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American Journal of Kidney Diseases :... Oct 2022Metabolic alkalosis is a widespread acid-base disturbance, especially in hospitalized patients. It is characterized by the primary elevation of serum bicarbonate and... (Review)
Review
Metabolic alkalosis is a widespread acid-base disturbance, especially in hospitalized patients. It is characterized by the primary elevation of serum bicarbonate and arterial pH, along with a compensatory increase in Pco consequent to adaptive hypoventilation. The pathogenesis of metabolic alkalosis involves either a loss of fixed acid or a net accumulation of bicarbonate within the extracellular fluid. The loss of acid may be via the gastrointestinal tract or the kidney, whereas the sources of excess alkali may be via oral or parenteral alkali intake. Severe metabolic alkalosis in critically ill patients-arterial blood pH of 7.55 or higher-is associated with significantly increased mortality rate. The kidney is equipped with sophisticated mechanisms to avert the generation or the persistence (maintenance) of metabolic alkalosis by enhancing bicarbonate excretion. These mechanisms include increased filtration as well as decreased absorption and enhanced secretion of bicarbonate by specialized transporters in specific nephron segments. Factors that interfere with these mechanisms will impair the ability of the kidney to eliminate excess bicarbonate, therefore promoting the generation or impairing the correction of metabolic alkalosis. These factors include volume contraction, low glomerular filtration rate, potassium deficiency, hypochloremia, aldosterone excess, and elevated arterial carbon dioxide. Major clinical states are associated with metabolic alkalosis, including vomiting, aldosterone or cortisol excess, licorice ingestion, chloruretic diuretics, excess calcium alkali ingestion, and genetic diseases such as Bartter syndrome, Gitelman syndrome, and cystic fibrosis. In this installment in the AJKD Core Curriculum in Nephrology, we will review the pathogenesis of metabolic alkalosis; appraise the precipitating events; and discuss clinical presentations, diagnoses, and treatments of metabolic alkalosis.
Topics: Aldosterone; Alkalies; Alkalosis; Bicarbonates; Calcium; Carbon Dioxide; Curriculum; Diuretics; Humans; Hydrocortisone
PubMed: 35525634
DOI: 10.1053/j.ajkd.2021.12.016 -
The Journal of Emergency Medicine Aug 2023The use of sodium bicarbonate to treat metabolic acidosis is intuitive, yet data suggest that not all patients benefit from this therapy. (Review)
Review
BACKGROUND
The use of sodium bicarbonate to treat metabolic acidosis is intuitive, yet data suggest that not all patients benefit from this therapy.
OBJECTIVE
In this narrative review, we describe the physiology behind commonly encountered nontoxicologic causes of metabolic acidosis, highlight potential harm from the indiscriminate administration of sodium bicarbonate in certain scenarios, and provide evidence-based recommendations to assist emergency physicians in the rational use of sodium bicarbonate.
DISCUSSION
Sodium bicarbonate can be administered as a hypertonic push, as a resuscitation fluid, or as an infusion. Lactic acidosis and cardiac arrest are two common scenarios where there is limited benefit to routine use of sodium bicarbonate, although certain circumstances, such as patients with concomitant acute kidney injury and lactic acidosis may benefit from sodium bicarbonate. Patients with cardiac arrest secondary to sodium channel blockade or hyperkalemia also benefit from sodium bicarbonate therapy. Recent data suggest that the use of sodium bicarbonate in diabetic ketoacidosis does not confer improved patient outcomes and may cause harm in pediatric patients. Available evidence suggests that alkalinization of urine in rhabdomyolysis does not improve patient-centered outcomes. Finally, patients with a nongap acidosis benefit from sodium bicarbonate supplementation.
CONCLUSIONS
Empiric use of sodium bicarbonate in patients with nontoxicologic causes of metabolic acidosis is not warranted and likely does not improve patient-centered outcomes, except in select scenarios. Emergency physicians should reserve use of this medication to conditions with clear benefit to patients.
Topics: Humans; Child; Bicarbonates; Sodium Bicarbonate; Acidosis, Lactic; Acidosis; Heart Arrest
PubMed: 37442665
DOI: 10.1016/j.jemermed.2023.04.012 -
Journal of the American Society of... Mar 2017The optimal approach to managing acid-base balance is less well defined for patients receiving hemodialysis than for those receiving peritoneal dialysis. Interventional... (Review)
Review
The optimal approach to managing acid-base balance is less well defined for patients receiving hemodialysis than for those receiving peritoneal dialysis. Interventional studies in hemodialysis have been limited and inconsistent in their findings, whereas more compelling data are available from interventional studies in peritoneal dialysis. Both high and low serum bicarbonate levels associate with an increased risk of mortality in patients receiving hemodialysis, but high values are a marker for poor nutrition and comorbidity and are often highly variable from month to month. Measurement of pH would likely provide useful additional data. Concern has arisen regarding high-bicarbonate dialysate and dialysis-induced alkalemia, but whether these truly cause harm remains to be determined. The available evidence is insufficient for determining the optimal target for therapy at this time.
Topics: Acid-Base Equilibrium; Bicarbonates; Humans; Kidney Failure, Chronic; Renal Dialysis
PubMed: 27881607
DOI: 10.1681/ASN.2016070780 -
International Journal of Molecular... May 2018Bicarbonate plays a fundamental role in the cell pH status in all organisms. In autotrophs, HCO₃ may further contribute to carbon concentration mechanisms (CCM). This... (Review)
Review
Bicarbonate plays a fundamental role in the cell pH status in all organisms. In autotrophs, HCO₃ may further contribute to carbon concentration mechanisms (CCM). This is especially relevant in the CO₂-poor habitats of cyanobacteria, aquatic microalgae, and macrophytes. Photosynthesis of terrestrial plants can also benefit from CCM as evidenced by the evolution of C₄ and Crassulacean Acid Metabolism (CAM). The presence of HCO₃ in all organisms leads to more questions regarding the mechanisms of uptake and membrane transport in these different biological systems. This review aims to provide an overview of the transport and metabolic processes related to HCO₃ in microalgae, macroalgae, seagrasses, and terrestrial plants. HCO₃ transport in cyanobacteria and human cells is much better documented and is included for comparison. We further comment on the metabolic roles of HCO₃ in plants by focusing on the diversity and functions of carbonic anhydrases and PEP carboxylases as well as on the signaling role of CO₂/HCO₃ in stomatal guard cells. Plant responses to excess soil HCO₃ is briefly addressed. In conclusion, there are still considerable gaps in our knowledge of HCO₃ uptake and transport in plants that hamper the development of breeding strategies for both more efficient CCM and better HCO₃ tolerance in crop plants.
Topics: Animals; Bicarbonates; Carbon Dioxide; Carbonic Anhydrases; Humans; Plants
PubMed: 29751549
DOI: 10.3390/ijms19051352 -
European Journal of Sport Science May 2022Sodium bicarbonate (SB) is considered an effective ergogenic supplement for improving high-intensity exercise capacity and performance, although recent data suggests... (Meta-Analysis)
Meta-Analysis
Sodium bicarbonate (SB) is considered an effective ergogenic supplement for improving high-intensity exercise capacity and performance, although recent data suggests that women may be less amenable to its ergogenic effects than men. Currently, an apparent paucity of data on women means no consensus exists on whether women benefit from SB supplementation. The aim of the current study was to quantify the proportion of the published literature on SB supplementation that includes women, and to synthesise the evidence regarding its effects on blood bicarbonate and exercise performance in women by performing a systematic review and meta-analysis. Electronic searches of the literature were undertaken using three databases (MEDLINE, Embase, SPORTDiscus) to identify relevant articles. All meta-analyses were performed within a Bayesian framework. A total of 149 SB articles were identified, 11 of which contained individual group data for women. Results indicated a pooled blood bicarbonate increase of 7.4 [95%CrI: 4.2-10.4 mmol·L] following supplementation and a pooled standardised exercise effect size of 0.37 [95%CrI: -0.06-0.92]. The SB literature is skewed, with only 20% (30 studies) of studies employing female participants, of which only 11 studies (7.4%) provided group analyses exclusively in women. Despite the small amount of available data, results are consistent in showing that SB supplementation in women leads to large changes in blood bicarbonate and that there is strong evidence for a positive ergogenic effect on exercise performance that is likely to be small to medium in magnitude.HighlightsThis study aimed to quantify the proportion of the published literature on sodium bicarbonate supplementation that includes women and to synthesise the evidence regarding its ergogenic effect on women, using a systematic review and meta-analytic approach.The sodium bicarbonate literature is skewed, with only 30 studies (20%) employing female participants, of which only 11 studies (7.4%) provided group analyses exclusively in women.Despite the small amount of available data, results are consistent in showing that sodium bicarbonate supplementation in women leads to large changes in blood bicarbonate and that there is strong evidence for a positive ergogenic effect on exercise performance that is likely small to medium in magnitude.Based on these findings, we do not believe there is any evidence to support sex-specific sodium bicarbonate dosing recommendations and that current recommendations of 0.2-0.3 g·kgBM of SB taken 60-180 min prior to high-intensity exercise appear appropriate for the female athlete.
Topics: Athletes; Athletic Performance; Bayes Theorem; Bicarbonates; Dietary Supplements; Female; Humans; Male; Performance-Enhancing Substances; Sodium Bicarbonate
PubMed: 33487131
DOI: 10.1080/17461391.2021.1880649 -
Acta Physiologica (Oxford, England) May 2022Bicarbonate is one of the major anions in mammalian tissues and fluids, is utilized by various exchangers to transport other ions and organic substrates across cell... (Review)
Review
Bicarbonate is one of the major anions in mammalian tissues and fluids, is utilized by various exchangers to transport other ions and organic substrates across cell membranes and plays a critical role in cell and systemic pH homoeostasis. Chloride/bicarbonate (Cl /HCO ) exchangers are abundantly expressed in erythrocytes and epithelial cells and, as a consequence, are particularly exposed to oxidants in the systemic circulation and at the interface with the external environment. Here, we review the physiological functions and pathophysiological alterations of Cl /HCO exchangers belonging to the solute carriers SLC4 and SLC26 superfamilies in relation to oxidative stress. Particularly well studied is the impact of oxidative stress on the red blood cell SLC4A1/AE1 (Band 3 protein), of which the function seems to be directly affected by oxidative stress and possibly involves oxidation of the transporter itself or its interacting proteins, with detrimental consequences in oxidative stress-related diseases including inflammation, metabolic dysfunctions and ageing. The effect of oxidative stress on SLC26 members was less extensively explored. Indirect evidence suggests that SLC26 transporters can be target as well as determinants of oxidative stress, especially when their expression is abolished or dysregulated.
Topics: Animals; Bicarbonates; Cell Membrane; Erythrocytes; Mammals; Membrane Transport Proteins; Oxidative Stress
PubMed: 35143116
DOI: 10.1111/apha.13796 -
American Journal of Physiology. Heart... Apr 2022
Topics: Bicarbonates; Dialysis Solutions
PubMed: 35324335
DOI: 10.1152/ajpheart.00057.2022 -
ChemPlusChem Nov 2022The development of synthetic anion transporters is motivated by their potential application as treatment for diseases that originate from deficient anion transport by... (Review)
Review
The development of synthetic anion transporters is motivated by their potential application as treatment for diseases that originate from deficient anion transport by natural proteins. Transport of bicarbonate is important for crucial biological functions such as respiration and digestion. Despite this biological relevance, bicarbonate transport has not been as widely studied as chloride transport. Herein we present an overview of the synthetic receptors that have been studied as bicarbonate transporters, together with the different assays used to perform transport studies in large unilamellar vesicles. We highlight the most active transporters and comment on the nature of the functional groups present in active and inactive compounds. We also address recent mechanistic studies that have revealed different processes that can lead to net transport of bicarbonate, as well as studies reported in cells and tissues, and comment on the key challenges for the further development of bicarbonate transporters.
Topics: Bicarbonates; Biological Transport; Ion Transport
PubMed: 36414387
DOI: 10.1002/cplu.202200266 -
International Journal of Molecular... Feb 2024Diets can influence the body's acid-base status because specific food components yield acids, bases, or neither when metabolized. Animal-sourced foods yield acids and... (Review)
Review
Diets can influence the body's acid-base status because specific food components yield acids, bases, or neither when metabolized. Animal-sourced foods yield acids and plant-sourced food, particularly fruits and vegetables, generally yield bases when metabolized. Modern diets proportionately contain more animal-sourced than plant-sourced foods, are, thereby, generally net acid-producing, and so constitute an ongoing acid challenge. Acid accumulation severe enough to reduce serum bicarbonate concentration, i.e., manifesting as chronic metabolic acidosis, the most extreme end of the continuum of "acid stress", harms bones and muscles and appears to enhance the progression of chronic kidney disease (CKD). Progressive acid accumulation that does not achieve the threshold amount necessary to cause chronic metabolic acidosis also appears to have deleterious effects. Specifically, identifiable acid retention without reduced serum bicarbonate concentration, which, in this review, we will call "covert acidosis", appears to cause kidney injury and exacerbate CKD progression. Furthermore, the chronic engagement of mechanisms to mitigate the ongoing acid challenge of modern diets also appears to threaten health, including kidney health. This review describes the full continuum of "acid stress" to which modern diets contribute and the mechanisms by which acid stress challenges health. Ongoing research will develop clinically useful tools to identify stages of acid stress earlier than metabolic acidosis and determine if dietary acid reduction lowers or eliminates the threats to health that these diets appear to cause.
Topics: Animals; Bicarbonates; Acid-Base Equilibrium; Diet; Acidosis; Renal Insufficiency, Chronic
PubMed: 38397012
DOI: 10.3390/ijms25042336 -
Journal of Nanobiotechnology Apr 2022Different from Fe ions in Fenton reaction, Mn ions can function both as catalyst for chemodynamic therapy and immune adjuvant for antitumor immune responses. In...
BACKGROUND
Different from Fe ions in Fenton reaction, Mn ions can function both as catalyst for chemodynamic therapy and immune adjuvant for antitumor immune responses. In Mn-mediated Fenton-like reaction, bicarbonate ([Formula: see text]), as the most important component to amplify therapeutic effects, must be present, however, intracellular [Formula: see text] is strictly limited because of the tight control by live cells.
RESULTS
Herein, Stimuli-responsive manganese carbonate-indocyanine green complexes (MnCO-ICG) were designed for intracellular marriage of bicarbonate and Mn ions as "immune ion reactors" to regulate intracellular redox homeostasis and antitumor immune responses. Under the tumor acidic environment, the biodegradable complex can release "ion reactors" of Mn and [Formula: see text], and ICG in the cytoplasm. The suddenly increased [Formula: see text] in situ inside the cells regulate intracellular pH, and accelerate the generation of hydroxyl radicals for the oxidative stress damage of tumors cells because [Formula: see text] play a critical role to catalyze Mn-mediated Fenton-like reaction. Investigations in vitro and in vivo prove that the both CDT and phototherapy combined with Mn-enhanced immunotherapy effectively suppress tumor growth and realize complete tumor elimination.
CONCLUSIONS
The combination therapy strategy with the help of novel immune adjuvants would produce an enhanced immune response, and be used for the treatment of deep tumors in situ.
Topics: Bicarbonates; Cell Line, Tumor; Homeostasis; Humans; Immunity; Neoplasms; Oxidation-Reduction
PubMed: 35440088
DOI: 10.1186/s12951-022-01404-x