PATHOLOGICAL METABOLISM OF THE BLOOD 559 



integrated erythrocytes, but also from substances added to the diet. In 

 fact, the available experimental evidence suggests that bile-pigment for- 

 mation normally may depend upon the functional activity of the liver 

 cell, and that pigments may be formed, in part at least, from other 

 substances than hemoglobin. It has been noted, for instance, that whereas 

 the excretion of pigment from a biliary fistula- is remarkably constant 

 in a dog fed on a mixed diet, the output increases, sometimes by 100 

 per cent, when the diet is changed to one of carbohydrate, and is de- 

 pressed on a diet of meat. Such evidence certainty strengthens the con- 

 ception that bile-pigments may be elaborated by the liver cell de novo 

 out of materials other than broken down hemoglobin, and that this con- 

 structive ability of the liver in pigment formation can be modified by 

 diet. 



The Building Up of Hemoglobin. Liver Cell Activity and Diet Fac- 

 tors. The constructive phase of the life cycle of hemoglobin pigment is 

 not well understood. 1 A working hypothesis, which is in accord with 

 certain of the facts of pigment metabolism, has been proposed by Addis. 

 According to this view hemoglobin is constantly liberated in the body 

 from the disintegration of worn-out red blood-cells. The hemoglobin thus 

 set free passes into the blood-plasma and is taken up by the Kupffer cells, 

 which pass it on to the liver cells. Here the pigment is separated from 

 the globin, and after the removal of iron and undergoing intramolecular 

 changes which involve the addition of oxygen is converted into bilirubin. 

 The bilirubin is reduced to urobilinogen in the intestine, a part escap- 

 ing in the feces, and an important part being absorbed into the blood, 

 polymerized into urobilin-complex, and taken up by the liver. In the 

 liver this complex has restored to its pyrrol nuclei the original side 

 chains, and then is used to form new hemoglobin molecules, or, if the 

 liver is abnormal, may escape into the blood and appear in the urine as 

 urobilinogen. 



This theory has been subjected to critical analysis by Whipple and 

 Hooper. And although it is as yet difficult to draw definite conclusions 

 from their findings, considerable doubt has been thrown by their well- 

 planned experiments upon the correctness of the older view that a con- 

 siderable fraction of the bile-pigments eliminated into the intestine from 

 the liver is reabsorbed and reutilized. Their work gives experimental evi- 

 dence against the conception of a circulation of bile-pigments and pre- 

 sents proof of the existence of the same relationship on the part of the 

 liver to the constructive mechanism of hemoglobin regeneration and its 

 modification by diet as has been shown to exist for bile-pigment pro- 

 duction. That the liver can form hemoglobin out of various materials 

 other than the degradation products of hemoglobin follows from the ob- 

 servation that blood-pigment regeneration proceeds at a normal rate in a 



