Mechanisms of Cell Injury

00:00 Okay, so, with that kind of overarching, broad concept, my view of the world, let's move on to some basic concepts again.

00:11 So, for mechanisms of cell injury, there are so many different ways that tissues can be injured.

00:17 One and probably one of the more common is hypoxia or lack of an oxygen supply.

00:22 That clearly is gonna cause problems because we're not gonna make -- be able to make ATP very efficiently and if you don't make Adenosine triphosphate, you're not gonna be able to power the cells and the tissues and everything else.

00:33 So, you will lose function. Infection is clearly a way that we can have injury.

00:38 So, we'll talk about pathogen host interactions because infection is a very important general mechanism of cell injury.

00:46 Trauma, clearly. I will walk out of the studio today and step in front of a bus, no, I won't, but I mean that's trauma. I could get burned.

00:54 I could get zapped, electrocuted.

00:56 I could have any variety of freezing or thawing or whatever and that trauma will cause physical chemical injury to me.

01:04 There's genetic injury, so, mutations or variations in the genetic code can lead to defective responses or to actual failure of certain functions.

01:17 The immune system. So, the immune system in general is gonna be our protection against infection but the immune system can also be a source of injury and as we will see when we talk about acute and chronic inflammation.

01:30 For example, there are a bunch of mediators that are made that can cause a world of damage as kind of innocent by standard image.

01:39 So, the immune system is a potentially very useful thing but in autoimmune disease and even in standard run of the mill inflammation can be a source of self-injury.

01:52 You can have nutritional injury. You can have too much or too little.

01:55 You can have too many vitamins or too much of a vitamin or too little.

02:00 So, nutrition is another way for cell injury to occur.

02:04 Clearly, senescence, aging, the accumulation of a thousand little papercuts to our genetic material and to the cells will lead to overall injury and then, chemical injury.

02:16 The toxins that we encounter or just the things like too much glucose or too much oxygen.

02:23 Okay, so, those are the things that -- those are the ideologies for cell injury.

02:29 Let's talk about the basic cellular components that are susceptible to injury.

02:35 So, when we get hit or when we -- traumatized, when we get ischemic, when we are exposed to a toxin, what are the cellular components that are susceptible? And cell injury will lead to loss of protein synthetic capacity.

02:52 As I said before, we're constantly turning over.

02:55 But if we're not because of some form of cell injury, that process of renewal will very quickly lead to degeneration and death.

03:05 Membrane structure, so, membranes, plasma membranes around every cell need to have integrity in order to preserve all the activities that are going on inside the cell.

03:16 If the membrane gets perturbed for any variety of reasons, we're in trouble and it's not just the plasma membrane but it's the membranes of all the organelles, the lysosomal membranes, mitochondrial membranes, nuclear membranes.

03:29 ATP generation clearly. For not making ATP, we're out of luck.

03:34 And so, maintaining that is important and cell injury will definitely recurrently hit our ability to generate ATP and we'll talk about why that causes ultimately cell death in greater detail.

03:49 And then, genetic integrity. If we don't protect the genome, we have no way of renewing everything else.

03:55 Everything is run at the level of the nucleus and we need to have the nuclear material intact and in the appropriate sequence without mutations or we're in trouble.

04:07 So, cell injury can inhibit all of these or affect all of these.

04:12 And again, response to injuries, you adapt or you die and that adaptation may be that you get more cells or you get bigger cells or you get smaller cells.

04:23 There are a variety of ways that we can adapt.

04:26 As a response to injury, you may actually have loss of function.

04:30 The cells may not be dead but they may not be doing their job.

04:33 So, for example, if I cut off the blood supply to a portion of your heart, within about a minute, you've lost the ATP necessary to get contraction.

04:47 Those cardiac myocytes however are still alive for the next 30 minutes.

04:51 So, we will lose function and then, hopefully, we will intervene with a clot buster or something and get blood supply back in before the heart dies.

05:01 So, one of the responses to injury is loss of function.

05:05 Clearly, if you don't adapt and after you've had loss of function, you'll get cell death and tissue breakdown and when we get to that cell injury thing, we will be talking about two major flavors.

05:18 One is necrosis which you can think of as cellular homicide.

05:21 Something happened to a cell and killed it and then, there's apoptosis which is a form of program cell death whereby the cell quietly commits suicide, apoptosis.

05:36 So, if cellular homicide, necrosis, cellular suicide, apoptosis.

05:40 Once you have cell death, you will have acute and chronic inflammation and those forms of inflammation are gonna be very important to understand.

05:49 We'll get into some incredible detail about that because there are a number of therapeutic interventions that we can use to impact that.

05:58 And then, once we've had cell death and acute and chronic inflammation have come in, the options for the tissue are that we regenerate or we make a scar and in most cases, it's neither one or the other, it's some combination of both and we'll talk much more about that. And then, finally, there's malignancy.

06:19 So, this is a response to injury. Yes, it is.

06:23 It is because of inflammation or genetic injury or toxins or something like that that we develop mutations that allow for expansion of a tumor.

06:36 But it's really important and we will spend probably four different topic discussion or more talking about malignancy and it's not just proliferation.

06:46 Malignancy is so much more than uncontrolled cell growth.

06:52 Okay, and with that, we have come to the end of the basic conceptual framework for all of pathology and if you just keep those in mind, as I said, all the rest are just details.