Acidification of urine

1. Acidification of urine
BY DR A AMAR SANDEEP

2. Content
1. Hydrogen ion secretion
2. Reabsorption of filtered HCo3
3. Excretion of H+ as titrable acid
4. Excretion of H+ as ammonium ion

4. Hydrogen ion secretion
1. Mechanism of H+ secretion by proximal tubule
2. Mechanism of H+ secretion by distal tubules and collecting ducts
3. Fate of H+ secreted in the renal tubule

5. Mechanism of H+ secretion by proximal
tubule
1. Formation of carbonic acid
2. Dissociation of carbonic acid
3. Secretion of H+ into the lumen
4. The secreted H+, in the lumen, combines
with the filtered HCO3 –
5. HCO3 - formed in the cell

6. Mechanism of H+ secretion by distal
tubules and collecting ducts
 In the distal tubule and collecting ducts, H+ secretion occurs independent of Na+
 Two mechanisms are involved in secretion of H+ by the intercalated cells in these parts
of tubules
1. ATP-driven proton pump is mainly responsible for the secretion of H+ in the distal
tubules and collecting ducts.
2. H+, K+–ATPase is also responsible for secretion of some of the H+ coupled with
reabsorption of K+ in these parts of renal tubules
 The tubular cells can secrete H+, up to a luminal fluid pH of about 4.5
 In the proximal tubule, the secreted H+ is buffered by the filtered HCO
 In the distal tubule and connecting ducts, the secreted H+ ions are buffered by
Na2HPO4 and NH3 and are excreted as titrable acid and ammonium ion

7. REABSORPTION OF FILTERED HCO3
 Reabsorption at various segments
 Regulation of HCO3 − reabsorption
 Generation of new HCo3-

8. Reabsorption at various
segments
 Proximal tubule
 Loop of Henle
 Distal tubules and collecting ducts

9. Regulation of HCO3 − reabsorption
1. Plasma HCO3 − level
2. pCO2 level
3. Extracellular fluid (ECF) volume
4. Aldosterone and angiotensin II
5. Parathyroid hormone
6. Plasma K+ levels

10. 1. Plasma HCO3 − level
 Increase in the plasma HCO3 − increases the filtered load of HCO3 − resulting in
increased HCO3 − reabsorption.
 Decrease in plasma HCO3 −, the filtered load is decreased and this results in
decreased HCO3 − secretion
2. pCO2 level
 Increased pCO2 results in increased rates of HCO3 − reabsorption
 Decreased pCO2 results in decreased rates of HCO3 − reabsorption

11. 3. Extracellular fluid (ECF) volume
 ECF volume expansion (positive Na+ balance) secondarily results in less H+
secretion (through Na+−H+ antiport) and thus decreased HCO3 − reabsorption
 ECF volume contraction (negative Na+ balance) secondarily results in increased
H+ secretion (through Na+−H+ antiport) and thus increased HCO3 −
reabsorption
4. Aldosterone and angiotensin II
 They affect the HCO3 − reabsorption by their effect on Na+ reabsorption and
associated H+ secretion through Na+–H+ antiporter

12. 5. Parathyroid hormone
 PTH inhibits HCO3 − reabsorption by
proximal tubules by inhibiting PKC
6. Plasma K+ levels
 They influence the secretion of H+ by
the proximal tubules, with hypokalaemia
stimulating and hyperkalaemia inhibiting
secretion

13. GENERATION OF NEW HCO3 −
 HCO3 − reabsorption alone does not replenish the HCO3 − lost during the
titration of non-volatile acids which are daily added to the plasma, from the diet
and produced by metabolism
 The kidneys replace this lost HCO3 − with new HCO3 − by following processes
1. Excretion of H+ as titrable acid
2. Excretion of H+ as NH4.

14. Excretion of H+ as titrable acid
 Excretion of H+ as titrable acid refers to the
excretion of secreted H+ along with the
primary urinary buffer the dibasic phosphate
(HPO42-)
 This reaction occurs in the distal tubules and
collecting ducts
 The acidification of the urine may lower its pH
to a minimum of 4.5, i H+ concentration of
urine is approximately 1000 times the
concentration of H+ in the plasma.
 Thus, the titrable acidity is a measure of acid
excreted in the urine by the kidney

15. Excretion of H+ as ammonium ion
1. Synthesis of NH4 + and new HCO3 − in proximal tubule
2. Reabsorption of NH4 + across thick ascending limb
3. Accumulation of NH4 + in medullary interstitium
4. Anionic diffusion and diffusion trapping in collecting ducts

16. Synthesis of NH4 + and new HCO3 − in
proximal tubule
 Glutamine is metabolised into two
molecules each of NH4 + and HCO3
 HCO3 − diffuses across the basolateral
membrane into the peritubular blood as
new HCO
 NH4 + is secreted into the lumen via Na+–
H+ antiporter. Some NH4 + is converted
into NH3 + and H+. NH3 + diffuses into
the lumen where it combines with the
secreted H+ to form NH4

17. Reabsorption of NH4 + across thick
ascending limb
 NH4 + then moves along the tubular
fluid.
 In the TAL of loop of Henle, a significant
amount of NH4 + is reabsorbed via two
mechanisms
1. Transcellularly, via 1Na+–1K+–2Cl–
symporter with NH4 + substituting for K+
and
2. Paracellularly driven by the lumen positive
transepithelial voltage in this segment

18. Accumulation of NH4 + in medullary
interstitium
 The NH4 + reabsorbed across the TAL accumulates in the medullary interstitium
 Here it exists in chemical equilibrium with NH3 +

19. Anionic diffusion and diffusion trapping in
collecting ducts
 The cells of collecting duct are not permeable to NH4 +, but permeable to NH3 +.
 From the medullary interstitium, NH3 + diffuses into the lumen of collecting ducts
by a process called non-ionic diffusion and is protonated to NH4 + by combining
with H+ secreted by the cells of the collecting duct.
 Since the cells of the collecting ducts are impermeable to NH4 +, so NH4 + is
trapped in the lumen of the collecting duct (diffusion trapping) and is excreted in
the urine.
 Thus, for every NH4 + excreted in the urine, a new HCO3 − is returned to the
systemic circulation.

21. Summary
 When renal tubule cells secrete H+ into the lumen, this H+ simultaneously titrates
three kinds of buffers: (1) HCO− 3, (2) HPO4 2− and other buffers that become the
titratable acid, and (3) NH3.
 Each of these three buffers competes with the other two for available H+
 The kidneys secrete 4390 mmol/day of H+ into the tubule lumen. The kidneys use
most of this secreted acid— 4320 mmol/day or ~98% of the total to reclaim
filtered HCO− 3.
 The balance of the total secreted H+ (70 mmol/day) the kidneys use to generate
new HCO− 3

22. Thank you