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Potassium content control
Tightly controlled
Usually changes less than ± 0.3 mEq/liter
Cell functions very sensitive to changes
Resting membrane potentials
98% located intracellular volume with only 2% extracellular
Daily intake usually ranges between 50 mEq/liter to 200 mEq/liter
Small changes in extracellular K+ can easily lead to hyper or hypokalemia
Only 5 to 10% of intake removed by feces (rest removed by kidneys
Movement between intra and extracellular compartments possible (first line of defense against changes in ECF concentration
Factors that shifts K+ into cells (Potential hypo)
• increase in Insulin • increase in Aldosterone (also es K+ secretion) • increase in Β-adrenergic stimulation • Alkalosis (high H+ reduces action of Na/K ATPase = less K+transfer into cells)
Factors that shifts K+ out of cells (Potential hyper)
- Insulin deficiency (diabetes mellitus)
- Aldosterone deficiency (Addison’s disease)
- Β-adrenergic blockade
- Acidosis
- Cell lysis
- Strenuous exercise
- Increased extracellular fluid osmolarity
Renal Excretion of Potassium determined by
Rate of potassium filtration
Rate of potassium reabsorption
Rate of potassium secretion
K+ filtration
180 liter/day x 4.2 mEq/liter = 756 mEq/day
K+ reabsorption
Consistent Reabsorption
65% proximal tubule
25 to 30% in loop (mainly thick ascending segment)
K+ secretion
Distal tubule & cortical collecting tubule
Approximately 1/3 of excreted potassium
Distal Tubule & Cortical Collecting Tubule: High potassium intake
Distal tubule & cortical collecting tubule increase potassium secretion
Very strong mechanism – rate of potassium excretion can exceed amount of potassium being filtered
Distal Tubule & Cortical Collecting Tubule: Low potassium intake
Secretion rate decreases
Can decrease secretion to point where there is net reabsorption
Excretion can fall to 1% of filtered potassium (756 mEq/day x 0.01 = 8 mEq/day)
Principal Cells – Potassium Secretion
Make up 90% of cells in late distal and cortical collecting tubule
Secretion driven by Na-K ATPase in basolateral border of cells
Move K+ into cell setting up concentration gradient
Concentration gradient drives diffusion from cell into tubular lumen
Tubular membrane contains special channels for K+ diffusion
Usually provide high permeability for K+ movement out of the cell
BK: High conductance Big K channels
ROMK: Renal outer medullary K channels
Intercalated Cells – Potassium Reabsorption
Reabsorb potassium especially during potassium depletion
Could be related to H-K ATPase
Located tubular membrane
Pumps H+ from tubular cell into lumen (secretion)
Pumps K+ from tubular lumen into cell (reabsorption)
K+ diffuses from cell into interstitial space via basolateral membrane
Major effect only during potassium depletion
Type A intercallated cells
K+ reabsorption
H+ secretion
Type B intercalated cells
K+ secretion
H+ reabsorption
Three factors that CONTROL rate of K+ secretion
Activity of Na-K ATPase
Electrochemical gradient for K+ movement from the blood to the tubular lumen
Permeability of tubular membrane to K+
Stimulation of Potassium Secretion
Increased extracellular [K+]
Increased [aldosterone]
Increased tubular flow rate
Increased [H+] will DECREASE potassium secretion
Increased Plasma Potassium
Always a certain level of secretion even at normal [K+
Increased [K+] stimulates action of Na-K ATPase
More K+ moved into cell from interstitial space which increases gradient from cell interior to tubular lumen
[K+] of renal interstitial fluid increases (increased plasma concentration) which decreases amount of K+ diffusing from cell interior into interstitial space
Increase [K+] in plasma stimulates release of aldosterone
Increased Aldosterone
- increases rate of sodium reabsorption by late distal tubule and collecting duct
Increases activity of Na-K ATPase
So an increase in sodium reabsorption will also increase potassium secretion
Increases tubular membrane permeability for potassium
Plasma Potassium & Aldosterone
Great example of negative feedback control system
Factor being controlled (potassium) has feedback effect on controller (aldosterone)
Small change in plasma [K+] produced huge change in aldosterone concentration
Regulation of Potassium Excretion
- Anything that affects our ability to produce aldosterone will have a big effect on potassium excretion!!
- High aldosterone (primary aldosteronism) -> Hypokalemia -> hypernaturemia
- Low aldosterone (Addison’s disease) -> Hyperkalemia
Increased K+ intake with intact aldosterone feedback
Big change in intake (x7 increase) small change [K+] (4.2 to 4.3 mEq/liter)
Increased K+ intake with blocked aldosterone feedback
Big change in intake (x7 increase) big change in [K+] (3.8 to 4.7 mEq/liter)
Relationship between tubular flow rate and potassium secretion
- greatly affected by potassium intake
Higher the intake, the greater the effect created by tubular flow
Increased distal tubular flow rate will increase potassium secretion
Increased tubular flow rate can be caused by volume expansion; high sodium intake; specific diuretics
Mechanism for Tubular Flow Effect
As potassium diffuses into tubular lumen, the increase in luminal concentration will decrease the gradient thus decreasing the movement of potassium
Increased tubular flow carries potassium away thus helping to preserve the gradient. The higher the flow the better the gradient is preserved, the more potassium is secreted
Preserving K+ Excretion With Changing Na+ Intake: Assume high Na+ intake
Aldosterone secretion decreases which will produce a decrease K+ secretion
BUT since sodium reabsorption is decreased, overall distal tubular flow is increased which results in an increase in K+ secretion
- THE TWO OFF SET EACH OTHER