Continuing our discussion on the concentration
of urine. Up until now, we looked at ADH,
looked at its control and then went into SIADH
in great detail. Now let us take a look at
diabetes insipidus, the opposite of but nonetheless
an important difference to keep in mind when
you have plasma and urine osmolarity at hand.
So we have nephrogenic diabetic insipidus.
Now what we will do here ladies and gentleman
is under renal or nephrology, we will strictly
only be managing nephrogenic diabetic insipidus.
I want to make sure that we are clear because
there is no important piece of information
that is left out in your lecture series with
me. The central diabetes insipidus, we will
be dealing with that in endocrinology. Is
that clear? So here let us keep things relevant
and all that I will bring to your attention
is the pathology of diabetes insipidus, nephrogenic
in the category of nephrology. With that said,
let us continue and before we move on, though,
let us talk about the basic definition and
predict as to what is going to happen in our
patient with nephrogenic diabetes insipidus.
Nephrogenic that means there is a problem
with the kidney in which ADH is not working
properly. Now just to make sure we are clear.
If you have a patient that has SIADH maybe
perhaps secondary to small cell lung cancer.
We talked about that in great detail. Then
you would purposely induce nephrogenic diabetes
insipidus by giving a drug such as demeclocycline
so that you can deal with SIADH. However now
we will come to the actual primary disease
of nephrogenic diabetes insipidus. There is
not going to be your V2 receptors working
properly. You are not going to be able to
properly reabsorb your water. If that is the
case, you are going to create massive diluted
urine. This clearance of that water, which
is free will be absolutely positive. Remember
the clearance of water is zero and that is
where all are really focused upon if clearance
of water was zero. It is the fact that you
are producing urine that is obligated meaning
with sodium. It is not free of solute, but
if you are producing lots of diluted urine
and you are clearing this and understand there
is going to be a lot more free water than
there is going to accompanied with solute.
So there is going to be a lot more free water
thus the clearance of water here is going
to be positive. All that is what we predicted.
Let us continue.
Plasma osmolarity increase. Are you seeing
it? You are losing diluted urine thus plasma
osmolarity increases. It stimulates the posterior
pituitary to do what? To produce even more
ADH, but obviously, it is not going to do
anything. So this is a condition in which
and let us now draw some parallels. If the
receptors are not working, give me some pathologies
in which the receptors are not working properly.
PTH receptors aren't working properly. What
is that diagnosis? That is pseudohypoparathyroidism.
Your testosterone receptors are not working
properly. Give me that diagnosis. Androgen
insensitivity syndrome. Your insulin receptors
are not working properly. Give me that diagnosis.
Diabetes mellitus type II. Here we have the
receptors for ADH not working properly. Why
am I bringing all this up? Technically speaking
clinically. Each one of those situations that
I just gave you including this one where we
have ADH receptors and B2 receptors are not
working. The PTH receptors in pseudohypoparathyroidism
is not working. The receptors of testosterone
is not working. The insulin receptor is not
working. Clinically at some point in time
in that disease course of those differentials
that I gave you, you would always expect that
whole amount level to be what? High, because
the receptor is not working you are going
to get feedback mechanism where all my goodness
I want, I want, I want, I want more hormone,
want more hormone, want more hormone, want
more hormone. Hence in pseudohypoparathyroidism,
you will find increased PTH. Hence an androgen
insensitivity syndrome, you find an increase
in testosterone. Listen. You could in diabetes
type II within obese patient with insulin
resistance actually have increased in insulin
and you will. Hence, you will have many of
the pathologic courses or sequelae that we
see in diabetes type II. Here we are going
to have too much ADH. Are you drawing the
parallels now? I cannot talk about this in
good faith without telling you that there
are other diseases that have behaved the same
way. Let us continue. So circulating ADH levels
now you can see confidently and understand as to
why it is elevated, but who is not responding?
The principal cells.
Let us take a look at etiology of nephrogenic
diabetes insipidus. The most common causes