00:01
Management of nephrogenic diabetes insipidus.
Before we move on, think about your patient.
00:06
The receptors aren’t working properly. Therefore
how much urine polyurine. What are you producing
diluted urine? Tell me about clearance of
water? It is increased. Increased free water.
00:17
So far so good. In the meantime, when you
are losing all the fluid, tell me about your
plasma. Your plasma osmolarity is increased.
Now if you have a child that has nephrogenic
diabetes insipidus in addition there is going
to be further a loss of fluid. Welcome to
vomiting, diarrhea, fever there might be sweating
taking place. What is your first step of management?
IV fluids. You have to granted the fluid might
be leaving excessively from the urine, but
please understand you still must give it because
if you don't have the fluids, then what happens
to your blood pressure? My goodness. It drops
like crazy. That is your first step of management.
00:58
Next D5W. What does it mean? It is basically
pure water. Now you have given it but the
only problem is the fact that you are looking
for and may then bring about dilutional hyponatremia.
01:11
What is important by D5W? It is the fact that
you have to have that dextrose where if it
gets rapidly metabolized, it slows down or
retards the entry of water into the cell.
01:22
What are you preventing? Rapid swelling and
lysis of your cell. Now, why would you even
think about giving D5W? What kind of fluid
is D5W? Hypotonic, isn't it? It is hypotonic
and tell me about your patient with nephrogenic
diabetes insipidus. Plasma osmolarity ridiculously
high. So, therefore, what might you want to
give to then decrease the plasma osmolarity?
How about some hypotonic fluid? You see as
to how our discussion earlier of IV fluids
is absolutely relevant to what is happening
here. Take a look at 0.22. 0.22 represents
extreme hypotonic. What is normal saline?
0.9. What is half normal saline? 0.45. Here
is 0.22. That is quite hypotonic. Next what
else might you want to do? Decreased dietary
solute preventing osmotic diueresis. Everything
that you turn to do ladies and gentleman after
your ABCs what ABC mean to you. Whenever you
have a patient what are some of the first
questions that you are asking so? It is the
airway block. What about the breathing or
what about the circulation? So if the circulation
is affected here in nephrogenic diabetes insipidus,
it is IV fluids. Next well why not decrease
some of the solutes? Maybe some of that "salt"
your sodium so that you prevent further osmotic
diuresis. Diuretics. This is interesting.
02:52
Please pay attention here. Okay. Let us go
way back to look at the nephron and we had
a distal convoluted tubule. Think about that.
Are you there? Distal convoluted tubule. Good.
03:05
What kind of symporter do you have? It is
called sodium chloride symporter. It is the
diluting segment and what receptor is it very
sensitive to or what hormone is the receptor
based sensitive to? PTH. What does that mean?
Calcium reabsorption. What kind of diuretic
works in that area? Thiazide. Now as counterintuitive
as it may see to give a diuretic, do not give
your patient with nephrogenic diabetes insipidus
or loop diuretic, you get kicked out of the
hospital. Oh! my goodness. But it is shown
that thiazide now really the mechanism and
the theory behind it is quite complicated.
So let us not go there. You go there on your
own time and our time let us make sure that
you are clear. A diuretic that you would only
use in the setting of the nephrogenic diabetes
insipidus will be thiazides. So, two unique
features actually three unique features of
thiazides that you must know. #1 the African
population, elderly that have hypertension.
Your drug choice or antihypertension is thiazide.
04:17
Point #1 that makes perfect sense. #2 if you
have a patient that has too much calcium where,
in the urine, then thiazides may be used to
remove the calcium from the urine. Isn't that
a unique feature? Yes, it is. #3. Thiazides
can be set or can be administered in the setting
of nephrogenic diabetes insipidus. Fascinating.
What does it do? Weight loss of 1.5 kg can
reduce the urinary output by 50 percent and
that has been shown to occur by giving thiazides.
04:52
Look at this. You are reducing the urine output
by greater than 50 percent. That seems pretty
effective to me that the mechanism let us
know at this point research has given us that
outcome. Next, the effect mediated by hypovoilemia-induced
increase in proximal sodium and water reabsorption,
thereby diminishing water delivery to the
ADH-sensitive site is the most common theory
to be tested and so therefore by doing this
then maybe just perhaps you are resulting
in reduced urinary output by giving it diuretic
known as thiazides. Now finally the problem
is this. Amiloride in patients with reversible
lithium-induced nephrotoxicity. Isn't this
interesting? What does this mean? Remember
that lithium and who is your patient? Adult
may be and why would the adult be taking lithium
for long periods of time. Maybe they are crazy
and then maybe they are depressed. Crazy,
depressed. Bipolarism right. With bipolarism,
taking lithium over long period of time, the
lithium then works in ENAC. We had that discussion
interesting. What about amiloride? Works in
the ENAC. So amiloride in a patient that has
had lithium induced nephrogenic diabetes insipidus
and you get to the point where it is irreversible.
06:17
Hopefully, amiloride is your drug of choice.
Management of nephrogenic diabetes insipidus
really ladies and gentleman this is out of
the press. You are probably hearing all of
this for the first time. You want to confirm
this sure. Walk into a clinic and kick butt
and be hoisted on the shoulders of your peers
and you will see as to how effective you are
as being a medical student or resident and
so forth. Let us continue.
06:43
Now, ultimately management of nephrogenic
diabetes insipidus. Now what we are going
to walk through here is the following of very
important table. Examples, we will talk about
the differentials in the first column. We
will talk about serum ADH, plasma osmolarity,
urine osmolarity and this is great here because
we can actually compare both of the osmolarity
compartments adjacent to one another by urine
flow rate and then free water clearance. Let
us begin. Let us say that you conducted water
deprivation test. Close your eyes. Water deprivation,
what happens to plasma osmolarity? Increased.
You see that. Next water deprivation well
you have now plasma osmolarity. You are inducing,
for the most part, none of the water in your
plasma. It is increased. So what is the body
trying to do? The body releases ADH. Take
a look at the second column. That ADH comes
in what is going to work? Collecting duct
and you are going to create what kind of urine?
Good. Hyperosmotic urine. What do you think
happens to your flow rate when ADH is working?
It is low. Stop. Tell me about free water
clearance. What does free water mean to you?
No obligation to any electrolytes. Okay. So
now you have increased ADH in the setting
of water deprivation. Let us say a better
word for this is reabsorption of water from
the collecting duct. What is your clearance
of free water? Negative. What is it meant
when you have clearance of water being zero?
It is not solute-free. What does it mean if
you have clearance of free water being positive?
That means that you are getting rid of too
much water in SIADH or in the setting of ADH
obviously your clearance would be negative.
That must be understood. Now that lays down
the foundation. Now we can move quicker through
the differentials. SIADH what does that mean?
Too much. Tell me. Plasma osmolarity, but
here it would be decreased because you are
moving too much of your ADH. Do you understand
that? I want you to compare this plasma osmolarity
with SIADH and water deprivation because it
is important that you walk through chronological
and logical steps. If you are water deprived,
where do you go first? The plasma. If it is
SIADH, what do you go first? ADH. Why? If
it is water deprivation, plasma osmolarity
increases thus resulting in increased ADH.
If it is SIADH, what is it? Yeah ADH is increased
in excess. Then you can go through the rest
with hyperosmotic urine sure. Low yes negative.
09:36
The rest are the same. But if you don't spend
time understanding those two differentials
and why ADH is increased and why the plasma
osmolarity is opposite to one another, then
you missed the entire point and you just memorize.
There is no way to memorize this table and
question gets questions right. You cannot.
You understand this table, then you go into
clinic and then you go into doing exams, guaranteed
to get everything right. First water drinking.
10:01
With water drinking, where do you want to
go first? Good. Plasma osmolarity. So when
you drink water, your plasma osmolarity would
be low especially excessively. If your plasma
osmolarity is low, tell me about your osmoreceptors.
They are not going to stimulate release of
ADH. Your ADH is now going to be suppressed.
If that is now suppressed, then tell me about
your urine osmolarity. It is going to be hypoosmotic
urine. So therefore when you have more dilute
urine that you are producing because the lack
of ADH, then tell me about your clearance
of free water. It would be positive and your
flow rate will be increased. Once you get
that done, you will notice the other two.
We will talk about here with diabetes insipidus.
10:47
Your focus here ladies and gentleman should
be on nephrogenic, but now jut to be complete
I have also listed central. With central diabetes
insipidus, where is my problem? Good. The
ADH was never released. If the ADH was never
released centrally, then what happens to your
urine osmolarity? It is going to be a really
low hypoosmotic and then you have positive
clearance. Next what about nephrogenic? We
just talked about this in great detail so
they should be perfectly clear your kidneys
and the receptors are known as V2 receptors.
11:24
May I ask you what that mutatio was one more time?
It was arginine vasopressin
receptor2 gene in which receptors are not
responding to ADH and so therefore what kind
of urine are going to produce? You are going
to produce really really hypoosmotic urine.
11:44
Good. Stop there for one second. I told you
this earlier. This was a concept. If the receptor
in a pathologic condition are not functioning,
what is always the state of the hormone that
should be working on it. High, high, high.
Good. Take a look to ADH, ridiculously high.
12:03
But why is it that your urine is too hyposomotic?
Because the receptors aren't functioning.
12:08
They are still clearing lots of free water
and urine flow rate is going to be high. You
spend a little bit of time on this table.
Understand the pathophysiology for each one
of these parameters. Seriously. Clinically
speaking, there is no way that you didn't
get a single question wrong.