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Electrolyte & Blood Pressure : E & BP Dec 2023Pseudo-Bartter syndrome is a well-known differential diagnosis that needs to be excluded in cases of normotensive hypokalemic metabolic alkalosis. Pseudo-Bartter...
Pseudo-Bartter syndrome is a well-known differential diagnosis that needs to be excluded in cases of normotensive hypokalemic metabolic alkalosis. Pseudo-Bartter syndrome and pseudo-Gitelman syndrome are often collectively referred to as pseudo-Bartter/Gitelman syndrome; however, pseudo-Gitelman syndrome should be considered as a separate entity because Gitelman syndrome is characterized by hypocalciuria and hypomagnesemia, while Bartter syndrome is usually associated with hypercalciuria. Herein, we report the cases of two young adult female patients who presented with severe hypokalemic metabolic alkalosis, hypocalciuria, and hypomagnesemia. Diuretic or laxative abuse and self-induced vomiting were absent, and a chloride deficit and remarkable bicarbonaturia were observed. Initial sequencing studies for , , and revealed no mutations, and whole-exome sequencing revealed no pathogenic variants. The metabolic alkalosis was saline-responsive in one case, and steroid therapy was necessary in the other to relieve chronic tubulointerstitial nephritis, which was diagnosed with kidney biopsy. A new category of pseudo-Gitelman syndrome should be defined, and various etiologies should be investigated.
PubMed: 38152600
DOI: 10.5049/EBP.2023.21.2.72 -
Journal of Animal Physiology and Animal... May 2024The effects of heat stress (HS) caused by high temperatures continue to be a global concern in poultry production. Poultry birds are homoeothermic, however, modern-day... (Review)
Review
The effects of heat stress (HS) caused by high temperatures continue to be a global concern in poultry production. Poultry birds are homoeothermic, however, modern-day chickens are highly susceptible to HS due to their inefficiency in dissipating heat from their body due to the lack of sweat glands. During HS, the heat load is higher than the chickens' ability to regulate it. This can disturb normal physiological functioning, affect metabolism and cause behavioural changes, respiratory alkalosis and immune dysregulation in birds. These adverse effects cause gut dysbiosis and, therefore, reduce nutrient absorption and energy metabolism. This consequently reduces production performances and causes economic losses. Several strategies have been explored to combat the effects of HS. These include environmentally controlled houses, provision of clean cold water, low stocking density, supplementation of appropriate feed additives, dual and restricted feeding regimes, early heat conditioning and genetic selection of poultry lines to produce heat-resistant birds. Despite all these efforts, HS still remains a challenge in the poultry sector. Therefore, there is a need to explore effective strategies to address this long-lasting problem. The most recent strategy to ameliorate HS in poultry is early perinatal programming using the in ovo technology. Such an approach seems particularly justified in broilers because chick embryo development (21 days) equals half of the chickens' posthatch lifespan (42 days). As such, this strategy is expected to be more efficient and cost-effective to mitigate the effects of HS on poultry and improve the performance and health of birds. Therefore, this review discusses the impact of HS on poultry, the advantages and limitations of the different strategies. Finally recommend a promising strategy that could be efficient in ameliorating the adverse effects of HS in poultry.
Topics: Animals; Animal Husbandry; Poultry Diseases; Heat-Shock Response; Heat Stress Disorders; Chickens; Hot Temperature; Poultry; Animal Feed
PubMed: 38152002
DOI: 10.1111/jpn.13916 -
Revista de La Facultad de Ciencias... Dec 2023Long COVID is a multi-organ pathology with important sequelae that affect the health and welfare of survivors from the cellular bioenergetics, in this case, the...
Long COVID is a multi-organ pathology with important sequelae that affect the health and welfare of survivors from the cellular bioenergetics, in this case, the importance of considering the acid-base balance within the processes of evaluation and treatment of long COVID by health and sports professionals was addressed, given that different investigations have found important modifications in mitochondrial function that result in ventilation failures, causing alterations in the compensation-decompensation of respiratory and renal pH control (metabolic-respiratory acidosis and alkalosis).
Topics: Humans; Acid-Base Equilibrium; Post-Acute COVID-19 Syndrome; COVID-19; Kidney
PubMed: 38150196
DOI: 10.31053/1853.0605.v80.n4.42580 -
Medical Journal, Armed Forces India Dec 2023Gitelman syndrome (GS) is a rare genetic renal disease characterized by hypomagnesemia, hypokalemia, hypocalciuria, and metabolic alkalosis. It usually presents in late...
Gitelman syndrome (GS) is a rare genetic renal disease characterized by hypomagnesemia, hypokalemia, hypocalciuria, and metabolic alkalosis. It usually presents in late childhood or early adulthood. A 30-year-old female diagnosed case of multidrug-resistant (MDR-TB) pulmonary tuberculosis 2 months ago presented to our outpatient department with intermittent painful spasms in all four limb muscles. Her treatment regimen consisted of kanamycin, levofloxacin, cycloserine, and ethionamide. On further evaluation, her investigations revealed hypokalemia, hypocalcemia, hypomagnesemia, metabolic alkalosis with normal serum creatinine level. She was initially treated with intravenous calcium and potassium. However, the electrolyte abnormalities and metabolic alkalosis persisted. All her lab parameters became normal after discontinuing kanamycin and electrolyte replacement for 4 weeks. She was discharged and advised to continue her antituberculosis treatment. There was no recurrence of symptoms on further follow up.
PubMed: 38144646
DOI: 10.1016/j.mjafi.2021.09.008 -
Current Issues in Molecular Biology Dec 2023The maintenance of plasma pH is critical for life in all organisms. The kidney plays a critical role in acid-base regulation in vertebrates by controlling the plasma...
The maintenance of plasma pH is critical for life in all organisms. The kidney plays a critical role in acid-base regulation in vertebrates by controlling the plasma concentration of bicarbonate. The receptor tyrosine kinase IRR (insulin receptor-related receptor) is expressed in renal β-intercalated cells and is involved in alkali sensing due to its ability to autophosphorylate under alkalization of extracellular medium (pH > 7.9). In mice with a knockout of the gene, which encodes for IRR, urinary bicarbonate secretion in response to alkali loading is impaired. The specific regulatory mechanisms in the kidney that are under the control of IRR remain unknown. To address this issue, we analyzed and compared the kidney transcriptomes of wild-type and knockout mice under basal or bicarbonate-loaded conditions. Transcriptomic analyses revealed a differential regulation of a number of genes in the kidney. Using TaqMan real-time PCR, we confirmed different expressions of the , , , , , , , , and genes in IRR knockout mice. Also, we found that the expression of the gene is increased in wild-type mice after bicarbonate loading but not in knockout mice. Gene set enrichment analysis between the IRR knockout and wild-type samples identified that knockout causes alterations in expression of genes related mostly to the ATP metabolic and electron transport chain processes.
PubMed: 38132452
DOI: 10.3390/cimb45120606 -
American Journal of Kidney Diseases :... Jan 2024
PubMed: 38129069
DOI: 10.1053/j.ajkd.2023.10.005 -
Intensive Care Medicine Experimental Dec 2023Clogging is characterized by a progressive impairment of transmembrane patency in renal replacement devices and occurs due to obstruction of pores by unknown molecules....
BACKGROUND
Clogging is characterized by a progressive impairment of transmembrane patency in renal replacement devices and occurs due to obstruction of pores by unknown molecules. If citrate-based anti-coagulation is used, clogging can manifest as a metabolic alkalosis accompanied by hypernatremia and hypercalcemia, primarily a consequence of NaCitrate infusion. An increased incidence of clogging has been observed during the COVID-19 pandemic. However, precise factors contributing to the formation remain uncertain. This investigation aimed to analyze its incidence and assessed time-varying trajectories of associated factors in critically ill patients on continuous renal replacement therapy (CRRT).
METHODS
In this retrospective, single-center data analysis, we evaluated COVID-19 patients undergoing CRRT and admitted to critical care between March 2020 and December 2021. We assessed the proportional incidence of clogging surrogates in the overall population and subgroups based on the specific CRRT devices employed at our institution, including multiFiltrate (Fresenius Medical Care) and Prismaflex System (Baxter). Moderate and severe clogging were defined as Na > 145 or ≥ 150 mmol/l and HCO > 28.0 or ≥ 30 mmol/l, respectively, with a total albumin-corrected calcium > 2.54 mmol/l. A mixed effect model was introduced to investigate factors associated with development of clogging.
RESULTS
Fifty-three patients with 240 CRRT runs were analyzed. Moderate and severe clogging occurred in 15% (8/53) and 19% (10/53) of patients, respectively. Twenty-seven percent (37/136) of CRRTs conducted with a multiFiltrate device met the criteria for clogging, whereas no clogging could be observed in patients dialyzed with the Prismaflex System. Occurrence of clogging was associated with elevated triglyceride plasma levels at filter start (p = 0.013), amount of enteral nutrition (p = 0.002) and an increasing white blood cell count over time (p = 0.002).
CONCLUSIONS
Clogging seems to be a frequently observed phenomenon in critically ill COVID-19 patients. The presence of hypertriglyceridemia, combined with systemic inflammation, may facilitate the development of an impermeable secondary membrane within filters, thereby contributing to compromised membrane patency.
PubMed: 38127207
DOI: 10.1186/s40635-023-00581-9 -
Cureus Nov 2023Paraneoplastic syndromes are rare and diverse conditions caused by either an abnormal chemical signaling molecule produced by tumor cells or a body's immune response...
Paraneoplastic syndromes are rare and diverse conditions caused by either an abnormal chemical signaling molecule produced by tumor cells or a body's immune response against the tumor itself. These syndromes can manifest in a variable, multisystemic and often nonspecific manner posing a diagnostic challenge. We report the case of an 81-year-old woman who exhibited severe hypokalemia, metabolic alkalosis, and worsening hyperglycemia. The investigation was consistent with adrenocorticotropin (ACTH)-dependent Cushing's syndrome and, eventually, the patient was diagnosed with stage IV primary small-cell lung cancer (SCLC). SCLC is known to be associated with paraneoplastic syndromes, including Cushing's syndrome caused by ectopic adrenocorticotropin (ACTH) secretion. Despite being associated with very poor outcomes, managing these syndromes can be challenging and may hold prognostic significance.
PubMed: 38125241
DOI: 10.7759/cureus.49124 -
Medicina 2023At the beginning of the SARS-CoV-2 pandemic, acute respiratory failure has been the most important cause of hospitalization in patients with COVID-19, being more severe...
INTRODUCTION
At the beginning of the SARS-CoV-2 pandemic, acute respiratory failure has been the most important cause of hospitalization in patients with COVID-19, being more severe in patients with comorbidities and risk factors. In these scenarios hypoxemia has been associated with increased mortality. Our objective was to identify parameters obtained from arterial blood gases (ABG) associated with mortality in patients with COVID-19 at hospital admission.
METHODS
GSA samples obtained by breathing room air (FiO2 21%) processed in the clinical laboratory were retrospectively studied in an ABL90 flex analyzer (Radiometer).
RESULTS
Acute respiratory alkalosis was the predominant acid-base disturbance. Considering those patients with respiratory failure (paO2 < 60 mmHg), "silent" hypoxemia was observed in 11/176 (6%) of studied patients. In a multivariate analysis, three gasometric parameters at admission showed a positive association with hospital mortality: paO2 (p=0.053), paO2/pO2e index (which expresses the paO2 adjusted to the paO2 expected for age) (p=0.047) and fractional saturation of hemoglobin (OxiHb%) (p=0.028).
DISCUSSION
GSA generate a key contribution in understanding the pathophysiology of the COVID-19 patient: in the initial evaluation, monitoring and prognosis of this disease.
Topics: Humans; COVID-19; Hospital Mortality; SARS-CoV-2; Retrospective Studies; Hypoxia; Hospitalization; Oxygen
PubMed: 38117706
DOI: No ID Found -
Clinical Pharmacology and Therapeutics Mar 2024The lethality of torsades de pointes (TdP) by drugs is one of main reasons that some drugs were withdrawn from the market. In order to assess drug-induced TdP risks, a...
The lethality of torsades de pointes (TdP) by drugs is one of main reasons that some drugs were withdrawn from the market. In order to assess drug-induced TdP risks, a model of cardiac ionic current suppression in human ventricular myocytes (ToR-ORd model), combined with the maximum effective free therapeutic plasma concentration or the maximum effective free therapeutic myocyte concentration was often used, with the latter proved to be more relevant and more accurate. We aimed to develop a whole-body physiologically-based pharmacokinetic (PBPK) model, incorporated with a human cardiomyocyte pharmacodynamic (PD) model, to provide a comprehensive assessment of drug-induced TdP risks in normal and specific scenarios. Quinidine served as an example to validate the PBPK-PD model via predicting plasma quinidine concentrations and quinidine-induced changes in QT interval (ΔQTc). The predicted plasma quinidine concentrations and ΔQTc values following oral administration or intravenous administration of quinidine were comparable to clinic observations. Visual predictive checks showed that most of the observed plasma concentrations and ΔQTc values fell within the 5th and 95th percentiles of simulations. The validated PBPK-PD model was further applied to assess the TdP risks using frequencies of early afterdepolarization and long-QT syndrome occurrence in 4 scenarios, such as therapeutic dose, supra-therapeutic dose, alkalosis, and hyperkalemia in 200 human subjects. In conclusion, the developed PBPK-PD model may be applied to predict the quinidine pharmacokinetics and quinidine-induced TdP risks in healthy subjects, but also simulate quinidine-induced TdP risks under disease conditions, such as hypokalemia and alkalosis.
Topics: Humans; Quinidine; Torsades de Pointes; Electrocardiography; Long QT Syndrome; Alkalosis; DNA-Binding Proteins
PubMed: 38117225
DOI: 10.1002/cpt.3156