1. AZRA NAHEED MEDICAL COLLEGE DEPARTMENT OF PHYSIOLOGY
DR.TAYYABA AZHAR
23-Nov-17

2. INTRODUCTION
Kidney plays an important role in maintenance of acid base balance by excreting hydrogen ions and retaining bicarbonate ions.
Normally, urine is acidic in nature with a pH of 4.5 to 6.
The metabolic activities in the body produce lot of acids (with lot of hydrogen ions) which threaten to push the body towards acidosis. However, kidneys prevent this by excreting hydrogen ions (H+) and conserving bicarbonate ions (HCO3~).

3. INTRODUCTION
Conservation or reabsorption of HCO3~ is an important process because of the high quantity of filtered HCO3- .
About 4320 mEq of HCO3~ is filtered by the glomeruli of kidneys everyday. It is called filtered load of HC03~.
Excretion of this much HCO3~ through urine will affect the acid base balance of body fluids. So, HCO3~ must be taken back from the renal tubule by reabsorption.
23-Nov-17

4. INTRODUCTION
The reabsorption of filtered HCO3~ utilizes secretion of H+ in the renal tubules.
About 4380 mEq of H+ appear every day in the renal tubule by means of filtration and secretion.
Not all the H+ pass through in urine. Out of mEq, about 4280 to 4330 mEq of H+ is utilized for the reabsorption of filtered HCO3~. Only the remaining 50 to 100 mEq is excreted.
It results in the acidification of urine.
23-Nov-17

5. Secretion of Hydrogen Ions
Secretion of H+ into the renal tubules occurs by the formation of carbonic acid. Carbon dioxide formed in the tubular cells combines with water to form carbonic acid.
Carbon dioxide enters the cells from tubular fluid also. Carbonic anhydrase is essential for the formation of carbonic acid. This enzyme is available in large quantities in the epithelial cells of the renal tubules. The carbonic acid immediately dissociates into H+ and HCO3~.
Acidification of Urine
23-Nov-17

6. Sodium-Hydrogen Antiport Pump
Sodium ion (Na+) is reabsorbed from the tubular fluid into the tubular cell, H+ is secreted from the cell into the tubular fluid in exchange for Na+.
The sodium-hydrogen antiport pump present in the tubular cells is responsible for the exchange of Na+ and H+.
This type of sodium-hydrogen counter transport occurs predominantly in distal convoluted tubule.
23-Nov-17

7. ATP Driven Proton Pump
In addition to sodium-hydrogen antiport pump, one more mechanism is present in distal convoluted tubule and collecting duct for the secretion of H+.
Distal convoluted tubule and collecting duct are made up of two types of epithelial cells namely, principal cells (P cells) and intercalated cells (I cells).
The P cells contain a pump called proton pump that transports the H+ from tubular cells into the tubular lumen. This pump operates by energy liberated from breakdown of ATP.
23-Nov-17

8. Acidification of Urine
The kidneys control acid-base balance by excreting either an acidic or a basic urine.
The mechanism by which slightly alkaline glomerular filtrate is converted into acidic urine is called Acidification of urine.
23-Nov-17

9. Principles of Urine Acidification
Secretion of H+ in exchange of cation usually Na+.
Conservation of HCO3- in the body fluid.
Secretion of NH3 into the tubular fluid.
23-Nov-17

10. Removal of H+ & Acidification of Urine
The H+, which enters the renal tubules by filtration and secretion, is removed by three mechanisms:
Bicarbonate (HCO3-) mechanism.
Phosphate (HPO4-) mechanism.
Ammonia (NH3) mechanism.
23-Nov-17

11. Secretion of Hydrogen Ions
H+ from the tubular cells are secreted into the lumen of proximal convoluted tubule, distal convoluted tubule and collecting duct.
There are two mechanisms for the secretion of H+:
Sodium-Hydrogen antiport pump.
ATP driven proton pump.
23-Nov-17

12. Bicarbonate Mechanism
All the filtered HCO3~ into the renal tubules is reabsorbed.
About 85% of it is reabsorbed in proximal convoluted tubule; 10% in DCT and 5% in CT.
The reabsorption of HCO3~ utilizes the H+ present in renal tubules.
23-Nov-17

13. H+ Secretion H+ comes from cellular H2CO3.
So, H+ is secreted and one Na+ and one HCO3- enter in the ISF.
23-Nov-17

14. Acidification of Urine
H+ Secretion
23-Nov-17
Primarily H+ secretes with Na+- H+ pump.
Na+ goes to ISF & K+ enters into the cell by Na+K+ pump. Due to lower intracellular Na+ again enters in the cell with secretion of H+.
23-Nov-17
Prepared by: Dr Raghib Ahsan

15. Reabsorption of Bicarbonate
Reabsorption of bicarbonate in different segments of the renal tubule.
The percentages of the filtered load of bicarbonate absorbed by the various tubular segments are shown, as well as the number of milliequivalents reabsorbed per day under normal conditions.
23-Nov-17

16. Bicarbonate Mechanism
The H+ secreted into the renal tubule, combines with filtered HCO3~ forming carbonic acid.
Carbonic acid dissociates into carbon dioxide and water in the presence of carbonic anhydrase. Carbon dioxide and water enter the tubular cell.
23-Nov-17

17. Bicarbonate Mechanism
In the tubular cells, carbon dioxide combines with water to form carbonic acid.
It immediately dissociates into H+ and HCO3~. HCO3~ from the tubular cell enters the interstitium. There it combines with Na+ to form NaHCO3.
Now, the H+ is secreted into the tubular lumen from the cell in exchange for Na+.
23-Nov-17

18. Bicarbonate Mechanism
Thus, for every hydrogen ion secreted into lumen of tubule, one bicarbonate ion is reabsorbed from the tubule. In this way, kidneys conserve the HCO3~. The reabsorp­tion of filtered HCO3~ is an important factor in maintaining pH of the body fluids.
Acidification of Urine
23-Nov-17

19. Pattern of H+ Secretion in PCT, Thick ALH & Early DCT
Active secretion of hydrogen ions into the renal tubule.
Tubular reabsorption of bicarbonate ions by combination with hydrogen ions to form carbonic acid, which dissociates to form carbon dioxide and water;
Sodium ion reabsorption in exchange for hydrogen ions secreted
23-Nov-17

20. Pattern of H+ Secretion in Late DCT & Collecting Tubule
Primary active secretion of hydrogen ions through the luminal membrane of the intercalated epithelial cells.
One bicarbonate ion is absorbed for each hydrogen ion secreted, and a chloride ion is passively secreted along with the hydrogen ion.
23-Nov-17

21. Phosphate Mechanism
In the tubular cells, carbon dioxide combines with water to form carbonic acid. It immediately dissociates into H+ and HCO3~. HCO3- from the tubular cell enters the interstitium.
Simultaneously Na+ is reabsorbed from renal tubule under the influence of Aldosterone. Na+ enters the interstitium and combines with HCO3~.
The H+ is secreted into the tubular lumen from the cell in exchange for Na+ .
23-Nov-17

22. Phosphate Mechanism
The H+, which is secreted into renal tubules reacts with phosphate buffer system. It combines with sodium hydrogen phosphate to form Sodium dihydrogen phosphate.
Sodium dihydrogen phosphate is excreted in urine.
23-Nov-17

23. Phosphate Mechanism
The H+, which is added to urine in the form of Sodium dihydrogen, makes the urine acidic.
It happens mainly in distal tubule and collecting duct because of the presence of large quantity of sodium hydrogen phosphate in these segments.
23-Nov-17

24. Phosphate Mechanism
23-Nov-17

25. Ammonia Mechanism
This is the most important mechanism by which kidneys excrete H+ and make the urine acidic.
In the tubular epithelial cells, ammonia is formed when the amino acid glutamine is converted into glutamic acid in the presence of the enzyme glutaminase.
Ammonia is also formed by the deamination of some of the amino acids such as glycine and alanine.
23-Nov-17

26. Ammonia Mechanism
The ammonia (NH3) formed in tubular cells is secreted into tubular lumen in exchange for sodium ion.
Here, it combines with H+ to form ammonium (NH4). The tubular cell membrane is not permeable to ammonium. Therefore, it remains in the lumen and combines with sodium acetoacetate to form ammonium acetoacetate.
Ammonium acetoacetate is excreted through urine. Thus, H+ is added to urine in the form of ammonium compounds resulting in Acidification of urine.
23-Nov-17

27. Ammonia Mechanism
This process takes place mostly in the PCT because glutamine is converted into ammonia in the cells of this segment.
Thus, by excreting H+ and conserving HCO3~, kidneys produce acidic urine and help to maintain the acid base balance of body fluids.
23-Nov-17

28. NH3 secretion
NH3 being lipid soluble diffuses across the cell membrane into ISF & lumen. In the lumen H+ + NH3 = NH4+ remains in urine.
Acidification of Urine
23-Nov-17

29. NH3 Secretion
NH3 enters the tubular lumen not by filtration but by synthesis & secretion in the Renal cell of collecting Ducts and DCT.
23-Nov-17

30. Generation of New HCO3- by NH3 Buffer System
Production and secretion of ammonium ion (NH4+) by proximal tubular cells.
Glutamine is metabolized in the cell, yielding NH4+ and bicarbonate. The NH4+ is secreted into the lumen by a sodium-NH4+ pump.
For each glutamine molecule metabolized, two NH4+ are produced and secreted and two HCO3– are returned to the blood.
23-Nov-17

31. Ammonia Mechanism
23-Nov-17