00:00
Actions of ADH. Once again I wish to reiterate
the emphasis here with ADH is going to be
its effect on the kidney and when it comes to
pathology. In nephrology, we will be focusing
and have been focusing upon nephrogenic diabetes
insipidus, which just came up of a very important
discussion as to the mechanics of your ADH
receptors on your V2 receptors and the fact
that it works with GS. Spend a little bit
of time with that concept so that you understand
at some point in time if they do oppose a
question, how do you bypass the receptor while
you do everything in your power to then increase
production of the cyclic AMP so that you can
then insert the aquaporins and continue through
the process of reabsorption of water. Now
with that said once again we reiterate the
V2 receptors are on the kidney and specifically
in the collecting duct and as long as your
ADH is present. Would you please take a look
at the picture here where you will find on
your left side the actual medulla and the
lumen and as you move distally through the
collecting duct, we go from proximally less
than 300 all way down to 1200. Wow! what is
normal isotonic plasma osmolarity? Approximately
300. Here we have urine osmolarity at 300
moving all way to 1200. Do you think that
the effective ADH is present here? Of course,
it is and so, therefore, you are going to
reabsorb that water and as you move from the
lumen and over to your right is your vasa
recta. What does that mean to you? Your peritubular
capillaries. Reabsorption is taking place
and putting that water back into the plasma
with the help of ADH. Now that will be your
primary focus. Now what I wish to bring to
your attention one more time is the fact that
ADH also known as arginine vasopressin may
then work upon your blood vessel in which
as you see here would be responsible for releasing
some of its von Willebrand factor. Now what
will you also find to be interesting is the
most of your factors, your coagulation factors,
in fact, are being produced where? You see
the liver there on top. On your right a big
gray mass that is your liver and that is going
to be producing all of your coagulation factors
except a few and those few include von Willebrand
factor and that you have factor VIII. Where
would these be coming from? These would be
then coming from your endothelial cells. Now
the receptors that you find here are V1 receptors.
They are responsible for, do you see this?
It is kind of looks like a bottleneck, doesn't
it? Mean to say that as we take a look at
the diameter of the blood vessel on top, it
looks narrowed and there would be the effects
of ADH being exerted upon your blood vessel
whereas if you take a look at the bottom portion
blood vessel, you will find any ADH down here?
No, you don't. So, therefore, what is this
state of my blood vessel? Not vasoconstricted.
Let us continue. So now you are releasing
von Willebrand factor. What must factor VIII
have in its association? It is optimum functioning
of factor VIII. Obviously von Willebrand factor.
I am going to bring another pathology appear
one more time all about reinforcement. If
you have a female and she is bleeding excessively
during her menses, then you get labs in which
you start reading the following. You will
find an increase in PTT and you will find
an increase in bleeding time and with that
type of history, you are most likely. Well,
what is your next step of management? There
is something called and we will talk about
this called ristocetin assay. Now ristocetin
is a very expensive test. That is important
for you to know. That is why you don’t readily
call or request for a test of ristocetin because
it is too expensive. Now as said it may be
seen in the idealistic world, oh! you can
order whatever you want. Now that is not the
case. You have a doctor but hospital is a
business. When you have a business, what are
you looking for? Cost effectiveness and how
to generate revenue. Unfortunately, you are
in a situation where you are responsible for
that as well. So, therefore, you next step
of management to confirm your von Willebrand
disease, in fact, is your risocetin. Now what
I wish to also brings to attention now this
makes sense. Take a look at factor VIII. If
you don't have von Willebrand factor, factor
VIII isn't working properly. If factor VIII
isn't working properly, well you remember
from hemodynamics the factor VIII is part
of the intrinsic coagulation pathway. The
intrinsic coagulation pathway is then tested
with PTT. What was the that I gave you in
von Willebrand disease that was elevated PTT.
04:53
Is that clear? Why? Because then factor VIII
isn't working properly. That is test #1. Okay,
but then what is the other test that I mentioned?
Bleeding time. I will give you the times later,
but actually, I will give it to you now. Why
not? Two to seven minutes is bleeding time.
05:10
Well, here you will find your bleeding time
to be greater than seven minutes. How does
this occur, please? It is a fact that you
require von Willebrand factor to then bind
to platelets. So if you don't have the von
Willebrand factor, guess what? Your bleeding
time is going to be elevated. Confirming von
Willebrand disease. Let us continue.
05:30
Vasopressin analogs for the management of
von Willebrand disease type I. Now understand
there are five if not more different types
of von Willebrand disease, the one that you
want to know for sure in which you are deficient
of von Willebrand factor is type I von Willebrand
D disease. What is an analog here that you
want to use to release the von Willebrand
factor? How about some vasopressin? There
it is. In addition, what are the conditions
might you be thinking about to treat with
vasopressin? There is hemophilia A. What is
hemophilia A? AB89. What I am saying? In the
alphabetic order, A comes first. Chronological
order 8 comes first. Factor VIII deficiency
is hemophilia A. Vasopressin may release factor
VIII. Let us continue. Now the supra-physiologic
levels. ADH works
on V1, where is that? On your blood vessel,
therefore, bringing about vasoconstriction
that is which you are seeing here bold
in green.