STUDY OF DISEASE 



to negative feedback, homeostasis results. The secondary 

 disturbances may, however, ampHfy the defect. As an example 

 may be cited the nausea, emesis, and coma of diabetic ketosis, 

 all leading to cessation of food intake and thereby contributing 

 further to the ketosis. Such a situation is analogous to positive 

 feedback, and if uncorrected, may lead to a fatal outcome. 



The several vectors that have been discussed in relation to 

 blood glucose are diagrammed in Figure 1. The magnitude of 

 vector A is determined by the abundance of ingested carbohy- 

 drate, the duration and effectiveness of intestinal digestion, and 

 the integrity of the intestinal mucosa. It may be markedly 

 diminished in starvation, in disease of pancreatic acinous tissue, 

 or in sprue. Vector B depends upon a supply of hepatic glyco- 

 gen of normal constitution and an intact enzyme system to 

 convert it to glucose. It is exaggerated by excess epinephrine or 

 glucagon and is diminished in von Gierke's disease. It is like- 

 wise influenced by the gluconeogenic rate which is in turn under 

 adrenocortical regulation, is diminished in Addison's disease, 

 and is exalted in hyperadrenalism. Vectors C and D depend 

 critically upon insulin, the anterior pituitary gland, and possibly 

 other anti-insulin agents. Both of these vectors decrease in 

 diabetes and are exaggerated in hyperinsulinism. Vector E 

 depends upon the concentration of glucose in the blood and the 

 integrity of the enzyme architecture of the renal tubule. 



This analysis of factors affecting the concentration of blood 

 glucose in health and disease is of course merely exemplary. 

 Given suflficient information, the deviation from normal in the 

 concentration of any tissue constituent might be subjected to a 

 similar analysis. It is the purpose of this discussion to emphasize 

 the complex and highly integrated nature of the normally 

 operating intact organism and to point up the difficulties in- 

 herent in the elucidation of the disturbances which are en- 

 countered in clinical medicine. 



Much has been learned about diabetes from comparative 

 studies of liv^er slices (4) or enzyme solutions (17) derived from 

 normal and from diabetic animals. The ability of such prepara- 



173 



