Age-associated abnormalities of water homeostasis

Abstract

Findley first proposed the presence of age-related dysfunction of the hypothalamic-neurohypophyseal-renal axis more than 60 years ago. More sophisticated studies have since corroborated his findings. As a result, it is now clear that multiple abnormalities in water homeostasis occur commonly with aging, and that the elderly are uniquely susceptible to disorders of body volume and osmolality. This article summarizes the distinct points along the hypothalamic-neurohypophyseal-renal axis where these changes have been characterized, as well as the clinical significance of these changes, with special attention to effects on cognition, gait instability, osteoporosis, fractures, and morbidity and mortality.

Figure 1

Restrictive cubic spline depicting the unadjusted relationship between hospital admission serum sodium concentrations and predicted probability of in-hospital mortality. Dashed lines represent the 95% confidence interval. (From Wald R, Jaber BL, Price LL, Upadhyay A, Madias NE. Impact of hospital-associated hyponatremia on selected outcomes. Arch Intern Med 2010; 170(3):294-302)

Figure 2

“Total traveled way” (TTW) measured by the center of pressure during a dynamic walking test consisting of 3 stereotyped steps “in tandem,” eyes open, in 3 patients (A, B, C) with mild asymptomatic hyponatremia before (left) and after correction (right). Patients are walking from right to left. Markedly irregular paths of the center of pressure were observed in the hyponatremia condition (arrows). (From Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 2006; 119(1):71)

Figure 3

Changes of bone mineral density (BMD) at multiple sites at the end of phase I (10 weeks) and phase II (18 weeks) in normonatremic (open bars) and hyponatremic (black bars) aged F344BN rats (22 months old at the start of the study). The BMD decreases from baseline were significantly greater in the hyponatremic rats than in the normonatremic rats (p<0.001). During phase II, hyponatremic rats received high dose vitamin D supplement that mitigated further declines of BMD. Asterisks indicate statistically significant differences from the normonatremic controls. (From Barsony J, Manigrasso MB, Xu Q, Tam H, Verbalis JG. Chronic hyponatremia exacerbates multiple manifestations of senescence in male rats. Age, 2012, Jan 5. [Epub ahead of print])

Figure 4

Histology of hearts from normonatremic and chronically hyponatremic aged F344BN rats. Representative low-power (20× objective; upper panels) and high power (40× objective; lower panels) microscopic images of 5-micron sections from the hearts stained with Masson's trichrome protocol that marks collagen fibers with blue color. Note increased interstitial and perivascular collagen deposits in micrographs of the left ventricle from hyponatremic rats (right panels) compared to micrographs from normonatremic rats (left panels). (From Barsony J, Manigrasso MB, Xu Q, Tam H, Verbalis JG. Chronic hyponatremia exacerbates multiple manifestations of senescence in male rats. Age, 2012, Jan 5. [Epub ahead of print])

Figure 5

Mean changes, pre and post fluid deprivation in young (open boxes) and elderly (closed boxes) subjects after equivalent degrees of induced weight loss. (From Rolls BJ, Phillips PA. Aging and Disturbances of Thirst and Fluid Balance. Nutrition Reviews 48:137. 1990)

Figure 6

Correlation between serum osmolality and AVP concentration in 8 young and 8 older subjects during a 2-hour 3% saline infusion following mild dehydration. The older subjects had significantly higher plasma levels of AVP per unit increase in plasma osmolality, strongly suggesting an enhanced osmotically-stimulated secretion. (From Helderman JH. The response of arginine vasopressin to intravenous ethanol and hypertonic saline in man: The impact of aging. J Gerontol 1978;33(1):39-47)

Figure 7

Plasma sodium concentration and total water intake in healthy elderly and young subjects following 24 hours of dehydration. Baseline sodium concentration before dehydration (pre) and after dehydration (post) are shown. Free access to water was allowed for 60 minutes following dehydration starting at time=0 minutes. Cumulative water intake during the free drinking period by young and old subjects is depicted in the bar graph. Despite a greater initial increase in serum [Na⁺], elderly subjects drank significantly less water, resulting in lesser correction of the elevated serum [Na⁺]. (From Phillips PA, Johnston CI, Gray L. Disturbed fluid and electrolyte homeostasis following dehydration in elderly people. Age and Aging 1993;22:26-33)