-
Kidney International Jun 2022The homeostatic regulation of a stable systemic pH is of critical importance for mammalian survival. During metabolic acidosis (a reduction in systemic pH caused by a... (Review)
Review
The homeostatic regulation of a stable systemic pH is of critical importance for mammalian survival. During metabolic acidosis (a reduction in systemic pH caused by a primary decrease in serum bicarbonate concentration), as seen in clinical disorders such as the later stages of chronic kidney disease, renal tubular acidosis, or chronic diarrhea, bone buffers the accumulated acid; however, this homeostatic function of the skeleton occurs at the expense of the bone mineral content and leads to decreased bone quality. During short-term studies to model acute metabolic acidosis, there is initial physiochemical bone mineral dissolution, releasing carbonate and phosphate proton buffers into the extracellular fluid. In addition, there is net proton influx into the mineral with release of bone sodium and potassium. During long-term studies to model chronic metabolic acidosis, there is also inhibition of osteoblast activity, resulting in reduced bone formation, and an increase in osteoclast activity, resulting in increased bone resorption and release of calcium and anionic proton buffers. These physicochemical and cell-mediated bone responses to metabolic acidosis, in addition to an acidosis-induced increased urine calcium excretion, without a corresponding increase in intestinal calcium absorption, induce a net loss of body calcium that is almost certainly derived from the mineral stores of bone.
Topics: Acidosis; Animals; Bone and Bones; Calcium; Hydrogen-Ion Concentration; Mammals; Phosphates; Protons
PubMed: 35351460
DOI: 10.1016/j.kint.2022.02.032 -
Annals of Hepatology 2022In addition to the kidneys and lungs, the liver also plays an important role in the regulation of the Acid-Base Equilibrium (ABE). The involvement of the liver in the... (Review)
Review
In addition to the kidneys and lungs, the liver also plays an important role in the regulation of the Acid-Base Equilibrium (ABE). The involvement of the liver in the regulation of ABE is crucial because of its role in lactic acid metabolism, urea production and in protein homeostasis. The main acid-base imbalance that occurs in patients with liver cirrhosis is Respiratory Alkalosis (RAlk). Due to the fact that in these patients additional pathophysiological mechanisms that affect the ABE are present, other disorders may appear which compensate or enhance the primary disorder. Conventional ABE reading models fail to identify and assess the underlying disorders in patients with liver cirrhosis. This weakness of the classical models led to the creation of new physicochemical mathematical models that take into account all the known parameters that develop and affect the ABE. In addition to the RAlk, in patients with liver cirrhosis, metabolic alkalosis (due to hypoalbuminemia), hyponatremic metabolic acidosis, hyperchloremic metabolic acidosis, lactic acidosis and metabolic alkalosis due to urea metabolism are some of the pathophysiological mechanisms that affect the ABE.
Topics: Acidosis; Alkalosis; Humans; Liver Cirrhosis; Liver Diseases; Urea
PubMed: 35074477
DOI: 10.1016/j.aohep.2022.100675 -
Diabetes Care Sep 2021Fluid replacement to correct dehydration, acidosis, and electrolyte abnormalities is the cornerstone of treatment for diabetic ketoacidosis (DKA), but little is known... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Fluid replacement to correct dehydration, acidosis, and electrolyte abnormalities is the cornerstone of treatment for diabetic ketoacidosis (DKA), but little is known about optimal fluid infusion rates and electrolyte content. The objective of this study was to evaluate whether different fluid protocols affect the rate of normalization of biochemical derangements during DKA treatment.
RESEARCH DESIGN AND METHODS
The current analysis involved moderate or severe DKA episodes ( = 714) in children age <18 years enrolled in the Fluid Therapies Under Investigation in DKA (FLUID) Trial. Children were assigned to one of four treatment groups using a 2 × 2 factorial design (0.90% or 0.45% saline and fast or slow rate of administration).
RESULTS
The rate of change of pH did not differ by treatment arm, but Pco increased more rapidly in the fast versus slow fluid infusion arms during the initial 4 h of treatment. The anion gap also decreased more rapidly in the fast versus slow infusion arms during the initial 4 and 8 h. Glucose-corrected sodium levels remained stable in patients assigned to 0.90% saline but decreased in those assigned to 0.45% saline at 4 and 8 h. Potassium levels decreased, while chloride levels increased more rapidly with 0.90% versus 0.45% saline. Hyperchloremic acidosis occurred more frequently in patients in the fast arms (46.1%) versus the slow arms (35.2%).
CONCLUSIONS
In children treated for DKA, faster fluid administration rates led to a more rapid normalization of anion gap and Pco than slower fluid infusion rates but were associated with an increased frequency of hyperchloremic acidosis.
Topics: Acidosis; Adolescent; Child; Diabetic Ketoacidosis; Electrolytes; Fluid Therapy; Humans; Sodium
PubMed: 34187840
DOI: 10.2337/dc20-3113 -
Biomedicine & Pharmacotherapy =... Feb 2023Metabolic acidosis is frequent in chronic kidney disease (CKD) and is associated with accelerated progression of CKD, hypercatabolism, bone disease, hyperkalemia, and... (Review)
Review
Metabolic acidosis is frequent in chronic kidney disease (CKD) and is associated with accelerated progression of CKD, hypercatabolism, bone disease, hyperkalemia, and mortality. Clinical guidelines recommend a target serum bicarbonate ≥ 22 mmol/L, but metabolic acidosis frequently remains undiagnosed and untreated. Sodium zirconium cyclosilicate (SZC) binds potassium in the gut and is approved to treat hyperkalemia. In clinical trials with a primary endpoint of serum potassium, SZC increased serum bicarbonate, thus treating CKD-associated metabolic acidosis. The increase in serum bicarbonate was larger in patients with more severe pre-existent metabolic acidosis, was associated to decreased serum urea and was maintained for over a year of SZC therapy. SZC also decreased serum urea and increased serum bicarbonate after switching from a potassium-binding resin in normokalemic individuals. Mechanistically, these findings are consistent with SZC binding the ammonium ion (NH) generated from urea by gut microbial urease, preventing its absorption and, thus, preventing the liver regeneration of urea and promoting the fecal excretion of H. This mechanism of action may potentially result in benefits dependent on corrected metabolic acidosis (e.g., improved well-being, decreased catabolism, improved CKD mineral bone disorder, better control of serum phosphate, slower progression of CKD) and dependent on lower urea levels, such as decreased protein carbamylation. A roadmap is provided to guide research into the mechanisms and clinical consequences of the impact of SZC on serum bicarbonate and urate.
Topics: Humans; Hyperkalemia; Bicarbonates; Acidosis; Potassium; Renal Insufficiency, Chronic
PubMed: 36916426
DOI: 10.1016/j.biopha.2022.114197 -
PLoS Pathogens Jan 2021Lactic acidosis and hyperlactatemia are common metabolic disturbances in patients with severe malaria. Lactic acidosis causes physiological adverse effects, which can... (Review)
Review
Lactic acidosis and hyperlactatemia are common metabolic disturbances in patients with severe malaria. Lactic acidosis causes physiological adverse effects, which can aggravate the outcome of malaria. Despite its clear association with mortality in malaria patients, the etiology of lactic acidosis is not completely understood. In this review, the possible contributors to lactic acidosis and hyperlactatemia in patients with malaria are discussed. Both increased lactate production and impaired lactate clearance may play a role in the pathogenesis of lactic acidosis. The increased lactate production is caused by several factors, including the metabolism of intraerythrocytic Plasmodium parasites, aerobic glycolysis by activated immune cells, and an increase in anaerobic glycolysis in hypoxic cells and tissues as a consequence of parasite sequestration and anemia. Impaired hepatic and renal lactate clearance, caused by underlying liver and kidney disease, might further aggravate hyperlactatemia. Multiple factors thus participate in the etiology of lactic acidosis in malaria, and further investigations are required to fully understand their relative contributions and the consequences of this major metabolic disturbance.
Topics: Acidosis, Lactic; Humans; Malaria; Plasmodium
PubMed: 33411818
DOI: 10.1371/journal.ppat.1009122 -
Clinical Journal of the American... Feb 2021
Topics: Acidosis; Ammonium Compounds; Animals; Bicarbonates; Citric Acid; Disease Progression; Humans; Hydrogen-Ion Concentration; Renal Insufficiency, Chronic
PubMed: 32769096
DOI: 10.2215/CJN.07990520 -
Cells May 2021Many invasive cancers emerge through a years-long process of somatic evolution, characterized by an accumulation of heritable genetic and epigenetic changes and the... (Review)
Review
Many invasive cancers emerge through a years-long process of somatic evolution, characterized by an accumulation of heritable genetic and epigenetic changes and the emergence of increasingly aggressive clonal populations. In solid tumors, such as breast ductal carcinoma, the extracellular environment for cells within the nascent tumor is harsh and imposes different types of stress on cells, such as hypoxia, nutrient deprivation, and cytokine inflammation. Acidosis is a constant stressor of most cancer cells due to its production through fermentation of glucose to lactic acid in hypoxic or normoxic regions (Warburg effect). Over a short period of time, acid stress can have a profound effect on the function of lysosomes within the cells exposed to this environment, and after long term exposure, lysosomal function of the cancer cells can become completely dysregulated. Whether this dysregulation is due to an epigenetic change or evolutionary selection has yet to be determined, but understanding the mechanisms behind this dysregulation could identify therapeutic opportunities.
Topics: Acidosis; Animals; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Ductal, Breast; Energy Metabolism; Female; Humans; Hydrogen-Ion Concentration; Lysosomes; Molecular Targeted Therapy; Tumor Microenvironment; Warburg Effect, Oncologic
PubMed: 34067971
DOI: 10.3390/cells10051188 -
Seminars in Nephrology Mar 2023Metabolic acidosis is a common complication in patients with chronic kidney disease that occurs when the daily nonvolatile acid load produced in metabolism cannot be... (Review)
Review
Metabolic acidosis is a common complication in patients with chronic kidney disease that occurs when the daily nonvolatile acid load produced in metabolism cannot be excreted fully by the kidney. A reduction in urine net acid excretion coupled with a high nonvolatile acid load may play a role in its pathogenesis. Diet is important in generation of the nonvolatile acid load. Acids are produced from metabolism of dietary protein and from the endogenous production of organic anions from neutral precursors. Acids can be balanced by alkali precursors ingested in the diet in the form of combustible organic anions. These typically are reflected indirectly by the excess of mineral cations to mineral anions in a food or diet. These principles underscore widely used methods to estimate the nonvolatile acid load from dietary intake using formulas such as the net endogenous acid production equation and the potential renal acid load equation. Empiric data largely validate these paradigms with high net endogenous acid production and potential renal acid load contributed by foods such as protein, grains, and dairy, and low net endogenous acid production and potential renal acid load contributed by fruits and vegetables along with corresponding dietary patterns. Although further studies are needed to understand the health benefits of altering nonvolatile acid load via diet, this review provides a detailed assessment on our current understanding of the role of diet in chronic kidney disease-related acidosis, providing an updated resource for researchers and clinicians.
Topics: Humans; Diet; Renal Insufficiency, Chronic; Acidosis; Acid-Base Equilibrium; Anions; Minerals
PubMed: 37898028
DOI: 10.1016/j.semnephrol.2023.151425 -
Cellular and Molecular Life Sciences :... Mar 2020Crystallins were firstly found as structural proteins of the eye lens. To this family belong proteins, such as ζ-crystallin, expressed ubiquitously, and endowed with... (Review)
Review
Crystallins were firstly found as structural proteins of the eye lens. To this family belong proteins, such as ζ-crystallin, expressed ubiquitously, and endowed with enzyme activity. ζ-crystallin is a moonlighting protein endowed with two main different functions: (1) mRNA binding with stabilizing activity; (2) NADPH:quinone oxidoreductase. ζ-crystallin has been clearly demonstrated to stabilize mRNAs encoding proteins involved in renal glutamine catabolism during metabolic acidosis resulting in ammoniagenesis and bicarbonate ion production that concur to compensate such condition. ζ-crystallin binds also mRNAs encoding for antiapoptotic proteins, such as Bcl-2 in leukemia cells. On the other hand, the physiological role of its enzymatic activity is still elusive. Gathering research evidences and data mined from public databases, we provide a framework where all the known ζ-crystallin properties are called into question, making it a hypothetical pivotal player in cancer, allowing cells to hijack or subjugate the acidity response mechanism to increase their ability to resist oxidative stress and apoptosis, while fueling their glutamine addicted metabolism.
Topics: Acidosis; Ammonia; Animals; Apoptosis; Glutamine; Humans; Neoplasms; Oxidative Stress; Protein Binding; RNA, Messenger; zeta-Crystallins
PubMed: 31563996
DOI: 10.1007/s00018-019-03301-3 -
European Journal of Medical Research May 2024The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO (mmHg), sO (%) and cHb (g/dl) is a diagnostic tool for several... (Review)
Review
The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO (mmHg), sO (%) and cHb (g/dl) is a diagnostic tool for several in vivo events, e.g., mortality after multiple trauma or shock, acidosis, bleeding, clotting, artificial ventilation. In everyday clinical practice a few microlitres of blood (arterial, mixed venous or venous) are sufficient for optimal diagnostics of any metabolic acidosis or alkalosis.The same applies to a therapeutic tool-then referred to as potential base excess (BEpot)-for several in vitro assessments, e.g., solutions for infusion, sodium bicarbonate, blood products, packed red blood cells, plasma. Thus, BE or BEpot has been a parameter with exceptional clinical significance since 2007.
Topics: Humans; Acidosis; Acid-Base Imbalance; Acid-Base Equilibrium; Alkalosis
PubMed: 38735983
DOI: 10.1186/s40001-024-01796-6