0:00:00.000,0:00:01.880


0:00:01.880,0:00:04.040
I'm actually just going[br]to take a step back,

0:00:04.040,0:00:06.360
clear out some of this stuff.

0:00:06.360,0:00:09.380
You've understood[br]the first half of how

0:00:09.380,0:00:14.120
this process of[br]atherosclerosis happens.

0:00:14.120,0:00:17.080
And we're going to finish[br]off the second half.

0:00:17.080,0:00:19.750
So all of the action[br]is still going

0:00:19.750,0:00:21.340
to happen in the tunica intima.

0:00:21.340,0:00:24.069
So that much is going[br]to stay the same.

0:00:24.069,0:00:25.735
And so far, we talked[br]about macrophages.

0:00:25.735,0:00:28.690
And we talked about how[br]they form foam cells

0:00:28.690,0:00:32.520
and they eat up all[br]the fat and they

0:00:32.520,0:00:35.130
form this kind of lake of fat.

0:00:35.130,0:00:37.630
And so let me leave it there.

0:00:37.630,0:00:39.700
So that's where the[br]picture's at so far.

0:00:39.700,0:00:43.090
And now let's talk about[br]what happens after that.

0:00:43.090,0:00:48.700
So the next step,[br]step five, basically

0:00:48.700,0:00:50.929
what happens is the[br]smooth muscle cells--

0:00:50.929,0:00:52.970
smooth muscle cells, we[br]haven't talked about them

0:00:52.970,0:01:01.930
so far-- they shimmy,[br]or they dance over.

0:01:01.930,0:01:08.650
Let's write dance[br]over to tunica intima.

0:01:08.650,0:01:11.610
So really, again, everything is[br]happening in the tunica intima,

0:01:11.610,0:01:12.110
right?

0:01:12.110,0:01:12.869
You can see that.

0:01:12.869,0:01:14.160
That's where all the action is.

0:01:14.160,0:01:15.780
And so when I say[br]they dance over,

0:01:15.780,0:01:17.310
I'm being a little bit silly.

0:01:17.310,0:01:19.460
But basically, what happens[br]is that these cells,

0:01:19.460,0:01:24.210
these red, smooth muscle cells--[br]these are the smooth muscle

0:01:24.210,0:01:30.640
cells-- they are going[br]to start migrating.

0:01:30.640,0:01:33.220
They're going to start[br]migrating or moving.

0:01:33.220,0:01:35.730
And they're going to start[br]migrating into this space.

0:01:35.730,0:01:37.540
Maybe that one[br]will go over there.

0:01:37.540,0:01:40.920
Maybe this one will go over[br]here, perhaps this one.

0:01:40.920,0:01:42.780
And the way they[br]start migrating is

0:01:42.780,0:01:45.010
that there's a lot[br]of action going on.

0:01:45.010,0:01:46.160
The macrophages are there.

0:01:46.160,0:01:49.500
They've got the LDL[br]in that lake of fat.

0:01:49.500,0:01:52.350
And a lot of chemicals are[br]being released by these cells.

0:01:52.350,0:01:54.790
And so they sense that[br]something's happening.

0:01:54.790,0:01:56.340
So they kind of move over there.

0:01:56.340,0:02:01.560
And what they begin to[br]do is make a fibrous cap.

0:02:01.560,0:02:03.570
That's step six.

0:02:03.570,0:02:07.090
So they make a fibrous cap.

0:02:07.090,0:02:10.310
Actually, let me write who[br]makes it, so it's very clear.

0:02:10.310,0:02:15.060
Smooth muscle cells,[br]S-M-C, smooth muscle cells

0:02:15.060,0:02:18.010
make a fibrous cap.

0:02:18.010,0:02:20.396
And what a fibrous[br]cap is is think

0:02:20.396,0:02:21.770
about when you[br]were really young.

0:02:21.770,0:02:22.645
And you were playing.

0:02:22.645,0:02:25.610
And you didn't really pay[br]attention and fell a lot.

0:02:25.610,0:02:27.950
You might have come[br]home with skinned knees.

0:02:27.950,0:02:28.790
And I certainly did.

0:02:28.790,0:02:31.230
And my mom used to[br]always remark on that.

0:02:31.230,0:02:34.980
And those skinned knees[br]turn into scabs, right?

0:02:34.980,0:02:38.540
And so these smooth muscle[br]cells, these fibrous caps,

0:02:38.540,0:02:42.450
basically think of[br]it as a scab, a scab

0:02:42.450,0:02:47.190
that forms over[br]this lake of fat.

0:02:47.190,0:02:50.490
So I've been drawing for[br]you this yellow lake of fat.

0:02:50.490,0:02:52.270
And now these[br]smooth muscle cells,

0:02:52.270,0:02:54.640
they come in and[br]say, well, we've

0:02:54.640,0:02:59.050
got to make a cap[br]over this thing.

0:02:59.050,0:03:02.880
Let me erase again and draw for[br]you what that might look like.

0:03:02.880,0:03:06.610
So let's say that this[br]lake is getting bigger.

0:03:06.610,0:03:09.900
This lake, over time, has[br]gotten really quite big.

0:03:09.900,0:03:14.065
And you've got more fat in[br]here from all that LDL that

0:03:14.065,0:03:16.800
keeps depositing,[br]because, going backwards,

0:03:16.800,0:03:19.510
the endothelial cells[br]are not working well.

0:03:19.510,0:03:23.070
And so you've got[br]this kind of weird set

0:03:23.070,0:03:26.480
of endothelium[br]kind of around it.

0:03:26.480,0:03:31.220
And the smooth muscle[br]cells come over,

0:03:31.220,0:03:34.790
and they decide they're going to[br]help with making a fibrous cap.

0:03:34.790,0:03:38.560
So let me do that[br]in a new color.

0:03:38.560,0:03:39.860
Let's do it in red.

0:03:39.860,0:03:41.670
I guess that would[br]come up nicely.

0:03:41.670,0:03:46.320
So they basically[br]make this cap here.

0:03:46.320,0:03:53.010
And this cap mixes in to this[br]layer and settles in right

0:03:53.010,0:03:55.120
there, right?

0:03:55.120,0:03:58.010
And you've got some[br]endothelium over it,

0:03:58.010,0:03:59.780
but sometimes you don't.

0:03:59.780,0:04:03.960
And so this layer of endothelium[br]is pretty well disrupted,

0:04:03.960,0:04:04.890
I would say.

0:04:04.890,0:04:07.350
You've got this nice,[br]thick fibrous cap.

0:04:07.350,0:04:11.740
And what's in that cap is things[br]like collagen, or elastin.

0:04:11.740,0:04:14.120
So proteins are in this cap.

0:04:14.120,0:04:18.470
So you've got a fibrous cap.

0:04:18.470,0:04:25.655
And it's made of[br]collagen and elastin.

0:04:25.655,0:04:27.535
So these are the[br]proteins that we

0:04:27.535,0:04:33.240
know help with keeping all of[br]the cells in our body in place.

0:04:33.240,0:04:36.450
And so you can always point[br]to your bones, or your nose,

0:04:36.450,0:04:38.890
and you can find[br]these proteins there.

0:04:38.890,0:04:40.930
So it makes this fibrous cap.

0:04:40.930,0:04:46.700
And so now, really, what[br]you have is fat with a cap.

0:04:46.700,0:04:48.755
So that's kind of[br]how I think of this.

0:04:48.755,0:04:55.020
This is fat with a cap.

0:04:55.020,0:04:56.530
And it sounds simple.

0:04:56.530,0:04:59.270
And in a way, that's a very[br]reasonable way to think of it.

0:04:59.270,0:05:01.430
You've got the lake of fat.

0:05:01.430,0:05:03.970
And over it, you've[br]got this fibrous cap.

0:05:03.970,0:05:06.389
And what that does[br]is two things.

0:05:06.389,0:05:07.930
You've already seen[br]that this is kind

0:05:07.930,0:05:11.242
of starting to bulge into[br]the blood vessel, right?

0:05:11.242,0:05:13.700
I'm going to go to that little[br]diagram in the corner again.

0:05:13.700,0:05:16.850
So you had a beautiful[br]blood vessel, nice and kind

0:05:16.850,0:05:18.670
of circular.

0:05:18.670,0:05:21.640
And then, now,[br]you've got this fat

0:05:21.640,0:05:26.910
that's sitting in here,[br]this giant lake, right?

0:05:26.910,0:05:29.760
And over it, I put a cap.

0:05:29.760,0:05:32.081
So now you've got a cap here.

0:05:32.081,0:05:33.830
So what has happened[br]to this blood vessel?

0:05:33.830,0:05:37.990
Well, you had a certain[br]radius on that blood vessel.

0:05:37.990,0:05:41.110
And that radius[br]has gotten smaller.

0:05:41.110,0:05:49.360
So in terms of big key[br]ideas, key changes,

0:05:49.360,0:05:53.200
your blood vessel has[br]actually gotten smaller.

0:05:53.200,0:05:57.489
So one is smaller radius.

0:05:57.489,0:05:59.280
And you can see that[br]in the picture, right?

0:05:59.280,0:06:01.180
Smaller radius.

0:06:01.180,0:06:04.800
And we know that radius[br]is related to resistance.

0:06:04.800,0:06:08.080
So that means[br]increased resistance.

0:06:08.080,0:06:12.500
Increased resistance[br]here to blood flow.

0:06:12.500,0:06:16.310
And of course, I'm talking[br]about the distance from here

0:06:16.310,0:06:19.430
over to here is smaller, now[br]that you've got something

0:06:19.430,0:06:22.430
pooching out into the lumen.

0:06:22.430,0:06:24.540
And the other change--[br]and this is actually

0:06:24.540,0:06:28.110
quite interesting-- is[br]that the wall itself

0:06:28.110,0:06:30.170
is actually tougher.

0:06:30.170,0:06:31.870
It's more stiff.

0:06:31.870,0:06:34.810
And so right here, one[br]of the other things--

0:06:34.810,0:06:37.050
actually, I didn't[br]talk about it much,

0:06:37.050,0:06:39.640
but maybe I should say very[br]quickly right now-- maybe even

0:06:39.640,0:06:46.650
a step seven is that the smooth[br]muscle cells make-- or let's

0:06:46.650,0:06:53.690
say here-- lay down calcium.

0:06:53.690,0:06:56.420
So when I say lay down,[br]what does that mean exactly?

0:06:56.420,0:06:58.357
Are they like bricklayers?

0:06:58.357,0:07:00.190
But when I say lay down[br]calcium, what I mean

0:07:00.190,0:07:03.530
is that these cells[br]are actually going

0:07:03.530,0:07:07.900
to start pretending in a way[br]that they are making bone.

0:07:07.900,0:07:10.430
And actually, the[br]dead foam cells

0:07:10.430,0:07:13.860
create this little[br]micro-environment

0:07:13.860,0:07:17.100
where these smooth muscles start[br]thinking, oh, my gosh, maybe I

0:07:17.100,0:07:19.380
should lay down some calcium,[br]put some calcium here.

0:07:19.380,0:07:22.330
So they'll put a little[br]calcium nugget right here.

0:07:22.330,0:07:24.840
I'll put another calcium[br]nugget right there.

0:07:24.840,0:07:28.220
And I'll put another calcium[br]nugget there and there.

0:07:28.220,0:07:30.410
And all of a sudden,[br]if you start looking,

0:07:30.410,0:07:32.210
you start thinking,[br]oh, wow, this

0:07:32.210,0:07:34.950
is actually very calcified.

0:07:34.950,0:07:40.210
And this is actually looking[br]a little bit like bone.

0:07:40.210,0:07:42.560
This is what happens with bone.

0:07:42.560,0:07:45.620
So they start calcifying[br]this entire area.

0:07:45.620,0:07:49.620
And if you calcify this area,[br]if you start putting down

0:07:49.620,0:07:51.700
these little[br]crystals of calcium,

0:07:51.700,0:07:54.970
then what's going to happen is[br]that your arteries literally

0:07:54.970,0:07:59.940
become crispy, crunchy, which[br]sounds kind of disgusting.

0:07:59.940,0:08:01.150
I guess it is.

0:08:01.150,0:08:04.102
But they're[br]essentially more stiff.

0:08:04.102,0:08:05.560
And that's really[br]the key point, is

0:08:05.560,0:08:10.835
that you get more stiffness,[br]or lower compliance.

0:08:10.835,0:08:16.280


0:08:16.280,0:08:21.470
And that goes back to the[br]crunchiness of the vessel,

0:08:21.470,0:08:24.510
or the inability to[br]be kind of flexible.

0:08:24.510,0:08:30.910
So lower compliance,[br]less flexible.

0:08:30.910,0:08:34.299
Just as a little reminder[br]of what that means.

0:08:34.299,0:08:36.210
So those are the big[br]changes that you see.

0:08:36.210,0:08:39.780
And the lower radius[br]increases resistance.

0:08:39.780,0:08:42.610
And the lower compliance[br]means that it's

0:08:42.610,0:08:45.770
harder for these large[br]and middle-sized arteries

0:08:45.770,0:08:50.050
to expand like a balloon every[br]time the blood pulses through.

0:08:50.050,0:08:54.540
So both those things are[br]going to cause increase

0:08:54.540,0:08:56.590
in your blood pressure.

0:08:56.590,0:08:58.632