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.