Granuloma. Types and types of granulomas, variants of their localization and possible symptoms. Tuberculous granuloma: what is it
Granulomatous inflammation is a variant of productive inflammation, in which activated macrophages (or their derivatives) are the dominant cell type, and granuloma is the main morphological substrate.
granuloma, or knot(tubercle, according to R. Virchow), is a focal accumulation of cells capable of phagocytosis of a monocyte-macrophage nature. The main representative of SMF cells is a macrophage, which, as already mentioned, is formed from a monocyte. On the "field" of inflammation, the monocyte divides only once, and then, as the experience with tissue culture has shown, it is transformed into a macrophage. But the transformations don't end there. 7 days after the emergence and reproduction of the macrophage turns into an epithelioid cell. This requires products of activated T-lymphocytes, especially 7-interferon. Epithelioid cells compared to macrophages have a lower phagocytic ability (they lack secondary lysosomes and macrophage granules), but better developed bactericidal and secretory activity - they synthesize growth factors (FGF, TGF), fibronectin-1, IL-1. In the second week, epithelioid cells are transformed by nuclear fission without cell division (less often by fusion with each other) into giant multinucleated Pirogov-Langhans cells, and after 2-3 weeks into giant cells of foreign bodies.
The peculiarities of Pirogov-Langhans giant cells are large sizes (up to 40-50 microns), the presence of a large (up to 20) number of nuclei, which are located eccentrically on one side in the shape of a horseshoe. In a giant cell of foreign bodies, there are even more nuclei - up to 30 (even up to 100 are described), but they are located mainly in the center of the cell. Both types of giant cells are distinguished by the absence of lysosomes, therefore, capturing various pathogenic factors, giant cells are not able to digest them, i.e. phagocytosis in them is replaced by endocytobiosis. In cases of microbial invasion, endocytobiosis is maintained by the presence of secretory granules in the cytoplasm, such as lipid inclusions in tuberculosis. However, in general, their secretory function is sharply suppressed, growth factors and cytokines, in particular, are not synthesized at all.
The morphogenesis of a granuloma consists of the following four stages:
▲ accumulation of young monocytic phagocytes in the tissue damage site;
▲ maturation of these cells into macrophages and the formation of macrophage granulomas;
▲ maturation and transformation of monocytic phagocytes and macrophages into epithelioid cells and the formation of epithelioid cell granuloma;
▲ transformation of epithelioid cells into giant ones (Pirogov - Langhans and / or foreign bodies) and the formation of giant cell granulomas.
Thus, given the predominant cellular composition of the granuloma, three types of granulomas are distinguished by morphological features: 1) macrophage granuloma (simple granuloma, or phagocytoma); 2) epithelioid cell granuloma; 3) giant cell granuloma.
Etiology granulomatosis. There are endogenous and exogenous etiological factors in the development of granulomas. Candogenic include sparingly soluble products of damaged tissues, especially adipose tissue (soap), as well as products of impaired metabolism, such as urates. Exogenous factors that cause the formation of granulomas include biological (bacteria, fungi, protozoa, helminths), organic and inorganic substances (dust, fumes, etc.), including drugs.
Currently, granulomas are divided into two groups according to etiology: 1) granulomas of established etiology and 2) granulomas of unknown etiology [Strukov A.I., Kaufman O.Ya., 1989]. The first group, in turn, is divided into two subgroups: infectious and non-infectious granulomas.
Infectious granulomas include typhoid fever, rabies, viral encephalitis, actinomycosis, schistosomiasis, tuberculosis, leprosy, syphilis, etc.
Non-infectious granulomas develop when organic and inorganic dust, wool, flour, silicon oxide (IV), asbestos, etc., foreign bodies, drug exposure (granulomatous hepatitis, oleogranulomatous disease) enter the body.
Granulomas of unknown etiology include granulomas in sarcoidosis, Crohn's disease, primary biliary cirrhosis, etc.
The pathogenesis of granulomatosis. far from complete list etiological factors reveals a completely obvious pattern - granulomatous inflammation occurs, as a rule, chronically and develops under the following two conditions: 1 the presence of substances that can stimulate SMF, the maturation of the transformation of macrophages; 2) resistance of the stimulus to phagocytes. Under conditions of incomplete phagocytosis and altered reactivity of the organism, such an irritant turns out to be the strongest antigenic stimulator for macrophages and T- and B-lymphocytes. An activated macrophage with the help of IL-1 attracts lymphocytes to an even greater extent, contributing to their activation and proliferation - the mechanisms of cell-mediated immunity are tied up, in particular the mechanisms of HRT (for more details, see lecture 17 "Hypersensitivity reactions") - In these cases, they talk about immune granuloma.
Immune granulomas are more often built according to the type of epithelioid cell nodules, but they always contain an admixture of a fairly large number of lymphocytes and plasma cells. They develop primarily in infections such as tuberculosis, leprosy, syphilis, scleroma. Sometimes the products of tissue damage become a source of antigenic irritation, and in these cases, autoimmune mechanisms of granuloma formation may be involved. Finally, granulomas caused by organic dust particles and aerosols containing proteins from birds, fish, animal hair, as a rule, are also antigen-mediated by the mechanism of their development. Although sometimes there are mechanisms for the formation of granulomas mediated by antibodies.
Non-immune granulomas include most granulomas that develop around foreign bodies, consisting primarily of organic dust particles (for example, beryllium (II) oxide is a compound that causes sarcoid-type immune granulomas). Phagocytosis in the cells of non-immune granulomas is more perfect, and they are often built according to the type of phagocytoma or giant cell granuloma, consisting of cells of foreign bodies. When comparing these granulomas with immune ones, a smaller number of lymphocytes and plasma cells are noted.
The criteria for assessing granulomas include an indicator of cellular kinetics, i.e. the degree of speed of exchange (renewal) of cells inside the granuloma, on the basis of which rapidly and slowly renewing granulomas are isolated. Rapidly renewing (in 1-2 weeks) granulomas produce very toxic substances (mycobacterium tuberculosis, leprosy), are built mainly according to the epithelioid-cellular type, are characterized by the fact that their cells quickly die and are replaced by new ones, and foreign material is only partially located in macrophages - all this indicates the intensity of cellular renewal. In slowly renewing granulomas, the pathogenic agent is entirely located in macrophages, while the kinetics of metabolism is sharply slowed down. Such granulomas occur when exposed to inert low-toxic substances.
and are built most often from giant cells. This criterion is important for comparing granulomas around foreign bodies of exogenous and endogenous origin (suture material, tattoo sites, inorganic dust particles).
Some granulomas of infectious etiology have a relative morphological specificity. Identification of the pathogen is necessary to confirm the diagnosis. Specific call those granulomas that are caused by specific pathogens (mycobacterium tuberculosis, leprosy, pale treponema and scleroma bacillus), are characterized by relatively specific morphological manifestations (only for these pathogens and for no others), and the cellular composition, and sometimes the location of the cells inside the granulomas (for example, in tuberculosis) are also quite specific.
Granulomas of all four types occur in diseases that are chronic, moreover, undulating, the nature of the course, i.e. with periods of exacerbations and remissions. As a rule, with all these diseases, a special type of necrosis develops - caseous necrosis.
The tuberculous granuloma has the following structure: in its center there is a focus of caseous necrosis, behind which there is a shaft of radially located (elongated along the length from the center to the periphery) epithelioid cells; behind them are single giant Pirogov-Langhans cells and, finally, on the periphery of the granuloma there is another shaft of lymphoid cells. Among these typical cells there may be an admixture of a small number of plasma cells and macrophages. When impregnated with silver salts, a thin network of argyrophilic (reticular) fibers is found among the granuloma cells. Blood vessels usually do not occur in a tuberculous granuloma. When stained according to Ziehl - Nielsen, mycobacterium tuberculosis is detected in giant cells.
Given the predominance of epithelioid cells in the granuloma described above, such a granuloma is called epithelioid cell. This specific granuloma is an illustration of a typical infectious (by etiology), immune (by pathogenesis), epithelioid cell (by morphology) granuloma.
Usually tuberculous granulomas are small - their diameter does not exceed 1-2 mm, more often they are found only microscopically. However, macroscopically, the changes are quite typical - numerous merging granulomas outwardly resemble small, like millet, tubercles, which is why the process is commonly called miliary (from Latin miliarius - millet) tuberculosis.
Syphilitic granuloma is called "gumma" (from Latin gummi - gum). It, like tuberculous granuloma, in the center is represented by a focus of caseous necrosis, but much larger in size. On the periphery of necrosis are many lymphocytes, plasma cells and fibroblasts. These three cell types are predominant, but in a small amount epithelioid cells, macrophages and single giant cells of the Pirogov-Langhans type can be found in the gumma. Syphilitic granuloma is characterized by rapid growth of massive dense connective tissue, which forms a kind of capsule, due to the proliferation of fibroblasts. On the inside of this capsule, among the cells of the infiltrate, numerous small ones are visible, and on the outside - more large vessels with symptoms of productive endovasculitis. It is extremely rare to detect pale treponema among the cells of the infiltrate by silvering according to Levadity.
Gumma is characteristic of the tertiary period of syphilis, which usually develops after a few years (4 -5 and later) after infection and lasts for decades. At the same time, in different organs - bones, skin, liver, brain, etc. - solitary (from lat. solitarius - prone to loneliness) nodes appear in size from 0.3-1.0 cm on the skin and the size of a chicken egg - in the internal organs. When cut, a yellow jelly-like mass is released from these nodes, resembling gum arabic (gum arabic) glue, from which the name syphilitic granuloma arose.
In addition to gummas, gummous infiltration can develop in the tertiary period of syphilis. Gummatous infiltrate is usually represented by the same cells that are dominant in gumma, i.e. lymphocytes, plasma cells and fibroblasts. At the same time, a tendency to sclerosis is very quickly revealed - granulation tissue grows. Among the cells of the infiltrate, many small, capillary-type vessels are revealed: productive vasculitis is also found in these vessels. Such changes most often develop in the ascending part and in the thoracic aortic arch and are called syphilitic mesaortitis. The gummous infiltrate, located in the middle and outer shells of the aorta, together with the affected vasa vasorum, destroys the elastic framework of the aorta - when stained with fuchselin, peculiar "bald spots" appear in place of the former elastic fibers. Connective tissue grows in place of elastic fibers. It is in these areas of the former gummous infiltrate that the inner lining of the aorta becomes uneven, wrinkled, with many cicatricial retractions and bulges, resembling "shagreen skin". The low-elastic wall of the aorta in the lesions under blood pressure becomes thinner, bulges outward and an aneurysm of the thoracic aorta is formed. If the gummous infiltrate from the aorta "descends" to its valves, then aortic heart disease is formed.
Diffuse gummous infiltration in the liver has a similar structure and leads to the development of a lobular liver due to shrinkage of the connective tissue that grows at the site of a specific lesion. Similar changes in the skin and mucous membranes sometimes lead to a sharp disfigurement of the face - ulcers, scars, destruction of the nasal septum, etc.
Leprosy granuloma (leproma) has a polymorphic cellular composition: macrophages, epithelioid cells, as well as giant, plasma cells, fibroblasts are visible in it in large numbers. Mycobacteria Hansen - Neisser are found in large quantities in macrophages (it has been established that 1 g of "blooming" leprosy contains 5 10 9 lepromatous mycobacteria). The latter, overflowing with pathogens, increase, as if swell, and fatty inclusions appear in their cytoplasm. Such macrophages, called Virchow's leprosy cells, are overflowing with mycobacteria, which lie in them in strictly ordered rows, resembling cigarettes in a pack, which is especially clearly seen when stained by Ziehl-Nielsen. Subsequently, mycobacteria, sticking together, form leprosy balls. The macrophage is destroyed over time, the fallen leprous balls are phagocytosed by giant cells of foreign bodies. The presence of a huge amount of mycobacteria in leprosy is due to incomplete phagocytosis in macrophages during leprosy.
Tissue reactions in leprosy are closely related to the body's resistance, which entirely depends on its relationship with leprosy mycobacteria and determines the whole variety of clinical manifestations of the disease. There are several variants of the course of leprosy, but two "extreme" clinical and anatomical forms look most clearly: 1) with high resistance - tuberculoid; 2) with low resistance - lepromatous.
Tuberculoid form proceeds clinically benignly, sometimes with self-healing, against the background of pronounced cellular immunity. The skin lesion is diffuse, with many spots, plaques and papules, followed by depigmentation of the affected areas. Morphologically, epithelioid cell granulomas are detected, and mycobacteria are detected in rare cases. All this is a confirmation of the development of leproma according to the type of HRT. The change in nerves is characterized by diffuse infiltration by their epithelioid cells, which is manifested by early
sensitivity disorders. Changes internal organs not typical for this form.
Lepromatous form is the complete opposite of the tuberculoid form. Skin lesions are often diffuse character, involved, and then completely destroyed skin appendages - sweat and sebaceous glands vessels are damaged. In leproma, macrophages, giant cells and many mycobacteria are found. Diffuse infiltration of the skin of the face sometimes leads to complete disfigurement of the appearance (" lion muzzle"). Leprosy neuritis is ascending, diffuse infiltration of all elements of sensory nerves by macrophages develops with gradual replacement of the nerve fiber with connective tissue. Granulomas from macrophages with high content Mycobacteria are found in the liver, spleen, bone marrow, lymph nodes, the mucous membrane of the upper respiratory tract, in the endocrine organs. All of the above may be evidence of a significant inhibition of cellular immune responses in the lepromatous form of leprosy, while a pronounced dysfunction of the humoral link is noted.
Scleroma granuloma is characterized by accumulation of macrophages, lymphocytes, a large number plasma cells and their degradation products - eosinophilic Roussel bodies. Specific for scleroma granuloma are very large mononuclear cells with vacuolated cytoplasm - Mikulich cells. Macrophages intensively capture diplobacilli, but phagocytosis in them is incomplete. Part of the macrophages is destroyed, and part, becoming larger, turns into Mikulich cells, in which they find the causative agent of scleroma - Volkovich's stick - Frisch.
Scleroma granuloma is usually located in the mucous membrane of the upper respiratory tract - the nose, larynx, trachea, less often - the bronchi. The process ends with the formation of coarse scar tissue granulomas in place, as a result, the mucous membrane is deformed, the airways narrow sharply and sometimes even completely close, causing the risk of asphyxia.
Outcomes of granulomas. The following outcomes of granulomatous inflammation are possible:
▲resorption of cellular infiltrate. This is a rare outcome, since granulomatosis in the bulk is a chronic inflammation. This is possible only in cases of low toxicity of the pathogenic factor and its rapid elimination from the body. Examples are such acute infections as rabies, typhoid and typhus.
▲ fibrous transformation of the granuloma with the formation of a scar or fibrous nodule. This is the most common and typical outcome of granulomatosis. The development of sclerosis is stimulated by IL-1 secreted by granuloma macrophages, and often by the pathogen itself.
▲ granuloma necrosis. This outcome is typical primarily for tuberculous granulomas, which can completely undergo caseous necrosis, and also for a number of infectious granulomas. In the development of necrosis, in all cases, proteolytic enzymes of the macrophage, as well as products secreted by a pathogenic agent, which have a direct toxic effect on fabric. An experiment with granulomas that developed after the introduction of BCG made it possible to prove the antibody mechanism of necrosis, while immune complexes were found in the walls of blood vessels, where a pattern of productive vasculitis developed. In the case of necrosis of granulomas located on the skin, mucous membranes, tissue melting inevitably occurs with the formation of ulcers.
▲ Suppuration of granulomas. This usually occurs with fungal infections. With many infections (glanders, yersiniosis, tularemia) and fungal infections, many neutrophils appear at the first stages, but only in the case of mycotic lesions they cannot cope with the pathogen, they die, and the products of their death, being chemoattractants, attract macrophages. So there are peculiar granulomas with an abscess in the center.
GRANULOMATOUS DISEASES
Granulomatous diseases (GB) is a heterogeneous group of diseases (nosological forms) of various etiologies, the structural basis of which is granulomatous inflammation. These diseases (currently more than 70 have been isolated) manifest themselves in a variety of ways. clinical syndromes and variants of tissue changes, heterogeneous sensitivity to therapy. However, they share a number of characteristics:
▲ Presence of granuloma. At the same time, granulomatous inflammation in GB, which, as a rule, have a staged course, is the structural basis of the most characteristic and clinically most important stages and does not develop in all forms of these diseases, for example, leprosy (only in the lepromatous form), syphilis (only in the tertiary period);
▲ violation of immunological homeostasis;
▲ polymorphism of tissue reactions;
▲ tendency to chronic course with frequent relapses;
▲ often vascular damage in the form of vasculitis.
Classification of granulomatous diseases[Strukov A.I., Kaufman O.Ya., 1989]
I Granulomatous diseases of infectious etiology:
rabies, viral encephalitis, cat scratch disease, typhus, typhoid fever, paratyphoid, yersiniosis, brucellosis, tularemia, glanders, rheumatism, scleroma, tuberculosis, syphilis, leprosy, malaria, toxoplasmosis, leishmaniasis, actinomycosis, candidiasis, schistosomiasis, trichinosis , alveococcosis
II. Granulomatous diseases of non-infectious etiology: silicosis, asbestosis, talcosis, anthracosis, aluminosis, berylliosis, zirconiasis, bogassosis, byssinosis, amylosis
III. Drug-induced granulomatous diseases: granulomatous drug-induced hepatitis, oleogranulomatous disease, gluteal granuloma of infants
IV. Granulomatosis disease of unknown etiology: sarcoidosis, Crohn's disease, Horton's disease, rheumatoid arthritis, primary biliary cirrhosis, Wegener's granulomatosis, Weber-Christian panniculitis, xanthogranulomatous pyelonephritis, xanthogranulomatous cholecystitis
Granulomas in granulomatous diseases of infectious etiology caused by viruses, rickettsia, bacteria, as a rule, are immune according to the mechanism of development. According to the morphological picture, they are basically similar to each other, which is explained by the commonality of morpho- and pathogenesis. The exceptions are granulomas in syphilis (nodules visible to the naked eye with massive necrosis and vasculitis), leprosy (Virchow cells stuffed with mycobacteria), scleroma (Mikulich cells) and tuberculosis (classic epithelioid cell granulomas with caseous necrosis in the center and giant Pirogov cells - Langhans), which can be distinguished into a special group - specific granulomatosis (see earlier).
In all cases, infectious granulomas are represented by an accumulation of SMF cells. Numerous neutrophils appear in some granulomas and eventually necrosis develops, as is observed with glanders, felinosis (cat-scratch disease caused by chlamydia), yersiniosis.
Granulomatous diseases caused by fungi are characterized by the formation of immune granulomas, in which necrosis or abscesses usually occur. Sometimes the response of the body, and hence the cellular composition of the granulomas, is directly dependent on the morphology of the fungi.
Granulomatous diseases of a non-infectious nature include a large group of diseases that are caused by the action of organic and inorganic dust, fumes, aerosols, and suspensions. If the dust is inorganic, then the diseases proceed for a long time, but benignly, immune disorders in these cases it is not observed, and granulomas are mainly built from giant cells of foreign bodies. Such granulomatosis usually develops as an occupational disease in miners, cement workers, glass workers, etc. (silicosis, asbestosis). At the same time, beryllium (IV) oxide causes the development of an immune granuloma, since beryllium has the properties of a hapten and, by combining with body proteins, forms substances that trigger autoimmune processes. Organic dust usually causes a disseminated lesion of the lungs, called interstitial diseases (see the lecture on the private course of pathological anatomy "Chronic non-specific lung diseases") - The common thing that all these diseases have in common is the presence of granulomatous lesions due to the development of cell-mediated or immunocomplex mechanisms .
Around foreign bodies, granulomatous inflammation usually develops, but very rarely it takes on the character of a disease. A typical example of such a disease is gout, when, in response to the deposition of urate in tissues, typical giant cell non-immune granulomas occur.
Drug-induced granulomatous diseases most often occur and have been studied in detail as a result of toxic-allergic damage to the lungs and the development of fibrosing alveolitis in them, as well as the liver - drug-induced granulomatous hepatitis.
The group of granulomatous diseases of unknown etiology is especially large. One of the common diseases is sarcoidosis, in which characteristic granulomas of the sarcoid type appear in many organs, and especially often in the lymph nodes and lungs. The granuloma is built from epithelioid cells and giant cells of two types - Pirogov - Langhans and foreign bodies. A feature of this granuloma is the absence of caseous necrosis, which makes it possible to distinguish it from tuberculous granuloma, clear boundaries (stamped granulomas) and rapid scarring. The disease is characterized by increasing damage to all new groups of lymph nodes and lungs, which leads to progressive respiratory failure or compression of vital organs by the lymph nodes.
By etiology. I. Granulomas of established etiology: 1. infectious granulomas, 2. non-infectious granulomas (dust, drug, around foreign bodies). II. Granulomas of unknown etiology.
By morphology. I. Mature macrophages. II. Epithelioid cell granulomas. Perhaps the following subdivision according to morphology: 1) with the formation of granulomatous infiltrate (diffuse type), 2) with the formation of granulomas (tuberculoid type). Among the criteria for assessing granulomas include their specificity. specific called granulomas that are formed under the action of specific pathogens and are characterized by relatively specific morphological manifestations. Depending on the characteristics of cell maturation, granulomas with a slow metabolism (for example, granulomas of foreign bodies, with a long period of life of monocytes) and granulomas with high level exchange (in response to the penetration of bacteria into the body that live in macrophages for several days), they differentiate into epithelioid.
Outcomes of granulomas: 1. resorption, 2. necrosis, 3. suppuration, 4. scarring. In most cases, granulomatosis leaves behind a relatively long-term immunity, sometimes lifelong, to the same disease.
SPECIFIC GRANULOMA
tuberculosis granuloma. The causative agent is mycobacterium, Koch's wand. Granuloma - tubercle, macroscopically a tubercle in the form of a gray nodule the size of a millet grain ( miliary tubercle). Microscopically it consists of epithelioid cells, lymphocytes, multinucleated Pirogov-Langhans cells. Among typical cells, plasma cells, macrophages, a thin network of argyrophilic fibers can be found. Subsequently (with adverse conditions) there is an increase in tissue permeability, leukocytes and plasma proteins penetrate into the tubercle. This contributes to the reproduction of mycobacteria, the release of toxins by them. A cheesy necrosis appears in the center of the tubercles, and their color turns from gray to yellow, yellow-gray, resembling cottage cheese (curdled tubercle). If large areas of tissue with purulent fusion are exposed to cheesy necrosis, then cavities are formed - cavities. Depending on the reactivity of the organism, one or the other cells predominate in the structure of the tubercle. With a favorable course, the tubercle acquires a fibrous character, i.e. a scar is formed. The focus can be calcified - petrification. According to the macroscopic picture, they distinguish 1) submiliary tubercles - small, with poppy seeds; 2) miliary(milium - millet grain); 3) solitary- large, single, with round contours; four) conglomerate- large tubercles with scalloped contours (formed by the confluence of several miliary).
Syphilis granuloma. The causative agent is a pale spirochete, a Shaudin-Hoffmann stick. In the development of acquired syphilis, three periods are distinguished: primary, secondary, tertiary. Granuloma - gumma- characteristic of the Tertiary period (from lat. gummi - glue). Usually gumma is single, solitary. Gumma can be localized in different bodies and tissues: bones, skin, liver, brain, etc. Macroscopically, it is a tumor-like node from a few millimeters to 2-3 cm, central part which is occupied by a sticky viscous mass (fibrous necrosis), along the periphery - a dense connective tissue. Microscopically, the inner layer of this fibrous capsule, bordering on the necrotic mass, is represented by lymphocytes, an abundance of plasma cells (Marshalko-Unna cells), a few epithelioid cells, fibroblasts, and single Pirogov-Langhans giant cells. There are many capillaries and reticular fibers in the granuloma. In addition to gummas in the tertiary period, which usually develops several years later (4–5 or more) after infection, diffuse granulomatous inflammation can develop - gummous infiltration. The composition of the infiltrate is the same as in the gum. At the same time, a tendency to sclerosis quickly manifests itself. Gummous infiltration often occurs in the middle and outer shells of the aorta and is called syphilitic mesaortitis. The outcome is sclerosis with a sharp deformation of the tissues.
Leprosy granuloma (leprosy). The causative agent is Hansen's bacillus, stained red according to Ziehl-Neelsen. This disease affects the skin, peripheral nervous system, and other tissues. Granuloma - leproma- consists mainly of large macrophages with vacuolated cytoplasm, in which Hansen sticks are found in the form of cigarettes in a pack (Virchow cells), as well as lymphocytes, plasma cells, fibroblasts.
It is customary to distinguish three clinical and anatomical forms of leprosy depending on the resistance of the organism: 1) with high resistance - tuberculoid, 2) with low – lepromatous, 3) intermediate - dimorphic.
In the tuberculoid form, which proceeds clinically benignly, sometimes with self-healing, epithelioid cells, Pirogov-Langhans giant cells, are found in the granuloma. Diffuse skin lesions with many spots, plaques, followed by depigmentation. Diffuse infiltration of epithelioid cells is determined in the nerve fibers. Changes in internal organs are not typical.
The lepromatous form is characterized by the development of diffuse granulomatous inflammation. Thus, lesions of the skin of the face are sometimes accompanied by disfigurement of the appearance - the “lion's face”. Lepromatous neuritis is characterized by diffuse infiltration of all elements of the sensory nerves by macrophages with a gradual replacement of the nerve fiber with connective tissue. Anesthesia develops. Granulomas are found in the liver, lymph nodes, spleen, bone marrow, endocrine organs, etc. With an unfavorable outcome due to tissue destruction, ulcers form, deep extensive tissue necrosis up to self-amputation of body parts.
Rhinoscleroma granuloma. The causative agent is the Volkovich-Frisch wand. There is inflammation of the mucous membrane of the respiratory tract, nose with the growth of a kind of granulation tissue of a dense consistency, narrowing their gaps. Macroscopically, the tissue is brown-red in color, the surface of the mucous membranes is finely bumpy. Microscopically, granulomas consist of lymphocytes, epithelioid cells, plasma cells, large macrophages - Mikulich cells (with light, softly foamy cytoplasm, sometimes containing a pathogen), Roussel bodies (plasma cells with hyaline accumulation in them), fibroblasts. Granulomas very quickly undergo sclerosis, which leads to stenosis of the respiratory tract, sometimes asphyxia.
Sapa granuloma. The causative agent is the glanders bacillus. Nasal mucosa, skin, lungs are affected. Nodules, granulomas, consisting of epithelioid cells, neutrophilic leukocytes and characteristic karyorrhexis develop. There is a purulent fusion with a special ductility of glanders pus.
With multilocular echinococcosis ( alveococcosis) among the fields of necrosis, a chitinous membrane is found. Proliferative inflammation in this case is delimited and nonspecific in terms of cellular composition.
Leishmania(class of protozoa) are pathogens cutaneous leishmaniasis, called pendinsky or eastern ulcer, as well as visceral lesions (kala-azar). Typically, the formation of multiple granulomas from epithelioid cells containing leishmania.
At schistosomiasis productive inflammation occurs in response to trematode eggs, which are laid by the female along the venous system of the liver, intestines or genitourinary system. The eggs are oblong in shape and have spines. Granulomas around them consist of epithelioid cells, lymphocytes, individual multinucleated cells, eosinophils.
An example of a non-infectious granuloma can be an oleogranuloma (it occurs in response to the accumulation of fat breakdown products), or granulomas develop around foreign bodies (for example, suture material), in response to dusting.
IMMUNOPATOLOGICAL PROCESSES
To immunopathological processes include pathological changes in the organs of the immune system (thymus, lymph nodes, etc.) and impaired immune response. The main forms of impaired immune response are its insufficiency (immunodeficiency) and excessive severity (allergy).
STRUCTURE OF THE IMMUNE SYSTEM
The immune system includes organs and tissues in which maturation (differentiation) of T- and B-lymphocytes occurs. Distinguish between primary and secondary organs of the immune system. AT primary (central) bodies passes the first stage of differentiation of lymphocytes, before their interaction with the antigen ( stage of antigen-independent differentiation). At the same time, T-lymphocytes mature in the thymus (after the involution of the thymus, stratified squamous epithelium takes over its role), B-lymphocytes - in the red bone marrow. Secondary (peripheral) bodies provide subsequent maturation of T- and B-lymphocytes after their interaction with antigens ( stage of antigen-dependent differentiation). In the lymph nodes and in the lymphoid tissue of the spleen, both T- and B-lymphocytes differentiate. In MALT-structures and facultative lymphoid formations, mainly B-lymphocytes mature, in SALT-structures - mainly T-lymphocytes.
MALT structures(MALT is an abbreviation of English. mucosa-associated lymphoid tissue: lymphoid tissue of the mucous membranes) - lymphoid formations of the mucous membranes of the digestive tract, respiratory and urinary tract, conjunctiva. MALT structures include the tonsils of the Waldeyer–Pirogov ring, the appendix of the caecum, Peyer's patches, and solitary follicles. SALT structures(SALT - from English. skin-associated lymphoid tissue: lymphoid tissue of the skin) are small clusters of immunocompetent cells around small vessels in the papillary and reticular layers of the dermis. Facultative lymphoid formations are called lymphoid structures that occur only during pathological processes in those organs where normally lymphoid tissue is absent. For example, lymphoid follicles form in the portal tracts of the liver during chronic viral hepatitis C, in the thyroid gland with autoimmune thyroiditis or in the mucous membrane and submucosa of the stomach with helicobacteriosis.
Age involution of the thymus. The thymus undergoes physiological atrophy ( age involution). In this case, first of all, the volume of the lymphoid tissue of the organ decreases. The age-related involution of the thymus begins at the age of 5–7 years and is mainly completed by the pubertal period (puberty). The thymus parenchyma is replaced by white adipose tissue (thymic lipomatosis). However, small fragments of the active parenchyma persist throughout a person's life. The function of the thymus in the postinvolutive period passes to the integumentary tissues lined with multilayer squamous epithelium(skin, some mucous membranes, especially the oral mucosa). A clear illustration of this is the changes in immunity during DiGeorge syndrome. The immunodeficiency state in this disease, caused by congenital hypoplasia of the thymus, persists for the first five years of a child's life; in subsequent years, the function of the immune system is restored due to the fact that the cells of stratified squamous (squamous) epithelium acquire the ability to produce thymic hormones and, due to this, to attract T-lymphocyte precursors from the bone marrow, ensuring their maturation in integumentary tissues.
THYMUS PATHOLOGY
A variety of pathological processes can develop in the thymus - inflammation (thymitis), benign and malignant tumors. But the most important are glucocorticoid-dependent lesions - accidental transformation and glucocorticoid-associated thymic hyperplasia. Glucocorticoids (hormones of the fascicular zone of the adrenal cortex) are differentiating factors (i.e. factors that promote maturation) for all lymphocytes, including thymic lymphocytes.
Effect of glucocorticoids on lymphocytes:
1. Glucocorticoid hormones in normal concentration inhibit the reproduction (proliferation) of lymphocytes and promote their differentiation.
2. With a lack of glucocorticoids ( chronic adrenal insufficiency) there is an increased proliferation of lymphocytes ( glucocorticoid-associated hyperplasia of lymphoid tissue), but their normal maturation does not occur. A large number of functionally defective lymphocytes are formed, therefore, an immunodeficiency state develops. Lymphoid organs (thymus, lymph nodes, tonsils, spleen, etc.) increase in size. A significant increase in the thymus is denoted by the term thymomegaly; an increase in all groups of lymph nodes is called generalized lymphadenopathy.
3. With a high concentration of glucocorticoids in the body, which is typical for chronic distress syndrome, lymphocytes under the influence of these hormones are destroyed by apoptosis (an excess of glucocorticoids activates the apoptosis program in lymphocytes). This reduces the number of lymphocytes and, consequently, the volume of lymphoid tissue. Thymus shrinkage is referred to as accidental transformation(from lat. accidentalis - accidental). This process was called "accidental" because the reasons for it were not clear. Chronic distress syndrome accompanies various serious diseases (malignant tumors, infectious pathology). Accidental transformation of the thymus contributes to the development of an immunodeficiency state, aggravating the already severe course of the underlying pathological process.
Glucocorticoid-associated hyperplasia of lymphoid tissue. Depending on the period of ontogenesis in which chronic adrenal insufficiency develops, two forms of glucocorticoid-associated hyperplasia of lymphoid tissue are distinguished: congenital (lymphatic-hypoplastic diathesis, or status thymicolymphaticus) and acquired. The congenital form develops in the prenatal period, the acquired form develops in postnatal ontogenesis. For lymphatic-hypoplastic diathesis, in addition to dyshormonal hyperplasia of lymphoid tissue, malformations of internal organs, especially the heart, are characteristic in the form of their underdevelopment (hypoplasia). In such patients, in cases of significant tension of protective and adaptive mechanisms (serious illness, trauma, surgical intervention, intense physical activity) may occur sudden death. Its cause is a deficiency in the body of glucocorticoid hormones, as a result of which vascular collapse and shock.
Accidental transformation of the thymus. Morphogenesis of the accidental transformation of the thymus. The scheme of morphogenesis of accidental transformation, proposed by T.E. Ivanovskaya, has become widespread in Russia:
1 stage – moderate hyperplasia thymus in the acute phase of the stress syndrome.
2 stage- focal delymphatization (death of lymphocytes) of the thymic lobule cortex.
3 stage– total delymphatization of the cortex (stage of inversion of layers). Thymus lymphocytes in the medulla quantitatively predominate over the thymocytes of the cortex, and in histological preparations stained with hematoxylin and eosin, it becomes darker than the cortical one (in normal conditions, vice versa).
4 stage- total delymphatization of thymic lobules (both cortical and medulla) and death of thymic epithelial cells (stage of Hassal's giant bodies). At this stage, Hassall's bodies, normally located only in the medulla, appear throughout the entire lobule, including the cortex. There are many of them, they are of various sizes (polymorphism of Hassall's bodies), some of the bodies are sharply enlarged (giant bodies). Basically, Hassall's bodies are formed by detritus (destroyed epithelial cells), while normally they consist of keratinized epithelial cells.
5 stage- irreversible atrophic changes in the thymus. The first four stages of accidental transformation are reversible.
ALLERGY
Allergy(synonym: hypersensitivity reactions) is a manifestation of an overly expressed immune response. Antigen, allergic, is called allergen. Allergy forms are classified depending on the nature of the allergen, the rate and mechanisms of development of hypersensitivity reactions.
I. Classification of allergy forms depending on the nature of the allergen:
1. Allergy to external antigens (exoallergens). Diseases that develop in this case are called exogenous allergies(eg allergic bronchial asthma, hay fever).
2. Autoallergy Allergic to self antigens autoantigens). Diseases that are based on autoallergy are called autoimmune(see below).
3. Graft-versus-host reaction (GVHD) - aggression of the immune factors contained in the graft against the organs and tissues of the recipient. GVHD often develops during bone marrow transplantation, is accompanied by damage to various organs and can lead to death of the patient.
II. Classification of allergy forms according to the rate of development of changes:
1. Allergy immediate type (immediate type hypersensitivity reactions, ANT, or HHT reactions) usually develops within a few minutes. Tissue changes are described by the term acute immune(allergic)inflammation.
2. Allergy delayed type(delayed-type hypersensitivity reactions, AZT, or HRT reactions) develops after 24-48 hours. Tissue changes are referred to as chronic immune(allergic)inflammation.
Special variants of delayed-type allergy are transplantation immunity reactions, tuberculin-type reactions and contact hypersensitivity.
1. Reactions transplantation immunity also called transplant rejection reactions. Microscopic examination reveals two types of changes in the graft: a productive inflammatory reaction (lymphohistiocytic infiltrate) and alterative changes in the graft cells up to their death. Close contacts between the cells of the infiltrate and the cells of the transplanted tissue are characteristic.
2. Tuberculin type reactions develop with skin allergy tests, with which you can diagnose the severity of the immune response to a specific antigen (for example, tests with tuberculin, brucellin and other antigenic drugs).
3. Contact hypersensitivity- a delayed-type reaction at the point of contact of the integumentary tissue (skin, mucous membrane) and the allergen. This form of allergy underlies diseases such as allergic contact dermatitis and contact allergic stomatitis.
III. Classification of allergy forms according to the mechanism of its development (S. Sell, 1978):
1. Reaginic (IgE-dependent) reactions [type I allergic reactions].
2. Humoral cytotoxic reactions[type II allergic reactions].
3. Immunocomplex reactions [type III allergic reactions].
4. Cellular cytotoxic reactions [type IV allergic reactions].
5. Allergic reactions of autoantibodies [type V allergic reactions].
6. Granulomatous inflammation [allergic reactions type VI] (see the topic "Productive inflammation").
Type I reactions- allergic reactions developing under the influence of IgE (reagins). This results in degranulation. mast cells(labrocytes, tissue basophils), causing the occurrence of edema, plethora of microvessels and bronchospasm. Necrosis usually does not develop. The presence of numerous eosinophilic granulocytes in the tissue is characteristic. There are two forms of reagin reactions - anaphylactic and atopic. Anaphylactic reaction(anaphylactic shock) under certain conditions can develop in every person. In contrast to this, atopy does not occur in all people, but only in predisposed individuals. Atopic reactions underlie diseases such as allergic forms hives and angioedema, hay fever (allergic rhinosinusopathy), atopic(non-infectious-allergic)bronchial asthma, diffuse neurodermatitis, atopic diathesis (exudative catarrhal diathesis).
Type II reactions- allergic reactions, during which target cells are damaged under the action of humoral immune factors (immunoglobulins). These reactions have practically no independent significance in pathology.
Type III reactions(immunocomplex reactions) - tissue damage that develops under the influence of an excess of circulating complete immune complexes. Complete immune complexes are formed by an antigen, antibodies to it, and complement proteins. The main manifestation of immunocomplex reactions is immune complex vasculitis. Most often, the capillaries of the renal glomeruli are involved in the process ( immunocomplex glomerulonephritis). Immune complex inflammation is characterized by a combination of alterative and exudative reactions. Alterative changes are manifested, as a rule, by fibrinoid necrosis of the walls of blood vessels and perivascular tissue. Typical formation of fibrinous and hemorrhagic exudate.
Type IV reactions- allergic reactions, in which target cells are destroyed under the influence of killer cells - cytotoxic T-lymphocytes and K-cells. Killer T-lymphocytes destroy only those cells to whose surface antigens they are sensitized. K-cells ("killer B-lymphocytes") destroy target cells coated with antibodies ( antibody-dependent cellular cytotoxicity).
Type V reactions- change (loss or increase) in the activity of protein molecules under the influence of autoantibodies. For example, autoantibodies to insulin or insulin receptors of cells inactivate (neutralize) them, which may result in the development of diabetes mellitus. Autoantibodies to follicular thyrocytes, on the contrary, stimulate these cells through special cytolemmal receptors and increase their production of thyroid hormones, which can cause thyrotoxicosis.
AUTOIMMUNE DISEASES
Autoimmunization(autoimmune response) - an immune response to self antigens. Distinguish physiological(not accompanied by tissue damage) and pathological autoimmunization (autoallergy), in which damage occurs to those tissue structures against which the autoimmune response is directed. Significant damage to the tissue of any organ leads to the development of its functional failure. So, with autoimmune thyroiditis, hypothyroidism is formed (insufficient production of thyroid hormones), with autoimmune agranulocytosis, leukopenia develops due to the destruction of neutrophilic granulocytes of the blood during the autoimmune response. There are two types of autoimmune factors: cellular autoimmunity factors (killer lymphocytes, primarily autosensitized killer T-cells) and humoral autoimmune response factors ( autoantibodies). The main role in the development of tissue damage is played by cellular autoimmune factors.
There are four main mechanisms for the development of pathological autoimmunization: modification of a normal autoantigen (change in the structure of the autoantigen), sequestration of the autoantigen of the tissue of the trans-barrier organ (exit of tissue elements of the trans-barrier organs beyond the histohematic barrier when it is damaged), antigenic mimicry (the similarity of the epitopes of autoantigens and exoantigens, resulting in an immune response to an external antigen is accompanied by a cross-reaction to a similar autoantigen) and insufficiency of suppressor cells.
Autoimmune diseases- diseases in which autoallergy is the main link in pathogenesis. There are three main groups of autoimmune diseases:
1. Organ-specific autoimmune diseases develop as a result of damage to the histohematic barriers and are characterized by a primary lesion of any one trans-barrier organ (for example, the thyroid gland in Hashimoto's thyroiditis, the thymus in autoimmune thymitis).
2. Organ-specific autoimmune diseases differ in the primary involvement in the process of many organs. At the same time, in some cases, an autoimmune lesion is formed in the connective tissues ( diffuse connective tissue diseases), in others - in the walls of blood vessels ( systemic vasculitis). Diffuse connective tissue diseases include rheumatoid arthritis, systemic lupus erythematosus, systemic scleroderma, polymyositis (dermatomyositis), ankylosing spondylitis (ankylosing spondylitis). Among systemic vasculitis, the most common are nodular polyarteritis (periarteritis nodosa), Takayasu's nonspecific aortoarteritis, Horton's temporal arteritis, Wegener's granulomatosis, Goodpasture's pneumorenal syndrome, Moshkowitz's thrombotic thrombocytopenic purpura, Winivarter-Buerger's thromboangiitis obliterans, and Schoenlein-Genoch hemorrhagic vasculitis. The leading mechanism for the development of pathological autoimmunization in these diseases is the insufficient function of suppressor cells.
3. At the heart of the majority intermediate type autoimmune diseases lie allergic autoantibody reactions (see above).
In autoimmune diseases, a lymphocytic or lymphoplasmacytic infiltrate is formed in the affected organ.
Distinguish from autoimmune diseases pseudo-autoimmune diseases (diseases with autoimmune disorders), in which the emerging autoimmune response is not a leading factor in pathogenesis. A typical pseudo-autoimmune disease is rheumatism, tissue damage in which is primarily due to the action of aggression factors Streptococcus pyogenes, and pathological autoimmunization makes a less significant contribution to the development of the disease.
IMMUNODEFICIENT CONDITIONS
Immunodeficiency states (immunodeficiencies) - pathological changes characterized by insufficient immune response. They are the background for the development of infectious processes ( opportunistic infections) and malignant tumors.
Primary immunodeficiencies- hereditary and acquired in the prenatal (prenatal) period immunodeficiency states. These include primary deficiencies in cellular immunity (eg, DiGeorge syndrome- thymus hypoplasia), primary deficiencies of humoral immunity (for example, Bruton's syndrome- the complete absence of immunoglobulins), as well as primary combined deficiencies, in which both cellular and humoral immunity develops (for example, ataxia-telangiectasia Louis Bar).
Secondary immunodeficiencies- immunodeficiency states that develop in postnatal ontogenesis. These include the following forms of immunodeficiency:
1. Immunodeficiency in chronic distress. Prolonged intense stress (chronic distress) is accompanied by an increase in the content of glucocorticoid hormones in the body, which in high concentrations have an immunosuppressive effect.
2. Nosogenic immunodeficiencies. Nosogenic (from the Greek. nosos- disease) are called immunodeficiencies, the development of which is associated with any serious illness. Most often, a pronounced secondary immunodeficiency is formed when viral infections(for example, HIV infection or measles) and malignant neoplasms.
3. Iatrogenic immunodeficiencies. Iatrogenic (treatment-induced) immunodeficiencies, as a rule, occur with the appointment of cytostatics and long-term use preparations of glucocorticoid hormones. In some cases, immunodeficiency may be due to radiation therapy when large volumes of tissues are exposed to irradiation. Iatrogenic immunodeficiencies include postoperative immunodeficiency in patients who underwent surgery with a massive surgical tissue injury, and operated under general anesthesia. The peak of postoperative immunodeficiency occurs 2-3 days after surgery. Postoperative immunodeficiency explains the increased incidence of opportunistic and hospital infections in this period, especially postoperative pneumonia. Therefore, in terms of management of operated patients, measures aimed at preventing infectious complications should be provided.
4. Age (senile) immunodeficiency. Age-related immunodeficiency is caused by the aging of the body.
5. Alimentary immunodeficiencies. Nutritional immunodeficiencies are caused by a lack of protein, vitamins and trace elements in food. Of the trace elements, the most important for the normal function of the immune system are zinc and cobalt.
ACCOMMODATION AND COMPENSATION
The human body is forced to constantly respond to changes in the environment. The organism provides its independence with the help of various and complex reactions, allowing in each this moment adapt to the environment. And such reactions are called adaptive. A broad biological interpretation of adaptation determines a number of provisions that reveal its essence: 1) adaptation covers not only health, but also illness; 2) being associated with the conservation and development of species, it has specific significance; 3) adaptive reactions are reactions, in fact, homeostatic; 4) adaptive reactions cannot be identified with the so-called protective ones, which are aimed at liberation from a direct or indirect threat to life.
Adaptation (adaptation) can be manifested by various pathological processes: 1) atrophy, 2) hypertrophy (hyperplasia), 3) organization, 4) tissue restructuring, 5) metaplasia, 6) dysplasia.
Compensation- a narrower concept that characterizes the reactions of a particular person in conditions of illness. These include reactions that occur under conditions when the action of environmental factors is accompanied by damage to the organ, and to normalize the function, its remaining parts and other organs are turned on. Thus, compensatory processes differ from adaptive ones 1) by reactions not specific, but individual, 2) “situational” reactions, i.e. reactions of "preservation of oneself" in case of damage, 3) reactions arising from diseases and being their integral part. Another difference in compensation is the staged (phase) nature of the process: 1) formation, 2) consolidation - the process of structural restructuring (a new morphological quality arises), 3) depletion - newly formed structures are not fully provided with oxygen, energy, enzymes, which leads to dystrophic processes. The main morphological sign of compensation is compensatory hypertrophy (working, vicarious).
Hypertrophy. term hypertrophy denote an increase in the size and mass of individual cells, tissues, organs. Under the term hyperplasia understand the multiplication of cells, which can lead to an increase in the volume of an organ - its hypertrophy. These processes are often combined and often cannot be separated. Hyperplasia is physiological (for example, the proliferation of epithelial structures in the uterus, mammary gland during pregnancy) and pathological (with excessive hormonal stimulation or due to the effect of growth factors on target cells; for example, in viral infections, hyperplasia is provided by growth factors, for example, papillomavirus with hyperplasia epithelium). Now hypertrophy is characterized as an increase in the volume of cells, tissues due to cell reproduction or an increase in the number and size of intracellular ultrastructures. There are two types of compensatory hypertrophy: working (compensatory) and vicarious.
Working hypertrophy of the organ develops with its excessive load. It can be observed in physiological conditions, for example, in athletes, people of physical labor (with increased physical exertion) and in conditions of pathology (disease), for example, in the myocardium, chronic hemodynamic stress due to arterial hypertension or heart disease. Yes, lack bicuspid valve leads to hypertrophy of the left atrium and left ventricle; hypertension causes left ventricular hypertrophy. But any increasing hypertrophy at some stage of development turns into decompensation. Microscopically, decompensation is manifested by dystrophy of cardiomyocytes and sclerosis of the interstitium. Macroscopically, compensation and decompensation of cardiac activity is judged by the type of dilatation (increase in the volume of the cavity) of the ventricles. Tonogenic dilatation is typical for the period of compensation. In the ventricles, this expansion is longitudinal, the outflow tract of the heart lengthens, and the relative increase in ventricular strength. Myogenic dilatation is characteristic of decompensation when the ventricular cavity is enlarged in diameter.
Vicar(replacement) hypertrophy occurs when one of the paired organs (lungs, kidneys, adrenal glands, etc.) is damaged or destroyed. So, vicarious hypertrophy of the kidney after the removal of one of them develops within 40 days.
In addition, there are two types of adaptive hypertrophies: 1) neurohumoral- occurs when the function of the endocrine glands is impaired (an example of neurohumoral hypertrophy can be glandular hyperplasia endometrium, developing with ovarian dysfunction), 2) hypertrophic growths accompanied by an increase in organs and tissues (for example, in violation of lymphatic circulation - elephantiasis, with chronic inflammation of the mucous membranes - polyps, etc.).
Atrophy- lifetime decrease in the volume of cells, tissues, organs, accompanied by a decrease or cessation of their function. It can be physiological and pathological, general (exhaustion) and local. Physiological atrophy is observed throughout a person's life. So, after birth, the arterial (botallian) duct atrophies and becomes obliterated, the gonads atrophy in the elderly, etc. Pathological atrophy occurs at any age and is caused by various factors. This is a reversible process, and after eliminating the cause of atrophy (if it has not reached a high degree), a complete restoration of the structure and function of the organ is possible. But atrophy can progress up to cell death. The general one occurs during exhaustion (starvation, oncological, neuroendocrine diseases, etc.). In this case, the disappearance of fatty tissue, a decrease in the size of the internal organs, which acquire a brown color (accumulation of the pigment lipofuscin). There are the following types of local atrophy: 1) dysfunctional (from inactivity); so, atrophy of the muscles of the limbs with a fracture of its bone, 2) from insufficient blood supply - develops due to narrowing of the arteries that feed the organ; for example, sclerosis of cerebral vessels causes atrophy of the cerebral cortex, 3) from pressure (for example, atrophy of the kidney with difficulty in outflow of urine and the development of hydronephrosis), 4) neurotrophic (lack of innervation), with poliomyelitis, due to the destruction of motor neurons, atrophy of skeletal muscles develops, 5 ) from the action of physical and chemical factors - the development of bone marrow atrophy under the action of radiation energy. Outcomes of atrophy: sclerosis of organs, their deformation.
Organization- this is the replacement of areas of necrosis, inflammatory exudate and thrombi with connective tissue, as well as their encapsulation.
Dysplasia characterized by a violation of the proliferation and differentiation of the epithelium with the development of cellular atypia (various size and shape of cells, an increase in nuclei and their hyperchromia, an increase in the number of mitoses), a violation of histoarchitectonics (loss of the polarity of the epithelium, its histo- and organ specificity). Dysplasia is classified as a precancerous process. There are three degrees of dysplasia. I degree(light) is characterized by a tendency to cell proliferation. II degree(moderate) is characterized by atypia of cells in the deep layers of the epithelium, proliferation captures no more than half the thickness of the epithelial layer. III degree (severe) - a violation of the structure of almost the entire epithelial layer while maintaining the complexity of the location of atypical cells.
REGENERATION
Regeneration- restoration (reimbursement) of structural elements of the tissue to replace the dead. In a biological sense, regeneration is an adaptive process developed in the course of evolution and inherent in all living things. Regeneration is the restoration of both structure and function, and its significance is in the material support of homeostasis. In most tissues of an adult organism, the volume of the population of certain cells is determined by the degree of their proliferation, differentiation, and death. An increase in the number of cells can be caused either by an increase in the rate of their proliferation or a decrease in the rate of death. Forms regeneration: 1) cellular, 2) intracellular, 3) mixed. Cellular regeneration is characterized by cell multiplication (in the form of mitotic and amitotic division). So, in the cells of the epidermis, bone tissue. Two phases of regeneration of such labile cells can be distinguished: a) proliferation of undifferentiated cells, b) differentiation of cells. Intracellular regeneration is characterized by hyperplasia and hypertrophy of ultrastructures. The work of acad. D.S. Sarkisov and his students proved the universal nature of this form of regeneration, which is characteristic of all organs and tissues and proceeds in the same way. Intracellular regeneration is the only possible form of renewal in the myocardium, nerve cells of the central nervous system. In most tissues, regeneration is carried out in a mixed way.
Types of regeneration: 1) physiological, 2) reparative, 3) pathological. Physiological regeneration ensures the functioning of organs and systems in normal conditions. pathological regeneration arises in those cases when, as a result of one reason or another, there is a perversion of the regenerative process. Okay, slow wound healing, metaplasia. Reparative regeneration(repair) occurs in response to tissue damage. The mechanisms of physiological and reparative regeneration are the same. It may be complete or incomplete. Complete regeneration, or restitution, is characterized by the restoration of the damaged area with an identical tissue. In case of incomplete regeneration, or substitutions, the defect is replaced by connective tissue (scar). Substitution predominates in pathology. In this case, the formation of a scar is preceded by the appearance and maturation of granulation tissue. This tissue is universal, repair in most organs occurs precisely with its participation. The beginning of its formation is the activation of fibroblasts, lymphocytes, macrophages, leukocytes with the release of many growth factors. As a result, new microvessels are formed that provide metabolic processes. The resulting scar does not have a specific function and its formation at the site of damage is a manifestation of the body's adaptation. In intact surrounding tissue, hyperplasia of structures occurs with cell hypertrophy - regenerative hypertrophy.
Regeneration proceeds differently depending on age, nutrition and the state of metabolism, the state of blood circulation, innervation, hematopoiesis and tissue properties (plasticity and determinism). Regulation mechanisms: humoral, neurotrophic, immunological. Regulation of cell proliferation is carried out using the following growth factors: 1. platelet (causes chemotaxis of fibroblasts and smooth muscle cells, enhances their proliferation), 2. epidermal (activates the growth of endothelium, epithelium, fibroblasts), 3. fibroblast growth factor, 4. transforming growth factors associated with different types of fibrosis, 5. macrophage growth factors (interleukin-1 and tumor necrosis factor). Growth factors also affect cell movement, contractility and differentiation. An important role is played by the regulating and stimulating effects of the immune system, with the help of lymphocytes. There can be no complete regeneration without regulation of the trophism of the nervous system. A very important role in the regulation of regeneration is played by the "functional request", i.e. the level of functions necessary for life, which must be provided by appropriate morphological structures.
Metaplasia- this is the transition of one type of tissue to another, a kind related to it. More common in epithelium or connective tissue. In some cases, metaplasia is associated with some pathological process (for example, bone formation, cartilage formation in post-traumatic scars, a focus of tuberculosis; or in chronic inflammation - in the bladder, the transitional epithelium is replaced (transfers) to a stratified squamous epithelium, in the bronchial tree - in place of the ciliated - islands of a multilayer flat appear, etc.), others - arise in the process of a number of physiological restructuring of tissues, without tissue loss preceded it (myeloid metaplasia of the spleen, lymph nodes during infections, leukemia). The clinical significance is varied, often unfavorable. So, we are talking about the transition to anaplasia, as a precancerous condition.
It should be noted the inseparable unity of the inflammatory and proper regenerative (reparative) components in a holistic tissue response to damage. Inflammation and regeneration are conditionally separated, all phases of the process overlap in time.
REGENERATION OF INDIVIDUAL TISSUES
Regeneration of the integumentary epithelium takes place in two stages. Initially, proliferation of cells of the Malpighian layer is noted, then the resulting cells cover the defect first with one layer, then the cells multiply and differentiate, and the epithelium becomes multilayered.
Mucosal epithelium regenerates due to the proliferation of cells of the germ layer (crypts and excretory ducts of the glands), which then differentiate.
Connective tissue regeneration begins with the proliferation of young cells and neoplasms of blood vessels. A young connective tissue is formed - granulation. Macroscopically, it is a juicy bright red tissue with a granular surface, as if strewn with large granules. Microscopically, the tissue consists of many vertically arranged capillary-type vessels, between which are located cells of both the inflammatory process (lymphocytes, leukocytes, erythrocytes, often eosinophils) and regenerative (epithelioid, fibroblasts, histiocytes). As the tissue matures, its composition changes: the number of leukocytes decreases, decreases and total cells, but the number of fibrous structures increases, vessels are recalibrated and most capillaries regress. The maturation of granulation tissue culminates in the formation of scar tissue. Granulation tissue fills not only wound and ulcerative skin defects, but is also formed when mucous membranes are damaged, hematomas, blood clots, necrosis, inflammatory exudate, etc. are organized.
Regeneration of small vessels It is carried out in two ways: by autochthonous growth (slits are formed that are lined with endothelium) and by budding, i.e. proliferation of the endothelium.
Regeneration of striated muscles occurs when the sarcolemma is preserved. There is a regeneration of the sarcoplasm and its organelles, satellite cells.
Myocardial regeneration occurs exclusively in the form of intracellular renewal and hyperplasia of ultrastructures in intact muscle fibers. A scar forms at the site of injury.
Bone regeneration occurs in three stages: 1) formation preliminary connective tissue callus associated with the activation and proliferation of osteoblasts in the periosteum and endosteum; 2) education preliminary callus with randomly arranged plates of new bone; 3) education final callus with an ordered arrangement of bone beams.
Liver regeneration. The liver is one of the organs in which cell renewal is slow. Under normal conditions, only a few hepatocytes located near the portal tracts are capable of dividing. The site of damage (necrosis) is always subject to scarring. But in the preserved part of the organ, both new cell formation and hypertrophy of hepatocytes occur due to hyperplasia of intracellular structures. The liver has a very high capacity for reparative regeneration. After resection of two-thirds of the liver, its initial mass increases by 600 times and is restored after 2 weeks.
Peripheral nerve regeneration occurs due to the central segment, which maintains a connection with neurons. Restoration of the nerve fiber sheath occurs by reproduction of the cells of the Schwann sheath, and the axial cylinders grow from the central segment. Regeneration of nerve fibers ends with their myelination and restoration nerve endings. In CNS neurons, only intracellular regeneration is possible. Mixed - cellular and intracellular - regeneration occurs in the neurons of the autonomic ganglia.
Wound healing. According to I.V.Davydovsky, the following types of wound healing are distinguished: 1) direct closure of an epithelium defect - epithelium creeps from the edges onto the defect (on mucous membranes, cornea). 2) under the scab - with small defects, on the surface of which a drying crust (scab) appears from coagulated blood, lymph. The epidermis is restored under the crust, which falls off after 3-5 days. 3) healing by primary intention - occurs in wounds with damage not only to the skin, but also to the underlying tissue. The edges of the wound are even. In the tissues of the wound - edema, hyperemia. The wound fills up with blood. Granulation tissue appears on the 2nd or 3rd day. By 10–15 days, it matures and the wound heals with a delicate scar. 4) wound healing by secondary intention, or healing through suppuration. It is observed with extensive injuries with crushing of tissues, penetration of microbes and foreign bodies into the wound. Within 5–6 days, rejection of necrotic masses occurs, then granulation tissue develops in the wound, which matures with the formation of a scar.
Modern research methods have shown that even the most subtle fluctuations in functional activity, occurring both in a healthy organism and in its diseases, are associated with corresponding structural changes. Therefore, now they do not talk about functional diseases, functional stages. Morphological analysis of various pathological processes showed that one of the characteristic features of the processes of compensation and adaptation is that hyperplastic and regenerative processes are very often localized not at the site of the lesion, but near it. Compensation of disturbed functions due to hyperplasia of cells and intracellular ultrastructures outside the lesion creates a situation in which morphological manifestations are evident (necrosis, sclerosis), and its clinical signs are completely absent due to the neutralization of these changes by intact tissues. And the higher the compensatory capabilities of the body, the longer the appearance of the norm remains. Obviously, the first clinical signs of a disease are very often a signal not of the beginning of it, but of a breakdown in compensation.
GENERAL PATTERNS OF TUMOR GROWTH
Definition.tumor is called tissue growth, which has no adaptive value. Tumor cells differ from normal cells primarily by a decrease in sensitivity to regulatory influences. This property of tumor cells is called relative autonomy(independence). The degree of autonomy of tumor cells can be different. The proliferation of tissues, which has an adaptive value, is called hyperplasia(while remembering the possibility of transforming the hyperplastic process into a tumor).
In domestic oncopathology, the definition of tumors proposed by L.M. Shabad has become widespread: a tumor is an excessive pathological growth of tissues that has become atypical in terms of differentiation and growth and transmits these properties to its derivatives, uncoordinated with the body.
Terminology. Synonyms for the concept of tumor are the following terms: neoplasm, neoplasm(neoplasma), blastoma(blastoma), tumor. Blastomas are often referred to as immature tumors. The term "tumor" refers not only to the tumor process, but also to any swelling of tissues, including inflammatory edema. concept carcinoma (crayfish) is used to refer to immature malignant epithelial tumors. term sarcoma(Greek "fleshy tumor") refers to some types of immature malignant non-epithelial tumors. In international oncological classifications based on English terminology, the concept cancer("cancer") is used to refer to any malignant tumors, and the concept carcinoma("cancer") - only for epithelial malignant neoplasms.
Epidemiology. The epidemiology of tumors is the study of their prevalence. Epidemiological data make it possible to judge the causes and conditions of tumor growth. Tumors develop in every person (the vast majority are benign), in animals and plants, i.e. in all multicellular organisms. Approximately 1–2% of the population develop malignant neoplasms during their lifetime. The most common malignant tumor in men in developed countries is lung cancer (except the United States), in women - breast cancer.
The structure of tumors. Two components are distinguished in the tumor tissue - parenchyma and stroma. Parenchyma is a collection of tumor cells stroma formed by fibrous connective tissue with vessels and nerves, in which the parenchymal elements of the tumor are located. The stroma ensures the vital activity of tumor cells. Depending on the severity of the stroma, two types of tumors are distinguished: organoid(tumors with prominent stroma) and histioid(tumors with an unexpressed stroma).
The effect of tumors on the body. The tumor, increasing in size and at the same time reaching a certain size (different in different organs), causes compression of neighboring organs
MAIN PROPERTIES OF TUMORS
The main properties of tumors include growth, metastasis and the degree of maturity of the parenchymal elements of the tumor.
Page 2 of 16
Chapter 1
GRANULOMATOUS INFLAMMATION AND GRANULOMATOUS DISEASES (GENERAL PROVISIONS, CLASSIFICATION, PATHO- AND MORPHOGENESIS)
According to the concept of G. T. Williams and W. J. Williams, granulomatous inflammation is a variant of chronic inflammation, in which blood monocyte derivatives predominate in the inflammatory cell infiltrate: macrophages, epithelioid and giant multinucleated cells that form limited, compact clusters - granulomas. Thus, granuloma is the main morphological feature of granulomatous inflammation. In the Encyclopedic Dictionary medical terms(vol. I, p. 311) it is indicated that “Gr anulema is a focus productive inflammation, which looks like a dense nodule. This characterization is incomplete and not entirely accurate. A better definition is given by D. O. Adams (1983). He believes that a granuloma is a compact accumulation of macrophages and (or) epithelioid cells with a number of additional features: 1) infiltration by other leukocytes (lymphocytes, plasma cells, neutrophilic or eosinophilic granulocytes); 2) the presence of fibroblasts and the development of sclerosis; 3) the development of destructive changes and necrosis. Given these ideas, as well as data on the etiological factors that cause granulomas, granulomatous inflammation can also be defined as local chronic inflammation caused by insoluble or slowly decaying (persistent) irritants and accompanied by focal accumulations of macrophages or macrophages and epithelioid cells with the presence of giant multinucleated cells, lymphocytes and granulocytes or without them.
It was believed that granulomatous inflammation and the formation of granulomas are caused by insoluble or poorly soluble compounds, however, in recent years, the possibility of granuloma formation in response to colloidal solutions has been shown: antigens adsorbed on carrier granules, immune complexes, haptens that have formed complexes with body proteins. Granulomatous inflammation in the liver and lungs can be caused by persistent circulation of the Hb5 antigen of the hepatitis B virus in the blood (Serov V.V., 1984; Lopatkina T.N. et al., 1985]. An important mechanism in the reproduction of granulomatous inflammation, along with inertia and the foreignness of a substance is its ability to cause delayed-type hypersensitivity (DTH) in the body, i.e., to influence the state of cellular immunity.
Summarizing the literature on the etiology of granulomatous inflammation, endogenous and exogenous factors should be distinguished. Endogenous products include hardly soluble products of tissue damage, primarily fat (for example, soaps), as well as products of impaired metabolism, for example, urates, which cause gout. Among the exogenous - biological (bacteria, fungi, protozoa, helminths, etc.), organic and inorganic substances (dust, aerosol, smoke, etc.), including drugs. A special group is made up of granulomas of unknown etiology.
According to G. Williams and W. Williams (1983), there are several classifications based on certain principles of patho- and morphogenesis.
- Classification based on morphological principle. According to the structure of granulomas, foreign body granulomas and epithelioid granulomas are distinguished, taking into account the presence or absence of epithelioid cells. However, some foreign body granulomas appear to have small numbers of epithelioid cells. According to the point of view of D. O. Adams (1983), three types of chronic inflammatory macrophage reaction to a persistent stimulus can be distinguished in the experiment:
- chronic inflammation with diffuse infiltration by mononuclear phagocytes; 2) with the formation of mature macrophage granulomas; 3) with the formation of epithelioid cell granulomas.
Chronic inflammation with diffuse infiltration by mononuclear phagocytes is caused by: soluble antigens in the presence of delayed-type hypersensitivity (DTH) to them, particles of coal and carmine, fibrin, typhoid bacteria, particles of barium sulfate in low concentration.
Chronic (granulomatous) inflammation with the formation of mature macrophage granulomas, according to D. O. Adams (1983), is caused by high concentrations of barium sulfate, plastic balls, plastic balls coated with antigen in a non-sensitizing dose, high molecular weight polymers, Brucella bacilli, carrageenan , shells of streptococcus.
Chronic (granulomatous) inflammation with the formation of epithelioid cell granulomas is caused by tuberculosis microbacteria, BCG, antigen-coated plastic balls in a sensitizing dose, Freund's complete adjuvant of schistosomes in a sensitizing dose.
In recent years, it has been shown that a number of antigens (organic dusts, thermophilic actinomycetes, avian serum antigen in the form of serum albumin or litter particles and extracts) can cause lung damage - exogenous allergic alveolitis with the formation of epithelioid cell granulomas. Typical epithelioid cell granulomas are caused by beryllium oxide. In addition, epithelioid cell granulomas of unknown etiology may occur, such as in sarcoidosis.
A working group of WHO experts [Cottier A., Turk J. et al., 1974] proposes to distinguish infiltrates with an indication of the cellular composition (for example, macrophage, epithelioid-cellular, etc.) and granulomas. Granulomas are divided into: a) histiocytic; b) epithelioid small; c) epithelioid large (tubercles); d) fibroblastic; e) granulomas with central necrosis; e) granulomas with a central abscess.
This classification resembles the classification of D. O. Adams (1983), however, there are clarifications to it: the terms "histiocytic granulomas" and "histiocyte" are recommended to be used to characterize macrophages of a certain localization (loose connective tissue); therefore, the term "mature macrophage granuloma" is more accurate.
- Classification based on the principle of the rate of cell turnover within the granuloma, i.e., on indicators of cell kinetics. Since a persistent stimulus has a damaging effect on granuloma cells, the latter die, and new ones come in their place. The intensity of this exchange reflects the toxicity of the damaging factor.
Due to the speed of cell metabolism, rapidly and slowly renewing granulomas are isolated.
Rapidly renewing granulomas with the replacement of the bulk of cells within 1-2 weeks produce very toxic substances, primarily infectious agents. In this case, granuloma cells quickly die and are replaced by new ones, so that the pathogenic product, or agent, is present in the cytoplasm of only a part of them. Quite often, such granulomas are epithelioid cells, but silicotic granulomas, which do not have epithelioid cells, are also among them. At the same time, monocytes arriving at the focus of inflammation in the process of differentiation can divide once, which makes it possible to assess the intensity of cell influx into the granuloma by intensity cell division. Two patterns were noted: 1) the influx of cells corresponds to death, i.e., reflects the circulation of cells in the granuloma; 2) with slow cell renewal in the granuloma, most macrophages contain foreign material in the cytoplasm; with rapid cell renewal, only a part of macrophages contains this material. The above classification is applicable to granulomas around foreign bodies.
So, with the introduction of carrageenan, slowly renewing granulomas are formed. With a pulse label of such a granuloma with thymidine-3H, the labeling index is 0.1-0.4%. At the same time, according to W. L. Epstein (1980), granulomas caused by paraffin oil or complete Freund's adjuvant are rapidly renewing: with a pulse label with thymidine-3H, the labeling index is 3-4%. An intermediate position in the rate of cell renewal is occupied by granulomas caused by metals that do not cause allergies.
It should be noted that special research methods can be used to determine the etiology of granulomas around foreign bodies: phase contrast microscopy, polarization analysis, electron microscopy (X-ray diffraction analysis of the material contained in macrophage phagolysosomes). W. L. Epstein et al. (1960), who caused the formation of granulomas around foreign bodies with colloidal solutions, found that they can have two forms: colloidal and corpuscular. Both forms of granulomas differ in structure. In the colloidal form, macrophages lie more densely, may look like epithelial cells with a foamy or fuzzy cytoplasmic structure; such granulomas are similar to granulomas resulting from HRT to antigens.
- Classification based on the principle of the presence or absence of immune complexes during granuloma formation. On this basis, K-Warren (1976) divides all types of granulomatous inflammation into immune and non-immune. Immune granulomatous inflammation includes cell-mediated immune granulomas, in particular those caused by eggs of Schistosoma mansoni, and antibody-mediated, caused by Schistosoma japonice.
Among the non-immune granulomas are most of the granulomas that form around foreign bodies, which K. Warren divides into inactive and active. The former are caused by plastic granules, bentonite, the latter by particles of silicon dioxide, streptococcus shell. W. L. Epstein (1980) designates active non-immune granulomas as cytotoxic, and inactive as benign. At the same time, it should be emphasized that the antibody-mediated mechanisms of granuloma formation have not been fully deciphered. Apparently, they include the absorption of immune complexes by macrophages with subsequent activation of these cells, as well as lymphocyte-mediated regular mechanisms.
- Classification based on diagnostic value(specificity) of the cellular composition of granulomas. On this basis, a number of authors propose to distinguish between specific and nonspecific granulomatous inflammation. We are opposed to this proposal. We consider it necessary to note that each individual granuloma in any granulomatous disease acquires some structural and cellular features, expressed, however, not to such an extent that they should be guided by morphological diagnostics, i.e. recognize them as special. In all works recent years about granulomas in granulomatous diseases and, first of all, infectious granulomas, it is emphasized that in order to establish the etiology of these diseases, which is extremely important for the clinic, in addition to morphological methods in the study of biopsy specimens, for example, lymph nodes, immunocytochemical and bacterioscopic (staining of bacteria in sections) are necessary, as well as bacteriological (crops) and serological studies. With non-infectious granulomas, spectrographic, mineralogical and other special research methods are needed to establish the etiology of granulomatous disease. The formation of a granuloma and its cellular composition can be determined by the biological characteristics of the pathogen. So, on the model of experimental brucellosis, it was shown that the transition of the main species S-form of Brucella to the R-form gives, upon infection, the development of reduced granulomas that do not reach the stage of epithelioid granuloma [Kononov A. V., Zinoviev A. S., 1984]. Similar observations were obtained during experimental infection with L-forms of tuberculous mycobacteria [Zemskova 3. S., Dorozhkova K. R., 1984]. There is evidence of genetic control of the granulomatous immune response. It can be assumed that the problem of reactivity in granulomatous diseases goes beyond the study of only cellular reactions and is closely connected with genetics.
In addition to the classification of granulomas presented above, others have been proposed. So, at present, an attempt has been made to isolate mixed granulomas. Such granulomas are understood as focal accumulations of cells derived from monocytes, combined with accumulations of neutrophilic, eosinophilic granulocytes, with the development of suppuration.
Mixed inflammatory granulomas: 1) North American blastomycosis; 2) South American blastomycosis (paracoccidioidomycosis); 3) chromomycosis; 4) cryptococcosis; 5) coccidioidomycosis; 6) sporotrichosis; 7) swimming pool granuloma (Swimming pool granuloma); 8) primary inoculation tuberculosis; 9) tongue granuloma; 10) protothecosis.
This kind of granulomatous lesions are characteristic of mycoses: such lesions are characterized by a combination of a “foreign body granuloma” type reaction with hypersensitive epithelioid granulomas. In this regard, the term "mixed" granulomas is justified.
However, D. O. Adams (1983) emphasized the possibility of infiltration by granulocytes as an additional feature that is not essential for the allocation of granuloma as a sui generis process.
In the report of the WHO expert commission [Cottier A., Turk J-et al., 1974], when characterizing granulomatous inflammation, the possibility of the formation of necrosis and abscess is indicated, which makes it possible to characterize the features of the granuloma quite fully without resorting to a new term.
J. Michalany and N. S. Michalany (1984) outlined the concept of "polar granulomas". The classification of "polar granulomas", along with the cellular structure, is based on the principle of activity and completeness of phagocytosis, on the one hand, and the etiological agent, on the other. There are two types of "polar" granulomas that exist in leprosy. The first type is tuberculoid. It is characterized by a small amount or absence of infection in the granuloma, which is associated with effective phagocytosis. The second type is non-tuberculoid, characterized by large quantity bacteria due to incomplete phagocytosis. In the latter case, there may be giant cell granulomas and granulomas with "persistent macrophages" that are not able to kill the pathogen and accumulate it in the cytoplasm, i.e., they can be an "environment" for the development of the etiological factor. The authors also distinguish bipolar or interpolar granulomas when both types of polar granulomas are present in the development of the same disease.
The presented materials show that granulomatous inflammation is a complex and multifaceted general pathological process, the classification of which can hardly be limited to just one principle. That is why there have been attempts to give a combined classification of granulomatous inflammation. As an example, we give the classification of granulomatous inflammatory processes in the gastrointestinal tract, proposed by K. Warren (1976). The author identified three groups of such lesions: 1) infectious granulomas; 2) granulomas of foreign bodies; 3) granulomas of unknown etiology. K. Warren attributed tuberculosis, syphilis, actinomycosis, South American blastomycosis, histoplasmosis, amebiasis, schistosomiasis, etc. to infectious granulomas of the gastrointestinal tract.
K. Warren (1976) attributed starch and talc granulomas, suture granulomas, granulomas caused by fats, barium, mercury to foreign body granulomas. Granulomas of unknown etiology include regional enteritis, sarcoidosis, granulomatous gastritis, eosinophilic granuloma, allergic granulomas, and primary biliary cirrhosis.
We believe that the most rational classification of granulomas observed in granulomatous diseases, based on etiology and pathogenesis, which we have developed on the basis of observations and literature data. Classification, or rather, the systematics of granulomas, consists of three parts: A-by etiology; B - by morphology; B - by pathogenesis. According to the etiology, granulomas are divided into four groups. The etiology of some of the granulomas has not been elucidated. Granulomatous diseases of this group have a descriptive morphological designation (for example, sarcoidosis) or are designated by the name of the author who described this disease (for example, Wegener's granulomatosis). Granulomas, isolated according to the mechanism of their occurrence, are divided into two groups: 1st - immune (hypersensitive) granulomas with four subspecies, depending on the nature of the immunopathological mechanism underlying them; 2nd - non-immune granulomas with two subspecies depending on the etiology, the nature of the impact on the tissue of the pathogenic factor and the non-participation of immune mechanisms. This group consists of granulomas observed in acute infections (toxic-infectious, according to our classification) and the majority of granulomas around foreign bodies, both endogenous and exogenous (non-immune toxic granulomas, according to our classification).
At the same time, it should be noted that under practical work The pathologist's study of granulomatous inflammation begins with a macroscopic and microscopic (histological) description. In the macroscopic description, it is important to assess the possibility of granulomatous inflammation, as well as the size and topography of the lesions, the prevalence in organs and within the organ. In histological examination, it is desirable to be guided by a certain classification of granulomas according to their morphology.
We propose the following classification-scheme for the histological description of micropreparations in granulomatous inflammation [Strukov AI, Kaufman O. Ya., 1985].
WORKING CLASSIFICATION OF GRANULOMAS
- Etiology
A.1. Granulomas of established etiology.
ALL. Infectious granulomas.
AL.2. Granulomas are noninfectious.
ALL L. Dust granulomas (inorganic dusts).
A.1.2.2. Dust granulomas (organic dust).
A L.2.3. Medical granulomas.
A. 1.2.4. Granulomas around foreign bodies.
A.1.2.4.1. Granulomas around exogenous foreign bodies.
A.1.2.4.2. Granulomas around endogenous foreign bodies.
- 2. Granulomas of unknown etiology
B. Histology
B.1. Mature macrophage granulomas with size indication.
B. 1.1. No giant multinucleated cells.
B. 1.2. Without epithelioid cells.
B. 1.3. With giant multinucleated cells (give the type of these cells and the ratio of different types).
B. 1.4. With a small number of epithelial cells.
B. 1.5. With the presence of foreign particles (characterize the location of particles: extracellular, intracellular, what percentage of cells contain particles, characterize if possible chemical composition particles: hemosiderin, coal, silicon, etc.).
B.2.1. Epithelioid cell granulomas with indication of size (small and large, or tubercles).
B.2.2. With giant multinucleated cells (cell type, quantitative assessment of the ratio of types and total number).
B.2.3. with fibrous changes.
B.2.4. with necrosis in the center.
B.2.4L. with caseous necrosis
B.2.4.2. with fibrinoid necrosis.
B.2.5. With suppuration in the center.
- Pathogenesis
- 1. Immune hypersensitive granulomas.
B. 1.1. Immune granulomas arising on the basis of granulomatous hypersensitivity (GH) and delayed-type hypersensitivity (DTH) with a predominance of epithelioid cells in the structure of granulomas.
B.1.1.1. Granulomas with established antigen.
B.1.1.2. Granulomas with unknown antigen.
B. 1.2. Immune granulomas resulting from immediate hypersensitivity (IHT) with the formation of circulating immune complexes, vascular damage (capillaries, arteries, veins), increased vascular tissue permeability, development of granulomatous-necrotic vasculitis (antigen is not established in most cases).
B.1.3. Immune granulomas of mixed type.
B.1.3.1. Granulomas with established antigen, infectious-allergic.
B.1.3.2. Granulomas with unknown antigen.
B. 1.4. Immune granulomas with drug hypersensitivity, immunoallergic.
IN 2. Non-immune granulomas, the participation of immune mechanisms in the formation of which has not been proven.
B.2.1. Non-immune infectious-toxic granulomas that occur in acute infectious diseases.
B.2.2. Non-immune granulomas are toxic (most of both exogenous and endogenous granulomas that form around foreign bodies).
In addition, for each form of granuloma, it is desirable to indicate the stage of the process (young, mature, in the stage of necrosis), as well as to characterize the vascularization and the state of the blood and lymphatic vessels in and around the granuloma. In the immunomorphological study of granuloma, along with ascertaining the presence or absence of fixation of immunoglobulins with a characteristic of type and complement, which is important for identifying the mechanisms of granuloma formation, it is desirable to use monospecific sera to various pathogens, as well as to surface antigens of lymphocytes, macrophages, epithelioid cells to characterize the cellular organization of granuloma.
The first group of granulomas is designated as "Mature macrophage granulomas" (Fig. 1, 2). As a rule, these are non-infectious, non-immune granulomas associated with the introduction of insoluble or slightly soluble particles into the internal environment of the body: inorganic and organic: silicate, talc, coal, insoluble minerals, oils. The source of such granulomas can also be endogenous products: keratin, hair, fat, uric acid crystals. In particular, foreign particles can penetrate tissues when dermoid cysts rupture. Cases of granulomatous peritonitis caused by cheesy lubrication of the skin of the fetus during spontaneous rupture of the membranes in pregnant women are described.
A foreign irritant can be corpuscular or colloidal. In a colloidal granuloma, the cells lie dispersed and concentrated around large foreign particles. In addition, foreign material is found in macrophages or giant multinucleated cells. Special meaning has the fact that colloidal granulomas can be caused by lipids, soaps, lipopolysaccharides.
Rice. 1. Macrophage granuloma of the gallbladder wall with single multinucleated cells. operating material. Stained with hematoxylin and eosin. X 150.
Corpuscular granulomas are more studied. In the experiment, they arose when exposed to plastic and other balls and particles: bentonite, sepharose, polyacrylamide, latex, and some metal particles, such as zirconium. Quite often, such granulomas form around the suture material (Fig. 3), sometimes around the accumulation of a drug that is difficult to absorb, such as an antibiotic.
It follows from the classification that some mature macrophage granulomas (rarely) do not contain giant multinucleated cells, while others (more often) do. There are no giant multinucleated cells in the "dust" granulomas of the lungs. S. Y. Vaz and S. C, Costa (1983) described the reaction of the rectal wall to barium sulfate introduced during X-ray examination: macroscopically there was a yellowish-white spot on the rectal wall, and in the submucosal layer, macrophages containing granules in the cytoplasm were found in the form of clusters, similar to barium sulfate granules. R. Camproden et al. (1984) described a ceroid granuloma of the gallbladder wall, consisting of macrophages ("histiocytes", in the terminology of the authors). In the cytoplasm of macrophages, there was a greenish-brown pigment in the form of grains, which was identified as a ceroid.
Rice. 2. Macrophage granuloma in the lungs. Electrongram. Macrophages of varying degrees of maturity are visible. X 3,000 (preparation by O. O. Orekhov).
More often, however, giant multinucleated cells may be present in a mature macrophage granuloma. Identification of giant multinucleated cells cannot serve as a basis for establishing the diagnosis of "foreign body granulomas". As the analysis of literature data shows, the term "foreign body granuloma" is used and used as an indicator of a reaction to a foreign body, regardless of the nature of the structure of the granuloma. So, S. Thomas and I Ruschoff (1984) refer to "foreign body granulomas" the so-called beryllium granulomas, which, according to the authors, are difficult to distinguish from sarcoid or tuberculous. The same can be said for epithelioid granulomas associated with the use of deodorants containing zirconium lactate.
Other researchers, such as W. L. Epstein (1980), who studied "foreign body granulomas", put the immune mechanisms of the process as the basis for determining this type of granuloma.
Rice. 3. Granuloma around a foreign body - suture material. Stained with hematoxylin and eosin. X 150.
According to the definition of W. L. Epstein (1980), foreign body granuloma is a non-immune reaction of mononuclear phagocytes to an insoluble endogenous or exogenous stimulus. At the same time, in the course of inflammation, according to W. L. Epstein, immune mechanisms can also be activated. W. L. Epstein distinguishes, according to the nature of the action of a pathogenic agent on tissues, benign (slowly renewing) forms of tattoo type granulomas and cytotoxic (silicotic type) - see. classification by K. Warren (1976). It is clear that foreign body granulomas in the definitions of W. L. Epstein (1980) are similar to "mature macrophage granulomas" according to D. O. Adams (1983). We recommend using the latter term to eliminate the ambiguity of the name "foreign body granuloma". According to W. L. Epstein (1980), at the first moment, the reaction to a foreign body is in the nature of acute inflammation with the migration of not only mononuclear cells, but also non-trophilic granulocytes. However, by the end of the day, blood monocytes already predominate in the cell infiltrate, rapidly differentiating into macrophages. 
Rice. 4. Epithelioid cell granuloma of the sarcoid type with two giant multinucleated Pirogov-Langhans cells. Staining g (preparation by O. O. Orekhov).
After 32 hours, there are signs of macrophage fusion and giant cell formation.
Epithelioid cell granulomas are of two types: 1) noncaseating sarcoid type (Fig. 4) and 2) epithelioid cell with caseous necrosis (Fig. 5). As an example of two types of granulomas, let's take skin granulomas:
- Sarcoidosis.
- Tuberculosis: a) primary skin tuberculosis; b) secondary inoculation tuberculosis of the skin; c) lupus vulgaris; d) verrucosa cutis; e) scrofuloderma; e) tuberculides.
- Tuberculoid leprosy.
- Tertiary syphilis.
- Zirconium granuloma.
- beryllium granuloma.
- Mercury granuloma.
- Lichen nitidus.
According to O. A. Uvarova et al. (1982), based on the analysis of literature and own research, sarcoid granuloma consists of two clearly defined zones separated by a layer of fibroblasts. 
Rice. 5. Epithelioid cell granuloma with caseous necrosis in the center. Staining with hematoxylin and eosin X2B0
The central zone is formed mainly by epithelioid cells with a small admixture of mature macrophages, lymphocytes, and giant multinucleated cells. In the peripheral zone, the cellular composition is more diverse: macrophages are detected simultaneously with lymphocytes, plasma cells and fibroblasts. As modern data show, lymphocytes located on the periphery of the epithelioid cell center play an important role in the development of inflammation. N. Cain and B Kraus (1982) showed that the center of the granuloma is mainly composed of epithelioid cells, macrophages that do not contain phagosomes, in contact with lymphocytes. The peripheral part of the granulomas consists mainly of large macrophages with many phagosomes, dark epithelioid cells, necrotic elements and other cells. Apparently, the outer zone performs a transitional function. Most "alien" monocytes contain two nuclei, th. probably due to a defect in the divergence of the spindles during mitosis that follows cell injury.
The main cell type of epithelioid cell granulomas of the sarcoid type is the epithelioid cell. Along with the previously characterized cell types, hypertrophied and atrophied epithelioid cells are isolated in the sarcoid granuloma. Hypertrophied cells are found in the center of fresh granulomas [Uvarova OA et al., 1982], atrophied cells are found along the outer border of old granulomas. In hypertrophied epithelioid cells, the endoplasmic granular network, the lamellar complex, a large number of mitochondria and lysosomes, which give an active reaction to acid phosphatase, are well developed. In atrophied epithelioid cells, the number of cell organelles decreases.
Giant multinucleated cells in sarcoid granulomas have a structure corresponding to Pirogov-Langhans cells and giant cells of foreign bodies. In the cytoplasm of giant multinucleated cells and in epithelioid cells, there are special inclusions (asteroid bodies, Schaumann bodies). Sometimes a zone of fibrinoid necrosis can be determined in the center of the granuloma. Hyalinization of epithelioid sarcoid granulomas, according to W. Gusek (1982), is a special case of paraamyloidosis.
Giant multinuclear cells of the Pirogov-Langhans type, under the influence of centrioles and cytoskeleton, have a central organization. These cells have a phagocytic pole, a large multipolar compact cell center, and a nuclear pole. The internal structure of weakly stained giant cells is an indicator of their functional activity. On the contrary, the authors consider intensely stained giant cells to be “depleted”, on the way to possible coagulative necrosis. Cell contacts in granulomas, for example, between macrophages, have the form of desmosome-like connections. It is assumed that their function is fixation and participation in the transmission of information. Epithelioid cells are characterized by the presence of a permanent secretory apparatus, as well as a large centrosphere with numerous radially located dictyosomes of the lamellar complex (Golgi apparatus).
Epithelioid cell granuloma with caseous necrosis is characteristic of tuberculosis. Such a granuloma is called "tubercula" (tubercle) [Davydovsky IV, 1956]. In the tubercle, the main mass of cells are epithelioid cells. Lymphocytes are located along the periphery of the tubercle, and in the center there are 1-2 giant multinucleated cells of the Pirogov-Langhans cell type. Often at the height of proliferation, the center of the tubercle undergoes caseous necrosis. BCG granulomas have a similar structure. The basis of the granuloma is also made up of epithelioid cells. When animals are infected with live BCG, epithelioid granuloma cells contain many lysosomes and are characterized by high activity of lysosomal enzymes - acid hydrolases, while when granulomas are induced by intravenous administration of killed BCG, there are few such structures and enzymes. An important indicator maturity and functional activity of epithelioid cells is beta-galactosidase. A large amount of this enzyme in cells correlates with a small amount of intact BCG in epithelioid cells. According to I. L Turk et al. (1980), BCG granuloma is intensively formed on the 2nd week after infection, when there is a peak of cell infiltration and intensive differentiation of macrophages into epithelioid cells. Caseous necrosis is formed later (in the lymph nodes at the 10th week after infection). However, according to O. O. Orekhov (1986), in the first days after intravenous administration of killed BCG to sensitized rats, pneumonitis occurred with a large number of monocytes and macrophages in the intraalveolar exudate; by the end of the 2nd week, epithelioid cell granulomas with caseous necrosis were formed in the center of some of them, and on the 4-6th week, mature, clearly defined granulomas were visible.
When comparing the structure of mature macrophage granulomas, arising under the influence of non-immune mechanisms, and epithelioid cell granulomas, which are based on immunopathological mechanisms, a cellular grouping of lymphocytes in the epithelioid granuloma is noted, reflecting the regulatory role of these cells in the formation of immune granulomas.
In non-immune granulomas, including granulomas that form around foreign bodies (without the participation of immune mechanisms), lymphocytes and plasma cells are present in small quantities.
The presence of lymphocytes in epithelioid cell granulomas of both types - sarcoid and caseous
necrosis is not only characteristic, but also reflects complex regulatory interactions between classes and various subpopulations of these cells. So, according to
V. V. Mishra et al. (1983), J. J. van den Oord et al., there are certain patterns in the distribution of various subpopulations of T-lymphocytes within epithelioid cell granulomas in both sarcoidosis and tuberculosis. In the center of the granuloma are epithelioid cells bearing on their surface OKM1-- and OK1A+ antigens and multinucleated giant cells; together with them, T-lymphocytes-helpers (OKT4+) are contained in a small amount and T-lymphocytes-suppressors with cytotoxic properties (OKT8+) are in a significant amount. B-lymphocytes were absent in the center of the granuloma, but formed a cap along its periphery and carried predominantly or only igD on their surface. Between this tire and the center of the granuloma, T-lymphocytes were located in the form of a ring of OKT8+ (suppressors).
The presented materials allow us to raise the question of the differences in the regulatory mechanisms of non-immune and immune granulomas. According to W. L. Epstein (1980), in the formation of non-immune granulomas around foreign bodies, autoregulation mechanisms predominate due to biologically active substances, primarily prostaglandins synthesized by granuloma macrophages, as well as other derivatives of arachidonic acid.
An experimental study of this issue was carried out on different models, in particular, on the model of carrageenan granuloma. It has been shown that in the homogenate of such a granuloma there is a low production of PgE and PgF and enzymes involved in the metabolism of prostaglandins. At the same time, there was an increase in the production of thromboxane Bo and 6-KeTo-PgF-2. The content of the latter was more elevated in early period granuloma formation, while the production of thromboxane B2 increased on days 9-13. At the same time, when studying carrageenan granuloma in other experiments, on the 8-12th day of granuloma formation, a significant increase in the content of PgE2 was found, as well as a large number of metabolic products of arachidonic acid. However, regardless of the revealed facts, the important role of biologically active substances in the morphogenesis of non-immune granulomas is undeniable. In some situations, in experiments with the administration of arachidonic acid derivatives, in particular prostaglandins, to animals in which a carrageenan granuloma had previously been reproduced, an increase in the number of cells and mass of such a granuloma was observed (PgF effect), but in other cases there was no such effect or, conversely, a decrease in the mass of the granuloma was found.
Derivatives of the kallikrein-kinin system and the system of blood coagulation and fibrinolysis are also important in the formation of non-immune granulomas.
An important role in the mechanisms of granulomatous inflammation in non-immune, as well as in immune granulomas, is played by neutral and acidic (lysosomal) proteases of macrophages. When characterizing this cell type, we pointed out that macrophages secrete a number of enzymes with an optimum action in a neutral environment: plasminogen activator, collagenase, elastase, angiotensin-converting enzyme, arginase. In addition, macrophages are also able to secrete lysosomal enzymes that “work” at an acidic pH of the environment: esterases, acid hydrolases, etc. These enzymes not only damage and break down tissue structures, but also cause the formation of substances that are chemoattractants for macrophages. Finally, macrophages are able to produce peroxide compounds that have bactericidal activity and can also damage tissue structures.
Products of tissue damage can be a source of antigenic irritation and include immune mechanisms of granuloma formation. Finally, macrophages secrete a special class of biologically active substances - monokines. In the formation of epithelioid granulomas, the mechanisms of cell-mediated immunity, in particular the mechanisms of DTH, play an important role.
The role of HRT can be clearly seen when comparing morphological changes in tuberculoid and lepromatous forms of leprosy. In the tuberculoid form of leprosy, there are epithelioid granulomas with a small number of bacteria, while there is a high reactivity of patients to the intradermal injection of killed M. leprae: it is formed after 2
3 weeks epithelioid granuloma (Mitsud reaction lepromintest, HRT indicator). In leiromatous leprosy, there are widespread infiltrates consisting of
undifferentiated macrophages with foamy cytoplasm and a large number of bacteria. The test for killed M. leprae is negative.
The value of HRT to agents that cause granulomatous inflammation in the morphogenesis of epithelioid granulomas was emphasized by D. O. Adams (1976) and D. L. Boros (1978). HRT, according to D. O. Adams (1983), plays a role in the development of most epithelioid granulomas, but is not a sufficient and mandatory factor for the formation of such granulomas. However, the granulomatous response to corpuscular agents is dramatically enhanced and accelerated in the presence of HRT.
As is known, the mechanisms of HRT are inextricably linked with the function of lymphocytes “sensitized” to a certain antigen. As it turned out, such cells (T-l lymphocytes) secrete a wide range of biologically active substances - lymphokines, which have a variety of regulatory effects on leukocytes, including macrophages (Table 1). This mechanism is extremely important in the formation of epithelioid granulomas, although the ability to form the latter is also present in thymectomy mice.
Table 1. Lymphokines acting on mononuclear phagocytes [Freidlin I. S., 1984]
Lymphokines that act primarily on macrophages |
Lymphokines with cross and multiple biological effects |
Macrophage migration inhibitory factor (MIF) |
Interferon gamma Skin reactive factor; when acting on macrophages, it is similar to MIF and CP Transfer factor |
Note. MIF, in addition to inhibition of macrophage migration, causes aggregation of macrophages, stimulates adhesion and spreading of these cells, fusion of macrophages into giant multinucleated cells; MAF, in addition to activating macrophages, enhances macrophages, increases the phagocytic and digestive activity of these cells.
As can be seen from Table. 1, lymphokines are able to provide the main conditions for the formation of granulomas, which, according to D. O. Adams (1983), consist in: 1) differentiated accumulation of macrophages in the focus of inflammation under the influence of specific chemoattractants;
- differentiated persistence of such an attractant in the presence of specific inhibitors of chemotaxis in the focus of accumulation; 3) organization of a cell-specialized tissue environment. At the same time, macrophages themselves, activated by a pathogenic agent, or by immune complexes, or by products of tissue damage, or by neutrophilic granulocytes, can ensure the implementation of these reactions, which is confirmed by experiments with thymectomy animals.
The most important factor in the formation of a granuloma is a factor that inhibits the migration of macrophages (MIF), as well as a factor that activates the migration of macrophages "(MAF) [Freidlin I. S., 1984; Mishels E. et al., 1983; David J. R. et al. , 1983], interleukins... The factors produced by T-lymphocytes cause the "stop" (accumulation) of macrophages in the focus of granulomatous inflammation, where they are attracted by the action of the stimulus itself or the chemotactic factor (HF) produced by lymphocytes, the aggregation of these cells, their fusion with the formation of giant multinucleated cells, the activation of macrophages with an increase in their microbicidal and cytotoxic functions.Interleukins, in turn, serve for regulatory effects on lymphocytes.Thus, interleukin-1 (IL-1) is a monokine, it is produced by SPS cells and is a regulatory signal for T- lymphocytes - helpers... The latter secrete interleukin-2 (IL-2), which regulates the differentiation of natural killer cells... The significance of these factors in the formation of granulomatous immune inflammation was demonstrated in the work of K-Kobayashi et al. The authors intratracheally administered live BCG to mice of two lines: one, giving a pronounced formation of epithelioid granulomas, the other - giving a low granulomatous response. In granulomas formed in the lungs of mice of a "strongly responding" line, a factor inhibiting the migration of macrophages and IL-1 were found in high concentrations. In parallel with an increase in the concentration of these cytokines, an increase in the suppression of cell-mediated immunity to a specific antigen was noted.
The regulatory function of lymphocytes and the lymphokines secreted by them is important at all stages of the process, especially for maintaining the structure of the granuloma and performing its last protective role. This role is well traced in works on tuberculosis, leprosy, histoplasmosis. In the presence of a defect in the formation of granulomas, a rapid generalization of the process occurs with the identification of a large number of pathogens in the affected tissues. It was also shown that in mice with depletion of the T-lymphocyte system and impaired granuloma formation, when infected with schistosomiasis, extensive foci of necrosis develop around eggs in the liver without a noticeable cellular reaction, severe necrotic lesions of the liver parenchyma in schistosomiasis are also found in thymectomized mice. Mice with impaired T-lymphocyte function and an impaired ability to produce a granulomatous inflammatory response have been found to have an increased susceptibility to BCG.
Granulomatous inflammation, although it is a form of chronic inflammation, but like any inflammation proceeds as a cyclic reaction. The following outcomes (complications) of granulomatous inflammation are possible:
1) resorption of cellular infiltrate; 2) dry (caseous) or wet necrosis with the formation of a tissue defect; 3) suppuration in the granuloma with the formation of an abscess; 4) fibrous transformation of the granuloma with the formation of a fibrous nodule or scar; 5) growth of a granuloma, sometimes with the formation of a pseudotumor.
Let's take a look at each process.
- Complete resorption of the cellular elements of the granuloma, apparently, is possible with a low toxicity of the pathogenic agent and its removal in the early * period of granuloma formation. More often, however, the formation of a focus of sclerosis occurs, followed by remodeling of the scar [Serov VV, Shekhter AB, 1981].
- Necrosis in the granuloma is especially characteristic of tuberculous granuloma, but it also occurs with other infectious granulomas. At the same time, not only proteolytic enzymes secreted by neutrophilic leukocytes and macrophages are involved in the process of necrosis, but also the damaging agent itself, which has a toxic effect, which can be enhanced due to HRT and sensitization of granuloma cells.
Therefore, in mycobacterial and beryllium granulomas, intensive death of macrophages can occur, which determines the so-called rapid cell renewal in the granuloma.
Antibody (immunocomplex mechanisms) play an important role in the development of necrosis. So, with HRT in granulomas caused by intravenous administration of killed BCG to sensitized rats, O. O. Orekhov et al. (1985) noted the fixation of immune complexes in the wall of venules with the development of productive venulitis and arteriolitis and obliteration of the vessel lumen, i.e., changes close to the Arthus phenomenon.
Immune complexes can also be captured by macrophages of the granuloma, which causes damage to the structure of the granuloma [Orekhov O. O. et al., 1985].
- Suppuration in the granuloma is very characteristic of fungal infections. It should be noted that neutrophils are found in most granulomas. At the same time, at an early stage of granuloma formation (the first hours), neutrophils predominate in the exudate, only then the number of monocytes and macrophages increases. The appearance of neutrophy. The molecular granulocytes, as well as macrophages, are determined by the chemotactic properties of the agent, while nonptrophilic granulocytes, as more mobile cells, are the first to arrive at the site of damage. However, in the future, changes in the focus of inflammation are determined by the specificity of the action of chemoattractants on macrophages: in the presence of such specificity, neutrophils gradually disappear from the focus of granulomatous inflammation, suppuration does not develop.
However, in a number of infections: yersiniosis (Fig. 6), tularemia, brucellosis, sapa, microses, substances chemotactic for neutrophilic granulocytes are formed in the inflammation focus, which appear in the inflammation focus and form an infiltrate (the first line of defense). At the same time, in a number of cases (mushrooms), according to V. L. Belyanin et al. (1984), these cells cannot cope with the pathogen, they die, and the products of their death attract macrophages to the focus of inflammation (the second line of defense). A similar mechanism, apparently, is also observed in long-term banal focal suppurative processes. 
Rice. 6. Epithelioid cell granuloma with suppuration (yersiniosis). Stained with hematoxylin and eosin. X150 (preparation D. II Pokoil).
So there are granulomas with an abscess in the center; which the authors call them "mixed".
- Fibrous transformation of the granuloma is the most common outcome of the process. At the same time, the induction of sclerotic processes is possible under the influence of both monokines secreted by macrophages in the granuloma, in particular, secreting epithelioid cells, and the pathogenic agent itself, which has a stimulating effect on fibrogenesis.
Granulomatous inflammation
Granulomatous inflammation -- a specialized form of chronyinflammatory reaction, in which the predominant type cells are activated macrophages having a modified epithelioid appearance. Granulomatous inflammation develops both in chronic immune and infectious diseases, closely related to immune reactions, and in non-immune diseases. Granulomatous inflammation occurs in tuberculosis, sarcoidosis, cat-scratch disease, inguinal lymphogranuloma, leprosy, brucellosis, syphilis, certain fungal infections, berylliosis, and reactions to irritant lipids.
Granuloma -- focal accumulation of cells capable of phagocytosis monocyte-macrophage origin. The main representative of CMF cells is a macrophage, which is formed from a monocyte. In the area of inflammation, the monocyte divides only once, and then transforms into macrophage.
The main conditions for the formation of granulomas are as follows: 1) the damaging agent cannot be removed by phagocytes, cannot be inert and must cause a cellular response; 2) activation of macrophages and their accumulation around the damaging agent should occur. Granuloma formation is a way to eliminate substances that cannot be removed by phagocytosis or digested by macrophages (Granulomatous inflammation as an independent form of inflammation is important mainly in the chronic course of the process. At the same time, granulomatous inflammation can also occur acutely, which is usually observed , with acute infectious diseases - typhus, typhoid fever, rabies, epidemic encephalitis, acute anterior poliomyelitis and some others.
At the heart of the granulomas arising in nervous tissue, lie necrosis of groups of neurons or ganglion cells, as well as small-focal necrosis of the gray or white matter of the head or spinal cord, surrounded by glial elements that perform the function of phagocytes. Glial cells after resorption of necrotic tissue are also involved in the formation of glial scars in the central nervous system. The pathogenetic basis of necrosis is most often inflammatory lesions of microcirculation vessels by infectious agents or their toxins, which is accompanied by the development of hypoxia of the perivascular tissue. In typhoid fever, granulomas occur in lymphoid formations. small intestine and represent accumulations of phagocytes transformed from reticular cells - “typhoid cells”. These are large round cells with a light cytoplasm that phagocytize S. tiphi, as well as detritus formed in solitary follicles. Typhoid granulomas undergo necrosis, which is associated with Salmonella phagocytosed by typhoid cells. Upon recovery, acute granulomas either disappear without a trace, as in typhoid fever, or after them glial scars remain, as in neuroinfections, and in this case, the outcome of the disease depends on the location and volume of these scar formations of the portal tracts.
Granuloma- this is an accumulation of cells of a macrophage nature with the presence or absence of a focus of necrosis in the center. Macroscopically, it is usually a nodule with a diameter of 1-2 mm.
Stages of granuloma formation:
1. The accumulation of monocytes in the focus of inflammation (from the bloodstream).
2. Maturation of monocytes and formation of macrophages.
3. Transformation of macrophages into epithelioid cells.
4. Fusion of epithelioid cells with the formation of giant multinucleated cells. (which as a rule are of 2 types - giant multinucleated cells of the Pirogov-Langhans type and giant multinucleated cells of foreign bodies, see below).
Classification of granulomas.
Depending on the histological structure granulomas can be with the presence of a focus necrosis in the center and the absence. From the predominance of certain cellular elements, there are:
1. Macrophage granulomas.
2. Epithelioid-cellular.
3. Giant cell.
4. Mixed.
Giant cell and, which occurs as a result of an immune response, and macrophages are activated by lymphokines of specific T-cells;
Granuloma foreign those l, in which non-immune phagocytosis of foreign non-antigenic material by macrophages is carried out.
Epithelioid cell granuloma is a collection of activated macrophages.
Epithelioid cells (activated macrophages) appear microscopically as large cells with an excess of pale, foamy cytoplasm; they are called epithelioid because of their distant resemblance to epithelial cells. Epithelioid cells have increased ability to the secretion of lysozyme and various enzymes, but have a reduced phagocytic potential. The accumulation of macrophages is caused by lymphokines, which are produced by activated T cells. Granulomas are usually surrounded by lymphocytes, plasma cells, fibroblasts, and collagen. A typical feature of epithelioid cell granulomas is the formation of giant cells of the type Lankhgansa, which are formed during the fusion of macrophages and are characterized by the presence of 10-50 nuclei along the cell periphery.
An epithelioid cell granuloma forms if two conditions are present:
when macrophages successfully phagocytose the damaging agent, but it remains alive inside them. Excessive pale, foamy cytoplasm reflects an increase in the rough endoplasmic reticulum (secretory function);
when the cellular immune response is active. Lymphokines produced by activated T-lymphocytes inhibit the migration of macrophages and cause their aggregation in the area of damage and the formation of granulomas.
Epithelioid granulomas occur in various diseases.
Depending on the etiology, 2 types of granulomas are distinguished : known and unknown etiology.
Etiology of granulomatosis. There are endogenous and exogenous etiological factors in the development of granulomas. To endogenous factors include sparingly soluble products of damaged tissues, especially adipose tissue (soap), as well as products of impaired metabolism (urates). To exogenous factors that cause the formation of granulomas include biological (bacteria, fungi, protozoa, helminths), organic and inorganic substances (dust, fumes, etc.), incl. medicinal. According to the etiology, granulomas are divided into two groups: granulomas of established etiology and unidentified.
Among the granulomas of established etiology, infectious and non-infectious granulomas are distinguished.
Infectious granulomas include granulomas in typhus and typhoid fever, rabies, viral encephalitis, actinomycosis, schistosomiasis, tuberculosis, leprosy, syphilis, etc.
Non-infectious granulomas develop when organic and inorganic dust enters the body: wool, flour, silicon oxide, asbestos, etc.; foreign bodies; drug effects (granulomatous hepatitis, oleogranulomatous disease).
Granulomas of undetermined etiology include granulomas in sarcoidosis, Crohn's disease, primary biliary cirrhosis, etc.
The pathogenesis of granulomatosis. Granulomatous inflammation proceeds, as a rule, chronically and develops under the following two conditions: the presence of substances that can stimulate SMF, the maturation and transformation of macrophages; resistance of the stimulus to phagocytes. Under conditions of incomplete phagocytosis and altered reactivity of the organism, such an irritant turns out to be the strongest antigenic stimulator for macrophages and T- and B-lymphocytes. Activated macrophage with the help of IL-1 attracts lymphocytes to an even greater extent, contributing to their activation and proliferation, the mechanisms of cell-mediated immunity, in particular, the mechanisms of delayed-type hypersensitivity (DTH), are tied up. In this case, one speaks of an immune granuloma.
Immune granulomas are built according to the type of epithelioid cell granulomas, however, they always contain an admixture of a large number of lymphocytes and plasma cells.
They develop with infections - tuberculosis, leprosy, syphilis, scleroma. Products of tissue damage sometimes become a source of antigenic irritation, and in these cases, autoimmune mechanisms of granuloma formation can be involved. Granulomas caused by dust particles and aerosols containing proteins of birds, fish, animal hair, are antigen-mediated by the mechanism of development.
Non-immune granulomas include most of the granulomas that develop around foreign bodies and consist primarily of organic dust particles. Phagocytosis in the cells of non-immune granulomas is more perfect. They are built according to the type of phagocytoma or giant cell granuloma, consisting of cells of foreign bodies. When comparing these granulomas with immune ones, a smaller number of lymphocytes and plasma cells are noted.
Those are called specific granulomas that cause specific pathogens (mycobacterium tuberculosis, leprosy, pale treponema and scleroma bacillus). They are characterized by relatively specific morphological manifestations (only for these pathogens and for no others), and the cellular composition, and sometimes the location of the cells inside the granulomas (for example, in tuberculosis) are also quite specific.
Distinguish infectious and non-infectious granulomas. In addition, distinguish specific and nonspecific granulomas.
Specific granulomas- this is a type of granulomatous inflammation in which, by its morphology, it is possible to determine the nature of the pathogen that caused this inflammation. Specific granulomas include granulomas in tuberculosis, syphilis, leprosy, and scleroma.
Non-infectious granulomas occur with dust diseases (silicosis, talcosis, asbestosis, etc.), drug effects (oleogranulomas), around foreign bodies.
To granulomas unidentified nature include granulomas in sarcoidosis, Crohn's disease, Wegener's granulomatosis, etc.
Initially microscopic, the granulomas enlarge, merge with each other, and may take the form of tumor-like nodes. Necrosis often develops in the granuloma zone, which is subsequently replaced by scar tissue.
In a large number of infectious granulomas (for example, in specific infectious diseases), caseous necrosis develops in the center. Macroscopically, the caseous masses appear yellowish-white and look like cottage cheese; microscopically, the center of the granuloma appears granular, pink, and amorphous. similar shape necrosis, called gummous necrosis, occurs with syphilis, it is macroscopically similar to rubber (hence the term "hummous"). In non-infectious epithelioid granulomas, caseosis is not observed.
When foreign material is so large that it cannot be phagocytized by a single macrophage, inert and non-antigenic (does not cause any immune response), penetrates into the tissue and remains there, foreign body granulomas are formed. Non-antigenic material, such as suture material, talc particles, is removed by macrophages by non-immune phagocytosis. Macrophages accumulate around phagocytosed particles and form granulomas. They often contain giant cells of foreign bodies, which are characterized by the presence of numerous nuclei scattered throughout the cell, and not around the periphery, as in giant cells of the Langhans type. Foreign material is usually found in the center of the granuloma, especially when examined in polarized light, because it has refractive power.
Foreign body granuloma has a slight clinical significance and indicates only the presence of poorly phagocytosed foreign material in the tissue; eg, granulomas around talc particles and cotton fibers in the alveolar septum and portal areas of the liver
Granulomas occur in diseases that have a chronic, undulating nature of the course, i.e. with periods of exacerbations and remissions. As a rule, with all these diseases, a special type of necrosis develops - caseous necrosis.
tuberculous granuloma contains a rounded zone in the center telltale (caseous) necrosis. Surrounding the necrosis are activated macrophages known as epithelioid cells. They form a circulatory layer of varying thickness. Among them there are multinucleated Langhans giant cells resulting from the fusion of epithelioid cells. Mycobacterium tuberculosis is found in the cytoplasm of epithelioid and giant cells when stained by Ziehl-Neelsen. The outer layers of the granuloma are sensitized T-lymphocytes. When impregnated with silver salts, a thin network of argyrophilic (reticular) fibers is found among the granuloma cells. Blood vessels in a tuberculous granuloma do not meet.
Most early stage development of tuberculous granuloma - epithelioid cell granuloma- does not yet have a zone of necrosis in the center. Possible options for the progression of a developed granuloma are rapid development of caseous necrosis (caseification), reaching significant volumes with an unfavorable course of the disease.
Fibrosis and petrification(calcification, calcification) are observed during the healing of tuberculous foci. Syphilitic granuloma (gumma) contains in the center a focus of caseous necrosis, larger than in a tuberculous granuloma. On the periphery of the necrosis zone there are many lymphocytes, plasma cells and fibroblasts. Epithelioid cells, macrophages, and single Langhans giant cells can be found in a small amount in the gumma. Syphilitic granuloma is characterized by rapid growth of dense connective tissue due to the proliferation of fibroblasts, which forms a kind of capsule. On the inside of this capsule, among the cells of the infiltrate, numerous small vessels with symptoms of productive endovasculitis. It is extremely rare among the cells of the infiltrate with the help of silvering it is possible to identify pale treponema. In addition to gum in the tertiary period of syphilis, gummous infiltration. Gummatous infiltrate is represented by the same cells as in gumma, i.e. lymphocytes, plasma cells and fibroblasts. At the same time, granulomatous tissue grows very quickly. Among the cells of the infiltrate, a large number of capillary-type vessels with signs of productive vasculitis are detected. Such changes most often develop in the ascending part and in the thoracic aortic arch and are called syphilitic mesaortitis. The gummous infiltrate, located in the middle and outer shells of the aorta, together with the affected vasa vasorum, destroys the elastic framework of the aorta. Connective tissue develops in place of elastic fibers. It is in these areas that the inner shell of the aorta becomes uneven, wrinkled, with many cicatricial retractions and protrusions and resembles shagreen skin. Under the pressure of blood in the lesions, the aortic wall swells, forming thoracic aortic aneurysm.
Leprosy granuloma (leproma) has a polymorphic cellular composition: macrophages, epithelioid cells, giant cells, plasma cells, fibroblasts. Mycobacteria are found in macrophages in large quantities. These macrophages are called Virchow's leprosy cells. They are full of mycobacteria, which lie in them in strictly ordered rows, resembling cigarettes in a pack. Mycobacteria then stick together to form leprosy balls. The macrophage is destroyed over time, and the precipitated leprosy balls are phagocytosed by giant cells of foreign bodies. The presence of a huge amount of mycobacteria in leprosy is due to incomplete phagocytosis in macrophages during leprosy.
The tuberculoid form of leprosy proceeds clinically benignly, sometimes with self-healing, against the background of pronounced cellular immunity. The skin lesion is diffuse, with many spots, plaques and papules, followed by depigmentation of the affected areas. Morphologically detect epithelioid-cellular granulomas, and mycobacteria are found in rare cases. All this confirms the development of leproma according to the type of HRT. Nerve changes are characterized by diffuse infiltration of epithelioid cells, which is manifested by early sensory disturbances. Changes in the internal organs for this form are uncharacteristic.
Leprosy form of leprosy. The skin lesion is often diffuse in nature, and the appendages of the skin are involved, and then completely destroyed - the sweat and sebaceous glands, the vessels are damaged. In leproma, macrophages, giant cells and many mycobacteria are found. Diffuse infiltration of the skin of the face sometimes leads to complete disfigurement of the appearance (“lion's face”). Leprosy neuritis is ascending, diffuse infiltration of all elements of sensory nerves by macrophages develops with gradual replacement of the nerve fiber with connective tissue. Granulomas are found in the liver, spleen, bone marrow, lymph nodes, the mucous membrane of the upper respiratory tract, and in the endocrine glands.
Scleroma granuloma characterized by the accumulation of macrophages, lymphocytes, a large number of plasma cells and their degradation products - eosinophilic Roussel bodies. Specific to granuloma scleroma are very large mononuclear cells with vacuolated cytoplasm -- mikulich cells . The macrophage actively captures diplobacilli, but phagocytosis in them is incomplete. Part of the macrophages is destroyed, and part, becoming larger, turns into Mikulich cells, in which the causative agent of scleroma, the Volkovich-Frisch stick, is found.
Scleroma granuloma is usually located in the mucous membrane of the upper respiratory tract - the nose, larynx, trachea, less often - the bronchi. The process ends with the formation of coarse scar tissue in place of granulomas. As a result, the mucous membrane is deformed, the airways are sharply narrowed and even sometimes completely closed, causing the risk of asphyxia.
Outcomes of granulomas:
1. Resorption of cellular infiltrate- a rare outcome, since granulomatosis is most often a variant of chronic inflammation. This is possible only in cases of low toxicity of the pathogenic factor and its rapid elimination from the body. Examples are acute infections - rabies, typhoid fever.
2. Fibrous transformation of granuloma with the formation of a scar or fibrous nodule. This is the most common and typical outcome of the granuloma. The development of sclerosis is stimulated by IL-1 secreted by granuloma macrophages, and often by the pathogen itself.
3. granuloma necrosis it is characteristic primarily for tuberculous granuloma, which can completely undergo caseous necrosis, as well as for a number of infectious granulomas. The development of necrosis involves proteolytic enzymes of macrophages, as well as products secreted by a pathogenic agent, which have a direct toxic effect on tissues.
4. suppuration granuloma occurs with fungal infections, many infections (sap, yersiniosis, tularemia) and fungal infections. Initially, many neutrophils appear, but only in cases of mycotic lesions they do not cope with the pathogen and die, and the products of their death, being chemoattractants, attract macrophages.
Literature
1. Lectures on general pathological anatomy. Textbook./ Ed. academician of RAS and RAMS, professor M.A. Paltseva. - M., 2003. - 254 p.
2. Pathological anatomy. A.I. Strukov, V.V. Serov.
Granulomatous inflammation Granulomatous inflammation is a specialized form of chronic inflammatory response in which activated macrophages with a modified epithelioid appearance are the predominant cell type. Granulomatous inflammation develops both in chronic immune and infectious diseases closely related to immune reactions, and in non-immune diseases. Granulomatous inflammation occurs in tuberculosis, sarcoidosis, cat scratch disease, inguinal lymphogranuloma, leprosy, brucellosis, syphilis, some fungal infections, berylliosis and reactions to the introduction of irritating lipids.
Granuloma is a focal accumulation of cells capable of phagocytosis of monocyte-macrophage origin. The main representative of CMF cells is a macrophage, which is formed from a monocyte. In the area of inflammation, a monocyte divides only once, and then transforms into a macrophage. The main conditions for the formation of granulomas are as follows: 1) the damaging agent cannot be removed by phagocytes, cannot be inert and must cause a cellular response; 2) activation of macrophages and their accumulation around the damaging agent should occur.
Granuloma formation is a way to eliminate substances that cannot be removed by phagocytosis or digested by macrophages (Granulomatous inflammation as an independent form of inflammation is important mainly in the chronic course of the process. However, granulomatous inflammation can also occur acutely, which is usually observed with acute infectious diseases - typhus, typhoid fever, rabies, epidemic encephalitis, acute anterior poliomyelitis and some others.
The granulomas arising in the nervous tissue are based on necrosis of groups of neurons or ganglion cells, as well as small-focal necrosis of the gray or white matter of the brain or spinal cord, surrounded by glial elements that perform the function of phagocytes. After resorption of necrotic tissue, glial cells also participate in the formation of glial scars in the central nervous system.
The pathogenetic basis of necrosis is most often inflammatory lesions of the microcirculation vessels by infectious agents or their toxins, which is accompanied by the development of hypoxia of the perivascular tissue. In typhoid fever, granulomas occur in the lymphoid formations of the small intestine and are accumulations of phagocytes transformed from reticular cells - “typhoid cells”. These are large round cells with a light cytoplasm that phagocytize S. tiphi, as well as detritus formed in solitary follicles.
Typhoid granulomas undergo necrosis, which is associated with Salmonella, phagocytized typhoid cells. When recovering, acute granulomas disappear either without a trace, as in typhoid fever, or glial scars remain after them, as in neuroinfections, and in this case, the outcome of the disease depends on the location and volume of these cicatricial formations of the portal tracts.
A granuloma is an accumulation of cells of a macrophage nature with or without a focus of necrosis in the center. Macroscopically, it is usually a nodule with a diameter of 1-2 mm. Stages of granuloma formation: 1. The accumulation of monocytes in the focus of inflammation (from the bloodstream). 2. Maturation of monocytes and formation of macrophages. 3. Transformation of macrophages into epithelioid cells. 4. Fusion of epithelioid cells to form giant multinucleated cells. (which as a rule are of 2 types - giant multinucleated cells of the Pirogov-Langhans type and giant multinucleated cells of foreign bodies, see below). Classification of granulomas. Depending on the histological structure, granulomas can be with or without necrosis in the center.
From the predominance of certain cellular elements, there are: 1. macrophage granulomas. 2. Epithelioid-cellular. 3. Giant cell. 4. Mixed. Giant cell and epithelioid cell granuloma, which occurs as a result of an immune response, and macrophages are activated by specific T-cell lymphokines; Foreign body granuloma, in which non-immune phagocytosis of foreign non-antigenic material by macrophages is carried out.
An epithelioid cell granuloma is a collection of activated macrophages. Epithelioid cells (activated macrophages) appear microscopically as large cells with excess pale, foamy cytoplasm; they are called epithelioid because of their distant resemblance to epithelial cells.
Epithelioid cells have an increased ability to secrete lysozyme and various enzymes, but have a reduced phagocytic potential. The accumulation of macrophages is caused by lymphokines, which are produced by activated T cells. Granulomas are usually surrounded by lymphocytes, plasma cells, fibroblasts and collagen. A typical feature of epithelioid cell granulomas is the formation of giant Lanchhans-type cells, which are formed by the fusion of macrophages and are characterized by the presence of 10-50 nuclei at the cell periphery.
An epithelioid cell granuloma is formed if there are two conditions: when macrophages successfully phagocytize the damaging agent, but it remains alive inside them. Excessive pale, foamy cytoplasm reflects an increase in the rough endoplasmic reticulum (secretory function); when the cellular immune response is active.
Lymphokines produced by activated T-lymphocytes inhibit the migration of macrophages and cause their aggregation in the area of damage and the formation of granulomas. Epithelioid granulomas occur in various diseases. Depending on the etiology, 2 types of granulomas are distinguished: known and unknown etiology. Etiology of granulomatosis. There are endogenous and exogenous etiological factors in the development of granulomas. Endogenous factors include sparingly soluble products of damaged tissues, especially adipose tissue (soap), as well as products of impaired metabolism (urates). Exogenous factors that cause the formation of granulomas include biological (bacteria, fungi, protozoa, helminths), organic and inorganic substances (dust, fumes, etc.), incl. medicinal.
According to the etiology, granulomas are divided into two groups: granulomas of established etiology and unidentified. Among granulomas of established etiology, infectious and non-infectious granulomas are distinguished. Infectious granulomas include granulomas with typhus and typhoid fever, rabies, viral encephalitis, actinomycosis, schistosomiasis, tuberculosis, leprosy, syphilis, etc. Non-infectious granulomas develop when organic and inorganic dust enters the body: wool, flour, silicon oxide, asbestos, etc. .; foreign bodies; drug effects (granulomatous hepatitis, oleogranulomatous disease). Granulomas of undetermined etiology include granulomas in sarcoidosis, Crohn's disease, primary biliary cirrhosis, etc. Pathogenesis of granulomatosis .
Granulomatous inflammation proceeds, as a rule, chronically and develops under the following two conditions: the presence of substances that can stimulate SMF, the maturation and transformation of macrophages; resistance of the stimulus to phagocytes.
Under conditions of incomplete phagocytosis and altered reactivity of the organism, such an irritant turns out to be the strongest antigenic stimulator for macrophages and T- and B-lymphocytes.
Activated macrophage with the help of IL-1 attracts lymphocytes to an even greater extent, contributing to their activation and proliferation, the mechanisms of cell-mediated immunity, in particular, the mechanisms of delayed-type hypersensitivity (DTH), are tied up. In this case, one speaks of an immune granuloma. Immune granulomas are built according to the type of epithelioid cell granulomas, however, they always contain an admixture of a large number of lymphocytes and plasma cells. They develop with infections - tuberculosis, leprosy, syphilis, scleroma.
Products of tissue damage sometimes become a source of antigenic irritation, and in these cases, autoimmune mechanisms of granuloma formation can be involved. Granulomas caused by dust particles and aerosols containing proteins of birds, fish, animal hair, are antigen-mediated by the development mechanism. Most of the granulomas that develop around foreign bodies and consist primarily of organic dust particles belong to non-immune granulomas. Phagocytosis in the cells of non-immune granulomas is more perfect. They are built according to the type of phagocytoma or giant cell granuloma, consisting of cells of foreign bodies. When comparing these granulomas with immune ones, a smaller number of lymphocytes and plasma cells are noted.
Specific call those granulomas that cause specific pathogens (mycobacterium tuberculosis, leprosy, pale treponema and scleroma bacillus). They are characterized by relatively specific morphological manifestations (only for these pathogens and for no others), and the cellular composition, and sometimes the location of the cells inside the granulomas (for example, in tuberculosis) are also quite specific. There are infectious and non-infectious granulomas.
In addition, specific and nonspecific granulomas are distinguished. Specific granulomas are a type of granulomatous inflammation in which, by its morphology, it is possible to determine the nature of the pathogen that caused this inflammation.
Specific granulomas include granulomas in tuberculosis, syphilis, leprosy, and scleroma. Non-infectious granulomas are found in dust diseases (silicosis, talcosis, asbestosis, etc.), drug exposure (oleogranulomas), around foreign bodies. Granulomas of an unknown nature include granulomas in sarcoidosis, Crohn's disease, Wegener's granulomatosis, etc. Initially, microscopic, granulomas increase, merge with each other, and may take the form of tumor-like nodes. Necrosis often develops in the granuloma zone, which is subsequently replaced by scar tissue.
In a large number of infectious granulomas (for example, in specific infectious diseases), caseous necrosis develops in the center. Macroscopically, the caseous masses appear yellowish-white and look like cottage cheese; microscopically, the center of the granuloma appears granular, pink, and amorphous. A similar form of necrosis, termed humous necrosis, occurs in syphilis and is macroscopically similar to rubber (hence the term "humous"). In non-infectious epithelioid granulomas, caseosis is not observed.
When foreign material is so large that it cannot be phagocytized by a single macrophage, inert and non-antigenic (does not cause any immune response), penetrates into the tissue and remains there, foreign body granulomas are formed. Non-antigenic material, such as suture material, talc particles, is removed by macrophages by non-immune phagocytosis. Macrophages accumulate around phagocytized particles and form granulomas.
They often contain giant cells of foreign bodies, which are characterized by the presence of numerous nuclei scattered throughout the cell, and not around the periphery, as in giant cells of the Lanchhans type. Foreign material is usually found in the center of the granuloma, especially when examined in polarized light, because it has refractive power. Foreign body granuloma is of little clinical significance and only indicates the presence of poorly phagocytosed foreign material in the tissue; for example, granulomas around talc particles and cotton fibers in the alveolar septum and portal areas of the liver. Granulomas occur in diseases that have a chronic, undulating course, i.e. with periods of exacerbations and remissions.
As a rule, with all these diseases, a special type of necrosis develops - caseous necrosis. A tuberculous granuloma contains a rounded area of cheesy (caseous) necrosis in the center. Around the necrosis are activated macrophages known as epithelioid cells.
They form a circulatory layer of varying thickness. Among them are multinucleated giant Langhans cells, resulting from the fusion of epithelioid cells. Mycobacterium tuberculosis is found in the cytoplasm of epithelioid and giant cells when stained by Ziehl-Neelsen. The outer layers of the granuloma are represented by sensitized T-lymphocytes. When impregnated with silver salts, a thin network of argyrophilic (reticular) fibers is found among the granuloma cells.
Blood vessels in a tuberculous granuloma do not meet. The earliest stage in the development of tuberculous granuloma - epithelioid cell granuloma - does not yet have a zone of necrosis in the center. Possible options for the progression of a developed granuloma is the rapid development of caseous necrosis (caseification), which reaches significant volumes with an unfavorable course of the disease. Fibrosis and petrification (calcification, calcification) are observed during the healing of tuberculous foci.
A syphilitic granuloma (gumma) contains a focus of caseous necrosis in the center, larger than in a tuberculous granuloma. On the periphery of the necrosis zone there are many lymphocytes, plasma cells and fibroblasts. Epithelioid cells, macrophages and single Langhans giant cells can be found in a small amount in the gumma. Syphilitic granuloma is characterized by rapid growth of dense connective tissue due to the proliferation of fibroblasts, which forms a kind of capsule.
On the inside of this capsule, among the cells of the infiltrate, numerous small vessels with manifestations of productive endovasculitis are visible. It is extremely rare among the cells of the infiltrate with the help of silvering it is possible to identify pale treponema. In addition to gummas, gummous infiltration can develop in the tertiary period of syphilis. The gummous infiltrate is represented by the same cells as in gumma, i. lymphocytes, plasma cells and fibroblasts.
At the same time, granulomatous tissue grows very quickly. Among the cells of the infiltrate, a large number of capillary-type vessels with signs of productive vasculitis are detected. Such changes most often develop in the ascending part and in the thoracic aortic arch and are called syphilitic mesaortitis. The gummous infiltrate, located in the middle and outer shells of the aorta, together with the affected vasa vasorum, destroys the elastic framework of the aorta. Connective tissue develops in place of the elastic fibers.
It is in these areas that the inner shell of the aorta becomes uneven, wrinkled, with many cicatricial retractions and protrusions and resembles shagreen skin. Under the pressure of blood in the lesion, the wall of the aorta bulges, forming an aneurysm of the thoracic aorta. Leprosy granuloma (leproma) has a polymorphic cellular composition: macrophages, epithelioid cells, giant cells, plasma cells, fibroblasts. Mycobacteria are detected in macrophages in large quantities. Such macrophages are called Virchow's leprosy cells.
They are full of mycobacteria, which lie in them in strictly ordered rows, resembling cigarettes in a pack. The mycobacteria then stick together to form leprosy balls. The macrophage is destroyed over time, and the precipitated leprosy balls are phagocytosed by giant cells of foreign bodies. The presence of a huge amount of mycobacteria in leprosy is due to incomplete phagocytosis in macrophages during leprosy. The tuberculoid form of leprosy proceeds clinically benignly, sometimes with self-healing, against the background of pronounced cellular immunity.
The skin lesion is diffuse, with many spots, plaques and papules, followed by depigmentation of the affected areas. Morphologically, epithelioid cell granulomas are detected, and mycobacteria are detected in rare cases. All this confirms the development of leproma by the type of HRT. Nerve changes are characterized by diffuse infiltration of epithelioid cells, which is manifested by early sensory disturbances.
Changes in the internal organs for this form are uncharacteristic. Leprosy form of leprosy. Skin lesions are often diffuse in nature, and appendages of the skin are involved and then completely destroyed - sweat and sebaceous glands, vessels are damaged. Macrophages, giant cells and many mycobacteria are found in leprosy. Diffuse infiltration of the skin of the face sometimes leads to complete disfigurement of the appearance (“lion's face”). Leprosy neuritis is ascending, diffuse infiltration of all elements of sensory nerves by macrophages develops with gradual replacement of the nerve fiber with connective tissue.
Granulomas are found in the liver, spleen, bone marrow, lymph nodes, the mucous membrane of the upper respiratory tract, and in the endocrine glands. Scleroma granuloma is characterized by an accumulation of macrophages, lymphocytes, a large number of plasma cells and their degradation products - Roussel's eosinophilic bodies. Specific for scleroma granuloma are very large single-nuclear cells with vacuolated cytoplasm - Mikulich cells.
The macrophage actively captures diplobacilli, but phagocytosis in them is incomplete. Part of the macrophages is destroyed, and part, becoming larger, turns into Mikulich cells, in which the causative agent of scleroma, the Volkovich-Frisch bacillus, is found. Scleroma granuloma is usually located in the mucous membrane of the upper respiratory tract - the nose, larynx, trachea, less often - the bronchi. The process ends with the formation of coarse scar tissue in place of granulomas.
As a result, the mucous membrane is deformed, the airways are sharply narrowed and even sometimes completely closed, causing the risk of asphyxia. Outcomes of granulomas: 1. Resorption of cellular infiltrate is a rare outcome, since granulomatosis is most often a variant of chronic inflammation. This is possible only in cases of low toxicity of the pathogenic factor and its rapid elimination from the body.
Examples are acute infections - rabies, typhoid fever. 2. Fibrous transformation of the granuloma with the formation of a scar or fibrous nodule. This is the most common and typical outcome of the granuloma. The development of sclerosis is stimulated by IL-1 secreted by granuloma macrophages, and often by the pathogen itself. 3. Granuloma necrosis is characteristic primarily for tuberculous granuloma, which can completely undergo caseous necrosis, as well as for a number of infectious granulomas. Proteolytic enzymes of macrophages are involved in the development of necrosis, as well as products secreted by a pathogenic agent that have a direct toxic effect on tissues. 4. Granuloma suppuration occurs with fungal infections, many infections (glanders, yersiniosis, tularemia) and fungal infections.
Initially, many neutrophils appear, but only in cases of mycotic lesions they do not cope with the pathogen and die, and the products of their death, being chemoattractants, attract macrophages. Literature 1. Lectures on general pathological anatomy.
Textbook./ Ed. Academician of RAS and RAMS, Professor M.A. Paltsev. - M 2003. - 254 p. 2. Pathological anatomy. A.I. Strukov, V.V. Serov.
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