The kidneys play a major role in regulating pH levels in the body through net acid excretion. The kidneys reabsorb nearly all filtered bicarbonate and add new bicarbonate during acid loads by excreting ammonium. Proximal tubular absorption of bicarbonate occurs through NHE-2, NHE-3, and H+-ATPase transporters. Distal tubular acidification involves reabsorption of remaining bicarbonate and secretion of fixed acids and ammonium through buffering and recycling in the collecting duct. Hormones like endothelin-1, glucocorticoids, and PTH regulate renal acidification in response to acid-base conditions.

1. RENAL ACIDIFICATION

2. H+ and HCo3-
• H+ ion , smallest ion
• Million fold lesser in concentration than HCo3-
• H+ play a major role in ETC- generation of ATP
• If their conc. exceeds a tight range, it can lead to
acidemia.
• Binding of H + to proteins ( functioning as
enzymes, transporters, contractile elements, and
structural compounds) can lead to their altered
function

3. Body needs some mechanism to keep H + in check
Answer to this are buffers
EXTRACELLULAR BUFFER
a) Bicarbonate buffer system
(H+ )+ ( HCO3 -) ↔ (CO2)+(H20)
b) Plasma proteins
c) Phosphate
d) Bone apatite

4. INTRACELLULAR BUFFER
a) Hemoglobin
b) Cellular proteins
c) Organophosphate complexes
d) HCO3
Excess acid or alkali generated needs to be
removed from body……
Portals – LUNG & KIDNEY

5. RENAL REGULATION OF pH
Kidneys cause Net Acid Excretion (NAE) which is
summation of
a) Ammonium excretion (60 %)
b) Titrable acid (PO4, UA, Cr)excretion (40 %)
c) Bicarbonate excretion (0% in normal states)
Thus kidney should-
• Reabsorb near total filtered bicarb by excreting
H +
• Add new bicarb in acid load by excreting
Ammonium

7. Renal handling of acid bases at
different levels of nephrons
GLOMERULUS –
No significant role in regulation
Only causes about 4500 mmol/day of HCo3 loss
(GFR multiplied by bicarbonate concentration)
The major business of acid base regulation is in
tubules

8. HCo3- absorption

9. Renal acid-base homeostasis may be broadly
divided into 2 processes
1. Proximal urinary acidification
i.e Proximal tubular absorption of HCO3
-
2. Distal urinary acidification.
 Reabsorption of remaining HCO3
- that escapes
proximally.
 Excretion of fixed acids through buffering &
Ammonia recycling and excretion of NH4
+.

10. Proximal tubular HCo3 - absorption
NHE – 2/3
H ATPase – 1/3
IV II
NA K ATPase
NA HCO3
COTRANSPORTER
Cl HCO3 ANTIPORTER

11. THICK ASCENDING LOOP OF HENLE
NA H ANTIPORTER
NA K
ATPase
NA HCO3
COTRANS
PORTER
Cl
HCO3
EXC

12. COLLECTING DUCT
The segments of the collecting duct include
A) Cortical collecting duct
B) Outer medullary collecting duct
C) Inner medullary collecting duct.
There are two distinct cell types in the cortical
collecting duct histologically:
a) The principal cell and
b) The intercalated cell.

13. Principal cell- Reabsorbs Na+ and
Secretes K+
Intercalated cells- secrete acid - α cells
secrete base – β cells

14. H ATPase
H K ATPase
CA II
Cl HCO3 EXCHGR

15. H ATPase
HCO3 Cl EXC

16. Ammonia metabolism
The proximal tubule is responsible for both
a) Ammonia production
(from glutamine metabolism resulting in
production of two NH4+ and two HCO3 ions from
each glutamine ion)
b ) Luminal secretion
(NH4 + transport by the apical Na+-H+ antiporter
NHE3)

17. Metabolic acidosis increases the mobilization of
glutamine from skeletal muscle and intestinal
cells.
Glutamine is preferentially taken up by the proximal
tubular cell through the Na+- and H+-dependent
glutamine transporter SNAT3.
SNAT3 expression increases several fold in metabolic
acidosis, and it is preferentially expressed on the cell’s
basolateral surface

18. Proximal tubule

19. Distal tubule

20. Net Acid
Excretion
NH4 +
Excretion
Titrable
Acid
Excretion
HCO3
Excretion
ACIDOSIS ↑ ↑ ↑ ↓
ALKALOSIS ↓ ↓ ↓ ↑

21. REGULATION OF RENAL ACIDIFICTION
CONDITION SITE OF NEPHRON
ECF VOLUME CONTRACTION
ANGIOTENSIN II
PCT , DCT
HYPERALDOSTERONISM PCT , CD
HYPOKALEMIA PCT, CD – INTERCALATED CELLS
DECREASED ACID EXCRETION

22. REGULATION OF RENAL ACIDIFICTION
CONDITION SITE OF NEPHRON
ECF VOLUME EXPANSION
ANGIOTENSIN II
PCT , DCT
HYPOALDOSTERONISM PCT , CD
HYPOKALEMIA PCT, CD – INTERCALATED CELLS
INCREASED ACID EXCRETION

23. Hormonal Regulation
• Endothelin-1
a) Acidosis causes increased ET-1 expression by
proximal tubule
b) Increased transcription, translation and
expression of NHE-3 and NBCe1
c) ET-1 may also be involved in distal nephron
regulation
• Glucocorticoid
a) Acidosis triggers secretion
b) Increased transcription, translation and
expression of NHE-3 and NBCe1
c) Stimulation of ammoniagenesis

24. Hormonal Regulation
• Parathyroid Hormone (PTH)
a) Secretion stimulated by acidosis
b) PTH inhibits proximal Pi reabsorption
c) Pi delivered distally results in an increase in
titratable acid excretion