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      Adaptation of the Brain to Hyponatremia and Its Clinical Implications

      Journal of Clinical Medicine
      MDPI AG

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          Abstract

          Hyponatremia is the most common electrolyte disorder, occurring in up to 25% of hospitalized patients. Hypo-osmotic hyponatremia when severe and left untreated invariably results in cell swelling, which can lead to fatal consequences, especially in the central nervous system. The brain is particularly vulnerable to the consequences of decreased extracellular osmolarity; because of being encased in the rigid skull, it cannot withstand persistent swelling. Moreover, serum sodium is the major determinant of extracellular ionic balance, which in turn governs crucial brain functions such as the excitability of neurons. For these reasons, the human brain has developed specific ways to adapt to hyponatremia and prevent brain edema. On the other hand, it is well known that rapid correction of chronic and severe hyponatremia can lead to brain demyelination, a condition known as osmotic demyelination syndrome. In this paper, we will discuss the mechanisms of brain adaptation to acute and chronic hyponatremia and the neurological symptoms of these conditions as well as the pathophysiology and prevention of osmotic demyelination syndrome.

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          Most cited references68

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          Physiology of cell volume regulation in vertebrates.

          The ability to control cell volume is pivotal for cell function. Cell volume perturbation elicits a wide array of signaling events, leading to protective (e.g., cytoskeletal rearrangement) and adaptive (e.g., altered expression of osmolyte transporters and heat shock proteins) measures and, in most cases, activation of volume regulatory osmolyte transport. After acute swelling, cell volume is regulated by the process of regulatory volume decrease (RVD), which involves the activation of KCl cotransport and of channels mediating K(+), Cl(-), and taurine efflux. Conversely, after acute shrinkage, cell volume is regulated by the process of regulatory volume increase (RVI), which is mediated primarily by Na(+)/H(+) exchange, Na(+)-K(+)-2Cl(-) cotransport, and Na(+) channels. Here, we review in detail the current knowledge regarding the molecular identity of these transport pathways and their regulation by, e.g., membrane deformation, ionic strength, Ca(2+), protein kinases and phosphatases, cytoskeletal elements, GTP binding proteins, lipid mediators, and reactive oxygen species, upon changes in cell volume. We also discuss the nature of the upstream elements in volume sensing in vertebrate organisms. Importantly, cell volume impacts on a wide array of physiological processes, including transepithelial transport; cell migration, proliferation, and death; and changes in cell volume function as specific signals regulating these processes. A discussion of this issue concludes the review.
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            Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits.

            The study objective was to determine the eventual consequences (falls, unsteadiness, and cognitive impairment) of mild chronic hyponatremia, which is generally considered as asymptomatic. In a case-control study, we focused on the incidence of falls among 122 patients (mean age 72+/-13 years) with asymptomatic chronic hyponatremia (mean serum sodium concentration [SNa] 126+/-5 mEq/L), who were admitted to the medical emergency department, compared with 244 matched controls. To explore the mechanisms of the excess of falls, we prospectively asked 16 comparable patients (mean age 63+/-15 years; SNa+/-2 mEq/L) to perform 8 attention tests and a gait test consisting of 3 steps "in tandem," in which we measured the "total traveled way" by the center of pressure or total traveled way. Thereafter, the patients were treated and tested again (50% of the patients were tested first with normal SNa to avoid learning biases). Epidemiology of falls: Twenty-six patients (21.3%) of 122 were admitted for falls, compared with only 5.3% of the control patients (adjusted odds ratio: 67; 95% confidence: 7.5-607; P <.001). The frequency of falls was the same regardless of the level of hyponatremia. Gait: The total traveled way by the center of pressure significantly increased in hyponatremia (1336+/-320 mm vs 1047+/-172 mm with normal SNa; P=.003). Attention tests: The mean response time was 673+/-182 milliseconds in hyponatremia and 615+/-184 milliseconds in patients with normal SNa (difference: 58 milliseconds, P <.001). The total error number in hyponatremia increased 1.2-fold (P=.001). These modifications were comparable to those observed after alcohol intake in 10 volunteers. Mild chronic hyponatremia induces a high incidence of falls possibly as the result of marked gait and attention impairments. Treating these patients might prevent a considerable number of hospitalizations.
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              Clinical practice guideline on diagnosis and treatment of hyponatraemia.

              Hyponatraemia, defined as a serum sodium concentration <135 mmol/l, is the most common disorder of body fluid and electrolyte balance encountered in clinical practice. It can lead to a wide spectrum of clinical symptoms, from subtle to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay in patients presenting with a range of conditions. Despite this, the management of patients remains problematic. The prevalence of hyponatraemia in widely different conditions and the fact that hyponatraemia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution- and speciality-based approaches to diagnosis and treatment. To obtain a common and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA), represented by European Renal Best Practice (ERBP), have developed the Clinical Practice Guideline on the diagnostic approach and treatment of hyponatraemia as a joint venture of three societies representing specialists with a natural interest in hyponatraemia. In addition to a rigorous approach to methodology and evaluation, we were keen to ensure that the document focused on patient-important outcomes and included utility for clinicians involved in everyday practice.
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                Author and article information

                Journal
                JCMOHK
                Journal of Clinical Medicine
                JCM
                MDPI AG
                2077-0383
                March 2023
                February 21 2023
                : 12
                : 5
                : 1714
                Article
                10.3390/jcm12051714
                18778389-0a05-4426-bf19-7db4bdcbba1d
                © 2023

                https://creativecommons.org/licenses/by/4.0/

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