17 Introduction to Potassium

467

S. Faubel and J. Topf 17 Introduction to Potassium

1717 Introduction to Potassium

468

The Fluid, Electrolyte and Acid-Base Companion

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

Introduction�Potassium…the final frontier.

K+

Na+ Cl–

HCO3

–

BUNglucose

CrK+

K +

K+

K+

K+ K+

K+

K+

K+

K+

K+

K +

Potassium is the ________ intracellular cation while sodium is theprimary ___________ cation.

Disturbances in _______ concentration result in altered electrical ac-tivity which can affect the __________, muscles and nerves.

primaryextracellular

potassiumheart

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, K+ > 5.0 mEq/L.• Kaluresis: loss of potassium in the urine.

Sodium• Primary extracellular cation.

• Alterations in sodium concentra-tion affect the osmotic movementof water in and out of cells. Mostclinical symptoms are related tocerebral edema or dehydration.

Potassium• Primary intracellular cation.

• Alterations in potassium concen-tration result in electrical signalsthat interrupt normal cardiacrhythm, muscle activity and nerveconduction.

469


ATP AMP

3 Na+

2 K+K+

K +

K +

K+

Introduction�The vast majority of the total body potassium isintracellular.

When thinking about potassium physiology, two facts should always beconsidered:

• 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.

Total body water for a70 kg man is 42 liters.

14 liters isextracellular

28 liters isintracellular

Total extracellularpotassium is(14 L × 4 mEq/L).

56 mEq

Total intracellularpotassium is(28 L × 140 mEq/L).

3,920 mEq

The two central aspects of potassium physiology which must al-ways be considered are:

• The vast majority of potassium is ___________.• Small changes in the extracellular _________ concentra-

tion can have dramatic clinical consequences.

Movement of only ____ percent of the intracellular potassiumpool to the extracellular compartment can stop the _______.

aaa

intracellularpotassium

oneheart

intracellular compartmentK+ =140 mEq/L

extracellular compartmentK+ = 4 mEq/L

470


Potassium balance�Potassium balance is maintained by thecells and the kidney.

The immediate defense against a change in plasma potassiumis intracellular ____________.

The long term control of plasma potassium is the responsibilityof the _________.

tightlyaaabuffering

kidney

K +

K+

K+

Renal regulationlong-term control

The body has both an immediate and a long-term strategy to regulate theplasma 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• insulin• plasma pH

• cellular synthesis• cellular destruction• plasma potassium

Renal potassium regulation is governed by:• plasma potassium• aldosterone

• flow in the distal nephron

An understanding of these systems is necessary to comprehend the disor-ders which cause hypokalemia and hyperkalemia. The remainder of thischapter reviews the important concepts in intracellular and renal regula-tion of plasma potassium.

K +

K +

Intracellular bufferingimmediate response

471


The Na-K-ATPase pump is a membrane protein found on all cells. It isresponsible for maintaining an intracellular environment which is high inpotassium and low in sodium. The Na-K-ATPase pump is central to theability of the intracellular compartment to buffer against changes in plasmapotassium 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

Potassium balance�Cells�Cellular distribution of potassium ismaintained by Na-K-ATPase activity.

�2 K+�

ATP

AMP

3 Na+

K +K+

�potassium 140 mEq/L�

sodium 4 mEq/Lsodium 140 mEq/L�potassium 4 mEq/L

The ________ pump moves potassium into the cell and sodiumout of the cell. It is responsible for maintaining low _______ andhigh ________concentrations within the cell.

Increased Na-K-ATPase activity ________ (lowers/raises) plas-ma potassium concentration.

Na-K-ATPase activity is stimulated by ________, catechola-mines and increased plasma ___________.

Na-K-ATPasesodium

potassium

lowers

insulinpotassium

Extracellular compartment Intracellular compartment

472


Potassium balance�Cells�Activation of beta-2 receptors in-creases Na-K-ATPase activity.

�

2 K+

ATP

AMP

3 Na+

K +K+

�

ß-2 receptor

catecholamines

Catecholamines, via beta-2 receptors, stimulate Na-K-ATPase activitywhich increases the uptake of potassium into cells. The beta-2 receptorsinfluence potassium levels in three situations:

• Stress (physiologic or emotional) increases release of endogenousepinephrine. 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 inhaledin 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 treatmentof hypertension and angina. The inhibition of beta activitythrough the use of these medications can blunt the ability of cellsto absorb potassium, potentially increasing plasma potassium.

_____________ can bind to ß2-receptors and activate the Na-K-ATPase pump.

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

Catecholamines

lowerraise

Think: Beta BottomsBanana

473


Potassium balance�Cells�Insulin stimulates Na-K-ATPaseactivity, lowering plasma potassium.

The primary action of insulin is to facilitate the movement of glucose fromthe blood into cells. Insulin also affects the movement of potassium intocells. This dual action of insulin is adaptive because it compensates for boththe glucose and potassium ingested in meals.

�

2 K+

ATP

AMP

3 Na+

K +K+

�

insulin�receptor

insulin

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

Insulin causes the _______ of glucose and potassium into cells.

stimulates; cells

movement

Think: INsulin causes bothglucose and potassium to goINto cells.

474


K+

K+

The intracellular compartment buffers changes in both potassium andhydrogen concentration. Increased plasma hydrogen (↓ pH) causes cells toabsorb 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 ofacid-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 pHand potassium. Pick one and commit it to memory:

Potassium balance�Cells�Changes in pH affect the movementof potassium into and out of cells.

Think: potassium and pH alwaysmove in opposite directions.

pH causes potassium

pH causes potassium

Think: potassium and hydrogenconcentration walk together.

hydrogen causes potassium

hydrogen causes potassium

AlkalosisLow plasma hydrogen concentration causesthe cellular release of hydrogen and the resorp-tion of potassium.

AcidosisHigh plasma hydrogen concentration causesthe cellular uptake of hydrogen and the excre-tion of potassium.

Think: aLKalosis

Low K+

A drop in pH means the hydrogen concentration is _________(decreased/increased).

In acidosis, extracellular pH is partly stabilized by movementof excess _________ into cells; potassium moves out of cells inorder to maintain ________________.

increased

hydrogenelectroneutrality

475


Potassium balance�Cells�Cell destruction and cell construc-tion can dramatically affect plasma potassium concentration.

The intracellular compartment contains 99% of the body’s potassium and⅔ of total body water. Because of this, changes in cell number can alter theplasma potassium concentration. This is seen in two clinical settings:

• Massive cell destruction. Both chemotherapy and trauma cancause large-scale cell destruction and the release of intracellularpotassium, causing hyperkalemia.

• Cell production. The treatment of severe megaloblastic ane-mia with folic acid or vitamin B-12 decreases plasma potassiumas it is used to create the intracellular environment for the newred blood cells.

140 mEq/L

K+ K +

K+

K+

140 mEq/L

Cell destruction Cell synthesis

Because the majority of the body’s potassium is found in _____,changes in cell number can alter plasma _________.

Cell destruction with ____________ or trauma releases potassium,causing ___________.

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

cellspotassium

chemotherapyhyperkalemia

folate

476


Potassium balance�Kidney�Long-term potassium control is ac-complished by the resorption and selective secretion of potassium.

The kidney balances potassium intake with potassium excretion so thatK+

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 doesplasma.

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 about90% of filtered potassium.

The primary site of potassium regulation is the collecting tubule. The studyof renal potassium excretion can be focused almost exclusively on the activity ofthe collecting tubule.

The proximal tubuleresorbs potassium.

The loop of Henleresorbs potassium.

The collecting tubulesecretes potassium.

Potassium is resorbed in the _________ tubule and the ________ _______.

Potassium is _________ by the distal nephron.

The most important part of the nephron in potassium regula-tion is the _______ ________.

proximalloop of Henle

secreted

distal nephron

K +

K+

K+

K+

K+

K +

K+

477


Na+

K+

3 Na+ATP

2 K+

AMP

K+

K+= 140 mEq/L

Na+= 4 mEq/L

principle celltubular lumen

high potassiumlow potassium

low sodium

Potassium balance�Kidney�Secretion of potassium in the dis-tal nephron is a four-step process.

The positively charged po-tassium flows down bothconcentration and electricalgradients into the tubule.

Potassium secretion in the distal nephron is a multistep process whichculminates in potassium flowing down electrical and chemical (concentra-tion) gradients into the tubular fluid:

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

In the cell, the Na-K-ATPasepump keeps the potassiumconcentration high and thesodium concentration low.

Sodium flows down its con-centration gradient into thetubular cell through sodiumchannels.

The movement of the posi-tively charged sodium ionsmakes the tubular fluid nega-tively charged (electronega-tive).

The ___________ of potassium in the distal nephron depends onestablishing favorable electrical and __________ gradients.

excretionchemical

1

2

3

4

high sodium

478


Potassium balance�Kidney�Potassium handling in the distalnephron is affected by four factors.

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 factorswhich affect potassium excretion are:

mineralocorticoid activityplasma potassiumdistal flownonresorbable anions in the distal nephron

K +

K+

K+

K+

K+

K+

K+

K +

Plasma potassium

Distal flow

K+

K+

K+

Nonresorbable anions

A-

HCO3

Mineralocorticoid activity

ALDOSTERONE

The excretion of potassium in the _______ nephron is regulatedby ________ different factors.

The factors which affect potassium excretion include________________ activity, plasma potassium concentration, dis-tal flow and nonresorbable ________ in the distal nephron.

distalfour

mineralocorticoidanions

PO43

479


Potassium balance�Kidney�Aldosterone is one of the prima-ry factors which regulates potassium excretion.

In addition to its central role in volume regulation, aldosterone is an im-portant factor in potassium regulation. Increases in plasma potassium assmall as 0.1 mEq/L will cause a measurable increase in aldosterone release.Aldosterone stimulates the production of the following proteins in order toincrease potassium excretion:

Na-K-ATPase pump. Increased Na-K-ATPase activity keeps theintracellular sodium concentration low and the intracellular potas-sium concentration high.Sodium channels. The addition of sodium channels allows moresodium 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 electricalgradient into the tubule lumen.

Increased aldosterone activity ________ (decreases/increases)potassium excretion.

increases

Aldosterone increases thenumber of potassium chan-nels which facilitate the ex-cretion of potassium.

Aldosterone increases thenumber of Na-K-ATPasepumps in the basolateralmembrane.

Aldosterone increases thenumber of sodium channelswhich facilitates increasedsodium resorption.

Increased sodium resorptiondue to aldosterone increasesthe electrical gradient for po-tassium secretion.

1

2

3

4

Na+

K+

3 Na+ATP

2 K+

AMP

K+

K+= 140 mEq/L

Na+= 4 mEq/L

principle cell

480


Na+

K+

3 Na+ATP

2 K+

AMP

K+

K+= 140 mEq/L

Na+= 4 mEq/L

principle cell

Potassium balance�Kidney�Increased plasma potassium stim-ulates the excretion of potassium independent of aldosterone.

Increased plasma ___________ stimulates the excretion of potas-sium in the distal ____________.

Elevated plasma potassium stimulates the production of Na-K-ATPase pumps and __________ channels.

potassiumnephron

sodium

1

2

3

4The positively charged potas-sium flows down chemicaland electrical gradients intothe tubule.

Increased plasma potassiumconcentration increases thenumber of Na-K-ATPasepumps.

Increased plasma potassiumconcentration increases thenumber of sodium channelswhich facilitates sodium re-sorption.

Increased sodium resorptionincreases the electrical gradi-ent for potassium secretion.

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 excretionis weaker than aldosterone’s effect on potassium excretion.

481


Potassium balance�Kidney�Increased flow in the distal neph-ron leads to increased potassium excretion.

When the flow rate in the distal nephron is increased, it enhances boththe chemical and electrical gradients for potassium secretion. Increased distalflow refers to the increased delivery of water and sodium to the distal neph-ron.

Increased distal flow enhances the chemical gradient by quickly washingaway any secreted potassium. This prevents the accumulation of potassiumin 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-um and can lead to ________.

Increased flow to the distal nephron causes potassium excretion by_____ mechanisms:

• Increased sodium resorption increases the _______ gradient.

• Increased flow prevents the accumulation of potassium inthe tubule and maintains a ____________ gradient in favorof potassium excretion.

secretionhypokalemia

two

electrical

chemical

K +

K+

K+

K+

K+

K+

Increased delivery of sodium increases sodiumresorption to enhance the electrical gradient.

Increased flow of fluid quickly washes away se-creted potassium to maintain the concentrationgradient.

482


Potassium balance�Kidney�Increased nonresorbable anionsin the tubular fluid enhance potassium excretion.

Cl–Cl–

Cl–

Cl–

K+

K+

HCO3

HCO3

Na+ Na+

A-

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 resorptionof sodium without chloride by the tubular cell. As the movement of sodiumcauses 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 negativecharge is lost, the tubule will attract more potassium.

Normally, the movement of chloride decreas-es the electrical gradient and reduces potas-sium secretion.

Nonresorbable anions (including bicarbonate) inthe tubular fluid increase the electrical gradient,drawing potassium into the tubule.

Renal loss of ___________ can be accelerated by nonresorbable__________ in the tubular fluid.

Chloride normally disrupts the electrical _____________ by movingfrom the negative ___________ to the positive interstitium.

The electrical gradient normally draws _________ into the tubule.

potassiumanions

gradienttubule

potassium

483


Cellular redistribution is con-trolled by the Na-K-ATPase pumpsin the cell membrane. The Na-K-ATPase pump maintains a high con-centration of potassium and a lowconcentration of sodium inside ofcells. Factors which influence Na-K-ATPase affect the movement of po-tassium in and out of cells.

Potassium is the primary intracel-lular ion. 99% of total body potassiumis located in cells. Movement of 1% ofthe cellular potassium to the extra-cellular compartment can cause car-diac arrhythmias.

Summary�Introduction to potassium.

To accomplish this tight control,the body employs two systems for po-tassium regulation: intracellularbuffering and renal excretion.

ATP

AMP

K+

The important factors which influ-ence the Na-K-ATPase pump arebeta-2 receptor activity, insulin andpH.

Epinephrine and beta-2 selectivedrugs (e.g., albuterol) stimulate theNa-K-ATPase pumps and can lowerplasma potassium. Beta-blockers(e.g., metoprolol, propranolol) havethe opposite effect.

ATP

AMP

K+

ß-2

Insulin stimulates the Na-K-ATPasepumps and causes movement of po-tassium into cells.

When plasma hydrogen increases(pH decreases), potassium is drawnout of cells; when plasma hydrogendecreases (pH increases) potassiumis driven into cells.

H+

��

ATP AMP

3 Na+

2 K+K+

K+

K +

potassium = �140 mEq/L

potassium =�4 mEq/L

K +

K +

K +

K+

K+

ATP

AMP

K+

insulin�receptor

484


Cell lysis releases potassium intothe plasma and can cause hyperkale-mia.

Summary�Introduction to potassium.

140 mEq/L

140 mEq/L

K+ K +

K+

K+

Sudden increases in cell productioncause the new cells to absorb extra-cellular potassium, lowering theplasma potassium.

Renal potassium excretion isregulated by aldosterone, plasma po-tassium concentration, and increaseddistal flow.

Aldosterone is the primary hormoneinvolved in potassium homeostasis.In the distal nephron, aldosterone in-creases the production of Na-K-AT-Pase pumps, sodium channels andpotassium channels. These all facili-tate the excretion of potassium.

Plasma potassium concentration isan important factor in the kidney’shandling of potassium. Increased lev-els stimulate potassium excretionwhile low levels trigger potassiumretention.

Increased distal flow increases theexcretion of potassium. The increaseddelivery of fluid maintains the con-centration gradient in favor of potas-sium secretion. Increased delivery ofsodium increases the resorption ofsodium which maintains the electri-cal gradient in favor of potassiumsecretion.

ALDOSTERONE

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17 Introduction to Potassium