Today we're going to do an
overview, a roadmap for cell injury
and talk about the various
components of cell injury.
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.
So, the topic for today is
going to be an overview.
But in subsequent discussions,
we're going to look
at the various ways
that injury can occur.
That's the etiologies of injury.
We're going to look at
the specific components
of a cell or tissue
that get injured.
That's the mechanisms of injury.
We'll talk about how the body fights
back or how tissue fights back
and adapts to injury and
hopefully maintains viability.
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.
When we say something has been injured,
whether it's reversible or irreversible.
And we can, looking down a microscope, say
that cell is dead and we'll show you how.
And then finally, we'll wrap it
all up with a look at apoptosis,
which is in fact,
So with that kind of setting,
let's do the overview and
give you a broad structure
to think about cell
injury and cell death.
So life is like this.
There's homeostasis, and you see that
kind of oscillating green sign wave
on the left hand side,
and we have variations in temperature.
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.
And then life happens
and you get injury,
and I haven't specified with the
injury, it's just injury of some sort.
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.
Say, for example,
the heart now suddenly has to pump
against a much higher
It responds by having much
greater cellular mass,
so we can pump better against that
pressure, so it has increased activity.
Let's take another injury.
And we get decreased activity,
so that if I make the heart,
for example, again,
a little bit ischemic.
I cut off the blood
supply a little bit,
not enough to kill it but
diminish the blood supply.
It will respond in turn by
So that's decreased activity.
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.
So the stressors recede and we refer
to baseline, and that's perfect.
Okay, that's the ideal goal.
And in general, responses to
injury are somewhere on this curve,
and you may have permanently
or permanently slightly
or you return to
But somewhere in there,
the body goes about it's
business and we continue living.
Terrific, that's the goal.
Except sometimes the injury is of
such duration or such severity.
The death occurs,
and that is going to be necrosis.
And I'm going to specifically talk
about necrosis as opposed to apoptosis.
As I mentioned previously,
necrosis is cellular homicide.
Something happens to a cell.
Something happens to a tissue or to
the body and that causes necrosis.
so that's kind of the big picture.
And if you get that,
a lot of the rest of it, just details.
Okay, so other variables
in cell injury.
It's the nature of the injuries.
So it's the type of injury,
and some injuries are worse than others.
We'll talk about
hypoxia versus ischemia,
and it seems like G that
would be the same thing.
We're reducing oxygen delivery
to the tissue, but not quite so.
So keep that in mind.
The type of injury is
important to understand.
The duration of injury is
important to understand.
If it just happens for a split
second, no problem.
But if it goes on for
hours, now we got a problem.
And the severity,
so a little bit of extra temperature
not so bad.
But if it's now scalding hot on your skin,
yeah, you're probably going to get a burn.
So this is kind of yeah,
I got that pretty much straightforward.
But it's important to think
about the nature of the injury
when we talk about injury.
And then we also want to talk about
the nature of the traumatized cell.
It makes a difference.
Cells are not created equal,
so the lineage makes a difference.
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.
So that's going to be
an important variable.
Not only that,
but if we look at skeletal muscle
muscle, versus neuron,
there's differences in the
sensitivity and susceptibility
of those various
lineages to injuries.
So, for example,
you can put a tourniquet on leg.
Cut off the blood supply
to the skeletal muscle,
for hours 2 to 3 hours,
and that leg will still be fine.
You take off the tourniquet
it and you're good to go.
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.
And if I cut off the blood
supply to a neuron in the brain,
only get a couple minutes.
So different cells have
The current nutritional and
hormonal status is also important.
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 ischemia or whatever,
then a poor hepatocyte that has just run a
marathon and has no glycogen reserve.
And finally, the adapt, adaptability,
the ability of the cell to respond.
How many tricks does it
have in its bag of tricks
when it gets traumatized
in various ways.
So we'll come back to these.
But this is important kind of
general concepts, broad concepts.
So the forms of cell
death, there's necrosis.
This is accidental
something happens to
a cell and it dies.
We'll talk about that
Apoptosis is programmed cell
death or cellular suicide.
And 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.
It's a really important
pathway of cell death.
There's autolysis, and sometimes
it gets confused with necrosis.
But autolysis is,
I cut out a piece of tissue,
I put it on a bench someplace,
it will eventually break down.
There's no longer any blood supply to it
obviously, it's not getting any nutrition.
It's membranes breakdown, the lysosomes
breakdown and it dissolves itself.
It's basically cellular soup.
should be distinguished from necrosis
and the necrosis is happening within
a living tissue or a living organism.
Autolysis is something where we
take it out of the living organism
and put it over here
and it falls apart.
This also happens
clearly in death.
When the body dies,
then all the tissues
will begin to undergo
varying degrees of autolysis.
We talked about autophagy in
a previous topic discussion,
when we were talking about how
cells breakdown big things.
you can be a mechanism for cell death.
If you have overaggressive,
breakdown of your own organelles
within a cell, it eventually will die.
But it's also a mechanism
to preserve viability.
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.
But if it goes too far,
that autophagic process can
be a mechanism of cell death.
So it turns out,
when we started playing
around or understanding
the mechanisms of apoptosis,
that is to say, cellular suicide.
We identified a bunch of enzymes that
are important in this program cell death.
So clever scientist,
knock them out.
They eliminated them in cells.
And yet we found that the cells could
still undergo a programmed cell death.
So this is a fail safe.
It's a different
set of mechanisms.
We won't really cover it anymore, but you
may encounter it later on in your careers.
And so just be aware that this
is another mechanism of suicide.
It's a fail safe in case the
apoptotic mechanism fails.
This is also a truism, overall.
Our bodies are overengineered,
they're overengineered because
there's a lot of redundancy.
But they're also overengineered and
that they find multiple ways to die.
So there you have it.
And the final one is pyroptosis.
And this is suicide
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.
But in doing so, we're also gonna
cause a lot of localized cell death.
That's suicide by inflammation.
So pyroptosis is another
thing that you will encounter.
We won't spend any more
time talking about it.
But you should be aware that it's
not just one flavor of cell death.
There are all these various
flavors of cell death.
And with that,
we've kind of had a general overview
of the entire kind of
pathway of cell death.
And with subsequent topic discussions,
we're going to get into greater detail.