Week 2: Renal mechanisms of acid excretion

Question 1

What are two functions of tubule acid secretion?

Answer 1

• reabsorb filtered HCO3- back to the blood and prevent urinary buffer loss
• form new HCO3- which is transported into blood to alkalinize the body fluids, to replace HCO3- lost in compensation for metabolic acidosis
• limited by transporters that stop working when tubular lumen falls below pH 4.4 (steep uphill gradient) (NHE and H-ATPase.

Question 2

Review bicarbonate reabsorption in PT/TALH and intercalated cells.

Answer 2

1. PT and TALH
   - CA in luminal membranes and inside cell
   - bicarb absorbed as CO2 and H2O and converted back to bicarb in cell. Acid secreted by H-ATPase and NHE. Bicarb secreted by Na/3HCO3- cotransporter and HCO3-/Cl- anti-port on basolateral membrane
2. Intercalated cells
   - CA inside the cell only, slow formation of water and CO2 from bicarb to enter cell
   - acid secreted from K/H+ anti-port and H-ATPase
   - bicarb exits cell through HCO3-/Cl anti-port

Question 3

What are ways new HCO3- is formed in the kidneys?

Answer 3

1. Titratable acid
   - HCO3- made from water and CO2 inside cell via Carbonic Anhydrase. The CO2 inside the cell is not from filtered HCO3-
   - filtered buffers in the tubular fluid can trap the secreted H+ and buffer fall in lumen pH (phosphates, sulfates, urate).
   - amount of bicarb formed by this route defined by amount of H+ that can be trapped before pH falls to 4.0 ( H+ made from formation of new bicarb)
2. Ammoniagenesis
   - glutamine transported into PT cell metabolized by glutaminase to NH4+ and a-ketoglutarate, which is converted to glucose. 2 HCO3- formed in the process for each a-ketoglutarate.
   - acidosis increases glutaminase activity by increasing gene expression and mRNA stability
   - new HCO3- formed without secreting H+
   - NH4+ is secreted into the tubule lumen via NHE mediated Na/NH4 exchange, K channels, and as NH3

Question 4

Describe handling of NH4+ in the nephron?

Answer 4

• important because it needs to be excreted for new HCO3- to have an impact. Otherwise 2NH4+–>urea +2H+ with H+ combining with HCO3- in the blood
• NH4+ is reabsorbed in the TALH into ISF by NKCC
• NH4+ can be secreted from ISF into lumen of collecting duct by NH4+ transporter
• Na/K ATPase is major mechanism of NH4+ uptake from ISF to cell on basolateral membrane
• NH3 can diffuse from ISF to CD lumen but must be trapped to remain there. Trapped by H+ secreted by CD intercalated cells via H-ATPase and H/K-ATPase

Question 5

How do the kidneys respond to metabolic alkalosis?

Answer 5

-intercalated ells in CD, beta cells, that have H-ATPase flipped to basolateral side cell, secrets H+ into ISF
-has Cl/HCO3- pedrin exchanger, secrets HCO3- into lumen
goal is to produce alkaline urin which will acidify the body fluids

Question 6

How do ECF pH and potassium status influence tubular acid secretion?

Answer 6

1. ECF pH
   - drop in pH (H+ increase) will increase driving force for H+ secretion
2. Potassium status: fixed negative charges on cell proteins are balanced by cell K+ and H+. So H+ and K+ have reciprocal relationship
   - Hyperkalemia: increased K+ ICF will lead to decreased H+ ICF. Decreased H+ secretion and bicarb reabsorption–> metabolic acidosis
   - Hypokalemia: leads to decreased K+ and increased H+ in cell. Increased H+ secretion and HCO3- reabsorption in kidney–>metabolic alkalosis
3. GFR
   - increased GFR–>increased H+secretion and increased NaHCO3 reabsorption
4. Decreased ECF volume
   - leads to contraction alkalosis
   - Increased AngII–>increased Na/H transport in PT–>increased H+ secretion and HCO3- reabsorption
   - increased aldosterone–>increased Na+ reabsorption, increased H+ secretion and K+ secretion in collecting ducts
5. PCO2
   - increased CO2 (e.g. respiratory acidosis) increased H+ secretion and HCO3- reabsorption