Atherosclerosis – part 1 | Circulatory system diseases | Health & Medicine | Khan Academy

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.

9 comments

  1. Is the fatty streak similar to the atheroma, as atheroma is the build up of fatty material, such as lipids, cholestoral etc?

  2. You forgot to mention that LDL gets oxidized (oxLDL) in the endothelial space, and that the macrophages only start phagocytosing them because the oxLDL is toxic to the endothelial cells. Non-oxLDL actually gets absorbed much slower. This is because once LDL becomes oxidized, the lipids in the APOE (a.k.a. LDL) undergo chain reaction oxidation of adjacent lipids, as well as protein denaturation in the LDL, and the oxidative stress, if unchecked, could affect other lipid membranes (i.e. the endothelial cell membrane). 

  3. monocyte adhere to the endothelium => migrate to intima => transformation of monocyte to macrophage which engulfs the entering cholesterol and becomes foam cells.

  4. Atherosclerosis = hardening, narrowing, and block of the artery, caused by the consumption saturated fats from animal consumption. Primarily poultry (chicken) and dairy (cheese). So this includes all flesh (meat, chicken), dairy, and oils (olive, palm, etc etc)

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