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S. Faubel and J.

Topf 17 Introduction to Potassium

17
17 Introduction to Potassium

467
The Fluid, Electrolyte and Acid-Base Companion

IntroductionPotassium…the final frontier.

K
+
K

K+
+
K+ K
+

+
K
K +

BUN
Na+ Cl– glucose
+
K
K+ HCO3– Cr
K+

+
K+

K
+
K

Potassium is the final electrolyte which will be covered in this book. Some
of the major differences between sodium and potassium are outlined below:

Sodium Potassium
• Primary extracellular cation. • Primary intracellular cation.
• Alterations in sodium concentra- • Alterations in potassium concen-
tion affect the osmotic movement tration result in electrical signals
of water in and out of cells. Most that interrupt normal cardiac
clinical symptoms are related to rhythm, muscle activity and nerve
cerebral edema or dehydration. conduction.

Medical Latin:
• Hypokalemia: low plasma potassium,+ K < 3.5 mEq/L.
• Eukalemia: normal plasma potassium, 3.5 <+ <K 5.0 mEq/L.
• Hyperkalemia: increased plasma potassium,+ >K5.0 mEq/L.
• Kaluresis: loss of potassium in the urine.

Potassium is the ________ intracellular cation while sodium is the primary


primary ___________ cation. extracellular

Disturbances in _______ concentration result in altered electrical ac- potassium


tivity which can affect the __________, muscles and nerves. heart

468
S. Faubel and J. Topf 17 Introduction to Potassium

IntroductionThe vast majority of the total body potassium is


intracellular.

+
K

K +

Total body water for a Total extracellular


70 kg man is 42 liters. potassium is
extracellular compartment (14 L × 4 mEq/L).
14 liters is K+ = 4 mEq/L
extracellular 56 mEq

K
+
+
K
2 K+

28 liters is ATP AMP

intracellular 3 Na+

Total intracellular
potassium is
(28 L × 140 mEq/L).

3,920 mEq
intracellular compartment
K+ =140 mEq/L

When thinking about potassium physiology, two facts should always be


considered:
• 99% of total body potassium is in cells.
• Small changes in plasma potassium can have dramatic clinical
consequences.
Tight control over both the intracellular and extracellular potassium pools
is necessary because the movement of only 1% of the intracellular potas-
sium to the extracellular compartment can stop the heart.

The two central aspects of potassium physiology which must al- aaa
ways be considered are:
• The vast majority of potassium is ___________. intracellular
• Small changes in the extracellular _________ concentra- potassium
tion can have dramatic clinical consequences.

Movement of only ____ percent of the intracellular potassium one


pool to the extracellular compartment can stop the _______. heart

469
The Fluid, Electrolyte and Acid-Base Companion

Potassium balancePotassium balance is maintained by the


cells and the kidney.

Intracellular buffering Renal regulation


immediate response long-term control
K +

K+

+
K

K +

K+

The body has both an immediate and a long-term strategy to regulate the
plasma potassium concentration. Cellular buffering is the immediate de-
fense against a change in plasma potassium, while the kidneys control long-
term potassium balance.
Cells secrete potassium when plasma potassium falls; cells absorb potas-
sium when plasma potassium rises. The secretion and absorption of potas-
sium by cells is referred to as buffering. The kidneys affect long-term potas-
sium balance through the excretion and resorption of potassium.
Cellular control of potassium movement is influenced by:
• catecholamines • cellular synthesis
• insulin • cellular destruction
• plasma pH • plasma potassium
Renal potassium regulation is governed by:
• plasma potassium • flow in the distal nephron
• aldosterone
An understanding of these systems is necessary to comprehend the disor-
ders which cause hypokalemia and hyperkalemia. The remainder of this
chapter reviews the important concepts in intracellular and renal regula-
tion of plasma potassium.

The immediate defense against a change in plasma potassium tightlyaaa


is intracellular ____________. buffering

The long term control of plasma potassium is the responsibility


of the _________. kidney

470
S. Faubel and J. Topf 17 Introduction to Potassium

Potassium balanceCellsCellular distribution of potassium is


maintained by Na-K-ATPase activity.

K+ K +

2 K+ 3 Na+
ATP

AMP

sodium 140 mEq/L potassium 140 mEq/L


potassium 4 mEq/L sodium 4 mEq/L

Extracellular compartment Intracellular compartment

The Na-K-ATPase pump is a membrane protein found on all cells. It is


responsible for maintaining an intracellular environment which is high in
potassium and low in sodium. The Na-K-ATPase pump is central to the
ability of the intracellular compartment to buffer against changes in plasma
potassium concentration.
Increased Na-K-ATPase activity lowers the plasma potassium concentra-
tion, and decreased activity raises plasma potassium concentration. Na-K-
ATPase activity is stimulated by:
• catecholamines
• insulin
• increased plasma potassium

The ________ pump moves potassium into the cell and sodium Na-K-ATPase
out of the cell. It is responsible for maintaining low _______ and sodium
high ________concentrations within the cell. potassium

Increased Na-K-ATPase activity ________ (lowers/raises) plas- lowers


ma potassium concentration.

Na-K-ATPase activity is stimulated by ________, catechola- insulin


mines and increased plasma ___________. potassium

471
The Fluid, Electrolyte and Acid-Base Companion

Potassium balanceCellsActivation of beta-2 receptors in-


creases Na-K-ATPase activity.

catecholamines

K+ K +

ß-2 receptor
2 K+

ATP

AMP
3 Na+

Think: Beta Bottoms


Banana

Catecholamines, via beta-2 receptors, stimulate Na-K-ATPase activity


which increases the uptake of potassium into cells. The beta-2 receptors
influence potassium levels in three situations:
• Stress (physiologic or emotional) increases release of endogenous
epinephrine. Epinephrine binds to beta-2 receptors and can tran-
siently drop plasma potassium.
• Beta-agonists are primarily used in the treatment of bronchoc-
onstriction (e.g., asthma). Beta-agonists like albuterol are inhaled
in order to open constricted bronchioles. A side effect of beta-
agonists is a transient lowering of serum potassium.
• Beta-blockers are life-saving medications used in the treatment
of hypertension and angina. The inhibition of beta activity
through the use of these medications can blunt the ability of cells
to absorb potassium, potentially increasing plasma potassium.

_____________ can bind to ß2-receptors and activate the Na-K- Catecholamines


ATPase pump.

Stress and beta-agonists can ___________ (lower/raise) plasma po- lower


tassium, while beta-blockers can _________ (lower/raise) plasma po- raise
tassium.

472
S. Faubel and J. Topf 17 Introduction to Potassium

Potassium balanceCellsInsulin stimulates Na-K-ATPase


activity, lowering plasma potassium.

insulin

K+ K +
insulin
receptor
2 K+

ATP

AMP Think: INsulin causes both


glucose and potassium to go
3 Na+ INto cells.

The primary action of insulin is to facilitate the movement of glucose from


the blood into cells. Insulin also affects the movement of potassium into
cells. This dual action of insulin is adaptive because it compensates for both
the glucose and potassium ingested in meals.

Insulin _________ Na-K-ATPase activity, driving K+ into ______. stimulates; cells

Insulin causes the _______ of glucose and potassium into cells. movement

473
The Fluid, Electrolyte and Acid-Base Companion

Potassium balanceCellsChanges in pH affect the movement


of potassium into and out of cells.

K+

K+
Acidosis Alkalosis
High plasma hydrogen concentration causes Low plasma hydrogen concentration causes
the cellular uptake of hydrogen and the excre- the cellular release of hydrogen and the resorp-
tion of potassium. tion of potassium.

The intracellular compartment buffers changes in both potassium and


hydrogen concentration. Increased plasma hydrogen (↓ pH) causes cells to
absorb hydrogen and secrete potassium. Decreased plasma hydrogen con-
centration (↑ pH) causes cells to secrete hydrogen and absorb potassium.
The movement of hydrogen and potassium are linked to maintain electro-
neutrality.
The effect of pH on plasma potassium varies depending on the type of
acid-base disorder. For example, plasma potassium does not change in res-
piratory acidosis and changes only minimally in lactic acidosis and ketoaci-
dosis.
Below are various mnemonics to remember the relationship between pH
and potassium. Pick one and commit it to memory:

Think: potassium and pH always Think: aLKalosis Think: potassium and hydrogen
move in opposite directions. concentration walk together.
Low K+
pH causes potassium hydrogen causes potassium

pH causes potassium hydrogen causes potassium

A drop in pH means the hydrogen concentration is _________ increased


(decreased/increased).

In acidosis, extracellular pH is partly stabilized by movement


of excess _________ into cells; potassium moves out of cells in hydrogen
order to maintain ________________. electroneutrality

474
S. Faubel and J. Topf 17 Introduction to Potassium

Potassium balanceCellsCell destruction and cell construc-


tion can dramatically affect plasma potassium concentration.
Cell destruction Cell synthesis

+
K K +

140 mEq/L

140 mEq/L

+
K
+
K

The intracellular compartment contains 99% of the body’s potassium and


⅔ of total body water. Because of this, changes in cell number can alter the
plasma potassium concentration. This is seen in two clinical settings:
• Massive cell destruction. Both chemotherapy and trauma can
cause large-scale cell destruction and the release of intracellular
potassium, causing hyperkalemia.
• Cell production. The treatment of severe megaloblastic ane-
mia with folic acid or vitamin B-12 decreases plasma potassium
as it is used to create the intracellular environment for the new
red blood cells.

Because the majority of the body’s potassium is found in _____, cells


changes in cell number can alter plasma _________. potassium

Cell destruction with ____________ or trauma releases potassium, chemotherapy


causing ___________. hyperkalemia

Acute increases in cell number are uncommon but can occur dur-
ing the treatment of megaloblastic anemia with _______ or B-12. folate

475
The Fluid, Electrolyte and Acid-Base Companion

Potassium balanceKidneyLong-term potassium control is ac-


complished by the resorption and selective secretion of potassium.

K +

The proximal tubule The collecting tubule


resorbs potassium. secretes potassium.
+
K
K
+

K
+

K+

K+
+
K

The loop of Henle


resorbs potassium.

The kidney balances potassium intake with potassium excretion so that


K in = K+out. This is done through coordinated potassium handling in the proxi-
+

mal tubule, the loop of Henle and the distal nephron.


Potassium, like all electrolytes, is freely filtered at the glomerulus. Ini-
tially, the tubular fluid has the same concentration of potassium as does
plasma.
In the proximal tubule, bulk resorption of potassium occurs without re-
gard for the potassium status of the body. The loop of Henle resorbs potas-
sium due to the activity of the Na-K-2Cl pump in the thick ascending limb.
Working together, the proximal tubule and the loop of Henle resorb about
90% of filtered potassium.
The primary site of potassium regulation is the collecting tubule. The study
of renal potassium excretion can be focused almost exclusively on the activity of
the collecting tubule.

Potassium is resorbed in the _________ tubule and the ______ proximal


__ _______. loop of Henle

Potassium is _________ by the distal nephron. secreted

The most important part of the nephron in potassium regula-


tion is the _______ ________. distal nephron

476
S. Faubel and J. Topf 17 Introduction to Potassium

Potassium balanceKidneySecretion of potassium in the dis-


tal nephron is a four-step process.
tubular lumen principle cell
In the cell, the Na-K-ATPase
1 pump keeps the potassium K+= 140 mEq/L ATP
concentration high and the 2 K+
3 Na+
sodium concentration low.
Na+= 4 mEq/L AMP
Sodium flows down its con-
2 centration gradient into the
tubular cell through sodium
channels. Na+
high sodium low sodium
The movement of the posi-
3 tively charged sodium ions
makes the tubular fluid nega-
tively charged (electronega-
tive).

The positively charged po-


4 tassium flows down both
concentration and electrical
+
K

K+
gradients into the tubule.
low potassium high potassium

Potassium secretion in the distal nephron is a multistep process which


culminates in potassium flowing down electrical and chemical (concentra-
tion) gradients into the tubular fluid:
Step one: the Na-K-ATPase pump maintains a low concentration
of sodium and a high concentration of potassium in the cells.
Step two: the low intracellular sodium concentration allows sodium
to flow down its concentration gradient into the tubular cells. The
flow of sodium into the tubular cell is the rate-limiting step in potas-
sium secretion.
Step three: the movement of positively charged sodium into the
tubular cell without an associated anion creates an electrical gra-
dient between the tubule and the tubular cells. The tubular lumen
is negatively charged.
Step four: potassium passively flows down both electrical and
chemical (concentration) gradients into the tubular fluid.

The ___________ of potassium in the distal nephron depends on excretion


establishing favorable electrical and __________ gradients. chemical

477
The Fluid, Electrolyte and Acid-Base Companion

Potassium balanceKidneyPotassium handling in the distal


nephron is affected by four factors.
Mineralocorticoid activity Distal flow

ALDOSTERONE
+
K

+
K

K+ +
K

+
K

Plasma potassium K+
Nonresorbable anions

PO4 3 A-
K
+
+
K

+
K

HCO3
K
+

K+

Because it is in charge of fine-tuning the excretion of potassium, the dis-


tal nephron is under tight control from various inputs. The primary factors
which affect potassium excretion are:
mineralocorticoid activity
plasma potassium
distal flow
nonresorbable anions in the distal nephron

The excretion of potassium in the _______ nephron is regulated distal


by ________ different factors. four

The factors which affect potassium excretion include


________________ activity, plasma potassium concentration, dis- mineralocorticoid
tal flow and nonresorbable ________ in the distal nephron. anions

478
S. Faubel and J. Topf 17 Introduction to Potassium

Potassium balanceKidneyAldosterone is one of the prima-


ry factors which regulates potassium excretion.
principle cell
Aldosterone increases the
1 number of Na-K-ATPase
K+= 140 mEq/L ATP
pumps in the basolateral
3 Na+ 2 K+
membrane.
Na+= 4 mEq/L AMP
Aldosterone increases the
2 number of sodium channels
which facilitates increased
sodium resorption. Na+

Increased sodium resorption


3 due to aldosterone increases
the electrical gradient for po-
tassium secretion.

Aldosterone increases the


4 number of potassium chan- +
K
nels which facilitate the ex-
cretion of potassium. K+

In addition to its central role in volume regulation, aldosterone is an im-


portant factor in potassium regulation. Increases in plasma potassium as
small as 0.1 mEq/L will cause a measurable increase in aldosterone release.
Aldosterone stimulates the production of the following proteins in order to
increase potassium excretion:
Na-K-ATPase pump. Increased Na-K-ATPase activity keeps the
intracellular sodium concentration low and the intracellular potas-
sium concentration high.
Sodium channels. The addition of sodium channels allows more
sodium to enter the tubular cell. This increases the electrical gradi-
ent across the tubular wall which enhances excretion of potassium.
Potassium channels. The addition of potassium channels facili-
tates the movement of potassium down its chemical and electrical
gradient into the tubule lumen.

Increased aldosterone activity ________ (decreases/increases) increases


potassium excretion.

479
The Fluid, Electrolyte and Acid-Base Companion

Potassium balanceKidneyIncreased plasma potassium stim-


ulates the excretion of potassium independent of aldosterone.
principle cell
Increased plasma potassium
1 concentration increases the K+= 140 mEq/L ATP
number of Na-K-ATPase 3 Na+ 2 K+
pumps.
Na+= 4 mEq/L AMP

Increased plasma potassium


2 concentration increases the
number of sodium channels
Na+
which facilitates sodium re-
sorption.

Increased sodium resorption


3 increases the electrical gradi-
ent for potassium secretion.

+
K
The positively charged potas-
4 sium flows down chemical K+
and electrical gradients into
the tubule.

Increased plasma potassium directly stimulates the secretion of potas-


sium into the tubule. This effect of potassium is independent of aldosterone.
Increased plasma potassium increases Na-K-ATPase activity and the num-
ber of sodium channels. Plasma potassium’s effect on potassium excretion
is weaker than aldosterone’s effect on potassium excretion.

Increased plasma ___________ stimulates the excretion of potas- potassium


sium in the distal ____________. nephron

Elevated plasma potassium stimulates the production of Na-K-


ATPase pumps and __________ channels. sodium

480
S. Faubel and J. Topf 17 Introduction to Potassium

Potassium balanceKidneyIncreased flow in the distal neph-


ron leads to increased potassium excretion.

K +

+
K
K+

+
K
+
K
+
K

Increased flow of fluid quickly washes away se- Increased delivery of sodium increases sodium
creted potassium to maintain the concentration resorption to enhance the electrical gradient.
gradient.

When the flow rate in the distal nephron is increased, it enhances both
the chemical and electrical gradients for potassium secretion. Increased distal
flow refers to the increased delivery of water and sodium to the distal neph-
ron.
Increased distal flow enhances the chemical gradient by quickly washing
away any secreted potassium. This prevents the accumulation of potassium
in the tubule which would decrease the chemical gradient.
Increased delivery of sodium to the distal nephron increases sodium re-
sorption and enhances the electrical gradient, favoring potassium excre-
tion.

Increased flow in the distal nephron enhances ________ of potassi- secretion


um and can lead to ________. hypokalemia

Increased flow to the distal nephron causes potassium excretion by


_____ mechanisms: two

• Increased sodium resorption increases the _______ gradient. electrical

• Increased flow prevents the accumulation of potassium in


the tubule and maintains a ____________ gradient in favor chemical
of potassium excretion.

481
The Fluid, Electrolyte and Acid-Base Companion

Potassium balanceKidneyIncreased nonresorbable anions


in the tubular fluid enhance potassium excretion.

Na+ Na+

A-
HCO3
Cl–
Cl– HCO3
Cl– Cl–

K+

+
K

Normally, the movement of chloride decreas- Nonresorbable anions (including bicarbonate) in


es the electrical gradient and reduces potas- the tubular fluid increase the electrical gradient,
sium secretion. drawing potassium into the tubule.

Increased nonresorbable anions in the distal nephron increase the elec-


trical gradient for the secretion of potassium.
Normally, the tubule fluid is negatively charged and attracts the posi-
tively charged potassium. The negative charge is created by the resorption
of sodium without chloride by the tubular cell. As the movement of sodium
causes the tubule fluid to become more electronegative, some of this nega-
tive charge is lost as chloride slips between the tubule cells and is resorbed.
If the predominant anion in the tubules is not chloride, but rather a nonre-
sorbable anion, none of the negative charge is lost. If none of the negative
charge is lost, the tubule will attract more potassium.

Renal loss of ___________ can be accelerated by nonresorbable potassium


__________ in the tubular fluid. anions

Chloride normally disrupts the electrical _____________ by moving gradient


from the negative ___________ to the positive interstitium. tubule

The electrical gradient normally draws _________ into the tubule. potassium

482
S. Faubel and J. Topf 17 Introduction to Potassium

SummaryIntroduction to potassium.
Potassium is the primary intracel- The important factors which influ-
lular ion. 99% of total body potassium ence the Na-K-ATPase pump are
is located in cells. Movement of 1% of beta-2 receptor activity, insulin and
the cellular potassium to the extra- pH.
cellular compartment can cause car- Epinephrine and beta-2 selective
diac arrhythmias. drugs (e.g., albuterol) stimulate the
Na-K-ATPase pumps and can lower
+
K
plasma potassium. Beta-blockers
potassium = (e.g., metoprolol, propranolol) have
4 mEq/L
K
+
the opposite effect.
+
K

2 K+

potassium =
140 mEq/L ATP AMP ß-2
3 Na+

ATP
K+

To accomplish this tight control,


AMP
the body employs two systems for po-
tassium regulation: intracellular
buffering and renal excretion. Insulin stimulates the Na-K-ATPase
K +

pumps and causes movement of po-


tassium into cells.

K+

+
K insulin
receptor
K+
K +

ATP
Cellular redistribution is con- K+

trolled by the Na-K-ATPase pumps AMP


in the cell membrane. The Na-K-
When plasma hydrogen increases
ATPase pump maintains a high con-
(pH decreases), potassium is drawn
centration of potassium and a low
out of cells; when plasma hydrogen
concentration of sodium inside of
decreases (pH increases) potassium
cells. Factors which influence Na-K- is driven into cells.
ATPase affect the movement of po-
tassium in and out of cells.

ATP H+
K+

AMP

483
The Fluid, Electrolyte and Acid-Base Companion

SummaryIntroduction to potassium.
Cell lysis releases potassium into Plasma potassium concentration is
the plasma and can cause hyperkale- an important factor in the kidney’s
mia. handling of potassium. Increased lev-
els stimulate potassium excretion
while low levels trigger potassium
retention.
140 mEq/L

Sudden increases in cell production


cause the new cells to absorb extra-
cellular potassium, lowering the Increased distal flow increases the
plasma potassium. excretion of potassium. The increased
+
K K +
delivery of fluid maintains the con-
centration gradient in favor of potas-
sium secretion. Increased delivery of
sodium increases the resorption of
140 mEq/L sodium which maintains the electri-
cal gradient in favor of potassium
secretion.

+
K
+
K

Renal potassium excretion is


regulated by aldosterone, plasma po-
tassium concentration, and increased
distal flow.
Aldosterone is the primary hormone
involved in potassium homeostasis.
In the distal nephron, aldosterone in-
creases the production of Na-K-AT-
Pase pumps, sodium channels and
potassium channels. These all facili-
tate the excretion of potassium.

ALDOSTERONE

484

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