4.3B. Renal Na+ and K+ excretion and regulation.

Question 1

I. Na excretion and regulation
1. The role of Na+ in ECF

Answer 1

• The amount of Na in the ECF determines the ECF volume. (↑Na=↑ECF vol, blood vol, BP)
• Effective arterial blood volume (EABV): portion of ECF vol contained in arteries and is vol effectively
  perfusing tissues.

Question 2

I. Na+ excretion and regulation
2. What are the 4 mechanisms of Na+ excretion and regulation

Answer 2

1) Sympathetic nerve activity
2) Atrial natriuretic peptide (ANP)
3) Starling forces in peritubular capillaries
4) Renin-angiotensin-aldosterone system

Question 3

I. Na+ excretion and regulation
3. How does Sympathetic nerve activity participate in Na+ excretion and regulation?

Answer 3

• activated by baroreceptor when ↓BP
• causes vasoconstriction of afferent arterioles and ↑Na reabsorption in PT.

Question 4

I. Na+ excretion and regulation
4. How does Atrial natriuretic peptide (ANP) participate in Na+ excretion and regulation?

Answer 4

• Secreted by atria when EABV↑(↑BP)
• Causes vasodilation of afferent a and vasoconstriction of efferent a. = ↑GFR and ↓Na reabsorption
• Also inhibits ENaC channels in connecting and collecting ducts = ↓Na reabsorption, ↑Na and H2O excretion = ↓BP

Question 5

I. Na+ excretion and regulation
5. How does Starling forces in peritubular capillaries participate in Na+ excretion and regulation

Answer 5

• Increases in ECF volume dilute oncotic P in capillary, inhibiting PT Na reabsorption and vice versa

Question 6

I. Na+ excretion and regulation
6. How does Renin-angiotensin-aldosterone system participate in Na+ excretion and regulation?

Answer 6

• Activated in response to ↓BP, ↑Na &H2O reabsorption⇒ ↑BP

Question 7

II. K+ excretion and regulation
1. What are the characteristics of Urinary excretion of K

Answer 7

Urinary excretion of K is exactly equal to the dietary K
- K excretion<intake = hyperkalemia
- K excretion>intake = hypokalemia.

Because dietary intake can vary greatly, renal mechanism for K balance are quite flexible

Question 8

II. K+ excretion and regulation
2. What are the steps in K+ excretion?

Answer 8

1. Filtration: K is freely filtered across the glomerular capillaries
2. PCT: 2/3 of the filtered load of K is reabsorbed paracellularly with Na (isosmotic reabsorption driven by Cl
   movement)
3. TAL: additional 20% of the filtered load of K is reabsorbed via NaK2Cl cotransporter and they can either leave the cell basolaterally via K channel or can go back into the lumen via ROMK1 = lumen + potential difference
4. DT and CD: where K excretion is adjusted depending on dietary K intake.
   - Normal or high K diet: K is secreted by principal cells. Na-K ATPase creates high KIC, driving K into the lumen. This mechanism is regulated by aldosterone (↑Na & H2O reabsorption, ↑BP, ↑K secretion)
   - Low K diet: K is reabsorbed by ⍺ intercalated cells. H-K ATPase transports H into lumen and K into the cell which then goes to interstitium via K+ channel

Question 9

II. K+ excretion and regulation
3. How is K+ excreted via DT and CD?

Answer 9

DT and CD: where K excretion is adjusted depending on dietary K intake.
- Normal or high K diet: K is secreted by principal cells. Na-K ATPase creates high KIC, driving K into the lumen. This mechanism is regulated by aldosterone (↑Na & H2O reabsorption, ↑BP, ↑K secretion)
- Low K diet: K is reabsorbed by ⍺ intercalated cells. H-K ATPase transports H into lumen and K into the cell which then goes to interstitium via K channe

Question 10

II. K+ excretion and regulation
4. What are the characteristics of K+ regulation?

Answer 10

The alternation of K secretion depends on the magnitude of the electrochemical gradient for K across the luminal membrane.

Question 11

II. K+ excretion and regulation
5. What are the 4 factors participating in K+ regulation?

Answer 11

1. Aldosterone
2. Acid-base disturbances
3. Diuretics
4. Luminal anions

Question 12

II. K+ excretion and regulation
6. How can Aldosterone participate in K+ regulation?

Answer 12

Aldosterone = ↑K secretion
- Induces the synthesis of ENaC (luminal) and Na-K ATPase (basolateral) which ↑KIC, and also ↑# K channels which ↑driving force for secretion

Question 13

II. K+ excretion and regulation
7. How can Acid-base disturbances participate in K+ regulation?

Answer 13

• Alkalosis = deficit of H in ECF→H leaves and K enters→↑KIC=↑K secretion
• Acidosis = excess of H in ECF →H enters and K leaves→↓ KIC=↓K secretion. Also, ROMK1 is inhibited by acidosis.

Question 14

II. K+ excretion and regulation
8. How can diuretics participate in K+ regulation?

Answer 14

• Loop diuretics (inhibit NaK2Cl cotransport in TAL) and thiazide diuretics (inhibit NaCl cotransport in DCT) inhibit Na reabsorption, which results in increased delivery of Na to the collecting tubule site. This will increase Na reabsorption thus increases K secretion as a consequence. The diuretics also increase the flow rate, which dilutes the luminal K conc, thus increases the driving force for K secretion.
• K sparing diuretics such as amiloride (inhibit ENaC), act against aldosterone, thus inhibiting K secretion

Question 15

II. K+ excretion and regulation
9. How can Luminal anions participate in K+ regulation?

Answer 15

The presence of large anions such as sulfate and bicarbonate increase the electronegativity of lumen, thus
increasing the driving force for K secretion.