SULFHEMOGLOBINEMIA 523 



in the energy transfers required for the maintenance of the structure 

 of the cell, their inactivation would have serious consequences for 

 the cell. 



It has been shown, however, in Chapter X that hemiglobin forma- 

 tion and reduction in the presence of oxygen is closely allied to chole- 

 globin formation. This hypothesis of slow irreversible hemoglobin 

 destruction as initiating erythrocyte disintegration was put forward 

 independently by Lemberg and by Barkan. 



In favor of the former hypothesis one may adduce the experiments 

 of Richardson (3245), who found that ingestion of 1 to 4% nitrite 

 in the diet caused mice to develop anemia in which spectroscopic 

 observations showed hemiglobin to be the only abnormal pigment. 

 In the absence of reducing substances nitrite forms only hemiglobin, 

 but in their presence it catalyzes irreversible oxidation by H2O2 

 (cf. Chapter X). Cells containing only irreversible breakdown prod- 

 ucts would readily disintegrate so that the detection of these com- 

 pounds in the corpuscle might be difficult. The same considerations 

 hold for all substances able to form hemfglobin in the intact red cell. 



Heubner {1255), Jung {IJ^^I}), and van Loon and Clark {1780) 

 conclude that hemiglobin formation jper se does not damage the 

 erythrocyte; while this is probably correct, a frequent repetition of the 

 cycle might cause a premature destruction of the cell enzymes. 



At present it is therefore impossible to decide which of the two 

 mechanisms causes the normal death of the erythrocyte. It will be 

 seen below, however, that the balance of evidence favors the second 

 theory, which certainly accounts for the shortening of the normal 

 life span in a variety of pathological or experimental conditions. 



5.2. Sulfhemoglobinemia 



Not all irreversible changes in intracorpuscular pigment result in 

 deleterious effects on cell stability. It suffices to recall that cells 

 containing true sulfhemoglobin may be used as indicators of the 

 normal life span of the cell {cf. Section 2.). 



Sulfhemoglobin is found in the blood after administration of drugs 

 of the aromatic amine class, such as phenacetin and acetanilide 

 {2216,2584,2813,1139), pyridium (phenylazoaminopyridine) {236, 

 240,2121), or sulfonamides {466,593,929,2121,2245,2577,3007); after 

 dosage with sulfur; in severe constipation; in cases of septicemia, 

 particularly in severe Clostridium welchii bacteremia; occasionally 

 also in trinitrotoluene workers {1427), although in this case far more 



