648 METABOLISM 



of food taken provided this be purine-free; when, however, the amounts 

 are extremely variable, changes are produced (see page 614). 



In disease, fever causes an increased excretion. This has been most 

 clearly shown by Leathes, who took a large enough dose of antityphoid 

 serum to produce a distinct degree of fever (103 F.), and found that 

 an increase in uric-acid excretion occurred. That increased combustion 

 processes occurring in the tissues were responsible for the uric acid, 

 was shown by the same author, who caused a similar increase by sub- 

 jecting himself to cold baths for a considerable period of time. The in- 

 creased loss of heat thus induced stimulated the combustion processes in 

 the body so as to maintain the body temperature, and as a result there 

 was an increase in uric-acid excretion. It has long been known that an 

 excessive amount of uric acid is excreted in leucocythemia. The nuclein 

 of disintegrated leucocytes is commonly held responsible for the increase. 

 Naturally, much work has been done on the endogenous and exogenous 

 purine excretion in gout. No very striking anomalies of excretion have, 

 however, been brought to light, except perhaps that after the ingestion 

 of purine-rich foodstuffs it takes longer for the resulting exogenous ex- 

 cretion to develop and pass away. 



Certain drugs affect the excretion of uric acid. Salicylic acid is said 

 to cause an increased excretion, and citrates certainly have this effect. 

 In both cases the increase is followed by a compensatory fall, which 

 indicates that these drugs act by facilitating the excretion rather than 

 by influencing the metabolic processes that are the source of the uric 

 acid. The effect of caffeine has been very carefully investigated. Given 

 to the Dalmatian dog, referred to above, S. R. Benedict found that a 

 small dose caused a slight decrease, but that a larger dose had practically 

 no effect, although there was a notable retention of nitrogen. On man, 

 however, different results were secured, for it was found that when 1 

 gram of caffeine was given daily for several days, a slight but definite 

 progressive increase in the endogenous uric-acid excretion occurred, and 

 it lasted for 10 days after the caffeine administration was discontinued. 

 Liberal allowance of this alkaloid may, therefore, not be quite so innocu- 

 ous as it is assumed to be. 



Uric Acid of Blood. In all of the investigations considered above, 

 the behavior of uric acid is judged from the amount of it excreted in 

 the urine. Valuable though such results must be, their interpretation is 

 always difficult, since two factors that are quite independent of each 

 other have to be kept in mind namely, the production of the uric acid 

 in the organs and tissues and its excretion by the kidneys. In connection 

 with the latter factor, we must also consider the method of transporta- 

 tion of uric acid by the blood from its place of production (or absorp- 



