Physiology 5th Ed.


Distribution of Water in the Body Fluid Compartments

In the human body, water constitutes a high proportion of body weight. The total amount of fluid or water is called total body water, which accounts for 50% to 70% of body weight. For example, a 70-kilogram (kg) man whose total body water is 65% of his body weight has 45.5 kg or 45.5 liters (L) of water (1 kg water ≈ 1 L water). In general, total body water correlates inversely with body fat. Thus, total body water is a higher percentage of body weight when body fat is low and a lower percentage when body fat is high. Because females have a higher percentage of adipose tissue than males, they tend to have less body water. The distribution of water among body fluid compartments is described briefly in this chapter and in greater detail in Chapter 6.

Total body water is distributed between two major body fluid compartments: intracellular fluid (ICF) and extracellular fluid (ECF) (Fig. 1-1). The ICF is contained within the cells and is two thirds of total body water; the ECF is outside the cells and is one third of total body water. ICF and ECF are separated by the cell membranes.


Figure 1–1 Body fluid compartments.

ECF is further divided into two compartments: plasma and interstitial fluid. Plasma is the fluid circulating in the blood vessels and is the smaller of the two ECF subcompartments. Interstitial fluid is the fluid that actually bathes the cells and is the larger of the two subcompartments. Plasma and interstitial fluid are separated by the capillary wall. Interstitial fluid is an ultrafiltrate of plasma, formed by filtration processes across the capillary wall. Because the capillary wall is virtually impermeable to large molecules such as plasma proteins, interstitial fluid contains little, if any, protein.

The method for estimating the volume of the body fluid compartments is presented in Chapter 6.

Composition of Body Fluid Compartments

The composition of the body fluids is not uniform. ICF and ECF have vastly different concentrations of various solutes. There are also certain predictable differences in solute concentrations between plasma and interstitial fluid that occur as a result of the exclusion of protein from interstitial fluid.

Units for Measuring Solute Concentrations

Typically, amounts of solute are expressed in moles, equivalents, or osmoles. Likewise, concentrations of solutes are expressed in moles per liter (mol/L), equivalents per liter (Eq/L), or osmoles per liter (Osm/L). In biologic solutions, concentrations of solutes are usually quite low and are expressed in millimoles per liter (mmol/L), milli equivalents per liter (mEq/L), or milli osmoles per liter (mOsm/L).

One mole is 6 × 1023 molecules of a substance. One millimole is 1/1000 or 10−3 moles. A glucose concentration of 1 mmol/L has 1 × 10−3 moles of glucose in 1 L of solution.

An equivalent is used to describe the amount of charged (ionized) solute and is the number of moles of the solute multiplied by its valence. For example, one mole of potassium chloride (KCl) in solution dissociates into one equivalent of potassium (K+) and one equivalent of chloride (Cl). Likewise, one mole of calcium chloride (CaCl2) in solution dissociates into two equivalents of calcium (Ca2+) and twoequivalents of chloride (Cl); accordingly, a Ca2+ concentration of 1 mmol/L corresponds to 2 mEq/L.

One osmole is the number of particles into which a solute dissociates in solution. Osmolarity is the concentration of particles in solution expressed as osmoles per liter. If a solute does not dissociate in solution (e.g., glucose), then its osmolarity is equal to its molarity. If a solute dissociates into more than one particle in solution (e.g., NaCl), then its osmolarity equals the molarity multiplied by the number of particles in solution. For example, a solution containing 1 mmol/L NaCl is 2 mOsm/L because NaCl dissociates into two particles.

pH is a logarithmic term that is used to express hydrogen (H+) concentration. Because the H+ concentration of body fluids is very low (e.g., 40 × 10−9 Eq/L in arterial blood), it is more conveniently expressed as a logarithmic term, pH. The negative sign means that pH decreases as the concentration of H+ increases, and pH increases as the concentration of H+ decreases. Thus,


SAMPLE PROBLEM. Two men, Subject A and Subject B, have disorders that cause excessive acid production in the body. The laboratory reports the acidity of Subject A’s blood in terms of [H+] and the acidity of Subject B’s blood in terms of pH. Subject A has an arterial [H+] of 65 × 10−9 Eq/L, and Subject B has an arterial pH of 7.3. Which subject has the higher concentration of H+ in his blood?

SOLUTION. To compare the acidity of the blood of each subject, convert the [H+] for Subject A to pH as follows:






Thus, Subject A has a blood pH of 7.19 computed from the [H+], and Subject B has a reported blood pH of 7.3. Subject A has a lower blood pH, reflecting a higher [H+] and a more acidic condition.

Electroneutrality of Body Fluid Compartments

Each body fluid compartment must obey the principle of macroscopic electroneutrality; that is, each compartment must have the same concentration, in mEq/L, of positive charges (cations) as of negative charges (anions). There can be no more cations than anions, or vice versa. Even when there is a potential difference across the cell membrane, charge balance still is maintained in the bulk (macroscopic) solutions. Because potential differences are created by the separation of just a few charges adjacent to the membrane, this small separation of charges is not enough to measurably change bulk concentrations.

Composition of Intracellular Fluid and Extracellular Fluid

The compositions of ICF and ECF are strikingly different, as shown in Table 1-1. The major cation in ECF is sodium (Na+), and the balancing anions are chloride (Cl) and bicarbonate (HCO3). The major cations in ICF are potassium (K+) and magnesium (Mg2+), and the balancing anions are proteins and organic phosphates. Other notable differences in composition involve Ca2+ and pH. Typically, ICF has a very low concentration of ionized Ca2+(≈10−7 mol/L), whereas the Ca2+ concentration in ECF is higher by approximately four orders of magnitude. ICF is more acidic (has a lower pH) than ECF. Thus, substances found in high concentration in ECF are found in low concentration in ICF, and vice versa.

Table 1–1 Approximate Compositions of Extracellular and Intracellular Fluids

Substance and Units

Extracellular Fluid

Intracellular Fluid*

Na+ (mEq/L)



K+ (mEq/L)



Ca2+, ionized (mEq/L)


  1 × 10−4

Cl (mEq/L)



HCO3 (mEq/L)






Osmolarity (mOsm/L)



*The major anions of intracellular fluid are proteins and organic phosphates.

The corresponding total [Ca2+] in extracellular fluid is 5 mEq/L or 10 mg/dL.

pH is −log10 of the [H+]; pH 7.4 corresponds to [H+] of 40 × 10−9 Eq/L.

Remarkably, given all of the concentration differences for individual solutes, the total solute concentration (osmolarity) is the same in ICF and ECF. This equality is achieved because water flows freely across cell membranes. Any transient differences in osmolarity that occur between ICF and ECF are quickly dissipated by water movement into or out of cells to reestablish the equality.

Creation of Concentration Differences across Cell Membranes

The differences in solute concentration across cell membranes are created and maintained by energy-consuming transport mechanisms in the cell membranes.

The best known of these transport mechanisms is the Na+-K+ ATPase (Na+-K+ pump), which transports Na+ from ICF to ECF and simultaneously transports K+ from ECF to ICF. Both Na+ and K+ are transported against their respective electrochemical gradients; therefore, an energy source, adenosine triphosphate (ATP), is required. The Na+-K+ ATPase is responsible for creating the large concentration gradients for Na+ and K+ that exist across cell membranes (i.e., the low intracellular Na+ concentration and the high intracellular K+ concentration).

Similarly, the intracellular Ca2+ concentration is maintained at a level much lower than the extracellular Ca2+ concentration. This concentration difference is established, in part, by a cell membrane Ca2+ATPase that pumps Ca2+against its electrochemical gradient. Like the Na+-K+ ATPase, the Ca2+ ATPase uses ATP as a direct energy source.

In addition to the transporters that use ATP directly, other transporters establish concentration differences across the cell membrane by utilizing the transmembrane Na+ concentration gradient (established by the Na+-K+ ATPase) as an energy source. These transporters create concentration gradients for glucose, amino acids, Ca2+, and H+ without the direct utilization of ATP.

Clearly, cell membranes have the machinery to establish large concentration gradients. However, if cell membranes were freely permeable to all solutes, these gradients would quickly dissipate. Thus, it is critically important that cell membranes are not freely permeable to all substances but, rather, have selective permeabilities that maintain the concentration gradients established by energy-consuming transport processes.

Directly or indirectly, the differences in composition between ICF and ECF underlie every important physiologic function, as the following examples illustrate: (1) The resting membrane potential of nerve and muscle critically depends on the difference in concentration of K+ across the cell membrane; (2) The upstroke of the action potential of these same excitable cells depends on the differences in Na+concentration across the cell membrane; (3) Excitation-contraction coupling in muscle cells depends on the differences in Ca2+ concentration across the cell membrane and the membrane of the sarcoplasmic reticulum; and (4) Absorption of essential nutrients depends on the transmembrane Na+ concentration gradient (e.g., glucose absorption in the small intestine or glucose reabsorption in the renal proximal tubule).

Concentration Differences between Plasma and Interstitial Fluids

As previously discussed, ECF consists of two subcompartments: interstitial fluid and plasma. The most significant difference in composition between these two compartments is the presence of proteins (e.g., albumin) in the plasma compartment. Plasma proteins do not readily cross capillary walls because of their large molecular size and, therefore, are excluded from interstitial fluid.

The exclusion of proteins from interstitial fluid has secondary consequences. The plasma proteins are negatively charged, and this negative charge causes a redistribution of small, permeant cations and anions across the capillary wall, called a Gibbs-Donnan equilibrium. The redistribution can be explained as follows: The plasma compartment contains the impermeant, negatively charged proteins. Because of the requirement for electroneutrality, the plasma compartment must have a slightly lower concentration of small anions (e.g., Cl) and a slightly higher concentration of small cations (e.g., Na+ and K+) than that of interstitial fluid. The small concentration difference for permeant ions is expressed in the Gibbs-Donnan ratio, which gives the plasma concentration relative to the interstitial fluid concentration for anions and interstitial fluid relative to plasma for cations. For example, the Cl concentration in plasma is slightly less than the Cl concentration in interstitial fluid (due to the effect of the impermeant plasma proteins); the Gibbs-Donnan ratio for Cl is 0.95, meaning that [Cl]plasma/[Cl]interstitial fluid equals 0.95. For Na+, the Gibbs-Donnan ratio is also 0.95, but Na+, being positively charged, is oriented the opposite way, and [Na+]interstitial fluid/[Na+]plasma equals 0.95. Generally, these minor differences in concentration for small cations and anions are ignored.