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
    1. It is an energy-dependent process.
    2. It causes damage to the surrounding cells.
    3. It elicits inflammatory reactions.
    4. It involves replacing the dead cells with fibrous tissue.
    5. It is characterized by the appearance of Langhans giant cells on microscopy.

    Author of lecture Apoptosis: Physiology and Pathology

     Richard Mitchell, MD, PhD

    Richard Mitchell, MD, PhD

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