138 The Chemistry of the Injured Cell 



Finally, it has been found that rats reared to be completely germ- 

 free nevertheless develop shock in the usual fashion when suitably 

 injured (Zweifach et. al., 1958) . 



TOXIC TISSUE PRODUCTS 



The appearance of shock in germ-free rats coupled with the 

 evidence of the importance of endotoxin in shock suggests that 

 damaged tissues themselves might liberate substances with endo- 

 toxin-like properties. In fact, polysaccharides of this type are known 

 to exist in a wide variety of animal and plant tissues and may well 

 contribute to the phenomena of shock (Lardy and Shear, 1957) . A 

 great deal of work has been done in injecting tissue fluid and ex- 

 tracts from damaged parts of the body into animals and observing 

 shock-like effects. Few of these active principles have been ade- 

 quately characterised. Proteins and peptides may contribute to 

 their effects but tissue polysaccharides of the endotoxin type may 

 also be involved. Proteolytic enzymes may be involved in the de- 

 velopment of shock. Thus shock increases the activity of the pro- 

 teases in blood whereas animals rendered resistant to shock main- 

 tain a normal level of blood protease activity after injury. Pro- 

 teolytic activity may be linked in some way with the action of 

 endotoxin since injected endotoxin increases the proteolytic activ- 

 ity of blood and since the presence of increased proteolytic activity 

 is associated with hypersensitivity to the actions of endotoxin. 



THE RETICULOENDOTHELIAL SYSTEM 



One of the more curious features of experimental shock is the 

 evidence recently reviewed (Zweifach, 1958) implicating the 

 phagocytic properties of the cells of the reticulo-endothelial system 

 (RES) . These cells line sinusoids in liver (Kupffer cells) , spleen, 

 lymph nodes and elsewhere. 



Thus animals rendered resistant to shock by treatment with 

 antibiotics, or autonomic-blocking drugs or repeated small trau- 

 mata lose their resistance if the RES is saturated and blockaded by 

 injection of thorotrast or carbon. Conversely, both antibiotics and 

 autonomic-blocking drugs will reverse the depression of phagocytic 

 activity in the RES induced by injection of endotoxin. 



