Potassium

Joel M. Topf, M.D.

Attending Nephrologist
1 PBFluids.blogspot.com
248.470.8163
 Introduction
Potassium: Cool electrolyte

Potassium is a favorite
electrolyte of both medical
students and renal physi-
ologists. It is illustrative,
important and relevant in
ways that most other elec-
trolytes are not.
Potassium physiology is
straight forward and logi-
cal. It is the electrolyte that
demonstrates much of the
elegance of renal physiology. Potassium follows logical and eas-
ily visualized rules.
In addition to being a great exercise in renal physiology it is an
important ion with severe implica-
tions from disregulation: How do
cardiac surgeons stop the heart af-
ter hooking a patient to a heart lung
bypass machine? They inject it with
potassium. The heart which has
been beating since 14 days after
conception is stopped deadby po-
tassium.
Lastly, potassium disregulation is
common, so lessons learned can
be used on a daily basis.

2
 Table of Contents
Potassium 4
Total body potassium 4
Potassium handling in three steps 5
Potassium intake 5
Cellular distribution 6
Renal potassium handling 7
Potassium handling at the CCD 8
Regulation of potassium excretion 10

Hypokalemia 12
Definition 12
Etiologies 12
Consequences of low potassium 14
Treatment 17

Hyperkalemia 19
Etiologies 19
Pseudohyperkalemia 22
EKG Changes 22
Treatment 24
Calcium 24
Remove potassium from the body 25
Stop oral intake 25
Move extracellular potassium into the cells 26
Remove the potassium from the body: 27

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 Potassium
Potassium is the primary intracellular cation
Total body potassium
Potassium is the dominant in-
tracellular cation and because
the intracellular compartment
is twice the size of the extra-
cellular compartment it is the
most common electrolyte in
the body.
The intracellular K concentra-
tion runs from 120-153 mmol/
L
The extracellular concentra-
tion runs from 3.5-4.5 mmol/L.
A typical 70 kg man has nearly
4000 mmol of K. Of that only
56 mmol are extracellular.
Humans typically have only
2000 mmol of Na.
Question: what sizes do potas-
sium pills come in?
what is the typical dose of IV po-
tassium? How does that compare to the extracellular potassium con-
tent?

4
Potassium handling in three steps

Potassium is regulated at three fundamental steps in the body:

intake, cellular distribution and renal excretion.
Potassium intake
Diets are relatively rich in potassium with the average American
ingesting 40 mmol of potassium a day. Unfortunately the RDA
for potassium is 90 mmol. The kidney is good at being very po-
tassium avid and can reduce potassium losses to 10 mmol/day.
This avidity prevents potassium poor diets from resulting in hy-
pokalemia unless they are maintained for a long time. On the
other side of the potassium coin the kidney is able to ramp po-
tassium excretion up to over 400 mmol/day. Because of this
phenominal ability to excrete excess potassium, increased po-
tassium intake is rarely the cause of persistant hyperkalemia.
There are also clandestine sources of parenteral potassium:
• Maintenance fluids
• Penicillin G (1.7 mEq/1,000,000 units)
• Hyperalimentation

5
• Red cell transfusions
• Dialysate
Cellular distribution
Since 98.6% of total body potassium is found in the cells it
should not be surprising that the forces that govern the distribu-
tion of potassium into and out of the cells is a major factor gov-
erning serum potassium. Movement of only 1% of the intracellu-
lar potassium will double the serum potassium and likely kill the
patient.
Every cell membrane in the body is studded with Na-K-ATPase
which serves to maintain the high intracellular potassium con-
tent. These Na-K-ATPases are under physiologic control and
factors which increase their ac-
tivity lower the serum potassium
and factors which decrease their
activity increase potassium.
Insulin stimulates Na-K-ATPase.
This makes sense because in-
sulin is released after eating
which allows the body to use the
newly arrived blood sugar but
also it allows the body to safely
store the newly arrived potas-
sium.
Activation of the ß-2 receptors
stimulates the Na-K-ATPase and
lowers the serum potassium.
This is seen with endogenous
epinephrine, norepinephrine,
and acetylcholine. It has also
been shown to occur with al-
buterol and dobutamine. On the
other hand, blocking the recep-
tors with beta-blockers will in-
crease the potassium.

6
Acid-base status also influences the cellular distribution of po-
tassium. During acidemia, there is an excess of hydrogen cati-
ons in the blood. One of the buffers for this in the intracellular
compartment. Hydrogen cations move into cells. All ion move-
ment is ultimately electroneutral, so the movement of a cation
into the cells must be balanced either by an anion moving in the
same direction or a cation moving in the opposite direction.
• If the acidosis is due to an inorganic acid (non-anion gap) then
hydrogen is exchanged for potassium. The opposite occurs
with alkalemia.

• If the acidosis is due to an organic acid (think ketoacidosis,

lactic acidosis) then the anion moves into the cell with the hy-
drogen ion. In this situation no potassium moves out of the
cell.

Renal potassium handling

The kidney is responsible for excreting all of the potassium in-
gested by the body. Potassium handling by the nephron is com-

7
plex with potassium reabsorption early in the nephron and ex-
cretion in the late nephron.

Distal convoluted tubule

Reabsorb 5% of filtered po-
tassium

Cortical collecting duct

Only part of the nephron
that secretes potassium
Proximal Tubule
Reabsorb two-thirds of
filtered potassium Thick Ascending Limb
Loop of Henle
Reabsorb a quarter of filtered
potassium

The critical concept that the students of renal physiology must

take home is that renal excretion of potassium is entirely done
by the cortical collecting tubule. The standard model for renal
excretion is that plasma is filtered at the glomerulus and then
the rest of the nephron reabsorbs any particle of value and ex-
cretes additional waste products does not apply to potassium.
The filtered potassium is not excreted. All of the filtered potas-
sium is reabsorbed. Then in a second step excess potassium is
secreted in the cortical collecting ducts.
This complex mixture of reabsorption and secretion actually al-
lows one to use a simplified model of renal potassium handling.
One only has to worry about the CCD and can ignore the rest of
the nephron.
Potassium handling at the CCD
Potassium excretion is a multistep process:

8
1. sodium is reabsorbed through the ENaC. Sodium moves
down its concentration gradient.
2. The movement of sodium is electrogenic and results in a
negative charge in the tubule.
3. Chloride in the tubule can be reabsorbed paracellularly. The
more chloride that is reabsorbed the less potassium is se-
creted.
4. Potassium flows down a electrical and chemical gradient into
the tubule.

1.
ENaC

2.

4.

3.

9
Regulation of potassium excretion
The rate of potassium excretion is controlled by two factors:
1. Aldosterone
2. Tubular flow (also called distal delivery of sodium)
Aldosterone is a steroid hormone
secreted by the Zona Glomerulosa
of the adrenal glands. Aldosterone
secretion is stimulated by angio-
tensin 2 and increased serum po-
tassium. Aldosterone acts by in-
creasing the number and activity of
all the principle proteins involved in
potassium secretion.
Tubular flow is just a measure of
how fast fluid is moving past the principle cells. If the fluid is
sluggish due to decreased flow, secreted potassium accumu-
lates in the tubule and disrupts
the chemical gradient favoring
potassium excretion. Addition-
ally, high flow means enhanced
sodium delivery. This sodium is
critical for the initial step in po-
tassium excretion: sodium re-
absorption.
The last important concept for
renal potassium handling is
understanding that aldosterone
and tubular flow typically move in opposite direction. One of the
chief determinants of aldosterone activity is volume status,
when patients are hypovolemic aldosterone is increased, when
patients are volume overloaded, aldosterone is suppressed. Tu-
bular flow is also determined by volume status, when patients
are hypovolemic, tubular flow slows. When they are hypervo-
lemic flow increases.
10
 hypovolemic hypervolemic

Aldosterone increased decreased

Tubular flow decreased increased

This reciprocal relationship between aldosterone and tubular

flow allows renal potassium handling to remain independent of
volume status.

Tubular flow

Aldosterone

11
 Hypokalemia
If there isnʼt enough potassium...give some.
Definition
Potassium less than 3.5 mmol/L is defined as hypokalemia. Low
potassium can result in:
• Hypertension
• Increased stroke risk
• Arrhythmias
• Illeus
• Rhabdomyolysis

Etiologies
The causes of hypokalemia can best be categorized in the
same way we broke down total body potassium handling: in-
take, cellular distribution and renal secretion of potassium.

decreased intake: Intracellular movement: Renal losses

• alcoholics • beta agonists • diuretics
• malnutrition • dobutamine • hyperaldosteronism
• grey clay ingestion • rapid cell growth • decreased chloride delivery

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 0.4

0.2

0.0
0 30 60 90 120
Change in K

-0.2

-0.4

-0.6

-0.8

-1.0
Time (min)

Saline 10 mg 20 mg

Change in potassium after treatment with nebu-

lized albuterol

Allon Et al. Annals of Int Med; 1989: 110, 426-429.

Renal casuses of hypokalemia occur when the reciprocal rela-

tionship of aldosterone and tubular flow breaks down and both
of them are activated simultaneously:

Tubular flow
Aldosterone

The classic case of renal potassium loss is diuretic induced hy-

13
pokalemia. In this situation, the diuretic directly increases distal
delivery of sodium/tubular flow and by causing volume defi-
ciency triggers an increase in aldosterone. So patients lose the
reciprocal relationship of aldosterone and tubular flow and get
both forces activated at the same time.
In primary hyperaldosteronism, the increase in aldosterone is
easy but the increase in tubular flow is less obvious. Increased
aldosterone leads to hypertension which then induces a phe-
nomena called pressure natriuresis which triggers an increase
in tubular flow. Interestingly the pressure natriuresis is a late
finding in primary hyperaldosteronism and the hypokalemia is
delayed until that occurs.
Vomiting is a special case of renal potassium loss leading to hy-
pokalemia. First off vomiting does not cause hypokalemia be-
cause of the potassium lost in the vomit. The potassium content
of puke is pretty modest. Vomiting causes volume depletion
which triggers the release of aldosterone. Vomiting also causes
metabolic alkalosis. The increase in serum bicarbonate means
that some of this bicarbonagte ends up being excreted in the
urine. The bicarb in the urine nudges out chloride. Bicarbonate
is not reabsorbed paracellularly, so there is no disruption of the
electronegative tubule which enhances potassium excretion.

Consequences of low potassium

Low potassium increases fatal strokes in men

Low potassium predisposes to hypertension and correction of

that potassium lowers the blood pressure.
14
1

0
MAP Delta K

-1

-2

-3

-4

-5

-6

16 hypertensive patients with diuretic

induced hypokalemia were started on 60
mmol of KCl per day.
Kaplan, N. M., Carnegie, A., Raskin, P., Heller, J. A. &
Simmons, M. Potassium supplementation in hypertensive
patients with diuretic-induced hypokalemia. N. Engl. J.
Med. 312, 746-749 (1985).

15
 0

-2
SBP DBP AA SBP AA DBP
-4

-6

-8

-10

-12

-14

-16

-18

-20

101 hypertensive patients RANDOMIZED

TO 120 mmol of KCl per day (blue)
versus placebo (red).
Svetkey, L. P., Yarger, W. E., Feussner, J. R., DeLong, E.
& Klotman, P. E. Double-blind, placebo-controlled trial of
potassium chloride in the treatment of mild hypertension.
Hypertension 9, 444-450 (1987).

Hypokalemia produces EKG changes:

• Flattening of T waves
• Increased prominence of U waves (look at V4, 5, 6)
• ST depression
• Increased prominence of P waves
• Inversion of T waves
16
Low potassium predisposes to arrhythmia, especially in the peri-
MI period.

50

40

30

20

10

0
≤3.0 3.1-3.5 3.6-4.0 4.1-4.5 4.6-5.1 ≥5.2
VF, VFl, VT, AF VT, VF VF

Treatment
If the potassium is low, give potassium. The potassium can be
given IV or PO but oral is preferred. Use 20-40 mEq qd-q6h.
KCl is superior to Kphos or K-acetate. Reserve IV potassium for
patients who are NPO or have dangerously low potassium.
Make sure you consider potassium sparing diuretics, especially
for diuretic induced hypokalemia. Check and correct Mg defi-
ciency.

17
Complications of IV potassium replacement: hyperglycemia, volume
overload, phlebitis and hyperkalemia (not pictured).

How much potassium to give? A standerd rule of thumb is to use

the following formula: Four minus the current potassium times
100. This will correct roughly half the defecit and should mini-
mize subsequent hyperkalemia.

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 Hyperkalemia
The condition that will kill you in a hurry
Hyperkalemia is defined as a plasma potassium over 5.5 mEq/
L. The primary clinical problems with high potassium is weak-
ness and arrhythmias, specifically bradycardia and ventricular
fibrillation.

Etiologies

Increased intake:
oral
• Salt substitutes
65 mmol/tsp
• Shohlʼs solution Extracellular movement:
1 mmol/mL • Cell death
• Red clay • Tumor lysis syndrome
• Kiwi 6.5 mmol Decreased renal K
• Rhabdomyolysis
• Banana 12 mmol clearance
• Hemolysis
parenteral • Hypothermia • Renal failure
• IVF • Solute drag • Heart failure
• LR • Lack of insulin • Potassium sparing diu-
• TPN retics
• Beta blockers
• Dialysate • Digoxin • ACEi and ARB
• Metabolic • RTA (type IV)
acidosis (inorganic) • Hypoaldosteronism

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 6.0 310

5.5
300
5.0

4.5 290

4.0
280
3.5

3.0 270
Control Mannitol
Potassium Osmolality

5% rise in osmolality results

in a 13% rise in K
Kurtzman, N. A., Et. Al. Am. J. Kidney Dis. 15, 333-356 (1990).

20
 2.0

1.5

1.0

0.5

ol

e
ro

in
ol
nt

m
an
co

a
op

tol
Pr

en
Ph
Williams, M. E. et al. Catecholamine
modulation of rapid potassium shifts
during exercise. N. Engl. J. Med. 312,
823-827 (1985).

Hypothermia

Trauma

Tumor lysis syndrome

21
Pseudohyperkalemia
since there is a large amount of potassium in cells, a traumatic
blood draw can cause hemolysis and artificially raise the potas-
sium. Additionally blood samples with thrombocytosis and leu-
kocytosis can cause falsely elevated potassium readings.

EKG Changes
Peaked Ts are the initial finding

Shortened QT interval

Widened QRS

Sinosoidal

22
23
Treatment
The treatment of hyperkalemia follows a multistep process. The
first step is a specific therapy which acts as an antidote for the
cardiac changes induced by hyperkalemia, calcium. After that all
of the therapies aim at reducing the potassium.
Calcium
If EKG signs are present give calcium. Calcium chloride is more
effective than calcium gluconate because a gram of CaCl con-
tains three times as much calcium (0.68 mmol) as a gram of
calcium gluconate (0.23 mmol). The onset of action is essen-
tially instant and lats about 1 hour. The calcium can be repeated
and should be repeated until the EKG normalizes.
Most text books say that calcium should be avoided if the pa-
tient has digoxin toxicity. In that case use of digoxin FAB will
rapidly and reliably lower the serum potassium.

24
Remove potassium from the body

Stop all K intake

Oral
• Salt substitutes
• Shohlʼs solution
• Red clay Induce intracellular shift:
• protein supplements • insulin
Parenteral • albuterol
Remove K from the body:
• IVF • correct hyperglycemia
• correct digoxin toxicity • diuretics
• LR
• increase Na intake
• TPN
• kayexylate
• Dialysate
• dialysis

Stop oral intake

Look for and eliminate stealth potassium: maintenance IVs,
CVVH fluid, Penicillin G, CHA, dietary sources (salt substitutes).

25
Move extracellular potassium into the cells
The traditional therapy for this is sodium bicarbonate and insulin
with glucose. Blumberg Et al. Amer J Med; 1988: 85, 507-512.
After Blumberg showed no hypokalemic effect after 60 minutes
he followed it up with an extended protocol for 6 hours and
found a minimal reduction of potassium after 4.
0.3 0.3

0.1 0.1

-0.1 0 -0.1 0 60 120 180 240 300 360

10 20 30 40 50 60
-0.3 -0.3
Change in K

Change in K
-0.5 -0.5
-0.7 -0.7
-0.9 -0.9
-1.1 -1.1
-1.3 -1.3
-1.5 -1.5
Time (min) Time (min)

NaHCO3 8.4% NaHCO3 1.4% p>0.05 P<0.05

Epinephrine Insulin Glucose

Dialysis

The use of albuterol is a newer therapy for hyperkalemia but is

quite effective and is synergistic with insulin and glucose:

0.4 0.0
0 15 30 45 60
0.2
-0.3
0.0
Change in K

0 30 60 90 120
Change in K

-0.6
-0.2

-0.4 -0.9

-0.6
-1.2
-0.8
-1.5
-1.0
Time (min)
Time (min)
Insulin Albuterol Combination
Saline 10 mg 20 mg

The orders to get optimal hypokalemic effect are:

26
1. 10 units IV insulin
2. 50 g of D50
3. repeat blood sugar q 1 hour for 6 hours
4. Albuterol 20 mg per nebulizer
Remove the potassium from the body:
Increase the excretion of potassium via the kidneys by rehydrat-
ing patients with normal saline and giving a trial of furosemide
(Lasix). If the patient has kidney disease use 20 x sCr IV push.
Sodium polystyrene resins (Kayexalate) in patients whose kid-
neys donʼt work, use 30 grams in adults.
Call nephrology early for dialysis.

27
 Joel M. Topf, MD
Nephrology
248.470.8163

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