ISOTOPIC INDICATORS IN HAEMATOLOGY 647 



The possibility must also be considered that conditions exist in infect- 

 ious diseases which promote dissociation of the iron transferrin, a step 

 which must precede the penetration of the protein-linked iron through 

 the capillary wall, and thus these conditions accelerate the escape of 

 iron from the blood fluid. 



The escape of iron from the plasma and the entry of iron into it are two 

 independent processes which are presumably coupled by means of hormo- 

 nes. Since the daily metabolism of iron amounts to about 30 mgm and the 

 uptake from the gut constitutes only a small fraction of this quantity, 

 the metabolism takes place essentially between the plasma, the intercellu- 

 lar fluid, the organs and the red blood corpuscles. The rate of escape of 

 iron from the plasma is promoted by an increasing haemopoiesis and also 

 by an enhancement of the metabolism taking place in the storage organs. 

 The two processes are possibly responsible for the 20 to 90 per cent 

 increase of plasma-iron level observed in the early hours of the day. 



In animals which have been deprived of the suprarenal capsule, and 

 still more powerfully in normal dogs, adrenalin leads to a temporary 

 lowering of the iron level, wdiereas ACTH causes this effect only in normal 

 animals. Cabtwright and co-workers^i even found that an intramuscular 

 injection of physiological saline solution lowers the plasma iron content 

 in dogs by from to 41 per cent, which presumably also is brought 

 about by a hormonal effect. Oestrogen raises and androgen lowers the 

 amount of iron stored in the liver of chickens^22) ^nd, therefore, these 

 hormones also should affect the escape of iron from the plasma or its 

 entry from the liver, or both of these processes. 



As Laurell^^' 25 has already found, it is highly probable that iron 

 dissociated from the protein compound, and not iron transferrin, which 

 is transferred from the plasma into the extra vascular extracellular space. 

 With the aid of paper-electrophoretic methods, Ehrenstein of our 

 laboratory has recently proved that the iron present in the lymph, and 

 therefore the iron present in the spaces between the cells, is also combined 

 with j5i globulin. He found that the iron content of the lymph of the 

 rabbit is one-half to one-third the content in the plasma, which amounted 

 to about 150 mgm %. He also found that the combining capacity of the 

 lymph for iron, and therefore the transferrin content, is also about one- 

 third that of the plasma. Laurell^^^^ pointed out that an importance 

 attaches to the ratio (Fe transferrin content)/(Fe-free transferrin) = 

 = K[Fe+"'" + ] in respect of the metabolism of iron, and it is not without 

 interest that this ratio is found to be about the same in the plasma 

 as in the lymph. Since the iron content of the intercellular space should 

 be lower than that of the lymph, the values quoted represent an upper 

 limit for the intercellular space and a lower limit for the space within 

 the cehs. The volume of the intercellular space has been assumed to be 

 four times the plasma volume. 



