00:00
So when cells die by
cellular homicide,
there are two...
00:06
basic competing pathways.
00:08
One is that the
proteins denatured.
00:10
They are still there.
00:12
They will eventually break down
under the influence of inflammation.
00:15
But they're still there,
and we can recognize the structure,
that's coagulation necrosis.
00:20
So it's just denaturation
the proteins.
00:23
And that's coagulation necrosis.
00:25
On the flip side is
that we degrade it.
00:28
We have enzymatic digestion,
and that's liquefactive necrosis.
00:32
It's still all dead,
but depending on the tissue,
depending on the length of time, etc.,
we may seem or less of one over the
other, and we'll talk about that.
00:42
So those are the
two basic flavors.
00:44
Coagulation necrosis,
liquefactive necrosis,
denaturation of proteins,
enzymatic digestion.
00:50
We can also recognize cells
is being eosinophilic.
00:53
So they get pinker on our typical
hematoxylin and eosin stain.
00:59
And that's because we've lost
a lot of the nucleic acids.
01:02
Nucleic acids,
negatively charged things stained blue
on the H and E hematoxylin
and the eosin stain.
01:10
As cells die, that DNA and RNA and
ribosomes, the things like that fragment
and they don't pick up
the hematoxylin and die.
01:18
So the cells look pinker
because they're less blue.
01:23
They're also look pinker
because denature proteins
tend to pick up the ES
and die more avidly.
01:28
So we can recognize that stuff
because it's more eosinophilic.
01:32
It loves the pink better.
01:35
Also, we've mention that we
have this influx of calcium,
and that influx of calcium
can bind and accumulate
on negatively charged
things like phospholipid.
01:46
So we may see calcium phosphate deposition
as another marker of dead cells.
01:53
Mainly what we're going
to see in terms of
necrosis at the light microscopy
level are these four elements.
02:03
So here's a good example.
02:04
This is myocardium
and at the top,
we have coagulated necrosis.
02:10
The tissue that's
alive is at the bottom,
and we can see that it's got
a certain light pink color,
and we see the material at the top is
having a much more darker pink color.
02:21
That's the hypereosinophilia
because we've lost
all the nucleic acids
and we stained better with ESN,
and it's still though
somewhat recognizable
as cardiac myocytes.
02:35
And that's the denaturation process,
the proteins of denatured in place.
02:40
So,
denaturation of proteins,
coagulation necrosis, enzymatic digestion,
liquefaction necrosis will show
you an example in a minute.
02:50
Hypereosinophilia
and calcification,
those are kind of the four elements
that we've seen the light microscope.
02:55
There are also some characteristic
nuclear changes in dead cells.
02:59
So we talked about chromatin,
dissolving or chromatin falling apart.
03:05
Okay, there's some general changes
that we need to also understand.
03:08
There's some characteristic
nuclear changes.
03:11
On the top,
we have your average hepatocyte.
03:15
With a nice, oval looking,
normal sized nucleus.
03:20
As the nucleus, the nuclear material,
the chromatin starts to degrade
because of endonucleases,
and proteases acting on it.
03:28
The nucleus can actually shrink.
03:30
It gets more condensed, it gets brighter
blue, and that's called pyknosis.
03:37
You can also have complete fragmentation
of that little pyknotic nucleus
or the normal nucleus
called karyorrhexis.
03:44
So you get little fragments
of nuclear material
kind of dispersed throughout the
cell, that's karyorrhexis.
03:50
And then as we go further
and further in the process,
we break that down and it's not even
recognizable as nuclear material anymore.
03:57
We've had endonucleases and
proteases degrade everything
that's going to stain blue
and we get karyolysis.
04:03
So these patterns of
nuclear fragmentation,
pyknosis, karyorrhexis,
karyolysis
are also gonna be recognizable
by light microscopy,
as cells being dead.
04:15
This is just an example.
04:16
Again, this is in liver,
and we have various arrows here.
04:20
So one we're seeing with the
blue arrowheads, vacuolization.
04:26
These are just cells undergoing
that cloudy swelling that edema.
04:30
So they have accumulating water
and they look very swollen.
04:34
They're not yet dead,
so those might be still alive.
04:38
And then we have
pyknotic nuclei.
04:40
So in the middle of this image,
you see rather large blue nuclei.
04:45
Now look up where the yellow
arrowheads air pointing,
those are little tiny condensed residual
nuclei, those are pyknotic nuclei.
04:54
Where the chromatin
is condensed,
the nucleus has shrunk and
that's all that's left.
04:57
That's a cell that's dying.
05:00
Then we have karyorrhexis.
05:02
And you can see the
green arrow heads,
representing areas of
karyorrhexis altogether,
where you can see little kind
of stippling of the blue,
that's fragmentation
of the nucleus.
05:13
And then we have cells that
have lost nuclear altogether,
that would be the karyolysis and
those are within the black circles.
05:20
So these are all the changes associated,
nuclear changes with cell death.
05:26
So general patterns of necrosis.
05:28
We've talked about coagulated necrosis,
which is basically denaturation
and loss of nuclear staining.
05:36
And that's what this looks like.
05:37
So we have normal
myocardial on the left.
05:40
You can see the nuclei,
you can see everything.
05:42
And then on the right,
in the right upper corner
of the right hand side,
where this coagulative necrosis
those survival myocytes.
05:50
But in the middle, all the way
across, hypereosinophilic
and no nuclei in the cells,
and that's coagulated
necrosis of the myocardium.
06:01
Let's talk about
contraction band necrosis.
06:03
This is a special form of necrosis that
occurs in cells that are able to contract,
so this is gonna
be skeletal muscle.
06:11
This will be to some extent, in smooth
muscle, but it's mostly in cardiac muscle,
and what happens is cells
have become ischemic.
06:19
They're no longer able
to keep calcium out
they get reperfused.
06:25
And now calcium that's in the blood
in that reperfused environment
comes screaming across
into the myocyte.
06:34
When that happens, we will activate
calpains and other things, of course,
but that calcium is also a
signal for this contract our cell
to have the sarcomeres contract.
06:43
So we get these very
hypertonic contractions.
06:47
It turns out that all you need for
a muscle to contract is calcium.
06:50
It actually requires
ATP for it to relax.
06:54
So when the cells are
ischemic and dead,
calcium comes in, they contract but they
don't have any ATP, so they can't relax.
07:01
And we see these
contraction bands.
07:04
Let's talk about
liquefactive necrosis.
07:07
So liquefactive necrosis basically
means there's no architecture left.
07:10
Enzymes have
degraded everything.
07:14
So, you see around the periphery
that we have normal liver parenchyma.
07:18
At the edges all the way around.
07:20
But in the middle, where asterisks
gives, there's no architecture.
07:23
It doesn't look like anything.
07:25
It's all been dissolved,
and that's liquefactive necrosis.
07:30
This happens very commonly
when there are infections,
bacterial infections
in particular,
and always in the brain.
07:37
We don't get coagulative
necrosis in the brain.
07:40
For whatever reason,
it's always liquefactive necrosis.
07:45
All right, let's talk about
gangrene or gangrenous necrosis.
07:48
And there's nothing
magical about these.
07:50
Once we've talked about coagulative
necrosis and liquefactive necrosis.
07:54
We've pretty much
covered the landscape,
but there are three other
terms at the bottom,
that you need to be familiar with,
because they will appear in the literature
and you'll talk about them when you're
on the wards and everything else.
08:05
So gangrene is really coagulative
necrosis of an extremity.
08:11
And as it's typically used,
if there is infection,
meaning that there's going
to be liquefactive necrosis,
it's going to be wet necrosis,
so there'll be a lot of liquefaction
that's in there as well.
08:25
And if there is no infection, it's
going to be dry, it's just going to be,
coagulative necrosis and is
just looking at gangrene.
08:32
That toe is dead.
08:34
And if we did a histology of that,
it would be mostly coagulative necrosis.
08:38
At the base of the toe,
there's a superimposed infection,
and we'd see liquefaction.
08:44
Caseous necrosis, so caseous necrosis
is classically characteristically
associated with tuberculosis.
08:52
So when we talk about caseous necrosis,
we're saying TB in another form.
08:57
Caseous? What does caseous mean?
Caseous actually means cheesy
for the Latin scholars out there,
and it looks cheesy not through
the microscope, but grossly,
Grossly.
09:09
Grossly, it looks like cheese.
09:11
It looks like cottage
cheese, but microscopically,
we have zones of necrosis with lots
of inflammation, and it's basically,
it's basically
liquefactive necrosis.
09:23
But there's a higher calcium content
in this because of the bacteria,
and we have a lot more necrosis
in a central area with
surrounding inflammation.
09:32
And that's where we get cheesy.
09:33
But it's basically liquefactive
necrosis, of a different flavor.
09:38
And if we say caseous necrosis,
we are talking about,
in most cases, tuberculosis.
09:44
And finally, fat necrosis.
09:46
And fat necrosis occurs
when there is activation
of enzymatic activity
that can break down lipid,
and it gives us kind of an
amorphous look to it overall.
09:58
So this is an example where there's
fat necrosis in an infection
in a breast tissue, which has got
a fair amount of fat within it.
10:08
When that happens,
the inflammatory cells that come in
will degrade the fat and they
break it down into little lobules.
10:17
Those little lobules actually have charge
on them and calcium combined to them.
10:21
And we can actually get calcium soaps
that form as a result of the calcium,
that's in the tissues,
interacting with the lipid
that has been broken down
from all of the adipocytes.
10:34
And we get this kind of gumesh.
10:38
It is just a variety of different
sorts of necrotic debris.
10:43
So it's a variation truly on the
liquefactive necrosis spectrum.
10:48
So let's fat necrosis.
10:49
So you will hear
about each of these.
10:51
But in essence,
everything is either coagulative
or liquefactive necrosis
or some combination.
10:59
And with that, we've kind of discovered
and discussed the morphology of death.