One last topic in this topic,
of kind of cell injury
and mechanisms there of
is Ischemia and Reperfusion.
So, in the typical clinical
setting where this occurs,
a patient comes in there having
crushing substernal chest pain.
They're having a heart attack.
We know that most commonly this is due to
a plaque rupture in the coronary artery
with a blood clot on top of it.
So we rushed them into
the angiography suite,
and we inject tissue plasminogen activator,
a clot buster, and we break up the clot.
Except that the heart has been
ischemic for a certain period of time.
Now we're restoring blood flow into
tissues that have had partial injury.
So when that happens, we have a high
concentration of extra cellular calcium
that's coming into a
potentially compromise cell.
We already talked about cells.
If they see a spike of calcium, we'll
start down that calpain activation pathway,
and we'll end up
with some cell death.
So that's one part of
When we reperfuse
we also get increased recruitment
of inflammatory cells.
And recall the inflammatory
cells have a rich resource of
for generating reactive
So as a result of that,
we will get more damage
because we recruit more
inflammatory cells into
this area of reperfusion.
The damage mitochondria
in that tissue.
So the mitochondria been scheming
for a certain period of time to,
and they are not firing
on all cylinders.
They are not working
as well as they should.
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.
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.
and then reperfusion, even when
it's saving the life of the patient
can have secondary consequences
in terms of injury to the tissue.
That's important to understand,
because there is clearly a therapeutic
intervention that we need to do.
We want to save patients lives,
so we will do the reperfusion.
But we don't want to
have any more damage.
So, we all,
you and I need to be more clever
about preventing that
And with that,
we've covered the biochemical mechanisms
by which cells get injured.