hypothalamic neuron to release ADH and provoke thirst (Figure 15.2).
Figure 15.2 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.
Figure 15.3 Renal action of ADH in water conservation.
Figure 15.4 Comparisons of disorders of thirst. Serum ADH levels increase with serum osmolality at a threshold of 280 mOsmol/kg (solid line). Thirst responses (rate of fluid intake or sensation of thirst) start to increase at approximately 5–10 mOsmol/kg 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 (‐ ‐ ‐ ‐ ‐ interrupted dashed line).
Syndromes of hyponatremia 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 that eliminates appropriate physiological ADH responses. The discussion of hyponatremia includes both ‘appropriate’ and SIADH syndromes.
Hyponatremia may be defined as a serum sodium <135 mEq/L, or at a level <130 mEq/L for clinically significant hyponatremia.1,2 Aside from water intoxication associated with excessive water intake during exercise, most causes of hyponatremia are associated with imbalances in ADH levels.4,8 Clinical syndromes of hyponatremia (and true hypo‐osmolality) are associated with decreased effective serum osmolality9,10 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‐hyperglycemic state is serum sodium with its corresponding anions. Severe clinically significant hyponatremia is usually associated with serum sodium in the range of <120 mEq/L, or with the rapid decline of serum sodium as in water intoxication or post‐anaesthesiology hyponatremia.8 The major toxicities are due to changes in neurological functions (defined as hyponatremic encephalopathy).8 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 hyponatremia (which has developed over >48 hours) usually results in central nervous system intracellular adaptation, with the extrusion of intra‐neuronal organic and inorganic osmoles. During the treatment of symptomatic hyponatremia, the concern therefore is that overly rapid correction of hyponatremia (defined as an increase of >8 mEq/L over 24 hours) may result in cerebral dehydration and pontine and extrapontine osmotic demyelination syndromes (ODS).2,8 These ODS syndromes may be delayed in onset and associated with severe neurological morbidity and mortality.
Water homeostasis in the elderly
The elderly are prone to disorders of both hyper‐ and hyponatremia.1‐3,11 These abnormalities may be due to the normal physiological changes in the ageing process, intercurrent illnesses, or side effects of medications. Normal physiological changes due to ageing may result in a tendency toward hypernatremia (sodium >145 mEq/L).6 Although renal function declines with age, fluid homeostasis is not affected by this decline until glomerular filtration rates are as low as 30 to 50 mL/minute.12 Compared with younger individuals subjected to water deprivation, healthy older adults have decreased thirst responses and increased serum ADH levels but decreased urinary concentration and ability to excrete free water.7,13‐15 The decreased responsiveness of aquaporin‐2 to ADH may be due to a physiological decreased aquaporin‐2 receptor expression associated with ageing.16 Also, after age >75, there is a decrease in total body water from 60 to 50%, potentiating the risk for dehydration over short periods.3,11
The institutionalized elderly may be more prone to hypernatremia.3,11 Whereas normal elderly patients subjected to fluid restriction may have a decrease in thirst response compared to younger subjects, they retain their ability to secrete ADH. Those with Alzheimer’s disease may be more severely compromised by having a more pronounced decrease in both thirst and ADH responses compared to even age‐matched controls.17 In patients with Alzheimer’s disease, these thirst responses may fall in the range compatible with essential hypernatremia,6 and the ADH levels may be inappropriately low for the degree of dehydration and comparable with levels found in states of partial central diabetes insipidus.17 Unless patients are monitored, elderly institutionalized individuals dependent on caregivers for fluid intake (due to previous stroke or degenerative brain diseases) may not receive adequate fluids at or between meals.18 These groups of people may have an 18% incidence of hypernatremia.6 The incidence of hypernatremia may be exacerbated during acute intercurrent febrile upper respiratory illness to levels as high as 63%.19 They may also have concurrent illnesses (such as hypercalcemia or hypokalemia) or be prescribed medications (such as lithium), all of which are associated with nephrogenic diabetes insipidus (renal insensitivity to ADH action) and inability to retain water.
Hyponatremia is also very common in the elderly, as outpatients, inpatients, and those in long‐term care.4,8,20 The prevalence of hyponatremia among elderly outpatients is 7 to 11%12 and between 11 and 53% for those in long‐term care.5,20 The causes of hyponatremia are less clearly defined than for hypernatremia. There are physiological changes in the kidneys with ageing, resulting in a decreased ability to concentrate urine and excrete free water.21,22
The onset of hyponatremia may be associated with medications or involvement in concomitant illnesses such as chronic heart failure and cirrhosis.4,8,23 Many medications involved in central nervous system modulation and opioid transmission are associated with ADH secretion. Common agents associated with hyponatremia in all people include antidepressants (both tri‐ and tetracyclics), antipsychotic drugs (phenothiazines, butyrophenones), antiepileptic drugs (carbamazepine, oxycarbazepine, sodium valproate), and opioids.1 The elderly appear to be more sensitive to the hyponatremic effects of selective serotonin reuptake inhibitors (SSRIs).24,25 Diuretics, due to their frequent use, are probably the most common medication associated with hyponatremia, with a prevalence as high as 11% in the geriatric population.26 Less commonly, other antihypertensive agents such as angiotensin‐converting enzyme inhibitors and calcium channel antagonist produce a decrease in EABV, with physiological ‘appropriate’ increases in ADH.24