1. Renal control of acid base balance
Mahmoud A. Alfaqih BDS PhD
Jordan University of Science and Technology
School of Medicine
Department of Biochemistry and Physiology

2. Textbook of Medical Physiology by Guyton and Hall, 11th Edition
Reading material
Textbook of Medical Physiology by Guyton and Hall, 11th Edition
Pages

3. Overview
The kidneys control acid-base balance by excreting either an acidic or a basic urine
Excreting an acidic urine reduces the amount of acid in extracellular fluid
Excreting a basic urine removes base from the extracellular fluid.

4. Basic concepts of renal control of acid base balance
Each day the body produces about 80 milliequivalents of nonvolatile acids.
The primary mechanism for removal of these acids from the body is renal excretion.
The kidneys must also reabsorb all of the filtered bicarbonate in the urine (4320 milliequivalents are filtered daily)
The reabsorption of bicarbonate and excretion of H+ are accomplished through H+ secretion by the tubules

5. Basic concepts of renal control of acid base balance
Bicarbonate must react with a secreted H+ to form H2CO3 before it can be reabsorbed
4320 milliequivalentsof H+ must be secreted each day just to reabsorb the filtered bicarbonate
An additional 80 milliequivalents of H+ must be secreted to rid the body from non-volatile acids

6. Basic mechanism of renal control of acid base balance
Kidneys regulate extracellular fluid H+ concentration through 3 mechanisms:
Secretion of H+.
Reabsorption of filtered bicarbonate.
(3) production of new bicarbonate.

7. Secretion of Hydrogen Ions and Reabsorption of Bicarbonate Ions by the Renal Tubules

8. Hydrogen Ions Are Secreted by Secondary Active Transport in the Early Tubular Segments
Proximal tubule, thick segment of ascending loop of Henle, and early distal tubule
More than 90% of the bicarbonate is reabsorbed
Does not establish a high H+ concentration

9. The net result is that for every H+ secreted into the tubular lumen, an HCO3 – enters the blood

10. Filtered Bicarbonate Ions Are Reabsorbed by Interaction with Hydrogen Ions in the Tubules
Each time an H+ is formed in the tubular epithelial cells, an HCO3 - is also formed and released back into the blood.
The reabsorption of filtered HCO3 – does not result in net secretion of H+
Secreted H+ combines with the filtered HCO3– and is therefore not excreted

11. H+ secretion by primary active transport
Primary Active Secretion of Hydrogen Ions in the Intercalated Cells of Late Distal and Collecting Tubules
H+ secretion by primary active transport
Occurs in intercalated cells
Important for forming a maximally acidic urine

12. Combination of Excess Hydrogen Ions with Phosphate and Ammonia Buffers
Mechanism for generation of new bicarbonate
For each Litre of urine formed, a maximum of 0.03 milliequivalent of free H+ can be excreted
The excretion of large amounts of H+ in urine is accomplished by combining H+ with buffers in the tubular fluid
The most important buffers are phosphate buffer and ammonia buffer

13. Composed of HPO4 = and H2PO4 –
Phosphate Buffer System Carries Excess Hydrogen Ions into the Urine and Generates New Bicarbonate
Composed of HPO4 = and H2PO4 –
pK of this system is 6.8
30 to 40 mEq/day is available for buffering H+

14. Whenever an H+ secreted into the tubular lumen combines with a buffer
other than bicarbonate the net effect is addition of a new bicarbonate to the blood

15. Excretion of Excess Hydrogen Ions and Generation of New Bicarbonate by the Ammonia Buffer System
More important quantitatively than phosphate buffer system
Composed of ammonia (NH3) and the ammonium ion (NH4+)
Ammonium ion is synthesized from glutamine
Glutamine is metabolized to form two NH4+ and two HCO3 –
NH4+ is secreted into the tubular lumen by a counter-transport in exchange for sodium
Bicarbonate ions are absorbed in the blood and form new bicarbonate

17. What happens in the collecting tubules?
H+ is secreted by the tubular membrane into the lumen.
H+ combines with NH3 to form NH4+ which is excreted.
For each NH4+ excreted, a new HCO3- is generated and added to the blood.

19. Chronic Acidosis Increases NH4+ Excretion
Renal ammonium-ammonia buffer system is subject to physiologic control
Acidosis stimulates glutamine metabolism and increases the formation of NH4+ and new HCO3– to be used in H+ buffering
With chronic acidosis, the dominant mechanism by which acid is eliminated is excretion of NH4+

20. Quantifying Renal Acid-Base Excretion
We need to define three terms first:
Bicarbonate excretion
Urinary titratable acid
Ammonium (NH4+) excretion

21. Bicarbonate excretion
Calculated as the urine flow rate multiplied by urinary bicarbonate concentration.
Is equal to zero under normal conditions.
Has a positive value in metabolic alaklosis

22. Urinary titratable acid
A non-bicarbonate buffer excreted in the urine
Titratable acid measurement does not include H+ in association with NH4+
Mainly contributed by phosphate buffer

23. NH4+ excretion
One of the non-bicarbonate buffers excreted in the urine
Mathematically equal to urine flow rate multiplied by urinary NH4+ concentration
Combined with titratable acid are equal to amount of new bicarbonate generated and added to the blood

24. Net acid excretion = NH4 + excretion + Urinary titratable acid – Bicarbonate excretion

25. Regulation of Renal Tubular Hydrogen Ion Secretion
The most important stimuli for increasing H+ secretion by the tubules in acidosis are:
(1) An increase in PCO2 of the extracellular fluid (2) An increase in H+ concentration of the extracellular fluid (decreased pH)

26. Other factors that increase hydrogen ion secretion
Aldosterone secretion
Factors that stimulate Na+ reabsorption (Because of the H+/Na+ antiporter)
Changes in plasma potassium concentration (hypokalemia stimulates hydrogen ion secretion while hypekalemia inhibits)????