00:01
Let's take a tour
through our nephrons,
so that we can understand exactly
how water is handled.
00:06
So, if we start at
our proximal tubule,
the proximal tubule reclaims
most of the water, and electrolytes
that's filtered through the
glomerular basement membrane.
00:15
So, in the tubular fluid,
right there at the proximal tubule,
our tubular fluid is going to be
iso-osmotic
to our plasma osmolality.
00:24
Once we get to the
thicky ascending limb
of the loop of Henle
remember what's there,
that's the NKCC2.
00:30
We are going to reabsorb
sodium, potassium, and chloride
and that helps to generate our
osmotic gradient in the medulla
associated with the vasa recta.
00:39
But remember,
that also
that segment is impermeable
to water.
00:43
So it's what we refer to
as our diluting segment.
00:48
The next segment to pay attention to
is the distal convoluted tubule,
an early collecting duct.
00:53
Which will again, reabsorb
more sodium chloride
that sodium chloride cotransporter,
and impermeable to water.
00:59
So it generates a very diluted
tubular fluid or urine
at the top of the collecting duct.
01:06
Once we get at the collecting duct,
then the ultimate concentration
of urine
is really going
to be determined
by whether or not
we have ADH present.
01:17
Now, ADH stands for
antidiuretic hormone,
it's also termed vasopressin.
01:22
We're going to be talking
a little bit more about that
in some slides to come.
01:26
So what happens when
we have an acute water load
or need to excrete free water?
We can accomplish this by
reducing our urine osmolality
to as low as 50 to 75 mOsmol/L.
01:38
But it requires
normal renal function to do that.
01:41
Meaning that
a couple of things have to be true.
01:44
Number one, we have to have
delivery of solute and water
to those diluting sites.
01:49
So if that's compromised by things
like renal failure, for example,
or volume depletion,
where we don't have appropriate
solute delivery to those sites
that can impact our ability
to actually get that urino some down
as low as possible.
02:05
We also have to have
proper functioning
of the diluting segments.
02:09
Again, this can be compromised by
people who are taking diuretics.
02:13
Things that block that
Na-K- 2 Cl cotransporter
like loop diuretics
and the thicky ascending limb
of the loop of Henle
can really impair our ability
to get our urine dilute as possible
to excrete that free water load.
02:28
ADH also has to be absent
at that collecting duct.
02:32
Meaning that it has to be
impermeable to water.
02:34
So if ADH is present,
remember what's going to happen
is it's going to cause
reabsorption of water
by insertion of aquaporin channels
into that collecting duct.
02:43
So, again, in order for us
to make a dilute urine,
we have to have solute delivery,
we have to have those
diluting segments open,
and we have to make sure
that ADH is suppressed.
02:58
Now, what if we want to retain
significant free water?
We can actually do that by
concentrating our urine osmolality
to as high as 1000
or 1200 mOsmol/liter.
03:10
And we can do this by developing a
concentrated medullary interstitium
by solute reabsorption in the
thick ascending limb.
03:16
Again, that thicky ascending limb,
and that diluting segment
has to be intact
in order to reabsorb sodium
to generate that
concentrated medullary interstitium.
03:26
We also have to have
the presence of ADH.
03:28
ADH has to be
released and present
in order to stimulate the
insertion of aquaporin channels
into the apical membranes
of our collecting ducts cells.
03:37
Not only does it have to be present,
the ability of the
collecting duct cells
to respond to the ADH
by inserting those
aquaporin channels
has to be intact as well.
03:45
So these three things
are critical
in order to maintain or generate
a very concentrated urine.