UREA. 



Urea represents the end-product of the metabolism of proteids. Next in 

 order there stand, as lower stages of oxidation, uric acid, guanin, xanthin, hypo- 

 xanthin, alloxan and allantoin. Uric acid administered as urates appears in the 

 urine as urea, being transformed by the liver, with increase in the secretion of 

 bile. Muscle-extractives have the same effect, and in general increased formation 

 of bile is attended with augmented formation of urea. After administration of 

 leucin, glycin, aspartic acid or of ammonium-salts an increase in the excretion of 

 urea takes place. 



The liver is the principal, but not the sole seat of the formation of 

 urea. The correctness of the supposition of Schmiedeberg that the urea 

 is derived from ammonium carbonate through loss of water was demon- 

 strated by v. Schroder, who found urea in large amount in blood to 

 which ammonium carbonate had been added, and made to pass through 

 a recently removed liver. It is, therefore, to be concluded that am- 

 monium-combinations derived from nitrogen-containing tissues as meta- 

 bolic products pass over into the circulation, through which they are 

 conveyed to the liver for the formation of urea. The organism is 

 capable of converting considerable amounts of ammonia, as, for instance, 

 in the form of lactate or acetate, into urea. The liver forms urea also 

 from the ammonia in the blood of the portal vein. In the metabolism 

 especially of proteids there is formed in many organs by oxidation car- 

 bamic acid, CO 2 NH 3 , which likewise is transformed principally in the 

 liver into urea, and also the amido-acids. If acids are taken into the 

 body before the ammonium-combinations are transformed into urea, 

 there result ammonium-salts, with a corresponding reduction in the 

 amount of urea in the urine. Under pathological conditions the 

 urea-forming activity of the liver may be diminished. 



After extirpation of the liver, the urine no longer contains urea, and likewise 

 after exclusion of the hepatic circulation, but on the other hand large amounts 

 of ammonium- salts. 



Eck, in the dog, diverted the blood of the portal vein directly into the inferior 

 vena cava, by establishing an artificial communication between the two vessels, 

 and then ligated the portal vein close to the liver. The dogs were seized with 

 severe nervous attacks and convulsions. As, according to v. Schroder, ammonium- 

 salts are transformed in the liver into urea, this transformation is thus almost 

 wholly prevented, and the substances named now exert a toxic effect upon the 

 nervous system. 



By injection of a 6.2 per cent, solution of sulphuric acid into the bile duct, 

 in the dog, all of the liver-cells became necrotic, and the animal died in 

 one or two days with signs of prostration, mental derangement, loss of sensibility, 

 central narcosis and finally convulsions. From this it has been concluded that 

 the liver serves the purpose of converting a toxic metabolic product, carbamic 

 acid, into an innocuous one, urea. 



In birds the liver thus produces the largest amount of uric acid from the 

 ammonium supplied. As birds readily tolerate ablation of the liver, Minkowski 

 observed after this operation reduction in the amount of uric acid and in- 

 crease in the amount of ammonium-salts in the urine. 



Urea is present in the following parts of the body: Blood (i : 10,000) ; lymph, 

 chyle (2 : 1,000); liver, lymphatic glands, spleen, lungs, brain, eye, bile, saliva, 

 amniotic fluid; by Schondorff it was found in the muscles and the erythrocytes 

 and in almost all of the organs of the dog; besides, pathologically, in the sweat, 

 as, for instance, in cases of cholera, as well as in the vomitus and in dropsical 

 fluids of uremic patients. 



The preparation of urea can be accomplished directly from dogs' urine, after 

 generous feeding with meat, the fluid being evaporated to a syrupy consistency, 

 extracted with alcohol, the filtered extract again evaporated, the crystals thus 

 separated freed of the adherent extractives by means of alcohol and then dis- 

 solved in absolute alcohol. Filtration is practised again and evaporation is per- 

 mitted to take place until crystallization occurs. A given volume of human urine 



