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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-
ric Medicine, Department of Medicine, Sinai Hospital of Balti-
of urine flow is paralleled by similar rhythms of re- 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; mmiller@lifebridgehealth.org
yr when a shift to a greater proportion of urine pro- Copyright 2009 by the American Society of Nephrology
In healthy adults, 24-h urine production is usually in the range Nocturnal Polyuria in Multiple System Atrophy
of 1000 to 1500 ml and bladder capacity generally ranges from Multiple system atrophy (MSA) is a central nervous system
approximately 400 to 750 ml. This is associated with a daytime degenerative disease that most commonly occurs in older
voiding frequency of four to five times in men and five to six persons. It affects many areas of the central nervous system
times in women and with rare voiding during normal periods and has central autonomic insufficiency or Shy-Drager syn-
of sleep. There is a suggestion that voiding frequency increases drome as one its components. Patients with central auto-
with age, especially in men. With advancing age, there is a nomic insufficiency have been observed to excrete large
progressive increase in the prevalence of urgency, most com- amounts of urine when recumbent at night, and this noc-
monly caused by detrusor instability. The prevalence of ur-
Table 3. Association between nocturnal urine flow rate,
Table 2. Typical parameters related to circadian water bladder volume, and nocturnal urinary frequency in healthy
excretion in healthy young and elderly adults* young and elderly adults*
Young Elderly Young Elderly
Day Night Day Night Nighttime urine flow rate (ml/h) 35 70
Urine volume (ml/h) 75 35 50 70 Time in bed (h) 8 8
Urine osmolality (mosm/kg) 700 830 510 450 Nighttime urine production (ml) 280 560
Plasma AVP (pg/ml) 1.1 2.0 1.9 1.3 Bladder capacity (ml) 400 200
Plasma ANH (pg/ml) 19 17 40 55 Number of voids during sleep period 0 2
*Data show typical values based on literature and/or authors experience. *Data show typical values based on literature and/or authors experience.