Introduction

Water and volume homeostasis are under meticulous control through a complex interrelationship of the hypothalamus–posterior pituitary and the renin–angiotensin–adrenal axis.1 The elderly, however, are at increased risk for both syndromes of hyponatraemia and hypernatraemia and these disorders are associated with further clinical complications.2–4 It is therefore important to understand the physiology involved in normal water homeostasis, the potential problems associated with ageing and the possible therapeutic modalities to correct these disorders.

Normal Physiology

The supraoptic and paraventricular nuclei of the hypothalamus respond primarily to increases in serum osmolality with the release of vasopressin [antidiuretic hormone (ADH)] Figure 96.1a. The release of ADH is mediated through changes in an electrochemical gradient in these magnocellular neurons to maintain serum osmolality at 285 ± 2 mOsm kg−1. These neurons are also under the influence of neurotransmitters, such as acetylcholine (i.e. through the vagus nerve, as described below), catecholamines, opioids and angiotensin. Small changes in osmolality allow for acute adjustment of serum ADH levels with resulting water retention or free water clearance in the kidney.1

Figure 96.1 (a) Osmotic control of water balance. The hypothalamus supraoptic (SO) and paraventricular (PV) nuclei release antidiuretic hormone (ADH) through neural tracts to the posterior pituitary. Thirst is under control of a closely located series of hypothalamic neurons in the organum vasculosum of the lamina terminalis (OVLT). (b) Pressure–volume control of water and sodium balance. Baroreceptors (systemic blood pressure) in the aortic arch and volume receptors in the atria respond to changes in effective arterial blood volume (EABV) to induce release of ADH through vagal stimuli. Decreased intrarenal perfusion induces renin activation of the renin–angiotensin-aldosterone system to increase sodium retention.

There is also a parallel autonomic nervous system regulation of water retention in which vascular receptors respond to decreases in total body water and changes in organ perfusion. There are high-pressure (blood pressure) baroreceptors in the carotid sinus and aortic arch and low-pressure stretch receptors in the cardiac atria and pulmonary venous systems. Both types of receptors transmit regulatory impulses via the vagus nerve to the hypothalamic neurons to stimulate ADH in the event of low effective arterial blood volume (EABV).1 Pathophysiological states of diminished EABV will stimulate the release of ADH above that due to osmolality. Thus ADH may be ‘appropriate’ for the diminished EABV, but appears inappropriate for serum osmolality. Conditions which may increase ADH release are shown in Figure 96.1b. The baroreceptors may respond to changes in blood pressure associated with volume loss (gastrointestinal losses or diuretic-induced volume loss), decreased intravascular volume in hypoalbuminaemic oedema-forming states (ascites or nephrotic syndrome), orthostatic hypotension (due to adrenal cortical insufficiency, mineralocorticoid insufficiency or autonomic neuropathy) and decreased arterial perfusion (due to reduced cardiac output such as cardiac tamponade, cardiomyopathy or severe hypothyroidism). Decreased stretch of the volume receptors in the cardiac left atrium may occur in states of low EABV as described above. Diminished stretch in these receptors may also ‘appear’ as low pressure due to restrictions in pulmonary vascular return to the heart, as a result of increased intra-thoracic pulmonary pressure in severe reactive airway disease or with mechanical ventilation.1

Vasopressin activates V2 receptors in the distal collecting tubule of the kidney (Figure 96.2). In the absence of ADH, the tubule is impermeable to water transport. As shown in Figure 96.2, 15–30 l per day of free water may reach the distal collecting tubule. The entire volume may potentially be lost through the urine in central diabetes insipidus (lack of renal concentration ability due to either partial or complete ADH deficiency). In the presence of ADH, water is transported from the intraluminal collecting duct through aquaphorin-2 channels, across a concentration gradient to the intra-renal capillaries to reabsorb free water. The concentration gradient is derived at the loop of Henle through the medullary urea countercurrent system. The urea is freely permeable into the collecting duct. In the presence of ADH, the kidney may concentrate the urine to a volume of 0.7 l per day with an osmolality of 600–1200 mOsm kg−1, made up primarily of the secreted urea.

Figure 96.2 Renal action of ADH in water conservation.

Thirst, the conscious desire to drink, is another active component of water retention.1, 5 Thirst is under control of a closely located series of hypothalamic neurons in the organum vasculosum of the lamina terminalis (OVLT). This area is independent of the blood–brain barrier. These neurons, like the ADH-secreting neurons, are under a similar influence of serum osmolality, neurotransmitters and angiotensin. Normally thirst lags ADH release in response to increases in serum osmolality. The threshold of thirst, as measured on a visual analogue scale or the volume of water ingested, is ∼10 mOsm kg−1 greater than the ADH threshold.5 There are pathological conditions in which thirst may be independent of ADH release. Thirst is inappropriately diminished in response to serum osmolality in central nervous system conditions characterized by a reset or diminished thirst response to serum osmolality (essential hypernatraemia) or in complete lack of thirst response to severe hypernatraemia (adipsia) (Figure 96.3).5

Figure 96.3 Comparisons of disorders of thirst. Serum ADH increases with serum osmolality at a threshold of 280 mOsm kg−1 (solid line). Thirst responses increase at approximately 5–10 mOsm kg−1 higher than that of ADH release (dotted line). Abnormally decreased thirst responses are found in essential hypernatreamia (dashed line) and severely impeded thirst responses are found in adipsia (dashed-dotted line).

Whereas ADH is the main hormone involved in water homeostasis, the renin–angiotensin–aldosterone system is the main factor in sodium retention and systemic blood pressure/volume control. Renin is released from the juxtaglomerular apparatus of the kidney in response to low perfusion, low intravascular volume and low tubular sodium. Renin is an enzyme which converts liver-derived angiotensinogen to angiotensin 1 and lung-derived angiotensin-converting enzyme further metabolizes conversion to angiotensin 2. Angiotensin 2 both stimulates the release of the mineralocorticoid aldosterone to retain sodium and stimulates the hypothalamic neurons to release ADH and provoke thirst (Figure 96.1b).

Syndromes of hyponatraemia may reflect physiological ‘appropriate’ release of ADH in response to vagal stimuli due to decreased perfusion pressure or decreased plasma volume (decreased EABV). In these situations, the elevated ADH is inappropriate for the serum osmolality. The syndrome of inappropriate ADH secretion (SIADH) is a research definition which eliminates appropriate physiological ADH responses. The discussion of hyponatraemia includes both ‘appropriate’ and SIADH syndromes.

Hyponatraemia may be defined as a serum sodium level <135 mequiv l−1 and for clinically significant hyponatraemia <130 mequiv l−1.1 Aside from water intoxication associated with excessive water intake during exercise, most causes of hyponatraemia are associated with imbalances in ADH levels.2–4, 6 Clinical syndromes of hyponatraemia (and true hypo-osmolality) are associated with decreased effective serum osmolality,7, 8 where

Serum concentrations of urea, which are included in the calculation of plasma osmolality, are not considered as part of the calculation of effective extracellular osmolality, since urea is freely permeable through cell membranes.

Therefore, the major component of extracellular osmolality in the non-hyperglycaemic state is serum sodium with its corresponding anions. Severe clinically significant hyponatraemia is usually associated with serum sodium in the range <120 mequiv l−1 or with the rapid decline of serum sodium as in water intoxication or post-anaesthesiology hyponatraemia.1, 6 The major toxicities are due to changes in neurological functions (defined as hyponatraemic encephalopathy).1, 6 Symptoms may range from headache, nausea, disorientation and confusion to more severe symptoms of cerebral oedema with seizures, coma and, in extreme cases, cerebral tentorial herniation and death. Chronic hyponatraemia (which has developed over a time course of >48 h) usually results in central nervous system intracellular adaptation, with the extrusion of intra-neuronal organic and inorganic osmoles. During the treatment of symptomatic hyponatraemia, the concern therefore is that overly rapid correction of hyponatraemia (defined as an increase of >12 mequiv l−1 over 24 h or >18 mequiv l−1 over 48 h) may result in cerebral dehydration and pontine and extrapontine osmotic demyelination syndromes (ODS). These ODS may be delayed in onset and associated with severe neurological morbidity and mortality.1, 6

Water Homeostasis in the Elderly

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