Acidification of urine

1. Acidification of urine
Dr. Sai Sailesh Kumar G
Associate Professor
Department of Physiology
R.D. Gardi Medical College, Ujjain, Madhya Pradesh.
Email: dr.goothy@gmail.com

2. Question
Hormone required to produce concentrated urine is
1. Oxytocin
2. Adrenalin
3. Prolactin
4. ADH

3. Introduction
 The kidneys control acid-base balance by excreting either acidic
or basic urine.
Excretion of acidic urine reduces the amount of acid in ECF
Excreting basic urine reduces the base in ECF

4. Introduction
 Each day body produces 80 mEq of nonvolatile acids from the
metabolism of the proteins
They are called non-volatile because they are not H2CO3 and can
not be excreted by the lungs
The primary mechanism by which these acids are removed from
body is by renal excretion

5. Introduction
 The kidneys also prevent loss of bicarbonate in the urine
This task is more important than the excretion of non-volatile acids
Each day kidney filters 4320 mEq of HCO3-
Under normal conditions almost all of this is reabsorbed in the renal
tubules
Helps to conserve the primary buffer system of ECF

6. Fundamental mechanisms of kidney in regulating ECF H+ conc
1. Secretion of H+
2. Reabsorption of filtered HCO3-
3. Production of new HCO3-

7. Secretion of H+ and reabsorption of HCO3-
 H+ ion secretion and HCO3- reabsorption occurs in all the parts of
renal tubules except descending and ascending thin limbs of LH
About 80-90 % of HCO3- reabsorption ( and H+ secretion) occurs in PCT
Only small amounts of HCO3- flow into distal tubules and collecting
ducts
In the thick ascending LH another 10% of HCO3- is reabsorbed
Remaining is reabsorbed in the distal tubules and collecting duct

9. Mechanism
 CO2 diffuses into the tubular cells
CO2 under the influence of CA combines with H20 and forms H2CO3
H2CO3 dissociates into HCO3- and H+
H+ is secreted into the tubular lumen by sodium –hydrogen counter
transport
The energy for this is given by the Na+-K+ Atp ase pump in the
basolateral membrane

11. Mechanism
 The net result is that for every H+ secreted into the tubular lumen,
an HCO3- enters the blood

12. H+ secretion in late distal and collecting tubule
 Only 5% of total H+ secretion
by primary active transport
Occurs in intercalated cells of luminal membrane
Hydrogen transporting ATPase and hydrogen-potassium-ATPase
Energy required is derived from break down of ATP
 CO2 in these cells combines with water to form H2CO3
H2CO3 dissociates into H+ and HCO3-

13. H+ secretion in late distal and collecting tubule
 H+ is secreted by means of hydrogen ATPase and hydrogen-
potassium- ATPase transporters
For each H+ secreted, a HCO3- is reabsorbed, similar process in
the proximal tubules
The main difference is secretion of H+ is by active H+ pump
transport rather co transport

14. H+ secretion in late distal and collecting tubule
 Though only 5% of H+ is secreted by this mechanism, this is
important in the formation of maximum acidic urine
In the proximal tubules H+ concentration can be increased only 3-
4 folds whereas in the distal tubules 900 folds it can be increased

16. Generation of new bicarbonate ions
 Excretion of large amounts of H+ is accomplished primarily by
combining the H+ with buffers in the tubular fluid
The most important buffers are phosphate buffers and ammonia
buffers
Other weak buffer systems such as urate and citrate are much
less important

17. Generation of new bicarbonate ions
 When there is excess H+ in the tubular fluid, it combines with the
buffers other than HCO3- and it leads to the generation of new
HCO3-
This HCO3- also enter the blood
Thus when there is an excess of H+, the kidney not only reabsorbs
all HCO3- but also generates new HCO3-

18. Phosphate buffer system
 Composed of HPO4- and H2PO4-
As long as HCO3- is available, it combines with H+
Once all HCO3- is completed, the excess of H+ combines with
Phosphate buffer
H+ combines with HPO4-
And forms H2PO4-
Excreted as NaH2PO4-

19. Phosphate buffer system
 when ever H+ combines with buffer other than HCO3- the net
effect is the addition of new HCO3- to the blood

21. Ammonia buffer system
 More important than phosphate buffer system
Composed of NH3 and NH4+
Ammonium ion is synthesized from glutamine which comes from the
metabolism of amino acids in the liver
Glutamine delivered to kidneys is transported into the epithelial cells
Glutamine is metabolized in the cells and forms two NH4+ and two
HCO3- ions

22. Ammonia buffer system
 NH4+ is secreted in a counter transport mechanism in exchange
for sodium
HCO3- is transported across the basolateral membrane into the
peritubular capillaries
The HCO3- generated by this process is new HCO3-
This mechanism is seen in proximal tubules, thick AL of LH and
distal tubules

24. Ammonia buffer system
 In the collecting tubules
Luminal membrane is permeable to NH3
NH3 is secreted into the lumen
H+ is secreted by active transport into the lumen
H+ combines with NH3 and forms NH4+
NH4+ is excreted into the urine
For each NH4+ excreted one new HCO3- is added to blood

26. Alkalosis
 Tubular secretion of H+ is reduced too low to achieve complete
reabsorption of HCO3-
No excess H+ available to combine with non-bicarbonate buffers
No new HCO3- added to blood

27. Acidosis
 Tubular secretion of H+ is increased sufficiently to reabsorb all
HCO3- and enough H+ left over for excretion of NH4+ and titrable
acid
 A Large amount of new HCO3- added to blood

28. Acidosis
 The most important stimuli to increase H+ secretion by tubules is
acidosis
An increase in PCO2 of ECF in respiratory acidosis
An increase in H+ conc of ECF in metabolic acidosis

29. Acidosis
 Respiratory and metabolic acidosis causes decrease in the ratio
of HCO3- to H+ in the renal tubular fluid
Excess H+ in renal tubules
Complete reabsorption of HCO3-
Still H+ available to combine with non-bicarbonate buffers
 A Large amount of new bicarbonate is added to blood

30. Acidosis
 In chronic acidosis regardless of Respiratory and metabolic acidosis there is
an increase in the production of ammonia
Contribute to increases H+ excretion
Addition of new bicarbonate to blood
500 mEq of H+ excreted
500 mEq of HCO3- added to blood
Increase the HCO3- part of bicarbonate buffers
Corrects acidosis

31. Respiratory acidosis
 Any factor that decreases the rate of pulmonary ventilation
Increase PCO2 of ECF
Increased H2CO3 and H+ concentration
Acidosis
Damage of respiratory center in the medulla
Decrease in the ability to eliminate CO2 like emphysema
Compensated by buffers of body fluids and kidneys

32. Respiratory alkalosis
 Any factor that increases the rate of pulmonary ventilation
decrease PCO2 of ECF
decreased H2CO3 and H+ concentration
Alkalosis
Psychoneurosis – at high altitudes
Low oxygen content in the air stimulate respiration

33. Metabolic acidosis
 All other types of acidosis besides those caused by excess CO2
in the body fluids
Failure of kidneys
Formation of excess amounts of metabolic acids
Addition of metabolic acids to the body by infusion of acids
Loss of base from body

34. Renal tubular acidosis
 Defect in the renal secretion of H+
Defect in renal reabsorption of HCO3-
Or both

35. Diarrhea
 Severe diarrhea is most frequent cause of metabolic acidosis
Loss of large amount of sodium bicarbonate in feces
Same effect as loss of HCO3- in urine
It can be serious and cause death

36. Vomiting of intestinal contents
 Vomiting of gastric contents alone causes loss of acid and a
tendency towards alkalosis because stomach secretions are
highly acidic
Vomiting contents deeper in the intestinal tract cause loss of
bicarbonates and lead to acidosis

37. Diabetes mellitus
 Lack of insulin
Lack of insulin sensitivity
Glucose can not be used
Depends on fats
Increased production of acetoacetic acid
Acidosis – large amounts of acid excreted in urine

38. Ingestion of acids
 ingestion of aspirin – acetyl salicylates
Ingestion of methyl alcohol – forms formic acid when it is
metabolized

39. Treatment
 Best treatment is to correct the condition that caused the
abnormality
However, it may be difficult in chronic respiratory or renal failure
Various agents can be used to neutralize the excess of acids and
bases
To neutralize excess acid, sodium bicarbonate can be ingested by
mouth

40. Treatment
 Sodium bicarbonate is absorbed from GIT into the blood
Increases the HCO3- portion of bicarbonate buffer system
Increases PH towards normal
For intra venous infusion, sodium lactate, sodium gluconate are
used

41. Treatment
 For the treatment of alkalosis, ammonium chloride can be administered
from mouth
Ammonium chloride is absorbed into the blood
In the liver ammonia is converted to urea
This reaction liberates HCl
Shifts H+ concentration to the acidic direction
Ammonium chloride is occasionally infused intravenously but the NH4+
is toxic and this procedure can be dangerous

42. diagnosis
 Convenient way to diagnose the acid-base disorder is using an
acid-base nomogram
To determine the type of acidosis or alkalosis
To determine the severity
In this diagram PH, PCO2, and HCO3- concentration intersect
According to the Henderson-Hasselbalch equation

44. diagnosis
 The central open circle shows normal values
The shaded areas shows type of disorders
If the values of PH, HCO3- and PCO2 are within the shaded area, it
indicates simple acid-base disorder
If the values are outside the shaded area, it indicates mixed acid-
base disorder