A prerequisite to the anatomy of body fluids and the physiologic principles that maintain normal fluid and electrolyte balance is a firm understanding of the extent and composition of the various body fluid compartments. Homeostasis is the maintenance of the composition of the internal environment that is essential for health. This includes consideration of the distribution of water in the body, along with appropriate maintenance of pH and electrolyte balance.

Water is the major constituent of the body and accounts for between 50 and 70 percent of total body weight ( Fig 23-1). The proportion of total body water (TBW)

varies with age, gender, and lean body mass. For example, fat contains very little water; therefore, the more lean body mass there is, the larger is the proportionate TBW. In the healthy average male, TBW approximates up to 60 percent of weight. 1 Since females have relatively more subcutaneous adipose tissue and less muscle, they have less water or about 50 percent TBW. Similarly, muscle mass decreases with age and sometimes is replaced by fat, leading to a lower percentage of TBW.

FIG. 23-1. Relationship of fluid compartment to body weight and each other. Abbreviations: IVF, intravascular fluid; IF, interstitial fluid, ECF, extracellular fluid; ICF, intracellular fluid; TBW, total body water.

The water of the body is divided into two basic functional compartments. The intracellular fluid (ICF) compartment accounts for approximately two-thirds of TBW, and the extracellular fluid (ECF) compartment accounts for approximately one-third of TBW. Most cell membranes are freely permeable to water, and thus, at steady state, the osmolality (discussed below) of these two compartments is equal. A change in osmolality of one compartment results in the passive movement of water from the area of lower osmolality to the area of higher osmolality.

The electrolyte concentration of ICF varies greatly from tissue to tissue. Skeletal muscle accounts for a large proportion of the intracellular component, and thus it is customary to use its electrolyte concentration as representative of the total body intracellular electrolyte concentration. Electrolytes are further classified according to electronic charge, cations (positively charged ions) and anions (negatively charged ions). The principal cations in the intracellular compartment are K + and Mg2+, whereas the principal anions are p04- and proteins (Table23-1).

TABLE 23-1 The Electrolyte Concentration of Body Fluids (meq/L)

The ECF is partitioned by vascular epithelium into an intravascular compartment and the interstitial (sometimes referred to as extravascular) compartment. The intravascular compartment contains circulating plasma and accounts for approximately 20 to 25 percent of extracellular water. The interstitial compartment bathes all cells and accounts for approximately 75 to 80 percent of extracellular water. The interstitial compartment is much more complicated in that it has a rapidly equilibrating functional component and several slowly equilibrating nonfunctioning components. The nonfunctioning components account only for a small percentage of extracellular water, which includes the connective tissue water and the "transcellular" water, made up of the cerebrospinal and joint fluids. A dynamic equilibrium exists between the intravascular and interstitial compartments. There is a constant movement of fluid back and forth across the capillary bed between the intravascular and interstitial spaces. This movement is determined by the permeability of the membrane, the net difference between the hydrostatic pressure gradient (which drives fluid out of the intravascular space), the oncotic pressure gradient (which holds fluid within the intravascular space), and tissue turgor pressure countering the hydrostatic pressure. At the arteriolar end, there is a net efflux. At the venule end, there is a net influx. This simple system known as the Starling hypothesis2 is insufficient to account for the large volume of fluid exchange that actually occurs and for the transport of nutrients and materials to and from tissues. It has been calculated that capillaries exchange water with interstitial fluid up to 300 times/min in the forearm capillary beds. NaCl, urea, and glucose exchange 40 to 120 times/min.3 Vasomotion of the capillaries (rhythmic contraction and relaxation) determines rate of flow. During the dilator phase, hydrostatic pressure is high, and fluid filters out readily. During the constrictor phase, flow is diminished, and fluid readily enters the capillaries throughout their length. Vasomotion depends on vasomotor nerve outflow, hormones, and local concentrations of tissue metabolites.

One can readily appreciate how a malfunction or imbalance in this system can be buffered to some extent but will ultimately lead to edema (high hydrostatic pressures, loss of vasomotion, decreased oncotic pressure, and decreased tissue turgor).

The proportionate relationship of the fluid compartment to body weight and TBW can be quite confusing, depending on whether the compartment is spoken in terms of body weight or TBW (see Fig 23.-1.). For example, the ECF is 20 percent of total body weight but 33 percent of TBW.


The other difficulty in understanding fluid and electrolytes is in the understanding of the various terms that are used and commonly misused to describe them. In considering the effects of various physiologically important substances and the interactions between them, the number of molecules, electrical charges, or particles of a substance per unit volume of a particular body fluid are more meaningful than simply the weight of a substance per unit volume. Therefore, concentrations are often expressed in moles, equivalents, or osmoles per liter. The use of grams per 100 mL expresses the weight of electrolytes per unit volume but does not enable a physiologic comparison of the solutes in solution.

The term mole describes the chemical basis for quantifying substances. It represents the molecular weight of a substance in grams (g) and is the standard unit of expressing the amount of a substance in the Systeme International d'Unites (SI) unit system. However, this quantification gives no direct information as to the number of osmotically active ions in a solution or to the electrical charges they carry. For example,

J mol (male) orNaCI - 21 £ (Na) + 35,5 g (CI) - 58.5 g

Equivalents represent the chemical combining activity of electrolytes. An equivalent (eq) of an ionized (charged) substance is 1 mol divided by its valence, whereas a milliequivalent (meq) is that figure expressed in milligrams (mg). In any given solution, the number of milliequivalents of cations is balanced precisely to the same number of milliequivalents of anions. This is referred to as electroneutrality. For example,

I mot ufNuCI itissociiifc ] fljofNa* ami 1 eq of Q" 1 eq of Na' g!L - 21 g. bill ] eq of Crf4- 4U gf2 - g

When considering the osmotic pressure of a solution, it is more descriptive to discuss this in terms of osmoles and milliosmoles. The osmolal concentration of a substance in a fluid is measured by the degree to which it depresses the freezing point, 1 mol/L of ideal solute depressing the freezing point 1.86°C. Osmoles refer to the actual number of osmotically active particles present in a solution. One osmole (osm) equals the molecular weight of the substance (in grams) divided by the number of freely moving particles each molecule liberates in solution. This is not dependent on the equivalents (electrochemical combining activity) each substance possesses.

Osmolarity is the number of osmoles per liter of solution, whereas osmolality is the number of osmoles per kilogram of solvent. Thus, the volume of the various solutes in the solution and the temperature affect osmolarity but not osmolality. The density of water is 1, so 1 L = 1 kg. Therefore, in water-based systems (such as the human body) where osmotically active substances are dissolved in plasma that is 91 to 93 percent H 2O, osmolal concentrations can be expressed as osmoles per liter (osm/L). This more closely approximates osmotic pressure, since osmolarity will be 7 to 9 percent lower than osmolality.

The serum osmolality can be measured directly by determining the freezing point of the serum, or it can be estimated by adding the measured [Na +], [Cl-], and bicarbonate to the glucose and blood urea nitrogen (BUN) divided by their respective molecular weights divided by 10 (to yield mg/dL):

Since the sum of the measured [Cl ] and bicarbonate approximate the measured [Na+], twice the measured [Na+] is generally used in this calculation.

The normal serum osmolality ranges from 275 to 295 mosm/L. The urine and serum osmolality are much more accurate to use to diagnose the state of hydration than hematocrit, serum proteins, or BUN, since these are dependent on factors other than hydration. The presence of other osmotically active agents must be taken into account, since they influence serum osmolality. The presence of these osmotically active agents should be suspected when the measured osmolality differs from the calculated osmolality by greater than 10. This is termed an osmotic gap. If an osmotic gap is encountered, the following should be considered:

1. Laboratory analytic error

2. Decreased serum water content Hyperlipidemia Hyperproteinemia

3. Additional low-molecular-weight substances in the serum

Ethanol, methanol, isopropyl alcohol, ethylene glycol, acetone, ethyl ether, paraldehyde, lactate, or mannitol

The osmolal gap can be used to estimate the blood alcohol level (BAL), since osmolality increases 22 mg/dL for every 100 mg/dL of ethanol. Other substances can be similarly estimated (T.a..b.!.e 2..3..:2.).


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TABLE 23-2 Contribution to Osmolal Gap of Osmotic Substances

The differences in ionic concentrations between the ICF and ECF are maintained by a semipermeable cell membrane. A semipermeable membrane is one that allows the free passage of solvent (H2O) but not solute (crystalloid such as cations and anions, or colloids such as plasma proteins). At equilibrium, the concentration of molecules in the fluid of one compartment is equal to that in all the others. If free water is lost from one compartment, its concentration of molecules increases. This attracts water into that compartment until the concentration equalizes. The solutes (particles) that can not freely pass from one compartment to the next through the semipermeable membrane create the osmotic gradient (i.e., exert a force on water) and are termed effective osmoles. These include the electrolytes and, in most tissues, glucose. Glucose readily enters red blood cells, hepatocytes, and osmoreceptors in the brain and thus exerts no force on water in relation to these cellular compartments. The solutes (particles) that distribute across the semipermeable membrane freely and therefore don't contribute to the osmotic gradient are termed "ineffective" osmoles.

Tonicity is used to describe the osmolality of a solution relative to plasma. Solutions with the same osmolality are said to be isotonic, those with comparatively higher osmolality are hypertonic, and those with lower osmolality are hypotonic. Tonicity is created by effective osmoles. Effective osmoles exert a force on water. The ineffective osmoles (urea, ethanol, methanol, or ethylene glycol) contribute to serum osmolality but not to tonicity. They do not exert a force on water across a semipermeable membrane as they freely diffuse.


Fluid balance is exceedingly important to maintain homeostasis. To maintain balance, an average normal adult requires approximately 2000 to 3000 mL intake of water per day. This accounts for the volume of water lost in a day due to insensible and urinary losses. The insensible losses include the respiratory tract (500 to 700 mL/day), the skin (250 to 350 mL/day), and the feces (100 mL/day). This insensible loss can accelerate dramatically in the setting of fever (500 mL per 1°C fever), sweating (up to 1500 mL), and gastrointestinal losses.

The disorders of fluid balance may be classified into three categories: volume, concentration, and composition. Although all of these are interrelated, they are each separate entities.

1. Disturbances of volume occur when an isotonic solution is added or lost from a fluid compartment. Solute will not transfer from an adjacent compartment; only the volume of that compartment will change as long as the osmolality remains the same in the different compartments.

2. Disturbances of concentration occur when water alone is added or lost from a fluid compartment. The concentration of osmotically active particles will change, exerting an osmotic force into the compartment with the higher osmolality. This will continue until osmolality balances between the two compartments.

3. Disturbances of composition occur when the concentration of ions changes within a compartment without significantly altering the total number of osmotically active particles.

It is important to note that the volume lost is relative to the overall volume. A child who loses fluid is much more susceptible to its effects since this absolute quantity is a greater percentage of its overall volume. Signs of volume loss are related to not only volume but also to rate of loss. The faster the loss, the less time the body has to counterregulate and the greater the deleterious effects will be. They include weight loss, thirst, tachycardia, oliguria, and dry mucous membranes.

Flexibility in the body's ability to control water volume is provided by two mechanisms: antidiuretic hormone (ADH) and aldosterone. In the setting of volume depletion with increased serum osmolality and/or decreased plasma volume, the posterior pituitary is stimulated to release ADH and renin (from the kidney), stimulating the adrenal gland to release aldosterone. The ADH leads to retention of free water in the collecting ducts of the kidneys while aldosterone stimulates retention of Na + in the renal tubules, leading to further retention of water. In the setting of extra body water, there is a decrease in serum osmolality and/or an increase in plasma volume. This leads to a suppression of ADH secretion from the posterior pituitary and suppression of aldosterone release from the adrenal gland. The suppression of ADH leads to free water diuresis.

Overall, volume status is a much more potent stimulator of ADH than is osmolality. Therefore, change in volume alone will have a greater influence on ADH. For example, hypovolemia is a stronger stimulus for ADH secretion than hypo-osmolality is an inhibitor. Nausea and pain are considered to be of even greater potency for ADH stimulation.

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