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Chapter 17: Fluid Balance Disorders in the Elderly

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Chapter 17: Fluid Balance Disorders in the Elderly Myron Miller Department of Medicine, Johns Hopkins University School of Medicine, and Division of Geriatric Medicine, Department of Medicine, Sinai Hospital of Baltimore, Baltimore, Maryland Disorders of fluid balance are common in the el- duction to the nighttime period becomes evident. derly and often are caused by age-related alterations With further increase in age, there is often reduc- in urinary tract function, which can present clini- tion in the ratio of day to night urine flow to the cally as urinary frequency, nocturia, and inconti- point that nighttime flow rates become equal to or nence. Among the factors predisposing to the de- exceed daytime rates. Despite the change in circa- velopment of these clinical disturbances are aging dian pattern of urine excretion, total urine produc- changes in the renal and hormonal systems that tion per 24 h is not affected.3 control water and sodium excretion along with changes in the reservoir function of the bladder1 (Table 1). This chapter will examine the effect of ARGININE VASOPRESSIN SECRETION aging on the systems involved in urine formation and consider how these changes interact with those Arginine vasopressin [AVP; antidiuretic hormone of bladder function and lead to urinary frequency, (ADH)] is the major hormone responsible for the nocturia, and incontinence. regulation of urine formation. The magnocellular In young, healthy persons there is a circadian supraoptic and paraventricular nuclei of the hypo- pattern to urine production in which nighttime thalamus where AVP is synthesized do not seem to urine flow rate is less than daytime flow rate. In undergo age-related degenerative changes with ei- association with the normal aging process, there is ther morphologic features of cell destruction or de- an increase in nocturnal production of urine, so cline in cell hormone synthetic ability or hormone that nighttime urine flow rate equals or exceeds content. daytime production rate.2 When of sufficient mag- There is some controversy regarding the influ- nitude to result in nocturia, this change has been ence of normal aging on daytime blood AVP levels. termed nocturnal polyuria syndrome. A number of studies have indicated that, under The establishment of a circadian rhythm of urine basal conditions, daytime plasma AVP concentra- flow takes place during childhood, generally be- tion is not affected by increasing age. In contrast, tween the ages of 2 to 5 yr. In normal children with several other studies have reported increased basal a mean age of 7 yr, daytime rate of urine production plasma AVP levels in healthy elderly persons. Fur- is two to three times that of the nighttime period. ther adding to controversy are reports that healthy Delay or failure of the circadian rhythm to develop elderly subjects have daytime plasma AVP concen- during childhood is associated with the presence of trations that are significantly lower than in young nocturnal enuresis. In adulthood, the ratio of day- subjects. time to nighttime urine production is usually In healthy adults, there is a diurnal release of greater than 2:1, so that about 25% or less of daily AVP into the circulation with peak blood concen- urine output occurs during sleep. Typical urine tration occurring during the hours of sleep. This production rates are approximately 70 to 80 ml/h rhythm seems to be linked to the wake-sleep cycle during the waking period and 30 to 40 ml/h during sleep. This circadian pattern seems to be linked to the day-night sleep pattern. The circadian pattern Correspondence: Myron Miller, MD, Director, Division of Geriat- of urine flow is paralleled by similar rhythms of re- ric Medicine, Department of Medicine, Sinai Hospital of Balti- more, 2401 West Belvedere Avenue, Baltimore, MD 21215. nal plasma flow and GFR. The circadian pattern is Phone: 410-601-6852; Fax: 410-601-9146; E-mail: myrmiller@pol. maintained in healthy persons until around age 60 net; [email protected] yr when a shift to a greater proportion of urine pro- Copyright ᮊ 2009 by the American Society of Nephrology American Society of Nephrology Geriatric Nephrology Curriculum 1 Table 1. Physiologic changes of aging associated with the thick ascending loop of Henle is impaired and can contrib- increased urine production ute to both sodium loss and to impaired tonicity in the renal Age-associated impaired renal concentrating capacity medulla. After the administration of an acute water load with Resistance to AVP action, i.e., “acquired partial nephrogenic consequent expansion of intravascular volume, there is an ex- diabetes insipidusЉ aggerated natriuresis in elderly individuals compared with Impaired sodium conservation younger subjects. An excess of sodium excretion with increas- Decreased nocturnal AVP secretion ing age has been described in patients with mild hypertension. Decreased renin-angiotensin-aldosterone secretion The ability of the aged kidney to conserve sodium in response Increased atrial natriuretic hormone secretion to salt restriction is sluggish. Restriction of dietary sodium in- take to 10 mEq/d resulted in a half-life for reduction of urinary rather than to time of day. The circadian rhythm becomes es- sodium excretion of 17.6 h in young individuals in contrast to tablished during childhood and delay in its maturation is often 30.9 h in old subjects. The tendency to sodium wasting in el- associated with enuresis. With advanced age, there seems to be derly persons can lead to natriuresis with an accompanying blunting of the nocturnal phase of AVP secretion so that day- obligatory osmotic diuresis, especially when individuals are in time and nighttime blood levels of the hormone are similar.4,5 the recumbent position. In contrast, elderly persons may have greater response of AVP secretion to several stimuli than younger persons. The plasma AVP response to intravenous hypertonic saline infu- RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM sion in healthy elder subjects (age 54 to 92 yr) is almost double that of the younger subjects, suggesting that aging results in The ability of the kidney to conserve sodium is partly depen- increased osmoreceptor sensitivity. Studies using water depri- dent on the actions of the renin-angiotensin-aldosterone sys- vation, intravenous metoclopramide, or cigarette smoking as tem, a system affected by the normal aging process.6,7 Healthy stimuli for AVP secretion have also shown a similar age-related older individuals (age 62 to 70 yr) who consume a normal enhancement of response. In contrast, the stimulation of AVP amount of dietary sodium have lower levels of both plasma release by BP reduction or upright posture seen in young per- renin activity and aldosterone in the supine position than sons did not occur in elderly subjects, indicating an age-related young healthy persons age 20 to 30 yr. After the combined impairment of volume/pressure mediated AVP release most stimuli of low dietary sodium intake and upright posture, likely related to impaired baroreceptor function. plasma renin activity and aldosterone concentration increase in both age groups, but the mean values achieved are signifi- cantly lower in the elderly persons group. Decreased conver- RENAL WATER LOSS sion of inactive to active renin may be at least partially respon- sible for the reduction in active renin concentration in elderly In association with normal aging, there is a decline in renal persons. The age-related decrease in plasma renin results in concentrating capacity. After 24 h of dehydration, there is a decreased aldosterone production by the adrenal gland. Age progressive decline in maximal urine osmolality with increas- itself does not affect the ability of the adrenal gland to synthe- ing age. This effect of aging persists even after correction for the size and secrete aldosterone because stimulation of the adrenal age-related decline in GFR. The decline in renal concentrating by corticotropin infusion results in similar increases of both ability of the aging kidney is not caused by an inadequate re- plasma cortisol and aldosterone in young and elderly subjects. sponse of AVP to the stimulus of water deprivation but rather It is likely that the age-related reduction in aldosterone con- to impaired renal tubular response to AVP. Thus, aging can be centration is one of the factors associated with impaired renal considered to lead to the development of an acquired form of sodium conserving ability in elderly persons. There does not partial nephrogenic diabetes insipidus. Age-associated in- seem to be an effect of age on renal tubular responsiveness to creased excretion of urea can also contribute to increased urine aldosterone. excretion through its osmotic effect. Under conditions of ade- quate intake of fluid, these changes may result in no apparent clinical consequence other than mild increase in urine flow ATRIAL NATRIURETIC HORMONE rate, but the elderly person who has restricted fluid intake may be unable to adequately reduce urine formation and therefore ANH may be a significant factor in mediating the altered renal be at increased risk of dehydration. sodium handling of the elderly. Through its action on the kid- ney, it produces natriuresis and obligatory diuresis. A number of studies have shown that ANH concentration in the blood is RENAL SODIUM LOSS increased with aging. Mean basal plasma ANH levels were five- fold higher in elderly male nursing home residents than in Normal aging is associated with impaired ability of the kidney young normal men. to retain sodium. In very old persons, sodium reabsorption in In addition, the intravenous infusion of normal saline re- 2 Geriatric Nephrology Curriculum American Society of Nephrology sulted in an exaggerated rise in plasma ANH concentration in gency increases to 40 to 49% in men from the fifth to seventh the elderly persons group. Several other studies involving decades and to 40 to 50% in women in their fifth decade and healthy elderly persons have also established that basal plasma beyond.
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