Acidification Of Urine Notes

 Acidification Of Urine

Acidification of urine is important to maintain acid base balance of body.

Mechanism of acidification of urine includes

• H+ secretion
• HCO3 – reabsorption
• H+ excretion with titrable acid and ammonium
• Generation of new HCO3-

H+ Secretion

It takes Place in all part of nephron except ascending and descending thin limb of loop of henle.

For each H+ selected one HCO3-cl absorbed

Reabsorption of HCO3-

Plasma concentration of HCO3- is 24 meq/L

Filtration load: plasma concentration X GFR

Filtration load of HCO3- is 24meq/L X 180L/day = 4320me1/day

4320 meq/L of HCO3- must be reabsorbed to maintain acid base balance. HCO3- is reabsorbed with H+ ions. Therefore 4320 meq H+ ions are required to absorb 4320 meq HCO3-.

 

It is absorbed by following mechanism. Filtered HCO3- combines with H+ ion secreted on luminal side to form H2CO3. H2CO3 dissociates to form co2 and H2O which easily diffuse through luminal membrane to cell. within cell, H2O combines with co2 to form H2CO3 that dissociate into H+ and HCO3-. HCO3- is absorbed on basolateral side with help of 2 active mechanism.

• Na+ HCO3- co – transporter = it moves both Na+ and HCO3- in same direction
• Cl- HCO: – exchanger = it moves Cl- and HCO3- in opposite direction.

For each H+ secreted one HCOI- is reabsorbed.

H+ Excretion

Human body produces 80 meq of nonvolatile acid (those acids which cannot be excreted by lungs) which has to be excreted by kidney. They are excreted with help of H+ ions. So to remove 80 meq of nonvolatile acid 80 meq of H+ is required. 4320 meq H+ ions are required to absorb 4320 meq HCO3-. So total 4320 meq+ 80 meq of H+ ions are required to be seueted every day.

When a patient have alkalosis, more HCO3- are produced than capacity to reabsorbed by H+ and excess HCO3- filtered and lost from urine, thus body acid base balance is maintained.

When a patient have acidosis, H+ are produced in excess of HCO3- filtered, and it is excreted in two forms.

Ionic form – very small amount of H+ can be excreted in ionic form. Minimum Urinary Ph is 4.5 which means only 10-4.5 meq/l (0.03meq/l) of H+ can be exueted in ionic form. Thus for each liter of urine 0.03meq of H+ can be excreted. To excrete 80meq of nonvolatile acid 2667 liter wine would be required to excrete all g+ in ionic form. To solve this problem special mechanism is developed by body i.e. Tubular buffers.

Combine with buffers – Urinary buffering serves two purposes;

• Excrete the daily acid load and
• Regenerate bicarbonate lost during extracellular buffering.
  • Phosphate buffer
  • Ammonia buffer
  • Urate buffer
  • Citrate buffer
  • Creatinine
  • Uric acid
  • Keto anions in in Diabetes Ketoacidosis serve as a source of titratable acids.

Excretion of H+ with weak acids (titratable acidity) i.e. Phosphate buffer (HPO42- and H2PO4).

• It is qualitatively important buffer – it is most effective buffer in tubular fluid as its Pk (6.8) is nearer to urinary Ph.
• Phosphate concentration in tubules depends on the quantity of phosphate filtered and excreted by the kidneys, which is dependent on intake and also PTH levels. The excretion of titratable acids is not regulated by acid base balance and cannot be easily increased to excrete the daily acid load. Therefore this buffer is not quantitatively important. Under normal condition only 30-40 meq of phosphate is available to buffer H+ ions.

Excretion of H+ with Ammonium ion i.e. Ammonia Buffer.

• It consist of ammonia (NH3) and Ammonium ions (NHa+).
• It is quantitatively important buffer as ammonia production can be regulated in respond to acid base status of body.
• It helps in 50% -66% acid secretion and 50% new HCO3- regeneration.
• It can be studied by 3 steps.
  • Amminogenesis / HCO3- generation in proximal tubule.
  • Ammonium reabsorption / medullary recycling in thick ascending loop.
  • Ammonia trapping in collecting tubule.

Amminogenesis/ HCO3- generation/ HCO3- synthesis:

protein metabolism in liver produces glutamine, which is delivered to kidney and then filtered. Glutamine is reabsorbed in PCT, thick ascending limb and DCT.

In tubular cell, glutamine is metabolized to two molecules of NH4+ and two molecules of HCO3. Two HCO3 is absorbed in peritubular capillaries. The ammonium is secreted into the lumen by replacing for H+ on the Na+ – H+ exchanger. In the tubular fluid, NH4+ circulates partly in equilibrium with NHs.

The ammonium and not ammonia is produced in the proximal tubule. So, how does ammonium production increase hydrogen excretion if it cannot bind to hydrogen ions secreted in the proximal tubular lumen?

Production of new bicarbonate ions is theoretically similar to excretion of H+. Important function of amminogenesis is HCO:- generation’ In order for amminogenesis to be effective NH4+ must be excreted in urine. If NH4+ re-enter the, circulation then it will be metabolized in liver to form urea, but this process will consume two bicarbonate ions.

Thus two HCO3- generated in tubular cell during amminogenesis will be cancelled out, and there would be no net acid secretion. NH4+ + 2HCO3- => urea + COu + 3 H2O.

This re-enter of NH4+ in circulation is minimized by producing acidic urinary Ph which keeps NH4+ in pronated form’ Urine becomes maximally acidic in collecting duct where intercalated cells secrete H* ions. Kidney prevent loss of ammonium by reabsorbing NH4+ in thick ascending limb and pumping it back in collecting duct where urinary PH is low’

Ammonium reabsorption /Medullary recycling in thick ascending loop: Ammonium is reabsorbed from thick ascending limb by substituting K* on Na* K+ 2C1- co-transporter into medullary interstitium. Less acidic medullary interstitium allow dissociation of NH4+ to NH3 and H+ Luminal membrane of thick ascending limb is impermeable to NH3, but luminal membrane of PCT and Collecting duct is permeable to NH3.

NH3 diffuse out from interstitium to along concentration gradient into PCT and Collecting duct. In PCT NHr is again pronated to NH++ and recycled in medullary interstitium via absorption at thick ascending limb, leading to high NH3 concentration in medullary interstitium

Ammonia trapping in collecting tubule:

NH3 diffuse out from interstitium to along concentration gradient and into collecting duct. Due to acidic urine NH3 combines with H+ ions to form NH4+ (ammonium). Membrane of collecting duct is impermeable to NH4+ thus ammonium is trapped and excreted in urine. This process primarily dependent on acidification of urine in collecting duct and negligible till the Ph falls below 6.

Regulation of Renal H+ Excretion / HCO3- reabsorption

• Acidosis – Increase H+ secretion by
  • Increased insertion of H+ ATPase on luminal (Apical) membrane.
  • Increased activity of Na+- H+ Antiport on luminal (Apical) membrane.
  • Increased activity of Na+- HCO:- antiport on basolateral membrane.

Alkalosis decrease H+ secretions

• Extracellular volume – H+ Secretion is lined with Na+ Reabsorption so factors affecting Na+ absorption will secondarily affect H+ Secretion. Change in ECF volume will stimulate rennin angiotensin aldesterone system (RAAS).

RAAS stimulates Na+ K+ Pump and Na+ H+ anti-port on luminal side. Thus increase the H+ excretion leading to alkalosis.

• Plasma K+ concentration
  • ↓ K+ ➜ increase K+ absorption in exchange of H+ and increased HCO3 reabsorption leads to alkalosis.
  • ↑ K+ ➜ decreases K+ absorption in exchange of H+ leads to acidosis.
• Arterial pCO2
  An increase in arterial pco2 results in increased renal H+ secretion and increased bicarbonate reabsorption. The converse also applies.

• Ammonium
  The kidney responds to an acid load by increasing tubular production and urinary excretion of NH4+. The mechanism involves an acidosis-stimulated increase of glutamine metabolism by the kidney leading to increased production of NH4+ and HCO3- by the tubule cells. This is very important step during chronic metabolic acidosis. This increase in ammonium excretion takes several days to reach its maximum following an acute acid load which is known as lag period. Ammonium excretion can increase up to 300 mmol/day.

Renal net acid secretion

Net acid excretion (NAE) is the net amount of acid excreted in the urine per unit time. It is expressed in units of milliliters per minute (ml/min).

NAE : urine flow rate X (urine acid concentration – urine bicarbonate concentration).

Urine acid concentration includes urine concentration of ammonium, titratable acid.

Urine bicarbonate concentration is subtracted from urine acid concentration as the loss of bicarbonate is physiologically equivalent to a gain in acid. As H+ is added to the body because of urinary HCo3- loss.

NAE = v X(UNH4 + UTA – UHCO3) where

NAE = net acid excretion

V = volume of urine produced per unit time

UNH4 = urine concentration of ammonium

UTA = urine concentration of titratable acid

UHCO3 = urine concentration of bicarbonate

Normally there is no urinary HCO3- and therefore: Net acid excretion (NAE) = titratable acidity + NH4+.

Summary

• Titratable acidity depend on the dietary intake of phosphate and PTH levels so it cannot be regulated to increase acid excretion.
• The kidney’s respond to increased acid load by increasing ammonium Production and excretion.
• Significant feature of buffers (titrable acidity and ammonium) excretion is the regeneration of bicarbonate ions.
• The kidney should reabsorb all filtered HCO3- to maintain acid base balance.
• Maximal acidification of urine takes place in collecting tubule.
• In acidosis, ammonium production increases and for adequate ammonium excretion maximal acidification of the urine in the collecting tubule must take place.
• Aldosterone stimulates secretion of hydrogen ion in the collecting duct.
• The extracellular pH is the major physiologic controller of net acid excretion, but in pathological conditions, the effective circulating volume, aldosterone, plasma Ki concentration all can affect acid excretion, independent of the systemic PH.