EFFECTS OF CERTAIN DRUGS AND POISONS 759 



found under radium therapy very large increases in the excretion of total 

 urea, ammonia, and phosphate, the latter sometimes attaining 400 per 

 cent of the normal figure*. The slight increase in uric acid excretion was 

 attributed to the disintegration of nuclein tissue in the spleen. 



Phlorhizin. Although not used in therapeutics this poison is of great 

 interest on account of the type of glycosuria it produces. Its effects upon 

 the metabolism resemble. somewhat those of the heavy metals. 



Carbohydrate Metabolism. Mering, the discoverer of phlorhizin 

 glycosuria, found dextrose values in the urine as high as eighteen per cent ; 

 the absolute amount may be very large. The condition is characterized 

 by absence of hyperglvcemia, showing that it is essentially of renal origin. 

 Zuntz showed that the effect upon the kidney was peripheral rather than 

 central by injecting the poison into a single renal artery which gave rise 

 to glycosuria at first on that side alone. 



Although the important factor of increased glomerular permeability 

 has recently been well demonstrated by Brinkmann(a) in Hamburger's 

 laboratory some have deemed it necessary to seek further for the origin 

 of such large amounts of sugar. Pavy, Brodie and Siau, for example, 

 maintained that the kidneys form sugar from the proteins of the blood. 

 Underbill, however, produced hyperglvcemia by phlorhizin in animals in 

 which the renal arteries were ligated, thus excluding the kidneys. Le- 

 pine(fe) has long championed the "virtual sugar" theory in which much 

 sugar is supposed to exist normally in combination with blood colloids, 

 being demonstrable only on hydrolysis. From this source he believes sugar 

 is derived in phlorhizin poisoning. 



At all events the glycogen stores are never entirely exhausted by 

 phlorhizin, even during fasting (Sansum and Woodyatt(a)). Epstein and 

 Baer even maintain tlwt phlorhizin stimulates glycogenesis, as hepatic 

 glycogen seems to accumulate when the kidneys are excluded. 



The sugar percentage in Brinkmarin's perfusate being sometimes 

 higher than in the perfusion fluid and no opportunity existing for re- 

 absorption of water the renal secretory theory must still be given some 

 consideration. 



In complete phlorhizin poisoning Stiles and Lusk found that dextrose 

 given subcutaneously fails to increase the respiratory quotient; thus the 

 power to oxidise sugar becomes lost. 



Protein Metabolism. The body being deprived of the sparing influ- 

 ence of sugar there is often a very marked rise in the protein metabolism. 

 Reilly, Nolan and Lusk have found this as high as 450 per cent of normal 

 in dogs. After the extra sugar was flushed out the D:N ratio in this 

 species was found to be 3.05 as against 2.8 in rabbits, cats, and goats. 

 58.7 per cent of the protein is therefore excreted as dextrose. 



Fat Metabolism. Mering in his experiments noted fatty infiltration 

 of the liver when starving animals were phlorhizinized. This was asso- 



