Determination of pKA of nonvolatile weak acids in plasma of healthy volunteers and critically ill patients
Abstract Background The dissociation constant of nonvolatile weak acids in plasma (KA), expressed as pKA, is essential for electroneutrality-based acid–base analysis. To date, its normal value in human plasma has been determined in only one study involving eight healthy volunteers. We hypothesized t...
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SpringerOpen
2025-06-01
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| Series: | Intensive Care Medicine Experimental |
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| Online Access: | https://doi.org/10.1186/s40635-025-00762-8 |
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| author | Martin Krbec Serena Brusatori Petr Waldauf Alberto Zanella Francesco Zadek Victor van Bochove František Duška Thomas Langer Paul Elbers |
| author_facet | Martin Krbec Serena Brusatori Petr Waldauf Alberto Zanella Francesco Zadek Victor van Bochove František Duška Thomas Langer Paul Elbers |
| author_sort | Martin Krbec |
| collection | DOAJ |
| description | Abstract Background The dissociation constant of nonvolatile weak acids in plasma (KA), expressed as pKA, is essential for electroneutrality-based acid–base analysis. To date, its normal value in human plasma has been determined in only one study involving eight healthy volunteers. We hypothesized that pKA would differ in ICU patients, whose plasma protein composition is altered by disease and medication, and that changes in protein charge—rather than undetected strong acids—could account for the unexplained anions observed in sepsis. Methods Using CO2 tonometry, we determined pKA and total weak nonvolatile acids (ATOT) in plasma from 30 healthy volunteers and two ICU cohorts (27 postoperative and 30 septic patients). Additionally, we calculated the strong ion gap in plasma and protein-free serum filtrates from 10 healthy volunteers and 20 septic patients. Results In healthy volunteers, pKA was 7.55 ± 0.16 (KA = 2.8 × 10⁻⁸) and ATOT was 15.9 ± 3.0 mmol/L (0.222 ± 0.043 mmol/g of TP). In postoperative and septic patients, ATOT was significantly reduced (10.1 ± 5.4 and 11.9 ± 4.0 mmol/L, p < 0.001), but pKA and ATOT/TP remained unchanged, yielding an average pKA of 7.55 ± 0.35 (KA = 2.8 × 10⁻⁸) and ATOT/TP of 0.230 ± 0.097 mmol/g. We found elevated strong ion gap in both plasma and protein-free filtrates of septic patients, which confirms the presence of unmeasured low-molecular-weight anions. Conclusion Our findings confirm stable pKA and ATOT/TP values in human plasma in both health and disease, supporting the Staempfli-Constable model for clinical acid–base diagnostics. Unexplained anions in sepsis are attributed to low molecular weight strong ions rather than alterations in plasma protein dissociation. |
| format | Article |
| id | doaj-art-498e29387a8a4c50be3e01319732e45f |
| institution | DOAJ |
| issn | 2197-425X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | SpringerOpen |
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| series | Intensive Care Medicine Experimental |
| spelling | doaj-art-498e29387a8a4c50be3e01319732e45f2025-08-20T03:10:38ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2025-06-0113111210.1186/s40635-025-00762-8Determination of pKA of nonvolatile weak acids in plasma of healthy volunteers and critically ill patientsMartin Krbec0Serena Brusatori1Petr Waldauf2Alberto Zanella3Francesco Zadek4Victor van Bochove5František Duška6Thomas Langer7Paul Elbers8Department of Anaesthesia and Intensive Care Medicine, Third Faculty of Medicine, Charles University and FNKV University HospitalFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoDepartment of Anaesthesia and Intensive Care Medicine, Third Faculty of Medicine, Charles University and FNKV University HospitalFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoDepartment of Medicine and Surgery, University of Milano-BicoccaDepartment of Intensive Care Medicine, Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Science (ACS), Amsterdam Institute for Infection and Immunity (AII), Amsterdam Public Health, Amsterdam UMC, Vrije UniversiteitDepartment of Anaesthesia and Intensive Care Medicine, Third Faculty of Medicine, Charles University and FNKV University HospitalDepartment of Medicine and Surgery, University of Milano-BicoccaDepartment of Intensive Care Medicine, Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Science (ACS), Amsterdam Institute for Infection and Immunity (AII), Amsterdam Public Health, Amsterdam UMC, Vrije UniversiteitAbstract Background The dissociation constant of nonvolatile weak acids in plasma (KA), expressed as pKA, is essential for electroneutrality-based acid–base analysis. To date, its normal value in human plasma has been determined in only one study involving eight healthy volunteers. We hypothesized that pKA would differ in ICU patients, whose plasma protein composition is altered by disease and medication, and that changes in protein charge—rather than undetected strong acids—could account for the unexplained anions observed in sepsis. Methods Using CO2 tonometry, we determined pKA and total weak nonvolatile acids (ATOT) in plasma from 30 healthy volunteers and two ICU cohorts (27 postoperative and 30 septic patients). Additionally, we calculated the strong ion gap in plasma and protein-free serum filtrates from 10 healthy volunteers and 20 septic patients. Results In healthy volunteers, pKA was 7.55 ± 0.16 (KA = 2.8 × 10⁻⁸) and ATOT was 15.9 ± 3.0 mmol/L (0.222 ± 0.043 mmol/g of TP). In postoperative and septic patients, ATOT was significantly reduced (10.1 ± 5.4 and 11.9 ± 4.0 mmol/L, p < 0.001), but pKA and ATOT/TP remained unchanged, yielding an average pKA of 7.55 ± 0.35 (KA = 2.8 × 10⁻⁸) and ATOT/TP of 0.230 ± 0.097 mmol/g. We found elevated strong ion gap in both plasma and protein-free filtrates of septic patients, which confirms the presence of unmeasured low-molecular-weight anions. Conclusion Our findings confirm stable pKA and ATOT/TP values in human plasma in both health and disease, supporting the Staempfli-Constable model for clinical acid–base diagnostics. Unexplained anions in sepsis are attributed to low molecular weight strong ions rather than alterations in plasma protein dissociation.https://doi.org/10.1186/s40635-025-00762-8Acid–base equilibriumModelsTheoreticalAcidsSerum albuminHydrogen-ion concentration |
| spellingShingle | Martin Krbec Serena Brusatori Petr Waldauf Alberto Zanella Francesco Zadek Victor van Bochove František Duška Thomas Langer Paul Elbers Determination of pKA of nonvolatile weak acids in plasma of healthy volunteers and critically ill patients Intensive Care Medicine Experimental Acid–base equilibrium Models Theoretical Acids Serum albumin Hydrogen-ion concentration |
| title | Determination of pKA of nonvolatile weak acids in plasma of healthy volunteers and critically ill patients |
| title_full | Determination of pKA of nonvolatile weak acids in plasma of healthy volunteers and critically ill patients |
| title_fullStr | Determination of pKA of nonvolatile weak acids in plasma of healthy volunteers and critically ill patients |
| title_full_unstemmed | Determination of pKA of nonvolatile weak acids in plasma of healthy volunteers and critically ill patients |
| title_short | Determination of pKA of nonvolatile weak acids in plasma of healthy volunteers and critically ill patients |
| title_sort | determination of pka of nonvolatile weak acids in plasma of healthy volunteers and critically ill patients |
| topic | Acid–base equilibrium Models Theoretical Acids Serum albumin Hydrogen-ion concentration |
| url | https://doi.org/10.1186/s40635-025-00762-8 |
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