Renal regulation of acid base balance

Bicarbonate

Proximal renal tubule

Bicarbonate (HCO₃^-) is freely filtered at the glomerulus. Filtrate HCO₃^- concentration is therefore roughly the same as plasma.


<0.1% of filtered HCO₃^- is normally excreted in the urine. Approximately 80% of filtered bicarbonate is reabsorbed in the proximal tubule.

Bicarbonate (HCO₃^-) is not transported directly, It associates with hydrogen (H⁺) ions to form carbonic acid (H₂CO₃) which rapidly dissociates into carbon dioxide and water in the presence of carbonic anhydrase as shown in the equation below.


CO₂ + H₂O diffuse into the tubular cells where they recombine into H₂CO₃ which then dissociates into H⁺ + HCO₃- i.e. the equation above happens in reverse.



Bicarbonate (HCO₃^-) is transported into the interstitial fluid primarily via Na⁺-HCO₃^- symporters.

For every 1 hydrogen ion (H⁺) secreted into the lumen 1 bicarbonate (HCO₃^-) and 1 sodium (Na⁺) ion enter the plasma. This mechanism does not lead to the net excretion of any H⁺ from the body as the H⁺ is consumed in the reaction with the filtered bicarbonate in the tubular lumen

Thick ascending loop

A further 10-15% of bicarbonate is reabsorbed in the thick ascending loop via similar mechanisms.

Distal renal tubule

The secretion of H⁺ into the distal tubule promotes reabsorption of any remaining HCO₃^-. In total 4000-5000 mmol of bicarbonate is reabsorbed each day.

H⁺ secretion in the early distal tubule is primarily via Na⁺-H⁺ exchange. More distally H⁺ secretion is from H⁺-ATPase and H⁺-K⁺ATPase pumps in intercalated cells.




Note that the H⁺ formed is derived from the breakdown of carbonic acid which is itself formed by combining carbon dioxide and water. Intercalated cells contain plentiful carbonic anhydrase to drive the initial formation of carbonic acid from CO₂ and H₂O.

H⁺ secretion is proportional to intracellular [H⁺]. Tubular fluid becomes more acidic as it moves through the nephron due to this.

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Ammonia

Proximal renal tubule

Glutamate metabolism in tubular cells generates ammonia (NH₃). NH₃ may diffuse out of cells into the tubular fluid as NH₃ or be transported by the Na⁺-H⁺ antiporter as ammonium (NH₄⁺) which substitutes for H⁺ .

In the tubular fluid NH₃ will combine with H⁺ to form ammonium (NH₄⁺). Ammonium cannot diffuse freely through membranes and requires transporters.

Thick ascending loop to distal tubule

Approximately 50% of secreted NH₄⁺ is reabsorbed in the thick ascending limb of the loop of Henle by the Na⁺-K⁺-2Cl^- symporter where is substitutes for K⁺. This NH₄⁺ enters the medullary interstitium and dissociates into NH₃ and H⁺. NH₃ re-enters the tubular fluid in the collecting duct by diffusion and recombines with H⁺ reforming NH₄⁺ which is then trapped in the lumen and excreted in the urine.




Distal renal tubule, urinary buffers & acid excretion
The combination of H⁺ with NH₃ and phosphate (PO₄^3-) prevents H⁺ recycling and allows acid excretion.