Barrier Function

BARRIER FUNCTION. Barriers are adaptations that protect the organism or its individual organs from the environment, making it, to a certain extent, independent of changes occurring in it. Two kinds of barriers are distinguished: I. External barriers, protecting the organism as a whole from the external environment. Such barriers include: 1) the skin with its appendages, protecting the organism from physical agents of the environment (temperature, humidity, light, etc.); 2) the digestive tract, protecting the general internal environment—the blood—from chemical agents and thereby maintaining the constancy of the chemical composition of the blood: food substances enter the blood only after being converted into low-molecular-weight forms suitable for assimilation by the body. Among the appendages of the digestive tract, the liver plays a prominent role, regulating the influx into the general circulation of substances processed in the digestive tract and entering the portal vein system. Many authors (especially of the French school) consider impairment of the liver barrier to be the cause of a series of pathological phenomena exhibiting the characteristics of certain intoxications resembling anaphylaxis or idiosyncrasy. The detoxifying role of the liver with respect to a number of poisons and toxins is well-known, causing violent poisoning phenomena when directly introduced into the general circulation but having no effect when introduced into the portal vein system; 3) the reticulo-endothelial apparatus (see), playing a protective role in the fight against infections due to its ability to retain and prevent pathogenic elements (viruses, microbes, and other foreign bodies) from entering the bloodstream. -II. Internal barriers, protecting individual organs and tissues from the general internal environment—the blood; they maintain the constancy of the composition of the immediate fluid environment in which cells live; this is achieved by regulating the passage of substances circulating accidentally or normally in the blood into the interstitial fluid. The existence of such barriers explains the uneven distribution of substances introduced into the blood in different organs, as well as the localization of the action of different poisons and toxins. The so-called affinity of individual organs for certain poisons, toxins, viruses, etc. manifests as greater or lesser sensitivity of the given organ to a specific substance; this affinity can be largely attributed to these internal barriers. The anatomical substrate of these internal barriers is, in all probability, first and foremost the endothelium of blood vessels (capillaries). The most vivid and illustrative example of such barriers is the hemato-encephalic and placental barriers. The hemato-encephalic barrier is a mechanism regulating the exchange between the blood on one hand, and the cerebrospinal fluid and central nervous system on the other, and controlling the composition of that fluid environment in which nerve elements live. Numerous clinical and experimental data concerning the composition of cerebrospinal fluid, which maintains remarkable constancy despite various changes in blood composition, indicate the existence of such a barrier. Stern and Gautier established that not all substances introduced into the blood penetrate into the cerebrospinal fluid, whereas all substances introduced into the cerebrospinal fluid, after a short time, appear in the blood, urine, and other secretions. Thus, the hemato-encephalic barrier acts as a selective filter in the direction 'blood → cerebrospinal fluid' and as a valve in the direction 'cerebrospinal fluid → blood'. The mechanism of the selective action of the hemato-encephalic barrier has not yet been clarified. With respect to substances very close to each other in their chemical and physicochemical properties, the hemato-encephalic barrier relates to them differently, and conversely, with respect to the same substance, it reacts differently in different species of animals and even in individuals of the same species, depending on various factors (age, general condition, etc.). There is a complete parallelism between the penetration of a given substance into the cerebrospinal fluid, the presence of this substance in nerve centers, and its action on them. In cases where the activity of the hemato-encephalic barrier is an obstacle to the penetration of necessary and useful substances (antibodies, medicinal substances) from the blood into the cerebrospinal fluid and nervous tissue, it is necessary to temporarily weaken or destroy this barrier. This is achieved in animals by various methods: 1) introduction of the desired substance directly into the cerebrospinal fluid (e.g., into the cerebral ventricles); 2) reducing pressure in the spinal canal by removing some of the fluid; 3) introduction into the blood of hypertonic salt solutions several hours before introducing the therapeutic substance into the blood; 4) infection with malaria, relapsing fever, etc., or introduction into the blood of certain toxins (e.g., tuberculin) or simply protein substances; 5) introduction of various substances into the spinal canal with the aim of causing aseptic meningitis.--The activity of this barrier changes under the influence of various chemical and physical factors (poisoning, cooling, etc.), and often a decrease in resistance to some substances is observed while normal resistance to others is maintained. The anatomical substrate of this barrier is, first and foremost, the vascular endothelium (with respect to colloidal substances) and the choroid plexuses (with respect to crystalloids). Damage to these anatomical elements leads to impairment of the normal activity of the hemato-encephalic barrier and is to a large extent the cause of various pathological phenomena of the central nervous system. The placental barrier - an apparatus regulating the passage of substances from the mother's blood to the fetus and back, and thereby controlling the composition of the immediate fluid environment in which fetal cells develop - plays a primary role in fetal development, and on the other hand, protects the mother's organism from certain substances arising in the fetal organism during its metabolic processes. Most authors consider the placenta either as a permeable membrane obeying the laws of osmotic pressure, or as a dialyzer allowing crystalloids to pass through and retaining colloids. Individual authors attribute selective ability and the ability to process substances circulating in the mother's blood to the placenta. Experimental work has established that the placental barrier shows greater analogy with the hemato-encephalic barrier with respect to substances introduced or circulating in the mother's blood, but the selective ability of the placental barrier also manifests with respect to substances introduced or circulating in the fetal blood. Impairment of the normal activity of the placental barrier under the influence of various pathological factors undoubtedly affects fetal development and may also affect the mother's organism, as seen in pathological processes exhibiting the characteristics of certain intoxications that sometimes arise during pregnancy and cease with the removal of the fetus (for example, eclampsia).

The hemato-ophthalmic barrier is a special mechanism that retains and prevents various substances circulating in the blood from entering the eye. Numerous studies of the physical and chemical properties of the anterior chamber fluid unanimously show that the aqueous humor of the anterior chamber differs significantly from blood plasma both quantitatively and qualitatively. Some substances, such as, for example, enzymes and antibodies existing in normal or pathological blood, are completely or almost completely absent in the anterior chamber fluid. According to the theory of Leber, this fluid is filtered from the blood vessels without the participation of the secretory activity of special cells in this process. The newest doctrine of colloidal chemistry and, mainly, the law of Donnan equilibrium explain many phenomena which were difficult to reconcile with Leber's theory regarding the formation of the anterior chamber fluid by simple filtration. A whole series of corresponding experiments conducted on animals has shown that the law of Donnan equilibrium is unable to explain the differences in the passage of various substances. Some substances introduced into the blood can be found in the anterior chamber fluid, while others, very close to them in their chemical and physical properties, cannot be detected in it. Such chemically related substances as sodium iodide and sodium bromide differ sharply from each other in their ability to pass into the anterior chamber. This difference cannot be explained by physical or chemical laws known to date. The situation is as if there is a special mechanism between the blood and the anterior chamber fluid that possesses the property of making a selection between substances normally or accidentally present in the blood, letting some pass and retaining others. This presumed mechanism has been given the name of the hemato-ophthalmic barrier. From the point of view of the barrier, such cases from everyday practice are explainable when, for example, out of several people poisoned by methyl alcohol, some go blind, while others show no visual disturbances. Here, perhaps, the matter lies not in the different sensitivity of the optic nerve to methyl alcohol in different people, but in the more or less effective protection of the eye from the penetration of this poison, which depends on the activity of the barrier. The autonomic nervous system and the endocrine apparatus exert an influence on the function of the hemato-ophthalmic barrier. Sympathectomy leads to a strengthening of the barrier, while the introduction of atropine, both into the general bloodstream and under the conjunctiva, entails a weakening of the barrier; the elimination of ovarian hormones by castration of animals affects the hemato-ophthalmic barrier in such a way that its function regarding colloids is weakened, while in relation to crystalloids it remains unchanged or even strengthens. The anatomical substrate with which the function of the hemato-ophthalmic barrier is associated is, apparently, the endothelium of the capillaries.