00:01
We are into a topic where students tend to have
once again, problems with organization, but
likely have done the entire time the more
organized you are with your thoughts, the more
methodically you can go through the material
and the more number of times you do this,
then it becomes part of your reflex and this
brings us to the concentration of urine. And
with this lecture series, we will be getting
into issues of ADH either, too much or too
little. At first, let us say that you have
a patient that is deprived of water. The best
thing to do before you go through all of these
chronological order, you want to pay attention
or predict as to what you can expect in your
patient. Once you have done that, then you
take a look at the chronology and all of it
will make sense. You deprive your patient of water.
00:58
What does that mean to you? It means that
your plasma osmolarity is going to increase,
doesn't it? Once your plasma osmolarity increases,
then the osmoreceptors by the hypothalamus
will be triggered and you will be releasing
your ADH. That ADH then runs down to the collecting
duct that works to then insert these aquaporins
via V2 receptors so that you can reabsorb
that water, so that you can bring the plasma
osmolarity back down to normal, right? So in essence,
it is exactly what this illustration is showing
you. Deprivation of water, increased plasma
osmolarity. What happens next? Operative word,
stimulation of your osmoreceptors. Next, you
increase ADH. That ADH will then run down
to the collecting duct, they'll work through V2
receptors. It will then insert the aquaporins
so that you reabsorb water purely.
01:56
As you do so, it then causes the urine
osmolarity to do what? Increase, good. And by
removing the water and putting into the plasma,
it is bringing the plasma osmolarity back
to normal. Response to water drinking. This
is the opposite scenario so even though
the graph might look similar, the starting
event, completely the opposite of what we just
discussed. Here let us say that you are drinking
water. Then what happens to your plasma osmolarity?
Almost immediately, it drops a little bit.
Now your plasma osmolarity is low, so, therefore,
tell me about those osmoreceptors, they are
not going to respond because there is no osmolarity
to attend to. So, therefore, what happens
to ADH release? It is suppressed. If there
is no ADH, then as far as your urine is concerned,
you tell me is it dilute or concentrated?
If the ADH isn’t working, then the fluid within
the collecting duct is then going to be in
fact diluted urine. So, therefore, your urine
osmolarity would be? Good, decreased. Now if you
are not going to then reabsorb that water,
then you can expect your plasma osmolarity
to come back up toward normal. This is, in
essence, the overall mechanics of ADH in response
to plasma osmolarity. Now, ADH has three major
actions in the renal
tubule. This we have talked about plenty.
On the principal cells, in addition to aldosterone,
it has the ability through V2 receptors and
putting those aquaporins so that you can then
bring out the water. But take a
look at this. Remember the sodium-potassium-
2 chloride, where are you? The sodium-potassium-
2 chloride cotransporter it is located on
the thick ascending limb and what does that
have to do with ADH, Dr. Raj? Well, a lot
actually. Remember those diseases called Bartter
and Gitelman. You are bringing them up again?
Yes, I am. And the reason that I am bringing
up now specifically which one of these diseases
have we discussed the results in dysfunction
of that sodium-potassium-2 chloride cotransporter.
04:18
Bartter and so therefore if you knock out
this symport or cotransporter, you have lost
ability to do what? To properly concentrate.
Do you remember that? If you don't properly concentrate,
then please understand you have also lost
ability to properly dilute. If you don't properly
dilute, where is your diluting segment? Going
up the thick ascending limb and really moving
up towards the distal convoluted tubule. So
that is your diluting segment, if you can’t
properly concentrate, you sure as heck can't properly
dilute as far as its ability way down in the
collecting duct for providing an environment
for ADH to work properly may then be impeded.
05:03
And pretty much saw that both with the diluting
ability in both Gitelman
and Bartter if you remember correctly. But
here understand that symport is absolutely
required for proper functioning of the ADH
later on down in the collecting duct. What
else ADH do? Now this is important. Many
students end up forgetting about this. Last
time we have even talked about urea. It was
rather insignificant. Alright. So no one likes
to feel insignificant. That is for sure. Here
urea with the help of ADH, in the medullary
collecting duct, where are you? Way down deep,
in the kidney, medullary collecting duct. ADH
sure it brings up water, but what do you know
about water? How do you move water? Osmosis.
05:55
Has to be. There is no way that you could
move water with that osmosis in the body.
05:59
Do you understand that? So tell me as to what
kind of gradient this is? It is moving from
low solute concentration to high solute concentration,
isn't it? What is this solute that water is
following in the collecting duct? The urea.
So ADH is the third and final function really
to assist in reabsorption of water is going
to be the fact that it actually places urea
into the interstitium thus creating an osmotic
gradient to then reabsorb the water. 1, 2
and 3, three major actions of ADH. Beautiful
table here for us to truly understand.