Irritation

IRRITATION. Irritant — any change in the internal or external environment capable of causing a state of excitation or inhibition in cells and tissues. Apparently, there is no change in the environment surrounding living tissue that could not cause an excitatory process in it. An irritant can be heating or cooling, drying, hypertension, hypotension, electromagnetic waves (especially in the short part of the spectrum), and the most diverse chemical agents. At a certain intensity, all these factors can cause a state of excitation in excitable tissues, and therefore all of them are irritants. In this case, all living cells always respond to the most diverse irritants first with a process of excitation or (with a low intensity of the irritant) an increase in excitability. In the future, with the deepening action of the irritant, excitation can be replaced by inhibition, suppression (see Parabiosis). Any change in the conditions of activity of excitable objects can be an irritant. However, the intensity of the irritant at which a process of excitation occurs in a given tissue is sharply different for different tissues and different irritants. If we schematically imagine any irritant as a certain amount of energy acting on the tissue, then it can be said that the amount of energy required to cause a process of excitation in a given tissue is extremely different for different irritants. A typical example is the retina of the eye, excited by the most insignificant amounts of energy when the latter is represented by light rays. To excite the retina with mechanical or electrical irritation, much larger amounts of energy are required. Based on these facts, Johann Müller developed the doctrine of "specific energy," understanding by the latter that kind of energy which, with a minimal amount of it, causes a process of excitation in a given tissue. Reducing all the action of an irritant only to the introduction of a certain amount of energy of one or another kind into an excitable tissue is incorrect, at least because the excitatory action of chemical irritants does not depend on the energy accumulated during their formation — exothermic compounds (e.g., HCl) can be no less strong irritants than endothermic ones (e.g., lactic acid). But Müller's concept of specific energy correctly emphasizes the most important fact that different excitable objects respond ambiguously to the same irritants and that different specific irritants exist for different tissues. This specificity must be understood not in the sense that a given tissue can be excited only by one group of irritants, but in the sense that certain irritants are incomparably more active for certain tissues than others. We must always consider both the possibility of causing a process of excitation when any agent acts on a tissue, and the special significance of strictly defined irritants in the vital activity of certain tissues. Irritations that cause excitation in a given tissue under ordinary conditions of its activity and at minimal intensity (concentration) are called adequate R. The selectivity of the action of certain irritants is probably developed in the process of differentiation of the functional role of various tissues, and the selectively acting irritants turn out to be those which are connected with the functioning of a given organ. For example, the specific adequate irritant for the depressor nerve, reflexorily causing a decrease in blood pressure, is an increase in the latter in the aorta. The specific irritant of the respiratory center is the increase in the content of CO₂ (more correctly H^- ions) in the blood occurring with respiratory insufficiency. The specific adequate irritant for the sensitive endings in muscles is a change in muscle tension, etc. The normal behavior of a normal organism is determined first of all by those adequate irritants (i.e., specific for each receiving apparatus) which act on the sense organs, sensitive nerve endings (receptors), or directly on the cells of the nervous centers, or on a larger or smaller group of cells of various organs and organ systems. Representatives of the first group of irritants will be all agents acting from the side of the environment, representatives of the second and third — arising in the organism itself. These include hormones and metabolic products acting both on the cells of the nervous centers and on a number of organs (see excitation of the respiratory center, increase in metabolism from the irritating action of amino acids, dilation of vessels under the influence of products of intensified tissue activity, reflexes from the duodenum to the pyloric sphincter upon entry into the duodenum of gastric HCl, etc.). However, irritations that primarily influence directly the cells of those apparatuses where they arise can also excite the sensitive endings of the afferent nerves embedded in the tissue. Only in relatively rare cases does the action of some irritant remain confined only to those tissues where the given irritant arose. With an increase in the irritating action, reflex shifts can occur due to the excitation of afferent nerves. The properties of a given irritant, its chemical and physical nature, are still far from being a factor predetermining its action. The latter depends both on the intensity of the irritant and on the state of the reacting apparatuses. The intensity of the irritant is usually expressed either in physical units of energy, concentration, or in conditional units, for example, the unit of action of hormones. An increase in the irritant causes an increase in the reaction caused by it up to a certain limit. There is no linear dependence here. The minimum intensity of the irritant sufficient to cause a minimal effect is called the threshold of irritation. With an increase in the strength of the irritant, it either captures a larger number of cellular elements or, together with this, if one does not stand on the point of view of the "all or nothing" law (see), strengthens the excitatory process in each cell. A certain strength (or duration of action) of R corresponds to a maximum effect of excitation. In a number of cases (mainly in the nervous centers) one R, even of very great strength, does not cause a process of excitation. A series of R is required for excitation to occur. Changes caused by each individual R_g are summed up, as it were, accumulated, leading to a visible effect of excitation, which is intensified with a further increase in the number of R or the time of its action. Very often, with a significant increase in the irritant, the effect is distorted: for example, dilation of vessels with extremely small doses of adrenaline is replaced by their constriction with ordinary doses. Small concentrations of bile salts strengthen the new formation of erythrocytes, large ones cause the opposite effect (Verzar). Similar examples can be cited in great numbers (see Pessimum). Finally, depending on the state of the tissue, the same irritant can cause a different effect; for example, doses of adrenaline that constrict the vessels of resting muscles dilate the vessels of active muscles. Cases of "distortion of effects" acquire special significance in the study of the action of an irritant on the central nervous system (see reflexes, dominants). This dependence of the final result of the action of an irritant on its strength and the state of tissues must always be kept in mind, for example, when accounting for reactions to pharmacological agents, analyzing pain sensations with strictly defined lesions, etc. It is also necessary to consider that the action of an irritant strongly depends on the duration of its application. Irritants of insignificant duration may not give any effect, for example, currents of very high frequency (see chronaxy). With prolonged exposure to an irritant, phenomena of adaptation (Adrian) can occur; despite the continuing action of the irritant on the sensitive nerve endings, impulses of excitation in the outgoing afferent nerve fiber subside.

G. Konradi.