Effects Of Hypernatremia Research Articles

Effects of hypernatremia on the microglia

Signs and symptoms of hypernatremia largely indicate central nervous system dysfunction. Acute hypernatremia can cause demyelinating lesions similar to that observed in osmotic demyelination syndrome (ODS). We have previously demonstrated that microglia accumulate in ODS lesions and minocycline protects against ODS by inhibiting microglial activation. However, the direct effect of rapid rise in the sodium concentrations on microglia is largely unknown. In addition, the effect of chronic hypernatremia on microglia also remains elusive. Here, we investigated the effects of acute (6 or 24 h) and chronic (the extracellular sodium concentration was increased gradually for at least 7 days) high sodium concentrations on microglia using the microglial cell line, BV-2. We found that both acute and chronic high sodium concentrations increase NOS2 expression and nitric oxide (NO) production. We also demonstrated that the expression of nuclear factor of activated T-cells-5 (NFAT5) is increased by high sodium concentrations. Furthermore, NFAT5 knockdown suppressed NOS2 expression and NO production. We also demonstrated that high sodium concentrations decreased intracellular Ca2+ concentration and an inhibitor of Na+/Ca2+ exchanger, NCX, suppressed a decrease in intracellular Ca2+ concentrations and NOS2 expression and NO production induced by high sodium concentrations. Furthermore, minocycline inhibited NOS2 expression and NO production induced by high sodium concentrations. These in vitro data suggest that microglial activity in response to high sodium concentrations is regulated by NFAT5 and Ca2+ efflux through NCX and is suppressed by minocycline.

Effects of Acute Hypernatremia on the Electrophysiology of Single Human Ventricular Cardiomyocytes: An In Silico Study.

Clinical and experimental data on the cardiac effects of acute hypernatremia are scarce and inconsistent. We aimed to determine and understand the effects of different levels of acute hypernatremia on the human ventricular action potential. We performed computer simulations using two different, very comprehensive models of the electrical activity of a single human ventricular cardiomyocyte, i.e., the Tomek-Rodriguez model following the O'Hara-Rudy dynamic (ORd) model and the Bartolucci-Passini-Severi model as published in 2020 (known as the ToR-ORd and BPS2020 models, respectively). Mild to extreme levels of hypernatremia were introduced into each model based on experimental data on the effects of hypernatremia on cell volume and individual ion currents. In both models, we observed an increase in the intracellular sodium and potassium concentrations, an increase in the peak amplitude of the intracellular calcium concentration, a hyperpolarization of the resting membrane potential, a prolongation of the action potential, an increase in the maximum upstroke velocity, and an increase in the threshold stimulus current at all levels of hypernatremia and all stimulus rates tested. The magnitude of all of these effects was relatively small in the case of mild to severe hypernatremia but substantial in the case of extreme hypernatremia. The effects on the action potential were related to an increase in the sodium-potassium pump current, an increase in the sodium-calcium exchange current, a decrease in the rapid and slow delayed rectifier potassium currents, and an increase in the fast and late sodium currents. The effects of mild to severe hypernatremia on the electrical activity of human ventricular cardiomyocytes are relatively small. In the case of extreme hypernatremia, the effects are more pronounced, especially regarding the increase in threshold stimulus current.

Effect of Hypernatremia on Protein Reabsorption in Renal Proximal Tubules of the Lake Frog Pelophylax ridibundus

Effect of Hypernatremia on Protein Reabsorption in Renal Proximal Tubules of the Lake Frog Pelophylax ridibundus

Clinical audit on management of hypernatremia in the Gastroenterology Department of Assiut University Children Hospital

IntroductionHypernatremia is a sodium concentration more than 145 mEq/l, although it is sometimes defined as more than 150 mEq/l. Mild hypernatremia is fairly common in children, especially among infants with gastroenteritis. Hypernatremia in hospitalized patients may be iatrogenic due to inadequate water administration or, by excessive administration of sodium. Moderate or severe hypernatremia has significant morbidity, including the result of the underlying illness, the effects of hypernatremia on the central nervous system, and the risks of rapid correction. Hypernatremia may be mild [Na+] 146–149 mmol/l, moderate [Na+] 150–169 mmol/l or severe [Na+] more than or equal to 170 mmol/l. Patients and methodsThis study was a clinical audit on the management of hypernatremia among children admitted to the Gastroenterology and Hepatology Unit in Assiut University Children Hospital during the period spanning from the 1st of March 2017 to the 31st of August 2017. All children with gastroenteritis who were admitted were investigated, and those with hypernatremia were included in this study. ResultsThe present study included 220 children with hypernatremia who were admitted to the Gastroenterology Unit of Assiut University Children Hospital over a period of 6 months. During this period, 2665 patients were admitted in the Gastroenterology Unit; 220 cases of them were hypernatremic (8.25% of admitted cases).

Effect of Hypernatremia on Outcomes After severe Traumatic Brain Injury: A Nationwide Inpatient Sample analysis

Induced hypernatremia is frequently used to reduce intracranial pressure in patients with severe traumatic brain injury (TBI). This technique is controversial, and some studies have independently associated hypernatremia with worse outcomes after TBI. We sought to investigate this potential association in a large healthcare database. The Nationwide Inpatient Sample was used to obtain data on all adults who had been discharged from 2002 to 2011 with a primary diagnosis of TBI who required mechanical ventilation, intracranial pressure monitoring, or craniotomy/craniectomy. Patients with diabetes insipidus were excluded. The patients with hypernatremia were assigned to the hypernatremia group, and the rest were assigned to the control group. The primary outcome was in-hospital mortality, and the secondary outcomes included the length of stay, nonroutine hospital discharge, total hospital charges, tracheostomy, and gastrostomy placement. A total of 85,579 patients without a diagnosis of hypernatremia (control group) and 4542 patients with a diagnosis of hypernatremia (hypernatremia group) were identified. When controlling for age, comorbidities, gender, and cerebral edema, hypernatremia was associated with an increased rate of in-hospital mortality (odds ratio, 1.51; 95% confidence interval, 1.39-1.65), a longer mean length of stay (23.65 vs. 12.12 days; P < 0.001), an increased rate of nonroutine hospital discharge (odds ratio, 2.58; 95% confidence interval, 2.28-2.92), and greater mean total hospital cost ($227,112 vs. $112,507; P < 0.001). The patients with hypernatremia also had greater rates of tracheostomy and gastrostomy placement. Hypernatremia was associated with poorer outcomes in patients with severe TBI. This finding warrants further investigation in a prospective, randomized study.

The influence of hypernatremia on mortality in intensive care unit patients: a meta-analysis

To evaluate the incidence of hypernatremia and its influence on mortality in intensive care unit (ICU) patients. PubMed, EMBASE, Cochrane central registration of controlled trials, CNKI and Wanfang Data were searched, and relevant data of the study regarding hypernatremia in ICU patients published before September 2013 were retrieved. Meta analysis was conducted with STATA 12.0, and the effect of hypernatremia on hospital mortality and ICU mortality was evaluated. The pooled results from 14 articles from 449 ICU in 9 countries involving 365,103 patients showed that the morbidity rate of hypernatremia in ICU was 6.9% (25,326/365,103), and the mortality rate was 32.7% (8,291/25,326). The mortality of non-hypernatremic patients was 11.9% (40,588/339,777), but the mortality of hypernatremic patients was about 2.75 times higher than non-hypernatremic patients. In patients with hypernatremia, the mortality of iatrogenic hypernatremia was 31.6% (3 790/11,976), which was similar to that of non-iatrogenic hypernatremia [33.7% (4 501/13 350)]. Further Meta analysis showed that hypernatremia was an independent risk factor of hospital mortality [relative risk (RR) 1.86, 95% confidence interval (95%CI) 1.57-2.20], and ICU mortality (RR 2.58, 95%CI 2.00-3.33), but the heterogeneity was high. The source of heterogeneity was found with subgroup analysis according to sample size (>1000 cases or ≤1000 cases), ICU type (surgical ICU or other types), study type (retrospective cohort study, prospective cohort study or case-control study), hypernatremia type (iatrogenic hypernatremia or not). Funnel plot showed no publication bias. Hypernatremia could obviously raise the mortality rate in ICU patients, and it was an independent risk factor for critically ill patients.

A Clinical Approach to the Treatment of Chronic Hypernatremia

Hypernatremia is a commonly encountered electrolyte disorder occurring in both the inpatient and outpatient settings. Community-acquired hypernatremia typically occurs at the extremes of age, whereas hospital-acquired hypernatremia affects patients of all age groups. Serum sodium concentration is linked to water homeostasis, which is dependent on the thirst mechanism, arginine vasopressin, and kidney function. Because both hypernatremia and the rate of correction of hypernatremia are associated with significant morbidity and mortality, prompt effective treatment is crucial. Chronic hypernatremia can be classified into 3 broad categories, hypovolemic, euvolemic, and hypervolemic forms, with each form having unique treatment considerations. In this teaching case, we provide a clinically based quantitative approach to the treatment of both hypervolemic and hypovolemic hypernatremia, which occurred in the same patient during the course of a prolonged illness.

The Role of Organic Osmolytes in the Response of Cultured Astrocytes to Hyperosmolarity

Idiogenic osmoles are volume-regulatory organic solutes that accumulate within a cell in response to hyperosmolar conditions such as those found in diabetic ketoacidosis or hypernatremic dehydration in infants. Intracellular metabolites known to play this role include certain amino acids and taurine, polyols, and trimethylamines. In this study, in vitro astrocyte cultures prepared from the cerebral cortices of 1-day-old Sprague-Dawley rats were exposed to graded conditions of hypernatremia (325-375 mOsm/kg), a range that can be observed in vivo, for 24, 48, and 72 hours. Cell survival and generation of idiogenic osmoles were determined. Next, we assessed the ability of selected exogenous osmoles to protect the cultured cells from the effects of hypernatremia. Significant cell loss occurred after 48 to 72 hours of exposure and was proportional to the degree of hyperosmolarity. Addition of myoinositol (1 mM) to the cultures reduced cell loss resulting from hypernatremia by approximately 50%. In agreement with previous studies, intracellular levels of myoinositol and taurine correlated with the degree of in vitro hypernatremic exposure and play a significant role in increasing survival of astrocytes subjected to hypertonic insult.

Direct suppressive effect of acute metabolic and respiratory alkalosis on parathyroid hormone secretion in the dog.

Acute alkalosis may directly affect PTH secretion. The effect of acute metabolic and respiratory alkalosis was studied in 20 dogs. PTH values were lower in the metabolic (5.6 +/- 0.8 pg/ml) and respiratory (1.8 +/- 0.6 pg/ml) alkalosis groups than in the control group (27 +/- 5 pg/ml). Acute alkalosis is an independent factor that decreases PTH values during normocalcemia and delays the PTH response to hypocalcemia. We recently showed that acute metabolic and respiratory acidosis stimulated PTH secretion. This study was designed to evaluate whether acute metabolic and respiratory alkalosis suppressed parathyroid hormone (PTH) secretion. Three groups of 10 dogs were studied: control, acute metabolic alkalosis, and acute respiratory alkalosis. Metabolic alkalosis was induced with an infusion of sodium bicarbonate and respiratory alkalosis by hyperventilation. Calcium chloride was infused to prevent alkalosis-induced hypocalcemia during the first 60 minutes. During the next 30 minutes, disodium EDTA was infused to induce hypocalcemia and to evaluate the PTH response to hypocalcemia. Because the infusion of sodium bicarbonate resulted in hypernatremia, the effect of hypernatremia was studied in an additional group that received hypertonic saline. After 60 minutes of a normocalcemic clamp, PTH values were less (p < 0.05) in the metabolic (5.6 +/- 0.8 pg/ml) and respiratory (1.8 +/- 0.6 pg/ml) alkalosis groups than in the control group (27 +/- 5 pg/ml); the respective blood pH values were 7.61 +/- 0.01, 7.59 +/- 0.02, and 7.39 +/- 0.02. The maximal PTH response to hypocalcemia was similar among the three groups. However, the maximal PTH response was observed after a decrease in ionized calcium of 0.20 mM in the control group but not until a decrease of 0.40 mM in the metabolic and respiratory alkalosis groups. In contrast to the metabolic alkalosis group, hypernatremia (157 +/- 2 mEq/liter) in the hypertonic saline group was associated with an increased PTH value (46 +/- 4 pg/ml). Finally, the half-life of intact PTH was not different among the control and two alkalosis groups. Acute metabolic and respiratory alkalosis markedly decreased PTH values during normocalcemia and delayed the PTH response to hypocalcemia. Whether acute metabolic and respiratory alkalosis affect PTH and calcium metabolism in such settings as the postprandial alkaline tide (metabolic alkalosis) and acute sepsis (respiratory alkalosis) deserves to be evaluated in future studies.

Prognostic significance of hypernatremia and hyponatremia among patients with aneurysmal subarachnoid hemorrhage.

Abnormal serum sodium levels (hyponatremia and hypernatremia) are frequently observed during the acute period after aneurysmal subarachnoid hemorrhage (SAH) and may worsen cerebral edema and mass effect. We performed this study to determine the prognostic significance of serum sodium concentration abnormalities. We analyzed prospectively collected data for the placebo treatment group in a clinical trial conducted at 54 neurosurgical centers in North America. The presence of hypernatremia (serum sodium concentration of >145 mmol/L) and hyponatremia (serum sodium concentration of <135 mmol/L) was determined with serum sodium measurements obtained at admission and 3, 6, and 9 days after SAH. The effects of hypernatremia and hyponatremia on the risk of symptomatic vasospasm and on 3-month outcomes were analyzed after adjustment for the following potential confounding factors: age, sex, preexisting hypertension, admission Glasgow Coma Scale score, initial mean arterial pressure, subarachnoid clot thickness, intraventricular blood or intraparenchymal hematoma, ventricular dilation, and aneurysm size and location. Of 298 patients in the analysis, 58 (19%) developed hypernatremia and 88 (30%) developed hyponatremia. Hypernatremia was significantly associated with poor outcomes (odds ratio, 2.7; 95% confidence interval, 1.2-6.1). A positive correlation was observed between the highest sodium values recorded and Glasgow Outcome Scale scores at 3 months (P < 0.0001 by analysis of variance). Hyponatremia was not associated with 3-month outcomes (odds ratio, 1.9; 95% confidence interval, 0.9-4.3). Neither hypernatremia nor hyponatremia was associated with the risk of symptomatic vasospasm. Hyponatremia seems to be more common than hypernatremia after SAH. However, hypernatremia after SAH is independently associated with poor outcomes, and this association is independent of previously identified outcome predictors, including age and admission Glasgow Coma Scale scores. Further studies are needed to define the underlying mechanism of this association.

The Effects of Donor Sodium Levels on Recipient Liver Graft Function

A great deal of discussion has been generated regarding the effects of donor hypernatremia on recipient liver graft function. Much of this discussion is anecdotal and focuses on the detrimental effects of hypernatremia in the organ donor. The treatment of donor hypernatremia often leads to changes in donor management protocols. A retrospective study was conducted to determine if donor hypernatremia measurably alters the liver graft function of recipients. Results indicated that donor sodium values were unrelated to any recipient parameter assessed. Although further studies are pending, these findings suggest that a moderate rather than a severe approach to the management of donor hypernatremia may be preferred.

The effects of donor sodium levels on recipient liver graft function

A great deal of discussion has been generated regarding the effects of donor hypernatremia on recipient liver graft function. Much of this discussion is anecdotal and focuses on the detrimental effects of hypernatremia in the organ donor. The treatment of donor hypernatremia often leads to changes in donor management protocols. A retrospective study was conducted to determine if donor hypernatremia measurably alters the liver graft function of recipients. Results indicated that donor sodium values were unrelated to any recipient parameter assessed. Although further studies are pending, these findings suggest that a moderate rather than a severe approach to the management of donor hypernatremia may be preferred.

Energy turnover and the production of ammonium by the kidney: effect of hypernatremia

The purpose of this study was to explore further the relation between the rates of oxygen consumption and ammonium (NH4+) production in the kidney during chronic metabolic acidosis. The experimental model was the dog with chronic metabolic acidosis because of the extensive background literature in this species. Chronic metabolic acidosis was produced by the ingestion of 10 mmol NH4Cl/kg body weight for 5 days. There was a significant increase in the rate of oxygen extraction when hypernatremia was present. Despite this rise in the rate of oxygen consumption, there was no increase in the rate of NH4+ production nor in the rate of glutamine extraction. These data suggest that hypernatremia might prevent a further augmentation in glutamine extraction when the rate of oxygen consumption rises. In addition, a larger proportion of the NH4+ produced was excreted in the urine during hypernatremia. This increase was associated with a rise in the urine flow rate, but not with a fall in urine pH.

Effects of hypernatremia on organic brain osmoles.

We studied the effects of varying degrees and durations of hypernatremia on the brain concentrations of organic compounds believed to be important, so-called "idiogenic" osmoles in rats by means of conventional biochemical assays, nuclear magnetic resonance spectroscopy, and high-performance liquid chromatography. There were no changes in the concentrations of these osmoles (specifically myoinositol, sorbitol, betaine, glycerophosphorylcholine [GPC], phosphocreatine, glutamine, glutamate, and taurine) in rats with acute (2 h) hypernatremia (serum Na 194 +/- 5 meq/liter). With severe (serum Na 180 +/- 4 meq/liter) chronic (7 d) hypernatremia, the concentrations of each of these osmoles except sorbitol increased significantly: myoinositol (65%), betaine (54%), GPC (132%), phosphocreatine (73%), glutamine (143%), glutamate (84%), taurine (78%), and urea (191%). Together, these changes account for 35% of the change in total brain osmolality. With moderate (serum Na 159 +/- 3 meq/liter) hypernatremia, more modest but significant increases in the concentrations of each of these osmoles except betaine and sorbitol were noted. When rats with severe chronic hypernatremia were allowed to drink water freely, their serum sodium as well as the brain concentrations of all of these organic osmoles except myoinositol returned to normal within 2 d. It is concluded that: idiogenic osmoles play an important role in osmoregulation in the brain of rats subjected to hypernatremia; the development of these substances occur more slowly than changes in serum sodium; and the decrease in concentration of myoinositol occurs significantly more slowly than the decrease in serum sodium which occurs when animals are allowed free access to water. These observations may be relevant to the clinical management of patients with hypernatremia.