Regulation of Plasma Potassium Flashcards
how much of total body K+ is intracellular? what functions does it serve?
98%
participates in pH regulation, is a cofactor for cellular enzymes and keeps plasma K in normal range
what is the K concentration gradient across the cell membrane a major determinant of? in which cells does this occur?
the voltage difference across the cell membrane in both electrically excitable and unexcitable cells
how does K contribute to potential difference?
positive charge carried out by K current through membrane channels is dominant ionic current determining membrane potential
what equation describes the thermodynamic relationship of a transmembrane voltage difference to an ion concentration difference?
nernst equation
what constitutes hyperkalemia? what does this do to the K gradient and how does this affect resting membrane potential?
K>5 mM
decreases outward K gradient depolarizing the cell
what is the effect of hyperkalemia on muscles, cardiac conduction and blood pH?
muscles are hyperexcitable
ventricular arrhythmias and fibrilation (uncoordination)
metabolic acidosis
what constitutes hypokalemia? what does this do to the K gradient and how does this affect resting membrane potential?
K<3.5 mM
increases outward K gradient hyperpolarizing the cell
what is the effect of hypokalemia on muscles, cardiac conduction and blood pH?
muscles are hypoexcitable
cardiac pacemaker disturbance: arrhythmias
metabolic alkalosis
why can varying levels of plasma potassium cause metabolic alkalosis and acidosis?
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+
how can hypokalemia cause respiratory failure?
muscles have a higher threshold for excitability and therefore don’t contract as well. weakened respiratory muscles may not contract sufficiently
describe the input and export of K in the body. how does the daily uptake compare to the amount of K in the ECF?
GI uptake (greater than ECF amount) balanced by renal and fecal removal of K (10%)
how does the GI tract remove plasma K? what hormone may change the amount?
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)
what is the role of the kidneys in K homeostasis?
to match intake with removal from the body precisely to prevent change in plasma K levels
what is the renal handling of K?
K is freely filtered at the glomerulus, reabsorbed in some nephron segments and secreted in others
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?
distribution between intracellular and extracellular fluids maintained by the Na/K pump
would increase plasma levels by 50%
what is the first line of defense against hyperkalemia?
increased uptake of potassium into cells by the Na/K pump (acts as buffer)
what are the sources of hyperkalemia?
increased dietary K and release of intracellular K from diseased or injured tissue
what hormones promote increased cellular uptake of K? how?
insulin, epinephrine and aldosterone
induce synthesis of Na/K pumps so more can be removed from surrounding fluids
why are diabetics predisposed to hyperkalemia?
because the dysregulation of insulin release and circulating levels may decrease tolerance of diabetic patients to a K load
how does acidemia result in hyperkalemia?
increased uptake of H+ inhibits the Na/K pump and Na/K/2Cl cotransporter causing a loss of K+ from cells into ECF
how does alkalemia result in hypokalemia?
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
describe absorption of K from the GI tract and how it changes with high K load.
most of K consumed is absorbed from the GI tract and regulation of K balance does not occur here
how do the endocrine organs respond to an increase in plasma K concentration?
it is detected as a change in membrane potential and cells respond by releasing aldosterone (adrenal cortex), insulin (pancreas) and epinephrine (adrenal medulla)
how long does it take for the body to respond to an increased K load? how long does it take for it to resolve?
minutes
within an hour
what is the less rapid mechanism for correcting increased K load? what can this occur in absence of?
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)
where is most of the filtered K reabsorbed? how is this regulated?
in the proximal tubule (80%)- loop of henle absorbs 10%
not regulated- constant (in either)
where is renal excretion of K regulated? what is the renal handling of K there?
distal nephron
may resorb or secrete K depending on the K balance and plasma levels
when is K balance negative? how is this balance restored? can it always be fully corrected?
when levels of intake are low
increased resorption in the distal nephron to correct
if there is chronic dietary deficiency- hypokalemia
how does the filtered load of K+ compare to the daily consumption?
it is about 10 times as much (must reabsorb all but about 10%)
when is K balance positive? to what degree can secretion of K increase excretion?
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
what is the difference between sodium and potassium clearance? how do they compare to inulin and creatine clearance?
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
describe K reabsorption in the proximal tubule?
it is paracellular and occurs by solvent drag (early PT) and passive electrodiffusion (late PT)
describe the driving force of solvent drag of K and where it occurs in the proximal tubule.
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
describe the driving force of electrodiffusion of K and where it occurs in the proximal tubule.
the transepithelial voltage changes from lumen negative to positive, pushing K through the paracellular pathway.
this occurs in the late proximal tubule
where is the Na/K pump in the nephron? what is its function?
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
does the Na/K pump participate in K transport in the proximal tubule?
no. it only participates in Na transport as the channels and transporters that recycle K are also at the basolateral membrane
what is the mechanism of K transport in the thick ascending limb of the loop of henle?
there is both transcellular and paracellular absorption
paracellular driven by electrodiffusion
transcellular driven by transporters
what causes the positive lumen voltage difference in the thick ascending lumb?
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
how much of K resorption in the thick ascending limb is transcellular? what transporters are responsible?
1/2
Na/K/2Cl symporter at the basolateral membrane
K channel at the basolateral membrane
How does the efflux of K into the lumen impact absorption in the thick ascending limb? what does the potential this creates drive?
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
resorption of K in the distal nephron occurs in which cells?
alpha intercalated cells of the initial and cortical collecting tubules and the medullary collecting duct
describe resorption of K in the distal nephron.
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
K absorption in the distal nephron drives which process?
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
because of the link to HCO3 transport, increased K resorption may induce what? how is this exacerbated?
secondary metabolic alkalosis because of increased HCO3 production
exacerbated because of the shift of K+ into other body cells in exchange for H+
what cells of the distal nephron secrete K? do they also absorb K?
principal cells of the initial and cortical collecting tubules
absorption in different cell types
describe the secretion of K in the distal tubule.
transcellular active transport by Na/K pump at the basolateral membrane with K channels and K/Cl cotransport at the lumenal membrane
what property of principal cells accounts for the tubular flow dependance of K secretion? how does rate impact it?
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
how is sodium resorption coupled to potassium secretion in the distal nephron?
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
how can high amounts of Na in the distal tubule result in hypokalemia?
because there will be a compensatory increase in sodium resorption coupled to potassium secretion
what two factors does distal tubule secretion depend upon?
tubular flow rateand amount of K in the diet
increased secretion with increased amount in diet and flow rate
other than the K gradient, what principal is illustrated in the flow dependence of distal tubule K secretion?
it increases or decreases the delivery of Na
increase in delivery (high flow rate) results in increased absorption and therefore increased K secretion
what three factors increase distal nephron secretion of K with high consumption?
increased plasma K increases uptake by the baslolateral Na/K pump, increased intracellular K for luminal export and increased aldosterone
what happens in the alpha intercalated cells with high plasma calcium levels?
there is decreased resorption of K
how does aldosterone increase K secretion?
increases expression of Na/K pumps, Na and K channels and mitochondrial enzymes
what prompts aldosterone release?
angiotensin II and high circulating K levels
what does increased luminal membrane Na conductance do to the membrane potential? what does this drive?
depolarizes the membrane potential increasing the driving force for K efflux across the luminal membrane
what three factors decrease distal nephrone secretion of K with low consumption?
decreased plasma K decreases uptake by Na/K pump, decreased intracellular K for luminal transport and decreased aldosterone levels
how does alkalosis affect distal nephron K secretion?
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
how does acidosis affect distal nephron K secretion?
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
