A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A medical student is conducting an experiment related to body fluids. Part of his research requires a relatively precise estimation of extracellular body fluid in each volunteer. He knows that extracellular body fluid accounts for approximately 33% of the volume of total body water. Which of the following substances is most likely to be helpful to measure the volume of the extracellular body fluid?
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A
Evans blueIncorrect. Evans blue binds albumin and stays in the vascular space, measuring PLASMA volume — not extracellular fluid.
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B
Heavy waterIncorrect. Heavy water (D2O) distributes through all body water, measuring TOTAL BODY WATER, not extracellular fluid specifically.
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C
MannitolCorrect. mannitol does not cross cell membranes and distributes throughout the extracellular fluid, making it ideal for ECF volume measurement.
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D
Radio-iodine labeled serum albuminIncorrect. Radio-iodinated serum albumin (RISA) measures PLASMA volume because it stays bound to albumin within the intravascular compartment.
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E
InulinIncorrect. Inulin is filtered freely and not reabsorbed, making it the standard for measuring GLOMERULAR FILTRATION RATE, not extracellular fluid volume; mannitol is the preferred ECF marker.
↑ Tap an answer to reveal the reasoning
Answer: C. Estimation of body fluid compartment volumes uses the INDICATOR-DILUTION method: an indicator that distributes exclusively (and only) within the compartment of interest is administered, allowed to equilibrate, and then its plasma concentration is measured. Volume = (amount given) / (concentration after equilibration).
Different indicators are used for different compartments based on size, charge, and membrane permeability:
- TOTAL BODY WATER: tritiated water (3H2O), deuterium oxide (heavy water, D2O), or antipyrine — all cross all membranes and distribute everywhere.
- EXTRACELLULAR FLUID (ECF): MANNITOL, inulin, sucrose, or radiolabeled sulfate — these molecules are too large to cross cell membranes but distribute through both interstitial and plasma compartments.
- PLASMA VOLUME: Evans blue dye (binds albumin) or radio-iodine labeled albumin (RISA, 125I-albumin) — too large/protein-bound to cross capillaries significantly.
- INTRACELLULAR FLUID: cannot be measured directly; calculated as TBW minus ECF.
- BLOOD VOLUME: calculated from plasma volume / (1 - hematocrit) or directly with chromium-51-labeled red cells.
For ECF measurement specifically, mannitol is the textbook tracer — it does not enter cells but disperses through the entire extracellular compartment.
**Why each option:**
**A.** Evans blue binds albumin and stays in the vascular space, measuring PLASMA volume — not extracellular fluid.
**B.** Heavy water (D2O) distributes through all body water, measuring TOTAL BODY WATER, not extracellular fluid specifically.
**C.** Correct — mannitol does not cross cell membranes and distributes throughout the extracellular fluid, making it ideal for ECF volume measurement.
**D.** Radio-iodinated serum albumin (RISA) measures PLASMA volume because it stays bound to albumin within the intravascular compartment.