Alkalosis-induced hypoventilation in cystic fibrosis: The importance of efficient renal adaptation.

The lungs and kidneys are pivotal organs in the regulation of body acid-base homeostasis. In cystic fibrosis (CF), the impaired renal ability to excrete an excess amount of HCO3- into the urine leads to metabolic alkalosis [P. Berg et al., J. Am. Soc. Nephrol. 31, 1711-1727 (2020); F. Al-Ghimlas, M. E. Faughnan, E. Tullis, Open Respir. Med. J. 6, 59-62 (2012)]. This is caused by defective HCO3- secretion in the ß-intercalated cells of the collecting duct that requires both the cystic fibrosis transmembrane conductance regulator (CFTR) and pendrin for normal function [P. Berg et al., J. Am. Soc. Nephrol. 31, 1711-1727 (2020)]. We studied the ventilatory consequences of acute oral base loading in normal, pendrin knockout (KO), and CFTR KO mice. In wild-type mice, oral base loading induced a dose-dependent metabolic alkalosis, fast urinary removal of base, and a moderate base load did not perturb ventilation. In contrast, CFTR and pendrin KO mice, which are unable to rapidly excrete excess base into the urine, developed a marked and transient depression of ventilation when subjected to the same base load. Therefore, swift renal base elimination in response to an acute oral base load is a necessary physiological function to avoid ventilatory depression. The transient urinary alkalization in the postprandial state is suggested to have evolved for proactive avoidance of hypoventilation. In CF, metabolic alkalosis may contribute to the commonly reduced lung function via a suppression of ventilatory drive.

Acid-base transporters and pH dynamics in human breast carcinomas predict proliferative activity, metastasis, and survival.

Breast cancer heterogeneity in histology and molecular subtype influences metabolic and proliferative activity and hence the acid load on cancer cells. We hypothesized that acid-base transporters and intracellular pH (pHi) dynamics contribute inter-individual variability in breast cancer aggressiveness and prognosis. We show that Na+,HCO3- cotransport and Na+/H+ exchange dominate cellular net acid extrusion in human breast carcinomas. Na+/H+ exchange elevates pHi preferentially in estrogen receptor-negative breast carcinomas, whereas Na+,HCO3- cotransport raises pHi more in invasive lobular than ductal breast carcinomas and in higher malignancy grade breast cancer. HER2-positive breast carcinomas have elevated protein expression of Na+/H+ exchanger NHE1/SLC9A1 and Na+,HCO3- cotransporter NBCn1/SLC4A7. Increased dependency on Na+,HCO3- cotransport associates with severe breast cancer: enlarged CO2/HCO3--dependent rises in pHi predict accelerated cell proliferation, whereas enhanced CO2/HCO3--dependent net acid extrusion, elevated NBCn1 protein expression, and reduced NHE1 protein expression predict lymph node metastasis. Accordingly, we observe reduced survival for patients suffering from luminal A or basal-like/triple-negative breast cancer with high SLC4A7 and/or low SLC9A1 mRNA expression. We conclude that the molecular mechanisms of acid-base regulation depend on clinicopathological characteristics of breast cancer patients. NBCn1 expression and dependency on Na+,HCO3- cotransport for pHi regulation, measured in biopsies of human primary breast carcinomas, independently predict proliferative activity, lymph node metastasis, and patient survival.

Automatic real-time analysis and interpretation of arterial blood gas sample for Point-of-care testing: Clinical validation.

BACKGROUND: Point-of-care arterial blood gas (ABG) is a blood measurement test and a useful diagnostic tool that assists with treatment and therefore improves clinical outcomes. However, numerically reported test results make rapid interpretation difficult or open to interpretation. The arterial blood gas algorithm (ABG-a) is a new digital diagnostics solution that can provide clinicians with real-time interpretation of preliminary data on safety features, oxygenation, acid-base disturbances and renal profile. The main aim of this study was to clinically validate the algorithm against senior experienced clinicians, for acid-base interpretation, in a clinical context. METHODS: We conducted a prospective international multicentre observational cross-sectional study. 346 sample sets and 64 inpatients eligible for ABG met strict sampling criteria. Agreement was evaluated using Cohen's kappa index, diagnostic accuracy was evaluated with sensitivity, specificity, efficiency or global accuracy and positive predictive values (PPV) and negative predictive values (NPV) for the prevalence in the study population. RESULTS: The concordance rates between the interpretations of the clinicians and the ABG-a for acid-base disorders were an observed global agreement of 84,3% with a Cohen's kappa coefficient 0.81; 95% CI 0.77 to 0.86; p < 0.001. For detecting accuracy normal acid-base status the algorithm has a sensitivity of 90.0% (95% CI 79.9 to 95.3), a specificity 97.2% (95% CI 94.5 to 98.6) and a global accuracy of 95.9% (95% CI 93.3 to 97.6). For the four simple acid-base disorders, respiratory alkalosis: sensitivity of 91.2 (77.0 to 97.0), a specificity 100.0 (98.8 to 100.0) and global accuracy of 99.1 (97.5 to 99.7); respiratory acidosis: sensitivity of 61.1 (38.6 to 79.7), a specificity of 100.0 (98.8 to 100.0) and global accuracy of 98.0 (95.9 to 99.0); metabolic acidosis: sensitivity of 75.8 (59.0 to 87.2), a specificity of 99.7 (98.2 to 99.9) and a global accuracy of 97.4 (95.1 to 98.6); metabolic alkalosis sensitivity of 72.2 (56.0 to 84.2), a specificity of 95.5 (92.5 to 97.3) and a global accuracy of 93.0 (88.8 to 95.3); the four complex acid-base disorders, respiratory and metabolic alkalosis, respiratory and metabolic acidosis, respiratory alkalosis and metabolic acidosis, respiratory acidosis and metabolic alkalosis, the sensitivity, specificity and global accuracy was also high. For normal acid-base status the algorithm has PPV 87.1 (95% CI 76.6 to 93.3) %, and NPV 97.9 (95% CI 95.4 to 99.0) for a prevalence of 17.4 (95% CI 13.8 to 21.8). For the four-simple acid-base disorders and the four complex acid-base disorders the PPV and NPV were also statistically significant. CONCLUSIONS: The ABG-a showed very high agreement and diagnostic accuracy with experienced senior clinicians in the acid-base disorders in a clinical context. The method also provides refinement and deep complex analysis at the point-of-care that a clinician could have at the bedside on a day-to-day basis. The ABG-a method could also have the potential to reduce human errors by checking for imminent life-threatening situations, analysing the internal consistency of the results, the oxygenation and renal status of the patient.

Prognostic role of perioperative acid-base disturbances on the risk of Clostridioides difficile infection in patients undergoing cardiac surgery.

BACKGROUND: It is unclear whether acid-base balance disturbances during the perioperative period may impact Clostridium difficile infection (CDI), which is the third most common major infection following cardiac surgery. We hypothesized that perioperative acid-base abnormalities including lactate disturbances may predict the probability of incidence of CDI in patients after cardiac procedures. METHODS: Of the 12,235 analyzed patients following cardiac surgery, 143 (1.2%) developed CDI. The control group included 200 consecutive patients without diarrhea, who underwent cardiac procedure within the same period of observation. Pre-, intra and post-operative levels of blood gases, as well as lactate and glucose concentrations were determined. Postoperatively, arterial blood was drawn four times: immediately after surgery and successively; 4, 8 and 12 h following the procedure. RESULTS: Baseline pH was lower and PaO2 was higher in CDI patients (p < 0.001 and p = 0.001, respectively). Additionally, these patients had greater base deficiency at each of the analyzed time points (p < 0.001, p = 0.004, p = 0.012, p = 0.001, p = 0.016 and p = 0.001, respectively). Severe hyperlactatemia was also more common in CDI patients; during the cardiac procedure, 4 h and 12 h after surgery (p = 0.027, p = 0.004 and p = 0.001, respectively). Multivariate logistic regression analysis revealed that independent risk factors for CDI following cardiac surgery were as follows: intraoperative severe hyperlactatemia (OR 2.387, 95% CI 1.155-4.933, p = 0.019), decreased lactate clearance between values immediately and 12 h after procedure (OR 0.996, 95% CI 0.994-0.999, p = 0.013), increased age (OR 1.045, 95% CI 1.020-1.070, p < 0.001), emergent surgery (OR 2.755, 95% CI 1.565-4.848, p < 0.001) and use of antibiotics other than periprocedural prophylaxis (OR 2.778, 95% CI 1.690-4.565, p < 0.001). CONCLUSION: This study is the first to show that perioperative hyperlactatemia and decreased lactate clearance may be predictors for occurrence of CDI after cardiac surgery.

The therapeutic importance of acid-base balance.

Baking soda and vinegar have been used as home remedies for generations and today we are only a mouse-click away from claims that baking soda, lemon juice, and apple cider vinegar are miracles cures for everything from cancer to COVID-19. Despite these specious claims, the therapeutic value of controlling acid-base balance is indisputable and is the basis of Food and Drug Administration-approved treatments for constipation, epilepsy, metabolic acidosis, and peptic ulcers. In this narrative review, we present evidence in support of the current and potential therapeutic value of countering local and systemic acid-base imbalances, several of which do in fact involve the administration of baking soda (sodium bicarbonate). Furthermore, we discuss the side effects of pharmaceuticals on acid-base balance as well as the influence of acid-base status on the pharmacokinetic properties of drugs. Our review considers all major organ systems as well as information relevant to several clinical specialties such as anesthesiology, infectious disease, oncology, dentistry, and surgery.

Mechanisms of acid-base regulation following respiratory alkalosis in red drum (Sciaenops ocellatus).

Respiratory acidosis and subsequent metabolic compensation are well-studied processes in fish exposed to elevated CO2 (hypercapnia). Yet, such exposures in the marine environment are invariably accompanied by a return of environmental CO2 to atmospheric baselines. This understudied phenomenon has the potential to cause a respiratory alkalosis that would necessitate base excretion. Here we sought to explore this question and the associated physiological mechanisms that may accompany base excretions using the red drum (Sciaenops ocellatus). As expected, when high pCO2 (15,000 µatm CO2) acclimated red drum were transferred to normal pCO2, their net H+ excretion shifted from positive (0.157 ± 0.044 µmol g-1 h-1) to negative (-0.606 ± 0.116 µmol g-1 h-1) in the 2 h post-transfer period. Net H+ excretion returned to control rates during the 3 to 24 h flux period. Gene expression and enzyme activity assays demonstrated that while the acidosis resulted in significant changes in several relevant transporters, no significant changes accompanied the alkalosis phase. Confocal microscopy was used to assess alkalosis-stimulated translocation of V-type H+ ATPase to the basolateral membrane previously seen in other marine species; however, no apparent translocation was observed. Overall, these data demonstrate that fluctuations in environmental CO2 result in both acidic and alkalotic respiratory disturbances; however, red drum maintain sufficient regulatory capacity to accommodate base excretion. Furthermore, this work does not support a role for basolateral VHA translocation in metabolic compensation from a systemic alkalosis in teleosts.

Determination of reference intervals for equine arterial blood-gas, acid-base and electrolyte analysis.

OBJECTIVE: To establish reference intervals for arterial blood-gas (ABG), acid-base and electrolyte values from a healthy equine population. STUDY DESIGN: Retrospective clinical study. ANIMALS: A total of 139 client-owned, systemically healthy horses, 1 year of age and older, presented for elective surgical procedures. METHODS: Blood samples were collected anaerobically from the transverse facial or common carotid artery of horses breathing room air, prior to administration of preanaesthetic medication. Samples were analysed immediately, without correction for body temperature, using an automated bench-top analyser. Variables analysed included pH, arterial partial pressure of carbon dioxide (PaCO2) and arterial partial pressure of oxygen (PaO2) and plasma concentrations of sodium (Na+), potassium (K+), calcium (Ca2+) and chloride (Cl-). Actual and standardized plasma bicarbonate concentration [HCO3- (P) and HCO3- (P, st)], blood and extracellular fluid base excess [base (B) and base (ECF)] and anion gap (AG) were calculated by the machine from preprogrammed algorithms. Methods used for determination of PaCO2, PaO2, HCO3- (P), HCO3- (P, st), base (B) and base (ECF) met the guidelines of the Clinical and Laboratory Standards Institute. Reference intervals were determined with the nonparametric or the standard parametric method dependent on data distribution. RESULTS: Reference intervals were determined for pH, 7.37-7.49; PaCO2, 4.84-7.20 kPa (36.3-54.0 mmHg); PaO2, 11.01-14.97 kPa (82.6-112.3 mmHg); Na+, 133-141 mmol L-1; K+, 3.05-4.65 mmol L-1; Ca2+, 1.34-1.72 mmol L-1; Cl-, 100-110 mmol L-1; HCO3- (P), 23.55-33.90 mmol L-1; HCO3- (P, st), 23.87-32.45 mmol L-1; base (B), 0.51-8.80 mmol L-1; base (ECF), -0.53 to 9.39 mmol L-1 and AG, 1.5-11.5 mEq L-1. CONCLUSIONS AND CLINICAL RELEVANCE: These data were derived from the largest group of horses reported in a single study and may aid in interpretation of ABG, acid-base and electrolyte measurements in clinical practice.

pH regulation in hibernation: Implications for ventilatory and metabolic control.

Mammals in hibernation retain a relatively constant blood plasma pH (extracellular pH; pHe) that is typically alkaline relative to the pH of neutral water (pHnw). Given that pHnw increases as temperature falls, however, a constant pHe in hibernation represents a reduction in the relative degree of alkalinity (i.e. a relative acidosis) of plasma and extracellular fluids. The manner in which this is achieved during entrance into, and arousal from hibernation, however, is not straightforward and has implications for the control of ventilation. Furthermore, intracellular pH (pHi) changes in different ways in different tissues during hibernation. The dominant buffers involved in pH regulation are the imidazole buffer groups of histidyl residues of proteins and polypeptides. As a result, changes in the dissociation ratio of this buffer group (alpha imidazole; αim) directly affect the net electric charge of all functional proteins. The pKa of the imidazole ring on histidine is close to pHnw at 37 °C and increases with decreasing temperature with an almost identical slope to that seen for pHnw. As a result, it has been suggested that the metabolic activity of tissues in which changes in pHi parallel changes in pHnw should be sustained while tissues in which changes in pHi parallel changes in pHe become relatively acidic and that this may contribute to metabolic suppression during hibernation. In this review we explore these implications.

Molecular Pathophysiology of Acid-Base Disorders.

Acid-base balance is critical for normal life. Acute and chronic disturbances impact cellular energy metabolism, endocrine signaling, ion channel activity, neuronal activity, and cardiovascular functions such as cardiac contractility and vascular blood flow. Maintenance and adaptation of acid-base homeostasis are mostly controlled by respiration and kidney. The kidney contributes to acid-base balance by reabsorbing filtered bicarbonate, regenerating bicarbonate through ammoniagenesis and generation of protons, and by excreting acid. This review focuses on acid-base disorders caused by renal processes, both inherited and acquired. Distinct rare inherited monogenic diseases affecting acid-base handling in the proximal tubule and collecting duct have been identified. In the proximal tubule, mutations of solute carrier 4A4 (SLC4A4) (electrogenic Na+/HCO3--cotransporter Na+/bicarbonate cotransporter e1 [NBCe1]) and other genes such as CLCN5 (Cl-/H+-antiporter), SLC2A2 (GLUT2 glucose transporter), or EHHADH (enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase) causing more generalized proximal tubule dysfunction can cause proximal renal tubular acidosis resulting from bicarbonate wasting and reduced ammoniagenesis. Mutations in adenosine triphosphate ATP6V1 (B1 H+-ATPase subunit), ATPV0A4 (a4 H+-ATPase subunit), SLC4A1 (anion exchanger 1), and FOXI1 (forkhead transcription factor) cause distal renal tubular acidosis type I. Carbonic anhydrase II mutations affect several nephron segments and give rise to a mixed proximal and distal phenotype. Finally, mutations in genes affecting aldosterone synthesis, signaling, or downstream targets can lead to hyperkalemic variants of renal tubular acidosis (type IV). More common forms of renal acidosis are found in patients with advanced stages of chronic kidney disease and are owing, at least in part, to a reduced capacity for ammoniagenesis.

Intercalated Cells of the Kidney Collecting Duct in Kidney Physiology.

The epithelium of the kidney collecting duct (CD) is composed mainly of two different types of cells with distinct and complementary functions. CD principal cells traditionally have been considered to have a major role in Na+ and water regulation, while intercalated cells (ICs) were thought to largely modulate acid-base homeostasis. In recent years, our understanding of IC function has improved significantly owing to new research findings. Thus, we now have a new model for CD transport that integrates mechanisms of salt and water reabsorption, K+ homeostasis, and acid-base status between principal cells and ICs. There are three main types of ICs (type A, type B, and non-A, non-B), which first appear in the late distal convoluted tubule or in the connecting segment in a species-dependent manner. ICs can be detected in CD from cortex to the initial part of the inner medulla, although some transport proteins that are key components of ICs also are present in medullary CD, cells considered inner medullary. Of the three types of ICs, each has a distinct morphology and expresses different complements of membrane transport proteins that translate into very different functions in homeostasis and contributions to CD luminal pro-urine composition. This review includes recent discoveries in IC intracellular and paracrine signaling that contributes to acid-base regulation as well as Na+, Cl-, K+, and Ca2+ homeostasis. Thus, these new findings highlight the potential role of ICs as targets for potential hypertension treatments.

Association between computed tomographic thoracic injury scores and blood gas and acid-base balance in dogs with blunt thoracic trauma.

OBJECTIVE: To determine the association between thoracic injuries evaluated by computed tomography (CT) and arterial blood gas and acid-base status in dogs with blunt thoracic trauma caused by motor vehicle accidents. DESIGN: Prospective observational clinical study. SETTING: University teaching hospital. ANIMALS: Thirty-one client owned traumatized dogs and 15 healthy dogs. PROCEDURES: All trauma group dogs underwent a CT scan and simultaneous arterial blood gas analysis within 24 hours, but not before 4 hours, after the traumatic incident within a 45-month enrollment period. MEASUREMENTS AND MAIN RESULTS: Thorax injuries were classified as pulmonary, pleural space, or rib cage and each of these components was scored for severity using a CT composite pulmonary, pleural, and rib score. The trauma group arterial blood gas and acid-base status were evaluated for statistical difference from the control group. The pulmonary-arterial oxygen pressure was significantly lower in the trauma group compared to the control group that was supported by significant differences in the calculated variables of arterial blood oxygenation as well. There was also a significant correlation between the composite lung score and pleural score and the variables of arterial oxygen status. The pulmonary-arterial carbon dioxide pressure was not significantly different to any of the thoracic injury variables indicating normal alveolar ventilation. Acid-base imbalances were generally mild, insignificant, and variable. CONCLUSIONS AND CLINICAL RELEVANCE: Blunt thoracic trauma causes significant pulmonary and pleural injury and the blood oxygen economy is significantly affected by this. The functional measures of arterial blood oxygenation were well correlated with thoracic CT pathology. Alveolar ventilation was mostly spared but a clinically significant ventilation perfusion mismatch was present.

Kinetics of acid-base parameters in conventional hemodialysis

Details about the acid-base changes in hemodialysis are scarce in the literature but are potentially relevant to adequate management of patients. We addressed the acid-base kinetics during hemodialysis and throughout the interdialytic period in a cross-sectional study of adults undergoing conventional hemodialysis. Samples for blood gas analysis were obtained from the arterial limb of the arteriovenous fistula before the first session of the week (HD1), immediately at the end of HD1, and on sequential collections at 15, 30, 45, 60, and 120 min post-HD1. Additional blood samples were collected after ∼20 h following the end of the first dialysis and immediately prior to the initiation of the second dialysis of the week. Thirty adult patients were analyzed (55±15 years, 50% men, 23% diabetic; dialysis vintage 69±53 months). Mean serum bicarbonate levels increased at the end of HD1 (22.3±2.7 mEq/L vs 17.5±2.3 mEq/L, P<0.001) and remained stable until 20 h after the end of the session. The mean values of pCO2 before HD1 were below reference and at 60 and 120 min post-HD1 were significantly lower than at the start (31.3±2.7 mmHg and 30.9±3.7 mmHg vs 34.3±4.1 mmHg, P=0.041 and P=0.010, respectively). The only point of collection in which mean values of pCO2 were above 35 mmHg was 20 h post-dialysis. Serum bicarbonate levels remained stable for at least 20 h after the dialysis sessions, a finding that may have therapeutic implications. During dialysis, the respiratory response for correction of metabolic acidosis (i.e., pCO2 elevation) was impaired.

Prognostic value of lactates in relation to gas analysis and acid-base status in patients with pulmonary embolism.

AIM: To assess the prognostic value of lactate level for mortality in patients with pulmonary embolism (PE) and Pulmonary Embolism Severity Index (PESI) I-III and its independence of gas-analysis parameters and acid-base status. METHODS: This prospective observational study was conducted at the University Clinical Hospital Mostar from 2013 to 2017. On the first day after PE diagnosis, 1.5 mL of arterial blood was collected from 103 patients with PE. Partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, blood pH value, concentration of bicarbonates in arterial blood (HCO3-), base deficit, and oxygen saturation were analyzed. Lactate levels were assessed using blood samples taken from the cubital vein. Logistic regression analysis was used to assess the predictive value of gas-analysis variables, lactate level, PESI score, age, and sex for in-hospital death due to PE. RESULTS: The mortality in the group of PE patients was 19.1% (18 of 103 patients). Lactate level was an independent predictor of mortality (P=0.002, odds ratio 0.06). HCO3- was also found to be a significant predictor (P=0.022, odds ratio 2.4). Lactates were independent of other variables. Other gas-analysis parameters were not significant predictors of mortality. CONCLUSION: In PE patients at low-intermediate risk of mortality (PESI I-III), lactate level was associated with a short-term mortality, independently of other gas-analytic parameters. Oxford Centre for Evidence-based Medicine level of evidence: 2.

Recent Advances In Developing Novel Anti-Cancer Drugs Targeting Tumor Hypoxic and Acidic Microenvironments.

BACKGROUND: Solid tumors often contain hypoxic microenvironments due to abnormal vasculatures and outweighing demands of oxygen. Cancer cells rely on anaerobic respiration, leading to sequential acidic microenvironments. Hypoxic and acidic microenvironments cause genetic instability and activate signaling pathways, contributing to cancer progression and therapy resistance, and have become targets for developing novel anti-cancer agents. OBJECTIVE: This article reviews recent advances in the development of novel anti-cancer drugs targeting hypoxic and acidic microenvironments. METHODS: Recent patents and published literature related to anti-cancer agents targeting tumor hypoxic and acidic microenvironments were searched and reviewed. Key termed used in the searching included cancer, anti-cancer drug, neoplasm, clinical trials, tumor microenvironment, hypoxic microenvironment, acidic microenvironment, hypoxia-inducible factors, hypoxia; metabolism; Warburg effect and aerobic glycolysis. RESULTS: A number of Hypoxia-Inducible Factor (HIF) inhibitors have been developed or discovered, but most of them have only exhibited indirect effects on HIFs, and a limited number of drugs are able to directly interfere with mRNA and protein of HIFs, the dimerization of α and ß subunits, or the interaction between HIFs and its activators. The development of agents targeting acidic microenvironments focuses on V-ATPase, monocarboxylic acid transporters, Na+/H+ exchangers and carbonic anhydrases. Proton pump inhibitors as V-ATPase inhibitors have been applied in treating various tumors as an adjuvant therapy, but none of the other inhibitors has been approved for cancer treatment. CONCLUSION: Developing more specific agents, and seeking sensitive, applicable and accurate biomarkers may improve the efficacy of drugs targeting hypoxic and acidic microenvironments.

Impacto del componente hiperclorémico de la acidosis metabólica en el estado de hidratación y en el tratamiento de la cetoacidosis diabética / Impact of the hyperchloremic component of metabolic acidosis on the patient's hydration status and the treatment of diabetic ketoacidosis

Introducción. La cetoacidosis diabética (CAD) se caracteriza por acidosis metabólica (AM) con anión restante (AR) elevado, aunque, ocasionalmente, puede presentar hipercloremia. Se postuló que la presencia de hipercloremia inicial podría reflejar un mejor estado de hidratación; sin embargo, su prevalencia y su impacto en el tratamiento de la CAD se desconoce. Objetivos. Determinar la prevalencia de AM con componente hiperclorémico previo al inicio del tratamiento y evaluar si su presencia se asocia con mejor estado de hidratación y con menor tiempo de salida de la CAD, en comparación con los pacientes con AR elevado exclusivo. Pacientes y métodos. Se agruparon los pacientes internados con CAD (período entre enero de 2014 y junio de 2016) según presentaran, al ingresar, AM con AR elevado exclusivo o con hipercloremia y se compararon sus variables clínicas, de laboratorio y la respuesta al tratamiento. Resultados. Se incluyeron 40 pacientes -amp;#91;17 varones, mediana de edad: 14,5 años (2,4-18)-amp;#93;, 22 con AM con componente hiperclorémico (prevalencia de 55%) y 18 con AR elevado exclusivo. La presencia de hipercloremia no se asoció con mejor estado de hidratación (porcentaje de déficit de peso en ambos grupos: 4,9%; p= 0,81) ni con una respuesta terapéutica más rápida (con componente hiperclorémico: 9,5 horas; con AR elevado exclusivo: 11 horas; p= 0,64). Conclusiones. En niños con CAD, la prevalencia de AM con componente hiperclorémico fue del 55% y no se asoció con un mejor estado de hidratación ni con una salida más temprana de la descompensación metabólica.

Introduction. Diabetic ketoacidosis (DKA) is characterized by metabolic acidosis (MA) with a high anion gap (AG), although, occasionally, it can present with hyperchloremia. It has been postulated that the early presence of hyperchloremia could reflect a better hydration status; however, its prevalence and impact on DKA treatment remain unknown. Objectives. To determine the prevalence of the hyperchloremic component in MA prior to treatment and to assess whether it is associated with a better hydration status and a shorter recovery time from DKA compared to patients with high AG only. Patients and Methods. Patients hospitalized with DKA (between January 2014 and June 2016) were grouped according to whether they were admitted with MA with high AG only. or with hyperchloremia, and clinical and laboratory outcome measures and response to treatment were compared. Results. Forty patients (17 males, median age: 14.5 years -amp;#91;2.4-18-amp;#93;) were included; 22 with hyperchloremic metabolic acidosis (prevalence of 55%) and 18 with metabolic acidosis with high AG only. The presence of hyperchloremia was not associated with a better hydration status (weight loss percentage in both groups: 4.9%; p= 0.81) nor with a faster treatment response (MA with a hyperchloremic component: 9.5 hours; MA with high AG only: 11 hours; p= 0.64). Conclusions. The prevalence of MA with a hyperchloremic component among children with DKA was 55% and was not associated with a better hydration status nor with a faster recovery from the metabolic decompensation.

Acid/base alterations during major abdominal surgery: 6% hydroxyethyl starch infusion versus 5% albumin.

BACKGROUND: To compare the effects of intraoperative infusions of balanced electrolyte solution (BES)-based hydroxyethyl starch (HES) and saline-based albumin on metabolic acidosis and acid/base changes during major abdominal surgery conducted using Stewart's approach. METHODS: Forty patients, aged 20-65 years, undergoing major abdominal surgery, were randomly assigned to the HES group (n = 20; received 500 ml of BES-based 6% HES 130/0.4) or the albumin group (n = 20; received 500 ml of normal saline-based 5% albumin). Acid-base parameters were measured and calculated using results obtained from arterial blood samples taken after anesthesia induction (T1), 2 hours after surgery commencement (T2), immediately after surgery (T3), and 1 hour after arriving at a postanesthetic care unit (T4). RESULTS: Arterial pH in the HES group was significantly higher than that in the albumin group at T3 (7.40 ± 0.04 vs. 7.38 ± 0.04, P = 0.043), and pH values exhibited significant intergroup difference over time (P = 0.002). Arterial pH was significantly lower at T3 and T4 in the HES group and at T2, T3, and T4 in the albumin group than at T1. Apparent strong ion difference (SIDa) was significantly lower at T2, T3, and T4 than at T1 in both groups. Total plasma weak nonvolatile acid (ATOT) was significantly lower in the HES group than in the albumin group at T2, T3 and T4 and exhibited a significant intergroup difference over time (P < 0.001). CONCLUSIONS: BES-based 6% HES infusion was associated with lower arterial pH values at the end of surgery than saline-based 5% albumin infusion, but neither colloid caused clinically significant metabolic acidosis (defined as an arterial pH < 7.35).

Functional and molecular characterization of transmembrane intracellular pH regulators in human dental pulp stem cells.

OBJECTIVE: Homeostasis of intracellular pH (pHi) plays vital roles in many cell functions, such as proliferation, apoptosis, differentiation and metastasis. Thus far, Na+-H+ exchanger (NHE), Na+-HCO3- co-transporter (NBC), Cl-/HCO3- exchanger (AE) and Cl-/OH- exchanger (CHE) have been identified to co-regulate pHi homeostasis. However, functional and biological pHi-regulators in human dental pulp stem cells (hDPSCs) have yet to be identified. DESIGN: Microspectrofluorimetry technique with pH-sensitive fluorescent dye, BCECF, was used to detect pHi changes. NH4Cl and Na+-acetate pre-pulse were used to induce intracellular acidosis and alkalosis, respectively. Isoforms of pHi-regulators were detected by Western blot technique. RESULTS: The resting pHi was no significant difference between that in HEPES-buffered (nominal HCO3--free) solution or CO2/HCO3-buffered system (7.42 and 7.46, respectively). The pHi recovery following the induced-intracellular acidosis was blocked completely by removing [Na+]o, while only slowed (-63%) by adding HOE694 (a NHE1 specific inhibitor) in HEPES-buffered solution. The pHi recovery was inhibited entirely by removing [Na+]o, while adding HOE 694 pulse DIDS (an anion-transporter inhibitor) only slowed (-55%) the acid extrusion. Both in HEPES-buffered and CO2/HCO3-buffered system solution, the pHi recovery after induced-intracellular alkalosis was entirely blocked by removing [Cl-]o. Western blot analysis showed the isoforms of pHi regulators, including NHE1/2, NBCe1/n1, AE1/2/3/4 and CHE in the hDPSCs. CONCLUSIONS: We demonstrate for the first time that resting pHi is significantly higher than 7.2 and meditates functionally by two Na+-dependent acid extruders (NHE and NBC), two Cl--dependent acid loaders (CHE and AE) and one Na+-independent acid extruder(s) in hDPSCs. These findings provide novel insight for basic and clinical treatment of dentistry.

[Bicarbonate: From physiology to treatment for all clinicians]. / Bicarbonate : de la physiologie aux applications thérapeutiques pour tout clinicien.

Acid-base regulation is essential to maintain homeostasis in humans. Carbonic acid/bicarbonate (H2CO3/HCO3-) couple is the most predominant extracellular buffer to keep plasma pH within a physiological range. The ability to (re)generate such a buffer is a key milestone that necessitates to understand a precise physiology of both renal tubule and digestive tract. Here, we first reviewed renal and digestive cycles of bicarbonate in physiology. We also reviewed pathological findings where acid-base disequilibrium is involved and nutritional and/or alkali therapy could be necessary. Secondly, data from clinical trials were synthesized. Alkali therapy, oral and parenteral, from mineral-based water, masterful preparations or pharmaceutics drugs, is regularly used in a wide range of clinical findings, even if supporting data are (often) of a low level of evidence. Bicarbonate is primarily used during contrast-induced nephropathy, metabolic acidosis in chronic kidney disease or nephrolithiasis in which alkaline urine is necessary. Cast nephropathy, rhabdomyolysis and tumor lysis syndrome make usually physicians prescribe alkali therapy even if this prescription is only supported by physiopathological data without any proven clinical results. Finally, bicarbonate is essential in the composition of dialysate in both hemodialysis and peritoneal dialysis.