Lecture 4: Regulation of K+ secretion, Regulation of pH

is most of the K+ in our body intracellular and extracellular

intracellular

explain effects of low extracellular K+ concentration (hypokalemia) on neuronal and skeletal muscle action potentials

bigger K+ gradient → more negative equilibrium potential for K+ (Ek) → pulls the resting potential toward K+ equilibrium potential → Vm farther from threshold → more difficult to generate action potential

explain effects of high extracellular K+ concentration (hyperkalemia) on neuronal and skeletal muscle action potentials

smaller K+ gradient → Ek is less negative → resting Vm less negative → not as far from threshold → hyper-excitability → easier to generate AP

is K+ synthesized in the body?

no

where is K+ filtered

• freely filtered at the glomerulus

• 55% of filtered load is reabsorbed in the proximal tubule

• 30% of filtered load is reabsorbed in loop of Henle

how is secretion of K+ controlled

• aldosterone

• ECF [K+]

• flow rate

what is the relationship between plasma [K+] and aldosterone

• increased plasma K+ → acts on adrenal → increased aldosterone release

• decreased plasma K+ → acts on adrenal → decreased aldosterone release

what is the relationship between ECF [K+] and K+ secretion

• hyperkalemia (high ECF K+) → acts on Na/K ATPases on CD basolateral membrane → increases K+ secretion

• hypokalemia (low ECF K+) → acts on Na/K ATPases on CD basolateral membrane → decreases K+ secretion

what is the relationship between flow rate and K+ secretion

• high flow rate → acts in CCD → increases K+ secretion

• low flow rate → acts in CCD → decreases K+ secretion

explain the action mechanism of aldosterone on K+ secretion

1. aldosterone combines with cytoplasmic receptor

2. initiates transcription, translation, and protein synthesis in nucleus

3. proteins modulate increased ROMK channel activity and increased Na+/K+ pump activity

4. result is increased K+ secretion (and Na+ reabsorption)

explain action mechanism of tubular flow rate on K+ secretion

1. high flow rate

2. deflects cilia

3. Ca+ influx

4. increased cytosolic Ca2+

5. opens BK (big K) channels

6. increased K+ secretion

how does flow rate also affect ROMK

increased sodium delivery typically occurs with increased tubular fluid flow → increased ENac activity → enhanced ROMK-mediated K+ secretion

explain what happens when low MAP (low GFR) and high RAA (but K+ is normal)

• Ang II stimulates Na+ reabsorption by proximal tubule → high Na+ and H2O retention

• Aldo stimulates Na+ reabsorption in connecting tubule and CCD (via ENaC and Na/K ATPases) → high Na+ and H2O retention

• Ang II inhibits ROMK in CCD → relatively less K+ secretion

• low flow rate (due to low GFR and high Na+ and H2O reabsorption in CCD) → BK channels in CD are closed → reduced K+ secretion

explain what happens when High K+ and high aldo (but MAP is normal)

• ang II is low → low reabsorption of Na+ and H2O in proximal and distal tubule → flow rate is higher

• higher flow rate opens BK channels → high K+ secretion

• aldo stimulates K+ secretion in CCD (ROMK and Na/K ATPases)

• high K in ECF stimulates K+ secretion (ROMK and Na/K ATPases)

what is the CO2*HCO3- system

what is the major extracellular buffer

CO2*HCO3- system

what is the major intracellular buffer

phosphates and proteins

acidosis can develop if

• H+ is added to the blood

• HCO3- is removed from the blood

• CO2 is added to the blood

alkalosis can develop if

• H+ is removed from the blood

• HCO3- is added to the blood

• CO2 is removed from the blood

blood Pco2 changes have a significant impact on blood __ levels, but an insignificant impact on blood __ level

H+, HCO3-

if we get/lose 1 H+ and 1 HCO3-, then why does pH change

when Pco2 increases, [H]+ increases signficantly but [HCO3-] increases insignificant amount. so a Pco2 increase → a pH decrease

if increase HCO3-/Pco2, then _________

alkalosis

if decrease HCO3-/Pco2, then ________

acidosis

plasma Co2 is controlled by

the lungs (rapid)

plasma HCO3 is controlled by

the kidneys (slower)

what happens when HCO3 is excreted via kidney

renal excretion of HCO3- → gain of H+ → decreased ECF pH

what happens when new HCO3 is added by the kidney

renal addition of new HCO3- → lose H+ → increased ECF pH

explain the mechanism of reabsorption of filtered HCO3- at proximal tubule

1. H2O + CO2

2. carbonic anhydrase (CA)

3. H2CO3 splits into H+ and HCO3-

4. HCO3- added to ECF by facilitated diffusion and H+ is secreted by active transport into tubule lumen

5. secreted H+ combines with filtered bicarbonate to form H2O and CO2

6. H2O and CO2 diffuses back into the proximal tubule cells — so H+ not excreted