Lecture 22: renal contribution to respiratory acidosis

Question 1

What renal mechanisms come into play to bring the PH back closer to normal when [H+] is elevated in the body?

ie the compensation for respiratory acidosis

Answer 1

• the kidney secretes more H+ by reabsorbing HCO3- - PCT & distal regions of nephron
• the kidney makes additional HCO3- mainly in the PCT

Question 2

Describe the cellular mechanisms for PCT transport of H+ and HCO3-

Answer 2

• the** basolateral Na+-K+-ATPase** maintains a** low intracellularNa+ concentration** - this gradient provides energy for other pumps
• H+ secretion occurs on the apical membrane into the tubular fluid via the Na+/H+ antiporter (NHE3) and via H+-ATPase
• H+ **combines with filtered HCO3- **and **forms H2CO3 **which is dissociated into co2 and H20 by carbonic anhydrase 4 by brush border
• intracellular CA 2 converts the CO2 and H20 into H2CO3 which dissociates into H+ and HCO3-
  * HCO3- exits the cell via a Na+-HCO3- symporter (NBC1) and via a Cl-HCO3-antiporter (AE2)

Question 3

Compare the 2 different carbonic anhydrase enzymes and where they are located

Answer 3

• CA4 is located on the brush border of the PCT cells
• CA2 is located inside the PCT cell

Question 4

In the PCT, what transporters are present on the apical membrane to facilitate H+ secretion?

Answer 4

• Na+-H+ antiporter (NHE3)
• H+-ATPase

Question 5

what different transporters are present on the apical membrane for H+ secretion in the TAL and early DCT?

Answer 5

• Na+-H+antiporter called NHE2
• H+-ATPase

Question 6

What different transporters are located on the** basolateral membrane** for HCO3- reabsorption in the TAL and early DCT?

Answer 6

• Na+-HC03- symporter NBCn1
• Cl–HCO3- antiporter

Question 7

what type of cell is involved in H+ secretion and HCO3- reabsorption in the late distal tubule and collecting duct?

Answer 7

type A intercalated cells

Question 8

Describe the cellular mechanisms for H+ and HCO3- transport by type A intercalated cells of the collecting duct

Answer 8

• H+ secretion across the apical membrane occurs by H+K+-ATPase and H+-ATPase
• HCO3- reabsorption across the basolateral membrane via Cl–HCO3- antiporter (AE-1)

Question 9

what is titratable acid in renal physiology?

Answer 9

• a titratable acid refers to a non-volatile acid eg phosphoric acid that is used to exclude ammonium NH4+ as a source of acid

Question 10

What are the 2 mechanisms that generate additional HCO3- in the nephron?

Answer 10

1. secreted H+ combines with another filtered titratable acid buffer other than HCO3- such as uric acid etc
2. renal production and secretion of NH4+

Question 11

what is the net effect of a secreted H+ ion combining to a buffer other than HCO3-?

Answer 11

• the net effect is the production of additional HCO3-

Question 12

describe how NH4+ is formed in PCT

Answer 12

• glutanimase catalyses the conversion of glutamine to glutamic acid which forms an ammonium ion -NH4+

Question 13

what does glutamic acid get converted to and what is produced as a result?

Answer 13

• alpha - ketoglutarate
• HCO3- is produced as a result and ets reabsorbed into the plasma

Question 14

What happens to the NH4+ that is produced along the nephron?

Answer 14

• NH4+ is secreted into the tubular fluid in the PCT
• however, much of the secreted NH4+ is reabsorbed by the TAL - which results in the accumulation of NH4+ in the** medullary interstitium **
• NH4+ in the MI dissociotes into NH3 & H+
• NH3 diffuses into the collecting duct (from high to low conc) and becomes protonated by a H+ to become NH4+
• NH4+ is excreted