urine acidification and it's importance

Dewan Institute Of Rehabilitation Sciences

Shaheed Benazir Bhutto

Dewan University

2

SAADIYA NAEEMI.

• Kidney plays an important role in maintenance of acid-base balance by excreting H+ ions and retaining bicarbonate ions.

•The two main functions in Urine Acidification includes:

1- H+ Secretion.

2- Bicarbonate ions Reabsorption.

Urine Acidification:

• Proximal and distal tubular cells secrete hydrogen ions.

• Acidification also occurs in collecting ducts.

• Na–H exchange is responsible for H+ secretion in proximal tubules.

About 4,380 mEq of H+ appear in the renal tubules by means of filtration and secretion.

Not all the H+ are excreted in urine. Out of 4,380 mEq about 4,280 to 4,330 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.

Renal H+ Secretion:

Excretion of H+ occurs by three mechanisms:

1. Phosphate Mechanism.

2. Bicarbonate Mechanism.

3. Ammonia Mechanism.

Renal H+ Secretion:

Step-1:

We have sodium-potassium pump on the baso-lateral membrane.

We have low-sodium in the cell and we have high potassium in the cytoplasm.

Renal H+ Secretion:(Phosphate

Mechanism)

Tubular Fluid Peritubular space(Interstitium)

Na+

K+

1

Step-2:

The concentration of sodium in the lumen of proximal convulated tubulue is high and the concentration of H+ ions is low in the tubular cell.

Thus Na+ moves inside the cell, extruding H+ ions in the Tubular Fluid and this phenomenon is known as Sodium-hydrogen counter transport.

Renal H+ Secretion:(Phosphate

Mechanism)

Tubular Fluid Peritubular space(Interstitium)

Na+

K+

1

Na+2

H+

Step-3:

The concentration gradient of H+ ions in the cell being low indicates that the H+ ions are transported through Primary active transport.

This step is also called Secretion of H+ ions.

Renal H+ Secretion:(Phosphate

Mechanism)

Tubular Fluid Peritubular space(Interstitium)

Na+

K+

1

Na+2

H+3

H+

Step-4:

The secreted H+ ions combines with Bicarbonate ions HCO3 that are already in the Tubular Fluid.

H+ ions and HCO3 together will allow to form Carbonic Acid H2CO3.

Carbonic Acid (Bicarbonate

Mechanism)

Tubular Fluid Peritubular space(Interstitium)

Na+

K+

1

Na+2

H+3

H+

H(+) + HCO3(-)

H2CO3

4

Step-5:

Carbonic Acid goes to the border of cell and dissociates into Carbondioxide and Water in the presence of Carbonic Anhydrase Enzyme.

Carbonic Anhydrase(Bicarbonate

Mechanism)

Tubular Fluid Peritubular space(Interstitium)

Na+

K+

1

Na+2

H+3

H+

H(+) + HCO3(-)

H2CO3

4

CA

H2O + CO2

5

Step-6:

Carbondioxide moves inside the cell and combines with the water molecules that are already present inside.

Carbondioxide and water molecules once again forms Carbonic Acid.

Carbonic Anhydrase(Bicarbonate

Mechanism)

Tubular Fluid Peritubular space(Interstitium)

Na+

K+

1

Na+2

H+3

H+

H(+) + HCO3(-)

H2CO3

4

CA

H2O + CO2

5

H2O + CO26 H2CO3

Step-7:

Carbonic Acid further breaks down into H+ ions and Bicarbonate ions.

Sodium Bi-carbonate Co-Transport(Bicarbonate

Mechanism)

Tubular Fluid Peritubular space(Interstitium)

Na+

K+

1

Na+2

H+3

H+

H(+) + HCO3(-)

H2CO3

4

CA

H2O + CO2

5

H2O + CO2 H2CO36

H(+) + HCO3(-)7

Step-8:

Bicarbonate from the tubular cell enters the interstitium.

Simultaneously, Na+ is reabsorbed from the renal tubule under the influence of aldosterone.

Sodium Bi-carbonate Co-Transport(Bicarbonate

Mechanism)

Tubular Fluid Peritubular space(Interstitium)

Na+

K+

1

Na+2

H+3

H+

H(+) + HCO3(-)

H2CO3

4

CA

H2O + CO2

5

H2O + CO2 H2CO36

H(+) + HCO3(-)7

Na+

HCO3(-)

8

Step-9:

We have bicarbonate being re-absorbed by using Chloride transporter.

Chloride ions moves inside the cell while bicarbonate moves in the interstitial space.

This step is also called Chloride-Bicarbonate Counter-Transport.

Bicarbonate Reabsorption

Tubular Fluid Peritubular space(Interstitium)

Na+

K+

1

Na+2

H+3

H+

H(+) + HCO3(-)

H2CO3

4

CA

H2O + CO2

5

H2O + CO2 H2CO36

H(+) + HCO3(-)7

Na+

HCO3(-)

8

HCO3(-)

Cl-9

Step-10:

Bicarbonate combines with Sodium to form Sodium Bicarbonate.

Now the H+ is secreted into the tubular lumen from the cell in exchange for Na+.

Renal H+ Secretion(Bicarbonate

Mechanism)

Tubular Fluid Peritubular space(Interstitium)

Na+

K+

1

Na+2

H+3

H+

H(+) + HCO3(-)

H2CO3

4

CA

H2O + CO2

5

H2O + CO2 H2CO36

H(+) + HCO3(-)7

Na+

HCO3(-)

8

HCO3(-)

Cl-9

Na(+) + HCO3(-)

NaHCO3

10

Step-11:

Amonia in tubular cell is formed when the amino acid Glutamine is converted into Glutamic Acid in the presence of the enzyme Glutaminase.

Ammonia (NH3) formed in tubular cells is secreted into tubular lumen in exchange for sodium ion.

Renal H+ Secretion(Ammonia Mechanism)

Tubular Fluid Peritubular space(Interstitium)

Na+

K+

1

Na+2

H+3

H+

H(+) + HCO3(-)

H2CO3

4

CA

H2O + CO2

5

H2O + CO2 H2CO36

H(+) + HCO3(-)7

Na+

HCO3(-)

8

HCO3(-)

Cl-9

Na(+) + HCO3(-)

NaHCO3

10

Glutamine

NH3Na+

NH3

Na+

11

Step-12:

Here, it combines with H+ to form Ammonium(NH4).

Thus, H+ is added to urine in the form of Ammonium Compounds resulting in acidification of urine.

For each NH4 excreted one HCO3 is added to interstitial fluid.

Thus, by excreting H+ and conserving HCO3, kidneys produce acidic urine and help to maintain the acid-base balance of body fluids.

Renal H+ Secretion(Ammonia Mechanism)

Tubular Fluid Peritubular space(Interstitium)

Na+

K+

1

Na+2

H+3

H+

H(+) + HCO3(-)

H2CO3

4

CA

H2O + CO2

5

H2O + CO2 H2CO36

H(+) + HCO3(-)7

Na+

HCO3(-)

8

HCO3(-)

Cl-9

Na(+) + HCO3(-)

NaHCO3

10

Glutamine

NH3Na+

NH3

Na+

11NH3 + H(+)

12

NH4

• A moderate drop in pH occurs in the proximal

tubular fluid.

• Most secreted H+ has little effect on luminal pH.

• Distal tubule has less capacity to secrete H+, but

secretion in this segment has a greater effect on

urinary pH.

pH Changes Along the Nephrons:

• Renal acid secretion is altered by changes in the intracellular

PCO 2, K+ concentration, carbonic anhydrase level, and

adrenocortical hormone concentration.

• When the PCO 2 is high (respiratory acidosis), more intracellular

H2CO3 is available and acid secretion is enhanced, whereas the

reverse is true when the PCO2 falls.

• K+ depletion enhances acid secretion.

• K+ excess in the cells inhibits acid secretion.

Factors Affecting Acid Secretion:

• When carbonic anhydrase is inhibited, acid secretion is inhibited

because the formation of H2CO3 is decreased.

• Aldosterone and the other adrenocortical steroids that enhance

tubular reabsorption of Na+ also increase the secretion of H+ and

K+.

Factors Affecting Acid Secretion:

• pH of the urine in humans varies from 4.5 to 8.0.

• The H2CO3 forms CO2 and H2O, and the CO2 is expired, while the Na+ appears in the glomerular filtrate.

• To the extent that the Na+ is replaced by H+ in the urine, Na+ is conserved in the body.

• For each H+ ion excreted with phosphate or as NH4+, there is a net gain of one HCO3– ion in the blood, replenishing the supply of this important buffer anion.

Implications of Urinary pH Changes :

• Normal Na+ concentration of arterial plasma that has been equilibrated with red blood cells is about 140 mEq/L, whereas the H+ concentration is 0.00004 mEq/L .

• pH is therefore 7.4.

• A decrease in pH of 1 unit, for example, from 7.0 to 6.0, represents a 10-fold increase in H+ concentration.

• Acidosis is arterial pH below 7.40, and

• Alkalosis is above 7.40.

Implications of Urinary pH Changes :

• To promote antibacterial action of methenamine in urine:

Below pH 5.5, methenamine releases formaldehyde, which is antibacterial.Acidifying agents are given with methenamine to lower urinary pH.

• Prevention of calcium phosphate renal stones:An alkaline pH favors the crystallization of calcium- and phosphate-containing stones hence acidification of urine will prevent the formation of these stones.

Importance Of Acidification Of Urine

A highly acidic urine pH occurs in:

Acidosis

Uncontrolled diabetes

Diarrhea

Starvation and dehydration

Respiratory diseases in which carbon dioxide retention occurs and acidosis develops.

A highly alkaline urine pH occurs in:

Urinary tract obstruction

Renal tubular acidosis

Chronic renal failure

Respiratory diseases that involve hyperventilation (blowing off carbon dioxide and the development of alkalosis)

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