71: Regulation of Plasma Potassium

Question 1

K+ is the most abundant ____cellular cation.

Intracellular K+ is a reservoir serving to maintain plasma [K+] in the normal range.

[K+] participates in pH regulation: when protons go up in acidosis (pH down) protons move ____ cells down their gradient and potassium moves ____ of cells down their gradient.

Potassium Is the most abundant intracellular cation because of the presence and function of the ion-translocating “pump”, Na/K ATPase, in the plasma membrane of virtually all cells.

Answer 1

K+ is the most abundant intracellular cation.

Intracellular K+ is a reservoir serving to maintain plasma [K+] in the normal range.

[K+] participates in pH regulation: when protons go up in acidosis (pH down) protons move into cells down their gradient and potassium moves out of cells down their gradient.

Potassium Is the most abundant intracellular cation because of the presence and function of the ion-translocating “pump”, Na/K ATPase, in the plasma membrane of virtually all cells.

Question 2

In excitable tissues (cardiac, neural, muscle), cellular membrane K+ currents are central to the property of “excitability” defining these specialized tissues.

K+ current is the charge “carried” by the movement of the cation, K+, across the cell membrane and K+ current across the cell membrane may arise from passive, protein mediated transport, through “channels”, or by “simple diffusion” through the plasma membrane lipid bilayer, which is ____ protein mediated.

The positive charge carried out of the cell by K+ current through membrane channels is the dominant ionic current determining the inside-____ cell membrane potential difference.

Answer 2

In excitable tissues (cardiac, neural, muscle), cellular membrane K+ currents are central to the property of “excitability” defining these specialized tissues.

K+ current is the charge “carried” by the movement of the cation, K+, across the cell membrane and K+ current across the cell membrane may arise from passive, protein mediated transport, through “channels”, or by “simple diffusion” through the plasma membrane lipid bilayer, which is not protein mediated.

The positive charge carried out of the cell by K+ current through membrane channels is the dominant ionic current determining the inside-negative cell membrane potential difference.

Question 3

HYPERKALEMIA: high plasma K

plasma [K+] above 5.0 mM

____ outwardly directed K gradient

resting membrane potential ____

muscle ____

cardiac conduction ____: ventricular arrhythmia and fibrillation

metabolic acidosis cause K goes ____ the cell and proton comes ____ of the cell, which adds acid (H+) to the plasma.

Answer 3

HYPERKALEMIA: high plasma K

plasma [K+] above 5.0 mM

decreases outwardly directed K gradient

resting membrane potential depolarized

muscle hyperexcitability

cardiac conduction disturbances: ventricular arrhythmia and fibrillation

metabolic acidosis cause K goes into the cell and proton comes out of the cell, which adds acid (H+) to the plasma.

Question 4

HYPOKALEMIA: low plasma K

Plasma [K+] below 3.5 mM

____ outwardly directed K gradient

resting membrane potential ____

muscle ____excitability

cardiac pacemaker disturbance: arrhythmias

metabolic ____osis

Answer 4

HYPOKALEMIA: low plasma K

Plasma [K+] below 3.5 mM

increases outwardly directed K gradient

resting membrane potential hyperpolarized

muscle hypoexcitability

cardiac pacemaker disturbance: arrhythmias

metabolic alkalosis

Question 5

External K+ balance is gastro-intestinal K+ uptake into the body ( typically 100 mMoles/day) balanced by renal (90 mMoles/day) and fecal (10 mMoles/day) removal of K+ from the body.

The regulatory role of the ____ is essential for maintaining K+ balance and preventing variable increases or decreases in plasma [K+] above or below the normal range.

The “renal handling” of K+ is:

K+ excreted in the urine = ____

Answer 5

External K+ balance is gastro-intestinal K+ uptake into the body ( typically 100 mMoles/day) balanced by renal (90 mMoles/day) and fecal (10 mMoles/day) removal of K+ from the body.

The regulatory role of the kidney is essential for maintaining K+ balance and preventing variable increases or decreases in plasma [K+] above or below the normal range.

The “renal handling” of K+ is:

K+ excreted in the urine = K+ filtered at the glomerulus – K+ reabsorbed + K+ secreted

Amount of K+ excreted in the urine = amount of K+ filtered at the glomerulus – amount of K+ reabsorbed in the different segments of the nephron + amount of K+ secreted in the different segments of the nephron

Question 6

The most common challenge to maintaining K+ balance is consumption of ____ K+ because the food consumed in our diets arises, in large part, from plant and animal cells, which contain high intracellular concentrations of K+. The release of intracellular K+ from the cells of diseased or injured tissues is also a possible source of increased extracellular K+ , which must be compensated for.

Translocation and sequestration of K+ into cells, mediated by the ____ase, is the first line of defense against a K+ load and rise in plasma [K+]. Insulin, epinephrine, and aldosterone promote an increased cellular ____ of K+ and a shift of K+ from the extracellular fluid into cells. These hormones induce “de novo” ____ of Na/K-ATPase and induce fusion of intracellular membrane vesicles, populated with Na/K-ATPase, with the plasma membrane, thus introducing a greater capacity for intracellular ____ and sequestration of K+.

Interestingly, red blood cells ____ a cell nucleus and the capacity for protein synthesis necessary to respond to insulin, epinephrine, and aldosterone by increasing plasma membrane Na/K-ATPase activity. Consequently, RBC’s do ____ participate in the cellular regulatory response induced by insulin, epinephrine, and aldosterone .

The dysregulation of insulin release and circulating levels of insulin in poorly controlled diabetes mellitus may compromise the tolerance of diabetes patients to a K+ load and predispose them to ____kalemia.

____ stimulates the Na/K ATPase and gets K into the cell to fight against hyperkalemia.

Answer 6

The most common challenge to maintaining K+ balance is consumption of excess K+ because the food consumed in our diets arises, in large part, from plant and animal cells, which contain high intracellular concentrations of K+. The release of intracellular K+ from the cells of diseased or injured tissues is also a possible source of increased extracellular K+ , which must be compensated for.

Translocation and sequestration of K+ into cells, mediated by the Na/K-ATPase, is the first line of defense against a K+ load and rise in plasma [K+]. Insulin, epinephrine, and aldosterone promote an increased cellular uptake of K+ and a shift of K+ from the extracellular fluid into cells. These hormones induce “de novo” synthesis of Na/K-ATPase and induce fusion of intracellular membrane vesicles, populated with Na/K-ATPase, with the plasma membrane, thus introducing a greater capacity for intracellular uptake and sequestration of K+.

Interestingly, red blood cells lack a cell nucleus and the capacity for protein synthesis necessary to respond to insulin, epinephrine, and aldosterone by increasing plasma membrane Na/K-ATPase activity. Consequently, RBC’s do not participate in the cellular regulatory response induced by insulin, epinephrine, and aldosterone .

The dysregulation of insulin release and circulating levels of insulin in poorly controlled diabetes mellitus may compromise the tolerance of diabetes patients to a K+ load and predispose them to hyperkalemia.

Aldosterone stimulates the Na/K ATPase and gets K into the cell to fight against hyperkalemia.

Question 7

An increase in extracellular H+ concentration (acidemia) will induce a shift in intra- and extracellular K+ distribution resulting from cellular ____ of H+ and cellular ____ of K+. In this instance, a consequence of this H+ for K+ exchange is an increase in plasma K+ (hyperkalemia) resulting from an effective shift of K+ from the intracellular to the extracellular fluid compartment.

A decrease in extracellular H+ concentration (alkalemia) will induce a shift in intra- and extracellular K+ distribution resulting from cellular ____ of H+ and cellular ____ of K+. In this instance, a consequence of this H+ for K+ exchange is a decrease in plasma K+ (hypokalemia), resulting from an effective shift of K+ from the extracellular to the intracellular fluid compartment.

The cellular mechanism mediating the effective H+ for K+ exchange arises from an effect of intracellular H+ on the transport activity of the ____ATPase as well as the ____ co-transporter.

Answer 7

An increase in extracellular H+ concentration (acidemia) will induce a shift in intra- and extracellular K+ distribution resulting from cellular uptake of H+ and cellular efflux of K+. In this instance, a consequence of this H+ for K+ exchange is an increase in plasma K+ (hyperkalemia) resulting from an effective shift of K+ from the intracellular to the extracellular fluid compartment.

A decrease in extracellular H+ concentration (alkalemia) will induce a shift in intra- and extracellular K+ distribution resulting from cellular efflux of H+ and cellular uptake of K+. In this instance, a consequence of this H+ for K+ exchange is a decrease in plasma K+ (hypokalemia), resulting from an effective shift of K+ from the extracellular to the intracellular fluid compartment.

The cellular mechanism mediating the effective H+ for K+ exchange arises from an effect of intracellular H+ on the transport activity of the Na/K-ATPase as well as the Na/K/Cl co-transporter.

Question 8

Regulation of K+ balance does ____ occur by limiting uptake from the gastro-intestinal tract and most of K+ consumed is absorbed from the gastro-intestinal tract.

Answer 8

Regulation of K+ balance does NOT occur by limiting uptake from the gastro-intestinal tract and most of K+ consumed is absorbed from the gastro-intestinal tract.

Question 9

Following an acute increase in plasma K+ concentration, whether from K+ consumed or otherwise, the increase in plasma K+ concentration is most likely detected as a change in membrane potential in cells which respond, within minutes, by (1) release of ____ from the adrenal cortex, by (2) release of ____ from the adrenal medulla and by (3) ____ of insulin from the pancreas.

The rapid increase in circulating levels of these hormones induce cells to increase K+ ____ and the acute rise in plasma K+ is mitigated and is nearly completely reversed within an hour. In contrast to the rapid buffering of an increase in plasma K+ concentration by cellular uptake, the ultimate correction in K+ balance occurs more slowly by increasing the renal excretion of K+ in the urine over a period of several hours.

Answer 9

Following an acute increase in plasma K+ concentration, whether from K+ consumed or otherwise, the increase in plasma K+ concentration is most likely detected as a change in membrane potential in cells which respond, within minutes, by (1) release of aldosterone from the adrenal cortex, by (2) release of epinephrine from the adrenal medulla and by (3) release of insulin from the pancreas.

The rapid increase in circulating levels of these hormones induce cells to increase K+ uptake and the acute rise in plasma K+ is mitigated and is nearly completely reversed within an hour. In contrast to the rapid buffering of an increase in plasma K+ concentration by cellular uptake, the ultimate correction in K+ balance occurs more slowly by increasing the renal excretion of K+ in the urine over a period of several hours.

Question 10

The “renal handling” of K+ is:

K+ excreted = ____

Most of filtered K+( ≈ 80%) is reabsorbed “constitutively (unregulated)” in the ____ tubule, where reabsorption is constant (not regulated) at low, normal or high plasma K+ levels

Renal excretion of K+ is regulated in the ____ nephron nephron (late distal tubule and cortical collecting duct), which may reabsorb or secrete K+, depending on K+ balance and plasma K+ levels

Answer 10

The “renal handling” of K+ is:

K+ excreted = K+ filtered – K+ reabsorbed + K+ secreted

Most of filtered K+( ≈ 80%) is reabsorbed “constitutively (unregulated)” in the proximal tubule, where reabsorption is constant (not regulated) at low, normal or high plasma K+ levels

Renal excretion of K+ is regulated in the distal nephron nephron (late distal tubule and cortical collecting duct), which may reabsorb or secrete K+, depending on K+ balance and plasma K+ levels

Question 11

• 90% of filtered K+ is absorbed by the ____ tubule and Loop of Henle regardless of dietary K+ intake and K+ balance (positive or negative).
• When K+ balance is negative at low levels of dietary K+ intake and plasma K+, increased K+ ____ in the distal nephron restores K+ balance.
• Despite a compensating increase in K+ reabsorption by the distal nephron, ____ kalemia may result from chronic dietary K+ deficiency. (K+ clearance is low)

Answer 11

• 90% of filtered K+ is absorbed by the proximal tubule and Loop of Henle regardless of dietary K+ intake and K+ balance (positive or negative).
• When K+ balance is negative at low levels of dietary K+ intake and plasma K+, increased K+ reabsorption in the distal nephron restores K+ balance.
• Despite a compensating increase in K+ reabsorption by the distal nephron, hypokalemia may result from chronic dietary K+ deficiency. (K+ clearance is low)

Question 12

• When K+ balance is positive at high levels of dietary K+ intake and plasma K+, ____ K+ reabsorption as well as K+ secretion in the distal nephron restores K+ balance.
• ____ of K+ by the distal nephron may increase to levels sufficient to increase K+ excretion to 10 – 150% of the filtered load. (K+ clearance is high)

We can secrete ____ and decrease its reabsorption. We can only decrease reabsorption of ____, not secrete it. This is because we are constantly eating potassium because many of the foods we eat are high in potassium (& not in sodium).

Answer 12

• When K+ balance is positive at high levels of dietary K+ intake and plasma K+, decreased K+ reabsorption as well as K+ secretion in the distal nephron restores K+ balance.
• Secretion of K+ by the distal nephron may increase to levels sufficient to increase K+ excretion to 10 – 150% of the filtered load. (K+ clearance is high)

We can secrete potassium and decrease its reabsorption. We can only decrease reabsorption of sodium, not secrete it. This is because we are constantly eating potassium because many of the foods we eat are high in potassium (& not in sodium).

Question 13

The “filtered load” of K+ = ____

Answer 13

The “filtered load” of K+ = GFR x plasma [K+]

Question 14

K+ reabsorption in the proximal tubule is paracellular and occurs by 1) solvent ____ and by 2) ____ electro-diffusion.

Approximately 80% of the filtered load of K+ is reabsorbed immediately beyond the glomerulus in the proximal tubule, where ____ smotic reabsorption of NaCl also occurs. Net reabsorption of K+ results from trans ____, NOT transcellular, transfer of K+ from the tubular fluid to the interstitial space between cells by two paracellular pathways. As shown above, a process of “ solvent drag” mediates paracellular transfer of K+ in the early proximal tubule and simple electro-diffusion mediates paracellular transfer of K+ in the late proximal tubule.

In the early proximal tubule, ____ transcellular Na+ transport resulting from uptake across the luminal membrane and pasice efflux across the basolateral membrane drives net fluid reabsorption by osmosis transcellularly and via a paracellular pathway between cells. Importantly, a flow of K+ is “entrained” in the flow of fluid between cells (paracellular) driven by ____ and is described as a process of “solvent drag”, where, in this instance, K+ is effectively dragged along in the flow of fluid from the tubular fluid to the interstitial fluid.

In the late proximal tubule, the transepithelial voltage changes from lumen negative to lumen ____ and this provides an electrical driving force effectively “pushing” movement of K+ through the paracellular pathway. Thus, simple electro-diffusion describes the process of paracellular transfer of K+ in the late proximal tubule.

A defining feature of the nephron as an ion-translocating epithelium is the presence of Na/K ATPase in the ____, but NOT the luminal membrane of cells in every segment of the nephron. The basolateral membrane Na/K ATPase is a “Na/K-pump”, which mediates K+ uptake and concentrative, intracellular accumulation of K+ across the basolateral membrane and mediates Na+ efflux and concentrative, extracellular accumulation of Na+ in the interstitial space, thus increasing the osmolarity of the interstitial space relative to the tubular fluid. Intracellular K+ taken up across the basolateral membrane by the Na/K ATPase recycles back out of the cell through basolateral K+ channels and KCl ____, and therefore, does not participate in paracellular reabsorption of K+.

Answer 14

K+ reabsorption in the proximal tubule is paracellular and occurs by 1) solvent drag and by 2) passive electro-diffusion.

Approximately 80% of the filtered load of K+ is reabsorbed immediately beyond the glomerulus in the proximal tubule, where isosmotic reabsorption of NaCl also occurs. Net reabsorption of K+ results from transepithelial, NOT transcellular, transfer of K+ from the tubular fluid to the interstitial space between cells by two paracellular pathways. As shown above, a process of “ solvent drag” mediates paracellular transfer of K+ in the early proximal tubule and simple electro-diffusion mediates paracellular transfer of K+ in the late proximal tubule.

In the early proximal tubule, active transcellular Na+ transport resulting from uptake across the luminal membrane and pasice efflux across the basolateral membrane drives net fluid reabsorption by osmosis transcellularly and via a paracellular pathway between cells. Importantly, a flow of K+ is “entrained” in the flow of fluid between cells (paracellular) driven by osmosis and is described as a process of “solvent drag”, where, in this instance, K+ is effectively dragged along in the flow of fluid from the tubular fluid to the interstitial fluid.

In the late proximal tubule, the transepithelial voltage changes from lumen negative to lumen positive and this provides an electrical driving force effectively “pushing” movement of K+ through the paracellular pathway. Thus, simple electro-diffusion describes the process of paracellular transfer of K+ in the late proximal tubule.

A defining feature of the nephron as an ion-translocating epithelium is the presence of Na/K ATPase in the basolateral, but NOT the luminal membrane of cells in every segment of the nephron. The basolateral membrane Na/K ATPase is a “Na/K-pump”, which mediates K+ uptake and concentrative, intracellular accumulation of K+ across the basolateral membrane and mediates Na+ efflux and concentrative, extracellular accumulation of Na+ in the interstitial space, thus increasing the osmolarity of the interstitial space relative to the tubular fluid. Intracellular K+ taken up across the basolateral membrane by the Na/K ATPase recycles back out of the cell through basolateral K+ channels and KCl co-transporters, and therefore, does not participate in paracellular reabsorption of K+.

Question 15

Approximately 10% of filtered K+ is ____ from the tubular fluid in the Thick Ascending limb of the Loop of Henle (TAL). As shown above, transcellular transfer of K+ from the tubular fluid to the interstitial space in the TAL occurs by both ____ and ____ pathways. A lumen ____ voltage difference across the tubule epithelium drives K+ passively through the paracellular pathway by simple electro-diffusion. The lumen positive voltage difference across the tubule epithelium in the TAL arises from the presence of luminal membrane K+ channels mediating efflux of positive charge across the luminal membrane as well as from the presence of Cl channels in the basolateral membrane, which mediate efflux of negative across the basolateral membrane. Approximately half of K+ reabsorption in the TAL occurs via a paracellular pathway.

Approximately half of K+reabsorption in the TAL occurs via a transcellular pathway. The process of transcellular potassium reabsorption from the tubular fluid to the interstitial space results from the presence and coordinate function of membrane-specific transporters at the luminal (tubular fluid) and basolateral (interstitial) side of the TAL cell. At the ____ membrane a Na-K-2Cl cotransporter mediates the uptake and intracellular accumulation of Na, K, and Cl. At the ____ membrane ion-specific channels mediate efflux of intracellular Cl and K and Na/K ATP’ase mediates efflux of intracellular Na. The presence of K channels in the luminal membrane mediates efflux of a small amount of intracellular K back into the tubular fluid which together with Cl efflux across the basolateral membrane generates a lumen positive potential difference across the TAL tubular epithelium. The lumen positive potential difference also serves as a driving force for Ca and Mg reabsorption across the TAL tubular epithelium.

Answer 15

Approximately 10% of filtered K+ is reabsorbed from the tubular fluid in the Thick Ascending limb of the Loop of Henle (TAL). As shown above, transcellular transfer of K+ from the tubular fluid to the interstitial space in the TAL occurs by both paracellular and transcellular pathways. A lumen positive voltage difference across the tubule epithelium drives K+ passively through the paracellular pathway by simple electro-diffusion. The lumen positive voltage difference across the tubule epithelium in the TAL arises from the presence of luminal membrane K+ channels mediating efflux of positive charge across the luminal membrane as well as from the presence of Cl channels in the basolateral membrane, which mediate efflux of negative across the basolateral membrane. Approximately half of K+ reabsorption in the TAL occurs via a paracellular pathway.

Approximately half of K+reabsorption in the TAL occurs via a transcellular pathway. The process of transcellular potassium reabsorption from the tubular fluid to the interstitial space results from the presence and coordinate function of membrane-specific transporters at the luminal (tubular fluid) and basolateral (interstitial) side of the TAL cell. At the luminal membrane a Na-K-2Cl cotransporter mediates the uptake and intracellular accumulation of Na, K, and Cl. At the basolateral membrane ion-specific channels mediate efflux of intracellular Cl and K and Na/K ATP’ase mediates efflux of intracellular Na. The presence of K channels in the luminal membrane mediates efflux of a small amount of intracellular K back into the tubular fluid which together with Cl efflux across the basolateral membrane generates a lumen positive potential difference across the TAL tubular epithelium. The lumen positive potential difference also serves as a driving force for Ca and Mg reabsorption across the TAL tubular epithelium.

Question 16

The reabsorption of K+ in the ____ nephron occurs in the α-intercalated cells of the initial collecting tubule (ICT), cortical collecting tubule (CCT), and medullary collecting duct (MCD). The reabsorption of K+ in the distal nephron is ____ and occurs by active, concentrative accumulation of K+ across the luminal membrane mediated by a K/H ATPase, which actively transports K+ into the cell in exchange for H+ transported out of the cell. The deficit of intracellular protons (H+) resulting from this exchange alkalinizes the cell and drives, by mass action, OH + CO2 → HCO3 the increased formation of ____ inside the cell. The presence of a Cl/HCO3 exchanger in the basolateral membrane mediates efflux of intracellular HCO3 to the interstitial space. Intracellular K+ transported into the cell across the luminal membrane by the K/H ATPase exits the cell across the ____ membrane to the interstitial space through K+ channels.

The increase in HCO3 ____ occurring simultaneously with increased K+ ____ may induce a secondary metabolic ____ (increased plasma [HCO3]) when K+ reabsorption is maximal to reverse a deficit in plasma K+ (hypokalemia). This clinical finding is described as hypokalemic metabolic alkalosis. When plasma K+ is low, the cell-to-plasma shift of K+ from cells and the plasma to cell shift of H+ into cells, may exacerbate the metabolic alkalosis.

Answer 16

The reabsorption of K+ in the distal nephron occurs in the α-intercalated cells of the initial collecting tubule (ICT), cortical collecting tubule (CCT), and medullary collecting duct (MCD). The reabsorption of K+ in the distal nephron is transcellular and occurs by active, concentrative accumulation of K+ across the luminal membrane mediated by a K/H ATPase, which actively transports K+ into the cell in exchange for H+ transported out of the cell. The deficit of intracellular protons (H+) resulting from this exchange alkalinizes the cell and drives, by mass action, OH + CO2 → HCO3 the increased formation of HCO3 inside the cell. The presence of a Cl/HCO3 exchanger in the basolateral membrane mediates efflux of intracellular HCO3 to the interstitial space. Intracellular K+ transported into the cell across the luminal membrane by the K/H ATPase exits the cell across the basolateral membrane to the interstitial space through K+ channels.

The increase in HCO3 absorption occurring simultaneously with increased K+ reabsorption may induce a secondary metabolic alkalosis (increased plasma [HCO3]) when K+ reabsorption is maximal to reverse a deficit in plasma K+ (hypokalemia). This clinical finding is described as hypokalemic metabolic alkalosis. When plasma K+ is low, the cell-to-plasma shift of K+ from cells and the plasma to cell shift of H+ into cells, may exacerbate the metabolic alkalosis.

Question 17

The reabsorption and secretion of K+ in the ____ nephron occurs in different cell types. The secretion of K+ in the distal nephron occurs in the principal cells of the initial collecting tubule (ICT) and the cortical collecting tubule (CCT). The secretion of K+ in the ____ nephron is transcellular and occurs by active, concentrative accumulation of K+ across the basolateral membrane mediated by Na/K ATPase, which actively transports K+ into the cell in exchange for Na+ transported out of the cell. The transcellular secretion of K+ is completed by passive diffusion of intracellular K+ out of the cell across the luminal membrane through K+ channels and by mediated cotransport of K+ and Cl.

The high luminal membrane K+ permeability of principal cells (large number of K+ channels) accounts for the strong tubular fluid flow dependence of the rate of transcellular K+ secretion. Elevated rates of tubular fluid flow induced by volume expansion, osmotic diuresis, or diuretic drugs, prevent the tubular fluid accumulation and concentration of K+ from rising at the lumenal membrane surface in the distal nephron and thus maintains a steep, inside-to-outside, K+ concentration gradient driving the ____ efflux of K+ from the cells to the tubular fluid across the luminal membrane. In effect, K+ is swept away in the tubular fluid as fast as it is transported out of the cell across the luminal membrane.

Conversely, at low rates of tubular fluid flow in the distal nephron, efflux of K+ across the luminal membrane accumulates to higher concentrations at the lumenal membrane surface in the tubular fluid, which decreases the magnitude or “steepness” of the inside-to-outside, K+ concentration gradient driving the passive efflux of K+ from the cells to the tubular fluid across the luminal membrane. Accordingly, a ____ rate of K+ efflux across the luminal membrane will occur, which, in turn, decreases the rate of transcellular K+ secretion.

Sodium reabsorption in the distal nephron is functionally coupled to potassium ____ such that an increase or decrease in transcellular sodium reabsorption occurs simultaneously with an increase or decrease in transcellular potassium secretion. Transcellular sodium reabsorption results from uptake across the luminal membrane mediated by sodium ____ and efflux across the ____ membrane mediated by Na/K ATP’ase. Transcellular potassium secretion results from uptake across the basolateral membrane mediated by Na/K ATP’ase and efflux across the luminal membrane mediated by potassium channels. The functional coupling of transcellular sodium reabsorption to transcellular potassium secretion, in the same cell, arises from the Na/K ATP’ase which mediates the obligate coupling of sodium ____ to potassium ____ across the basolateral membrane, thus, maintaining a low intracellular sodium concentration and high intracellular potassium concentration. The functional coupling of sodium reabsorption to potassium secretion in the distal nephron is important because an increased delivery of sodium to these terminal nephron segments will not only result in a compensatory increase in sodium reabsorption but also an increase in potassium secretion which increases potassium loss in the urine and possible hypokalemia.

Answer 17

The reabsorption and secretion of K+ in the distal nephron occurs in different cell types. The secretion of K+ in the distal nephron occurs in the principal cells of the initial collecting tubule (ICT) and the cortical collecting tubule (CCT). The secretion of K+ in the distal nephron is transcellular and occurs by active, concentrative accumulation of K+ across the basolateral membrane mediated by Na/K ATPase, which actively transports K+ into the cell in exchange for Na+ transported out of the cell. The transcellular secretion of K+ is completed by passive diffusion of intracellular K+ out of the cell across the luminal membrane through K+ channels and by mediated cotransport of K+ and Cl.

The high luminal membrane K+ permeability of principal cells (large number of K+ channels) accounts for the strong tubular fluid flow dependence of the rate of transcellular K+ secretion. Elevated rates of tubular fluid flow induced by volume expansion, osmotic diuresis, or diuretic drugs, prevent the tubular fluid accumulation and concentration of K+ from rising at the lumenal membrane surface in the distal nephron and thus maintains a steep, inside-to-outside, K+ concentration gradient driving the passive efflux of K+ from the cells to the tubular fluid across the luminal membrane. In effect, K+ is swept away in the tubular fluid as fast as it is transported out of the cell across the luminal membrane.

Conversely, at low rates of tubular fluid flow in the distal nephron, efflux of K+ across the luminal membrane accumulates to higher concentrations at the lumenal membrane surface in the tubular fluid, which decreases the magnitude or “steepness” of the inside-to-outside, K+ concentration gradient driving the passive efflux of K+ from the cells to the tubular fluid across the luminal membrane. Accordingly, a decreased rate of K+ efflux across the luminal membrane will occur, which, in turn, decreases the rate of transcellular K+ secretion.

Sodium reabsorption in the distal nephron is functionally coupled to potassium secretion such that an increase or decrease in transcellular sodium reabsorption occurs simultaneously with an increase or decrease in transcellular potassium secretion. Transcellular sodium reabsorption results from uptake across the luminal membrane mediated by sodium channels and efflux across the basolateral membrane mediated by Na/K ATP’ase. Transcellular potassium secretion results from uptake across the basolateral membrane mediated by Na/K ATP’ase and efflux across the luminal membrane mediated by potassium channels. The functional coupling of transcellular sodium reabsorption to transcellular potassium secretion, in the same cell, arises from the Na/K ATP’ase which mediates the obligate coupling of sodium efflux to potassium influx across the basolateral membrane, thus, maintaining a low intracellular sodium concentration and high intracellular potassium concentration. The functional coupling of sodium reabsorption to potassium secretion in the distal nephron is important because an increased delivery of sodium to these terminal nephron segments will not only result in a compensatory increase in sodium reabsorption but also an increase in potassium secretion which increases potassium loss in the urine and possible hypokalemia.

Question 18

As tubular fluid flow increases there is an ____ in potassium secretion.

Answer 18

As tubular fluid flow increases there is an increase in potassium secretion.

Question 19

When there is high dietary K+:

A. ____ Distal Nephron Secretion of K+

1. Increased plasma [K+] increases uptake of K+ by the basolateral membrane Na/K ATPase
2. Increased driving force for K+ transport across the apical membrane 
3. Increased synthesis and release of aldosterone by the adrenal cortex. Increased sodium reabsorption is coupled to increased potassium excretion.

B. ____ Distal Nephron Reabsorption of K+

Answer 19

When there is high dietary K+:

A. Increased Distal Nephron Secretion of K+

1. Increased plasma [K+] increases uptake of K+ by the basolateral membrane Na/K ATPase
2. Increased driving force for K+ transport across the apical membrane 
3. Increased synthesis and release of aldosterone by the adrenal cortex. Increased sodium reabsorption is coupled to increased potassium excretion.

B. Decreased Distal Nephron Reabsorption of K+

Question 20

Aldosterone ____ transcription and translation of mRNA increasing transcellular Na+ reabsorption and K+ secretion: Na/K ATPase, Na+ and K+ channels, & mitochondrial enzymes.

ALDOSTERONE ____ PLASMA K+ SECRETION AND SODIUM REABSORPTION.

The aldosterone-induced increase in K+ ____ causes an increase in K+ excretion.

Answer 20

Aldosterone induces transcription and translation of mRNA increasing transcellular Na+ reabsorption and K+ secretion: Na/K ATPase, Na+ and K+ channels, & mitochondrial enzymes.

ALDOSTERONE INCREASES PLASMA K+ SECRETION AND SODIUM REABSORPTION.

The aldosterone-induced increase in K+ secretion causes an increase in K+ excretion.

Question 21

At low dietary K+:

A. ____ Distal Nephron Secretion of K+

1. Decreased plasma [K+] decreases uptake of K+ by the
    basolateral membrane Na/K ATPase

2. Decreased driving force for K+ secretion across the
    apical membrane 

3. Decreased synthesis and release of aldosterone by
    the adrenal cortex

B. ____ Distal Nephron Reabsorption of K+

Answer 21

At low dietary K+:

A. Decreased Distal Nephron Secretion of K+

1. Decreased plasma [K+] decreases uptake of K+ by the
    basolateral membrane Na/K ATPase

2. Decreased driving force for K+ secretion across the
    apical membrane 

3. Decreased synthesis and release of aldosterone by
    the adrenal cortex

B. Increased Distal Nephron Reabsorption of K+

Question 22

Alkalosis increases Distal Nephron K+ secretion

____ plasma [H+] ( pH) induces a shift in cell-to-plasma “K+-H+ exchange” increasing intracellular K+ (H+ out and K+ in) and decreasing extracellular K+. Hypokalemia = hypokalemic metabolic alkalosis.

In the distal nephron, increased intracellular K+ ____ the driving force and rate of K+ transport across luminal membrane.

Acidosis decreases Distal Nephron K+ secretion:

____ plasma [H+] (↓ pH) induces a shift in cell-to-plasma “K+-H+ exchange” decreasing intracellular K+ (H+ in and K+ out) and increasing extracellular K+. Protons go into the cell and potassium comes out = hyperkalemia. Hyperkalemia = hyperkalemic metabolic acidosis.

In the distal nephron, decreased intracellular K+ decreases the driving force and rate of K+ transport across luminal membrane

Answer 22

Alkalosis increases Distal Nephron K+ secretion

Decreased plasma [H+] ( pH) induces a shift in cell-to-plasma “K+-H+ exchange” increasing intracellular K+ (H+ out and K+ in) and decreasing extracellular K+. Hypokalemia = hypokalemic metabolic alkalosis.

In the distal nephron, increased intracellular K+ increases the driving force and rate of K+ transport across luminal membrane.

Acidosis decreases Distal Nephron K+ secretion:

Increased plasma [H+] (↓ pH) induces a shift in cell-to-plasma “K+-H+ exchange” decreasing intracellular K+ (H+ in and K+ out) and increasing extracellular K+. Protons go into the cell and potassium comes out = hyperkalemia. Hyperkalemia = hyperkalemic metabolic acidosis.

In the distal nephron, decreased intracellular K+ decreases the driving force and rate of K+ transport across luminal membrane

Question 23

A respiratory or metabolic alkalosis, where plasma pH is increased, will induce a “shift” of protons (H+) from cells to plasma and a “shift” of K+ from plasma to cells, effectively exchanging intracellular H+ for extracellular K+ . Where this effective K+-H+ exchange occurs in the K+ secreting epithelial cells of the distal nephron, the resulting increase in intracellular K+ increases transcellular K+ secretion and an increase in K+ excretion. Accordingly, a chronic respiratory or metabolic alkalosis may put the patient at risk for ____ kalemia secondary to “K+ wasting” by the kidney.

A respiratory or metabolic acidosis where plasma pH is decreased will induce a “shift” of protons (H+) into cells from plasma and a “shift” of K+ out of cells to plasma, effectively exchanging intracellular K+ for extracellular H+ . Where this effective K+-H+ exchange occurs in the K+ secreting epithelial cells of the distal nephron, the resulting decrease in intracellular K+ decreases transcellular K+ secretion and a decrease in K+ excretion. Accordingly, a chronic respiratory or metabolic acidosis may put the patient at risk for ____ kalemia secondary to “K+ retention” by the kidney.

Answer 23

A respiratory or metabolic alkalosis, where plasma pH is increased, will induce a “shift” of protons (H+) from cells to plasma and a “shift” of K+ from plasma to cells, effectively exchanging intracellular H+ for extracellular K+ . Where this effective K+-H+ exchange occurs in the K+ secreting epithelial cells of the distal nephron, the resulting increase in intracellular K+ increases transcellular K+ secretion and an increase in K+ excretion. Accordingly, a chronic respiratory or metabolic alkalosis may put the patient at risk for hypokalemia secondary to “K+ wasting” by the kidney.

A respiratory or metabolic acidosis where plasma pH is decreased will induce a “shift” of protons (H+) into cells from plasma and a “shift” of K+ out of cells to plasma, effectively exchanging intracellular K+ for extracellular H+ . Where this effective K+-H+ exchange occurs in the K+ secreting epithelial cells of the distal nephron, the resulting decrease in intracellular K+ decreases transcellular K+ secretion and a decrease in K+ excretion. Accordingly, a chronic respiratory or metabolic acidosis may put the patient at risk for hyperkalemia secondary to “K+ retention” by the kidney.

Question 24

A negative K+ balance where plasma K+ is reduced (hypokalemia) will induce a “shift” of K+ from cells to plasma and a “shift” of H+ from plasma to cells, effectively exchanging intracellular K+ for extracellular H+ . The resulting ____ in extracellular H+ increases plasma pH, possibly causing a metabolic alkalosis. Where this effective K+-H+ exchange occurs in the K+ secreting epithelial cells of the distal nephron, the resulting decrease in intracellular K+ decreases transcellular K+ secretion and decreases K+ excretion. Should the decrease in renal K+ excretion be insufficient to correct the hypokalemia, chronic hypokalemia may put the patient at risk for metabolic ____.

A positive K+ balance where plasma K+ is increased (hyperkalemia) will induce a “shift” of K+ into cells from the plasma and a “shift” of H+ from cells to the plasma, effectively exchanging intracellular H+ for extracellular K+ . The resulting ____ in extracellular H+ decreases plasma pH, possibly causing a metabolic acidosis. Where this effective K+-H+ exchange occurs in the K+ secreting epithelial cells of the distal nephron, the resulting increase in intracellular K+ increases transcellular K+ secretion and increases K+ excretion. Should the increase in renal K+ excretion be insufficient to correct the hyperkalemia, chronic hyperkalemia may put the patient at risk for metabolic ____.

Answer 24

A negative K+ balance where plasma K+ is reduced (hypokalemia) will induce a “shift” of K+ from cells to plasma and a “shift” of H+ from plasma to cells, effectively exchanging intracellular K+ for extracellular H+ . The resulting decrease in extracellular H+ increases plasma pH, possibly causing a metabolic alkalosis. Where this effective K+-H+ exchange occurs in the K+ secreting epithelial cells of the distal nephron, the resulting decrease in intracellular K+ decreases transcellular K+ secretion and decreases K+ excretion. Should the decrease in renal K+ excretion be insufficient to correct the hypokalemia, chronic hypokalemia may put the patient at risk for metabolic alkalosis.

A positive K+ balance where plasma K+ is increased (hyperkalemia) will induce a “shift” of K+ into cells from the plasma and a “shift” of H+ from cells to the plasma, effectively exchanging intracellular H+ for extracellular K+ . The resulting increase in extracellular H+ decreases plasma pH, possibly causing a metabolic acidosis. Where this effective K+-H+ exchange occurs in the K+ secreting epithelial cells of the distal nephron, the resulting increase in intracellular K+ increases transcellular K+ secretion and increases K+ excretion. Should the increase in renal K+ excretion be insufficient to correct the hyperkalemia, chronic hyperkalemia may put the patient at risk for metabolic acidosis.