154 FRANKLIN C. McLEAN 



circulation. His observations as to the diminished protein content, with 

 subsequent lowering of the specific gravity of the serum, were confirmed 

 by numerous observers, and for some years the impression was current 

 that there was, in effect, an hydremia, due to the loss of albumin through 

 the urine, and that this resulted in increased transudation of fluid from 

 the capillaries into the tissues. 



Stewart (1871) and Bartels (1875), while recognizing the possibility 

 of such an effect of loss of albumin, called attention to the parallel between 

 diminished output of urine and the occurrence of edema, a phenomenon 

 which, in fact, had been recognized by Hippocrates. Both of these authors 

 observed that edema might occur before there had been any significant 

 loss in albumin from the blood serum, and that there was a marked dis- 

 turbance, in all cases, in the normal balance between daily fluid intake 

 and output. They concluded that the kidneys, by failing to excrete water, 

 caused its retention in the body ; this water tending to dilute the blood and 

 resulting, by transudation, in edema. 



Cohnheim and Lichtheim (1877) injected large amounts of physio- 

 logical salt sodium intravenously into rabbits, and found that amounts up 

 to 92 per cent of the body weight could be injected without causing edema, 

 and that edema only occurred when the capillaries were injured. They 

 concluded that both hydremic plethora and injury to the capillary walls 

 were essential to the production of edema. 



Senator(e) (1895) believed that poisonous substances circulating in the 

 blood injured first the glomeruli and later the capillary endothelium, and 

 that such toxic action produced the conditions regarded by Cohnheim and 

 Lichtheim as necessary for edema to occur. 



Magnus(a) (1899) offered further experimental evidence in support of 

 the conclusions of Cohnheim and Lichtheim. He found that edema could 

 not be produced in animals by an artificially produced hydremic plethora, 

 unless the capillaries had previously been injured by such poisons as 

 arsenic, chloroform, chloral hydrate, or phosphorus. Similarly, Rich- 

 ter(d) (1905) produced edema in rabbits by injections of uranium nitrate, 

 which effect he attributed to injury to the capillaries. 



Landerer (1884) introduced another point of view. His conception 

 of the process was that edema was due to faulty nutrition of the tissues, 

 resulting in a loss of their normal elasticity, and a consequent infiltration 

 of fluid into them. 



Lazarus-Barlow (a) (&) (1895) also regarded edema as due to a primary 

 disturbance in the tissues, an abnormal metabolism resulting in the -break- 

 ing down of large molecules into smaller ones and an increase in osmotic 

 pressure in the tissues, with a consequent withdrawal of fluid from the 

 capillaries. Loeb(a) (1898) also believed that there was an increased 

 osmotic pressure in the tissues, and attributed it to acid formation, due to 

 diminished oxygen supply. 



