ICTERUS 491 



ences: Icterus due to hemolysis appears sooner than icterus from 

 bile-duct occlusion, and reaches a much higher degree; the obstruction 

 in hemolytic icterus, when present, is intra-acinous; in stasis it is 

 chiefly inter-acinous; in hemolytic icterus there is a large splenic 

 tumor due to accumulation of degenerated red cells in the spleen, 

 where they become disintegrated preliminary to the formation of bile- 

 pigment. If the spleen is removed, hemolytic agents may not cause 

 icterus, because the corpuscles are not then prepared for pigment 

 formation. ^^ In obstructive icterus from gall stones there is a choles- 

 terolemia in proportion to the amount of icterus, which is not usually 

 true of icterus from other causes." 



Toxicity of Bile. — In any event, we must appreciate that in 

 icterus not only are abnormally large quantities of bile-pigment present 

 in the blood, but also usually the other less conspicuous constituents 

 of the bile. Whole bile of rabbits is fatal to rabbits in doses of 0.2.5 

 to 0.5 cc. per kilo, by intraperitoneal injection, and about half as much 

 intravenously (Bunting and Brown^"). Death is the result of changes 

 in the myocardium, where necrosis is produced; and severe degenera- 

 tive changes are also found in the kidneys and liver; when the bile is 

 injected into the peritoneum, pancreatitis and fat necrosis result. The 

 relative toxicity of the bile-pigments and the bile salts is not as yet 

 uniformly agreed upon. 



Bile-pigments. — Bouchard" and others have claimed that the bile- 

 pigments are far more toxic than the bile salts, which is contradicted 

 by Rywosch and others. Bihrubin is normally present in the blood, 

 and is probably responsible for the yellow color of the plasma. ^^ It 

 is always present in excess in icterus of whatever degree. ^^ A series 

 of analyses by Gilbert^" and others gave the following results: Normal 

 blood-serum contains 0.027-0.08 gram bilirubin per liter; in obstructive 

 icterus they found 0.7 to 1.0 gram of bihrubin per hter, in biliary cir- 

 rhosis 0.33 gram per liter, in icterus neonatorum 0.2 to 0.5 gram; in 

 pneumonia 0.068 gram was found. These figures, however, are far 

 in excess of those described by later investigators. Bauer and Spiegel"*^ 

 give figures of about 1 part in 100,000 to 200,000, or 0.01 to 0.005 gm. 

 per hter. In icterus the highest figure given by these authors was 

 0.07 gm. There is a marked variation between different normal 

 individuals, but for the same person the figures are nearly constant. 

 The threshhold value for the blood seems to be about 1 part in 50,000; 



** The etiology of icterus neonatorum (when not obstructive) has not been 

 ascertained, but a natural tendency towards icterus is said to exist in the new- 

 born, their blood containing much more bile pigment then than later. (Hirsch, 

 Zeit. Kinderheilk., 1913 (9), 196; \lppa, Miinch. med. Woch., 1913 (39), 2161.) 



" Rothschild and Felsen, Arch. Int. Med., 1919 (24), 520. 



3« Jour. Exper. Med., 1911 (1-4), -145. 



" Literature and discussion by Stadelmann, Zeit. f. Biol., 1896 (34), 57. 



3s Blankenhorn, Arch. Int. Med., 1917 (19), 344; 1918 (21), 282. 



'9 Feigl and C^uerner, Zeit. exp. Med., 1919 (9), 153. 



"» Compt. Rend. Soc. Biol., 1905 and 1906. 



^1 Deut. Arch. klin. Med., 1919 (129), 17. 



