Water and Electrolytes 7 



these, melting point depression was utilised and autolysis and 

 thermal artefacts excluded by the use of very low temperatures. The 

 results show without doubt that the intracellular compartment is 

 isotonic with the extracellular fluid. 



The second blow to the view that failure of water extrusion was 

 the basic cause of swelling of injured cells came from direct 

 measurement of other ionic concentrations after injury. Thus slices 

 of kidney or other tissues injured by chilling, oxygen lack or 

 metabolic poisons show a net uptake not only of water, but also of 

 sodium and chloride (Mudge, 1951; Leaf, 1956). The inflow of 

 chloride ion into the injured cell is particularly striking and in- 

 dicates clearly that in injury there is an entry of isotonic extracellu- 

 lar fluid into the cell and that the defect is not essentially a disorder 

 of water transport. 



In summary, in tissue injury there is an influx of isotonic fluid 

 into an isotonic cell. Ions other than sodium and chloride may 

 enter, notably calcium which may accumulate within the cell to a 

 considerable extent. These events are of course associated with a 

 massive loss of potassium from the cell into the environment. 



Relative to the extracellular fluid the cell is rich in potassium 

 and lacking in sodium and chloride. However, the cell wall is freely 

 permeable to all these ions in the sense that intracellular sodium, 

 potassium and chloride will exchange readily with similar extra- 

 cellular ions, the movements being followed with the aid of isotopes. 

 If a normal cell is placed in a solution of potassium chloride, the 

 potassium ion enters the cell and accumulates therein until the cell 

 swells and possibly dies. A similar experiment in sodium chloride, 

 however, is not followed by intracellular accumulation of sodium. 

 Thus in another sense the permeability of the cell to sodium is re- 

 stricted. 



Much evidence indicates that these ionic gradients are main- 

 tained by the expenditure of energy derived from cell metabolism. 

 The detailed picture of this mechanism and of its failure after in- 

 jury remains obscure. It is, however, a problem which lies at the 

 heart of contemporary physiology and pathology. 



Any hypothesis advanced must take into account six basic facts. 

 These are: 

 1. The existence of sodium exclusion and of potassium accumula- 



