INTRACRANIAL AND INTRAOCULAR FLUIDS 



110 



half an hour the pressure may be back to normal. 14 

 The newly formed 'plasmoid aqueous humor' con- 

 tains a high concentration of protein and may best be 

 described as aqueous humor mixed with plasma ex- 

 udate. Clearly, the blood-aqueous barrier, which 

 normally permits only traces of protein to escape into 

 the fluid, has broken down. The exudation probably 

 occurs mainly from the capillaries of the ciliary body 

 (205) which becomes edematous. Histological study 

 of the epithelium shows the appearance of character- 

 istic vesicles (115, 176, 188) which are presumably full 

 of plasma exudate; they apparently burst, ejecting 

 their contents into the posterior chamber. The effect 

 of emptying the anterior chamber is due to the sudden 

 fall in intraocular pressure, permitting a sudden dila- 

 tation of the capillaries of the ciliary body, since the 

 effect is most pronounced in eyes that contain rela- 

 tively large volumes of aqueous humor, for example 

 those of the cat (1). A similar breakdown may be 

 caused by a variety of drugs and mechanical insults, 

 and the feature common to all these interventions is, 

 apparently, a dilatation of the vessels of the ciliary- 

 body and iris (247). As a result of the breakdown of 

 the barrier, the chemical composition of the aqueous 

 humor becomes closer to that of the plasma, for ex- 

 ample the chloride (69), urea (160), and glucose (70, 

 71) concentrations alter in this direction. Essentially 

 the breakdown of the barrier represents the develop- 

 ment of more than the normal number of leaks in the 

 barrier, leaks that normally permit a limited degree 

 of admixture of plasma proteins with the secreted 

 aqueous humor. It is not surprising, therefore, that 

 the most obvious manifestation of the breakdown is 

 the increased quantity of protein in the fluid. We 

 may expect, furthermore, to find the rates of penetra- 

 tion of the barrier affected to different extents by the 

 breakdown, according as the substance can make use 

 of the various routes from plasma to aqueous humor 

 discussed earlier. Thus, the effects of a breakdown will 

 be large with sucrose and />-aminohippurate but small 

 with a lipoid-soluble substance such as sulphanilam- 

 ide (65). 15 



14 Actually the pressure may rise above normal (205); this is 

 presumably due to the blockage of the escape route by the 

 fibrinogen that passes into the anterior chamber in the re- 

 formed fluid (259). 



15 The breakdown of the carrier is most commonly studied 

 by measuring the rate of penetration of fluorescein into the v\v , 

 this normally penetrates very slowly, mainly because it is 

 largely adsorbed to the plasma proteins (70, 71,1 10). A break- 

 down of the barrier therefore has a large effect on the rate of 

 penetration of this dyestuff. [For a useful review of the clinical 

 applications of this test see Weinstein & Forgacs (246).] 



Withdrawal of cerebrospinal fluid has no such ob- 

 vious effect on the blood-cerebrospinal fluid barrier, 

 presumably because the fall in pressure is not so pro- 

 nounced; inflammatory conditions and a number of 

 other insults do lead to an increased concentration of 

 protein in the fluid. The proteins are obviously derived 

 from the plasma (129), and it is considered that the 

 breakdown in the barrier is a reflection of an increased 

 permeability of the pial blood vessels, although the 

 involvement of the central nervous tissue and the 

 choroid plexuses should not be excluded. As with the 

 plasmoid aqueous humor, the composition of cerebro- 

 spinal fluid, under these conditions, appears to ap- 

 proach more closely that of plasma, the concentration 

 of magnesium falling (49) and that of phosphate (48, 

 98) and potassium (147, 181) rising. Exogenous bro- 

 mide is normally distributed between blood and cere- 

 brospinal fluid to give a much lower concentration in 

 the latter fluid (126, 230, 231 ); in meningitis, the con- 

 centration rises. The common!) accepted explanation 

 for the changes in concentrations in meningitis is 

 along the lines already indicated in interpreting simi- 

 lar changes in the plasmoid aqueous humor, namely 

 that the breakdown of the barrier permits the readier 

 diffusion from blood to cerebrospinal fluid, so can- 

 celing, to some extent, the effects of the primary secre- 

 tion in the ventricles. The behavior of chloride is 

 interesting in this respect. As we have seen, the con- 

 centration in the normal cerebrospinal fluid is much 

 higher than in a dialysate of plasma, a breakdown in 

 the barrier might be expected to cause the concentra- 

 tion to fall. In fact, the concentration of chloride in 

 the cerebrospinal fluid is abnormally low in menin- 

 gitis (159, 166) but, as Lindcr & Carmichael (142) 

 first showed, and Wright et al. (258) and Fremont- 

 Smith ft nl. (93) later confirmed, the fall in chloride 

 concentration in the cerebrospinal fluid is associated 

 with a concomitant fall of that in the plasma so that 

 the value of R Csf remains substantially unchanged. If 

 the barrier is abnormal in meningitis — and the evi- 

 dence strongly suggests this — then we must conclude 

 that the high concentration of chloride in the cerebro- 

 spinal fluid is not merely a sign of secretory activity 

 on the part of the choroid plexuses, but that it is also 

 maintained by the secretory activity of the cells of the 

 nervous or glial tissue. A breakdown of the barrier, 

 permitting a freer exchange between the blood and 

 the cerebrospinal fluid, would tend to cause a fall in 

 the concentration of chloride in the cerebrospinal 

 fluid, but if the extracellular fluid of the nervous par- 

 enchyma itself had a high concentration of chloride 

 — maintained by the secretory activitv of its cells — 



