00:01
Hello and welcome back to
the nephrology curriculum.
00:04
Today we're going to be talking
about potassium disorders
and in particular
the clinical entities
of hypo and hyperkalemia.
00:12
Let's start with the physiology
of potassium metabolism.
00:15
So in terms of potassium intake,
the average intake
in a western diet
would be somewhere between
70 and 150 millimoles
of potassium per day.
00:24
Now, you might be surprised
to see where some of those
highest sources of
potassium are coming from.
00:28
Look at avocado for instance.
00:30
One medium sized avocado
has about 38 millimoles
of potassium.
00:34
Tomato paste
has a high amount of potassium
as well as sirloin steak
and some of the
meats that we ingest.
00:40
Things like orange
juice potatoes
and raisins are also
very high in potassium
and that becomes very
important in patients
who have to limit
their potassium.
00:50
Now once we in take
potassium through our diet,
it's absorbed efficiently
by the GI tract.
00:56
It's then distributed
into primarily the
intracellular compartment.
01:00
So about 98% of our potassium
resides within that
intracellular fluid compartment
and only 2% is actually
distributed to the
extracellular fluid compartment.
01:10
The normal plasma potassium,
that's what's in that ECF
is about 3.5 to 5.2
milliequivalents per liter.
01:18
Now our electrogenical
sodium potassium ATPase
drives that asymmetrical
potassium distribution
between that ICF and ECF.
01:27
So remember that
sodium potassium pump
that's located at those cells.
01:30
It actively transports
two potassium ions into the cell
in exchange for extrusion
of three sodium ions
into the extracellular
fluid compartment.
01:41
Now that maintenance of
that intracellular potassium
and that asymmetry between
those two compartments
is critical for nerve conduction
and muscular contraction,
so we have to have that.
01:51
When we think about
potassium balance,
there's four main mechanisms
that we really have to remember.
01:57
Number one is the intake
that we get through our diet.
01:59
So what are we eating in
terms of our potassium.
02:02
Number two is GI losses.
02:04
The GI tract is going to
secrete anywhere from 5-10%
of our absorbed potassium daily.
02:10
But look at the renal losses
90 to 95% of potassium is
really regulated by the kidney.
02:18
And then of course, there's an element
of transcellular potassium shift.
02:22
That means that the
actual potassium levels
are total body
potassium is the same
but there is a redistribution
between the ICF and ECF.
02:31
So we just said that
90 to 95% of potassium
is regulated by the kidney.
02:37
Let's take a little
tour through our nephron
and find out how this occurs.
02:42
So potassium is freely
filtered at the glomerulus.
02:46
About 65% to 70% of
that filter potassium
is going to be reabsorbed
in the proximal tubule.
02:53
Now when it's reabsorbed there.
02:54
This is a passive
transport process.
02:57
It gets reabsorbed
paracellularly,
That means between cells by
solvent drag and diffusion.
03:03
So this is as opposed or in
contrast to active transport,
which is what is diagrammed
in my top diagram there.
03:11
That's one of my proximal
tubular epithelial cells
and you can see
there's an ion channel
and apical transport protein.
03:18
When we have proteins or ions
that are actually absorbed
through these channels.
03:22
That's an active transport
process requiring energy.
03:25
However,
the way potassium gets reabsorbed
at that proximal
tubule is passive,
meaning that again,
it's moving between the
pair cellular pathway
between cells and it's
going through diffusion
and solvent drag.
03:37
An easy way to remember that
is P passive transport
proximal tubular paracellular.
03:45
Now the next stop in our
nephron that's important
when it comes to potassium
is the thick ascending limb
of the loop of henle.
03:52
This area is responsible
for reabsorbing about
10 to 25% of potassium.
03:58
And it's driven by our luminol
sodium potassium two chloride
or NKCC2 Multi Porter.
04:05
Now, this is also the
site of loop diuretics.
04:08
It's an active transport process
Meaning that this
is actually driven
by that basolateral
sodium-potassium ATPase
located on the right.
04:18
Our transporter affinity is
going to be very very high
for both sodium and potassium
and have max activity
when the tubular
fluid concentration
for sodium and potassium
or below 5 to 10
Milli equivalents.
04:32
Now, one of the elegant
things about this cell
is the whole idea of
potassium recycling.
04:36
Potassium can actually recycle
across that luminol membrane
allowing for continued
activation of the NKCC2
and that makes sense
to us because sodium
is in much higher concentration
compared to potassium.
04:48
So in order for us to be able
to absorb all of the sodium,
we would have to recycle
that potassium in order
to make that transporter work
and that's exactly what happens.
04:58
The activity of that
potassium channel
is actually inhibited by ATP
and it allows us to
link to the level
of sodium reabsorption.
05:06
So as more sodium
enters the cell
sodium gets transported
out of the cell
into that peritubular capillary
by that sodium potassium ATPase
that lowers the
cellular ATP level
and it stimulates the activity
of that luminol potassium
channel also called
the renal outer medullary
potassium channel.
05:26
That will then allow
permit the return
of reabsorbed potassium
into the lumen
and then further linked
to sodium reabsorption.
05:34
So moving on from the thick
ascending limb of the loop of henle.
05:37
The next important stop
is in the principal cell.
05:41
Our principal cells are located
in that cortical collecting duct,
and they have a
very important job
when it comes to
potassium handling.
05:48
So initially potassium
is actively transported
into that cell by our
sodium potassium ATPase
at the basolateral membrane.
05:56
It's then secreted
into the tubular fluid
down of favorable
electrochemical gradient
by luminal potassium channels
and that apical membrane.
06:03
These are governed by factors
that affect passive transport.
06:07
So things like a concentration
gradient across the luminal membrane
think about where
potassium is distributed.
06:12
We just said that it's primarily
in the intracellular compartment.
06:16
So we have a very high amount
of potassium intracellularly
a very low amount of potassium
in the tubular fluid.
06:21
So it will favor
to move or E-flux
into that tubular fluid down
its concentration gradient.
06:28
We also have an
electrical gradient here.
06:30
So that is generated
by reabsorption of sodium
sodium is going to go
to that epithelial sodium
channel be reabsorbed
into that principle cell
when it does so,
it leaves a negative charge behind
because even though it's
paired with sodium chloride
chloride gets reabsorbed
at a later time.
06:45
So that negative charge
then is going to favor
potassium reflux in e-flux
into that tubular fluid.
06:52
And finally, we have potassium
permeability of those
luminal membranes.
06:56
So not only are those
luminal membranes present.
06:59
They have to be open.
07:01
So with all of these together,
these are some of the regulators
of potassium excretion
in our principal cell.
07:07
Now there's four main factors
that you really have to
think about when it comes
to potassium secretion
at that principle cell
and I promise you if you
remember these four things
you will be able to solve
any potassium problem that
you are ever confronted with.
07:20
The first factor that I want you
to think about is aldosterone.
07:24
Aldosterone remember is
created by the Zona glomerulosa
in the adrenal gland
and it's job with
regards to potassium
is going to be to augment
potassium secretion
from that principle cell in e-flux
that into the tubular fluid.
07:37
It does so by a number of ways.
07:39
1. It increases the number
of open sodium channels
and potassium channels
in that luminal membrane.
07:44
So not only are they there
they have to be open.
07:47
It also enhances the activity
of the sodium ATPase that
basolateral membrane.
07:53
Second factor to think
about in terms of
what regulates potassium
e-fux at the principal cell
is plasma potassium.
07:59
If I have a very high
plasma potassium,
I'm going to need
to actually get rid
of extra potassium
the same mechanism that applies
with aldosterone is
going to happen here.
08:09
So high potassium levels
cause patients to increase
the number of open sodium
and potassium channels
in that luminol membrane
and also will
enhance the activity
of the sodium-potassium ATPase
at that basolateral membrane.
08:20
Now, the third factor to think
about is the distal flow rate.
08:24
And what that means is the
flow of the tubular fluid
and how fast it's moving.
08:29
When you have an increase
in distal flow rate or
increase in tubular fluid rate.
08:33
It's going to watch the
secreted potassium away
and replace it with
relatively low potassium fluid
that's going to then favor
that concentration gradient.
08:43
It's going to favor
potassium moving
from the intracellular
compartment to the tubular fluid.
08:49
It's going to move down
its concentration gradient.
08:52
Now when that distal
flow rate is reduced,
you're going to have a high
luminal potassium content
because of less washout
and low urine flow.
09:00
So less potassium is going to
e-flux into that tubular fluid.
09:05
Now you also there are
some other mechanisms
that are at play here.
09:09
There are something
called Maxi-K channels.
09:11
These are voltage-gated channels
that sense that
tubular flow rate.
09:14
And again,
they will help in the response
of potassium e-flux
into that tubular fluid.
09:19
So take home point when you
have a high tubular fluid rate,
so that would be a patient
who might be polyurethane
meaning that they make
greater than 3 liters of fluid
that is going to stimulate
potassium secretion
when you have a low
tubular fluid rate
meaning somebody who
might be oliguric
they're going to have
less e-flex up potassium
into that tubular flow rate and
have a higher plasma potassium.
09:42
Now last factor to remember
is distal sodium delivery.
09:46
So think about what happens
when you have sodium
that is presented to
that principle cell,
you've got entry of sodium
by that epithelialsodium channel
that makes the lumen
electronegative
Remember sodium's going to
leave behind a negative charge
as it gets reabsorbed.
10:01
You then have transport
of sodium into the peritubular
capillaries by that atpase
at the basolateral pump
and that's going to pump more
potassium into that cell,
and then you have more
potassium secreted
into the electronegative lumen.
10:14
So when we think about
distal sodium delivery,
that would be the mechanism
by which loop diuretics
and thiazide diuretics
cause hypokalemia.
10:23
They allow for an increase
in distal delivery
of sodium to this site.
10:29
Our last stop in the nephron,
as it pertains to potassium
is the alpha intercalated cell
at the collecting duct.
10:35
This cell is critical because
it reabsorbs potassium
and it does it through the
apical hydrogen potassium ATPase
shown here.
10:42
This is an active
transport process
meaning that it requires energy.
10:46
So it will actively secrete
protons into that tubular lumen
or the tubular fluid in exchange
for potassium reabsorption.
10:56
The act of reabsorption
by that hydrogen ATPase
really enables us
to be able to reduce
our urinary potassium excretion
to less than 15 millimoles
per day in severe
potassium deficiency.