-
Clinical Journal of the American... Aug 2021Sodium-glucose cotransporter-2 (SGLT2) inhibitors are drugs designed to lower plasma glucose concentration by inhibiting Na-glucose-coupled transport in the proximal... (Review)
Review
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are drugs designed to lower plasma glucose concentration by inhibiting Na-glucose-coupled transport in the proximal tubule. Clinical trials demonstrate these drugs have favorable effects on cardiovascular outcomes to include slowing the progression of CKD. Although most patients tolerate these drugs, a potential complication is development of ketoacidosis, often with a normal or only a minimally elevated plasma glucose concentration. Inhibition of sodium-glucose cotransporter-2 in the proximal tubule alters kidney ATP turnover so that filtered ketoacids are preferentially excreted as Na or K salts, leading to indirect loss of bicarbonate from the body and systemic acidosis under conditions of increased ketogenesis. Risk factors include reductions in insulin dose, increased insulin demand, metabolic stress, low carbohydrate intake, women, and latent autoimmune diabetes of adulthood. The lack of hyperglycemia and nonspecific symptoms of ketoacidosis can lead to delays in diagnosis. Treatment strategies and various precautions are discussed that can decrease the likelihood of this complication.
Topics: Blood Glucose; Humans; Ketosis; Kidney; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33563658
DOI: 10.2215/CJN.17621120 -
Medizinische Klinik, Intensivmedizin... May 2020Acid-base disorders and in particular metabolic acidosis are very common in critically ill patients and contribute significantly to morbidity and mortality. We shed... (Review)
Review
Acid-base disorders and in particular metabolic acidosis are very common in critically ill patients and contribute significantly to morbidity and mortality. We shed light on the most common causes, the pathophysiology and treatments. Particular attention will be paid to the common practice of substituting sodium bicarbonate in the light of recent study results.
Topics: Acid-Base Equilibrium; Acidosis; Bicarbonates; Critical Illness; Humans
PubMed: 30725274
DOI: 10.1007/s00063-019-0538-y -
American Journal of Kidney Diseases :... Oct 2021The anion gap (AG) is a mathematical construct that compares the blood sodium concentration with the sum of the chloride and bicarbonate concentrations. It is a helpful... (Review)
Review
The anion gap (AG) is a mathematical construct that compares the blood sodium concentration with the sum of the chloride and bicarbonate concentrations. It is a helpful calculation that divides the metabolic acidoses into 2 categories: high AG metabolic acidosis (HAGMA) and hyperchloremic metabolic acidosis-and thereby delimits the potential etiologies of the disorder. When the [AG] is compared with changes in the bicarbonate concentration, other occult acid-base disorders can be identified. Furthermore, finding that the AG is very small or negative can suggest several occult clinical disorders or raise the possibility of electrolyte measurement artifacts. In this installment of AJKD's Core Curriculum in Nephrology, we discuss cases that represent several very common and several rare causes of HAGMA. These case scenarios highlight how the AG can provide vital clues that direct the clinician toward the correct diagnosis. We also show how to calculate and, if necessary, correct the AG for hypoalbuminemia and severe hyperglycemia. Plasma osmolality and osmolal gap calculations are described and when used together with the AG guide appropriate clinical decision making.
Topics: Acid-Base Equilibrium; Acid-Base Imbalance; Acidosis; Adult; Aged; Curriculum; Diabetic Ketoacidosis; Female; Fluid Therapy; Humans; Male; Middle Aged; Osmolar Concentration; Young Adult
PubMed: 34400023
DOI: 10.1053/j.ajkd.2021.02.341 -
Minerva Endocrinologica Dec 2019Metabolic acidosis is defined as a pathologic process that, when unopposed, increases the concentration of hydrogen ions (H+) in the body and reduces the bicarbonate... (Review)
Review
Metabolic acidosis is defined as a pathologic process that, when unopposed, increases the concentration of hydrogen ions (H+) in the body and reduces the bicarbonate (HCO3-) concentration. Metabolic acidosis can be of a kidney origin or an extrarenal cause. Assessment of urinary ammonium excretion by calculating the urine anion gap or osmolal gap is a useful method to distinguish between these two causes. Extrarenal processes include increased endogenous acid production and accelerated loss of bicarbonate from the body. Metabolic acidosis of renal origin is due to a primary defect in renal acidification with no increase in extrarenal hydrogen ion production. This situation can occur because either the renal input of new bicarbonate is insufficient to regenerate the bicarbonate lost in buffering endogenous acid as with distal renal tubular acidosis (RTA) or the RTA of renal insufficiency, or the filtered bicarbonate is lost by kidney wasting as in proximal RTA. In either condition, because of loss of either NaHCO3 (proximal RTA) or NaA (distal RTA), effective extracellular volume is reduced and as a result the avidity for chloride reabsorption derived from the diet is increased and results in a hyperchloremic normal gap metabolic acidosis. The RTA of renal insufficiency is also characterized by a normal gap acidosis, however, with severe reductions in the glomerular filtration rate an anion gap metabolic acidosis eventually develops.
Topics: Acid-Base Equilibrium; Acidosis; Acidosis, Renal Tubular; Aldosterone; Ammonia; Bicarbonates; Buffers; Chlorides; Diarrhea; Glomerular Filtration Rate; Humans; Hypokalemia; Kidney; Kidney Tubules; Models, Biological; Postoperative Complications; Protons; Renal Insufficiency, Chronic; Urinary Diversion
PubMed: 31347344
DOI: 10.23736/S0391-1977.19.03059-1 -
Management of acute metabolic acidosis in the ICU: sodium bicarbonate and renal replacement therapy.Critical Care (London, England) Aug 2021This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at... (Review)
Review
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .
Topics: Acidosis; Buffers; Humans; Intensive Care Units; Renal Replacement Therapy; Sodium Bicarbonate
PubMed: 34461963
DOI: 10.1186/s13054-021-03677-4 -
Nature Metabolism Feb 2023The accumulation of acidic metabolic waste products within the tumor microenvironment inhibits effector functions of tumor-infiltrating lymphocytes (TILs). However, it...
The accumulation of acidic metabolic waste products within the tumor microenvironment inhibits effector functions of tumor-infiltrating lymphocytes (TILs). However, it remains unclear how an acidic environment affects T cell metabolism and differentiation. Here we show that prolonged exposure to acid reprograms T cell intracellular metabolism and mitochondrial fitness and preserves T cell stemness. Mechanistically, elevated extracellular acidosis impairs methionine uptake and metabolism via downregulation of SLC7A5, therefore altering H3K27me3 deposition at the promoters of key T cell stemness genes. These changes promote the maintenance of a 'stem-like memory' state and improve long-term in vivo persistence and anti-tumor efficacy in mice. Our findings not only reveal an unexpected capacity of extracellular acidosis to maintain the stem-like properties of T cells, but also advance our understanding of how methionine metabolism affects T cell stemness.
Topics: Animals; Mice; Neoplasms; Cell Differentiation; Tumor Microenvironment; Acidosis; Carbon
PubMed: 36717749
DOI: 10.1038/s42255-022-00730-6 -
American Journal of Kidney Diseases :... Aug 2019Maintenance of normal acid-base homeostasis is one of the most important kidney functions. In chronic kidney disease, the capacity of the kidneys to excrete the daily... (Review)
Review
Maintenance of normal acid-base homeostasis is one of the most important kidney functions. In chronic kidney disease, the capacity of the kidneys to excrete the daily acid load as ammonium and titratable acid is impaired, resulting in acid retention and metabolic acidosis. The prevalence of metabolic acidosis increases with declining glomerular filtration rate. Metabolic acidosis is associated with several clinically important complications, including chronic kidney disease progression, bone demineralization, skeletal muscle catabolism, and mortality. To mitigate these adverse consequences, clinical practice guidelines suggest treating metabolic acidosis with oral alkali in patients with chronic kidney disease. However, large clinical trials to determine the efficacy and safety of correcting metabolic acidosis with oral alkali in patients with chronic kidney disease have yet to be conducted. In this Core Curriculum article, established and emerging concepts regarding kidney acid-base regulation and the pathogenesis, risk factors, diagnosis, and management of metabolic acidosis in chronic kidney disease are discussed.
Topics: Acid-Base Equilibrium; Acidosis; Female; Humans; Middle Aged; Renal Insufficiency, Chronic
PubMed: 31036389
DOI: 10.1053/j.ajkd.2019.01.036 -
Revista Espanola de Anestesiologia Y... Jan 2020Abnormalities in the acid-base balance are common clinical problems and can have deleterious effects on cellular function and be a clue to various disorders. Therefore,... (Review)
Review
Abnormalities in the acid-base balance are common clinical problems and can have deleterious effects on cellular function and be a clue to various disorders. Therefore, it is important for the clinician to make a precise diagnosis of the acid-base disorder(s) present for a proper treatment. Three approaches have been proposed to evaluate acid-base disorders: a bicarbonate-centric approach; the Stewart approach, and the base excess approach. Although the latter two have many adherents, we will only discuss the bicarbonate-centric approach. This approach is simpler to utilize at the bedside, has a physiological evaluation of the acid-base disorder, presents an easily understandable approach to assess severity, and provides a more solid foundation for the development of effective therapies. Therefore, the following discussion will be limited to an examination of this approach. In this case-centric review, important new concepts will be introduced first; their benefits and limitations discussed; and then their utilization to analyze actual cases will be shown. A systematic approach algorithm that incorporates these new concepts has been generated and will be highlighted.
Topics: Acid-Base Equilibrium; Acid-Base Imbalance; Acidosis; Algorithms; Alkalosis; Bicarbonates; Blood Gas Analysis; Humans; Hydrogen-Ion Concentration; Reference Values
PubMed: 31826801
DOI: 10.1016/j.redar.2019.04.001 -
BioMed Research International 2020Two enantiomers of lactic acid exist. While L-lactic acid is a common compound of human metabolism, D-lactic acid is produced by some strains of microorganism or by some... (Review)
Review
Two enantiomers of lactic acid exist. While L-lactic acid is a common compound of human metabolism, D-lactic acid is produced by some strains of microorganism or by some less relevant metabolic pathways. While L-lactic acid is an endogenous compound, D-lactic acid is a harmful enantiomer. Exposure to D-lactic acid can happen by various ways including contaminated food and beverages and by microbiota during some pathological states like short bowel syndrome. The exposure to D-lactic acid cannot be diagnosed because the common analytical methods are not suitable for distinguishing between the two enantiomers. In this review, pathways for D-lactic acid, pathological processes, and diagnostical and analytical methods are introduced followed by figures and tables. The current literature is summarized and discussed.
Topics: Acidosis; Animals; Humans; Lactic Acid; Metabolic Networks and Pathways; Metabolome
PubMed: 32685468
DOI: 10.1155/2020/3419034 -
The Journal of Emergency Medicine Sep 2020Diabetic ketoacidosis (DKA) is a hyperglycemic emergency that presents commonly to the emergency department. Severe DKA has the potential for significant morbidity and... (Review)
Review
BACKGROUND
Diabetic ketoacidosis (DKA) is a hyperglycemic emergency that presents commonly to the emergency department. Severe DKA has the potential for significant morbidity and mortality if not recognized early and treated appropriately. It is incumbent on the emergency clinician to be vigilant in the management of these critically ill patients.
OBJECTIVE
This narrative review evaluates the emergency medicine management of the adult patient with severe DKA.
DISCUSSION
DKA is a condition found most commonly in patients with insulin-dependent diabetes, often due to nonadherence with diabetic medications or an inciting event, such as infection or ischemia. The severity of DKA is classified based on the level of acidosis present rather than absolute glucose level. The management of severe DKA involves assessing and treating the inciting event, fluid hydration, insulin, and potassium repletion. Close monitoring is necessary to prevent the complications that can occur.
CONCLUSIONS
DKA is a medical condition that has the potential for significant morbidity and mortality if not recognized and managed appropriately.
Topics: Acidosis; Adult; Critical Illness; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Humans; Insulin
PubMed: 32763063
DOI: 10.1016/j.jemermed.2020.06.059