INTRACRANIAL AND INTRAOCULAR FLUIDS 



! 779 



steady-state distributions between plasma, on the one 

 hand, and the aqueous humor and cerebrospinal fluid 

 on the other. The main problem of the physiologist 

 concerned with these specialized tissue fluids is to find 

 out to what extent the steady-state concentration of 

 any given constituent is determined by secretory activ- 

 ity in which it itself is directly involved, to what extent 

 it is determined by secretory activity in which other 

 substances are involved, and to what extent various 

 other factors — such as the consumption, or synthesis, 

 of the substance in the eye or cerebrospinal system — 

 contribute. Space will not permit a detailed analysis 

 of each component of the normal fluids, and even if 

 it did, our knowledge is not sufficiently detailed to 

 permit a clear exposition of all the factors determining 

 the concentration of even one component. A few ex- 

 amples, however, will be of value in illustrating the 

 complexities of the problems and the general modes 

 of approach to their solution. 



Urea 



The concentrations of urea in the aqueous humor 

 and cerebrospinal fluid are about 70 to 80 per cent of 

 that in the plasma. When the plasma concentration is 

 raised, either experimentally or pathologically, urea 

 passes into both fluids (47, 54, 61 ), but the process is 

 slow — in other words, the barriers to the penetration 

 of urea are fairly high. It is possible, therefore, that 

 during the elaboration of the primary secretion, the 

 passage of urea from the plasma into the secretory cells 

 is so slow that the concentration in the fluid as finally 

 secreted does not reach that in the plasma. The low 

 concentrations of urea in the fluids may thus be an 

 accidental consequence of the low permeability of the 

 secretory cells to this substance rather than to any 

 specific secretory activity directed toward keeping 

 urea out of the fluids. A similar state prevails with the 

 even more slowly penetrating />-aminohippurate (19), 

 sucrose (65), and creatinine and iodide (58). With 

 more rapidly penetrating substances, such as thiourea 

 and its substituted derivatives, some sulphonamides, 

 and alcohol, the secretory cells may apparently reach 

 equilibrium with the plasma so that the steady-state 

 distribution is unity. 23 



Glucose 



Glucose is a relatively rapid penetrator into both 

 the aqueous humor and cerebrospinal fluid (58, 61, 



23 In the ocular system it may frequently happen that fairly 

 rapidly penetrating substances approach a steady state of 

 less than unity; this steady state is only apparent, however, and 

 results from diffusion into the lens and vitreous body (58, 155). 



119) so that we might expect to find it equally distrib- 

 uted between plasma and the fluids; yet we have seen 

 that values of R Aq and Rc s f in the rabbit are 0.86 

 and 0.64, respectively. The explanation for this is 

 clearly the utilization of glucose by the lens and retina 

 of the eye and by the nervous and glial tissue adjacent 

 to the cerebrospinal fluid. Thus, the concentration in 

 the vitreous body is considerably less than in the 

 aqueous humor, presumably because the retina and 

 lens are utilizing this metabolite. Newly formed aque- 

 ous humor may well have a concentration equal to 

 that in the plasma; but because the fluid flows over the 

 vitreous body and lens, it rapidly loses glucose and a 

 steady-state is reached, with the aqueous humor and 

 vitreous body having concentrations less than in the 

 plasma.- 4 



Phosphate 



The concentration of inorganic phosphate is low in 

 both aqueous humor and cerebrospinal fluid. The 

 rates of penetration from the plasma are apparently 

 slow so that, at first thought, we might attribute the 

 low concentrations to a slow penetration into the 

 secretory cells, as with urea, sucrose, etc. However, 

 the concentration in the vitreous body is considerablv 

 less than in the aqueous humor (44, 211, 222), and 

 this suggests that the retina is continually removing 

 inorganic phosphate, incorporating it, presumably, 

 into organic phosphate complexes. As a result, the 

 inorganic phosphate entering in the primary secretion 

 diffuses back into the vitreous body so that a steady- 

 state is established with a lower concentration in the 

 aqueous humor and vitreous body than in the plasma. 

 A similar state of affairs is probably present in the 

 cerebrospinal system, the cerebrospinal fluid probably 

 losing phosphate to the nervous tissue. As Friedmann 

 & Levinson (98) have pointed out, the activity of the 

 nervous tissue in determining the concentration of 

 phosphate in the cerebrospinal fluid cannot be ig- 

 nored, at any rate not in pathological conditions. 



I n orbic Acid 



This vitamin has a high concentration in the aque- 

 ous humor. The degree of accumulation varies with 

 the species, being some 1 5- to 20-fold in man, rabbit, 



21 Ross (189-191) has shown that insulin and growth-pro- 

 moting hormone increase the rate of penetration of glucose into 

 the aqueous humor, in alloxan diabetes the rate of penetration 

 is very much reduced. Geiger el a/. (99) have shown that the 

 blood-brain barrier to glucose is strongly influenced by some 

 normally circulating substance in the blood. 



