454 THE METABOLIC PROCESSES OF THE BODY. 



frogs, which survive the operation for some considerable time ; but the same 

 results have been obtained in birds (geese and ducks). There can be no 

 doubt, therefore, that these substances are formed in the liver, arid not sim- 

 ply withdrawn from the blood by the liver in some such way as we have 

 seen reason to think urea is withdrawn from the blood by the kidney. 



When the plasma of circulating blood is made to contain haemoglobin 

 detached from the corpuscles, bile pigment frequently makes its appearance 

 in the urine. The presence of free haemoglobin may be obtained by inject- 

 ing into the veins a solution of haemoglobin or blood made " laky " by freez- 

 ing and thawing or by the addition of a small quantity of bile salts, or by 

 simply injecting into the veins a quantity of distilled water or a small 

 quantity of ether or chloroform or of bile salts, all of which tend to " break 

 up " red corpuscles and set free haemoglobin. A similar result occurs in 

 poisoning by certain drugs, such as toluylendiamine. Under these circum- 

 stances not only does bile pigment, bilirubin, make its appearance in the 

 urine, but the quantity of bilirubin secreted by the liver is increased. 

 Obviously the presence of dissolved haemoglobin in the plasma of the blood, 

 and, presumably more especially of the blood reaching the liver by the 

 portal vein, leads to an increased formation of bilirubin, which take place 

 in such a manner that the whole of the bilirubin so formed does not pass 

 into the bile but part is retained in or thrown back into the circulation and 

 appears in the urine. 



We have already mentioned the chemical connection between haemoglo- 

 bin and bilirubin. Haemoglobin after the detachment of its proteids com- 

 ponent becomes haematin (C 32 H3 2 N 4 FeO 4 ). By treatment with sulphuric 

 acid or otherwise ( 294), haematin may be deprived of its iron ; and this 

 iron-free haematin (sometimes called haematoporphyrin) is said to have the 

 composition C 32 H3. 2 N 4 O 5 , differing from bilirubin only in its oxygen and hy- 

 drogen (C3 2 H 32 N 4 O 5 +2H 2 O O^C^HggNA). 1 Moreover, in old blood-clots 

 in the body the haemoglobin of the clot becomes in time transformed into 

 an iron-free body which has been called haematoidin, but which both in com- 

 position and reactions appears to be identical with bilirubin. 



These several facts lead us to the conclusion that the bilirubin of the 

 bile is simply some of the haemoglobin of the blood transformed by the 

 throwing off of its proteid and its iron components. It is natural to sup- 

 pose that the transformation takes place in, and is effected by, the agency of 

 the hepatic cells ; and this view is supported by the fact that the hepatic 

 cells are characterized by containing certain peculiar iron compounds. 

 When all the blood is carefully washed out of the liver by injection through 

 the bloodvessels, by which means the remaining bile is got rid of at the same 

 time, the hepatic substance is found to contain a small quantity of iron, 

 sufficient to give the cells a diffused dark color when treated with ammo- 

 nium sulphide ; the exact amount appears to vary largely, but the causes of 

 the variation have not been determined. That this iron is in organic com- 

 bination is indicated by the fact that with potassium ferrocyanide and sul- 

 phocyanide the blue or red action is not observed until after treatment with 

 hydrochloric acid. Apparently there are several such compounds, of a pro- 

 teid or of a nuclein ( 29) nature, from some of which the iron is more easily 

 removed than others, and these compounds appear to be present in both the 

 cell substance and the nucleus. It will be remembered ( 213) that bile 

 contains a distinct quantity of iron, which probably has its origin in the 

 iron thus set free from haemoglobin and retained in the hepatic cell ; but it 

 does not follow that all the iron thus set free makes its way into the bile ; 

 and, indeed, the quantity of iron discharged in the bile in twenty-four hours 



1 Doubling the formula for bilirubin given in $ 214. 



