The Three Compartment Model for Transport of Water Across Epithelium

An early observation by physiologists studying absorption of water in the gut was that fluid absorption did not cease when the the lumenal contents were hyperosmolar. They correctly deduced that the intestinal epithelium can transport water against an osmotic gradient, but were unable to explain how this occurred. There is still considerable uncertainty about how water is absorbed in such a situation, but Curran and Macintosh presented a explanation known the "three compartment - two membrane model" that accounts for many aspects of water transport in the gut and other tissues.

It is proposed that the epithelium consists of three compartments separated by two membranes which differ in permeability, as shown diagramatically below:

In this situation, water will move against an osmotic gradient from compartment A to compartment C as long as two conditions are met:

• The osmolarity in compartment B is greater than in compartment A.
• The permeability of membrane 1 is less than that of membrane 2.

In such a case, the higher osmolarity in compartment B relative to A or C provides the driving force for movement of water from A to B. As water flows into compartment B, the hydrostatic pressure in that compartment increases, forcing water to flow through membrane B and into the lowest osmolarity compartment C.

In epithelia such as the intestine or kidney, compartment B corresponds to the lateral intercellular spaces beneath tight junctions and between epithelial cell. The relatively high osmolarity of fluid within this space results from the active pumping of sodium out of the cells. Membrane 1 in the model (least permeable) appears to be the tight junctions and basolateral membrane of the enterocyte, while and the function of membrane 2 (most permiable) is served by the basement membrane and/or capillary endothelial cell.

References and Reviews

• Curran P and Macintosh J: A model system for biological water transport. Nature 193:347-348, 1962.
• Larsen EH, Sorensen JB and Sorensen JN: Analysis of the sodium recirculation theory of solute-coupled water transport in small intestine. J Physiology 542:33-50, 2002.
• Spring KR: Routes and mechanism for fluid transport by epithelia. Annu Rev Physiol 60:105-119, 1998.