00:01
Alright,
so let's move on to renal losses.
00:03
And this is really where
all of the money is at.
00:07
So when we think about
renal losses of potassium,
there's three different
categories that we can look at.
00:11
Disorders that are associated
with a metabolic alkalosis
disorders that are associated
with a metabolic acidosis,
magnesium which deserves
its own little category.
00:22
When you have disorders
with a metabolic alkalosis
or hypokalemia with
metabolic alkalosis,
we can further subdivide
those into people who present
with either hypertension
or normal or hypotension.
00:37
So let's discuss that
a little bit further.
00:39
So conditions that are associated
with a metabolic alkalosis
and somebody who either has a
normal or low blood pressure
are going to include
things like diuretics,
and these can be Loop Diuretics
at the thick ascending
limb Loop of henle
or thiazide diuretics located
that distal convoluted tubule
affecting that sodium
chloride co-transporter.
01:00
So remember when that
happens, what's happening,
we've got an increase in
distal delivery of sodium
to that principle cell
and that's the mechanism
of potassium secretion
into the tubular fluid.
01:12
We're also activating
aldosterone
by volume depletion, right?
We're giving somebody a
diuretic they're losing sodium.
01:19
They're losing volume
when that happens
that activates aldosterone
and remember what
aldosterone does
it increases the
number of sodium
and potassium channels and turns
on that sodium potassium ATPase
so that it favors potassium
e-flux into the tubular fluid.
01:32
We also have salt-wasting
nephropathies.
01:35
This includes bartter's syndrome
and gitelman's syndrome.
01:38
Let's take a closer look
at those two syndromes
bartter's syndrome
when you think about
that and that happens typically
in our pediatric population.
01:45
I want you to think
about a loop diuretic
because it's almost
behaves exactly like that.
01:50
So bartter's syndrome is
an autosomal recessive disorder
again at presents early in life.
01:54
So my pediatric nephrology
colleague see this more than I do.
01:58
This is going to be a defect
in sodium chloride reabsorption
at that thick ascending
limb of the loop of henle.
02:03
So there are three
main Transporters
that can be involved
by mutations.
02:08
The first is the sodium potassium
to chloride cotransporter
or that NKCC2 which has a
loss-of-function mutation.
02:15
And that's also the site of
the loop of Loop Diuretics
and that shown in the X here.
02:21
The luminol potassium
channel can also be involved.
02:24
That's that reno outer
medullary potassium channel
and remember that's the site
where potassium returns
and gets recycled by the NKCC2.
02:32
And finally the basaloteral
chloride channel
can be involved with
mutations as well.
02:38
How do our patients
clinically present?
That's going to be typically
with either normal or
lower blood pressure.
02:44
Remember they're getting
volume depleted slightly
because of the fact that
they're losing sodium
by this mutation.
02:50
They also have impaired
concentrating ability.
02:53
So they don't concentrate their urine
and it's often times isosthenuric.
02:57
This is because again,
they don't have that medullary gradient
if they're not reabsorbing
sodium at the NKCC2
that's impairing the ability
to concentrate their
medullary gradient.
03:07
And then of course,
they really present with a
hypokalemic metabolic alkalosis.
03:12
Why are they hypokalemic?
Same mechanism as diuretics.
03:15
If you don't absorb sodium
here you have an increase
in distal delivery of sodium
and tubular flow rate.
03:21
Now how about Gitelman's,
Gitelman's really when
you think about that
I want you to think
about a thiazide diuretic
because it's very
much like that.
03:29
This is going to involve
the distal convoluted tubule
and the site at where the sodium
chloride co-transporter reside.
03:37
It's an autosomal
recessive disorder
that can present later in
childhood or in early adulthood
and it's not uncommon
for me as an adult nephrologist
to actually make this diagnosis
in our patients.
03:48
The defect is in the
gene encoding that
thiazide sensitive sodium
chloride co-transporter
in that distal convoluted tubule
as shown here by the X.
03:56
Now in terms of their
clinical presentation.
03:58
These patients also are
slightly on the hypotensive side
or normal tensive, however,
over time,
because they have such
profound hypokalemia
they can actually
become hypertensive
when they're an adult.
04:12
Similarly, they have an
impaired concentrating capacity
and they also present with the
hypokalemic metabolic alkalosis.
04:18
Now again that hypokalemia is
because of that distal delivery
of sodium that's going
to the principal cell
because you're
not reabsorbing it
at that sodium
chloride co-transporter
the metabolic alkalosis
really comes from
activation of aldosterone
because these patients
remember are losing sodium
which is going to turn on
aldosterone and we talked about
how aldosterone augments
potassium secretion,
but it also activates
that hydrogen atpase.
04:41
Patients here are going to
have a low urinary calcium
and that's important,
I want you to remember that
because that's what's
going to distinguish
gitelman's from Bartter's.
04:51
So I'm going to see
that one more time
because that really is going
to show up on your USMLE.
04:56
The difference
in terms of looking at
labs in your patients
with Gitelman's and Bartter's
is that Gitelman's will
have a low urinary calcium.
05:04
So let's talk about patients
who have a metabolic alkalosis
and present with hypertension.
05:12
So these are patients who
have mineralocorticoid excess.
05:16
Patients who have primary
hyperaldosteronism.
05:18
These can be due to
either adrenal tumors
or bilateral
adrenal hyperplasia.
05:23
Now remember if I'm
turning on aldosterone
remember what's happening.
05:27
I'm activating my
sodium potassium ATPase.
05:29
I'm inserting more sodium
and potassium channels
in the apical region.
05:32
I am favoring potassium e-flux
into that tubular fluid.
05:37
People who have glucocorticoid
remediable aldosterone is mm.
05:40
This is one of those things that
cause secondary hypertension.
05:43
This is essentially an
autosomal dominant disorder
that causes ACTH dependent
production of aldosterone.
05:49
The bottom line and why
it causes hypokalemia,
you're turning on aldosterone
or you have a
mineralocorticoid receptor
that is activated
and that is going to
favor potassium e-flux
in the tubular fluid.
06:01
Reno vascular disease,
again, one of these secondary
hypertension diseases
that we have to think about.
06:07
That's due to things like
renal artery stenosis
that turns on renin
due to a decrease
in renal artery perfusion.
06:13
Renin will then ultimately
lead to aldosterone activation.
06:16
So once again,
this is due to aldosterone.
06:19
You can have defects in 11 beta
hydroxysteroid dehydrogenase type 2.
06:23
This is responsible
for converting cortisol to the
inactive form corticosterone.
06:28
When that happens.
06:29
Remember what happens
cortisol you have
if you have excess
cortisol hanging around
that can activate
mineralocorticoid receptors,
and when that happens
you're going to favor
again potassium e-flux
into that tubular fluid.
06:41
Black licorice especially
European black licorice
contains an enzyme that
also turns this pathway on
so that you cannot convert
cortisol to its inactive form.
06:51
Again, you have mineralocorticoid
receptor activation.
06:55
And finally apparent
mineralocorticoid excess, again,
a similar phenomena,
finally,
congenital adrenal hyperplasia
with 11 beta
hydroxylase deficiency
has precursors
that activate those
mineralocorticoid receptors
and once again,
you have potassium e-flux
into that tubular fluid.
07:13
Now another thing to think
about when patients present
with a metabolic
alkalosis hypokalemia,
and hypertension
is little syndrome.
07:21
Little syndrome is an
autosomal dominant disorder
and it affects the
principal cell.
07:27
So specifically,
it works at the
epithelial sodium channel
presents during adolescence
and early adulthood
and it is a gain of
function mutation
in that epithelial
sodium channel,
which is what I
have outlined here.
07:39
You have excessive
because of that excessive
sodium reabsorption.
07:43
So if I'm reabsorbing
and I'm turning on that
epithelial sodium channel
remember what I'm doing,
I am leaving a
negative charge behind
because chloride always lags
behind in its reabsorption.
07:54
So because of that
electrical gradient,
then I am going to
favor potassium e-flux
and that Triad of how that patient
is going to clinically present
is with hypertension
a slight metabolic
alkalosis and hypokalemia.