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Alright, welcome.
00:03
What we're going to cover right now
is a overview of inflammation.
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We've already talked about
cell injury and cell death.
00:12
We've talked about the
acute inflammatory response,
the response
that comes first after injury.
00:20
And now we're going to get
into the world
of chronic inflammation
and wound healing.
00:26
So that's where we are
in the sequence.
00:29
And we're going to start with this.
00:31
So this is kind of where we left off
with the acute inflammation.
00:36
This is sterile necrosis.
00:38
This represents
a myocardial infarct,
and all of those big pink areas
are coagulation necrosis,
and those are myocytes
that have died
as part of a heart attack,
a myocardial infarct.
00:49
And we have now
and about 24 to 48 hours,
after that acute infarct,
we've recruited in
all these neutrophils.
00:57
So there is a huge inrush of
neutrophils who are going to start
the degradation process.
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And make sure
that that is sterilized.
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So no bacteria can set up shop
in this necrotic debris.
01:10
So that's just the beginning
of the process.
01:13
Likewise, let's look at this.
This is kidney.
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You can see the glomeruli,
you can see renal tubules,
you can see
vascular congestion.
01:20
In the middle of that
there's no architecture,
that's an abscess.
01:25
So in this setting,
we have had an accumulation
of bacteria and neutrophils
that are basically duking it out
with one another.
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And as a consequence, we have
vast dead zone in the middle,
just necrotic debris,
and bacteria, and neutrophils.
01:43
That's an abscess.
01:44
And again,
that's just the beginning.
01:46
We can't leave that there.
We need to somehow clean this up.
01:50
Similarly, you can have
inflammatory states
where we've had markedly
increased vascular permeability.
01:55
We've had exudates,
where we have
protein and red cells,
and occasionally other white cells
that get out into that.
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And that's what
we're looking at here.
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All that pink stuff is because of a
significant exudation of protein.
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But we can't leave that line
around either.
02:14
That's a really good tissue medium
for culturing bacteria
and that would be a terrible thing.
02:20
So we need to get rid of that.
02:22
So coagulation necrosis
with acute inflammation,
abscess formation, exudates.
02:29
We need to get rid of those.
02:31
So this is just the beginning.
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This is at the end of the
acute inflammation,
and now into the
chronic inflammation repair.
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So that's kind of setting the stage.
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Outcomes of acute inflammation.
02:45
So once we have
acute inflammatory cells,
and all of their mediators
brought in
there are couple different pathways
for outcomes.
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One, is that we progress
in a very stereotyped way
to chronic inflammation.
02:59
And if we have
minimal tissue injury,
and the tissues can regenerate,
the chronic inflammatory result
will be resolution.
03:08
We'll get things pretty much
back to normal.
03:10
We will neutralize
the mediators
that got made during the
acute inflammatory process.
03:15
The vessels will go back
to being normal,
they won't be leaking anymore,
and they won't be dilated.
03:20
Will drain away
through the lymphatics,
all the necrotic debris, and
all the extra cells that came in,
and the macrophages will clean up
and drive the regeneration process.
03:31
That's beautiful.
03:32
That's what we want
to have happen
every time we have
acute inflammation.
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Goes through the
chronic inflammatory pathway,
and then resolve.
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But sometimes we have
pyogenic organisms.
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Pyogenic just means pus forming,
and we'll get a huge abscess.
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Once that happens,
we are going to have to go through
chronic inflammation
to resolve this.
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But there's been as we already saw
with that first example,
there's going to be so much
tissue injury and that abscess,
We can't regenerate it.
It's gone, it's absolutely gone.
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So there's
substantial tissue destruction.
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The tissues may not be able
to regenerate.
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And in the setting of abscess,
or just increased
vascular permeability,
we get those exudates,
we have to organize those
through chronic inflammation.
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But in that setting, we have maximal
substantial tissue destruction
and tissues cannot regenerate.
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So the result is going to be scar.
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And in reality,
in almost every situation
after acute inflammation,
the tissues are somewhere
on the spectrum
between complete resolution,
and complete scar.
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And it's never usually perfectly
one or the other.
04:47
So the outcomes of
injury and inflammation.
04:50
It's a spectrum from
regeneration to scar.
04:51
And it's dependent
on the type of the injury,
the nature of the injury.
04:55
How intense the injury was?
How much tissue
has been damaged?
How much host response there was?
So if we have a huge
inflammatory response,
and all those mediators
get released,
and all the proteases
get released,
we're gonna have big time
tissue destruction.
05:10
On the other hand,
if we don't have much host response
and the bacteria run amok,
we're gonna have
a lot more damage.
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So it's, there's a lot
of variables in there.
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The cell and tissue type.
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So some tissues
will regenerate beautifully.
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Skin does a pretty good job.
05:27
Heart doesn't do
a very good job at all.
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And that's because of the
regenerative capacity of the cells,
and each cells in the skin
can regenerate
cells in the heart, cannot.
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What happens on the spectrum
from regeneration to scar
also depends on how well
we maintain the matrix integrity.
05:46
So if we completely destroy it,
seen an abscess,
that's going to end up
being mostly a scar.
05:53
And then the ability of stem cells
to regenerate the tissues
and how capable the tissues are
of kind getting back to normalcy.
06:05
So it all depends on
a number of variables,
as indicated on this slide.
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I'm going to give you a particular
kind of schematic roadmap
that's going to be seen,
over, and over, and over again,
as we talk about the stages
after acute inflammation.
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So we have some activity
on the y-axis
and time on the x-axis.
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And we'll put in some hours
and some days on the x-axis.
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But the activity on the y-axis
is going to be quite variable.
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When we have our initial insult
at time zero,
we have that vascular response.
We've talked about that.
06:41
That's the edema, the tumor,
the increased vascular permeability,
that is the initial vascular
response of injury. Okay.
06:51
Shortly thereafter, we have the
peak of the neutrophil infiltrate.
06:56
that's the acute
inflammatory response.
06:58
So edema,
the vascular response is first,
neutrophils second.
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Even as the neutrophils
are beginning to go away,
we are now recruiting
in the chronic inflammatory phase.
07:08
the macrophages, okay.
And they will come in as a wave.
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And then all goes according to plan,
we get regeneration.
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That's the ideal.
07:20
So <inaudible> inflammation,
leading to
acute and chronic inflammation,
and then to regeneration.
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But what happens
if the tissue can't regenerate?
Or we have too much damage?
Well, there are
a couple more steps then, okay.
07:32
So we will still
have the edema,
the acute inflammation
and chronic inflammation.
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But now in tissues
that will lead to scarring
or damage that
will lead to scarring,
we will have a stage
where we will have
new growth of blood vessels.
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This is called granulation tissue.
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It's a neovascularization process.
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and we will spend a little bit of
time talking about how that happens.
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And then on top of that
granulation tissue
is a provisional matrix.
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You can kind of think of it
as railroad tracks.
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We will bring in fibroblasts
that will synthesize matrix
and will get scar.
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So, as I said before,
the process of resolving injury
is somewhere on the spectrum
between complete regeneration
and complete scar.
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And most things in most tissues is
somewhere between those two.
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So just kind of keep this series
of peaks in mind
and then we will fill in
some of the details
but this is the big picture.
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So welcome to the world now of
chronic inflammation and healing.
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And you're going to love
talking about this.