Cell Injury General Overview PDF

[00:00:01] >> To understand health and disease, we need to have a strong understanding of, cellular stress, cellular injury, and cellular death, and how all of these relate to one another. Is the general paradigm that will describe how cells respond to stressors placed upon them. So we're going to s...

[00:00:01] >> To understand health and disease, we need to have a strong understanding of, cellular stress, cellular injury, and cellular death, and how all of these relate to one another. Is the general paradigm that will describe how cells respond to stressors placed upon them. So we're going to start off with our normal cell, our normal healthy cell, that is in a state of homeostasis or equilibrium, everything is functioning as normal. [00:00:37] And what could happen is if we can place some sort of stressor upon it, and there's lots of different types of stressors. This could be something like exercise, so if we are lifting weights and contracting our muscles and applying this force onto our muscles, that self is stressful. [00:01:00] And as anybody that's ever lifted weights knows, that stress that we put upon the cell will maybe result in some changes to the cell. In the short term, we might get a little bit sore, we'll talk about that in detail another point, but eventually it's going to lead to adaptation, adaptation is a good thing, okay? [00:01:19] If we've put a lot of stress upon a cell, it's going to to adapt to it, in the case of strength training, we put physical forces upon the cell and eventually we adapt. How do we adapt? By getting bigger muscles, we develop more contractile proteins, so that's one possible thing that we could do. [00:01:38] Stress a cell, and it adapts, and that's good, okay? However, if we place too many stressors upon a cell, before they have a time sufficient, time to adapt, or the cells don't have the resources that they need to fully repair either the cells. Or the extracellular matrix that they surround, if we can't adapt for some reason, then we're going to have an injury, okay? [00:02:09] And an injury is obviously something that there's something bad that has happened, we're either impairing the structure of the cell, or function of the cell, okay? That is in injury, now, we talked about if we put stressors upon the cell and we fail to adapt, or if we just have a downright injurious stimulus. [00:02:32] So, it's one thing if I go and do a bunch of weight training and maybe I do too much fit beyond the ability to adapt. It's a very different thing If I just take a muscle and I hit it with a hammer or baseball bat as hard as I can, that's just going to be blatantly injuring the cells, okay? [00:02:49] So some things are going to be stressors, and some things are going to be injurious stimuli. Either way, we're going to result in an injury in this concept of cell injury. Now, two things can happen from here, we can have a reversible injury. And again, that's going to be mild and transient, transient just means temporary. [00:03:11] And so it reverses, and eventually it gets back together, now it goes back to normal homeostasis. Now again, we have to differentiate between Normal homeostasis and adaptation. If I go and I lift weights, and my muscles are going to adapt to that, and now my muscles are stronger than before, that's adaptation. [00:03:33] If I lift weights, and I'm doing way too much, and over-exerting myself, and I'm not giving my muscles a chance to adapt. Maybe I'm actually not going to have much of an adaption, I'm just going to get injury and eventually it's going to be reversible, and I'm going to go back to my normal healthy self, okay? [00:03:51] Same thing with an injurious stimuli, if I take an injurious stimuli like hitting my muscles with a baseball bat, or something like that, that's not a way to train. We're not going to get bigger muscles by just, clubbing ourselves with a baseball bat. It's just going to cause injury, and best case scenario it's this reversible injury and we go back to as good as we were before. [00:04:12] So again that's something that's important to recognize, stressors will cause adaptation. Injuries, if they're reversible, best case scenario, we go back to where we started, okay? So, that's the difference between, stress that leads to adaptation, versus a reversible injury, a reversible injury just gets us back to where we started. [00:04:32] However, that's in the case of mild and temporary injuries, if we have something that's really severe, and really potentially progressive, that can result in an irreversible injury. The cells structure, and or function, is permanently altered, and so it's irreversible. And from there, we could go down two general pathways, we could have something called necrosis. [00:04:59] Which is one type of cell death, or we could have apoptosis, which is a different type of cell death, okay? Necrosis is going to be a little bit more we'll call it messy, there's going to to be cell membranes, kind of exploding and leaking out stuff. And it's a lot of times it might require some kind of clinical intervention to clean it up. [00:05:27] Apoptosis, you might have heard of it as programmed cell death, where there's going to be a series of events where the cell just kind of it implodes, or self destruction. You think of that way, and it's a little bit cleaner of a phenomenon for lack of a better term, don't get too caught up in the difference between necrosis and apoptosis right now. [00:05:47] Just recognize that they are different types of cell death, and they are going to to come after an irreversible injury. One important factor that's going to determine whether an injury is reversible, and leads back to a normal, healthy, functional cell, back in homeostasis or irreversible is the duration of injury. [00:06:12] And so that's what this figure here shows, on the x-axis, we have duration of injury, and this is just as a general model. This is going to to be different for each type a tissue, it's going to be different for different types of injurious stimuli. So we're not saying that this x axis represents seconds or days or weeks or anything. [00:06:29] It just depends, just kind of tryna share the concept here, and on the y axis here, we've got the magnitude of effect, and so, as an example, we'll talk about something like a crush injury. Imagine that you're going rock climbing, and a boulder falls on your leg and starts to crush the muscles in it. [00:06:54] And you could probably imagine, that if we got a bunch of friends with you, and they see this happen. And they see your muscles get crushed by this boulder, which again, is an unfortunate situation, but it does happen. And if your friends all quickly band together and lift that heavy boulder off of your leg, is your muscle going to be lingered? [00:07:16] Yeah, but if that boulder was only crushing those muscles on your leg, for a few seconds, or maybe even a few minutes. You're probably going to to have something that's a little bit more reversible of a cell injury. However, if this boulder is stuck on your leg for three or five days, you could probably imagine that there's going to to be a lot more damage that's going to to continue to happen during that time period. [00:07:42] And it's going to be an irreversible injury, and so that's an example of how the duration of injury is going to affect the ultimate outcome. If you're able to try to reverse your eliminate injurious stimuli quickly, it has more chances of becoming reversible, if not, it's going to be more likely Irreversible. [00:08:03] Same thing if you think about something like a myocardial infarction, or a heart attack. If the cardiac muscle is starved of oxygen for a few seconds, it might get injured, but it can recover. If it's starved of oxygen for an hour, it's going to be a lot less likely to recover, so that's the idea behind that. [00:08:21] That's the first general idea, of, time is going to to determine if an injury is reversible or irreversible. And then just a little bit more on that, is once we cross this line into irreversible injury. So again, it's going to to be dependent on cell function if we're able to intervene pretty quickly. [00:08:41] So if we're able to intervene, very quickly in the cycle a few seconds or maybe, a few minutes depending on the injurious stimulus, okay? Maybe there's only a slight decrease in cell function, but after a certain period of time. We're going to be getting to a point where the cell function is so far down that the cell is not able to maintain its homeostasis, and it's going to start dying. [00:09:02] And so what this has just meant to show here is that at the early stages of, if you've had an injury that has been long enough to be irreversible, but not necessarily ongoing for a really prolonged time. There might be some sort of biochemical alterations that lead to cell death, and you might not even see any immediate signs of cell death. [00:09:34] But eventually, the longer the injury has gone on, over time, we're going to start seeing changes on electron microscope. And eventually, under a light microscope, you'll see cellular changes, and eventually, if something is really severe and really prolonged, you're going to to see gross morphological changes. So something that's visible to naked eye, and so this is more important from a pathology perspective for a pathologist. [00:09:57] This is going to help give a little bit more of an idea about how long an age Injury took to happen, how severe it was. But again that's just the basic concept of, how cell injuries might be reversible or not and how it's related to the timeline of injury. [00:10:20] This is just meant to be a brief overview of necrosis versus apoptosis, again, these are two different pathways of cell death. And again, just a general overview to get an appreciation, we have with necrosis here's our normal cell. And there's some sort of injury that happens to it, and we'll say it's reversible injury well, then it'll recover. [00:10:44] But if this injury is so severe, there's so much disruption that it's going to happen, then we're going to get to this point of a progressive, irreversible injury. And what you can see in this diagram here, is there's inflammatory cells that come in, we'll talk about inflammatory inventory cells separately in the course. [00:11:03] So there's going to be a lot of inflammation that's going to be happening, and then the cells can be breaking down. There's going to be a bunch of stuff leaking out of it, and it's going to look a very certain way under a microscope, and that's going to be our necrosis. And again, anytime we see inflammation, inflammation is going to a lot of times be associated with some sort of clinical manifestation. [00:11:26] You might there might be some pain, there might be a greater risk of infection. So anytime we've got death by necrosis, it's going to be, for lack of a better word, messier. And we might be more likely to need some kind of clinical intervention to clean it up, okay? [00:11:46] So that's just the idea behind that, if somebody has gone hiking in, mountain climbing or something and gets a gang. And they get frostbite and their fingers or their nose become gangrene, gangrene is one four minute necrosis and that's it's going to have to be treated by somebody. Otherwise, there's going to be a risk of infection, there might be some amputations and stuff that happen. [00:12:08] That's necrosis, it's messy, apoptosis is going to happen, we've got this normal cell. There's some sort of injury that happens to it, and what we see here, again, don't get caught up in the details, but it's going to look different, it's going to look different under a microscope than this. And there's going to to be this whole programming inside the cell, that's going to to be this organized breakdown of the cell. [00:12:33] And eventually, it's going to to come in and be eaten by a phagocyte, which is just one type of immune cell we'll talk about. We'll talk about some macrophages and stuff, a little bit later, so it's going to be some sort of immune system cell that comes and eats it up. [00:12:47] But it's going to be a different immune process than necrosis, okay? And so this is just kind of, you've got the cell breaking itself down kind of, just self destructing itself. But it's not going to have as much leaking out and you've got, a different immune response happening to clean up the debris. [00:13:07] And so a lot of times, the immune system is kind of doing the cleaning up, as a general statement, there's no intervention necessary that's to clean up the mess from cell death. Now that might have some sort of clinical consequences that might need to be addressed, but there's not a mess that's an inflammatory mess that's left behind. [00:13:31] Again, just as a broad general statement of, apoptosis versus necrosis.