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American Journal of Physiology. Renal... Nov 2018To better understand the role of the inward-rectifying K channel Kir4.1 (KCNJ10) in the distal nephron, we initially studied a global Kir4.1 knockout mouse (gKO), which...
To better understand the role of the inward-rectifying K channel Kir4.1 (KCNJ10) in the distal nephron, we initially studied a global Kir4.1 knockout mouse (gKO), which demonstrated the hypokalemia and hypomagnesemia seen in SeSAME/EAST syndrome and was associated with reduced Na/Cl cotransporter (NCC) expression. Lethality by ~3 wk, however, limits the usefulness of this model, so we developed a kidney-specific Kir4.1 "knockdown" mouse (ksKD) using a cadherin 16 promoter and Cre-loxP methodology. These mice appeared normal and survived to adulthood. Kir4.1 protein expression was decreased ~50% vs. wild-type (WT) mice by immunoblotting, and immunofluorescence showed moderately reduced Kir4.1 staining in distal convoluted tubule that was minimal or absent in connecting tubule and cortical collecting duct. Under control conditions, the ksKD mice showed metabolic alkalosis and relative hypercalcemia but were normokalemic and mildly hypermagnesemic despite decreased NCC expression. In addition, the mice had a severe urinary concentrating defect associated with hypernatremia, enlarged kidneys with tubulocystic dilations, and reduced aquaporin-3 expression. On a K/Mg-free diet for 1 wk, however, ksKD mice showed marked hypokalemia (serum K: 1.5 ± 0.1 vs. 3.0 ± 0.1 mEq/l for WT), which was associated with renal K wasting (transtubular K gradient: 11.4 ± 0.8 vs. 1.6 ± 0.4 in WT). Phosphorylated-NCC expression increased in WT but not ksKD mice on the K/Mg-free diet, suggesting that loss of NCC adaptation underlies the hypokalemia. In conclusion, even modest reduction in Kir4.1 expression results in impaired K conservation, which appears to be mediated by reduced expression of activated NCC.
Topics: Alkalosis; Animals; Aquaporin 3; Gene Knockdown Techniques; Genotype; Hypercalcemia; Hyperkalemia; Hypernatremia; Kidney Concentrating Ability; Mice, Inbred C57BL; Mice, Knockout; Nephrons; Phenotype; Phosphorylation; Potassium Channels, Inwardly Rectifying; Potassium, Dietary; Renal Reabsorption; Solute Carrier Family 12, Member 3
PubMed: 30110571
DOI: 10.1152/ajprenal.00022.2018 -
The Biochemical Journal Apr 1997Modulation by alkalosis of basal leak Ca2+ entry and store-depletion-induced Ca2+ entry was investigated in the vascular endothelial cell line ECV 304. Ca2+ entry was...
Modulation by alkalosis of basal leak Ca2+ entry and store-depletion-induced Ca2+ entry was investigated in the vascular endothelial cell line ECV 304. Ca2+ entry was monitored as the increase in the intracellular free Ca2+ concentration ([Ca2+]i) induced by elevation of the extracellular Ca2+ concentration. When ECV 304 cells were challenged with 100 nM thapsigargin in nominally Ca2+-free solution, [Ca2+]i increased transiently, and the increase in [Ca2+]i during a subsequent cumulative elevation of extracellular Ca2+ (from nominally Ca2+-free up to 5 mM) was markedly enhanced compared with non-stimulated cells (i.e. basal Ca2+ leak). Prolonged elevation of the extracellular pH (pHo) from 7.4 to 7.9 did not affect resting [Ca2+]i or the thapsigargin-induced [Ca2+]i transient evoked in nominally Ca2+-free solution, but increased leak Ca2+ entry as well as store-depletion-activated Ca2+ entry significantly. Basal Ca2+ leak and store-depletion-activated Ca2+ entry were enhanced either by acute elevation of pHo from 7.4 to 7.9 or by chronic alkalosis (pHo=7.9). Stimulation of Ca2+ entry by extracellular alkalosis was observed both in normal and in high extracellular K+ (110 mM) solution, suggesting that the effects of alkalosis are independent of membrane potential. The intracellular pH (pHi) increased slightly during both acute and chronic extracellular alkalosis (from 7.22+/-0.01 to 7.37+/-0.04 and 7. 45+/-0.05 respectively). Elevation of pHi to 7.60+/-0.06 at constant pHo by administration of 20 mM NH4Cl failed to stimulate, and in fact inhibited, store-depletion-activated Ca2+ entry. Our results demonstrate that a decrease in the extracellular but not the intracellular proton concentration promotes both basal and stimulated Ca2+ entry into endothelial cells.
Topics: Alkalosis; Ammonium Chloride; Animals; Calcium; Cells, Cultured; Endothelium, Vascular; Hydrogen-Ion Concentration; Potassium
PubMed: 9163353
DOI: 10.1042/bj3230567 -
The Journal of Veterinary Medical... Jun 1997Values of blood gas, serum chloride, and potassium were tabulated for 21 dairy cows with coliform mastitis. Severe cases showed marked clinical signs such as loss of...
Values of blood gas, serum chloride, and potassium were tabulated for 21 dairy cows with coliform mastitis. Severe cases showed marked clinical signs such as loss of appetite and depression of digestive tract motility, and metabolic alkalosis such as an increase in blood pH, hypochloremia and hypokalemia compared with normal and mild cases (p < 0.01). The results showed that metabolic alkalosis can be detected more easily than acidosis in cases of severe coliform mastitis.
Topics: Alkalosis; Animals; Blood Gas Analysis; Cattle; Cattle Diseases; Escherichia coli; Female; Klebsiella; Mastitis, Bovine; Potassium; Sodium Chloride
PubMed: 9234224
DOI: 10.1292/jvms.59.471 -
Scientific Reports Sep 2017The control of pre-analytical-factors in human biospecimens collected for health research is currently required. Only two previous reports using post-mortem brain...
The control of pre-analytical-factors in human biospecimens collected for health research is currently required. Only two previous reports using post-mortem brain samples have tried to address the impact of cold-ischemia on tissue pH. Here we report pH variations according to time (third-order polynomial model) in mice for liver, kidney and lung samples. Tissue alkalosis in cold-ischemia time may be an underlying mechanism of gene expression changes. Therefore, tissue-pH regulation after organ removal may minimize biological stress in human tissue samples.
Topics: Alkalosis; Animals; Cold Temperature; Female; Hydrogen-Ion Concentration; Ischemia; Kidney; Liver; Lung; Male; Mice; Time Factors
PubMed: 28883635
DOI: 10.1038/s41598-017-11284-z -
Anesthesiology Jan 2021
Topics: Acid-Base Equilibrium; Acidosis; Alkalosis; Altitude; Blood Gas Analysis; Carbon Dioxide; Female; Humans; Hydrogen-Ion Concentration; Male; Pulmonary Disease, Chronic Obstructive
PubMed: 33016980
DOI: 10.1097/ALN.0000000000003581 -
British Journal of Anaesthesia Jun 2016
Topics: Alkalosis; Bartter Syndrome; Gitelman Syndrome; Humans; Hyponatremia; Perioperative Care; Practice Guidelines as Topic
PubMed: 27199308
DOI: 10.1093/bja/aew102 -
Renal Failure Nov 2020This study aims to delineate the incidence of electrolyte and acid-base disorders (EAD) in cancer patients, to figure out the risk factors of EAD, then to assess the...
This study aims to delineate the incidence of electrolyte and acid-base disorders (EAD) in cancer patients, to figure out the risk factors of EAD, then to assess the impact of EAD on patients' in-hospital clinical outcomes. Patients with the diagnosis of malignancies hospitalized during 1 October 2014 and 30 September 2015 were recruited in Zhongshan Hospital, Fudan University in Shanghai of China. Demographic characteristics, comorbidities, and clinical data, including survival, length of stay and hospital cost, were extracted from the electronic medical record system. Electrolyte and acid-base data were acquired from the hospital laboratory database. Of 25,881 cancer patients with electrolyte data, 15,000 (58.0%) cases had at least one electrolyte and acid-base abnormity. Hypocalcemia (27.8%) was the most common electrolyte disorder, followed by hypophosphatemia (26.7%), hypochloremia (24.5%) and hyponatremia (22.5%). The incidence of simple metabolic acidosis (MAC) and metabolic alkalosis (MAL) was 12.8% and 22.1% respectively. Patients with mixed metabolic acid-base disorders (MAC + MAL) accounted for 30.2%. Lower BMI score, preexisting hypertension and diabetes, renal dysfunction, receiving surgery/chemotherapy, anemia and hypoalbuminemia were screened out as the major risk factors of EAD. In-hospital mortality in patients with EAD was 2.1% as compared to those with normal electrolytes (0.3%). The risk of death significantly increased among patients with severe EAD. Similarly, the length of stay and hospital cost also tripled as the number and grade of EAD increased. EAD is commonly encountered in cancer patients and associated with an ominous prognosis. Patients with comorbidities, renal/liver dysfunction, and anti-tumor therapy have a higher risk of EAD. Regular monitoring of electrolytes, optimum regimen for intravenous infusion, timely correction of modifiable factors and appropriate management of EAD should not be neglected during anti-tumor treatment.
Topics: Acid-Base Imbalance; Acidosis; Aged; Alkalosis; China; Female; Hospital Costs; Hospital Mortality; Humans; Hyperkalemia; Hypernatremia; Hypocalcemia; Hypokalemia; Hyponatremia; Hypophosphatemia; Length of Stay; Male; Middle Aged; Neoplasms; Retrospective Studies; Risk Factors; Survival Analysis; Water-Electrolyte Imbalance
PubMed: 32138574
DOI: 10.1080/0886022X.2020.1735417 -
Kidney International May 1972
Review
Topics: Alkalosis; Ammonia; Animals; Bicarbonates; Diarrhea; Diet, Sodium-Restricted; Diuretics; Extracellular Space; Gastric Lavage; Glomerular Filtration Rate; Humans; Hydrocortisone; Hydrogen; Ions; Kidney Tubules; Nephrons; Potassium; Sodium; Sodium Chloride; Vomiting
PubMed: 4600132
DOI: 10.1038/ki.1972.43 -
Proceedings of the National Academy of... Feb 2022The 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...
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 HCO into the urine leads to metabolic alkalosis [P. Berg et al., 31, 1711-1727 (2020); F. Al-Ghimlas, M. E. Faughnan, E. Tullis, 6, 59-62 (2012)]. This is caused by defective HCO secretion in the β-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., 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.
Topics: Acid-Base Equilibrium; Alkalosis; Animals; Bicarbonates; Chloride-Bicarbonate Antiporters; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Disease Models, Animal; Female; Hypoventilation; Ion Transport; Kidney; Lung; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Renal Elimination; Renal Reabsorption
PubMed: 35173044
DOI: 10.1073/pnas.2116836119 -
Physiological Reports Oct 2019To compare the effect of 500 mg·kg body mass (BM) sodium citrate ingested in solution or capsules on induced alkalosis, gastrointestinal symptoms and palatability.... (Randomized Controlled Trial)
Randomized Controlled Trial
To compare the effect of 500 mg·kg body mass (BM) sodium citrate ingested in solution or capsules on induced alkalosis, gastrointestinal symptoms and palatability. Twenty-four healthy and active participants completed two testing sessions, ingesting 500 mg·kg BM sodium citrate within solution or capsules. Capillary blood samples were collected pre-ingestion, and every 30-min for 240-min post-ingestion; samples were analyzed for blood pH and [HCO ]. A validated questionnaire was used to quantify gastrointestinal symptoms at the same 30-min intervals. Palatability was quantified immediately after ingestion using a validated scale. There was a greater peak and change from baseline for capsules versus solution for blood pH (P < 0.001) and [HCO ] (P = 0.013). Blood pH and [HCO ] time to peak was 199 and 204 min, respectively, after capsule ingestion, both significantly later than after solution (P = 0.034, P = 0.001). Gastrointestinal symptoms were significantly elevated above baseline for both ingestion modes at each time point between 30 and 120 min after ingestion (P = 0.003), with no differences between modes at any time point (P = 0.644). Capsules were significantly more palatable than solution (P < 0.001). We recommend 500 mg·kg BM sodium citrate ingestion in capsules, at least 200 min before exercise, to achieve greater alkalosis, minimize gastrointestinal symptoms, and maximize.
Topics: Alkalosis; Capsules; Cross-Over Studies; Dietary Supplements; Female; Gastrointestinal Tract; Humans; Male; Sodium Citrate; Taste; Young Adult
PubMed: 31602822
DOI: 10.14814/phy2.14216