URIC ACID. 593 
Variation* in the amount — (a) The relation to urea; the effects 
of diet. — Variations in the quantity of uric acid have been considered 
from two different points of view. By some, these variations have 
been expressed always in relation to the quantity of urea excreted 
simultaneously. Such observers have felt that an increase or decrease 
in uric acid, which merely accompanies a corresponding change in the 
general nitrogenous metabolism, is of less physiological significance than 
a variation which (..curs independently of (or out of proportion to) the 
latter; and since the urea excretion is a measure of this general 
metabolism, the uric has been, Iry such writers, referred to the urea 
output as a standard. Other and more recent authorities, seeing the 
origin of uric acid in an entirely distinct series of events within the 
body, and observing that the urea : uric acid ratio has no stable 
value, have recommended the entire neglect of this relation, prefer- 
ring to express the uric acid output always in terms of its absolute 
amount. 
An attempt has been made to show that urea and uric acid are 
always produced in the body, so as to bear a constant and definite ratio 
to each other, and that any alterations in this ratio indicate either a 
retention of uric acid on the one hand, or a sweeping out of previously 
retained acid on the other. 1 That this position cannot be maintained in 
its entirety is quite certain. Consideration of the effect of varying diet 
alone gives sufficient evidence against it. If the two analyses by Bunge, 
given in an early section of this article, be examined, we see that upon a 
diet of bread, not 'only is the absolute amount of uric acid less than upon 
a diet of beef, but also that the relation to urea is also strikingly less. 
On bread the ratio is 1 to 81, on beef it is 1 to 48. Similar results are 
obtained, as the writer has found, if the experiments are continued for 
many days. If the two substances were always produced in constant ratio 
we should have to conclude that a bread diet produces a continuous 
storing up of uric acid in the body ; and for this conclusion there is 
certainly no evidence. 
Again, if we consider the effect of varying the quantity of the 
ingested food — its composition being maintained uniform — we find that 
on the whole the uric-acid excretion is less affected by such variations 
than is the urea, so that we change the value of the ratio merely by 
altering the amount of food taken. 
It is therefore impossible to look upon the ratio wdiich uric acid 
bears to urea as an independent physiological constant, or to conclude 
that even wide variations in its value are necessarily pathological. 
But some authorities go further than to say that the uric acid 
output is more stable than that of the urea, claiming, indeed, that it is 
quite unaffected by the absorption of the ordinary proteids of diet — the 
albumins and globulins with their derivatives. If this lie a fact, and 
the production of the acid is independent of variations in these main 
nitrogenous constituents of food, we ought certainly, in studying the 
quantity in the urine, to neglect its ratio to urea altogether. This ratio 
will then be little more, under ordinary circumstances, than an expression 
for the urea variations, measured from the more stable uric acid output, 
so to speak, as a base line ; while, if we are studying the effect of special 
factors upon uric acid production, reference to the urea will be un- 
necessary and misleading. 
1 Haig, "Uric Acid in Disease."' 
VOL. I. — ^8 
