Intracellular vs. extracellular fluid
Also known as: ICF vs. ECF
Intracellular fluid (ICF) is the water inside cells — about two-thirds of total body water — while extracellular fluid (ECF) is the remaining third outside cells, divided between interstitial fluid and blood plasma.
Body water is divided into two major compartments. Intracellular fluid (ICF) is the water contained within cells, and extracellular fluid (ECF) is everything outside them. The classic 60-40-20 rule summarizes the proportions: total body water is about 60% of body weight, ICF about 40%, and ECF about 20% — meaning roughly two-thirds of body water is intracellular and one-third extracellular.
The ECF is further subdivided: about three-quarters is interstitial fluid bathing the cells, and about one-quarter is plasma, the fluid portion of blood. A small transcellular component includes cerebrospinal, pleural, and synovial fluid.
The two compartments differ sharply in composition. ICF is rich in potassium, magnesium, phosphate, and protein; ECF is rich in sodium, chloride, and bicarbonate. The Na+/K+-ATPase pump maintains these gradients, and because water crosses cell membranes freely while most solutes do not, osmolarity equalizes between compartments — so changes in ECF sodium concentration drive water into or out of cells. This is why hyponatremia causes cellular swelling and hypernatremia causes cellular shrinkage, and why different IV fluids distribute differently across compartments.
USMLE Step 1 tests body fluid compartments through the 60-40-20 rule, the ionic composition of each compartment, indicator-dilution methods for measuring compartment volumes, and Darrow-Yannet-style questions predicting how fluid gains and losses shift volume and osmolarity between ICF and ECF.
Key takeaways
- ICF is water inside cells (~two-thirds of total body water); ECF is water outside cells (~one-third).
- The 60-40-20 rule: total body water ≈ 60% of body weight, ICF ≈ 40%, ECF ≈ 20%.
- ECF splits into interstitial fluid (~75%) and plasma (~25%).
- ICF is high in potassium and phosphate; ECF is high in sodium, chloride, and bicarbonate — gradients maintained by Na+/K+-ATPase.
- USMLE Step 1 tests compartment sizes, compositions, measurement methods, and fluid-shift predictions.