24 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



principle is used by all current methods, though not 

 in the form proposed by Valentin. The basic proposi- 

 tion is that in any solution in which a quantity of 

 solute Q, is dissolved in a \olume F, the concentration 



V 



(0 



so that if both Q and c arc known, the equation may be 

 solved for V. In \"alentin"s proposal, Q, represents the 

 total normal blood solids, whose value need not be 

 known if they remain unchanged by the infusion of 

 water, since 



Vci = Q., before the infusion, and 

 (F + v)ct = (2, after a volume v of water has been infused, 

 so that 



and 



V = 



VCi 



(2) 



Even if more physiological diluents than water are 

 employed, the use of equation 2 demands the addition 

 of relatively large \olumes to the circulation, with the 

 possibility that I', v, or Q may change as a conse- 

 quence. It is accordingly of limited usefulness in blood 

 volume studies. This equation, however, makes it 

 possible to obtain the space occupied by normal cells 

 or plasma if a foreign substance, attached to cell or 

 plasma constituents, has previously been injected and 

 allowed to achieve a .stable distribution. If a volume v 

 of normal cells or plasma is then infused, and the re- 

 sulting dilution of the circulating foreign substance is 

 measured as c i — rj, solution of equation 2 for T gives 

 the distribution space of the infused normal cells or 

 plasma (142). 



Equation i is used by all current methods. In these 

 methods Q, is a recognizable foreign material called 

 label or tag, and c is its measured concentration in the 

 circulation after mixing is complete. The volume of 

 label is usually kept so small that it may be ignored. It 

 is apparent that two basic requirements must ijc met, 

 if solution of the equation for V is to represent the 

 actual volume of the blood vascular system. The first 

 is that the value taken for c must be equal to the mean 

 concentration for the entire system. The second is that 

 the value CI must be known at the time c is measured. 



Of primary concern is the selection of a suitable 

 label. No substance which meets the technical require- 

 ments is partitioned equally between the cells and the 

 plasma. No single foreign substance, accordingly, is a 

 label for blood as such. The commonly employed cell 



labels, carbon monoxide, Fe^^, Cr^', and P^-, and the 

 plasma labels, which include protein-bound dyes such 

 as Evans blue, and radioactive tracers such as P^', are 

 discussed individually in the last sections of this chap- 

 ter. The volume V which is obtained in equation i is 

 defined by the dimensions of Q^ and c. If Q, is a red 

 cell label, and its concentration or activity is measured 

 in packed red cells, V is the apparent volume of red 

 cells in the circulatory system. If plasma label is in- 

 jected, and its concentration in circulating plasma is 

 measured, V is the apparent volume of circulating 

 plasma. 



Little attention has been given to the volume of 

 white cells and platelets. In centrLfuged samples of 

 blood they rarely contribute more than 2 per cent to 

 the total volume of the sample. Whether they are 

 included in the estimate of plasma volume or of red 

 cell volume depends upon the procedure chosen for 

 reading the hematocrit of blood samples. They are 

 included in the estimate of the plasma compartment 

 if the hematocrit reading is taken at the top of the 

 packed red cell column; in the estimate of the cell 

 compartment, if the reading is taken at the top of the 

 buffy coat. 



Agreement between the conceptual definition of 

 blood volume and its operational quantitation cannot 

 be taken for granted. It is the purpose of this chapter 

 to examine the extent of agreement. Since blood \ol- 

 ume as such cannot be defined operationally, the 

 chapter considers cell and plasma labels and their 

 distribution, separately. Little attention is given to 

 technical details, which are exhaustively described 

 elsewhere (see refs. 29, 95, 189), or to the values ob- 

 tained by different methods, except as these are essen- 

 tial to the stated purpose. (Reference 53 may be con- 

 sulted for tables of values in \-arious species.) 



CIRCULATORY MIXING 



The first requirement, that the value c used in the 

 calculation of distribution space be equal to the mean 

 for the entire system, is not easily met when im- 

 permanent labels are employed. If a liberal period is 

 allowed for mixing within the circulation, unknown 

 amounts of label may be lost, so that the second 

 requirement, for a known \alue of (), may be con- 

 tra\ened. Correction for such loss is discussed 

 subsequently. It requires that the exact time of injec- 

 tion be known and, for this reason, labels are usually 

 injected rapidly, with little chance of mixing with 

 i)lood at the injection site. The concentrated slug of 



