This graph is quite important. We are going
to dissect this in great detail. This information
sometimes goes unnoticed and at some point
when a medical student or resident or doctor
whatever is posed with such questions, they
have no idea how to interpret this. Learn it now
so that you will never be confused. So let
set this up and this exactly what is taking
place in your body. I love this graph and
you shall as well by the time it were done. Why?
Well let us take a look. On the X axis, you
have your plasma concentration of a particular
substance and there is many here. We have
para aminohippuric acid(PAH), we have inulin here,
we have creatinine here and glucose. So those
are the major ones that we will compare and
as we go from left to right it means that
the plasma concentration of that substance
is increasing. Stop there. Understand that. Good.
Next, on the Y axis, we have clearance. You tell
me what clearance means. Did it get filtered?
It did but that is the different definition.
What gets filtered might be modified? What do I mean by
modification? Go into the PCT, meet me there, good.
Shake hands in the PCT, excellent. welcome. Next then what
kind of modification processes could take place in the
PCT. Reabsorption, what is happening?
Removing your substance out
of your urine lumen into the blood meaning
always reabsorbing into the blood.
Secretion is the second modifiable issue and
that means you are going into the lumen correct.
So that is a modification. Depending on the
characteristics of the substances, the PAH, inulin
creatinine, glucose, then you will have certain
changes that will take place with clearance.
You tell me. Tell me about creatinine already.
With creatinine, you will get slightly secreted.
So, therefore, you will have your clearance
which is greater than GFR. We have discussed
this a few times. We are going to bring this
into play. So now on the Y axis, let us say
we have normal GFR or add approximately. Take
a look at the Y axis. Right along 100. We
are hovering around there and as a surrogate
marker, we will be using creatinine as being
an assessment of your GFR and so we will be right
around that range and we will see that as being
shaded between let us say 100-120 because
that will be normal of GFR. So let us talk
about each one of these substances and you
will find this to be fascinating. Let us go
to the one you are all quite familiar with
and then what I will talk to you about will
be PAH and that gets a little tricky, but still
doable, very, must be. Let us begin with glucose.
So where is this? While we talk about clearance.
Initially, as we take a look at glucose, which
is the green line on the X axis, we have plasma
concentration increasing, increasing, increasing
from left to right, but Dr. Raj I see that
line being at 0 for a certain period of time
for clearance. Why is that? Whats clearance
mean? It is the amount of glucose that you
are getting rid of. There is no pathology
here. So therefore normally speaking when
you have glucose in your plasma, does it get
filtered? Yes, it does, right? And then in the PCT,
how much of your glucose or what kind of modifiable
factors taking place in the PCT. Is it reabsorption
or is the secretion into the urine. What is
it? Should you normally have right now? Normally
speaking when you urinate and you did dipstick
for glucose, should you find glucose in urine.
Of course not and if you have diabetes mellitus,
then I don't know what your situation is but
you get at my point. Normally you should
never find glucose because it is always being
reabsorbed. Thus for a certain period of time,
you will notice for glucose, the green
line that it is at zero. But now the plasma
concentration is increasing, you tell me about
your patient. Your patient is developing hyperglycemia.
So, therefore, there is diabetes mellitus
now. Then all of a sudden, we will talk about
this in greater detail is the fact that you
start hitting renal threshold. What does
renal threshold mean? It is one of the
first signs of your glucose that is appearing
in your urine. So from the first time that
you find your glucose appearing in the urine.
Do not confuse the threshold with Tmax and
these are things that you have seen in physiology
and if you are weak there, then I would recommend
that you review that so that you can work
with me in pathology. So here you have had
a threshold. Now you see that green line increasing,
increasing and doing what? Increasing on the
Y axis, which is what clearance. So now you
are finding a little bit more glucose, little
bit more glucose, little bit more glucose
in the urine and as you do so, you find that
you have glucose, which is increasing in plasma
concentration so much so and you might have
hit now Tmax let us say 370 and it is getting
very close to normal GFR. But but but your
next question and I am just going to ask it
to you here. So you start pondering it and
when the time is right, I am going to elaborate
on this because right now it is about giving
an idea of this graph. Why is it that glucose
in that line no matter how high your plasma
concentration in glucose gets. It is always
going to be below GFR. Clearance of glucose
is always going to be little less than GFR.
Why is that? If you are able to answer that
question right now, you are in fantastic shape,
but if you are not that is okay. I like to tease
a little bit as you know and at this point
it's just so that you understand this graph. Your
question at this point is even with the
glucose level being at 370 with all these
glucose being in the urine, it is still going
to be less than GFR. Amazing, why? Because
we could talk about this glucose transport
and everyone does a glucose transport as in
PCT. It is still trying to rebasorb. They
are not damaged. Stop there. We have talked about glucose
and we talked about creatinine and well there
you have your inulin and that inulin there
is whatever is GFR is pretty much equal to
clearance. So therefore as inulin is filtered
as it goes to the PCT none of it is reabsorbed,
none of it is secreted. Whatever is filtered
is cleared. So, therefore, inulin is the perfect
theoretical substance. Do not confuse the
inulin that is not saying insulin. That is
not a type of inulin. Inulin is the perfect
measure of GFR. So, therefore, clearance in
GFR will be the same. Are you loving this
graph? A lot of information. A lot of integration
which you are doing this. Finally, we have
PAH, para-aminohippuric acid. Walk me through
PAH. What do you know about PAH? It measures
you tell me. Use the P to advantage or PF,
renal plasma flow is what
it equals. Now remember from physio, what
normal renal plasma flow is? It is 600. I
want you to begin at the afferent arteriole.
You are at 600 renal plasma flow. What is your
filtration fraction. Twenty percent. So I've
taken up 120 from 600. What are you left with? 480.
Where is that 480 remaining? In the efferent
arteriole. Are we clear? You understand how
important terminology is here and I know it
it's intense, but lets walk through this likely
you can pause me for a second. Take a breath
and then continue. So here is your 600 and
you have 120 filtration fraction, you are
left with 480 in the efferent arteriole and
what are you going to use PAH for? Using PAH to measure
renal plasma flow. If everything is perfectly
normal, then what should your measurement
of para-aminohippuric acid be for renal plasma
flow? 600. Dr. Raj how in the world am i going
to use PAH as a measurement from the urine
to measure renal plasma flow. How am I going
to do that or how are you going to do that?
What is the physiologic process? Because as
we get into the peritubular capillary, are
you there now? What must you do for every
single one of those PAH so that when you measure
the PAH in the urine, it tells you oh! renal
plasma flows is 600 in this normal patient.
Every single para-aminohippuric acid or hippurate
must be secreted into the urine so thus, we
do find it, that it's measuring renal plasma
flow of 600. I want you to now come to point
0 for PAH. At PAH, plasma concentration
is quite low and the red line there for a
certain amount where plasma concentration
of PAH is at very very low levels. Zero
slightly increasing. For lower levels of para-aminohippuric
acid or hippurate, it is going to be completely
secreted thus giving you renal plasma of 600.
Dr. Raj why is it that PAH is not decreasing?
Why is it that the clearance of it is decreasing?
Well, this is a question that you will get.
There is an experiment in which you had a
bunch of students that were injecting in mouse
with tons of PAH. When PAH is in abundance,
and plasma concentration is ridiculously
high. I want you to go all way to the right
side and I want to take a look at the red
line. It is almost equal to your GFR and that
is what happens physiologically. When an increase
in plasma concentration of para-aminohippuric
acid to the umpteen or extreme level, it will
almost equal GFR. But at low levels, it is
almost perfectly equal to 600. You have understood
that much right now and if any point of time,
you have a little bit of a question either
get back to me or review your physio because
I need you to know at least this much so that
I can feel comfortable walking you through
some important pathologies that are going
to come in dealing with glucose, dealing with
Renal blood flow, what is it? It is renal
plasma flow plus your nonplasma blood. What
is your plasma? Your plasma is going to be
minus RBCs and it has many many many alveolar
coagulation factors and it has proteins. What
are you going to use to measure renal plasma
flow? Para-aminohippuric acid. At what plasma
concentration concept? Low plasma concentration
of PAH gives you a perfect approximation of
renal plasma flow. What is renal blood flow?
It is renal plasma flow/(1-hematocrit). You
tell me what normal hematocrit is approximate.
Use 40, You will be fine. What is hematocrit?
You take a test tube. You do a centrifuge
and what ends up at the bottom. What would
be the concentration or percentage of your
RBC? The sediment. So what is renal plasma flow?
We just got then talking about this. Clearance
of substance completely cleared by a single
pass. Welcome to PAH. Talk about that filtration
fraction. Guess what we're going to do. We're
going to use that clearance formula. Remember what that
was? ultraviolet over P, UV/P. So before we
begin, though, close your eyes. What is filtration
fraction? GFR/RPF. Stop there. You tell me.
What is the perfect measurement theoretically,
physiologically for GFR? Perfect. Inulin. What
do you use clinically? Creatinine. Are we
clear? You as a doctor, you as a clinician,
will use plasma creatinine to measure kidney
function or to measure GFR. Now physiologically
you might get questions in which you want
to use inulin. That is the perfect theoretical
substance. So if we are going to use GFR and
we are going to use inulin, take a look
at filtration fraction and it is equal to
the clearance of what substance? Inulin. Stop
there. Now we have RPF. What did you and I
just talk about as being a good measurement
for renal plasma flow? PAH and with this take
a look at the denomintor. RPF clearance of
renal plasma flow or excuse me, para-aminohippuric acid.
What do you do next? If you were given information
with that clearance, what is the equation
for clearance? UV/P. So what are you going
to do for GFR? You are going to take a look
at step by step. Urine concentration of whom.
Inulin x flow rate UV/P. Plasma concentration
of whom? Inulin because what we are measuring?
GFR. It would be the same concept for clearance
of para-aminohippuric acid. What is the normal
filtration fraction? 15 to 20 percent, you
will be fine to use 20 percent.