4.8. Role of the kidneys in the regulation of acid-base balance.

Question 1

I. Basics
1. What are the 2 main functions of kidney

Answer 1

1. Reabsorb the filtered HCO3-
2. Excrete fixed H+ by mechanisms of:
   a. excretion of H+ as titratable acid (urinary phosphate)
   b. excretion of H+ as NH4+
   => mechanisms are accompanied by synthesis and reabsorption of new HCO3- in order to replenish the
   HCO3- that were used in buffering H+

Question 2

I. Basics
2. What is the requirement for the pH-level of bodily fluids to remain stable?

Answer 2

Net acid excretion(NAE) must equal the net acid production, in order for the pH-level of bodily fluids to remain stable
- NAE: total amount of acid excreted in the urine per unit time

Question 3

I. Basics
3. What is the formula of Net acid excretion(NAE) ? Interpret it

Answer 3

NAE = titratable acidity (+) NH4+-excretion (–) HCO3- -excretion
- Titratable acidity: amount of excreted H+ that is bound to urinary buffers (buffered amount)
- NH4+-excretion: amount of excreted H+ bound to NH4+ (trapped amount)
- Amount of HCO3 – excreted: loss of HCO3- that results in buffering capacity

Question 4

I. Basics
4. What is the main urinary buffer?

Answer 4

Phosphate (inorganic) is the main urinary buffer, but creatinine also exists in the tubular fluid and can buffer H+.

Question 5

I. Basics
5. How does phosphate & creatinine work as a renal buffer?

Answer 5

Phosphate (inorganic) is the main urinary buffer, but creatinine also exists in the tubular fluid and can buffer H+. However, its pK (5) is lower than that of phosphate (6,8), so it does not buffer urine as well in the physiological range of urine pH (4,5 – 8)
- Phosphate can buffer more acid than creatinine before the pH of 4,4 is reached
- Filtered load remaining of the phosphate buffer is 10% and not 1% as expected
+) The phosphate is getting more concentrated as we go along the nephron
- Out of 70mmole H+/day, phosphate can buffer about 18mmole
- Creatinine will buffer around 5,5mmole
=> Total 23mmole H+ buffered out of 70mmole

Question 6

II. HCO3- - reabsorption
1. What is the mechanism of HCO3- - reabsorption?

Answer 6

HCO3- primarily reabsorbed with sodium in the PT
- H+-secretion via Na/H-exchanger, where Na+ is reabsorbed
- H+ in the tubular lumen combines with filtered HCO3- to form H2CO3, which is rapidly degraded to H2O and CO2 by carboanhydrase
- H2O + CO2 diffuse back into the PT epithelium, and reform H2CO3 via carboanhydrase
- H+ is recycled by the Na/H-exchanger, while HCO3- is reabsorbed basolaterally via Na/HCO3 – symporter
=> pH is beginning to go down because of the increased presence of H+ in the tubular lumen

Question 7

II. HCO3- - reabsorption
2A. What are Intercalated cells?

Answer 7

The cells which perform this mechanisms are the intercalated cells of the distal tubule and collecting ducts. The α- and β-intercalated cells

Question 8

II. HCO3- - reabsorption
2B. What are 2 types of Intercalated cells?

Answer 8

The α- and β-intercalated cells

Question 9

II. HCO3- - reabsorption
2C. What are the role and mechanism of α-intercalated cell?

Answer 9

α-intercalated cell: H+-secretion and HCO3- - reabsorption
- proton pump (H+-ATPase) and H/K-ATPase on luminal membrane secretes H+ into tubule
- for every H+ secreted, an HCO3- is reabsorbed via Cl/HCO3- - exchanger

Question 10

II. HCO3- - reabsorption
2D. What are the role and mechanism of β-intercalated cell?

Answer 10

β-intercalated cell: HCO3- - secretion and H+-reabsorption
- Cl/HCO3- - exchanger on luminal side secretes HCO3-
into the lumen
- proton pump (H+-ATPase) on basolateral side reabsorbs H+
=> there are cells which can have the function of acid excretion/secretion OR acid release (reabsorption) into interstitial space = intercalated cells at different positions (Hensin)

Question 11

III. Excretion of H+ as titratable acid
1. What is Excretion of H+ as titratable acid in kidney?

Answer 11

1. Titratable acid is excreted with urinary buffers, inorganic phosphate is the most important of these buffers because of its relatively high conc in urine and its ideal pK (6.8).
2. Titratable acid is excreted throughout nephron but
   primarily in the ⍺-intercalated cells in connecting and collecting duct.

Question 12

IV. Excretion of H+ as NH4+
1. How does Excretion of H+ as NH4+ occur in proximal tubule?

Answer 12

Glutaminase metabolizes glutamine to glutamate and NH4+.
=> Dissociated NH3 is lipid soluble which can diffuse into lumen down the concentration gradient. H+ is secreted into lumen via Na-H exchanger. Once in lumen they recombine into NH4+.

Question 13

IV. Excretion of H+ as NH4+
2. What is Mechanism of excretion of titratable acid (also HCO3- synthesis and reabsorption)?

Answer 13

• H+ ATPase (stimulated by aldosterone) and H-K ATPase for pumping H+ into the lumen.
• Secreted H+ combines with HPO4-2 (hydrogenphosphate, A- ), to produce H2PO4- (dihydrogenphosphate, HA the titratable acid), which is excreted.
• H+ used in H+ ATPase is produced from CO2 and H2O in the renal cells. The new HCO3- is reabsorbed into blood via Cl- HCO3- exchanger.
  => For each H+ excreted as titratable acid, one new HCO3- is synthesized and reabsorbed.

Question 14

IV. Excretion of H+ as NH4+
2. How does Excretion of H+ as NH4+ occur in TAL (thick ascending limb of Henle loop)?

Answer 14

NH4+ secreted in PT is absorbed here by substituting for K+ on NaK2Cl cotransporter.
=> NH4+ participate in countercurrent multiplication, is concentrated in the interstitial fluid of the inner medulla

Question 15

IV. Excretion of H+ as NH4+
3. How does Excretion of H+ as NH4+ occur in collecting duct?

Answer 15

• Here the NH3+ diffuses from its high concentration in the medullary interstitial fluid into the lumen of CD. H+ is secreted via H+-ATPase and H-K ATPase.
  => They combine to form NH4+.