Red cells placed in hypotonic media swell until a certain "critical volume" is reached, after which the cell haemolyses. Shortly before reaching this critical volume, the cell becomes a perfect sphere, and in hypotonic serum the area of the sphere is substantially the same as the area of the disk in an isotonic medium. Thus the increase in cell volume is not accompanied by an increase in cell surface, but rather by a change in cell shape, and lysis occurs when the volume has increased to such an extent that the cell membrane is subject to stretching forces. In hypotonic NaCl the critical volume is smaller than it is in hypotonic plasma, and the cell haemolyses before its membrane is subject to extension.

The volume increase which a cell can undergo by becoming a sphere with the same surface area as that of the disk obviously depends on the shape of the disk, and approximately on its length/breadth ratio, so cells of different shapes haemolyse at different critical volumes, attained in different tonicities. This idea, originally due to Haden, can be made to explain quantitatively the differences in resistance which are observed in the case of the red cells of different mammals, and also to account for the frequency distribution of resistances found in the case of the different red cells of the same animal.

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