202 G. W. CASARETT 



Internal radioactive substances distributed more or less diffusely througii- 

 out the body, such as ^^P, tend to mimic the picture produced by total- 

 body irradiation from external sources. 



Intermediate types of exposure from internal emitters which, although 

 diffusely deposited throughout the body, tend to concentrate differentially 

 among a variety of tissues, may result in different degrees of premature ageing 

 change in different parts of the body. For example, ^^"Po is widely distributed 

 in the body, but tends to concentrate highly in spleen and kidney and certain 

 other organs. Consequently, although the fibro-atrophy may be a widespread 

 effect, it tends to be more advanced generally in tissues and organs of highest 

 jDolonium concentration or radiation exposure, and the causes of death 

 related to nephrosclerosis, hypertension and renal failure are relatively high 

 in incidence (Casarett, 1952) at life-shortening dose levels. 



PHYSIOLOGICAL CHANGES 



Associated with the gradual development of the degenerative ageing 

 changes generally described as fibro-atrophy or involutional change, there 

 seems to be a gradual decline in functional abilities, or, more exactly, a decline 

 in reserve functional capacities in related tissues and organs. This gradual 

 decrease of reserve capacity may be detectable early provided suitable 

 sensitive tests of the functions are used and provided the functions are 

 stressed. If not stressed but tested under basal conditions, the functional 

 decline may not become apparent until so much of the reserve capacity has 

 been lost that the decline first becomes manifest as symj)toms. As the 

 functional reserve of tissue is decreased gradually to a point where ordinary 

 stresses tax function, or function is deficient even under basal conditions, tlie 

 tendency to disease from internal conditions and the susceptibility to 

 diseases from environmental factors are gradually increased, as is the pro- 

 bability of death. 



A decrease in functional reserve of one vital part by precocious localized 

 ageing far in advance of other vital parts tends to increase relatively, the 

 probability of disease in the affected part or dependent parts with respect to 

 the natural probability of other common diseases of the species. 



Once the degenerative changes and decreasing functional reserve capaci- 

 ties of ageing have reached the point at which serious chronic diseases begin 

 to emerge, especially the various chronic progressive disorders of later life, the 

 correlated effects of ageing and disease on physiological processes tend to 

 contribute to the pathogenesis of related disorders, perpetuate themselves by 

 circular reactions, exacerbate other pre-existing difficulties, and cause further 

 changes characteristic of ageing, further decreasing functional reserves. The 

 pathogenesis of nephrosclerosis and the renal-hypertensive syndrome with 



