17 Introduction To Potassium
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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 glucose K+
Cr
K
+
K
K+
+
+
K
Na+ Cl– K+ HCO3–
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 concentration affect the osmotic movement of water in and out of cells. Most clinical symptoms are related to cerebral edema or dehydration.
• Alterations in potassium concentration result in electrical signals that interrupt normal cardiac rhythm, muscle activity and nerve conduction.
Medical Latin: • Hypokalemia: low plasma potassium,+ K < 3.5 mEq/L. • Eukalemia: normal plasma potassium, 3.5 <+K5.0 mEq/L. • Kaluresis: loss of potassium in the urine. Potassium is the ________ intracellular cation while sodium is the primary ___________ cation. Disturbances in _______ concentration result in altered electrical activity which can affect the __________, muscles and nerves.
468
primary extracellular potassium heart
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 70 kg man is 42 liters. 14 liters is extracellular
+
extracellular compartment K+ = 4 mEq/L
Total extracellular potassium is (14 L × 4 mEq/L).
56 mEq
K
+
+
K
28 liters is intracellular
2 K+
ATP AMP 3 Na+
Total intracellular potassium is (28 L × 140 mEq/L). intracellular compartment K+ =140 mEq/L
3,920 mEq
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 potassium to the extracellular compartment can stop the heart.
The two central aspects of potassium physiology which must always be considered are: • The vast majority of potassium is ___________. • Small changes in the extracellular _________ concentration can have dramatic clinical consequences. Movement of only ____ percent of the intracellular potassium pool to the extracellular compartment can stop the _______.
aaa intracellular potassium one 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 defense against a change in plasma potassium, while the kidneys control longterm potassium balance. Cells secrete potassium when plasma potassium falls; cells absorb potassium when plasma potassium rises. The secretion and absorption of potassium by cells is referred to as buffering. The kidneys affect long-term potassium balance through the excretion and resorption of potassium. Cellular control of potassium movement is influenced by: • cellular synthesis • catecholamines • cellular destruction • insulin • plasma potassium • plasma pH Renal potassium regulation is governed by: • plasma potassium • flow in the distal nephron • aldosterone An understanding of these systems is necessary to comprehend the disorders which cause hypokalemia and hyperkalemia. The remainder of this chapter reviews the important concepts in intracellular and renal regulation of plasma potassium. The immediate defense against a change in plasma potassium is intracellular ____________. The long term control of plasma potassium is the responsibility of the _________.
470
tightlyaaa buffering kidney
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 4 mEq/L
potassium 140 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 concentration, and decreased activity raises plasma potassium concentration. Na-KATPase activity is stimulated by: • catecholamines • insulin • increased plasma potassium
The ________ pump moves potassium into the cell and sodium out of the cell. It is responsible for maintaining low _______ and high ________concentrations within the cell. Increased Na-K-ATPase activity ________ (lowers/raises) plasma potassium concentration. Na-K-ATPase activity is stimulated by ________, catecholamines and increased plasma ___________.
Na-K-ATPase sodium potassium lowers insulin potassium
471
The Fluid, Electrolyte and Acid-Base Companion
Potassium balanceCellsActivation of beta-2 receptors increases Na-K-ATPase activity.
catecholamines
K+
K
+
2 K+
ß-2 receptor
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 transiently drop plasma potassium. • Beta-agonists are primarily used in the treatment of bronchoconstriction (e.g., asthma). Beta-agonists like albuterol are inhaled in order to open constricted bronchioles. A side effect of betaagonists 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-KATPase pump. Stress and beta-agonists can ___________ (lower/raise) plasma potassium, while beta-blockers can _________ (lower/raise) plasma potassium.
472
Catecholamines lower raise
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 3 Na+
Think: INsulin causes both glucose and potassium to go 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 ______. Insulin causes the _______ of glucose and potassium into cells.
stimulates; cells movement
473
The Fluid, Electrolyte and Acid-Base Companion
K+
Potassium balanceCellsChanges in pH affect the movement of potassium into and out of cells.
K+
Acidosis
Alkalosis
High plasma hydrogen concentration causes the cellular uptake of hydrogen and the excretion of potassium.
Low plasma hydrogen concentration causes the cellular release of hydrogen and the resorption 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 concentration (↑ pH) causes cells to secrete hydrogen and absorb potassium. The movement of hydrogen and potassium are linked to maintain electroneutrality. The effect of pH on plasma potassium varies depending on the type of acid-base disorder. For example, plasma potassium does not change in respiratory acidosis and changes only minimally in lactic acidosis and ketoacidosis. Below are various mnemonics to remember the relationship between pH and potassium. Pick one and commit it to memory: Think: potassium and pH always move in opposite directions.
Think: aLKalosis
Think: potassium and hydrogen 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 _________ (decreased/increased). In acidosis, extracellular pH is partly stabilized by movement of excess _________ into cells; potassium moves out of cells in order to maintain ________________.
474
increased
hydrogen electroneutrality
S. Faubel and J. Topf
17 Introduction to Potassium
Potassium balanceCellsCell destruction and cell construction 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 anemia 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 _____, 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 during the treatment of megaloblastic anemia with _______ or B-12.
cells potassium chemotherapy hyperkalemia folate
475
The Fluid, Electrolyte and Acid-Base Companion
Potassium balanceKidneyLong-term potassium control is accomplished by the resorption and selective secretion of potassium.
K
The proximal tubule resorbs potassium.
+
The collecting tubule 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 proximal tubule, the loop of Henle and the distal nephron. +
Potassium, like all electrolytes, is freely filtered at the glomerulus. Initially, the tubular fluid has the same concentration of potassium as does plasma. In the proximal tubule, bulk resorption of potassium occurs without regard for the potassium status of the body. The loop of Henle resorbs potassium 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 ______ __ _______. Potassium is _________ by the distal nephron. The most important part of the nephron in potassium regulation is the _______ ________.
476
proximal loop of Henle secreted distal nephron
S. Faubel and J. Topf
17 Introduction to Potassium
Potassium balanceKidneySecretion of potassium in the distal nephron is a four-step process. tubular lumen
1 2
In the cell, the Na-K-ATPase pump keeps the potassium concentration high and the sodium concentration low. Sodium flows down its concentration gradient into the tubular cell through sodium channels.
4
K+= 140 mEq/L
ATP 3 Na+
Na+= 4 mEq/L
AMP
2 K+
Na+ high sodium
3
principle cell
low sodium
The movement of the positively charged sodium ions makes the tubular fluid negatively charged (electronegative).
The positively charged potassium flows down both concentration and electrical gradients into the tubule.
+
K
K+ low potassium
high potassium
Potassium secretion in the distal nephron is a multistep process which culminates in potassium flowing down electrical and chemical (concentration) 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 potassium secretion. Step three: the movement of positively charged sodium into the tubular cell without an associated anion creates an electrical gradient 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 establishing favorable electrical and __________ gradients.
excretion 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
Nonresorbable anions
A-
K+
K
+
+
K
PO4 3 +
K
+
K
HCO3
K+
Because it is in charge of fine-tuning the excretion of potassium, the distal 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 by ________ different factors. The factors which affect potassium excretion include ________________ activity, plasma potassium concentration, distal flow and nonresorbable ________ in the distal nephron.
478
distal four mineralocorticoid anions
S. Faubel and J. Topf
17 Introduction to Potassium
Potassium balanceKidneyAldosterone is one of the primary factors which regulates potassium excretion. principle cell
1 2
3
4
Aldosterone increases the number of Na-K-ATPase pumps in the basolateral membrane. Aldosterone increases the number of sodium channels which facilitates increased sodium resorption.
K+= 140 mEq/L
ATP 3 Na+
Na+= 4 mEq/L
AMP
2 K+
Na+
Increased sodium resorption due to aldosterone increases the electrical gradient for potassium secretion. Aldosterone increases the number of potassium channels which facilitate the excretion of potassium.
+
K
K+
In addition to its central role in volume regulation, aldosterone is an important 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 potassium concentration high. Sodium channels. The addition of sodium channels allows more sodium to enter the tubular cell. This increases the electrical gradient across the tubular wall which enhances excretion of potassium. Potassium channels. The addition of potassium channels facilitates the movement of potassium down its chemical and electrical gradient into the tubule lumen.
Increased aldosterone activity ________ (decreases/increases) potassium excretion.
increases
479
The Fluid, Electrolyte and Acid-Base Companion
Potassium balanceKidneyIncreased plasma potassium stimulates the excretion of potassium independent of aldosterone. principle cell
1 2
3
Increased plasma potassium concentration increases the number of Na-K-ATPase pumps. Increased plasma potassium concentration increases the number of sodium channels which facilitates sodium resorption.
K+= 140 mEq/L
ATP 3 Na+
Na+= 4 mEq/L
AMP
2 K+
Na+
Increased sodium resorption increases the electrical gradient for potassium secretion.
+
4
The positively charged potassium flows down chemical and electrical gradients into the tubule.
K
K+
Increased plasma potassium directly stimulates the secretion of potassium into the tubule. This effect of potassium is independent of aldosterone. Increased plasma potassium increases Na-K-ATPase activity and the number 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 potassium in the distal ____________. Elevated plasma potassium stimulates the production of Na-KATPase pumps and __________ channels.
480
potassium nephron sodium
S. Faubel and J. Topf
17 Introduction to Potassium
Potassium balanceKidneyIncreased flow in the distal nephron leads to increased potassium excretion.
K
+
+
K K+ +
K
+
K
+
K
Increased flow of fluid quickly washes away secreted potassium to maintain the concentration gradient.
Increased delivery of sodium increases sodium resorption to enhance the electrical 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 nephron. 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 resorption and enhances the electrical gradient, favoring potassium excretion.
Increased flow in the distal nephron enhances ________ of potassium and can lead to ________.
secretion 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 of potassium excretion.
chemical
481
The Fluid, Electrolyte and Acid-Base Companion
Potassium balanceKidneyIncreased nonresorbable anions in the tubular fluid enhance potassium excretion.
Na+
Na+ A-
Cl–
Cl–
HCO3 HCO3
Cl–
Cl–
K+
+
K
Normally, the movement of chloride decreases the electrical gradient and reduces potassium secretion.
Nonresorbable anions (including bicarbonate) in the tubular fluid increase the electrical gradient, drawing potassium into the tubule.
Increased nonresorbable anions in the distal nephron increase the electrical gradient for the secretion of potassium. Normally, the tubule fluid is negatively charged and attracts the positively 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 negative 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 nonresorbable 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 __________ in the tubular fluid. Chloride normally disrupts the electrical _____________ by moving from the negative ___________ to the positive interstitium. The electrical gradient normally draws _________ into the tubule.
482
potassium anions gradient tubule potassium
S. Faubel and J. Topf
17 Introduction to Potassium
SummaryIntroduction to potassium.
K
+
Potassium is the primary intracellular ion. 99% of total body potassium is located in cells. Movement of 1% of the cellular potassium to the extracellular compartment can cause cardiac arrhythmias.
+
K
+
K
potassium = 4 mEq/L
2 K+
potassium = 140 mEq/L
The important factors which influence the Na-K-ATPase pump are beta-2 receptor activity, insulin and pH. Epinephrine and beta-2 selective drugs (e.g., albuterol) stimulate the Na-K-ATPase pumps and can lower plasma potassium. Beta-blockers (e.g., metoprolol, propranolol) have the opposite effect.
ATP AMP
ß-2
3 Na+
ATP K+
To accomplish this tight control, AMP the body employs two systems for potassium regulation: intracellular buffering and renal excretion. Insulin stimulates the Na-K-ATPase pumps and causes movement of potassium into cells. K
+
K+
insulin receptor
+
K
K+
K
+
ATP
Cellular redistribution is controlled by the Na-K-ATPase pumps in the cell membrane. The Na-KATPase pump maintains a high concentration of potassium and a low concentration of sodium inside of cells. Factors which influence Na-KATPase affect the movement of potassium in and out of cells.
ATP
K+
AMP
When plasma hydrogen increases (pH decreases), potassium is drawn out of cells; when plasma hydrogen decreases (pH increases) potassium is driven into cells.
H+
K+
AMP
483
The Fluid, Electrolyte and Acid-Base Companion
SummaryIntroduction to potassium. Cell lysis releases potassium into the plasma and can cause hyperkalemia.
Plasma potassium concentration is an important factor in the kidney’s handling of potassium. Increased levels stimulate potassium excretion while low levels trigger potassium retention.
140 mEq/L
Sudden increases in cell production cause the new cells to absorb extracellular potassium, lowering the plasma potassium. +
K
K
+
140 mEq/L
+
K
+
K
Renal potassium excretion is regulated by aldosterone, plasma potassium concentration, and increased distal flow. Aldosterone is the primary hormone involved in potassium homeostasis. In the distal nephron, aldosterone increases the production of Na-K-ATPase pumps, sodium channels and potassium channels. These all facilitate the excretion of potassium.
ALDOSTERONE
484
Increased distal flow increases the excretion of potassium. The increased delivery of fluid maintains the concentration gradient in favor of potassium secretion. Increased delivery of sodium increases the resorption of sodium which maintains the electrical gradient in favor of potassium secretion.
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 glucose K+
Cr
K
+
K
K+
+
+
K
Na+ Cl– K+ HCO3–
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 concentration affect the osmotic movement of water in and out of cells. Most clinical symptoms are related to cerebral edema or dehydration.
• Alterations in potassium concentration result in electrical signals that interrupt normal cardiac rhythm, muscle activity and nerve conduction.
Medical Latin: • Hypokalemia: low plasma potassium,+ K < 3.5 mEq/L. • Eukalemia: normal plasma potassium, 3.5 <+
468
primary extracellular potassium heart
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 70 kg man is 42 liters. 14 liters is extracellular
+
extracellular compartment K+ = 4 mEq/L
Total extracellular potassium is (14 L × 4 mEq/L).
56 mEq
K
+
+
K
28 liters is intracellular
2 K+
ATP AMP 3 Na+
Total intracellular potassium is (28 L × 140 mEq/L). intracellular compartment K+ =140 mEq/L
3,920 mEq
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 potassium to the extracellular compartment can stop the heart.
The two central aspects of potassium physiology which must always be considered are: • The vast majority of potassium is ___________. • Small changes in the extracellular _________ concentration can have dramatic clinical consequences. Movement of only ____ percent of the intracellular potassium pool to the extracellular compartment can stop the _______.
aaa intracellular potassium one 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 defense against a change in plasma potassium, while the kidneys control longterm potassium balance. Cells secrete potassium when plasma potassium falls; cells absorb potassium when plasma potassium rises. The secretion and absorption of potassium by cells is referred to as buffering. The kidneys affect long-term potassium balance through the excretion and resorption of potassium. Cellular control of potassium movement is influenced by: • cellular synthesis • catecholamines • cellular destruction • insulin • plasma potassium • plasma pH Renal potassium regulation is governed by: • plasma potassium • flow in the distal nephron • aldosterone An understanding of these systems is necessary to comprehend the disorders which cause hypokalemia and hyperkalemia. The remainder of this chapter reviews the important concepts in intracellular and renal regulation of plasma potassium. The immediate defense against a change in plasma potassium is intracellular ____________. The long term control of plasma potassium is the responsibility of the _________.
470
tightlyaaa buffering kidney
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 4 mEq/L
potassium 140 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 concentration, and decreased activity raises plasma potassium concentration. Na-KATPase activity is stimulated by: • catecholamines • insulin • increased plasma potassium
The ________ pump moves potassium into the cell and sodium out of the cell. It is responsible for maintaining low _______ and high ________concentrations within the cell. Increased Na-K-ATPase activity ________ (lowers/raises) plasma potassium concentration. Na-K-ATPase activity is stimulated by ________, catecholamines and increased plasma ___________.
Na-K-ATPase sodium potassium lowers insulin potassium
471
The Fluid, Electrolyte and Acid-Base Companion
Potassium balanceCellsActivation of beta-2 receptors increases Na-K-ATPase activity.
catecholamines
K+
K
+
2 K+
ß-2 receptor
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 transiently drop plasma potassium. • Beta-agonists are primarily used in the treatment of bronchoconstriction (e.g., asthma). Beta-agonists like albuterol are inhaled in order to open constricted bronchioles. A side effect of betaagonists 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-KATPase pump. Stress and beta-agonists can ___________ (lower/raise) plasma potassium, while beta-blockers can _________ (lower/raise) plasma potassium.
472
Catecholamines lower raise
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 3 Na+
Think: INsulin causes both glucose and potassium to go 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 ______. Insulin causes the _______ of glucose and potassium into cells.
stimulates; cells movement
473
The Fluid, Electrolyte and Acid-Base Companion
K+
Potassium balanceCellsChanges in pH affect the movement of potassium into and out of cells.
K+
Acidosis
Alkalosis
High plasma hydrogen concentration causes the cellular uptake of hydrogen and the excretion of potassium.
Low plasma hydrogen concentration causes the cellular release of hydrogen and the resorption 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 concentration (↑ pH) causes cells to secrete hydrogen and absorb potassium. The movement of hydrogen and potassium are linked to maintain electroneutrality. The effect of pH on plasma potassium varies depending on the type of acid-base disorder. For example, plasma potassium does not change in respiratory acidosis and changes only minimally in lactic acidosis and ketoacidosis. Below are various mnemonics to remember the relationship between pH and potassium. Pick one and commit it to memory: Think: potassium and pH always move in opposite directions.
Think: aLKalosis
Think: potassium and hydrogen 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 _________ (decreased/increased). In acidosis, extracellular pH is partly stabilized by movement of excess _________ into cells; potassium moves out of cells in order to maintain ________________.
474
increased
hydrogen electroneutrality
S. Faubel and J. Topf
17 Introduction to Potassium
Potassium balanceCellsCell destruction and cell construction 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 anemia 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 _____, 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 during the treatment of megaloblastic anemia with _______ or B-12.
cells potassium chemotherapy hyperkalemia folate
475
The Fluid, Electrolyte and Acid-Base Companion
Potassium balanceKidneyLong-term potassium control is accomplished by the resorption and selective secretion of potassium.
K
The proximal tubule resorbs potassium.
+
The collecting tubule 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 proximal tubule, the loop of Henle and the distal nephron. +
Potassium, like all electrolytes, is freely filtered at the glomerulus. Initially, the tubular fluid has the same concentration of potassium as does plasma. In the proximal tubule, bulk resorption of potassium occurs without regard for the potassium status of the body. The loop of Henle resorbs potassium 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 ______ __ _______. Potassium is _________ by the distal nephron. The most important part of the nephron in potassium regulation is the _______ ________.
476
proximal loop of Henle secreted distal nephron
S. Faubel and J. Topf
17 Introduction to Potassium
Potassium balanceKidneySecretion of potassium in the distal nephron is a four-step process. tubular lumen
1 2
In the cell, the Na-K-ATPase pump keeps the potassium concentration high and the sodium concentration low. Sodium flows down its concentration gradient into the tubular cell through sodium channels.
4
K+= 140 mEq/L
ATP 3 Na+
Na+= 4 mEq/L
AMP
2 K+
Na+ high sodium
3
principle cell
low sodium
The movement of the positively charged sodium ions makes the tubular fluid negatively charged (electronegative).
The positively charged potassium flows down both concentration and electrical gradients into the tubule.
+
K
K+ low potassium
high potassium
Potassium secretion in the distal nephron is a multistep process which culminates in potassium flowing down electrical and chemical (concentration) 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 potassium secretion. Step three: the movement of positively charged sodium into the tubular cell without an associated anion creates an electrical gradient 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 establishing favorable electrical and __________ gradients.
excretion 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
Nonresorbable anions
A-
K+
K
+
+
K
PO4 3 +
K
+
K
HCO3
K+
Because it is in charge of fine-tuning the excretion of potassium, the distal 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 by ________ different factors. The factors which affect potassium excretion include ________________ activity, plasma potassium concentration, distal flow and nonresorbable ________ in the distal nephron.
478
distal four mineralocorticoid anions
S. Faubel and J. Topf
17 Introduction to Potassium
Potassium balanceKidneyAldosterone is one of the primary factors which regulates potassium excretion. principle cell
1 2
3
4
Aldosterone increases the number of Na-K-ATPase pumps in the basolateral membrane. Aldosterone increases the number of sodium channels which facilitates increased sodium resorption.
K+= 140 mEq/L
ATP 3 Na+
Na+= 4 mEq/L
AMP
2 K+
Na+
Increased sodium resorption due to aldosterone increases the electrical gradient for potassium secretion. Aldosterone increases the number of potassium channels which facilitate the excretion of potassium.
+
K
K+
In addition to its central role in volume regulation, aldosterone is an important 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 potassium concentration high. Sodium channels. The addition of sodium channels allows more sodium to enter the tubular cell. This increases the electrical gradient across the tubular wall which enhances excretion of potassium. Potassium channels. The addition of potassium channels facilitates the movement of potassium down its chemical and electrical gradient into the tubule lumen.
Increased aldosterone activity ________ (decreases/increases) potassium excretion.
increases
479
The Fluid, Electrolyte and Acid-Base Companion
Potassium balanceKidneyIncreased plasma potassium stimulates the excretion of potassium independent of aldosterone. principle cell
1 2
3
Increased plasma potassium concentration increases the number of Na-K-ATPase pumps. Increased plasma potassium concentration increases the number of sodium channels which facilitates sodium resorption.
K+= 140 mEq/L
ATP 3 Na+
Na+= 4 mEq/L
AMP
2 K+
Na+
Increased sodium resorption increases the electrical gradient for potassium secretion.
+
4
The positively charged potassium flows down chemical and electrical gradients into the tubule.
K
K+
Increased plasma potassium directly stimulates the secretion of potassium into the tubule. This effect of potassium is independent of aldosterone. Increased plasma potassium increases Na-K-ATPase activity and the number 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 potassium in the distal ____________. Elevated plasma potassium stimulates the production of Na-KATPase pumps and __________ channels.
480
potassium nephron sodium
S. Faubel and J. Topf
17 Introduction to Potassium
Potassium balanceKidneyIncreased flow in the distal nephron leads to increased potassium excretion.
K
+
+
K K+ +
K
+
K
+
K
Increased flow of fluid quickly washes away secreted potassium to maintain the concentration gradient.
Increased delivery of sodium increases sodium resorption to enhance the electrical 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 nephron. 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 resorption and enhances the electrical gradient, favoring potassium excretion.
Increased flow in the distal nephron enhances ________ of potassium and can lead to ________.
secretion 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 of potassium excretion.
chemical
481
The Fluid, Electrolyte and Acid-Base Companion
Potassium balanceKidneyIncreased nonresorbable anions in the tubular fluid enhance potassium excretion.
Na+
Na+ A-
Cl–
Cl–
HCO3 HCO3
Cl–
Cl–
K+
+
K
Normally, the movement of chloride decreases the electrical gradient and reduces potassium secretion.
Nonresorbable anions (including bicarbonate) in the tubular fluid increase the electrical gradient, drawing potassium into the tubule.
Increased nonresorbable anions in the distal nephron increase the electrical gradient for the secretion of potassium. Normally, the tubule fluid is negatively charged and attracts the positively 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 negative 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 nonresorbable 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 __________ in the tubular fluid. Chloride normally disrupts the electrical _____________ by moving from the negative ___________ to the positive interstitium. The electrical gradient normally draws _________ into the tubule.
482
potassium anions gradient tubule potassium
S. Faubel and J. Topf
17 Introduction to Potassium
SummaryIntroduction to potassium.
K
+
Potassium is the primary intracellular ion. 99% of total body potassium is located in cells. Movement of 1% of the cellular potassium to the extracellular compartment can cause cardiac arrhythmias.
+
K
+
K
potassium = 4 mEq/L
2 K+
potassium = 140 mEq/L
The important factors which influence the Na-K-ATPase pump are beta-2 receptor activity, insulin and pH. Epinephrine and beta-2 selective drugs (e.g., albuterol) stimulate the Na-K-ATPase pumps and can lower plasma potassium. Beta-blockers (e.g., metoprolol, propranolol) have the opposite effect.
ATP AMP
ß-2
3 Na+
ATP K+
To accomplish this tight control, AMP the body employs two systems for potassium regulation: intracellular buffering and renal excretion. Insulin stimulates the Na-K-ATPase pumps and causes movement of potassium into cells. K
+
K+
insulin receptor
+
K
K+
K
+
ATP
Cellular redistribution is controlled by the Na-K-ATPase pumps in the cell membrane. The Na-KATPase pump maintains a high concentration of potassium and a low concentration of sodium inside of cells. Factors which influence Na-KATPase affect the movement of potassium in and out of cells.
ATP
K+
AMP
When plasma hydrogen increases (pH decreases), potassium is drawn out of cells; when plasma hydrogen decreases (pH increases) potassium is driven into cells.
H+
K+
AMP
483
The Fluid, Electrolyte and Acid-Base Companion
SummaryIntroduction to potassium. Cell lysis releases potassium into the plasma and can cause hyperkalemia.
Plasma potassium concentration is an important factor in the kidney’s handling of potassium. Increased levels stimulate potassium excretion while low levels trigger potassium retention.
140 mEq/L
Sudden increases in cell production cause the new cells to absorb extracellular potassium, lowering the plasma potassium. +
K
K
+
140 mEq/L
+
K
+
K
Renal potassium excretion is regulated by aldosterone, plasma potassium concentration, and increased distal flow. Aldosterone is the primary hormone involved in potassium homeostasis. In the distal nephron, aldosterone increases the production of Na-K-ATPase pumps, sodium channels and potassium channels. These all facilitate the excretion of potassium.
ALDOSTERONE
484
Increased distal flow increases the excretion of potassium. The increased delivery of fluid maintains the concentration gradient in favor of potassium secretion. Increased delivery of sodium increases the resorption of sodium which maintains the electrical gradient in favor of potassium secretion.
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