The body tightly regulates the acid-base balance of the blood, maintaining a narrow pH range between 7.35 and 7.45. A low blood pH, known as acidosis, signals an excess of hydrogen ions (\(\text{H}^+\)) or a deficit of the primary buffering agent, bicarbonate (\(\text{HCO}_3^-\)). While the lungs offer a rapid, minute-to-minute adjustment by altering carbon dioxide (\(\text{CO}_2\)) excretion, the kidneys provide the definitive, long-term solution. The renal system manages the total body acid load through three coordinated strategies: conserving existing bicarbonate, eliminating fixed acids, and creating new bicarbonate.
Reclaiming the Body’s Bicarbonate Supply
The first and most immediate step the kidneys take to combat acidosis is to prevent the loss of the filtered bicarbonate supply. Bicarbonate acts as the body’s main alkaline buffer, capable of “soaking up” excess acid, and is freely filtered from the blood into the renal tubules. If this filtered \(\text{HCO}_3^-\) were lost in the urine, the acidosis would worsen significantly.
Approximately 80% of the filtered bicarbonate is reclaimed in the proximal tubule, with nearly all of the remaining amount reabsorbed further down the nephron. This process begins with the kidney cells secreting a hydrogen ion (\(\text{H}^+\)) into the tubular fluid, which combines with the filtered \(\text{HCO}_3^-\) to form carbonic acid (\(\text{H}_2\text{CO}_3\)). Enzymes called carbonic anhydrase then rapidly convert this carbonic acid into carbon dioxide (\(\text{CO}_2\)) and water.
The \(\text{CO}_2\) easily diffuses back into the tubule cell, where a reverse reaction occurs, catalyzed by intracellular carbonic anhydrase, to regenerate \(\text{H}^+\) and a new \(\text{HCO}_3^-\). The regenerated \(\text{H}^+\) is promptly secreted back into the lumen to restart the cycle. The newly formed \(\text{HCO}_3^-\) is transported across the cell and returned to the bloodstream, ensuring the existing buffer is conserved and recycled.
Excreting Hydrogen Ions Using Urinary Buffers
Even after conserving all available bicarbonate, the body must still eliminate the daily load of non-volatile, or “fixed,” acids generated by metabolism. The direct excretion of free \(\text{H}^+\) into the urine is limited because the lowest urine pH the tubules can safely tolerate is around 4.5. To excrete a large volume of acid, the kidney must bind the \(\text{H}^+\) to a urinary buffer.
The primary substance used for this purpose is phosphate, which is filtered into the tubular fluid as dibasic phosphate (\(\text{HPO}_4^{2-}\)). When the kidney actively secretes a hydrogen ion into the lumen, the \(\text{H}^+\) immediately binds to the \(\text{HPO}_4^{2-}\), converting it into monobasic phosphate (\(\text{H}_2\text{PO}_4^-\)). This new molecule, \(\text{H}_2\text{PO}_4^-\), is then excreted in the urine.
This mechanism, known as titratable acid excretion, allows for the removal of acid without a severe drop in the final urine pH. The binding effectively neutralizes the acid in the tubule, protecting the nephron structures. However, the amount of acid that can be excreted this way is limited by the amount of phosphate available in the filtrate.
Generating New Bicarbonate Through Ammonia Metabolism
The most powerful and sustainable mechanism the kidneys use to correct chronic acidosis is the generation of completely new bicarbonate through a process called ammoniagenesis. This mechanism not only excretes acid but also produces a fresh supply of \(\text{HCO}_3^-\) to replenish the depleted blood buffer stores.
This process is highly upregulated during acidosis and takes place predominantly in the proximal tubule cells. The kidney cells metabolize the amino acid glutamine, breaking it down to produce two molecules of ammonium (\(\text{NH}_4^+\)) and two molecules of new bicarbonate (\(\text{HCO}_3^-\)). The bicarbonate is immediately transported out of the cell and back into the peritubular capillaries, directly raising the blood \(\text{pH}\).
The ammonium ion (\(\text{NH}_4^+\)) is secreted into the tubular fluid, effectively carrying the excess acid out of the body. The total amount of urinary \(\text{NH}_4^+\) excretion serves as a direct measure of the new \(\text{HCO}_3^-\) the kidney has generated. This dual-action mechanism of acid removal and buffer creation makes ammoniagenesis the primary means of correcting a long-term acid-base imbalance.
The Timeframe and Limits of Kidney Compensation
The kidney’s response to low blood \(\text{pH}\) is not instantaneous; it is a slow but robust process that takes time to fully develop. While the lungs can begin compensating within minutes by altering breathing rate, renal compensation begins working within hours but requires several days, typically 3 to 5 days, to reach its maximal effectiveness. This delay is due to the time needed to upregulate the enzymes and transport proteins involved in the various mechanisms, especially ammoniagenesis.
Despite its slow onset, the renal system’s ability to excrete fixed acids and produce new \(\text{HCO}_3^-\) is substantial, allowing for the complete correction of most chronic acid-base disturbances. The limits of this compensation are related to the underlying health of the kidney and the availability of substrates. For example, severe kidney disease significantly impairs the ability to generate \(\text{NH}_4^+\) and excrete acid, which can lead to persistent acidosis.