Overview of Cellular Injury

by Richard Mitchell, MD, PhD

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    00:01 Hello.

    00:02 Today we're going to do an overview, a roadmap for cell injury and talk about the various components of cell injury.

    00:12 Very important that we understand once we built a beautiful cell, a beautiful tissue, a beautiful body, that there are things that happen to it, that's pathology.

    00:20 So, the topic for today is going to be an overview.

    00:23 But in subsequent discussions, we're going to look at the various ways that injury can occur.

    00:29 That's the ideologies of injury.

    00:31 We're going to look at the specific components of a cell or tissue that get injured.

    00:35 That's the mechanisms of injury.

    00:37 We'll talk about how the body fights back or how tissue fights back and adapts to injury and hopefully maintains viability.

    00:44 Then we'll look at the patterns of injury and cell death that we, as pathologists and you, as future pathologist, will be able to recognize.

    00:52 When we say something has been injured, whether it's reversible or irreversible.

    00:56 And we can, looking down a microscope, say that cell is dead and we'll show you how.

    01:02 And then finally, we'll wrap it all up with a look at apoptosis, which is in fact, cellular suicide.

    01:08 So with that kind of setting.

    01:11 Let's do the overview and give you a broad structure to think about cell injury and cell death.

    01:19 So life is like this.

    01:20 There's homeostasis, and you see that kind of oscillating green sign wave on the left hand side, and we have variations in temperature.

    01:29 We have variations in blood pressure, variations in pH, variations in nutrition, and we kind of our body and the tissues within it and the cells within the tissues, respond and kind of go up and down, up and down in terms of their functional ability.

    01:44 And then life happens and you get injury, and I haven't specified with the injury, it's just injury of some sort.

    01:52 Now what happens at that time point? Well, you can adapt, so you can have, in some cases increased activity as a mechanism for adaptation.

    02:03 Say, for example, the heart now suddenly has to pump against a much higher pressure, hypertension.

    02:10 It responds by having much greater cellular mass, so we can pump better against that pressure, so it has increased activity.

    02:18 Let's take another injury.

    02:20 And we get decreased activity, so that if I make the heart, for example, again, a little bit ischemic.

    02:26 I cut off the blood supply a little bit, not enough to kill it but diminish the blood supply.

    02:31 It will respond in turn by diminished contractility.

    02:35 So that's decreased activity.

    02:36 But that's adaptation, okay? And hopefully when the injury goes away, we will have, we will return to normal homeostasis, that's the whole goal, we want to get back into that nice, kind of uniform middle zone, where we kind of just obsolete a little bit.

    02:55 So the stressors recede and we refer to baseline, and that's perfect.

    03:00 Okay, that's the ideal goal.

    03:03 And in general, responses to injury are somewhere on this curve, and you may have permanently increased activity or permanently slightly decreased activity, or you return to normal homeostasis.

    03:16 But somewhere in there, the body goes about it's business and we continue living.

    03:21 Terrific, that's the goal.

    03:23 Except sometimes the injury is of such duration or such severity.

    03:29 The death occurs, and that is going to be necrosis.

    03:32 And I'm going to specifically talk about necrosis as opposed to apoptosis.

    03:37 As I mentioned previously, necrosis is cellular homicide.

    03:40 Something happens to a cell.

    03:42 Something happens to a tissue or to the body and that causes necrosis.

    03:48 Alright, so that's kind of the big picture.

    03:51 And if you get that, a lot of the rest of it, just details.

    03:55 Okay, so other variables in cell injury.

    03:59 It's the nature of the injuries.

    04:00 So it's the type of injury, and some injuries are worse than others.

    04:04 We'll talk about hypoxia versus ischemia, and it seems like G that would be the same thing.

    04:11 We're reducing oxygen delivery to the tissue, but not quite so.

    04:15 So keep that in mind.

    04:16 The type of injury is important to understand.

    04:18 The duration of injury is important to understand.

    04:20 If it just happens for a split second, no problem.

    04:23 But if it goes on for hours, now we got a problem.

    04:28 And the severity, so a little bit of extra temperature not so bad.

    04:34 But if it's now scalding hot on your skin, yeah, you're probably going to get a burn.

    04:39 So this is kind of yeah, I got that pretty much straightforward.

    04:42 But it's important to think about the nature of the injury when we talk about injury.

    04:47 And then we also want to talk about the nature of the traumatized cell.

    04:51 It makes a difference.

    04:52 Cells are not created equal, so the lineage makes a difference.

    04:57 So, for example, if we have injury to a cardiac myocyte, that is a very severe problem, because if we kill the cell, it's not going to come back.

    05:07 So that's going to be an important variable.

    05:10 Not only that, but if we look at skeletal muscle versus cardiac muscle, versus neuron, there's differences in the sensitivity and susceptibility of those various lineages to injuries.

    05:22 So, for example, you can put a tourniquet on leg.

    05:26 Cut off the blood supply to the skeletal muscle, for hours 2 to 3 hours, and that leg will still be fine.

    05:32 You take off the tourniquet it and you're good to go.

    05:35 If I cut off the blood supply to the heart, I only get about 20 to 30 minutes before those heart muscle cells check out before they die.

    05:42 And if I cut off the blood supply to a neuron in the brain, only get a couple minutes.

    05:47 So different cells have different susceptibility.

    05:50 The current nutritional and hormonal status is also important.

    05:54 So if I look, for example, at a liver cell that is plumped up with glycogen and is you know can, It can sustain a whole lot more trauma in terms of a schema or whatever, then a hepatocyte that has just run a marathon and has no glycogen reserve.

    06:12 And finally, the adapt, adaptability, the ability of the cell to respond.

    06:18 How many tricks does it have in its bag of tricks when it gets traumatized in various ways.

    06:24 So we'll come back to these.

    06:25 But this is important kind of general concepts, broad concepts.

    06:30 So the forms of cell death, there's necrosis.

    06:34 This is accidental cellular homicide, something happens to a cell and it dies.

    06:40 We'll talk about that particular pathway.

    06:42 Apoptosis is programmed cell death or cellular suicide.

    06:47 A nd at the end, that one of the last portions of the last topics in this series, we'll talk about apoptosis in greater detail because we need to understand this.

    06:56 It's a really important pathway of cell death.

    07:00 There's autolysis, and sometimes it gets confused with necrosis.

    07:03 But autolysis is, I cut out a piece of tissue, I put it on a bench someplace, it will eventually break down.

    07:11 There's no longer any blood supply to it obviously, it's not getting any nutrition.

    07:15 It's membranes breakdown, the lysosomes breakdown and it dissolves itself.

    07:20 It's basically cellular soup.

    07:22 So autolysis, should be distinguished from necrosis and the necrosis is happening within a living tissue or a living organism.

    07:30 Autolysis is something where we take it out of the living organism and put it over here and it falls apart.

    07:36 This also happens clearly in death.

    07:39 When the body dies, then all the tissues will begin to undergo varying degrees of autolysis.

    07:45 Autolysis.

    07:47 There's autophagy.

    07:49 We talked about autophagy in a previous topic discussion, when we were talking about how cells breakdown big things.

    07:57 In autophagy, you can be a mechanism for cell death.

    08:00 If you have over aggressive, breakdown of your own organelles within a cell, it eventually will die.

    08:08 But it's also a mechanism to preserve viability.

    08:12 So autophagy is gonna be one of those mechanisms that can be either way and when we have loss of nutrition, cut off the blood supply for a while or reduce blood supply, say two neurons, they can preserve for a while by basically breaking down their own constituents and undergoing a degree of atrophy.

    08:34 But if it goes too far, that autophagic process can be a mechanism of cell death.

    08:42 There's necroptosis.

    08:43 So it turns out, when we started playing around or understanding the mechanisms of apoptosis, that is to say, cellular suicide.

    08:51 We identified a bunch of enzymes that are important in this program cell death.

    08:57 So clever scientist, knock them out.

    09:00 They eliminated them in cells.

    09:02 And yet we found that the cells could still undergo a programmed cell death.

    09:08 So this is a fail safe.

    09:09 It's a different set of mechanisms.

    09:11 We won't really cover it anymore, but you may encounter it later on in your careers.

    09:16 And so just be aware that this is another mechanism of suicide.

    09:19 It's a fail safe in case the apoptotic mechanism fails.

    09:23 This is also a truism, overall.

    09:26 Our bodies are over engineered, they're over engineered because there's a lot of redundancy.

    09:31 But they're also over engineered and that they find multiple ways to die.

    09:35 So there you have it.

    09:36 And the final one is pyroptosis.

    09:38 And this is suicide by inflammation.

    09:41 This is actually a mechanism to ensure that if we're under attack by a microorganism, that we not only get rid of microorganism to save the body.

    09:53 But in doing so, we're also gonna cause a lot of localized cell death.

    09:56 That's suicide by inflammation.

    09:58 So pyroptosis is another thing that you will encounter.

    10:02 We won't spend any more time talking about it.

    10:05 But you should be aware that it's not just one flavor of cell death.

    10:08 There are all these various flavors of cell death.

    10:12 And with that, we've kind of had a general overview of the entire kind of pathway of cell death.

    10:19 And with subsequent topic discussions, we're going to get into greater detail.

    10:24 Thanks.

    About the Lecture

    The lecture Overview of Cellular Injury by Richard Mitchell, MD, PhD is from the course Cellular Injury.

    Included Quiz Questions

    1. Neurons
    2. Cardiac muscle cells
    3. Skeletal muscle cells
    4. Epithelial cells of the skin
    5. Fibroblasts
    1. ...suicide by inflammation.
    2. ...programmed cell death.
    3. ...cellular soup.
    4. ...cellular homicide.
    5. suicide.
    1. Autophagy
    2. Autolysis
    3. Necrosis
    4. Apoptosis
    5. Necroptosis
    1. ...adaptation.
    2. ...necrosis.
    3. ...apoptosis.
    4. ...homeostasis.
    5. ...remodeling.

    Author of lecture Overview of Cellular Injury

     Richard Mitchell, MD, PhD

    Richard Mitchell, MD, PhD

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    Muy claro
    By Javier J. on 25. April 2021 for Overview of Cellular Injury

    Profesor entretenido y claro, clase recomendada como introducción a la muerte célular

    deep explanation and great examples
    By Tracy M. on 07. February 2021 for Overview of Cellular Injury

    the lecture is in great content , easy to grasp the concepts and very detailed and rich examples are given.

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