1. RENAL CONTROL OF ACID-BASE BALANCE
12/6/2018
Renal Control of Acid-Base Balance

2. RENAL CONTROL OF ACID-BASE BALANCE
The kidneys control acid-base balance by excreting either an acidic or a basic urine.
It does so by regulating the rate of secretion of H+ and reabsorption of HCO3-
12/6/2018
Renal Control of Acid-Base Balance

3. SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES.
Occur in virtually all parts of the tubules except the thin segments of the loop of Henle.
 85% of HCO3- reabsoption,(also H+ secretion) occur in the proximal tubules.
 10% in the thick segment of the loop of Henle.
12/6/2018
Renal Control of Acid-Base Balance

4. SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES.
 5% in he distal tubules and collecting ducts.
HCO3- reabsoption involves H+ secretion.
12/6/2018
Renal Control of Acid-Base Balance

5. SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES.
H+ secretion in the
proximal tubules, thick segment of the ascending loop of Henle, and early distal tubules
is by secondary active transport (Na+ -H+ countertransport)
In the late distal tubule, and collecting tubules and ducts, secretion is by primary active transport (H+-ATPase pump in the luminal.
12/6/2018
Renal Control of Acid-Base Balance

6. Renal Control of Acid-Base Balance
Tubular cells
Renal ISF
Tubular lumen`
HCO3- + H+
Na+
Na+
ATP K+
H+ + HCO3-
H2CO3 
H2CO3
H2O
CO2 +
CO2 + H2O
CO2
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Renal Control of Acid-Base Balance

7. Renal Control of Acid-Base Balance
Renal ISF
Intercalated tubular cells
Tubular lumen
HCO3- + H+
Cl-
Cl-
H+ + HCO3-
H2CO3
ATP 
H2CO3
H2O
CO2
CO2 + H2O
CO2
12/6/2018
Renal Control of Acid-Base Balance

8. SECRETION OF H+ AND HCO3-REABSOPTION BY HE RENAL TUBULES.
CO2 either diffuses into the tubular epithelial cell or is formed by metabolism in the tubular cells.
H+ is secreted into tubular lumen by
Secondary active transport (in early tubular segments)
Primary active transport (late tubular segment)
12/6/2018
Renal Control of Acid-Base Balance

9. SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES.
HCO3- generated in the cell, move down hill across the basolateral membrane into the renal ISF and peritubular capillary.
For every H+ secreted into the tubular lumen, a HCO3- enters he blood.
12/6/2018
Renal Control of Acid-Base Balance

10. SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES.
HCO3- don’t ready permeate the luminal membrane.
the filtered HCO3- can’t be directly reabsorbed.
They first combine with H+  H2CO3 H2CO3  CO2 + H2O.
12/6/2018
Renal Control of Acid-Base Balance

11. SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES.
CO2 instantly diffuses into tubular cells where,
CO2+H2O H2CO3 H+ +HCO3-.
HCO3- then diffuses through the basolateral membrane into ISF  peritubular capillary blood.
12/6/2018
Renal Control of Acid-Base Balance

12. SECRETION OF H+ AND HCO3- REABSORPTION BY THE RENAL TUBULES.
HCO3- must combine with H+ before it can be reabsorbed.
Thus it is said that HCO3- and H+ titrate each other in the renal tubules. Although the titration process is not quite exact, because there is usually excess H+ excreted in urine.
12/6/2018
Renal Control of Acid-Base Balance

13. SECRETION OF H+ AND HCO3- REABSOPTION BY THE RENAL TUBULES.
these excess H+ ( 80mEq/day) rid the body of nonvolatile acids produced by metabolism
12/6/2018
Renal Control of Acid-Base Balance

14. RENAL CONTROL OF ACID-BASE BALANCE.
Each day the kidney filer  4320 mEq of HCO3- and under normal condition almost all of this is reabsorbed from the tubules.
The body produces  80mEq of non volatile acid daily, mainly from protein metabolism.
The primary mechanism for removal of these acids from the body is by renal excretion.
12/6/2018
Renal Control of Acid-Base Balance

15. RENAL CONTROL OF ACID-BASE BALANCE.
Therefore 4320mEq of H+ must be secreted daily just to reabsorb the filtered HCO3-.
and additional 80mEq of H+ must be secreted to rid the body of the nonvolatile acids produced each day.(total of 4400mEq)
12/6/2018
Renal Control of Acid-Base Balance

16. RENAL CONTROL OF ACID-BASE BALANCE.
When there is reduction in ECF H+,
The kidneys fail to reabsorb all the filtered HCO3- thereby ↑ HCO3- excretion.
In acidosis the kidneys reabsorb all the filtered HCO3-
and produce new HCO3-, which is added back to the ECF,
excess H+ pass into the urine, they are buffered by phosphate and ammonia.
12/6/2018
Renal Control of Acid-Base Balance

17. RENAL CONTROL OF ACID-BASE BALANCE.
thus, the kidneys regulate ECF [H+] through
Secretion of H+
Reabsorption of HCO3-
Production of new HCO3-
Excess H+ combine with phosphate and ammonia buffers in the tubules generating new HCO3-
Only small part of excess H+ are excreted in ionic form (H+) in urine.
Large amount excreted as salt.
12/6/2018
Renal Control of Acid-Base Balance

18. RENAL CONTROL OF ACID-BASE BALANCE.
Minimum urine pH = 4.5 corresponding to 0.03mEq/L of [H+],
liter of urine has 0.03mEq of free H+.
 80mEq of nonvolatile acids are excreted daily, this would require  2667 Liters of urine.
When there are excess H+ in urine, they combine with non bicarbonate buffers, resulting in generation of new HCO3- that can enter the blood.
In acidosis the kidneys not only reabsorb all the filtered HCO3- but also generate new HCO3-.
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Renal Control of Acid-Base Balance

19. PHOSPHATE BUFFER SYSTEM.
Both HPO42- and H2PO4- become concentrated in the tubular fluid
Poorly reabsorbed
Reabsorption of water from tubular fluid.
Under normal condition urine pH is near the pK of phosphate buffer system (pK = 6.8)
Excess H+ combine with HPO42- to form H2PO4- which is excreted in urine
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Renal Control of Acid-Base Balance

20. Renal Control of Acid-Base Balance
tubular cells
Tubular lumen
Renal ISF
Na2HPO4
Na+
Na+ + NaHPO4-
ATP K+
H+ + NaHPO4-
H2CO3- + H+
HCO3- 
H2CO3 CA
CO2
NaH2PO4
CO2 + H2O
New HCO3- is generated
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Renal Control of Acid-Base Balance

21. Renal Control of Acid-Base Balance
AMMONIA BUFFER SYSTEM.
Composed of NH3 and NH4+
Under normal condition only 30 –40mEq/day of phosphate is available for buffering H+
Much of buffering of excess H+ in the tubular fluid in acidosis occurs through ammonia buffer system.
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Renal Control of Acid-Base Balance

22. Renal Control of Acid-Base Balance
AMMONIA BUFFER SYSTEM.
NH4+ is synthesized from Glutamine which is actively transported into the epithelial cells of proximal tubule,
thick ascending limb of the loop of Henle and distal tubules.
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Renal Control of Acid-Base Balance

23. Renal Control of Acid-Base Balance
Renal ISF
tubular cells
Tubular lumen
Each molecule of Glutamine is metabolized → 2NH4+ and 2HCO3-.
NH4+ is secreted into tubular lumen by a counter transport mechanism in exchange for Na+.
HCO3- mores across the basolateral membrane Into ISF, then peritubular capillaries.
2HCO3-
2NH4+
Na+
ATP K+
Glutamine
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Renal Control of Acid-Base Balance

24. Renal Control of Acid-Base Balance
AMMONIA BUFFER SYSTEM.
In the collecting tubules and collecting ducts.
The epithelial cells are permeable to NH3
Luminal membranes are much less permeable to NH4+
H+ is secreted into the luminal where it combines with NH3 to form NH4+ which is then excreted in urine.
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Renal Control of Acid-Base Balance

25. Renal Control of Acid-Base Balance
Renal ISF
tubular cells
Tubular lumen
NH3
NH3
HCO3- + H+
H+ + NH3
ATP
H2CO3
NH4+
CO2
CO2 + H2O
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Renal Control of Acid-Base Balance

26. Renal Control of Acid-Base Balance
AMMONIA BUFFER SYSTEM.
Chronic acidosis ↑NH4+ excretion.
↑[H+] stimulates renal glutamine metabolism.
→ ↓[H+] in ECF has opposite effect.
Under normal condition, the amount of H+eliminated,
buffer system accounts for 50% of the acid excreted and 50% of the new HCO3- generated by the kidney.
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Renal Control of Acid-Base Balance

27. Renal Control of Acid-Base Balance
AMMONIA BUFFER SYSTEM.
But with chronic acidosis the dominant mechanism by which acid is eliminated is excretion of NH4+,
NH4+ excretion can
↑to as much as 500mEq/day.
12/6/2018
Renal Control of Acid-Base Balance

28. REGULATION OF RENAL TUBULAR H+ SECRETION.
H+ secretion must be carefully regulation for effective renal control of acid-base balance.
Necessary for both HCO3- reabsorption and generation of new HCO3-
Normally H+ secretion is slightly more than the HCO3- that is filtered.
12/6/2018
Renal Control of Acid-Base Balance

29. REGULATION OF RENAL TUBULAR H+ SECRETION.
In alkalosis secretion of H+ must be ↓enabling the kidneys to ↑HCO3- excretion.
 no excess H+ to combine with non HCO3- buffers in urine.
During acidosis the tubular H+ secretion must be
↑, to reabsorb all the filtered HCO3- and to generate new HCO3-
Excess H+ combine with non HCO3- buffers in urine.
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Renal Control of Acid-Base Balance

30. REGULATION OF RENAL TUBULAR H+ SECRETION.
Stimuli for ↑ H+ secretion by the tubules.
↑PCO2 of ECF
↑ECF [H+] ( ↓pH )
Adosterone stimulate H+ secretion by the intercalated cell of the collecting duct.
Tubular cells respond to a ↓in [H+] by reducing H+ secretion.
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Renal Control of Acid-Base Balance

31. RENAL CORRECTION OF ACIDOSIS.
Decrease ratio of HCO3-/H+ because of
Fall in [ HCO3-] – metabolic acidosis
Increase in PCO2-respiratory
There will be excess H+ in tubular fluid
↓filtration of HCO3-
Raise in ECF PCO2 which stimulates H+ secretion
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Renal Control of Acid-Base Balance

32. RENAL CORRECTION OF ACIDOSIS.
Complete reabsorption of HCO3-
Excess H+ combine with urinary buffers, also generating new HCO3-
Note: with chronic acidosis, there is ↑NH4+ production
In metabolic acidosis additional compensation by lungs causes a reduction in PCO2.
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Renal Control of Acid-Base Balance

33. RENAL CORRECTION OF ALKALOSIS
Increased HCO3-/H+ ratio
Metabolic or respiratory
There will be excess HCO3- in the renal tubules
Incomplete reabsorption of HCO3- no enough H+ to react with all the HCO3- that is filtered.
No H+ to combine with non HCO3- urinary buffers
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Renal Control of Acid-Base Balance

34. RENAL CORRECTION OF ALKALOSIS
This results in a decrease in plasma[HCO3-]
The compensatory response in respiratory alkalosis is a reduction in [HCO3-] caused by renal excretion of HCO3-
In metabolic alkalosis the compensatory response are:
Decrease ventilation which raises PCO2
↑renal HCO3- excretion
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Renal Control of Acid-Base Balance

35. CHARACTERISTICS OF PRIMARY ACID BASE DISTURBANCES.
pH [H+] PCO [HCO3-]
Normal nEq/L 40mmHg 24mEq/L
Acidosis
Respiratory ↓ ↑ ⇈ ↑
Metabolic ↓ ↑ ↓ ⇊
Alkalosis
Respiratory ↑ ↓ ⇊ ↓
Metabolic ↑ ↓ ↑ ⇈
12/6/2018
Renal Control of Acid-Base Balance