Apoptosis: Physiology and Pathology

by Richard Mitchell, MD, PhD

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    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.

    About the Lecture

    The lecture Apoptosis: Physiology and Pathology by Richard Mitchell, MD, PhD is from the course Cellular Injury.

    Included Quiz Questions

    1. ...the depletion of autoreactive lymphocytes.
    2. ...angiogenesis.
    3. ...hormone-dependent tissue hyperplasia.
    4. ...the defense against bacterial infections.
    5. ...exercise-induced hypertrophy.
    1. Malignancy
    2. Neurodegenerative disease
    3. Aging
    4. Toxic injury
    5. Tay–Sachs disease

    Author of lecture Apoptosis: Physiology and Pathology

     Richard Mitchell, MD, PhD

    Richard Mitchell, MD, PhD

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