Going to SIADH. Think about what is occuring
here. ADH once down to the collecting duct
in excess and you are going to remove more
free water. As more
free water is being produced or should I say
free water is being reabsorbed, the plasma
osmolarity will decrease at crazy. What is
the state of my urine? Look at the statement
here. What is this state of my urine? Hyperosmotic
urine. Urine remember I told you whenever
you deal with osmolarity, always pay attention
to the adjective. Is it my urine compartment
or is it my plasma compartment? From here
too much ADH.
Circulating levels of ADH abnormally high.
How may this occur? Pay attention here now.
Head injury. From henceforth, head injury,
do not think that you have destroyed the posterior
pituitary resulting in lack of ADH. Many students
do that and they get everything wrong either
in clinics and make a fool of themselves or
in the boards and get the questions wrong.
So from henceforth, when you have a head injury,
it can be rather unpredictable. So what do you
do? You base your question on the labs that
are given. What does that mean? If there is
head injury and you find your plasma osmolarity.
Listen. If you have head injury and you find your plasma
osmolarity really low and you find your urine
osmolarity really high. What is your patient
suffering from? Release of too much ADH from
the posterior pituitary. What if we do the
opposite? I'm gonna thrown in the mix here what if
you find on a lab that your urine osmolarity is
really low and your plasma osmolarity is really
high? What is your diagnosis there? Central
diabetes insipidus. Are you seeing this now?
To be careful with head injury. You will not
always think that you exhaust all the ADH,
in fact you might release too much. Where
else could ADH come from? Lung tumor. Which
one? Small cell or squamous cell. Small cell,
perineoplasic. ADH secreted autonomously, without
an osmotic stimulus, that could also occur.
So there is no osmoreceptor that is telling
the ADH or posterior pituitary to release from
the hypothalamus, but you are autonomously
releasing it. ADH is secreted when it is not
needed. So, generally speaking, important
clinical situation is head injury and perhaps
your small cell lung cancer and the fact that
you might have autonomous secretion. Level
of ADH increase your reabsorption of water
from the distal tubule and CD, collecting duct.
If hyperosmotic, urine. Stop. Hypoosmolar, plasma.
Two compartments for osmolarity always. Keep
those compartments seperate. Keep them organized
so that you have proper differentials. Hypoosmolar
plasma inhibits the secretion of ADH. It should. Listen.
Hypo, normal individual. Let me give you an example.
Drinking too much water, what is your plasma
osmolarity? Decrease. What should you do normally?
Suppress my ADH or if it doesn't, then we have SIADH.
The feedback inhibition in SIADH, syndrome
of inappropriate antidiuretic hormone, does
not occur because ADH secretion is now autonomous.
How does this occur? Well, I gave you a prime
example. Head injury maybe a small cell lung
cancer so on and so forth. Now, what about
management? All demeclocycline inhibits ADH
action on the renal principal cell. So we
have demaclocycline inhibits ADH action on
the renal principal cell. There is something
that may behave like this on purpose.
The other big one would be something like lithium.
Lithium and demeclocycline actually induces
nephrogenic diabetes insipidus. So, let us
step back here and make you understand what
is happening. SIADH is your primary pathology
and this is how the questions and the stems
and the things that are boarded may confuse
you if you are not paying attention,
you are going to choose the wrong thing. Please,
let me walk you through this. If patient
initially is coming with SIADH, you know that
because of the labs they have been giving
you. An increase in urine osmolarity, a decrease
in plasma osmolarity. Fantastic. You know
your patient has small cell lung cancer most
likely chest x-ray next step of management
and you try to look for that small cell lung
cancer, there might be perineoplastic releasing
your ADH. Okay, fantastic. Now with all that
ADH being secreted into circulation, it has
excess activity on your collecting duct. Would
you tell me a step of management in which
you are introducing a "disease" to deal with
SIADH? Well if ADH works on the principal
cell, why not give a drug that is going to
impair the action of the principal cell. Why
not give a drug that actually kind of knocks out the
ADH receptors? What are those receptors? V2
receptors on the kidney. Amazing. So here,
you are going to induce, what does nephrogenic
mean? The V2 receptors aren't working. You
are going to induce nephrogenic diabetes insipidus
in a patient with SIADH. How might you do that?
Demeclocycline. Now that is one of those tetracycline
drugs that might do that. Lithium could be
a little interesting. With lithium yes it
may then cause nephrogenic diabetes insipidus
now. Is that something that you want to use
in a patient with SIADH or just keep that
in mind because you want to keep as many angles
as possible so that you are open to possible
questions coming at you in any direction.
My job here is to give you as many angles
of possible. At some point, where I will talk
to you about lithium is going to be how you
have a bipolar patient taking lithium, therefore,
resulting in nephrogenic diabetes insipidus.
Not so much treatment for SIADH. Demeclocycline,
sure treatment for SIADH. Keep that clear.
Make sure you review this. I have given you
a bunch of information here that could be
rather confusing, lot of terminology, but
understand the topic at hand and deal with
management and you will be in good shape.