Titratable acidity: A Pitts concept revisited

Abstract

Titratable Acidity (TA) in urine can be measured directly or calculated from actual and reference pH, by using the pKa₂ 6,8 for phosphate. In urine, H₂PO₄⁻ represents the excretion of filtered H₂PO₄⁻, filtrated HPO₄²⁻ being completely reabsorbed by the proximal tubule (the Van Slyke approach). Since excretion of H₂PO₄⁻ frequently exceeds its glomerular filtration, this approach is considered inadequate by Pitts. He claimed that it is the tubular H⁺ secretion which converts filtered HPO₄²⁻ to H₂PO₄⁻, thereafter excreted in urine. This is only true under conditions of inorganic acid or neutral phosphate loading, when the maximum tubular phosphate reabsorption (TmPi) is overcharged. In controls, H₂PO₄⁻ excretion is lower than its glomerular filtration, provided that acid-base status is normal and tubular phosphate reabsorption is below the TmPi. The TmPi is lower than its glomerular filtration, provided that acid-base status is normal and tubular phosphate reabsorption is below the TmPi. When the TmPi is exceeded, a portion of HPO₄²⁻ escapes proximal reabsorption, reaching the distal tubule where its absorption is precluded, while tubular H⁺ secretion converts HPO₄²⁻ to H₂PO₄⁻. In man and dog, the attainment of TmPi is evidenced by a FE% of 20%, and only beyond this limit H₂PO₄⁻ excretion exceeds glomerular filtration. When FE% is lower than 20%, H₂PO₄⁻ filtration exceeds excretion, HPO₄²⁻ being completely reabsorbed at the proximal tubule by NaPi-2a and 2c cotransporters. While Van Slyke's approach is always valid, Pitts’ approach is only valid under loading conditions, when the two processes of H₂PO₄⁻ excretion overlap each other. NH ^+₄ increases inversely to TA excretion in conditions of acidosis and tP restriction, but is independent of TA in Pi-replete dogs, independently of acidosis.

Key Words::

• Acid phosphate
• dibasic phosphate
• fractional phosphate excretion
• inorganic phosphate
• sodium hydrogen antiporter
• sodium phosphate-2a cotransporter
• sodium phosphate-2c cotransporter
• sodium phosphate T2 cotransporter
• tubular maximum Pi transport

Acknowledgements

This research has received no specific grant from any funding agency in the public, commercial or non-profit sectors.

No experiment has been carried out on human beings or animals.

The authors have contributed equally to the different sections of the paper.

We are grateful to our friends Giuseppe Maschio, Former Professor of Nephrology, University of Verona, and Angela D’Angelo, Former Professor of Nephrology, University of Padova, for their stimulating participation in the work.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.