title: Acid-base analysis: a critique of the Stewart and bicarbonate-centered approaches.
abstract: When approaching the analysis of disorders of acid-base balance, physical chemists, physiologists, and clinicians, tend to focus on different aspects of the relevant phenomenology. The physical chemist focuses on a quantitative understanding of proton hydration and aqueous proton transfer reactions that alter the acidity of a given solution. The physiologist focuses on molecular, cellular, and whole organ transport processes that modulate the acidity of a given body fluid compartment. The clinician emphasizes the diagnosis, clinical causes, and most appropriate treatment of acid-base disturbances. Historically, two different conceptual frameworks have evolved among clinicians and physiologists for interpreting acid-base phenomena. The traditional or bicarbonate-centered framework relies quantitatively on the Henderson-Hasselbalch equation, whereas the Stewart or strong ion approach utilizes either the original Stewart equation or its simplified version derived by Constable. In this review, the concepts underlying the bicarbonate-centered and Stewart formulations are analyzed in detail, emphasizing the differences in how each approach characterizes acid-base phenomenology at the molecular level, tissue level, and in the clinical realm. A quantitative comparison of the equations that are currently used in the literature to calculate H(+) concentration ([H(+)]) is included to clear up some of the misconceptions that currently exist in this area. Our analysis demonstrates that while the principle of electroneutrality plays a central role in the strong ion formulation, electroneutrality mechanistically does not dictate a specific [H(+)], and the strong ion and bicarbonate-centered approaches are quantitatively identical even in the presence of nonbicarbonate buffers. Finally, our analysis indicates that the bicarbonate-centered approach utilizing the Henderson-Hasselbalch equation is a mechanistic formulation that reflects the underlying acid-base phenomenology.
authors.affiliation: Division of Nephrology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave., Rm. 7-155 Factor Bldg., Los Angeles, California 90095, USA. ikurtz@mednet.ucla.edu
authors.forename: Ira
authors.initials: I
authors.lastname: Kurtz
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kraut
authors.forename: Vahram
authors.initials: V
authors.lastname: Ornekian
authors.forename: Minhtri K
authors.initials: MK
authors.lastname: Nguyen
mesh_terms: D000136:Acid-Base Equilibrium / Q000502:physiology*; D000137:Acid-Base Imbalance / Q000378:metabolism / Q000503:physiopathology; D000465:Algorithms; D000818:Animals; D001639:Bicarbonates / Q000032:analysis*; D004583:Electrons; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011522:Protons
chemical_list: D001639:Bicarbonates; D011522:Protons