Let's talk first
about ATP depletion.
And it is a combination,
as we reduce ATP of reduced
oxidative phosphor relations.
So we're not generating
the ATP and the cell,
knowing that it needs to maintain
some level of ATP generation
going to anaerobic glycolysis.
So if we cut off the oxygen
supply, we switch to anaerobic
metabolism and that has its
on its own consequences.
So oxygen completion,
what happens here?
You're looking at a heart and we're
looking at a blocked blood vessel.
In a subsequent topic, we will discuss
atherosclerosis and all of us in detail.
But for right now, let's just say
that we have an occlusion of a vessel
and all of the heart downstream of that
occlusion is now depleted of oxygen.
Well, that diminished
oxygen will mean that
we're getting diminished
ATP right off the bat.
We have nothing to accept electrons
down the electron transport chain,
so we will generate no ATP
via oxidative phosphorylation.
So we will not have enough ATP
for our sodium-potassium-ATPase
and as a result of that,
we will have increased
amounts of sodium
getting into the cell,
and when that sodium
is in the cell,
it brings with it water,
and we're gonna have cellular swelling.
We will also not be able to keep
calcium out at appropriate levels.
And so we'll see increased
and we're going to see is a
result of these ions moving in
with their obligate water, increased
intracellular and intraorganellar edema.
So things we're just gonna get
swollen, swollen, swollen, until they
1. don't function and 2. rupture.
We are going to try,
however, to maintain some ATP.
And cells have this anaerobic
mechanism when they don't have oxygen
to generate ATP at
very low levels.
So oxidative phosphorylation per each
glucose will generate 36 to 38 ATPs,
depending on how you keep score.
When you do it by
you get 2 free ATP.
So it's more than an order
of magnitude difference
in terms of how
much ATP you can get
from breaking down sugars,
etc. in the absence of oxygen.
So nevertheless, the cell is
frantically trying to generate ATP,
so it will have
It will break down all of the glycogen
and sugars that it has at its disposal,
which will reduce the amount
of glycogen that's present.
In doing so though, we don't get the
final movement of the metabolic pathway
into the TCA cycle and
So we accumulate lactic acid.
Lactic acid will reduce the pH.
So now we're getting an
When that happens, pH is very important in
maintaining normal chromatin architecture,
and we will get
disruption of that.
At the same time,
we are breaking down whatever ATP we have
and we're not synthesizing new
ATP at a high enough level.
So we're accumulating
So we're increasing the
intracellular ionic environment
big time from all those ions sodium
and calcium and everything else.
We have increased lactic acid,
which is reducing the pH, and we have
high levels of
This is going to make the
cells swell even more.
That's what that picture
is representing above that.
And then as we're changing the pH,
as we're changing the ionic environment,
as we are making
things more edematons,
we are going to get
Oh darn! Now that means we're not
maintaining normal protein synthesis.
That all goes away.
And if we don't have
then we don't make
And we get accumulation of excess
phospholipid which curls up into balls
that we can see as kind
of multilamellar bodies.
And that's what's being demonstrated
on the electron micrograph
that you see on the
right hand side.
So we have clearly started losing
most of the cellular function,
just a result of having
low oxygen levels.