00:01
Let’s talk about PNH further
and its pathophysiology.
00:03
You must know the following.
00:05
You have a component called –
Your focus here, please find
decay-accelerating factor.
00:12
So decay accelerating factor is a
factor which normally controls
how much complement
activation takes place.
00:20
Is that clear?
So for the most part, think about this,
say that you have too
much complement activity,
examples of increased complement pathologies
that you’re quite familiar with.
00:32
If the patient has angioedema
and it’s the hereditary type,
and so what’s happening?
Around the mucus membrane, you
have increased vasodilation,
you all know about C1 inhibitor
deficiency, correct?
That’s hereditary angioedema.
00:50
Too much complement activation.
00:54
You can have too much complement
activation that may then cause, well,
destruction to the glomerular
basement membrane.
00:59
That brings you to type II MPGN
and it’s called nephritic factor
where it stabilizes C3 convertase.
01:07
This is another major
complement pathology
where you cannot control
the complement activity.
01:15
And so what happens is that we’ll
take a look at this further
and we have a mutation to
decay accelerating factor,
which isn’t
functioning properly,
and so therefore, you cannot regulate
the amount of complement activity.
01:29
Once again, where is
this complement activity
and what kind of cells
is this influencing?
RBCs and platelets.
01:35
Those are the two that you
pay attention to clinically.
01:39
Technically, yes, it’s
the neutrophils as well.
01:41
Platelets, what are you going to have?
Excess activity, thrombosis.
01:46
What about the RBC?
You will destroy it.
01:50
Most likely where?
Based on the name, hemoglobinuria.
01:53
Intravascular hemolysis.
01:55
Intravascular, right?
So you have destruction of the RBC, right
there and then in your blood vessel.
02:02
The absence of these
proteins, which proteins?
The decay-accelerating factor.
02:06
There’s another one that
I will introduce to you.
02:09
It’s called membrane-inhibitor
reactive lysis, MIRL.
02:13
We’re going to build bit by bit by
bit so that when you deal with PNH,
any angle that you’re asked on your
boards, you’ll be able to answer it.
02:23
Let it be the biochemistry, the
pathology, the clinical picture,
and even some of the
pharmacology here.
02:29
So in the absence of your
proteins, who is now susceptible?
The RBCs.
02:34
When?
Well, now, take a look at the
middle name of paroxysmal.
02:38
It’s nocturnal, so at night is when
the RBCs are being destroyed by whom?
The complement.
02:47
Why?
Because decay-accelerating factor
can’t control the complement anymore.
02:53
Why at night?
Well, when you sleep at night, what happens
to your breathing, your respiratory rate?
Hopefully, you’re relaxing and
your breathing rate decreases.
03:05
When your breathing rate decreases,
then you end up building up transiently
a little bit of carbon dioxide
that is just enough carbon dioxide
that the body’s retaining
in which you created what
kind of environment?
Acidotic or alkalotic environment?
Acidotic environment.
03:20
Good.
03:22
So at night, acidotic environment, wow!
This is the perfect
environment for complement.
03:27
You go crazy.
03:29
So they’re partying all
night, the complement is,
and in the process, they’re
destroying your RBCs.
03:33
You wake up in the
morning, what do you find?
Oh, look at the third name.
03:38
Hemoglobinuria.
03:40
The name has everything
that you require
for you to properly diagnose
your patient clinically.
03:43
The only thing that you
cannot forget is the fact
that your patient is going
to present with thrombosis.
03:50
Do not forget that, please,
when you’re dealing with PNH.