Disorders of Water Balance

Guided by the hypothalamic antidiuretic hormone vasopressin, the kidney’s ability to conserve electrolyte–free water when it is needed and to excrete large volumes of water when there is too much of it normally prevents the serum sodium concentration from straying outside its normal range. The serum sodium concentration determines plasma tonicity and affects cell volume: a low concentration makes cells swell, and a high concentration makes them shrink. An extremely large water intake, impaired water excretion, or both can cause hyponatremia. A combination of too little water intake with too much salt, impaired water conservation, or excess extrarenal water losses will result in hypernatremia. Because sodium does not readily cross the blood-brain barrier, an abnormal serum sodium concentration alters brain water content and composition and can cause serious neurologic complications. Because bone is a reservoir for much of the body’s sodium, prolonged hyponatremia can also result in severe osteoporosis and fractures. An understanding of the physiologic mechanisms that control water balance will help the clinician determine the cause of impaired water conservation or excretion; it will also guide appropriate therapy that can avoid the life-threatening consequences of hyponatremia and hypernatremia.

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Disorders of Water Balance

10.2310/im.12006 ◽

2017 ◽

Author(s):

Richard H Sterns ◽

Stephen M. Silver ◽

John K. Hix ◽

Jonathan W. Bress

Keyword(s):

Water Balance ◽

Water Intake ◽

Serum Sodium ◽

Water Conservation ◽

Free Water ◽

Sodium Concentration ◽

Serum Sodium Concentration ◽

Water Losses ◽

Water Excretion ◽

Impaired Water

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Disorders of water and sodium homeostasis

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0473 ◽

2020 ◽

pp. 4729-4747

Author(s):

Michael L. Moritz ◽

Juan Carlos Ayus

Keyword(s):

Water Intake ◽

Serum Sodium ◽

Free Water ◽

Sodium Concentration ◽

Serum Sodium Concentration ◽

Water Losses ◽

Free Water Clearance ◽

Water Excretion ◽

Electrolyte Disorder ◽

Water Clearance

Water intake and the excretion of water are tightly regulated processes that are able to maintain a near-constant serum osmolality. Sodium disorders (dysnatraemias—hyponatraemia or hypernatraemia) are almost always due to an imbalance between water intake and water excretion. Understanding the aetiology of sodium disorders depends on understanding the concept of electrolyte-free water clearance—this is a conceptual amount of water that represents the volume that would need to be subtracted (if electrolyte-free water clearance is positive) or added (if negative) to the measured urinary volume to make the electrolytes contained within the urine have the same tonicity as the plasma electrolytes. It is the concentration of the electrolytes in the urine, not the osmolality of the urine, which ultimately determines the net excretion of water. Hyponatraemia (serum sodium concentration <135 mmol/litre) is a common electrolyte disorder. It is almost invariably due to impaired water excretion, often in states where antidiuretic hormone release is (1) a normal response to a physiological stimulus such as pain, nausea, volume depletion, postoperative state, or congestive heart failure; or (2) a pathophysiological response as occurs with thiazide diuretics, other types of medications, or in the syndrome of inappropriate diuresis; with both often exacerbated in hospital by (3) inappropriate iatrogenic administration of hypotonic fluids. Hypernatraemia (serum sodium concentration >145 mmol/litre) is a common electrolyte disorder that occurs when water intake is inadequate to keep up with water losses. Since the thirst mechanism is such a powerful stimulus, hypernatraemia almost invariably occurs in the context of an illness and care that restricts the patient’s access to water. This chapter discusses the clinical features, management, and prevention of hyponatraemia and hypernatraemia.

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Absence of AVPR2 copy number variation in eunatremic and dysnatremic subjects in non-Hispanic Caucasian populations

Physiological Genomics ◽

10.1152/physiolgenomics.00157.2009 ◽

2010 ◽

Vol 40 (3) ◽

pp. 121-127 ◽

Cited By ~ 2

Author(s):

Yi Fu ◽

Zhan Chen ◽

Alexandra I. F. Blakemore ◽

Eric Orwoll ◽

David M. Cohen

Keyword(s):

Water Balance ◽

Copy Number Variation ◽

Serum Sodium ◽

Water Conservation ◽

Copy Number ◽

Osteoporotic Fractures ◽

Sodium Concentration ◽

Serum Sodium Concentration ◽

Comparative Genomic ◽

Number Variation

Copy number variation (CNV) is increasingly recognized as a source of phenotypic variation among humans. We hypothesized that a CNV in the human arginine vasopressin receptor-2 gene ( AVPR2) would be associated with serum sodium concentration based on the following lines of evidence: 1) the protein product of the AVPR2 gene is essential for renal water conservation; 2) mutations in the AVPR2 gene are associated with aberrant water balance in humans; 3) heritability of serum sodium concentration may be greater in females than in males; 4) the AVPR2 gene is X-linked; and 5) a common CNV spanning the AVPR2 gene was recently described in a non-Hispanic Caucasian population. We developed a highly reproducible assay for AVPR2 CNV. Among 279 subjects with measured serum sodium concentration in the Offspring Cohort of the Framingham Heart Study, no subjects exhibited CNV at the AVPR2 locus. Among 517 subjects in the Osteoporotic Fractures in Men Study (MrOS)—including 152 with hyponatremia and 183 with hypernatremia—no subjects with CNV at the AVPR2 locus were identified. CNV at the AVPR2 locus could not be independently confirmed, and CNV at the AVPR2 gene is unlikely to influence systemic water balance on a population-wide basis in non-Hispanic Caucasian subjects. A novel AVPR2 single nucleotide polymorphism affecting the reporter hybridization site gave rise to an artifactually low copy number signal (i.e., less than unity) in one male African American subject. Reanalysis of the original comparative genomic hybridization data revealed bona fide CNVs flanking—but not incorporating—the AVPR2 gene, consistent with our new genotyping data.

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Intensive Care Unit Acquired Hypernatremia after Major Surgery is Associated with Urine Concentrating Defect: An Observational Study

10.21203/rs.3.rs-41777/v1 ◽

2020 ◽

Author(s):

Philipp Deetjen ◽

Ulrich Jaschinski ◽

Axel Heller

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Water Balance ◽

Water Conservation ◽

Sodium Excretion ◽

Free Water ◽

Major Surgery ◽

Surgical Intensive Care Unit ◽

Surgical Intensive Care ◽

Water Excretion

Abstract Background: Although intensive care acquired hypernatremia is a common event, limited knowledge exists about the pathogenesis of this disorder. The present study attempts to show that patients undergoing major surgery develop hypernatremia in the presence of both high salt and volume load and concentration disorder of the kidney with insufficient sodium excretion.Methods: In a retrospective study, all patients who were admitted to a 40-bed tertiary surgical intensive care unit of a university hospital from July 2019 to December 2019 with major surgery were examined. Hypernatremia was defined as a sodium value exceeding 145 mmol/l. In addition to the analysis of all patients, complete water and salt balances were performed in a smaller subgroup with 142 patients.Results: 23.9% of patients undergoing major surgery developed hypernatremia, whereby hypernatremia was associated with increased mortality. Patients with hypernatremia showed a renal concentration defect with decreased urine sodium concentration (65 (IQR: 44.8-90) mmol/l vs 78 (IQR: 46-107) mmol/l, p = 0.007) and decreased urine osmolality (514 (IQR: 465-605) mmol/l vs 602 (IQR: 467-740) mmol/l, p < 0.001). In the subgroup of patients with complete sodium and water balance, a positive salt and water balance was observed. After propensity score matching, we found a significantly increased electrolyte free water clearance (1020 ±1740 ml vs -560 ±1620 ml, p <0.001) in the hypernatremia group, together with an inadequately lower total sodium urine excretion (401 ±303 mmol vs 593 ±400 mmol, p = 0.02). Conclusion: The present study shows that postoperative hypernatremia is associated with an imbalance between perioperative salt and water load and renal sodium and water handling with inadequately low renal sodium excretion and inadequately high renal water excretion. The underlying renal concentration disorder may be explained by a defect in a natriuretic-ureotelic response a recently described renal urea-mediated water conservation mechanism after salt exposure.

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Increased risk of heart failure is associated with chronic habitual hypohydration that elevates serum sodium above 142 mmol/l suggesting lifelong optimal hydration as preventive measure

European Heart Journal ◽

10.1093/eurheartj/ehab724.0980 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

N.I Dmitrieva ◽

D Liu ◽

M Boehm

Keyword(s):

Heart Failure ◽

Serum Sodium ◽

Water Conservation ◽

Middle Age ◽

Sodium Concentration ◽

Left Ventricular ◽

Serum Sodium Concentration ◽

Data Repository ◽

Increased Risk ◽

Aric Study

Abstract Background With increasing prevalence of heart failure (HF) owing to the aging population, identification of preventive measures that delay onset of the disease and their implementation become increasingly important. Recent studies demonstrated that chronic subclinical hypohydration accelerates degenerative changes and increases prevalence of many age-dependent degenerative diseases including heart failure (1). Worldwide surveys find wide differences in habitual water intake between and within countries and substantial prevalence of hypohydration in general population (2). Hypohydration elevates extracellular sodium triggering activation of water conservation mechanisms when serum sodium exceeds a threshold around 142 mmol/l. These adaptive responses include secretion of antidiuretic hormone and activation of the renin angiotensin aldosterone system (3), important contributors to pathogenesis of HF. Purpose The purpose of this study was to evaluate whether serum sodium concentration at middle age of 44–66 years as a measure of hydration habits is a significant predictor for left ventricular hypertrophy (LVH) and HF events 25 years later at age of 70–90 years. Methods Data from Atherosclerosis Risk in Communities (ARIC) study were obtained from the BioLINCC data repository. In ARIC study, 15,792 44–66 year-old participants were evaluated over 5 visits spanning 25 years (Figure 1A). Two separate logistic regression models were used in the study, where the dependent variable is diagnosis of LVH and HF at visit 5 (age:70–90 years), and the predictors are serum sodium concentration measured at visits 1 and 2 (age: 44–66 years), age, gender, total cholesterol, glucose, eGFR, BMI, smoking and hypertension statuses. Results Midlife serum sodium is associated with LVH and HF diagnosis 25 years later at visit 5 both with adjustment for age only (LVH: OR=1.24, 95% CI 1.15–1.34, P<0.001; HF: OR=1.06, 95% CI 1.02–1.10, P=0.006) and in fully adjusted model (LVH: OR=1.20, 95% CI 1.11–1.30, P<0.001; HF: OR=1.11, 95% CI 1.01–1.22, P=0.031) (Figure 1B). Cornell voltage criteria used for LVH diagnosis is elevated in participants with higher serum sodium and demonstrates sharper increase with age indicating accelerated hypertrophic LV remodeling (Figure 1C). These associations are reflected in increased prevalence of HF and LVH in 70–90 year-old participants whose middle age serum sodium exceeded 142 mmol/l (Figure 1D). Conclusions Habitual life-long hypohydration increases risk to develop LVH and HF. Keeping serum sodium below 142 mmol/l by drinking appropriate amount of liquids may slow down decline in cardiac function and decrease prevalence of HF. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): NHLBI Intramural program

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Heritability of serum sodium concentration: evidence for sex- and ethnic-specific effects

Physiological Genomics ◽

10.1152/physiolgenomics.00153.2011 ◽

2012 ◽

Vol 44 (3) ◽

pp. 220-228 ◽

Cited By ~ 12

Author(s):

Beth Wilmot ◽

V. Saroja Voruganti ◽

Yen-Pei C. Chang ◽

Yi Fu ◽

Zhan Chen ◽

...

Keyword(s):

African American ◽

Water Balance ◽

American Indian ◽

Serum Sodium ◽

Population Level ◽

Sodium Concentration ◽

Serum Sodium Concentration ◽

Osmotic Effect ◽

Specific Effects ◽

Heart Study

Serum sodium concentration is the clinical index of systemic water balance. Although disordered water balance is common and morbid, little is known about genetic effects on serum sodium concentration at the population level. Prior studies addressed only participants of European descent and either failed to demonstrate significant heritability or showed only modest effect. We investigated heritability of serum sodium concentration in large cohorts reflecting a range of races/ethnicities, including the Framingham Heart Study (FHS, non-Hispanic Caucasian), the Heredity and Phenotype Intervention Heart Study (HAPI, Amish Caucasian), the Jackson Heart Study (JHS, African American), the Strong Heart Family Study (SHFS, American Indian), and the Genetics of Kidney Disease in Zuni Indians Study (GKDZI, American Indian). Serum sodium was transformed for the osmotic effect of glucose, and participants with markedly elevated glucose or reduced estimated glomerular filtration rate (eGFR) were excluded. Using a standard variance components method, incorporating covariates of age, glucose, and eGFR, we found heritability to be high in African American and American Indian populations and much more modest in non-Hispanic Caucasian populations. Estimates among females increased after stratification on sex and were suggestive among female participants in FHS (0.18 ± 0.12, P = 0.057) and male participants in JHS (0.24 ± 0.16, P = 0.067) and statistically significant among female participants in JHS (0.44 ± 0.09, P = 1 × 10−7), SHFS (0.59 ± 0.05, P = 9.4 × 10−46), and GKDZI (0.46 ± 0.15, P = 1.7 × 10−4), and male participants in HAPI (0.18 ± 0.12, P = 0.03) and SHFS (0.67 ± 0.07, P = 5.4 × 10−26). Exclusion of diuretic users increased heritability among females and was significant in all cohorts where data were available. In aggregate, these data strongly support the heritability of systemic water balance and underscore sex and ethnicity-specific effects.

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