Regulation of Plasma Potassium

Question 1

how much of total body K+ is intracellular? what functions does it serve?

Answer 1

98%

participates in pH regulation, is a cofactor for cellular enzymes and keeps plasma K in normal range

Question 2

what is the K concentration gradient across the cell membrane a major determinant of? in which cells does this occur?

Answer 2

the voltage difference across the cell membrane in both electrically excitable and unexcitable cells

Question 3

how does K contribute to potential difference?

Answer 3

positive charge carried out by K current through membrane channels is dominant ionic current determining membrane potential

Question 4

what equation describes the thermodynamic relationship of a transmembrane voltage difference to an ion concentration difference?

Answer 4

nernst equation

Question 5

what constitutes hyperkalemia? what does this do to the K gradient and how does this affect resting membrane potential?

Answer 5

K>5 mM

decreases outward K gradient depolarizing the cell

Question 6

what is the effect of hyperkalemia on muscles, cardiac conduction and blood pH?

Answer 6

muscles are hyperexcitable
ventricular arrhythmias and fibrilation (uncoordination)
metabolic acidosis

Question 7

what constitutes hypokalemia? what does this do to the K gradient and how does this affect resting membrane potential?

Answer 7

K<3.5 mM

increases outward K gradient hyperpolarizing the cell

Question 8

what is the effect of hypokalemia on muscles, cardiac conduction and blood pH?

Answer 8

muscles are hypoexcitable
cardiac pacemaker disturbance: arrhythmias
metabolic alkalosis

Question 9

why can varying levels of plasma potassium cause metabolic alkalosis and acidosis?

Answer 9

because there is an effective exchange of intracellular H+ for extracellular K+ to reestablish the gradient. In hyperkalemia H+ is added to plasma to remove K+ and in hypokalemia H+ is removed to add K+

Question 10

how can hypokalemia cause respiratory failure?

Answer 10

muscles have a higher threshold for excitability and therefore don’t contract as well. weakened respiratory muscles may not contract sufficiently

Question 11

describe the input and export of K in the body. how does the daily uptake compare to the amount of K in the ECF?

Answer 11

GI uptake (greater than ECF amount) balanced by renal and fecal removal of K (10%)

Question 12

how does the GI tract remove plasma K? what hormone may change the amount?

Answer 12

K+ is excreted in the colon and amount may be changed by circulating levels of aldosterone (not enough to compensate for absence of increased renal excretion)

Question 13

what is the role of the kidneys in K homeostasis?

Answer 13

to match intake with removal from the body precisely to prevent change in plasma K levels

Question 14

what is the renal handling of K?

Answer 14

K is freely filtered at the glomerulus, reabsorbed in some nephron segments and secreted in others

Question 15

what is the internal K balance? what is it maintained by? a shift of 1% of intracellular K would cause what kind of shift in plasma?

Answer 15

distribution between intracellular and extracellular fluids maintained by the Na/K pump
would increase plasma levels by 50%

Question 16

what is the first line of defense against hyperkalemia?

Answer 16

increased uptake of potassium into cells by the Na/K pump (acts as buffer)

Question 17

what are the sources of hyperkalemia?

Answer 17

increased dietary K and release of intracellular K from diseased or injured tissue

Question 18

what hormones promote increased cellular uptake of K? how?

Answer 18

insulin, epinephrine and aldosterone

induce synthesis of Na/K pumps so more can be removed from surrounding fluids

Question 19

why are diabetics predisposed to hyperkalemia?

Answer 19

because the dysregulation of insulin release and circulating levels may decrease tolerance of diabetic patients to a K load

Question 20

how does acidemia result in hyperkalemia?

Answer 20

increased uptake of H+ inhibits the Na/K pump and Na/K/2Cl cotransporter causing a loss of K+ from cells into ECF

Question 21

how does alkalemia result in hypokalemia?

Answer 21

decreased cellular uptake of H+ and efflux of H+ will occur. this stimulates the Na/K pump and Na/K/2Cl cotransporter causing an uptake of K from ECF

Question 22

describe absorption of K from the GI tract and how it changes with high K load.

Answer 22

most of K consumed is absorbed from the GI tract and regulation of K balance does not occur here

Question 23

how do the endocrine organs respond to an increase in plasma K concentration?

Answer 23

it is detected as a change in membrane potential and cells respond by releasing aldosterone (adrenal cortex), insulin (pancreas) and epinephrine (adrenal medulla)

Question 24

how long does it take for the body to respond to an increased K load? how long does it take for it to resolve?

Answer 24

minutes

within an hour

Question 25

what is the less rapid mechanism for correcting increased K load? what can this occur in absence of?

Answer 25

renal excretion of K in the urine is increased over a period of several hours
can occur in absence of elevated plasma K (buffered by cells)

Question 26

where is most of the filtered K reabsorbed? how is this regulated?

Answer 26

in the proximal tubule (80%)- loop of henle absorbs 10%

not regulated- constant (in either)

Question 27

where is renal excretion of K regulated? what is the renal handling of K there?

Answer 27

distal nephron

may resorb or secrete K depending on the K balance and plasma levels

Question 28

when is K balance negative? how is this balance restored? can it always be fully corrected?

Answer 28

when levels of intake are low
increased resorption in the distal nephron to correct
if there is chronic dietary deficiency- hypokalemia

Question 29

how does the filtered load of K+ compare to the daily consumption?

Answer 29

it is about 10 times as much (must reabsorb all but about 10%)

Question 30

when is K balance positive? to what degree can secretion of K increase excretion?

Answer 30

at high levels of dietary intake
can increase the tubular K from 10% of filtered (leftover from the proximal tubule and loop of henle resorption) to 150% of filtered K

Question 31

what is the difference between sodium and potassium clearance? how do they compare to inulin and creatine clearance?

Answer 31

Na cannot be secreted while K can be. we are better adapted to handling high K diet compared to Na. this means K clearance can exceed that of inulin and creatine while Na cannot

Question 32

describe K reabsorption in the proximal tubule?

Answer 32

it is paracellular and occurs by solvent drag (early PT) and passive electrodiffusion (late PT)

Question 33

describe the driving force of solvent drag of K and where it occurs in the proximal tubule.

Answer 33

solvent drag is driven by Na transport, which in turn drives water uptake from the lumen. Paracellular water flow drags K along with it. occurs in the early protixmal tubule

Question 34

describe the driving force of electrodiffusion of K and where it occurs in the proximal tubule.

Answer 34

the transepithelial voltage changes from lumen negative to positive, pushing K through the paracellular pathway.
this occurs in the late proximal tubule

Question 35

where is the Na/K pump in the nephron? what is its function?

Answer 35

it is only on the basolateral membrane of tubular cells (not luminal membrane). mediates formation of a K gradient and Na efflux through its transcellular pathway

Question 36

does the Na/K pump participate in K transport in the proximal tubule?

Answer 36

no. it only participates in Na transport as the channels and transporters that recycle K are also at the basolateral membrane

Question 37

what is the mechanism of K transport in the thick ascending limb of the loop of henle?

Answer 37

there is both transcellular and paracellular absorption
paracellular driven by electrodiffusion
transcellular driven by transporters

Question 38

what causes the positive lumen voltage difference in the thick ascending lumb?

Answer 38

presence of luminal membrane K channels mediating the efflux of K into the tubular fluid and Cl channels mediating efflux out of the basolateral membrane

Question 39

how much of K resorption in the thick ascending limb is transcellular? what transporters are responsible?

Answer 39

1/2
Na/K/2Cl symporter at the basolateral membrane
K channel at the basolateral membrane

Question 40

How does the efflux of K into the lumen impact absorption in the thick ascending limb? what does the potential this creates drive?

Answer 40

only small amounts are transported by the luminal K channel so there is not much of an effect
the potential drives further K absorption paracellularly, paracellular Na uptake and Ca and Mg reabsorption

Question 41

resorption of K in the distal nephron occurs in which cells?

Answer 41

alpha intercalated cells of the initial and cortical collecting tubules and the medullary collecting duct

Question 42

describe resorption of K in the distal nephron.

Answer 42

trancellular active tansport mediated by a K/H pump (antiport) transporting K into the cell that is released into the interstitial space through K channels

Question 43

K absorption in the distal nephron drives which process?

Answer 43

H removal from the cell promotes HCO3 formation inside the cell by mass action (OH- and CO2) and removal from the basolateral membrane by HCO3/Cl antiport

Question 44

because of the link to HCO3 transport, increased K resorption may induce what? how is this exacerbated?

Answer 44

secondary metabolic alkalosis because of increased HCO3 production
exacerbated because of the shift of K+ into other body cells in exchange for H+

Question 45

what cells of the distal nephron secrete K? do they also absorb K?

Answer 45

principal cells of the initial and cortical collecting tubules
absorption in different cell types

Question 46

describe the secretion of K in the distal tubule.

Answer 46

transcellular active transport by Na/K pump at the basolateral membrane with K channels and K/Cl cotransport at the lumenal membrane

Question 47

what property of principal cells accounts for the tubular flow dependance of K secretion? how does rate impact it?

Answer 47

high numbers of K channels
slower flow results in less secretion because there is less of a gradient difference between tubular fluid and cell
faster flow results in more secretion because the secreted K is quickly swept away and the gradient is maintained

Question 48

how is sodium resorption coupled to potassium secretion in the distal nephron?

Answer 48

because both are mediated by the Na/K pump with Na and K channels at the lumenal membrane. more activity results in more uptake of Na and secretion of K

Question 49

how can high amounts of Na in the distal tubule result in hypokalemia?

Answer 49

because there will be a compensatory increase in sodium resorption coupled to potassium secretion

Question 50

what two factors does distal tubule secretion depend upon?

Answer 50

tubular flow rateand amount of K in the diet

increased secretion with increased amount in diet and flow rate

Question 51

other than the K gradient, what principal is illustrated in the flow dependence of distal tubule K secretion?

Answer 51

it increases or decreases the delivery of Na

increase in delivery (high flow rate) results in increased absorption and therefore increased K secretion

Question 52

what three factors increase distal nephron secretion of K with high consumption?

Answer 52

increased plasma K increases uptake by the baslolateral Na/K pump, increased intracellular K for luminal export and increased aldosterone

Question 53

what happens in the alpha intercalated cells with high plasma calcium levels?

Answer 53

there is decreased resorption of K

Question 54

how does aldosterone increase K secretion?

Answer 54

increases expression of Na/K pumps, Na and K channels and mitochondrial enzymes

Question 55

what prompts aldosterone release?

Answer 55

angiotensin II and high circulating K levels

Question 56

what does increased luminal membrane Na conductance do to the membrane potential? what does this drive?

Answer 56

depolarizes the membrane potential increasing the driving force for K efflux across the luminal membrane

Question 57

what three factors decrease distal nephrone secretion of K with low consumption?

Answer 57

decreased plasma K decreases uptake by Na/K pump, decreased intracellular K for luminal transport and decreased aldosterone levels

Question 58

how does alkalosis affect distal nephron K secretion?

Answer 58

it induces plasma to cell shift of K by pumping H out of the cell. the increased intracellular K increases driving force of K secretion and can cause hypokalemia

Question 59

how does acidosis affect distal nephron K secretion?

Answer 59

it induces a cell to plasma shift of K by pumping H into the cell. the decreased intracellular K decreases driving force of K secretion and can cause hyperkalemia