Next, your RBC only has glycolysis
as you know for energy.
It has no mitochondria.
In pyruvate kinase deficiency,
PK, very little ATP.
The block was before the
pyruvate, wasn’t it?
Can you picture it?
If you can’t produce the pyruvate,
can you then go into TCA cycle?
You don’t feel or excuse me –
You don’t create the
necessary FADH or NADH
to then feed into your electron
transport chain, right?
Therefore, I cannot produce ATP
properly or abundantly or adequately.
In fact, you have inadequate
amounts of ATP, point number one.
Point number two, you’re stuck at pyruvate.
You can’t go into TCA cycle.
So what does that mean?
Remember from the TCA cycle,
what are you giving off?
Do not confuse that with NADPH.
What is then NADPH?
It was pentose phosphate pathway.
This is NADH.
So we have too little ATP and
you have too little NADH.
What kind of picture is
this going to give you?
We shall see.
just keep this in mind.
This is actually now current day
practice a separate diagnosis.
It really is.
It’s a particular sodium-potassium
type of channel type of pathology.
However, to keep things really,
really simple here is the following.
We know that we are not going
to produce enough ATP.
There is going to be a
problem with the membrane,
meaning to say that if the sodium potassium
pump was or did not have enough ATP,
then it’s kind of like the ischemia that
we’ve been talking about in basic pathology.
And so therefore, you will have increased
amount of osmotic pressure within the cell.
The RBC is now –
Well, it has increased osmotic pressure
and then therefore accepts more fluid.
Now, based on all of that, we do know for
a fact that pyruvate kinase deficiency,
the RBC does take
on a bizarre form.
And there is some kind of
influence of the inadequate ATP
with membrane problem or malformations.
Keep that in mind as you read
through the third bullet point.
Now, as I said, current day
practice in pathology,
this is actually a
But to make your life simpler and
much more, let’s say, relevant.
We do know that it’s going to
influence the ATPase pump.
Let’s move on.
What about that NADH though?
Now the NADH is important.
NADH in basic pathology, we talked
about the conversion of FE3+,
which is a methemoglobin
your normal iron.
So remember in order
for us to utilize the
type of iron that gets
incorporated into heme,
you have to have it in
the ferrous form, FE2+.
When we consume iron from the
diet and such in the stomach,
it will be in the
form of FE3+, ferric.
So now, we need methods in which we
convert the ferric into ferrous.
remember, when we’re born or delivered,
it’s rather difficult for us to immediately
convert our ferric into ferrous.
We need to build up enough NADH
and there is an enzyme called
So the combination of
cytochrome-b5 reductase and NADH,
all of this
helps us to convert
ferric into ferrous.
In pyruvate kinase deficiency,
what’s my NADH supply?
What does this mean?
That means that the patient is stuck
in the state of methemoglobin.
Hemoglobin with FE3+.
Next, tell me about that 2,3-BPG.
If you have block at the pyruvate or
at the enzyme because it’s not there
You’re going to build up the proximal
substrates including 2,3-BPG.
What kind of shift?
And so therefore, it is then going
to release the oxygen prematurely.
Now, just to be technical,
would you tell me
you would have what kind of effect
in your oxygen dissociation curve?
A left shift, okay?
So from basic pathology and physiology,
a couple of things here with shifting
of your oxygen dissociation curve.
Fascinating, isn’t it?
Pyruvate kinase deficiency.
If you take a look at the
oxygen dissociation curve here,
you’ll notice the solid
line is the green one
and that then represents a normal
oxygen dissociation curve.
Y-axis, saturation of oxygen.
I need you to focus
upon the right shift.
The right shift, the dash line, you’ll
focus upon the increase in DPG.
You see that in the middle.
That DPG, same thing as your BPG,
and in pyruvate kinase deficiency, that
will be elevated causing the right shift.