Hyalinosis of the pleura. Hyalinosis: how terrible is the pathology

Stromal-vascular (mesenchymal) dystrophies develop as a result of metabolic disorders in the connective tissue and are detected in the stroma of organs and vessel walls. They develop in histion, which, as you know, is formed by a segment of the microvasculature with surrounding elements of connective tissue (ground substance, fibrous structures, cells) and nerve fibers. In connection with this, the predominance among the mechanisms of development of stromal-vascular

dystrophies of violations of trophic transport systems, commonality of morphogenesis, the possibility of not only combining different types of dystrophy, but also the transition of one type to another.

In case of metabolic disorders in the connective tissue, mainly in its intercellular substance, metabolic products accumulate, which can be brought with blood and lymph, be the result of perverse synthesis, or appear as a result of disorganization of the basic substance and connective tissue fibers.

Depending on the type of impaired metabolism, mesenchymal dystrophies are divided into protein (dysproteinoses), fatty (lipidoses) and carbohydrate.

Stromal-vascular protein dystrophies (dysproteinoses)

Among connective tissue proteins, collagen, macromolecules of which collagen and reticular fibers are built. Collagen is an integral part of the basement membranes (endothelium, epithelium) and elastic fibers, which, in addition to collagen, include elastin. Collagen is synthesized by connective tissue cells, among which the main role is played by fibroblasts. In addition to collagen, these cells

synthesize glycosaminoglycans the main substance of the connective tissue, which also contains proteins and polysaccharides of blood plasma.

Connective tissue fibers have a characteristic ultrastructure. They are well identified using a number of histological methods: collagenous - by staining with a picrofuchin mixture (according to van Gieson), elastic - by staining with fuchselin or orcein, reticular - by impregnation with silver salts (reticular fibers are argyrophilic).

In the connective tissue, in addition to its cells that synthesize collagen and glycosaminoglycans (fibroblast, reticular cell), as well as a number of biologically active substances (labrocyte, or mast cell), there are cells of hematogenous origin that carry out phagocytosis (polymorphonuclear leukocytes, histiocytes, macrophages) and immune reactions (plasmoblasts and plasmocytes, lymphocytes, macrophages).

Stromal vascular dysproteinoses include mucoid swelling, fibrinoid swelling (fibrinoid), hyalinosis, amyloidosis.

Often, mucoid swelling, fibrinoid swelling, and hyalinosis are successive stages. disorganization of connective tissue; this process is based on the accumulation of blood plasma products in the ground substance as a result of an increase in tissue-vascular permeability (plasmorrhagia), destruction of connective tissue elements and the formation of protein (protein-polysaccharide) complexes. Amyloidosis differs from these processes in that the composition of the resulting protein-polysaccharide complexes includes a fibrillar protein that is not usually found, synthesized by cells - amyloidoblasts (Scheme II).

Scheme II. Morphogenesis of stromal-vascular dysproteinoses

swelling

Mucoid

Mucoid swelling- superficial and reversible disorganization of the connective tissue. In this case, the accumulation and redistribution of glycosaminoglycans occur in the main substance due to an increase in the content, primarily of hyaluronic acid. Glycosaminoglycans have hydrophilic properties, their accumulation leads to an increase in tissue and vascular permeability. As a result, plasma proteins (mainly globulins) and glycoproteins are mixed with glycosaminoglycans. Hydration and swelling of the main intermediate substance develop.

The main substance is basophilic, when stained with toluidine blue - lilac or red (Fig. 30, see color inc.). Arises phenomenon of metachromasia, which is based on a change in the state of the main intermediate substance with the accumulation of chromotropic substances. Collagen fibers usually retain a bundle structure, but swell and undergo fibrillar defibration. They become less resistant to collagenase and appear yellow-orange instead of brick red when stained with picrofuchsin. Changes in the ground substance and collagen fibers during mucoid swelling may be accompanied by cellular reactions - the appearance of lymphocytic, plasma cell and histiocytic infiltrates.

Mucoid swelling occurs in various organs and tissues, but more often in the walls of arteries, heart valves, endocardium and epicardium, i.e. where chromotropic substances occur and are normal; at the same time, the amount of chromotropic substances increases sharply. Most often it is observed in infectious and allergic diseases, rheumatic diseases, atherosclerosis, endocrinopathies, etc.

Appearance. With mucoid swelling, the tissue or organ is preserved, characteristic changes are established using histochemical reactions during microscopic examination.

Causes. Of great importance in its development are hypoxia, infection, especially streptococcal, immunopathological reactions (hypersensitivity reactions).

Exodus can be twofold: complete tissue repair or transition to fibrinoid swelling. In this case, the function of the organ suffers (for example, dysfunction of the heart due to the development of rheumatic endocarditis - valvulitis).

Fibrinoid swelling (fibrinoid)

fibrinoid swelling- deep and irreversible disorganization of the connective tissue, which is based on destruction its main substance and fibers, accompanied by a sharp increase in vascular permeability and the formation of fibrinoid.

fibrinoid is a complex substance, which includes proteins and polysaccharides of decaying collagen fibers, the main substance and blood plasma, as well as cellular nucleoproteins. Histochemically, in various diseases, fibrinoid is different, but its essential component is fibrin(Fig. 31) (hence the terms

"fibrinoid swelling", "fibrinoid").

31. fibrinoid swelling:

a - fibrinoid swelling and fibrinoid necrosis of the capillaries of the renal glomeruli (systemic lupus erythematosus); b - in fibrinoid among swollen collagen fibers that lost their transverse striation (CLF), fibrin masses (F). electronogram. x35,000 (according to Gieseking)

microscopic picture. With fibrinoid swelling, bundles of collagen fibers impregnated with plasma proteins become homogeneous, forming insoluble strong compounds with fibrin; they are eosinophilic, stain yellow with pyrofuchsin, sharply PAS-positive and pyroninophilic in the Brachet reaction, and argyrophilic when impregnated with silver salts. Metachromasia of the connective tissue is not expressed or expressed weakly, which is explained by the depolymerization of glycosaminoglycans of the main substance.

In the outcome of fibrinoid swelling, sometimes develops fibrinoid

necrosis, characterized by complete destruction of connective tissue. Around the foci of necrosis, the reaction of macrophages is usually expressed.

Appearance. Various organs and tissues where fibrinoid swelling occurs, outwardly change little, characteristic changes are usually found only during microscopic examination.

Causes. Most often, this is a manifestation of infectious-allergic (for example, vascular fibrinoid in tuberculosis with hyperergic reactions), allergic and autoimmune (fibrinoid changes in connective tissue in rheumatic diseases, renal glomerular capillaries in glomerulonephritis) and angioedema (arteriole fibrinoid in hypertension and arterial hypertension) reactions . In such cases, fibrinoid swelling has common (system)

character. locally fibrinoid swelling can occur with inflammation, especially chronic (fibrinoid in the appendix in appendicitis, in the bottom of a chronic stomach ulcer, trophic skin ulcers, etc.).

Exodus fibrinoid changes are characterized by the development of necrosis, replacement of the focus of destruction with connective tissue (sclerosis) or hyalinosis. Fibrinoid swelling leads to disruption and often cessation of organ function (for example, acute renal failure in malignant hypertension, characterized by fibrinoid necrosis and changes in glomerular arterioles).

Hyalinosis

At hyalinosis(from Greek. hyalos- transparent, vitreous), or hyaline dystrophy, homogeneous translucent dense masses (hyaline) resembling hyaline cartilage are formed in the connective tissue. The tissue thickens, so hyalinosis is also considered as a type of sclerosis.

Hyaline is a fibrillar protein. Immunohistochemical examination reveals not only plasma proteins, fibrin, but also components of immune complexes (immunoglobulins, complement fractions), as well as lipids. Hyaline masses are resistant to acids, alkalis, enzymes, PAS-positive, well accept acid dyes (eosin, acid fuchsin), picrofuchsin stains yellow or red.

Hyaline. Smooth muscle cells take part in the formation of vascular hyaline.

Hyalinosis can develop as a result of various processes: plasma impregnation, fibrinoid swelling (fibrinoid), inflammation, necrosis, sclerosis.

Classification. There are hyalinosis of the vessels and hyalinosis of the connective tissue itself. Each of them can be widespread (systemic) and local.

Hyalinosis of vessels. Hyalinosis is predominantly small arteries and arterioles. It is preceded by damage to the endothelium, its membrane and smooth muscle cells of the wall and its impregnation with blood plasma.

Microscopic examination. Hyaline is found in the subendothelial space, it pushes outward and destroys the elastic lamina, the middle membrane becomes thinner, and finally the arterioles turn into thickened vitreous tubules with a sharply narrowed or completely closed lumen (Fig. 32).

Hyalinosis of small arteries and arterioles is systemic, but is most pronounced in the kidneys, brain, retina, pancreas, and skin. It is especially characteristic of hypertension and hypertensive conditions (hypertensive arteriological disease), diabetic microangiopathy (diabetic arteriological disease) and diseases with impaired immunity. As a physiological phenomenon, local arterial hyalinosis is observed in the spleen of adults and the elderly, reflecting the functional and morphological features of the spleen as an organ of blood deposition.

Vascular hyaline is a substance of a predominantly hematogenous nature. In its formation, not only hemodynamic and metabolic, but also immune mechanisms play a role.

Guided by the peculiarities of the pathogenesis of vascular hyalinosis, 3 types of vascular hyaline are distinguished: 1) simple, arising from insudation of unchanged or slightly changed blood plasma components (more common in benign hypertension, atherosclerosis and in healthy people); 2) lipogyalin, containing lipids and β-lipoproteins (found most often in diabetes mellitus); 3) complex hyaline, built from immune complexes, fibrin and collapsing structures of the vascular wall (see Fig. 32) (typical for diseases with immunopathological disorders, such as rheumatic diseases).

32. Hyalinosis of the vessels of the spleen:

a - the wall of the central artery of the spleen follicle is represented by homogeneous masses of hyaline; b - fibrin among hyaline masses when stained according to the Weigert method; c - fixation of IgG immune complexes in hyaline (fluorescent microscopy); d - masses of hyaline (G) in the arteriole wall; En - endothelium; Pr - lumen of the arteriole. electronogram.

Hyalinosis of the connective tissue proper. It usually develops as a result of fibrinoid swelling, leading to the destruction of collagen and impregnation of the tissue with plasma proteins and polysaccharides.

Microscopic examination. Find the swelling of the connective tissue bundles, they lose fibrillation and merge into a homogeneous dense cartilage-like mass; cellular elements are compressed and undergo atrophy. This mechanism of development of systemic hyalinosis of the connective tissue is especially common in diseases with immune disorders (rheumatic diseases). Hyalinosis can complete fibrinoid changes in the bottom of a chronic gastric ulcer, in

appendix with appendicitis; it is similar to the mechanism of local hyalinosis in the focus of chronic inflammation.

Hyalinosis as an outcome of sclerosis is also mainly local in nature: it develops in scars, fibrous adhesions of serous cavities, the vascular wall in atherosclerosis, involutional sclerosis of the arteries, in the organization of a blood clot, in capsules, tumor stroma, etc. At the heart of hyalinosis in these cases are metabolic disorders of the connective tissue.

A similar mechanism has hyalinosis of necrotic tissues and fibrinous overlays.

Appearance. With severe hyalinosis, the appearance of the organs changes. Hyalinosis of small arteries and arterioles leads to atrophy, deformation and wrinkling of the organ (for example, the development of arteriolosclerotic nephrocyrrhosis).

With hyalinosis of the connective tissue itself, it becomes dense, whitish, translucent (for example, hyalinosis of the heart valves in rheumatic disease).

Exodus. In most cases, unfavorable, but resorption of hyaline masses is also possible. So, hyaline in scars - the so-called keloids - can be loosened and resorbed. Let us reverse the hyalinosis of the mammary gland, and the resorption of hyaline masses occurs under conditions of hyperfunction of the glands. Sometimes the hyalinized tissue becomes mucilaginous.

functional value. It varies depending on the location, degree and prevalence of hyalinosis. Widespread hyalinosis of arterioles can lead to functional insufficiency of the organ (renal failure in arteriolosclerotic nephrocyrrhosis). Local hyalinosis (for example, heart valves with its defect) can also be the cause of functional organ failure. But in scars, it may not cause much distress.

Amyloidosis

Amyloidosis(from lat. amylum- starch), or amyloid degeneration,- stromal-vascular dysproteinosis, accompanied by a profound violation of protein metabolism, the appearance of an abnormal fibrillar protein and the formation of a complex substance in the interstitial tissue and vessel walls - amyloid.

In 1844, the Viennese pathologist K. Rokitansky described peculiar changes in parenchymal organs, which, in addition to a sharp compaction, acquired a waxy, greasy appearance.

The disease in which such changes in organs occurred, he called "sebaceous disease." A few years later, R. Virchow showed that these changes are associated with the appearance in the organs of a special substance, which turns blue under the action of iodine and sulfuric acid. Therefore, he called it amyloid, and "sebaceous disease" - amyloidosis. The protein nature of amyloid was established by M.M. Rudnev together with Kuehne in 1865.

Chemical composition and physical properties of amyloid. Amyloid is a glycoprotein, the main component of which are fibrillar proteins(F-component).

They form fibrils with a characteristic ultramicroscopic structure (Fig. 33).

Fibrillar amyloid proteins are heterogeneous. There are 4 types of these proteins that are characteristic of certain forms of amyloidosis: 1) AA protein (not associated with immunoglobulins), which is formed from its serum counterpart - SAA protein; 2) AL- protein (associated with immunoglobulins), its precursor is L-chains (light chains) of immunoglobulins; 3) AF-protein, in the formation of which prealbumin is mainly involved; 4) ASC^-protein, the precursor of which is also prealbumin.

Amyloid fibril proteins can be identified using specific sera in immunohistochemical studies, as well as a number of chemical (reactions with potassium permanganate, alkaline guanidine) and physical (autoclaving) reactions.

Fibrillar amyloid proteins that cells produce - amyloidoblasts, enter into complex compounds with glucoproteins of blood plasma. This plasma component The (P-component) of amyloid is represented by rod-shaped structures (“periodic rods” - see Fig. 33). The fibrillar and plasma components of amyloid have antigenic properties. Amyloid fibrils and the plasma component enter into combinations with tissue chondroitin sulfates and the so-called hematogenous additives join the resulting complex, among which fibrin and immune complexes are of primary importance. The bonds of proteins and polysaccharides in the amyloid substance are extremely strong, which explains the lack of effect when various body enzymes act on amyloid.

33. Amyloid ultrastructure:

a - amyloid fibrils (Am), x35,000; b - rod-shaped formations consisting of pentagonal structures (PSt), x300,000 (according to Glenner et al.)

Characteristic of amyloid is its red staining of Congo red, methyl (or gentian) violet; specific luminescence with thioflavins S or T is characteristic. Amyloid is also detected using a polarizing microscope. It is characterized by dichroism and anisotropy (the birefringence spectrum lies within

540-560 nm). These properties make it possible to distinguish amyloid from other fibrillar proteins. For macroscopic diagnosis of amyloidosis, they use the effect on the tissue with a Lugol solution, and then with a 10% solution of sulfuric acid; amyloid becomes blue-violet or dirty green.

The colorful reactions of amyloid associated with the peculiarities of its chemical composition may be different depending on the form, type and type of amyloidosis. In some cases, they are absent, then they speak of achromatic amyloid, or achroamyloid.

Classification amyloidosis takes into account the following features: 1) possible cause; 2) the specificity of the amyloid fibril protein; 3) prevalence of amyloidosis; 4) the originality of clinical manifestations due to the predominant lesion of certain organs and systems.

1. Guided the reason allocate primary (idiopathic), hereditary (genetic, family), secondary (acquired) and senile amyloidosis. Primary, hereditary, senile amyloidoses are considered as nosological forms. Secondary amyloidosis, which occurs in certain diseases, is a complication of these diseases, a “second disease”.

For primary (idiopathic) amyloidosis characteristic: the absence of a previous or concomitant "causal" disease; defeat of predominantly mesodermal tissues - the cardiovascular system, striated and smooth muscles, nerves and skin (generalized amyloidosis); tendency to form nodular deposits, inconstancy of colorful reactions of the amyloid substance (negative results are frequent when stained with Congo red).

Hereditary (genetic, family) amyloidosis. The significance of genetic factors in the development of amyloidosis is confirmed by the peculiarity of its geographical pathology and the special predisposition to it of certain ethnic groups of the population. The most common type of hereditary amyloidosis with a predominant kidney lesion is characteristic of a periodic disease (familial Mediterranean fever), which is more often observed in representatives of ancient peoples (Jews, Armenians, Arabs).

There are other types of hereditary amyloidosis. So, familial nephropathic amyloidosis is known, occurring with fever, urticaria and deafness, described in English families (the form of Mackle and Wells). Hereditary nephropathic amyloidosis has several variants. Type I hereditary neuropathy (Portuguese amyloidosis) is characterized by damage to the peripheral nerves of the legs, and type II neuropathy, which occurs in American families, damage to the peripheral nerves of the hands. In type III neuropathy, which is also described in Americans, there is a combination of it with non-

phropathy, and with type IV neuropathy described in Finnish families, there is a combination not only with nephropathy, but also with reticular degeneration of the cornea. Hereditary

the cardiopathic amyloidosis found in Danes is not much different from generalized primary amyloidosis.

Secondary (acquired) amyloidosis unlike other forms, it develops as a complication of a number of diseases (“second disease”). These are chronic infections (especially tuberculosis), diseases characterized by purulent-destructive processes (chronic non-specific inflammatory diseases of the lungs, osteomyelitis, suppuration of wounds), malignant neoplasms (paraproteinemic leukemia, lymphogranulomatosis, cancer), rheumatic diseases (especially rheumatoid arthritis). Secondary amyloidosis, in which, as a rule, many organs and tissues are affected (generalized amyloidosis), occurs most frequently compared to other forms of amyloidosis.

At senile amyloidosis lesions of the heart, arteries, brain and pancreatic islets are typical. These changes, like atherosclerosis, cause senile physical and mental degradation. In old people there is an undoubted connection between amyloidosis, atherosclerosis and diabetes, which combines age-related metabolic disorders. In senile amyloidosis, local forms are most common (amyloidosis of the atria, brain, aorta, pancreatic islets), although there is also generalized senile amyloidosis with a predominant lesion of the heart and blood vessels, which clinically differs little from generalized primary amyloidosis.

2. Amyloid fibril protein specificity allows you to highlight AL-, AA-, AF- and ASC1- amyloidosis.

AL amyloidosis includes primary (idiopathic) amyloidosis and amyloidosis in

"plasma cell dyscrasia", which combines paraproteinemic leukemias (multiple myeloma, Waldenström's disease, Franklin's heavy chain disease), malignant lymphomas, etc. AL-amyloidosis is always generalized with damage to the heart, lungs and blood vessels. AA amyloidosis covers secondary amyloidosis and two forms of hereditary - periodic disease and McCle and Wells disease. This is also generalized amyloidosis, but with a primary lesion of the kidneys. AF amyloidosis- hereditary, represented by familial amyloid neuropathy (FAP); primarily peripheral nerves are affected. ASC amyloidosis- senile generalized or systemic (SSA) with a primary lesion of the heart and blood vessels.

3. Considering prevalence of amyloidosis distinguish between generalized and local forms. To generalized amyloidosis, as can be seen from what has already been said, include primary amyloidosis and amyloidosis with "plasma cell dyscrasia" (forms of AL-amyloidosis), secondary amyloidosis and some types of hereditary (forms of AA-amyloidosis), as well as senile systemic amyloidosis (ASC-amyloidosis) . Local amyloidosis

combines a number of forms of hereditary and senile amyloidosis, as well as local tumor-like amyloidosis (“amyloid tumor”).

4. The peculiarity of clinical manifestations due to the predominant damage to organs and systems will allow to allocate cardiopathic, nephropathic, neuropathic, hepatopathic, epinephropathic, mixed types of amyloidosis and APUD amyloidosis. The cardiopathic type, as mentioned earlier, is more common in primary and senile systemic amyloidosis, the nephropathic type in secondary amyloidosis, periodic illness, and McCle and Wells disease; mixed types are also characteristic of secondary amyloidosis (combination of damage to the kidneys, liver, adrenal glands, gastrointestinal tract). Neuropathic amyloidosis is usually hereditary. APUD-amyloid develops in the organs of the APUD-system with the development of tumors (apudomas) in them, as well as in pancreatic islets in senile amyloidosis.

Morpho- and pathogenesis of amyloidosis. Function amyloidoblasts, protein-producing fibrils of amyloid (Fig. 34), in various forms of amyloidosis, different cells perform. In generalized forms of amyloidosis, these are mainly macrophages, plasma and myeloma cells; however, the role of fibroblasts, reticular cells and endotheliocytes is not excluded. In local forms, cardiomyocytes (amyloidosis of the heart), smooth muscle cells (amyloidosis of the aorta), keratinocytes (amyloidosis of the skin), B-cells of the pancreatic islets (insular amyloidosis), C-cells of the thyroid gland and other epithelial cells of APUD- systems.

34. Amyloidoblast. Amyloid fibrils (Am) in invaginates of the plasmolemma of stellate reticuloendotheliocyte with hyperplasia of the granular endoplasmic reticulum (ER), indicating its high synthetic activity. x30 000

The appearance of a clone of amyloidoblasts explains mutation theory amyloidosis (Serov V.V., Shamov I.A., 1977). In secondary amyloidosis (excluding amyloidosis in

"plasma cell dyscrasia") mutations and the appearance of amyloidoblasts can be associated with prolonged antigenic stimulation. Cellular mutations in "plasma cell dyscrasia" and tumor amyloidosis, and possibly in tumor-like local amyloidosis, are caused by tumor mutagens. With genetic (familial) amyloidosis, we are talking about a gene mutation that can occur at different loci, which determines the differences in the composition of the amyloid protein in different people and animals. In senile amyloidosis, most likely, similar mechanisms take place, since this type of amyloidosis is considered as a genetic phenocopy. Since the protein antigens of amyloid fibrils are extremely weak immunogens, mutating cells are not recognized by the immunocompetent system and are not eliminated. Immunological tolerance to amyloid proteins develops, which causes the progression of amyloidosis, an extremely rare resorption of amyloid - amyloidoclasia- with the help of macrophages (giant cells of foreign bodies).

The formation of amyloid protein can be associated with reticular (perireticular amyloidosis) or collagen (pericollagenic amyloidosis) fibers.

For perireticular amyloidosis, in which amyloid falls out along the membranes of blood vessels and glands, as well as the reticular stroma of parenchymal organs, a predominant lesion of the spleen, liver, kidneys, adrenal glands, intestines, intima of small and medium-sized vessels (parenchymal amyloidosis) is characteristic. For pericollagen amyloidosis, in which amyloid falls out along the course of collagen fibers, the adventitia of vessels of medium and large caliber, myocardium, striated and smooth muscles, nerves, and skin are predominantly affected (mesenchymal amyloidosis).

Thus, amyloid deposits have a fairly typical localization: in the walls of blood and lymphatic capillaries and vessels in the intima or adventitia; in the stroma of organs along the reticular and collagen fibers; in its own shell of glandular structures. Amyloid masses displace and replace the parenchymal elements of organs, which leads to the development of their chronic functional failure.

Pathogenesis amyloidosis is complex and ambiguous in its various forms and types. The pathogenesis of AA and AL amyloidosis has been studied better than other forms.

At AA amyloidosis amyloid fibrils are formed from the plasma precursor of amyloid fibrillar protein entering the macrophage - amyloidoblast - squirrel SAA, which is intensively synthesized in the liver (scheme III). Enhanced SAA synthesis by hepatocytes stimulates macrophage mediator interleukin-1, which leads to a sharp increase in the content of SAA in the blood (pre-amyloid stage). Under these conditions, macrophages are unable to carry out the complete degradation of SAA, and from

Scheme III. Pathogenesis of AA-amyloidosis

Its fragments in the invaginates of the plasma membrane of the amyloidoblast assemble amyloid fibrils (see Fig. 34). Stimulates this assembly amyloid-stimulating factor(ASF), which is found in tissues (spleen, liver) in the pre-amyloid

stages. Thus, the macrophage system plays a leading role in the pathogenesis of AA amyloidosis: it stimulates increased synthesis of the precursor protein SAA by the liver, and it is also involved in the formation of amyloid fibrils from degrading fragments of this protein.

At AL amyloidosis the serum precursor of the amyloid fibril protein is the L-chain of immunoglobulins. It is believed that there are two possible mechanisms for the formation of AL-amyloid fibrils: 1) violation of the degradation of monoclonal light chains with the formation of fragments capable of aggregation into amyloid fibrils; 2) the appearance of L-chains with special secondary and tertiary structures during amino acid substitutions. Synthesis of amyloid fibrils from L-chains of immunoglobulins can occur not only in macrophages, but also in plasma and myeloma cells synthesizing paraproteins (Scheme IV). Thus, the lymphoid system is primarily involved in the pathogenesis of AL-amyloidosis; the appearance of "amyloidogenic" light chains of immunoglobulins, the precursor of amyloid fibrils, is associated with its perverted function. The role of the macrophage system is secondary, subordinate.

Macro- and microscopic characteristics of amyloidosis. The appearance of organs in amyloidosis depends on the degree of the process. If the amyloid deposits are small, the appearance of the organ changes little and amyloidosis

Scheme IV. Pathogenesis of AL-amyloidosis

found only under microscopic examination. With severe amyloidosis, the organ increases in volume, becomes very dense and brittle, and on the cut has a peculiar waxy, or greasy, appearance.

AT spleen amyloid is deposited in the lymphatic follicles (Fig. 35) or evenly throughout the pulp. In the first case, amyloid-modified follicles of an enlarged and dense spleen on the cut look like translucent grains resembling sago grains. (sago spleen). In the second case, the spleen is enlarged, dense, brown-red, smooth, has a greasy sheen on the cut. (sebaceous spleen). The sago and sebaceous spleens represent successive stages in the process.

AT kidneys amyloid is deposited in the vascular wall, in capillary loops and glomerular mesangium, in the basement membranes of the tubules, and in the stroma. The kidneys become dense, large and "greasy". As the process increases, the glomeruli and pyramids are completely replaced by amyloid (see Fig. 35), connective tissue grows and amyloid wrinkling of the kidneys develops.

AT liver amyloid deposition is observed between the stellate reticuloendotheliocytes of the sinusoids, along the reticular stroma of the lobules, in the walls of blood vessels, ducts, and in the connective tissue of the portal tracts. As amyloid accumulates, liver cells atrophy and die. At the same time, the liver is enlarged, dense, looks "greasy".

AT intestines amyloid falls out along the reticular stroma of the mucous membrane, as well as in the walls of the vessels of both the mucous membrane and the submucosal layer. With a pronounced amyloidosis, the glandular apparatus of the intestine atrophies.

Amyloidosis adrenal, usually bilateral, amyloid deposition occurs in the cortex along the vessels and capillaries.

35. Amyloidosis:

a - amyloid in the follicles of the spleen (sago spleen); b - amyloid in the vascular glomeruli of the kidneys; c - amyloid between the muscle fibers of the heart; d - amyloid in the walls of the vessels of the lungs

AT a heart amyloid is found under the endocardium, in the stroma and vessels of the myocardium (see Fig. 35), as well as in the epicardium along the veins. The deposition of amyloid in the heart leads to its sharp increase (amyloid cardiomegaly). It becomes very dense, the myocardium becomes greasy.

AT skeletal muscles, as in the myocardium, amyloid falls out along the intermuscular connective tissue, in the walls of blood vessels and in nerves.

Perivascularly and perineurally, massive deposits of amyloid substance are often formed. Muscles become dense, translucent.

AT lungs amyloid deposits appear first in the walls of the branches of the pulmonary artery and vein (see Fig. 35), as well as in the peribronchial connective tissue. Later, amyloid appears in the interalveolar septa.

AT brain in senile amyloidosis, amyloid is found in senile plaques of the cortex, vessels, and membranes.

Amyloidosis skin characterized by diffuse deposition of amyloid in the papillae of the skin and its reticular layer, in the walls of blood vessels and along the periphery of the sebaceous and sweat glands, which is accompanied by destruction of elastic fibers and a sharp atrophy of the epidermis.

Amyloidosis pancreas has some uniqueness. In addition to the arteries of the gland, there is also amyloidosis of the islets, which is observed in extreme old age.

Amyloidosis thyroid gland also idiosyncratic. Amyloid deposits in the stroma and vessels of the gland can be a manifestation of not only generalized amyloidosis, but also medullary cancer of the gland (medullary thyroid cancer with stromal amyloidosis). Stroma amyloidosis is common in tumors of the endocrine organs and APUD systems (medullary thyroid cancer, insuloma, carcinoid, pheochromocytoma, tumors of carotid bodies, chromophobe pituitary adenoma, hypernephroid cancer), and the participation of epithelial tumor cells in the formation of APUD amyloid has been proven.

Exodus. Adverse. Amyloidoclasia- an extremely rare occurrence in local forms of amyloidosis.

Functional value determined by the degree of development of amyloidosis. Severe amyloidosis leads to atrophy of the parenchyma and sclerosis of organs, to their functional failure. With severe amyloidosis, chronic renal, hepatic, cardiac, pulmonary, adrenal, intestinal (malabsorption syndrome) insufficiency is possible.

Stromal vascular fatty degenerations (lipidoses)

Stromal vascular fatty degenerations occur in violation of the exchange of neutral fats or cholesterol and its esters.

Metabolic disorders of neutral fats

Disturbances in the metabolism of neutral fats are manifested in an increase in their reserves in adipose tissue, which may be of a general or local nature.

Neutral fats are labile fats that provide the body with energy reserves. They are concentrated in fat depots (subcutaneous tissue, mesentery, omentum, epicardium, bone marrow). Adipose tissue performs not only an exchange, but also a supporting, mechanical function, so it is able to replace atrophying tissues.

Obesity, or obesity,- an increase in the amount of neutral fats in fat depots, which is of a general nature. It is expressed in the abundant deposition of fat in the subcutaneous tissue, omentum, mesentery, mediastinum, epicardium. Adipose tissue also appears where it is usually absent or present only in small quantities, for example, in the myocardial stroma, pancreas (Fig. 36, a). Great clinical significance

36. Obesity:

a - proliferation of adipose tissue in the stroma of the pancreas (diabetes mellitus); b - obesity of the heart, under the epicardium a thick layer of fat

value has obesity of the heart with obesity. Adipose tissue, growing under the epicardium, envelops the heart like a sheath (Fig. 36, b). It sprouts the myocardial stroma, especially in the subepicardial sections, which leads to atrophy of muscle cells. Obesity is usually more pronounced in the right half of the heart. Sometimes the entire thickness of the myocardium of the right ventricle is replaced by adipose tissue, in connection with which a heart rupture may occur.

Classification. It is based on various principles and takes into account the cause, external manifestations (types of obesity), the degree of excess of the "ideal" body weight, morphological changes in adipose tissue (obesity options).

By etiological principle distinguish primary and secondary forms of obesity. Cause primary obesity unknown, therefore it is also called idiopathic. Secondary obesity represented by the following types: 1)

alimentary, the cause of which is an unbalanced diet and physical inactivity; 2) cerebral, developing with trauma, brain tumors, a number of neurotropic infections; 3) endocrine, represented by a number of syndromes (Frohlich and Itsenko-Cushing syndromes, adiposogenital dystrophy, hypogonadism, hypothyroidism); 4) hereditary in the form of Laurence-Moon-Biedl syndrome and Gierke's disease.

By external manifestations There are symmetrical (universal), upper, middle and lower types of obesity. With symmetrical type

fats are deposited relatively evenly in different parts of the body. The upper type is characterized by the accumulation of fat mainly in the subcutaneous tissue of the face, neck, neck, upper shoulder girdle, and mammary glands. With the middle type, fat is deposited in the subcutaneous tissue of the abdomen in the form of an apron, with the lower type - in the thighs and legs.

By excess body weight of the patient distinguish several degrees of obesity. With I degree of obesity, excess body weight is 20-29%, with II - 30-49%, with III - 50-99% and with IV - up to 100% or more.

When characterizing morphological changes adipose tissue in obesity take into account the number of adipocytes and their size. On this basis, hypertrophic and hyperplastic variants of general obesity are distinguished. At hypertrophic variant fat cells are enlarged and contain several times more triglycerides than normal; while the number of adipocytes does not change. Adipocytes are insensitive to insulin, but highly sensitive to lipolytic hormones; the course of the disease is malignant.

At hyperplastic variant the number of adipocytes is increased (it is known that the number of fat cells reaches a maximum in the puberty period and does not change further). However, the function of adipocytes is not impaired, there are no metabolic changes; the course of the disease is benign.

Causes and mechanisms of development. Among the causes of general obesity, as already mentioned, unbalanced nutrition and physical inactivity, impaired nervous (CNS) and endocrine regulation of fat metabolism, hereditary (family-constitutional) factors are of great importance. The immediate mechanism of obesity lies in the imbalance of lipogenesis and lipolysis in the fat cell in favor of lipogenesis (Scheme V). As can be seen from Scheme V, an increase in lipogenesis, as well as a decrease in lipolysis,

Scheme V Lipogenesis and lipolysis in the fat cell

It is associated not only with the activation of lipoprotein lipase and the inhibition of lipolytic lipases, but also with a violation of hormonal regulation in favor of anti-lipolytic hormones, the state of fat metabolism in the intestines and liver.

Meaning. Being a manifestation of a number of diseases, general obesity determines the development of severe complications. Being overweight, for example, is one of the risk factors for coronary heart disease.

Exodus general obesity is rarely favorable.

The antipode of general obesity is exhaustion, which is based on atrophy. Depletion is also observed in the terminal stage cachexia(from Greek. kakos- bad, hexis- condition).

With an increase in the amount of adipose tissue, which has local character, they say

o lipomatosis. Among them, the most interesting is Derkum's disease. (lipomatosis dolorosa), in which nodular painful deposits of fat, similar to lipomas, appear in the subcutaneous tissue of the limbs and trunk. The disease is based on polyglandular endocrinopathy. A local increase in the amount of adipose tissue is often an expression vacant obesity(fat replacement) with atrophy of a tissue or organ (for example, fatty replacement of the kidney or thymus gland with their atrophy).

The antipode of lipomatosis is regional lipodystrophy, the essence of which is the focal destruction of adipose tissue and the breakdown of fats, often with an inflammatory reaction and the formation of lipogranulomas (for example, lipogranulomatosis with recurrent non-suppurating panniculitis, or Weber-Christian disease).

Metabolic disorders of cholesterol and its esters

Disturbances in the metabolism of cholesterol and its esters underlie a serious illness - atherosclerosis. At the same time, not only cholesterol and its esters, but also low-density β-lipoproteins and blood plasma proteins accumulate in the intima of the arteries, which is facilitated by

increased vascular permeability. The accumulating macromolecular substances lead to the destruction of the intima, disintegrate and saponify. As a result, fat-protein detritus is formed in the intima. (there- mushy mass), connective tissue grows (sclerosis- compaction) and a fibrous plaque is formed, often narrowing the lumen of the vessel (see Fig. Atherosclerosis).

Hereditary dystrophy, which develops in connection with a violation of cholesterol metabolism, is familial hypercholesterolemic xanthomatosis. It is classified as a storage disease, although the nature of the fermentopathy has not been established. Cholesterol is deposited in the skin, the walls of large vessels (atherosclerosis develops), heart valves and other organs.

Hyalinosis - this is the appearance in cells and tissues of a peculiar substance, heterogeneous in composition and mechanism of its appearance. The basis of hyaline is fibrillar protein, fibrin, immunoglobulins (immune complexes), lipids are mixed here. Based on differences in the composition of hyaline, there are:

a) simple hyaline - its main part is blood plasma proteins, immunoglobulins;

b) lipogyalin - lipoproteins are found in its composition. Lipohyalin is most often found in diabetes mellitus;

c) complex hyaline - cell fragments, destroyed connective tissue components and immune complexes are attached to plasma proteins in a significant amount.

Despite its heterogeneity, hyaline, different in localization and origin, has common tinctorial properties when stained with hematoxylin-eosin; when stained according to Van Gieson, it is picrinophilic and gives a PAS positive reaction.

Hyalinosis is more correctly attributed not to dystrophies, but to the outcomes of dystrophies, to the outcomes of alteration, and mainly to alteration of the connective tissue. Hyaline can be found in the epithelium, in thrombotic masses, and mainly in the connective tissue. Depending on the nature of the hyaline deposition, there are: hyalinosis of the vessels and hyalinization of the connective tissue. Hyaline is similar in color to fibrinoid. It is oxyphilic, characterized by homogeneity and density. The connective tissue that has undergone hyalinization resembles hyaline cartilage in appearance - vitreous and translucent. Very typical hyalinization of scars or cicatricial thickenings of serous integuments, capsules of internal organs (for example, the so-called "glazed" spleen, as an outcome of perisplenitis). In the epithelium, hyaline drops appear as a result of protein dystrophies (hyaline-droplet degeneration of the epithelium of the convoluted tubules of the kidney). In hepatocytes with alcohol intoxication or hepatitis, "Mallory bodies" appear - drops of hyaline in the cytoplasm. In fact, hyaline drops are dead ultrastructures impregnated with protein - focal necrosis.

In the mechanism of hyaline changes in the connective tissue, a stereotyped mechanism can be traced. It consists in structural changes in the connective tissue, which cause an increase in permeability and lead to the insudation of proteins that impregnate the altered connective tissue.

Connective tissue hyalinization consists in impregnating protofibrils with proteins, pushing them apart. In the hyalinized tissue, elementary fibrils are disassembled, but the collagen matrix is preserved, the cells are compressed and atrophy. Hyalinization of the connective tissue is accelerated by the perversion of the function of fibroblasts and the synthesis of atypical collagen. Factors accelerating hyalinization are numerous: hypoxia, intoxication, decreased iron content, avitaminosis C, exposure to immune complexes, genetic defects. Hyalinization of the connective tissue is most often focal. However, in some diseases, defined as the pathology of immunity, the effect of IR with damage to the connective tissue and subsequent hyalinization becomes systemic. One such disease is systemic scleroderma.

Hyalinosis of vessels most of the time it is systemic. Most often it occurs in arterioles (arteriolosclerosis in hypertension). Hyalinosis of capillaries is typical for diabetes mellitus. In the arteries, hyalinosis is observed at the locations of atherosclerotic plaques. Local hyalinosis of vessels is observed in organs undergoing involution (ovary, thymus).

Systemic hyalinosis of vessels in hypertension is of the greatest importance. The process of hyalinosis, due to its systemic nature, determines the course of hypertension, its progression and the development of complications. The prevalence and degree of damage to arterioles is determined by:

1) the degree of alteration of the vascular wall,

2) degree of insudation,

3) the presence of the attachment of immune damage during the structural disorganization of the arteriole wall and a change in the antigenic properties of the structures that deliver it.

Therefore, in hypertension, two forms of vascular damage are distinguished.

1. Hyaline arteriolar sclerosis. Vasospasm occurs, damage to the glycocalyx of endothelial cells, pinocytosis increases, and the inner layer of the vessel becomes highly permeable to plasma proteins and alpha-lipoproteins. Fibrous structures (basement membranes) are in a state of mucoid swelling. There is a slow insudation with the accumulation of plasma proteins. At the same time, smooth muscle cells penetrate into the inner layer from the middle layer through the opening of the basement membranes. They are arranged circularly, forming the so-called "inner muscle layer". There is a slow formation of hyaline. Picrinophilic fresh proteins become oxyphilic. In addition to hyaline formed by insudation (an infiltrative mechanism), hyaline appears in a small number of smooth muscle cells, which begin to synthesize fibrillar proteins. Fibrosis gradually increases, collagenization occurs, followed by sclerosis. Such changes lead to functional inertness of the arterioles, narrowing of the lumen fixes blood pressure at a high level, the tissues of this region experience a state of hypoxia due to impaired microcirculation.

2. Plasma arteriolonecrosis. Occurs with a rapid violation of vascular permeability due to strong and persistent spasms (crises). The effect of catecholamines and glucocorticoids on the endothelium leads to necrosis. There are ruptures of basement membranes, fibrinoid swelling of fibrous structures. There is an acute insudation, plasmorrhagia with the death of smooth muscle cells. Against this background, there is a deposition of immune complexes. In the composition of hyaline, ferritin, immunoglobulins M and G, immune complexes with AG of damaged structures and complement are detected. Immune action deepens the damage, fibrinoid necrosis develops. Protein deposits have the character of a complex hyaline. This is how plasma arteriolonecrosis or acute plasma impregnation occurs. Necrosis of the vascular wall with complete obliteration of the lumen is accompanied by the cessation of transcapillary exchange and leads to tissue death in the affected region. The result of this is sclerosis and scarring with obliteration of the vessel and cicatricial sclerosis of the parenchyma. Such changes represent the morphological substrate of the malignant form of hypertension.

Hyalinosis

(as a type of stromal-vascular dystrophy).

(according to V.V. Serov, M.A. Paltsev)

Stromal-vascular (mesenchymal) dystrophies develop as a result of metabolic disorders in the connective tissue and are detected in the stroma of organs and vessel walls.

Characterized accumulation in the tissues of translucent dense masses resembling hyaline cartilage.
Occurs as a result of fibrinoid swelling, plasmorrhagia, sclerosis, necrosis.
Hyaline - complex fibrillar protein.
The mechanism of hyaline formation consists of destruction of fibrous structures and their impregnation with fibrin and other plasma components(globulins, beta-lipoproteins, immune complexes, etc.).

Allocate hyalinosis of the connective tissue proper and hyalinosis of the vessels; both of these types of hyalinosis can be widespread and local.

An example of local hyalinosis of the connective tissue itself, which developed as a result of mucoid swelling and fibrinoid changes, is hyalinosis of the cusps of the heart valves in rheumatism (rheumatic heart disease).

Macroscopic picture: the heart is enlarged, the cavities of the ventricles are dilated. The leaflets of the mitral valve are dense, whitish in color, fused together and sharply deformed. The atrioventricular orifice is narrowed. Chordal filaments are thickened and shortened.

There are 3 types of vascular hyaline:

a) simple hyaline- occurs due to plasmorrhagia of unchanged plasma components (more common in hypertension, atherosclerosis);

b) lipogyalin — contains lipids and beta-lipoproteins (most characteristic of diabetes mellitus);

in) complex hyaline- is built from immune complexes, fibrin and collapsing structures (typical for diseases with immunopathological disorders, such as rheumatic diseases).

Common hyalinosis of arterioles occurs with hypertension and diabetes mellitus as an outcome of plasmorrhagia.
In hypertension due to hyalinosis of arterioles, arteriolosclerotic nephrosclerosis develops, or primary wrinkled kidneys: small dense kidneys with a fine-grained surface and a sharply thinned cortical layer.

Widespread hyalinosis of small vessels (mainly arterioles) underlies diabetic microangiopathy.


Rice. 6, 7. Moderate and severe hyalinosis of the walls of the renal arterioles. Stain: hematoxylin-eosin. Magnification x250.


		Rice. 8-10. Severe hyalinosis of the walls of the afferent arterioles of the renal glomeruli. Severe sclerosis and hyalinosis of the glomeruli (Fig. 9, 10). Stain: hematoxylin-eosin. Magnification x250.


Rice. 11-16. Moderate and severe hyalinosis of the walls of the central arteries of the lymphatic follicles of the spleen. In some of them, atrophy of the lymphatic follicles and delymphatization of the white pulp. Hematoxylin-eosin. Magnification x250.

Hyalinosis

Mechanism hyalinosis is difficult. Leading in its development are the destruction of fibrous structures and an increase in tissue-vascular permeability (plasmorrhagia) due to angioedema (dyscirculatory), metabolic and immunopathological processes. Plasmarrhagia is associated with the impregnation of tissue with plasma proteins and their adsorption on altered fibrous structures, followed by precipitation and the formation of a protein - hyaline. Smooth muscle cells take part in the formation of vascular hyaline. Hyalinosis can develop as a result of various processes: plasma impregnation, fibrinoid swelling (fibrinoid), inflammation, necrosis, sclerosis.

Classification. There are hyalinosis of the vessels and hyalinosis of the connective tissue itself. Each of them can be widespread (systemic) and local.

Hyaline is found in the subendothelial space, it pushes outwards and destroys the elastic lamina, the middle membrane becomes thinner, in the end the arterioles turn into thickened vitreous tubules with a sharply narrowed or completely closed lumen

Hyalinosis of the vessels of the spleen:

a - the wall of the central artery of the spleen follicle is represented by homogeneous masses of hyaline; b - fibrin among hyaline masses when stained according to the Weigert method; c - fixation of IgG immune complexes in hyaline (luminescence microscopy); d - masses of hyaline (G) in the arteriole wall; En - endothelium; Pr - lumen of the arteriole. electronogram.

Vascular hyaline is a substance of a predominantly hematogenous nature. In its formation, not only hemodynamic and metabolic, but also immune mechanisms play a role. Guided by the peculiarities of the pathogenesis of vascular hyalinosis, 3 types of vascular hyaline are distinguished:

1) simple, arising from insudation of unchanged or slightly changed blood plasma components (more common in benign hypertension, atherosclerosis and in healthy people);

2) lipogyalin, containing lipids and β-lipoproteins (found most often in diabetes mellitus);

3) complex hyaline, built from immune complexes, fibrin and collapsing structures of the vascular wall (typical for diseases with immunopathological disorders, such as rheumatic diseases).

Microscopic examination. Swelling of connective tissue bundles is found, they lose their fibrillarity and merge into a homogeneous dense cartilage-like mass; cellular elements are compressed and undergo atrophy. This mechanism of development of systemic hyalinosis of the connective tissue is especially common in diseases with immune disorders (rheumatic diseases). Hyalinosis can complete fibrinoid changes in the bottom of a chronic stomach ulcer, in the appendix in appendicitis; it is similar to the mechanism of local hyalinosis in the focus of chronic inflammation.

With hyalinosis of the connective tissue itself, it becomes dense, whitish, translucent (for example, hyalinosis of the heart valves in rheumatic disease).

Mechanisms of cell damage and death 1. The formation of free radicals (with insufficient oxygen supply to the tissues) occurs free radical lipid peroxidation (SPOL). 2. Violation of calcium homeostasis. Free calcium in the cytoplasm of cells is found in very low concentrations compared to extracellular calcium. This state is maintained by Ca2+, Mg2+-ATPases. Ischemia, intoxication cause an increase in the calcium concentration in the cytoplasm, which leads to the activation of enzymes that damage the cell: phospholipases (damage to the cell membrane), proteases (destruction of the membrane and cytoskeletal proteins), ATPases (depletion of ATP reserves) and endonucleases (chromatin fragmentation). 3. Insufficiency of ATP leads to the loss of the integrity of the plasma membrane and, consequently, to cell death. 4. Early loss of selective permeability by the plasma membrane. It occurs with ATP deficiency, and with the activation of phospholipases. The plasma membrane can be damaged by direct exposure to bacterial toxins, viral proteins, complement, physical, chemical agents.

Forms of cell damage

Distinguish: Ischemic and hypoxic damage; · Damage caused by free radicals, including activated oxygen; · Toxic damage. Ischemic and hypoxic injury. Most often due to occlusion of the arteries. The main mechanisms of cell death during hypoxia are a violation of oxidative phosphorylation, leading to ATP deficiency, damage to cell membranes. The most important mediator of irreversible biochemical and morphological changes is calcium. Cell damage caused by free radicals. Occurs under the influence of chemicals, radiation, oxygen, cell aging, destruction of tumors by macrophages. Free radicals react with inorganic and organic compounds - proteins, lipids and carbohydrates. Three reactions that free radicals enter into are of greatest importance for cell damage. · Free radical lipid peroxidation (SPOL) of membranes, leading to damage to membranes, organelles and the cells themselves. Oxidative transformation of proteins. Free radicals cause cross-linking of amino acids (methionine, histidine, cystine, lysine). Destroys enzymes through neutral proteases. DNA damage. Free radicals react with thymine, which is part of DNA, which leads to cell death or its malignant transformation. · Toxic damage. Chemicals (in the form of water-soluble compounds) can act directly by binding to the molecules or organelles of the cell. For example, mercury binds sulfhydryl groups of the cell membrane and causes an increase in cell membrane permeability and inhibition of ATPase-dependent transport. When mercury chloride enters the body, the cells of the gastrointestinal tract and kidneys suffer the most. Cyanide acts on mitochondrial enzymes. Anticancer chemotherapy drugs (including antibiotics) cause cell damage through cytotoxic action. Chemical compounds (fat-soluble) are first converted into toxic metabolites, which then act on target cells. This creates free radicals.

In classical morphology, non-lethal cell damage is called dystrophy.

8. Cell death. Apoptosis. Concept definition. Morphological manifestations of apoptosis and the mechanism of their development. Physiological and pathological significance of apoptosis.

Cell death is irreversible cell damage.

Apoptosis is a genetically programmed cell death in a living organism. For the removal (elimination) of unnecessary cell structures during embryogenesis.

Morphological manifestations:

1-condensation of nuclear heterochromatin and wrinkling of cells while maintaining the integrity of the organelles and cell membrane.

2-cell decay into apoptosis-e bodies, which are membrane structures with confinement and inside organelles and particles of the nucleus

3- then apoptotic bodies are phagocytosed and destroyed by lysosomes surrounding and cells.

Mechanism:

1-Condensation of chromatin is associated with the cleavage of nuclear DNA, which occurs in the areas of connections between the m / y nucleosomes and leads to the formation of fragments.

2- Violation of the volume and size of cells is explained by the activity of transglutaminase. This enzyme catalyzes the cross-linking of cytoplasmic proteins that form an envelope under the plasma membrane.

3-Phagositosis of apoptotic bodies by macrophages and other cells.

4. Dependence of apoptosis on gene activation - this is one of its important features. This is provided by proto-oncogenes. Apoptosis-specific genes have been identified that stimulate or inhibit cell death. 5. Oncogenes and suppressor genes play a regulatory role in the induction of apoptosis (the p53 oncogene normally stimulates apoptosis; p53 is required for the development of apoptosis after DNA damage by radiation).

Physiological and pathological significance of apoptosis:

1- mediates the programmed removal of cells during embryogenesis (including implantation, organogenesis and involution)

2- Hormone-dependent cell involution occurs in adults

3-ensures the destruction of cells in proliferating cell populations, such as the epithelium of the crypts of the small intestine and the death of cells in tumors

4-h / h apoptosis, the death of autoreactive clones of T-lymphocytes and pathological atrophy of hormone-dependent cells are realized

5- apoptosis underlies pathological atrophy of parenchymal organs after duct occlusion

6- apoptosis is associated with cell death caused by cytotoxic- and T-cell and cell death in certain viral diseases.

7-apoptosis underlies cell death caused by various and weak damaging effects, which in large doses lead to the death of cells (the term is everywhere, radiation, cytotoxic antitumor drugs and, possibly, hypoxia)

9. Necrosis. Concept definition. Macroscopic and microscopic signs of necrosis.

Necrosis - necrosis, death of cells and cells in a living organism; at the same time, their life activity completely ceases. This is the result of the destructive action of enzymes on lethally damaged cells. In fact, two competing processes develop: enzyme digestion cells and protein denaturation.

Morphogenesis of necrosis:

1-paranecrosis-like necrotic m, but reversible change.

2-necrobiosis-irreversible dystrophic changes, characterized by the predominance of catabolic reactions over anabolic reactions

3-death kt, the time of the onset of kt is difficult to install

4-autolysis-decomposition of a dead substrate under the action of hydrolytic fers of dead cells and macrophages.

Macro: signs of necrosis can manifest themselves in different ways: they depend on the originality of the organ, in which necrosis occurs, and also on the nature of the damaging factor.

Micro: signs concern both the nucleus and the cytoplasm of cells, as well as the extracellular matrix.

Change kernel on:

Karyopyknosis - wrinkling of nuclei due to chromatin condensation;

Karyorrhexis - disintegration of nuclei into clumps

Karyolysis - dissolution of the nucleus due to the activation of hydrolases (RNase and DNase)

Quote changes:

Plasma coagulation - denaturation and coagulation of the protein with the appearance of bright pink clumps in the cytoplasm

Plasmorexis - disintegration of the cytoplasm into clumps

Plasmolysis - melting of the cytoplasm

Changes to off-o matrix development:

In the splitting of reticular, collagen and elastic fibers under the influence of proteases, elastase, collagenases. Necrotic masses are often impregnated with fibrin with the development of fibrinoid necrosis.