of the diluting segment. What does the diluting
mean? There it is. Hypotonic. So down here.
Lets talk about this. A lot of words. Let me
give you the overview. We will get into specific
pathologic problems. One is called Bartter,
the other one is called Gitelman, okay. Now
we are going to put this together right now
because I need you to at least know that these
are pathologic conditions that you are mandated
to know within the nephron starting from the
thick ascending limb and then finally end
up at the collecting duct.
The overview as far as common, distinctive
and then we will get into distinctive features
are going to be the following. The tubular
defects in sodium chloride transport and two
different places. Think about that for one
second. If it is the thick ascending limb,
how is the sodium being reabsorbed? Sodium-
potassium-2 chloride. If it is the distal
convoluted tubule, how is that sodium being
reabsorbed? Sodium, chloride. Next thick ascending
limb. What kind of diuretic? Loop. What about
the distal convoluted tubule? What kind of
diuretic? Thiazide. Next, well to make your life a
little bit easier, let us now do our alphabetic
order. B before G at the same time I want
to go from proximal to distal in your nephron.
The loop diuretic, which would be a problem
with the sodium-potassium-2 chloride that
pathology is called Bartter.You see what it
says loop diuretic mimicking Bartter syndrome.
Stop there. Where are you? Thick ascending
limb. It behaves like a loop diuretic. You
tell me now the pathology for Bartter syndrome
is dealing with which sodium channel? Sodium-
potassium-2 chloride. Are we done? Not at
all. I have to give you clinical manifestations,
then I must give you the genes.
Next, I want you to go distal convoluted tubule.
What was the name of that sodium channel? Sodium
chloride is thiazide-sensitive. Right. So,
therefore, this will be Gitelman. What is
the next letter? G. Gitelman is like a thiazide
drug. These are pathologies that mimic the
pharmacologic agents in terms of how you want
to approach this.
Next, impaired sodium chloride reabsorption
leads to mild volume depletion, hypotension
thus what does it activate? Highlight highlight
highlight RAAS. Next the combination of, why
do we call the secondary hyperaldosteronism,
why? Why? If you are losing fluid, then what
are you going to release? Renin, how? Secondarily.
You give me a differential in which you are
releasing aldosterone primarily. Conn. You
see the difference. Conn's syndrome is primary
hypoaldosteronism. When you have warm depletion,
this is going to be secondary hyperaldosteronism.
Walk through this further. Where does aldosterone
work? It works in the distal convoluted tubule.
What is it going to do? You see the bolden
words there. That is the key. Normal physio.
Aldosterone works to do what? To get rid of
potassium. You are at risk for hypokalemia.
What are you worried about with hypokalemia
please? The more that you get rid of the potassium,
the more that you have hypokalemia. Think
about your resting membrane potential, the
resting membrane potential is going to become more
negative right. It is going to become hyperpolarized,
more negative. Meaning that it's further way
from what? Further way from threshold. What
kind of issues might you have? You have issues
with the heart obviously, and you have issues
with skeletal muscle, fatigue.
Next, aldosterone gets rid of your hydrogen
result in metabolic alkalosis respectively.
Move on. Okay now. Point by point by point,
we are going to walk through this so that
we talked about the overview. Now we are going
to give you some distinctive feature for each
disease so that you will quickly be able to
figure this out. In the meantime, Bartter, Bartter,
Bartter. Reflexibly where is my problem?
Thick ascending limb, sodium-potassium-
2 chloride. Gitelman syndrome, where are you?
Distal convoluted tubule and behaves like
a thiazide drug meaning sodium chloride channel.
Keep repeating that over and over again. Lay
down the foundation. Now come back here. Patients
in both conditions have suppressed activity
of ADH why? Due to physiologic loss of renal
diluting capacity really. The fact that ADH
isn't working properly is why? I told you
earlier about that kind of countercurrent
mechanism. I told you that if that has been
somehow impaired that you are going to lose
the ability to properly concentrate and may
be perhaps even, be able to properly dilute. In
both conditions, please understand that the
diluting ability of the nephron has been completely
or severely impaired. Thus what hormone are
you now influencing negatively? ADH. So ADH is going
to be suppressed. Make sure you understand
that in both conditions. Now, listen here. Concentrating.
Remember that sodium-potassium-2 chloride.
Where? Thick ascending limb and what is that
called when you have the thick ascending limb
that communicates with the descending limb. The two
loops or ends of the loops are communicating
with one other. Can I help you? Is what the
thick ascending limb is asking the descending
limb? The descending limb says yes actually
I do. I do need a little bit of help. What
might I want to give you? How about some solute
so I can give you some water. Oh! Yes, I can
give that to you. So thick ascending limb
provide the sodium-potassium-2 chloride.
There it is. Put to the interstitium creates
an osmotic gradient so that water can
come out. Simple. What is this? Countercurrent
mechanism. What is this? The concentrating
ability. Where is my concentrating ability?
Down in the loop. Right? Are you with me? So if you
haven't understood the physio how in the world
is the pathology going to come in to play?
How are we going to make sense of this? So
we now got the sodium-potassium-2 chloride,
What ability are you losing? Good. The
concentrating ability. Relatively spared in
Gitelman. How come? Where is Gitelman? Good.
Distal convoluted tubule. What's over there.
It is a thiazide-sensitive sodium chloride.
Does that really participate in concentrating
ability? No. More so diluting. I will give
you that. But concentrating? Border. Much
more slow, much more slow. In both conditions,
though. What about ADH? Suppressed. Take a
look at the previous bullet point. Good. Pay
attention to this one, because this is a distinguishing
feature. Another big one. Urinary calcium
excretion. Take a look. Stop. Pay attention.
Hypercalciuria. Take a look at the suffix.
Uria. So where is there more calcium right
now? In the urine. Are we okay now? Okay.
What is happening? If you knock out that sodium-
potassium-2 chloride, are you able to properly
take up your calcium? No. Remember the back
leak. Remember that. What was the name of that
receptor? ROMK. Good. So if you don't have
proper functioning of that ROMK with back
leak because the sodium-potassium-2 chloride
channel has been knocked out due to Bartter,
how in the world are you able to properly
take up your calcium? You cannot. Urinary
calcium excretion is normal or high in patients
with Bartter, not the case with Gitelman.
Are we okay there? So that bullet point of
second and third become very important for
you to distinguish between Bartter versus
your Gitelman. Continue.