Thirst

Thirst is thought to be a corrective mechanism which acts as a support to the physiological control of fluid balance in the body. The main factor which maintains this balance is the secretion of anti-diuretic hormone (ADH). ADH, also known as vasopressin, is secreted by the hypothalamus when plasma osmolality increases. The main site of action is the distal renal tubule, where ADH binds to receptor sites and stimulates the resorbption of water.¹
The physiological driving force behind the desire to drink liquid is thus the maintenance of blood osmolality. In Western societies this primary mechanism is supplemented by secondary factors such as social convention and the habit of drinking with meals (secondary drinking), which in fact results in most people being in a state of mild water excess. This is compensated for under normal circumstances by renal excretion.
Sensory osmoreceptors in the lamina terminalis and other areas of the brain stimulate cortical effector regions, principally in the anterior cingulate cortex and insula, to trigger the sensation of thirst in response to a rise in blood osmolality. This sensation usually starts at 280mosmol/kg. The intensity of thirst and the amount of water required to quench it is directly proportional to blood osmolality. Other areas of the brain integrate these signals and provide inhibitory responses when thirst is quenched, to prevent fluid overload.²
Circulating angiotensin II is known to play a role, but the exact biochemical pathways governing fluid intake and thirst have yet to be elucidated.³ It is known that the area of the hypothalamus which releases angiotensin II is anatomically close to, and linked neuronally with, the area that releases ADH, so there is clearly a close connection between the two systems.⁴
It is likely that oropharyngeal sensors quell the thirst desire before any changes in osmolality, when water is drunk rapidly.³
Acute falls in blood pressure and/or blood volume will also stimulate thirst. 15% or more reduction in circulating blood volume is required for this effect.
With increasing age the thirst stimulus become blunted with a reduction in primary drinking. This is usually compensated for by secondary drinking.⁵ In pregnancy, the thirst stimulus is thought to be set at a lower osmolality, which leads to increased intake of water and an increase in circulating blood volume.

Excessive thirst, also known as polydipsia, has a number of causes (see Differential Diagnoses, below).

• Diabetes Insipidus - congenital or acquired (can also be classified as cranial or nephrogenic)
• Chronic renal disease
  • Systemic or metabolic disease
  • Myeloma
  • Amyloidosis
  • Hypercalcaemia
  • Hypokalaemia
  • Sickle cell disease
• Osmotic diuresis
  • Hyperglycaemia - i.e. Diabetes mellitus
  • Poorly resorbed solutes (mannitol, sorbitol, urea)
• Drugs - e.g. lithium, anticholinergics, diuretics
• Psychogenic

• Renal function tests and glucose levels should be assessed to rule out chronic kidney disease and diabetes mellitus.
• Urine specific gravity, urinary sodium, simultaneous plasma and urine osmolality should be arranged when diabetes insipidus is suspected. A urine specific gravity of 1.005 or less and a urine osmolality less than 200 mosmol/kg is highly suggestive of diabetes insipidus. Random plasma osmolality is usually greater than 287 mosmol/kg.
• A water deprivation test (Miller-Moses test) is helpful in cases of diagnostic difficulty.⁷ Water is withheld until the patient can tolerate it no further, there is a significant drop in blood pressure, or signs of dehydration develop. Urine osmolality and weight are recorded hourly. Once two sequential urine osmolalities vary by less than 30mosmol or if the weight drops by more than 3%, 5 units of aqueous vasopressin is given subcutaneously. 60 minutes later, urine and plasma osmolality and if appropriate ADH levels are measured.

What the results mean

• In normal individuals, the urine osmolality is 2-4 times greater than the plasma osmolality. Administration of vasopressin results only in a small increase in urine osmolality (less than nine per cent). It takes between 4-18 hours to achieve maximal concentration of urine.
• In central diabetes insipidus (due to decreased production of antidiuretic hormone (ADH), there is an excessive increase in plasma osmolality, but not in urine osmolality. Administration of vasopressin results in an increase in urine osmolality of 50% or more. ADH levels are minimal.
• In nephrogenic diabetes insipidus (due to resistance of renal tissue to the action of ADH), ADH levels are normal to elevated, and the kidney fails to respond to exogenous ADH during the water deprivation test.
• In psychogenic polydipsia, water deprivation will show the same changes as normal individuals, although occasionally urine osmolality will increase moderately. There is no response to exogenous ADH. Such patients may have considerable mental health problems, and may not be prepared to tolerate prolonged periods of water restriction.

The management of polydipsia depends on the underlying cause.
Psychogenic polydipsia is often a difficult condition to treat. In severe cases the phenomenon is often part of a wider psychotic illness. Treatment with antipsychotics such as risperidone, in combination with an angiotensin II inhibitor such as irbesartan has proved effective in some patients.²

A distinction has to be drawn between organic and psychogenic polydipsia. In the former, once the underlying condition is treated, complications from the polydipsia per se are few. This is because homeostasis tends to be preserved. In psychogenic polydipsia, however, water continues to be drunk in excess irrespective of the osmotic status of plasma and urine. This can result in water intoxication with subsequent cardiac failure, pathological fractures, and urinary tract abnormalities.⁸