1TO FRANKLIN C. McLEAN 



found, for instance, that artificially induced hydremic plethora would 

 cause edema after the administration of arsenic, cantharides, uranium, 

 chloral hydrate, or ether, or after extirpation of the kidneys. This evi- 

 dence, while demonstrating increased rate of transfer through the capil- 

 lary walls, does not necessarily indicate altered permeability, since the 

 possibility of a direct influence on the cell metabolism has not been ex- 

 cluded. 



Those investigators who have been impressed by the importance of 

 increased permeability of the capillaries as a factor in the occurrence of 

 edema are not unanimous in their opinions as to the cause. Certain 

 writers have assumed that there is retention of toxic substances by the 

 kidneys, others that there is formation of toxic substances in diseased 

 kidneys. Others believe that toxic substances responsible for nephritis 

 itself exert also a damaging effect on the capillary endothelium. In heart 

 failure it has been assumed that either excess of carbon dioxid or reduced 

 oxygen tension is injurious to the endothelial cells, resulting in an in- 

 crease in their permeability. 



Circulatory Changes and Edema. Complete obstruction of the chief 

 vein from an extremity or a viscus, under experimental conditions, is usu- 

 ally not sufficient to cause local edema, unless there is also obstruction to 

 the lymph return. In man, however, venous obstruction causes edema in 

 a lower extremity. Obstruction to the portal circulation, in cirrhosis of 

 the liver, is generally assumed to be the cause of ascites. The most impor- 

 tant factors involved in circulatory disturbances are the rate and volume 

 of blood flow, the arterial, capillary and venous blood pressure, the volume 

 of circulating blood, and the physico-chemical constitution of the blood. 



Rate and Volume of Blood Floiv. In heart failure, alterations in the 

 peripheral circulation of blood are well recognized (Lundsgaard(&) (d)}. 

 These include changes in the rate and volume of blood flow, and in the 

 capillary and venous pressure. The degree of edema usually parallels the 

 degree of circulatory disturbance. Alterations in the blood flow are also 

 seen in the edema of chronic interstitial nephritis, when the edema is due 

 to associated heart failure. That such edema is due simply to the mechan- 

 ical influence of the altered pressure, or rate and volume of blood flow, is 

 not clear, for these changes are associated with certain changes in the 

 chemical constitution of the blood, due mainly to insufficient aeration in 

 the lungs. 



Blood and Plasma Volume in Edema. Various theories of edema 

 depend upon the assumption that there is alteration of blood or plasma 

 volume. Attention has already been called to the theories of Stewart and 

 of Bartels, who assumed that retention of fluid by the kidneys causes 

 hydremic plethora, which in turn leads to edema. On the other hand, those 

 writers who have concluded that the cause of edema lies in disturb- 



