9 1 o ME TABOLISM. 
salts is followed by can increase of uric acid in the urine, such substances 
o-iven with the food to mammals and man produce only an increase in 
the urea excreted. The same thing occurs even when uric acid itself is 
oiven to dogs, whereas the addition of urea to the food of birds produces 
an increase in the uric acid excreted. 1 There is in fact a fundamental 
difference in this respect between the proteid metabolism of mammals as 
compared with birds and reptiles, but the difference is in the later stage 
of such metabolism, which occurs in the liver, and not in the earlier 
stage, which occurs in the muscles. It has been noticed that in 
mammals the diet which most tends to produce an increase of uric 
acid is glandular substance and especially thymus gland, which con- 
tains a large amount of nucleo-proteid. It is not increased by a 
flesh diet, unless this includes nucleo-proteids ; whereas in affections in 
which there is an increased formation (and presumably therefore also an 
increased destruction) of lymph cells (leucocytosis), a marked increase of 
uric acid has been noticed {e.g. in leukaemia). 3 
For a further discussion of this subject, see " Chemistry of the 
Urine," pp. 593-596. 
Mares 3 found the uric acid of the urine to be increased during digestion ; 
he ascribes this to the activity of glandular cells and increased metabolism of 
nucleo-proteids. In accordance with this view, he found pilocarpine to 
produce a similar increase. Horbaczewski 4 found the uric acid diminished 
in cases of cirrhosis of the liver, and concludes, therefore, that it is not 
formed in man in this organ. On the other hand, by digesting spleen 
pulp (which normally contains neither uric acid nor xanthin nor hypo- 
xanthin) with arterial blood at 40° C, he obtained a considerable forma- 
tion of uric acid, and the same when nuclein was used instead of spleen 
P ul P- 
Uric acid given to mammals (dogs) with their food does not increase the 
uric acid of the urine but the urea. In all probability it becomes transformed 
into urea in the liver. The uric acid which is found in the urine, and which 
has probably been formed from the nucleo-proteid of the food, or of degenerated 
cells of the tissues, may be supposed to have reached the kidneys without 
having passed through the liver. 
If in a dog with an Eck's fistula the uric acid in the urine be estimated, 
and the hepatic artery then tied, it is found that the uric acid in the urine is 
largely increased. This may be explained by supposing that the uric acid 
formed from the products of disintegration of nucleo-proteids of cells, such as 
those of the spleen and lymphatic glands, has not been transformed into urea, 
as would be the case were it allowed to pass through the liver. Those 
products of disintegration are proteids, phosphates, and xanthin- (alloxuric) 
bases. The latter partly undergo further oxidation into uric acid, partly are 
eliminated directly by the kidneys as xanthin or hypoxanthin. They are 
increased in blood which has been perfused through almost all organs of 
1 Hypoxanthin given to birds also markedly increases the uric acid of the urine ; this 
also occurs, however, when the liver is removed. It is therefore probably transformed by 
a process of simple oxidation in the tissues (v. Mach, with Minkowski, Arch. f. exper. 
Path. u. Pharmakol., Leipzig, 1887, Bd. xxiii. S. 139). 
2 Stadthagen, Firchow's Archiv, 1887, Bd. cix. S. 390, found no uric acid in the spleen 
or liver in cases of leukemia, but abundance of xanthin and hypoxanthin. There was a great 
increase of uric acid in the urine, but this was not further increased by giving uric acid 
with the food. 
s Arch, slaves de biol., Paris, 1887, tome iii. p. 207. 
4 Sitzungsb. d. k. Akad. d. Wissensch., Wien, 1889, Bd. xcviii., Abth. 3, S. 301 ; ibid., 
1891, Bd. c. S. 78 ; Arch. f. Physiol., Leipzig, 1893, S. 109. Cf. Mares, Sitzungsb. d. k. 
Akad. d. Wissensch., Wien, Bd. ci., Abth. 3, S. 12. 
