We previously had an overview
of cell injury and death,
and then we've also talked about the
various ways that our environment
or life can conspire
to injure cells.
Now we're going to talk
about what actually happens
when a cell gets traumatized and
that's the mechanisms of injury.
Here's our road map, and you can
see that we've done an overview.
We've talked about principles
and basic etiologies of injury,
and now we're gonna do
mechanisms of injury.
There are four basic targets.
Parts of the cell that are vulnerable,
susceptible to injurious injury.
And that includes the cell membrane,
the ability to generate ATP,
the ability to make protein
and the integrity of the genome
these are all very
So if we don't make enough ATP,
we can't synthesize proteins.
If we have genetic defects, we will
probably impact cell membrane function.
So the point about this is that
although individual injurious stimuli
a particular toxin might hit
one or the other very quickly,
all four elements of
this will come into play,
and the cell rapidly
spirals into death.
So the take home message here is it's very
difficult to dissect the primary insult
versus all the secondary things that
happened very quickly thereafter.
There are four major biochemical
mechanisms of injuries.
So we did talk about how
the membrane is important
and we talked about how the genetic
components are important in ATP.
Synthesis is important, but now let's
talk about specifically what happens.
And so we're gonna talk
about ATP depletion,
and that's happening as an inhibition
of oxygen phosphorylation occurs
and also because of
the switch of the cell,
metabolically to anaerobic pathways to
try to maintain normally ATP synthesis.
It turns out that calcium channels, calcium
concentrations air also really important,
and if we lose
that would be a major biochemical
mechanism of cell death cell injury.
Now that's not to minimize
the effect on sodium,
potassium and proton
gradiants as well,
but we're going to emphasize for
this discussion calcium homeostasis.
The generation of oxygen free radicals
is going to be a very important
concept that we will
carry forward in many
different ways when we
talk about pathology.
But the generation of oxygen free radicals
that occurs during injurious stimuli
is a very important biochemical
mechanism of cell death.
And finally the mitochondria and a lot
of things come back to the mitochondria.
But if they are damaged,
they're not just making less ATP,
but they are also potentially
driving cell death.
So that's where
we're headed today,
we're gonna talk about
each one of those in turn.