Up until now we have looked at overview
of the nephron and we have introduced the
different parts of the nephron and I have
gone through an overview. And at some point
if you got a little confused or perhaps even tripped
up with some of the information that I have
given you, not to worry, reinforcement. So
here we will walk into and dive into further
detail of each segment of the nephron and
go through all the relevant information so
that you can get your questions on any aspect
of medicine on the nephron absolutely correct.
So let us take a look at the PCT in that respect.
Once again, to review, take a look at this.
Obviously, I am not going to spend time going
through each one in details, but I will
go through the details of what I referred
to. For example, the carbonic anhydrase and
its inhibition and what that means to you?
Stop here for one second and what does that
mean to you if you inhibit that enzyme? You
are getting rid of your bicarb. Why might
you want to do that? Do you remember our discussion
on high altitude? How fast are you breathing?
Very quickly. Blowing off the carbon dioxide
so maybe perhaps you might want to on purpose,
help your patient by inhibiting the carbonic
anhydrase so that patient can then compensate
by getting rid of that bicarb in the kidney.
At this point, you should be able to figure
out what the figure looks like in its organization
pattern? I have established that over and
over again in previous discussions. For example,
on the left is your urine, in the middle is
your cell and on the right is your interstitium,
moving towards your blood. We have also very
much established our definitions as to what
it means to be reabsorbing versus what it
means to be secreting? Now with the PCT, further
detail. And the early
portion is where we are, and we will go ahead
and call this a brush border. What does that
mean to you? Now once again you know me well
enough where I draw parallels to many organ
systems, from head to toe. Here well in the
proximal convoluted tubule when you say brush
border, you must be referring to the luminal
membrane, the apical membrane. If you are
referring to the brush border membrane, more
importantly in the duodenum, really think about
where you would be if it is a duodenum. So
if it is a duodenum especially second part
where there is quite a bit of guess what?
Reabsorption. Guess what that apical membrane
is known as? Brush border. Is that clear?
So simple definitions in which you can apply
to different organ systems.
Let us continue.
What kind of things that you are going to
absorb in the proximal convoluted tubule?
We have spent a heck of lot of time with reabsorbing
bicarb, reabsorbing glucose especially with
the graph where we talked about the normal
plasma glucose, talked about threshold, transport
maximum, talked about reabsorptions, splay, and so
forth. And if you finished
that discussion, then I would recommend that
you go back and take a look at that graph
on glucose transport in great detail and then
come back here and then just take a look at
as to where it gets reabsorbed. It has to be
a secondary type of transport with sodium-
potassium pump at the basolateral membrane.
Let us continue please.
Isotonic. Now this is important. In a little
bit, I am going to show another graph. And this graph,
at some point right now, maybe you might be feeling
a little overwhelmed, maybe perhaps even frustrated,
or that are yet you are feeling fantastic
about these graphs because you saw them in
medical school. And maybe you looked at it,
glanced at it, maybe you even memorized it, but you
didn't truly understand that until now and
so therefore you feel enlightened. You feel
confident. You feel really you can tackle
this. And there is another graph that's upcoming
in which we will take a look at transport
especially in the PCT. Now before we get there
though you need to understand as to how you
might be taking up some of the substances.
It is important. I have just left the Bowman
space. I have entered the PCT. That is where
we are. So now what are you going to reabsorb?
Many electrolytes. How much of sodium? 2/3,
66 percent approximately, same thing. Is that
sodium that you only reabsorbing? I want you
to think PCT, what's my next segment of the nephron?
Tell me that, I hear you say descending loop
of Henle. The descending limb of the loop
of Henle. What is going on there? You are
reabsorbing water. So if you start reabsorbing
the water, what kind of urine are you producing?
Hypertonic by the time you get to the loop
of Henle. Are we clear? Good. So in the
PCT though, so further proximal, you are going
to reabsorb your sodium along with water in
what kind of fashion? Isotonic. What does
isotonic mean to you? Approximately how much?
Keep it simple. 300 mOsm. So that
term isotonic becomes very crucial for you
to recognise here in the PCT. Now what else
is the PCT known for? It is all important,
ammonia. What is ammonia? NH3. What if you
add another hydrogen? Why would you add another
hydrogen? To buffer. When was the last time
you have heard of ammonia in medicine as far
as your level of education what you need to
know? A few times. Number 1, you have heard of ammonia
in terms of microbiology. Really? Yeah, in the kidney
actually. So at some point when we talk about
nephrolithiasis or renal stone, we will talk
about a particular stone that is huge. It
is called a staghorn stone or you call it
a struvite. What is it made up of? M, magnesium.
A, ammonia. P, phosphate. So you tell me what
kind of organisms would be involved with the
stone that is made up of magnesium, ammonia,
phosphate? Alkaline organism, give me one.
Proteus mirabilis. So you have heard of ammonia
before. You know that it is already alkaline
in nature. These are things that you have
it memorized, which you have given a clinical
correlations and in a disease such as that,
well then you know that it is already alkaline.
Where else have you heard of ammonia?
What am I doing here? I like you
too. I am waving, but I cannot help this.
I am doing resting tremors. What is this called?
Asterixis. Tell me what organ has been involved,
resting flapping tremors like
this. It means my liver alright. Liver is
responsible for proper metabolizing of the
ammonia. What if you have cirrhosis? Then
ammonia starts accumulating in the head. It
is called hepatic encephalopathy, and what's your sign?
Asterixis. So you have heard of ammonia
in a couple of places that are very important. Let
us talk about ammonia here. Where am I? PCT.
And if it is alkaline, what does that mean
to you? Its responsibility here. In
the PCT, where it is generated. See that right there,
generated here. That is important. Not recycled,
but generated in the PCT. At some point, down
in the DCT, guess what it picks up? The hydrogen.
When it does, then you call it ammonium. So
when you add a H, you add a M, you take off that
H, you have ammonia NH3. NH4.
Let us move on.
Still in the PCT and at this point
let us talk about PTH. Isn't it interesting as
to how in the PCT, we have so many different
things going on that are so clinically relevant.
Spend a little bit time, make sure that
you understand this well. Now PTH, tell me
two things that it does in the kidney. In
general, in the kidney, reabsorption of calcium,
is that taking place here? No. Where am I?
PCT. What is the other job of PTH? It is to
flush out the phosphate. In other words, it
inhibit the reabsorption of phosphate. Isn't
that the same thing in terms of the consequence?
Yes. So you are flushing out the phosphate,
inhibiting the reabsorption of phosphate where?
This ladies in gentleman is in the PCT. I
did mention this prior, but now we are
now actually stating it here. You increase
phosphate excretion. So this bullet point,
say that your pathology in which you increase
your PTH, either primary or secondary. Let
us talk more about primary. I will tell you
why when I am using secondary later. We are
only going to talk about primary. Primary
hyperparathyroidism. Where is your adenoma?
In the parathyroids where you producing too
much of PTH. Where are you going? Down to
the kidney. Here specific in the PCT, what
are you going to do? You are going to excessively
inhibit the reabsorption of phosphate. Tell
me about your phosphate levels in your urine.
Hyperphosphaturia, hypophosphatemia. You see
what I just did there? I have increased the
phosphate in my urine and that is exactly
how medicine works it. It is hyperphosphaturia,
hypophosphatemia. The more that you get rid
of your phosphate into the urine, the less
that you have it in your plasma. Are we clear?
Next, where more in the PCT? Brings us way
back to angiotensin II. Now before you just
memorize this which you know that I don't want you
to do. When you do want to release angiotensin
II? Anything that causes decrease perfusion
of fluid or plasma to the kidney. Right? Give
yourself two major examples. One would be
renal artery stenosis. Are you seeing it?
And the other one is congestive heart failure.
Two totally different reasons, but ultimately
what happens? Decreased perfusion to the kidney.
So therefore what are you going to release?
Renin and here comes my angiotensin II. And
angiotensin II, too many other different places
that it works, universal vasoconstrictor, so it
works on major systemic arteries to cause
vasoconstriction, increasing thus afterload.
Angiotensin II works on adrenal cortex. It
works specifically in the glomerular, to do
what? Release aldosterone. Angiotensin II
also works in the efferent arteriole, preferentially
efferent, to constrict it so that you can restore
GFR. Angiotensin II works here in the proximal
convoluted tubule so that you can reestablish
that lost blood pressure. So it reabsorbs
sodium and exchange for hydrogen. Are we clear?
Permitting contraction alkalosis. Remember,
the more that you reabsorb sodium, I want
to take a look at that on that apical membrane,
right there, on the luminal side, not the sodium-
glucose symport. The sodium-hydrogen antiport
is what I want you to pay attention here
because that is where angiotensin II is going
to work. Are we clear? So what do you think
angiotensin II is going to do? Why you are
releasing this? Decrease blood pressure.
So you are going to reabsorb sodium and exchange
for what? Hydrogen. You get rid of your
hydrogen, what happens to your pH? Increased.
Welcome to contraction alkalosis.
Now, this table we are going to spend time
here. And by the time we are done, you will