6i8 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



Studies of transmembrane transport processes may be 

 cited as examples in which isotopic tracers have 

 opened to investigation areas previously regarded as 

 being inaccessible. On the contrary, the circulatory 

 kinetic features known from the classical methods have 

 been of value in the interpretation of tracer data 

 obtained in studies of the turnover rates of various 

 tissue constituents. 



RELATIONSHIP BETWEEN EXCH.^NGE RATES AND 

 BLOOD FLOW RATES 



The blood is perhaps the most continuously busy 

 tissue in the body. As it rushes through the capillaries, 

 delivering food and oxygen to the other tissues while 

 receiving various metabolic products from them, it 

 carries chemical messages from one tissue to another 

 and achieves numerous tasks related to the body's 

 defense against infection, regulation of temperature, 

 etc. With all this acti\ity under way, it is nevertheless 

 true that samples of the blood will show a remarkable 

 constancy of composition with respect to most con- 

 stituents. Although, for example, there is an in- 

 cessant exchange of water and electrolytes between 

 the blood and the tissues, simple chemical analyses 

 of the blood give no indication that anything is 

 happening. Study of the rates of exchange of many 

 substances between the circulation and the various 

 tissues by nontracer methods is very difficult to 

 impossible, and such techniques as disturbing the 

 normal state in order to observe the consequences 

 are often open to the criticism of being "unphysi- 

 ological." 



Studies of isotopically labeled forms of normal 

 constituents of the blood, particularly water and the 

 electrolytes, however, readily demonstrate that there 

 is in fact a rapid and continuous exchange of many 

 of these substances between the blood and the extra- 

 vascular volumes. 



The rates of transfer or exchange of some sub- 

 stances are limited by the degree of permeability of 

 the capillary walls. For others, however, the rates of 

 exchange across the capillary walls are very rapid 

 relative to the i)lood flow rate, so that the latter is 

 the limiting or rate-governing process for exchange of 

 these substances between the total blood volume (as 

 distinct from the blood in the capillaries only) and 

 the extravascular volumes. Thus, to the extent that 

 the rates of exchange of substances between the 

 circulation and the tissues are limited by the tissue 

 blood perfusion rates, measurement of the ''effective" 



exchange rates with tracers provides a convenient 

 method for determining the blood flow rates. (The 

 "effective" exchange rate measures the blood-tissue 

 exchange and should not be confused with the true 

 transcapillary exchange rate, which may be much 

 faster.) 



PURPOSE, SCOPE, AND LIMIT.'>iTIONS OF THIS CH.\PTER 



The present chapter is written in the belief that 

 much more remains to be achieved and can be 

 achieved with isotopic tracers, particularly with 

 radioactive isotopic tracers, in circulatory studies. 

 The use of radioisotopic tracers in some static meas- 

 urements (red cell mass, plasma volume) has become 

 standard practice. There is even more reason to use 

 isotopic labels in kinetic studies where, in addition 

 to the advantages of convenience, sensitivity, and 

 accuracy, their use extends the area of feasibility of 

 measurement. Isotopes make it possible to work with 

 normal constituents of the blood, to avoid disturbing 

 physiological conditions, to utilize data obtained 

 over long time intervals, and to study many parts 

 of the body simultaneously and by external detection 

 methods. 



Full utilization of the advantages of isotopic tracers 

 requires an understanding of the relationships be- 

 tween the labeled and the nonlabeled species of the 

 substance being studied and, for clarity and precision, 

 it is necessary to express these relationships in mathe- 

 matical terms. 



The purpose of the present chapter is to present 

 the elementary aspects of the mathematical relation- 

 ships between tracers and the substances being studied, 

 and it is hoped that this exposition will be of par- 

 ticular value to novices in this field. The more sophisti- 

 cated workers are referred to a book by Sheppard 

 (59), in which advanced aspects of the subject are 

 treated in detail, and which provides numerous 

 references to applications of the tracer method in 

 studies of circulatory kinetics. 



The emphasis in this chapter will be on events 

 occurring soon after the injection of labeled material 

 into the circulation but subsequent to the first few- 

 circulation times treated by Zierler (74). Although 

 the methods of analysis to be discussed have applica- 

 tions in other phases of tracer kinetics, attention will 

 be directed to applications pertinent to blood flow 

 rate analysis. In particular, questions of metabolic 

 turnover of materials in tissues, metabolic pathways, 

 and active transport are not treated Although the 



