SCIENCE REVIEW
Diabetes insipidus: a trio of case histories
Water is essential to life. The approximate 40–45 litres of water present in the human body constitutes nearly two- thirds (55–65%) of total body weight, and, while it is possible to survive for many weeks without food, if water is withheld then dehydration, circulatory failure and death follow in quick succession in a matter of days. Good health demands not only access to water but water balance – the amount of water lost from the body must match water intake. The regulatory mechanism that ensures water balance involves the integrated action of the thirst response, specialised cells in the brain that detect minute changes in blood osmolality, the pituitary hormone arginine vasopressin (AVP; also known as antidiuretic hormone [ADH]), and the kidneys. As many different disease states can disturb this regulatory mechanism, disordered water balance is a common clinical problem that can only be recognised and resolved with the help of laboratory testing. Disturbances of water balance can be divided into two groups depending on whether there is tendency to either reduced or raised plasma osmolality. Thus, there are the hypo-osmolar water disturbances, in which there is excess body water, and the hyperosmolar water disturbances, in which there is a water
Around two-thirds of the 40-45 litres of water present in the adult human body is contained within cells; this is the intracellular fluid (ICF). The remaining one-third is contained in the extracellular fluid (ECF). The approximate 14 litres of water in the ECF is divided between the interstitial fluid, which occupies the space between tissue cells, and the intravascular fluid (blood). Total blood volume is around 4.5 litres, of which around 80% (3.6 litres) is water. As cell membranes are freely permeable
to water but not all solutes, it is the concentration of solutes (specifically those that are membrane-impermeable) that determines the compartmental distribution of body water and thereby maintenance of blood volume. As long as osmolality (a measure of total solute concentration) is the same on either side of the cell membrane, there is no movement of water between ECF and ICF. Sodium, the major extracellular solute
and principal contributor to ‘effective’ plasma (ECF) osmolality, is central to the maintenance of ECF and blood volume. Thus, sodium and water metabolism are inextricably linked, as demonstrated by the hyponatraemia (reduced plasma sodium
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deficit. The main representative condition of hypo-osmolar disturbance is the syndrome of inappropriate antidiuretic hormone (SIADH), which is the result of inappropriately increased AVP secretion. Diabetes insipidus (DI), which by contrast is the result of AVP deficiency, is representative of hyperosmolar water disturbances. A trio of case reports illustrate the variation in the way hyperosmolar disturbances manifest. The first (Hayanga AJ, Kohen R, Egeland B et al. Central diabetes insipidus: a rare perioperative cause of severe hypernatraemia. Anaesth Intensive Care 2008; 36 [2]: 235–41) described the case history of a young woman whose diabetes insipidus was recognised by chance during recovery from unrelated surgery when her plasma sodium concentration suddenly and unaccountably rose to a life-threatening 196 mmol/L. Two recent case reports illustrate the effect of drugs (Fung E, Anand S, Bhalla V. Pemetrexed-induced nephrogenic diabetes insipidus. Am J Kidney Dis 2016 May 28. Epub ahead of print) and the possibility of congenital acquisition of DI (Zheng K, Xie Y, Li H. Congenital nephrogenic diabetes insipidus presented with bilateral hydronephrosis and urinary infection: a case report. Medicine [Baltimore] 2016; 95 [22]: e3464).
concentration) that typically characterises hypo-osmolar water disturbances, and the hypernatraemia (increased plasma sodium concentration) that occurs in hyperosmolar water disturbances.
Water balance With free access to water, total body water never normally varies by more than 1–2%, reflecting the balance between water intake and water loss that characterises good health. Total water loss is normally approximately 2500 mL/day. This comprises water lost via the kidneys in urine (around 1500 mL/day), water lost via the skin in sweat (around 600 mL/day), water lost via the lungs in expired air (around 400 mL/day) and water lost via the gastrointestinal tract
‘Total body water never normally varies by more than 1–2%, reflecting the balance between water intake and water loss that characterises good health’
in faeces (around 100 mL/day). Normal metabolism is associated with production of around 200 mL water/day. Water contained in foods provides a further 1000 mL, and fluid intake (water, beverages, juices etc) is usually around 1300 mL. The only regulatory control of water
intake operates via the thirst response, which protects against water deficit by promoting fluid consumption. Thirst is mediated by osmoreceptor cells located in the anterior hypothalamus of the brain, in response to the rising plasma osmolality that water deficit induces. There is an inevitable shift of water from ICF to ECF when plasma (ECF) osmolality rises because water moves to equalise osmolality on either side of the cell membrane. This shift of water leaves all cells (including osmoreceptors) relatively dehydrated and it is osmoreceptor dehydration that gives rise to the sensation of thirst. The thirst response also can be invoked by a severe reduction in plasma volume (hypovolaemia), even if plasma osmolality (hydration) is normal. The only regulated route of water loss is
that via the kidneys in urine. A minimum urine volume (water loss) of around 500 mL/day is required to excrete the solute
AUGUST 2016 THE BIOMEDICAL SCIENTIST
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