THE SUPRARENAL SYSTEM 239 



degree of hyperaemia of all the internal organs; a serous, and 

 occasionally sanguineous, fluid is present in the pleural, peri- 

 toneal, and pericardial cavities; there are sub-pleural, sub- 

 pericardial, and epicardial ecchymoses, relaxed heart muscle, 

 pulmonary haemorrhages and, occasionally, pulmonary oedema. 

 The abdominal viscera, especially the intestine, are not only 

 markedly hyperaemic, but they are frequently covered with exten- 

 sive haemorrhagic patches. 



There are, undoubtedly, good grounds for ascribing the fatal 

 termination which follows the intravenous injection of large 

 quantities of adrenalin, to profound circulatory disturbances; but 

 where the substance is introduced either subcutaneously or into 

 the peritoneum, there is no evidence as to the cause of death. 

 The destructive influence which adrenalin has upon the tissues, 

 which will be fully discussed later, suggests, however, that the 

 cause of death in these cases is to be sought in a destruction of 

 the vital tissues. 



Of the toxic effects which adrenalin exercises upon individual 

 tissues, the most conspicuous is the necrosis which it sometimes 

 produces at the site of either subcutaneous or intraperitoneal 

 injection. As far as my observation goes, this process is of very 

 frequent occurrence; it affects the subcutaneous cellular tissue 

 and is more marked in proportion to the weakness of the adrenalin 

 solution employed. The subcutaneous injection of .1 mg. of the 

 usual solution of i : 1000 into rabbits, rarely produces necrosis; 

 but necrosis almost invariably appears if the same dose is diluted 

 with large quantities (50 to 100 c.cm.) of sterilized normal saline 

 solution. If this method is employed, marked oedema will appear 

 at the site of injection, and this will be distinctly visible the next 

 day, becoming haemorrhagic later. In the course of the next few 

 days, the skin becomes more or less extensively necrosed and 

 finally heals, after forming a scab. 



The subcutaneous or intravenous injection of adrenalin is 

 followed by inflammatory and degenerative changes, not at the 

 site of application only, but also in organs distant from it. These 

 changes are observed after a single injection and are more marked 

 where the injections are repeated. The kidneys show signs of 

 inflammation and infiltration, together with haemorrhages and 

 necrosis; there are haemorrhages and necrotic and cirrhotic 

 changes in the liver; symptoms of inflammation appear in the 

 lungs ; and necrotic processes are seen in the mucosa and muscular 

 structure of the stomach, intestines and urinary bladder. Schlayer 

 found that the injection of adrenalin was followed by changes in 

 the renal tissue resembling those of contracted kidney. Both 

 Erb and Fischer found that the repeated injection of adrenalin 

 into the veins of rabbits, was followed by multiple cerebral haemor- 

 rhages, associated with pathological changes in the substance of 

 the brain. The cause of these haemorrhages probably lies in a 

 primary lesion of the cerebral vessels. 



