00:01
Let's talk a little bit more about
ADH and its regulation.
00:04
So again, antidiuretic hormone
or ADH is a decapeptide.
00:07
It's synthesized in the
supraoptic nucleus
of the hypothalamus
and it's secreted
by the posterior pituitary.
00:14
It's regulated by both
osmotic and nonosmotic mechanisms.
00:22
Now, there is two types of
ADH receptors
that ADH combined to.
00:26
In terms of this top,
what's most important is the
V2 or Type 2 receptors
that are located in the
basal lateral surface
of the collecting duct.
00:34
That's what mediates
water reabsorption.
00:36
So again,
we've got ADH,
it binds to the
basal lateral surface
of that V2 receptor.
00:41
It then causes stimulation
of aquaporin channels
into the apical membrane
of the collecting duct to cell.
00:48
ADH can also bind to V1A or
Type1 A receptors
that are located in the vasculature
and help to control vascular tone.
00:56
If you recall in the ICU
in the critical care setting,
we oftentimes use vasopressin
as a vasopressor and our patients.
01:05
so we just talked about before
how there's two main mechanisms
that stimulate ADH release
from that posterior pituitary.
01:12
One is an osmotic mechanism,
meaning that our osmolarity
gets high,
and our body knows that we need
to actually drink more water
to bring that osmolarity down low.
01:21
So that's our osmotic stimulus.
01:24
The other is a
nonosmotic stimulus.
01:27
Stimulated by
a decrease in volume.
01:29
So let's go over
what that means.
01:31
In the Osmo regulation,
things like serum osmolarity,
when that gets high,
that's sensed
our sensors, our hypothalamic,
osmoreceptors.
01:41
When they sense
an increase in osmolarity
they will then
produce and release ADH.
01:48
ADH then acts
at that kidney
in order to insert
those aquaporin channels
so we reabsorb water.
01:53
And at the same time
we get thirsty,
so we will drink water.
01:59
In the situation of
volume regulation,
if we have too little volume,
then remember our body
wants to preserve
that vascular tone
in that vascular volume.
02:08
So it wants us
to reabsorb water.
02:12
What's actually sensed
is the effective tissue perfusion.
02:16
So the actual sensors
or our Macula densa
our afferent arterial,
our atria,
and our carotid sinus.
02:24
Our effectors
are going to be the
Renin Angiotensin
Aldosterone System.
02:28
So if I have
too little perfusion,
RAAS is going to be activated
in order to reabsorb sodium.
02:34
Atrial natriuretic peptide,
and some of the ANP related peptides
are going to be suppressed.
02:39
We want to preserve our sodium.
02:42
And then norepinephrine
will be stimulated
in order to increase
vascular tone.
02:45
And finally,
ADH will be released.
02:48
Why? Because ADH will help us
reabsorb water
and in concert
with everything else,
sodium, vasoconstriction
we can preserve our vascular volume.
03:00
So this is a
graphical representation
of what I'm talking about
and the relationship between
ADH release
and these two different mechanisms.
03:07
So on the left,
what we can see is a graph
on the y-axis of plasma ADH.
03:13
The x-axis is plasma osmolality.
03:16
So these were human subjects
that basically were
restricted from water.
03:20
And as their osmolarity rises,
you can see
that there is a
reliable relationship
between ADH release.
03:27
So at about 285 to 290 mOsm/kg,
we can see that ADH is released.
03:33
Remember, what happens
when ADH is released
is not only do we have those
aquaporin channels
that are inserted
to reabsorb water.
03:40
We also get very thirsty.
03:42
So we're going to consume
more water.
03:45
Now, on the graphical representation
on the right,
this was actually an experiment
done in rats,
where they manipulated
the total blood volume of rats.
03:53
So on the y-axis,
we have plasma ADH again,
and on the x-axis, here we have
blood volume depletion.
04:01
And you can see that
when rats were depleted by about
10% of their total body volume,
that we have an increase in ADH,
and this mechanism is so important
that it will supersede osmolarity.
04:14
Meaning that if our patients
are hyperosmolar,
but they have their
total body volume is low,
ADH will still be released
even though they have
a low osmolality.
04:25
So it's a very important concept
to understand.