The indicator dilution method can be used to determine the size of body fluid compartments (see Chapter 14). A known amount of a substance (the indicator), which should be confined to the compartment of interest, is administered. After allowing sufficient time for uniform distribution of the indicator throughout the compartment, a plasma sample is collected. The concentration of the indicator in the plasma at equilibrium is measured, and the distribution volume is calculated from this formula
Volume = Amount of indicator/ Concentration of indicator
If there was loss of indicator from the fluid compartment, the amount lost is subtracted from the amount administered.
To measure total body water, heavy water (deuterium oxide), tritiated water (HTO), or antipyrene (a drug that distributes throughout all of the body water) is used as an indicator. For example, suppose we want to measure total body water in a 60-kg woman. We inject 30 mL of deuterium oxide (D2O) as an isotonic saline solution into an arm vein. After a 2-hr equilibration period, a blood sample is withdrawn, and the plasma is separated and analyzed for D2O. A concentration of 0.001 mL D2O/mL plasma water is found. Suppose during the equilibration period, urinary, respiratory, and cutaneous losses of D2O are 0.12 mL. Substituting these values into the indicator dilution equation, we get
Total body water = (30 - 0.12 mL D2O) X 0.001 mL D2O/mL water = 29,880 mL or 30 L
Therefore, total body water as a percentage of body weight equals 50% in this woman.
To measure extracellular water volume, the ideal indicator should distribute rapidly and uniformly outside the cells and should not enter the cell compartment. Unfortunately, there is no such ideal indicator, so the exact volume of the ECF cannot be measured. A reasonable estimate, however, can be obtained using two different classes of substances: impermeant ions and inert sugars. ECF volume has been determined from the volume of distribution of these ions: radioactive Na+, radioactive Cl_, radioactive sulfate, thio-cyanate (SCN~), and thiosulfate (S2O32-); radioactive sulfate (35SO42-) is probably the most accurate. However, ions are not completely impermeant; they slowly enter the cell compartment, so measurements tend to lead to an overestimate of ECF volume. Measurements with inert sugars (such as mannitol, sucrose, and inulin) tend to lead to an underestimate of ECF volume because they are excluded from some of the extracellular water—for example, the water in dense connective tissue and cartilage. Special techniques are required when using these sugars because they are rapidly filtered and excreted by the kidneys after their intravenous injection.
Cellular water cannot be determined directly with any indicator. It can, however, be calculated from the difference between measurements of total body water and extracellular water.
Plasma water is determined by using Evans blue dye, which avidly binds serum albumin or radioiodinated serum albumin (RISA), and by collecting and analyzing a blood plasma sample. In effect, the plasma volume is measured from the distribution volume of serum albumin. The assumption is that serum albumin is completely confined to the vascular compartment, but this is not entirely true. Indeed, serum albumin is slowly (3 to 4% per hour) lost from the blood by diffusive and convective transport through capillary walls. To correct for this loss, repeated blood samples can be collected at timed intervals, and the concentration of albumin at time zero (the time at which no loss would have occurred) can be determined by extrapolation. Alternatively, the plasma concentration of indicator 10 minutes after injection can be used; this value is usually close to the extrapolated value. If plasma volume and hema-tocrit are known, total circulating blood volume can be calculated (see Chapter 11).
Interstitial fluid and lymph volume cannot be determined directly. It can be calculated as the difference between ECF and plasma volumes.
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