Now the three mechanisms or three plausible
mechanisms as to why this is plausible. So
this slide is then explaining to you. Take
a look at the words or sentence in bold here.
Three plausible explanations for the absence
of pitting edema. Have I place enough emphasis
on the fact that may be that you are not going
to find pitting edema in your patient. I hope
so. This is called aldosterone escape. You
are paying attention to this graph that I
just went through and it's a fact that in the
middle there in experiment that is mimicking
Conn in which your blood pressure no doubt
is going to be elevated even though you are
getting rid of your sodium, it diureses. This
ladies and gentlemen is called aldosterone
escape. You see that. Returning excretion
of sodium to level of intake. Here once
more what then happens to your effective arterial
blood volume or you reabsorbed your sodium,
increased effect of arterial blood volume?
Next question pays attention. What happens
to your hydrostatic pressure in the peritubular
capillary? What happens to hydrostatic pressure
in peritubular capillary when you have increased
in effective arterial blood volume? Increased
hydrostatic pressure in the peritubular capillary.
So now it's resisting reabsorption. What
happens to filtration fraction? Good. It decreases.
Are we good here?. Lets continue. The three
plausible of effects or explanations for the
absence of the pitting edema, pressure natriuresis
and with the whole thing results in sodium in the urine
from inhibition of
proximal reabsorption, why? Because of decrease
in filtration fraction. Hence, I spent so
much time attempting to explain to you how
important it is for you to know that increase
in hydrostatic pressure of the peritubular
capillaries is going to then inhibit reabsorption
resulting in a decrease in filtration fraction.
Next, there could be an increase in ANP. How
is that occurring? Increase in volume, sure
with Conn's syndrome. Next, we are going to
dilate the atria, sure you will and what are
you going to release. Called atrial natriuretic
peptide. A possible plausible explanation.
Is it relevant for you? Yes it is, because you
need to know ANP big time and that ANP will
do everything in it's power to do what? Atrial
natriuretic factor. What's natri means? Sodium.
Uretic means diuresis. Number 3. Decreased concentration
of thiazide-sensitive sodium chloride cotransporter
possibly. The two big ones are the first and
second one. This is called aldosterone escape
thus giving you a plausible explanation as
to why you wouldn't have pitting edema. What
is pitting edema by the way? What is that?
Transudate or exudate? I am sorry. What did
you say? Good. Transudate. Be confident.
You are right. Good. That transudate is what
pitting edema is, only. What does that mean
in terms of protein? It is protein poor, but
it is full of what? Sodium, isn't it? It is
protein poor transudate is. You are absolutely
right, but do not forget. It is full of sodium.
So if you don't have sodium even accumulating
in there, can't have. What does pitting mean? You
put your thumb or whatever on the inflammation
and you take off your finger and oh my goodness
there is no thumbprint. Well, I like my thumbprint.
That is not so much good for your patient,
but anyhow can I be any more dramatic. That
is pitting edema, isn't it? Let us continue.
Medullary collecting duct, where are you?
Way down the collecting duct were just about
to do what? We are about to enter my minor,
major calyx. We are about to enter collecting
duct in and out. You go into the ureter. Divided
into inner and outer so be it. Responsible
for a little bit of sodium reabsorption. We
talked about all this in terms of aldosterone.
Let us now move on to water. It is a major
set of free. Stop there. Free water. What
does that mean to you? Remember the difference
that we talked about and you have discussed
what physiology and in terms of free and obligated
water. Allow the name to speak to you. An
obligated water is one in which the water
has been attached to some type of sodium or
solute. Okay. Where are you? But the obligated
water this was the water that was coming in
from the Loop of Henley and it was moving
through the thick ascending limb. What then
happen to the thick ascending limb? You wept
the sodium-potassium-2 chloride away from
the water and now lets just call it a mother
and I am just going to be dramatic here, the mother
and the baby and that you are ripping the baby
away from the mother. Come back, come back.
But no, it doesn't want to. The child is free
now. So that water is completely free of any
type of attachment. That is free water. This
is the diluting segment. That free water continues
through the distal convoluted tubule comes
down the collecting duct and ADH has an opportunity
if needed to then reabsorb the free water
only. What do you know about antidiuretic
hormone? It only reabsorbs water, but there
is a huge exception in which the ADH can only
work by removing that urea as well.
Overall summary, I have talked about every
single segment of the nephron from proximal
through descending limb, through the loop,
through the thick distal collecting duct.
Aldosterone in great detail. We put in all
the major drugs. I just wish to ask you a
couple of things before we end our lecture series
on this note. Bartter's syndrome. Alphabetical
order. What are you hitting first? It behaves
like a loop diuretic. It works in the sodium-
potassium-2 chloride channel. It works to
disturb the concentrating ability of the nephron.
You have hypercalciuria. That you do not have in Gitelman.
Bartter syndrome may have hyperprostaglandinemia.
Increased prostaglandin, management indomethacin
big time, potassium sparing drug such as spironolactone.
Bartter. If you go to Gitelman, we are working
on the thiazide sensitive, in fact, the gene
sodium chloride, thiazide sensitive gene or
receptor, and Gitelman syndrome much more
common than Bartter and with Gitelman some
of the biggest differences is with Gitelman
you have an issue with diluting ability not
so much concentrating ability. Correct.
Next as far as calcium is concerned, you do
not have hypercalciuria, with Gitelman you
have hypocalciuria. So these are some major
pathologies we talked about there and down by
the collecting duct, we talked about Addion's
and Conn's and dealing with aldosterone. Full
picture ladies and gentleman of the nephron
from beginning to end, the physio, the pathology,
the management. You know this, you are solid.