Acid-base analysis: a critique of the Stewart and bicarbonate-centered approaches

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.

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Extracellular Acid-Base Balance and Ion Transport Between Body Fluid Compartments

Physiology ◽

10.1152/physiol.00007.2017 ◽

2017 ◽

Vol 32 (5) ◽

pp. 367-379 ◽

Cited By ~ 9

Author(s):

Julian L. Seifter ◽

Hsin-Yun Chang

Keyword(s):

Ion Transport ◽

Ph Regulation ◽

Extracellular Fluid ◽

Transport Processes ◽

Electrolyte Balance ◽

Ph Homeostasis ◽

Acid Base Balance ◽

Acid Base ◽

Base Balance ◽

Fluid Compartments

Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of these disorders concerns intracellular events. Intracellular and interstitial compartment acid-base balance is complex and heterogeneous. This review considers the determinants of the extracellular fluid pH related to the ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment. The generation of acid-base disorders and the associated disruption of electrolyte balance are considered in the context of these membrane transporters. This review suggests a process of internal and external balance for pH regulation, similar to that of potassium. The role of secretory gastrointestinal epithelia and renal epithelia with respect to normal pH homeostasis and clinical disorders are considered. Electroneutrality of electrolytes in the ECF is discussed in the context of reciprocal changes in Cl−or non Cl−anions and [Formula: see text].

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Sodium–hydrogen exchangers in the nematode Caenorhabditis elegans: investigations towards their potential role in hypodermal H+ excretion, Na+ uptake, and ammonia excretion, as well as acid–base balance

Canadian Journal of Zoology ◽

10.1139/cjz-2016-0243 ◽

2017 ◽

Vol 95 (9) ◽

pp. 623-632 ◽

Cited By ~ 2

Author(s):

Aida Adlimoghaddam ◽

Michael J. O’Donnell ◽

Alex Quijada-Rodriguez ◽

Dirk Weihrauch

Keyword(s):

Caenorhabditis Elegans ◽

Cell Volume Regulation ◽

Ammonia Excretion ◽

Transport Processes ◽

Soil Nematode ◽

Acid Base Balance ◽

Nematode Caenorhabditis Elegans ◽

Acid Base ◽

C Elegans ◽

Base Balance

Cation/proton exchangers of the cation proton antiporter 1 (CPA1) subfamily (NHEs, SLC 9) play an important role in many physiological processes, including cell volume regulation, acid–base homeostasis, and ammonia excretion. The soil nematode Caenorhabditis elegans (Maupas, 1900) (N2, 1968) expresses nine paralogues (NHX-1 to NHX-9). The current study was undertaken to investigate the role of the cation/proton exchanger in hypodermal Na+ and H+ fluxes, as well in ammonia excretion processes. Measurements using SIET (scanning ion-selective electrode technique) showed that the hypodermis promotes H+ secretion and Na+ uptake. Inhibitory effects on fluxes were observed upon application of amiloride but not EIPA, suggesting that NHXs are not involved in the transport processes. In response to stress induced by starvation or exposure to 1 mmol·L−1 NH4Cl, pH 5.5, or pH 8.0, body pH stayed fairly constant, with changes in mRNA expression levels detected in intestinal NHX-2 and hypodermal NHX-3. In conclusion, the study suggest that hypodermal apically localized EIPA-sensitive Na+/H+ exchangers do not likely play a role in ammonia excretion and Na+ uptake in the hypodermis of C. elegans, whereas apical amiloride-sensitive Na+ channels seem to be involved not just in hypodermal Na+ uptake but indirectly also in NH4+ and H+ excretion.

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The 100th anniversary of the invention of pH (1909-2009) - Part II. Was it really necessary to replace the Henderson equation with that of Henderson-Hasselbalch?

Italian Journal of Medicine ◽

10.4081/itjm.2011.215 ◽

2012 ◽

pp. 215-226

Author(s):

Francesco Sgambato ◽

Sergio Prozzo ◽

Ester Sgambato ◽

Rosa Sgambato ◽

Luca Milano

Keyword(s):

Medical School ◽

Clinical Application ◽

Human Life ◽

100Th Anniversary ◽

Acid Base Balance ◽

Historical Events ◽

Acid Base ◽

Base Balance ◽

Hasselbalch Equation ◽

School Curricula

Introduction: The year 2009 marked the centenary of the ‘‘invention’’ of the concept of pH by the Danish chemist-mathematician Søren Peder Lauritz Sørensen (1868-1939), who was working at the time in the chemistry laboratories of the Carlsberg Brewery in Copenhagen. The occasion provides an opportunity to re-examine a concept that is crucial for the understanding of human life–—namely, acid-base balance. This article provides an overview of acid-base pathophysiology and the historical events that led from the simple equation of Henderson to the much more complex one developed by Hasselbalch. Conclusions: The authors conclude that the issue of acid-base balance would be easier to understand, more exciting, and even more pleasant if it were taught without recourse to the infamously abstruse Henderson-Hasselbalch equation. Unquestionably, the whole rationale underlying the understanding and clinical application of this vital concept is already inherent in the simpler, more manageable formula of Henderson (without logs), which is both useful and sufficient for use in medical school curricula.

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Tubular disorders

Paediatric Nephrology ◽

10.1093/med/9780198784272.003.0007 ◽

2019 ◽

pp. 161-200

Author(s):

Lesley Rees ◽

Nicholas J.A Webb ◽

Detlef Bockenhauer ◽

Marilynn G. Punaro

Keyword(s):

Collecting Duct ◽

Sodium Reabsorption ◽

Correct Identification ◽

Acid Base Balance ◽

Acid Base ◽

Plasma Electrolyte ◽

Tubular Disorders ◽

Appropriate Treatment ◽

Base Balance ◽

Underlying Disorder

Tubular function is critical for the maintenance of electrolyte and acid–base balance. Consequently, acid–base disorders typically manifest with alterations in plasma electrolyte concentrations and/or pH. Tubular handling of the various electrolytes is often linked on a molecular level. For example, secretion of potassium and protons in the collecting duct is dependent on sodium reabsorption. Consequently, tubular disorders typically present with characteristic patterns of electrolyte and acid–base abnormalities, which can serve as biochemical ‘fingerprints’ for the accurate diagnosis of the underlying disorder. Recognition of these ‘fingerprints’ is critical as correct identification of the underlying disorder is key for appropriate treatment.

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Higher Dietary Acidity is Associated with Lower Bone Mineral Density in Postmenopausal Iranian Women, Independent of Dietary Calcium Intake

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000207 ◽

2014 ◽

Vol 84 (3-4) ◽

pp. 0206-0217 ◽

Cited By ~ 8

Author(s):

Seyedeh-Elaheh Shariati-Bafghi ◽

Elaheh Nosrat-Mirshekarlou ◽

Mohsen Karamati ◽

Bahram Rashidkhani

Keyword(s):

Calcium Intake ◽

Dietary Calcium ◽

Dietary Calcium Intake ◽

Dietary Intakes ◽

Iranian Women ◽

Acid Base Balance ◽

Mineral Density ◽

Acid Base ◽

Base Balance ◽

Dietary Acid

Findings of studies on the link between dietary acid-base balance and bone mass are relatively mixed. We examined the association between dietary acid-base balance and bone mineral density (BMD) in a sample of Iranian women, hypothesizing that a higher dietary acidity would be inversely associated with BMD, even when dietary calcium intake is adequate. In this cross-sectional study, lumbar spine and femoral neck BMDs of 151 postmenopausal women aged 50 - 85 years were measured using dual-energy x-ray absorptiometry. Dietary intakes were assessed using a validated food frequency questionnaire. Renal net acid excretion (RNAE), an estimate of acid-base balance, was then calculated indirectly from the diet using the formulae of Remer (based on dietary intakes of protein, phosphorus, potassium, and magnesium; RNAERemer) and Frassetto (based on dietary intakes of protein and potassium; RNAEFrassetto), and was energy adjusted by the residual method. After adjusting for potential confounders, multivariable adjusted means of the lumbar spine BMD of women in the highest tertiles of RNAERemer and RNAEFrassetto were significantly lower than those in the lowest tertiles (for RNAERemer: mean difference -0.084 g/cm2; P=0.007 and for RNAEFrassetto: mean difference - 0.088 g/cm2; P=0.004). Similar results were observed in a subgroup analysis of subjects with dietary calcium intake of >800 mg/day. In conclusion, a higher RNAE (i. e. more dietary acidity), which is associated with greater intake of acid-generating foods and lower intake of alkali-generating foods, may be involved in deteriorating the bone health of postmenopausal Iranian women, even in the context of adequate dietary calcium intake.

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