Body Fluid Compartments & Osmolality

Overview: the 60-40-20 rule

Total body water (TBW). Water makes up about 60% of body weight, roughly 42 L in a 70-kg man. Two-thirds of it (40% of body weight, ~28 L) is intracellular fluid (ICF) and one-third (20% of body weight, ~14 L) is extracellular fluid (ECF). The capillary wall divides the ECF into interstitial fluid (about three-quarters, ~10.5 L) and plasma (about one-quarter, ~3.5 L). Blood volume, about 7% of body weight, equals plasma volume ÷ (1 − Hct).

Who has less water. Adipose tissue holds little water compared with lean tissue, so TBW is lower in women (~50%), older adults (~45–50%) and people with obesity, and highest in infants (~70–75%). A smaller TBW means a smaller volume of distribution for water-soluble drugs: the same dose of ethanol produces a higher blood level in a woman or an older adult.

Barriers and composition. Cell membranes separate ICF from ECF; they are freely permeable to water but not to most solutes, which the Na⁺/K⁺-ATPase keeps apart. Na⁺ (with Cl⁻ and HCO₃⁻) dominates the ECF, whereas K⁺ and Mg²⁺ (with organic phosphates and proteins) dominate the ICF. Capillary walls let small solutes pass, so plasma and interstitial fluid have nearly identical electrolyte concentrations, but plasma proteins are held in the vessels.

Measuring compartments by indicator dilution

Principle. A known amount of a marker that distributes only within the compartment of interest is injected and allowed to equilibrate. Volume = (amount injected − amount excreted) ÷ equilibrium plasma concentration. For example, 700 mg of mannitol that equilibrates at 0.05 mg/mL occupies 14,000 mL, which is the ECF.

Osmolality, tonicity and the osmolar gap

Calculated osmolality. Plasma osmolality ≈ 2[Na⁺] + glucose/18 + BUN/2.8, with glucose and BUN in mg/dL; the normal range is about 285–295 mOsm/kg. Sodium is doubled to account for its accompanying anions and supplies most of the total; dividing by 18 and 2.8 converts glucose and urea nitrogen to mmol/L.

Osmolar gap. The laboratory measures osmolality directly by freezing-point depression. Measured minus calculated osmolality is normally below about 10 mOsm/kg; a larger gap means an unmeasured, osmotically active small molecule such as methanol (which also injures the retina), ethylene glycol, isopropanol, ethanol, mannitol or propylene glycol. Glucose, urea and sodium cannot create a gap because they are already in the formula.

Effective vs ineffective osmoles. Only solutes that cannot cross cell membranes set tonicity and move water between ICF and ECF. Na⁺ (held in the ECF by the pump), mannitol, and glucose when insulin is lacking are effective osmoles that pull water out of cells. Urea and ethanol diffuse across membranes and are ineffective osmoles: they raise measured osmolality without changing cell volume, so a uremic patient is hyperosmolar but not hypertonic. Effective osmolality (tonicity) can be estimated as 2[Na⁺] + glucose/18.

Severe hyperglycemia pulls water out of cells and dilutes plasma Na⁺ (translocational hyponatremia), so a low sodium in uncontrolled diabetes does not mean the plasma is hypotonic; Na⁺ falls roughly 1.6–2.4 mEq/L for every 100 mg/dL rise in glucose.

Predicting fluid shifts: Darrow–Yannet logic

Three rules. At steady state ICF and ECF osmolality are equal; gained or lost NaCl stays in the ECF; and water crosses cell membranes freely until the two osmolalities match. Draw ICF and ECF as side-by-side rectangles whose width is volume and height is osmolality, apply the gain or loss to the ECF, then let water move.

Reading the blood. Plasma protein concentration always moves opposite to ECF volume. Hematocrit depends on both plasma volume and RBC size: RBCs shrink when ECF turns hypertonic and swell when it turns hypotonic, and when the two effects oppose each other Hct stays about the same.

Contractions. Losing hypotonic fluid (sweat, insensible losses with fever, dilute urine in diabetes insipidus) removes water in excess of salt: ECF osmolality rises, water leaves cells and both compartments shrink, with higher Na⁺ and protein but little change in Hct. In adrenal insufficiency, lack of aldosterone makes the kidney lose NaCl in excess of water: ECF osmolality falls, water enters cells, the ECF shrinks while the ICF swells, and Hct rises because plasma volume falls and RBCs swell.

Expansions. Isotonic saline stays in the ECF without changing osmolality, so the ICF is untouched. Hypertonic saline or mannitol raises ECF osmolality and draws water out of cells, the basis for using them against cerebral edema. Mannitol initially lowers serum Na⁺ by dilution even though osmolality rises; its later osmotic diuresis can strip free water and cause hypernatremia. In SIADH or water intoxication, retained water spreads through both compartments, lowering osmolality and Na⁺ while expanding ICF and ECF.

Where IV fluids go

An infused fluid spreads through whatever compartment its solute can reach, and plasma receives its proportional share of that compartment.

D5W is free water once its glucose is metabolized: it cannot restore blood pressure, and excessive amounts lower Na⁺ and swell cells, including neurons.