1. General knowledge about inflammation
2. Etiology of an inflammation
3. Classification of an inflammation
4. Pathogenesis of an inflammation:
- violation of microcirculation;
- exudation and leucocytes emigration
- kinds of exudates;
5. Role reactivity in inflammation manifestation
General knowledge about inflammation
The inflammation is the most often pathological process, which arises in a human organism. It is a typical pathological process, which arises after damage of tissues and consists of three main vessel-tissues components: alteration, violation of microcirculation with exudation and emigration of leucocytes and proliferation. Inflammation, as typical pathological process has common regularities, which always are present and don’t depend on the cause, localization, species of an organism and its individual features. The inflammation can arise in various organs. Each concrete case has it’s own features, but the scheme of the inflammatory reaction response will always be identical, that is typical. The inflammation is the local process, but all organism reacts definitely too. Immune, endocrine and the nervous systems are main engaged systems inflammation.
The inflammation can arise as result of influence of any agent. Force and duration of such influence should be stronger, than adaptive possibilities of the tissue, organ. The external causes of an inflammation are classified as follows: the physical factors (foreign bodies, strong pressure on a tissue, high and low temperature, ionizing and ultra-violet rays, high and low barometric pressure, electrical current); chemical factors (acid, alkali, salts of heavy metals); biological factors (microorganisms – bacteria, viruses, fungi; animal organisms – worms, insects). The internal factors are the factors, which arise in organism, as the result of any other diseases, for example cholic acids, complex antigen-antibody and others.
There are five classical local signs of the inflammation. The Roman physician Celsus described four signs, such as: swelling (tumor), redness (rubor), heat (calor), pain (dolor) and the Greek physician Galen added fifth sing – loss of the function (functio laesa). Swelling is the result of the vessels permeability increase. Redness is the result of local arterial hyperemia. Heat (the local rise of temperature) is the result of arterial hyperemia and impermanent intensification of metabolism in the center of inflammation. The pain is the result of the painful receptors irritation by biological active substances, metabolites, and pressing. The loss of the function is the result of the functional active tissue injury.
Fig. Unchanged timpana (1) and inflammation of timpana (2), which is swollen and red.
Depending on clinical course, there are two kinds of inflammation: acute and chronic. During the acute inflammation the pathological agent is destroyed completely and the process ends in liquidation of the inflammation and reparation of full value. The chronic inflammation develops as the result of persistent influence of the pathological agent on an organism, organ, and tissue, which cannot be destroyed and eliminated by the organism.
There are normoergic, hyperergic and hypoergic inflammation when taking into account intensity of local and general changes in organism. The normoergic inflammation is characterized by the adequate reaction of organism, as the response to the invasion of the pathological agent; the hyperergic inflammation is characterized by a very strong reaction of organism even on an insignificant influence of the pathological agent, the hypoergic inflammation is characterized by insignificant changes in tissues.
During the inflammation one of stages of an inflammation can prevail, therefore there can be alterative inflammation, exudative inflammation and proliferative inflammation. The alterative inflammation is characterized by hard damage of tissues (dystrophy, necrosis), the exudative inflammation is characterized by derivation of big quantity of exudates, and the proliferative inflammation is characterized by reproduction of cells.
The inflammation, as typical pathological process, consists of three stages: the first is the alteration stage; the second is violation of microcirculation with exudation and emigration of leucocytes in the center of an inflammation and the third – proliferation.
The first stage is a stage, with which all forms of an inflammation begin. This stage is characterized by the violation of cells structure and function, of fibrous structures, of the microcirculatory system, nervous derivations. The damages of tissues are characterized by the disorder of proteins, fats, and carbohydrates metabolism, physical-chemical and morphological changes of tissues. The more complicated protein fibrous derivations (collagen, elastin) ñàn also be destroyed. Necrobiosis and necrosis can take place in tissues. It is the reversible (sublethal) damage of cells, if they can adapt and restore their structure and function, and the irreversible (lethal) damage of cells, which is characterized by irrevocable change of cells structure.
There are two type of the alteration: primary and secondary. The primary alteration is the result of the influence of the pathological (flogogenic) agent on a tissue. Metabolic and structural changes arise therefore. Various cells react differently: some cells perish, others – remain alive, and others become activated. The activated cells are responsible for the creation of following stages of an inflammation. The secondary alteration is the consequence of the primary alteration and it arises even at the absence of the damaging agent.
The signs of cells damage are the follows: the lessening ðÎ2; limitation or termination of Î2 consumption by cells; the decrease of ÀÒÐ and ÀDÐ and the increase of the inorganic phosphorus concentration; the intensification of glycolysis, which cause the accumulation of lactic acid and piruvate acid; the decrease of cells ðÍ. The decrease of ÀÒÐ concentration reduces the activity of ionic pumps of cells membranes, the parity of Na, K, Ca and Mg in cytoplasm is violated, and the activity of biochemical systems of cells is violated too. Then content of water in cells changes, the synthesis of protein decreases, the density of cytoplasm raises, the amount of Í+ increases, the outlines of the cell change. These changes are reversible.
The constant deficiency of energy provokes the rise of permeability of organelles membranes and swelling of the cell takes place. These changes are the result of the significant damage of cells membrane structures. Free radicals and peroxides play the significant role in this process. They are the result of hypoxia of the damaged tissues and the violation of biochemical processes in cells. The accumulation of free radical substances exceeds the possibility of the cell to neutralize them. Therefore these substances damage membrane structures of the cell.
Especially dangerous is a damage of lysosomic membranes. Enzymes, which are localized in lysosomes, can acts on all kinds of macromolecules of cytoplasm. Primary lysis of the cell can be result of the lysosome membrane destruction by the pathological agent. Lysosome enzymes can get in the intracellular space. The secondary lysis of cells is the result of destruction of lysosomal membrane by free radicals. There is protein complex in blood of the man, which consists from 20 proteins (complement’s system). These proteins are activated during the invasion of microorganisms, promote damage of cells membranes and stimulate the protective phagocytic response. The main task of the complement’s system is destruction of all foreign agents, which get or derivate in human organism. These proteins, as well as lysosomes enzymes, promote development of the first stage of an inflammation. The damage of cells is accompanied by disorder of metabolism. Lisosomal enzymes uncontrol destroy of carbohydrates, proteins, fats, nuclear acids, and the activity of enzymes of glycolysis raises.
The consumption of oxygen in this stage of inflammation is increased. But it lasts not for long (2-3 hours). Then the alteration of cells provokes the damage of mytochondries membranes. The Krebs cycle is violated; the ÀÒÐ derivation is sharply oppressed, so the energy deficiency and accumulation of toxic substances, such as polypeptides, fatty acids, and ketone bodies take place. Simultaneously derivation of ÑÎ2 is violated, and the respiratory coefficient decreases.
The inflammation always begins with the rise of metabolism. The main characteristic of this stage is the activation of metabolism; this is process of substances disintegration and as result destruction of glycoproteins and glicosaminoglican’s complexes, formation of free aminoacids, polypeptides. Some of these substances are mediators of inflammation, and determine dynamics of inflammatory process.
The accumulation of partly-oxidated products in cytoplasm, as the result of violation of Krebs cycle, is accompanied by the development of metabolic acidosic (decrease of ðÍ) and the conditions which are necessary for enzymes systems operation are also violated. The tissue destruction is accompanied by the release of Na+, K+, Ca2+ out the cells and the rise of osmotic pressure (hyperosmia, the increase of proteins concentration, as the result of katabolism intensification, causes the oncotic pressure increase (hyperonkia). The swelling, pain, violation of organ’s functions are the result of these changes.
The secondary alteration is the result of disorder metabolism, the derivation of free radicals, the influence of lysosomic enzymes, local acidosis, hyperonkia, hyperosmia and the influence of inflammatory mediators (biological active substances, which generate in inflammation area).
Mediators of the inflammation
Mediators of the inflammation are united in groups of substances with defined chemical structure: biogenic amines (histamine, serotonine); polipeptides (bradykinine, kallidine); proteins (complement’s system and lysosomal enzymes); derivatives of arachidonic acid (prostaglandines and leucotriens).
Mediators of the inflammation are divided into humoral mediators (proteins of complement’s system, bradykinine, kallidine) and cellular ones (histamine, serotonine, lymphokines, and prostaglandines). This classification is based on an origin of these substances. Humoral mediators are characterized by the widespread effects; spectrum of their influence is very wide.
The effects of cellular mediators are local. Histamine (most important mediator) is found in high concentration in platelets, basophils and mast cells granules together with heparine and factor of thrombocytes activation. The effects of histamine are mediated by histamine receptors (Í1 and Í2).
The main effects of histamine are the result of irritation Í1-histamine receptors of vessel wall (especially in venous). Histamine causes vasodilation and increased permeability of capillaries (main effects of histamine), promotes emigration of leucocytes, stimulates phagocytosis, increases adhesive property of vessels endothelium, and causes a pain.
The neurons, labrocytes, basophiles and thrombocytes contain of serotonin, which couses arterioles constriction, shortening of venules walls myocytes and promote the stagnation of blood in venous.
There are three most important blood systems, which play main role during inflammation: kinines, hemostasis, fibrinolysis and complement’s systems. The ÕII factor of blood coagulation activates derivation such kinines as the bradykinine and kallidine. Their main effects are pain, dilatation of vessels, rise of vascular wall permeability, activation of hemostasic and fibrinolysis systems.
The system of hemostasis and fibrinolysis directly participate in the generation of highly active mediators. The appearance of fibrinopeptides promotes the increase of microvessels permeability, activation of chemotaxis. Plasmine plays the main role in the system of fibrinolysis; it promotes the derivation of biological active substances, which increase of vessels permeability.
The system of complement is the complex of plasma proteins (C1-C9). Their main function is the destruction of alien and own changed cells. Activated Ñ2 operates as kinines; Ñ3 raises vascular permeability and stimulates the motion of phagocytes; Ñ5 has properties of Ñ3 (but is more active) and stimulates the selection of leucocytes of lysosomic enzymes; Ñ5-Ñ9 is provided by the reactions of alien and own cells lysis; Ñ5 stimulates the splitting of arachidonic acid and the synthesis of leucotriens, promotes the forming of oxygen radicals and hydroperoxides of lipids.
Derivatives of arachidonic acid include prostaglandines (PG), thromboxan A2 (TXA2) and leucotriens (LT). PG and TXA2 are formed as the result of splitting of arachidonic acid, which is allocated from phospholipids of membranes cells, by cycloxigenase. Endothelial cells of vessels synthesize PG, thrombocytes synthesize TXA2. PGÅ2 promotes the dilatation of vessels and the increase of their permeability, and also stimulates the excretion of histamine. Leucotriens are formed as the result of splitting of arachidonic acid by lipoxygenase. The leucotriens LÒÑ4, LÒD4, LÒÅ4 are excreted from labrocytes and basophiles and promote the increase of permeability of vessels (especially of venules). LÒÂ4 is excreted by endotheliocytes and promotes chemotaxis of leucocytes, causes adhesion and aggregation of neutrophiles.
Lymphocytes excret lymphokines, which play main role during the immune inflammation. Among them, lymphotoxines realize killer activity of monocytes and lymphocytes and destroy cells-target. The migration-inhibiting factor (MIF) promotes accumulation leucocytes-phagocytes in the center of the inflammation. The factors of blasttransformation provide the reproduction of immunocytes and the excretion of interleukines (IL-1, IL-2, IL-3 etc.). Very important for immune inflammation is an interferone. This protein brakes compilation m-RNA of viruses or cells, this effect promotes the oppression of cells reproduction. The effects of interferone can be realized by means prostaglandins. Sensibilizated T- and B-lymphocytes excret γ-interferone, which regulates the macrophagocytes activity.
Granulocytes excret the platelet-activating factor, which stimulates the excretion serotonine, adrenalin from the thrombocytes. Main effects of the platelet-activating factor are the intensification of microvessels permeability, strengthens the exudation of the blood plasma and the emigration of leucocytes out the vessels.
Polymorphonuclearic leucocytes excrete kationic proteins, neutral and acidic proteases. Kationic proteins can release histamine and raise of vessels permeability, to strengthen the reactions of phagocytes. Neutral proteases (elastase, collagenase, katepsies) destroy the proteins of basal membrane and raise of vascular wall permeability. Acidic proteases acts in conditions of low ðÍ and destroy membranes of microorganisms and own tissues.
Mediators of an inflammation, as the signal’s system, provide the exchange of the information between the cells, which cooperate and destroy the pathological agent. The system of mediators not only provokes various responses of tissues, but also is responsible for their interrelation.
Therefore inflammation has stereotyped components, such as alteration, vascular response, exudation, phagocytosis, and proliferation. The inflammation has some stages, which arise consistently. A principal value for each stage has the defined group of mediators. Histamine and serotonine play the main role on the initial stage of the acute inflammation development. These mediators increase the permeability of microvessels walls, strengthen the exudation, and start the system of kinines, complement and hemostasis. Then the cascade of reactions of arachidonic acid transformation and the derivation of prostaglandines and leucotriens is stimulated. Then the cellular mechanisms of protection start very actively. At the beginning, polimorphonuclearic leucocytes then monocytes and lymphocytes accumulate in the center of the inflammation, and the damaging agent or the products of tissues disintegration are destroyed and eliminated from an organism. The excretion of the inflammation mediators is cascade process. The question about the limitation of their excretion and action is really important. High concentration in blood can cause shock, collapse, DIC-syndrome. In the center of the inflammation, the substances, which block redundant accumulation and stop their influence, are excreted. Such processes take place during all stages of the inflammation.
All these substances are united in the system of antimediators. Enzymes are the main antimediators: histaminase destroys the histamine; carboxypeptidase destroys the kinines; esterases inhibits the complement proteins; prostaglandindehydrogenase destroys the prostaglandines; superoxyddismutase and catalase neutralize radicals of oxygen (eosinophiles are the important cells, which generate and delivery antimediators). Cortisole, cortisone, corticosterone have antimediator’s activity too. They weaken vascular reactions, stabilize membranes of microvessels cells, reduce the exudation and the emigration of leucocytes, weaken phagocytosis, reduce the excretion of histamine, stabilize of lysosomes membranes, reduce activity of lysosomic enzymes and the derivation of kinines and prostaglandines. These effects of corticosteroides doctors use for patients treatment. The inflammation is characterized by local violation of blood and lymph of circulation, especially microcirculation (in terminal vessels – arterioles, metarterioles, capillaries and venules).
Disturbance of the microcirculation in the inflammation area. Y.Kongame has described the stages of disturbance of the microcirculation in the inflammation area. The first stage is the short-term spasm of vessels (arterioles), the second is the arterial hyperemia, the third stage is the venous hyperemia, the fourth stage is the prestasis, and the stasis is the fifth stage. Spasm (constriction) of arterioles is a result of vasoconstrictive adrenergic nerves stimulation by the catecholamines. Catecholamines stimulate a-adrenoreceptors and promote the contraction of smooth muscles of vascular wall. The duration of first stage is short, because the depot of catecholamines in the nervous endings is exhausted very fast and monoamineoxydase destrois the released mediators. The activation of cholinergic nerves and the excretion of acetylcholine promote the development of the second stage of microcirculation violation – the arterial hyperemia. This mechanism is short-term, because acetylcholinesterase destrois acetylcholine. The significant duration of this stage is stipulated by the excretion of vasoactive mediators of the inflammation, which influences on the walls of arterioles and precapillaries (histamine, serotonine, bradykinine, kallidine, prostaglandines).
The change of metabolism in the inflammation area and the damage of cells promote the increase of lactic acid, adenosinemonophosphatic acids, potassium ions concentration and the violation of the functional condition of the connective tissue, surrounding the vessels. The connective tissue becomes less elastic and it promotes the extension of vessels.
The effects of arterial hyperemia are the increase of blood flow speed, the increase of functioning capillaries amount, and the rise of blood pressure, strengthens of the tissues oxygenation. Arterial hyperemia promotes the derivation of the oxygen radicals for the protection of the organism against the microorganisms, forming of humoral plasma factors of the organism protection (complement, properdine, fibronectine), causes the movement of leucocytes into the area of injury. Arterial hyperemia causes the redness and warmth of the injurious area. Venous hyperemia is characterized by the deceleration of blood circulation, the change of blood viscosity (it’s a result of exudation), and the chaotic placement of blood cells. Blood becomes very viscous; erythrocytes swell and move slowly, sometimes they stick in capillaries.
The development of venous hyperemia is promoted by three groups of actors: ² – intravascular, ²² – vascular, Ø – extravascular. Intravascular factors are follows: erythrocytes swelling and blood viscousness, which are the result of the increase vessels permeability; the forming of mycrothrombuses, the disposition of the leucocytes near the vessel wall. Vascular factors: the development of venous hyperemia is promoted by the increase of endoteliocytes sizes and as a result the diameter of capillaries decreases. The elasticity of venal and lymph vessels decreases as a result of collagen and elastine destroy caused by lysosomic enzymes. Extravascular factors: edematic fluid easily squeezes vessels and deepens the violation of blood circulation. Venous hyperemia, which lasts very long time, creates conditions for the development of prestasis. The movements of blood are similar to the movements of a pendulum: blood moves from arteries to veins during systole of the heart and comes back during diastole of the heart.
The increase of blood viscosity, platelets aggregation causes the development of stasis, which is characterized by the stop of blood movement, swelling and aggregation of erythrocytes and their destruction. Changes of the erythrocytes membrane cause the aggregation of erythrocytes. The erythrocytes during the inflammation becomes swollen; the decrease of the blood albumins amount, as the result of the amplified penetration of blood plasma out the vessel,causes the decrease of negative charge of membrane erythrocytes and their conglutination.
Lymphatic system also participates in mechanisms of the inflammation. In a healthy organism lymphatic system executes the drainage function. Their major functions are the extract of microparticles, macromolecules, detritus of the cells and the exchange of liquid between blood and tissues. The inflammation involves many sites of lymph system. Liquid compreses lymph capillaries and it changes local lymphatic circulation. The damage of cells membranes breaks the pump function of lymphatic collective vessels. The inflammation is accompanied by the increase of lymphatic capillaries permeability and their overflow. The detritus of the damaged cells and proteins get into lymph. The injurious factors can cause the inflammation of lymphatic vessels and lymphatic nodes. Due to the drainage function of lymphatic system the amplification of lymphcirculation promotes the decrease of swelling and carries antigens to the lymphatic nodes. Besides the amplification of the drainage function of lymphatic vessels can promote the distribution of the infectious agent and the toxic products of proteins disintegration. Spasm of the lymphatic vessels, which usually arises proximately from the area inflammation and inflammation of the lymphatic nodes deepen the swelling in the area inflammation and evidence development of lymphatic circulation insufficiency. The principal value of the alteration and violations of microcirculation is the creation of unfavorable conditions for further penetration of the pathological agent into the organism.
Exudative and proliferative processes
The increase of vascular wall permeability provokes exudation (penetration of a liquid from the blood into the tissue), emigration of leucocytes. The permeability of microvessels increases first of all (especially of venules). The amplification of exudation provokes: of reologic properties blood change and microperfusion as the result of blood condensation; of laminar blood stream violation; of plasma structure change after the output into the tissue proteins; of microvessels compression by the edematic liquid. These processes provide of phagocytosis (protective process); it is sufficient activity and restoring of the injury tissue. In a stage of arterial hyperemia and especially in venous hyperemia stage fluid with the proteins and salts, dissolved in it, penetrates out the vessel. The high hydrodynamic pressure in vessels and the low colloid-osmotic pressure of blood increase of the vessels permeability and penetration of plasma proteins into the tissue.
There are three ways penetration of fluid through the vessel wall (exudation). The 1st way is interendotelial (between nearby endotheliocytes). Histamine promotes contraction of endothelial cells, the slots between nearby endotheliocytes extend, and basal membrane is exposed. The second way of exudation is transendotelial (through the endoteliocytes cytoplasm). Vesicles pinocytosis activity (the catch of fluid) of the endoteliocytes increases. The blood plasma is inside vesicles, which move through the cell and some time form channels. Various substances can pass without any control through channels (microvesicle transport). The third way of the exudation is the vessels wall area, where are injure endoteliocytes.
The development of the inflammation promotes the amplification of the exudation and the output of blood plasma and the mediators outside the vessels. The main cause of the exudation is mediators of inflammation, but amplifying disorder of the metabolism, the injury cells and leucocytes promotes other pathological mechanisms, which increase vascular permeability. They are lysosomes hydrolytic enzymes of various phagocytes and parenchimal cells (collagenase, elastase) and bacterial enzymes (hyaluronidase), lactic acid and piruvate acid, other non-oxidated substances, which are the result of tissues hypoxia, adenosine, Í+ and K+, especially during the decrease of Ñà2+ level. First of all albumins, than globulins and fibrinogen, which promotes the formation of fibrins clots, penetrate outside the vessels.
The serious damage of vessels wall is accompanied with the erythrocytes diapedesis (penetration through the vessel wall) and the bleeding.
The exudation peculiarity and its structure depend on osmotic, oncotic and hydrodynamical factor of inflammation. Hyperosmia (high osmotic pressure) and hyperoncia (high oncotic pressure) of the tissue in the area inflammation) and osmotic-oncotic pressure of blood are differed, so fluid penetrates out the vessels and amplifies swelling. Hyperosmia is the result of the accumulation osmotic active particles (K+, Na+, salts, light-weight organic substances) of injurious tissue. Hyperoncia is the result of the macromolecules disintegration substances of the injurious tissue accumulation.
There are three types of microvessels permeability change. The first type is the, second type – immediate-continuous, third type – deferred-prolonged increase of permeability of walls of vessels during inflammation. The first type is called the immediate-transient and occurs during weak damages. The main cause of it is the release of histamine, serotonine, and bradykinine. The contraction of endothelial cells and extension of interendothelial slots in small and average venue occurs under the influence of histamine. The permeability of walls of capillaries does not change. Endothelial cells of small and average venue have more histaminic receptors, than the similar cells of capillaries and arterioles; therefore only venue are involved in the process of such type.
The second type of vessels permeability violation arises during hard tissue damages (for example, extensive serious burn). The sharp increase of microvessels permeability arises immediately after damage and lasts up to five day, because endothelial cells of microvessels perish and is characterized by plasmorrhea.
The third type of vessel permeability changes is characterized by the lasting latent period after the damage. After that the permeability of vessels sharply increases and last for some hours or days. This type of vessels response is the most frequently with the human being (thermal damages, tissues injury by ionizing and ultra-violet rays, operation of bacterial toxines, delayed type of the allergy). In these cases endothelial cells don’t round, but juncture between endotheliocytes of the capillaries and venules is broken. The combination of several mechanisms in dynamics the inflammation is possible.
Amplified exudation promotes the development of edema, pain and the function violation. The pain is the result of the nervous ending compression caused by exudates. The violation of the organ or tissue function is the result of the increase of diffuse distance between the capillary and parenchymal cells, and also their compression. The exudation deepens negative effects of the inflammation: the disorder of metabolism and microcirculation of the injurious tissue, hemoconcentration, derivation of thrombus. But at the same time the pathological factor operation weakens due to injuries area.
Vascular changes and the blood stream deceleration promote the reallocation of blood cells: leucocytes move to the vessel wall and begin to attach to it. Then, leucocytes adhere on the endotheliocytes and form the cover along the vessels walls. The process of the edge standing of leucocytes is necessary two following conditions: the increase of endothelial cells adhesive properties and the activation of leucocytes. The increase of adhesive properties of endotheliocytes is promoted by the lowering of their negative membrane charge (it’s the result of the accumulation in the area of inflammation Í+, Ca2+, Ìg2+, Mn2+, cationic proteins, excreted by activated leucocytes). These ions reduce the leucocytes negative charge too, and also activate leucocytes enzymes, which increase adhesive properties of these cells.
Complement, fibronectine, immunoglobulins, histamine, interleukines, leucotriens are the most important initiators of the activation of leucocytes adhesive properties. C5, IgG (Fc-fragment) and IL-8 (chemotactic factors) promote the activation of these cells and their movement to endotheliocytes. Gradually leucocytes begin to pass through the vascular wall and to emigrate into the tissues (positive chemotaxis).
The penetration of leukocytes through the vessels wall is promoted by the alteration of leukocytes, endotheliocytes, interendothelial contacts basal membrane and perivascular tissue states. After the adhesion of the leukocyte to the endotheliocytes membrane it moves on its surface and goes to the interendothelial slot. The leukocyte forms a pseudopodium, which moves through the interendothelial slot into the underendothelial space. All contents of leukocyte move into the pseudopodium, and the leukocyte places in between the endothelial cells and the basal membrane of the microvessel. Then the leukocyte excretes collagenase and elastase, partly alters basal membrane and passes through the vessel wall and gets out the vessel.
In most cases of acute inflammation neutrophyles emmigrate the first (that process lasts 6-24 hours). In 24-48 hours monocytes emigrate most actively. Lymphocytes emigrate a little bit later. Lymphocytes emmigrate first time during virus infection and tuberculosis, and eosinophiles – during allergic reactions. Leukocytes regulate of the cells cooperation and delete the alien agents or the detritus of defective tissues. The neutrophiles (microphages) destroy pathological agents due to the following properties: the absorption of the foreign agent (phagocytosis), the microbicydity and cytotoxicity (these are the mechanisms of the foreign agent destroy by such biooxidants as superoxide anions, hydroxyl- radicals, singlet oxygen, peroxide), the intra- and extracellular lysis.
The neutrophiles excrete the proteolytic enzymes and oxidants into the phagosoma and destroy pathological agent. The excretion of proteolytic enzymes, biooxidants, thromboxans, prostaglandines, and leucotriens out the neutrophiles promotes a self-regulation of the inflammation.
The main functions of the monocytes (macrophages) are the phagocytosis of foreign agent or damaged tissue and the immune reactions stimulation. The high-specifically phagocytosis of the foreign object is carried out due to the electrostatic interaction forces, and especially due to the membranes receptors for Fñ-fragment of immunoglobuline G and ÑÇ component of the complement system, which taking part in a destruction of foreign agent too. The fastening and phagocytosis of the microorganisms promotes stimulation of macrophage, its oxidizing processes and secretion of the bactericide products (lysosomal enzymes, cationic non-enzyme proteins). But some of the particles, especially the inorganic ones, can be stable against such effect and even can cause damage of macrophage. So, the condition of the impossibility of pathological agent elimination is created. In such situation the macrophages execute their protective function in another way: they surround the hard-phagocytible particles and form a cellular conglomeration–node or a granuloma. The macrophages also excrete the factors, which stimulate or inhibit the cellular prolipheration and regulate the regeneration processes (tissues structure restoring).
The lymphocytes play the main role during virus infections. The mowing of lymphocyte out the vessel is promoted by substances (monokines), which are secreted by blood and tissues macrophages. The cooperation of T- and B-lymphocytes with phagocytes is necessary for immune reaction stimulation and phagocytosis activation with the involvement of complement system. All inflammation effectors cells have Fñ-receptors of immunoglobuline G and C- receptors of complement.
The inflammation is named the exudative if this component is expressed stronger than others. The exudate type determines type of an inflammation. There are serous, fibrinous, purulent, decaying, and hemorrhagic and combination types of the exudates and inflammation. The serous inflammation develops in mucous and serous coats, interstitial tissue, skin, and kidneys glomes capsules. The amount of cells in the serous exudate is not large.
The serous exudate promotes washing off of microorganisms and their toxines from the damaged surfaces. But the serous exudate in brain coats can squeeze the brain and violate its function. The serous infiltration of lungs alveolar septs can cause the development of acute respiratory insufficiency syndrome.
The fibrinous exudate contains a plenty of fibrinogen, which forms clots of fibrin in tissues. Such inflammation occurs when an organism is affected by corinebacterium diphtheriae, pneumococcus, Fridlander's bacillus, Frencel's diplococcus, streptococcus, and mycobacterium of tuberculosis. Such type of an inflammation occurs on mucous or serous coats more often.
The causes of purulent inflammation are staphylococcus, streptococcus, gonococcus, meningococcus, and Frenkel’s diplococcus. Purulent exudate consists of many viable leukocytes and purulent bodies (perishing leukocytes), cells detritus, microorganisms, plenty of proteins (especially globulines).
The decaying inflammation develops after the invasion of decaying microflora into the purulent inflammation site. During this type of inflammation necrosis of injurious tissues progresses, the inflammation area doesn’t localize, and this provokes the arrival of alien and toxic products into vessels and the development of intoxication due to which the patients usually dies.
The hemorrhagic inflammation, as the form of the serous, the fibrinous or the purulent inflammation, is characterized by erythrocytes impurity to the exudate (Siberian ulcer, natural smallpox, influenza).
The combination forms of inflammation are characterized by connection of one type of exudate to another. Any combinations are possible. Such forms usually develop as the result of connection of a new infection to the lasting process. The tissues damage and the process of inflammation cause the restoring of broken structure and function (reparative regeneration).
The inflammation proliferative phase
The inflammation proliferative phase is simultaneously a phase of the reparatory regeneration. The restoring of the damaged tissues structure depends on the interaction of connective tissues cells among themselves (fibroblasts, macrophages, labrocytes, lymphocytes, endotheliocytes), on the interaction of connective tissues cells with the intercellular matrix (collagen, proteoglicans, fibronectine), on the interaction of connective tissue cells with blood cells and parenchymal ones.
The process of cells proliferation is regulated by substances, which can stimulate (mitogens) or oppress (keilones) the reproduction of cells. Cambial cells are the tissues source of regeneratory material. The damage of tissues causes intensive proliferation trunk cells. The reparative stage of inflammation begins when phagocytes actively swallow the microorganisms or the tissues detritus. At that time labrocytes activate interaction with macrophages, fibroblasts, and intercellular matrix, clotting blood system and promote the excretion and the synthesis of substances, which stimulate proliferative processes.
Thrombocytes produce substances, which strengthen the proliferation and the chemotaxis of fibroblasts to the injurious area: the thrombocytal factor growth of fibroblasts, the factor of epidermis and fibroblasts growth, the peptide, which activates connective tissue etc.
The labrocytes excrete histamine and leucutrien Â4, which activate fibroblasts proliferation. The neutrophiles excrete peptide, which activates the growth of fibroblasts and leucotrien, which cause the migration of fibroblasts into the injurious tissue.
The macrophages are the main cells, which regulate the reparative processes. Macrophages enclose (segregate) of the injurious tissue, form neutrophile-macrophagal, macrophagal and macrophagal-fibroblasts barriers – the granulating tissue.
The macrophagal-fibroblastic interaction conduces migration, proliferation, and differentiation of fibroblasts, synthesis and secretion of collagen and other components of tissues matrix. The accumulation of fibroblasts in the inflammation site inhibits their growth and stimulates the biosynthesis of collagen. Fibroblasts contact interaction stimulates the production of keilons.
The macrophages, lymphocytes, neutrophiles produce the intercellular matrix (collagen, fibronectine). The further stage of connective tissue growth autoregulation is characterized by the collagen synthesis inhibition, the destruction of the majority cells, the transformation of the fibroblasts in fibrocytes (inactive cells). The fibroblasts destroy unnecessary collagen fibres by means of their phagocytosis, or the secretion of collagenase. All of these promote the stop of connective tissue growth.
Granulation tissue one of the very important products of inflammatory-reparative process is, this is a young connective tissue with a plenty of vessels. This tissue fills wound and ulcer skin defects; it is formed during the damage of mucous coats and internal organs, during bones fractures, hematomes organization, at necrosis and infarctions sites, and during chronic inflammation.
The functions of granulation tissue are as follows: mechanical (filling of defect), trophic (microcirculation regulation, oxygen and metabolites transport, filtering of substances), morphogenetic (influence on epithelium and muscular tissue differentiation). But the main function of the granulation tissue is the protection against unfavorable influences of the external environment, against infection and intoxication, incapsulation (closing) of necrosis area and alien bodies, and also reconstruction of anatomic and functional structure of injurious tissues. During the proliferative processes activation, the cells, which are constantly stimulated by mitogens, become very sensitive to carcinogenic substances. Abnormal mitosis can lead to tumour formation.
The course of inflammatory reaction depends on the organism reactivity, on the nervous, endocrine and immune systems condition. The meaning of the nervous system in the dynamics of the inflammation proves to be true by numerous cases of inflammation sings development in the patients under the influence of suggestion during hypnosis. The occurrences of hyperergic inflammation during the local action of the damaging factor at maniac excitement are often in psychiatric clinic, and at serious depressions the inflammatory reaction proceeds very languidly. The change of nervous – impulse and nervous – trophic influences on the damaged tissue promotes the amplification of exudative processes and the violation of microcirculation.
Neuromediators and trophogens, activate the phagocytosis and the free-radical processes. The violation of afferent innervation strengthens alteration processes and decelerates the reparation of parenchymal cells. Proliferative processes pass most actively on the periphery of the inflammation area, because just there nervous fibres regenerate first and anabolic processes on the periphery proceed more actively.
Neuropeptides take active part in the regulation of proliferative-regeneratory processes in tissues of organs, especially the opiod peptides. The stimulation of C-fibres opioid receptors by these peptides weakens the pain, reduces the release of noradrenalin from sympathetic nervous endings, the activation of labrocytes and trombocytes stops, the disorders of microcirculation and violation of hemostasis are eliminated.
The influence of endocrine system on the inflammation is proved by numerous clinical observations. Hyperthyroidism amplifies manifestations of the inflammation and hypothyroidism is characterized by the insignificant sings. Mineralocorticoids promote the development of inflammatory reaction and glucocorticoids weaken it. The ability of glucocorticoids to weaken the inflammation is constantly used in clinics because they reduce the amount of tissues basophiles, increase the activity of histaminase (enzyme, which destroys histamine), reduce serotonine formation, stabilize lysosome membranes and inactivate their enzymes. Glucocorticoids induce synthesis of proteins, which block prostaglandines and leucotriens synthesis. Mineralocorticoids are capable to strengthen the exudation, to accelerate the reproduction of cells, the derivation of new capillaries, and synthesis of the connective tissue.
The inflammatory reaction in the process of phylogenesis has arisen as a protective response of the organism of hot-blood biological individuals. The organism protects itself from the influence of the pathological factor due to limitation of the inflammatory area from the whole organism. The barrier is formed around the inflammation area; it allows various substances to flow in one direction (to the centre of the inflammation site) due to blockade of lymphatic and blood vessels. The unfavorable conditions for microorganisms are created in the centre of the inflammation. But in the conditions of significant tissues damage or microcirculation violations, the hard metabolism disorder in the damaged tissue or organ, hypoxia and the common intoxication strengthening patient’s sufferings can be provoked. The inflammation is the example, which connects both the elements of injury and the elements of organism protective forces.