Now, this table we are going to spend time
here. And by the time we are done, you will
get a firm understanding as to what is happening
with this entire graph and so therefore any
questions that are posed at you, you will
sit back, relax, take a deep breath and you will
approach it and you will conquer this. Let us take
a look at the table. The X axis represents
only, pay attention only represents the proximal
convoluted tubule only. It is not the distal
convoluted tubule and it is sure as heck isn't
your DCT, only the PCT. That is the entire
length here. One hundred percent on the X-axis
represents the percentage of what segment
of the nephron? PCT. Stop. What is on the Y
axis? This is going to be a ratio. You will
have ratios now, I hope so because ratios
mean what to you? Concepts. Your goal in medicine
is to strive for concepts. The more concepts
you put into your head, the more that you are
able to truly understand in medicine, and no
matter what kind of question is thrown at
you. You will think about it, but then
immediately go to your foundation and you eventually
come up with the right answer. At least you
will be in the right vicinity right. At least
you are not barking up the wrong tree. So
the concept of ratio on the Y-axis is the
following. Dissect the following. Tubular
fluid, what does that mean to you? Urine.
Plasma is the denominator. Where are you?
Blood. Okay. May I ask you something? If your
numerator increases, what happens to your
ratio? Increases. Okay. I can't help if you
got that wrong just now. So if your numerator
increases, the ratio increases. Now if you
are going to increase your tubular fluid, then
what have you done? Is that secretion or reabsorption?
Pay attention. Get this right. Secretion, more
important. Isn't that secretion? Yes. Well if you
increase the denominator, what happens to
your ratio? It decreases. What does it mean
medically, to increase the plasma level of
a substance? That is reabsorption. How can
you prove this, Dr. Raj? With this graph, I
want you to pay attention to 1.0. You see
it? 1.0 is the middle ground. So now if you
go below 1, which means the ratio is decreasing,
what component or parameter of this ratio
are you increasing? The plasma. What does
that mean to you? Reabsorption. How can I
prove this to you? Take a look at the substances
on this graph specifically glucose, find it,
amino acids, bicarb. Always pay attention
to those three. Those three, as you travel
through the PCT on the X axis, what are its
features? Reabsorption, reabsorption, reabsorption.
Remember once again are you supposed to normally
find glucose in your urine? No. Why? Almost
one hundred percent. If not one hundred percent,
gets reabsorbed. What does reabsorption mean
to you? Increase my plasma because it is being
reabsorbed. There you have it. So by the time
you get to the end of the PCT, the X axis,
look how much glucose you have, please? Zipped.
Your tubular fluid to plasma ratio is decreased
like crazy, for glucose. So anything below
1, you are increasing the concentration
of that substance into my plasma, hence reabsorption.
Now, does that mean that anything at 1.0 means
not reabsorption? Listen. I want you to take
a look at sodium. That sodium right there is
at dash line and it is right around 1.0. So
what does 1.0 mean? It means isotonic. It
means that you are exactly where the osmolarity
should be with the tubular fluid and plasma
and it is at the equal ratio of 1.0. Do you see
where sodium is? Sodium is almost exactly at 1.0 from
the beginning of your PCT onto the end of
the PCT and stop there for one second. If
you were to tell me based on this, that sodium
is not being reabsorbed in the proximal convoluted
tubule, does that make any physiologic sense
to you? No. Because you know that sodium, in
the PCT, 2/3 of it is reabsorbed where?
Sixty-six percent of your sodium is reabsorbed
in the PCT. So what is this close to this flat
line at 1.0 mean to you? It means that you
are reabsorbing sodium in the PCT. Do you
remember in the previous discussion just now,
that I told you that in the PCT, the reabsorption
is in what form? Isotonic. What
does that mean to you? A plasma osmolarity
of proximal 300, that means that
not only are you reabsorbing sodium, but then
also water in an isotonic fashion from the
beginning of the PCT until the end, and thus
you will find sodium to be almost exactly
at 1.0. You need to interpret
sodium as such.
Now things that are important for us. I want you
to move up to the green lines here. The green
lines indicate creatinine and inulin. I want
you to focus on inulin first. On inulin, now you
tell me, close your eyes and tell me about
the characteristics of inulin? Filtered, yes
or no? Yes. Inulin, PCT reabsorbed, yes or
no? No. Inulin, PCT secreted, yes or no? No.
No modification of inulin in your PCT. What
gets filtered, gets excreted, correct? So therefore,
filtered load equals excretion rate. In other
words, clearance equals GFR. You understand
that from physio, we are good to go. Now we
can move on with our discussion of inulin,
we're not done it because now you are thinking
to yourself "Dr. Raj, I see that inulin. I
understand what you are saying from before.
I get all about inulin, but I am not quite
sure of why by the time I start from the beginning
of my PCT with inulin, and I get to the end of
the PCT and I will find an inulin is 3.0."
This is why. So you know there is no modification
of inulin. It remains firmly steadfast in
your PCT. There it is. It is never going to
move. No modification of PCT. Inulin remains,
you think about water in the PCT. Two-thirds
of your water is reabsorbed from the PCT.
So what happens to the concentration relatively
to inulin? If all that you're doing is reabsorbing
water, what is left back in the PCT? The solute,
which is inulin. If you absorbed your two-thirds
of your water, how much do you increase your
inulin relatively? Three times, hence by the
time you get to the end of the PCT, you have
increased your inulin to a level of 3.0. Once
you understand that math, we can move on,
but you want that to be digested first before
we move on. What does this graph represent?
Inside the PCT, the more that you reabsorb
your water, the more that you have inulin
left in your PCT, moved up to 3.0. So tell
me about inulin. That is the perfect measure
of GFR on this graph, isn't it? Clearance
equals GFR. Okay. Let us move on to creatinine,
how important is that? You know that it is
constantly being broken down by muscle. It
is being filtered, correct? Yes. Is it being
reabsorbed? Not at all. Is it secreted? Yes.
How much? Slightly. So therefore if you find
that your tubular fluid to plasma ratio in
which you will find your line to be counterclockwise
what that means is to the left of inulin,
then you know secretion has taken place and
you know that already about creatinine and
you should find a little bit more of your
substance inside my urine compared to that
what you find at the beginning of the PCT
because it gets slightly secreted. Now, what
is the substance that you know that is at
low levels purely secreted from the PCT? Welcome
to PAH, para-aminohippuric acid hippurate
and you know that pH you tell me is going
to measure what parameter? Renal plasma flows
at low levels. We have discussed that like
crazy. You understand at least what I have
told you earlier in terms of the graph of
physio, then in pathology, the different things
that are going to go on would make perfect
sense and they can’t shake you. At least
lay down this foundation for me before moving
Now the only thing that I wish to bring to your
attention is a little bit more detail here
because these are the type of questions that
you will get. Take a look at chloride. At
first, it looks like it is increasing, but no.
Chloride here, well once again, at first
water is being reabsorbed. So relatively what
is happening to chloride concentration? It
is increasing. Then it hits the flat line.
What does that flat line mean to you? It is
still being reabsorbed, but how? Isotonically.
Exactly what we are saying. Chloride
reabsorption is a little bit slower thus,
you find initial increase because water is
being reabsorbed faster or should I say chloride
is being reabsorbed slower, then isotonic.
What about sodium reabsorption? We already
said that it was isotonic in nature. So it
nearly matches that 1.0. Now, overall things
we've talked about a few times, and actually
multiple times here, we have renal plasma flow
600. Here it comes to the afferent arteriole.
We are going to go through this quickly.
We have done this plenty.
600 mL/min of renal plasma flow coming through
the afferent arteriole. Of that, what is filtration
fraction? You tell me. Twenty percent, that
means 120 is being filtered, how much is left
over in my efferent arteriole? 480.
Next, what are you going to do?
What kind of substance might you want to use
so that you can measure all of your renal
plasma flow? Low dose para-aminohippurate.
Everything gets secreted and you are going
to find renal plasma flow. So net effect, what
kind of things are we looking for? We already
talked about reabsorption and we talked about
secretion? I need to put in something else. Ready?
What is it that allows for filtration to take
place? That is my question. What is it allows
filtration to take place? What is that? Up
in the glomerulus. It is hydrostatic pressure.
What is hydrostatic? Pushing.
What letter do you use medically to designate
hydrostatic pressure? PPP. Use it in your
advantage because that is your pushing pressure.
Hydrostatic. And it is quite high when you
are traveling through the afferent arteriole
and filtration will take place. In the meantime,
what are the strong force do
you have in your plasma? I believe it is called
oncotic pressure and actual protein should
albumin ever pass through your endothelial
cells? Never. It should never pass through
the glomerulus. So therefore as you go from
the afferent to the efferent arteriole, what
then remains behind in your plasma? Your albumin.
What then happens to oncotic pressure? It
increases. Oncotic pressure physiologically
should increase as you go from the afferent
to efferent arteriole. By the time you get
down to the peritubular capillary, look where
you are now. By the time you get down the
peritubular capillary, your oncotic pressure
has increased. That makes perfect sense, why?
Tell me about water. 2/3 of your water
is reabsorbed. So, therefore, aren’t you
pulling the water out? Who is going to contribute
to that? The oncotic pressure. Who is that?
Albumin. The albumin that never should have
physiologically normally filtered through.