ALTERATION OF ERYTHROCYTE STABILITY 527 



The fact that Heinz bodies are generally observed on the periphery 

 of the red cell led to the suggestion that they might be due to some 

 change in the cell wall, thus explaining the instability of the cells. 

 Bratley and co-workers (329) conclude, however, from a study of the 

 effect of acetylphenylhydrazine on red cells in hanging drops that 

 the change in the stability of the cell is secondary to the pigment 

 changes. Erythrocytes treated with ascorbic acid in hypotonic 

 phosphate buffer contain choleglobin (1694.). On being brought back 

 to isotonic conditions they are found to be very fragile, and even 

 centrifugation may produce hemolysis. More recently, Gajdos and 

 Tiprez (977) found that treatment of washed cells with ascorbic 

 acid under more physiological conditions caused Heinz bodies to 

 appear. Cruz observed abnormal fragility in red cells after adminis- 

 tration of acetylphenylhydrazine (514) and also the fact that the 

 cells were ingested by phagocytes like foreign bodies from the cir- 

 culating blood in a few days. More easily detachable iron is to be 

 found in those erythrocytes which are more readily hemolyzed by 

 hypotonic solutions (Barkan and Walker, 167). 



A number of points arise from Case's experiments on siderocytes Hl6). 

 The integrity of the cell is apparently necessary for the reaction between 

 acetylphenylhydrazine and oxyhemoglobin to give rise to siderocytosis, since 

 he could not observe hemoglobin destruction in hemolyzed cells. Cells in 

 3.8% citrate are able to react only once, a second addition of acetylphenyl- 

 hydrazine being neither able to break down any more hemoglobin, nor to 

 form siderocytes. The iron-containing granules were extruded from the 

 intact cell and could be observed in the extracellular fluid, the cell in the post- 

 siderocyte stage being histologically indistinguishable from the normal 

 erythrocyte. The cells in the siderocyte or post-siderocyte stage were 

 phagocytosed by leucocytes, mainly mononuclears, while the polymorphs 

 present were found to contain many iron granules. The evaluation of the 

 siderocyte experiments is difficult. It is doubtful whether the position of 

 iron granules inside or outside the cell can be established with certainty. 

 Iron granules outside the cell may be artifacts; with some techniques, at 

 least, particularly those applying ammonium sulfide for "unmasking" the 

 iron, there is also the danger that iron may be set free from hemoglobin 

 during the processes of preparation of the slides. The fact that there is no 

 satisfactory agreement on the siderocyte counts in normal adult human 

 blood {cf. below) also indicates that a reliable technique has not yet been 

 developed. 



It is clear from the fact that neither the Heinz bodies nor the 

 deposits of stainable iron occupy the entire erythrocyte that the 

 altered stability of the cell, predisposing it to hemolysis or to phago- 



