Inflammation is one of the most complex processes often encountered in human pathology and often the cause of many impairments to the vital functions of the human body and animals.

Inflammation is important issue  and the subject of study of all branches of medicine and refers to those phenomena of discussion about the essence of which for centuries have been conducted by physicians, biologists, philosophers. The problem of inflammation is as old as medicine itself.

However, there is still no single idea of ​​where the place of inflammation is in biology, medicine, and pathology. Therefore, there is not yet an exhaustive definition of this process.

For the first time, the most complete definition of the essence of inflammation was given by G.Z.Movat (1975).

Inflammation (Greek. - phlogosis; Lat. - inflammatio) is the reaction of living tissue to damage, consisting in certain changes in the terminal vascular bed, blood, connective tissue, aimed at destroying the agent causing the damage, and at restoring the damaged tissue.

Currently, most experts believe that inflammation (B) is a protective-adaptive homeostatic response of the body to pathogenic factors formed during the evolution process, which consists of a vascular-mesenchymal reaction to damage. The protective and adaptive value of V. was first described by I.I. Swordsmen. The biological meaning of inflammation as an evolutionarily established process consists in the elimination or restriction of the source of damage and the pathogenic agents that caused it. Inflammation is ultimately aimed at “cleansing” the internal environment of the body from an alien factor or damaged, altered “its” with the subsequent rejection of this damaging factor and the elimination of the consequences of damage.

V. quite often appears as a protective-adaptive reaction in its imperfect form. In pathology, being more often an individual rather than a species-specific reaction, inflammation depends on the characteristics of both the damaging agent and the damage and the nonspecific and specific reactivity of the organism. Inflammation in these conditions from the phenomenon of biological, often becomes purely medical.

V., as well as any protective reaction of the organism, is excessive relative to its stimuli and therefore often transforms into a typical pathological process. Being an evolutionarily developed protective process, V. at the same time has a damaging effect on the body. Locally, this is manifested by excessive damage to normal cellular elements during the destruction and elimination of all foreign matter. This whole, predominantly local process in one way or another involves the whole organism and, above all, such systems as the immune, endocrine and nervous systems.

Thus, V. in the history of the animal world was formed as a dual process, in which there are and always are elements of protective and harmful. On the one hand, it is damage with a threat to the organ and even to the whole organism, and on the other hand, it is a favorable process that helps the body in the struggle for survival. In general pathology, inflammation is usually regarded as a “key” general pathological process, since has all the features inherent in general pathological processes.

Inflammation is a typical pathological process formed in evolution as a protective and adaptive response of the body to the effects of pathogenic (phlogogenic) factors, aimed at localizing, destroying and removing the phlogogenic agent, as well as eliminating the consequences of its action and is characterized by alteration, exudation and proliferation.

ETIOLOGY OF INFLAMMATION

Inflammation occurs as a reaction of the body to the pathogenic stimulus and the damage it causes. Pathogenic, called in this case phlogogenic, stimuli, i.e. causes of inflammation can be diverse: biological, physical, chemical, both exogenous and endogenous.

Endogenous factors, factors arising in the body as a result of another disease include tissue decay products, blood clots, heart attacks, hemorrhages, gallstones or urinary stones, salt deposits, salt complexes, antigen-antibody complexes. Inflammation may occur as a reaction to the tumor. The cause of inflammation may be saprophytic microflora.

With a huge variety of causes, inflammation in its main features is of the same type, whatever the cause and wherever it is located. A variety of effects like extinguished in the uniformity of response. That is why inflammation refers to typical pathological processes.

The development of inflammation, its nature, course and outcome, are determined not only by the etiological factor (the power of the phlogogenic stimulus, its features), but also by the reactivity of the organism, by the conditions in which it acts.

MAIN CLINICAL SIGNS OF INFLAMMATION

Inflammation is predominantly a local manifestation of the general reaction of the body to the action of a pathogenic extreme irritant. This, mainly local process, in one way or another involves the whole organism and, above all, such systems as nervous, endocrine and immune.

Local signs of inflammation.

The main signs of inflammation known for a long time. The Roman scholar Encyclopedist A. Celsus also highlighted the following main local symptoms of inflammation in his treatise “On Medicine”: redness (rubor), swelling (tumor), fever (color) and pain (dolor). Roman doctor and naturalist K. Galen to the four signs of inflammation, highlighted by A. Celsus, added the fifth - dysfunction (functio laesa). Although these symptoms, characteristic of acute inflammation of the external integument, have been known for more than 2000 years, they have not lost their significance even today. Over time, not only their explanation, pathophysiological and pathomorphological characteristics changed.

Redness  - a bright clinical sign of inflammation associated with the expansion of arterioles, the development of arterial hyperemia and “arterialization” of venous blood in the focus of inflammation.

Swelling  during inflammation due to the formation of infiltration, due to the development of exudation and edema, swelling of tissue elements.

Heat, an increase in temperature, develops as a result of an increased inflow of warm arterial blood, as well as as a result of the activation of metabolism, an increase in heat production and heat transfer in the focus of inflammation.

Pain  - a constant satellite of inflammation, occurs as a result of irritation of the sensory nerve endings with various biologically active substances (histamine, serotonin, bradykinin, etc.), a shift in the pH of the internal environment to the acidic side, the occurrence of disionia, an increase in osmotic pressure in the focus of damage caused by increased tissue breakdown, mechanical compression of tissue released from the bloodstream into the surrounding tissue fluid.

Dysfunction  on the basis of inflammation occurs, as a rule, always; sometimes it can be limited to a disorder of the function of the affected tissue, but more often the whole body suffers, especially when inflammation occurs in vital organs. Impaired function of the inflamed organ, which is a permanent and important symptom of inflammation, is associated with structural damage, the development of pain, and the disorder of its neuroendocrine regulation.

In chronic inflammation and inflammation of the internal organs, some of these symptoms may be absent.

Common signs of inflammation

Inflammation is a process that is manifested not only by pronounced local signs, but also by very characteristic and often significant changes in the whole organism. Among the factors responsible for the interrelation of local and general changes in inflammation, along with autocoids formed and circulating in the blood (clinics, components of the complement, prostaglandins, interferons, etc.), so-called acute-phase reactants are of great importance. These substances are not specific for inflammation, they appear after a variety of tissue damage, including after injury during inflammation. Of these, C-reactive protein,-Eglycoprotein, haptoglobin, transferrin, appoferritin have the greatest value. Most of the acute phase reactants are synthesized by macrophages, hepatocytes and other cells.

The following changes on the level of the whole organism, so-called signs of a general nature, may indicate the development of inflammation:

I. Leukocyte count change  in peripheral blood.

Overwhelming majority inflammatory processes  accompanied by leukocytosis, much less frequently, with inflammation of viral origin - leukopenia. By its nature, leukocytosis is mainly redistributive, i.e. due to the redistribution of leukocytes in the body, their release into the bloodstream. A certain contribution to the increase in the number of leukocytes in peripheral blood is made by the activation of leukopoiesis. The main causes of leukocytosis include the stimulation of the sympathoadrenal system, the effects of certain bacterial toxins, tissue decomposition products, as well as a number of inflammatory mediators (IQ-I, an induction factor of monocytopoiesis, etc.).

2. Fever  develops under the influence of pyrogenic factors coming from the inflammation center: primary pyrogens of exogenous and endogenous origin (endotoxins - lipopolysaccharide nature; structural elements of cell membranes of various bacteria, various antigens of microbial and nonmicrobial origin, alloantigens, various exotoxins, etc.) and secondary pyrogens (interleukin I -, tumor necrosis factor (TNF), interleukin-6).

3. Changes in the amount and quality of proteins  blood plasma. In the acute inflammatory process in the blood accumulate synthesized by hepatocytes, macrophages, etc. The cells of the so-called “proteins of the acute phase” of inflammation. The chronic course of inflammation is characterized by an increase in blood levels of -and especially -globulins.

Changes in the activity and composition of the enzymes of the blood are expressed in an increase in the activity of transaminases (for example, alanine transaminase in hepatitis, aspartate transaminase in myocarditis), hyaluronidase, thrombokinase, etc.

4. Erythrocyte sedimentation rate increase  (ESR), which is especially the case for chronic inflammatory processes, is caused by an increase in blood viscosity, a decrease in negative charge and agglomeration of erythrocytes, changes in the composition of blood proteins, a rise in temperature.

5. Changes in hormone levels  in the blood are, as a rule, to increase the concentration of catecholamines, corticosteroids.

In addition, the focus of inflammation can be a source of pathological reflexes (for example, the development of angina pectoris in cholecystitis, cardiac arrhythmias in appendicitis).

PATHOGENESIS OF INFLAMMATION

It is known that damaging factors of various origins cause in many ways stereotypical in their manifestations process, including local changes in the form of alteration of tissues and their constituent cells, release of physiologically active substances (the so-called inflammatory mediators), which entails the reaction of the microcirculatory vessels, increasing permeability of capillary walls and venules, changes in the rheological properties of blood, and leads to exudation and proliferation. Such non-specificity of tissue changes when exposed to various damaging factors is associated with the realization of their influence through a common mechanism, which forms the main manifestations of B.

It has been established that the dynamics of the inflammatory process, the natural character of its development, are largely due to a complex of physiologically active substances formed in the focus of damage and mediating the action of phlogogenic factors, called inflammatory mediators.

To date, a large number of such mediators have been found, which are intermediaries in the implementation of the action of agents that cause inflammation. Released under the influence of a damaging agent, mediators change a variety of processes occurring in tissues - vascular tone, permeability of their walls, emigration of leukocytes and other blood cells, their adhesion and phagocytic activity, cause pain, etc.

There are various approaches to the systematization of inflammatory mediators. They are classified according to chemical structure, for example, bilogenic amines (histamine, serotonin), polypeptides (bradykinin, kallidin, methionyl lysyl bradykinin) and proteins (components of the complement system, lysosomal enzymes, cationic granulocyte proteins of origin, monokines, lymphokines), derivatives of the system, lysosomal enzymes, cationic granulocyte proteins of the origin, monokines, lymphokines, derivatives of polymers, lysosomal enzymes, cationic granulocyte proteins of the origin, monokines, lymphokines, derivatives of polymeptides, cationic proteins of granulocyte origin, monokines, lymphokines, derivatives of polymers, lysosomal enzymes, cationic granulocyte proteins of the origin of , thromboxanes, leukotrienes).

By origin, mediators are divided into cellular (histamine, serotonin, granulocyte factors, monokines, lymphokines) and humoral or plasma (C 3 and C 5 complement fractions, anafylotoxin, blood coagulation factors, some kinins).

Humoral mediators are usually characterized by generalized effects and their spectrum of action is wider than that of cellular mediators, the effects of which are largely local. In turn, cellular mediators can be divided according to the type of cells that release inflammatory mediators (polymorphonuclear leukocyte factors, monokines, lymphokines). According to the peculiarities of their release from cells, inflammatory mediators can be classified into non-cytotoxic and cytotoxic release mediators. In the first case, the output of mediators stimulated through physiological exocytosis is stimulated through the corresponding cell receptor, in the second case, cell destruction occurs, as a result of which the mediators exit from it into the environment. The same neurotransmitter (histamine or serotonin) can enter it both ways (from the fibrocyte or platelet).

Depending on the rate of inclusion in the process of inflammation, there are mediators of immediate (kinins, anaphylatoxins) and delayed (monokines, lymphokines) type of action. There are also mediators of direct, or indirect, action. The first include mediators that are in the process of the stimulus itself (histamine, serotonin, etc.), the second are mediators that appear later, often as a result of the action of the first mediators (complement fraction, granulocyte factors of polymorphonuclear leukocytes).

The division of inflammatory mediators into groups is to some extent arbitrary. The separation of inflammatory mediators into humoral and cellular does not take into account the functional and structural unity of humoral and cellular mechanisms of protection of the body from damaging influences. So the humoral mediator bradykinin or fractions of C 3 and C 5 - complement released in blood plasma and acting as mediators of inflammation, stimulate labrocytes, releasing the cellular mediator histamine.

Major cellular and humoral inflammatory mediators

STAGES OF INFLAMMATION

The pathogenetic basis of inflammation consists of three components, the stages — alteration, exudation and proliferation. They are closely interrelated, mutually complement and transform into each other, there are no clear boundaries between them. Therefore, depending on the process that prevails at a certain stage of inflammation, the following stages are distinguished.

The stage of alteration (damage).

A. Primary Alteration

B. Secondary alteration.

Stage of exudation and emigration.

Stage of proliferation and reparation.

A. Proliferation.

B. Completion of inflammation.

V. always begins with tissue damage, a complex of metabolic, physico-chemical, and structural-functional changes, i.e. alterations (from Lat. alteratio - change). Alteration - starting, start-up stage B.

Primary alteration  - This is a set of changes in metabolism, physicochemical properties, structure and function of cells and tissues under the influence of the direct influence of etiological factor B. Primary alteration as a result of the interaction of etiological factor with the body is preserved and causes inflammation even after this interaction is terminated. The reaction of the primary alteration as if prolongs the action of the cause B. The causative factor itself may no longer be in contact with the body.

Secondary alteration  - occurs under the influence of a phlogogenic stimulus, as well as factors of primary alteration. If the primary alteration is the result of the direct action of the inflammatory agent, then the secondary does not depend on it and can continue even when this agent no longer has an effect (for example, upon radiation exposure). The etiological factor was the initiator, the trigger mechanism of the process, and then V. will proceed according to the laws peculiar to the tissue, organ, body as a whole.

The action of the phlogogenic agent is manifested primarily on cell membranes, including lysosomes. This has far-reaching consequences, since when the lysosome is damaged, the enzymes (acid hydrolases) enclosed in them are released that can break down various substances that make up the cell (proteins, nucleic acids, carbohydrates, lipids). Further, these enzymes, with or without an etiological factor, continue the process of alteration, as well as destruction, resulting in the formation of products of limited proteolysis, lipolysis, biologically active substances - inflammatory mediators. For this reason, lysosomes are also called the “launching pad” of inflammation. It can be said that the primary alteration is the damage done from the side, and the secondary alteration is self-harm.

The stage of alteration should be considered as a dialectical unity of changes caused by the action of damaging factors and the response of protective local reactions of the body to these changes. There are biochemical and morphological phases of alteration. To begin with, the nature and severity of biochemical and physico-chemical changes in the area of ​​tissue damage and metabolic disturbances are primarily important.

Changes in metabolism during the development of alteration, in the process of V. include the intensification of the process of decomposition of carbohydrates, fats and proteins (the result of exposure to lysosomal hydrolases, etc.), increased anaerobic glycolysis and tissue respiration, separation of biological oxidation processes, reduced activity of anabolic processes . The consequence of these changes are an increase in heat production, the development of a relative deficit of macroergs, accumulation of к-ketoglutaric, malic, lactic acids, low molecular weight polysaccharides, polypeptides, free amino acids, ketone bodies.

The term “fire of exchange” has long been used to characterize the metabolism. The analogy consists not only in the fact that the metabolism in V.'s focus is sharply increased, but also in the fact that the “burning” does not occur to the end, but with the formation of oxidized oxidation products.

V. always starts with increased metabolism. In the future, the intensity of the metabolism decreases, and with it its directionality changes. If at the beginning of V. decay processes prevail, then in the future - the processes of synthesis. To distinguish them in time is almost impossible. Anabolic processes appear very early, but they predominate in the later stages of a disease, when regenerative (reparative) tendencies appear. As a result of the activation of certain enzymes, DNA and RNA synthesis is enhanced, and the activity of histiocytes and fibroblasts increases.

The complex of physicochemical changes includes acidosis (due to impaired tissue oxidation and accumulation of insufficiently oxidized products in tissues), hyperionia (accumulation of K +, Cl -, NRA 4 ions from dying cells) in V.’s cell, changes in the ratio of individual ions , for example, an increase in the K + / Ca 2+ coefficient), hyperosmia, hyperkonia (due to an increase in protein concentration, dispersion and hydrophilicity).

Structural and functional changes in vitro are very diverse and can develop at the subcellular (mitochondria, lysosomes, endoplasmic reticulum, etc.), cellular and organ levels.

Exudation  (from lat. exsudatio) - bleeding. This component B. includes the triad:

a) vascular reactions and changes in blood circulation in the outbreak B.

b) the output of the liquid part of the blood of their vessels - exudation itself;

c) emigration (from Lat. emigratio - eviction) - the release of leocytes to the hearth B. and the development of phagocytosis.

Dynamics of vascular reactions and changes in blood circulation during the development of B. stereotype: first there is a short-term reflex spasm of orteriole and precapillaries with slower blood flow, then, replacing each other, arterial and venous hyperemia develops, prestasis and stasis - stop blood flow.

Arterial hyperemia  is the result of the formation in the center of V. a large number of vasoactive substances - mediators V., which suppress the automaticity of the smooth muscle elements of the wall of arterioles and precapillaries, causing them to relax. This leads to an increase in arterial blood flow, accelerates its movement, opens previously not functioning capillaries, increases the pressure in them. In addition, the adductor vessels expand as a result of the “paralysis” of vasoconstrictors and the dominance of parasympathetic effects on the vessel wall, acidosis, hypercalium ionia, and a decrease in the elasticity of the surrounding connective tissue.

Venous hyperemia arises from a number of factors that can be divided into three groups: 1) blood factors, 2) vascular wall factors, 3) factors of surrounding tissues. The factors associated with blood include the regional arrangement of leukocytes, the swelling of red blood cells, the release of liquid blood into the inflamed tissue and the thickening of blood, the formation of microthrombus due to the activation of Hagemann factor and a decrease in heparin content.

The influence of factors of the vascular wall on the venous hyperemia is manifested by swelling of the endothelium, as a result of which the lumen of small vessels narrows even more. Altered venules lose their elasticity and become more pliable to the compressive action of the infiltrate. And, finally, the manifestation of tissue factors consists in the fact that a hundred edematous tissue, squeezing the veins and lymphatic vessels, contributes to the development of venous hyperemia.

Pathological anatomy of inflammation

Inflammation (inflammatory response, inflammatio, flogosis) - protective and adaptive mechanism that provides the necessary conditions for the restoration of damaged tissue. The inflammatory response is also briefly defined as a tissue reaction to damage.

Inflammation in itself is not a pathological process, but under certain conditions, like any other protective-adaptive reaction (thrombosis, stress, immune response, regeneration, etc.), can proceed pathologically. Therefore, it is advisable to distinguish inflammation  and pathology of inflammation  (pathological variants of the inflammatory response).

Peculiarities of inflammation. Unlike other protective and adaptive mechanisms (non-logogenic response of scavenger cells, non-inflammatory encapsulation, immune response), during inflammation occurs delimitation  (demarcation) of damaged tissues from healthy (due to vascular changes and cellular infiltration), cleansing  phagocytes of the focus of damage from detritus and phlogogen (for example, microorganisms), and most importantly - the creation of conditions for further recovery the integrity of the damaged tissue (i.e. for reparative regeneration). The inflammatory response is a mandatory intermediate between tissue damage and its repair.

Classical theory of morphogenesis of inflammation

1. With the formation of fibroepithelial polyps (reactive papillomas)
2. With the formation of hyperplastic polyps
3. Papillary synovitis
4. Papillary serositis
5. With the formation of viral warts.

Interstitial inflammation

Interstitial (interstitial) inflammation  - productive inflammation, in which the cells of the inflammatory infiltrate are distributed more or less evenly in the tissue, without the formation of focal accumulations. Infiltration in interstitial inflammation is formed mainly by lymphocytes and ordinary macrophages (histiocytes), so it is called lymphohistiocytic. Often in the infiltrate derivatives of B-lymphocytes (plasma cells) are detected, and then it is designated as lymphohistioplasmocytic. The presence of plasma cells reflects the formation of humoral immunity.

A characteristic outcome of a long-term interstitial inflammation is widespread fibrosis in the affected organ. Against the background of post-inflammatory fibrosis, parenchyma atrophy develops and, as a result, functional deficiency syndrome  body. Often the body is deformed ( "Cicatricial wrinkling", or cirrhosis). Interstitial inflammation is the basis of chronic pyelonephritis (without exacerbation of the process), chronic hepatitis, many forms of myocarditis (thyrotoxic myocarditis, toxic myocarditis in diphtheria, myocarditis in tertiary syphilis), interstitial pneumonia.

Granulomatous inflammation

Granulomatous inflammation  - productive inflammation, in which the infiltrate cells form focal accumulations ( granulomas). Granulomas are sometimes called "knots", however this designation is inaccurate, because granulomas can be not only nodules, but also nodes (for example, gum or leproma). Granulomas are formed in conditions of excessive activity immune system (allergies), therefore, granulomatous inflammation is also defined as one of the types of allergic reactions (type VI in the S. Sell classification, type V in the O. Günther classification). The severity of the immunopathological reaction in the formation of granulomas is different: from the minimum ( non-immune granulomas) up to significant ( immune granulomas).

Classification of granulomas

Granulomas are classified according to their composition, pathogenetic features, speed of change of cell generations and morphological specificity.

I. Cell composition

1. Phagocytoma (mature macrophage granuloma)
2. Epithelioid cell granuloma
3. Giant cell granuloma  (with langans cells  or with foreign cells)
4. Lymphocytic granuloma  [for example, in viral encephalomyelitis, typhus fever]
5. Granuloma "with suppuration"  [for example, with sape].

Ii. Features of pathogenesis

1. Immune granuloma
2. Non-immune granuloma.

Iii. The intensity of the change of cells in the granuloma

1. Granuloma with high level  exchange
2. Granuloma with low level  exchange.

Iv. The specificity of the structure

1. Nonspecific granulomas
2. Specific granulomas.

Specific granulomas (tubercles and sapna granulomas are not specific):

• Gumma
• Leproma
• (scleroma)
• Granulema Ashoff-Talalayev  (specific rheumatic granuloma)
• .

The composition of granulomas are divided into five main types: phagocytomas  (granulomas from ordinary phagocytic macrophages), epithelioid cell granulomas  (granulomas with epithelioid macrophages), giant cell  (granulomas with giant multi-core macrophages), lymphocytic  (formed mainly by lymphoid cells) and suppuration granulomas  (granulomas with centrally located disintegrating neutrophilic granulocytes and phagocytic macrophages located on the periphery).

Epithelioid macrophages  differ from the usual larger size, light cytoplasm than resemble some epithelial cells (hence the term "epithelioid"). Their main function is not phagocytosis, but the formation, like neutrophilic granulocytes, of active oxygen metabolites. Epithelioid macrophages often appear in lesions with the presence of an aggressive phlogogen and an insufficient number of neutrophils, for example, in tuberculosis.

Giant multi-core macrophages  formed by the merger of conventional phagocytic macrophages. Epithelioid cells practically do not participate in this process. In pathological anatomy, two types of multinuclear macrophages occur in granulomas: (1) langans cells  and 2) foreign body cells. The difference between them lies in the location of the nuclei. In the cells of Langans, the nuclei are located on the periphery of the cytoplasm, near the plasmolemma, forming the “crown” (“crown”) figure, the cell center from the nucleus is free (there are collected centrioles of all the fused histiocytes). In foreign cells, the nuclei are distributed throughout the cytoplasm, located both on the periphery and in the center. Langans cells are characteristic of lesions in tuberculosis, cells of foreign bodies (as the name implies) - for granulomas of foreign bodies.

Granulomas "with suppuration"  - conditional term, since purulent exudate in the center of the granuloma is not formed due to the numerous macrophages on the periphery, phagocytic neutrons destroyed. However, in diseases involving the formation of such granulomas, purulent inflammation may develop, for example, with sapa.

According to the features of pathogenesis emit immune  (formed on the background of severe allergies) and non-immune  granulomas. The term "non-immune granulomas" can not be considered successful, because all granulomas are the essence of the manifestation of an allergic process, only for them it does not play a decisive role, it is less pronounced. The morphological marker of immune granulomas are epithelioid macrophages, non-immune granulomas are cells of foreign bodies.

According to the rate of change of cell generations, granulomas are distinguished with a high (the cells in the granuloma die quickly, they are replaced by new ones) and with a low level of cell metabolism. The first are mainly infectious granulomas, the second - the granulomas of foreign bodies.

By morphological specificity, granulomas are subdivided into non-specific  (the same structure of granulomas in different diseases) and specific  (the structure of granulomas is characteristic only for one disease). In diseases for which specific granulomas are typical, non-specific granulomas may also be formed. For example, rheumatism is characterized by a specific granuloma (granuloma Aschoff-Talalayeva), but this does not mean that with this disease in the tissue there are only specific granulomas; along with them, granulomas of non-specific structure are detected. Currently, specific granulomas are considered leproma  (granuloma with lepromatous leprosy), gumma  (granuloma with tertiary syphilis), granuloma Ashofa-Talalayev  (with rheumatism), specific granuloma with rhinosclerosis  and specific granuloma in actinomycosis. Until recently, the specific attributed tubercle  (granuloma in tuberculosis), but a similar structure may have granulomas in sarcoidosis, some mycoses, berylliosis and a number of other diseases. In old textbooks, the group of specific granulomas also included a granuloma with glanders, which has a “suppuration” granuloma morphology, but granulomas of the same structure were found in many diseases (yersiniosis, atypical mycobacterioses, some mycoses, etc.).

Gumma

A specific granuloma for syphilis is called gumma. Gumma are found in tertiary syphilis. Macromorphologically, it is a dense gray knot. A typical gumma in the center contains a gray translucent sticky mass (“fibrous necrosis”), around which granulation tissue is located, ripening along the periphery into cicatricial. Necrosis in the center of the gum was called “fibrous” in classical pathological anatomy, since In the detritus, the first researchers constantly found retained reticular fibers, but later it turned out that this type of fibers remains in the focus of any necrosis longer than other tissue structures. The main cells of the inflammatory infiltrate are plasma cells and B lymphocytes. Gumma marker cells - plasma cells (some authors call the gum's plasma cells unny-Marshalko-Yadasson cells). Pathogen ( Treponema pallidum) can be detected in tissue sections with levaditi silver impregnation  (bacterial cells are stained black and have a convoluted shape).

Leproma

Specific leprosy granuloma ( leproma) is found only in the case of lepromatous leprosy (a form with lesion internal organs). Leproma, like gum, outwardly represents a knot, it is formed mainly by phagocytic macrophages (phagocytoma), called virchow cells. The cytoplasm of Virchow cells contains fat droplets and pathogen ( Mycobacterium leprae), which is stained by the Ziel-Nielsen method with a basic magenta in red color, similar to the causative agent of tuberculosis. Bacteria are usually arranged parallel to each other, like "matches in a box" or "cigarettes in a pack."

Specific granuloma in rhinosclerosis (scleroma)

Specific granuloma with rhinosclerosis (scleroma) as well as leproma, is mainly formed by phagocytic macrophages ( mikulich cells), in the cytoplasm of which are found light vacuoles that do not contain fat, and the causative agent of the disease ( Klebsiella rhinoscleromatispreviously called bacillus Volkowicz-Frisch). The typical localization of granulomas in this disease is the upper respiratory tract; the characteristic outcome of granulomas in rhinosclerosis is scarring, sometimes so pronounced that obliteration of the trachea and bronchi occurs.

Specific actinomycotic granuloma

Specific granuloma in actinomycosis  formed around druze  (so called colonies of hyphae-forming bacteria). It consists of granulation tissue rich in neutrophilic granulocytes and large macrophages with light, frothy cytoplasm ( "Foam cells"). Numerous closely located “frothy macrophages” are granuloma marker cells. Over time, the druse is surrounded by purulent exudate, which is formed during the disintegration of neutrophilic granulocytes, and the granulation tissue matures into coarse-fibered tissue, determining the density of the tissue in the lesion. Pathogen (some species of the genus Actinomyces) is painted in red-purple with PAS reactions. Actinomycosis is more often localized in the orofacial region, neck tissues and in the female genital organs (uterus, tubes), but the process can develop in any organ.

Tubercle

A characteristic morphological sign of productive inflammation in tuberculosis is the formation of tuburkulov  (epithelioid cell tuberculosis granulomas), which until recently were considered as specific, but granulomas similar in structure can be detected in other diseases (mycoses, sarcoidosis, berylliosis, etc.). Macromorphologically, the tubercle is a dense, whitish foci. Microscopic examination in a typical tubercle around the central caseous necrosis cells are located inflammatory infiltrate. Marker cells of the tubercle are langans cells  (inaccurately called pirogov-Langans cells) - giant multinuclear macrophages, the central part of which is free from nuclei. The predominant elements in the tubercle are epithelioid macrophages. On the periphery of the granuloma, T-lymphocytes are detected ( lymphocytic cuff). In macrophages, it is possible to identify the causative agent ( Mycobacterium tuberculosis, M. bovis, M. africanum), they turn red with basic fuchsin when dyeing the Zil-Nielsen tissue section. Tubercules are not formed in cases of tuberculosis without signs of productive inflammation, for example, in caseous pneumonia.

Granuloma with sapa

Granuloma with sapa  (an infectious disease mainly among horses; when a person is infected, it usually proceeds as septicopyemiawas first studied by pathologists granuloma "with suppuration"therefore, for a long time was considered as specific. It has been established that such granulomas are found in many diseases (atypical mycobacterioses, intestinal yersiniosis and pseudotuberculosis, some mycoses, etc.). Disintegrating neutrophilic granulocytes are located in the center of the granuloma, along the periphery are numerous phagocytic macrophages. Despite the name, purulent exudate in the granuloma itself is not formed, because disintegrating neutrophils are rapidly phagocytosed by macrophages.

Granulomatous diseases (granulomatosis)

Classification of granulomatous diseases:

I. Etiological principle

1. Idiopathic granulomatosis  [sarcoidosis, Wegener's granulomatosis, Horton's disease, etc.]
2. Granulomatous infections and invasions  [some viral and bacterial infections, mycoses, protozoa, helminth infections (for example, alveococcosis)]
3. Pneumoconiosis (dust diseases of the lungs) [silicosis, berylliosis]
4. Drug granulomatosis  [drug hepatitis]
5. Granulomatous reactions to foreign bodies  [surgical talcosis, granulomas around suture material]
6. Lipogranulomatosis.

Ii. With the flow

1. Acute granulomatosis  [eg typhoid fever]
2. Chronic granulomatosis.

Granulating inflammation

Granulating inflammation  - productive inflammation, in which granulation tissue grows in the lesion. Examples of processes with the development of granulating inflammation are granulating pulpite  and granulating periodontitis. Granulation tissue usually matures into coarse-fibrous (scar) tissue.

Productive inflammation of integumentary tissues  (skin, mucous membranes, synovial and serous membranes) is accompanied by the formation of connective tissue outgrowths of these tissues, covered with a typical or metaplastic epithelium. Outgrowths of epithelial tissues due to productive inflammation are hypertrophic growths. Depending on the location, hypertrophic growths have different names: (1) fibroepithelial polyps, or reactive papillomas  (on the skin and mucous membranes covered with stratified squamous epithelium), (2) hyperplastic polyps  (on mucous membranes covered with a single layer of the epithelium). Analogs of fibroepithelial polyps arising under the influence of DNA containing human papillomavirus  from the family Papovaviridae  traditionally denoted viral warts, among which there are (1) ordinary (verrucae vulgares), (2) plantar, (3) juvenile  warts and (4) genital warts. The latter are formed in zones bordering the skin and mucous membranes (perineum, genitals, face around the openings of the mouth and nose). The previously distinguished "giant genital warts of the Auschke-Lowenstein" is currently regarded as verrucous squamous cell carcinoma.

see also

• Destructive processes
• Circulatory disorders
• Kaliteevsky PF Macroscopic differential diagnosis of pathological processes.- M., 1987.
• General human pathology: a Guide for doctors / Ed. A.I. Strukova, V.V. Serov, D.S. Sarkisova: In 2 t. T. 2.- M., 1990.
• Paltsev M. A., Ivanov A. A. Intercellular interactions. - M., 1995.
• Pathological anatomy of diseases of the fetus and child / Ed. T. E. Ivanovskaya, B. S. Gusman: In 2 T.- M., 1981.
• Sarkisov D.S., Paltsev M.A., Khitrov N.K. General human pathology.- M., 1997.
• Sarkisov D.S. Essays on the history of general pathology.- M., 1988 (1st ed.), 1993 (2nd ed.).
• Strukov AI, Kaufman O. Ya. Granulomatous inflammation and granulomatous diseases. - M., 1989.
• Strukov AI, Serov V.V. Pathological anatomy.- M., 1995.

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Inflammation

Professor M.K.Nedzved

Inflammation is a pathological process, which is a compensatory defense response of the body to the effects of a pathogenic agent (irritant), which is realized at the microcirculatory level. Morphologically, inflammation is characterized by a different combination of three main components: alteration, exudation and proliferation. The morphological type of the inflammatory process depends on the severity of one or another component. Inflammation is aimed at eliminating the products of tissue damage and the pathogenic agent.

These components are considered as successive stages of inflammation. All blood cells (neutrophils, basophils, eosinophils, monocytes, platelets and even erythrocytes), endothelial cells, connective tissue cells (labrocytes, macrophages, fibroblasts) are involved in the inflammatory process, resulting in one or another cell cooperation, the elements of which interact with each other. a friend.

Inflammation is characterized by five clinical signs: redness -rubor, swelling - tumor, pain - dolor, increase in temperature - calor, dysfunction - functio laesa, which are caused by morphological changes in the area of ​​the inflammatory process.

Alteration  morphologically it represents various types of damage to tissues and individual cells, in mild cases being limited to dystrophic changes, in severe cases to the appearance of common or focal necrosis. Alteration arises as a result of the direct action of the pathogenic agent, and the effects of inflammatory mediators. At the same time, the alteration can be secondary - as a consequence of circulatory disorders.

Alteration is the trigger mechanism of inflammation, which determines its kinetics, since in this phase there is a release of biologically active substances - inflammatory mediators.

Mediators are divided by their origin into humoral (plasma) and cellular.

Humoral mediators (kinins, kallikreins, components C 3 and C 5 complement, XII coagulation factor (Hageman factor), plasmin) increase the permeability of the vessels of the ICR, activate the chemotaxis of polymorphonuclear leukocytes (PML), phagocytosis and intravascular coagulation. The spectrum of their action is wider than cellular mediators, whose action is local.

Mediators of cellular origin (histamine, serotonin, granulocyte factors, lymphokines and monokines, derivatives of arachidonic acid / prostaglandins /) increase vascular permeability, ICR and phagocytosis, have a bactericidal effect, causing secondary alteration. These mediators include immune mechanisms in the inflammatory response, regulate the proliferation and differentiation of cells in the inflammatory focus. The conductor of intercellular interactions in the inflammation are macrophages.

Macrophages have properties that allow them to act not only as a local regulator of the inflammatory process, but also to determine the severity of general body reactions.

One of the most important mediators of inflammation are histamine, which is formed in labrocytes, basophils and platelets from the amino acid histamine and deposited in the granules of these cells. After release, histamine is rapidly destroyed by the enzyme histaminase.

The release of histamine is one of the first tissue reactions to damage, its effect manifests itself after a few seconds as an instant spasm, alternating with vasodilation and the first wave of increasing vascular permeability at the level of the ICR, increases the adhesive properties of the endothelium. It activates kininogenesis, stimulates phagocytosis. In the outbreak of acute inflammation, histamine causes pain. Since histamine is rapidly destroyed, further microcirculation changes are supported by other inflammatory mediators.

Inclusion of kinins in the pathogenesis of acute inflammation means the beginning of the activity of the second cascade of mediators. Formed kinins from a  2 -globulin plasma (kininogen), the splitting of which occurs under the influence of proteolytic enzymes of plasma (kallikrein I) and tissues (kallikrein II). These enzymes are activated by coagulation factor XII (Hageman factor).

In the focus of inflammation, kinins dilate blood vessels, increase their permeability, increasing exudation. Kinins are destroyed by kininases, which are contained in red blood cells, PMNs, and also inhibited  1-antitrypsin, inactivator C-fraction of complement.

Kallikrein, plasmin, thrombin, proteases of bacteria and its own cells activate complement, fragments of which are the most important mediators of inflammation. Activated C 2-fragment of complement has the properties of kinins, C 3 -fragment - increases vascular permeability and is a granulocyte chemoattractant. C 5 -fragment is more active, because, having similar properties, it releases lysosomal hydrolases of neutrophils and monocytes, stimulates the lipoxygenase arachidonic acid decomposition pathway, participating in the formation of leukotrienes, enhances the generation of oxygen radicals and lipid hydroperoxide. C 5-9 fragments provide reactions aimed at the lysis of foreign and own cells.

Arachidonic acid is released from the phospholipid cell membranes as a result of the action of the enzyme phospholipase A  2 The activators of this enzyme, in addition to the C 5 fragment of the compliment, are microbial toxins, kinins, thrombin, antigen-antibody complexes, and Ca 2+.

Splitting of arachidonic acid goes in two ways: the first is cyclooxygenase, with the formation of prostaglandins, the second is lipoxygenase, with the formation of leukotrienes.

In the morphogenesis of inflammation, oppositely acting prostacyclin and thromboxane A are important.  2 Prostacyclin is synthesized by the endothelium and inhibits platelet aggregation, maintains the liquid state of the blood, and causes vasodilation. Thromboxane is produced by platelets, causing their aggregation and vasoconstriction.

Leukotrienes are formed in the membranes of platelets, basophils, endotheliocytes and have a chemotactic effect, cause vasoconstriction and increase the permeability of the vascular walls, especially venules.

In the focus of inflammation in the mitochondria and microsomes of cells, especially phagocytes, various oxygen radicals are formed, which damage the membranes of microbes and their own cells, contribute to the splitting of antigens and immune complexes.

In acute inflammation, histamine and serotonin promote the release of platelet activating factor (PAF) from platelets. This mediator enhances the release of hydrolytic enzymes from the lysosomes of polymorphoncellular leukocytes (PMNs), stimulates free radical processes in them.

In the focus of inflammation of PMN, special substances for them (granulocyte factors) are emitted: cationic proteins, neutral and acid proteases. Cationic proteins are able to release histamine, possess chemotactic properties for monocytes, and inhibit granulocyte migration. Neutral proteases in the focus of inflammation cause the destruction of the fibers of the basal membrane of blood vessels. Acid proteases are active in conditions of acidosis and affect the membranes of microorganisms and their own cells.

Monocytes and lymphocytes also secrete mediators (monokines and lymphokines), which are actively involved in the development of immune inflammation.

The impact of mediators in the dynamics of the inflammatory process is diverse. Separate mediators are deposited together in the same cells. When released, they form various manifestations of inflammation. Thus, when alterations from labrocytes and basophils, histamine and PAF are released, which leads not only to an increase in vascular permeability, but also to activation of the hemostasis system and the appearance of blood clots in ICRs. In contrast, with severe immune inflammation, the release of heparin and histamine from labrocytes leads to a decrease in blood clotting.

In turn, the neurotransmitters in the inflammatory focus promote the accumulation of enzymes that destroy these mediators. Thus, the release of chemotactic eosinophil factor (CPE) from labrocytes attracts these cells, which contain a large amount of enzymes that destroy the mediators, to the inflammatory focus.

Inflammation is a dynamic process and proceeds in stages, replacing each other. At each stage of inflammation a certain group of mediators matters. Thus, in acute inflammation, biogenic amines play the initial role: histamine and serotonin. In other forms of inflammation, other patterns of inclusion of mediators are possible. For example, the release of histamine can immediately lead not only to the activation of the kinin system, but also to the inclusion of free radical mechanisms and leukocyte infiltration. PMNs in some cases (especially when the course of the process deteriorates) additionally stimulate labrocytes, activate the kinin system, generate oxygen radicals, increase the formation of prostaglandins and leukotrienes. Such feedbacks prolong the inflammatory process, worsen its course or cause its exacerbation from time to time.

Excessive accumulation of inflammatory mediators and their entry into the blood can lead to shock, collapse, DIC.

At all stages of inflammation, substances that prevent the excessive accumulation of mediators or inhibit their effects are released and act. These substances constitute a system of anti-inflammatory mediators. The ratio of mediators and antimediators determine the features of the formation, development and termination of the inflammatory process.

An important role in the formation and delivery of anti-medications to the inflammatory focus is played by eosinophils, which perform functions to end the inflammatory process. Eosinophils not only absorb antigens and immune complexes, but also secrete almost all anti-mediator enzymes: histaminase, carboxypeptidase, esterase, prostaglandine dehydrogenase, catalase, arylsulfatase. Anti-mediator function can be performed by humoral and neural effects, maintaining an optimal mediator mode of inflammation. This role is played by a  1-antitrypsin formed in hepatocytes. Plasma antiproteases inhibit the formation of kinins. The antimediators of inflammation include glucocorticoid hormones (cortisone, corticosterone). They reduce the manifestations of inflammation, vascular reactions, stabilize the vascular membranes of the ICR, reduce exudation, phagocytosis and leukocyte emigration.

Corticosteroids also have an anti-mediator effect: they reduce the formation and release of histamine, reduce the sensitivity of H  1 -histamine receptors, stabilize the membrane of lysosomes, reduce the activity of acidic lysosomal hydrolases, the production of kinins and prostaglandins. In immune inflammation, they reduce the inclusion of mediators in the pathochemical stage of allergy. As a result, T-killer activity is reduced, proliferation and maturation of T-lymphocytes is inhibited.

The system of inflammatory mediators ensures the transition of the inflammatory process to the exudation phase and ensures the development of the proliferation phase.

Depolymerization in the focus of inflammation of the protein – glycosaminoglycan complexes leads to the appearance of free amino acids, polypeptides, uronic acid, polysaccharides, which results in an increase in osmotic pressure in the tissues, their further swelling and water retention. The accumulation of products of fat and carbohydrate metabolism (fatty acids, lactic acid) leads to tissue acidosis and hypoxia, which further enhances the alteration phase.

Considering the fact that alteration can develop at any stage of the inflammatory process, including chronic inflammation, and can prevail over other components of inflammation, it is completely unjustified to exclude an alterative form from inflammation.

Morphologically exudation goes through several stages: 1) microcirculatory reaction and disturbance of the rheological properties of blood, 2) increase in vascular permeability of the microvasculature, 3) exudation of plasma components, 4) emigration of blood cells, 5) phagocytosis 6) formation of exudate and inflammatory cell infiltrate. These stages correspond to the phases of cellular interactions in the inflammatory process.

In morphogenesis   exudation  there are two stages - plasma exudation and cell infiltration.

After a short-term vasoconstriction, not only arterioles expand, but venules also expand, which increases the inflow and outflow of blood. However, the inflow exceeds the outflow, as a result of which the hydrodynamic pressure in the vessels rises in the inflammation center, which causes the liquid part of the blood to exit from the vessels.

Inflammatory hyperemia eliminates acidosis, increases tissue oxygenation, increases biological oxidation in tissues, promotes the influx of humoral factors of body defense (complement, properdin, fibronectin), leukocytes and antibodies to the center of inflammation, is accompanied by enhanced leaching of the products of disturbed metabolism and toxins of microorganisms.

Increased vascular permeability becomes an important factor in the release of liquid blood into the tissue, emigration of leukocytes and red blood cell diapedesis. When inflammation occurs, the flow of fluid from the blood into the tissue, not only in the arterioles, but also in the venules.

There are two ways of passing substances through the walls of the vessel, which complement each other: interendothelial and transendothelial. When the first is the reduction of endothelial cells, the intercellular cracks widen, exposing the basement membrane. At the second stage, plasmolemosis invasions appear in the cytoplasm of the endothelium cells, turning into vesicles, which move to the opposite cell wall. They then unfold, freeing the contents. On both sides, vesicles can merge, forming channels through which various substances pass (microvesicular transport).

A moderate increase in permeability leads to the release of fine fractions of proteins (albumin), then globulins, which usually occurs during serous inflammation. With a significant increase in permeability, fibrinogen is released, which in the focus of inflammation forms fibrin clots (fibrinous inflammation). Severe damage to the walls of blood vessels in the form of fibrinoid necrosis leads to erythrocyte diapedesis.

When inflammation is often observed selective increased permeability for certain substances or cells, the mechanism of which is still unknown. Such selectivity determines the development of various forms of exudative inflammation: serous, fibrinous, hemorrhagic, purulent.

In the focus of inflammation, microcirculation changes and the behavior of blood cells undergo six phases. AT   In the first phase, the blood cells retain their position in the center of the vessel. In   In the second phase, the leukocytes approach the vessel wall and roll along the surface of the endothelium, then begin to attach to it. AT   The third phase is the adhesion of leukocytes, which form the clutches along the walls. In the II and III phases, adhesive molecules play an important role, providing the interaction between the endothelium and leukocytes: integrins, immunoglobulins, selectins. PMN integrins and selectins provide adhesion of circulating cells to the endothelium, and selectins and immunoglobulins on the endothelium serve as ligands for leukocyte receptors.

Neurophils constantly express adhesive molecules on their surface ( 2 -integrin and  -selectin), the number and function of which quickly change depending on the action of a specific stimulus.  2-integrins (three types of them installed) are constantly present in the plasma membrane of neutrophils. The adhesive ability of these cells increases dramatically when they are activated due to the movement of the integrin CD 11a / CD18 and CD 11c / CD 18, which are usually located in leukocyte granules.

Activated endothelium cells synthesize a number of biologically active molecules, of which platelet activation factor (PAF) is of great importance. Normally, this factor is not present in endothelial cells. It appears only after stimulation of the endothelium by thrombin, histamine, leukotriene C  4 and other agonists. PAF is expressed on the surface of the cell membrane as an associated mediator and activates neutrophils by acting on their surface receptors. This is what enhances the expression of CD 11a / CD18 and CD 11c / CD 18 in leukocytes. Consequently, PAF acts as a signal inducing adhesion of neutrophils through the ег 2 -integrin system. This phenomenon of adhesion and activation of target cells by membrane-bound molecules of other cells is called juxtacrin activation (J. Massague, 1990). This activation of neutrophils is highly targeted. PAF in the activated endothelium rapidly disintegrates, which limits the duration of the signal.

Under the influence of another group of agonists (IL-1, TNF 6, lipopolysaccharides / LPS /) endothelial cells synthesize another signaling molecule - IL-8 (neutrophilicity factor), the synthesis of which takes 4-24 hours. IL-8 is a potential chemoattractant for neutrophils, facilitates their passage through the vascular wall.

Unlike PAF, IL-8 is secreted in the liquid phase and is associated with the basal surface of endothelial cells. IL-8 activates neutrophils by binding to a specific receptor belonging to the G-protein family. As a result, the density increases 2-integrins, leukocyte adhesion to endothelial cells and the extracellular matrix is ​​enhanced, but adhesion to cytokine-activated endothelium expressing сел -selectin is reduced.

Like neutrophils, endothelial cells also express a number of adherent molecules on their surface. In addition to ligands for -selectin and  2 -integrin on these cells identified p and сел -selectins.

Transient expression of p-selectin, which is formed from secretory granules activated by histamine or thrombin of the endothelium, occurs in parallel with the adhesion of neutrophils to the endothelium. Activation of the endothelium by some oxidants prolongs the expression of p-selectin on the cell surface. It should be noted that p-selectin can bind to non-activated leukocytes without 2 -integrin system. This effect is inhibited by monoclonal antibodies that identify the Ca 2+ -dependent lectin domain epitopes.

-selectin is synthesized by endothelium, stimulated by IL-1, TNF  2 and LPS. Its surface expression takes about 1 hour.  -selectin adhesion is also carried out without activation of the  2 -integrin system.

Ligands for p and  -selectins at the molecular level are not yet sufficiently characterized. However, it is known that sialic acid is an important part of their structure.

In endothelial-leukocyte interaction, different molecular systems act complexly in a specific combination sequence.

For the initial stage of adhesion of neutrophils to histamine or thrombin-stimulated endothelium, co-expression of PAF and p-selectin is necessary, followed by active interaction of PAF with its receptor on neutrophils. Coexpression of these two molecular systems provide for the specificity of the interaction, since other blood cells, such as platelets, have receptors for PAF only and do not have receptors for p-selectin.

The involvement of the  2 -integrin system and PAF increases the density of adhesion, since the expression of p-selectin is transient. At the same time, prolonged expression of p-selectin causes tight adhesion without the participation of  2-integrins.

A combination of molecular systems is used for the adhesion of eosinophils and basophils, which are associated with endothelium by 2 integrins. Eosinophils also express  1 -integrin (VLA-4), which is not found on neutrophils. With it, adhesion of neutrophils to cytokine-activated endothelium cells occurs.

Coexpression of α-selectin and IL-8 regulates the degree of binding of neutrophils to activated endothelial cells. IL-8 can change the activity of the  -selectin ligand and, together with PAF, provide for the process of neutrophil migration from the vascular bed.

Inflammation is a dynamic process. After 4 hours, the number of neutrophils decreases in the vascular bed and the number of monocytes and lymphocytes increases, which completely corrects with the change of phenotin of adhesive molecules expressed by endothelial cells. So after 6-8 hours the expression-Selectin (ELAM-1) begins to decrease due to a decrease in its synthesis and degradation. The synthesis of intercellular adherence molecules (ICAM-1), on the contrary, increases dramatically and reaches a stable level of expression 24 hours after the onset of inflammation. Another adhesive molecule appears on the surface of endothelial cells (V CAM - a vascular cell adhesion molecule). The ligand for it is the  2 -integrin molecule (VZA-4), which is expressed on monocytes. The binding of T-lymphocytes to the endothelium provides an adhesive molecule CD 44. Like neutrophils, T-lymphocytes appear in the focus of inflammation as a result of the action of IL-8. In contrast, monocytes appear later, as they are insensitive to the action of IL-8, however, they react to the JE gene product (monocytic chemotactic protein - MCP-1) expressed by endothelium during stimulation of IL-1 and TNF.

In the development of marginal standing and adhesion of leukocytes with endothelial cells, the elimination of their negative charge is of great importance, which in normal conditions prevents adhesion. The negative charge of the membrane of the endothelial cell decreases due to the accumulation in the focus of inflammation H  + and K + and cationic proteins secreted by activated leukocytes. The divalent plasma cations (Ca 2+, Mn 2+ and Mg 2+) also reduce the negative charge of the endothelium and leukocytes.

In the development of the inflammatory process, there is a rigid control system in the form of a mechanism of positive feedbacks that limit its development. This control is carried out by a balanced system of cytotoxic and inhibitory factors. If the inflammatory process is not controlled by feedback mechanisms, the synthesis and release of inflammatory mediators is enhanced, the level of inhibitors is critically reduced, as a result of which local inflammatory reactions develop into extensive processes. The result is significant damage to the endothelium, excessive cellular infiltration, and increased vascular permeability.

  Fourth phaseexudation is the passage of leukocytes through the vascular wall and their emigration into the tissue.

After adhesion with the membrane of the endothelial cell, the leukocyte moves along its surface to the interendothelial gap, which, after the reduction of the endothelium, expands significantly.

Not only granulocytes, but also monocytes and, to a lesser extent, lymphocytes, with different speeds, react to the chemotactic stimulus.

At present, some mechanisms are known as a leukocyte, “sees” or “feels” a chemotactic agent, and what determines its movement.

The association of the chemotactic factor with specific receptors on the cell membrane of a leukocyte leads to the activation of phospholipase C through protein G and hydrolysis of cell phosphates and diacylglycerol. This leads to the release of Ca, first from the cellular stock, then to the entry of extracellular Ca into the cell, which includes the complex of contractile elements responsible for cell movement.

White blood cell moves (   5 phase of exudation) by throwing pseudopodia in the direction of motion. This pseudopodia consists of a network of filaments constructed from actin and a contractile protein, myosin. Actin monomers are rearranged into linear polymers directed to the edge of the pseudopodia. This process is controlled by the action of Ca ions and phosphoinositol on actin-regulated proteins: filamin, gelsolin, profilin, calmodulin.

The process of leukocyte passage through the basement membrane is associated with the action of leukocyte and endothelial enzymes. Such cytokines as IL-1, TNF  a, IFN , TGF  alter the protease / antiprotease balance, which leads to damage to the proteins of the basement membrane. Cytokine-activated endothelium also synthesizes a large number of glycosaminoglycans, which is a characteristic feature of areas of increased migration of leukocytes.

Enhancing or weakening the expression of various cytokines and adhesive molecules has a time dependence and regulates the evolution of the inflammatory process.

When activated, leukocytes form metabolites arachidonic acid, an increase in intracellular Ca occurs. Activation of protein kinase leads to degranulation and secretion of lysosomal enzymes and subsequent oxidative burst.

Intravascular movement, including marginal standing, takes several hours, passing through the vessel wall - 30 min-1 hour. In the first 6-24 hours, neutrophils are dominant, in 24-48 hours - monocytes. This is due to the fact that when neutrophils are activated, chemotactic substances for monocytes are released. However, there are known conditions in which lymphocytes play a major role in emigration ( viral infections, tuberculosis) or eosinophils (with allergic reactions).

Phagocytosis follows emigration (   6 phase of exudation), which takes place in three distinct interdependent stages: 1) recognition and attachment of leukocytes pathogenic particles, 2) their absorption with the formation of a phagocytic vacuole, 3) death or degradation of the absorbed material.

Most microorganisms are not recognized by leukocytes until they are absorbed by a substance, opsonins, which bind to specific leukocyte receptors. There are two main types of opsonins: 1) Fc fragment of immunoglobulin G (lgG) and 2) Szv, the so-called opsonin fragment C  3, formed by the activation of complement. There is also nepsonin phagocytosis, when some bacteria are recognized by their lipopolysaccharides.

The binding of opsonized particles to leukocyte receptors triggers absorption, in which the cytoplasmic current surrounds the object, followed by its imprisonment in the phagosome formed by the cytoplasmic cell membrane and the release of leukocyte granules into the vacuole formed.

The death of bacteria is carried out mainly with the help of oxygen-dependent processes, the result of which is the formation of H  2 O 2, which turns into HOCl -, which is the result of the action of the enzyme myeloperoxidase contained in the azurophilic granules of neutrophils. It is this substance that destroys bacteria by halogenation or oxidation of proteins and lipids. A similar mechanism is carried out against fungi, viruses, protozoa and worms. Myeloperoxidase-deficient white blood cells also have, but to a lesser extent, bactericidal properties, forming hydroxyl radicals, superoxides and free oxygen atoms.

Membrane changes in neutrophils and monocytes during chemotaxis and phagocytosis are not only accompanied by the entry of substances into phagolysosomes, but also into the extracellular space. The most important of these are: 1) lysosome enzymes represented by neutrophilic granules; 2) active metabolites of oxygen; 3) products of arachidonic acid metabolism, including prostaglandins and leukotrienes. All of them are the strongest mediators and cause damage not only to the endothelium, but also to the tissue. If this effect of leukocytes is long and massive, then leukocyte infiltration itself becomes dangerous, which underlies many human diseases, for example, rheumatoid arthritis and certain types of chronic lung diseases. The exocytosis of such mediators occurs in the case of non-closing of the phagocytic vacuole, or in the case of phagocytosis of membranolytic substances, such as urats. There is evidence that specific granules of neutrophils can be secreted by exocytosis.

Genetic and acquired leukocyte function defects cause hypersensitivity  human to infections.

For example, Chediak-Higashi syndrome (an autosomal recessive mode of inheritance) is based on impaired microtubule function, which form the basis of leukocyte azurophilic granules. The disease manifests itself only in cases of invasion of bacteria in the body.

Lymphokine-activated macrophages already in the exudation phase secrete not only chemotactic and tissue-damaging factors, but also growth factors, angiogenesis, and fibrogenic cytokines that influence the modeling of the proliferation phase.

Proliferation   characterized by the release into the focus of inflammation of a large number of macrophages that multiply and secrete monokines that stimulate the multiplication of fibroblasts. Other cells take an active part in proliferation: lymphocytes and plasma cells, eosinophils and labrocytes, endothelium and epithelium. Proliferation is the final stage of inflammation, providing tissue regeneration at the site of the lesion.

Proliferation occurs a few hours after the onset of inflammation and after 48 hours in the inflammatory infiltrate, monocytes are the main cell type. The release of monocytes from the vessels of the ICR is regulated by the same factors as the emigration of neutrophils (adhesive molecules and mediators with chemotactic and activating properties). After release, the monocyte is transformed into a large phagocytic cell - the macrophage. Activation signals, including cytokines, are produced by sensitized E-lymphocytes, bacterial endotoxins, other chemical mediators, fibronectin. After activation, the macrophage secretes a large number of biologically active substances.

In cases of acute inflammation, when the pathogenic agent is dead or eliminated, macrophages also die or enter the lymphatic vessels and nodes.

In cases of chronic inflammation, macrophages do not disappear, continue to accumulate and secrete toxic products that damage not only pathogenic agents, but also their own tissues. These are primarily metabolites of oxygen and arachidonic acid, proteases, neutrophil chemotactic factors, nitrogen oxides, coagulation factors. Consequently, tissue damage is one of the most important signs of chronic inflammation.

During proliferation, epithelioid cells appear in the focus of inflammation, which are more often formed from macrophages in the foci of granulomatous inflammation, starting from the 7th day of the formation of granulomas and perform mainly secretory function. Aggregation of epithelioid cells with the formation of close (interdigital) clutches of the zipper type is characteristic of this type of inflammation. These cells are considered hyperstimulated “super-mature” macrophages. Epithelioid cells have less phagocytic ability compared to macrophages, but their bactericidal and secretory properties are much stronger.

In cases of fusion of macrophages with each other or division of their nuclei without separation of the cytoplasm, the formation of multinucleated giant cells of two types occurs: Pirogov-Lanhans cells and resorption cells of foreign bodies. The merger of macrophages occurs always in the part of the cells where the lamellar complex and the concave part of the nucleus are located. In HIV and herpes infections, a third type of multinucleated giant cell occurs when the nuclei are grouped at opposite poles of the cell.

Antigen-activated lymphocytes produce lymphokines, which stimulate monocytes and macrophages. The latter form monokines that activate lymphocytes. Plasma cells form antibodies against the antigen at the site of inflammation, or against components of the damaged tissue.

The morphological marker of healing is the formation of granulation tissue, signs of which appear on day 3-5 of the inflammatory process.

The repair process consists of 4 components: 1) formation of new blood vessels (angiogenesis), 2) migration and proliferation of fibroblasts, 3) formation of an intercellular matrix, 4) maturation and organization of connective tissue.

Angiogenesis is carried out in the following ways: 1) proteolytic degradation of the basal membrane of the ICR vessel. 2) migration of endothelial cells to an angiogenic stimulus, 3) proliferation of endothelial cells, and 4) maturation of these cells and organization into capillary tubes. This process is regulated by activated macrophages that secrete endothelial and other growth factors.

The migration and proliferation of fibroblasts is also due to the factgrowth sites and fibrogenic cytokines produced by inflammatory macrophages. On the first day of the inflammatory process, low-differentiated fibroblasts appear in the vessels and in the exudate, which turn into young fibroblasts capable of secreting acid glycosaminoglycans and synthesizing collagen. Young forms are transformed into mature fibroblasts.

Mature fibroblasts lose their ability to reproduce, but continue to intensively synthesize and secrete collagen. Most of the mature fibroblasts die; preserved cells are transformed into long-lived fibroblasts.

Angiogenesis and proliferation of fibroblasts leads to the formation of the extracellular matrix, through the formation of young (granulation) connective tissue with its subsequent maturation. These processes delimit the inflamed area from healthy tissue. With a favorable course, granulation tissue completely replaces the foci of alteration

or purulent inflammation. In the formation and restructuring of the scar in the inflammation, a large role is played by fibroclasts (cells of the fibroblastic series), which phagocytize and lyse collagen fibers. This balances synthesis and catabolism of collagen, which are alternative functions of fibroblasts.

Proliferation is the final stage of the inflammatory process, in which both the cells of the blood system and the cells of the tissue in which inflammation develops take part.

Terminology and nomenclature of inflammation.

The name of inflammation of a tissue or organ is formed from their name, to which is added the ending - it, to the Latin or Greek name - the ending -itis. For example, inflammation of the brain - encephalitis (encephalitis)., inflammation of the stomach - gastritis (gastritis). Latin names are more commonly used, less commonly Greek, for example, inflammation of the pia mater - leptomeningitis (leptomeningitis). There are exceptions to this rule. So, pneumonia is called pneumonia, and pharynx inflammation is called sore throat.

The nomenclature of inflammation is represented by the names of the inflammatory processes of various parts of a particular body system. For example, inflammation of various parts of the gastrointestinal tract: cheilitis, gingivitis, glossitis, pharyngitis, esophagitis, gastritis, enteritis (duodenitis, fever, ileitis), colitis (tiflit, sigmoiditis, proctitis), hepatitis, pancreatitis.

Classification of inflammation.

The classification of inflammation takes into account the etiology, the nature of the process and the predominance of a particular phase of inflammation.

According to etiology, inflammation is divided into a banal (caused by any etiological factor) specific (has characteristic morphological manifestations and is caused by a certain infectious agent).

By the nature of the course of inflammation is acute, subacute and chronic.

According to the predominance of the phase of inflammation: alterative, exudative and proliferative (productive) inflammation.

Alterative inflammation .

Alterativny inflammation is characterized by the predominance of distrofic and necrotic changes, exudation and proliferation are also present, but weakly expressed. Such inflammation is most often observed in parenchymatous organs - myocardium, lungs, liver, kidneys. According to the type of course, alterative inflammation refers to acute.

Causes of alterative inflammation can be poisoning with chemical poisons and toxins, infectious agents. Examples of alterative inflammation include caseous pneumonia in tuberculosis, fulminant (necrotic) hepatitis B and C, acute alterative encephalitis of herpetic etiology, alterative myocarditis in diphtheria. Alterative inflammation is usually a manifestation of an immediate-type hyperergic reaction (Arthus phenomenon) or prevails on early stages development of autoimmune diseases (for example, with rheumatism). Such inflammation can also develop with a decrease in the body's defenses and in secondary and primary immunodeficiencies (acute tuberculosis sepsis in hematogenous generalized tuberculosis, necrotizing tonsillitis in acute leukemia, severe scarlet fever, and in acute form of radiation sickness.

The outcome of alterative inflammation depends on the location, extent and severity of alterative changes. With a favorable outcome, foci of necrosis with alterative inflammation undergo organization.

Exudative inflammation.

Exudative inflammation is characterized by the predominance of exudateactive phase in which the liquid part of the blood leaves the vascular bed and the formation of exudate. The composition of the exudate may be different. The classification takes into account two factors: the nature of the exudate and the localization process. Depending on the nature of the exudate emit: serous, fibrinous, purulent, putrid, hemorrhagic, mixed inflammation. The peculiarity of the process localization on the mucous membranes determines the development of one type of exudative inflammation - catarrhal.

Serous inflammation   It is characterized by the formation of exudate containing a small amount of  protein (2-3%), single leukocytes and desquamated cells of the affected tissue. Serous inflammation can develop in any organs and tissues: serous cavities, pia mater, skin, heart, liver, etc.

Causes of serous inflammation can be infectious agents, physical factors, auto-intoxication. For example: serous inflammation in the skin with the formation of vesicles (vesicles) caused by the herpes simplex virus ..

Serous inflammation can be acute and chronic.

The outcome of acute serous inflammation is usually favorable: the exudate is absorbed, there is a complete restoration of the structure of tissues. However, often this type of inflammation serves only as a transitional stage, the onset of fibrinous, purulent, or hemorrhagic inflammation. For example, the transition of serous pneumonia into purulent. In some cases, serous inflammation is life threatening: serous enteritis with cholera, serous encephalitis with rabies. Chronic serous inflammation can lead to organ sclerosis.

Fibrinous inflammation. It is characterized by exudate, rich in fibrinogen, which turns into fibrin in tissues, which is a grayish filamentous tissue. Fibrinous inflammation often localized on the serous and mucous membranes.

Causes of fibrinous inflammation - bacteria, viruses, chemicals of exogenous and endogenous origin. An example of fibrinous inflammation is the occurrence of polyserositis, including pericarditis, with uremia. At the same time, but filamentary overlays of fibrin appear in sheets of the pericardium, in connection with which such a macroscopic career is called the "hairy" heart.

Depending on the depth of necrosis, the film can be loosely or firmly connected with the underlying tissues, and therefore there are two types of fibrinous inflammation: croupous and diphtheritic.

Croupous inflammation often develops on a monolayer epithelium of the mucous or serous membrane. Necrosis with this type of inflammation is shallow, and the fibrinous film is thin, easily removed. With the separation of such a film, surface defects are formed. Fibrinous inflammation in the lung with the formation of exudate in the alveoli of the lobe of the lung is called lobar pneumonia.

Dipheritic inflammation develops in organs covered with stratified squamous epithelium. In this case, there are deep necrosis, and the fibrinous film is thick, it is difficult to remove, when it is rejected, a deep tissue defect occurs.

The dependence of the occurrence of a particular type of fibrinous inflammation can be traced by the example of diphtheria. On the mucous membranes of the pharynx, tonsils, which are lined with stratified squamous epithelium, Leffler's wand causes diphtheria inflammation, and on the mucous membranes of the larynx, trachea and bronchi, lined with a single-layered prismatic epithelium, the lobar. In this case, since fibrin films are easily removed, they can block the respiratory tract and cause choking (true croup). However, in a disease such as dysentery, diphtheria inflammation occurs in the intestine lined with a single-layer epithelium, since the sticks of dysentery can cause deep tissue necrosis.

The outcome of fibrinous inflammation may be different. Fibrinous exudate can melt, then the structure of the organ can be fully restored. But fibrin filaments germinate connective tissueand if inflammation is localized in the cavity, then adhesions form there, or the cavity is obliterated.

Purulent inflammation characterized by the presence in the exudate of a large number of neutrophils, both unchanged and lost and dead. Along with neutrophils, purulent exudate is rich in proteins. The pus contains many decay products of diseased tissues rich in enzymes that carry out the lysis of necrotic tissue elements. Macroscopically, pus is a thick, creamy mass of yellow-green color.

The causes of purulent inflammation can be various factors, but more often these are microorganisms (staphylococci, streptococci, gonococci, meningococci, etc.).

The course of purulent inflammation is acute and chronic.

Purulent inflammation can occur in any organs and tissues. The main forms of purulent inflammation are abscess, phlegmon, empyema.

Abscess - focal purulent inflammation characterized by meltingthe appearance of tissue with the formation of a cavity filled with pus. The tissue located around the cavity turns into a pyogenic membrane - a large number of vessels appear in it, from the lumen of which there is a constant emigration of leukocytes. An abscess can be located both in the thickness of tissues and organs, and in their superficial parts. In the latter case, it can break out to form a fistulous course. In chronic course, the abscess wall thickens and grows connective tissue.

Cellulitis - diffuse purulent inflammation, in which purulent exudate diffuse into tissues, dissecting and melting tissue elements. Typically, cellulitis develops in tissues where there are conditions for the easy spread of pus — in the fatty tissue, in the areas of tendons, fascia, along the neurovascular bundles. Diffuse purulent inflammation can also be observed in parenchymal organs.

Empyema is a purulent inflammation characterized by the accumulation of pus in the natural cavity. In the cavities of the body empyema can be formed in the presence of purulent foci in adjacent organs (for example, empyema in the abscess of the lung). Empyema of the hollow organs develops in violation of the outflow of pus with purulent inflammation (empyema of the gallbladder, appendix).

Outcomes of purulent inflammation may be different. Purulent exudate can sometimes completely dissolve. With extensive or prolonged inflammation, it usually ends with sclerosis with scar formation. With an unfavorable course, purulent inflammation can spread to the blood and lymph vessels with further generalization of infection and the development of sepsis. Long-term chronic suppurative inflammation is often complicated by secondary amyloidosis.

Putrid inflammation. It develops when putrefactive microorganisms get into the focus of inflammation (group of clostridia, causative agents of anaerobic infection).

The putrid inflammation develops when the putrid microflora enters the center of inflammation. The outcome is usually unfavorable, due to the massiveness of the lesion and the decrease in resistance of the microorganism.

Hemorrhagic inflammation is characterized by a predominance in exered blood cell udate. This type of inflammation is characteristic of some severe infectious diseases  - plague, anthrax, smallpox.

Mixed inflammation is observed in cases when another type is attached to one type of exudate. As a result, serous-purulent, serous-fibrinous, purulent-hemorrhagic and other types of inflammation occur.

Catarrh develops on mucous membranes and harais crated abundant excretion  exudate. A distinctive feature of catarrhal inflammation is the admixture of mucus to any exudate (serous, purulent, hemorrhagic).

The course of catarrhal inflammation can be acute and chronic. Acute inflammation  may end in complete recovery. Chronic inflammation  can lead to atrophy or hypertrophy of the mucous.