INTERNAL SECRETION AND DISORDERS OF LIVER 683 



and Whipple and Hurwitz (1911) and others have shown that the fibrino- 

 gen of the blood may be reduced to a very low level by poisoning with 

 phosphorus or chloroform. Whipple (a) (1912) has shown that when the 

 fibrinogen is present in only small amounts in the circulating blood, exten- 

 sive hemorrhages may be observed from small wounds in the skin, oozing 

 from the mucous membranes and purpura. This drop in blood fibrinogen 

 is invariably associated with extensive injury to the hepatic tissue, usu- 

 ally with extensive necrosis of the liver cells. Observations on dogs suffer- 

 ing from acute liver injury (chloroform) with hepatic insufficiency, and 

 parallel observations on human cases of cirrhosis, with progressive hepatic 

 insufficiency, prove beyond doubt that the liver is the essential factor in 

 maintaining the normal fibrinogen balance of the blood. 



Meek (a) (6) (1912) noted that after an Eck fistula, ligation of both 

 portal vein and hepatic artery and partial defibrination, fibrinogen is no 

 longer reformed, and that the amount remaining in the blood rapidly disap- 

 pears. In the normal dog it is regenerated at a rapid rate after partial de- 

 fibrination. In three hours the amount may be increased as much as 100 

 per cent. From this he concluded that the liver itself forms fibrinogen. 

 Whipple (b) (1914) and Goodpasture (1914) are of the opinion that nor- 

 mal fibrinogen production is the result of the combined activity of the liver 

 and the intestine. However, they admit that the intestine is not essential to 

 fibrinogen regeneration, but it is an important contributing factor in its 

 rapid formation. 



Experimental evidence conclusively indicates that fibrinogen is formed 

 in the liver, and that this organ is the essential factor in maintaining the 

 normal fibrinogen balance of the blood. 



Urea as a Hepatic Internal Secretion 



The complete story of urea formation in the body is not entirely known. 

 Present knowledge indicates that the main bulk of urea is formed in the 

 liver. It is then given to the blood as an internal secretion and finally 

 excreted by the kidney. Schroder (1882) established an artificial circu- 

 lation in the excised dog liver, and made a chemical analysis of the blood 

 before and after it passed through this organ. He found that blood taken 

 from well fed dogs showed a distinct increase in urea after passing through 

 the liver, while blood from fasting dogs showed no change. Blood from 

 well fed animals showed no increase after being circulated through the 

 isolated kidney or muscle. Further, he showed that if ammonium carbo- 

 nate was added to the blood circulating through the liver it was converted 

 into urea. This conversion is affected by the liver cells by a. process equiv- 

 alent to dehydration, in which the ammonium carbonate loses water and is 

 converted into urea. The experiments of Hahn, Massen, Nencki and 



