Rapid blood acid-base regulation by European sea bass (Dicentrarchus labrax) in response to sudden exposure to high environmental CO2

Fish in coastal ecosystems can be exposed to acute variations in CO2 of between 0.2-1 kPa CO2 (2,000 - 10,000 µatm). Coping with this environmental challenge will depend on the ability to rapidly compensate the internal acid-base disturbance caused by sudden exposure to high environmental CO2 (blood and tissue acidosis); however, studies about the speed of acid-base regulatory responses in marine fish are scarce. We observed that upon sudden exposure to ∼1 kPa CO2, European sea bass (Dicentrarchus labrax) completely regulate erythrocyte intracellular pH within ∼40 minutes, thus restoring haemoglobin-O2 affinity to pre-exposure levels. Moreover, blood pH returned to normal levels within ∼2 hours, which is one of the fastest acid-base recoveries documented in any fish. This was achieved via a large upregulation of net acid excretion and accumulation of HCO3− in blood, which increased from ∼4 to ∼22 mM. While the abundance and intracellular localisation of gill Na+/K+-ATPase (NKA) and Na+/H+ exchanger 3 (NHE3) remained unchanged, the apical surface area of acid-excreting gill ionocytes doubled. This constitutes a novel mechanism for rapidly increasing acid excretion during sudden blood acidosis. Rapid acid-base regulation was completely prevented when the same high CO2 exposure occurred in seawater with experimentally reduced HCO3− and pH, likely because reduced environmental pH inhibited gill H+ excretion via NHE3. The rapid and robust acid-base regulatory responses identified will enable European sea bass to maintain physiological performance during large and sudden CO2 fluctuations that naturally occur in coastal environments.

Obesity, Anion Accumulation, and Anion Gap Metabolic Acidosis: A Cohort Study

Background: Obesity is associated with low serum bicarbonate, an indicator of metabolic acidosis and a CKD risk factor. To further characterize acid-base disturbance and subclinical metabolic acidosis in this population, we examined prospective associations of body mass index (BMI) with elevated anion gap, and whether anion gap values in obesity associate with low bicarbonate. Methods: Data from adult outpatients (n = 94,448) in the Bronx, NY were collected from 2010-2018. Mixed effects models and Cox proportional hazards models were used to examine associations of BMI with elevated anion gap and anion gap metabolic acidosis, and of baseline anion gap with incident low bicarbonate and anion gap metabolic acidosis. Anion gap was defined using traditional and albumin-corrected calculations. Results: Greater BMI was associated with higher anion gap over time, and with progressively greater risk of developing an elevated anion gap (HRs for BMI ≥ 40 vs. 18-<25 kg/m2: 1.32 [95% CI: 1.23 - 1.42] for traditional and 1.74 [95% CI: 1.63 - 1.85] for corrected). Higher BMI was also associated with increased risk of developing anion gap metabolic acidosis (HR for BMI ≥ 40: 1.53 [95% CI: 1.39 - 1.69]). Among patients with obesity, higher anion gap was associated with increased risk of incident low bicarbonate (HRs for 4th vs 1st quartile: 1.29 [95% CI: 1.23 - 1.44] for traditional and 1.36 [95% CI: 1.26 - 1.48] for corrected); and higher risk of anion gap metabolic acidosis (HR for 4th vs 1st quartile 1.78 [1.59 - 1.99]). Conclusions: Obesity is characterized by unmeasured anion accumulation and acid retention or overproduction. Modest elevations in anion gap among patients with obesity are associated with previously unrecognized anion gap metabolic acidosis.

FC 025ACID BASE DISORDERS IN COVID-19

Background and Aims Acid-base disorders are common in severely ill patients and reflect the severity of the underlying pathologic process. The incidence and effects of acid-base derangement in COVID-19 patients have been poorly evaluated until now. Tropism of the virus for the lungs and kidneys may theoretically lead to frequent acid-base alterations due to pneumonia and kidney injury, respectively. To verify the derangement of acid-base disorders in COVID-19, we investigated the distribution and the impact of acid-base disorders on the survival of symptomatic patients with a diagnosis of COVID-19. Method We retrospectively collected data from electronic charts of all COVID-19 patients hospitalized at the University Hospital of Modena from 4 March to 20 June 2020. Arterial blood gas (ABG) analysis was required to monitor pulmonary gas exchange and acid-base status. A pH of less than 7.37 was categorized as acidemia and a pH of more than 7.42 was categorized as alkalemia. 211 patients were included in the study population. In patients with multiple ABG analyses, we selected only the first measurement. Results The estimated mean age of the population was 64.7 ±15,3 years with a high predominance of males (71.6%). Half of the population referred dyspnea and 61.4% at physical examination. Most patients (82.6%) were on oxygen therapy when ABG analysis was performed. Overall, ABG analyses revealed acute respiratory compromise manifesting with a low arterial partial pressure of oxygen (P02, 70.2±25.1 mmHg), oxygen saturation (SO2, 92%) and a mild reduction of PO2/FiO2 ratio (231±129). Acid-base disturbance was found in the 79.7% of the patients, and contrary to our expectation, metabolic alkalosis (33.6%) was the main alteration followed by respiratory alkalosis (30.3%), combined alkalosis (9.4%) respiratory acidosis (3.3%) metabolic acidosis (2.8%) and other compensated acid-base disturbances (3.6%). ANOVA with post hoc Tukey, revealed statistically significant differences in age, sex, serum level of K, Na, bicarbonate, creatinine of PCO2, PO2/FiO2 ratio, CKD, symptoms (caught, diarrhea) and fatality rate among groups. Metabolic acidosis was associated with death (HR=8.2; CI 95%, 1,93-32,39; P&lt;0.004), after adjustment for lung injury (PaO2/FiO2 ratio) tissue hypoperfusion (lactate) and renal involvement (estimated as GFR&lt; 60 ml/min or development of acute kidney injury), Pathological pH (alkalosis or acidosis), variations of PCO2 or hypobicarbonatemia were not associated with mortality in our study population. Metabolic acidosis occurred in patients with a mean creatinine of 4.5±4.5 mg/dl. Notably, 33.3% of patients were on hemodialysis, 33.3% developed COVID-19-associated acute kidney injury and 33.3% had a GFR &lt;60 ml/min. Patients with metabolic acidosis had the highest death-fatality rate (100%) after 7±5.6 days from admission, 50% died of acute respiratory distress syndrome and 50% of septic shock. Conclusion In conclusion, all kinds of acid-base alterations were found in patients with COVID-19. Metabolic and respiratory alkalosis were the most common acid-base disorders, whereas metabolic acidosis was the only acid-base disturbance associate with poor outcome in our cohort of patients.

Rapid blood acid-base regulation by European sea bass (Dicentrarchus labrax) in response to sudden exposure to high environmental CO2

Fish in coastal ecosystems can be exposed to acute variations in CO2that can approach 1 kPa CO2(10,000 μatm). Coping with this environmental challenge will depend on the ability to rapidly compensate the internal acid-base disturbance caused by sudden exposure to high environmental CO2(blood and tissue acidosis); however, studies about the speed of acid-base regulatory responses in marine fish are scarce. We observed that upon exposure to ~1 kPa CO2, European sea bass (Dicentrarchus labrax) completely regulate erythrocyte intracellular pH within ~40 minutes, thus restoring haemoglobin-O2affinity to pre-exposure levels. Moreover, blood pH returned to normal levels within ~2 hours, which is one of the fastest acid-base recoveries documented in any fish. This was achieved via a large upregulation of net acid excretion and accumulation of HCO3− in blood, which increased from ~4 to ~22 mM. While the abundance and intracellular localisation of gill Na+/K+-ATPase (NKA) and Na+/H+exchanger 3 (NHE3) remained unchanged, the apical surface area of acid-excreting gill ionocytes doubled. This constitutes a novel mechanism for rapidly increasing acid excretion during sudden blood acidosis. Rapid acid-base regulation was completely prevented when the same high CO2exposure occurred in seawater with experimentally reduced HCO3− and pH, likely because reduced environmental pH inhibited gill H+excretion via NHE3. The rapid and robust acid-base regulatory responses identified will enable European sea bass to maintain physiological performance during large and sudden CO2fluctuations that naturally occur in coastal environments.Summary statementEuropean sea bass exposed to 1 kPa (10,000 μatm) CO2regulate blood and red cell pH within 2 hours and 40 minutes, respectively, protecting O2transport capacity, via enhanced gill acid excretion.

Connecting two worlds: positive correlation between physicochemical approach with blood gases and pH in pediatric ICU setting

Objective Physicochemical approach such as strong ion difference provides a novel concept in understanding and managing acid–base disturbance in patients. However, its application in pediatrics is limited. This study aimed to evaluate a correlation between the physicochemical approach and blood gas pH for acid–base determination in critically ill pediatric patients. Results A total of 130 pediatric patients were included, corresponding to 1338 paired measures for analyses. Of these, the metabolic subgroup (743 paired measures) was defined. Among physicochemical parameters, the effective strong ion difference showed the best correlation with the blood gas pH in the whole cohort (R = 0.398; p < 0.001) and the metabolic subgroup (R = 0.685; p < 0.001). Other physicochemical parameters (i.e., the simplified and the apparent strong ion difference, the strong ion gap, and the sodium chloride gap) and the traditional measures (standard base excess, lactate, chloride and bicarbonate) also showed varying degrees of correlation. This study revealed the positive correlation between physicochemical parameters and the blood gas pH, serving as a connecting dot for further investigations using physicochemical approach to evaluate acid–base disturbance in pediatric population.

Immune-inflammatory activation after a single laparotomy in a rat model: effect of adenosine, lidocaine and Mg2+ infusion to dampen the stress response

Our aim was to examine the effect of low-volume 0.9% NaCl adenosine, lidocaine and Mg2+ (ALM) ‘drip’ on early immune-inflammatory activation after a single laparotomy with no further manipulation. Male Sprague–Dawley rats were anesthetized and randomly assigned to one of the groups, baseline, 1 h infusion 0.9% NaCl ± ALM and metrics, 1 h infusion and 6-h metrics, and 6 h continuous infusion and metrics. Complete blood count, acid–base balance, systemic levels of IL-6 and IL-10, and coagulation status were measured. After 1 h, there was a disproportionate increase in circulating neutrophils between saline and ALM groups despite an identical 45% fall in lymphocytes. Disproportionate increases also occurred in platelet counts 1 h after surgery, and saline controls had increased respiratory alkalosis at 6 h with higher lactate. Systemic inflammation was also evident after 1 h in both groups (plasma IL-6 increase) and was amplified in saline-controls after 6 h. The ALM group increased anti-inflammatory cytokine IL-10. Surgery was not associated with acute coagulopathy; however, there were significant reductions in fibrinolysis. Following a single laparotomy, ALM infusion appeared to reduce stress-induced release of neutrophils and platelets into the circulation, and reduced acid–base disturbance. After 1 h, both groups had similar IL-6 levels, but ALM animals had increased IL-10, indicating improved inflammatory balance. The uncoupling of inflammation and coagulation activation but not fibrinolysis may offer a unique opportunity to investigate differential activation of innate immunity in response to sterile injury in this model.