Unit 7 - Regulation of Potassium Flashcards
how is K+ related to H+?
[K+] participates in pH regulation, due to effective K+/H+ exchange across cell membrane
extracellular VS intracellular K+ concentrations
extracellular: 3.5-5.0 mM
intraceullar: 120 mM (98% of total body K+)
how is K+ related to the cell voltage?
major determinant of cell voltage of [K+] gradient
- if extracellular K+ increases, the gradient decreases, so voltage depolarizes (less negative)
- if intracellular K+ increases, gradient increases, so hyperpolarizes (more negative; this is what it is usually)
how is K+ important in excitable and unexcitable cells?
K+ gradient across cell membrane is major determinant of potential in both types of cells
-in excitable (cardiac, neural, muscle), the currents are central to property of “excitability”
what defines hyperkalemia?
plasma [K+] above 5.0 nM
- decreases outwardly directed K+ gradient
- resting membrane potential is depolarized
- -muscle hyperexcitability
- -cardiac conduction disturbances (ventricular arrythmia and fibrilation, tachycardia)
- metabolic acidosis (since K+ enters cells, H+ exits cells)
what defines hypokalemia?
plasma [K+] below 3.5 mM
- increases outwardly directed K+ gradient
- resting membrane potential is hyperpolarized
- -muscle hypoexcitability
- -cardiac pacemaker disturbance (arrythmia, bradycardia)
- metabolic alkalosis (since K+ exits cells, H+ enters cells)
K+ balance and distribution throughout body (external VS internal VS kidney) daily
external: GI uptake (100 mmol)
- 10 mmol in feces
- 90 mmol to ECF
internal: ECF constant at 65 mmol (4.5 mM); exchange with organs
- muscle: 2600 mmol
- liver: 250 mmol
- bone: 300 mmol
- RBC: 250 mmol
kidney: 90 mmol excretion = 810 mmol filtration + 50 mmol secretion - 770 mmol reabsorbtion
what is the first line of defense against hyperkalemia? what is the one cell that doesn’t participate in this?
increased uptake of [K+] into cells
- acute increase in plasma [K+] triggers release of insulin (pancreatic beta cells), epinephrine (adrenal medulla chromaffin cells), and aldosterone (adrenal cortex glomerulosa cells)
- these all act to activate K+/N+ ATPase, such that K+ can enter cells and Na+ can exit cells
since RBC don’t have a nucleus or the ability to respond to the above hormones, they don’t participate in this response
how is hyperkalemia related to diabetes?
since insulin is released in response to acute increases in [K+], poorly-controlled BM may compromise tolerance of diabetes patients to K+ load, and predispose them to hyperkalemia
why does acidemia cause hyperkalemia?
acidemia inhibits the Na/K ATPase and Na/K/2Cl cotransporters, which lowers intraceullar [K+] and causes K+ loss from cells
-also, H+ enters cells and K+ exits cells via K+/H+ antiport
how does alkalemia stimulate hypokalemia?
alkalemia stimulates Na/K ATPase and Na/K/2Cl cotransporters, so more uptake of K+ into cells, causing hypokalemia
how does the body handle K+ after an acute K+ load?
plasma K+ will slowly decrease back to baseline due to:
- initially high net cumulative translocation of K+ into cells (slowly tapers off)
- slowly increasing cumulative renal excretion of K+ above baseline
how does K+ reabsorption in proximal tubule change at low, normal, or high plasma K+ levels? in the distal tubule?
PT: IT DOESN’T; reaborption is constitutive (not regulated) in proximal tubule
-it’s always most of the filtered K+ (~80%)
DT: either reabsorbs or secretes K+, depending on K+ balance and plasma K+ levels
K+ handling when dietary K+ intake is low and K+ balance is negative
- 80% reabsorbed in proximal tubule constitutively
- 10% reabsorbed in TAL constitively
- since low K+: 2% reabsorbed in collecting tubule + 6% reabsorbed in medullary collecting duct
- remainder: 2% of filtered load is remaining for excretion
what is an instance where hypokalemia can result, despite compensating increase in K+ reabsorption by distal nephron?
chronic dietary K+ deficiency
K+ handling when dietary K+ intake is high and K+ balance is positive
- 80% reabsorbed in proximal tubule constitutively
- 10% reabsorbed in TAL constitively
- since high K+: instead of reabsorption, there can be 20-180% K+ secretion at collecting tubule
- 20-40% can be reabsorbed in medullary collecting duct
- remainder: 10-150% of filtered load remaining
how is K+ reaborption in proximal tubule?
paracellular, by 2 methods
- early PT: solvent drag (due to H2O entering paracellularly)
- late PT: since the voltage increases from negative (early) to positive (late), there is a driving force for the K+ to enter lumen paracellularly
how is K+ reabsorption in TAL?
both transcellular and paracellular
- since there is a positive voltage (due to PT actions), K+ and Na+ are driven across paracellularly
- Na+/K+/2Cl- co-transport on luminal side brings all into cell
- -Cl-, K+ channels send through basolateral membrane, while Na+/K+ ATPase sends Na to blood, and K+ in
- K+ channel on luminal membrane sends K+ into lumen if need be
where does furosemide act?
on the TAL
-it inhibits the transcellular Na/K/2Cl cotransport on the luminal side, keeping Na+ and K+ in tubular lumen
mechanism of K+ reabsorption by distal nephron
transcellular
- there is an H+ pump to the luminal side, then a K+/H+ exchanger pump that sends K+ into cell and H+ out
- for every H+ exiting the cell, an OH- left in cell binds to CO2 to make HCO3-
- HCO3-/Cl- exchanger, Na/K ATPase, K+ and Cl- channels in basolateral membrane
why can hypokalemia cause secondary metabolic alkalosis?
there is increased reabsorption of k+ mediated by increased luminal membrane K+/H+ exchange
- the H+ secreted into lumen leaves behind OH- in cell to bind to CO2 and make HCO3-
- the HCO3- exits via HCO3/Cl antiport to cause alkalosis
mechanism of K+ secretion by distal nephron; what is it dependent on? what happens if furosemide is used?
transcellularly, and dpendent on flow and Na
- increased flow causes increased K+ secretion, pulling it forward
- if furosemide is used, Na+ hasn’t been reabsorbed in TAL, so Na+ is absorbed here, and K+ secretion increases (hypokalemia)
how is tubular fluid flow related to distal tubule K+ secretion in high, normal, and low K+ diets?
no matter the diet, there will be increased K+ secretion with increased distal flow
- if high K+ diet, there is slower flow
- if low K+ diet, there is faster flow
regulation of K+ excretion at high dietary K+
- increased distal nephron secretion of K+
- increased plasma [K+] increases uptake of K+ by basolateral membrane Na/K ATPase
- increased driving force for K+ transport across apical membrane
- increased synthesis and release of aldosterone by adrenal cortex - decreased distal nephron reabsorption of K+
how does aldosterone affect K+?
increases K+ secretion
- induces increased “capacity” for Na+ reabsorption and K+ secretion in distal nephron
- induces transcription and translation of mRNA, increasing transcellular Na+ reabsorption and K+ secretion (Na/K ATPase, Na+ and K+ channels, mitochondrial enzymes)
- increased luminal membrane Na conductance depolarizes luminal membrane potential, thus increasing driving force for K+ efflux across luminal membrane
regulation of K+ excretion at low dietary K+
- decreased distal nephron secretion of K+
- decreased plasma [K+] decreases uptake of K+ by basolateral membrane Na/K ATPase
- decreased driving force for K+ secretion across apical membrane
- decreased synthesis and release of aldosterone by adrenal cortex - increased distal nephron reabsorption of K+
how does alkalosis affect K+ in distal nephron?
increased pH induces shift in K/H exchange, increasing intracellular k+ (H+ out and K+ in)
- increased K+ increases driving force and rate of K+ transport across luminal membrane
- hypokalemic metabolic alkalosis
how does acidosis affect K+ in distal nephron?
decreased pH induces decreased intracellular K+ (H+ in, K+ out)
- decreased intracellular K+ decreases driving force and rate of K+ transport across luminal membrane
- kyperkalemic metabolic acidosis
