Kidneys provide the long-term regulation of body pH by controlling plasma bicarbonate and eliminating non-volatile acids. Their response begins over hours and becomes maximal over several days.
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Reabsorption of filtered bicarbonate (HCO₃⁻)
Almost all filtered HCO₃⁻ is reabsorbed, mainly in the proximal convoluted tubule. This prevents loss of the major extracellular buffer. The collecting duct provides final adjustment of bicarbonate reabsorption.
Brenner and Rector's The Kidney, 2-Volume Set, Acid-Base Regulation.
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Secretion of hydrogen ions (H⁺)
Renal tubular cells secrete H⁺ into tubular fluid, chiefly through Na⁺/H⁺ exchange in the proximal tubule and H⁺-ATPase/H⁺-K⁺-ATPase pumps in the distal nephron and collecting duct. This acidifies urine, which may reach a pH of about 4.5.
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Excretion of acid as titratable acid
Secreted H⁺ is buffered in urine by phosphate and other urinary buffers, then excreted as titratable acid, mainly H₂PO₄⁻. This eliminates fixed acids without an extreme fall in urine pH.
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Ammonium (NH₄⁺) excretion
In the proximal tubule, glutamine metabolism produces NH₄⁺ and new HCO₃⁻. NH₄⁺ is excreted in urine, while the newly formed HCO₃⁻ enters blood. Ammonium excretion rises greatly during acidosis and is the main adaptive renal mechanism for removal of excess acid.
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Generation of new bicarbonate
For every H⁺ excreted as titratable acid or NH₄⁺, one new HCO₃⁻ is added to the blood. This replaces bicarbonate used in buffering fixed acids.
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Response to acid-base disturbances
- Acidosis: increased H⁺ secretion, NH₄⁺ formation/excretion, titratable acid excretion, and HCO₃⁻ reabsorption/generation.
- Alkalosis: decreased H⁺ secretion and HCO₃⁻ reabsorption; type B intercalated cells can secrete HCO₃⁻ into urine.
In summary: renal net acid excretion equals urinary NH₄⁺ plus titratable acid minus urinary HCO₃⁻. Thus, kidneys maintain pH by conserving bicarbonate, excreting H⁺, and generating new bicarbonate. The kidneys have the predominant role in regulating systemic bicarbonate concentration, as summarized in this
NCBI review.