Conn's syndrome, the opposite of Addison's,
really. What is Conn's? It is the primary
tumor located at the adrenal cortex. Where?
As it produces too much cortisol. Listen.
If you produce too much cortisol, how could
you call that Conn's? You cannot. So if you
produce too much cortisol that automatically
puts you into the category in disease of and
this is how black and white it is of Cushing
syndrome. This is Conn's syndrome. Therefore,
all I have is too much. Look at the first
statement. A benign adenoma of the zona glomerulosa.
So, therefore, resulting in you tell me, sodium
quickly come on come on come on. Good. Increased
sodium. Give me lab. Increased greater than
145. Next, potassium too much aldosterone you
are getting rid of it, hypokalemia, potassium
less than 3.5. Tell me about pH. Increased.
You are getting rid of your hydrogen. That is
probably one that is a little
tricky. So whenever you go through acidosis,
just make sure that you walk through that
for me okay. So remember, too much aldosterone
you get rid of hydrogen. You know I agree with
you there. That gets a little tricky, but
with the sodium-potassium that should be reflex.
So in Conn's syndrome, you can expect to see
metabolic alkalosis. Increased excretion of
potassium, hypokalemia. We talked about all
this. Look at this. Resting membrane potential,
one more time, RMP. Close your eyes. Work with
me. Don't just look at the words here. Conceptualize.
Your potassium has been lost, hypokalemia.
Resting membrane potential, more negative or
more positive, please? More negative. What
do you call that? If it becomes more negative,
you do not call that depolarization. Look at what it
says. Hyperpolarization okay. So if it become more
negative, who is? The resting membrane potential,
you're aware, further away from threshold. Are we clear
now? So, therefore what happens to your muscle?
It's much more difficult to have a all or none
type of effect. Therefore, you will have muscle
fatigue. Increased hydrogen secretion with
Conn's syndrome, metabolic alkalosis. Now
you tell me with all that sodium that we have
here in Conn's, what kind of hypertension?
It is not primary. It is secondary. So would
you think that Conn's syndrome is not common?
Just the opposite. It is common. It behoove
you to really know Conn's syndrome in great
detail. It behoove you to know aldosterone
in great detail. Hence, all the time that we have
spent really laying down the foundation of
aldo, Conn's here, excess sodium. Let me
ask you this one. This one is neat. Watch
this. You have increased effective arterial
blood volume. Not again Dr. Raj. I am. I have to.
Alright. So, lets do this. If too much effective arterial
blood volume, what does that even mean to you? It
is the plasma component right. So you have
all this blood coming to the kidney afferent
arteriole increased, increased, increased.
Right now skip over the glomerulus for me.
I want you to enter the efferent arteriole
and then I want you to enter the peritubular
capillary. What happens to the hydrostatic
pressure in the peritubular capillary with
all of these blood volume? It increases. So
what happens to reabsorption? It decreases
because you are offering resistance, right.
So with increased effect of arterial blood
volume, what happens to your filtration fraction?
Good. It decreases. We talked about that earlier.
If you are not clear about that, I have given
you specific slides about effective arterial
blood volume and one in which we had a decrease
effective arterial blood volume. Examples,
hypovolemia may be due to hemorrhage or may
be due to congestive heart failure. Remember
that and the opposite. I gave you examples
clinically of increased effective arterial
blood volume in the headline of one of the
causes was mineralocorticoid excess. What
is Conn's syndrome? Mineralocorticoid excess.
Stroke volume increases systolic blood pressure.
Peritubular capillary, there it just then
explains the filtration fraction. If you have
too much volume, don't you want to get rid
of your sodium? Of course, enhancing
clearance of your sodium prevents the proximal
tubule for reabsorbing sodium. What then happens
to your filtration fraction, please? Diminishes.
RAAS, now pay attention here. This we haven’t
talked yet but it is important. So this is
primary hypoaldosteronism. Who controls or
regulates your aldosterone? If you say ACTH,
I am not going to come out and slap you. I
am not, but you begin the process or the cascade
begins with ACTH. Picture this alright, okay. Be serious.
Focus. ACTH anterior pituitary, adrenocorticotrophic
hormone comes in through the blood hits the
adrenal cortex. I agree. Next rate limiting enzyme, desmolase
fantastic adrenal cortex. Where am I? Glomerulosa.
So granted you begin the cascade of your adrenal
cortical hormones with ACTH. I will give you
that. Who finishes the job? There you go. Renin,
renin, renin. So, therefore, for aldosterone
the key regulator in terms of feedback is
going to be what is known as plasma renin
activity. Please, this is what you want to
know clinically. Everything else of course
things could be technical, but I will tell
you one to be technical and one to be clinical.
I am asking you kindly to be clinical
with me. So if you have too much aldosterone,
you are going to shut down plasma renin activity
because why? A benign tumor in the adrenal
cortex is producing too much aldosterone without
even the need and the help and assistance of
your renin. That is important.
Next, excess sodium enters smooth muscle,
but what does it cause it to do? Then there
might be increased arteriolar pressure or resistance.
It opens up calcium channel? We have increase
in TPR. What do we have? Increase in diastolic
blood pressure and these are the pathophysiologic
explanations as to why you have an increase
in a systolic blood pressure with increase
in volume and sodium and increased diastolic
blood pressure because of increased total
peripheral resistance of the arterioles. But
all together here you have it, you cannot
miss a question from all the way down from
basic sciences all the way up to your patient
Summary, hypertension, polyuria, muscle weakness,
hypernatremia, hypokalemia, metabolic alkalosis.
We walked through all of this in great detail.
Now in your head, as you go through each one
of these because you as a resident medical
student, what have you? You walk into rotation
and you see these things and you were explaining
to your attending or to even your patient or your colleagues,
this is what is going on? They will push you
onto their shoulders and parade you around in
rotation. How good do you feel? Pretty nice.
Decreased PRA. What is happening? Plasma renin
activity with primary hypoaldosteronism. What
if you find an increase in renin? What
would you call that perhaps? Secondary hypoaldosteronism,
correct. Give me an example. Decreased perfusion
to the kidney. You will find this to be interesting.
I want you to focus upon the graph. There
are three parameters on the Y axis here. Three
different phases mean arterial pressure, cumulative
sodium balance, urinary sodium excretion.
There is an important concept that medicine
wants you to know okay really is and is called
aldosterone escape. We know it occurs
because this is how patients present. That
is why I have to give this to you and occurs
very common because I told you Conn is found
to be common. On the X axis are days. So lets
say right in the middle this is an experiment
to give you an understanding of Conn. In the middle
is aldosterone. You see that. In the middle
is the aldosterone that has been given. Immediately
take a look at the mean arterial pressure.
Shooting up. That is which you are paying
attention right now. Listen to what I am saying
and I am going to walk you through this. What
is interesting too is the fact the sodium
actually is going to decrease, amazingly. So
even if you have Conn's syndrome and you have
an increase in aldosterone granted, overall
your sodium in your body is going to increase.
Thus, the blood pressure will remain elevated
as long as aldosterone is present. However,
the way that the kidney works is the fact
that you have a phenomenon called aldosterone
escape where for aldosterone over the next
few days, take a look at the X axis. What
then happens to urinary sodium? Take a look
at the bottom phase here. The bottom phase,
the third bottom on, the urinary sodium, it quickly
increases and you diuresis your sodium. Is
this clinically relevant? Oh yes. This is
how your patient is going to present. May
I ask you something? Would you most likely
find pitting edema in Conn's syndrome? No,
not necessarily. That is why this experiment
was necessary so that you clearly understand
as to why you will not find pitting edema
in Conn's syndrome as you would with congestive
heart failure and congestive heart failure
that's it you have continues to death of
the heart. It is going to be systolic dysfunction
and every single time aldosterone removes
removes removes removes the fluid it keeps
going into the interstitium because it can't
move forward. Are we clear? Especially with
right sided. In Conn's syndrome, your heart
is perfectly fine and Conn is the problem
with aldosterone in the adrenal cortex.