From Big Medical Encyclopedia

REGENERATION (late lat. regeneratio revival, resuming) — updating of structures of an organism in the course of life activity and recovery of those structures, to-rye were lost as a result of pathological processes.

R.'s phenomena were familiar to people in an extreme antiquity. By the end of 19 century the material disclosing patterns of regenerator reaction at the person and animals was saved up, but especially intensively the problem P. is developed from 40th 20 century.

Distinguish two types of R. — physiological and reparative. Physiological R. — continuous updating of structures on cellular (change of blood cells, epidermis p other) and intracellular (updating of cellular organellas) levels, the Crimea is provided functioning of bodies and fabrics. Reparative R. — process of elimination of structural damages after action of pathogenic factors. Both types of R. are not isolated, not dependent from each other. So, reparative R. is developed on the basis of physiological, i.e. on the basis of the same mechanisms, and differs only in bigger intensity of manifestations. Therefore reparative R. should be considered as the normal reaction of an organism to damage which is characterized by sharp strengthening fiziol. mechanisms of reproduction of specific fabric elements of this or that body.

Value P. for an organism is defined by the fact that on the basis of cellular and intracellular updating of bodies the broad range of adaptive fluctuations of their functional activity in the changing conditions of the environment, and also recovery and compensation of the functions broken under the influence of various pathogenic factors is provided. Physiological and reparative R. also pathologies are a structural basis of all variety of manifestations of life activity of an organism normal.

R.'s process is developed at the different levels of the organization — system, organ, fabric, cellular, intracellular. It is carried out by direct (see. Amitotic division ) and indirect (see. Mitosis ) cell fissions, updates of intracellular organellas and their reproduction. Updating of intracellular structures and them hyperplasia (see) are the universal form P. inherent in one and all bodies of mammals and the person. It is expressed or in the form of actually intracellular R. when after death of a part of a cell its structure is recovered due to reproduction of the remained organellas, or in the form of increase in number of organellas (a compensatory hyperplasia of organellas) in one cell at death another.

Recovery of initial mass of body after its damage is carried out in various ways. In one cases the remained part of body remains not changed or low-changed, and its missing part grows from a wound surface in the form of accurately delimited regenerate. Such way of recovery of the lost part of body is called an epimorphosis. In other cases there is a reorganization of the rest of body, in process a cut it gradually gets an initial form and the sizes. This option of process of R. is called morfallaksisy. More often an epimorphosis and morfallaksis meet in various combinations. Observing increase in the sizes of body after its damage, before spoke about its compensatory hypertrophies (see). Tsitol. the analysis of this process showed that reproduction is its cornerstone cells (see), i.e. regenerator reaction. In this regard process received the name «regeneration hypertrophy».

It is considered to be that reparative R. is developed after approach of dystrophic, necrotic and inflammatory changes. So, however, happens not always. Much more often immediately after the beginning of action of a pathogenic factor the physiological R. directed to compensation of a decrease of structures in connection with their sudden accelerated expenditure or death is sharply intensified. At this time it represents in essence the reparative River.

About R.'s sources there are two points of view. It agrees one of them (the theory of reserve cells), there is a proliferation of cambial, unripe cellular elements (so-called stem cells and progenitors), to-rye, intensively breeding and being differentiated, fill a decrease of the high-differentiated cells of this body providing its specific function. Other point of view assumes that the high-differentiated cells of body, to-rye in conditions patol can be R.'s source. process can be reconstructed, lose a part of the specific organellas and at the same time gain ability to mitotic division with the subsequent proliferation (see) and differentiation.

The result of process of R. can be various. In one cases of R. comes to an end with formation of the part identical which died in a form and constructed of the same fabric. In these cases speak about full R. (a restitution, or a homomorphosis). As a result of R. other body than removed can be formed and absolutely that is designated as a heteromorphosis (e.g., education at Crustacea of an extremity instead of a short mustache). Observe also ateliosis of the regenerating body — a gipotipiya (e.g., emergence of smaller number of fingers on an extremity at a triton). There is also the return — formation of bigger number of extremities, than normal, a plentiful new growth of a bone tissue in the place of a change, etc. (excess R., or superregeneration). In some cases at mammals and the person as a result of R. in a zone of damage fabric, not specific to this body, and the connecting fabric which further is exposed to scarring is formed (see. Hem ), what is designated as incomplete R., or a restitution. Completion of recovery process of full R., or substitution, considerably is defined by safety or damage of a connective tissue framework of body. If only the parenchyma of body, napr, a liver selectively perishes, then usually there comes its full R.; if also the stroma is exposed to a necrosis, process always comes to an end with formation of a hem, owing to various reasons (hypovitaminosis, exhaustion, etc.) reparative R.'s current can accept long character, is qualitative be perverted, being followed by formation of inertly granulating, is long not healing ulcers, formation of a nearthrosis instead of accretion of bone fragments, hyper regeneration of fabric, metaplasia (see), etc. In similar cases speak about pathological R.

Stepen and forms of expression of regenerative ability are not identical at different animals. A number of the elementary, coelenterates, flat worms, nemertin, annlides, erinaceouses, semi-chordates and larval and chordates have ability to recover the whole organism from a separate fragment or a piece of a body. Many representatives of the same groups of animals are capable to recover only big body parts (naira., head or tail its ends). Others recover only the separate lost bodies or their part (regeneration of the amputated extremities, short moustaches, an eye — at Crustacea; parts of a leg, a cloak, the head, eyes, shchu-paleets, a sink — at mollusks; extremities, a tail, eyes, jaws — at amphibians having a tail, etc.). Manifestations of regenerative ability at high-organized animals, and also the person differ in a considerable variety — large parts of internals (e.g., a liver), muscles, bones, skin, etc., and also separate cells after death of a part of their cytoplasm and organellas can be recovered.

Because the highest animals are not capable to recover entirely an organism or its large parts from small fragments, as one of important patterns of regenerative ability in 19 century situation was put forward that it decreases in process of increase in the organization of an animal. However in the course of profound development of a problem P., especially R.'s manifestations mammals and the person, had more and more obvious an inaccuracy of this situation. Numerous examples demonstrate that occur among rather low-organized animals such, to-rye differ in weak regenerative ability (sponges, roundworms) while many rather high-organized animals (erinaceouses, the lowest chordates) have this ability in rather high degree. Besides, quite often occur among closely related animal species as it is good, and badly regenerating.

The numerous researches of recovery processes at mammals and the person which were systematically conducted from the middle of 20 century also testify to insolvency of idea of falloff or even to full loss of regenerative ability in process of increase in the organization of an animal and specialization of his fabrics. The concept of a regeneration hypertrophy demonstrates that recovery of an initial form of body is not the only criterion of existence of regenerative ability and that for internals of mammals even more important indicator in this respect is their ability to recover the initial weight, i.e. total quantity of the structures providing specific function. As a result of elektronnomikroskopichesky researches ideas of the range of manifestations of regenerator reaction radically changed and, in particular, became obvious that an elementary form of this reaction is reproduction not of cells, and recovery and a hyperplasia of their ultrastructures. It, in turn, was the basis for reference to R.'s processes of such phenomenon as a hypertrophy of a cell. Was considered that simple increase in a kernel and mass of a colloid of cytoplasm is the cornerstone of this process. Electronic microscopic examinations allowed to establish that a hypertrophy of a cell — process structural, caused by increase in number of nuclear and cytoplasmatic organellas and on the basis of it providing normalization of specific function of this body at death of this or that its part, i.e. in principle is process regenerator, recovery. With the help submicroscopy (see) the essence and such eurysynusic phenomenon as reversibility of dystrophic changes of bodies and fabrics was deciphered. It turned out that it is not just normalization of structure of a colloid of the kernel and cytoplasm broken as a result patol. process, and much more complex process of normalization of very tectonics of a cell due to recovery of structure of the damaged organellas and their new growth. Thus and this phenomenon which was earlier standing independently among other all-pathological processes was manifestation of regenerator reaction of an organism.

In general all these data were the basis for essential expansion of ideas of a role and value of processes of R. in life activity of an organism, and in particular for promotion of essentially new provision that these processes are related not only to healing of damages, and are a basis of functional activity of bodies. The important role in the adoption of these new ideas of range and essence of processes of R. was played by the point of view that the main thing in R. of body is not only achievement of initial anatomic parameters by it, but also the normalization of the broken function provided with various options of structural transformations (see. Vicarious processes ). In such essentially new lighting under a structurally functional visual angle the doctrine about R. loses the preferential biological sounding (recovery of remote bodies) and becomes paramount important for the solution of the main problems modern a wedge, medicine, in particular problems of compensation of the broken functions (see. Compensatory processes ).

These new data convince that regenerative ability at the highest animals and, in particular, at the person is characterized by a considerable variety of the manifestations. So, in nek-ry bodies and fabrics, napr, in marrow, a cover epithelium, mucous membranes, bones, physiological R. is expressed in continuous updating of cellular structure (see. Appozitsionny growth ), and reparative R. — in a complete recovery of defect of fabric and reconstruction of its initial form by intensive mitotic division of cells. In other bodies, napr, in a liver, kidneys, a pancreas, bodies of endocrine system, lungs, etc., updating of cellular structure happens rather slowly, and elimination of damage and normalization of the broken functions are provided on the basis of two processes — reproduction of cells and accumulation of mass of organellas in the preexisting remained cells therefore they are exposed hypertrophies (see) and according to it their functional activity increases. It is characteristic that the initial form of these bodies after damage most often is not recovered, in the place of an injury the hem is formed, and completion of the lost part happens at the expense of the unimpaired departments, i.e. recovery process proceeds as a regeneration hypertrophy. Internals of mammals and the person have huge potential ability to a regeneration hypertrophy; e.g., the liver during 3 — 4 weeks after a resection of 70% of its parenchyma concerning benign tumors, an echinococcus, etc. recovers initial weight and in full — functional activity. In c. N of page and a myocardium, cells to-rykh have no ability to mitotic division, structural and functional recovery after damage is reached only or consider only the account of increase in mass of organellas in the remained cells and their hypertrophy, i.e. reducing power is expressed only in the form of intracellular regeneration.

In various bodies at the heart of characteristic of mammals and the person of a variety of manifestations of physiological and reparative R. structurally functional features of each of them lie most likely. E.g., the well-marked productive capacity of cells inherent to an epithelium of skin and mucous membranes is connected with its main function — continuous maintenance of an integrity of covers on border with the environment. Also high ability is explained by features of function marrow (see) to cellular R. continuous department all of new and new cells from lump in blood. The epithelial cells covering fibers of a small bowel regenerate on cellular type since for implementation of enzymatic activity they descend from a fiber in a gleam of a gut, and their place is taken immediately by new cells, in turn already ready to be torn away the same as it just happened to their predecessors. Recovery of basic function bones (see) it can be reached only by proliferation of cells, and in the field of a change, but not in any other place (see. Bone callosity ). In some other bodies, napr, in a liver, kidneys, lungs, a pancreas, adrenal glands, the required amount of work after damage is ensured first of all by recovery of initial weight as the main function of these bodies is connected not so much with preservation of a form how many with a certain quantity and the sizes of the base units which are carrying out specific activity in each of them — hepatic segments, alveoluses, pancreatic islands, nephrons, etc. In a myocardium and in c. the N of page a mitosis was considerably or completely forced out by intracellular mechanisms of a reparation of damage. In c. the N of page, in particular, function, e.g., of a pyramidal cell (a pyramidal neurocyte) of a cerebral cortex consists in continuous maintenance of bonds with people around and the nervous cells which are located in the most various bodies. It is provided with the relevant structure — the numerous and various shoots connecting a body of a cell to various bodies and fabrics. To change such cell as physiological or reparative R. — it means to change also all these its exclusively difficult bonds as in a nervous system, and is far on the periphery. Therefore in the characteristic, most reasonable and economic way of recovery of the broken function for cells of c. the N of page is strengthening of work of the cells next to the dead, at the expense of a hyperplasia of their specific ultrastructures, i.e. is exclusive by the intracellular River.

Thus, evolutionary process in fauna was characterized not by gradual easing of regenerative ability, and the increasing variety of its manifestations. At the same time regenerative ability in each specific body got that form, edges provided the most effective ways of recovery of its broken functions.

At the heart of all variety of manifestations of regenerative ability at mammals and the person two of its forms — cellular and intracellular lie, to-rye in different bodies or are combined in various combinations, or exist separately. At the heart of these it would seem extreme forms of process of R. the uniform phenomenon — a hyperplasia of nuclear and cytoplasmatic ultrastructures lies. In one case this hyperplasia is developed in the pre-existing cells and each of them increases, and in another — the same number of neogenic ultrastructures is placed in the divided cells keeping the normal sizes. As a result total number of the elementary functioning units (mitochondrions, kernels, ribosomes, etc.) in both cases it is identical. Therefore among all these combinations of forms of regenerator reaction there are no «worst» and «best», more or less effective; each of them is to the most relevant structure and function of this body and at the same time improper for all others. Sovr. the doctrine about intracellular regenerator and hyperplastic processes confirms insolvency of ideas of a possibility of normalization of work patholologically of the changed bodies on the basis of «purely functional tension» of the remained departments; any, even almost inaudible functional shifts of a compensatory order are always caused by the corresponding proliferative changes of nuclear and cytoplasmatic ultrastructures.

Efficiency of process of R. to a great extent is defined by conditions, in to-rykh it proceeds. In this respect the general condition of an organism is important. Exhaustion, hypovitaminosis, disturbances of an innervation, etc. exert considerable impact on reparative R.'s course, slowing down it and promoting transition to pathological. Degree of a functional load has significant effect on reparative R.'s intensity, the correct dosing a cut favors to this process. Reparative R.'s speed to a certain extent is defined also by age that is of particular importance in connection with increase in life expectancy and according to number of operative measures at persons of the senior age groups. Usually essential deviations of process of R. at the same time are not noted also bigger value, apparently, have disease severity and its complications, than age easing of regenerative ability.

Change of the general and local conditions, in to-rykh proceeds R.'s process, can lead as to quantitative, and its qualitative changes. E.g., R. of bones of a calvaria usually does not come from edges of defect. If, however, to fill this defect with bone sawdust, it is closed by a full-fledged bone tissue. Studying of various conditions of regeneration bones (see) promoted considerable improvement of methods of elimination of injuries of a bone tissue. Changes of conditions of reparative R. of skeletal muscles are followed by considerable strengthening and increase in its efficiency. It is carried out due to education on the ends of the remained fibers of muscular kidneys, reproduction of free myoblasts, releases of reserve cells — the satellites which are differentiated in muscle fibers. The most important condition of full-fledged R. of the injured nerve is connection of its central end with peripheral, on a case to-rogo the neogenic nervous trunk moves ahead. The general and local conditions influencing R.'s current are always implemented only within that way P., to-ry in general svoystven to this body, i.e. meanwhile no changes of conditions did succeeded to transform R. cellular in intracellular and vice versa.

Numerous factors endo-and the exogenous nature participate in regulation of processes of R. Antagonistic influences of various factors on the course of intracellular regenerator and hyperplastic processes are established. Influence on R. various is most studied hormones (see). Regulation of mitotic activity of cells of various bodies is carried out by adrenal hormones, a thyroid gland, gonads, etc. An important role is played in this respect by so-called gastrointestinal hormones. Powerful endogenous regulators of mitotic activity are known — chalones (see), prostaglandins (see), their antagonists and other biologically active agents. The important place in researches of mechanisms of regulation of processes of R. is taken by studying of a role of various parts of the nervous system in their current and outcomes. A recent trend in development of this problem is studying immunol. regulation of processes of R., and in particular establishment of the fact of transfer by lymphocytes of the «regeneration information» stimulating proliferative activity of cells of various internals. The regulating impact on the course of process of R. is exerted also by the dosed functional load.

Knowledge of mechanisms of regulation of regenerative ability of bodies and fabrics opens perspectives for development of scientific bases of stimulation of reparative R. and management of processes recovery (see).

See also Compensatory processes .

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D. S. Sarkisov.