RENAL MECHANISM IN THE REGULATION OF ACID BASE BALANCE:

Since the pH of urine varies from 4.5-8.0, this indicates kidney has ability to excrete various amounts of acids and bases to maintain the normal pH of blood. This ability makes the kidney the final defense mechanism against change in body pH.

Various acids produced during metabolic process are buffered in ECF at the expense of HCO₃^-. Renal excretion of acid and conservation of bicarbonate occur through various ways.

1.      The Na⁺-H⁺ exchange
2.      Production of ammonia and excretion of NH₄⁺ and
3.      Reclamation of HCO₃^-.
1. Na⁺-H⁺ Exchange:
These are present in plasma membrane and have ATPase activity. This can exchange sodium with hydrogen (antiport) against concentration gradient by ATP hydrolysis. In kidney these exchanger extrude H⁺ ions into the tubular fluid in exchange for Na⁺ ions during acidosis but this is inhibited in alkalosis. In type I and type II renal tubular acidosis, this exchange is defective and lead to decrease in blood pH. The H⁺ ions thus produced can react with NH₃ of HPO₄^2-.

Potassium ion compete with hydrogen ion in the renal tubular Na⁺-H⁺ exchanger. If intracellular K⁺ of renal tubular cell is high more potassium ion and less hydrogen are exchanged for sodium. Thereby, increasing the acidity of body fluid. In hypokalaemia more hydrogen ions are excreted and body becomes more alkaline and urine more acidic. Thus hyperkalaemia contributes to acidosis and hypokalemia to alkalosis.

Also there is active secretion of hydrogen ion by cells distal tubules and collecting ducts.

2. Production of ammonia and excretion of ammonium ions.

This mechanism is a means whereby hydrogen ions can be excreted in a buffered form, it does not represent direct excretion of hydrogen ions. Glutaminase and Glutamate dehydrogenase are present in renal tubular cells. Ammonium ions formed dissociates into ammonia and hydrogen ion. Ammonia is a gas and diffuses readily across the cell membrane into the tubular lumen where it again forms ammonium ions which now cannot cross cell membrane and thus trapped in tubular urine and excreted with anions like phosphate, chloride, or sulfate. During acidosis formation of ammonium ions is favored. Finally 2-oxoglutarate produced is a gluconeogenic source a process that consumes hydrogen ion and produces bicarbonate that replenishes bicarbonate neutralized by metabolic acid production.

The hydrogen ions required from ammonium formation are either present in glomerular filtrate of formed within tubular cells by carbonic anhydrase from CO₂ these hydrogen ions are then excreted by NaHE. In type IV RTA, there is inability to produce ammonia to buffer the nonvolatile acids produced leading to acidosis.

Hydrogen ion secreted also reacts with HPO₄^2- and is excreted, so phosphate excretion (enhanced during acidosis) also provides buffering for hydrogen trapping or excretion.

In acidosis hepatic ureagenesis, ketogenesis is decreased while glutamine synthesis is increased. The net result is decreased in hydrogen ions formation and increase in its excretion.

3.      Reclamation of filtered bicarbonate

Bicarbonate reabsorption takes place almost entirely in the PCT. The excreted hydrogen ion reacts with filtered bicarbonate to form carbonic acid (catalyzed by CA in brush boarder of tubular cell) which is dissociated to CO₂ and H₂O. Carbon dioxide diffuses back and again forms H₂CO₃ which is again converted to bicarbonate. Normally about 90% of filtered bicarbonate is reclaimed in proximal tubule, and extent of its reclamation parallels sodium reabsorption. Thus for each hydrogen ion secreted into tubular fluid, one sodium and bicarbonate enter the tubular cell and return to general circulation. The renal threshold for reclamation is 27 mmol/L. The process of bicarbonate reclamation is enhanced in acidosis (and decreased in alkalosis) due to increased sodium hydrogen ion exchange. In type II RTA there is decreased ability to reabsorb bicarbonate in PCT, leading to decreased blood pH.