LIFE SPAN OF THE ERYTHROCYTE 509 



138J^,2I^I^J|.,2989). Only a small part of the data can be considered 

 here. 



2.2. Life Span of the Cell Deduced from Pigment Metabolism 



2.2.1. Bilirubin Excretion. Eppinger concluded from measurements of 

 bilirubin excretion in humans with bile fistulae that the normal life span of 

 the erythrocyte was about forty days, while the experiments of earlier 

 workers had indicated a period of between thirteen and fifty days. The 

 earlier values are certainly vitiated by lack of a pure bilirubin standard. 

 Eppinger's own value was calculated on the basis of a blood volume of 

 3.5 liters and a hemoglobin content of 14 g. per 100 ml. The blood volume 

 was undoubtedly assumed too low; the average blood volume of men is 

 about 5.5 liters (c/. 992). Eppinger's figures indicate the daily excretion of 

 about 300-350 mg., rather than of 400 mg., of bilirubin per day which was 

 the basis of his calculation. Assuming a blood volume of 5.5 liters and 

 15 g. of hemoglobin per 100 ml., the total circulating hemoglobin is 825 g., 

 corresponding to 29 g. of bihrubin. An excretion of 300-350 mg. per day 

 thus indicates a lifetime of 87-97 days, a figure in far better agreement with 

 modern results. Similar average values were obtained by Adler {18) and 

 With {3112). 



In the hands of Whipple and his co-workers, the quantitative measure- 

 ment of bile pigment excretion in dogs with bile fistulae may be regarded 

 as a more reliable index of hemoglobin destruction, although Drill and 

 co-workers {633) have recently also found signs of liver damage in these 

 animals. The bile is collected either in a sterile bag (method of Rous and 

 McMaster, 237Ji) or is diverted into the bladder by the formation of a renal 

 gall bladder fistula (method of Kapsinow, Engle, and Harvey, 1466). By 

 being fed bile salts, the animals may be kept in excellent condition for many 

 years after the operation. In nonanemic dogs Shribishaj, Hawkins, and 

 Whipple {25If8) found a bilirubin excretion of 4-6 mg. per kg. per day, 

 closely corresponding to the values quoted above for human bilirubin 

 excretion. The experiments of Whipple and his school have shown that the 

 bile pigment excreted in the bile almost exactly corresponds to the amount 

 of hemoglobin broken down. This will be discussed in Section 8. 



The excretion of bilirubin has been used more accurately for 

 measuring the life span of the erythrocyte by Hawkins and Whipple 

 {1196). As will be seen later, all the erythrocytes live for a fixed 

 period and are destroyed within a few days of the average life. If a 

 large number of new cells are suddenly put into circulation, as after 

 severe bleeding or destruction of cells by acetylphenylhydrazine, a 

 second peak of excretion of bilirubin will appear when these cells 

 reach their natural span of life. The bilirubin excretion was measured 

 regularly over a period of several months and a highly significant 

 rise was observed 112 to 113 days after the stimulus to new cell 



