

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And on the outside right here is the {tunica externa}. Externa, kind of the external layer.

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And sometimes you see that as {adventitia}, another word for it.

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So these are the three layers, we know this.

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And the way that atherosclerosis happens, now this is a process in --it's a,

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it's a process that affects millions and millions of people.

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The way this happens is that it usually affects these large vessels --large or middle arteries,

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and actually these vessels just --to give you a little bit an orientation,

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I'm talking about 1 mm size of vessels all the way about 25 mm in diameter.

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So kind of a --kind of biggest vessels, that you could actually see with your naked eye,

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this could be like the artery, that maybe-- maybe the aorta, the largest artery,

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or could be an artery that goes up to my arm, the brachial artery.

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So in here these large or middle size arteries fit in this category,

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and they're affected by atherosclerosis.

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So the first step in atherosclerosis, let's just jump and do it,

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it's that you have an irritant, some irritant.

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And that could be --I'm not talking about, maybe someone's annoying little brother or sister, annoying neighbour,

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but some irritant like, let's say you have --here I'll draw in red-- a toxin from cigarrette smoke.

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So let say you've got some toxin that's swimming through your blood vessels, and that could be an irritant.

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Another irritant could be --so I'll put smoking up here for that--

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another irritant could be, maybe having too much lipids, so maybe hyperlipidemia.

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Hyperlipidemia.

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And when I say lipid, I mean specifically fats and cholesterols.

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So, you could have little droplets --it's showed a little yellow droplets, 'cuz I think yellow as fat,

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of LDL, this is a protein. LDL stands for --actually I'll write that out--

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Low Density --that's what the L dan D are--

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Low Density Lipoprotein.

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So this is basically something that carries fat and cholesterol around your blood.

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So you could have too much of it. You could have too much LDL in your blood,

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in the blood vessels, in the arteries.

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And that could be an irritant.

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Or it could be --maybe I'll use a dark-- maybe a white colour here,

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maybe could be high blood pressure,

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high blood pressure pushing out on these vessels, could be an irritant.

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So any of these things could be an irritant, hyperlipidemia, smoking, or hypertension or high blood pressure.

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Could be an irritant.

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And what is being irritated?

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What is the thing that is being irritated?

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That's number two.

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It's the layer of cells right here, these inner layer cells in the tunica intima.

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and that layer itself we know as the endothelial layer. {endothelial cells}

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So that's the layer that's being offended somehow, so it's being upset or angry.

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It's getting upset at these irritants, so I'm going to show some unhappy faces here,

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maybe some unhappy faces down here from the LDL,

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maybe some unhappiness from that high blood pressure.

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And right behind it, --just to orient you-- is the basement membrane,

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but really again it's the endothelial cells that're being irritated.

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Right, so that would be step two, is endothelial --actually leaving the same colour--

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{endothelial disfunction}. This stop working the way they like to work,

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in all, try to be a little bit more specific,

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endothelial cells are basically a barrier, right?

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they're creating a barrier between what is flowing through the blood and the wall itself,

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right, they're the first thing that molecules and cells in the blood are gonna see.

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And so, if you have endothelial disfunction, what you get is

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that this barrier starts breaking down.

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And so this barrier --let me erase some of this stuffs now, just to make some space,

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we know that LDL is Low Density Lipoprotein, I'll erase that.

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And I'll erase this white areas for the hypertension.

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And I'll even erase that ciggarette smoke, the toxin.

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and I'll leave the LDL for a second, you'll see why.

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But please let me show you that these cells start getting unhappy,

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and they start breaking down, and --I guess I'll erase a lot of it and I'll draw some of it back.

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And what you get is something like this.

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We've --We have, now, a breach. A breach.

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So you have these cells here, but now they're letting stuff through.

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And the stuff they get through, primarily --and this is of importance to us, is the LDL.

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So even if something else was the irritant,

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let's say cigarrete smoke was the major irritant here,

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and you got endothelial disfunction from that,

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the next step in atherosclerosis, step three, is LDL goes into --I'll just write--

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into T. or tunica intima.

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This is kind of the next major step, is that LDL decides that it wants to go inside,

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it likes to be inside of this layer.

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And so you got LDL hanging out over here --I'll just write LDL here, so you'll know what we're talking about.

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So all this little molecule of LDL, which again, you bring with them a lot of fat and cholesterol,

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and they're all now in this tunica intima layer.

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So they're all within this tunica intima layer --let me try make that very clear,

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all within this layer tunica intima.

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So they're not usually there. And that's step three.

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Now step four, really really interesting,

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this is where things get really kind of wild,

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is you have cells in your immune system that are right here, called {macrophages}

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Macrophages.

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and these macrophages, they have huge mouth,

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and they're --actually macrophages really means 'big eater'.

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So, macro-big, and 'phage' meaning to eat.

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Macrophages actually swim through the blood, and they're patroling the blood,

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almost like police officers,

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and they sense that, "hey, something is not right with this wall, there's LDL in there"

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and they go in pursuit --they go after that LDL.

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And now they go into the wall.

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So now you got LDL on the wall, you got macrophages on the wall,

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and so I'm gonna draw these macrophages, it's not to scale, just again they're bigger than this.

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But they're now in the wall, they're hanging out in this area, right.

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And they start devouring, again they're big eaters.

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So they start devouring, gobbling up all that fat.

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So this is gonna get a little bit tricky, but let me try to sketch it out again up here for you.

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These're gobbling up fat, and they get loaded with this little fat,

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these little particles of LDL.

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So this is now LDL that's inside of the macrophages, right?

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and if you look through microscope, what this may look like?

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is --you have to use your imaginaton here, but is seafoam.

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So if you actually look --go out to the sea, you know, let's say you go to Mediteranean Sea.

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And you look at seafoam, that's actually what it would look like, potentially.

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That 's someone's thought anyway.

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And so they called these cells, these macrophages that've gobbled up LDL,

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and actually died, so these cells has now died.

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I'll draw a little Xs, because it is so much have died.

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These cells they called them {foam cells}.

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Foam cells. I'll just write a little arrow here,

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so you know which one I'm talking about. Foam cells.

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So if you look in the tunica intima again, that's for all the action is, right?

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this is --this is the important part here --I'll draw box around it.

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That's kind of the central stage.

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The LDL, the macrophages that chase down, now the dead foam cells,

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are all sitting in here, in this lake of fat.

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So now you got macrophages in step four --let me just make sure I catch up with our picture.

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Macrophages and plus foam cells.

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foam cells.

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into tunica intima, right.

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So now we're on the same page.

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And this --this intima now, really, starts looking a lot like this.

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Let me erase this, clean this up a little bit,

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because it's getting quite a mess here, then you'd --you'd agree it needs a little cleaning up.

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So let me erase all this stuff on the outside.

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We know that LDL was in the blood, but it went into the intima, we know that.

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So --so now you have, basically, this LDL, all of these molecules (...) is start merging,

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into literally a lake. Think about it like a lake of fat.

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and how disgusing about is that, right? Like a lake of lard, here, or fat, here.

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It's your fat, or this person's fat.

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And it's all, in this layer, called the tunica intima.

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In fact, let me even draw another dead macrophage.

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It's another foam cell, I'm making a foam cell out of this.

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Looks like seafoam, maybe.

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And so you have here a lake of LDL.

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You have foam cells, and it's all sitting in the tunica intima.

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And if you're actually to, let's say you're to fillet this cell open,

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or this blood vessel open --let me to try to show what I mean.

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If you're --let's say you have this blood vessel.

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I'm drawing you very simply now, you know that that there're three layers,

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it's not the one that I'm drawing there,

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but let's imagine that you took a knife and you slice through it.

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So now, you basically are looking at kind of just the inside of it.

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Right, it's the inside of it.

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What you would see is basically this giant streak of fat.

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And this is kind of that lake, that I just showed you, right.

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Now, looking at it lengthwise.

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So this lake of fat is called the {fatty streak}.

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So if you open up a blood vessel, and look at it,

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if this process has been going on, you might start seeing fatty streaks.

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and so that's basically the first half of atherosclerosis.

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So let's pick up there in the next video.

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~o0o~