00:01
All right, having covered
mechanisms of cell death
and the subcellular and
cellular adaptive responses.
00:10
We're not going to actually
look at what death looks like.
00:14
How do we as pathologist and
you as future pathologist,
understand or identify
death and injury in cells.
00:25
And we can do that.
00:26
There are many different kinds
of markers that we will look at
and at the end of this
particular topic discussion
you will be expert
in being able to say,
'oh that's a dead
cell or maybe not, '
that's where we're going.
00:39
You can see the road map where
we've been and where we're headed.
00:43
So we've had an overview, we've talked
about ways that cells get injured,
we talked about how
they get injured,
we talked about how
they adapt to injury.
00:50
And now we're going to talk
about, they gave up and they died
and what it looks like and
so how we can recognize that.
00:58
So there's reversible and
there's irreversible injury.
01:01
So just because a cell gets injured
doesn't mean it's going to die
and we can recognize some
of that reversible injury
what's shown on the left
hand side is cell swelling
or high dropping degeneration
or cloudy swelling that's got a
whole bunch of different names.
01:17
And why is this happening?
We're looking actually
at renal epithelial cells
where there has been
an ischemic hit.
01:24
So the cells are not yet dead.
01:26
These will be reversibly injured
and if we restore normal
perfusion to the kidney.
01:32
They will improve.
01:34
But what has happened?
So you can see in the upper
right hand corner of that panel,
there are dark pink cells
with nice-looking nuclei.
01:42
That's a normal tubule.
01:44
In the lower left-hand side and in
the middle with all the green arrows,
you see that the nuclei
are starting to condense
and we see a lot of clear
space around the nuclei.
01:55
It's not the same
pink looking cell.
01:57
What's happened there,
is that we have
reduced ATP synthesis,
as a result of the
reduced ATP synthesis,
we do not have good active
sodium potassium atpase.
02:09
We're not able to pump
out sodium effectively.
02:13
All that intracellular sodium is now
recruiting obligate water with it,
and we're getting
swelling of the cells.
02:20
They're basically getting
swollen with water.
02:25
That's hydraulic degeneration
or cell swelling.
02:27
And if we restore normal
mitochondrial function,
the ATP will come back will pump that
sodium out the water will go with it
and we're good to go.
02:35
So this is one of the
ways that we recognize
reversible injury
is cells swelling.
02:41
In tissues that have a
very high turnover of fat,
such as liver.
02:46
Then there's also something
called fatty change or steatosis.
02:51
I'm not going to go into all
the biochemistry that's there
but suffice it to say that the
liver is the major through way
by which free fatty acids are
turned into various components
turned into energy,
turned into storage components.
03:04
If we inhibit or..
03:08
Abrogate to some extent the
ability of that free fatty acid
to be converted into the
products that you see there,
triglycerides and lipoproteins and
things like that because we've..
03:20
Partially injured the liver.
03:24
Then we will accumulate fat.
03:27
Now that's completely reversible
but this is what it looks like.
03:30
They hepatosites instead
of being nice pink cells
are pink cells with big
globules of triglycerides.
03:36
This is the accumulated fat.
03:38
So the liver is got all
kinds of fatty acid coming in
if it's not able to
metabolize it or export it.
03:43
It accumulates.
03:44
These cells are not dead.
03:45
They may not be functioning
great, but they're not dead
and they're just fine
if we restore normalcy
by restoring normal
blood supply or whatever.
03:54
This will come back and be
completely normal liver.
03:58
So just as a side light,
because I'm a pathologist,
I like to talk about
interesting sidelights.
04:04
This is a very common change,
fatty change, steatosis,
extremely common
change with alcohol.
04:11
So in an evening of drinking,
maybe a six pack of beer,
you will, in fact,
use up your NAD
that would normally be
responsible for the NAD.
04:26
Sorry, that would normally
responsible for the oxidation
of alcohol to acetic acid.
04:36
So instead of using that
NAD for metabolizing fat,
you use it to
metabolize alcohol.
04:41
And so the fat is
just accumulating.
04:43
So after your six pack,
you may wake up in the morning with
a rather full upper right quadrant
because your liver hepatosites
have been filled up with fat.
04:52
Now if you don't have another
six pack for breakfast
that will all go back relatively
quickly, but it's happening
because you are using
metabolic pathways
to degrade the alcohol
and ignoring the fat
that's coming in
there all the time.
05:06
Just an interesting sidelight.
05:08
Fortunately reversible.