Renal regulation of acid-base balance

Bicarbonate Rescue - The Great Reclaim

• The kidneys reclaim almost all filtered bicarbonate ($HCO_3^-$), with ~85% of this occurring in the Proximal Convoluted Tubule (PCT).
• This is an indirect reabsorption; $HCO_3^-$ itself doesn't cross the apical membrane. The process hinges on proton ($H^+$) secretion.

⭐ Carbonic anhydrase inhibitors (e.g., Acetazolamide) block $H^+$ secretion by halting the intracellular production of $H^+$. This prevents $HCO_3^-$ reabsorption, leading to bicarbonaturia and a hyperchloremic metabolic acidosis.

Acid Excretion - Making New Buffer

• Kidneys generate new $HCO_3^-$ while excreting fixed acids, primarily via two pathways that couple $H^+$ secretion with $HCO_3^-$ synthesis.

• 1. Titratable Acidity:

  • Filtered phosphate ($HPO_4^{2-}$) buffers secreted $H^+$ in the tubular fluid.
  • $H^+ + HPO_4^{2-} \rightarrow H_2PO_4^-$ (excreted).
  • For each $H^+$ secreted, one new $HCO_3^-$ is reabsorbed into the blood.
  • Accounts for ~1/3 of new $HCO_3^-$ generation.

• 2. Ammonium ($NH_4^+$) Excretion:

  • Proximal tubule cells metabolize glutamine: $Glutamine \rightarrow 2 NH_4^+ + 2 HCO_3^-$.
  • The new $HCO_3^-$ enters the blood.
  • $NH_4^+$ is secreted into the lumen.
  • In the collecting duct, secreted $H^+$ is trapped by diffused ammonia ($NH_3$) forming $NH_4^+$, which is then excreted.
  • $NH_3 + H^+ \leftrightarrow NH_4^+$.

⭐ In chronic acidosis, renal glutamine metabolism and $NH_4^+$ excretion increase dramatically, becoming the dominant mechanism for acid excretion.

Ammonia Factory - The Glutamine Game

• The kidney's main long-term response to acidosis, primarily occurring in the Proximal Convoluted Tubule (PCT).
• Glutamine is transported into PCT cells and metabolized by glutaminase.
• This process yields two ammonia ($NH_3$) molecules and two new bicarbonate ($HCO_3^−$) molecules.
  • $NH_3$ diffuses into the tubular lumen, combining with secreted $H^+$ to form ammonium ($NH_4^+$).
  • $NH_4^+$ is charged, trapping it in the tubule for excretion (net acid loss).
  • The new $HCO_3^−$ is reabsorbed into the blood, buffering the acidosis.

⭐ In chronic acidosis, renal gene expression for glutaminase is upregulated over 3-5 days, dramatically increasing the kidney's capacity to excrete acid as $NH_4^+$.

Renal Tubular Acidosis - Leaky Pipes

Normal anion gap metabolic acidosis resulting from defective renal acid-base handling. All types cause ↓ serum $HCO_3^-$.

High‑Yield Points - ⚡ Biggest Takeaways

• The kidneys are the primary long-term regulators of acid-base balance, mainly by reabsorbing filtered HCO₃⁻ and secreting H⁺.
• Bicarbonate reabsorption occurs predominantly in the proximal convoluted tubule (PCT), recovering ~85%.
• Type A intercalated cells in the collecting duct actively secrete H⁺ via an H⁺-ATPase during acidosis.
• Ammoniagenesis in the PCT from glutamine is the principal mechanism for excreting a large acid load.
• Aldosterone stimulates H⁺ secretion, which can contribute to metabolic alkalosis.