00:01
So, Broad strokes.
00:03
Injury,
not otherwise specified,
could be infection, could be trauma,
could be just sterile necrosis.
00:10
It typically elicits
in a very stereotypical way,
vascular responses
and cellular responses,
that's acute inflammation.
00:18
We get the edema,
increased vascular permeability,
we get the
increased blood flow,
and we get the
recruitment of neutrophils,
acute inflammation.
00:27
And then in a stereotypical way,
acute inflammation,
as we've talked about,
gets converted to
chronic inflammation
involving
the macrophage population.
00:36
So that's the
usual sequence of events.
00:39
However, there are always exceptions
in medicine, and biology.
00:43
And there are a few exceptions
to this paradigm.
00:46
So some forms of injury,
don't go through
the acute inflammatory
to chronic inflammation process.
00:55
So, Persistent injury.
00:56
If I continue to injure a tissue
over and over and over again,
without giving any time
for kind of recovery,
the vasculature continues
to only recruit
chronic inflammatory cells.
01:09
It will not go back through
the process of doing
acute inflammatory
cell recruitment.
01:15
Viral infections.
01:17
Turns out,
neutrophils are worthless
against viruses.
01:21
Viruses, or intracellular pathogens.
01:24
Neutrophils
only really work on
things that they can see and eat,
and they cannot see a virus
when it's inside a cell.
01:30
So if we have
a viral infection,
in the vast majority of cases,
we will not recruit neutrophils.
01:36
We will only recruit
chronic inflammatory cells.
01:39
Lymphocytes, and macrophages.
01:42
And then autoimmune disease.
01:44
So when the body recognizes self
inappropriately,
So this is all sort of colitis.
This is rheumatoid arthritis.
01:52
This is lupus.
01:53
This is a variety of the
autoimmune diseases
that we'll cover
in a subsequent topic.
01:59
Autoimmune disease
also tends to elicit
primarily a chronic
inflammatory response.
02:03
There are some exceptions.
02:05
But in general,
persistent injury, viral infections,
and autoimmune disease,
all go directly into
chronic inflammatory infiltrates,
with all the
attendant mediators
that come with that
chronic inflammation.
02:20
So to give you,
I've been using the term
chronic inflammation.
02:24
And haven't really
explained myself.
02:26
So let's talk a little bit more
about this.
02:28
Chronic inflammation is
mononuclear cell inflammation.
02:31
As opposed to polymorphonuclear
leukocyte inflammation,
which is going to be neutrophils,
or acute inflammation.
02:37
So the mononuclear cells that are
part of chronic inflammation,
lymphocytes and macrophages.
02:42
And they both will contribute,
as we'll see,
in a subsequent talk,
they actually communicate
with each other,
they actually stimulate each other.
02:50
So they are important.
02:52
The major feature
and I'm going to emphasize this
many times
is the macrophage.
02:57
It's going to be the most
important mononuclear cell
that's involved
in chronic inflammation.
03:03
Chronic inflammation,
just like the name implies,
can be prolonged.
03:07
So it not only does it come on
second after acute inflammation,
but it can also persist
for weeks, or a year.
03:14
We show a whole calendar here,
or many years or for a lifetime.
03:18
So for example,
rheumatoid arthritis
can have a persistent injury
to joint for a person's lifetime.
03:26
So it's a very prolonged process.
03:29
An important concept
about chronic inflammation
is that it is responding
to a particular tissue injury,
whatever is driving that
initial tissue injury may persist.
03:39
So there will be some damage
that's from that.
03:42
But there will also be damage,
potentially, from the response.
03:47
Macrophages are not totally
benign creatures.
03:50
They elaborate a lot of mediators,
and can cause
substantial tissue injuries.
03:55
So it's not just the original
tissue injury,
but it's the chronic
inflammatory response
that also drives that.
04:02
What's shown here in the diagram
is a normal colon,
kind of histologic section.
04:07
And there is very few
inflammatory cells
and the little glands
nice and round,
they are very happy.
04:15
In the bottom one
is ulcerative colitis
an autoimmune disease
associated with
chronic inflammatory cells
that are basically attacking
the epithelium.
04:23
There's lots more inflamed
inflammation
that's in between the glands
and the glands now
become quite irregular.
04:30
In fact, the damage to these glands
can be so much
that over a period of time,
we increase the risk for
acquiring new mutations
and turning this into cancer.
04:41
So it's not just
the original insult.
04:43
In this case,
autoimmune disease,
but it's the response
and how it drives
subsequent events?
In chronic inflammation,
we are hopefully, in fact, the goal
is to go to regenerate the tissue
to make it whole again.
05:00
To restore completely
normal function.
05:02
But in the event that we can't,
we're going to make a scar.
05:07
And repair, in most cases,
healing in most cases,
as we'll talk about
in a subsequent talk
is all about somewhere
on that spectrum
between perfect regeneration
and complete scar.
05:19
In an almost no cases
that one or the other,
it's often some combination.
05:25
In the event that
we're going to have a scar,
we need to have
new blood vessels.
05:29
We've destroyed blood vessels
as part of the injury.
05:31
We need to now make new ones
that's angiogenesis.
05:34
and we'll talk more about that.
05:37
And then once we have angiogenesis,
we will have matrix deposition,
and that will form fibrosis.
05:44
And I'll use interchangeably
fibrosis with scar,
that's laying down
new extracellular matrix.
05:51
The picture there is a very
hypertrophic, angry looking scar.
05:55
We'll talk about that
at the very end of this series,
because it's one of the
complications of wound healing.