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American Journal of Physiology. Renal... Sep 2023The urinary potassium (K) excretion machinery is upregulated with increasing dietary K, but the role of accompanying dietary anions remains inadequately characterized....
The urinary potassium (K) excretion machinery is upregulated with increasing dietary K, but the role of accompanying dietary anions remains inadequately characterized. Poorly absorbable anions, including [Formula: see text], are thought to increase K secretion through a transepithelial voltage effect. Here, we tested if they also influence the K secretion machinery. Wild-type mice, aldosterone synthase (AS) knockout (KO) mice, or pendrin KO mice were randomized to control, high-KCl, or high-KHCO diets. The K secretory capacity was assessed in balance experiments. Protein abundance, modification, and localization of K-secretory transporters were evaluated by Western blot analysis and confocal microscopy. Feeding the high-KHCO diet increased urinary K excretion and the transtubular K gradient significantly more than the high-KCl diet, coincident with more pronounced upregulation of epithelial Na+ channels (ENaC) and renal outer medullary K (ROMK) channels and apical localization in the distal nephron. Experiments in AS KO mice revealed that the enhanced effects of [Formula: see text] were aldosterone independent. The high-KHCO diet also uniquely increased the large-conductance Ca-activated K (BK) channel β-subunit, stabilizing BKα on the apical membrane, the Cl/[Formula: see text] exchanger, pendrin, and the apical KCl cotransporter (KCC3a), all of which are expressed specifically in pendrin-positive intercalated cells. Experiments in pendrin KO mice revealed that pendrin was required to increase K excretion with the high-KHCO diet. In summary, [Formula: see text] stimulates K excretion beyond a poorly absorbable anion effect, upregulating ENaC and ROMK in principal cells and BK, pendrin, and KCC3a in pendrin-positive intercalated cells. The adaptive mechanism prevents hyperkalemia and alkalosis with the consumption of alkaline ash-rich diets but may drive K wasting and hypokalemia in alkalosis. Dietary anions profoundly impact K homeostasis. Here, we found that a K-rich diet, containing [Formula: see text] as the counteranion, enhances the electrogenic K excretory machinery, epithelial Na channels, and renal outer medullary K channels, much more than a high-KCl diet. It also uniquely induces KCC3a and pendrin, in B-intercalated cells, providing an electroneutral KHCO secretion pathway. These findings reveal new K balance mechanisms that drive adaption to alkaline and K-rich foods, which should guide new treatment strategies for K disorders.
Topics: Animals; Mice; Alkalosis; Anion Transport Proteins; Anions; Diet; Mice, Knockout; Potassium; Potassium, Dietary; Sodium; Sulfate Transporters
PubMed: 37498547
DOI: 10.1152/ajprenal.00193.2023 -
Endocrinologia Y Nutricion : Organo de... Feb 2015Hyperchloremic metabolic acidosis is a complication of urinary diversion using ileum or colon. Its prevalence ranges from 25% and 46% depending on the procedure used and... (Review)
Review
Hyperchloremic metabolic acidosis is a complication of urinary diversion using ileum or colon. Its prevalence ranges from 25% and 46% depending on the procedure used and renal function of the patient. It is a consequence of intestinal fluid and electrolyte exchange between intestinal mucosa and urine. The main mechanism is absorption of ammonium and chloride from urine. Long-term chronic metabolic acidosis in these patients may lead to impaired bone metabolism and osteomalacia. Regular monitoring of pH, chlorine, bicarbonate, and calcium-phosphorus metabolism is therefore essential for early diagnosis and treatment.
Topics: Acidosis; Alkalosis; Bicarbonates; Bone Diseases, Metabolic; Calcium; Chlorides; Colon; Gastric Mucosa; Humans; Hypokalemia; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; Osteomalacia; Phosphorus; Postoperative Complications; Stomach; Urinary Diversion
PubMed: 25481805
DOI: 10.1016/j.endonu.2014.10.007 -
Journal of Clinical Medicine Apr 2022Our aim was to investigate the distribution of acid-base disorders in patients with COVID-19 ARDS using both the Henderson-Hasselbalch and Stewart's approach and to...
Our aim was to investigate the distribution of acid-base disorders in patients with COVID-19 ARDS using both the Henderson-Hasselbalch and Stewart's approach and to explore if hypoxemia can influence acid-base disorders. COVID-19 ARDS patients, within the first 48 h of the need for a non-invasive respiratory support, were retrospectively enrolled. Respiratory support was provided by helmet continuous positive airway pressure (CPAP) or by non-invasive ventilation. One hundred and four patients were enrolled, 84% treated with CPAP and 16% with non-invasive ventilation. Using the Henderson-Hasselbalch approach, 40% and 32% of patients presented respiratory and metabolic alkalosis, respectively; 13% did not present acid-base disorders. Using Stewart's approach, 43% and 33% had a respiratory and metabolic alkalosis, respectively; 12% of patients had a mixed disorder characterized by normal pH with a lower SID. The severe hypoxemic and moderate hypoxemic group presented similar frequencies of respiratory and metabolic alkalosis. The most frequent acid-base disorders were respiratory and metabolic alkalosis using both the Henderson-Hasselbalch and Stewart's approach. Stewart's approach detected mixed disorders with a normal pH probably generated by the combined effect of strong ions and weak acids. The impairment of oxygenation did not affect acid-base disorders.
PubMed: 35456186
DOI: 10.3390/jcm11082093 -
Advances in Experimental Medicine and... 2016Hypoxia, depending upon its magnitude and circumstances, evokes a spectrum of mild to severe acid-base changes ranging from alkalosis to acidosis, which can alter many... (Review)
Review
Hypoxia, depending upon its magnitude and circumstances, evokes a spectrum of mild to severe acid-base changes ranging from alkalosis to acidosis, which can alter many responses to hypoxia at both non-genomic and genomic levels, in part via altered hypoxia-inducible factor (HIF) metabolism. Healthy people at high altitude and persons hyperventilating to non-hypoxic stimuli can become alkalotic and alkalemic with arterial pH acutely rising as high as 7.7. Hypoxia-mediated respiratory alkalosis reduces sympathetic tone, blunts hypoxic pulmonary vasoconstriction and hypoxic cerebral vasodilation, and increases hemoglobin oxygen affinity. These effects and others can be salutary or counterproductive to tissue oxygen delivery and utilization, based upon magnitude of each effect and summation. With severe hypoxia either in the setting of profound arterial hemoglobin desaturation and reduced O2 content or poor perfusion (ischemia) at the global or local level, metabolic and hypercapnic acidosis develop along with considerable lactate formation and pH falling to below 6.8. Although conventionally considered to be injurious and deleterious to cell function and survival, both acidoses may be cytoprotective by various anti-inflammatory, antioxidant, and anti-apoptotic mechanisms which limit total hypoxic or ischemic-reperfusion injury. Attempts to correct acidosis by giving bicarbonate or other alkaline agents under these circumstances ahead of or concurrent with reoxygenation efforts may be ill advised. Better understanding of this so-called "pH paradox" or permissive acidosis may offer therapeutic possibilities. Rapidly growing cancers often outstrip their vascular supply compromising both oxygen and nutrient delivery and metabolic waste disposal, thus limiting their growth and metastatic potential. However, their excessive glycolysis and lactate formation may not necessarily represent oxygen insufficiency, but rather the Warburg effect-an attempt to provide a large amount of small carbon intermediates to supply the many synthetic pathways of proliferative cell growth. In either case, there is expression and upregulation of many genes involved in acid-base homeostasis, in part by HIF-1 signaling. These include a unique isoform of carbonic anhydrase (CA-IX) and numerous membrane acid-base transporters engaged to maintain an optimal intracellular and extracellular pH for maximal growth. Inhibition of these proteins or gene suppression may have important therapeutic application in cancer chemotherapy.
Topics: Acidosis; Acids; Alkalies; Altitude; Exercise; Humans; Hypoxia; Neoplasms
PubMed: 27343105
DOI: 10.1007/978-1-4899-7678-9_21 -
International Urology and Nephrology Jan 2018Chronic hepatic patients, and particularly those suffering from cirrhosis, are predisposed to different sort of water, electrolyte, acid-base, and trace elements... (Review)
Review
Chronic hepatic patients, and particularly those suffering from cirrhosis, are predisposed to different sort of water, electrolyte, acid-base, and trace elements disorders due to their altered liver function, and also to their exposition to infectious, inflammatory, oncologic, and pharmacologic variables whose combination undermines their homeostatic capability. Hyponatremia, hypokalemia, hyperkalemia, hypocalcemia, metabolic acidosis, respiratory, and metabolic alkalosis are the main internal milieu alterations in this group.
Topics: Acid-Base Imbalance; Acidosis; Alkalosis; Humans; Hyperkalemia; Hypernatremia; Hypokalemia; Hyponatremia; Liver Cirrhosis; Magnesium; Sodium; Trace Elements; Water-Electrolyte Imbalance
PubMed: 28608260
DOI: 10.1007/s11255-017-1614-y -
The International Journal of Eating... Mar 2016Eating disorders that are associated with purging behaviors are complicated by frequent blood electrolyte and acid-base abnormalities. Herein, we review the major... (Review)
Review
OBJECTIVE
Eating disorders that are associated with purging behaviors are complicated by frequent blood electrolyte and acid-base abnormalities. Herein, we review the major electrolyte and acid-base abnormalities and their treatment methods. The body of rigorous, eating disorder-specific literature on this topical area is not robust enough to perform a systematic review as defined by PRISMA guidelines. Therefore, a qualitative review of mostly medical literature was conducted.
RESULTS
Hypokalemia, hyponatremia, and sodium chloride-responsive metabolic alkalosis are the most common serum changes that occur as a result of purging behaviors. They vary depending on the mode and frequency of purging behaviors. They can all potentially cause dangerous medical complications and are in need of definitive medical treatment.
DISCUSSION
Eating disorders that are associated with purging behaviors are associated with a number of electrolyte and acid-base changes which are complex in their origin, documented to be medically dangerous and this definitive treatment is necessary to help achieve a successful treatment outcome, and in need of definitive treatment as described herein.
Topics: Alkalosis; Electrolytes; Feeding and Eating Disorders; Humans; Hypokalemia; Hyponatremia
PubMed: 26876281
DOI: 10.1002/eat.22503 -
Kidney Diseases (Basel, Switzerland) Dec 2017Kidneys play a pivotal role in the maintenance and regulation of acid-base and electrolyte homeostasis, which is the prerequisite for numerous metabolic processes and... (Review)
Review
Kidneys play a pivotal role in the maintenance and regulation of acid-base and electrolyte homeostasis, which is the prerequisite for numerous metabolic processes and organ functions in the human body. Chronic kidney diseases compromise the regulatory functions, resulting in alterations in electrolyte and acid-base balance that can be life-threatening. In this review, we discuss the renal regulations of electrolyte and acid-base balance and several common disorders including metabolic acidosis, alkalosis, dysnatremia, dyskalemia, and dysmagnesemia. Common disorders in chronic kidney disease are also discussed. The most recent and relevant advances on pathophysiology, clinical characteristics, diagnosis, and management of these conditions have been incorporated.
PubMed: 29344508
DOI: 10.1159/000479968 -
Cureus Jun 2023Primary hyperaldosteronism typically leads to resistant hypertension, hypokalemia, and metabolic alkalosis. Excess aldosterone secretion by the adrenal glands may lead...
Primary hyperaldosteronism typically leads to resistant hypertension, hypokalemia, and metabolic alkalosis. Excess aldosterone secretion by the adrenal glands may lead to heart failure with preserved ejection fraction. Potassium-sparing diuretics and aldosterone antagonists directed to lower excess aldosterone levels may help treat the associated heart failure and lead to control of blood pressure, resulting in improved outcomes. We report a case of a 55-year-old male with poorly controlled hypertension and newly symptomatic heart failure with preserved ejection fraction in the setting of excess aldosterone activity and an adrenal adenoma suggesting primary aldosteronism-induced diastolic heart failure. The biochemical evaluation revealed elevated plasma aldosterone concentrations with low plasma renin activity, diuretic-induced hypokalemia, and metabolic alkalosis. A progressively enlarging left adrenal adenoma was found on abdominal imaging along with resistant hypertension despite the use of multiple antihypertensive medications. Medical management targeted to lower excess aldosterone levels with the use of aldosterone antagonists helped us achieve better blood pressure control and resolution of symptoms of diastolic dysfunction. Treating the underlying pathology helped us improve overt heart failure and may suggest that goal-directed therapy towards the inciting factors may potentially lead to a path to reverse the heart failure symptoms clinically.
PubMed: 37485117
DOI: 10.7759/cureus.40753 -
Pediatric Nephrology (Berlin, Germany) Aug 2022Acid-base balance is maintained by kidney excretion of titratable acids and bicarbonate reabsorption. Metabolic alkalosis is uncommon in dialysis-treated patients. The...
BACKGROUND
Acid-base balance is maintained by kidney excretion of titratable acids and bicarbonate reabsorption. Metabolic alkalosis is uncommon in dialysis-treated patients. The aim of this retrospective study was to assess the rate of metabolic alkalosis in pediatric patients treated with peritoneal dialysis.
METHODS
Medical records of children treated with peritoneal dialysis in Shaare Zedek Medical Center from January 2000 to June 2021 were reviewed and compared with young adults currently treated with peritoneal dialysis. Demographic, clinical, and peritoneal dialysis characteristics were extracted from the medical records.
RESULTS
Thirty chronic peritoneal dialysis patients were included in our study, seven under 2 years, 13 between 2 and 18 years, and 10 adults. 90.3% of the measurements in infants showed metabolic alkalosis compared to 32.3% in the 2-18-year group and none in the adult group. Higher size-adjusted daily exchange volume, lack of urine output, and high lactate-containing dialysate were associated with metabolic alkalosis. Alkalosis was not explained by vomiting, diuretic therapy, or carbonate-containing medications. High transport membrane, low dietary protein, and malnutrition, all previously reported explanations for metabolic alkalosis, were not found in our study.
CONCLUSIONS
Metabolic alkalosis is common in infants treated with peritoneal dialysis as opposed to older children and adults. High lactate-containing dialysate is a possible explanation. Higher size-adjusted daily dialysate exchange volume, which may reflect higher bicarbonate absorption, is another independent predictor of alkalosis. Acid-base status should be closely followed in infants, and using a dialysis solution with lower bicarbonate or lactate level should be considered. A higher resolution version of the graphical abstract is available as Supplementary Information.
Topics: Adolescent; Alkalosis; Bicarbonates; Child; Dialysis Solutions; Humans; Infant; Lactic Acid; Peritoneal Dialysis; Renal Dialysis; Retrospective Studies
PubMed: 35039929
DOI: 10.1007/s00467-021-05344-w -
Pediatrics International : Official... Apr 2020Bartter syndrome (BS) and Gitelman syndrome (GS) are syndromes associated with congenital tubular dysfunction, characterized by hypokalemia and metabolic alkalosis.... (Review)
Review
Bartter syndrome (BS) and Gitelman syndrome (GS) are syndromes associated with congenital tubular dysfunction, characterized by hypokalemia and metabolic alkalosis. Clinically, BS is classified into two types: the severe antenatal/neonatal type, which develops during the fetal period with polyhydramnios and preterm delivery; and the relatively mild classic type, which is usually found during infancy with failure to thrive. GS can be clinically differentiated from BS by its age at onset, usually after school age, or laboratory findings of hypomagnesemia and hypocalciuria. Recent advances in molecular biology have shown that these diseases can be genetically classified into type 1 to 5 BS and GS. As a result, it has become clear that the clinical classification of antenatal/neonatal BS, classic BS, and GS does not always correspond to the clinical symptoms associated with the genotypes in a one-to-one manner; and there is clinically no clear differential border between type 3 BS and GS. This has caused confusion among clinicians in the diagnosis of these diseases. It has been proposed that the disease name "inherited salt-losing tubulopathy" can be used for cases of tubulopathies accompanied by hypokalemia and metabolic alkalosis. It is reasonable to use this term prior to genetic typing into type 1-5 BS or GS, to avoid confusion in a clinical setting. In this article, we review causative genes and phenotypic correlations, diagnosis, and treatment strategies for salt-losing tubulopathy as well as the clinical characteristics of pseudo-BS/GS, which can also be called a "salt-losing disorder".
Topics: Alkalosis; Bartter Syndrome; Female; Genotype; Gitelman Syndrome; Hearing Loss, Sensorineural; Humans; Hypokalemia; Male; Phenotype; Pregnancy; Salts; Solute Carrier Family 12, Member 1
PubMed: 31830341
DOI: 10.1111/ped.14089