530 XI. HEMOGLOBIN CATABOLISM, I 



normal cells is decisive evidence for the physiological nature of the 

 operation. Measurement of the in vivo life of cells after transfusion 

 is therefore an excellent physiological measurement of the extent by 

 which their "normal" life has been shortened by particular treat- 

 ments in vitro. There can be little doubt that glucose prolongs the 

 life of stored cells as a chemical metabolite rather than as a physical 

 agent {197 If., 197 5). Its influence in delaying the appearance of sidero- 

 cytes (^i6) or visible hemolysis in vitro is paralleled by the longer 

 life of such cells in vivo, measured by Ashby's method {cf. also 

 20^,305). This is confirmed by measurements of the urobilinogen 

 excretion in the feces, or of the transitory increase of serum bilirubin 

 which occurs after the transfusion of blood which has been stored 

 long enough for degenerative changes to have taken place {cf. above 

 and 2861,2967). 



There is evidence, however, that the changes discussed in the previous 

 section do not represent the whole story. It has been reported, for example, 

 that the spherocytosis observed in blood stored for a sufficient length of 

 time disappears when the cells are transfused, a process of regeneration 

 apparently taking place in the fresh serum. Whether this is due to the 

 removal in vivo of metabolic products which accumulate or to some other 

 mechanism in vitro is not certain. It seems possible from the irregular 

 cyclical occurrence of the siderocytes which Case observed in stored blood 

 which was inverted daily, that some interaction between cells and plasma is 

 of importance. This is unlikely to be due to the Bergenhem-Flihraeus 

 mechanism {cf. Section 6.), which has not been entirely confirmed by other 

 workers {cf. 1109), and which is apparently without influence on the life- 

 time of the cell {1975). The appearance of a peak in the siderocyte level 

 which occurred in blood stored in citrate-glucose after 15 days is indicative 

 of a critical change at this period which is not found from measurement of 

 the decay rate in vivo {cf. Section 2.). 



The normal level of siderocytes in humans is found by Case to be 

 0.50-0.25% {417), while Greenberg {1065) found far less (below 



0.1%). 



It can be concluded, as far as the normal breakdown is concerned, 

 that the hypothesis of intracorpuscular hemoglobin breakdown as the 

 factor initiating the death of the cell is completely in harmony with 

 the shape of the normal decay curve. Knowledge of the factors initi- 

 ating this process is still in an unsatisfactory state, although there is 

 evidence that they are bound up with the physiological stresses to 

 which the cell is subjected during the performance of its function, 

 while much work remains to be done on detailed biochemical analysis 

 of the relation between intracellular metabolism and cell stability. 



