In a previous communication (Conway & McCormack, 1953) strong evidence was brought forward for the conclusion that the molar concentration inside mammalian tissue cells was the same as that of the plasma. The view had been entertained by Opie (1949) and Robinson (1950) that intracellular concentrations were much higher than those of the plasma (50-100% higher), and that as a consequence water entered the cells continuously in vivo and was pumped out again.Briefly, the evidence on which this view depended was the swelling of tissues, or tissue slices, when these were immersed in Ringer fluid isosmotic with plasma, under conditions when metabolism was inhibited, as by cold (00 C). The water so taken up was lost again on immersion of the slices in oxygenated Ringer fluid at 370 C. Cyanide (0.002M) also produced the same effect as low temperature and its action was shown to be reversible (Robinson, 1950). As supporting evidence the older observations of the freezing-points of tissues (Sabbatani, 1901; Gomori & Molnar, 1932) were cited. The implications of the view that Opie and Robinson put forward are such that the total molecular concentration inside mammalian tissue cells should be about 480-640 m-mole/l. Taking mammalian skeletal muscle, for example, it has been shown (e.g. Conway, 1950 b) that the sum of the concentrations of known substances of quantitative significance in the fibre water is about 320 m-mole/kg water, or approximately the same as the total extracellular concentration. Also, the dry weight of such substances corresponds to the total dry weight of muscle minus that of the known and analysed substances of high molecular weight. The difference between these two estimates of the total concentration of low-molecular weight substances is practically zero, while it would amount, on a conservative estimate, to 2-3 g/100 g muscle if the total osmolar concentration in the fibre water were double that of the extracellular fluid. Furthermore, it could be deduced that if such organic molecules existed they would be non-acidic. since

The physiological significance of plasma cholinesterase is not clearly understood, but attention has recently been focussed on its relation to protein metabolism. It has been identified in high concentration in the a2 globulin of Cohn's fraction IV-6-3 (1).The evidence which has accumulated suggests that the liver is the probable source of plasma cholinesterase; and low values of plasma cholinesterase activity have been reported in patients with liver disease (2-1 1). We have been investigating. acetylcholine and water metabolism in liver disease, and the present communication is an account of work undertaken to determine in which types of liver and biliary tract disease the plasma cholinesterase activity is deranged, and what diagnostic significance can be attached to these findings. Concurrent determinations of plasma proteins and flocculation tests were also made. MATERIAL AND METHODSThe observations were carried out on 43 patients with liver and biliary tract disease. Of these, 15 patients were suffering from acute, four from sub-acute, 14 from chronic liver disease, and ten from extra-hepatic biliary obstruction. The plasma cholinesterase activity of 144 normalsubjects was also studied; of these, 100 were healthy blood donors, and 44 were convalescent patients in hospital, who had no history or clinical evidence of liver disease; concurrent protein estimations were also made on the plasma of the latter patients.Specimens of venous blood were transferred immediately after collection to heparinized tubes and centrifuged. After separation of the plasma, the red cells were washed twice with normal saline, and then laked with an amount of distilled water equal to the original volume of the 1 The expenses of this work were defrayed partially by a grant from the Medical Research Council, from whom one of us (R. J. C.) is in receipt of a whole-time grant, and by financial assistance from the Ministry of Supply, from whom one of us (H. G.) receives a wholetime grant. Maizels (14).In assessing the value of plasma cholinesterase activity as a diagnostic test of liver and biliary tract disease a comparison has been made with the results obtained for plasma albumin and globulin and the serum flocculation tests. For the interpretation of the flocculation tests we have adopted as an index of abnormality the conventional standards used in this hospital (14), for the colloidal red and cephalin cholesterol tests, flocculation greater than one plus (+) at 24 hours, and for the thymol turbidity test a value greater than 4 units. RESULTSIt will be convenient to begin by comparing the total results of the 33 patients with liver disease with those of the normal subjects in respect of plasma cholinesterase activity, plasma albumin and globulin estimations. Our aim here is to determine the limits of normality for these tests. The results have been plotted and give the overlapping histograms seen in Figure 1. The best discrimination will be given by the point on the scale where the two distributions (A) normal and (B) diseased inte...

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