Hypernatraemia and Diabetes Insipidus: When Water Is Lost

The one idea: high sodium means a water deficit

Serum sodium is not a measure of how much salt you have — it is a measure of the ratio of salt to water. This is the single sentence that unlocks the whole topic. A high sodium concentration nearly always means the water has fallen relative to the salt, not that salt has been added. Because thirst is such a powerful, fast reflex, a healthy adult with free access to a glass of water essentially cannot become hypernatraemic — they would drink and correct it. So hypernatraemia is, at heart, a disorder of people who cannot drink to their thirst: the very young, the very old, the sedated, the neurologically impaired, the bed-bound — anyone whose thirst is blunted or whose hand cannot reach the cup. Keep that filter in mind and the causes fall into place. This mirrors the logic of the Hyponatraemia chapter exactly, run in reverse — there the problem was water excess, here it is water lack.

The causes, sorted by what was lost

Group the causes by the kind of loss and you never have to memorise a list. First and commonest: pure water loss or insufficient intake — the frail, dependent, febrile or sweating patient who simply cannot drink enough to keep up. This is the everyday hospital and care-home hypernatraemia, and diabetes insipidus (below) is its dramatic renal version, where the kidney pours out litres of dilute water. Second: hypotonic fluid loss — the body loses fluid that is watery relative to its salt, so what is left behind is saltier. Diarrhoea and vomiting do this (linking to the Gastrointestinal section on fluid loss), as does an osmotic diuresis — most importantly the massive glucose-driven water loss of uncontrolled hyperglycaemia, the mechanism behind the profound dehydration of a hyperosmolar hyperglycaemic state (see the Diabetes chapter). Third and rarest: a true sodium gain — hypertonic saline or sodium bicarbonate given in resuscitation, or salt poisoning. Notice that only this last, uncommon group actually adds sodium; the other two, which cover the overwhelming majority of patients, are water problems wearing a sodium number.

Why the symptoms are all neurological

Raise the sodium outside the cells and you raise the osmolality of the fluid bathing them; water then follows the osmotic gradient out of the cells to dilute it. Every cell shrinks a little, but only in the brain does shrinkage produce dramatic signs. Early there is thirst (if the thirst mechanism still works) and lethargy; then irritability, weakness, a coarse tremor; and in severe or fast cases, drowsiness, seizures and coma. In infants the classic picture is a high-pitched cry and irritability. The severity tracks not just the absolute sodium but how fast it rose — a brain has ways to defend its volume if given time, and that defence is exactly what makes treatment dangerous.

Diabetes insipidus: the pharmacology hub

"Insipidus" means tasteless — huge volumes of dilute, unsweet urine, the opposite of the sugary flood of diabetes mellitus. The kidney's ability to concentrate urine and conserve water depends entirely on one hormone: antidiuretic hormone (ADH, also called vasopressin), released from the posterior pituitary and acting on V2 receptors in the collecting duct to insert water channels and reabsorb water. Diabetes insipidus is the failure of this system, and it splits into two mechanistically opposite forms — the distinction that the whole management turns on. In cranial (central) DI the posterior pituitary does not make or release enough ADH — the signal is missing. Causes include head injury, pituitary surgery or tumours, and this connects directly to the Endocrine section, where ADH physiology and the posterior pituitary are covered in full. In nephrogenic DI the ADH is present but the kidney cannot hear it — the V2 receptor or its downstream machinery is unresponsive. The result is the same in both: the kidney cannot hold onto water, litres of dilute urine pour out, and unless the patient drinks enormous amounts, the sodium climbs.

The treatment forks completely at the cranial-versus-nephrogenic split. Cranial DI is a hormone-deficiency state, so you replace the hormone: desmopressin, a synthetic analogue of ADH that selectively activates the V2 receptor (with little of vasopressin's blood-pressure effect), given intranasally, orally or by injection. It works beautifully because the kidney's receptors are intact and simply waiting for a signal. Nephrogenic DI is the harder problem — giving more ADH is futile when the receptor is deaf. Here management means removing the cause first, then a low-salt, low-protein diet to reduce the solute the kidney must excrete, and, paradoxically, a thiazide diuretic. It seems absurd to give a diuretic to someone already urinating litres, but a thiazide causes a mild volume contraction that ramps up proximal sodium and water reabsorption, so less water reaches the collecting duct and urine volume actually falls — one of pharmacology's great counter-intuitive tricks (the thiazides themselves are covered in the Cardiovascular / Diuretics chapter). Amiloride and, sometimes, an NSAID are added particularly for lithium-induced nephrogenic DI, which brings us to the classic drug cause.

The drug you must link to nephrogenic DI is lithium. Lithium accumulates in the collecting-duct cells and blunts their response to ADH, and long-term use is the classic acquired cause of nephrogenic DI — a fact the Toxicology / Central Nervous System chapter on lithium underlines, alongside its narrow therapeutic index and thyroid effects. Other causes of the kidney going deaf to ADH are hypercalcaemia and hypokalaemia (both interfere with the concentrating mechanism — see the Calcium and Potassium chapters) and inherited receptor defects. To distinguish cranial from nephrogenic DI at the bedside, the water-deprivation test is used: withhold water and watch whether the urine concentrates. It won't in either DI, but then give desmopressin — the cranial kidney, its receptors intact, responds and concentrates the urine, while the nephrogenic kidney, deaf to ADH, does not. That single response splits the diagnosis and chooses the treatment.

Treatment: give water — and the cardinal safety rule

The disorder is a water deficit, so the treatment is water — plus fixing whatever is losing it. If the patient can drink and absorb, oral water is the safest, most physiological route. When intravenous replacement is needed, you give free water — as 5% dextrose (the glucose is metabolised, leaving pure water) or another hypotonic fluid — never the concentrated saline that would only feed the problem. Alongside, treat the cause: control the fever, stop the diarrhoea, correct the hyperglycaemia, replace ADH in cranial DI. It helps to estimate the free-water deficit — how many litres of pure water the body is short — from the patient's weight and how far the sodium sits above normal; this gives a target volume to replace, guiding the rate rather than dictating a blind infusion. This estimation and the assessment of fluid status link to the Fluids, Compartments & Acid–Base chapter, where the compartments and fluid choices are set out in detail.

One situation flips the treatment: hypervolaemic hypernatraemia, where the problem is not lost water but gained sodium — the iatrogenic case of a patient loaded with hypertonic saline or sodium bicarbonate, who is now both salt-overloaded and fluid-overloaded. Pouring in more water alone would worsen the overload. Here you must get the sodium out: a loop diuretic to excrete the excess sodium (with water replacement to cover the free-water loss the diuretic also causes), and dialysis if the kidneys cannot cope. Recognising that this small subgroup needs sodium removal rather than water repletion is the exam's favourite twist on the topic.