Health and medicine
Course: Health and medicine > Unit 3Lesson 2: Atherosclerosis, arteriosclerosis, and arteriolosclerosis
Atherosclerosis - part 1
See how Atherosclerosis (Fat in the blood vessel wall) hardens the arterial wall and makes it harder for blood to flow through. Rishi is a pediatric infectious disease physician and works at Khan Academy. Created by Rishi Desai.
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- Are there drugs or other non-invasive methods to get the 'lake of macrophages and foam cells' to migrate back across the endothelial membrane? Does the endothelial membrane have a mechanism of repair if lipids and other contaminants are removed or drastically decreased in concentration?(6 votes)
- Q1 - There could be, as new technology is rapidly forming, including Nano robots and others besides.
Q2 - The endothelial membrane should have a mechanism of repair as it is an important part of the body.(2 votes)
- What is the difference between atheroma and atherosclerosis? Thanks(3 votes)
- Atherosclerosis is a general term for the thickening of an artery due to lipid deposition along with macrophages and the rest of inflammatory junk as explained in the video (arteriosclerosis being even more general, meaning any hardening of a vessel, including calcification.)
Atheroma is a palpable, yellow elevation running down the affected artery, seen when cutting open the vessel. If the yellow strip can’t be felt, then pathologists call that a fatty streak. These are just ways of describing atherosclerosis.(4 votes)
- Diabetics tend to have very high levels of heart disease. Could high blood sugar be an irritant that causes the irritation that causes atherosclerosis?(6 votes)
- But how can hyperglycemia cause endothelial dysfunction? I suspect it has something to do with AGE?(0 votes)
- Is it possible to have atherosclerosis in the veins?(3 votes)
- Atherosclerosis occurs when Low Density Lipoproteins get oxidized. And the plasma in the arteries contains plenty of oxygen to oxidize the LDL's it occurs mostly in arteries. In the veins, there is little oxygen to be found, so it is much more likely to happen in the arteries for that reason.
Hope this helps!(3 votes)
- Is there a way to show how atheroma and atherosclerosis work by experimentation through everyday materials?(3 votes)
- How long could someone live without Endothelial cells?(2 votes)
- Endothelial cells line blood vessels, they make up capillaries. We need them.(3 votes)
- So how does the irritant irritate the wall? Do they just simply rub or do they attack?(3 votes)
- it's not macrophages in the blood, it should be monocytes?
Once they leave the blood they are called macrophages right?
great vid btw(3 votes)
- Monocytes don't become macrophages simply because they leave the blood. A monocyte "becomes" a macrophage when it has matured.(0 votes)
- Why does the LDL deposit only on the large or middle size blood vessel? Why aren't there any LDL accumulation inside the arteriolos?(2 votes)
- Why does your body send out macrophages even if they might not help because they'd stuff themselves with LDL cholesterol and turn into dead foam cells?(2 votes)
So I wanted to talk to you a little bit about atherosclerosis. And I have already cheated a little bit, and I've started drawing. I wanted to make it a slightly nicer drawing, because I wanted to make sure that the important things, we can actually see them and that it's pretty clear. So in the top left, I have a small vessel. And I have the three layers. And in the middle is the lumen, and on the outside is the outside. So this little white box I've drawn, I've tried to blow it up for you a little bit here. So again, over on this side, we have the lumen, just to orient you again. And this is the outside of a blood vessel. So we know blood vessels have three layers, and this particular blood vessel is-- actually, let me label it-- is a middle or large artery. So I'm specifically talking about large and middle-sized arteries here. And the reason that this makes a difference-- I'll point it out specifically again, but there are these green little coils I've drawn here, these little green squigglies. And this is a little protein called elastin. And I specifically want to talk about these arteries, because these large and middle arteries that have in them, in the walls, elastin, are very, very susceptible to atherosclerosis, this process. And so I thought that it makes sense to point it out, just so you know exactly which vessels are being affected by this process. So let's go through and very quickly refresh ourselves and talk about the three layers of the vessel. We have the intima, the tunica intima. And I'm just writing T for tunica. That's the innermost layer. The middle layer, right here in red, is the tunica media. And I remember that because it's the middle layer. So media, middle. And on the outside, right here, is the tunica externa, kind of the external layer. And sometimes you'll see that as adventitia, another word for it. So these are the three layers, and we know this. And the way that atherosclerosis happens-- now, this is a process. And it's a process that affects millions and millions of people. The way this happens is that it usually affects these large vessels, large and middle arteries. And actually, these vessels, just to give you a little bit of an orientation, I'm talking about one millimeter sized vessels, all the way to about 25 millimeters in diameter. So kind of biggish vessels that you could actually see with your naked eye. This could be like the artery that-- maybe the aorta, the largest artery. Or it could be an artery that goes out to my arm, the brachial artery. So any of these large or middle-size arteries fit into this category, and they're affected by atherosclerosis. And so the first step in atherosclerosis-- let's just jump into it-- is that you have an irritant, some irritant. And that could be-- I'm not talking about maybe someone's annoying little brother or sister or annoying neighbor, but some irritant like-- let's say you have here, I'll draw it in red, a toxin from cigarette smoke. So let's say you have some toxin that's swimming through your blood vessels. That could be an irritant. And other irritant could be-- so I'll put smoking up here for that. Another irritant could be maybe having too much lipids, so maybe hyperlipidemia. And when I say lipid, I mean specifically fats and cholesterol. So you could have little droplets. Let's show little yellow droplets, because I think of yellow as fat, of LDL. This is a protein. LDL stands for-- actually, I'll write that out-- low density. That's what the L and the D are, low-density lipoprotein. This is basically something that carries fat and cholesterol around your blood. So you could have too much of it. You could have too much LDL in your blood, in the blood vessels, in the arteries. And that could be an irritant. Or it could be-- maybe I'll use a dark-- then maybe a white color here. Maybe it could be high blood pressure. High blood pressure pushing out on these vessels could be an irritant. So any of these things could be an irritant. Hyperlipidemia, smoking, or hypertension, or high blood pressure could be an irritant. And what is being irritated? What is the thing that is being irritated? That's number two, is the layer of cells right here, this inner layer of cells in the tunica intima. And that layer of cells, we know, is the endothelial layer. So that's the layer that's being offended somehow, so it's being upset or angry. It's getting upset at these irritants. So I'm going to show some unhappy faces here, maybe some unhappy faces down here from the LDL, maybe some unhappiness from that high blood pressure. And right behind it, just to orient you, is the basement membrane. But really again, it's the endothelial cells that are being irritated, right? So that would be step two, is endothelial-- actually, let me leave it in the same color. Endothelial dysfunction. They stop working the way that they like to work, and I'll try to be a little bit more specific. Endothelial cells are basically a barrier, right? They're creating a barrier between what is flowing through the blood and the wall itself, right? They're the first thing that molecules and cells in the blood are going to see. And so if you have endothelial dysfunction, what you get is that this barrier starts breaking down. And so this barrier-- let me erase some of this stuff now just to make some space. We know that LDL is low density lipoprotein. I'll erase that. And I'll erase these white arrows for the hypertension. And I'll even erase that cigarette smoke, the toxin. And I'll leave the LDL for a second, you'll see why. But basically I'm going to show you that these cells start getting unhappy, and they start breaking down. And I guess I erased a lot of it, but I'll draw some of it back. And what you get is something like this. We basically have now a breach. So you have these cells here, but now they're letting stuff through. And the stuff that gets through primarily-- and this is of importance to us-- is the LDL. So even if something else was the irritant-- let's say cigarette smoke was the major irritant here, and you get endothelial dysfunction from that. The next step in atherosclerosis, step three, is LDL goes into-- I'll just write into T, or tunica intima. This is kind of the next major step, is that LDL decides that it wants to go inside. It likes to be inside of this layer. So you get LDL hanging out over here. I'll just write LDL here just so you know what we're talking about. See, all these little molecules of LDL, which again, bring with them a lot of fat and cholesterol, and they're all now in this tunica intima layer. So they're all within this tunica intima layer. Let me make sure I make that very clear. All within this layer of tunica intima. So they're not usually there, and that's step three. Now step four, really, really interesting-- this is where things get really kind of wild-- is you have cells in your immune system that are right here called macrophages. And these macrophages, they have huge mouths. And they are actually-- macrophage really means big eater. So macrophage, macro, big, and phage, meaning to eat. Macrophages actually swim through the blood and are patrolling the blood, almost like police officers. And they sense that hey, something is not right with this wall. There's LDL in there. and they go in pursuit. They go after that LDL. And now they go into the wall. So now you've got LDL in the wall. You've got macrophages in the wall. And so I'm going to draw these macrophages, not to scale, because again, they are bigger than this. But they're now in the wall. They're hanging out in this area, right? And they start devouring. Again, they're big eaters, so they start devouring, gobbling up all that fat. So this is going to get a little bit tricky, but let me try to sketch it out again up here for you. They start gobbling up fat. And they get loaded with this little fat, these little particles of LDL. So this is now LDL that's inside of the macrophage, right? And if you look through a microscope, what this might look like is-- now, you have to use your imagination here-- but is sea foam. So if you actually go out to the sea-- let's say that you go to the Mediterranean Sea, and you look at sea foam. That's actually what it would look like. Potentially. Someone thought so, anyway. And so they called these cells, these macrophages that have gobbled up LDL and actually died-- so this cell has now died. I'll draw little x's, because it ate so much it died. These cells, they call them foam cells. And I'll just write a little arrow here so you know which one I'm talking about. Foam cells. So if you look in the tunica intima again, that's where all the action is, right? This is the important part here. I'll draw a box around it, because that's kind of the center stage. The LDL, the macrophages that chased it down and now the dead foam cells are all sitting here in this lake of fat. So now you got macrophages as step four. Let me just make sure I catch up with our picture. Macrophages and plus foam cells. Foam cells into tunica intima. So now we're all on the same page, and this intima now really starts looking a lot like this. Let me erase this, clean this up a little bit, because it's getting quite messy. I think you'd agree it needs a little cleaning up. Let me erase all this stuff on the outside. We know that LDL was in the blood, but it went into the intima. We know that. So now you have, basically, this LDL-- all these little molecules of LDL start merging into literally a lake. Think of like a lake of fat. How disgusting a thought is that, right? Like a lake of lard here, or fat here. It's your fat or this person's fat, and it's all in this layer called the tunica intima. In fact, let me even draw another dead macrophage. This is another foam cell. I'm making a foam cell out of this. It looks like sea foam, maybe. And so you have here a lake of LDL. You have foam cells, and it's all sitting in the tunica intima. And if you were actually to-- let's say you were to fillet this cell open-- or this blood vessel open. Let me try to show what I mean. Let's say you have this blood vessel. I'm drawing it very simply now. You know that there are three layers, not the one that I'm drawing there. But just imagine that you took a knife and you sliced through it. So now you're basically looking at just the inside of it, right? Just the inside of it. What you would see is basically just a giant streak of fat. And this is kind of that lake that I just showed you, right? Now looking at it lengthwise. So this lake of fat is called a fatty streak. So if you open up a blood vessel and look at it, if this process has been going on, you might start seeing fatty streaks. And so that's basically the first half of atherosclerosis. So let's pick up there in the next video.