Diagnosis and Management of Disorders of Body Tonicity—Hyponatremia and Hypernatremia: Core Curriculum 2020  N. Winn Seay, Ruediger W. Lehrich, Arthur.

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Diagnosis and Management of Disorders of Body Tonicity—Hyponatremia and Hypernatremia: Core Curriculum 2020  N. Winn Seay, Ruediger W. Lehrich, Arthur Greenberg  American Journal of Kidney Diseases  DOI: 10.1053/j.ajkd.2019.07.014 Copyright © 2019 National Kidney Foundation, Inc. Terms and Conditions

Figure 1 Relationship between plasma vasopressin (PAVP) and change from baseline in either blood volume or plasma osmolality in rats. Plasma hypertonicity serves as the primary stimulus for vasopressin release; very small changes are associated with significant linear increases in AVP secretion. A greater degree of volume depletion is required to promote AVP release, which is exponential, and the magnitude of release may exceed that due to osmolality changes. Original figure is ©1973 American Society for Clinical Investigation; reproduced from Dunn et al (The role of blood osmolality and volume in regulating vasopressin secretion in the rat. J Clin Invest. 1973;52(12):3212-3219) with permission of the copyright holder. American Journal of Kidney Diseases DOI: (10.1053/j.ajkd.2019.07.014) Copyright © 2019 National Kidney Foundation, Inc. Terms and Conditions

Figure 2 Vasopressin–induced increase in water permeability in the collecting duct. Vasopressin binds to the vasopressin 2 receptor (VR2), leading to an increase in intracellular cyclic adenosine monophosphate (cAMP), which activates protein kinase A (PKA). The latter leads to translocation of preformed vesicles containing aquaporin 2 (AQP2) along cytoskeletal elements toward the apical membrane, where exocytic insertion of AQP2 into the apical membrane renders the membrane permeable to water. Using the osmotic gradient from tubular lumen to medullary interstitium, tubular water can now move to the interstitium through constitutively activated basolateral AQP3 and AQP4 channels. Of note, vasopressin receptor antagonists (vaptans) compete with vasopressin for the V2 receptor–binding site. Abbreviation: ATP, adenosine triphosphate. Original figure ©2013 National Kidney Foundation; reproduced from Lehrich et al (Role of vaptans in the management of hyponatremia. Am J Kidney Dis. 2013;62(2):364-76) with permission of the copyright holder. American Journal of Kidney Diseases DOI: (10.1053/j.ajkd.2019.07.014) Copyright © 2019 National Kidney Foundation, Inc. Terms and Conditions

Figure 3 Diagnostic approach to hyponatremia. Urine sodium concentration (UNa)>30 mEq/L suggests that volume depletion is absent, but numerous exceptions exist. See text for details. Patients with thiazide-induced hyponatremia typically appear clinically euvolemic, but they may be hypovolemic, and their UNa is variable. Abbreviations: AVP, vasopressin; CHF, congestive heart failure; ECV, extracellular fluid volume; GI, gastrointestinal; [Na+], serum sodium concentration; NSIAD, nephrogenic syndrome of inappropriate antidiuresis; SIADH, syndrome of inappropriate antidiuretic hormone secretion; SOsm, serum osmolality; UOsm, urine osmolality. American Journal of Kidney Diseases DOI: (10.1053/j.ajkd.2019.07.014) Copyright © 2019 National Kidney Foundation, Inc. Terms and Conditions

Figure 4 Rate of correction of chronic or acute severe hyponatremia. In this retrospective analysis, 56 patients with a starting serum sodium concentration ([Na+])<105 mEq/L were treated for chronic hyponatremia. Transient and permanent neurologic sequelae occurred only when hyponatremia was rapidly corrected in chronic cases. Posttherapeutic neurologic complications did not occur when [Na+] corrected<12 mEq/L in 24 hours or<18 mEq/L in 48 hours and at a rate<0.55 mEq/L/h to a value of 120 mEq/L. Figure drawn from data in Sterns et al (Neurologic sequelae after treatment of severe hyponatremia: a multicenter perspective. J Am Soc Nephrol. 1994;4(8):1522-1530). American Journal of Kidney Diseases DOI: (10.1053/j.ajkd.2019.07.014) Copyright © 2019 National Kidney Foundation, Inc. Terms and Conditions