00:02
One last topic in this topic,
of kind of cell injury
and mechanisms there of
is Ischemia and Reperfusion.
00:11
So, in the typical clinical
setting where this occurs,
a patient comes in there having
crushing substernal chest pain.
00:18
They're having a heart attack.
00:20
We know that most commonly this is due to
a plaque rupture in the coronary artery
with a blood clot on top of it.
00:27
So we rushed them into
the angiography suite,
and we inject tissue plasminogen activator,
a clot buster, and we break up the clot.
00:35
Except that the heart has been
ischemic for a certain period of time.
00:39
Now we're restoring blood flow into
tissues that have had partial injury.
00:45
So when that happens, we have a high
concentration of extra cellular calcium
that's coming into a
potentially compromise cell.
00:54
We already talked about cells.
00:56
If they see a spike of calcium, we'll
start down that calpain activation pathway,
and we'll end up
with some cell death.
01:03
So that's one part of
ischemia reperfusion.
01:07
When we reperfuse
ischemic tissue,
we also get increased recruitment
of inflammatory cells.
01:13
And recall the inflammatory
cells have a rich resource of
for generating reactive
oxygen species.
01:21
So as a result of that,
we will get more damage
because we recruit more
inflammatory cells into
this area of reperfusion.
01:30
The damage mitochondria
in that tissue.
01:32
So the mitochondria been scheming
for a certain period of time to,
and they are not firing
on all cylinders.
01:38
They are not working
as well as they should.
01:41
The electron transport chain
is not quite up to par yet,
and so as a result, those damaged
but still working mitochondria
will pump out more of the reactive oxygen
species because they're getting incomplete
oxygen reduction down the
electron transport chain.
01:59
It turns out that injured endothelium
in a hypoxic or ischemic tissue
will lead to the not specific deposition
of certain forms of antibodies
that will lead to complement activation,
so there will be damaged there too.
02:12
So ischemia,
and then reperfusion, even when
it's saving the life of the patient
can have secondary consequences
in terms of injury to the tissue.
02:24
That's important to understand,
because there is clearly a therapeutic
intervention that we need to do.
02:31
We want to save patients lives,
so we will do the reperfusion.
02:36
But we don't want to
have any more damage.
02:38
So, we all,
you and I need to be more clever
about preventing that
reperfusion damage.
02:46
And with that,
we've covered the biochemical mechanisms
by which cells get injured.