00:01
We're coming around now to
another form of cell death.
00:04
We've been mostly emphasizing
necrosis, which is cellular homicide.
00:10
Now we're going to talk
about cellular suicide.
00:12
And in fact,
cells do commit suicide,
and it has a really important
physiologic and pathologic importance.
00:21
So we're going to talk about
apoptosis, which is that final
segment in our roadmap
for cell injury.
00:30
We've had an overview.
00:32
We've talked about the
ways that injury can occur.
00:35
We talked about how injury actually
causes cell death and injury.
00:40
Talked about adaptation
in response to injury
and talked about how we
recognize that things are dead.
00:46
And to wind up, we're gonna
talk now about cellular suicide.
00:51
Apoptosis.
00:52
Apoptosis actually
means falling away from,
which is kind of a good
word, I guess.
00:58
Literally,
the cells just kind of wither away
and like a leaf and fall away.
01:04
So okay, apoptosis,
that's where it comes from.
01:08
Here's what it looks like when
we captured by light microscopy,
we will see at the end, it's actually
pretty hard to see apoptosis,
under most circumstances
unless there's a lot of it.
01:20
And what we have here, we have multiple
arrows pointing to various structures.
01:25
Apoptosis is very quick,
evanescent process of cells
fragmenting into
little digestible bits
that then fall away and get
gobbled up by neighboring cells.
01:38
And so we will see
bits of just cytoplasm,
or we'll see bits of cytoplasm
with fragmented nuclei,
and that's pretty much it.
01:48
It doesn't look
like a whole lie.
01:50
In fact, until about 20 years
ago, no one believes this existed.
01:54
And then there was a whole
series of discoveries,
and now we know how
important this is.
01:59
So it gets equal billing
almost with necrosis
because it's really
important to understand.
02:07
So, big picture things having to
do with programmed cell death.
02:12
It is regulated.
02:14
Hence its program.
02:15
The cellular suicide is
something that requires energy.
02:19
We have to put ATP
into the process.
02:22
So as opposed to necrosis,
where we take away ATP and the cell dies.
02:27
This one we're
actually putting in ATP
and having it commits
suicide in a regulated way.
02:32
It has a physiologic role.
02:35
For example, an embryogenesis.
02:36
So I'm holding up my hand.
02:38
If you looked at my hand when
I was developing in utero,
there would be webs between
every one of my fingers.
02:44
It would be a flipper.
02:45
And the reason I don't
have a flipper right now
and I have five fingers
that I can show up to you
is because all that
tissue in between
during development underwent
apoptosis, programmed cell death.
02:57
So I have five fingers
and not a flipper.
03:00
It's important for hormone
dependent tissue evolution.
03:04
So we have talked in previous
topics in this series.
03:08
About, for example, lactational breast
that undergoes massive hypertrophy
during the nine months of pregnancy,
hypertrophy and hyperplasia.
03:17
It's just there's many
more, many, many more cells.
03:21
When we take away the stimulus
and the mother is no longer
breast feeding the baby,
those cells have to go away.
03:29
We don't need them
anymore, and so,
and we don't want
to have them necrose
that would bring an
inflammation of the things.
03:36
We want to do it by a very
gentle, kinder, gentler breakdown.
03:41
And that is apoptosis.
03:44
So it has a physiologic role
in normal tissue in evolution.
03:49
It's important in getting
rid of proliferating cells.
03:52
So remember that we have
tissues and it's a balance
between proliferation
and cell death.
04:00
And we balance that
for our entire life.
04:02
We're constantly turning over
tissues, every tissue in the body.
04:06
In order to accomplish that,
we have to delete cells
that have proliferated
previously and are now cynicism.
04:12
That process doesn't
involve necrosis.
04:15
It involves encouraging them
to commit suicide or apoptosis.
04:20
It's also really very
important in the immune system.
04:24
So if we were to look at a
thymus, we would be calling in
millions of immature thymocytes.
04:33
And the vast majority of those
will either be unreactive
with the appropriate antigen
or too reactive with host.
04:41
We want somewhere in the middle,
in terms of reactivity and
all the other lymphocytes,
all the other immature
thymocytes that came in,
we want to get rid of those.
04:51
So we want to delete all the ones
that respond to well to self,
and that's important to
prevent auto-immune disease.
04:59
So you can see, apoptosis has a really
important role in a variety of pathways.
05:04
It also can have a
pathologic outcome.
05:09
So if you have
decreased apoptosis,
so you don't have as much
as you're supposed to have,
you can have autoimmune disease.
05:16
Yes, you're not deleting those
auto-reactive immature thymocytes,
and they get a chance
to grow and expand,
and now they can attack
a particular tissue.
05:25
Also, malignancy.
05:27
So malignancy is just,
can be in one way thought of,
is just unregulated growth.
05:33
Normal cells, at a certain
point will kill themselves.
05:36
And we won't have that unregulated
growth yet in cancer that happens.
05:41
So it's diminished apoptosis.
05:44
You could also have too much.
05:45
So if we don't regulate very carefully,
you can have neurodegenerative diseases
and a number of diseases, such as Tay
Sachs, such as Huntington's disease,
things that we've talked
about in this series,
will occur as a result
of increased apoptosis.
06:04
It's a mechanism of cell death
when there's toxic injury.
06:07
So we may have necrosis.
06:11
We've talked about that with
cyanide and other things,
but we can also have increased
apoptosis as a mechanism for cell death
and toxic injury and senescence.
06:20
So, in senescence, we may have increased
apoptosis with inadequate regeneration,
and that will lead to
aging of the organism.
06:31
So we can have a
pathologic role as well.
06:33
It could be a good guy,
it can be a bad guy.
06:35
We need to understand it.