Apoptosis: Physiology and Pathology

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.