Oral rehydration therapy: an epithelial transport success story.

Oral rehydration therapy prevents death in acute watery diarrhoea except in the most severe 1-3% of cholera cases. If started at the onset of illness, weakness, orthostasis, muscle cramps, lethargy, and other symptoms of a contracted circulating blood volume are entirely prevented.' Poor countries have rapidly expanded their use of this practical and inexpensive treatment2 while it has been largely neglected in wealthy nations in favour of the more hazardous and costly luxury of hospitalisation and intravenous therapy. Improved solutions are now emerging that not only rehydrate patients, but also reduce severity and shorten illness.3 To grasp this opportunity basic physiological research on the intestinal transport of amino acids, dipeptides and tripeptides, and clinical studies of solutions which optimise all cotransport pathways and minimise lumenal osmotic forces are needed. Such research should be connected to practical field trials of improved oral rehydration solutions. Of the origin of oral rehydration therapy it can be said that nothing is discovered unless it is already known. As it is a decisively effective treatment based on ingredients in common foods and drinks, glimpses of benefit have been repeatedly observed in many countries in what may be called 'grand-mother solutions'. The earliest recorded reference I have found is from Vedic texts.4 All such home solutions take partial and unwitting advantage of the potent cotransport capacity of the intestine which links the absorption of salt, water, and certain solutes. Unfortunately the empirical knowledge embodied in folk remedies before the scientific discovery of intestinal cotransport and its application to the correct formulation and administration of oral hydration solutions was rarely sufficient to prevent many deaths from diarrhoea. Few 'grand-mother solutions' were constituted adequately to tread the path of effective hydration without the hazards of hypertonicity or hypotonicity. The com-monest oversight in their use was failure to adequately replace losses. Few family members ever thought of drinking the several gallons of soup that may be essential to replace losses in severe cases of diarrhoea. The scientific basis for oral rehydration therapy evolved in physiology and biophysics laboratories from the late 1940s to the early 1960s. Of particular note were early observations from Oxford University by Parsons and Fisher who first showed in an in vitro preparation of rat small intestine that glucose enhanced the absorption of water.5 Later the biophysical laboratories of Harvard University fostered investigations of Curran6 and Crane.7 A full articulation of the obligatory transport of …