Let’s take a look at important arginine
vasopressin differential diagnoses.
Once you’ve understood all of different
topics that we covered up above, you go to
this table and you take a look at the labs
so that you’re able to clearly and quickly
differentiate one pathology from the other.
And not all these are pathology.
Some of these are pathophysiologic point.
For example, water deprivation.
Close your eyes.
The water deprivation, what’s your plasma
What’s your urine osmolarity?
Osmoreceptors of hypothalamus.
You tell me.
Stimulated, ADH comes out.
Therefore, you can expect your serum ADH to
You tell me about plasma urine osmolality.
Flow rate – obviously, low because you’re
Clearance means what?
It doesn’t mean filtration, doesn’t mean
reabsorption, it does not mean excretion.
It means what you’ve actually cleared out
of the body.
Clearance, in other words, excretion.
What does free water mean to you?
It’s water that is not obligated to sodium.
It’s not obligated water, it’s free water.
That’s a concept.
If there’s ADH, what you’re doing to free
You’re reabsorbing it.
So, therefore, how much free water are you
Give me some reasons.
Oh, the triphasic, first and second triphasic.
You might be releasing too much ADH.
Maybe there’s lung disease.
Maybe pneumonia, maybe there’s thoracic
surgery or maybe lung cancer such as small-cell.
Whatever the reason, increased serum ADH abundantly.
We know about plasma and urine and we know
about flow rate and there’s your clearance
of free water.
Then we have water drinking.
If you’re drinking water or let’s say
that you have primary polydipsia and you’re
drinking water too much, excessively.
Here, things are different, aren’t they?
You’re going to inhibit the release of ADH
Your plasma osmolarity will be low.
Urine osmolarity is going to be extremely...
well, if you’re drinking plenty of water,
it will be hypoosmotic.
The flow rate will be incredibly high and
the amount of water that you’re now clearing,
in terms of free water, will be excessive.
So, therefore, this will be positive.
Central diabetes insipidus.
Give me some causes.
Eventually during transsphenoidal surgery,
you may result in complete ablation of ADH.
Or we talked about infiltrative such as Langerhans
Here you have decreased ADH.
Tell me about your urine.
Tell me about plasma osmolarity.
It will be hypersmotic.
Flow rate will be high.
Clearance of free water, if ADH is not present,
will be positive.
If it’s nephrogenic, just to make sure we’re
clear here, receptors aren’t working properly.
Your urine will be diluted, hypoosmotic.
High flow rate.
Positive clearance of free water.
If the receptor, for whatever reason, is not
working maybe due to demeclocycline or lithium
or the V2 receptors are congenitally not functioning,
this is nephrogenic diabetes insipidus.
Your ADH levels will be really high, but the
receptors aren’t working properly.
Keep that in mind.
Let’s talk about hyponatremia and the different,
different types of hyponatremia.
You can have hypovolemic, euvolemic, hypervolemic.
I want you to really pause here for a second.
Take a look at the entire picture of this
My topic is hyponatremia.
If it’s hyponatremia, the patient has decreased
But, you can have different amounts of volume
and still result in hyponatremia.
What does that mean?
You could be hypovolemic, hypervolemic or
Then this gives you important differentials.
Let’s take a look at our first branch of
the algorithm for hyponatremia and we have
Examples: vomiting and diarrhoea.
You need to make sure that you rule out nephrotic
Here, the patient is hypovolemic and also
Overall picture of this slide is hyponatremia.
Let’s talk about euvolemia.
You rule out adrenal, adrenal insufficiency
and you rule out hypothyroidism then you have
This patient is euvolemic.
So, even though there is going to be hyponatremia
and increased amounts of fluid in your patient,
we still call this patient euvolemic.
Is that important?
Yes, clinically it is.
That’s why you’re paying attention to
In hypervolemic, you have renal failure, you
have congest-congestive heart failure or you
In all three instances, you’re going to
accumulate volume – hypervolemia.
In all three instances with renal failure,
we can talk about this as being nephrotic
syndrome perhaps or renal failure itself,
in which you are then retaining transudate
or fluid with sodium.
Think about right-sided heart failure, think
about cirrhosis with decreased albumin or
nephrotic syndrome with decreased albumin.
These patients are hypervolemic, hyponatremia.
I want to show you a graph here and show you
how to dissect your graphs from physio, but
then apply it in terms of what’s going on
here in pathology.
When the X-axis is urine flow rate, always,
always dissect your graph with the following
The Y-axis represents your urine plasma osmolarity.
You’ll notice, as you go from X to Y, that
the urine flow rate from left to right is
As you go from X to Y, your urine and plasma
osmolarity is decreasing.
You should already be predicting as to what
kind of patient is this.
Is this a patient who is having issues with
Is this a patient who’s having issues with
Let’s say that you’re drinking water.
If you’re drinking water, what can you expect
your plasma osmolarity to do?
Where are you on this graph?
If you’re drinking water, what should happen
to ADH release?
Are you going to stimulate the osmoreceptors
and therefore, triggering the release of ADH
or are you inhibiting the osmoreceptors, therefore
inhibiting the release of ADH?
If all you’re drinking is... all you’re
doing is drinking water, you’re causing
your plasma osmolarity to decrease.
You’re going to inhibit the release of ADH.
Therefore, a type of urine that you’re producing
is diluted urine.
You, at this point, should be able to predict
that the patient does not have a kidney issue.
In fact, this is a perfect normal patient
that is being doing what?
Once you’ve understood the concept, all
you’re doing is looking for the answer.
Is it A, oral ingestion of 1L water?
Is it oral ingestion of 200 mL of normal saline
or ingestion of 200 mL of hypertonic glucose
Is it oral ingestion of 200 mL of 3% saline
or injection of ADH?
The ones that you can rule out quickly, for
sure E as in epsilon, because if you injected
ADH, what kind of patient?
You definitely wouldn’t expect the urine
osmolarity to decrease, would you?
Take out E.
Now you’re left with A through D. Let’s
take a look at the normal saline.
If you have normal saline that you’re giving
your patient, then you can expect this to
be isotonic, isotonic.
Therefore, you’re not going to have any
Remember, this takes you back to physiology
with the [Inaudible 00:09:11].
And you should remember and accept that if
you are ingesting isotonic fluid, all that
you’re doing is increasing your [Inaudible
00:09:23] volume without changing the tonicity.
You can rule out B.
So, B and E has been ruled out.
Now, you’re left with hypertonic and hypertonic.
C and D. Look, what’s normal saline?
3% saline is hypertonic.
I mean, ridiculously hypertonic.
And then hypertonic glucose solution.
What is that going to do to your plasma osmolarity?
Should increase it.
What’s happening to my patient on the graph?
Plasma osmolarity is decreasing.
How in the world could it be C, as in Charlie,
or D, as in delta?
You’re left with A, as in alpha.
In this section, we’re looking at two hormones
of the posterior pituitary.
One of the great detail about ADH, oxytocin,
a much simpler hormone to deal with.
Oxytocin, wherever it functions, take look
at the picture, we have the uterus and we
have the myoepithelial cells of the breast.
Wherever it functions, either the uterus or
the breast, we’re talking about positive
feedback in which is responsible for contraction,
A simple question that you want to keep in
mind would be, well, if it’s contraction,
then what is the G protein that you’re referring
Oxytocin responsible for contraction of uterus
so that you deliver the child and then also
during suckling by an infant, with the mother
you’re going to then eject milk.
It’s synthetized where?
Paraventricular nuclei of the hypothalamus.
In fact, both posterior pituitary hormones
are synthetized in hypothalamus.
It is then bound to neurophysin, brought into
the posterior pituitary.
It’s important in parturition, meaning to
say stimulation of the uterus and then with
breast feeding with milk feeding.
Oxytocin – both circumstances, positive
Uterine contraction promotes uterine stretch.
Remember though that oxytocin and prostaglandin
work in tandem so that you’re able to properly
deliver your child.
The breast, specifically, histology here is
the myoepithelial cells, as you see in the
Oxytocin used intravenously to induce or reinforce
And we have a drug called Atosiban, oxytocin
receptor antagonist, used as a tocolytic in
Keep that in mind, please.
With slowing down contractions as being a
major, major concept with oxytocin.
Ultimately, ADH and oxytocin management summary
is what we’re looking at.
From the posterior pituitary, we have oxytocin.
With oxytocin, we have it at being a agonist
to induce labour... welcome to Plocin treatment
Or oxytocin in which you’re trying to slow
The term here tocolytic.
You’re trying to lys the contraction, tocolytic.
The drug here, once again, Atosiban.
You want to try to slow down preterm labour,
Now, on the other side, we have vasopressin
Maybe perhaps you want to have agonist action.
Welcome to... remember, arginine, desmopressin,
central diabetes inspidus.
Think about that patient in which, upon administration
of desmopressin, you would then find urine
osmolarity to then increase.
Antagonist, you remember that patient with
Would you tell me the steps of management?
Number one, restrict free water use or consumption.
Number two, you want to crack that sodium
maybe perhaps by giving?
Good, IV fluids.
Next, you want to try to get rid of the excess
fluid, so you give a loop diuretic, but once
again, make sure that you keep an eye on that
sodium because your patient is severely in
a state of hyponatremia.
Maybe perhaps you want to block your V2 receptors.
Welcome to Conivaptan (IV administration),
Tolvaptan (p.o. administration).
If your disease or your pathology still seems
refractory, you want to start thinking about
maybe injuring your V2 receptors on purpose.
Welcome to drugs such as demeclocycline or