W. N. M. RAMSAY 



The coin, however, has tails as well as heads. When ferrihaemo- 

 globin does occur in red cells, as under pathological and experimental 

 conditions, it has been repeatedly shown to be rapidly removed. As 

 long ago as 1930 O. Warburg, F. Kubowitz and W. Christian 3 

 showed that ferrihaemoglobin can be reduced by an enzyme system 

 in red cells which oxidizes glucose to gluconic acid. Although it may 

 be objected that this is a reaction which seems to have no great 

 physiological significance, the same criticism cannot be levelled at 

 the recent work of Q. H. Gibson 4 , who has made a detailed study of 

 the reduction of ferrihaemoglobin generated in red cells by the action 

 of amyl nitrite in phosphate-saline solution. He has found that the 

 reduction is brought about by the triose-phosphate and lactate dehy- 

 drogenating systems. The rate of removal of ferrihaemoglobin from 

 the blood of experimental animals was investigated by W. W. Cox 

 and W. B. Wendel 5 . They induced ferrihaemoglobinaemia in dogs, 

 to the extent of 25-60 per cent of the total blood pigment, by the 

 injection of nitrobenzene, aniline, acetanilide and a number of other 

 compounds. The rate of disappearance of ferrihaemoglobin was 

 independent of the causal agent, and was the same in a test-tube as in 

 the living animal. It was, however, influenced by temperature, and 

 while at 38°C the rate of reduction corresponded to 11 per cent of 

 the total pigment per hour, at 20°C it was only about one-quarter 

 of this. The fact that the rate was constant and independent of the 

 concentration of ferrihaemoglobin in each particular experiment seems 

 to indicate that it was limited by the amount of some other necessary 

 factor throughout the range of ferrihaemoglobin concentrations 

 studied. 



It is thus clear that red cells are amply provided with mechanisms 

 for the reduction of ferrihaemoglobin as well as for its formation by 

 the oxidation of ferrohaemoglobin. The accumulation of the ferric 

 compound in the blood of experimental animals or pathological 

 subjects may be due either to an increased rate of oxidation or to a 

 decreased rate of reduction, so that the state of balance between the 

 two tendencies in the normal erythrocyte assumes an importance 

 which, as far as the author is aware, has not previously been 

 emphasized. 



Until fairly recently the assumption that the whole of the blood 

 haemoglobin was normally in the ferrous state was implicit, if not 

 actually stated. In recent years, however, several independent lines 

 of work have suggested that this belief may not be wholly accurate. 

 For example, T. G. Klumpp 7 , who does not seem to have been 

 directly interested in ferrihaemoglobinaemia and made no pronounce- 

 ment on this aspect of the subject, published a careful comparison of 



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