INTRACRANIAL AND INTRAOCULAR FLUIDS 



!77I 



table 3. Values of kj„ for Rabbit Aqueous Humor* 



[After Davson (58)] 



ki„ being the transfer constant in the equation 



d<:, 

 dt 



kinC'Pi ~~ koutCxq, when Cxq and Cpi are the concentra- 

 tions in the aqueous humor and plasma, respectively. 



ability to penetrate the blood-aqueous barrier depends 

 critically on the nature of the molecule or ion that has 

 to pass across the barrier which is in marked contrast 

 to the state of affairs when the passage across the cap- 

 illaries into the interstitial fluid of muscle is consid- 

 ered. Under these conditions the rates of penetration 

 are so similar that it is difficult experimentally to as- 

 certain that there arc indeed any differences. In gen- 

 eral, it is considered that the passage from blood to 

 interstitial Hnid of muscle is determined by the ability 

 of the substance to pass out of the blood capillaries and 

 this, in turn, is thought to consist of a passage through 

 the relatively large spaces between the endothelial 

 cells of the capillaries. These spaces are large by com- 

 parison with noncolloidal molecules so that the capil- 

 lary membrane as a whole offers very little restraint to 

 their diffusion into the outside extracellular fluid. If 

 sodium, urea and glucose were studied, for example, 

 their respective rates of escape from the capillary 

 would certainly not differ by more than a factor of 

 two. The very large differences in rates of penetration 

 of the blood-aqueous barrier, shown in table 3, are 

 thus more reminiscent of the phenomena of cellular 

 permeability than of capillary permeability. When 

 substances penetrate from the outside of a cell to the 

 inside, or in the reverse direction, they have to pass 

 through the fatty envelope, or plasma membrane, of 

 the cell. The ability to do this varies enormously with 

 different molecular types and depends critically upon 

 the chemical constitution of the molecule or ion under 

 consideration. In particular, the factor of lipoid solu- 



bility is of importance, highly lipoid-soluble sub- 

 stances penetrating rapidly through cell membranes. 

 It will be seen from table 3 that highly lipoid-soluble 

 substances, like ethyl alcohol and the substituted thio- 

 ureas, penetrate the blood-aqueous barrier relatively 

 rapidly, while the lipoid-insoluble substances, like su- 

 crose, penetrate much more slowly. These results in- 

 dicate, in a general way, that passage from blood into 

 aqueous humor is to a large extent determined by a 

 passage across cellular membranes; thus on the basis 

 of this finding one is inclined to ascribe the barrier 

 existing between blood and aqueous humor to the 

 epithelial layer of cells lining the ciliary body. If the 

 capillaries in the ciliary body were similar to those in 

 muscle, they would not exert a serious restraint on the 

 passage out of the blood into the extracellular fluid of 

 this body. The epithelium, consisting of two layers of 

 closely packed cells, would, on the other hand, be ex- 

 pected to offer a restraint, since the substance would 

 most probably have to pass through the cells, i.e. 

 across the plasma membranes. The fact that the iris is 

 not covered l>\ a closer) packed epithelial layer on its 

 anterior surface mighl lead one to expect thai diffusion 

 from the blood into the aqueous humor would not be 

 the highly specific phenomenon actually observed. 

 ( )ne would expect the substance to diffuse rapidly out 

 of the capillaries of the iris and thence, without en- 

 countering .1 further barrier, into the fluid in the an- 

 terior chamber. The fact thai penetration of the bar- 

 rier is so highly specific forces one to one of several 

 conclusions: a) the capillaries of the iris and possibly 

 also of the ciliary body are fundamentally different 

 from those in muscle; b) the capillaries are not differ- 

 ent, but the degree of vascularization of the iris is so 

 poor that the amounts of material escaping by way of 

 the iris are small compared with the amounts passing 

 out of the ciliary processes where the vascularization 

 is relatively enormous; or c) the capillaries of the iris 

 are not different, but the feltwork of connective tissue 

 cells on the anterior surface of the iris itself constitutes 

 a serious barrier to diffusion. One may not be dog- 

 matic on this point, but it would seem that the two 

 last factors provide the explanation for the highly spe- 

 cific nature of the permeability of the blood-aqueous 

 barrier. 



Beside permitting us to say that permeability of the 

 blood-aqueous barrier is a highly specific phenome- 

 non, modern quantitative studies have enabled us to 

 build up the following picture of the modes of pene- 

 tration of different substances from blood into the 

 aqueous humor. 



a) The substance diffuses out of the capillaries of 



