GM 43, March 2013 

 

Dr Nabil M Aly 

The ageing process is frequently accompanied by various maladaptations to stress in different organ systems and physiologic functions. The complex mechanisms associated with water metabolism are particularly vulnerable to age-related maladaptations and to the various disease processes and medical interventions that frequently occur in older people. The sensation of thirst, renal function, concentrating abilities and hormonal modulators of salt and water balance are often impaired in older people, which makes such patients highly susceptible to morbid and iatrogenic events involving salt and water.1

Clinicians should use a systematic approach in evaluating water and sodium problems, utilising a comprehensive history and physical examination, and a few directed laboratory tests to make the clinical diagnosis. Furthermore, clinicians should have a clear appreciation of the roles that iatrogenic interventions and lapses in nutrition and nursing care frequently play in upsetting the homeostatic balance in older patients, particularly those who are in long-term institutional and inpatient settings.1

Normal water metabolism

The status of water homeostasis in the body is efficiently reflected by the serum sodium concentration. Sodium is the dominant cation in extracellular fluid and the primary determinant of serum osmolality. If a change in the total-body water (TBW) concentration occurs without an accompanying change in total-body solute, osmolality changes along with the serum sodium concentration (box 1).

Hypernatremia and hyponatremia are primary disturbances of free water and reflect pathologic alterations in water homeostasis. At steady state, water intake and water losses are matched. If losses exceed intake, thirst is stimulated and fluid intake increases. Thirst is stimulated when the serum osmolality rises above 290 to 295mOsm per kg (290 to 295mmol per kg).1 Thirst is also stimulated by hypotension and hypovolaemia. Thirst is a subjective perception that provides the urge for humans to drink fluids and it is a component of the regulatory mechanisms that maintain body fluid homeostasis. This urge to ingest fluids is generated from central processing in the brain (mainly: hypothalamus) and it may arise for several reasons that include habitual, cultural, and psychogenic drives as well as the regulatory response to reductions in the fluid content of various bodily compartments, hypertonicity of the extracellular fluid, or increases in the circulating concentration of some  hormones. 

Renal water conservation is the first-line defence against water depletion, but this mechanism is insufficient in settings of significant dehydration and hypertonicity. Moreover, the stimulation of thirst is required to ultimately maintain homeostasis. In conditions of volume depletion or hypertonicity, secretion of antidiuretic hormone (ADH) is stimulated, water is reabsorbed, and concentrated urine is excreted. In conditions of hypotonicity, ADH is normally suppressed, and dilute urine is excreted.1

Impact of ageing on water metabolism

The age-related decrease in total-body water (relative and absolute) makes older persons markedly susceptible to stresses on water balance.2 Average healthy 30–40 year olds have a TBW content of 55 to 60%. By the age of 75 to 80 years, the TBW content has declined to 50%, with even more of a decline in older women.3 In addition, the thirst mechanism diminishes with age, which significantly impairs the ability to maintain homeostasis and increases the risk for dehydration.4 

There is also a clear age-related decrease in maximal urinary concentrating ability, which also increases the risk for dehydration.4 ADH release is not impaired with ageing, but ADH levels are increased for any given plasma osmolality level, indicating a failure of the normal responsiveness of the kidney to ADH.5 

The ability to excrete a water load is delayed in older people.6  This propensity may contribute to the frequently observed episodes of hyponatremia in hospitalised older patients who are receiving hypotonic intravenous fluids or whose fluid intake is not properly monitored.2 Other changes in renal physiology and anatomy that increase the older patient’s susceptibility to alterations of water imbalance include decreased renal mass, cortical blood flow and glomerular filtration rate, as well as impaired responsiveness to sodium balance.5,7-8 The impact of a lifetime of accumulated disease and comorbidities must also be duly considered in every clinical situation with an older patient, in addition to age-related physiologic changes.

The older patient has a diminished reserve of water balance and an impaired regulatory mechanism.1 Thirst sensation, concentrating abilities and hormonal modulators of salt and water balance are sluggish and highly susceptible to being overtaken by morbid or iatrogenic events.

Hyponatraemia and SIADH

Hyponatraemia and hypernatraemia are common in older people, particularly among those who are hospitalised or living in long-term institutional care.1 Hyponatraemia is defined as a serum sodium concentration of less than 137mEq per L (137mmol per L). It is estimated that nearly 7% of healthy older persons have serum sodium concentrations of 137mEq per L or less.5 Cross-sectional studies suggest that hyponatraemia may be present in 15 to 18% of patients in chronic care facilities.5

A 12-month longitudinal study showed that more than 50% of nursing home residents had at least one episode of hyponatremia.9  Similarly, cross-sectional studies suggest a 1% prevalence of hypernatraemia in nursing home residents.10 Among nursing home patients who require acute hospitalisation, the prevalence of hypernatraemia has been reported to be more than 30%.11 Thus, it would be an unusual day in many family physicians’ practices that at least one diagnostic or therapeutic issue related to water metabolism did not arise.1

Euvolemic hyponatraemia is usually the result of an increase in free water with little change in body sodium. This condition is most commonly associated with non-osmotic vasopressin secretion. Causes of euvolemic hyponatraemia include certain drugs (such as hydrochlorothiazides), glucocorticoid deficiency, hypothyroidism, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and reset osmostat syndrome.12

SIADH is characterised by the continued release of ADH in the face of dilution of body fluids and increased extracellular volume. The urine is “inappropriately” concentrated when the body is trying to correct a state of hypotonicity.

SIADH is a diagnosis of exclusion (box 2). Patients with hyponatraemia usually are asymptomatic. Symptoms often do not occur until the serum sodium concentration drops below 125mEq per L (125mmol per L).1 The most common manifestations of hyponatraemia are neurologic, the result of swelling of brain cells secondary to intracellular movement of water. Patients with severe hyponatraemia may present with nausea, headache, lethargy, confusion, coma or respiratory arrest. If hyponatraemia develops rapidly, muscular twitches, irritability and convulsions can occur. The only manifestations of chronic hyponatraemia may be lethargy, confusion and malaise. Because hyponatraemia is usually only mildly symptomatic or asymptomatic, treatment should be tailored to the clinical situation.1

Hyponatraemia in a euvolemic patient can be managed with fluid restriction and discontinuation of any medications that affect free-water excretion, along with initiation of treatment of the underlying cause. Fluid restriction must be less than free-water losses, and total fluid intake should typically be less than 500 to 800mL per day in the older patient with euvolemic hyponatremia.5 If the cause of  hyponatraemia is secondary to a low extra-cellular volume (volume contraction), the fluid deficit should be corrected by administration of normal saline solution. Once the patient is clinically euvolemic, the drive for the body to produce ADH is gone, and the patient is able to excrete the excess free water.2 If the clinical picture is one of an “effective” low extracellular volume, but the patient appears to have fluid overload, the underlying cause of the low sodium level, such as congestive heart failure, nephrotic syndrome, cirrhosis or hypoalbuminemia, should be treated.

SIADH is treated with free-water restriction until the underlying cause of the disorder is corrected. Administration of normal saline is not an appropriate therapy because the sodium may be rapidly excreted while the water is retained, exacerbating hyponatremia.12

An adjunct to free-water restriction, in some circumstances, is the addition of therapy with demeclocycline (Declomycin) in a dosage of 600 to 1,200mg per day. Demeclocycline induces nephrogenic diabetes insipidus and helps to correct hyponatremia, especially in a patient in whom free-water restriction is highly difficult.13 Demeclocycline, however, is contraindicated in patients with renal or hepatic disease.1 Recently, clinical studies showed that in patients with euvolemic or hypervolemic hyponatremia, tolvaptan, an oral nonpeptide vasopressin V2-receptor antagonist, was effective in increasing serum sodium concentrations at day four and day 30.14 The adverse effects observed in clinical trials were predictable, given the mechanism of action, and included thirst and dry mouth as well as hypernatraemia. However, it remains to be shown that tolvaptan improves symptoms of hyponatraemia, especially neuropsychiatric disorders.

Hypovolaemia and fluid replacement

Hypovolaemia is one of the most common and potentially reversible crises in acute medicine. It occurs as the result of fluid loss (eg. bleeding, burns, vomiting and diarrhoea) or vasodilatation of the circulating volume (eg. septic shock). In either case, rapid correction is mandatory. The debate about whether to use crystalloids or colloids for the resuscitation of hypovolaemia is not as important as the challenge of continually maintaining a normal intravascular volume. The importance of maintaining the intravascular space (IVS or CV) is related to the deleterious effects of ischaemia and there is no conclusive data on exactly how much ischaemia can be safely tolerated.

Particularly important are cells with high metabolic rates such as the brain, heart and kidney. Organs with high metabolic rates initially have their blood supply protected by auto-regulation at the expense of decreased blood supply to non-vital organs such as the skin and muscle. Ischaemia can be better tolerated in organs such as the skin or muscle as they have a low metabolic rate. However, there comes a point when even these cells begin to malfunction.14 Even minor degrees of hypovolaemia predisposes to splanchnic hypoperfusion, predisposing to translocation of bacteria and bacterial breakdown products, which in turn can predispose to multi-organ dysfunction syndrome (MODS) and even death.14 Cytokines are also released as a result of the ischaemia itself, adding to the MODS.15

Colloids are molecules capable of exerting oncotic pressure (COP) and have limited (or zero) ability to cross a semi-permeable membrane due to their molecular size. At the same time, they have the ability to attract solvent (solvent drag) from the other side of the membrane into the compartment in which they are situated (in this case PV).  Colloids are mainly distributed to the IVS. Even with increased capillary leakage, a greater proportion of a colloid solution will remain in the IVS compared to a crystalloid solution. On the other hand,  crystalloid solutions are mainly distributed to the interstitial space (ISS). Approximately two-thirds of all infused crystalloid must be distributed to the ISS, according to basic physiology, ie. there are 17L of fluid in the ECF and a crystalloid solution, without any inherent COP, must distribute equally across the whole 17 litres, with little or no fluid going to the intracellular space (ICS or also ICF).  If the IVS is under-filled as measured by central venous pressure –CVP or jugular venous pressure-JVP, then a fluid that is distributed to that space such as blood or colloid is the ideal fluid.

To use a crystalloid, which is mainly distributed to the ISS, according to measurements of a different space (CVP/JVP measurements for the IVS), does not make physiological sense. Moreover, the ISS is rarely under-filled in the seriously ill patients and most of critically ill patients have peripheral oedema, which could be worsen by giving crystalloids.16 Increasing volumes of crystalloid result in overt hypoxia and increasing degrees of pulmonary oedema. This is not due to heart failure but simply due to the natural compartmentalising of saline into the ISS. In addition to the expansion of the ISS in the lungs by large volumes of crystalloid, peripheral oedema may also occur.17 A significant hyperchloraemic acidosis can occur when large amounts of isotonic saline are used, but the use of Ringer’s Lactate (Hartmann’s) solution is not associated with this phenomenon.18-19

Types of replacement fluids

The types of intravenous fluids used in fluid replacement are generally within the class of volume expanders. If given intravenously, isotonic crystalloid fluids will be distributed among the intravascular and interstitial spaces. Normal saline solution, or 0.9% sodium chloride solution, is often used because it is isotonic, and therefore will not cause potentially dangerous fluid shifts. In addition, if it is anticipated that blood will be given, normal saline is used because it is the only fluid compatible with blood administration. In general, for high risk patients, the rapidity of replacement of fluid is more important than the actual type of fluid administered. Lactated Ringer’s (Hartmann’s) solution is another isotonic crystalloid solution and it is designed to match most closely blood plasma.4

Blood products, non-blood products and combinations are used in fluid replacement, including colloid and crystalloid solutions. A systematic review found no evidence that resuscitation with colloids, instead of crystalloids, reduces the risk of death in patients with trauma, burns or following surgery.20

Conclusion

The age-related decrease in total-body water (relative and absolute) makes older persons markedly susceptible to stresses on water balance. The ageing process is frequently accompanied by various maladaptations to stress in different organ systems and physiologic functions. At steady state, water intake and water losses are matched. However, thirst sensation, renal function, concentrating abilities and hormonal modulators of salt and water balance are often impaired in older people, which make such patients highly susceptible to morbid and iatrogenic events involving salt and water. Hyponatraemia is common in older people, particularly among those who are hospitalised or living in long-term institutional care.

SIADH is characterised by excess release of ADH in the face of dilution of body fluids with increased extracellular volume and “inappropriately” concentrated urine. SIADH is treated with free-water restriction until the underlying cause of the disorder is corrected. Administration of normal saline is not an appropriate therapy in SIADH because the sodium may be rapidly excreted while the water is retained, exacerbating hyponatraemia.

Hypovolaemia is one of the most common and potentially reversible crises in acute medicine. The debate about whether to use crystalloids or colloids for the resuscitation of hypovolaemia is not as important as the challenge of continually maintaining a normal intravascular volume. Normal saline solution is often used in fluid replacement because it is isotonic, and therefore will not cause potentially dangerous fluid shifts. However, Hartmann’s (Lactated Ringer’s) solution is another isotonic crystalloid solution, which is designed to match most closely blood plasma. Clinicians should have a clear appreciation of the roles that iatrogenic interventions and lapses in nutrition and nursing care frequently play in upsetting the homeostatic balance in
older patients.

Conflict of interest: none declared

References

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