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Total body water (TBW) constitutes 50%–75% of the total body mass, depending on age, sex, and fat content. After an initial brisk postnatal diuresis, the TBW slowly decreases to the adult range near puberty. TBW is divided into the intracellular and extracellular spaces. Intracellular fluid (ICF) accounts for two-thirds of the TBW and extracellular fluid (ECF) for one-third. The ECF is further compartmentalized into plasma (intravascular) volume and interstitial fluid (ISF).

The principal constituents of plasma are sodium, chloride, bicarbonate, and protein (primarily albumin). The ISF is similar to plasma but lacks significant amounts of protein. Conversely, the ICF is rich in potassium, magnesium, phosphates, sulfates, and protein.

An understanding of osmotic shifts between the ECF and ICF is fundamental to understanding disorders of fluid balance. Iso-osmolality is generally maintained between fluid compartments. Because the cell membrane is water-permeable, abnormal fluid shifts occur if the concentration of solutes that cannot permeate the cell membrane in the ECF does not equal the concentration of such solutes in the ICF. Thus, NaCl, mannitol, and glucose (in the setting of hyperglycemia) remain restricted to the ECF space and contribute effective osmoles by obligating water to remain in or be drawn into the ECF compartment. In contrast, a freely permeable solute such as urea does not contribute effective osmoles because it is not restricted to the ECF and readily crosses cell membranes. Tonicity, or effective osmolality, differs from measured osmolality in that it accounts only for osmotically active impermeable solutes rather than all osmotically active solutes, including those that are permeable to cell membranes. Serum osmolality may be estimated by the following formula:


Although osmolality and osmolarity differ, the former being an expression of osmotic activity per weight (kg) and the latter per volume (L) of solution, for clinical purposes they are similar and occasionally used interchangeably. Oncotic pressure, or colloid osmotic pressure, represents the osmotic activity of macromolecular constituents such as albumin in the plasma and body fluids. The importance of albumin in maintaining intravascular volume status is reflected in the setting of the nephrotic syndrome, protein losing enteropathy, hepatic failure, and other low serum albumin states wherein fluids accumulate in the interstitial compartment leading to edema.

The principal mechanisms that regulate ECF volume and tonicity are thirst, vasopressin or antidiuretic hormone (ADH), aldosterone, and atrial and brain natriuretic peptide (ANP and BNP), the latter four exerting their influence by their effects on renal water and sodium handling.


Water intake is commonly determined by cultural and behavioral factors. Thirst is not physiologically stimulated until plasma osmolality reaches 290 mOsm/kg, a level at which ADH release induces maximal antidiuresis. Thirst provides control over a wide range of fluid states and allows maintenance of appropriate intravascular volume, even in polyuric states (such as central or nephrogenic ...

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