17 - Osmolality physiology

The osmolality of plasma is closely regulated by anti-diuretic hormone (ADH). In response to even small increases in plasma osmolality (usually rises in plasma sodium), ADH release from the pituitary is increased causing water resorption in the distal tubules and collecting ducts of the kidney and correction of the increased osmolality. The opposite happens in response to a low plasma osmolality with decreased ADH secretion and water loss through the kidneys. Note that ADH is also secreted in response to hypovolaemia and this stimulus will over-ride any response to serum osmolality.


Urine osmolality may vary between 50 and 1200 mmol/kg in a healthy individual depending on the state of hydration. The urine osmolality is the best measure of urine concentration with high values indicating maximally concentrated urine and low values very dilute urine. The main factor determining urine concentration is the amount of water which is resorbed in the distal tubules and collecting ducts in response to ADH. In a dehydrated patient with normally functioning pituitary and kidneys, a small volume of highly concentrated urine will be produced. In a patient with fluid overload the opposite will be an appropriate response. Note that there is no reference interval ("normal range") for urine osmolality as the interpretation depends on the clinical condition of the patient to determine an appropriate response.

16 - Osmolality introduction

Osmolality is a count of the number of particles in a fluid sample. The unit for counting is the mole which is equal to 6.02 x 10²³ particles (Avogadro's Number). Molarity is the number of particles of a particular substance in a volume of fluid (eg mmol/L) and molality is the number of particles disolved in a mass weight of fluid (mmol/kg). Osmolality is a count of the total number of osmotically active particles in a solution and is equal to the sum of the molalities of all the solutes present in that solution.


 For most biological systems the molarity and the molality of a solution are nearly exactly equal because the density of water is 1 kg/L. There is a slight difference between molality and molarity in plasma because of the non-aqueous components present such as proteins and lipids which make up about 6% of the total volume. Thus serum is only 94% water and the molality of a substance in serum is about 6% higher than its molarity. Except in unusual circumstances this difference is unimportant and the terms molarity to the molarity are often used interchangeably. Note that the size of the particle is unimportant so that a single ion, eg sodium, contributes as much to the serum osmolality as a single large protein molecule, eg albumin.


The osmolality of physiological fluids tends to be dominated by small molecules which are present in high concentrations. For example in serum, sodium, potassium, chloride, bicarbonate, urea and glucose are the only components present in high enough concentrations to individually affect the osmolality. Together these make up over 95% of total osmolality of serum. Large serum components contribute little to the overall osmolality.  For example the molar concentration of albumin, the most abundant serum protein, is only about 0.6 mmol/L. Only a few exogenous compounds such as ethanol, methanol, ethylene glycol and manitol can be present in the blood at high enough quantities to significantly affect the osmolality.