Maple syrup urine disease (MSUD) is a disease in which, due to a genetic defect in a key facilitative protein, cells in the body cannot take in the amino acids valine, leucine, and isoleucine. Because of this inability of cells to intake these amino acids, high levels of them build-up in the blood when a normal diet is followed. When excreted at high levels in urine or perspiration these amino acids produce a smell distinctly like that of maple syrup, hence the basis for the name of the disease. One of the most deadly consequences of this condition is a body wide build-up of water in the tissues (a condition formally called edema), with the actual cells making up those tissues being distinctly dehydrated. Edema in the skull resulting from this condition has severe neurological consequences for afflicted individuals (usually children), the increased water pressure on the brain severely impairing brain function and causing permanent, severe damage in individuals who do not properly manage this condition over the long term (management consists of heavily restricting levels of these amino acids in the diet; because these amino acids can be synthesized by cells when necessary, proteins requiring them can still be produced). Propose an explanation for why the massive build-up of amino acids in the blood caused by unmanaged MSUD should promote a corresponding build-up of water in body tissues, with its subsequent horrific effects upon the brain.

Solution: When a person with MSUD consumes a diet rich in the amino acids valine, leucine, and isoleucine, this amino acids build up heavily in the blood because the cells cannot absorb them properly. Just like Na and Cl ions, these amino acids occupy space with the result that the body fluids become functionally water poor (i.e. have a low water concentration) relative to the cells (the formal way to express this situation is to say the body fluids become hypertonic relative to the cells). Because water (like all other fluids) flows from high to low concentration, water flows out of the cells into the body fluids, increasing their volume and thus producing the edema that ultimately damages the brain. (Presumably in the short term, this condition could be treated with diuretics, drugs that increase urine production. The increased urine production would decrease the total body fluid volume, easing the pressure on the brain.)