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hello and welcome back to the nephrology
curriculum
today we're going to be talking about
potassium disorders and in particular
the clinical entities of hypo and
hyperkalemia let's start with the
physiology of potassium metabolism
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
now you might be surprised to see where
some of those highest sources of
potassium are coming from
look at avocado for instance one
medium-sized avocado has about 38
millimoles of potassium
tomato paste has a high amount of
potassium as well as sirloin steak and
some of the meats that we ingest
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
now once we intake potassium through our
diet it's absorbed efficiently by the gi
tract
it's then distributed into primarily the
intracellular compartment so about 98
of our potassium resides within that
intracellular fluid compartment
and only 2 percent is actually
distributed to the extracellular fluid
compartment
the normal plasma potassium that's
what's in that ecf
is about 3.5 to 5.2 ml equivalents per
liter
now our electrogenical sodium potassium
atpase derives that asymmetrical
potassium distribution between that icf
and ecf so remember that
sodium-potassium pump that's located at
those cells
it actively transports two potassium
ions
into the cell in exchange for extrusion
of three sodium ions
into the extracellular fluid compartment
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
when we think about potassium balance
there's four main mechanisms that we
really have to remember
number one is the intake that we get
through our diet so what are we eating
in terms of our potassium
number two is gi losses the gi tract is
going to secrete anywhere from five to
ten percent
of our absorbed potassium daily but look
at the renal losses 90 to 95 percent of
potassium is really
regulated by the kidney and then of
course there's an element of
transcellular potassium shift
that means that the actual potassium
levels or total body potassium is the
same
but there's a redistribution between the
icf
and ecf so we just said that 90 to 95
percent of potassium is regulated by the
kidney
let's take a little tour through our
nephron and find out how this occurs
so potassium is freely filtered at the
glomerulus
about 65 to 70 of that filtered
potassium is going to be reabsorbed in
the proximal tubule
now when it's reabsorbed there this is a
passive transport process it gets
reabsorbed paracellularly that means
between cells
by solvent drag and diffusion so
this is as opposed or in contrast to
active transport which is what is
diagrammed in my top diagram there
that's one of my proximal tubular
epithelial cells and you can see there's
an ion channel and
apical transport protein when we have
proteins or ions that are actually
absorbed through these channels that's
an
active transport process requiring
energy however
the way potassium gets reabsorbed at
that proximal tubule
is passive meaning that again it's
moving between the paracellular pathway
between cells
and it's going through diffusion and
solvent drag an easy way to remember
that
is p passive transport proximal tubule
paracellular
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
this area is responsible for reabsorbing
about 10 to 25
percent of potassium and it's driven
by our luminal sodium potassium 2
chloride or
nkcc2 multiporter now this is also the
site of loop diuretics
it's an active transport process meaning
that this is
actually driven by that basal lateral
sodium potassium atpase located on the
right
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 ml
equivalents
now one of the elegant things about this
cell is the whole idea of potassium
recycling
potassium can actually recycle across
that luminal membrane
allowing for continued activation of the
nkcc2
and that makes sense to us because
sodium is in much higher concentration
compared to potassium
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 the
activity of that potassium
channel is actually inhibited by atp and
it allows us
to link to the level of sodium
reabsorption 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 luminal potassium channel also
called the renal outer medullary
potassium
channel that will then allow permit the
return of reabsorbed potassium into the
lumen
and then further link to sodium
reabsorption
so moving on from the thick ascending
limb of the loop of henle the next
important stop
is in the principal cell our principal
cells are located in that cortical
collecting duct
and they have a very important job when
it comes to potassium handling
so initially potassium is actively
transported into that cell by our sodium
potassium atpase at the basolateral
membrane
it's then secreted into the tubular
fluid down a favorable electrochemical
gradient by
luminal potassium channels in that
apical membrane
and these are governed by factors that
affect passive transport
so things like a concentration gradient
across the luminal membrane
think about where potassium is
distributed we just said that it's
primarily in the intracellular
compartment so we have a very high
amount of potassium intracellularly
a very low amount of potassium in the
tubular fluid so
it will favor to move or efflux into
that tubular fluid down its
concentration gradient
we also have an electrical gradient here
so that is generated by reabsorption of
sodium sodium is going to go to that
epithelial sodium channel be reabsorbed
into that
principal 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 so that negative charge
then
is going to favor potassium reflux in
efflux into that tubular fluid and
finally we have potassium permeability
of those luminal membranes
so not only are those luminal membranes
present they have to be open
so with all of these together these are
some of the main regulators of potassium
excretion in our principal cell
now there's four main factors that you
really have to think about when it comes
to potassium
secretion at that principal 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
the first factor that i want you to
think about is aldosterone
aldosterone remember is created by the
zona glomerulosa and the adrenal gland
and its job with regards to potassium is
going to be to augment potassium
secretion
from that principal cell and efflux that
into the tubular fluid
it does so by a number of ways number
one it increases the number of open
sodium channels
and potassium channels in that luminal
membrane so not only are they there
they have to be open it also enhances
the activity of the sodium atpase at
that basal lateral membrane
second factor to think about in terms of
what regulates potassium efflux at the
principal cell
is plasma potassium 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
so high potassium levels cause patients
to increase the number of
open sodium and potassium channels in
that luminal membrane and it also will
enhance the activity of the sodium
potassium
atp set that basolateral membrane now
the third factor to think about is the
distal flow rate
and what that means is the flow of the
tubular fluid and how fast it's moving
when you have an increase in distal flow
rate or increase in tubular fluid rate
it's going to wash the secreted
potassium away
and replace it with relatively low
potassium fluid
that's going to then favor that
concentration gradient it's going to
favor potassium moving
from the intracellular compartment to
the tubular fluid
it's going to move down its
concentration gradient
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 so less potassium is
going to efflux into that tubular fluid
now you also there are some other
mechanisms that are at play here there
are something called maxi-k channels
these are voltage-gated channels that
sense that tubular flow rate
and again they will help in the response
of potassium efflux into that tubular
fluid
so take home point when you have a high
tubular flu fluid rate
so that would be a patient who might be
polyuric meaning that they make
greater than three liters of fluid that
is going to stimulate potassium
secretion
when you have a low tubular fluid rate
meaning somebody who might be
oligaric they're going to have less
effects of potassium into that tubular
flow rate and have a higher plasma
potassium
now last factor to remember is distal
sodium delivery
so think about what happens when you
have sodium that is presented
to that principal cell you've got entry
of sodium by that epithelial sodium
channel
that makes the lumen electronegative
remember sodium is going to leave behind
a negative charge as it gets reabsorbed
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 so when we think
about distal sodium delivery
that would be the mechanism by which
loop diuretics and thiazide diuretics
cause hypokalemia
they allow for an increase in distal
delivery of sodium to this site
our last stop in the nephron as it
pertains to potassium is the alpha
intercalated cell at the collecting duct
this cell is critical because it
reabsorbs potassium and it does it
through the apical hydrogen potassium
atpase
shown here this is an active transport
process meaning that it requires energy
so it will actively secrete protons into
that tubular lumen
or the tubular fluid in exchange for
potassium reabsorption the active
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
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