Continuing our discussion of, clinical
application of renal blood flow. We are going
to take that information that we have seen
prior, with that table and make sure that you
then associate it with that picture where for
example we looked at Bowman's space hydrostatic
pressure being increased with obstruction
such as BPH may be a renal stone or there
is increase in oncotic pressure in the
Bowman's space in those dealing with
something like minimal change disease,
the most common cause of nephrotic syndrome
in a child. Continuing our discussion and
putting in a
little bit more detail, but just enough where
you are able to create a story for yourself.
Lets take a look at this picture. Now in
the very beginning, we talked about the anatomy
of renal blood flow. We began by looking at
the renal artery headed towards where the
hilum of that kidney. Next, the interlobar and
you had your interlobular. In other words,
that would be your, well, arcuate gives rise to
your corticoradiate. This then gives rise
to your afferent arteriole. You tell me as to what
normally keeps the afferent arteriole open?
Prostaglandin. Keep that in mind.
Whereas on the efferent side, we continue
the blood flow. There is a very important
hormone known as angiotensin-II, which then
causes preferentially vasoconstriction at
the efferent arteriole. There is a balance
that is taking place constantly between the
afferent and efferent known as autoregulation
in which you will then have blood flow well depending,
as the range of blood pressure, maybe approximately
from 40 to 140 where that blood flow will
remain the same so that's your proper GFR.
Now on the efferent side, we are moving beyond
the arteriole, now what's really
interesting about this, is the fact the
afferent, what is that? That is an arteriole
is going to form a tuft of capillaries.
Now usually if it's most any other part of
the body, you go from arteriole, capillary
and you go to venule. Anatomically that is
not what is happening here, is it? It is afferent
arteriole, a tuft of capillaries, efferent
arteriolar. Okay. Now you go down and you travel
around the nephron. It's called peritubular
capillaries. This is the second set of capillary.
What's another name for this? Welcome to
vasa recta. Now, vasa recta eventually will give rise
to inter.. go backwards now, interlobular veins, interlobar
veins out through renal vein really important
that you know about your renal vein especially
the left side. Tell me about its course.
Renal vein, renal vein, renal vein, renal
vein. What's up with it? Oh look at that, that's my friend.
Who? Left gonadal vein and
you move towards what please? Inferior vena cava
is that going to come in handy. Oh yeah we'll see.
Okay now lets add some clinical correlations.
There is a prostaglandin. What is it doing?
It is causing vasodilation. You take me through
this, please. If there is vasodilation, then
what happens to renal blood flow or renal
plasma flow? Obviously increased. When you
increase the amount of blood passing through
afferent arteriole, please tell me what happens
to hydrostatic pressure. What does P mean?
Hydrostatic pressure. What is GC mean? Glomerular
capillaries. How important is it for you to
pay attention to those abbreviations? It will
tell you between where you are. Is the capillary
or is it the Bowman space. Here we're at the glomerular
capillary. What are you doing? You can use that P for
pushing pressure. What's your pushing pressure? Hydrostatic.
It's increased. What then happens to GFR? Increased.
Very good. Now we have afferent arteriolar
dilation. You tell me once more what may then
remove the prostaglandin. What about that
patient who had arthritis? For 10 or 15 years
was taking what? NSAIDs. Anti-inflammatory.
And therefore removed or inhibite the COX a
cyclooxygenase and therefore resulted in decreased
prostaglandin. That decrease in prostaglandin then
causes what, please? A decrease in the diameter
of the afferent arteriole. What then happens
to renal blood flow? It decreases. It hit
the constricted afferent arteriole. What happens
to hydrostatic pressure? Decrease. Pay attention
to P and GC. What is P? The pushing hydrostatic
pressure, pushing up the fluid out of your
GC into the Bowman space. That obviously has
been decreased in the setting of NSAIDs. What
happens to GFR? Decreased. Now you tell me. Hmm.
If this continues and that the patient is not paying
attention and family medicine doctor is not
paying attention, the primary care would
have you? What is this patient prone to? Renal
failure. Okay, lets move on. Let us now switch
over to the efferent arteriole shall we? Efferent
arteriole. Here we are going to bring in angiotensin II
This angiotensin II works in the efferent
arteriole preferentially to do what? Now let
me give you the setting. I am always going to do
this to you. Because otherwise you are just going
to sit here and memorize. We cannot have that.
So, we have a patient that has renal arterial
stenosis. Yet once again. We will take as
if 52-year-old male who has renal bruits and
has secondary hypertension. We talked about
this patient already. So renal artery stenosis.
Why was it that the angiotensin-II and the
renin system was activated to begin with?
That RAAS system. Renin, angiotensin II and aldosterone
system was stimulated so that it can then
restore some of this blood flow to the kidney
because if the GFR dies, as does the kidney.
So now in the setting of renal artery stenosis,
you are going to release renin. Here comes
my angiotensin II, what it is going to do?
Constrict the efferent arteriole. That is
Now close your eyes. May I ask you question
by question? You tell me. Ready? If you are
going to have efferent vasoconstriction, what is
it going to have renal blood flow? It is then
going to decrease. If you are going to have
efferent vasoconstriction, what happens to
hydrostatic pressure? Stop! Wait for me to
finish. What happens to the hydrostatic pressure
in your glomerular capillaries. It increases.
Why did I have you stopped? Because on your
exams, you want to make sure that you understand
where exactly are they asking you about that
hydrostatic pressure. Was it in the glomerular
capillary or was it in the Bowman space? It
was my question to you. Where was the hydrostatic
pressure increased? Here in the glomerular capillaries
obviously. When that is increased, what then
happens to your GFR? It is increased. Now
we go one step further. Early we talked about
filtration fraction. What is that equal to?
It is equal to GFR/RPF. In the setting of
angiotensin II, where vasoconstriction of
efferent arteriole, what happens to GFR? It
increases. What happens to renal plasma flow?
It decreases. What happens to filtration fraction,
please? Good, it increases. Excellent! Move on. How
might you move that angiotensin II and this
will be contraindicated in a patient with
renal artery stenosis. Why? This angiotensin II
was put here by the body, hormonally,
so that it can restore some of that GFR, wasn't
it? Why? Because the renal artery stenosis
in that patient was causing decreased perfusion.
Are you following me? So that angiotensin II
was there to protect the kidney. And you. Not you.
But a negligent doctor did what? Not that he or
she was going to take care of the blood pressure
by giving an ACE inhibitor. By giving an ACE
inhibitor gone is the angiotensin II, bye bye
goes the patient. What happened? Remove the
angiotensin II. Aren't you going to exacerbate
that renal failure? Yes, you are. ACE inhibitors
are absolutely contraindicated and definitely in
bilateral renal arterial stenosis, but clinically
also with unilateral. Keep that in mind. Lets
take a look at this. There is ACE inhibitor
and what does it do? Removes the effective
angiotensin II. What happen to efferent arteriole?
Vasodilation. I just walked you through
all this. I am going to walk you through something
that could be a little tricky. Watch this.
Renal blood flow, efferent arteriolar vasodilation
increased. Okay. Here's your question. Next
what then happens to hydrostatic pressure?
Efferent arteriolar vasodilation. Hydrostatic
pressure is going to decrease in the glomerular
capillary. Dr. Raj you said that it is increased
renal blood flow with vasodilation. How could
it be decreased hydrostatic pressure? Because
look where the vasodilation is. Way past the
glomerulus and when i said way, it is beyond the
glomerulus in the efferent arteriole. So you might have
increased renal blood flow, I am not arguing
that point, but because of vasodilation is not the
afferent, you will have a decrease in hydrostatic
pressure of your glomerular capillary. What
then will happen to your GFR? It will decrease.
When would this be contraindicated? One more
time, bilateral renal arterial stenosis and
as I said clinically even with unilateral
you don't get this. You just don't. Okay.
Beta-blocker, maybe that might not even be a good idea
because in that setting don't you need that
angiotensin II? What kind of beta receptor
is on your juxtaglomerular apparatus? Good. Beta-1.
So therefore by giving a beta-blocker, you
might also inhibit the release of renin. So
Dr. Raj what am I going to use? Maybe calcium
channel blocker. You have other options,
you definitely do. Might be a good time for
you to take a look at antihypertensive drugs.
So all that pathology is just a combination
of many things like tentacles, like an octopus
and all of it has different arms and branches
and it is all different points in which there
may be if you are weak in a particular area,
you go back and take a review of relevant
Come back though and we will continue our discussion,
until we hit another wall. We build and
build and build this information
until you are confident. We are going to put
all this together now with RAAS and make sure
that you are truly familiar with the entire
process of your RAAS system.
Lets begin. So here we are. I want you
to begin at the kidney. Please begin at the
kidney and why would you want to release the
renin? Decreased perfusion to the kidney.Okay good.
Give me some differentials. I've walked you through
renal artery stenosis adequately. What about
congestive heart failure? Decreased perfusion
to the kidney. In these cases, those juxtaglomerular
cells are going to release renin. Hence, take
a look, please. Decreased blood pressure is
then going to release your renin. Here continue
forward. I want you to make sure you clear
by this. You are going to be an MD. You are
going to be a doctor, but that MD stands for
macula densa. Macula densa will decrease blood
pressure. Walk me through this. Initially
decrease of blood pressure, decreased perfusion,
decreased GFR, where is our macula densa? Distal
convoluted tubule. What is the name of that
sensor? Macula densa. I showed you a picture
earlier. What is that macula densa sense?
It senses the sodium or chloride right. So
therefore now with decreased blood pressure,
what is it doing? It's not sensing as much.
So all of this is going to help contribute
to increasing renin. One last thing, when
we have a decrease in blood pressure, can
I ask you what branch of the autonomic nervous
has to come out? Good. Sympathetic. What kind
of receptor on your JGA? Good. Beta-1. Once
again get another factor to help you stimulate
renin. Here comes out and here is not ogen.
Now I would like for you to take a look at
this suffix. I would like for you to understand
this concept ogen. What
does that even mean? Trypsinogen, fibrinogen,
angiotensinogen so on and so forth. So the
term ogen means weak. Weak precursor right. Most
of your proteins come from where? The liver.
What is the most abundant protein in our bodies?
Albumin. Coming from where? Liver. Here is
angiotensin, angiotensinogen coming from the
liver. What does that renin do? Cleave off
the ogen. There it goes. What do you have? angiotensin
I. Where is the angiotensin I headed to? To
the lung. What's there? ACE. So here, ACE,
angiotensin converting enzyme, will take
the I and turn into the infamous angiotensin II.
Now lets plug in some pathologies. Are you ready?
What if you had a patient that ends up having
too much renin? Autonomously. There was no
decrease in blood pressure as an in setting event.
And imaging study you ended up finding a tumour.
Where? In the juxtaglomerular apparatus. Wow! And
you ended up finding increased blood pressure.
So if you have increase in renin, increase
in aldosterone, you have secondary hypertension.
Are we clear? What is this called? Reninoma.
You understand the physio. You can easy put
in the pathology and you see your patient.
You can actually see your patient. Next, give
me a pathology in which your ACE might be
elevated. A pathology. May be something like
What if I told you non-caseating granuloma,
bilateral hilar lymphadenopathy in
an African-American female. You will tell
me? Good. Sarcoidosis. And sarcoidosis you could
have increased production of ACE. What does
this mean? Increased production of angiotensin II
Now with all that said lets say that
you give an ACE inhbitor. When you have an
ACE inhibitor, then you knock it out and you
can never form angiotensin II and never release
your aldosterone. Stop there for
The branch that is important for us, bradykinin.
ACE, angiotensin converting enzyme is an enzyme
that you must know as being the enzyme responsible
for metabolism of bradykinin. Two major effects
of bradykinin that you would want to know as being
a side effect of what drug? ACE inhibitor.
A dry cough, And number 2, angioedema. So bradykinin,
increased capillary permeability. And number 2, Might
be something like dry cough. And with that dry
cough, which is incredibly irritating you
change the drug into ARBs. Got it? Lets move on.
Angiotensin II vasoconstriction preferentially what part
of the arteriole? Efferent.
What would it do to your blood vessels in general?
It will cause contraction, vasoconstriction.
What are you are trying to do? Increased blood
pressure. What was in setting event. Take
a look, please. The first box, over onto
your left is decreased blood pressure. You're
trying to increase your blood pressure. There is
my efferent arteriole. What does it do?
Do not memorize this. Close your eyes. Let me
ask you a question. Number one. You have
efferent arteriole vasoconstriction. Tell me about renal blood
flow when the plasma flow, decreased. Next
efferent arteriole vasoconstriction.
Tell me about GFR, Increased. Tell me the equation
for filtration fraction. GFR/renal plasma flow.
Good. You do the math. What do you get for
filtration fraction? Increased. Good move on.
What else happens? While angiotensin II
is going to go where, that's the organ, adrenal.
Which part? Cortex. What part of the cortex? and I am
going to keep pushing you here. What part of the cortex?
Glomerulosa. Angiotensin II is going
to work on the glomerulosa to stimulate what's
known as aldosterone synthase. Here comes
an aldosterone. Close your eyes. You know
this from physio already. Aldosterone turns
to your collecting duct. Aldosterone works
on your principal cells principally. What
does it do? It works on your sodium channels
everywhere. What do you mean everywhere? Well, principal cell.
You picturing that? Where am I? Collecting duct okay fine
and it is facing whom? Urine. It is facing
the urine. So that is known as the apical
membrane. That apical membrane has a sodium
channel. Aldosterone could work on that ENAC.
It is called Epithelial Sodium Channel. E,
epithelium; sodium channel, ENAC. Aldosterone
works there to remove the sodium from the
urine. You know that already. Next, on the
basolateral membrane only, you have your sodium-
potassium ATPase pump. So what kind of effect
does aldosterone have on your pump Tell me about that pump.
Sodium being kicked out. Kicked out into
where? Into your blood. Aldosterone will stimulate
that pump. We have addressed this. Insertion
in principal cells enhances stop there. So
you are going to reabsorb sodium. You are going to
take out two. What do you mean take out? You
are going to literally remove and secrete
two substances into urine. First will be potassium,
next will be hydrogen. Okay. You can see. We are going to
work through a lot of pathologies here, aren’t
we? Because you can have issues when you have too much
aldosterone, and you can have issues in which
you have two little aldosterone. Too much
aldosterone. Give me two differentials.Number 1
Conn exclusive aldosterone secreting tumour.
Cushing will be both cortisole and aldosterone.
Give me one aldosterone deficiency pathology,
Addison. Addison's disease. So are these things
that we talked about? Of course keep repeating.
So when we have aldosterone it will reabsorb sodium.
It will kick out the potassium meaning to
say urinated out and it gets rid of your hydrogen.
So in Conn's syndrome tell me about the pH
in that patient with Conn? Take your time.
Close your eyes. Reabsorbing too much sodium.
Getting rid of too much hydrogen. What happens
to your pH? Increases alkalosis in Conn. Confirm
it. Why? Because you will find many patients
with secondary hypertension and Conn syndrome.
Many, not rare. Many.
Great favourable sodium gradient and along
with sodium what comes out? Fluid. Tell me
what is it that contributes to the pitting edema
and congestive heart failure? The aldosterone.
Why? Because of this entire mechanism, we
just went through. Are we done? Not quite
yet because a decrease in blood pressure,
but there is another hormone that also comes
into play, and angiotensin II not only will
it be responsible for releasing that aldosterone
from adrenal cortex, but angiotensin II also
works on the posterior pituitary. Why, why,
why, why? Decreased blood pressure is what
the kidney is thinking? This angiotensin II
is then going to walk on the posterior pituitary
and so, therefore, you are going to release
ADH. Tell me about ADH, antidiuretic hormone.
That works on the, also collecting duct. What does
it do? It works through your V2 receptors.
How many kidneys do you have? I think one.
No no. Who? I think I have two. You have two
kidneys. So V2 receptors is what ADH works
on. Gotta have fun with this just a little bit huh.
So works on V2 receptors and what does it
do? It is then going to insert aquaporins.
So that you do only what please, antidiuretic
hormone. What is another name for ADH? Vasopressin
and you are only going to reabsorb water,
water, water in the hopes of doing what? In
the hopes of restoring osmolarity. In the hopes
of restoring some of your blood pressure.
Now couple of important things about angiotensin II
in addition, is that it does work. Please
pay attention. That's its proximal convoluted
tubule. Angiotensin II earlier through aldosterone.
May I ask you questions? Worked where? Collecting
duct. Angiotensin II here is working on proximal
tubule. What does it do? It reabsorbs your
sodium. Don't memorize this. What are we doing?
There was a decrease in blood pressure as
being the inciting event right. Now the angiotensin
II is going to work on your proximal convoluted
tubule so you can try to remove more sodium
in exchange for hydrogen. So water reabsorption
and then can permit what is known as contraction
alkalosis and what that basically means is
that you are going to have contraction and
along with it you have also hydrogen leaving
resulting in alkalosis.
Finally, in the hypothalamus, it has thirst.
Now all of this is then going to contribute
to release of ADH. So ladies and gentleman
angiotensin II as you can see here from the
origin of it all with that initial event of
whatever it may be is causing decreased perfusion
to the kidney. Once it gets into the renin
realm, now renin along with angiotensin II
and aldosterone my goodness gracious right
up and down the body has all kinds of incredible
effects, and all these pathologies that we're
going to put in here including some of our
issues with ADH and diabetes insipidus right.
Central nephrogenic, we are going to bring
all this into play, but if your foundation
isn't strong it is going to make it quite
difficult for me and you to work together
so that we can accomplish our goals effectively.