1870 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY III 



about 200 A between osmiophiiic lines. While no 

 doubt this is a potential space and probably serves 

 as a diffusion route, it is exactly the sort of space that 

 one finds between epithelial cells in general. In an 

 epithelium one thinks of this as a "cement layer' 

 binding adjacent cells together. It is reasonable to 

 think that it may play a similar role in the nervous 

 1 issue. The only extracellular gaps which are wider 

 than this are small pockets formed where the mem- 

 branes of adjacent cells diverge one from the other. . . . 



"For the above considerations we derive a picture 

 of nervous tissue that is rather different from what the 

 light microscopist often imagines. Essentially all of 

 the space is filled with living cell processes of one sort 

 or another. It is likely that these processes are more 

 or less fastened one to another, but there is no other 

 extracellular means for support. The special technical 

 methods developed for neurocytological investiga- 

 tions with the light microscope unfortunately often 

 produce serious shrinkage artefact which creates 

 spaces where none existed originally." 



So we are faced with the mystery of the disappearing 

 interstitial volume and, as yet, no satisfactory explana- 

 tion is available to unite these disparate data. The phys- 

 iologist finds comfort in dismissing the electronmicro- 

 graphs as artefacts bearing unknown relationship to 

 the "/ vivo situation, but this attitude has the familiar 

 ring of the pot calling the kettle black. If we accept the 

 electronmicrographs at face value, then considerable 

 revision of current concepts concerning the nature of 

 cell membranes and the composition of the intra- 

 cellular compartment is required. 



( mil/ osition oj Intel ttitial Fluid 



Figure ■<, illustrates the interrelationships of the 

 water compartments of the central nervous system and 

 provides an estimate of their relative volumes. The 

 interstitial compartment is shown as comprising ap- 

 proximately 15 per cent of the total water, although, 

 av discussed above, this figure is problematical. The 

 composition of the interstitial fluid with respect to 

 Vrj, [K.+] and [CI"] is proposed to be essentially 

 tin same, on the average, as ihe cerebrospinal fluid, 

 although no direct measurements of central nervous 

 system interstitial fluid have been made. However, 

 the ingenious experiments of Wallace & Hrodie 

 1 ,8 "ml to substantiate tins position. These 

 authors administered sodium or potassium s.ilts oi 

 iodide, thiocyanate and bromide to dogs, and de- 

 termined the latins of these ions to the normally 

 present chloride in the plasma and in the tissues. In 



TOTAL H,0 — 78ml/IOOgms brain 



CSF. 



142 



II 



120 



INTER 

 ■STITIAL 



142 



3.1 



120 



/ 135 

 VASCULAR , 

 '. tfli 



INTRACELLULAR 

 No* - 64 meq./L. 



K* - 162 

 CI" ■ 22.3 



5 / 



1 In 



■ 2 3 NRT 

 ■+4 2 

 '-0.9 



log 



C, (CSF) 



No • 

 K+ ■ 

 CI" - + 99 

 N *< w mln. - 10.9 col. /L. 



C, (plasma) 

 C « moles / Kg H,0 



fig. 3. Diagram of the fluid compartments of the central 

 nervous system. Size of each rectangle is proportional to esti- 

 mated volume of the compartment it represents. Concentra- 

 tions of \a' , K~ and Cl~ in cerebrospinal fluid [CSF) as well 

 as calculations for Il',„,„ are from Flexner (41 I. Intracellular 

 concentrations calculated on the basis of 1-/, interstitial 

 volume. 



all tissues examined except the brain, the three anions 

 were distributed in the same ratio to chloride as in 

 the plasma. In the central nervous sv stem, however, 

 the anion to chloride ratio was the same as in the 

 cerebrospinal fluid, and this ratio was considerably 

 smaller than that found in the plasma. From these 

 results they concluded that iodide, thiocyanate, 

 bromide and chloride are distributed in the interstitial 

 water of the central nervous system in ionic 

 equilibrium not with plasma, but with cerebrospinal 

 fluid, and that the composition of the interstitial fluid 

 is the same as the cerebrospinal fluid. 



Olsen & Rudolph (120) studied the transfer of 

 radioactive sodium (Na 24 ) and radioactive bromide 

 (Br 82 ) ions between blood, cerebrospinal fluid and 

 brain tissue. The entrv of the ions into cerebrospinal 

 fluid alter intravenous injection followed a single 

 exponential with rates of the two ions of the same 

 order. The ions equilibrated sluwlv between cerebro- 

 spinal fluid and serum, and rapidly between skeletal 

 tnuscle and serum, irrespective ol the mode o! ad- 

 ministration. However, equilibrium between brain 

 tissue and cerebrospinal fluid was rapid following 

 intravenous injection, bui slow after Lntracisternal 

 injections due to the long diffusion distances i" the 

 interior of the brain. I hese data indicate that the 

 intercellular fluid of nervous tissue is in equilibrium 



with cerebrospinal fluid and not serum, and that 



the formation ol central nervous svsti-m interstitial 



