Osmotic pressure is the force required to counterbalance the osmotic solvent flow that occurs through a semipermeable membrane, such as cell membranes. The osmotic forces between the intracellular fluid (ICF) and the ECF are determined by ECF [Na⁺] and [K⁺]. Osmotic forces between the intravascular fluid and extravascular fluid are determined by the opposing effects of plasma proteins drawing fluid intravascularly and hydrostatic forces pushing fluid extravascularly. Osmolality is the concentration of osmotically active particles in solution, expressed in osmoles of solute per kg of solvent (mmol/kg).

Control of osmolality

Antidiuretic hormone (ADH)

Nerve cell bodies in the hypothalamus respond to a change in osmolality by altering secretion of ADH. When plasma osmolality is high, ADH is released and water is retained by the kidneys. Plasma osmolality thus returns to normal.

Thirst regulation by hypothalamus

With increased plasma osmolality, increased thirst occurs in order to dilute the ECF and return the osmolality to normal.

Abnormal osmolality

Increased osmolality

Hyperosmolar states are seen with hypernatremia, hyperglycemia, azotemia, and certain exogenous agents, such as ethylene glycol. In all of these conditions, except azotemia, water shifts out of cells to the ECF in order to decrease the solute concentration. This results in shrinkage of cells. Water shifts do not occur with urea elevations (as with azotemia) because urea passes freely from the ECF to the ICF. Urea is, therefore, an ineffective osmole.

Decreased osmolality

Hypoosmolar states are caused only by hyponatremia. Hypoosmolarity results in shifts of water from the ECF into the ICF and cells will swell. If this occurs rapidly, the most detrimental effects are swelling and rupture of erythrocytes resulting in intravascular hemolysis, and swelling of neurons resulting in neurological signs.

“Osmol” Gap

The “osmol” gap is the difference between the measured osmolality (mOsm or mmol/kg of solvent) and the calculated osmolarity (mOsm or mmol/L of solution) of serum. Measured osmolality is the actual osmolality of the sample and is determined using an osmometer instrument. Calculated osmolarity may appear on some chemistry panels and is based on the following formula:

Calculated osmolarity = (2 x Na⁺) + urea + glucose mmol/L

(Note: If conventional units are used, the formula is altered to accommodate conversion of these to SI units. Variations in the formula include omitting urea, including K+, and using a factor slightly different than 2.) Both osmolal gap and osmolar gap are inaccurate terms since the units for osmolality and osmolarity differ, so “osmol” gap will be used here.

Normal values for osmolality vary slightly by species, but are generally about 300 mOsm/kg. There is normally a slight difference between measured osmolality and calculated osmolarity of about 10-15 mOsm, because there are solutes which are not included in the calculation for osmolarity. If the “osmol” gap is increased, there is an increase in osmotically active solutes in the serum (such as ethanol, ethylene glycol, lactic acid, ketones, mannitol, or salicylic acid, which would not contribute to the calculated value, but would be measured by the osmometer). If both measured osmolality and calculated osmolarity are increased, such that the gap between the two is normal, then sodium, glucose and/or urea are responsible for the abnormality.

Serum Electrolytes The sum of all cations (positively charged ions) must equal the sum of all anions (negatively charged ions) to fulfill the law of electroneutrality. This is often expressed as Na⁺ + K⁺ + UC = Cl^– + HCO₃^– + UA. UC and UA are unmeasured cations and anions, respectively, which contribute to electroneutrality but are not routinely measured.