Swelling in the focus of inflammation. The pathogenesis of inflammation

QUESTION N 1. Specify inflammatory mediators of cellular origin:

1. lymphokines; 3. histamine; 4. prostaglandins

QUESTION N 2. Who proposed the physicochemical theory of inflammation?

QUESTION N 3. The activator of the kallecriin-kinin system is:

1. Hageman factor

QUESTION N 4. Specify inflammatory mediators released during cell degranulation:

1. serotonin; 5. histamine

QUESTION N 5. The presence in the punctate of a significant number of lymphocytes, histiocytes,

plasma cells, macrophages is typical for:

3. chronic inflammation

QUESTION N 6. Specify physical and chemical changes in the focus of inflammation:

1. Acidosis; 2. Hyperonkia; 3. Hyperosmia

QUESTION N 7. Pathogenetic factors of inflammatory edema are:

1. increase in intravascular hydrostatic pressure; 2. increased permeability of the vascular wall

QUESTION N 8. Alternative inflammation is characterized by:

1. predominance of dystrophic, necrotic and necrobiotic processes

QUESTION N 9. Inflammation is a process caused by:

Correct answer:

1. local action of the damaging factor

QUESTION N 10. The destabilizer of lysosome membranes during inflammation is:

1. Aldosterone

QUESTION N 11. The composition of pus includes:

1. purulent bodies; 3. microorganisms; 5. collagen fibers

QUESTION N 12. Exudative inflammation can NOT be:

4. Granulomatous

QUESTION N 13. Indicate the most common sequence of blood cells entering the focus

inflammation:

2. Granulocytes - monocytes - lymphocytes

QUESTION N 14. Negative value of exudation:

3. development of pain syndrome; 4. aggravation of alteration; 5. deterioration of blood supply to tissues

QUESTION N 15. What substances inhibit the process of proliferation in the focus of inflammation?

4. glucocorticoids; 5. keylons

QUESTION N 16. Local signs of inflammation are:

2. swelling; 3. pain; 5. redness; 7. temperature increase in the damaged area

QUESTION N 17. Primary alteration:

1. occurs under the influence of a damaging factor

QUESTION N 21. The stages of the process of leukocyte emigration are:

1. marginal standing of leukocytes; 2. exit of leukocytes through the endothelial wall; 4. directional movement

leukocytes at the site of inflammation

QUESTION N 22. Mediators of inflammation of cellular origin are:

2. serotonin; 3. thromboxane; 4. histamine

QUESTION N 23. Physical and chemical changes in the alteration zone:

2. acidosis; 3. hyperosmia; 4. hyperonkia

QUESTION N 24. Redness during inflammation is a consequence of:

3. arterial hyperemia

QUESTION N 25. Hyperosmosis of tissues during alteration is caused by:

3. Massive release of K+ from cells

QUESTION N 26. What processes are present during inflammation:

2. alteration; 4. exudation; 5. proliferation

QUESTION N 27. The causes of secondary alteration are the action:

1. reactive oxygen species; 2. microcirculatory disorders; 3. inflammatory mediators

QUESTION N 28. What are the signs acute inflammation associated with the name of Celsus?

1. dolor; 2. tumor; 4.calor; 5. rubor

QUESTION N 29. What disturbances of peripheral blood circulation are observed in the focus of inflammation?

3. venous hyperemia; 4. arterial hyperemia; 5. spasm of arterioles; 6. stasis

QUESTION N 30. In what part of the vascular bed does the emigration of leukocytes predominantly occur?

2. postcapillary venule

QUESTION N 31. Which of the inflammatory mediators plays an important role in the development of fever?

2. interleukin-1

QUESTION N 32. What type of exudate is observed in diphtheria?

3. fibrinous

QUESTION N 33. How does the tone of arterioles change in the focus of inflammation under the influence of prostaglandin E and

prostacyclin?

2. decreases

QUESTION N 34. The anti-inflammatory effect of glucocorticoids is due to:

2. decrease in capillary permeability; 3. inhibition of the process of exudation; 4. inhibition of activity

lysosomal enzymes

QUESTION N 35. The site of action of endogenous pyrogens are:

2. neurons of the centers of thermoregulation of the hypothalamus

QUESTION N 36. The causative factors of inflammation are:

1. phlogogens

QUESTION N 37. Oxygen-dependent bactericidal systems of leukocytes:

1. superoxide anion radical; 3. hypochlorite

QUESTION N 38. characteristic features inflammation are:

3. complex, complex character; 4. protective and adaptive nature

QUESTION N 39. What processes are characteristic of the focus of inflammation?

1. intensive proteolysis; 2. alteration; 3. phagocytosis; 4. proliferation

QUESTION N 40. What signs of acute inflammation are associated with the name of Galen?

5. functio laesa

QUESTION N 41. Specify the features of thermoregulation in the 1st stage of fever:

3. heat production increases, heat transfer decreases

QUESTION N 42. Pain during inflammation occurs as a result of:

4. compression of receptors by exudate and cellular infiltrate

QUESTION N 43. Signs of exudate are:

3. specific gravity above 1018; 4. high concentration of hydrogen ions

QUESTION N 44. Swelling during inflammation occurs as a result of:

3. cell infiltration; 4. exudation

QUESTION N 46. How does pH change in the focus of inflammation?

1. decreases

QUESTION N 47. The presence in the exudative fluid of many erythrocytes, macrophages, lymphocytes,

neutrophils are characteristic for:

2. hemorrhagic effusion

QUESTION N 48. The infiltrate in acute purulent inflammation is dominated by:

3. neutrophils

QUESTION N 49. An abscess is a purulent inflammation:

2. limited

QUESTION N 50. How does the permeability of the vascular walls change in the focus of inflammation under the influence of

bradykinin?

1. increases

QUESTION N 51. Substances that cause the development of fever are called

3. pyrogens

QUESTION N 52. The causes of hyperonkia in the focus of inflammation are:

2. increase in the dispersion of colloids under conditions of enhanced decomposition; 3. release of blood proteins into the focus

inflammation; 5. increase in the hydrophilicity of colloids under conditions of acidosis

QUESTION N 53. List the physiologically active substances that activate adhesion

neutrophils to the endothelium of microvessels during inflammation:

1. C5a fragment of the complement system; 3. Tumor necrosis factor alpha; 4. Interleukin-1

QUESTION N 54. Specify the features of thermoregulation in the 3rd stage of fever:

4. heat transfer prevails over heat production

QUESTION N 55. Macrophages are:

1. monocytes; 2. histiocytes; 3. Kupffer cells of the liver

QUESTION N 56. Stabilizers of lysosome membranes are:

2. Hydrocortisone

QUESTION N 57. Who first proved the role of hormones in the development of inflammation?

QUESTION N 58. What exudate is closest in composition to the transudate?

4. serous

QUESTION N 59. Choose the WRONG statement:

2. Granulomatous inflammation is exudative

QUESTION N 60. Which of the following substances inhibit the development of a rough scar after surgery?

1. heparin; 3.? – interferon

QUESTION N 61. The adhesion of leukocytes to the endothelium of microvessels is activated by an increase in the number and

activities:

1. Integrins; 2. Factors of neutrophils and vascular membrane cells (cationic proteins, leukotrienes,

prostaglandins E, biooxidants, etc.); 3. Selectinov

QUESTION N 62. The following are involved in the process of phagocytosis:

3. lysosomes

QUESTION N 63. In chronic inflammation, the focus is dominated by:

2. Lymphocytes and monocytes

QUESTION N 64. The main effects of histamine in the focus of inflammation are:

2. expansion of the lumen of blood vessels; 3. increased permeability of vascular walls

QUESTION N 65. In case of inflammation, the trigger mechanism of vascular reactions is:

4. action of biologically active substances (mediators)

QUESTION N 66. What is the biochemical nature of the components of the kallecrein-kinin system?

3. peptides

QUESTION N 67. Humoral mediators of inflammation are:

4. Kallidin, bradykinin, Hageman factor

QUESTION N 68. Stasis in the focus of inflammation is characterized by:

1. stopping blood flow in the vessels

QUESTION N 69. Pathogenetic factors of inflammatory edema are:

1. increase in colloid osmotic pressure in the area of ​​damage; 4. Decreased lymph flow

QUESTION N 70. The processes of proliferation in the focus of inflammation stimulate:

4. Endothelial growth factor; 5. Trephons

QUESTION N 72. Phlegmon is a purulent inflammation:

3. common

QUESTION N 73. Specify lysosomal enzymes

1. hydrolases

QUESTION N 74. The source of endogenous pyrogens are:

1. phagocytes

QUESTION N 75. Positive value of exudation:

1. prevents the spread of microbes and toxins throughout the body; 4. breeding microbes, their toxins and

biologically active substances

QUESTION N 76. The main component of hemorrhagic exudate is:

3. erythrocytes

QUESTION N 77. In the zone of inflammation caused by Mycobacterium tuberculosis, there are:

3. lymphocytes; 4. Pirogov-Langhans cells

QUESTION N 78. Signs of exudate are:

QUESTION N 79. The occurrence of arterial hyperemia in the focus of inflammation is facilitated by:

1. bradykinin; 2. increased tone of vasodilators; 3. histamine

QUESTION N 80. Specify the founder of the cellular (nutritive) theory of inflammation:

QUESTION N 81. The causes of primary alteration are the action:

1. phlogogen

QUESTION N 82. Empyema is a purulent inflammation:

3. in cavities and hollow organs

QUESTION N 83. What is the biochemical nature of prostaglandins?

1. arachidonic acid derivatives via the cyclooxygenase pathway

QUESTION N 84. Systemic signs of inflammation are:

2. leukocytosis; 3. increased body temperature

QUESTION N 85. Biochemical changes in the alteration zone:

1. increase in hydrolysis processes; 2. increase in anaerobic glycolysis; 5. activation of peroxidation

QUESTION N 86. The source of mediators in the focus of inflammation are:

2. basophils; 4. monocytes; 5. neutrophils; 6. lymphocytes; 7. eosinophils; 8. mastocytes

QUESTION N 87. What is the emigration of leukocytes?

3. penetration of leukocytes from the blood into the focus of inflammation

QUESTION N 88. What is NOT a stage of phagocytosis?

4. degranulation

QUESTION N 89. Factors contributing to exudation are:

1. hyperonkia in the focus of inflammation; 2. increased capillary permeability; 5. hyperosmia in the focus of inflammation

QUESTION N 90. General changes in the body during inflammation are:

2. slowing down the ESR; 4. leukocytosis; 5. fever

QUESTION N 91. What is the sequence of changes in blood circulation in the focus of inflammation?

1. ischemia, arterial hyperemia, venous hyperemia, stasis

QUESTION N 92. Who is the founder of the biological (phagocytic) theory of inflammation?

1. Mechnikov

QUESTION N 93. What substances do NOT affect the process of proliferation in the focus of inflammation?

1. protease inhibitors; 4. potassium ions

QUESTION N 94. What is the biochemical nature of leukotrienes?

4. arachidonic acid derivatives via the lipoxygenase pathway

QUESTION N 95. What do macrophages phagocytize in the focus of inflammation?

1. products of tissue breakdown; 3. bacteria

QUESTION N 96. Inflammation is distinguished by the type of exudate:

2. Purulent; 3. Serous; 4. Catarrhal

QUESTION N 97. How does the tone of arterioles change in the focus of inflammation under the action of kinins?

2. decreases

QUESTION N 98. The development of venous hyperemia in the focus of inflammation is facilitated by:

1. thickening of the blood; 4. compression of veins by exudate; 5. microthrombosis

QUESTION N 99. Pain during inflammation is caused by:

1. H+ hyperionia; 3. Histamine, serotonin

QUESTION N 100. Signs of transudate are:

1. low concentration of hydrogen ions; 2. specific gravity below 1018

QUESTION N 101. An important role in the development of proliferation during inflammation is played by:

3. Fibroblasts; 4. Capillary endotheliocytes

QUESTION N 102. How does the osmotic pressure change in the focus of inflammation?

2. increases

QUESTION N 103. Marginal standing of leukocytes is promoted by:

1. change in the electrostatic charge of leukocyte membranes and endothelial cells; 3. formation of calcium

bridges; 4. loosening of the fibrin layer of the vessel wall

QUESTION N 104. High vascular permeability in the focus of inflammation is caused by:

1. increased micropinocytosis; 2. mechanical stretching of blood vessels by excess blood; 3. cell rounding

vascular endothelium under the influence of biologically active substances and acidosis

QUESTION N 105. The source of histamine in the focus of inflammation are:

2. basophils; 5. mast cells

QUESTION N 106. Primary alteration in the focus of inflammation is caused by:

5. phlogogenome

QUESTION N 107. Specify the types of inflammation depending on the characteristics of the immunological

body reactivity?

1. hypergic; 2. normergic; 4. hyperergic

QUESTION N 108. Exogenous phlogogens include:

2. infection; 3. thermal effects; 5. acids

QUESTION N 109. Secondary alteration:

2. occurs during the inflammatory process itself

QUESTION N 110. According to the rate of development and duration of the course, the following types of inflammation are distinguished:

2. Chronic; 4. Subacute; 6. Spicy

QUESTION N 111. The outcome of acute inflammation can be:

2. Scar; 3. Complete restoration of structures, metabolism, functions

QUESTION N 112. What processes play a protective role in the focus of inflammation?

2. exudation; 3. proliferation

QUESTION N 113. What do microphages phagocytize in the focus of inflammation?

1. staphylococci; 4. streptococci

QUESTION N 114. The following contribute to the development of exudation:

2. Increased permeability of microvessels; 3. Hyperonkia of tissues; 4. Venous congestion

QUESTION N 115. In the development of proliferation during inflammation, an important role is played by:

1. Decay products of cellular and tissue structures; 2. Metabolic products of cellular and tissue structures; 3.

QUESTION N 116. Oxygen-independent bactericidal systems of leukocytes:

3. lactoferrin; 4. non-enzymatic cationic proteins

QUESTION N 117. Signs of transudate are:

QUESTION N 118. Mediators of plasma origin are:

1. complement system; 5. kinin

QUESTION N 119. How does the permeability of the vascular walls change in the focus of inflammation under the influence of

histamine and serotonin?

1. increases

QUESTION N 120. How does the content of C-reactive protein in the blood plasma change during inflammation?

3. increases

QUESTION N 121. Have a pronounced ability to phagocytosis:

2. histiocytes; 5. monocytes; 6. neutrophils

QUESTION N 122. Specify the local signs of acute inflammation:

2. pain; 4. Redness

4 stages:
1- Transient spasm of the afferent arterioles is clearly pronounced with rapidly developing damage (burn)
2-Arterial hyperemia - an increase in the blood filling of the damaged part of the organ (10-30 minutes)
3-Venous hyperemia - maximum expansion of afferent arterioles and precapillary sphincters, the patent of blood flow velocity in microcirculatory vessels
4-stasis - preceded by a prostatic condition, characterized by a pendulum movement of blood, due to increasing stagnation of blood, loss of vascular tone and a sharp expansion of the capillaries and returned, during systole it moves from the arteries to the veins and during the diachtla in the opposite direction

4. The mechanism of formation of exudates.

Mechanisms of exudate formation.
Exudation is the release of the protein-containing liquid part of the blood through the vascular wall into the inflamed tissue. Plasma output is determined by an increase in blood pressure in the venous part of the capillaries of the inflamed tissue. Another factor is the increase in the permeability of the capillary wall caused by inflammatory mediators. When blood proteins begin to be delivered from the vessels into the extravascular space, the oncotic pressure falls and the oncotic pressure of the intestinal fluid increases. The transition of fluid from the vessels to the surrounding space begins due to an increase in oncotic and osmotic pressure in the focus of inflammation. Inflammatory edema has a certain protective value, the proteins of the edematous fluid bind toxins, delay their absorption into the blood and spread throughout the body.
An increase in the osmotic pressure of the interstitial fluid is due to the accumulation of osmotically active tissue breakdown products (sodium, potassium, calcium, chlorine) in the innrestia.

5. Types of exudates.

Serous exudate characterized by a moderate protein content (3-5%) and single polymorphonuclear leukocytes.

Fibrinous exudate is similar in composition to serous exudate, but there is also fibrinogen. feature chemical composition fibrinous exudate is the release of fibrinogen and its loss in the form of fibrin in inflamed tissue (croupous pneumonia, diphtheria)

Hemorrhagic exudate is formed during rapidly developing inflammation with severe damage to the vascular wall, when erythrocytes enter the inflamed tissue. (Anthrax, smallpox, plague) and others shaped elements blood, there is protein.

6. Emigration of leukocytes to the focus of inflammation. Mechanisms.

Emigration of leukocytes is an active process of their exit from the lumen of the vessels of the microvasculature into the intercellular space. After 1-2 hours after exposure of the tissue to the phlogogenic factor, a large number of emigrated neutrophils and other granulocytes are found in the focus of inflammation, later - after 15-20 hours or more - monocytes, and then lymphocytes.

The immigration process goes through the following stages:

Rolling (marginal standing - "rolling") of leukocytes,

Their adhesion to the endothelium and penetration through the vascular wall,

Directed movement of leukocytes in the focus of inflammation

7. Mediators of inflammation.

All known mediators of inflammation by origin can be divided into humoral(formed in liquid media - blood plasma and tissue fluid) and cellular. The former include complement derivatives, kinins and factors of the blood coagulation system, the latter include vasoactive amines, arachidonic acid derivatives (eicosanoids), lysosomal factors, cytokines (monokines), lymphokines, reactive oxygen metabolites, neuropeptides. While all humoral mediators are preexisting, i.e., they are present in the form of precursors before the activation of the latter, among cellular mediators one can single out both preexisting (deposited in cells in an inactive state) - vasoactive amines, lysosomal factors, neuropeptides, and newly formed (i.e., produced by cells during stimulation) - eicosanoids, cytokines, lymphokines, active oxygen metabolites.

8. Phagocytic activity of leukocytes in the focus of inflammation. Phagocytic number, phagocytic index.

To assess the phagocytic activity of peripheral blood leukocytes, 0.25 ml of a microbial culture suspension with a concentration of 2 billion microbes per 1 ml is added to citrate blood taken from a finger in a volume of 0.2 ml. The mixture is incubated for 30 min at 37°C, centrifuged at 1500 rpm for 5-6 min, the supernatant is removed. A thin silvery layer of leukocytes is carefully aspirated, smears are prepared, dried, fixed, stained with Romanovsky-Giemsa paint. The preparations are dried and microscopically.

The count of absorbed microbes is carried out in 200 neutrophils (50 monocytes). The intensity of the reaction is evaluated by the following indicators:

1. Phagocytic index (phagocytic activity) - the percentage of phagocytes from the number of cells counted.

2. Phagocytic number (phagocytic index) - the average number of microbes absorbed by one active phagocyte.

9. Phagocytosis, stages. Violations of the phagocytic activity of leukocytes.

Phagocytosis is an active biological process consisting in the absorption of foreign material and its intracellular digestion by phagocytes.

Stages:
1) convergence phagocyte with an object of phagocytosis
2) recognition phagocytome of the object of absorption and adhesion to it

3) absorption object phagocytome with the formation of phagolysosome

4) destruction of the object of phagocytosis

10. What hormones are anti-inflammatory and pro-inflammatory?

Pro-inflammatory hormones include GH, mineralocorticoids, thyroxine, hormone parathyroid glands, aldosterone, deoxycorticosterone. Anti-inflammatory hormones include ACTH, glucocorticoids, insulin, sex hormones.

11. What factors cause pain during inflammation?
One of the most important effects kinins is their inherent ability to irritate the endings of sensory nerves, causing the occurrence of inflammatory pain. Pain - associated with the release of other mediators, especially prostaglandins, serotonin. In addition, neuropeptides increase the sensitivity of nociceptors to the action of various mediators. And due to mechanical compression of the nerves.

12. What are the mechanisms of exudation during inflammation?

The main factors of the mechanism of exudation:

1) increased vascular permeability (venules and capillaries) as a result of exposure to inflammatory mediators and, in some cases, the inflammatory agent itself - the leading factor;

2) an increase in blood (filtration) pressure in the vessels of the focus of inflammation due to hyperemia;

3) an increase in osmotic and oncotic pressure in the inflamed tissue as a result of alteration and exudation that has begun, and, possibly, a decrease in blood oncotic pressure due to the loss of proteins during abundant exudation.

13. What factors contribute to the development of edema in the focus of inflammation?
Collagenase, histamine, bradykinin.

14. Features transudate from exudate in inflammation?

Exuda t-fluid leaving the microvessels, containing a large amount of protein, FEK.
transudate- edematous fluid that accumulates in body cavities and tissue crevices. The transudate is usually colorless or pale yellow, transparent, rarely cloudy due to the admixture of single cells of the deflated epithelium, lymphocytes, and fat. The content of proteins in the transudate usually does not exceed 3%; they are serum albumins and globulins. Unlike exudate, transudate lacks the enzymes characteristic of plasma..). To distinguish between transudate and exudate, the Rivalta test is used, based on the different protein content in them.

15. What physical and chemical changes are typical for the site of acute inflammation?

16. What are inflammatory mediators that cause an increase in vascular permeability during inflammation?

Complement components and derivatives, kinins (bradykinins, kallidin), prostaglandins, leukotrienes, serotonin, lysosomal enzymes, cationic proteins, superoxide anion radical, hydroxyl radical OH-, hydrogen peroxide H2O2. Neuropeptides. These are substance P, calciotonin (gene-linked peptide), neurokinin A. Acetylcholine, catecholamines.

17. What inflammatory mediators are cellular and plasma?

18.Mechanisms of action of inflammatory mediators.
Histamine Spasm of smooth muscles (increases the formation of prostaglandins E2 and F2a, thromboxane). Vasodilation (expansion of precapillary arterioles). Increased vascular wall permeability, suppression of chemotaxis and phagocytic activity of neutrophils, inhibition of lymphocyte activity and production of lymphokines. Labrocytes, basophilic leukocytes.
Serotonin Narrowing of postcapillary venules, increased permeability of the vascular wall. Pain. Itching. Platelets, labrocytes.
kinins (bradykinin, methionyl lysyl bradykinin). Vasodilation. Increased vascular permeability. Pain. Spasm of the eye muscles. a2-Globulin of blood plasma.
Components of the complement system (C3a, C5a). Degranulation of mast cells (release of histamine). Increased permeability of the vascular wall. Spasm of smooth muscles. Stimulation of leukocyte chemotaxis. Plasma proteins.
Interleukins and monokines : IL-1ß, tumor necrosis factor (TNF-a), etc. Stimulation of prostaglandin synthesis, phagocytosis, proliferation and activation of fibroblasts. Pyrogenesis. Macrophages, monocytes, neutrophilic granulocytes.
Lymphokines : IL-2, macrophage activating factor. Activation of natural killers. Stimulation of granulocytes. Lymphocytes.
Prostaglandins (PGE, PGF2α). Vasodilation. Increased permeability of the vascular wall. Pyrogenesis. Polyunsaturated fatty acids of phospholipids of membranes and blood plasma. Leukotrienes (LTV4 and others). Spasm of smooth muscles. Increased permeability of the vascular wall. Leukocyte activation. Granulocytes. Monocytes. platelets. Labrocytes. 17 1 2 3 Thromboxanes Vasoconstriction. Platelet aggregation. Activation of granulocytes. Macrophages, monocytes. Granulocytes.
Lysosomal factors , (acid hydrolases, non-enzymatic cationic proteins). Secondary alteration, “generation” of “inflammatory mediators”. Promote vasodilation, increase vascular permeability, development of edema and emigration of leukocytes, microthrombosis. Microbicidity. Neutrophilic granulocytes. Monocytes, macrophages.

19. What factors determine the release of plasma proteins from the microcirculatory vessels to the focus of inflammation.
-shrinkage of endothelial cells
-increased oncotic pressure of the interstitial fluid

20. what cells are the main source of histamine in the focus of acute inflammation.
in the focus of acute inflammation: mast cells.
mediators of acute inflammation (they are anaphylatoxins, i.e. histamine liberators from mast cells, increase the permeability of postcapillary venules both directly and indirectly through histamine; C5a, which is formed from C5a in plasma and tissue fluid under the influence of carboxypeptidase N, is not associated with histamine, but is neutrophil-dependent, i.e. increases the permeability of microvessels due to lysosomal enzymes and non-enzymatic cationic proteins, active oxygen metabolites released from polymorphonuclear granulocytes; C5a and C5a des Arg attract neutrophils; C5a and C3a also release interleukin-1, prostaglandins, leukotrienes, platelet activating factor and interact synergistically with prostaglandins and substance P); - C3b opsonizes the pathogenic agent and promotes immune adhesion and phagocytosis; - the C5b-C9 complex is responsible for the lysis of microorganisms and pathologically altered cells; - kinins - vasoactive peptides formed from kininogens (a2-globulins) under the influence of kallikreins in plasma (nonapeptide bradykinin) and in tissue fluid (decapeptide lysylbradykinin, or kallidin).

21. what causes the anti-inflammatory effect of glucocorticoids .
Glucocorticoids have anti-shock, anti-inflammatory, antiallergic, immunosuppressive, antitoxic action. The anti-inflammatory effect is due to the inhibition of the activity of phospholipase A 2 and the stabilization of cell membranes, a decrease in the formation of prostaglandins and leukotrienes. The antiallergic effect is associated with the stabilization of mast cells and the obstruction of their degranulation. In addition, anti-allergic and antidepressant effects are the result of a decrease in the migration of T- and B-lymphocytes and a violation of their interaction.
The main indications for the use of glucocorticoids are rheumatism, collagenosis, rheumatoid arthritis, polyarthritis, bronchial asthma, skin allergic diseases.

22. what causes the increase in osmotic and oncotic pressure in the inflammatory tissue.
A moderate increase in permeability leads to the release of fine fractions of proteins, primarily albumins. With a significant increase in permeability, globulins are released, and with an even more pronounced increase in fibrinogen, which forms fibrin clots in the extravascular bed.
In the tissue of the focus of inflammation, osmotic pressure (hyperosmia) increases, while the osmotic pressure of the blood usually does not change. The resulting gradient of osmotic pressure of blood and tissue is an important factor in enhancing exudation and development of edema. Tissue hyperosmia occurs as a result of an increase in the concentration of osmoactive particles in them, tissue acidosis.
In the tissue of the focus of inflammation, oncotic pressure (hyperonkia) also increases. This is due to an increase in the concentration, dispersion and hydrophilicity of protein products. In the blood, oncotic pressure, as a rule, decreases (hypoonkia) due to impaired liver function and a decrease in the formation of albumins by hepatocytes, an increase in the synthesis of less oncoactive globulins. The oncotic pressure gradient of tissue and blood plasma is an important factor in enhancing exudation and the development of edema.
mechanisms of exudation and formation of inflammatory edema:
1. Increasing the permeability of the walls of microvessels.
2. Strengthening the output of fluid with a moderate protein content (oncotic and osmotic pressure of the tissue in the focus of inflammation temporarily remains unchanged).
3. During the period of severe disorders of microcirculation and the occurrence of hypoxia, hyperosmia and hyperonkia of the tissue develop.

23. What causes acidosis in the focus of inflammation?
Liberation and accumulation a large number acids.
In the very initial period of the inflammatory reaction, a short-term primary acidosis develops, the content of acidic products increases. With the onset of arterial hyperemia, the acid-base state in the tissues of the inflammatory focus normalizes, and then a long-term pronounced metabolic acidosis develops, which is initially compensated (there is a decrease in alkaline reserves of tissues, but their pH does not change). As the inflammatory process progresses, already uncompensated acidosis develops due to an increase in the concentration of free hydrogen ions and the depletion of tissue alkaline reserves. During cell alteration, a large amount of intracellular potassium is released. In combination with an increase in the amount of hydrogen ions, this leads to hyperionia in the focus of inflammation, and the latter causes an increase in osmotic pressure. The accumulation of oligo- and monopeptides during the proteolysis of polypeptides by the released lysosomal hydrolases activated under conditions of acidosis leads to an increase in oncotic pressure.

24. Proliferation. Proliferation mechanisms.
As the focus of inflammation is cleared, proliferation occurs - characterized by an increase in the number of stromal parenchymal cells, as well as the formation of intercellular substance in the focus of inflammation. These processes are aimed at the regeneration of destroyed tissue elements. Various biologically active substances are essential at this stage of inflammation. The proliferation is completed by the involution of the scar, that is, the destruction and elimination of excess collagen structures. The main cell proliferation effectors are activated mononuclear phagocytes, fibroblasts, and immunocompetent cells. Fibroblasts in the focus of inflammation form and release collagen and the enzyme collagenase, which is responsible for the formation of collagen structures in the stroma. connective tissue. In addition, they secrete fibronectin, which determines the migration, proliferation and adhesion of fibroblasts. Mononuclear cells and lymphocytes secrete cytokines, both stimulating and suppressing these functions of fibroblasts. Neutrophils, as cellular effectors of inflammation, affect proliferation by secreting tissue-specific inhibitors that interact according to the feedback principle.

VI. Heredity.

1. Etiology of hereditary diseases.

Etiological factors of hereditary diseases are mutations of hereditary material. Mutations affecting the entire chromosome set or individual chromosomes in it (polyploidy and aneuploidy), as well as sections of chromosomes (structural rearrangements - deletions, inversions, translocations, duplications, etc.) lead to the development of chromosomal diseases. In chromosomal diseases, the balance of the gene set is disturbed, which can lead to intrauterine death of embryos and fetuses, congenital malformations, and other clinical manifestations. The more chromosomal material is involved in the mutation, the earlier the disease manifests itself and the more significant the disturbances in the physical and mental development of the individual. (Chromosomal diseases are rarely transmitted from parents to children, mainly a randomly occurring new mutation. But about 5% of people are carriers of balanced changes in chromosomes, therefore, in case of infertility, stillbirth, recurrent miscarriage, or the presence of a child with a chromosomal pathology in the family, it is necessary to examine the chromosomes of each from spouses Gene diseases are diseases caused by changes in the structure of the DNA molecule (gene mutations).) - you can not write.

2. Types of mutations.
For the reason that caused the mutation:
"spontaneous"
induced.
1. Spontaneous mutations occur under the influence of natural mutagens of exogenous or endogenous origin, without special (targeted) human intervention. Result of action chemical substances,
2. Induced mutations are caused by the directed action of external or internal environmental factors. Controlled - purposefully, in order to study the mechanisms of mutagenesis and / or its consequences.
Uncontrolled - when radioactive elements are released into the environment during accidents at nuclear power plants.
According to the type of cell in which the mutation occurred:
gametic and
somatic.
Gametic mutations are found in germ cells. They are inherited by descendants and, as a rule, are found in all cells of the body.
Somatic mutations occur in non-sex - somatic cells of the body and appear only in the individual in whom they occur. These mutations are only passed on to daughter somatic cells when they divide and are not inherited by the next generation of the individual.
By biological significance
pathogenic,
neutral and
favorable
Pathogenic mutations lead either to the death of the embryo (or fetus), or to the development of hereditary and congenital diseases.
Neutral causing freckles, discoloration of hair, iris).
Favorable ones increase the viability of an organism or species (for example, the dark color of the skin of the inhabitants of the African continent).

By the scale of changes in genetic material
genetic,
chromosomal or
genomic.

Gene (point) are changes in the molecular structure of DNA (deletion, duplication, doubling, inversion, insertion, transition, transversion). A significant part of point mutations disrupts the "functioning" of the gene and leads to the development of gene (monogenic) diseases. Phenotypically, gene diseases most often present with signs of metabolic disorders (eg, phenylketonuria, neurofibromatosis, cystic fibrosis, Duchenne-Becker muscular dystrophy).
Chromosomal mutations (aberrations) are characterized by a change in the structure of individual chromosomes, while genomic mutations are characterized by their number.

3. Types of inheritance
AUTOSOME DOMINANT (Marfan's syndrome, hemoglobinopathy M, Huntington's chorea, colonic polyposis
gut, familial hypercholesterolemia, neurofibromatosis, polydactyly)
signs: The same frequency of pathology in males and females. The presence of patients in each generation of the pedigree. The probability of the birth of a sick child is 50%. Unaffected family members usually have healthy offspring.
AUTOSOME RECESSIVE ( phenylketonuria, ocular albinism, sickle cell anemia, adrenogenital syndrome, galactosemia, glycogenosis, hyperlipoproteinemia, cystic fibrosis)
signs: Equal frequency of pathology in males and females. Manifestation of pathology in the pedigree “horizontally”, often in siblings. .Parents of the patient, as a rule, are healthy. The same disease can be found in other relatives, such as cousins ​​or second cousins ​​(sisters) of the patient.
CHROMOSOME-LINKED X-DOMINANT ( hypophosphatemia - vitamin D-resistant rickets; Charcot-Marie-Tooth disease X-linked dominant; orofacial-finger syndrome type I) Males and females are affected, but women are 2 times more likely. Transmission of a pathological allele by a sick man to all daughters and only daughters, but not sons. Sons receive the Y chromosome from their father. The transmission of the disease by a sick woman to both sons and daughters is equally likely. The disease is more severe in men than in women.
CHROMOSOME-LINKED X-RECESSIVE (hemophilia A, hemophilia B; X-linked recessive Charcot-Marie-Tooth disease; color blindness; Duchenne-Becker muscular dystrophy; Kallman's syndrome; Hunter's disease (mucopolysaccharidosis type II); Bruton's type hypogammaglobulinemia. Patients are born in the marriage of phenotypically healthy parents. The disease observed almost exclusively in males.The mothers of patients are obligate carriers of the pathological gene.The son never inherits the disease from the father.A carrier of the mutant gene has a 25% chance of having a sick child (regardless of the sex of the newborn); the probability of having a sick boy is 50%.
HOLANDRIC (ichthyosis skin, hypertrichosis auricles, excessive hair growth on the middle phalanges of the fingers, azoospermia) The transmission of a trait from the father to all sons and only sons. Daughters never inherit the trait from the father. The "vertical" nature of the inheritance of the trait. The probability of inheritance for males is 100%.
MITOCHONDRIAL HERITAGE (mitochondrial diseases): Leber's optic nerve atrophy, Ley's syndromes (mitochondrial myoencephalopathy), MERRF (myoclonic epilepsy), dilated familial cardiomyopathy. The presence of pathology in all children of a sick mother. that mitochondria are inherited from the mother. The proportion of the paternal mitochondrial genome in the zygote is DNA from 0 to 4 mitochondria, and the maternal genome is DNA of about 2500 mitochondria. In addition, it appears that after fertilization, paternal DNA replication is blocked.

4. diseases transmitted in an autosomal dominant manner.
With an autosomal dominant type of inheritance, most patients are born in marriages between the affected (heterozygous for the autosomal dominant gene Aa) and a healthy spouse (homozygous for the normal allele)
Familial hypercholesterolemia, hemochromatosis, Marfan's syndrome, type 1 neurofibromatosis (Recklinghausen's disease), Ehlers-Danlos syndrome, myotonic dystrophy, achondroplasia, osteogenesis imperfecta. Marfan's syndrome is a hereditary disease, which is a generalized lesion of the connective tissue with high penetrance and varying expressivity.
the main features of the autosomal dominant type of inheritance of the disease are: 1) the disease manifests itself in each generation 2) each child of a parent with an autosomal dominant disease has a 50% risk of inheriting this disease; 3) males and females are affected equally often and equally; 4) a sick child has a sick parent; 5) unaffected family members are free from the mutant gene

5.diseases transmitted in an autosomal recessive manner.
Autosomal recessive type most of the hereditary diseases that develop in homozygous children are transmitted, both of whose parents are heterozygous carriers of a pathological trait and are phenotypically healthy. The anomaly is transmitted in the form of albinism(lack of pigment in the skin, hair, iris due to the lack of tyrosinase, which normally converts tyrosine into melanin), congenital deaf-mutism, idiocy with blindness, schizophrenia diabetes, complete color blindness, microcephaly. Very often, various metabolic disorders are transmitted in an autosomal recessive type: phenylketonuria (which is based on a decrease in the activity of glucose-alanine hydroxylase, which leads to the accumulation of l-phenylalanine in tissues due to the blockade of its transition to tyrosine), generalized glycogenosis (a decrease in the activity of glucose-6-phosphatase organs, due to which glycogen accumulates in tissues), galactosemia (due to a defect in lactase, an enzyme that breaks down lactose; it is also characterized by an increase in the liver, the development of cataracts and mental abnormalities), sphingolipidosis (due to the absence of the enzyme sphingolipase in cell membranes , contributes to the deposition of cholesterol and disruption of lipid metabolism of both membrane vessels and other cellular structures; accompanied by the death of children under the age of 5 years, deficiency of pyridoxine - vitamin B6 (leads to impaired metabolism of proteins, amino acids, lipids, enzymes, the development of hypochromic anemia, seizures, etc.) adrenogenital syndrome: a genetically determined blockade of the synthesis of glucocorticoid hormones in the adrenal cortex (results from a deficiency of A-B-hydroxylase), accompanied by an increase in the last production of androgens. This leads to masculinization of girls and premature puberty of boys.

6. Methods for studying hereditary pathology.

Clinical and genealogical method This method is based on tracing any normal or pathological trait in a number of generations, indicating family ties between members of the pedigree. It starts from the proband, which is the name of the person who first came into the doctor's field of vision.

The method includes two steps:

Collection of family information

Genealogical analysis

twin method If the trait being studied is present in both twins of a pair, they are called concordant. Concordance is the percentage of similarity for a given trait. The absence of a sign in one of the twins is discordance.

Population-statistical method The study of signs in large groups people who differ in hereditary characteristics (race, nation, ethnic group, isolates) or living conditions.

Cytogenetic methods (analysis of karyotype and sex chromatin)

Dermatoglyphics - a method of studying relief patterns on the skin formed by papillary lines and scallops (under genetic control).

7. Chromosomal diseases. Down's disease, etc.

Down syndrome (trisomy on chromosome 21) - more often trisomy in the 21st pair of autosomes (45 autosomes + XX in girls or + XY in boys). In other cases, translocation transfer. Characteristic: oligophrenia of varying degrees, short stature, loose joints, muscular hypotonia, short fingers, transverse "monkey" fold on the palm, Mongoloid eye slit, epicanthus, underdevelopment of sexual characteristics. The consequence of excess synthesis of purines

8. Chromosomal diseases. Shereshevsky-Turner syndrome.

Shereshevsky-Turner syndrome is a chromosomal disease, which is characterized by either the complete absence of one chromosome, or the presence of a defect in one of the X chromosomes. The karyotype of such women is 45 X0. There is no sex chromatin in (Barr bodies) in the cell nuclei. Such women have short stature, a short wide neck, multiple age spots, underdevelopment of the glands and ovaries, primary amenorrhea and infertility, and mental development is normal.

9. Chromosomal diseases. trisomy syndrome.

An inherited disorder caused by the presence of an extra X chromosome is a special case of aneuploidy. In most cases, carriers of an additional X chromosome are women without noticeable signs of pathology (Two Barr bodies). Trisomy on the X chromosome leads to a slight increase in intrauterine mortality. Development may proceed with some disturbances, there may be problems with coordination, motor skills and speech development. In some cases, a smaller head size is noted (without a noticeable decrease in mental abilities)

10. Chromosomal diseases. Klinefelter syndrome.

Several types of polysomy for X and Y chromosomes have been found in males: 47, XXY; 47,XYY; 48,XXXY; 48,XYYY; 48XXYY; 49XXXXY; 49XXXYY. The most common is Klinefelter's syndrome (47, XXY). Characterized by high growth, asthenic physique of the eunuchoid type, gynecomastia, testicular atrophy and infertility, often osteoporosis. Sex chromatin (Barr bodies) is found in the nuclei.

11. Pathogenesis of hereditary diseases. Phenylketonuria.

Phenylketonuria is a rare hereditary disease of a group of fermentopathies associated with impaired metabolism of amino acids, mainly phenylalanine. If a low-protein diet is not observed, it is accompanied by the accumulation of phenylalanine and its toxic products, which leads to severe damage to the central nervous system, manifested, in particular, in the form of a violation mental development(phenylpyruvic oligophrenia). One of the few hereditary diseases, amenable successful treatment. As a result of the metabolic block, side pathways of phenylalanine metabolism are activated, and the body accumulates its toxic derivatives - phenylpyruvic and phenylolactic acids, which are practically not formed normally. In addition, phenylethylamine and orthophenylacetate, which are almost completely absent in the norm, are also formed, the excess of which causes a violation of lipid metabolism in the brain. Presumably, this leads to a progressive decrease in intelligence in such patients up to idiocy.

12. Sex-linked diseases.

Sex-linked inheritance is the inheritance of a gene located on the sex chromosomes. The inheritance of traits that appear only in individuals of the same sex, but are not determined by genes located on the sex chromosomes, is called sex-limited inheritance. The transmission of color blindness is associated with the X chromosome and is almost always transmitted from the mother of the gene carrier to the son, as a result of which it is twenty times more likely to occur in men with a set of XY sex chromosomes.

Hemophilia A (classic hemophilia) - genetic disease caused by a congenital deficiency of the coagulation factor VIII protein. Hemophilia is a disease associated with a recessive mutation on the X chromosome. It occurs in men and in homozygous women.

X-linked ichthyosis (X-linked ichthyosis) is an X-linked recessive skin disease caused by congenital deficiency of steroid sulfatase, an enzyme that converts steroids into their active form.

13. Mitochondrial inheritance.

Mitochondria have their own DNA - mitochondrial DNA. Unlike nuclear genes, mitochondrial DNA is transmitted exclusively through the maternal line. An example of a mitochondrial disease is hereditary atrophy. optic nerves Leber, myoclonic epilepsy with ragged red fibers, mitochondrial myopathy, encephalopathy, lactic acidosis.

VII. Fever.

What is a fever?

Fever is an increase in body temperature due to the appearance of pyrogenic substances in the body. At the same time, the temperature of the deep areas of the trunk and body is constant.

Distinguish infectious (bacteria, viruses) and non-infectious fever (attack of gout, allergic reactions). There are exogenous and endogenous pyrogenic substances. Everything is connected with the production of cytokines - primarily interleukin-1.

Overheating. Causes.

Pathological reactions of the body to high temperature environment associated with dehydration, loss of electrolytes and disruption of thermoregulatory mechanisms.

The reason is an excessive supply of heat from the outside (exogenous overheating) or intense pathological heat production in the body itself (endogenous overheating). It cannot be tolerated for a long time.

With obstructive inflammatory processes bronchi, formation respiratory distress syndrome adults, there is a several-fold increase in the content of MBR in the focus of inflammation. The highest concentration of this compound can be found in tissues during anaphylaxis and atopic processes. There is information that at bronchial asthma the main basic protein is able to damage bronchial epitheliocytes and thereby increase the severity of the inflammatory process. Its content in the sputum of patients correlates with the severity of bronchial asthma.

Allocate plasma, with a molecular weight of up to 97 kDa, and tissue kallikreins having a molecular weight of 33-36 kDa. Kallikreins, acting on a, plasma globulins, promote the formation of bradykinin and kallidin, consisting of 9 and 10 amino acid residues, respectively. The main physiological role of the components of the kallikrein-kinin system is normally associated with the regulation of the tone and permeability of the vessels of the microvasculature. In conditions of acute and chronic inflammation, the pronounced activation of the components of this system is accompanied by an increase in exudative processes in the focus of inflammation due to an increase in the permeability of the vascular wall and an increase in local blood flow due to the vasodilating effect of kinins.
Kallikrein takes an active part in the regulation of phagocytosis processes, influencing the chemotaxis of neutrophilic leukocytes.

Over-activation of components kallikrein-kinin system accompanied by an increase in vascular inflammatory reactions, an increase in hydrostatic pressure in the extracellular environment, an increase in tissue edema, a deterioration in its supply with oxygen and biological oxidation substrates. As a result, compensatory-adaptive reactions develop into pathological ones, resulting in an increase in the zone of secondary alteration.

Of the other factors, excessive activation of which gives predominantly pathological direction of the inflammatory process, of note are the complement system, lysosomal enzymes, cationic proteins, lymphokines, and monokines.

Complement system does not affect the course of all stages of inflammation due to both the impact on alteration and exudation, and the phagocytic activity of neutrophils and macrophages, the induction of an immune response. For example, C1 - leads to an increase in exudative processes, C3 and C5a - helps to increase the permeability of the vascular wall, activates the release of histamine from mast cells, C3 and C5 - activate chemotaxis, C5 and C9 - have cytoclitic activity.

Lysosomal enzymes at the site of inflammation accumulate as a result of their release from the lysosomes of neutrophilic leukocytes, macrophages and cells damaged during tissue alteration. Being released in a significant amount in the focus of inflammation, lysosome enzymes enhance secondary alteration, damage both intracellular membranes and the plasmolemma. Hydrolytic cleavage of the components of the basement membrane of microvessels and damage to the plasmolemma of endothelial cells are accompanied by a pronounced increase in the permeability of the vascular wall and an increase in exudative processes.

Cationic proteins are secreted in significant amounts by neutrophilic leukocytes. Possessing a wide range biological activity, they affect all stages of the inflammatory process. Their main effects include an increase in the permeability of the vascular wall, increased exudation, and induction of histamine release by mast cells.

At the site of inflammation there is an increase in the concentration of lymphokines and monokines, which affect phagocytosis, chemotaxis and proliferative processes. Excessive accumulation of these substances is accompanied by increased cytolytic processes.

In the last decade, there have been reports of pathogenetic role of nitric oxide in the development of inflammation. In humans and animals, nitric oxide is synthesized from arginine as a result of a reaction catalyzed by NO-nitric oxide synthetase (nitric oxide synthetase - COA).

L-arginine + NADPH2 + O2-» NO + L-citrulline

high activity nitric oxide synthase determined in endotheliocytes. Its level correlates with the content of the Ca-calmodulin complex in the cell. An increase in the content of nitric oxide in endotheliocytes occurs when Ca enters the cytosol.

It is assumed that among numerous properties This compound should be attributed to its participation in the processes of intercellular interaction, regulation of vascular tone and bronchial patency.

Benefits of nitric oxide in inflammation, associated with the activation of its release from L-arginine, lies in the antimicrobial properties of this compound and the effect on the migration of polymorphonuclear leukocytes through the capillary wall. Inflammation creates conditions for excessive production of nitric oxide. The key mechanism of this process should be considered an increase in the level of nitric oxide synthetase activity in the focus of inflammation, which is activated in the presence of the Ca-calmodulin complex. An increase in free calcium in the cytosol during inflammation must certainly be accompanied by an increase in the activity of the enzyme catalyzing the synthesis of nitric oxide. Excessive accumulation of nitric oxide by the cells of the inflammatory focus leads to immunosuppression, a decrease in the resistance of cytoplasmic membranes to hypoxic effects. Toxic concentrations of this compound lead to irreversible microcirculation disorders, which negatively affects the course of the inflammatory process as a whole.

As development of the inflammatory process in its focus there is an accumulation of biologically active substances with predominantly anti-inflammatory effects. In addition to nitric oxide, these include prostacyclin and adenosine.

Prostacyclin synthesized by endotheliocytes and has biological effects similar to nitric oxide. An increase in the concentration of this compound is accompanied by a decrease in platelet aggregation and an improvement in microcirculation processes due to this. Under the conditions of activation of free-radical oxidation observed during inflammation, prostacyclin has protective properties, protects the cytoplasmic membranes of endotheliocytes from destruction.

The second, more subtle system of innate immunity is the complement system (C). It includes eleven blood proteins, mostly represented by inactive protease precursors. The activation of the complement system in natural, that is, innate, immunity begins with its third component (C3). C3 spontaneously dissociates into C3a and C3b, forming trace amounts of these fragments. C3b covalently binds to the surface bacterial cell, stabilizes there and exhibits proteolytic activity towards protein B, converting it into a Bb fragment (Fig. 2). Bb specifically attaches to C3b fixed on the cell surface, forming an enzymatically active C3bBb complex directed to the initial C3 and the next complement component C5, which it cleaves into C5a and C5b. Thus, a stable and enzymatically active complex is formed on the bacterial cell membrane, which has a dual enzymatic activity - the generation of new C3b / C3a and C5b / C5a molecules. Components C3b and C5b are fixed on the membrane, they themselves have biological activity. As for C3a and C5a, these polypeptides, consisting of 77 and 74 amino acid residues, respectively, remain in the environment, being the strongest mediators of inflammation (see Fig. 2).

The C5b component forms new centers of enzymatic activity on the membrane, aimed at activating a specific complex that attacks the membrane. The latter consists of several components that sequentially activate each other and are fixed on the cell membrane, joining each other (C6-C8). The final component of the complement system (C9) is included in the complex that attacks the membrane and becomes the initial link in polymerization. Attaching to itself several molecules, the same as itself, it plunges into the membrane, polymerizes into a ring and forms pores that “perforate” the cell membrane, which leads to its death. Thus, the complement system recognizes the foreign cell and triggers chain reaction activation of biologically active proteins, which leads to the acquisition of toxic activity by the complex and cell death. In addition, the C3b component (and, to a lesser extent, C5b), fixed on the surface of bacterial bodies, sharply enhances their phagocytosis. This is due to the presence of receptors for C3b and C5b on the membrane of phagocytic cells, which significantly increase the affinity of phagocytes for bacteria coated with C3b and C5b. This is an extremely important phenomenon, one of the main ones in antibacterial immunity.

Soluble factors C3a and mainly C5a have a different fate. These biologically active peptides have a number of properties that are important for the development of inflammation: a direct effect on vascular permeability and, most importantly, the ability to activate the so-called mast cells (see Fig. 2). Mast cells actively synthesize and store large reserves of a powerful inflammatory mediator, a biologically active amine - histamine. Mast cells are scattered throughout the connective tissue and especially along blood vessels. They carry receptors for C3a and C5a on their surface, and when these peptides are attached to them, mast cells secrete histamine into the environment. The role of histamine in inflammation is multifaceted. Firstly, it quickly and dramatically affects the vascular capillary network. The endothelium of the capillaries under its influence releases vasodilating substances, and the blood flow through the focus of inflammation increases significantly (redness and heating). "Gaps" form between the endothelial cells, and the plasma exits the capillaries into the area of ​​inflammation, coagulating and thereby isolating the spread of infection from the focus. Along the histamine concentration gradient, phagocytes "rise" to the source of inflammation. Thus, histamine acts like bradykinin, but more actively and quickly, due to which it is a mediator of the acute phase of inflammation.

Returning to the complement, one should once again emphasize the multidirectional nature of its action (toxicity for microorganisms, increased phagocytosis, generation of inflammatory mediators) and the cascade enhancement of all directions of its activity. And again, in the case of complement, the question arises of how its initial component C3b distinguishes the “foreign” surface from the “own” one.

Inflammation(inflammatio, from lat. in flames- ignite) the reaction of the body to local damage formed in the process of evolution, characterized by the phenomena of alteration, microcirculation disorders (with exudation and emigration) and proliferation, aimed at localizing, destroying and removing the damaging agent, as well as restoring (or replacing) tissues damaged by it.

Alteration, microcirculation disorders (with exudation and emigration) and proliferation are the main components or internal signs of inflammation. In addition, the focus of inflammation is characterized by five external (local) manifestations: redness (rubor), swelling (tumor) fever, or fever (calor) soreness or pain (dolor), dysfunction functio laesa)(Fig. 10-1). These signs are especially well defined when the focus of inflammation is on the outer integument.

Inflammation can be manifested not only by local, but also by general signs, the severity of which depends on the intensity and prevalence of the process.

Common manifestations of inflammation include fever, hematopoietic tissue reactions with the development of leukocytosis, increased erythrocyte sedimentation rate, accelerated metabolism, altered immunological reactivity, and intoxication of the body.

Inflammation is one of the most common typical pathological processes. At the same time, it is an important protective and adaptive reaction that has evolved as a way to preserve the whole organism at the cost of damaging its parts. With the help of inflammation, provide

Rice. 10-1. The ancient foundations of the doctrine of inflammation (according to Willoughby and Specter). Heat, redness, swelling and pain lead to dysfunction

the localization and elimination of the inflammatory agent and (or) the tissue damaged under its influence are determined.

10.1. BASIC THEORIES OF INFLAMMATION

As the pathological process underlying most human diseases, inflammation has been a central problem of pathology throughout the history of the study of disease. The formation of ideas about the essence of inflammation has long been closely associated with the development of views on the nature of the disease.

In the early stages of the study of inflammation, the theories of R. Virchow (1858) and Yu. Konheim (1885) dominated. According to cellular(attractive, nutritional) theories of R. Virchow, inflammation is a violation of the vital activity of cellular elements in response to irritation, development dystrophic changes, consisting in the appearance of protein grains and clumps in the cells, the attraction (attraction) of nutrient (nutritive) material from the liquid part of the blood, and the occurrence of this cloudy swelling of the cytoplasm, which is characteristic of inflammation.

Rice. 10-2. I.I. Mechnikov (1845-1916). Laureate Nobel Prize 1908

By vascular theory of J. Kongeym inflammation is characterized by circulatory disorders leading to exudation and emigration and causing subsequent cellular (dystrophic) changes. However, as it was later found, inflammation is characterized by the simultaneous development and close relationship of vascular and tissue phenomena. Yu. Kongeym for the first time described in detail the entire set of changes in vascular tone and blood flow with exudation and emigration.

A particularly important contribution to the study of inflammation was made by I.I. Mechnikov(1892) (Fig. 10-2). He initiated the comparative pathology of inflammation, the theory of cellular and humoral immunity, the theory of phagocytosis and formulated biological(phagocytic) theory inflammation. According to her, the main and central link in the inflammatory process is the absorption of foreign particles, including bacteria, by phagocytes.

After analyzing the inflammatory response in various kinds animals standing at different stages of evolutionary development, I.I. Mechnikov showed its complication in phylogenesis. In the early stages of phylogenesis (in the simplest unicellular organisms), protection from foreign material is carried out by phagocytosis. At the same time, even in the simplest organisms, some phenomena of alteration occur. In multicellular organisms that do not have a vascular system, inflammation is manifested by the accumulation of phagocytic amoeboid cells (amoebocytes) around the site of injury. In higher invertebrates, inflammation is expressed as an accumulation at the site of injury. blood cells- lymphohematocytes. Despite the presence of a circulatory system (open type), vascular reactions characteristic of vertebrates do not occur. At the same time, phenomena of proliferation are already found at this stage of evolutionary development. In vertebrates and humans, the inflammatory response is significantly complicated due to vascular phenomena with exudation and emigration, participation nervous system.

The results of comparative pathological studies, indicating the involvement of increasingly complex protective and

adaptive phenomena as the inflammatory process evolved, allowed I.I. Mechnikov to show the importance of inflammation as a protective and adaptive reaction of the whole organism. I.I. Mechnikov was the first to establish a connection between inflammation and immunity, in the mechanisms of which phagocytosis also plays a significant role.

In the first half of this century, the doctrine of inflammation began to develop in connection with the emergence of biophysical and biochemical methods. The results of versatile physicochemical studies of the inflammatory focus allowed G. Sade(1923) nominate physical and chemical, or molecular pathological, hypothesis inflammation, according to which the leading in the pathogenesis of this process is a local metabolic disorder, leading to the development of acidosis and an increase in osmotic pressure in the tissue, which, in turn, underlie circulatory disorders and cellular phenomena during inflammation. However, it was soon shown that the physicochemical changes characteristic of the focus of inflammation are detected in the course of an already developed inflammatory reaction and, therefore, cannot be a trigger for vascular and cellular phenomena (DE Alpern, 1927). In some types of inflammation (for example, allergic), acidosis does not develop or is mild (A.D. Ado, 1935).

Based on the results of extensive pathochemical studies V. Menkin(1938) concluded the leading role biochemical shifts in the pathogenesis of inflammation. He singled out a number of inflammation-specific substances that mediate various inflammatory phenomena - necrosin, exsudin, leukotoxin, pyrexin, etc. studied. However, it would be wrong to reduce the entire pathogenesis of inflammation only to the disparate effects of individual mediators.

Since the beginning of this century, when the participation of the nervous system in the pathogenesis of inflammation was established, hypotheses have arisen that give the primary role to the nervous factor - reflex mechanisms, impaired trophic function of the nervous system. Yes, by vasomotor (neurovascular) theory of G. Ricker(1924) primary in the occurrence of inflammation is a disorder of the function of the vasomotor nerves. Depending on the degree

their irritation and, consequently, the developing vascular reaction develops such a relationship between tissue and blood, which leads to the occurrence of inflammatory hyperemia and stasis and, accordingly, determines the intensity and nature of metabolic disorders. However, the entire set of inflammatory phenomena cannot be explained only by the reaction of the vessels of the microvasculature.

D.E. Alpern(1959) paid special attention to the question of the unity of the local and the general in inflammation, the role of the organism's reactivity in the development of this process. He emphasized the essence of inflammation as a general reaction of the body to the action of a harmful agent. He justified neuro-reflex circuit pathogenesis of inflammation, according to which various vascular tissue reactions are regulated by the nervous and humoral (mainly pituitary-adrenal) systems.

10.2. ETIOLOGY OF INFLAMMATION

Since the most common cause inflammation are infectious agents, it is divided according to etiology into infectious (septic) And non-infectious (aseptic).

10.3. EXPERIMENTAL REPRODUCTION OF INFLAMMATION

In the experiment, as a rule, models of aseptic inflammation caused by chemical agents are used. Traditional

These are irritating phlogogens that lead to the development of acute purulent inflammation: turpentine, croton oil, lapis, xylene, formalin, etc. Chemically indifferent substances, such as kaolin, are also used. To reproduce aseptic inflammation with a predominance of exudative phenomena, dextran is used. IN last years The most commonly used aseptic agent is caraginan, a sulfated glycosaminoglycan isolated from Irish moss. Chondrus.

In order to avoid the further presence of a phlogogen in the focus, models of thermal or radiation (ultraviolet rays, ionizing radiation) inflammation are used.

Hyperergic inflammation is often modeled as immediate or delayed allergic reactions. This inflammation is of interest due to its rapid course, frequent necrosis, which is due to the increased reactivity of the sensitized organism.

In pathophysiological studies, models of infectious inflammation are used relatively rarely. This is due to the complexity of modeling such inflammation, due to a deeper interaction of microorganisms with immune systems oh in the process of its emergence and course. Currently from infectious agents Escherichia coli, staphylococci, Pseudomonas aeruginosa are predominantly used, since they are the most common causes of purulent-inflammatory diseases and infectious complications in humans. Models close to infectious inflammation are, for example, fecal peritonitis.

To study vascular phenomena in the focus of inflammation, the most convenient object is the mesentery of a frog (the experience of Yu. Kongeym), the ear of a rabbit (the transparent camera method - E.L. Clark and E.R. Clark), the hamster's cheek pouch, inflated with air (G. Selye ); to study the cellular dynamics of the focus of inflammation, it is advisable to use the "skin window" method (J. Ribak) or such models as the subcutaneous "air bag" (G. Selye), peritonitis, pleurisy, when exudate can be easily collected.

10.4. PATHOGENESIS OF INFLAMMATION

Any inflammation includes 3 main components:

Alteration - damage to cells and tissues;

Microcirculation disorder with exudation and emigration;

Proliferation - reproduction of cells and restoration of tissue integrity.

Accordingly, there are: alterative inflammation, exudative inflammation, proliferative (productive) inflammation and - as its separate variant - granulomatous inflammation.

The pathogenesis of inflammation is a complex combination of neural, humoral and effector mechanisms that underlie a large number of inflammatory phenomena that make up the above phenomena (Fig. 10-3).

Rice. 10-3. General scheme of the pathogenesis of inflammation

10.4.1. The role of tissue damage in the development of inflammation

Alteration(alteratio, from lat. alterare- change) or dystrophy, tissue damage, malnutrition (trophism) and metabolism in it, its structure and function. Distinguish between primary and secondary alteration.

primary alteration is the result of the damaging effect of the inflammatory agent itself, therefore, its severity, other things being equal (reactivity of the organism, localization), depends on the properties of the phlogogen. Strictly speaking, primary alteration is not a component of inflammation, since inflammation is a reaction to damage caused by a phlogogen, i.e. for the primary alteration. At the same time, practically primary and secondary alternative phenomena are difficult to separate from each other.

secondary alteration is a consequence of the impact on the connective tissue, microvessels and blood of extracellularly released lysosomal enzymes and active oxygen metabolites. Their source is activated immigrated and circulating phagocytes, partly - resident cells. In inflammation in animals with previously induced leukopenia, alteration is weakly expressed. A certain role in alteration can also be played by the lytic complex C5b-C9, which is formed during the activation of the complement of plasma and tissue fluid.

Secondary alteration does not depend on the inflammatory agent; for its development, the further presence of a phlogogen in the focus is not necessary. It is the body's response to damage already caused by a harmful onset. This is an expedient and necessary component of inflammation as a protective and adaptive reaction, aimed at the speedy delimitation (localization) of the phlogogen and (or) the tissue damaged under its influence from the rest of the body. At the cost of damage, other important protective phenomena are also achieved: a more pronounced microbicidal and lytic effect of lysosomal enzymes and active oxygen metabolites, since it is carried out not only in phagocytes, but also extracellularly; involvement of other mediators of inflammation and cells, increased exudation, emigration and phagocytosis. As a result, the inflammatory process ends faster. However, alteration is expedient only within certain limits. So, for example, with an imbalance in the system, lysosomal proteinases -

their inhibitors cause excessive manifestations of alteration with a predominance of necrosis.

Alternative events in inflammation include tissue breakdown And enhanced exchange substances (“metabolic fire”), leading to a number of physicochemical changes in the inflamed tissue: the accumulation of acidic products (acidosis, or H + -hyperionia), increase in osmotic pressure (osmotic hypertension, or hyperosmia), increase in colloid-osmotic, or oncotic, pressure (hyperonkia).

Depending on the strength of the damaging agent, the intensity and localization of inflammation, the morphological manifestations of alteration vary widely: from barely noticeable structural and functional changes to complete destruction. (necrobiosis) and death (necrosis) tissues and cells. Turbid swelling of the cytoplasm of cells, the phenomena of protein, fat and other types of their dystrophy are found. The permeability of cell membranes and cell organelles sharply increases. Subcellular structures also change - mitochondria, lysosomes, ribosomes, and the endoplasmic reticulum. Mitochondria swell or shrink, their cristae are destroyed. An increase in permeability and damage to lysosome membranes are accompanied by the release of various enzymes that play a role in the destruction of subcellular structures. The shape and size of the cisterns of the endoplasmic reticulum change, vesicles, concentric structures, etc. appear in the cytoplasm. The marginal location of chromatin and damage to the nuclear membrane are noted. In the stroma, mucoid and fibrinoid swelling up to necrosis, dissolution of collagen and elastic fibers are observed.

Increased metabolism during inflammation occurs predominantly at the expense of carbohydrates. Initially, both their oxidation and glycolysis increase. This phenomenon is based on the activation of the corresponding tissue enzymes. Oxygen consumption by the inflamed tissue increases markedly. With the accumulation of leukocytes in the focus, the lysosomal enzymes of which break down carbohydrates anaerobically, as well as damage and a decrease in the number of mitochondria during alteration, the oxidation reactions noticeably weaken, and glycolysis increases. Accordingly, the breakdown of carbohydrates does not always reach the final products - carbon dioxide and water. The respiratory quotient is reduced. Under-oxidized products of carbohydrate metabolism - lactic and tricarboxylic acids - accumulate in the tissue.

In addition, due to a violation of the metabolism of fats, proteins and the breakdown of nucleic acids in the focus, the content of fatty acids, ketone bodies, polypeptides, amino acids, nucleotides (ATP, adenylic acid), nucleosides (adenosine) increases. As a result, acidosis develops. Initially, it is compensated by tissue buffer systems and accelerated blood and lymph flow. As buffer systems are depleted and blood and lymph flow slows down, acidosis increases and becomes uncompensated. If the normal concentration of hydrogen ions in the tissue is 0.5?10 -7, i.e. pH is 7.34, then in case of inflammation it can be, respectively, 25?10 -7 and 5.6 and lower. The more acute the inflammatory process, the more pronounced acidosis. So, in acute purulent inflammation pH is 6.5-5.39, and in chronic - 7.1-6.6. Acidosis is involved in increasing vascular permeability. He creates favorable conditions to implement the destructive effects of lysosomal enzymes, in particular glycosidases, which break down the carbohydrate components of the connective tissue matrix.

Along with H + -hyperionia, the content of other ions also increases in the focus - potassium, sodium, calcium ions. This is due to the destruction of cells and increased dissociation of salts in an acidic environment. Due to the advanced increase in the level of extracellular potassium, the ratio of potassium and calcium ions is disturbed (dysionia). Changes in the homeostasis of Ca 2 + ions may underlie cell death in the focus of inflammation. Ca 2 + is one of the secondary messengers between the membrane and cellular enzyme systems, as well as the gene apparatus. An increase in the level of intracellular Ca 2 + leads to its absorption by mitochondrial membranes and subsequent blocking of the respiratory chain of electrons. Increased intracellular content of Ca 2 + activates non-lysosomal proteases, leading to lysis of the cytoskeleton, degradation of enzymes, membrane-associated proteins (ion channels, carriers, receptors, adhesion molecules). It has been noted that although a decrease in extracellular Ca 2+ is important for cell survival, it may be an obstacle to their new growth. In the focus of inflammation, the molecular concentration increases, since in the process of tissue decay and increased metabolism, large molecules are split into many small ones. Due to the increase in ionic and molecular concentration, hyperosmia develops. So, if normal depression of the interstitial fluid

Rice. 10-4. Schematic representation of the section through the inflammatory edema of the skin: I - changes in osmotic pressure (A ° C) in different zones of the focus of inflammation: 1 - the center of inflammation, 2 - the zone of plethora, 3 - the zone of obvious edema, 4 - the zone of latent edema; II - changes in the concentration of hydrogen ions: 1 - the center of purulent inflammation, 2 - the zone of inflammatory infiltrate, 3 - the zone of peripheral edema, 4 - the zone of transition to a normal state (according to Sade)

is 0.62°, i.e. osmotic pressure is 8 atm, then with purulent inflammation - respectively 0.80 ° and 19 atm (Fig. 10-4).

As a result of physical and chemical changes in the inflamed tissue, the breakdown of proteins to polypeptides and amino acids with an increase in the concentration of the latter, an increase in the dispersion of colloids, their ability to attract and retain water occurs. Hyperonkia develops. Changes in osmotic and oncotic pressure are an important factor in exudation and, accordingly, inflammatory edema.

10.4.2. Inflammatory mediators

During primary and secondary alteration, large amounts of various mediators and modulators of inflammation are released (Table 10-1).

Table 10-1. Inflammatory mediators

*All pre-existing.

Inflammatory mediators (mediators) are understood as biologically active substances that realize the occurrence and support of various inflammatory phenomena, for example, an increase in vascular permeability, emigration, etc. During normal life, these same substances in physiological concentrations are responsible for the regulation of cell or tissue functions. During inflammation, being released in large quantities, they acquire a new quality - inflammatory mediators. Almost all mediators are also modulators of inflammation; able to enhance or weaken the severity of inflammatory phenomena. Accordingly, the effect of a mediator can be additive (additive), potentiating (synergistic) and weakening (antagonistic), and the interaction of mediators is possible at the level of their synthesis, secretion or effects. The mediator link is the main one in the pathogenesis of inflammation. It coordinates the interaction of many cells - effectors of inflammation, the change of cell phases in the focus of inflammation.

Picks inflammations are divided into humoral(formed in liquid media - blood plasma and tissue fluid) and cellular. All humoral mediators are preexisting, those. available as precursors before activation of the latter; these include complement derivatives, kinins, and blood coagulation factors. Among cellular mediators, preexisting(deposited in cells in an inactive state) - vasoactive amines, lysosomal enzymes, neuropeptides, and newly formed(i.e. produced by cells during stimulation) - eicosanoids, cytokines, lymphokines, active oxygen metabolites.

The main sources of cellular mediators are:

1. neutrophils, which secrete cationic proteins, stimulate the release of biogenic amines from platelets and mast cells, contain a histamine release inhibitor and histaminase. Neutrophil proteases are involved in the formation of kinins and active complement fragments (C3a, C3b). Neutrophils produce prostaglandin (PG) E 2 and other eicosanoids. Neutrophil enzymes activate both blood coagulation and fibrinolysis.

2. Macrophages secrete angiotensin convertase, which inactivates bradykinin, converts angiotensin-I to angiotensin-II. They synthesize PGE 2, as well as thromboxanes and leu-

cotrienes (LT). Since PGE 2 prevents the release of cellular mediators of inflammation and inhibits platelet aggregation, macrophages, in addition to pro-inflammatory, also have an anti-inflammatory function. Macrophages synthesize various complement components, have coagulation and fibrinolytic activity.

3. Eosinophils serve as negative modulators of inflammation. They contain histaminase, kininase, enzymes that break down leukotrienes C and D (lysophosphalipase, arylsulfatase B, phospholipase D), the main alkaline protein that performs a cytotoxic function and neutralizes heparin. Thus, eosinophil enzymes neutralize the products of mast cells, contribute to the destruction of cellular debris. Eosinophils phagocytize granules secreted by mast cells and suppress the release of histamine. Of particular interest is the presence of lysophospholipase in eosinophils. Its substrate is partially degraded phospholipids contained in the membranes of dead cells. By releasing free fatty acids from phospholipids, lysophospholipase promotes the formation of arachidonic acid.

4. Mast cells and basophils secrete histamine and serotonin, heparin, neutrophil and eosinophil chemotaxis factors, platelet activating factor, proteolytic enzymes, they produce peroxidase, superoxide and hydrogen peroxide, as well as a protease that converts kininogen into kinin.

5. platelets secrete growth and coagulation factors, vasoactive amines and lipids, neutral and acid hydrolases.

Complement derivatives(Fig. 10-5) are the most important of the humoral inflammatory mediators. Among almost 20 different proteins formed during complement activation, its fragments C5a, C3a, C3b and the C5b-C9 complex are directly related to inflammation:

C5a and C3a are acute inflammatory mediators and anaphylatoxins (i.e., histamine liberators from mast cells), thus they increase capillary permeability both directly and indirectly through histamine (Fig. 10-6);

C5a des Arg and C3a are formed from C5a in plasma and tissue fluid under the influence of carboxypeptidase N and increase the permeability of postcapillary venules. Effect of C5a des Arg

Rice. 10-5. Components of the complement system: C3b, C5b - fragments of C3 and C5 associated with the membrane; C3a and C5a - peptides cleaved off from C3 and C5, respectively; С6-С8 - components of the complex attacking membranes; C9 - protein polymerized in the membrane; Bb - fragment of protein B associated with the membrane; arrows - cascade-increasing reaction components; MF - macrophage; C3R - receptor for the C3b complement component; K - capillary; E - endothelial lining of the capillary; H and M - diapedesis of neutrophil and monocyte

Rice. 10-6. Association of complement with mast cells in the focus of acute inflammation

not associated with histamine, but is neutrophil-dependent, i.e. carried out due to permeability factors released from polymorphonuclear granulocytes - lysosomal enzymes and non-enzymatic cationic proteins, active oxygen metabolites. In addition, C5a and C5a des Arg attract neutrophils. In contrast, C3a has practically no chemotactic properties;

C3b opsonizes the pathogenic agent and, accordingly, promotes immune adhesion and phagocytosis;

The C5b-C9 complex is responsible for the lysis of microorganisms and pathologically altered cells.

The source of complement is blood plasma and, to a lesser extent, tissue fluid. Enhanced flow of plasma complement into the tissue is one of the important purposes of exudation. The active components of complement release not only histamine, but also interleukin (IL) 1, prostaglandins, leukotrienes, platelet activating factor, and interact synergistically with prostaglandins and substance P.

kinins- vasoactive peptides formed from kininogens (a 2 -globulins) under the influence of kallikreins in plasma (bradykinin) and in tissue fluid (kallidin). The activation factor for the activation of the kallikrein-kinin system is the activation of the Hageman factor (XII), which converts prekallikreins into kallikreins, in case of tissue damage. Factor XII is present in the blood and has an affinity for negatively charged surfaces. In the liquid phase of the blood, it spontaneously dissociates into two fragments: CPa - an enzymatically active fragment and CPb. XIIa is adsorbed on the surface of a foreign agent (phlogogen), where it is stabilized. It has proteolytic activity, the substrate of which is the CP factor itself and another protein, prekallecrein. Further, prekallikrein under the action of CP is converted into the protease kallikrein. Kallikrein sharply enhances the formation of CN from the CP factor and at the same time acts on a new substrate - the so-called high molecular weight kininogen (HMK). Under the action of kallikrein, bradykinin is formed from the IUD, which is one of the main mediators of inflammation. Bradykinin acts on the vascular endothelium, causing the "opening" of the edges of the cells of the vascular endothelium and thereby opening the way for the blood plasma to the site of inflammation. Thus, this system detects a foreign body by its negatively charged

surfaces. The surfaces of their own cells are arranged in such a way that they do not adsorb CP, do not stabilize it, and thus do not induce a further chain of events. This is the simplest and most primitive way to distinguish "own" from "non-own".

Kinins mediate the expansion of arterioles and increase the permeability of venules by contraction of endothelial cells. They contract the smooth muscles of the veins and increase intracapillary and venous pressure, inhibit neutrophil emigration, modulate the distribution of macrophages, stimulate the migration and mitogenesis of T-lymphocytes and the secretion of lymphokines. In addition, they enhance fibroblast proliferation and collagen synthesis and therefore have a role in reparative phenomena in chronic inflammation. One of the most important effects of kinins is their ability to irritate sensory nerve endings, causing inflammatory pain. Kinins enhance histamine release from mast cells, prostaglandin synthesis by many cell types, so some of their main effects - vasodilation, smooth muscle contraction, pain - are associated with the release of other mediators, especially prostaglandins.

Activation of the Hageman factor triggers not only the process of kinin formation, but also blood coagulation and fibrinolysis. In this case, mediators such as fibrinopeptides and fibrin degradation products are formed, which are powerful chemattractants.

Eicosanoids(Fig. 10-7) are an important mediator link in the inflammatory response, as evidenced by their long-term production in the focus and a close relationship with the key event of inflammation - leukocyte infiltration, as well as a powerful anti-inflammatory effect of inhibitors of their synthesis. In the focus of inflammation, the main producers of eicosanoids are monocytes and macrophages, although they are formed by almost all types of nuclear cells when the latter are stimulated. The predominant eicosanoids in the focus of inflammation are prostaglandins(PGE 2), leukotrienes(LTB4) and 5-hydroperoxyeicosatetraenoic acid(5-HPETE). Thromboxane is also formed, although in a smaller amount. A 1(TxA 2), PGF 2a, PGD 2, prostacyclin (PGI 2), LTC 4 , LTD 4 , LTE 4 , other HPETE. The main effect of eicosanoids is their effect on leukocytes; as powerful chemattractants, they play an important role in the mechanisms of self-sustaining leukocyte infiltration.

Rice. 10-7. The formation of leukotrienes and prostaglandins from the cell membrane (according to D. Gemsa et al., 1981): Tx - thromboxane; PG (prostaglandin)- prostaglandin; LT (leukotrien)- leukotriene; HPETE (hydroxyperoxy-eicosatetranoic acid)- hydroperoxyeicosatetraenoic acid

Prostaglandins they do not increase vascular permeability themselves, but, being strong vasodilators, they increase hyperemia and, consequently, exudation. Prostaglandins and leukotrienes are important in the genesis of inflammatory pain. At the same time, PGE 2, having no direct pain activity, increases the sensitivity of receptors of afferent pain nerve endings to bradykinin and histamine. PGE 2 is a strong antipyretic agent and is involved in the development of fever. Prostaglandins play a key role in modulating the inflammatory process by regulating leukocyte exudation, emigration and degranulation, and phagocytosis. So, for example, PGE potentiate the development of edema caused by histamine or bradykinin, while PGF 1a, on the contrary, weaken. Similarly, PGE and PGF 1a act on the emigration of leukocytes.

Leukotrienes(synthesized in all blood cells except erythrocytes, as well as in vascular adventitia, mast cells, lungs) help to reduce the smooth muscles of the gastrointestinal tract, have a vasoconstrictive effect (including coronary arteries). LTC 4 , LTD 4 , LTE 4 increase vascular permeability by direct contraction of endothelial cells, and LTB 4 acts as a neutrophil-dependent mediator. Leukotrienes at-

lead to spasm of the smooth muscles of the bronchi (the effect of bronchospasm, unlike that caused by histamine, develops more slowly, but is longer), the development of edema, the involvement of eosinophils, increased secretion of mucus and disruption of its transport. The target organ for leukotrienes is the heart. Being released in excess, they inhibit (by 60%) the contractility of the heart muscle, reducing coronary blood flow and enhancing the inflammatory response. Leukotrienes interact extensively with other inflammatory mediators. They enhance the bronchospastic action of histamine, acetylcholine, prostaglandins and thromboxanes, stimulate the release of prostaglandins and thromboxanes.

Thromboxanes(formed in the tissue of the brain, spleen, lungs and in platelets, inflammatory granuloma cells) cause adhesion and aggregation of platelets, contribute to the development of thrombosis in coronary heart disease, and have a vasospastic effect.

The modulatory function of eicosanoids is carried out through changes in the ratio of cyclic nucleotides in cells.

Biogenic amines - histamine and serotonin are considered the main mediators of the initial microcirculatory disturbances in the focus of acute inflammation and the immediate phase of increased vascular permeability.

Small amount of neurotransmitter serotonin found in mast and enterochromaffin cells, but its main source is platelets. The effects of serotonin are ambiguous and vary depending on the amount. Under normal physiological conditions, serotonin is a vasoconstrictor, causes prolonged vasospasm, and increases their tone. With inflammation, the amount of serotonin increases dramatically. In high concentrations, serotonin is a vasodilator, dilates blood vessels, increases permeability, and is 100 times more effective than histamine. Serotonin is able to cause direct contraction of venule endothelial cells and is also a pain mediator. In addition, serotonin stimulates monocytes at the site of inflammation.

Histamine acts in two ways in relation to vessels and cells. Through H 1 receptors, it expands arterioles and inhibits the emigration and degranulation of leukocytes, and through H 1 receptors it narrows venules, thus increasing intracapillary pressure, and stimulates

stimulates emigration and degranulation of leukocytes. In the normal course of inflammation, histamine acts mainly through H 1 receptors on neutrophils, limiting their functional activity, and through H 1 receptors on monocytes, stimulating them. Thus, along with pro-inflammatory vascular effects, it has an anti-inflammatory effect. Possessing the ability to regulate the proliferation, differentiation and functional activity of fibroblasts, histamine is involved in the processes of repair. The modulatory effects of histamine are also mediated by cyclic nucleotides.

As for the interactions of biogenic amines in the focus of inflammation, it is known that histamine can trigger or enhance the synthesis of prostaglandins through H 1 receptors, and inhibit it through H 2 receptors. Interacting both with each other and with bradykinin, nucleotides and nucleosides, substance P, biogenic amines increase vascular permeability. The vasodilating effect of histamine is enhanced in combination with acetylcholine, serotonin, and bradykinin.

Lysosomal Enzymes are released in the focus of inflammation from granulocytes and macrophage monocytes during their chemotactic stimulation, migration, phagocytosis, damage, death. Neutrophil granules contain proteinases - elastase, cathepsin G and collagenases, which provide antimicrobial protection by lysing dead microorganisms. They have mediator and modulatory effects on vascular permeability, emigration, and phagocytosis.

An increase in vascular permeability under the influence of lysosomal enzymes occurs due to lysis of the subendothelial matrix, thinning and fragmentation of endothelial cells and is accompanied by hemorrhage and thrombosis. Forming or splitting the most important chemotaxins, lysosomal enzymes modulate leukocyte infiltration. Depending on the concentration, they themselves can enhance or inhibit the migration of neutrophils. Neutral proteinases are able to modulate phagocytosis. For example, elastase forms the C3b opsonin, which is necessary for particle adhesion to the neutrophil surface. Consequently, the neutrophil itself provides a mechanism for enhancing phagocytosis. Both cathepsin G and elastase increase the affinity of the neutrophil membrane Fc receptor for immunoglobulin complexes and, accordingly, enhance particle uptake efficiency.

Due to the ability of lysosomal enzymes to activate the complement, kallikrein-kinin, coagulation and fibrinolysis systems, release cytokines and lymphokines, inflammation develops and self-sustains for a long time.

non-enzymatic cationic proteins, contained in azurophilic and specific granules of neutrophils, have such an important property as high microbicidality. In this regard, they are in synergistic interaction with the myeloperoxidase-hydrogen peroxide system. Cationic proteins are sorbed on the negatively charged membrane of a bacterial cell by electrostatic interaction, violating the permeability and structure of its membrane. Then the death of the microorganism occurs, followed by effective lysis by its lysosomal proteinases. In addition, released cationic proteins mediate increased vascular permeability (promoting mast cell degranulation and histamine release) as well as leukocyte adhesion and emigration.

Cytokines during inflammation, they are produced mainly by stimulated monocytes and macrophages (monokines), as well as neutrophils, lymphocytes, endothelial and other cells. Cytokines increase vascular permeability (in a neutrophil-dependent way), adhesion and emigration of leukocytes. Along with pro-inflammatory properties, cytokines are also important for the direct protection of the body, since they stimulate neutrophils and monocytes to kill, absorb and digest invading microorganisms, and also enhance phagocytosis by opsonization of the pathogenic agent. By stimulating wound cleansing, cell proliferation and differentiation, cytokines enhance reparative processes. Along with this, they can mediate tissue destruction (degradation of the cartilage matrix and bone resorption) and thus play a role in the pathogenesis of connective tissue diseases, in particular rheumatoid arthritis. The action of cytokines also causes a number of metabolic effects that underlie the common manifestations of inflammation - fever, drowsiness, anorexia, metabolic changes, stimulation of hepatocytes to increased synthesis of acute phase proteins, activation of the blood system, etc. Cytokines interact with each other, with prostaglandins, neuropeptides and other mediators.

Inflammatory mediators (cytokines) also include a number of lymphokines- polypeptides produced by stimulated lymphocytes. Lymphokines coordinate the interaction of neutrophils, macrophages and lymphocytes, regulating the inflammatory response in general.

Active oxygen metabolites, First of all, free radicals - superoxide anion-radical (O * -), hydroxyl radical (HO *), hydroperoxide radical (HO *,), due to the presence of one or more unpaired electrons in their outer orbit, have increased reactivity with other molecules and, therefore , a significant destructive potential, which is important in the pathogenesis of inflammation (Fig. 10-8).

The source of reactive oxygen species - oxygen radicals, hydrogen peroxide (H 1 O 1), singlet oxygen (1 O 1), hypochlorite (HOCl), etc. - are: respiratory burst of phagocytes during their stimulation, arachidonic acid cascade in the process of formation of eicosanoids, enzymatic processes in the endoplasmic reticulum and peroxisomes, mitochondria, cytosol, as well as self-oxidation of small molecules such as hydroquinones, leukoflavins, catecholamines, etc.

Oxygen radicals increase the bactericidal ability of phagocytes, and also have mediator and modulatory functions.

Rice. 10-8. Induction of reactive oxygen species upon activation of the oxidase system of the cell membrane

tions. Being inflammatory mediators, active oxygen metabolites cause lipid peroxidation, damage to proteins, carbohydrates, nucleic acids, which increases vascular permeability (due to damage to endothelial cells) and stimulates phagocytes. As modulators, they can enhance inflammation (by releasing enzymes and interacting with them when tissue is damaged) or have an anti-inflammatory effect (inactivation of lysosomal hydrolases and other inflammatory mediators). Active oxygen metabolites are of great importance in maintaining chronic inflammation.

Also referred to as mediators and modulators of inflammation neuropeptides- substances released by C-fibers as a result of activation of polymodal nociceptors by an inflammatory agent, which play an important role in the occurrence of axon reflexes in the terminal branches of primary afferent (sensitive) neurons. The most studied are substance P, calcitonin-gene-related peptide, neurokinin A. Neuropeptides increase vascular permeability, and this ability is largely mediated by mediators derived from mast cells. There are membrane junctions between non-myelinated nerves and mast cells that provide communication between the central nervous system and the focus of inflammation. Neuropeptides synergistically interact in increasing vascular permeability both among themselves and with histamine, bradykinin, C5a, platelet activating factor, leukotriene B 4 ; antagonistically - with ATP and adenosine. They also have a potentiating effect on the attraction and cytotoxic function of neutrophils, enhance the adhesion of neutrophils to the venule endothelium. In addition, neuropeptides increase the sensitivity of nociceptors to the action of various mediators, in particular prostaglandin E 1 and prostacyclin, thus participating in the formation of pain during inflammation.

In addition to the above substances, inflammatory mediators also include acetylcholine and catecholamines, released upon excitation of choline and adrenergic structures. Acetylcholine causes vasodilation and plays a role in the axon-reflex mechanism of arterial hyperemia during inflammation. Norepinephrine and epinephrine inhibit the growth of vascular permeability, acting mainly as modulators of inflammation.

10.4.3. Circulatory and microcirculation disorders in inflamed tissue

Microcirculation disorders. Vascular phenomena develop following exposure to an inflammatory agent, since the initial ones are reflex in nature. They are well traced under a microscope in the classic experiment of Yu. Kongeym on the mesentery of a frog and include a number of stages:

1. short-term spasm arterioles, accompanied by tissue blanching. It is the result of reflex excitation of vasoconstrictors from exposure to an inflammatory agent. It lasts from several tens of seconds to several minutes, so it is not always possible to notice it.

2. arterial hyperemia, due to the expansion of arterioles, the mechanism of which, on the one hand, is associated with axon-reflex excitation of vasodilators, and on the other hand, with the direct vasodilating effects of inflammatory mediators: neuropeptides, acetylcholine, histamine, bradykinin, prostaglandins, etc. Arterial hyperemia underlies two main external local signs of inflammation - redness and increase in tissue temperature. In addition, in recreating heat, increased heat production in the focus due to increased metabolism is important.

3. Venous hyperemia. It can develop within a few minutes after exposure to a phlogogen and is characterized by a significant duration - it accompanies the entire course of the inflammatory process. At the same time, since with its participation the main inflammatory phenomena are carried out, it is considered true inflammatory hyperemia.

There are 3 groups of factors in the mechanism of venous hyperemia: a) violations of the rheological properties of blood and its circulation. These include an increase in blood viscosity due to its thickening due to exudation, loss of albumin, an increase in the content of globulins, changes in the colloidal state of proteins; increased resistance to blood flow as a result of marginal standing of leukocytes, swelling and aggregation of erythrocytes; thrombus formation due to activation of the blood coagulation system; a violation of the nature of the blood flow - a slowdown in blood flow in the axial zone, a decrease in the marginal plasma zone;

b) vascular wall changes which include loss of vascular tone due to paralysis of the neuromuscular apparatus of the vessels; decreased elasticity of the vascular wall; swelling of the endothelium and an increase in its adhesiveness, as a result of which the lumen of the vessels narrows, conditions are created for the adhesion of leukocytes to the endothelium;

V) tissue changes, consisting in compression of venules and lymphatic vessels by edematous, infiltrated tissue; decrease in elasticity of connective tissue. Many of these factors are both causes and, at the same time, consequences of developing venous hyperemia.

Inflammatory hyperemia differs from other types of hyperemia (caused, for example, by a mechanical factor) by a significant weakening or even perversion of the reaction of the vessels of the inflamed tissue to the action of vasoconstrictive agents (adrenaline, caffeine) and to irritation of the sympathetic nerves. This phenomenon may be associated with the "desensitization" of the vessels, i.e. their reduced or qualitatively altered sensitivity to the action of vasoconstrictor stimuli, which is due to the blockade of receptors. Other differences in inflammatory hyperemia are associated with a more pronounced blood supply to the inflamed area of ​​an organ or tissue, expansion and increase in the number of functioning capillaries, microcirculation intensity, lagging linear blood flow velocity, etc., which allows us to consider inflammatory hyperemia as a special type of microcirculation disorders.

4. Stasis. It can develop in some ramifications of the vessels of the inflamed tissue. Widespread stasis is characteristic of acute, rapidly developing, for example hyperergic, inflammation. As a rule, the disturbance of blood flow in inflammatory stasis is transient, however, if damage to the vascular wall and thrombi occur in many microvessels, the stasis becomes irreversible.

10.4.4. Exudation and exudates

Disorders of microcirculation during inflammation are accompanied by the phenomena of exudation and emigration.

Exudation(exudatio, from lat. exudare- sweat) - exudation of the protein-containing liquid part of the blood through the vascular wall

into inflamed tissue. Accordingly, the fluid that comes out of the vessels into the tissue during inflammation is called exudate. The terms "exudate" and "exudation" are used only in relation to inflammation. They are designed to emphasize the difference between the inflammatory fluid (and the mechanism of its formation) from the intercellular fluid and transudate - a non-inflammatory effusion that comes out with other, non-inflammatory, edema. If the transudate contains up to 2% protein, then the exudate contains more than 3 (up to 8%).

Mechanism of exudation includes 3 main factors:

1) increased vascular permeability (venules and capillaries) as a result of exposure to inflammatory mediators and, in some cases, the inflammatory agent itself;

2) an increase in blood (filtration) pressure in the vessels of the focus of inflammation due to hyperemia;

3) an increase in osmotic and oncotic pressure in the inflamed tissue as a result of alteration and exudation that has begun, and, possibly, a decrease in blood oncotic pressure due to the loss of proteins during abundant exudation (Fig. 10-9, 10-10).

The leading factor in exudation is increased vascular permeability, which is usually It has two phases - immediate and delayed.

Rice. 10-9. The release of Evans blue from the vessel of the mesentery of the frog during inflammation, X 35 (according to A.M. Chernukh)

Immediate Phase occurs after the action of an inflammatory agent, reaches a maximum within a few minutes and ends on average within 15-30 minutes, when the permeability can return to normal (in the event that the phlogogen itself does not have a direct damaging effect on the vessels). A transient increase in vascular permeability in the immediate phase is mainly due to contractile phenomena from the endothelium of the venules. As a result of the interaction of mediators with specific receptors on the membranes of endothelial cells, the actin and myosin microfilaments of the cytoplasm of cells are reduced, and endotheliocytes are rounded; two neighboring cells move away from each other, and an interendothelial gap appears between them, through which exudation occurs.

slow phase develops gradually, reaches a maximum after 4-6 hours and sometimes lasts up to 100 hours, depending on the type and intensity of inflammation. Consequently, the exudative phase of inflammation begins immediately after exposure to the phlogogen and lasts more than 4 days.

A persistent increase in vascular permeability in the slow phase is associated with damage to the vascular wall of venules and capillaries by leukocyte factors - lysosomal enzymes and active oxygen metabolites.

In relation to vascular permeability inflammatory mediators are divided into:

1) direct acting, affecting directly endothelial cells and causing their contraction - histamine, serotonin, bradykinin, C5a, C3a, LTC 4 and LTD 4 ;

2) neutrophil dependent, the effect of which is mediated by leukocyte factors. Such mediators are unable to increase vascular permeability in leukopenic animals. This is a component of complement C5a des Arg, LTB 4 , interleukins, in particular IL-1, partly a platelet activating factor.

The exit of the liquid part of the blood from the vessel and its retention in the tissue is explained by: increased vascular permeability, increased blood filtration pressure, osmotic and oncotic tissue pressure, filtration and diffusion through micropores in the endothelial cells themselves (transcellular channels) in a passive way; in an active way - with the help of the so-called microvesicular transport, which consists in micropinocytosis by endothelial cells of blood plasma, its transport in the form of microbubbles (microvesicles) towards the basement membrane and subsequent release (extrusion) into the tissue.

With inflammation, vascular permeability is increased to a greater extent than with any of the non-inflammatory edema, and therefore the amount of protein in the exudate exceeds that in the transudate. This difference is due to the difference in the amounts and set of released biologically active substances. For example, leukocyte factors that damage the vascular wall play an important role in the pathogenesis of exudation and less significant in non-inflammatory edema.

The degree of increase in vascular permeability is determined by and protein composition exudate. With a relatively small increase in permeability, only finely dispersed albumins can come out, with a further increase - globulins and, finally, fibrinogen.

Depending on the qualitative composition, the following types of exudates are distinguished: serous, fibrinous, purulent, putrefactive, hemorrhagic, mixed (Fig. 10-11, see color insert).

Serous exudate characterized by a moderate content of protein (3-5%), mostly finely dispersed (albumin), and a small amount of polymorphonuclear leukocytes, as a result of which it has a low specific gravity (1015-1020) and is

transparent enough. The composition is closest to the transudate. Characteristic for inflammation of the serous membranes (serous peritonitis, pleurisy, pericarditis, arthritis, etc.), less common with inflammation in parenchymal organs. Exudate with serous inflammation of the mucous membranes is characterized by a large admixture of mucus. This inflammation is called catarrhal (from the Greek. catarrheo- flow down, flow down; catarrhal rhinitis, gastritis, enterocolitis, etc.). Most often, serous exudate is observed with burn, viral, allergic inflammation.

fibrinous exudate is characterized by a high content of fibrinogen, which is the result of a significant increase in vascular permeability. Upon contact with damaged tissues, fibrinogen turns into fibrin and falls out in the form of villous masses (on serous membranes) or a film (on mucous membranes), as a result of which the exudate thickens. If the fibrinous film is located loosely, superficially, easily separated without violating the integrity of the mucosa, such inflammation is called croupous. It is observed in the stomach, intestines, trachea, bronchi. In the case when the film is tightly soldered to the underlying tissue and its removal exposes the ulcerative surface, we are talking about diphtheritic inflammation. It is characteristic of the tonsils, oral cavity, esophagus. This difference is due to the nature of the mucosal epithelium and the depth of damage. Fibrinous films can be spontaneously rejected due to autolysis, which develops around the focus, and demarcation inflammation, and go outside; undergo enzymatic melting or organizing, i.e. germination by connective tissue with the formation of connective tissue adhesions, or adhesions. Fibrinous exudate can form with diphtheria, dysentery, tuberculosis.

Purulent exudate characterized by the presence of a large number of polymorphonuclear leukocytes, mainly dead and destroyed (purulent bodies), enzymes, products of tissue autolysis, albumins, globulins, sometimes fibrin filaments, especially nucleic acids, which cause high viscosity of pus. As a result, the purulent exudate is quite cloudy, with a greenish tint. It is characteristic of inflammatory processes caused by coccal infection, pathogenic fungi or chemical phlogogens such as turpentine, toxic substances.

Putrid (ichorous) exudate It is distinguished by the presence of products of putrefactive decomposition of tissues, as a result of which it has a dirty green color and a bad smell. It is formed in case of accession of pathogenic anaerobes.

Hemorrhagic exudate characterized great content red blood cells, which gives it a pink or red color. Characteristic for tuberculosis lesions(tuberculous pleurisy), plague, anthrax, black pox, toxic influenza, allergic inflammation, i.e. for the impact of highly virulent agents, violent inflammation, accompanied by a significant increase in permeability and even destruction of blood vessels. Hemorrhagic character can take any kind of inflammation - serous, fibrinous, purulent.

Mixed exudates are observed during inflammation occurring against the background of weakened body defenses and the attachment of a secondary infection as a result. There are serous-fibrinous, serous-purulent, serous-hemorrhagic, purulent-fibrinous exudates.

The biological significance of exudation doubly. It performs an important protective role: it provides the supply of plasma mediators to the tissue - active complement components, kinins, coagulation system factors, plasma enzymes, biologically active substances released by activated blood cells. Together with tissue mediators, they participate in the killing and lysis of microorganisms, recruitment of blood leukocytes, opsonization of a pathogenic agent, stimulation of phagocytosis, wound cleansing, and reparative phenomena. With exudate, metabolic products, toxins come out of the blood stream into the focus, i.e. the focus of inflammation performs a drainage eliminative function. On the other hand, due to the coagulation of the lymph in the focus, the loss of fibrin, the aggravation of venous stasis and thrombosis of the venous and lymphatic vessels, the exudate is involved in the retention of microbes, toxins, and metabolic products in the focus.

Being a component of the pathological process, exudation can lead to complications - the flow of exudate into the body cavity with the development of pleurisy, pericarditis, peritonitis; compression of nearby organs; pus formation with the development of an abscess, empyema, phlegmon, pyemia. The formation of adhesions can cause displacement and dysfunction of organs. The localization of the inflammatory process is of great importance. For example,

the formation of fibrinous exudate on the mucous membrane of the larynx in diphtheria can lead to asphyxia.

The accumulation of exudate in the tissue causes such an external local sign of inflammation as swelling. In addition, along with the action of bradykinin, histamine, prostaglandins, neuropeptides, exudate pressure on the endings of sensory nerves is of some importance in the occurrence of inflammatory pain.

10.4.5. Release of leukocytes into inflamed tissue (leukocyte migration)

Emigration(emigration, from lat. emigrate- move out, relocate - the release of leukocytes from the vessels into the tissue. It is carried out by diapedesis mainly through the wall of venules. Emigration of leukocytes into the focus is a key event in the pathogenesis of inflammation. Leukocytes are the main effectors of inflammation. The extracellular bactericidal and lytic effects of leukocyte products and phagocytosis play a decisive role in the fight against phlogogen. At the same time, affecting cells, blood vessels and blood, leukocyte components act as important mediators and modulators of inflammation, including damage to their own tissues. Carrying out wound cleansing, phagocytes create the prerequisites for reparative phenomena, where they stimulate the proliferation, differentiation and functional activity of fibroblasts and other cells. The mechanism of emigration (according to I.I. Mechnikov) consists in the phenomenon of chemotaxis.

The starting point for the activation of leukocytes is the impact on the receptors (often specific) of cell membranes of various chemotactic agents. (chemattractants), released by microorganisms or phagocytes, as well as formed in the tissue as a result of the action of an inflammatory agent or under the influence of the phagocytes themselves. The most important chemattractants are: complement fragments, fibrinopeptides and fibrin degradation products, kallikrein, plasminogen proactivator, collagen fragments, fibronectin, arachidonic acid metabolites, cytokines, lymphokines, bacterial peptides, granulocyte degradation products.

As a result of the binding of hemattractants to receptors and the activation of plasma membrane enzymes, a respiratory burst develops in the phagocyte - a sharp increase in consumption

oxygen and the formation of its active metabolites. This process has nothing to do with providing the phagocyte with energy. It is aimed at additional arming of the phagocyte with highly reactive toxic substances to more effectively destroy microorganisms. Along with the respiratory burst, other changes occur in the phagocyte: increased production of special membrane glycoproteins that determine the adhesiveness of the phagocyte; a decrease in the surface tension of the membrane and a change in the colloidal state of cytoplasmic regions (a reversible transition from gel to sol), which is necessary for the formation of pseudopodia; activation of actin and myosin microfilaments, which is the basis of migration; increased secretion and release of substances that facilitate the attachment of the leukocyte to the endothelium (lactoferrin, cationic proteins, fibronectin, interleukins).

Leukocytes exit the axial blood flow into the plasma. This is facilitated by a violation of the rheological properties of blood, a slowdown in blood flow, a change in its nature, in particular, a decrease in the marginal plasma zone (Fig. 10-12).

Due to the increase in the adhesive properties of leukocytes and endothelial cells, leukocytes adhere to

Rice. 10-12. Scheme of blood flow in normal conditions and in inflammation: 1 - normal circulation: axial flow, marginal plasma zone with individual leukocytes; 2 - slowing down of blood flow: erythrocytes are visible, marginal standing of leukocytes and platelets; 3 - strong blood stasis: marginal standing of leukocytes and platelets, a decrease in the marginal plasma zone (according to D.E. Alpern)

Rice. 10-13. Marginal standing of a leukocyte in the venule of the rat mesentery during inflammation: Pr - lumen of the vessel; EN - endothelial cell; Pc - pericyte; K - collagen fibers; I am the core; Er - erythrocytes. Electron microscopy, x10,000 (according to A.M. Chernukh)

endothelium - develops the phenomenon of marginal standing of leukocytes

(Fig. 10-13).

Increased adhesiveness of the endothelium may be due to: increased production of adhesive glycoproteins (lectins) and other substances that are included in the composition of the fibrin film, which normally covers the endothelium from the lumen of the vessel, fixation of chemattractants on endothelial cells, subsequently interacting with specific receptors on leukocytes, increased expression on endotheliocytes receptors for immunoglobulin G and complement fragment C3b, which contributes to the fixation of immune complexes, and through them - leukocytes carrying receptors for immunoglobulin (Ig) G and C3b.

adherence of leukocytes to the endothelium mediated by the following factors:

Leukocytes in the phase of initiation of inflammation are activated and form aggregates; as a result of the activation of the leukocyte, its negative charge decreases, which reduces the forces of mutual repulsion between it and the negatively charged endothelium;

Calcium bridges form between leukocytes and the endothelium (Ca 2 + and other divalent ions play a key role in leukocyte adhesion);

During activation in leukocytes, the synthesis of specific granules is enhanced, some components of which, such as lactoferrin, enhance the adhesive properties of cells;

On the leukocyte membrane, the expression of adhesive glycoproteins of the Mac-1 and LAF-1 classes increases.

The initial contact of leukocytes with the endothelium is very fragile, and under the influence of blood flow they can roll over the surface of the fibrin film, however, the contact quickly stabilizes, since leukocytes secrete proteases into the adhesion zone, exposing lectin-like sections of the endotheliocyte membrane and giving them increased adhesiveness. Fibronectin secreted by phagocytes is directly related to the adhesion of phagocytes to the endothelium. The leukocytes that have taken the marginal position release pseudopodia, which penetrate into the interendothelial gaps and thus “overflow” through the endothelial layer (Fig. 10-14). Emigration is facilitated by an increase in vascular permeability and an increase in the flow of fluid from the vessel into the tissue, which greatly facilitates the passage of the vascular wall for the leukocyte.

Once between the endothelial layer and the basement membrane, the leukocyte secretes lysosomal proteinases that dissolve it, as well as cationic proteins that change the colloidal state of the basement membrane (reversible transition from gel to sol), which ensures its increased permeability for the leukocyte. The immigrated leukocytes are separated from the outer surface of the vascular wall and are directed by amoeboid movements to the center of the inflammation focus (Fig. 10-15), which is determined by the concentration gradient of chemotactic substances in the focus. A certain role can be played by electrokinetic phenomena due to the potential difference between a negatively charged leukocyte and a positive charge of a tissue characterized by H + - hyperionia.

Initially, among the leukocytes of the exudate in the focus of acute inflammation, granulocytes predominate, mainly neutrophils, and then monocytes/macrophages. Later, lymphocytes accumulate in the focus.

Since the slowdown in blood flow in individual branches of the microvasculature and the marginal standing of leukocytes can

Rice. 10-14. Neutrophil emigration: 1 - emigrating neutrophil; E - endothelial cell; Ps - long pseudopodia, located parallel to the endothelium; 2 - neutrophil in the lumen of the vessel; 3, 4 - emigrated neutrophils; P - platelet. x15 500 (according to Marchesi)

Rice. 10-15. Scheme of leukocyte emigration (according to Marchesi)

develop very quickly, and it takes 3-12 minutes for a migrating neutrophil to pass through the endothelium, the appearance of granulocytes in the focus can be observed already by the 10th minute from the onset of inflammation. The rate of accumulation of neutrophils in the focus is the highest in the first 2 hours, gradually decreasing in the next. Their number reaches a maximum after 4-6 hours. During this period, the leukocytes of the focus are represented by neutrophils by more than 90%. Granulocytes phagocytize bacteria or other foreign bodies and particles of dying cellular elements, simultaneously carrying out extracellular supply of enzymes, cationic proteins, active oxygen metabolites. At the same time, there is a massive destruction of neutrophils, the remains of which are an important stimulus for the expansion of infiltration - both neutrophilic and monocytic. As normal, most of the granulocytes released into the tissue never return to the bloodstream.

Monocytes usually predominate in the focus of acute inflammation after 16-24 hours and reach a peak, as a rule, on the third day. However, the migration of monocytes from the blood into the tissue begins simultaneously with the migration of neutrophils. It is assumed that, at first, the rate of accumulation of monocytes, which is lower than that of neutrophils, is associated with inhibition of the chemotaxis of these cells under the influence of neutrophil waste products for a certain time, which is necessary for the full expression of the neutrophil reaction and the prevention of its monocytic control. In the focus of inflammation, there is a gradual transformation of immigrated monocytes into macrophages and the maturation of the latter, during which the volume of the cytoplasm and organelles in it increases. In particular, the number of mitochondria and lysosomes increases, which is essential for the full performance by macrophages of their functions in the focus. The activity of pinocytosis increases, the number of phagolysosomes in the cytoplasm increases, and the number of filopodia increases. Monocytes/macrophages are also a source of inflammatory mediators (enzymes, oxygen metabolites, cytokines), phagocytize bacteria, but are of primary importance in the phagocytosis of the remains of dead cells, in particular neutrophils. Therefore, the dependence of the accumulation of monocytes on the previous output of neutrophils is understandable. So, in rabbits with neutropenia, monocytes do not appear in the focus of inflammation within 16 hours, while in natural conditions of inflammation they are detected already after 4 hours, and the introduction into the focus

inflammation in leukopenic animals of neutrophils restores the usual accumulation of mononuclear cells. The chemotactic effect of neutrophil lysates on monocytes is known, due in part to the cationic proteins of their lysosomal granules.

On the other hand, the accumulation of neutrophils is largely dependent on monocytes. This is especially true of that part of neutrophilic infiltration that is associated with increased hematopoiesis, since the latter is initiated by monocyte-macrophage hematopoietic factors, in particular IL-1, various types of so-called colony-stimulating factors - substances of a predominantly protein nature responsible for the proliferation and differentiation of hematopoietic cells in the bone marrow. cells. Currently, a number of chemotactic peptides from human monocytes for neutrophils have been isolated, which may play a role in the mechanism of self-regulation of the leukocyte reaction of the inflammatory focus. However, the question of the mechanisms of the change of cellular phases in the focus of inflammation, the transition from the development of an inflammatory reaction to its resolution is one of the least studied in the problem of inflammation.

Cellular composition of the exudate to a large extent depends on the nature and course of the inflammatory process, which in turn are determined by the inflammatory agent and the state of the organism's reactivity. So, the exudate is especially rich in neutrophils if the inflammation is caused by pyogenic microbes; in allergic inflammation, the focus contains many eosinophils. Chronic inflammatory processes are characterized by a low content of neutrophils, the predominance of monocytes and lymphocytes.

Immigrant leukocytes, together with proliferating cells of local origin, form an inflammatory infiltrate. At the same time, the exudate with the cells contained in it impregnates the tissue, being distributed between the elements of the inflammatory area and making it tense and dense. Infiltrate along with exudate causes swelling and is important in the occurrence of inflammatory pain.

10.4.6. Recovery processes in inflamed tissue

under inflammatory proliferation(proliferate, from lat. proles- offspring ferre- create) understand the multiplication of local cells

exact elements in the focus of inflammation. Proliferation develops from the very beginning of inflammation along with the phenomena of alteration and exudation, but becomes predominant in the later period of the process, as the exudative-infiltrative phenomena subside. Initially, it is more pronounced on the periphery of the focus. The most important condition for the progression of proliferation is the effectiveness of cleansing the focus of inflammation from microorganisms or other harmful agents, tissue alteration products, dead leukocytes (wound cleansing). The leading role in this is assigned to macrophages - hematogenous (monocytes) and tissue (histocytes) origin.

wound cleansing occurs mainly by extracellular degradation of damaged tissue and phagocytosis. It is carried out under the regulatory influence of cytokines with the help of enzymes such as proteoglycanase, collagenase, gelatinase. Activation of these enzymes can occur under the influence of a plasminogen activator released with the participation of cytokines from mesenchymal cells. Prostaglandins, being released along with enzymes, can, for their part, induce proteinases and contribute to degradation processes.

Phagocytosis was discovered and understood as an essential element of inflammation and natural immunity by I.I. Mechnikov in 1882

I.I. Mechnikov singled out 4 phases of phagocytosis:

1) approach phase: the exit of the leukocyte from the vessel and the approach to the object of phagocytosis under the action of hemattractants;

2) adhesion phase(contact);

3) dive phase: enveloping and immersing the object inside the phagocyte; a special vacuole is formed where lysosomes accumulate;

4) digestion phase, which can result in 2 outcomes: a) adequate dosed release of lysosomal enzymes, destroying only the phlogogen (the phagocyte itself remains intact); b) excessive release of lysosomal enzymes, which leads to the destruction of the object of phagocytosis and the phagocyte itself.

Phagocytes, interacting with bacteria, are activated, their membrane becomes “sticky”, as the number of various receptors on it increases dramatically, as does the “feeling” mobility of the cytoplasm of these cells. At the same time, peroxisomes and granules accumulate in the cytoplasm, filled with

nye powerful proteases. When such a cell encounters a microorganism, the bacterium “sticks” to the surface of the phagocyte, wraps itself around its pseudopodia, and ends up inside the cell, where it is destroyed. Macrophages begin to release tumor necrosis factor (TNF), interferon γ (IFN-γ) and IL-8 into the environment, which plays a special role in inflammation - it causes the appearance of receptors in endotheliocytes that react with monocytes and neutrophils with high affinity, so that these cells stop in the capillaries located in the area of ​​inflammation. IL-8 is most effective in creating a gradient for chemotaxis of phagocytic cells. Phagocytes have receptors for IL-8, which “feel” the difference in its concentration from the side facing its source and from the opposite side, and direct their movement along the axis of maximum difference. Thus, phagocytic cells accumulate in the focus of inflammation, actively absorb and destroy (intracellularly) bacteria and cell debris, and secrete enzymes that destroy the intercellular substance of the connective tissue. With suppuration skin covering, surrounding the focus of inflammation (abscess), becomes thinner and breaks: phlogogens, cell debris and accumulated phagocytes are ejected from the body. The affected area of ​​the tissue is gradually restored. By removing the remains of leukocytes and destroyed tissues, macrophages eliminate the most important source of their own chemotactic stimulation and suppress the further development of the local leukocyte reaction. As the focus of inflammation is cleared, the number of macrophages decreases due to a decrease in their intake from the blood. From the focus, they are carried away by the recovering lymph flow to the regional lymph nodes, where they die. Lymphocytes partly die, partly turn into plasma cells that produce antibodies, and then are gradually eliminated.

Proliferation is carried out mainly due to the mesenchymal elements of the stroma, as well as elements of the parenchyma of organs. It involves cambial, adventitial, endothelial cells. As a result of differentiation of connective tissue stem cells - polyblasts - epithelioid cells, fibroblasts and fibrocytes appear in the focus. The main cellular elements responsible for reparative processes in the focus of inflammation are fibroblasts. They produce the main intercellular substance - glycosaminoglycans, and also synthesize and secrete fibrous structures - collagen,

elastin, reticulin. In turn, collagen is the main component of scar tissue.

regulation of proliferation. The proliferation process is under complex humoral control. Crucial Here have again macrophages. They are the main source of fibroblast growth factor, a thermolabile protein that stimulates fibroblast proliferation and collagen synthesis. Macrophages also increase the attraction of fibroblasts to the site of inflammation, secreting IL-1 and fibronectin. Macrophages stimulate the proliferation of endothelial and smooth muscle cells of the vascular wall, basement membrane and, thus, the formation of microvessels. Inhibition or stimulation of the mononuclear phagocyte system, respectively, weakens or enhances the development of granulation tissue in the focus of purulent inflammation.

In turn, macrophages mediate the regulatory effect on fibroblasts and the proliferation of T-lymphocytes. The latter are activated by proteinases formed in the focus of inflammation as a result of tissue breakdown. Proteinases can have a direct effect on both macrophages and fibroblasts. Macrophages and lymphocytes can release mono- and lymphokines, which not only stimulate but also inhibit fibroblasts, acting as true regulators of their functions.

Fibroblasts also depend on platelet growth factor, which is a thermostable protein with a high content of cysteine ​​and a molecular weight of 30,000 D. Other growth factors for fibroblasts are called somatotropin, somatomedins, insulin-like peptides, insulin, glucagon.

play an important role in proliferative phenomena. keylons- thermolabile glycoproteins with a molecular weight of 40,000 D, capable of inhibiting cell division by inactivating enzymes involved in DNA replication. One of the main sources of chalons are segmented neutrophils. As the number of neutrophils decreases in the focus of inflammation, the content of chalones decreases, which leads to an acceleration of cell division. According to other assumptions, during inflammation, segmented neutrophils practically do not produce chaylons and intensively produce antikeylons(division stimulants); accordingly, cell division is accelerated, proliferation is enhanced.

Other cells and mediators can modulate the reparative process by influencing the functions of fibroblasts, macrophages

gov and lymphocytes. Significant importance in the regulation of reparative phenomena, according to D.N. Mayansky, they also have reciprocal relationships in the collagen-collagenase system, stromal-parenchymal interactions.

Proliferation is replaced by regeneration. The latter is not included in the complex of inflammatory phenomena proper, but it certainly follows them and is difficult to separate from them. It consists in the growth of connective tissue, the neoplasm of blood vessels, and to a lesser extent in the reproduction of specific tissue elements. With minor tissue damage, relatively complete tissue regeneration occurs. When a defect is formed, it is first filled with granulation tissue - young, rich in blood vessels, which is subsequently replaced by connective tissue with the formation of a scar.

10.5. CHRONIC INFLAMMATION

There are cases when, from the very beginning, not polymorphonuclear leukocytes accumulate in inflammatory infiltrates, but monocytes, lymphocytes and their derivatives. The formation of such an accumulation of mononuclear cells, called "granuloma" is a prerequisite for a long course of inflammation. Chronic inflammation serves as an illustration of the validity of the statement of I.I. Mechnikov: "Inflammation is a protective reaction in its biological essence, but, unfortunately, for the body it does not always reach perfection."

Unlike acute inflammation chronic inflammation begins not from microcirculation disorders and the previously described events in the vascular bed, but from the accumulation of a critical number irritated (activated) macrophages In one place.

Persistent irritation of macrophages can be caused in different ways.

A number of microbes are absorbed by macrophages, but, once in their phagosomes, they do not die and are able to persist and multiply inside the cell for a long time (these are the causative agents of tuberculosis, leprosy, listeriosis, toxoplasmosis, and many others). Macrophages containing microbes become active and begin to secrete inflammatory mediators.

Macrophages can absorb non-infectious particles that the cell is not able to break down or release into the environment (complex polysaccharide complexes - corragenan from seaweed, dextran, zymosan from baker's yeast). After intravenous administration in mice with zymosan granules, they are taken up by resident macrophages (Kupffer cells) of the liver and interstitium macrophages of the lung and activate them. After 2-3 days, around such macrophages, as around epicenters, monocytes that have entered with blood begin to accumulate and what is commonly called a granuloma, or mononuclear infiltrate, is formed. The attraction of new monocytes/macrophages to the localization zone of activated macrophages is associated with substances that cause chemotaxis. They are secreted by active macrophages in finished form (LTC 4 , LTD 4 , PGE 2) or in the form of precursors: C2, C4, C5, C6 complement components, which are converted into C3, C5a, C567 fractions with high chemotactic activity under the action of proteases, secreted by the same macrophages.

Lysosomal enzymes secreted by macrophages, like collagenase, break down collagen. Products of partial degradation of collagen have a powerful ability to attract fresh monocytes to the site of inflammation.

Activated macrophages secrete bio-oxidants that trigger lipid peroxidation in the membranes of other cells in the area of ​​infiltration. However, a simple increased chemotaxins in some part of the tissue would not yet mean the influx of new inflammation effector cells from the blood. It is necessary that, along with the formation of a gradient of these substances, increase in permeability microvessels, from which mononuclear leukocytes could enter the area of ​​localization of irritated macrophages. Activated macrophages increase the permeability of microvessels, producing LTC 4 , LTD 4 , platelet aggregation factor, O 2 *- , collagenase and plasminogen activator, loosening the capillary connective tissue barrier. They either decompress the capillary basement membrane, or contract endothelial cells and expose interendothelial fissures, or act in both ways. As a result, the release of leukocytes from the blood and their movement to the area of ​​high concentration of chemotaxins, where they join other cells of the infiltrate, is facilitated. Monocytes, having come into the infiltrate, secrete

fibronectin. Due to this, they are firmly associated with the connective tissue matrix, primarily with collagen fibers. They seem to "become anchored". In English literature, such immobilization of cells even received the name "anchoring"(from English. anchor- anchor). This is a very important point, because "on the go" phagocytes "do not have time to solve the problems" that arise in front of them in the focus of inflammation.

Phagocytosis proceeds most effectively only after monocytes are fixed and spread out on the structures of the connective tissue. Thus, active macrophages not only trigger but also determine the entire process of chronic inflammation. However, in real conditions, macrophages do not work in isolation, but in combination with other types of cells that are part of the inflammatory infiltrate (granuloma) (Fig. 10-16, see color insert).

best studied functional cooperation between macrophages And lymphocytes:

1. First of all, these cells enter into close interaction in a specific immune response that develops during infectious inflammation. Macrophages engulf and partially destroy microbial antigens in their phagolysosomes. In a modified form, these antigens resurface on the cytoplasmic membrane of the macrophage, where they enter into a complex relationship with specific proteins. Only in this combination, the antigen is recognized by T-lymphocytes. This interaction of macrophage and T-lymphocytes in the focus of chronic inflammation can be called antigen-dependent. It manifests itself most visibly in those forms of chronic inflammation that occur during microbial infection and proceed with delayed-type hypersensitivity (DTH) phenomena.

2. Along with this, macrophages are associated with lymphocytes not only through antigens, but also through their secrets. Macrophages secrete substances (for example, IL-1) that enhance the growth of lymphocytes and increase their activity.

3. At the same time, actively proliferating lymphocytes secrete lymphokines that activate macrophages and sharply increase their effector functions in the focus of chronic inflammation:

The macrophage migration inhibition factor increases the adhesiveness of macrophage membranes and enables them to firmly fix

cling to the substrate. The same factor disinhibits the secretion of inflammatory mediators by macrophages;

A factor that enhances the aggregation of macrophages, their proliferation, the fusion of macrophages with each other with the formation of giant multinucleated cells, so characteristic of foci of chronic inflammation. In particular, there are especially many such cells in tuberculous infiltrates in the lungs;

Ways of triggering and development of acute and chronic inflammation fundamentally different:

1. In acute inflammation, the process starts "from the vessels", while in chronic inflammation - from the territory of the connective tissue, where active macrophages are located.

2. The leading cell of acute inflammation - the effector - is a neutrophil, and of chronic inflammation - an active macrophage. All other mesenchymal cells (mast, lymphocytes, eosinophils) also contribute to the implementation of the process by modulating the reactivity of neutrophils and macrophages.

3. Acute inflammation ends quickly, in a matter of days, if there are no complications in the form of a purulent cavity (abscess).

4. Chronic inflammation cannot end quickly for the following reasons:

First, macrophages in the focus of inflammation have a long life cycle, which is calculated in weeks, months, and even years. Initially, at the stage of inception, fresh monocytes with blood, lymphocytes - with blood and lymph come to the granuloma. They do not yet have a sufficiently high microbicidal activity. Then the granuloma gradually matures, and differentiated macrophages accumulate in it, actively absorbing microbes. Finally, at the final stage, in an old granuloma, the number of actively phagocytic cells decreases, but the percentage increases relative to

Inert in the sense of phagocytosis of epithelioid and giant multinucleated cells; secondly, any granuloma is not a “frozen” formation. It is constantly followed by a stream of more and more monocytes with blood from the bone marrow. If there are many activated macrophages in the granuloma, the influx will exceed the outflow of cells from the granuloma. The fact is that irritated macrophages intensively produce special hematopoietins. They stimulate the formation of phagocytes in the bone marrow. Metcalfe's colony stimulating factor is one of them. Therefore, while irritated macrophages "work", the balance will be shifted towards the influx of cells into the infiltrate, and its resorption is impossible. If macrophages release a lot of bio-oxidants into their environment, they can not only sanitize the focus, but also damage their own body cells. With hyperproduction of H 2 O 2 and O 2 * - these factors can escape from the phagosomes into the cytosol of the macrophage and lead to its death. In order to prevent such a situation, macrophages have a system of emergency neutralization of excess biooxidants. It includes enzymes: catalase, glutathione peroxidase and glutathione reductase. In particular, under the action of glutathione reductase, hydrogen peroxide is neutralized in the reaction 2 HH + H 2 O 2 - G-G + 2H 2 O, where G is glutathione. The enzyme superoxide dismutase neutralizes the superoxide anion radical (O 2 *-) in the reaction O 2 *- + O 2 *- + 2H + - H 2 O 2 + O 2. When the antioxidant defense systems fail, inflammation persists.

Chronic inflammation can continue throughout life. Periodically, it worsens when neutrophils and fresh macrophages with high pro-inflammatory activity enter the focus. In the focus of mononuclear infiltration is the destruction of the connective tissue. In response to this, the growth of fibrous structures occurs. Ultimately, sclerosis may develop with partial or complete shutdown of the specialized functions of the organ. This is facilitated by the accumulation in the granuloma of a special class of macrophages that secrete fibroblast-stimulating factors. Doctors have to deal with such a situation with cirrhosis of the liver after viral hepatitis, chronic pneumonia, chronic glomerulonephritis and other chronic inflammatory diseases.

10.6. GENERAL MANIFESTATIONS OF INFLAMMATION

General manifestations of inflammation are due to influences from the focus of the process, mainly mediators of inflammation.

Fever is the result of the action of endogenous pyrogens, in particular IL-1, released by activated leukocytes of the focus of inflammation and peripheral blood, on the center of thermoregulation.

Accelerated metabolism is a consequence of increased secretion of catabolic hormones, in particular under the influence of monokines, and may also be secondary to fever. At the same time, it is noted in the blood increased content glucose, globulins, residual nitrogen.

ESR increase reflects the absolute or relative predominance of globulins over albumin in plasma, which occurs due to increased production by hepatocytes under the influence of monokines of "acute phase proteins" or an advanced loss of albumin during exudation. The predominance of large-dispersed proteins in plasma reduces the negative charge of erythrocytes and, accordingly, their mutual repulsion. This increases the agglutination of erythrocytes and, consequently, their sedimentation.

Changes in immune properties organisms, manifested, in particular, by increased resistance to repeated exposure to a phlogogen, especially an infectious one, are due to the formation of cellular and humoral immunity during inflammation. In this, lymphoid cells of the focus of inflammation play an important role, for example, B-lymphocytes, which turn into plasma cells that produce antibodies. Inflammation forms the body's immunological reactivity ("immunity through disease").

Reactions of the blood system with inflammation, they include the emigration of leukocytes to the focus and a number of changes in the hematopoietic tissue and peripheral blood:

1) an initial transient decrease in the number of circulating leukocytes in the blood (transient leukopenia), due to their margination and emigration;

2) a decrease in the number of mature and immature granulocytes and monocytes in the bone marrow as a result of their increased leaching into the blood, which is provided by a reflex and, possibly, humoral acceleration of blood flow in the bone marrow. When the number of leukocytes in the blood coming from the bone marrow

exceeds the number of those who have emigrated to the focus of inflammation, leukocytosis develops;

3) subsequent restoration of the number of immature and mature granulocytes and monocytes in the bone marrow, indicating the activation of hematopoiesis;

4) an increase (against the initial) in the total number of myelokaryocytes and cells of individual hematopoietic lineages in the bone marrow, which indicates the development of its hyperplasia. All this ensures the development and long-term maintenance of leukocyte infiltration of the focus of inflammation.

Activation of hematopoiesis during inflammation, it is due to increased production of hematopoietic substances by stimulated leukocytes of the focus of inflammation and blood - colony-stimulating factors, interleukins, etc., which are the initiating link in the mechanism of self-maintenance of leukocyte infiltration of the focus of inflammation. In the self-regulation of infiltration, lysosomal enzymes, reactive oxygen species, and eicosanoids are essential.

Acute inflammation is characterized by neutrophilic leukocytosis. with a shift to the left (an increase in the number of younger, stab and young neutrophils as a result of the involvement of the bone marrow reserve and activation of hematopoiesis), as well as monocytosis, for chronic inflammation - monocyte ary leukocytosis and lymphocytosis.

In the occurrence of general phenomena in inflammation, humoral and reflex influences from the focus are important. This is evidenced, for example, by an increase in the Goltz reflex in a frog (decrease in heart rate with light tapping on the abdomen) with inflammation of the abdominal organs.

10.7. ROLE OF REACTIVITY IN INFLAMMATION

The emergence, development, course and outcome of inflammation depend on the reactivity of the body, which, in turn, is primarily determined by the functional state of higher regulatory systems - nervous, endocrine, immune.

The role of the nervous system. The involvement of the nervous system in the pathogenesis of inflammation became apparent thanks to the research of I.I. Mechnikov on the comparative pathology of inflammation, which showed that the more complex the body, the more differentiated its nervous

system, the brighter and more fully expressed the inflammatory reaction. Subsequently, the essential role of reflex mechanisms in the onset and development of inflammation was established. Preliminary anesthesia of the tissue at the site of phlogogen application delays and reduces the inflammatory response. Damage and interruption of the afferent part of the reflex arc during inflammation weaken its further development. As mentioned, short-term ischemia and arterial hyperemia in the focus of inflammation are of a reflex nature. The role of reflex reactions is also evidenced by data from clinical observations that inflammation can spontaneously develop in symmetrical areas of the body.

The importance of the higher parts of the central nervous system is indicated by a developmental delay and a weakening of inflammation on the background of anesthesia or during hibernation. Known is the possibility of reproducing conditioned reflex inflammation and leukocytosis to the action of only a conditioned stimulus (scratching or heating the skin of the abdomen) after the development of a conditioned reflex using phlogogen (intraperitoneal injection of killed staphylococci) as an unconditioned stimulus.

The role of the underlying parts of the central nervous system is evidenced by data on the development of extensive inflammatory processes in the skin and mucous membranes in chronic damage to the thalamic region. It is believed that this is due to a violation of the nervous trophism of tissues and, thus, a decrease in their resistance to harmful agents.

The autonomic nervous system has a significant influence on the development of inflammation. On the desympathetic ear of the rabbit, the inflammation proceeds more rapidly, but also ends faster. On the contrary, irritation of the sympathetic nerves inhibits the development of inflammation. Acetylcholine causes vasodilation and promotes the development of arterial hyperemia, enhances emigration. Norepinephrine causes short-term ischemia, inhibits the growth of vascular permeability and emigration. Thus, the parasympathetic nervous system has a pro-inflammatory effect, while the sympathetic nervous system has an anti-inflammatory effect.

The role of the endocrine system. In relation to inflammation, hormones can be divided into pro- and anti-inflammatory. The former include somatotropin, mineralocorticoids, thyroid hormones, insulin, the latter - corticotropin, glucocorticoids, sex hormones.

The role of the immune system. In an immunized organism, as a result of increased resistance to a harmful agent, inflammation is characterized by a reduced intensity and ends faster. With reduced immunological reactivity (immunological deficiency - hereditary and acquired immunodeficiencies), a sluggish, protracted, often recurrent and repeated inflammation is observed. With increased immunological reactivity (allergy), inflammation proceeds more rapidly, with a predominance of alterative phenomena, up to necrosis.

Effectors of the nervous, endocrine and immune systems - neurotransmitters, neuropeptides, hormones and lymphokines - carry out both a direct regulatory effect on tissue, blood vessels and blood, hemo- and lymphopoiesis, and mediated by other inflammatory mediators, the release of which they modulate through specific receptors of cell membranes and changes concentrations of cyclic nucleotides in cells.

Depending on the reactivity of the body, inflammation can be normergic, hyperergic and hypergic.

Normergic inflammation- usually flowing, inflammation in a normal body.

hyperergic inflammation- rapidly flowing, inflammation in a sensitized organism. Classic examples are the Arthus phenomenon, the Pirquet reaction, etc. It is characterized by the predominance of alteration phenomena.

hyperinflammation- Mild or sluggish inflammation. The first is observed with increased resistance to a stimulus, for example in an immunized organism, and is characterized by reduced intensity and faster completion (positive hypergia). The second - with reduced general and immunological reactivity (immunodeficiencies, starvation, tumors, diabetes mellitus, etc.) and is characterized by weak dynamics, a protracted course, a delay in the elimination of phlogogen and tissue damaged by it, (negative hypergia).

The significance of reactivity in the pathogenesis of inflammation has made it possible to consider it as general reaction body for local damage.

10.8. TYPES OF INFLAMMATION

According to the nature of the vascular tissue reaction, alterative, exudative-infiltrative and proliferative inflammation are distinguished.

The type of inflammation depends on the reactivity of the organism, the localization of the process, the type, strength and duration of the action of the phlogogen.

Alterative inflammation characterized by a special severity of the phenomena of dystrophy (up to necrobiosis and necrosis) and, thus, their predominance over exudative-infiltrative and proliferative. Most often, alternative inflammation develops in parenchymal organs and tissues (myocardium, liver, kidneys, skeletal muscles) during infections and intoxications, therefore it is also called parenchymal. With pronounced necrobiotic changes, alterative inflammation is called necrotic, for example, immunocomplex allergic inflammation (experimental Arthus phenomenon and Arthus-like reactions in humans).

Exudative-infiltrative inflammation characterized by a predominance of circulatory disorders with exudation and emigration over alteration and proliferation. Depending on the nature of the exudate, it can be serous, fibrinous, purulent, putrefactive, hemorrhagic and mixed.

10.9. COURSE OF INFLAMMATION

The course of inflammation is determined by the reactivity of the organism, the type, strength and duration of the action of the phlogogen. There are acute, subacute and chronic inflammation.

Acute inflammation characterized by a fairly pronounced intensity and a relatively short duration

chronic inflammation characterized by low intensity and long duration - from several months to many years and decades. By the nature of the vascular tissue reaction, it is most often proliferative. The leading role in its pathogenesis is played by monocytes-macrophages and lymphocytes. Chronic inflammation can be primary and secondary (due to the transition of acute inflammation to chronic). The development of primary chronic inflammation is primarily determined by the properties of the phlogogen (tuberculosis, syphilis, etc.), secondary chronic inflammation is determined by the characteristics of the organism's reactivity.

subacute inflammation occupies an intermediate position. Its clinical duration is approximately 3-6 weeks.

Acute inflammation can acquire a protracted course, i.e. become subacute or secondary chronic. Perhaps an undulating course of chronic inflammation, when periods of subsidence of the process alternate with exacerbations. At the same time, during the period of exacerbation, exudative phenomena with infiltration by polymorphonuclear leukocytes and even alterative ones intensify and become predominant. In the future, proliferative phenomena again come to the fore.

In general, there are no fundamental differences in the general mechanisms of acute and protracted inflammation (inflammation is a typical process). The difference lies in the fact that during a protracted process, due to the altered reactivity of the organism, the unity of damage and protection is violated, and the inflammatory process acquires the character of a negatively hypoergic, proliferative one.

10.10. OUTCOMES OF INFLAMMATION

The outcome of inflammation depends on its type and course, localization and prevalence. The following outcomes of inflammation are possible:

1. Practically full recovery structures and functions(return to normal - restitutio ad integrum). It is observed with minor damage, when specific tissue elements are restored.

2. Scar formation(return to normal with incomplete recovery). It is observed with a significant defect at the site of inflammation and its replacement with connective tissue. The scar may not affect the functions or lead to dysfunction as a result of: a) deformation of the organ or tissue (for example, cicatricial changes in the heart valves); b) displacement of organs (for example, the lungs as a result of the formation of adhesions in the chest cavity as a result of pleurisy).

3. Organ death and the whole organism - with necrotic inflammation.

4. Death of an organism with a certain localization of inflammation - for example, from suffocation due to the formation of diphtheria films on the mucous membrane of the larynx. Threatening is the localization of inflammation in vital organs.

5. Development of complications inflammatory process: a) the flow of exudate into the body cavity with the development, for example, of peritonitis in inflammatory processes in the abdominal organs; b) the formation of pus with the development of an abscess, phlegmon, empyema, pyemia; c) sclerosis or cirrhosis of the organ as a result of diffuse proliferation of connective tissue during proliferative inflammation.

6. The transition of acute inflammation to chronic.

In the clinical outcome of inflammation great importance has an underlying disease if the occurrence of the focus (foci) of inflammation is associated with it.

10.11. THE SIGNIFICANCE OF INFLAMMATION FOR THE ORGANISM

In general biological terms inflammation is important protective and adaptive reaction, formed in the process of evolution as a way to preserve the whole organism at the cost of damaging its part. This is a method of emergency protection of the body, used in the case when the body could not cope with a harmful agent through its physiological elimination and damage occurred. Inflammation is a kind of biological and mechanical barrier, with the help of which the localization and elimination of the phlogogen and (or) the tissue damaged by it and its restoration or compensation of the tissue defect are ensured. Biological barrier properties are achieved

by adhesion, killing and lysis of bacteria, degradation of damaged tissue. The function of a mechanical barrier is carried out due to the loss of fibrin, coagulation of lymph in the focus, blockade of blood and lymphatic vessels, reproduction of connective tissue cells at the border of damaged and normal tissue (demarcation). All this prevents the absorption and spread of microbes, toxins, products of impaired metabolism and decay.

The inflammatory focus performs not only a barrier, but also drainage function: with exudate from the blood, products of impaired metabolism, toxins come out into the focus. As already mentioned, inflammation affects the formation of immunity.

At the same time, the expediency of inflammation as a protective and adaptive reaction is unconditional only in an evolutionary-biological sense. And as a local process with a certain localization and prevalence inflammation may be accompanied by general pathological manifestations(intoxication, changes in reactivity, etc.) and even in the usual course to harm the body. In addition, in connection with the altered reactivity, in practice, unusual forms and complications of inflammation are often encountered.