00:01
Welcome.
00:02
We're going to talk
about an important
and sometimes catastrophic occurrence
that happens within the aorta.
00:09
This is aortic dissection.
00:11
And often the predecessor to that is
aortic aneurysm dilation of the aorta.
00:17
In order to really understand how this
happens the aorta and the various causes,
we have to go back to the normal
structure and function of the aorta.
00:26
So this is our typical artery.
00:30
But now we're going to expand
the media in particular
because that's the most important
part of the aortic architecture.
00:38
So imagine this is an aorta, you have
endothelium that's identified there,
sits on a basement membrane,
basal lamina, whatever,
there is an internal
elastic membrane,
and then there is a very
thick, smooth muscle media.
00:52
The smooth muscle media in the aorta
has a very high elastic tissue content,
and a very high extracellular matrix
content collagens type l and lll,
that's because the aorta is a
high-pressure organ, a high-pressure artery,
and has to hold up pretty well to
120 mm of mercury peak systole.
01:16
It also has to have recoil.
01:18
So when blood flows
out at 120 mm of mercury,
a nice healthy aorta,
because the elastic tissue content
is able to slightly
ever so slightly dilate,
but then recover that volume and
pressure and squeeze it during diastole.
01:36
And that ability to recoil is
all due to the elastic tissue.
01:41
There's an external elastic membrane that
is variable, but it can be recognizable,
and that will between the
internal elastic membrane
and the external elastic
membrane, we'll have our media.
01:53
And then outside of that
are going to be the vessels of the
of the aorta, the vasa vasorum.
02:00
So vessels of the vessel that are
part and parcel of the adventitia.
02:05
Those vessels of the vasa vasorum are
particularly important in the aorta,
because the media is very thick.
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And we cannot maintain
that aortic media
just by simple diffusion
from the lumen of the aorta.
02:23
Let's look at this in a
slightly different way.
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So this is in a cross section.
02:28
And again,
going from the inside,
which is the lower right
hand corner to the outside,
which is the upper
left hand corner.
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We have an endothelium sitting on a basal
membrane, internal elastic membrane.
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And then we have this
very thick walled media
with lots and lots and lots
of smooth muscle cells,
interspersed with connective
tissue, elastic tissue,
and type l and type lll
collagen for the most part.
02:52
We'll have an external
elastic membrane,
and then we'll have the adventitia which
contain the vessels of the vasa vasorum.
02:58
And you see them as those
little red snaky lines
that are coming in to the
outer 2/3 of the media.
03:06
That is how we perfuse how we maintain the
viability of the outer 2/3 of the media.
03:14
The green arrow is
indicating the depth
by which we can support
the medius muscle cells
by diffusion just
from the lumen.
03:22
And there's clearly a substantial
thickness in the media
that won't live if we're dependent
on just luminal diffusion.
03:30
So that's an important kind
of organizational structure,
realizing that there is a
watershed zone within the media.
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And if we affect the
vessels of the vasa vasorum,
the outer 2/3 of
the media may die.
03:44
If we thicken the intima,
we will have a greater diffusion distance
in the inner third of the media may die.
03:52
And if we understand that we can
understand a lot of the etiologies,
the causes the pathogenesis, underlying
aortic dissection and aortic aneurysms.
04:02
Alright, let's look more specifically
at the smooth muscle cells
because it's not just them.
They're signalling that regulate
the various factors that they're
going to secrete the various proteins.
04:14
One of the important extracellular
matrix elements is fibrillin.
04:20
So fibrillin is a fibrillar
protein, it's rather large,
and it has kind of a globular
and a fibrillar structure
such as indicated there.
04:29
We're just showing that at higher power
or at a greater magnification at the top.
04:35
And if we look at the
image that's on the bottom,
it's going to be those blue little
fibrils and interspersed yellow dots
that sit between
the elastin core
and the overlying
smooth muscle cells.
04:49
So the pink, elongated things
are smooth muscle cells,
they are going to be responsible for
making all this extracellular matrix.
04:58
And sitting between the elastic
core and smooth muscle cells
are going to be the
fibrillin microfibrils.
05:05
They're going to be
a scaffolding upon
which we lay down a lot
of extracellular matrix,
but they're also going to be a
regulatory protein that will bind up
certain factors that are important for
regulating smooth muscle cell function.
05:22
What do I mean by that?
Well, so we have our
fibrillar microfibrils.
05:26
That's that kind of blue fibrillar
thing on top of the elastic core
and between it and
the smooth muscle cell
dotted with a little globular
subunits of that protein.
05:40
On the smooth muscle cells,
we have TGF-beta receptors.
05:45
TGF-beta stands for
transforming growth factor beta,
and it's an important
cytokine that regulates
smooth muscle cell behavior
and its synthetic function.
05:58
And too much TGF-beta
has an impact on how well
the normal architecture of the
smooth muscle media is maintained.
06:08
So smooth muscle cells
secrete TGF-beta.
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They also have the
receptors for TGF-beta.
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This is an autocrine
stimulatory loop.
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Collagen is another component that is
secreted by the smooth muscle cells
and it's type l predominantly but also
type lll collagen and to a lesser extent,
some of the other collagens.
06:31
So those are all of our
players within this media.
06:37
So it's rather complex, just looking
at all the different elements.