A couple of other things. There are different
types of Bartter and I wish I can tell you
that, that's all that you needed to know. With
Bartter, first and foremost with no foundation,
problem with thick ascending limb, sodium-
potassium-2 chloride. There is a problem
with concentrating ability and there is a
problem with hypercalciuria. Much more so.
So far so good. We have what is known as well
I, IV and IVB. There are different types okay.
So antenatal Bartter meaning right around
birth, antenatal, is a hyperprostaglandin
E2 syndrome. All that you need to know
is this. Keep this in mind. There are many
types of Bartter syndromes that are associated
with hyperprostaglandinemia, Why is that important?
Because at some point remember our entire
course here in pathology is you being a doctor.
You being able to identify your patient based
on knowing the normal, abnormal, at least be
able to know a little bit of management okay.
Because otherwise you miss questions and you
don't want that. So you will have many Bartter
syndromes that are associated with, what is
known as hyperprostaglandenemia. Okay. Now
if you want to know I, IV and IVB, that is
fine. It might be a litte bit too much detailed,
but keep in mind hyperprostaglandin. Now what
is important is you want to know these these
genes. It is called ClC, means to say
they are chloride cotransporter channel highly
expressed in the inner ear to maintain high
potassium concentration in the endolymph.
Why is that important? Because in these conditions
IV and IVB types of Bartter, keep this in mind
because these are distinguishing features
that I can't even tell you how important
is this clinically. Boards and wards they just love
asking questions like this and if you answer
this, you see as to how you will be a shining
star. So here IV and IVB type of what is known as
Bartter syndrome apart from having hyperprostaglandinemia,
these chloride channels ClC-K is also necessary
for proper endolymph in the ear to have a
hearing and vibration and if you don't have
these channels working properly not only are
you going to have issues in the kidney, but
then you have issues in the ear. Stop there.
This might be your very first time that you
have heard of this. You have heard it here
and you will be asked and when you are seeing
this and you are hearing this, you are getting
question and you are so confident about getting
this right. You will feel good. Point being
is there is another issue in cardiology in
which we talked about how you might have long
QT syndrome. Remember this. Long QT syndrome
and deafness and that was called Lange-Nielsen
and Lange-Nielsen is a congenital QT syndrome
associated with deafness. Romano-Ward was
congenital long QT syndrome without or no
deafness. So these here is to how these distinguishing
features or things are so loved to be asked.
So here we have Bartter syndrome and you have
type IV, IVB associated with deafness. You
want to know ClC-Ka. Move on. Epidemiology
clinically your patient here antenatal, childhood.
Now overall though understand the Gitelman
syndrome is much more common than Bartter,
but at least know these distinguishing features
of Bartter before moving on to Gitelman.
Lets move on.
In Type–I, antenatal Bartter syndrome things
that you want to keep
in mind. First of the bat, we talked about
sodium-potassium-2 chloride, two gene. stop there.
Next, pay attention to what is happening here.
Overall, you will lose your potassium, hypokalemia.
You have hypomagnesiumia and remember as to
what your level aldosterone is. It is increased. Right?
In the hopes of restoring the blood pressure.
So you get rid of your hydrogen, hence result
in metabolic alkalosis. That is the only one
that might be little tricky, but there is
enough information here. You should not miss
a single question on Bartter. Let us now move
on. Other aspects; growth and mental retardation,
volume depletion hence we talked about the
issues with aldosterone. Also, the most important
point here is look at increased prostaglandin
and so, therefore, management often times in Bartter
is try to antagonise the prostaglandin.
So what might you be thinking about? How about
COX inhibitors? That is interesting.
Ever heard of management of Bartter with NASIADs?
Now you have, and you should know it. Muscle
weakness due to hypokalemia. Now integration,
I can’t just walk past this knowing that
you will be asked other questions from physiology.
You lose your potassium. We have increased
aldosterone in company and when you lose
your potassium, resting membrane potential
becomes what? More negative. As your resting
membrane potential becomes more negative, where
is my threshold? It is further away. It is
more difficult to reach threshold thus in
terms of triggering an action potential, not
as ready. So, therefore, you are looking
at muscle weakness and heart issues. Do not
forget that. In general, hypokalema you should
know always causes muscle weakness for reasons we
just talked about. The secondary hyperaldosteronism
because of warm depletion, polyuria, polydypsia.
Remember you are going to lose quite a bit
of calcium. Normal or hypercalciuria, highlight that.
Leading to possible secondary hyperparathyroidism.
Stop there. More integration. What do you
mean? If you have hypocalciuria, where is
my calcium? In my urine. Good. More that you
are losing calcium in your urine, you might
actually have decreased calcium in the blood.
Pay attention to suffix here uria. If you
have decreased calcium in the blood, what are
you going to trigger? Secondary hyperparathyroidism.
Everything that you do here you want to make
sure you are alert, you have full of energy
and you are with me and give youreslf these tags
over, over, over and over again and really,
they can't fool you. What is your management?
Lets take care
of the prostaglandin. Indomethacin. What is
that? A cox inhibitor. NSAIDs. Why? Many types
associated with hyperprostaglandenemia. Next,
you are going to lose a lot of potassium.
Why not use the drugs to try to spare them.
For example, spirinolactone, which is what?
An aldosterone antagonist. Good and then ACE
inhibitors. ACE inhibitors might be used here
so that you can prevent some of these issues
with blood pressure and the fact that you
have problems with prostaglandins and so forth.
But main stay therapy indomethacin and potassium-sparing
diuretics. Lets continue the discussion.
After Bartter and thick ascending limb and
go further distally. So now we're in the distal
convoluted tubule. Quickly once again to recap.
Here is my sodium chloride channel. You see
where we are? Good. You see that receptor on the
basolateral membrane? That receptor is called
the parathyroid hormone receptor. Last time
we talked about that was well hypoparathyroidism
primary and what was the other one where I talked
to you about, where i have referred to it knuckle,
knuckle, dimple, dimple. Oh, that was your pseudohypoparathyroidism.
Mean to say the receptor is not responding
to parathyroid hormone. Just to make sure we are
clear that pseudohypoparathyroidism presentation,
you have a short patient. Short stature patient
and the dimple dimple refers to your fourth
and fifth, your pinky and ring finger, the metacarpophalangeal
joints and they are not present. I am going
to reinforce this. Not to worry. Just want you
to see as to where the problem is. Now getting
back on point we have sodium and chloride.
These are thiazide sensitive. In addition the
PTH works here to do what? Reabsorb calcium,
has no affect here in terms of inhibition
of phosphate, that was in the PCT remember
and PTh works in the PCT to stimulate the
enzyme 1 alpha-hydroxylase. Here it primarily
works. Take a look at the bottom box there
on the basolateral membrane so they can
reabsorb calcium. Give me a drug that might
also a diuretic obviously that is going to
reabsorb calcium. Welcome to thiazides. Now the distal
convoluted tubule actively reabsorb sodium
and chloride. It is known as the diluting
segment because it is water impermeable makes
the urine hypotonic further. Site of PTH action
highlight this in your mind you know that
it is calcium coming in. Calcium reabsorption.
So therefore, in a condition such as primary
hyperparathyroidism, there is too much activity
on the receptor by PTH thus there is going
to be increased reabsorption of calcium. Stop
there for a second and you give me a paraneoplastic
issue. A paraneoplastic issue is going to
increase production of not exactly PTH, but
PTH like. Good. Squamous cell cancer of the
lung. Give me another one. Renal cell cancer
of the kidney, obviously. So RCC, renal cell
cancer, squamous cell cancer of the lung.
These are two cancers two different organs
producing not exactly PTH. Hence we called
this PTHrP, the operative word RP. That is
related peptide to PTH. Does work on the
receptor? Yes it does. So therefore will it
reabsorb calcium excessively? Yes it will.
Is PTHrP the same thing as PTH? No it is related
but it is not the same thing. Are we clear?
Why? How are you going to intrepret the labs
here? You find excessive calcium, hypercalcemia
with PTHrP and that excess calcium tells my
parathyroids to be what? Shut down. Interesting,
isn't it? You have increased PTHrP, increased
calcium, but a decrease in actual PTH. Do
not forget that. We will reinforce it. You
can see that we are adding more and more pathology
through every single slide in every single
concept. Build, build.