Low Bicarbonate Concentration Research Articles

Characterization of a novel variant in KCNJ16, encoding Kir5.1 channel.

The essential role of the inwardly rectifying potassium channel Kir5.1 (KCNJ16) in controlling electrolyte homeostasis and blood pressure has been demonstrated in human and animal studies. Previous studies have identified several bi-allelic mutations of KCNJ16 in humans, causing severe hypokalemia, renal salt wasting, and disturbed acid-base homeostasis. Here, we identified a novel homozygous variant of KCNJ16, I26T, in an Amish patient affected with polydipsia, developmental delay, and chronic metabolic acidosis with low serum bicarbonate concentration. Subsequently, we generated the rat model with I26T mutation using Dahl salt-sensitive rat (I26T rat) to characterize this variant. The male mutant rats displayed similar blood pressure and electrolyte homeostasis under baseline and with a high salt (4% NaCl) challenge. Blood pH, HCO3 - and renal damage also remained similar between WT and I26T rats after high salt challenge. Additionally, single-channel patch clamp analysis revealed similar channel activity in CHO cells overexpressed with WT and I26T mutant Kir4.1/5.1 channels. In summary, this study reported a novel variant in KCNJ16, namely I26T, which is likely a benign variant and not associated with pathologic phenotype in either human or Dahl salt-sensitive rats, indicating that the type/location of variant should be considered when diagnosing and treating patients with KCNJ16 mutations.

Hemodynamic effects of low versus high dialysate bicarbonate concentration in hemodialysis patients.

Hemodialysis treatment using standard dialysate bicarbonate concentrations cause transient metabolic alkalosis possibly associated with hemodynamic instability. The aim of this study was to perform a detailed comparison of high and low dialysate bicarbonate in terms of blood pressure, intradialytic hemodynamic parameters, orthostatic blood pressure, and electrolytes. Fifteen hemodialysis patients were examined in a single-blind, randomized, controlled, crossover study. Participants underwent a 4-h hemodialysis session with dialysate bicarbonate concentration of 30 or 38 mmol/L with 1 week between interventions. Blood pressure was monitored throughout hemodialysis, while cardiac output, total peripheral resistance, stroke volume, and central blood volume were assessed with ultrasound dilution technique (Transonic). Orthostatic blood pressure was measured pre- and post-hemodialysis. With similar ultrafiltration (UF) volume (2.6 L), systolic blood pressure (SBP) tended to decrease more during high dialysate bicarbonate compared to low dialysate bicarbonate; the mean (95% confidence interval) between treatment differences in SBP were: 8 (-4; 20) mmHg (end of hemodialysis) and 7 (0; 15) mmHg (post-hemodialysis). Stroke volume decreased whereas total peripheral resistance increased significantly more during high dialysate bicarbonate compared to low dialysate bicarbonate with mean between treatment differences: Stroke volume: 12 (1; 23) mL; Total peripheral resistance: -2.9 (-5.3; -0.5) mmHg/(L/min). Cardiac output tended to decrease more with high dialysate bicarbonate compared to low dialysate bicarbonate with mean between treatment difference 0.7 (0.0; 1.4) L/min. High dialysate bicarbonate caused alkalosis, hypocalcemia, and lower plasma potassium, whereas patients remained normocalcemic with normal pH during low dialysate bicarbonate. Orthostatic blood pressure response after dialysis did not differ significantly. The use of high dialysate bicarbonate compared to low dialysate bicarbonate was associated with hypocalcemia, alkalosis, and a more pronounced hypokalemia. During hemodialysis with UF, a better preservation of blood pressure, stroke volume, and cardiac output may be achieved with low dialysate bicarbonate compared to high dialysate bicarbonate.

#1328 Haemodynamic effects of low versus high dialysate bicarbonate concentration in haemodialysis patients

Abstract Background and Aims Haemodialysis (HD) treatment using standard dialysate bicarbonate concentrations cause transient metabolic alkalosis possibly associated with haemodynamic instability. We performed a detailed comparison of blood pressure (BP), haemodynamic parameters, electrolytes and orthostatic BP response with low (LDB) versus high dialysate bicarbonate concentration (HDB). Method Fifteen HD patients were examined in a single-blind, randomised, controlled, crossover study. Participants underwent a 4-hour HD session with dialysate bicarbonate concentration of 30 mmol/l (LDB) or 38 mmol/l (HDB) with one week between interventions. During HD, cardiac output (CO), total peripheral resistance (TPR), stroke volume (SV) and central blood volume were measured with ultrasound dilution technique (Transonic). Throughout dialysis, blood samples were obtained from the arterial cannula. Orthostatic BP was measured pre and post HD. Results With similar ultrafiltration volume (2.6 litres), systolic BP tended to decrease more during HDB compared to LDB (Fig. 1 and Table 1); the mean (95% confidence interval) between treatment differences in systolic BP were: 8 (-4;20) mmHg (end of HD) and 7 (0;15) mmHg (post HD). SV decreased (Fig. 2) whereas TPR increased significantly more during HDB compared to LDB with mean between treatment differences: SV: 12 (1;23) ml; TPR: -2.9 (-5.3;-0.5) mmHg/(L/min). CO tended to decrease more with HDB compared to LDB with mean between treatment difference 0.7 (0.0;1.4) L/min. HDB caused alkalosis, hypocalcaemia and lower plasma potassium, whereas patients remained normocalcaemic with normal pH during LDB (Table 1). Orthostatic BP response after dialysis did not differ significantly. Conclusion HDB compared to LDB was associated with hypocalcaemia and alkalosis and a more pronounced hypokalaemia which may impair preservation of BP, SV and CO during HD.

Effects of organic matter and alkalinity on the ozonation of antiviral purine derivatives as exemplary micropollutant motif.

Ozonation of micropollutants strongly depends on the water matrix. Natural organic matter is known to highly affect the hydroxyl radical exposure due to radical promoting and inhibiting effects. Other important matrix components in ozonation are carbonate species which scavenge hydroxyl radicals. However, additional factors such as the formation of other radicals might also play a role but are generally not covered in research or considered in modelling of micropollutant degradation. Hence, the ozonation of purine derivatives, the basic structure of various antiviral micropollutants, in different artificial water matrices is investigated in this study with focus on the impact of natural organic matter and increasing alkalinity on the degradation and product formation. The degradation of purine and adenine is inhibited by bicarbonate in the water matrix due to the anion's scavenging of hydroxyl radicals. This effect is already observed for low bicarbonate concentrations of 0.3mM. However, formed carbonate radicals contribute to the compounds' degradation and also affect the stability of transformation products. This effect gains in relevance with increasing alkalinity and needs consideration in evaluating ozonation of very hard waters. Three ozonation products are evaluated in detail, which are affected by the matrix due to impacts on ozone stability, hydroxyl radical yield and carbonate radical formation. One product of adenine with the mass 147 was reported for the first time and only occurs in presence of matrix components. Under typical water treatment conditions rough predictions of pollutants' degradation are possible by the Rct concept using ozone and hydroxyl radical exposures. However, other reactive species such as carbonate radicals are not considered leading to deviations between modelled and experimental data at extreme conditions such as industrial wastewater. A general correlation between the Rct and the fraction f of hydroxyl radicals scavenged by bicarbonate (ln(Rct)=-5.9×f-16.3) calculated from the concentration of organic matter and alkalinity was observed for various water samples allowing the estimation of micropollutant degradation during ozone treatment at moderate conditions by simple organic and inorganic carbon measurements.

Boar sperm motility is modulated by CCK at a low concentration of bicarbonate under capacitation conditions.

In a previous study, our group detected the cholecystokinin (CCK) protein in the porcine oviduct. This fact, together with the involvement of CCK in the regulation of sperm protein tyrosine phosphorylation by the modulation of HCO3 - uptake (in mice and humans) suggests a role for CCK during sperm capacitation. Therefore, on the one hand, the expression of CCK receptors (CCK1R and CCK2R) on boar testes has been investigated and probed; on the other hand, boar spermatozoa (from seminal doses of 1-day and 5-day storage) were exposed to different concentrations of CCK (0-control, 25 or 50 μM) in a medium supporting capacitation supplemented with 0, 5 or 25 mmol/L of HCO3 - for 1 h at 38.5°C. Sperm motion (total and progressive motility), kinetic parameters, viability, acrosome status, and mitochondrial activity were determined. No differences between groups (0, 25 or 50 μM of CCK) were observed when HCO3 - was absent in the media (p > .05). However, the results showed that when the media was supplemented with 5 mmol/L HCO3 - in 1-day seminal dose storage, the linearity index (LIN, %), straightness index (STR, %) and oscillation index (WOB, %) (sperm kinetics parameters) increased in the presence of CCK regardless the concentration (p < .05). Nevertheless, CCK in sperm from 5-day storage only increased the WOB parameter in comparison to the control (p < .05). Furthermore, the average amplitude of the lateral displacement of the sperm head (ALH, μm) and curvilinear velocity (VCL, μm/s) decreased when CCK was present, depending on its concentration and sperm aging (1-day vs. 5-days) (p < .05). In the case of the media supporting capacitation supplemented with 25 mmol/L HCO3 - , any differences were observed except for sperm viability in the 5-day seminal doses, which increased in the 50 μM-CCK group compared to the control (p < .05). In conclusion, these data suggest an implication of CCK protein during sperm capacitation under low bicarbonate concentration increasing the sperm linear trajectory.

#3827 BICARBONATE PROFILING IN HEMODIALYSIS: MATHEMATICAL MODELING OF DATA FROM A CLINICAL TRIAL

Abstract Background and Aims During hemodialysis (HD), bicarbonate and other bases are added to the dialysis fluid to correct chronic acidosis that may develop in kidney-impaired patients, increasing plasma bicarbonate concentration to physiological levels. Previous studies have shown that both exceedingly high and low post-dialysis bicarbonate concentrations are associated with adverse clinical outcomes; however, no clear guidelines for the prescription of bicarbonate concentration in the dialysis fluid are available. Data from a recent controlled clinical trial, carried out at the Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw (Poland), were used to identify transport parameters of a mathematical model of acid-base homeostasis in HD patients, as the first step in the implementation of a tool to optimize bicarbonate profiling during HD. Method The study was carried out in 20 chronic patients, undergoing thrice weekly 4-hr HD. The patients underwent three treatment regimens: A) constant dialysis fluid bicarbonate concentration (HCO3,D) equal to 35 mEq/L; B) HCO3,D decreasing from 35 to 30 mEq/L after 2 hrs; C) HCO3,D increasing from 30 to 35 mEq/L after 2 hrs. The patients were divided in two cohorts: for the first (n = 11) treatment schedule was: treatment A during the first and third week, B during the second week and C during the fourth week. For the second cohort (n = 9) treatment C was carried out during the second week and treatment B during the fourth. Data were collected only during the second and third sessions of the week, and acid-base composition was determined using a blood gas analyzer. The mathematical model describes the transport of bicarbonate and dissolved CO2 from dialysis fluid to the patient and can predict changes in the acid-base equilibrium of arterial and venous plasma and erythrocytes, interstitial fluid, and tissue cells, using mass transport equations. The dialysances for bicarbonate (KHCO3) and dissolved CO2 (KCO2) were estimated via least square minimization. Results No significant difference was found comparing patients in the two cohorts, or comparing sessions of the same week. Pre-dialysis plasma bicarbonate, pH, or CO2 partial pressure (PCO2) were significantly lower for treatment B compared to treatment A. Average plasma bicarbonate concentrations for the different treatments are shown in Figure 1 for data and model simulations. Table 1 reports the average values of the estimated parameters for week. No statistically significant difference was found between sessions, cohorts, or treatments. The model fitted bicarbonate data with an average error of 2.5 ± 1.4%, and PCO2 with an error of 4.5 ± 3.6%. Simulations of mixed-venous blood, interstitial fluid, and tissue cells concentrations showed a similar response to different treatments as in arterial blood. Conclusion The model accurately describes plasma bicarbonate data with high accuracy regardless of the treatment conditions. The parameters estimated showed considerable variability between treatments (less so between the sessions of the same week), but without statistical significance. The model can be used to simulate the effect of dialysate bicarbonate profiling on acid-base equilibrium in HD patients.

The epidemiology of ketosis and low bicarbonate concentration in inpatients treated with sodium-glucose linked cotransporter inhibitors or dipeptidyl peptidase-4 inhibitors

AimsTo compare the level of ketones and bicarbonate in inpatients treated with sodium-glucose linked cotransporter 2 inhibitors (SGLT2i) and those treated with dipeptidyl peptidase-4 inhibitors (DPP4i). MethodsWe conducted an electronic medical records-based cohort study. We identified patients with type 2 diabetes, with ketone measurements available, who received SGLT2i (n = 82) or DPP4i (n = 308) during admission. We compared ketone levels between those who received SGLT2i or DPP4i using mixed ordinal logistic regression. The primary outcome was level of ketosis (<0.6, 0.6–1.5, 1.6–3.0, >3 mmol/L). Secondary outcomes included bicarbonate levels, hospital complications, ICU admission, and death. ResultsSGLT2i use was not associated with greater ketosis than DPP4i use, after adjusting for age, weight, Charlson Comorbidity Index, HbA1c, estimated glomerular filtration rate, principal diagnosis category, admission type and insulin administration (OR 4.52 95 % CI (0.33, 61.82)). After adjustment, there was no difference in complications (p = 0.14), ICU admissions (p = 0.64), mortality (p = 0.30), or bicarbonate levels (p = 0.97). ConclusionKetone levels were not greater in patients who received SGLT2i than those who received DPP4i. There were no differences in bicarbonate levels, complications, ICU admissions, or mortality, implying that, in inpatients, SGLT2i use is neither associated with ketosis nor adverse clinical outcomes.

Low Serum Bicarbonate in a Patient With Diabetes Mellitus:: A Quiz

Low Serum Bicarbonate in a Patient With Diabetes Mellitus:: A Quiz

Association of lactate to albumin ratio and bicarbonate with short-term mortality risk in patients with acute myocardial infarction

BackgroundPrevious studies have indicated that the ratio of lactate/albumin (L/A) has predictive value for the prognosis of critically ill patients with heart failure. Some studies have also indicated that a low serum bicarbonate concentration is inversely related to the mortality risk of patients with cardiogenic shock. However, the value of bicarbonate and the L/A ratio for predicting the mortality risk of patients with acute myocardial infarction (AMI) is still unclear. We therefore conducted a retrospective study to research this problem.MethodsThe subjects of this study were patients with AMI, and the data source was the Medical Information Mart for Intensive Care III database. The primary endpoint was 30-day all-cause mortality after admission. The Receiver operating characteristic (ROC) curve was used to compare the predictive value of L/A ratio, lactate and albumin for end-point events. The effects of different L/A ratio levels and different bicarbonate concentrations on 7-day and 30-day all-cause mortality were compared using Kaplan–Meier (K-M) curves. Hazard ratios for different L/A ratio and different bicarbonate concentrations were investigated using COX proportional hazards models.ResultsThe Area Under Curve (AUC) of L/A ratio, lactate, and albumin were 0.736, 0.718, and 0.620, respectively. (1) L/A ratio: The patients were divided into three groups according to their L/A ratio: tertile T1 (L/A ratio ≤ 0.47), tertile T2 (L/A ratio ≤ 0.97), and tertile T3 (L/A ratio > 0.97). The T2 and T3 groups had higher 30-day all-cause mortality risks than the T1 group. The restricted cubic spline (RCS) model indicated that there was a nonlinear relationship between L/A ratio and 30-day mortality (P < 0.05). (2) Bicarbonate concentration: The patients were also divided into three groups based on their bicarbonate concentration: G1 (22–27 mmol/L), G2 (< 22 mmol/L), and G3 (> 27 mmol/L). The G2 and G3 groups had higher 30-day all-cause mortality risks than the G1 group. The RCS model indicated that there was a nonlinear relationship between bicarbonate concentration and 30-day mortality (P < 0.05). The RCS model indicated that there was a nonlinear relationship between hemoglobin level and 30-day all-cause mortality (P < 0.05).ConclusionL/A ratio and bicarbonate concentration and hemoglobin level have predictive value for predicting 30-day mortality in patients with acute myocardial infarction.

Impact of Bicarbonate Interference on Routine Ion-Selective Electrode Chloride Measurements.

BackgroundChloride measurement is crucial for calculating the anion gap. Bicarbonate can interfere with chloride measurements; however, there is no information on the specific types of electrodes affected or the changes in bicarbonate non-selectivity over time. We evaluated the interference of bicarbonate on chloride measurements using different electrodes and the stability of this interference over time.MethodsThe effect of bicarbonate on chloride measured with electrodes of various manufacturers was assessed. When non-selectivity toward bicarbonate was observed, the stability of this interference during the electrode’s lifetime was explored. The impact of the bicarbonate concentration on the calibrator was also evaluated.ResultsNon-selectivity was observed for electrodes using quaternary ammonium salts (Beckman Coulter, Siemens, and Roche), with overestimated or underestimated chloride values observed at high or low bicarbonate concentrations, respectively. The degree of selectivity varied among electrodes. With the Roche electrode, interference became more pronounced over time, whereas the Siemens electrode appeared to gain selectivity during its lifetime. For the Roche system, adjusting the calibrator’s bicarbonate concentration from 30 mmol/L to 20–24 mmol/L reduced the number of samples with unacceptable bias (>3%) from 77.3% to 12.6%. Lot-to-lot variations in the calibrator bicarbonate concentration increased the uncertainty of chloride measurements.ConclusionsThe extent of bicarbonate-induced error varied according to the type, manufacturer, and wear of the electrode; the bicarbonate concentration in the calibrators and the tested sample; and the chloride content. Laboratories should be aware of the impact of bicarbonate on routine chloride measurements to establish appropriate QC procedures.

Bicarbonate concentration as a predictor of prognosis in moderately severe COVID-19 patients: A multicenter retrospective study.

Coronavirus disease 2019 (COVID-19) patients reportedly have high bicarbonate concentration. However, its relationship to the disease progression are obscure. In this two-center retrospective study, we included COVID-19 patients with moderate severity between March 2020 and May 2021. We classified patients into three groups according to bicarbonate concentrations: high (>27 mEq/L), normal (21 to 27 mEq/L), and low (<21 mEq/L). The primary outcome was the time to clinical worsening defined by the requirement of intubation or death during 90 days. We evaluated high or low bicarbonate concentration during the clinical course related to the primary outcome using multivariable Cox proportional hazard models. Of the 60 participants (median age 72 years), 60% were men. Participants were classified into high (13 patients), normal (30 patients), and low (17 patients) groups. Clinical worsening occurred in 54% of patients in the high group, 23% in the normal group, and 65% in the low group. Both high and low groups were associated with a higher clinical worsening rate: HR, 3.02 (95% CI, 1.05 to 8.63) in the high group; 3.49 (95% CI: 1.33 to 9.12) in the low group. Monitoring of bicarbonate concentrations may be useful to predict the prognosis.

Sodium Bicarbonate and Acetic Acid: An Effective Anaesthetic for Three Spotted Tilapia, Oreochromis andersonii Fingerlings

Abstract This study aimed to study the effectiveness of different concentrations of sodium bicarbonate (baking soda) combined with acetic acid (vinegar) in three spotted tilapia (Oreochromis andersonii) fingerlings. Fingerlings (body weight 0.82 ± 0.00 g, and body length of 3.91 ± 0.03 cm) were subjected to three concentrations of sodium bicarbonate (30 g/L, 40 g/L and 60 g/L) combined with three concentrations of acetic acid (30 ml/L, 45 ml/L and 60 ml/L), each replicated five times to assess the anaesthesia induction and recovery time. Sodium bicarbonate and acetic acid induced anaesthesia in three spotted tilapia fingerlings regardless of the concentration used. However, high concentrations induced anaesthesia within a short period of time. Meanwhile, the full recovery time increased with concentration combinations. In essence, low concentrations of sodium bicarbonate and acetic could be recommended for anaesthetizing three spotted tilapia fingerlings. However, more studies on sodium bicarbonate and acetic acids as anaesthetics in aquaculture and fisheries is deemed necessary.

Synergistic effects of ozone/peroxymonosulfate for isothiazolinone biocides degradation: Kinetics, synergistic performance and influencing factors

Synergistic effects of ozone (O3) and peroxymonosulfate (PMS, HSO5−) for isothiazolinone biocides degradation was studied. The synergistic ozonation process (O3/PMS) increased the efficiency of methyl-isothiazolinone (MIT) and chloro-methyl-isothiazolinone (CMIT) degradation to 91.0% and 81.8%, respectively, within 90 s at pH 7.0. This is 30.6% and 62.5% higher than the corresponding ozonation efficiency, respectively. Total radical formation value (Rct,R) for the O3/PMS process was 24.6 times that of ozonation alone. Calculated second-order rate constants for the reactions between isothiazolinone biocides and ▪ (kSO4-,MIT and kSO4-,CMIT) were 8.15 × 109 and 4.49 × 109 M−1 s−1, respectively. Relative contributions of O3, hydroxyl radical (OH) and ▪ oxidation to MIT and CMIT removal were estimated, which were 15%, 45%, and 40% for O3, OH and ▪ oxidation to MIT, and 1%, 67%, and 32% for O3, OH and ▪ oxidation to CMIT at pH 7.0, respectively. Factors influencing the O3/PMS process, namely the solution pH, chloride ions (Cl−), and bicarbonate (HCO3−), were evaluated. Increasing the solution pH markedly accelerated O3 decay and OH and ▪ formation, thus weakening the relative contribution of O3 oxidation while enhancing that of OH and ▪. Cl− had a negligible effect on MIT and CMIT degradation. Under the dual effect of bicarbonate (HCO3−) as inhibitor and promoter, low concentrations (1–2 mM) of bicarbonate weakly promoted MIT and CMIT degradation, while high concentrations (10–20 mM) induced strong inhibition. Lastly, oxidation performance of O3 and O3/PMS processes for MIT and CMIT degradation in different water matrices was compared.

Changes in electrolyte concentrations and hydration status in endurance horses following transport and an overnight stay prior to competition.

To evaluate changes in electrolyte concentrations and hydration status that take place in endurance horses prior to the start of a competition and determine whether these changes would be associated with elimination. 19 horses entered in the 2016 Tevis Cup 100-Miles (160 km) One-Day Western States Trail Ride. Heparinized blood samples were collected at 5 time points: prior to transport to the ride (T0), during check-in the day before the ride (T1), 1 to 2 hours before the start of the ride (T2), at the 15-km mark (T3), and at the 55-km mark (T4). Packed cell volume and plasma sodium, potassium, chloride, urea nitrogen, glucose, bicarbonate, and total protein concentrations were determined and compared across time points and between finishers and nonfinishers. Signif icant differences were detected among plasma sodium, potassium, and urea nitrogen concentrations measured prior to the start of the ride (ie, T0, T1, and T2). For all variables except chloride and bicarbonate concentrations, significant differences were detected between values obtained prior to the start of the ride and values obtained during the ride (ie, T3 and T4). Only bicarbonate concentration at the 15-km mark of the ride was significantly associated with finishing status. Results suggested that significant changes in plasma sodium, potassium, and urea nitrogen concentrations can occur in endurance horses during transport to a competition and when horses are stabled overnight before an event. Additionally, a lower bicarbonate concentration following a steep climb early during the ride was associated with subsequent elimination.

Treatment of cystic fibrosis airway cells with CFTR modulators reverses aberrant mucus properties via hydration.

Cystic fibrosis (CF) is characterised by the accumulation of viscous adherent mucus in the lungs. While several hypotheses invoke a direct relationship with cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction (i.e. acidic airway surface liquid (ASL) pH, low bicarbonate (HCO3 -) concentration, airway dehydration), the dominant biochemical alteration of CF mucus remains unknown. We characterised a novel cell line (CFTR-KO Calu3 cells) and the responses of human bronchial epithelial (HBE) cells from subjects with G551D or F508del mutations to ivacaftor and elexacaftor-tezacaftor-ivacaftor. A spectrum of assays such as short-circuit currents, quantitative PCR, ASL pH, Western blotting, light scattering/refractometry (size-exclusion chromatography with inline multi-angle light scattering), scanning electron microscopy, percentage solids and particle tracking were performed to determine the impact of CFTR function on mucus properties. Loss of CFTR function in Calu3 cells resulted in ASL pH acidification and mucus hyperconcentration (dehydration). Modulation of CFTR in CF HBE cells did not affect ASL pH or mucin mRNA expression, but decreased mucus concentration, relaxed mucus network ultrastructure and improved mucus transport. In contrast with modulator-treated cells, a large fraction of airway mucins remained attached to naïve CF cells following short apical washes, as revealed by the use of reducing agents to remove residual mucus from the cell surfaces. Extended hydration, but not buffers alkalised with sodium hydroxide or HCO3 -, normalised mucus recovery to modulator-treated cell levels. These results indicate that airway dehydration, not acidic pH and/or low [HCO3 -], is responsible for abnormal mucus properties in CF airways and CFTR modulation predominantly restores normal mucin entanglement.

Relationship Between Serum Total Carbon Dioxide Concentration and Bicarbonate Concentration in Patients Undergoing Peritoneal Dialysis.

BackgroundFew studies have assessed the relationship between serum total carbon dioxide (CO2) and bicarbonate ion (HCO3−) concentration in patients undergoing peritoneal dialysis. We determined the agreement between serum total CO2 and HCO3− concentration and the diagnostic accuracy of serum total CO2 for the prediction of low (HCO3− <24 mEq/L) and high (HCO3− ≥24 mEq/L) bicarbonate concentrations in patients on peritoneal dialysis.MethodsWe collected 245 samples of venous blood from 51 patients on peritoneal dialysis. Independent factors that correlated with the HCO3− concentration were analyzed using multiple linear regression analysis. The diagnostic accuracy of serum total CO2 was evaluated by receiver operating characteristic (ROC) curve analysis and a 2×2 table. Agreement between serum total CO2 and HCO3− concentration was assessed by Bland-Altman analysis.ResultsSerum total CO2 was independently correlated with HCO3− concentration (β = 0.354, p < 0.001). The area under the curve of serum total CO2 for the identification of low and high bicarbonate concentrations was 0.909. The diagnostic accuracy of serum total CO2 for the prediction of low and high bicarbonate concentrations was: sensitivity, 91.5%; specificity, 74.7%; positive predictive value, 53.5%; negative predictive value, 96.5%; and accuracy, 78.8%. Bland-Altman analysis showed a moderate agreement between serum total CO2 and HCO3− concentration.ConclusionSerum total CO2 correlated closely with the HCO3− concentration in patients undergoing peritoneal dialysis. Serum total CO2 might be useful for predicting low and high bicarbonate in peritoneal dialysis patients.

Modeling acid-base balance during continuous kidney replacement therapy.

Clinical studies have suggested that use of bicarbonate-containing substitution and dialysis fluids during continuous kidney replacement therapy may result in excessive increases in the carbon dioxide concentration of blood; however, the technical parameters governing such changes are unclear. The current work used a mathematical model of acid-base chemistry of blood to predict its composition within and exiting the extracorporeal circuit during continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodiafiltration (CVVHDF). Model predictions showed that a total substitution fluid infusion rate of 2 L/h (33% predilution) with a bicarbonate concentration of 32mEq/L during CVVH at a blood flow rate of 200mL/min resulted in only modest increases in plasma bicarbonate concentration by 2.0mEq/L and partial pressure of dissolved carbon dioxide by 4.4mmHg in blood exiting the extracorporeal circuit. The relative increase in bicarbonate concentration (9.7%) was similar to that in partial pressure of dissolved carbon dioxide (8.2%), resulting in no significant change in plasma pH in the blood exiting the CVVH circuit. The changes in plasma acid-base levels were larger with a higher infusion rate of substitution fluid but smaller with a higher blood flow rate or use of substitution fluid with a lower bicarbonate concentration (22mEq/L). Under comparable flow conditions and substitution fluid composition, model predicted changes in acid-base levels during CVVHDF were similar, but smaller, than those during CVVH. The described mathematical model can predict the effect of operating conditions on acid-base balance within and exiting the extracorporeal circuit during continuous kidney replacement therapy.

Clinicopathological abnormalities associated with increased animal triage trauma score in cats presenting for vehicular trauma: 75 cases (1998-2009).

To document the clinical and clinicopathological changes in cats presenting with vehicular trauma (VT) and to determine whether the calculated animal trauma triage (ATT) score was associated with any clinicopathological abnormalities. Retrospective descriptive study conducted between 1998 and 2009. University veterinary teaching hospital. Seventy-five client-owned cats that presented for VT to an urban veterinary hospital. None. Pertinent history, physical examination findings, results of biochemical testing, and outcome were extracted from medical records. ATT score was calculated based on physical examination. Patients were classified as having either a low (<5) ATT (n=30) or a high (≥5) ATT (n=45) score. Male cats were overrepresented (60.0%), and a majority of cats had outdoor access (65.3%). Low PCV (P= 0.024), low total plasma protein concentration (P= 0.032), low venous blood pH (P= 0.047), high plasma lactate concentration (P= 0.047), low plasma bicarbonate concentration (P= 0.047), low base excess (P= 0.047), and high plasma glucose concentration (P= 0.047) were associated with higher ATT scores. In addition, low noninvasive blood pressure measurements (P= 0.008) were associated with higher ATT scores. There was a significant association between lower PCV, lower total plasma protein concentration, lower venous blood pH, higher plasma lactate concentration, lower plasma bicarbonate concentration, lower base excess, higher whole blood glucose concentration, and lower noninvasive blood pressure and higher ATT scores at presentation in feline patients suffering from VT. Prospective evaluation of these values may prove useful in furthering understanding of the pathophysiology of trauma in cats.

Relationship between serum total carbon dioxide concentration and bicarbonate concentration in patients undergoing hemodialysis

BackgroundFew studies have investigated the relationship between serum total carbon dioxide (CO2) concentration and bicarbonate ion (HCO3-) concentration in patients undergoing hemodialysis. We determined the agreement and discrepancy between serum total CO2 and HCO3- concentrations and the diagnostic accuracy of serum total CO2 for the prediction of low (HCO3- < 24 mEq/L) and high (HCO3- ≥ 24 mEq/L) bicarbonate concentrations in hemodialysis patients.MethodsOne hundred forty-nine arteriovenous blood samples from 84 hemodialysis patients were studied. Multiple linear regression analysis was used to determine factors correlated with HCO3- concentration. Diagnostic accuracy of serum total CO2 was evaluated using receiver operating characteristic curve analysis and a 2 × 2 table. Agreement between serum total CO2 and HCO3- concentrations was assessed using Bland-Altman analysis.ResultsSerum total CO2 concentration was closely correlated with HCO3- concentration (β = 0.858, P < 0.001). Area under the curve of serum total CO2 for the identification of low and high bicarbonate concentrations was 0.989. Use of serum total CO2 to predict low and high bicarbonate concentrations had a sensitivity of 100%, specificity of 50.0%, positive predictive value of 96.5%, negative predictive value of 100%, and accuracy of 96.6%. Bland-Altman analysis showed moderate agreement between serum total CO2 and HCO3- concentrations. Discrepancies between HCO3- and serum total CO2 concentrations (serum total CO2 - HCO3- ≤ -1) were observed in 89 samples.ConclusionSerum total CO2 concentration is closely correlated with HCO3- concentration in hemodialysis patients. However, there is a non-negligible discrepancy between serum total CO2 and HCO3- concentrations.

Hemodialysis using a low bicarbonate dialysis bath: Implications for acid-base homeostasis.

The low bath bicarbonate concentration ([ ]) used by a nephrology group in Japan (25.5mEq/L), coupled with a bath [acetate] of 8mEq/L, provided an opportunity to study the acid-base events occurring during hemodialysis when flux is from the patient to the bath. We used an analytic tool that allows calculation of delivery during hemodialysis and the physiological response to it in 17 Japanese outpatients with an average pre-dialysis blood [ ] of 25mEq/L. Our analysis demonstrates that addition is markedly reduced and that all of it comes from acetate metabolism. The added to the extracellular fluid during treatment (19.5mEq) was completely consumed by H+ mobilization from body buffers. In contrast to patients dialyzing with higher bath [ ] values in the US and Europe, organic acid production was suppressed rather than stimulated. Dietary analysis indicates that these patients are in acid balance due to the alkaline nature of their diet. In a larger group of patients using the same bath solution, pre-dialysis blood [ ] was lower, 22.2mEq/L, but still in an acceptable range. Our studies indicate that a low bath [ ] is well tolerated and can prevent stimulation of organic acid production.