00:01
Increase Vascular Permeability.
00:03
So that's just increased flow
and we're getting increased
movement of water across the cells
just because of
hydrostatic pressure.
00:10
But we're also changing
how the endothelial cells
are behaving.
00:15
And very quickly,
after an initial
inflammatory injury,
or injury that's going to activate
an inflammatory pathway,
we have a transient and reversible
contraction of endothelial cells.
00:28
The cytoskeleton pulls them apart.
00:32
That's driven by histamine
released by the mast cells,
bradykinin,
and we'll talk more about that
that's inflammatory mediator
made by a variety of cells.
00:40
And leukotrienes,
one of those eicosanoids.
00:42
So endothelial cell contraction
happens very quickly.
00:47
Endothelial cell retraction because
of breakdown of the tight junctions
between the endothelial cells
also happens.
00:53
It's more of a passive process,
it takes many hours,
and it's very reversible.
00:57
In fact,
you've all experienced this,
if you've ever had a sunburn,
that late in the day
after you've had that wonderful
glorious day on the beach,
and you've got that nice rosy red
sunburn in your skin.
01:09
And at night, you feel like
your skin's a little tight,
and you feel a little warm.
01:13
Well, in fact, that is
being driven by cytokines.
01:18
Interleukin-1,
tumor necrosis factor
other inflammatory cytokines
that are causing
the endothelial cells
to pull ever so slightly apart.
01:27
And now you're getting a
transudation of fluid water,
making the skin feel
a little bit tight.
01:33
You're also get increased
vascular flow,
and that's why
you feel red and warm.
01:37
So just another little pathologic
take home nugget.
01:40
You can also get
increased permeability
by injury to the endothelium.
01:45
And it can be early
direct necrosis
due to a toxin, or due to trauma,
or due to ischemia.
01:52
It can also be late
due to apoptosis
driven by a variety of
inflammatory pathways.
01:57
So you can get leakage
increased vascular permeability,
because the endothelial cells
are hurt.
02:02
That makes sense.
02:03
You can also get it because
leukocytes mediate damage.
02:07
So there are multiple, multiple ways
that you can get
increased vascular permeability
in inflammatory area.
02:15
So we talked about
increased flow,
that's going to get rubor and calor.
02:19
And that increased flow will
also have a degree of the tumor,
the edema,
but now with increased permeability,
due to all these mechanisms
that we just talked about,
you have increased much more
increased edema fluid,
water, electrolytes,
and mediators
they are able to get into the
extravascular space.
02:37
Okay, now it's important
and this becomes
clinically relevant.
02:41
Not all vascular leakiness
increased permeability
is created equal.
02:47
So at the top, we see here,
hydrostatic pressure,
oncotic pressure being balanced,
in terms of moving fluid
into or out of a vessel.
02:58
We can change the
hydrostatic pressure
be by causing dilation
of an arteriole.
03:05
We can also have it because we block
the outflow in a venous circulation.
03:11
If we block the venous outflow,
all that pressure backs up
through the capillary
and into the other end,
and we will have
increased efflux of water.
03:20
Congestive heart failure
will also do this
by giving us kind of
retrograde pressure increases.
03:25
So we can increase
hydrostatic pressure.
03:27
In fact, the swollen ankles
associated with heart failure
is because of increased
hydrostatic pressure
due to kind of
retrograde increases.
03:39
You can also get this loss of fluid
into the extravascular space
by changing the oncotic pressure.
03:46
So if we decreased
protein synthesis,
the liver is damaged.
03:50
So we're not making
enough albumin,
or we have
increased protein loss
such as glomerulonephritis,
where we have
a lot of protein in the urine.
03:59
Then our oncotic pressure goes down
and we get that same
increased amount of fluid,
electrolyte water
into the extravascular space.
04:09
So that's one way to do it.
04:11
The other way
is with inflammation.
04:13
Inflammation is kind of
getting the same effects,
but now on steroids.
04:19
It is much more robust.
04:22
And you get increased
endothelial permeability
from all the things that we
talked about in previous slides.
04:27
You see endothelial damage,
and you see
massive vasodilation and stasis
because we're losing fluid.
04:34
And so inflammation gives us
a much greater degree of fluid
that gets out of the tissue
or out of the bloodstream
into the tissue.
04:45
This has ramifications in terms of
fluid accumulations.
04:48
So when we have increased
hydrostatic pressure,
or diminished oncotic pressure,
the fluid tends to come out
is protein poor.
04:57
It's basically an ultra filtrate
and it is mostly water,
and a little bit of electrolyte,
a little tiny bit of protein,
but it's really protein poor.
05:06
It's called a transudate.
05:07
And when we see it grossly,
it looks yellow.
05:10
It looks yellow and clear,
it's serous.
05:13
That's what the serous means.
05:15
On the other hand,
the inflammatory fluid
that gets out is called an exudate.
05:21
And transudate and exudate is a very
important distinguishing feature
in the clinical setting,
because if it's a transudate,
that's one thing,
if it's an exudate, it usually means
there's an infection.
05:30
So in exudates are protein rich.
05:32
So there's some much increased
vascular permeability,
that we're getting all kinds of
protein that's out there.
05:38
And we've even got cells.
05:39
We've got neutrophils,
we got macrophages,
we got all kinds
of other stuff there.
05:42
It tends to look bloody
because we've even had
leakage of red blood cells.
05:46
And that's what's going on
in the little diagram.
05:48
The red blood cells
are even getting across.
05:50
So it looks bloody,
hence sanguineous.
05:53
And it can look
also pussy or purulent.
05:56
So exudates have a very
different significance clinically
than transudates.
06:01
And they're just about different
levels of vascular leakiness.
06:06
So, we've covered the very first
stage of acute inflammation.
06:11
We've talked about
the vascular changes
that are going to give us
calor (heat), rubor (redness),
and a tumor or edema.
06:19
And then we're going to move on
to the cell recruitment
and eventually the mediators.