Granular dystrophy microscopy. Possible consequences and complications
General information
Dystrophy(from Greek dys- violation and trophe- nourish) is a complex pathological process, which is based on a violation of tissue (cellular) metabolism leading to structural changes. Therefore, dystrophies are considered as one of the types of damage.
Trophism is understood as a set of mechanisms that determine the metabolism and structural organization of tissue (cells), which are necessary for the performance of a specialized function. Among these mechanisms are cellular And extracellular (Fig. 26). Cellular mechanisms are ensured by the structural organization of the cell and its autoregulation. This means that the trophism of the cell is largely
Rice. 26. Mechanisms of trophic regulation (according to M.G. Balsh)
is determined by the property of the cell itself as a complex self-regulating system. The vital activity of the cell is ensured by the “environment” and is regulated by a number of body systems. Therefore, the extracellular mechanisms of trophism have transport (blood, lymph, microvasculature) and integrative (neuro-endocrine, neurohumoral) systems for its regulation. From the above it follows that immediate cause The development of dystrophies can be caused by violations of both cellular and extracellular mechanisms that provide trophism.
1. Cell autoregulation disorders can be caused by various factors (hyperfunction, toxic substances, radiation, hereditary deficiency or lack of enzyme, etc.). A major role is given to the sex of genes - receptors that carry out “coordinated inhibition” of the functions of various ultrastructures. Violation of cell autoregulation leads to energy deficiency and disruption of enzymatic processes in a cage. Enzymopathy, or enzymopathy (acquired or hereditary), becomes the main pathogenetic link and expression of dystrophy in cases of violations of cellular trophic mechanisms.
2. Disturbances in the function of transport systems that ensure metabolism and structural preservation of tissues (cells) cause hypoxia, which is leading in the pathogenesis discirculatory dystrophies.
3. In case of disorders of endocrine regulation of trophism (thyrotoxicosis, diabetes, hyperparathyroidism, etc.) we can talk about endocrine, and in case of disturbance of the nervous regulation of trophism (disturbed innervation, brain tumor, etc.) - about nervous or cerebral dystrophies.
Features of pathogenesis intrauterine dystrophies are determined by their direct connection with the mother’s diseases. As a result, if part of the rudiment of an organ or tissue dies, an irreversible malformation may develop.
With dystrophies, various metabolic products (proteins, fats, carbohydrates, minerals, water) accumulate in the cell and (or) intercellular substance, which are characterized by quantitative or qualitative changes as a result of disruption of enzymatic processes.
Morphogenesis. Among the mechanisms leading to the development of changes characteristic of dystrophies, there are infiltration, decomposition (phanerosis), perverted synthesis and transformation.
Infiltration- excessive penetration of metabolic products from the blood and lymph into cells or intercellular substance with their subsequent accumulation due to the insufficiency of enzyme systems that metabolize these products. These are, for example, infiltration of the epithelium of the proximal tubules of the kidneys with coarse protein in nephrotic syndrome, infiltration of the intima of the aorta and large arteries with cholesterol and lipoproteins in atherosclerosis.
Decomposition (phanerosis)- disintegration of cell ultrastructures and intercellular substance, leading to disruption of tissue (cellular) metabolism and accumulation of products of impaired metabolism in the tissue (cell). These are the living
red dystrophy of cardiomyocytes in diphtheria intoxication, fibrinoid swelling of connective tissue in rheumatic diseases.
Perverted Synthesis- is the synthesis in cells or tissues of substances that are not normally found in them. These include: synthesis of abnormal amyloid protein in the cell and abnormal amyloid protein-polysaccharide complexes in the intercellular substance; synthesis of alcoholic hyaline protein by hepatocytes; synthesis of glycogen in the epithelium of a narrow segment of the nephron in diabetes mellitus.
Transformation- the formation of products of the same type of metabolism from common initial products that are used to build proteins, fats and carbohydrates. This is, for example, the transformation of fat and carbohydrate components into proteins, enhanced polymerization of glucose into glycogen, etc.
Infiltration and decomposition - the leading morphogenetic mechanisms of dystrophies - are often successive stages in their development. However, in some organs and tissues, due to their structural and functional characteristics, one of the morphogenetic mechanisms predominates (infiltration in the epithelium of the renal tubules, decomposition in myocardial cells), which allows us to talk about orthologies(from Greek orthos- direct, typical) dystrophy.
Morphological specificity. When studying dystrophies at different levels - ultrastructural, cellular, tissue, organ - the morphological specificity manifests itself ambiguously. Ultrastructural morphology of dystrophies usually does not have any specifics. It reflects not only damage to organelles, but also their repair (intracellular regeneration). At the same time, the possibility of identifying a number of metabolic products (lipids, glycogen, ferritin) in organelles allows us to talk about ultrastructural changes characteristic of one or another type of dystrophy.
The characteristic morphology of dystrophies is revealed, as a rule, on tissue and cellular levels, Moreover, to prove the connection of dystrophy with disorders of one or another type of metabolism, the use of histochemical methods is required. Without establishing the quality of the product of impaired metabolism, it is impossible to verify tissue degeneration, i.e. classify it as protein, fat, carbohydrate or other dystrophies. Organ changes in case of dystrophy (size, color, consistency, structure on a section) in some cases they are presented exceptionally clearly, in others they are absent, and only microscopic examination makes it possible to reveal their specificity. In some cases we can talk about systemic nature changes in dystrophy (systemic hemosiderosis, systemic mesenchymal amyloidosis, systemic lipoidosis).
Several principles are followed in the classification of dystrophies. Dystrophies are distinguished.
I. Depending on the predominance of morphological changes in specialized elements of the parenchyma or stroma and vessels: 1) parenchymal; 2) stromal-vascular; 3) mixed.
II. According to the predominance of disorders of one or another type of metabolism: 1) protein; 2) fat; 3) carbohydrates; 4) mineral.
III. Depending on the influence of genetic factors: 1) acquired; 2) hereditary.
IV. According to the prevalence of the process: 1) general; 2) local.
Parenchymal dystrophies
Parenchymal dystrophies- manifestations of metabolic disorders in functionally highly specialized cells. Therefore, in parenchymal dystrophies, disturbances in the cellular mechanisms of trophism predominate. Various types of parenchymal dystrophies reflect the insufficiency of a certain physiological (enzymatic) mechanism that serves to perform a specialized function by the cell (hepatocyte, nephrocyte, cardiomyocyte, etc.). In this regard, in different organs (liver, kidneys, heart, etc.) during the development of the same type of dystrophy, different patho- and morphogenetic mechanisms are involved. It follows from this that the transition of one type of parenchymal dystrophy to another type is excluded; only a combination of different types of this dystrophy is possible.
Depending on the disturbances of one or another type of metabolism, parenchymal dystrophies are divided into protein (dysproteinoses), fatty (lipidoses) and carbohydrate.
Parenchymal protein dystrophies (dysproteinoses)
Most of the cytoplasmic proteins (simple and complex) are combined with lipids, forming lipoprotein complexes. These complexes form the basis of mitochondrial membranes, endoplasmic reticulum, lamellar complex and other structures. In addition to bound proteins, the cytoplasm also contains free ones. Many of the latter have the function of enzymes.
The essence of parenchymal dysproteinoses is a change in the physicochemical and morphological properties of cell proteins: they undergo denaturation and coagulation or, conversely, colliquation, which leads to hydration of the cytoplasm; in cases where the bonds of proteins with lipids are disrupted, destruction of cell membrane structures occurs. As a result of these disorders, it may develop coagulation(dry) or colliquation(wet) necrosis(Scheme I).
Parenchymal dysproteinoses include hyaline-drip, hydropic And horny dystrophy.
Since the time of R. Virchow, parenchymal protein dystrophies have been considered and many pathologists continue to consider the so-called granular dystrophy, in which protein grains appear in the cells of parenchymal organs. The organs themselves increase in size, become flabby and dull when cut, which was the reason for also calling it granular dystrophy dull (cloudy) swelling. However, electron microscopic and histoenzymatic
Scheme I. Morphogenesis of parenchymal dysproteinoses
chemical study of “granular dystrophy” showed that it is based not on the accumulation of protein in the cytoplasm, but on hyperplasia of the ultrastructures of the cells of parenchymal organs as an expression of the functional tension of these organs in response to various influences; hyperplastic cell ultrastructures are revealed during light-optical examination as protein granules.
Hyaline droplet dystrophy
At hyaline droplet dystrophy large hyaline-like protein droplets appear in the cytoplasm, merging with each other and filling the cell body; in this case, destruction of the ultrastructural elements of the cell occurs. In some cases, hyaline-droplet dystrophy ends focal coagulative cell necrosis.
This type of dysproteinosis often occurs in the kidneys, rarely in the liver, and very rarely in the myocardium.
IN kidneys at accumulation of hyaline droplets is found in nephrocytes. In this case, destruction of mitochondria, endoplasmic reticulum, and brush border is observed (Fig. 27). The basis of hyaline-droplet dystrophy of nephrocytes is the insufficiency of the vacuolar-lysosomal apparatus of the epithelium of the proximal tubules, which normally reabsorbs proteins. Therefore, this type of nephrocyte dystrophy is very common in nephrotic syndrome. This syndrome is one of the manifestations of many kidney diseases in which the glomerular filter is primarily affected (glomerulonephritis, renal amyloidosis, paraproteinemic nephropathy, etc.).
Appearance kidney disease in this dystrophy does not have any characteristic features; it is determined primarily by the characteristics of the underlying disease (glomerulonephritis, amyloidosis).
IN liver at microscopic examination in hepatocytes hyaline-like bodies (Mallory bodies) are found, which consist of fibrils
Rice. 27. Hyaline-droplet dystrophy of the epithelium of the renal tubules:
a - in the cytoplasm of the epithelium there are large protein droplets (microscopic picture); b - in the cytoplasm of the cell there are many oval-shaped protein (hyaline) formations (GO) and vacuoles (B); desquamation of microvilli (MV) of the brush border and release of vacuoles and protein formations into the lumen (L) of the tubule are noted. Electron diffraction pattern. x18,000
a special protein - alcoholic hyaline (see Fig. 22). The formation of this protein and Mallory bodies is a manifestation of the perverted protein-synthetic function of the hepatocyte, which occurs constantly in alcoholic hepatitis and is relatively rare in primary biliary and Indian childhood cirrhosis, hepatocerebral dystrophy (Wilson-Konovalov disease).
Appearance liver is different; the changes are characteristic of those diseases in which hyaline-droplet dystrophy occurs.
Exodus Hyaline droplet dystrophy is unfavorable: it ends in an irreversible process leading to cell necrosis.
Functional meaning this dystrophy is very great. Hyaline-droplet dystrophy of the epithelium of the renal tubules is associated with the appearance of protein (proteinuria) and casts (cylindruria) in the urine, loss of plasma proteins (hypoproteinemia), and disruption of electrolyte balance. Hyaline droplet degeneration of hepatocytes is often the morphological basis of disorders of many liver functions.
Hydropic dystrophy
Hydropic, or dropsy, dystrophy characterized by the appearance in the cell of vacuoles filled with cytoplasmic fluid. It is observed more often in the epithelium of the skin and renal tubules, in the hepa-
totocytes, muscle and nerve cells, as well as in the cells of the adrenal cortex.
Microscopic picture: parenchymal cells are increased in volume, their cytoplasm is filled with vacuoles containing clear liquid. The nucleus shifts to the periphery, sometimes vacuolates or shrinks. The progression of these changes leads to the disintegration of cell ultrastructures and the cell overflowing with water. The cell turns into fluid-filled balloons or into a huge vacuole in which a vesicular nucleus floats. Such changes in the cell, which are essentially the expression focal liquefaction necrosis called balloon dystrophy.
Appearance organs and tissues change little during hydropic dystrophy; it is usually detected under a microscope.
Development mechanism hydropic dystrophy is complex and reflects disturbances in water-electrolyte and protein metabolism, leading to changes in colloid-osmotic pressure in the cell. A major role is played by disruption of the permeability of cell membranes, accompanied by their disintegration. This leads to acidification of the cytoplasm, activation of hydrolytic enzymes of lysosomes, which break intramolecular bonds with the addition of water.
Causes The development of hydropic dystrophy in different organs is ambiguous. IN kidneys - this is damage to the glomerular filter (glomerulonephritis, amyloidosis, diabetes mellitus), which leads to hyperfiltration and insufficiency of the enzyme system of the basal labyrinth of nephrocytes, which normally ensures water reabsorption; Therefore, hydropic degeneration of nephrocytes is so characteristic of nephrotic syndrome. IN liver hydropic dystrophy occurs with viral and toxic hepatitis(Fig. 28) and is often the cause of liver failure. Cause of hydropic dystrophy epidermis there may be an infection (smallpox), swelling of the skin different mechanism. Vacuolization of the cytoplasm may be a manifestation physiological activity of the cell, which is noted, for example, in ganglion cells of the central and peripheral nervous system.
Exodus hydropic dystrophy is usually unfavorable; it ends with focal or total necrosis of the cell. Therefore, the function of organs and tissues in hydropic dystrophy suffers sharply.
Horny dystrophy
Horny dystrophy, or pathological keratinization, characterized by excessive formation of horny substance in the keratinizing epithelium (hyperkeratosis, ichthyosis) or the formation of horny substance where it normally does not exist (pathological keratinization on the mucous membranes, or leukoplakia; formation of “cancer pearls” in squamous cell carcinoma). The process may be local or widespread.
Rice. 28. Hydropic liver dystrophy (biopsy):
a - microscopic picture; vacuolization of hepatocytes; b - electron diffraction pattern: expansion of the tubules of the endoplasmic reticulum and the formation of vacuoles (B) filled with flocculent contents. The membranes limiting the vacuoles are almost completely devoid of ribosomes. The vacuoles compress the mitochondria (M) located between them, some of which undergo destruction; I am the nucleus of a hepatocyte. x18,000
Causes Horny dystrophy is varied: impaired skin development, chronic inflammation, viral infections, vitamin deficiencies, etc.
Exodus can be twofold: eliminating the causative cause at the beginning of the process can lead to tissue restoration, but in advanced cases cell death occurs.
Meaning Horny dystrophy is determined by its degree, prevalence and duration. Long-term pathological keratinization of the mucous membrane (leukoplakia) can be a source of cancer development. Severe congenital ichthyosis is, as a rule, incompatible with life.
The group of parenchymal dysproteinoses includes a number of dystrophies, which are based on disturbances in the intracellular metabolism of a number of amino acids as a result of hereditary deficiency of the enzymes that metabolize them, i.e. as a result hereditary fermentopathy. These dystrophies belong to the so-called storage diseases.
Most striking examples hereditary dystrophies associated with impaired intracellular metabolism of amino acids are cystinosis, tyrosinosis, phenylpyruvic oligophrenia (phenylketonuria). Their characteristics are presented in table. 1.
Table 1. Hereditary dystrophies associated with impaired amino acid metabolism
Parenchymatous fatty degenerations(lipidoses)
The cytoplasm of cells contains mainly lipids, which form complex labile fat-protein complexes with proteins - lipoproteins. These complexes form the basis of cell membranes. Lipids together with proteins are integral part and cellular ultrastructures. In addition to lipoproteins, the cytoplasm also contains neutral fats, which are esters of glycerol and fatty acids.
To identify fats, sections of unfixed frozen or formalin-fixed tissues are used. Histochemically, fats are detected using a number of methods: Sudan III and scarlet stain them red, Sudan IV and osmic acid stain them black, Nile blue sulfate stains fatty acids dark blue, and neutral fats red.
Using a polarizing microscope, it is possible to differentiate between isotropic and anisotropic lipids, the latter giving a characteristic birefringence.
Disturbances in the metabolism of cytoplasmic lipids can manifest themselves in an increase in their content in cells where they are found normally, in the appearance of lipids where they are not usually found, and in the formation of fats of unusual chemical composition. Neutral fats usually accumulate in cells.
Parenchymal fatty degeneration occurs most often in the same place as protein degeneration - in the myocardium, liver, kidneys.
IN myocardium fatty degeneration is characterized by the appearance of tiny fat droplets in muscle cells (pulverized obesity). As changes increase, these drops (small obesity) completely replace the cytoplasm (Fig. 29). Most of the mitochondria disintegrate, and the cross-striations of the fibers disappear. The process is focal in nature and is observed in groups of muscle cells located along the venous knee of capillaries and small veins.
Rice. 29. Fatty degeneration of the myocardium:
a - drops of fat (black in the figure) in the cytoplasm of muscle fibers (microscopic picture); b - lipid inclusions (L) having characteristic striations; Mf - myofibrils. Electron diffraction pattern. x21,000
Appearance heart depends on the degree of fatty degeneration. If the process is weakly expressed, it can only be recognized under a microscope using special stains for lipids; if it is strongly expressed, the heart looks enlarged in volume, its chambers are stretched, it has a flabby consistency, the myocardium on the section is dull, clay-yellow. From the side of the endocardium, yellow-white striations are visible, especially well expressed in the papillary muscles and trabeculae of the ventricles of the heart (“tiger heart”). This striation of the myocardium is associated with the focal nature of dystrophy, the predominant damage to muscle cells around the venules and veins. Fatty degeneration of the myocardium is considered as the morphological equivalent of its decompensation.
The development of fatty degeneration of the myocardium is associated with three mechanisms: increased intake of fatty acids into cardiomyocytes, impaired fat metabolism in these cells and the breakdown of lipoprotein complexes of intracellular structures. Most often, these mechanisms are implemented through infiltration and decomposition (phanerosis) during myocardial energy deficiency associated with hypoxia and intoxication (diphtheria). Moreover, the main significance of decomposition is not in the release of lipids from lipoprotein complexes cell membranes, but in the destruction of mitochondria, which leads to disruption of the oxidation of fatty acids in the cell.
IN liver fatty degeneration (obesity) is manifested by a sharp increase in fat content in hepatocytes and a change in their composition. Lipid granules first appear in liver cells (pulverized obesity), then small drops of them (small obesity), which in the future
merge into large drops (gross obesity) or into one fat vacuole, which fills the entire cytoplasm and pushes the nucleus to the periphery. Liver cells modified in this way resemble fat cells. More often, fat deposition in the liver begins at the periphery, less often - in the center of the lobules; with significantly pronounced dystrophy, liver cell obesity is diffuse.
Appearance liver is quite characteristic: it is enlarged, flabby, ocher-yellow or yellow-brown in color. When making a cut, a coating of fat is visible on the knife blade and the cut surface.
Among development mechanisms fatty liver disease is distinguished: excessive intake of fatty acids into hepatocytes or their increased synthesis by these cells; exposure to toxic substances that block the oxidation of fatty acids and the synthesis of lipoproteins in hepatocytes; insufficient supply of amino acids necessary for the synthesis of phospholipids and lipoproteins into the liver cells. It follows from this that fatty liver develops with lipoproteinemia (alcoholism, diabetes mellitus, general obesity, hormonal disorders), hepatotropic intoxications (ethanol, phosphorus, chloroform, etc.), nutritional disorders (lack of protein in food - alipotropic fatty liver, vitamin deficiencies, diseases of the digestive system).
IN kidneys with fatty degeneration, fats appear in the epithelium of the proximal and distal tubules. Usually these are neutral fats, phospholipids or cholesterol, which are found not only in the tubular epithelium, but also in the stroma. Neutral fats in the epithelium of the narrow segment and collecting ducts occur as a physiological phenomenon.
Appearance kidneys: they are enlarged, flabby (dense when combined with amyloidosis), the cortex is swollen, gray with yellow specks, noticeable on the surface and section.
Development mechanism Fatty kidney disease is associated with infiltration of the epithelium of the renal tubules with fat during lipemia and hypercholesterolemia (nephrotic syndrome), which leads to the death of nephrocytes.
Causes fatty degeneration are varied. Most often it is associated with oxygen starvation (tissue hypoxia), which is why fatty degeneration is so common in diseases of the cardiovascular system, chronic lung diseases, anemia, chronic alcoholism, etc. Under conditions of hypoxia, the parts of the organ that are under functional tension are primarily affected. The second reason is infections (diphtheria, tuberculosis, sepsis) and intoxication (phosphorus, arsenic, chloroform), leading to metabolic disorders (dysproteinosis, hypoproteinemia, hypercholesterolemia), the third is vitamin deficiencies and one-sided (with insufficient protein content) nutrition, accompanied by a deficiency of enzymes and lipotropic factors that are necessary for normal fat metabolism cells.
Exodus fatty degeneration depends on its degree. If it is not accompanied by gross breakdown of cellular structures, then, as a rule, it turns out to be reversible. Profound disruption of cellular lipid metabolism in
In most cases, it ends in cell death, the function of organs is sharply disrupted, and in some cases it even disappears.
The group of hereditary lipidoses consists of the so-called systemic lipidoses, arising due to hereditary deficiency of enzymes involved in the metabolism of certain lipids. Therefore, systemic lipidoses are classified as hereditary enzymopathies(storage diseases), since enzyme deficiency determines the accumulation of substrate, i.e. lipids in cells.
Depending on the type of lipids accumulated in cells, they are distinguished: cerebrosidelipidosis, or glucosylceramide lipidosis(Gaucher disease), sphingomyelin lipidosis(Niemann-Pick disease), gangliosidelipidosis(Tay-Sachs disease, or amaurotic idiocy), generalized gangliosidosis(Norman-Landing disease), etc. Most often, lipids accumulate in the liver, spleen, bone marrow, central nervous system (CNS), and nerve plexuses. In this case, cells characteristic of a particular type of lipidosis appear (Gaucher cells, Pick cells), which has diagnostic value when studying biopsy specimens (Table 2).
Name | Enzyme deficiency | Localization of lipid accumulations | Diagnostic criterion for biopsy |
Gaucher disease - cerebroside lipidosis or glucosideceramide lipidosis | Glucocerebrosidase | Liver, spleen, bone marrow, central nervous system (in children) | Gaucher cells |
Niemann-Pick disease - sphingomyelin lipidosis | Sphingomyelinase | Liver, spleen, bone marrow, central nervous system | Pick cells |
Amaurotic idiocy, Tay-Sachs disease - ganglioside lipidosis | Hexosaminidase | CNS, retina, nerve plexuses, spleen, liver | Changes in the Meissner plexus (rectobiopsy) |
Norman-Landing disease - generalized gangliosidosis | β-Galactosidase | Central nervous system, nerve plexuses, liver, spleen, bone marrow, kidneys, etc. | Absent |
Many enzymes, the deficiency of which determines the development of systemic lipidoses, are, as can be seen from the table. 2, to lysosomal. On this basis, a number of lipidoses are considered lysosomal diseases.
Parenchymal carbohydrate dystrophies
Carbohydrates, which are determined in cells and tissues and can be identified histochemically, are divided into polysaccharides, of which only glycogen is detected in animal tissues, glycosaminoglycans(mu-
copolysaccharides) and glycoproteins. Among glycosaminoglycans, there are neutral ones, tightly bound to proteins, and acidic ones, which include hyaluronic acid, chondroitinsulfuric acid and heparin. Acidic glycosaminoglycans, as biopolymers, are capable of forming weak compounds with a number of metabolites and transporting them. The main representatives of glycoproteins are mucins and mucoids. Mucins form the basis of mucus produced by the epithelium of the mucous membranes and glands; mucoids are part of many tissues.
Polysaccharides, glycosaminoglycans and glycoproteins are detected by the CHIC reaction or the Hotchkiss-McManus reaction. The essence of the reaction is that after oxidation with periodic acid (or reaction with periodate), the resulting aldehydes give a red color with Schiff fuchsin. To detect glycogen, the PHIK reaction is supplemented with enzymatic control - treatment of sections with amylase. Glycogen is stained red by Best's carmine. Glycosaminoglycans and glycoproteins are determined using a number of methods, of which the most commonly used are toluidine blue or methylene blue stains. These stains make it possible to identify chromotropic substances that give rise to the metachromasia reaction. Treatment of tissue sections with hyaluronidases (bacterial, testicular) followed by staining with the same dyes makes it possible to differentiate different glycosaminoglycans.
Parenchymal carbohydrate dystrophy may be associated with metabolic disorders glycogen or glycoproteins.
Carbohydrate dystrophies associated with impaired glycogen metabolism
The main stores of glycogen are in the liver and skeletal muscles. Liver and muscle glycogen is consumed depending on the body's needs (labile glycogen). Glycogen in nerve cells, the conduction system of the heart, aorta, endothelium, epithelial integuments, uterine mucosa, connective tissue, embryonic tissues, cartilage and leukocytes is an essential component of cells, and its content does not undergo noticeable fluctuations (stable glycogen). However, the division of glycogen into labile and stable is arbitrary.
Regulation of carbohydrate metabolism is carried out by the neuroendocrine pathway. The main role belongs to the hypothalamic region, the pituitary gland (ACTH, thyroid-stimulating, somatotropic hormones), (β-cells (B-cells) of the pancreas (insulin), adrenal glands (glucocorticoids, adrenaline) and the thyroid gland.
Content violations glycogen manifests itself in a decrease or increase in its amount in tissues and the appearance of where it is usually not detected. These disorders are most pronounced in diabetes mellitus and hereditary carbohydrate dystrophies - glycogenosis.
At diabetes mellitus, the development of which is associated with the pathology of β-cells of the pancreatic islets, insufficient use of glucose by tissues, an increase in its content in the blood (hyperglycemia) and excretion in the urine (glucosuria) occur. Tissue glycogen reserves decrease sharply. This primarily concerns the liver,
in which glycogen synthesis is disrupted, which leads to its infiltration with fats - fatty liver degeneration develops; at the same time, glycogen inclusions appear in the nuclei of hepatocytes, they become light (“holey”, “empty” nuclei).
Associated with glucosuria characteristic changes kidneys in diabetes. They are expressed in glycogen infiltration of the tubular epithelium, mainly narrow and distal segments. The epithelium becomes tall, with light foamy cytoplasm; glycogen grains are also visible in the lumen of the tubules. These changes reflect the state of glycogen synthesis (glucose polymerization) in the tubular epithelium during the resorption of glucose-rich plasma ultrafiltrate.
In diabetes, not only the renal tubules are affected, but also the glomeruli and their capillary loops, the basement membrane of which becomes much more permeable to sugars and plasma proteins. One of the manifestations of diabetic microangiopathy occurs - intercapillary (diabetic) glomerulosclerosis.
Hereditary carbohydrate dystrophies, which are based on disorders of glycogen metabolism are called glycogenoses. Glycogenoses are caused by the absence or deficiency of the enzyme involved in the breakdown of stored glycogen, and therefore belong to hereditary enzymopathies, or storage diseases. Currently, 6 types of glycogenosis, caused by hereditary deficiency of 6 different enzymes, have been well studied. These are Gierke (type I), Pompe (type II), McArdle (type V) and Hers (type VI) diseases, in which the structure of glycogen accumulated in the tissues is not disturbed, and Forbes-Cory (type III) and Andersen diseases ( IV type), in which it is sharply changed (Table 3).
Name of the disease | Enzyme deficiency | Localization of glycogen accumulations |
Without disrupting glycogen structure |
||
Gierke (type I) | Glucose-6-phosphatase | Liver, kidneys |
Pompe (II type) | Acid α-clucosidase | Smooth and skeletal muscles, myocardium |
McArdle (V type) | Muscle phosphorylase system | Skeletal muscles |
Gersa (type VI) | Liver phosphorylase | Liver |
With disruption of glycogen structure |
||
Forbes-Cori, limit dextrinosis (type III) | Amylo-1,6-glucosidase | Liver, muscles, heart |
Andersen, amylopectinosis (type IV) | Amylo-(1,4-1,6)-transglucosidase | Liver, spleen, lymph nodes |
Morphological diagnosis of glycogenosis of one type or another is possible with a biopsy using histoenzymatic methods.
Carbohydrate dystrophies associated with impaired glycoprotein metabolism
When the metabolism of glycoproteins in cells or in the intercellular substance is disrupted, mucins and mucoids, also called mucous or mucus-like substances, accumulate. In this regard, when glycoprotein metabolism is disrupted, they speak of mucous dystrophy.
It makes it possible to detect not only increased mucus formation, but also changes in the physicochemical properties of mucus. Many secreting cells die and desquamate, the excretory ducts of the glands become obstructed by mucus, which leads to the development of cysts. Often in these cases inflammation is associated. Mucus can close the lumens of the bronchi, resulting in the occurrence of atelectasis and foci of pneumonia.
Sometimes it is not true mucus that accumulates in the glandular structures, but mucus-like substances (pseudomucins). These substances can become denser and take on the character of a colloid. Then they talk about colloid dystrophy, which is observed, for example, with colloid goiter.
Causes mucosal dystrophies are varied, but most often it is inflammation of the mucous membranes as a result of the action of various pathogenic irritants (see. Catarrh).
Mucosal dystrophy underlies a hereditary systemic disease called cystic fibrosis, which is characterized by a change in the quality of mucus secreted by the epithelium of the mucous glands: the mucus becomes thick and viscous, it is poorly excreted, which causes the development of retention cysts and sclerosis (cystic fibrosis). The exocrine apparatus of the pancreas, glands of the bronchial tree, digestive and urinary tracts, bile ducts, sweat and lacrimal glands are affected (for more details, see. Prenatal pathology).
Exodus is largely determined by the degree and duration of increased mucus production. In some cases, regeneration of the epithelium leads to complete restoration of the mucous membrane, in others it atrophies and undergoes sclerosis, which naturally affects the function of the organ.
Stromal vascular dystrophies
Stromal-vascular (mesenchymal) dystrophies develop as a result of metabolic disorders in connective tissue and are detected in the stroma of organs and the walls of blood vessels. They develop in the territory histione, which, as is known, is formed by a segment of the microvasculature with surrounding connective tissue elements (ground substance, fibrous structures, cells) and nerve fibers. In this regard, the predominance of disturbances in trophic transport systems among the mechanisms of development of stromal-vascular dystrophies, the commonality of morphogenesis, and the possibility of not only a combination of different types of dystrophy, but also the transition of one type to another become clear.
In case of metabolic disorders in the connective tissue, mainly in its intercellular substance, metabolic products accumulate, which can be carried with blood and lymph, be the result of perverted synthesis, or appear as a result of disorganization of the main substance and fibers of the connective tissue.
Depending on the type of impaired metabolism, mesenchymal dystrophies are divided into protein (dysproteinoses), fat (lipidoses) and carbohydrate.
Stromal-vascular protein dystrophies (dysproteinoses)
Among connective tissue proteins, the main one is collagen, from the macromolecules of which collagen and reticular fibers are built. Collagen is an integral part of 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 connective tissue, which also contains proteins and polysaccharides of blood plasma.
Connective tissue fibers have a characteristic ultrastructure. They are clearly identified using a number of histological methods: collagen - by staining with picrofuchsin mixture (van Gieson), elastic - by staining with fuchselin or orcein, reticular - by impregnation with silver salts (reticular fibers are argyrophilic).
In connective tissue, in addition to its cells that synthesize collagen and glycosaminoglycans (fibroblast, reticular cell), as well as a number of biologically active substances (mabrocyte, or mast cell), there are cells of hematogenous origin that carry out phagocytosis (polymorphonuclear leukocytes, histiocytes, macrophages) and immune reactions (plasmoblasts and plasmacytes, lymphocytes, macrophages).
Stromal-vascular dysproteinoses include mucoid swelling, fibrinoid swelling (fibrinoid), hyalinosis, amyloidosis.
Often mucoid swelling, fibrinoid swelling and hyalinosis are successive stages connective tissue disorganization; This process is based on the accumulation of blood plasma products in the main substance as a result of increased 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 resulting protein-polysaccharide complexes include a fibrillar protein that is not usually found, synthesized by cells - amyloidoblasts (Scheme II).
Scheme II. Morphogenesis of stromal-vascular dysproteinoses
Mucoid swelling
Mucoid swelling- superficial and reversible disorganization of connective tissue. In this case, accumulation and redistribution of glycosaminoglycans occur in the main substance due to an increase in the content of primarily hyaluronic acid. Glycosaminoglycans have hydrophilic properties, their accumulation causes 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 interstitial substance develop.
Microscopic examination. The main substance is basophilic, and when stained with toluidine blue it appears lilac or red (Fig. 30, see color on). Arises phenomenon of metachromasia, which is based on a change in the state of the main interstitial substance with the accumulation of chromotropic substances. Collagen fibers usually retain their bundle structure, but swell and undergo fibrillar disintegration. They become less resistant to the action of collagenase and, when stained with picrofuchsin, appear yellow-orange rather than brick-red. Changes in the ground substance and collagen fibers during mucoid swelling can 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 normally; at the same time, the amount of chromotropic substances increases sharply. It is most often 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. Hypoxia, infection, especially streptococcal, and immunopathological reactions (hypersensitivity reactions) are of great importance in its development.
Exodus can be twofold: complete tissue restoration or transition to fibrinoid swelling. 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 connective tissue, which is based on destruction its main substance and fibers, accompanied sharp increase vascular permeability and fibrinoid formation.
Fibrinoid is a complex substance that includes proteins and polysaccharides of decomposing collagen fibers, the main substance and blood plasma, as well as cellular nucleoproteins. Histochemically, fibrinoid is different in different diseases, but mandatory component his is fibrin(Fig. 31) (hence the terms “fibrinoid swelling”, “fibrinoid”).
Rice. 31. Fibrinoid swelling:
a - fibrinoid swelling and fibrinoid necrosis of the capillaries of the renal glomeruli (systemic lupus erythematosus); b - in the fibrinoid among the swollen collagen fibers (CLF) that have lost their cross-striations, fibrin mass (F). Electron diffraction pattern. 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, stained yellow with pyrofuchsin, sharply CHIC-positive and pyroninophilic during the Brachet reaction, and also argyrophilic when impregnated with silver salts. Metachromasia of the connective tissue is not expressed or is weakly expressed, which is explained by the depolymerization of glycosaminoglycans of the main substance.
As a result, fibrinoid swelling sometimes develops fibrinoid necrosis, characterized by complete destruction of connective tissue. Around the foci of necrosis, the reaction of macrophages is usually pronounced.
Appearance. Various organs and tissues where fibrinoid swelling occurs change little in appearance; characteristic changes are usually detected only upon microscopic examination.
Causes. Most often, this is a manifestation of infectious-allergic (for example, fibrinoid of blood vessels in tuberculosis with hyperergic reactions), allergic and autoimmune (fibrinoid changes in connective tissue in rheumatic diseases, capillaries of the renal glomeruli in glomerulonephritis) and angioneurotic (fibrinoid of arterioles in hypertension and arterial hypertension) reactions . In such cases, fibrinoid swelling has common (systemic) nature. Locally fibrinoid swelling can occur during inflammation, especially chronic (fibrinoid in the appendix with 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, glassy), or hyaline dystrophy, in the connective tissue, homogeneous translucent dense masses (hyaline) are formed, reminiscent of hyaline cartilage. The tissue becomes denser, so hyalinosis is also considered a type of sclerosis.
Hyaline is a fibrillar protein. An immunohistochemical study reveals not only plasma proteins and fibrin, but also components of immune complexes (immunoglobulins, complement fractions), as well as lipids. Hyaline masses are resistant to acids, alkalis, enzymes, are CHIC-positive, accept acidic dyes (eosin, acid fuchsin) well, and are stained yellow or red with picrofuchsin.
Mechanism hyalinosis is complex. The leading factors in its development are the destruction of fibrous structures and increased tissue-vascular permeability (plasmorrhagia) in connection with angioneurotic (dyscirculatory), metabolic and immunopathological processes. Plasmorrhagia is associated with the impregnation of tissue with plasma proteins and their adsorption on altered fibrous structures, followed by precipitation and the formation of 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. A distinction is made between vascular hyalinosis and hyalinosis of the connective tissue itself. Each of them can be widespread (systemic) and local.
Vascular hyalinosis. Hyalinosis occurs mainly in small arteries and arterioles. It is preceded by damage to the endothelium, its membrane and smooth muscle cells of the wall and its saturation with blood plasma.
Microscopic examination. Hyaline is found in the subendothelial space, it pushes outwards and destroys the elastic lamina, the middle membrane becomes thinner, and finally the arterioles turn into thickened glassy tubes with a sharply narrowed or completely closed lumen (Fig. 32).
Hyalinosis of small arteries and arterioles is systemic in nature, but is most pronounced in the kidneys, brain, retina, pancreas, and skin. It is especially characteristic of hypertension and hypertensive conditions (hypertensive arteriolohyalinosis), diabetic microangiopathy (diabetic arteriolohyalinosis) and diseases with impaired immunity. As a physiological phenomenon, local arterial hyalinosis is observed in the spleen of adults and elderly people, reflecting the functional and morphological characteristics of the spleen as a blood deposition organ.
Vascular hyaline is a substance of predominantly hematogenous nature. Not only hemodynamic and metabolic, but also immune mechanisms play a role in its formation. Guided by the peculiarities of the pathogenesis of vascular hyalinosis, 3 types of vascular hyaline are distinguished: 1) simple, arising as a result of insudation of unchanged or slightly changed components of blood plasma (occurs more often in benign hypertension, atherosclerosis and in healthy people); 2) lipohyalin, 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, for example, rheumatic diseases).
Rice. 32. Hyalinosis of the vessels of the spleen:
a - the wall of the central artery of the splenic follicle is represented by homogeneous masses of hyaline; b - fibrin among hyaline masses when stained using the Weigert method; c - fixation of IgG immune complexes in hyaline (fluorescence microscopy); g - mass of hyaline (G) in the wall of the arteriole; En - endothelium; Pr - lumen of the arteriole. Electron diffraction pattern.
x15,000
Hyalinosis of the connective tissue itself. It usually develops as a result of fibrinoid swelling, leading to the destruction of collagen and saturation of the tissue with plasma proteins and polysaccharides.
Microscopic examination. The connective tissue bundles become swollen, 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 connective tissue hyalinosis 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, during the organization of a blood clot, in capsules, tumor stroma, etc. Hyalinosis in these cases is based on disorders of connective tissue metabolism. A similar mechanism occurs in hyalinosis of necrotic tissues and fibrinous deposits.
Appearance. With severe hyalinosis, the appearance of organs changes. Hyalinosis of small arteries and arterioles leads to atrophy, deformation and shrinkage of the organ (for example, the development of arteriolosclerotic nephrocirrhosis).
With hyalinosis of the connective tissue itself, it becomes dense, whitish, translucent (for example, hyalinosis of the heart valves with rheumatic disease).
Exodus. In most cases it is unfavorable, but resorption of hyaline masses is also possible. Thus, hyaline in scars - the so-called keloids - can undergo loosening and resorption. Let's reverse hyalinosis of the mammary gland, and the resorption of hyaline masses occurs in conditions of hyperfunction of the glands. Sometimes the hyalinized tissue becomes slimy.
Functional meaning. Varies depending on the location, degree and prevalence of hyalinosis. Widespread hyalinosis of arterioles can lead to functional failure of the organ (renal failure in arteriolosclerotic nephrocirrhosis). Local hyalinosis (for example, heart valves with heart disease) can also cause functional failure of the organ. But in scars it may not cause any particular distress.
Amyloidosis
Amyloidosis(from lat. amylum- starch), or amyloid dystrophy,- stromal-vascular dysproteinosis, accompanied by a profound disturbance of protein metabolism, the appearance of abnormal fibrillar protein and the formation of a complex substance in the interstitial tissue and vascular walls - amyloid.
In 1844, the Viennese pathologist K. Rokitansky described peculiar changes in parenchymal organs, which, in addition to sharp compaction, acquired a waxy, greasy appearance. He called the disease in which such changes in organs occurred “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, under the influence of iodine and sulfuric acid, turns blue. Therefore, he called it amyloid, and the “greasy 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 components 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, characteristic of certain forms of amyloidosis: 1) AA protein (not associated with immunoglobulins), formed from its serum analogue - the SAA protein; 2) AL protein (associated with immunoglobulins), its precursor is the L chains (light chains) of immunoglobulins; 3) AF protein, the formation of which mainly involves prealbumin; 4) ASC^-protein, the precursor of which is also prealbumin.
Proteins of amyloid fibrils can be identified using specific sera during immunohistochemical examination, 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 blood plasma glucoproteins. This plasma component The (P-component) 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 combine with tissue chondroitin sulfates and so-called hematogenous additives are added to 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 enzymes of the body act on amyloid.
Rice. 33. Ultrastructure of amyloid:
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 with 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 in the range of 540-560 nm). These properties allow amyloid to be distinguished from other fibrillar proteins. For macroscopic diagnosis of amyloidosis, tissue is exposed to a Lugol solution, and then a 10% sulfuric acid solution; The amyloid turns blue-violet or dirty green.
The colorful reactions of amyloid, associated with the characteristics of its chemical composition, may vary 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 signs: 1) possible cause; 2) specificity of amyloid fibril protein; 3) prevalence of amyloidosis; 4) the uniqueness of clinical manifestations due to the predominant damage to certain organs and systems.
1. Guided by reason There are 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; damage to predominantly mesodermal tissues - the cardiovascular system, striated and smooth muscles, nerves and skin (generalized amyloidosis); tendency to form nodular deposits, inconsistent color reactions of the amyloid substance (negative results are often obtained when staining with Congo red).
Hereditary (genetic, family) amyloidosis. The importance of genetic factors in the development of amyloidosis is confirmed by the uniqueness of its geographical pathology and the special predisposition of certain ethnic groups of the population to it. The most common type of hereditary amyloidosis with predominant kidney damage is characteristic of 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. Thus, familial nephropathic amyloidosis is known, occurring with fever, urticaria and deafness, described in English families (Mackle and Wells form). Hereditary nephropathic amyloidosis has several variants. Hereditary neuropathy type I (Portuguese amyloidosis) is characterized by damage to the peripheral nerves of the legs, and type II neuropathy, found in American families, is characterized by damage to the peripheral nerves of the arms. For neuropathy III type, which is also described among 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 corneal dystrophy. Hereditary 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 nonspecific inflammatory lung diseases, osteomyelitis, wound suppuration), malignant neoplasms (paraproteinemic leukemia, lymphogranulomatosis, cancer), rheumatic diseases (especially rheumatoid arthritis). Secondary amyloidosis, which usually affects many organs and tissues (generalized amyloidosis), occurs most often 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 undeniable connection between amyloidosis, atherosclerosis and diabetes, which combines age-related metabolic disorders. With senile amyloidosis, local forms are most common (amyloidosis of the atria, brain, aorta, pancreatic islets), although generalized senile amyloidosis with predominant damage to the heart and blood vessels, which clinically differs little from generalized primary amyloidosis, also occurs.
2. Specificity of amyloid fibril protein allows you to identify AL-, AA-, AF- and ASC 1 amyloidosis.
AL amyloidosis includes primary (idiopathic) amyloidosis and amyloidosis with “plasma cell dyscrasia”, which combines paraproteinemic leukemia (myeloma, Waldenström disease, Franklin 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 McClell and Wells disease. This is also generalized amyloidosis, but with predominant damage to the kidneys. AF amyloidosis- hereditary, represented by familial amyloid neuropathy (FAP); peripheral nerves are primarily affected. ASC amyloidosis- senile generalized or systemic (SSA) with predominant damage to the heart and blood vessels.
3. Considering prevalence of amyloidosis, There are generalized and local forms. TO generalized amyloidosis, as can be seen from the above, includes 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. Peculiarity of clinical manifestations due to the predominant damage to organs and systems will allow the identification of cardiopathic, nephropathic, neuropathic, hepapathic, 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 disease and McClell and Wells disease; Secondary amyloidosis is also characterized by mixed types (a combination of damage to the kidneys, liver, adrenal glands, and gastrointestinal tract). Neuropathic amyloidosis is usually hereditary. APUD amyloid develops in the organs of the APUD system when tumors develop in them (apudomas), as well as in the pancreatic islets during senile amyloidosis.
Morphological and pathogenesis of amyloidosis. Function amyloidoblasts, The protein-producing amyloid fibrils (Fig. 34) are performed by different cells in different forms of amyloidosis. In generalized forms of amyloidosis, these are mainly macrophages, plasma and myeloma cells; however, the role of fibroblasts, reticular cells and endothelial cells cannot be excluded. In local forms, the role of amyloidoblasts can be cardiomyocytes (cardiac amyloidosis), smooth muscle cells (aortic amyloidosis), keratinocytes (skin amyloidosis), B cells of the pancreatic islets (insular amyloidosis), C cells thyroid gland and other epithelial cells of the APUD system.
Rice. 34. Amyloidoblast. Amyloid fibrils (Am) in the invaginates of the plasma membrane of a stellate reticuloendotheliocyte with hyperplasia of the granular endoplasmic reticulum (ER), indicating its high synthetic activity. x30,000
The appearance of the amyloidoblast clone explains mutation theory amyloidosis (Serov V.V., Shamov I.A., 1977). In secondary amyloidosis (excluding amyloidosis with “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. In genetic (familial) amyloidosis, we are talking about a gene mutation that can occur at various loci, which determines differences in the composition of the amyloid protein in different people and animals. In senile amyloidosis, similar mechanisms most likely occur, since this type of amyloidosis is considered a phenocopy of genetic amyloidosis. Since amyloid fibril protein antigens are extremely weak immunogens, mutated cells are not recognized by the immunocompetent system and are not eliminated. Immunological tolerance to amyloid proteins develops, which causes the progression of amyloidosis, extremely rare resorption of amyloid - amyloidoclasia- with the help of macrophages (giant cells of foreign bodies).
The formation of amyloid protein may be associated with reticular (perireticular amyloidosis) or collagen (pericollagen 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 characteristic is characteristic spleen damage, liver, kidneys, adrenal glands, intestines, intima of small and medium-sized vessels (parenchymal amyloidosis). For pericollagenous amyloidosis, in which amyloid falls out along the collagen fibers, the adventitia of medium and large vessels, myocardium, striated and smooth muscles, nerves, and skin is 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 synthesis of SAA by hepatocytes is stimulated by 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 not able to complete the degradation of SAA, and from
Scheme III. Pathogenesis of AA amyloidosis
its fragments in the invaginates of the plasma membrane of the amyloidoblast, the assembly of amyloid fibrils occurs (see Fig. 34). Stimulates this build amyloid-stimulating factor(ASF), which is found in tissues (spleen, liver) in the pre-amyloid stage. 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 also participates in the formation of amyloid fibrils from degrading fragments of this protein.
At AL amyloidosis The serum precursor of amyloid fibril protein is the L-chains of immunoglobulins. It is believed that two mechanisms for the formation of AL amyloid fibrils are possible: 1) disruption 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. The synthesis of amyloid fibrils from L-chains of immunoglobulins can occur not only in macrophages, but also in plasma and myeloma cells that synthesize paraproteins (Scheme IV). Thus, the lymphoid system is primarily involved in the pathogenesis of AL amyloidosis; Its perverted function is associated with the appearance of “amyloidogenic” light chains of immunoglobulins - the precursor of amyloid fibrils. The role of the macrophage system is secondary and subordinate.
Macro- and microscopic characteristics of amyloidosis. The appearance of organs in amyloidosis depends on the extent of the process. If the amyloid deposits are small, the appearance of the organ changes little and amyloidosis
Scheme IV. Pathogenesis of AL amyloidosis
detected only by microscopic examination. With severe amyloidosis, the organ increases in volume, becomes very dense and brittle, and on a cut it has a peculiar waxy or greasy appearance.
IN spleen amyloid is deposited in the lymphatic follicles (Fig. 35) or evenly throughout the pulp. In the first case, amyloid-altered follicles of an enlarged and dense spleen on a section look like translucent grains, reminiscent of sago grains (sago spleen). In the second case, the spleen is enlarged, dense, brown-red, smooth, and has a greasy sheen when cut (sebaceous spleen). The sago and sebaceous spleen represent successive stages of the process.
IN kidneys amyloid is deposited in the wall of blood vessels, in the capillary loops and mesangium of the glomeruli, in the basement membranes of the tubules and in the stroma. The buds become dense, large and “greasy”. As the process progresses, the glomeruli and pyramids are completely replaced by amyloid (see Fig. 35), connective tissue grows and amyloid wrinkling of the kidneys develops.
IN 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. In this case, the liver is enlarged, dense, and looks “greasy.”
IN intestines amyloid falls out along the reticular stroma of the mucous membrane, as well as in the walls of blood vessels of both the mucous membrane and the submucosal layer. With severe amyloidosis, the glandular apparatus of the intestine atrophies.
Amyloidosis adrenal glands usually bilateral, amyloid deposition occurs in the cortex along the vessels and capillaries.
Rice. 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 pulmonary vessels
IN 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 a sharp increase in heart size (amyloid cardiomegaly). It becomes very dense, the myocardium takes on a greasy appearance.
IN skeletal muscles, as in the myocardium, amyloid falls out along the intermuscular connective tissue, in the walls of blood vessels and in the nerves.
Massive deposits of amyloid substance are often formed perivascularly and perineurally. The muscles become dense and translucent.
IN 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.
IN 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 sharp atrophy of the epidermis.
Amyloidosis pancreas has some originality. In addition to the arteries of the gland, amyloidosis of the islets also occurs, which is observed in old age.
Amyloidosis thyroid gland also unique. 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). Stromal amyloidosis is common in tumors of endocrine organs and APUD systems (medullary thyroid cancer, insulinoma, carcinoid, pheochromocytoma, carotid body tumors, 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 phenomenon in local forms of amyloidosis.
Functional meaning 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, and intestinal (malabsorption syndrome) failure is possible.
Stromal-vascular fatty degenerations (lipidoses)
Stromal-vascular fatty degenerations occur when there are disturbances in the metabolism of neutral fats or cholesterol and its esters.
Neutral fat metabolism disorders
Metabolism disorders of neutral fats manifest themselves in an increase in their reserves in adipose tissue, which can be general or local in nature.
Neutral fats are labile fats that provide energy reserves for the body. They are concentrated in fat depots (subcutaneous tissue, mesentery, omentum, epicardium, bone marrow). Adipose tissue performs not only an metabolic function, but also a supporting, mechanical function, so it is able to replace atrophying tissue.
Obesity, or obesity,- an increase in the amount of neutral fats in fat depots, which is of a general nature. It is expressed in abundant deposition of fat in the subcutaneous tissue, omentum, mesentery, mediastinum, and 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
Rice. 36. Obesity:
a - proliferation of adipose tissue in the stroma of the pancreas (diabetes mellitus); b - obesity of the heart, under the epicardium there is a thick layer of fat
matters obesity of the heart with obesity. Adipose tissue, growing under the epicardium, envelops the heart like a case (Fig. 36, b). It grows into the myocardial stroma, especially in the subepicardial regions, which leads to muscle cell atrophy. Obesity is usually more pronounced in right half hearts. Sometimes the entire thickness of the right ventricular myocardium is replaced by adipose tissue, which can cause heart rupture.
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 (types of obesity).
By etiological principle There are primary and secondary forms of obesity. Cause primary obesity unknown, so it is also called idiopathic. Secondary obesity is represented by the following types: 1) nutritional, the cause of which is unbalanced nutrition and physical inactivity; 2) cerebral, developing with trauma, brain tumors, and a number of neurotropic infections; 3) endocrine, represented by a number of syndromes (Froelich and Itsenko-Cushing syndromes, adiposogenital dystrophy, hypogonadism, hypothyroidism); 4) hereditary in the form of Lawrence-Moon-Biedl syndrome and Gierke's disease.
By external manifestations There are symmetrical (universal), upper, middle and lower types of obesity. For 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, back of the head, neck, upper shoulder girdle, and mammary glands. With the average type, fat is deposited in the subcutaneous tissue of the abdomen in the form of an apron, with the lower type - in the area of the thighs and legs.
By exceeding The patient's body weight is divided into 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, the number of adiposocytes and their size are taken into account. 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 ones; however, the number of adiposocytes 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 during puberty and does not change thereafter). However, the function of adipozocytes 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, disruption of the nervous (CNS) and endocrine regulation of fat metabolism, and 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 diagram V, an increase in lipogenesis, as well as a decrease in lipolysis,
Scheme V. Lipogenesis and lipolysis in a fat cell
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 antilipolytic 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. Excess body weight, 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. Exhaustion is also observed in the terminal stage cachexia(from Greek kakos- bad, hexis- state).
With an increase in the amount of fatty tissue, which has local character, talk about lipomatosis. Among them, Dercum's disease is of greatest interest. (lipomatosis dolorosa), in which nodular, painful deposits of fat, similar to lipomas, appear in the subcutaneous tissue of the limbs and torso. The disease is based on polyglandular endocrinopathy. A local increase in the amount of adipose tissue is often an expression Vacat obesity(fat replacement) with atrophy of a tissue or organ (for example, fat 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).
Metabolism disorders of cholesterol and its esters
Disturbances in the metabolism of cholesterol and its esters are the basis of a serious disease - atherosclerosis. At the same time, not only cholesterol and its esters accumulate in the intima of the arteries, but also low-density β-lipoproteins and blood plasma proteins, which is facilitated by an increase in vascular permeability. Accumulating high-molecular substances lead to 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. Atherosclerosis).
Hereditary dystrophy, developing in connection with a disorder 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, walls of large vessels (atherosclerosis develops), heart valves and other organs.
Stromal-vascular carbohydrate dystrophies may be associated with an imbalance of glycoproteins and glycosaminoglycans. Stromal-vascular dystrophy associated with impaired glycoprotein metabolism
ids are called sliming of tissues. Its essence lies in the fact that chromotropic substances are released from bonds with proteins and accumulate mainly in the interstitial substance. In contrast to mucoid swelling, this involves replacement of collagen fibers with a mucus-like mass. The connective tissue itself, the stroma of organs, adipose tissue, and cartilage become swollen, translucent, mucus-like, and their cells become stellate or bizarre-shaped.
Cause. Tissue mucus most often occurs due to dysfunction of the endocrine glands, exhaustion (for example, mucous edema, or myxedema, with thyroid insufficiency; mucus of connective tissue formations with cachexia of any origin).
Exodus. The process can be reversible, but its progression leads to tissue colliquation and necrosis with the formation of cavities filled with mucus.
Functional meaning determined by the severity of the process, its duration and the nature of the tissue that has undergone degeneration.
Hereditary violations metabolism of glycosaminoglycans (mucopolysaccharides) are represented by a large group of storage diseases - mucopolysaccharidoses. Among them, the main clinical significance is gargoilism, or Pfoundler-Hurler disease, which is characterized by disproportionate growth, deformation of the skull (“massive skull”), other skeletal bones, the presence of heart defects, inguinal and umbilical hernias, clouding of the cornea, hepato- and splenomegaly. It is believed that mucopolysaccharidosis is based on a deficiency of a specific factor that determines the metabolism of glycosaminoglycans.
Mixed dystrophies
ABOUT mixed dystrophies they say when morphological manifestations disorders of metabolism are detected both in the parenchyma and in the stroma, the wall of blood vessels of organs and tissues. They occur due to metabolic disorders complex proteins - chromoproteins, nucleoproteins and lipoproteins 1, as well as minerals.
Disorders of chromoprotein metabolism (endogenous pigmentation) 2
Chromoproteins- colored proteins, or endogenous pigments, play important role in the life of the organism. With the help of chromoproteins, respiration (hemoglobin, cytochromes), production of secretions (bile) and hormones (serotonin), protection of the body from the effects of radiation energy (melanin), replenishment of iron reserves (ferritin), balance of vitamins (lipochromes), etc. are carried out. The exchange of pigments is regulated by the autonomic nervous system and endocrine glands; it is closely related to the function of the hematopoietic organs and the monocytic phagocyte system.
1 Disorders of lipid metabolism are given in the sections on lipidogenic pigments, fatty and protein dystrophies.
2 In addition to endogenous ones, there are exogenous pigmentations (see. Occupational diseases).
Classification. Endogenous pigments are usually divided into 3 groups: hemoglobinogenic, representing various derivatives of hemoglobin, proteinogenic, or tyrosinogenic, associated with tyrosine metabolism, and lipidogenic, or lipopigments, formed during fat metabolism.
Disorders of hemoglobinogenic pigment metabolism
Normally, hemoglobin undergoes a series of cyclic transformations that ensure its resynthesis and the formation of products necessary for the body. These transformations are associated with the aging and destruction of red blood cells (hemolysis, erythrophagy), and the constant renewal of red blood cell mass. As a result of the physiological breakdown of red blood cells and hemoglobin, pigments are formed ferritin, hemosiderin And bilirubin. Under pathological conditions, due to many reasons, hemolysis can be sharply enhanced and occur both in the circulating blood (intravascular) and in foci of hemorrhage (extravascular). Under these conditions, in addition to an increase in the normally formed hemoglobinogenic pigments, a number of new pigments may appear - hematoidin, hematins And porphyrin.
Due to the accumulation of hemoglobinogenic pigments in tissues, various types of endogenous pigmentation can occur, which become a manifestation of a number of diseases and pathological conditions.
Ferritin - iron protein containing up to 23% iron. Ferritin iron is bound to a protein called apoferritin. Normally, ferritin has a disulfide group. This is the inactive (oxidized) form of ferritin - SS-ferritin. When oxygen is insufficient, ferritin is restored to its active form - SH-ferritin, which has vasoparalytic and hypotensive properties. Depending on the origin, anabolic and catabolic ferritin are distinguished. Anabolic ferritin formed from iron absorbed in the intestines, catabolic- from iron of hemolyzed erythrocytes. Ferritin (apoferritin) has antigenic properties. Ferritin forms Prussian blue (iron sulfide) under the action of potassium iron sulfide and hydrochloric or hydrochloric acid (Perls reaction) and can be identified using a specific antiserum in an immunofluorescence study. A large amount of ferritin is found in the liver (ferritin depot), spleen, bone marrow and lymph nodes, where its metabolism is associated with the synthesis of hemosiderin, hemoglobin and cytochromes.
In conditions pathology the amount of ferritin can increase both in tissues and in the blood. An increase in ferritin content in tissues is observed when hemosiderosis, since polymerization of ferritin leads to the formation of hemosiderin. Ferritinemia explain the irreversibility of shock accompanied by vascular collapse, since SH-ferritin acts as an adrenaline antagonist.
Hemosiderin is formed by the breakdown of heme and is a polymer of ferritin. It is colloidal iron hydroxide associated with proteins, glycosaminoglycans and cell lipids. The cells in which hemosiderin is formed are called sideroblasts. In their siderosomes hemosiderin granules are synthesized (Fig. 37). Sideroblasts can be either mesenchymal,
Rice. 37. Sideroblast. Large nucleus (N), narrow rim of cytoplasm with a large number sideros (Ss). Electron diffraction pattern. x 20,000
and epithelial nature. Hemosiderin is constantly found in reticular and endothelial cells of the spleen, liver, bone marrow, and lymph nodes. In the intercellular substance it undergoes phagocytosis siderophages.
The presence of iron in hemosiderin makes it possible to detect it using characteristic reactions: the formation of Prussian blue (Perls reaction), Turnbull blue (treatment of sections with ammonium sulfide, and then potassium iron sulfide and hydrochloric acid). Positive reactions to iron distinguish hemosiderin from similar pigments (hemomelanin, lipofuscin, melanin).
In conditions pathology excessive formation of hemosiderin is observed - hemosiderosis. It can be both general and local in nature.
General, or widespread, hemosiderosis observed with intravascular destruction of red blood cells (intravascular hemolysis) and occurs in diseases of the hematopoietic system (anemia, hemoblastosis), intoxication with hemolytic poisons, and some infectious diseases ( relapsing fever, brucellosis, malaria, etc.), transfusions of different blood groups, Rh conflict, etc. Destroyed red blood cells, their fragments, and hemoglobin are used to build hemosiderin. Sideroblasts become reticular, endothelial and histiocytic elements of the spleen, liver, bone marrow, lymph nodes, as well as epithelial cells of the liver, kidneys, lungs, sweat and salivary glands. A large number of siderophages appear that do not have time to absorb hemosiderin, which loads the intercellular substance. As a result, collagen and elastic fibers are saturated with iron. The spleen, liver, bone marrow and lymph nodes become rusty brown.
Close to general hemosiderosis is a peculiar disease - hemochromatosis, which can be primary (hereditary hemochromatosis) or secondary.
Primary hemochromatosis- independent disease from the group of storage diseases. Transmitted in a dominant autosomal manner and associated with an inherited enzyme defect small intestine which leads to increased absorption dietary iron, which in the form of hemosiderin is deposited in large quantities in organs. The exchange of iron in erythrocytes is not impaired. The amount of iron in the body increases
tens of times, reaching 50-60 g. Hemosiderosis of the liver, pancreas, endocrine organs, heart, salivary and sweat glands, intestinal mucosa, retina and even synovial membranes develops; at the same time, the content in the organs increases ferritin. In the skin and retina of the eyes the content increases melanin, which is associated with damage to the endocrine system and dysregulation of melanin formation. The main symptoms of the disease are bronze skin coloring, diabetes mellitus (bronze diabetes) And pigmented cirrhosis of the liver. It is possible to develop and pigmentary cardiomyopathy with increasing heart failure.
Secondary hemochromatosis- a disease that develops with acquired deficiency of enzyme systems that ensure the metabolism of dietary iron, which leads to common hemosiderosis. The cause of this deficiency may be excessive intake of iron from food (iron-containing preparations), gastric resection, chronic alcoholism, repeated blood transfusions, hemoglobinopathies (hereditary diseases based on impaired heme or globin synthesis). With secondary hemochromatosis, the iron content is increased not only in tissues, but also in blood serum. The accumulation of hemosiderin and ferritin, most pronounced in the liver, pancreas and heart, leads to liver cirrhosis, diabetes mellitus And cardiomyopathy.
Local hemosiderosis- a condition that develops with extravascular destruction of red blood cells (extravascular hemolysis), i.e. in areas of hemorrhage. The red blood cells that find themselves outside the vessels lose hemoglobin and turn into pale round bodies (“shadows” of red blood cells), free hemoglobin and fragments of red blood cells are used to build pigment. Leukocytes, histiocytes, reticular cells, endothelium, and epithelium become sideroblasts and siderophages. Siderophages can persist for a long time at the site of a former hemorrhage; they are often transported by the lymph current to nearby lymph nodes, where they linger and the nodes become rusty. Some of the siderophages are destroyed, the pigment is released and subsequently undergoes phagocytosis again.
Hemosiderin is formed in all hemorrhages, both small and large. In small hemorrhages, which are more often diapedetic in nature, only hemosiderin is detected. With large hemorrhages along the periphery, hemosiderin is formed among living tissue, and in the center - hemorrhages, where autolysis occurs without access to oxygen and the participation of cells, hematoidin crystals appear.
Depending on the development conditions, local hemosiderosis can occur within not only a tissue area (hematoma), but also an entire organ. This is hemosiderosis of the lungs, observed in rheumatic mitral heart disease, cardiosclerosis, etc. (Fig. 38). Chronic venous stasis in the lungs leads to multiple diapedetic hemorrhages, and therefore in the interalveolar septa, alveoli,
Rice. 38. Hemosiderosis of the lungs. The cytoplasm of histiocytes and alveolar epithelium (sideroblasts and siderophages) is loaded with pigment grains
In the lymphatic vessels and lung nodes, a large number of cells loaded with hemosiderin appear (see. Venous plethora).
Bilirubin - the most important bile pigment. Its formation begins in the histiocytic-macrophage system during the destruction of hemoglobin and the cleavage of heme from it. Heme loses iron and is converted to biliverdin, the reduction of which produces bilirubin in complex with protein. Hepatocytes capture the pigment, conjugate it with glucuronic acid and excrete it into the bile capillaries. With bile, bilirubin enters the intestine, where part of it is absorbed and again enters the liver, and part is excreted in feces in the form of stercobilin and urine in the form of urobilin. Normally, bilirubin is found dissolved in bile and in small amounts in blood plasma.
Bilirubin is presented as red-yellow crystals. It does not contain iron. To identify it, reactions are used based on the ability of the pigment to easily oxidize to form differently colored products. This is, for example, the Gmelin reaction, in which, under the influence of concentrated nitric acid, bilirubin first gives green and then blue or purple color.
Metabolic disorder bilirubin is associated with a disorder of its formation and excretion. This leads to an increased content of bilirubin in the blood plasma and a yellow coloring of the skin, sclera, mucous and serous membranes and internal organs - jaundice.
Development mechanism jaundice is different, which allows us to distinguish three types: suprahepatic (hemolytic), hepatic (parenchymal) and subhepatic (mechanical).
Prehepatic (hemolytic) jaundice characterized by increased formation of bilirubin due to increased breakdown of red blood cells. Under these conditions, the liver produces a larger amount of pigment than normal, but due to insufficient uptake of bilirubin by hepatocytes, its level in the blood remains elevated. Hemolytic jaundice is observed during infections (sepsis, malaria, relapsing fever) and intoxications (hemolytic poisons), during isoimmune (hemolytic disease of newborns, incompatible blood transfusion) and autoimmune (hemoblastoses, systemic connective tissue diseases) conflicts. It can also develop with massive hemorrhages.
yanies, hemorrhagic infarctions due to excessive entry of bilirubin into the blood from the site of breakdown of red blood cells, where bile pigment is detected in the form of crystals. The formation of bilirubin in hematomas is associated with a change in their color.
Hemolytic jaundice may be due to a defect in red blood cells. These are hereditary enzymopathies (microspherocytosis, ovalocytosis), hemoglobinopathies, or hemoglobinoses (thalassemia, or hemoglobinosis F; sickle cell anemia, or hemoglobinosis S), paroxysmal nocturnal hemoglobinuria, so-called shunt jaundice (with vitamin B12 deficiency, some hypoplastic anemias, etc.) .
Hepatic (parenchymal) jaundice occurs when hepatocytes are damaged, as a result of which their uptake of bilirubin, its conjugation with glucuronic acid and excretion are disrupted. Such jaundice is observed in acute and chronic hepatitis, cirrhosis of the liver, drug-induced damage and autointoxication, for example during pregnancy, leading to intrahepatic cholestasis. A special group consists of enzymatic hepatic jaundice, arising from hereditary pigmentary hepatosis, in which one of the phases of intrahepatic bilirubin metabolism is disrupted.
Subhepatic (obstructive) jaundice associated with impaired patency of the bile ducts, which complicates excretion and determines bile regurgitation. This jaundice develops when there is an obstruction to the outflow of bile from the liver, either inside or outside the bile ducts, which is observed with cholelithiasis, cancer of the biliary tract, head of the pancreas and duodenal papilla, atresia (hypoplasia) of the biliary tract, cancer metastases to the periportal lymph nodes and liver. When bile stagnates in the liver, foci of necrosis occur, followed by their replacement by connective tissue and the development of cirrhosis. (secondary biliary cirrhosis). Stagnation of bile leads to dilation of the bile ducts and rupture of bile capillaries. Developing cholemia, which causes not only intense coloration of the skin, but also the phenomenon of general intoxication, mainly from the effect on the body of bile acids circulating in the blood (cholaemia). Due to intoxication, the ability of blood to clot decreases, and multiple hemorrhages appear (hemorrhagic syndrome). Autointoxication is associated with kidney damage and the development of hepatic-renal failure.
Hematoidin - an iron-free pigment, the crystals of which look like bright orange rhombic plates or needles, less often - grains. It occurs during the breakdown of red blood cells and hemoglobin intracellularly, but unlike hemosiderin, it does not remain in the cells and when they die, it appears to lie freely among the necrotic masses. Chemically it is identical to bilirubin.
Accumulations of hematoidin are found in old hematomas, scarring infarctions, and in the central areas of hemorrhages - away from living tissues.
Hematina They are an oxidized form of heme and are formed during the hydrolysis of oxyhemoglobin. They look like dark brown or black diamond-shaped crystals or grains, exhibit birefringence in polarized light (anisotropic), and contain iron, but in a bound state.
Hematins detected in tissues include: hemomelanin (malarial pigment), hydrochloric acid hematin (hemin) and formalin pigment. The histochemical properties of these pigments are identical.
Hydrochloric acid hematin (hemin) found in erosions and ulcers of the stomach, where it occurs under the influence of gastric juice enzymes and hydrochloric acid on hemoglobin. The area of the defect in the gastric mucosa becomes brownish-black.
Formalin pigment in the form of dark brown needles or granules, it is found in tissues when they are fixed in acidic formalin (this pigment is not formed if formalin has a pH > 6.0). It is considered a derivative of hematin.
Porphyrins - precursors of the prosthetic part of hemoglobin, having, like heme, the same tetrapyrrole ring, but lacking iron. The chemical nature of porphyrins is similar to bilirubin: they are soluble in chloroform, ether, and pyridine. The method for identifying porphyrins is based on the ability of solutions of these pigments to produce red or orange fluorescence in ultraviolet light (fluorescent pigments). Normally, porphyrins are found in blood, urine, and tissues. They have the property of increasing the sensitivity of the body, especially the skin, to light and are therefore melanin antagonists.
At metabolic disorders porphyrins arise porphyria, which are characterized by an increase in the content of pigments in the blood (porphyrinemia) and urine (porphyrinuria), a sharp increase in sensitivity to ultraviolet rays (photophobia, erythema, dermatitis). There are acquired and congenital porphyrias.
Acquired porphyria observed with intoxication (lead, sulfazole, barbiturates), vitamin deficiencies (pellagra), pernicious anemia, and some liver diseases. There are dysfunctions of the nervous system, increased sensitivity to light, jaundice often develops, skin pigmentation, a large amount of porphyrins is found in the urine.
Congenital porphyria- a rare hereditary disease. When the synthesis of porphyrin in erythroblasts is impaired (insufficiency of uroporphyrinogen III - cosynthetase), the erythropoietic form develops,
and if the synthesis of porphyrin in liver cells is impaired (insufficiency of uroporphyrin III - cosynthetase) - the hepatic form of porphyria. At erythropoietic form porphyria develops hemolytic anemia, affecting the nervous system and gastrointestinal tract (vomiting, diarrhea). Porphyrins accumulate in the spleen, bones and teeth, which turn brown; urine containing large amounts of porphyrins turns yellow-red. At hepatic form porphyria, the liver enlarges, becomes gray-brown, in obese hepatocytes, in addition to porphyrin deposits, hemosiderin is found.
Disorders of the metabolism of proteinogenic (tyrosinogenic) pigments
TO proteinogenic (tyrosinogenic) pigments include melanin, the pigment of enterochromaffin cell granules and adrenochrome. The accumulation of these pigments in tissues is a manifestation of a number of diseases.
Melanin (from Greek melas- black) is a widespread brown-black pigment that is associated with the color of human skin, hair, and eyes. It gives a positive argentaffin reaction, i.e. has the ability to reduce an ammonia solution of silver nitrate to metallic silver. These reactions make it possible to distinguish it histochemically in tissues from other pigments.
Melanin synthesis occurs from tyrosine in the cells of melanin-forming tissue - melanocytes, having neuroectodermal origin. Their predecessors are melanoblasts. Under the influence of tyrosinase in melanosomes melanocytes (Fig. 39), dioxyphenylalanine (DOPA), or promelanin, is formed from tyrosine, which polymerizes into melanin. Cells that phagocytose melanin are called melanophages.
Rice. 39. Skin with Addison's disease:
a - in the basal layer of the epidermis there are accumulations of melanocytes; there are many melanophages in the dermis; b - skin melanocyte. There are many melanosomes in the cytoplasm. I am the core. Electron diffraction pattern. x10,000
Melanocytes and melanophages are found in the epidermis, dermis, iris and retina of the eyes, in the soft meninges. The content of melanin in the skin, retina and iris depends on individual and racial characteristics and is subject to fluctuations at different periods of life. Regulation melanogenesis carried out by the nervous system and endocrine glands. The synthesis of melanin is stimulated by melanostimulating hormone of the pituitary gland, ACTH, sex hormones, mediators of the sympathetic nervous system, and inhibited by melatonin and mediators of the parasympathetic nervous system. The formation of melanin is stimulated by ultraviolet rays, which explains the occurrence of tanning as an adaptive protective biological reaction.
Metabolic disorders melanin are expressed in its increased formation or disappearance. These disorders are widespread or local in nature and can be acquired or congenital.
Common acquired hypermelanosis (melasma) especially often and sharply expressed when Addison's disease(see Fig. 39), caused by damage to the adrenal glands, most often of a tuberculous or tumor nature. Hyperpigmentation of the skin in this disease is explained not so much by the fact that when the adrenal glands are destroyed, melanin is synthesized from tyrosine and DOPA, but by the increased production of ACTH in response to a decrease in adrenaline in the blood. ACTH stimulates the synthesis of melanin, the number of melanosomes increases in melanocytes. Melasma also occurs in endocrine disorders (hypogonadism, hypopituitarism), vitamin deficiencies (pellagra, scurvy), cachexia, and hydrocarbon intoxication.
Common congenital hypermelanosis (xeroderma pigmentosum) is associated with increased skin sensitivity to ultraviolet rays and is expressed in patchy skin pigmentation with symptoms of hyperkeratosis and edema.
TO local acquired melanosis include melanosis of the colon, which occurs in people suffering from chronic constipation, hyperpigmented areas of the skin (acanthosis nigricans) for pituitary adenomas, hyperthyroidism, diabetes mellitus. Focal increased formation of melanin is observed in age spots (freckles, lentigo) and in pigmented nevi. Malignant tumors can arise from pigmented nevi - melanoma.
Common hypomelanosis, or albinism(from lat. albus- white), is associated with hereditary tyrosinase deficiency. Albinism is manifested by the absence of melanin in the hair follicles, epidermis and dermis, in the retina and iris.
Focal hypomelanosis(leukoderma, or vitiligo) occurs when the neuroendocrine regulation of melanogenesis is disrupted (leprosy, hyperparathyroidism, diabetes mellitus), the formation of antibodies to melanin (Hashimoto's goiter), inflammatory and necrotic skin lesions (syphilis).
Enterochromaffin granule pigment cells scattered in various departments gastrointestinal tract, is a derivative of tryptophan. It can be detected using a number of histochemical reactions - argentaffin, Falk's chromaffin reaction, the formation of pigment is associated with the synthesis serotonin And melatonin.
Accumulation of granules pigment-containing enterochromaffin cells are constantly found in tumors of these cells, called carcinoids.
Adrenochrome - a product of the oxidation of adrenaline - found in the form of granules in the cells of the adrenal medulla. Gives a characteristic chromaffin reaction, which is based on the ability to turn dark brown with chromic acid and restore dichromate. The nature of the pigment has been little studied.
Pathology disorders of adrenochrome metabolism have not been studied.
Disorders of the metabolism of lipidogenic pigments (lipopigments)
This group includes fat-protein pigments - lipofuscin, vitamin E deficiency pigment, ceroid and lipochromes. Lipofuscin, vitamin E deficiency pigment and ceroid have the same physical and chemical (histochemical) properties, which gives the right to consider them varieties of the same pigment - lipofuscin. However, at present, lipofuscin is considered to be lipopigment of only parenchymal and nerve cells; Vitamin E deficiency pigment is a type of lipofuscin. Ceroid called lipopigment of mesenchymal cells, mainly macrophages.
Pathology The exchange of lipopigments is diverse.
Lipofuscin is a glycolipoprotein. It is represented by golden or brown grains, electron microscopically detected in the form of electron-dense granules (Fig. 40), surrounded by a three-circuit membrane that contains myelin-like structures.
Lipofuscin is formed by autophagy and goes through several stages. Primary granules, or propigment granules, appear perinuclearly in the zone of the most actively occurring metabolic processes. They contain mitochondrial and ribosomal enzymes (metalloflavoproteins, cytochromes) associated with the lipoproteins of their membranes. Propigment granules enter the lamellar complex, where the synthesis of granules occurs immature lipofuscin, which is sudanophilic, PAS-positive, contains iron, sometimes copper, and has light yellow autofluorescence in ultraviolet light. Granules of immature pigment move to the peripheral zone of the cell and are absorbed there by lysosomes; appears mature lipofuscin, having high activity of lysosomal rather than respiratory enzymes. Its granules become brown, they are persistently sudanophilic, CHIC-positive, iron is not detected in them, autofluorescence becomes red-brown. Lipofuscin accumulates in lysosomes and turns into residual bodies - telolysosomes.
In conditions pathology the content of lipofuscin in cells can increase sharply. This metabolic disorder is called lipofuscinosis. It can be secondary or primary (hereditary).
Rice. 40. Lipofuscin (Lf) in muscle cell heart, closely associated with mitochondria (M). Mf - myofibrils. Electron diffraction pattern. x21,000
Secondary lipofuscinosis develops in old age, with debilitating diseases leading to cachexia (brown atrophy of the myocardium, liver), with increased functional load (myocardial lipofuscinosis with heart disease, liver - with gastric and duodenal ulcers), with the abuse of certain drugs (analgesics), with vitamin E deficiency (vitamin E deficiency pigment).
Primary (hereditary) lipofuscinosis characterized by selective accumulation of pigment in the cells of a particular organ or system. It appears in the form hereditary hepatosis, or benign hyperbilirubinemia(Dabin-Johnson, Gilbert, Krieger-Najjar syndromes) with selective lipofuscinosis of hepatocytes, as well as neuronal lipofuscinosis(Bilschowsky-Jansky, Spielmeyer-Sjögren, Kaf syndrome), when pigment accumulates in nerve cells, which is accompanied by decreased intelligence, seizures, and visual impairment.
Ceroid formed in macrophages by heterophagy during the resorption of lipids or lipid-containing material; The basis of the ceroid is made up of lipids, to which proteins are secondarily attached. Endocytosis leads to the formation of heterophagic vacuoles (lipophagosomes). Lipophagosomes are transformed into secondary lysosomes (lipophagolysosomes). Lipids are not digested by lysosomal enzymes and remain in lysosomes, residual bodies appear, i.e. telolysosomes.
In conditions pathology the formation of a ceroid is most often observed during tissue necrosis, especially if lipid oxidation is enhanced by hemorrhage (this is why ceroid was previously called hemofuscin, which is the principle
pial incorrect) or if lipids are present in such quantities that their autoxidation begins earlier than digestion.
Lipochromes are represented by lipids that contain carotenoids, which are the source of the formation of vitamin A. Lipochromes give a yellow color to adipose tissue, the adrenal cortex, blood serum, and the corpus luteum of the ovaries. Their identification is based on the detection of carotenoids (color reactions with acids, green fluorescence in ultraviolet light).
In conditions pathology Excessive accumulation of lipochromes may occur.
For example, in diabetes mellitus, pigment accumulates not only in fatty tissue, but also in the skin and bones, which is associated with a sharp disturbance in lipid-vitamin metabolism. With sharp and rapid weight loss, condensation of lipochromes occurs in fatty tissue, which becomes ocher-yellow.
Disorders of nucleoprotein metabolism
Nucleoproteins built from protein and nucleic acids - deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is detected using the Feulgen method, RNA - the Brachet method. Endogenous production and intake of nucleoproteins from food (purine metabolism) are balanced by their breakdown and excretion, mainly by the kidneys, of the final products of nucleic metabolism - uric acid and its salts.
At metabolic disorders nucleoproteins and excessive formation of uric acid, its salts can precipitate in the tissues, which is observed with gout, urolithiasis and uric acid infarction.
Gout(from Greek podos- leg and agra- hunting) is characterized by periodic loss of sodium urate in the joints, which is accompanied by a painful attack. Patients exhibit elevated levels of uric acid salts in the blood (hyperuricemia) and urine (hyperuricuria). Salts are usually deposited in the synovium and cartilage of small joints of the legs and arms, ankles and knee joints, in tendons and joint capsules, in the cartilage of the auricles. Tissues in which salts fall out in the form of crystals or amorphous masses become necrotic. Around salt deposits, as well as foci of necrosis, an inflammatory granulomatous reaction develops with an accumulation of giant cells (Fig. 41). As salt deposits increase and connective tissue grows around them, gouty bumps form (tophi urici), joints are deformed. Changes in the kidneys during gout consist of accumulations of uric acid and sodium urate salts in the tubules and collecting ducts with obstruction of their lumens, the development of secondary inflammatory and atrophic changes (gouty kidneys).
In most cases, the development of gout is caused by inborn errors of metabolism. (primary gout), as evidenced by her family character; In this case, the role of dietary habits and the consumption of large quantities of animal proteins is great. Less commonly, gout is
Rice. 41. Gout. Deposits of uric acid salts with a pronounced inflammatory giant cell reaction around them
complication of other diseases, nephrocirrhosis, blood diseases (secondary gout).
Urolithiasis disease, like gout, it can be associated primarily with a violation purine metabolism, i.e. be a manifestation of the so-called uric acid diathesis. In this case, predominantly or exclusively urates are formed in the kidneys and urinary tract (see. Kidney stone disease).
Uric acid infarction occurs in newborns who have lived for at least 2 days, and is manifested by the loss of amorphous masses of sodium and ammonium urate in the tubules and collecting ducts of the kidneys. Deposits of uric acid salts appear on a section of the kidney in the form of yellow-red stripes converging at the papillae of the medulla of the kidney. The occurrence of uric acid infarction is associated with intense metabolism in the first days of a newborn’s life and reflects the adaptation of the kidneys to new living conditions.
Violations mineral metabolism(mineral dystrophies)
Minerals participate in the construction of structural elements of cells and tissues and are part of enzymes, hormones, vitamins, pigments, and protein complexes. They are biocatalysts, participate in many metabolic processes, play an important role in maintaining the acid-base state and largely determine the normal functioning of the body.
Mineral substances in tissues are determined by the microcombustion method in combination with histospectrography. Using autoradiography, it is possible to study the localization in tissues of elements introduced into the body in the form of isotopes. In addition, conventional histochemical methods are used to identify a number of elements released from bonds with proteins and precipitated in tissues.
Disorders of the metabolism of calcium, copper, potassium and iron are of greatest practical importance.
Calcium metabolism disorders
Calcium associated with the processes of cell membrane permeability, excitability of neuromuscular devices, blood clotting, regulation of acid-base status, skeletal formation, etc.
Calcium absorbed with food in the form of phosphates in the upper segment of the small intestine, the acidic environment of which ensures absorption. Vitamin D, which catalyzes the formation of soluble calcium phosphorus salts, is of great importance for the absorption of calcium in the intestine. IN recycling calcium (blood, tissues), protein colloids and blood pH are of great importance. In the released concentration (0.25-0.3 mmol/l), calcium is retained in the blood and tissue fluid. Most of the calcium is found in the bones (depot calcium), where calcium salts are bound to the organic basis of bone tissue. In the compact substance of bones, calcium is relatively stable, and in the spongy substance of the epiphyses and metaphyses it is labile. Bone dissolution and “washing out” of calcium are manifested in some cases by lacunar resorption, in others by so-called axillary resorption, or smooth resorption. Lacunar resorption bones are carried out with the help of cells - osteoclasts; at sinus resorption, as with smooth resorption, Bone dissolves without the participation of cells, and “liquid bone” is formed. Calcium in tissues is detected using the Coss silver method. The intake of calcium from food and from the depot is balanced by its excretion by the colon, kidneys, liver (with bile) and some glands.
Regulation Calcium metabolism is carried out via the neurohumoral route. The most important are the parathyroid glands (parathyroid hormone) and the thyroid gland (calcitonin). For hypofunction parathyroid glands(parathyroid hormone stimulates the leaching of calcium from bones), as with overproduction of calcitonin (calcitonin promotes the transition of calcium from the blood into bone tissue), the calcium content in the blood decreases; hyperfunction of the parathyroid glands, as well as insufficient production of calcitonin, on the contrary, is accompanied by leaching of calcium from the bones and hypercalcemia.
Disorders of calcium metabolism are called calcinosis, calcareous degeneration, or calcification. It is based on the precipitation of calcium salts from a dissolved state and their deposition in cells or intercellular substance. The matrix of calcification can be mitochondria and lysosomes of cells, glycosaminoglycans of the main substance, collagen or elastic fibers. In this regard, there is a distinction intracellular And extracellular calcification. Calcinosis may be systemic (common) or local.
Development mechanism. Depending on the predominance of general or local factors in the development of calcification, three forms of calcification are distinguished: metastatic, dystrophic and metabolic.
Metastatic calcification (calcareous metastases) is widespread. The main reason for its occurrence is hypercalcemia, associated with increased release of calcium salts from the depot, reduced excretion from the body, disruption of the endocrine regulation of calcium metabolism (overproduction of parathyroid hormone, under-
calcitonin balance). Therefore, the occurrence of calcareous metastases is noted with bone destruction (multiple fractures, myeloma, tumor metastases), osteomalacia and hyperparathyroid osteodystrophy, lesions of the colon (sublimate poisoning, chronic dysentery) and kidneys (polycystic disease, chronic nephritis), excessive introduction of vitamin D into the body, etc.
Calcium salts during metastatic calcification precipitate in various organs and tissues, but most often in the lungs, gastric mucosa, kidneys, myocardium and arterial walls. This is explained by the fact that the lungs, stomach and kidneys secrete acidic foods and their tissues, due to greater alkalinity, are less able to retain calcium salts in solution than the tissues of other organs. In the myocardium and arterial walls, lime is deposited due to the fact that their tissues are washed arterial blood and are relatively low in carbon dioxide.
The appearance of organs and tissues changes little; sometimes whitish dense particles are visible on the cut surface. In calcareous metastases, calcium salts encrust both the parenchyma cells and the fibers and ground substance of the connective tissue. In the myocardium (Fig. 42) and kidneys, primary deposits of lime are found in mitochondria and phagolysosomes, which have high phosphatase activity (formation of calcium phosphate). In the wall of arteries and in connective tissue, lime primarily precipitates along the membranes and fibrous structures. An inflammatory reaction is observed around lime deposits, sometimes there is an accumulation of macrophages, giant cells, and the formation of granulomas.
At dystrophic calcification, or petrification, deposits of calcium salts are local in nature and are usually found in tissue
Rice. 42. Calcareous metastases in the myocardium:
a - calcified muscle fibers (black) (microscopic picture); b - calcium salts (SC) are fixed on the mitochondrial cristae (M). Electron diffraction pattern. x40,000
nyahs, dead or in a state of deep degeneration; There is no hypercalcemia. The main cause of dystrophic calcification is physical and chemical changes in tissues that ensure the absorption of lime from the blood and fluid tissues. The greatest importance is attached to alkalization of the environment and increased activity of phosphatases released from necrotic tissues.
Mechanism metabolic calcification (calcareous gout, interstitial calcification) not clear: general (hypercalcemia) and local (dystrophy, necrosis, sclerosis) prerequisites are absent. In the development of metabolic calcification, the main importance is attached to the instability of buffer systems (pH and protein colloids), due to which calcium is not retained in the blood and tissue fluid even at low concentrations, as well as hereditarily caused increased sensitivity of tissues to calcium - calcergia, or calciphylaxis(Selye G., 1970).
There are systemic and limited interstitial calcification. At interstitial systemic (universal) calcinosis lime deposits in the skin, subcutaneous tissue, along the tendons, fascia and
Rice. 43. Dystrophic calcification of the artery wall. In the thickness atherosclerotic plaque lime deposits are visible
aponeuroses, in muscles, nerves and blood vessels; sometimes the localization of lime deposits is the same as with calcareous metastases. Interstitial limited (local) calcification, or calcareous gout, is characterized by the deposition of lime in the form of plates in the skin of the fingers, less often the feet.
Exodus. Unfavorable: fallen lime usually does not dissolve or dissolves with difficulty.
Meaning. The prevalence, localization and nature of calcifications matter. Thus, the deposition of lime in the vessel wall leads to functional disorders and can cause a number of complications (for example, thrombosis). Along with this, the deposition of lime in a caseous tuberculosis focus indicates its healing, i.e. has a reparative nature.
Copper metabolism disorders
Copper- an obligatory component of the cytoplasm, where it participates in enzymatic reactions.
Copper is found in very small quantities in tissues; only in the liver of a newborn is it relatively abundant. To detect copper, the most accurate is the Okamoto method, based on the use of rubeonic acid (dithiooxamide).
Metabolic disorder copper is most pronounced when hepatocerebral dystrophy (hepatolenticular degeneration), or Wilson-Konovalov disease. With this hereditary disease, copper is deposited in the liver, brain, kidneys, cornea (pathognomonic is the Kayser-Fleischer ring - a greenish-brown ring along the periphery of the cornea), pancreas, testicles and other organs. Liver cirrhosis and dystrophic symmetrical changes in brain tissue develop in the area of the lentiform nuclei, caudate body, globus pallidus, and cortex. The copper content in the blood plasma is reduced, and in the urine it is increased. There are hepatic, lenticular and hepatolenticular forms of the disease. Copper deposition is due to reduced formation of ceruloplasmin in the liver, which belongs to α2-globulins and is capable of binding copper in the blood. As a result, it is released from loose bonds with plasma proteins and falls into the tissue. It is possible that in Wilson-Konovalov disease the affinity of some tissue proteins for copper is increased.
Potassium metabolism disorders
Potassium- the most important element taking part in the construction of the cell cytoplasm.
Potassium balance ensures normal protein-lipid metabolism and neuroendocrine regulation. Potassium can be detected using the McCallum method.
Increase the amount of potassium in the blood (hyperkalemia) and tissues is observed when Addison's disease and is associated with damage to the adrenal cortex
nicks, whose hormones control the balance of electrolytes. Deficiency potassium and disruption of its metabolism explain the emergence periodic paralysis- a hereditary disease manifested by attacks of weakness and the development of motor paralysis.
Iron metabolism disorders
Iron is mainly contained in hemoglobin, and the morphological manifestations of disorders of its metabolism are associated with hemoglobinogenic pigments (see. Disturbances in the exchange of hemoglobinogenic pigments).
Stone formation
stones, or stones(from lat. concrementum- adhesion), are very dense formations that lie freely in the cavitary organs or excretory ducts of the glands.
Type of stones(shape, size, color, structure when cut) is different depending on their localization in a particular cavity, chemical composition, and mechanism of formation. There are huge stones and microliths. The shape of the stone often follows the cavity it fills: round or oval stones are found in the urinary and gall bladders, process stones are found in the pelvis and calyces of the kidneys, and cylindrical stones are found in the ducts of the glands. Stones can be single or multiple. In the latter case, they often have faceted surfaces ground to each other (faceted stones). The surface of the stones can be not only smooth, but also rough (oxalates, for example, resemble mulberries), which injures the mucous membrane and causes its inflammation. The color of the stones is different, which is determined by their different chemical composition: white (phosphates), yellow (urates), dark brown or dark green (pigment). In some cases, cut stones have a radial structure (crystalloid), in others - layered (colloidal), thirdly - layered radial (colloid-crystalloid). The chemical composition of the stones is also different. Gallstones can be cholesterol, pigment, calcareous or cholesterol-pigment-calcareous (complex, or combined, stones). Urine stones may consist of uric acid and its salts (urates), calcium phosphate (phosphates), calcium oxalate (oxalates), cystine and xanthine. Bronchial stones usually consist of lime-encrusted mucus.
Most often, stones form in the gall and urinary tract, causing the development of cholelithiasis and urolithiasis. They are also found in other cavities and ducts: in the excretory ducts pancreas And salivary glands, V bronchi And bronchiectasis (bronchial stones), in the crypts of the tonsils. A special type of stones are the so-called vein stones (phleboliths), representing petrified blood clots separated from the wall, and intestinal stones (coprolites), arising from the encrustation of compacted intestinal contents.
Development mechanism. The pathogenesis of stone formation is complex and is determined by both general and local factors. TO general factors which are of primary importance for the formation of stones should be attributed metabolic disorders acquired or hereditary nature. Of particular importance are metabolic disorders of fats (cholesterol), nucleoproteins, a number of carbohydrates, and minerals. For example, the connection between cholelithiasis and general obesity and atherosclerosis, and urolithiasis with gout, oxaluria, etc. is well known. Among local factors the importance of secretion disorders, stagnation of secretions and inflammatory processes in the organs where stones form is great. Secretion disorders like secretion stagnation, lead to an increase in the concentration of substances from which stones are built and their precipitation from solution, which is facilitated by increased reabsorption and thickening of the secretion. At inflammation Protein substances appear in the secretion, which creates an organic (colloidal) matrix into which salts are deposited and on which the stone is built. Subsequently stone And inflammation often become complementary factors that determine the progression of stone formation.
The direct mechanism of stone formation consists of two processes: organic matrix formation And crystallization of salts, Moreover, each of these processes in certain situations can be primary.
The meaning and consequences of stone formation. They can be very serious. As a result of the pressure of stones on tissue, tissue necrosis can occur (renal pelvis, ureters, gallbladder and bile ducts, appendix), which leads to the formation of bedsores, perforation, adhesions, fistulas. Stones often cause inflammation of the abdominal organs (pyelocystitis, cholecystitis) and ducts (cholangitis, cholangiolitis). By disrupting secretion, they lead to severe complications of a general (for example, jaundice due to blockage of the common bile duct) or local (for example, hydronephrosis due to obstruction of the ureter) nature.
Lecture 3. Dystrophies
1. Definition, etiology, classification, general characteristics
Under dystrophy (degeneration, degeneration) understand pathological changes in organs that arise as a result of metabolic disorders in them. These are qualitative changes in the chemical composition, physicochemical properties and morphology of cells and tissues of the body associated with metabolic disorders.
Dystrophies are classified as damage, or alterative processes: this is a change in the structure of cells, intercellular substance, tissues and organs, which is accompanied by disruption of their vital functions. These changes, as the phylogenetically most ancient type of reactive processes, occur in the most early stages development of a living organism.
Damage can cause the most various reasons. They affect cellular and tissue structures directly or through humoral and reflex influences. The nature and extent of damage depend on the strength and nature of the pathogenic factor, the structure and function of the organ, as well as on the reactivity of the body. In some cases, superficial and reversible changes occur in ultrastructures, while in others, deep and irreversible changes occur, which can result in the death of not only cells and tissues, but also the entire organ.
Dystrophy is based on a violation of the metabolism of cells and tissues, leading to structural changes.
The direct cause of the development of dystrophies can be violations of both cellular and extracellular mechanisms that provide trophism:
1) disorder of cell autoregulation (toxin, radiation, lack of enzymes) leads to energy deficiency and disruption of enzymatic processes in the cell;
2) disruption of the transport systems that ensure metabolism and cell structure causes hypoxia, which is the leading cause in the pathogenesis of dystrophy;
3) a disorder of the endocrine regulation of trophism or a disorder of the nervous regulation of trophism leads to endocrine or nervous dystrophy.
There are also intrauterine dystrophies.
With dystrophies, metabolic products (proteins, fats, carbohydrates, minerals, water) accumulate in cells or outside them, which are characterized by quantitative or qualitative changes.
Among the morphological mechanisms leading to the development of changes characteristic of dystrophies, a distinction is made between infiltration, decomposition, perverted synthesis and transformation.
The first two are the leading morphological mechanisms of dystrophy.
The characteristic morphology of dystrophies is revealed, as a rule, at the cellular and tissue levels.
Dystrophic processes are observed both in the cytoplasm and nucleus, and in the intercellular substance and are accompanied by a violation of the structure of cells and tissues, as well as a disorder of their function.
Dystrophy is a reversible process, but can lead to irreversible changes in cells and tissues, causing their decay and death.
In morphological terms, dystrophies are manifested by a violation of the structure, primarily the ultrastructure of cells and tissues, when regeneration is disrupted at the molecular and ultrastructural levels. In many dystrophies, inclusions of “grains”, stones or crystals of various chemical natures are found in cells and tissues, which under normal conditions do not occur or their number increases compared to the norm. In other cases, the amount of compounds decreases until they disappear (fat, glycogen, minerals).
The structure of the cell is lost (muscle tissue - cross-striation, glandular cells - polarity, connective tissue - fibrillar structure, etc.). In severe cases, discomplexation of cellular elements begins. The color, size, shape, consistency, and pattern of organs change microscopically.
The change in the appearance of the organ served as the basis for calling this process degeneration or degeneration - a term that does not reflect the essence of dystrophic changes.
The classification of dystrophies is associated with the type of metabolic disorder. Therefore, protein dystrophies are distinguished (intracellular dysproteinoses, extracellular and mixed); fatty (mesenchymal and parenchymal), carbohydrate (disorder of glycogen metabolism), mineral (stones - calculi, disturbance of calcium metabolism).
According to their prevalence, they are divided into general, systemic and local; by localization - parenchymal (cellular), mesenchymal (extracellular) and mixed; according to the influence of genetic factors - acquired and hereditary.
Dystrophies are reversible processes, but can lead to necrosis.
Etiology of dystrophies: the actions of many external and internal factors(biologically inadequate feeding, various conditions of keeping and exploitation of living things, mechanical, physical, chemical and biological effects, infections, intoxications, disorders of blood and lymph circulation, damage to the endocrine glands and nervous system, genetic pathology, etc.).
Pathogenic factors act on organs and tissues either directly or reflexively through the neurohumoral system that regulates metabolic processes. The nature of dystrophies depends on the strength, duration and frequency of exposure to a particular pathogenic irritation on the body, as well as the reactive state of the body and the type of damaged tissue.
Dystrophies are noted in all diseases, but in some cases they arise eternally and determine the nature of the disease, and in others they represent a nonspecific or non-physiological pathological process accompanying the disease.
The functional significance of dystrophies lies in the disruption of the basic functions of the organ (for example, the synthesis of protein, carbohydrates, lipoproteins in hepatosis, the appearance of protein in the urine in nephrosis, heart weakness in myocardial dystrophy in patients with foot-and-mouth disease, etc.).
2. Protein dystrophy (dysproteinoses), its essence and classification
The essence of protein dystrophies is that the protein of tissue elements in dystrophies often differs from the norm in terms of external signs: It is either liquefied or very compacted. Sometimes protein synthesis changes and their chemical structure is disrupted. Often, products of protein metabolism are deposited in tissues and cells, which are not found at all in a healthy body. In some cases, the processes are limited by disruption of the proteins that make up the cell, and in others, the structure of the proteins included in the intercellular substances is disrupted. Protein dysproteinoses, which occur mainly in cells, include the so-called intracellular dystrophic processes: granular dystrophy, hyaline-droplet, hydropic, horny dystrophy.
Extracellular dysproteinoses include hyalinosis and amyloidosis; mixed – disturbance of the metabolism of nucleoproteins and glucoproteins.
3. Intracellular dysproteinoses, their characteristics, outcome and significance for the body
Granular dystrophy the most common of all types of protein dystrophies. It manifests itself independently or as a component of the inflammatory process. The causes of granular dystrophies are various intoxications, blood and lymph circulation disorders, infectious diseases, febrile conditions etc. All these factors can reduce oxidative processes and contribute to the accumulation of acidic products in cells.
Granular dystrophy occurs in many organs, most clearly expressed in parenchymal ones: in the kidneys, heart muscle, and liver, which is why it is also called parenchymal.
Pathological and anatomical signs: upon external examination, the organ is slightly enlarged, the shape is preserved, the consistency is usually flabby, the color is usually much paler than normal, the pattern on the cut surface is smoothed.
When cutting, in particular the kidneys, liver, due to swelling, the edges of these organs can protrude significantly beyond the edges of the connective tissue capsule. In this case, the cut surface is cloudy, dull, and lacks natural shine. For example, the heart muscle resembles the appearance of meat scalded with boiling water; this gave grounds for many researchers, when describing the signs of granular dystrophy, to say that the muscle has the appearance of boiled meat. Turbidity, dullness, swelling of organs are very characteristic features for this type of dystrophy. Therefore, granular dystrophy is also called cloudy swelling. In animals with enhanced nutrition, soon after feeding, changes sometimes appear in the kidneys and liver, the same as in granular dystrophy, turbidity, dullness, but expressed to a weak degree. With granular dystrophy, the cell is swollen, the cytoplasm is filled with small, barely noticeable protein grains. When such tissue is exposed to a weak solution of acetic acid, the granularity (protein) disappears and no longer appears. This indicates the protein nature of the grain. The same thing is observed when studying the muscle fibers of the heart. Protein granules appear in the muscle, located between the fibrils. The fibers swell, and the transverse striation of the muscle fibers is lost with further development of the process. And if the process does not stop there, the fiber may disintegrate. But granular dystrophy rarely affects the entire heart muscle; more often the process occurs on the surface or internal part of the myocardium of the left ventricle; she has focal spread. The changed areas of the myocardium have a grayish-red color.
In pathology, there is a judgment about two stages of development of this process. Some believe that cloudy swelling is the primary stage of granular dystrophy, and pronounced phenomena of necrobiotic changes with cell necrosis are granular dystrophy. This division of dystrophy processes is conditional and not always justified. Sometimes, with cloudy swelling of the kidneys, cell necrosis occurs.
The essence of the process during dystrophy is the increased breakdown of proteins, fats, carbohydrates with the appearance of an acidic environment, with increased absorption of water and retention of metabolic products in the cells. All this leads to swelling of colloids and a change in the appearance of a group of coarsely dispersed proteins that are contained in the cytoplasm of the cells of these organs.
Particularly significant changes in protein dystrophies and, in particular, in granular dystrophy occur in mitochondria. It is known that redox processes occur in these organelles. Normally, depending on the intensity of redox processes, significant variability occurs in the shape and size of mitochondria. And when pathological conditions, especially accompanied by hypoxia, mitochondria swell, they increase in size, their outer membranes stretch, and the inner membranes move away from one another, and vacuoles appear. At this stage, mitochondrial vacuolization is reversible. With more intense and prolonged development of the process, vacuolization can lead to irreversible necrobiotic changes and necrosis.
The outcome of granular dystrophy depends on the degree of cell damage. The initial stage of this dystrophy is reversible. In the future, if the causes that caused it are not eliminated, then necrosis or a more severe type of metabolic disorder may occur - fatty, hydropic degeneration.
At long term process, for example during fever, not only cell degeneration occurs, but necrosis also occurs. The latter look like light areas.
Changes in granular dystrophy are sometimes similar to cadaveric changes. But with cadaveric changes there will be no swelling of cells, while with granular degeneration there will be uneven swelling of cells with the simultaneous presence of unchanged areas of tissue in the organ. This is how postmortem changes differ from granular dystrophy.
Hyaline-drip dystrophy is characterized by a disorder of protein metabolism and occurs in the cytoplasm with the formation of large protein droplets. At first, these drops are single, small, the nucleus in the cell is not disturbed. With the further action of the cause causing this process, the drops increase in volume and number, the core moves to the side, and then, as the drops continue to form, they gradually disappear. Protein deposits in the cytoplasm acquire a homogeneous appearance, similar to hyaline cartilage. Mitochondria are swollen or in a state of decay. Protein droplets that appear in cells have a hyaline structure. The buds are dense, the cortex is gray and dull, the pyramids are reddish. Most often, cells in such cases acquire the character of cloudy swelling, followed by denaturation of proteins in the cytoplasm of the cells. If the death of the nucleus occurs, then this refers to cell necrosis.
Hyaline droplet dystrophy is most often observed in the epithelium of the renal tubules, less often in the liver. Sometimes it is combined with fatty degeneration or amyloidosis. These dystrophies are observed in chronic infectious diseases, intoxication and poisoning of the body.
Dropsy (hydropic, or vacuolar) dystrophy is characterized by the fact that cells undergo dissolution-liquefaction. Initially, vacuoles with liquid are visible in the cytoplasm, and sometimes in the nucleus, and with further development of the process, the vacuoles merge and the entire cytoplasm is filled with liquid, the nucleus seems to float in it, which then turns into one bubble filled with liquid. Such cells usually die. The intercellular ground substance and connective tissue swell and the entire tissue liquefies. With hydrocele, vacuoles are visible on preparations treated with alcohol, so it is necessary to differentiate these processes from staining for fat.
Dropsy dystrophies occur with edema, burns, smallpox, foot-and-mouth disease, viral hepatitis, chronic neuroses and other septic diseases.
The outcome of hydrocele is favorable in the initial stages and with the restoration of normal water and protein metabolism, the process is easily reversible, and the cells acquire a normal appearance. Cells in a state of severe hydropia die.
Vacuolar dystrophy is determined only by microscopic examination. The appearance of the organ is not changed, but the color is paler than normal. The function of organs, as with any dystrophies, is reduced. Vacuolization often occurs in the epithelium of the kidneys, liver cells, skin cells, leukocytes, cardiac and skeletal muscles, and ganglion cells of the central nervous system.
Pathological keratinization or horny dystrophy is excessive (hyperkeratosis) or qualitatively impaired (parakeratosis, hypokeratosis) formation of horny substance.
Cell keratinization is physiological process, which develops in the epidermis and is characterized by the gradual transformation of the squamous epithelium of the skin into horny scales, forming the stratum corneum of the skin. Pathological keratinization develops in connection with disease or damage to the skin and mucous membranes. The basis of these processes is the excessive formation of the horny substance of the skin. This process is called hyperkeratosis. Sometimes there is a growth of horny substance in unusual places - on the mucous membranes. Sometimes in tumors, horny substance is formed in epithelial cells in some forms of cancer.
Pathological keratinization differs from physiological keratinization in that keratinization of the epithelium occurs due to factors that cause increased formation of horny substance. Often there is a process of hyperkeratosis of local origin, which occurs when the skin is irritated, for example, by improperly fitting harness on a horse; prolonged pressure on the skin causes calluses.
Parakeratosis is expressed in the loss of the ability of epidermal cells to produce keratohyalin. Microscopically, this disease reveals thickening of the epidermis as a result of hyperplasia of cells of the Malpighian layer and excessive accumulation of the stratum corneum. With para- and hypokeratosis, atrophy of the granular layer is expressed, the stratum corneum is loose, with discomplexed cells having rod-shaped nuclei (incomplete keratinization).
Macroscopically, with parakeratosis, the stratum corneum is thickened, loose, with increased desquamation of horny scales. In adult animals, especially dairy cows, abnormal growth of the hoof horn is noted, which loses its glaze and cracks.
With leukoplakia, foci of keratinized epithelium of varying sizes form on the mucous membranes in the form of raised gray-white plaques.
The outcome of horny dystrophy depends on the course of the underlying disease. When eliminating the cause causing pathological keratinization, damaged tissue can be restored.
4. Extracellular and mixed dysproteinoses
Extracellular dysproteinoses
This includes long-term pathological processes in the interstitial substance of connective tissue due to impaired protein metabolism.
The causes of such dystrophies may be various infections and intoxication, as well as long-term consumption of feed containing excess proteins.
Extracellular dysproteinoses include: mucoid, fibrinoid swelling, hyaline (hyalinosis) and amyloid (amyloidosis) dystrophies.
Mucoid swelling
Mucoid swelling is a superficial disorganization of connective tissue, the initial stage of its changes. In this case, in the ground substance and in the collagen fibers of the connective tissue, the breakdown of protein-polysaccharide complexes and the accumulation of acidic mucopolysaccharides, which have the properties of metachromasia, besophylic stainability and hydrophilicity, occur. These substances increase tissue and vascular permeability. Collagen fibers are preserved, but their colorability changes. When stained with picrofuchsin, they turn out to be yellow-orange rather than red. These changes are accompanied by the appearance of lymphocytic and histiolymphytic infiltrates; mucoid swelling is detected only microscopically. This dystrophy occurs in various organs, but most often in the arteries, heart valves, endocardium and epicardium. The outcome can be twofold: complete tissue restoration or transition to fibrinoid swelling. Causes: various forms of oxygen deficiency, metabolic and endocrine system diseases.
Fibrinoid swelling
Fibrinoid swelling is characterized by disorganization of connective tissue, which is based on the destruction of collagen and the main interstitial substance, and a sharp increase in vascular permeability. The process of fibrinoid swelling is a more severe stage of connective tissue disorganization than with mucoid swelling. Fibrinoid is observed in the stroma of the organ, in the wall of blood vessels. Moreover, this process occurs from superficial disorganization, i.e., from shallow changes, to the disintegration of the collagen substance and the main substance. At histological examination disruption of collagen fibers is very significant. They become very swollen, their fibrous structure is disrupted, and when stained they acquire the properties of fibrin, which is why this process is called fibrinoid, and also protein substances such as fibrin are released. With fibrinoid swelling, disorganization of connective tissue occurs with redistribution of protein and mucopolysaccharides. Moreover, mucopolysaccharides are depolarized and dissolved. And depending on the degree to which the decay process has reached, various plasma proteins appear - albumin, globulins, fibrinogen. Fibrinoid change is a series of connective tissue conditions that are based on swelling, destruction of collagen and the formation of pathological protein compounds with mucopolysaccharides and hyaluronic acid.
The fibrinoid process is most often irreversible and progresses to sclerosis or hyalinosis. The significance of fibrinoid swelling is that the functions of the tissues in which this process develops are turned on.
Hyalinosis (hyaline dystrophy)
With this type of protein metabolism disorder, a homogeneous, dense, translucent protein mass appears between cells - hyaline.
This substance has significant resistance: it does not dissolve in water, alcohol, ether, acids and alkalis. There are no special reactions to detect hyaline. In histological preparations it is stained red with eosin or fuchsin.
Hyalinosis is not always a pathological phenomenon. It can also occur as a normal phenomenon, for example, in the ovaries during involution of the corpus luteum and follicular atrophy, in the arteries of the uterus and postpartum period, in the splenic artery in adult animals. At painful conditions hyalinosis is usually observed in the outcome of various pathological processes. Hyalinosis can be local and general (systemic).
Local hyaline dystrophy
In old scars, in capsules surrounding abscesses, necrosis and foreign bodies, hyaline is deposited. The same is observed with the growth of connective tissue in atrophying organs, with chronic interstitial inflammation, in blood clots, fibrous adhesions, in arteries with sclerotic changes.
Often, hyalinosis does not manifest itself in anything during an external examination of the organ and is detected only during microscopic examination. In those cases where hyalinosis is pronounced, the tissue becomes dense, pale and translucent.
Local deposition of hyaline can be in the intrinsic or basal membranes various glands(in the thyroid, mammary, pancreas, kidneys, etc.), which most often occurs during atrophic processes and in the presence of proliferation of interstitial tissue. In these cases, the glandular vesicles and tubules find themselves surrounded, instead of a thin, barely noticeable membrane of their own, by a thick, uniform ring of hyaline substance. In epithelial cells, atrophy phenomena are detected.
Hyaline dystrophy is also observed in organs that have a reticular network, mainly in the lymph nodes. In this case, the reticular fibers turn into massive dense cords, the cellular elements between them atrophy and disappear.
The process consists of the deposition along the reticular fibers of first liquid and then compacting protein, which merges with the fibers into a homogeneous mass. In the lymph nodes, this is most often observed with atrophy, chronic inflammation, and tuberculosis. In this case, the collagen fibers swell and merge into homogeneous strands. Cells atrophy.
General hyalinosis
This process becomes especially important when hyaline is deposited in the walls of blood vessels. It appears in the intima and perivascular tissue of small arteries and capillaries. Narrowing or complete obliteration of the vessel occurs due to thickening and homogenization of the wall. The media atrophies and is replaced by hyalinous masses.
Hyalinosis of blood vessels and connective tissue can occur in two ways.
1. A special physical and chemical modification of the fibrous substance occurs, transforming it into a homogeneous hyaline mass. The fibrils of connective tissue bundles swell and merge, fibrillarity is lost, the bundles become homogeneous and structureless. Subsequently, adjacent bundles merge, resulting in the formation of more extensive hyaline fields. The connective tissue acquires a very dense, often cartilage-like consistency.
2. Hyalinosis occurs as a result of increased permeability of blood vessels and tissues. Protein leaks out of the lumen of the blood vessels, the protein coagulates, becomes denser and takes on the appearance of a glassy dense mass. This process is referred to as plasma impregnation, or plasmorrhagia.
Hyalinosis, as a rule, is an irreversible process, with the exception of hyalinization of scar connective tissue, in which loosening and resorption of hyaline is possible. If the process is local, then special functional disorders does not arise. With significant general hyalinosis, the functions of organs, especially blood vessels, are impaired.
Amyloidosis (amyloid dystrophy)
The process consists in the deposition of a protein substance in the tissues, whose chemical composition is close to globulins (amyloid protein). This substance is dense, homogeneous, translucent, and is resistant to acids, alkalis, gastric juice, autolysis and decay. Amyloid is similar in many ways to hyaline, but differs from it and other proteins in some chemical reactions.
· Reaction with iodine and sulfuric acid. If a Lugol's solution is applied to the cut surface of an organ that has undergone amyloidosis, the areas of amyloid accumulation become reddish-brown or brownish-brown. Upon subsequent exposure to 10% sulfuric acid, the amyloid becomes blue-violet in color and after some time becomes dirty green.
· Staining with methyl violet and gentian violet gives the amyloid a red color and the tissues a violet color.
· Stained with Congo red. Amyloid is stained brownish-red, and tissues are pale pink or not stained at all.
Sometimes these reactions do not give positive results. This is explained by changes in the chemical composition of amyloid. The non-staining amyloid substance is called achroamyloid. Its deposits become similar to hyaline.
When small amounts of amyloid are deposited, the appearance of the organ does not change. If the process becomes pronounced, the organ enlarges, becomes dense, brittle, anemic; when cut, it has a peculiar translucent, waxy or greasy appearance. Microscopy reveals that initially, the amyloid substance is usually deposited in the walls of small blood vessels, under the argyrophilic membrane of the endothelium, as well as along the reticular fibers and under the basement membrane of the endothelium.
Amyloid dystrophy can be general, widespread, when the process affects several organs. In other cases it is local: limited to one place.
Amyloidosis of the spleen is follicular and diffuse.
A. In the follicular form, amyloid deposits occur first along the periphery of the follicles in the reticulum, and then spread to the entire follicle. Lymphocytes are displaced.
The central artery is thickened and has a homogeneous appearance. Macroscopically it is found that the spleen is moderately enlarged. The section shows altered follicles in the form of grains of boiled sago (“sago spleen”).
B. When diffuse form amyloid is deposited in the follicles and red pulp. Initially, separate, irregularly shaped islands appear, which then merge into a continuous mass. Cells atrophy. The spleen is enlarged and dense (dough-like only in horses). The cut surface is light red-brown in color and resembles ham (“greasy, or ham, spleen”).
Amyloidosis of the liver. Changes spread from the periphery to the center of the lobules. Initially, amyloid is deposited between the endothelium of intralobular capillaries and hepatic beams, as well as in the walls of interlobular vessels. As the process progresses, continuous areas of amyloid masses form, and the liver cells atrophy. The liver is enlarged, dense, pale brown. Only in horses it is flabby and breaks easily.
Amyloidosis of the kidneys. The process begins with the glomeruli. Amyloid is deposited under the argyrophilic intimal membranes of arteries, arterioles and vascular loops of the glomeruli. Lumps accumulate, squeezing the loops. Gradually the entire glomerulus is replaced by amyloid. Amyloidosis also spreads in the walls of the vessels of the cortex and medulla under the membrane of the tubular epithelium. Dystrophic changes and atrophy occur in the tubular epithelium. The kidneys are enlarged, dense, the cut surface is waxy. The causes of amyloid dystrophy are various. This includes chronic infectious diseases in which suppuration and necrosis occur, for example actinomycosis, tuberculosis; less often this occurs in chronic diseases that occur without suppuration and necrosis. The cause of amyloidosis may be prolonged and abundant consumption of protein-rich feed (for example, fattening geese). As a rule, this type of dystrophy is observed in horses that produce serums.
The outcome of general amyloidosis is unfavorable, since dystrophic changes, atrophy and necrosis of the parenchyma, occur in the altered organs.
Mixed dysproteinoses
Mixed dysproteinoses are a disorder of the protein metabolism of cells and intercellular substances. Dystrophic processes occur when the metabolism of complex proteins - nucleoproteins, glycoproteins and chromoproteins - is disrupted.
Nucleoprotein metabolism disorder
Nucleoproteins consist of protein and nucleic acids (DNA and RNA). The end product of nucleoprotein metabolism is uric acid and its salts. IN normal conditions These disintegration products in a dissolved state are excreted from the body primarily by the kidneys. When the metabolism of nucleoproteins is disrupted, excessive formation of uric acid occurs, and its salts are deposited in the tissues; This is observed with uric acid diathesis and uric acid renal infarction.
Uric acid diathesis is the deposition of uric acid salts in various tissues and organs. This is usually noted on the articular surfaces of the fingers of the extremities, in the tendons, in the cartilage of the auricle, kidneys and on the serous integument. At the site of deposition of urinary salt crystals, tissue elements undergo necrosis, and an inflammatory reaction develops around the dead areas with the proliferation of connective tissue.
More often, birds (chickens, ducks) get sick with uric acid diathesis, less often – mammals. In birds, uric acid salts in the form of a thick whitish mass are deposited on the serous membranes of the thoraco-abdominal cavity, on the pericardium and epicardium, in the kidneys and on the articular surfaces of the toes. Under the overlays, an inflamed serous layer is revealed. The kidneys are enlarged in volume, covered with a whitish coating, and whitish-gray or yellowish-white patches are found on the cut surface. Under the microscope, radiant urate crystals are visible; the epithelium of the renal tubules is in a state of granular degeneration and necrosis, and the stroma is infiltrated with lymphoid and giant cells. A lesion characterized by the deposition of urate salts in the joints of the toes is called gout. In this case, the joints swell, become deformed, and dense nodes form.
Uric acid renal infarction is a physiological condition that occurs in newborn animals in the first seven days, after which it disappears. This is due to changes in metabolic processes. The concentration of uric acid in the blood temporarily increases, which does not have time to be completely excreted from the body in urine. Macroscopically, on the cut surface of the kidneys in the medulla, reddish-yellow stripes are located radially, representing an accumulation of uric salts in the lumen of the straight tubules and in the stroma of the kidneys. In adult animals, with inflammation and necrosis of the mucous membrane of the bladder and renal pelvis, there may be incrustation (impregnation) of uric acid fluids in the dead tissue.
Deposition of uric acid in organs causes irreversible (necrotic) changes in the affected tissues.
Glycoprotein metabolism disorder
Glycoproteins are complex protein compounds with polysaccharides containing hexoses, hexosamines and hexuronic acids.
Mucosal dystrophy as a pathological process occurs in the epithelial cells of the mucous membranes, cells of a number of glands and connective tissue. It is a consequence of a violation of glucoprotein metabolism and is characterized by the accumulation of mucins and mucoids in cells. In the epithelium, mucous degeneration may be a consequence of hypersecretion of the mucous glands with increased desquamation of epithelial cells and their transformation into a mucus-like mass. In the connective tissue, mucous degeneration occurs in the interstitial substance, in which mucoid substances accumulate.
In the presence of water, the mucus swells, and with the addition of acetic acid or alcohol it precipitates and falls out in the form of a thin, delicate fibrous network. This distinguishes mucus from mucus-like substances (mucoids) formed in tissues both under normal and pathological conditions. Mucus, like amyloid, has metachromosia. Thus, when stained with cresyl violet and thionin, normal tissue is stained blue, and mucus is stained red.
Mucous degeneration of epithelial cells is well expressed in catarrhal inflammations in the mucous membranes, especially the respiratory and digestive organs. Under physiological conditions, the secretion of mucus, a product of the secretion of goblet cells, occurs as follows. First, tiny transparent droplets of mucus appear in the cells, which, merging with each other, form larger droplets. The cell increases in volume, swells, and finally the mucus is poured out in the form of a secretion, after which the cell collapses and restores its former appearance. Then droplets of mucus begin to appear on it again.
Mucous degeneration of epithelial cells is accompanied by increased formation and separation of mucus, necrosis and rejection of dead epithelial cells, the remains of which are mixed with mucus.
Mucosal dystrophy can affect various types of connective tissue, including cartilage and bone, as well as tumors of the connective tissue type. Swelling and, as it were, dissolution of fibrils occurs in the connective tissue.
In bones with mucous dystrophy, lime first disappears, and then the osteoid substance liquefies. Under the microscope, the altered tissue appears as a homogeneous, structureless mass, from which threads of mucin fall out under the influence of acids and alcohol. Most common cause, contributing to the appearance of mucous dystrophy of connective tissue, is a violation of tissue trophism in chronic infectious diseases, intoxication, disorders of the endocrine glands and tumors.
When the causes that caused mucous dystrophy are eliminated, tissue restoration occurs.
5. Violation of chromoprotein (pigment) metabolism. Exogenous and endogenous pigments
All tissues and organs of animals are characterized by a certain color - pigmentation. Some pigments are found in tissues in a dissolved state, others have the form of granular, amorphous and crystalline deposits. All of them are formed by the body itself, are found under physiological conditions and are called endogenous. In addition, under certain pathological conditions, pigments from the external environment that are not normally characteristic of it can penetrate into the animal and human body. They are called exogenous.
Endogenous pigments are in turn divided into three groups depending on the source of their formation.
1. Hemoglobinogenic, which arise from hemoglobin during its various transformations. These include ferritin, hematoidin, hemosiderin and bilirubin studied in pathomorphology.
2. Proteinogenic pigments, which are not related to hemoglobin and are derivatives of tyrosine and tryptophan. These include melanin, andrenochromes and enterochromaffin cell pigment.
3. Lipidogenic pigments associated with fat metabolism. These include lipochromes, lipofuscin and ceroid.
Hemoglobinogenic pigments are formed as a result of the physiological and pathological breakdown of red blood cells, which contain the high molecular weight chromoprotein hemoglobin, which gives the blood a specific color.
Ferritin is a reserve iron protein. It is formed from dietary iron in the intestinal mucosa and pancreas and during the breakdown of red blood cells and hemoglobin in the spleen, liver, bone marrow and lymph nodes. In these organs it can be isolated by a histochemical reaction to Prussian glaze.
Hemosiderin is a fine-grained, amorphous iron-containing pigment of golden brown or brown color. It is located intracellularly, and in cases of cell breakdown lies freely in the tissues. Hemosiderin is formed by cells during phagocytosis of red blood cells or from hemoglobin dissolved in plasma. The appearance of hemosiderin in tissues is called hemosiderosis, which can be general and local.
General hemosiderosis occurs with intravascular hemolysis, for example with sepsis, equine infectious anemia, piroplasmosis, and with certain poisonings (arsenic, phosphorus, etc.). Hemoglobin released from red blood cells dissolves in plasma and is partially excreted in the urine. The other part is absorbed by reticuloendothelial cells and converted into hemosiderin, and general hemosiderosis occurs. Hemosiderin is formed only intracellularly. Hemosiderin deposits occur primarily in the spleen, then in the liver, bone marrow, lymph nodes, and also in the kidneys in the order of excretory function. These organs take up hemosiderin and are found in reticuloendothelial cells and in the epithelium of the convoluted tubules of the kidneys. Hemosiderin is soluble in acids, insoluble in alkalis, alcohol and ether, and is not discolored by hydrogen peroxide. To differentiate hemosiderin from other intracellular inclusions, the following reactions are used.
· Perls reaction: when histological sections are treated with potassium iron sulfide (yellow blood salt) in the presence of hydrochloric acid, the pigment turns greenish-blue (“Perlin glaze”).
· From the addition of ammonium sulfide, hemosiderin turns black, and with further treatment with potassium iron sulfide and hydrochloric acid, the pigment acquires a blue color (“Turnbull blue”).
Local hemosiderosis is observed with extravascular hemolysis of red blood cells, which is observed with hemorrhages. Hemosiderin accumulates in the cytoplasm of cells along the periphery of the hemorrhage.
Hematoidin is also formed during the breakdown of hemoglobin. This pigment does not contain iron and has the form of crystals that look like rhombic formations or resemble bunches of bright orange needles. When pigment accumulates, various shapes appear in the form of stars, panicles, sheaves, etc. Less commonly, hematoidin occurs in the form of amorphous granularity or lumps. This pigment dissolves in alkalis, decomposes with strong nitric and sulfuric acids, is difficult to dissolve in alcohol and ether, and does not discolor with hydrogen peroxide.
Hematoidin is formed in central parts hemorrhages where there are no cells and oxygen access.
Bilirubin. This pigment is constantly formed and constantly undergoes various transformations, participating in the metabolism of a normal body. It is formed in the reticuloendothelial system during the physiological destruction of red blood cells, enters the liver and is included in the composition of bile formed by liver cells. Bilirubin is dissolved in bile and causes its characteristic coloring. In its properties, this pigment is close to hematoidin and gives a positive Gmelin reaction: when exposed to nitric acid, colored rings are formed. Normally, bile is located in bile ducts and the gall bladder, from where it is excreted into the duodenum. Under pathological conditions, the normal formation and secretion of bile is disrupted; bilirubin enters the blood, which is accompanied by tissue staining yellow. Such yellow staining of all organs, and especially the sclera of the eyes, visible mucous membranes, serous integument and intima of blood vessels, is called jaundice, which, by origin and pathogenesis, is divided into three types: hemolytic, parenchymal and mechanical.
· Hemolytic jaundice occurs due to intravascular hemolysis of red blood cells. Large quantities of hemoglobin breakdown products enter the cells of the reticuloendothelial system. This increases the production of bilirubin or a pigment close to it, which enters directly into the blood.
· Parenchymal jaundice is caused by a violation of the outflow of bile from the liver, which occurs as a result of dysfunction of the liver cells. These cells lose the ability to secrete bile into the bile capillaries, so the bile diffuses into the blood through the walls of the blood and lymph capillaries. The causes of parenchymal jaundice are various. These are mainly infectious diseases and poisoning.
Proteinogenic pigments include melanin, andrenochomas and enterochominic cell pigment.
Melanin - this pigment determines the color of the skin, hair, plumage of birds, eyes. Normal melanin content depends on the type of animal, breed, age and individual characteristics. Under microscopy, melanin is detected in the form of brown or black grains lying in the protoplasm of cells. Chemically, melanoprotein contains sulfur, carbon and nitrogen, but lacks iron and fat. It does not dissolve in acids and alkalis, is colored black with silver nitrate and discolored by the action of hydrogen peroxide. Melanin formation occurs in the cells of the Malpighian layer of the epidermis and retina. The cells that produce melanin are called melanoblasts.
Disorders of melanogenesis are manifested by increased formation of melanin, its accumulation in unusual places, disappearance or absence of pigment. These disorders can be acquired or congenital and be widespread or local in nature.
Excessive formation of melanin in the skin and its deposition in internal organs called general melanosis. It is more common in large and small cattle, especially calves and sheep. It is believed that this process is of feed origin. Melanin is deposited in the liver, lungs and on the serous integument, less often in the membranes of the brain and spinal cord, which acquire a dark brown or brown-black color.
Local excess pigmentation of the skin is associated with benign or malignant proliferation of melanoblasts with the formation of melanomas.
They often occur in gray horses and dogs. The sources of their appearance are birthmarks.
Congenital insufficient formation of melanin or its complete absence in the body is called albinism. This condition is typical for some species and breeds of animals (white mice, rats, rabbits, etc.).
Local congenital depigmentation of the skin is called vitiligo. In some cases, after prolonged inflammation and other lesions (wounds, ulcers, breeding disease of horses), pigmentless spots called leukoderma form on the skin.
Lipidogenic pigments. These include lipochromes, lipofuscin and ceroid. They contain fat and protein substances.
Lipofuscin is a glycolipoprotein, has the appearance of brown grains or lumps. Its formation is associated with the oxidative process - autoxidation of phospholipids and fats. It is stained red by Sudan III and scarlet and does not react to iron. Insoluble in acids and alkalis; Unlike melanin, silver nitrate does not turn black. In animals, lipofuscin is found in cardiac, skeletal and smooth muscles, kidneys, adrenal glands, liver, nerve cells, seminal vesicles and testes.
Pathological pigmentation with lipofuscin usually manifests itself with atrophy of the heart muscle, liver, kidneys and in the cells of the central nervous system.
The pigments of hemofuscin, found in the liver of horses with infectious encephalomyelitis, and ceroid, the formation of which is associated with hypovitaminosis E, are identical in physicochemical composition to lipofuscin.
Lipochromes are yellow pigments that give a yellow color to adipose tissue, the adrenal cortex, egg yolk, blood serum, etc. Lipochromes also include lutein, the pigment of the corpus luteum of the ovary. These pigments dissolve in reagents - fat solvents and represent a lipid in which colored hydrocarbons - carotenoids and flavins - are dissolved. The formation of lipochrome and lutein is associated with the metabolism of fat and proteins. With atrophy of fatty tissue in old and emaciated animals, the fat becomes richly yellow.
Exogenous pigments
This is the name given to various colored substances that enter the body from the external environment, which can change the natural color of organs or give them a different shade. Most often, exogenous pigments are observed in the lungs and regional lymph nodes, less often in the spleen, liver, and kidneys. The deposition of foreign materials in the lungs is called pneumoconiosis. This can be observed when animals spend a long time in places where the air is polluted with dust particles of various origins. The most important is the dusting of the lungs with coal dust - anthracosis.
Under the pleura and inside the pulmonary lobes there are accumulations of coal in the form of black areas or in the form of diffuse dust. Under a microscope, carbon particles are visible around blood vessels, in the alveolar epithelium and interstitium. Coal dust also accumulates in the mediastinal and bronchial lymph nodes. With significant deposition, coal particles can cause inflammatory changes in the lungs with subsequent proliferation of connective tissue. When the lungs are dusted with lime particles, whitish lesions (chalicosis) appear. If the lungs become dusty with silica, alumina or quartz lumps, silicosis occurs, which is accompanied by pulmonary sclerosis.
In the case of prolonged treatment of animals with drugs containing silver, the latter is deposited in the epithelium of the vascular glomeruli, in the basement membrane of the renal tubules (renal argyrosis). Silver salts are also found in the liver, Kupffer cells and in the walls of blood vessels. Macroscopically, tissues with argyrosis acquire a gray (steel) color.
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Dystrophy is a pathological process reflecting a metabolic disorder in the body, in which cells and intercellular substance are destroyed.
Essence dystrophy is that an excess or insufficient amount of compounds is formed in the cell and intercellular substance, or substances that are not inherent in the cell are formed.
Mechanisms development of dystrophy:
infiltration- more substances enter the blood than necessary;
perverted synthesis- is the synthesis in cells or tissues of substances that are not normally found in them. These include: the synthesis of abnormal amyloid protein in the cell, which is normally absent in the human body;
transformation- the transition of one substance to another. For example, the transformation of carbohydrates into fats in diabetes mellitus;
decomposition or phanerosis - the breakdown of cellular and intercellular structures, which leads to the accumulation of excess proteins or fats in the cell.
Classification. Dystrophies can be reversible or irreversible.
Based on the distribution of dystrophy, there are general and local ones.
Depending on the causes, dystrophy can be acquired or hereditary.
According to the level of occurrence of dystrophy they are divided into:
parenchymal- arise at the cellular levels;
mesenchymal- arise at the intercellular level;
mixed- for disorders in cells and intercellular substance.
General etiology of the disease. The concept of risk factors. Heredity and pathology
General etiology of the disease. Etiology- this is the doctrine of the causes and conditions of the occurrence of diseases and pathological processes.
There are diseases whose causes are easy to determine (for example, a skull injury leads to a disease - a concussion).
The causes of diseases are the pathological factor that causes the disease.
Every disease has its own cause.
The reasons are exogenous and endogenous.
Concept of risk factors. Disease risk factors- these are factors that increase the likelihood of a particular disease.
Disease risk factors
Heredity and pathology. There are genetic diseases that are inherited.
According to the autosomal recessive type - they are inherited by both boys and girls - regardless of gender (phenylketonuria, butterfly wings).
There are hereditary diseases that are transmitted according to the dominant type - when one gene suppresses the action of another.
There are diseases linked to gender.
Chromosomal diseases - when children are born with a chromosome disorder (Down's disease).
The main mechanism of hereditary pathology is errors in hereditary information. Causes can be exogenous and endogenous
Pathogenesis and morphogenesis of diseases. The concept of “symptoms” and “syndromes”, their clinical significance
Pathogenesis(pathos - disease, genesis - development) - the doctrine of the general patterns of development, course and outcome of diseases. Pathogenesis reflects the essence of damage at different levels of life and the mechanisms of compensatory and adaptive reactions during the development of the disease.
The section of pathogenesis that considers the system of protective processes aimed at restoring disrupted processes and stopping the disease is called sanogenesis (sanis - health, genesis - development). Sanogenesis, like pre-disease, is not an established concept; some pathologists (the school of S. M. Pavlenko) assign it the role of a paired category with pathogenesis with its own numerous patterns.
Morphogenesis(morphos - form, genesis - development) considers the dynamics structural damage in organs and systems during the development of the disease. Over time, including under the influence of various treatment methods, there is a gradual change in the patho- and morphogenesis of the disease - the timing of the course, outcomes, percentage of complications, etc. change. This process is called pathomorphosis.
(The pathomorphosis is most clearly seen in the example of infectious diseases under the influence of systematic (in the population) use of antibiotics.)
The morphofunctional unity of the body (mutual dependence and interrelation of processes of disturbance of structure and function) is one of the main provisions of nosology. In accordance with this, in pathology there are no isolated “functional” or “structural” defects, but a system of them is always present. In this sense, it is much more logical to consider morphogenesis as a paired category to pathogenesis than sanogenesis.
An important category is the relationship local And general during the development of the disease. A disease is always a general process in the body, but the totality of local manifestations makes up its entire originality.
You should also note the category reversibility. When we are talking about a return to a similar state (for example, recovery from an illness), it is convenient to call such processes reversible, and those where a return does not occur - irreversible. A category can refer not only to the organism as a whole, but to its specific morphofunctional feature.
Specific And nonspecific In the development of the disease they also go side by side. The more general pattern detected in the disease, the less specific it is and is present in many other conditions.
As a disease develops under the influence of a causative factor, a sequential set of processes develops that determine the specificity, essence of the disease, and its uniqueness. Such a complex is usually called leading link in pathogenesis.
As the disease develops, the sequence of processes often closes in so-called “vicious circles”, when subsequent changes lead to an intensification of the primary damage.
In pathogenesis, the following levels of damage are distinguished:
molecular;
cellular;
fabric;
organ;
systemic;
organismic.
Symptom- a sign of illness.
There are symptoms: subjective and objective. TO objective include: examination of the patient, palpation, percussion (tapping) and auscultation (listening). Subjective symptoms represent the patient's sensation. This is a reflection in the patient’s consciousness of pathological changes in the body.
Syndrome is a set of closely related symptoms that reflect certain pathological changes in systems and tissues. For example: edema syndrome (edema, anasarca ascites, pallor or cyanosis of the skin); bronchospastic (suffocation, cough, wheezing on auscultation); shock syndrome (weakness, wet skin, thready pulse, low blood pressure).
5. Violation of chromoprotein (pigment) metabolism. Exogenous and endogenous pigments
1. Definition, etiology, classification, general characteristics
Under dystrophy (degeneration, degeneration) understand pathological changes in organs that arise as a result of metabolic disorders in them. These are qualitative changes in the chemical composition, physicochemical properties and morphology of cells and tissues of the body associated with metabolic disorders.
Dystrophies are classified as damage, or alterative processes: this is a change in the structure of cells, intercellular substance, tissues and organs, which is accompanied by disruption of their vital functions. These changes, as phylogenetically the most ancient type of reactive processes, occur at the earliest stages of the development of a living organism.
Damage can be caused by a variety of causes. They affect cellular and tissue structures directly or through humoral and reflex influences. The nature and extent of damage depend on the strength and nature of the pathogenic factor, the structure and function of the organ, as well as on the reactivity of the body. In some cases, superficial and reversible changes occur in ultrastructures, while in others, deep and irreversible changes occur, which can result in the death of not only cells and tissues, but also the entire organ.
Dystrophy is based on a violation of the metabolism of cells and tissues, leading to structural changes.
The direct cause of the development of dystrophies can be violations of both cellular and extracellular mechanisms that provide trophism:
1) disorder of cell autoregulation (toxin, radiation, lack of enzymes) leads to energy deficiency and disruption of enzymatic processes in the cell;
2) disruption of the transport systems that ensure metabolism and cell structure causes hypoxia, which is the leading cause in the pathogenesis of dystrophy;
3) a disorder of the endocrine regulation of trophism or a disorder of the nervous regulation of trophism leads to endocrine or nervous dystrophy.
There are also intrauterine dystrophies.
With dystrophies, metabolic products (proteins, fats, carbohydrates, minerals, water) accumulate in cells or outside them, which are characterized by quantitative or qualitative changes.
Among the morphological mechanisms leading to the development of changes characteristic of dystrophies, a distinction is made between infiltration, decomposition, perverted synthesis and transformation.
The first two are the leading morphological mechanisms of dystrophy.
The characteristic morphology of dystrophies is revealed, as a rule, at the cellular and tissue levels.
Dystrophic processes are observed both in the cytoplasm and nucleus, and in the intercellular substance and are accompanied by a violation of the structure of cells and tissues, as well as a disorder of their function.
Dystrophy is a reversible process, but can lead to irreversible changes in cells and tissues, causing their decay and death.
In morphological terms, dystrophies are manifested by a violation of the structure, primarily the ultrastructure of cells and tissues, when regeneration is disrupted at the molecular and ultrastructural levels. In many dystrophies, inclusions of “grains”, stones or crystals of various chemical natures are found in cells and tissues, which under normal conditions do not occur or their number increases compared to the norm. In other cases, the amount of compounds decreases until they disappear (fat, glycogen, minerals).
The structure of the cell is lost (muscle tissue - cross-striation, glandular cells - polarity, connective tissue - fibrillar structure, etc.). In severe cases, discomplexation of cellular elements begins. The color, size, shape, consistency, and pattern of organs change microscopically.
The change in the appearance of the organ served as the basis for calling this process degeneration or degeneration - a term that does not reflect the essence of dystrophic changes.
The classification of dystrophies is associated with the type of metabolic disorder. Therefore, protein dystrophies are distinguished (intracellular dysproteinoses, extracellular and mixed); fatty (mesenchymal and parenchymal), carbohydrate (disorder of glycogen metabolism), mineral (stones - calculi, disturbance of calcium metabolism).
According to their prevalence, they are divided into general, systemic and local; by localization - parenchymal (cellular), mesenchymal (extracellular) and mixed; according to the influence of genetic factors - acquired and hereditary.
Dystrophies are reversible processes, but can lead to necrosis.
Etiology of dystrophies: the effects of many external and internal factors (biologically inadequate feeding, various conditions of keeping and exploitation of living things, mechanical, physical, chemical and biological effects, infections, intoxications, disorders of blood and lymph circulation, damage to the endocrine glands and nervous system, genetic pathology and etc.).
Pathogenic factors act on organs and tissues either directly or reflexively through the neurohumoral system that regulates metabolic processes. The nature of dystrophies depends on the strength, duration and frequency of exposure to a particular pathogenic irritation on the body, as well as the reactive state of the body and the type of damaged tissue.
Dystrophies are noted in all diseases, but in some cases they arise eternally and determine the nature of the disease, and in others they represent a nonspecific or non-physiological pathological process accompanying the disease.
The functional significance of dystrophies lies in the disruption of the basic functions of the organ (for example, the synthesis of protein, carbohydrates, lipoproteins in hepatosis, the appearance of protein in the urine in nephrosis, heart weakness in myocardial dystrophy in patients with foot-and-mouth disease, etc.).
2. Protein dystrophy (dysproteinoses), its essence and classification
The essence of protein dystrophies is that the protein of tissue elements in dystrophies often differs from the norm in external signs: it is either liquefied or very compacted. Sometimes protein synthesis changes and their chemical structure is disrupted. Often, products of protein metabolism are deposited in tissues and cells, which are not found at all in a healthy body. In some cases, the processes are limited by disruption of the proteins that make up the cell, and in others, the structure of the proteins included in the intercellular substances is disrupted. Protein dysproteinoses, which occur mainly in cells, include the so-called intracellular dystrophic processes: granular dystrophy, hyaline-droplet, hydropic, horny dystrophy.
Extracellular dysproteinoses include hyalinosis and amyloidosis; mixed – disturbance of the metabolism of nucleoproteins and glucoproteins.
3. Intracellular dysproteinoses, their characteristics, outcome and significance for the body
Granular dystrophy the most common of all types of protein dystrophies. It manifests itself independently or as a component of the inflammatory process. The causes of granular dystrophies are various intoxications, blood and lymph circulation disorders, infectious diseases, febrile conditions, etc. All these factors can reduce oxidative processes and contribute to the accumulation of acidic products in cells.
Granular dystrophy occurs in many organs, most clearly expressed in parenchymal ones: in the kidneys, heart muscle, and liver, which is why it is also called parenchymal.
Pathological and anatomical signs: upon external examination, the organ is slightly enlarged, the shape is preserved, the consistency is usually flabby, the color is usually much paler than normal, the pattern on the cut surface is smoothed.
When cutting, in particular the kidneys, liver, due to swelling, the edges of these organs can protrude significantly beyond the edges of the connective tissue capsule. In this case, the cut surface is cloudy, dull, and lacks natural shine. For example, the heart muscle resembles the appearance of meat scalded with boiling water; this gave grounds for many researchers, when describing the signs of granular dystrophy, to say that the muscle has the appearance of boiled meat. Turbidity, dullness, and swelling of organs are very characteristic signs for this type of dystrophy. Therefore, granular dystrophy is also called cloudy swelling. In animals with enhanced nutrition, soon after feeding, changes sometimes appear in the kidneys and liver, the same as in granular dystrophy, turbidity, dullness, but expressed to a weak degree. With granular dystrophy, the cell is swollen, the cytoplasm is filled with small, barely noticeable protein grains. When such tissue is exposed to a weak solution of acetic acid, the granularity (protein) disappears and no longer appears. This indicates the protein nature of the grain. The same thing is observed when studying the muscle fibers of the heart. Protein granules appear in the muscle, located between the fibrils. The fibers swell, and the transverse striation of the muscle fibers is lost with further development of the process. And if the process does not stop there, the fiber may disintegrate. But granular dystrophy rarely affects the entire heart muscle; more often the process occurs on the surface or internal part of the myocardium of the left ventricle; it has a focal distribution. The changed areas of the myocardium have a grayish-red color.
In pathology, there is a judgment about two stages of development of this process. Some believe that cloudy swelling is the primary stage of granular dystrophy, and pronounced phenomena of necrobiotic changes with cell necrosis are granular dystrophy. This division of dystrophy processes is conditional and not always justified. Sometimes, with cloudy swelling of the kidneys, cell necrosis occurs.
The essence of the process during dystrophy is the increased breakdown of proteins, fats, carbohydrates with the appearance of an acidic environment, with increased absorption of water and retention of metabolic products in the cells. All this leads to swelling of colloids and a change in the appearance of a group of coarsely dispersed proteins that are contained in the cytoplasm of the cells of these organs.
Particularly significant changes in protein dystrophies and, in particular, in granular dystrophy occur in mitochondria. It is known that redox processes occur in these organelles. Normally, depending on the intensity of redox processes, significant variability occurs in the shape and size of mitochondria. And in pathological conditions, especially those accompanied by hypoxia, mitochondria swell, they increase in size, their outer membranes stretch, and the inner membranes move away from one another, and vacuoles appear. At this stage, mitochondrial vacuolization is reversible. With more intense and prolonged development of the process, vacuolization can lead to irreversible necrobiotic changes and necrosis.
The outcome of granular dystrophy depends on the degree of cell damage. The initial stage of this dystrophy is reversible. In the future, if the causes that caused it are not eliminated, then necrosis or a more severe type of metabolic disorder may occur - fatty, hydropic degeneration.
When the process lasts for a long time, for example during fever, not only cell degeneration occurs, but necrosis also occurs. The latter look like light areas.
Changes in granular dystrophy are sometimes similar to cadaveric changes. But with cadaveric changes there will be no swelling of cells, while with granular degeneration there will be uneven swelling of cells with the simultaneous presence of unchanged areas of tissue in the organ. This is how postmortem changes differ from granular dystrophy.
Hyaline-drip dystrophy is characterized by a disorder of protein metabolism and occurs in the cytoplasm with the formation of large protein droplets. At first, these drops are single, small, the nucleus in the cell is not disturbed. With the further action of the cause causing this process, the drops increase in volume and number, the core moves to the side, and then, as the drops continue to form, they gradually disappear. Protein deposits in the cytoplasm acquire a homogeneous appearance, similar to hyaline cartilage. Mitochondria are swollen or in a state of decay. Protein droplets that appear in cells have a hyaline structure. The buds are dense, the cortex is gray and dull, the pyramids are reddish. Most often, cells in such cases acquire the character of cloudy swelling, followed by denaturation of proteins in the cytoplasm of the cells. If the death of the nucleus occurs, then this refers to cell necrosis.
Hyaline droplet dystrophy is most often observed in the epithelium of the renal tubules, less often in the liver. Sometimes it is combined with fatty degeneration or amyloidosis. These dystrophies are observed in chronic infectious diseases, intoxication and poisoning of the body.
Dropsy (hydropic, or vacuolar) dystrophy is characterized by the fact that cells undergo dissolution-liquefaction. Initially, vacuoles with liquid are visible in the cytoplasm, and sometimes in the nucleus, and with further development of the process, the vacuoles merge and the entire cytoplasm is filled with liquid, the nucleus seems to float in it, which then turns into one bubble filled with liquid. Such cells usually die. The intercellular ground substance and connective tissue swell and the entire tissue liquefies. With hydrocele, vacuoles are visible on preparations treated with alcohol, so it is necessary to differentiate these processes from staining for fat.
Dropsy dystrophies occur with edema, burns, smallpox, foot-and-mouth disease, viral hepatitis, chronic neuroses and other septic diseases.
The outcome of hydrocele is favorable in the initial stages and with the restoration of normal water and protein metabolism, the process is easily reversible, and the cells acquire a normal appearance. Cells in a state of severe hydropia die.
Vacuolar dystrophy is determined only by microscopic examination. The appearance of the organ is not changed, but the color is paler than normal. The function of organs, as with any dystrophies, is reduced. Vacuolization often occurs in the epithelium of the kidneys, liver cells, skin cells, leukocytes, cardiac and skeletal muscles, and ganglion cells of the central nervous system.
Pathological keratinization or horny dystrophy is excessive (hyperkeratosis) or qualitatively impaired (parakeratosis, hypokeratosis) formation of horny substance.
Cell keratinization is a physiological process that develops in the epidermis and is characterized by the gradual transformation of squamous epithelium of the skin into horny scales, forming the stratum corneum of the skin. Pathological keratinization develops in connection with disease or damage to the skin and mucous membranes. The basis of these processes is the excessive formation of the horny substance of the skin. This process is called hyperkeratosis. Sometimes there is a growth of horny substance in unusual places - on the mucous membranes. Sometimes in tumors, horny substance is formed in epithelial cells in some forms of cancer.
Pathological keratinization differs from physiological keratinization in that keratinization of the epithelium occurs due to factors that cause increased formation of horny substance. Often there is a process of hyperkeratosis of local origin, which occurs when the skin is irritated, for example, by improperly fitting harness on a horse; prolonged pressure on the skin causes calluses.
Parakeratosis is expressed in the loss of the ability of epidermal cells to produce keratohyalin. Microscopically, this disease reveals thickening of the epidermis as a result of hyperplasia of cells of the Malpighian layer and excessive accumulation of the stratum corneum. With para- and hypokeratosis, atrophy of the granular layer is expressed, the stratum corneum is loose, with discomplexed cells having rod-shaped nuclei (incomplete keratinization).
Macroscopically, with parakeratosis, the stratum corneum is thickened, loose, with increased desquamation of horny scales. In adult animals, especially dairy cows, abnormal growth of the hoof horn is noted, which loses its glaze and cracks.
With leukoplakia, foci of keratinized epithelium of varying sizes form on the mucous membranes in the form of raised gray-white plaques.
The outcome of horny dystrophy depends on the course of the underlying disease. When the cause of pathological keratinization is eliminated, the damaged tissue can be restored.
4. Extracellular and mixed dysproteinoses
Extracellular dysproteinoses
This includes long-term pathological processes in the interstitial substance of connective tissue due to impaired protein metabolism.
The causes of such dystrophies can be various infections and intoxications, as well as long-term consumption of feed containing excess amounts of proteins.
Extracellular dysproteinoses include: mucoid, fibrinoid swelling, hyaline (hyalinosis) and amyloid (amyloidosis) dystrophies.
Mucoid swelling
Mucoid swelling is a superficial disorganization of connective tissue, the initial stage of its changes. In this case, in the ground substance and in the collagen fibers of the connective tissue, the breakdown of protein-polysaccharide complexes and the accumulation of acidic mucopolysaccharides, which have the properties of metachromasia, besophylic stainability and hydrophilicity, occur. These substances increase tissue and vascular permeability. Collagen fibers are preserved, but their colorability changes. When stained with picrofuchsin, they turn out to be yellow-orange rather than red. These changes are accompanied by the appearance of lymphocytic and histiolymphytic infiltrates; mucoid swelling is detected only microscopically. This dystrophy occurs in various organs, but most often in the arteries, heart valves, endocardium and epicardium. The outcome can be twofold: complete tissue restoration or transition to fibrinoid swelling. Causes: various forms of oxygen deficiency, metabolic and endocrine system diseases.
Fibrinoid swelling
Fibrinoid swelling is characterized by disorganization of connective tissue, which is based on the destruction of collagen and the main interstitial substance, and a sharp increase in vascular permeability. The process of fibrinoid swelling is a more severe stage of connective tissue disorganization than with mucoid swelling. Fibrinoid is observed in the stroma of the organ, in the wall of blood vessels. Moreover, this process occurs from superficial disorganization, i.e., from shallow changes, to the disintegration of the collagen substance and the main substance. On histological examination, the disruption of collagen fibers is very significant. They become very swollen, their fibrous structure is disrupted, and when stained they acquire the properties of fibrin, which is why this process is called fibrinoid, and also protein substances such as fibrin are released. With fibrinoid swelling, disorganization of connective tissue occurs with redistribution of protein and mucopolysaccharides. Moreover, mucopolysaccharides are depolarized and dissolved. And depending on the degree to which the decay process has reached, various plasma proteins appear - albumin, globulins, fibrinogen. Fibrinoid change is a series of connective tissue conditions that are based on swelling, destruction of collagen and the formation of pathological protein compounds with mucopolysaccharides and hyaluronic acid.
The fibrinoid process is most often irreversible and progresses to sclerosis or hyalinosis. The significance of fibrinoid swelling is that the functions of the tissues in which this process develops are turned on.
Hyalinosis (hyaline dystrophy)
With this type of protein metabolism disorder, a homogeneous, dense, translucent protein mass appears between cells - hyaline.
This substance has significant resistance: it does not dissolve in water, alcohol, ether, acids and alkalis. There are no special reactions to detect hyaline. In histological preparations it is stained red with eosin or fuchsin.
Hyalinosis is not always a pathological phenomenon. It can also occur as a normal phenomenon, for example, in the ovaries during involution of the corpus luteum and atrophy of the follicles, in the arteries of the uterus and the postpartum period, in the splenic artery in adult animals. In painful conditions, hyalinosis is usually observed as a result of various pathological processes. Hyalinosis can be local and general (systemic).
Local hyaline dystrophy
In old scars, in capsules surrounding abscesses, necrosis and foreign bodies, hyaline is deposited. The same is observed with the growth of connective tissue in atrophying organs, with chronic interstitial inflammation, in blood clots, fibrous adhesions, in arteries with sclerotic changes.
Often, hyalinosis does not manifest itself in anything during an external examination of the organ and is detected only during microscopic examination. In those cases where hyalinosis is pronounced, the tissue becomes dense, pale and translucent.
Local deposition of hyaline can be in the own, or basal, membranes of various glands (in the thyroid, mammary, pancreas, kidneys, etc.), which most often occurs during atrophic processes and in the presence of proliferation of interstitial tissue. In these cases, the glandular vesicles and tubules find themselves surrounded, instead of a thin, barely noticeable membrane of their own, by a thick, uniform ring of hyaline substance. In epithelial cells, atrophy phenomena are detected.
Hyaline dystrophy is also observed in organs that have a reticular network, mainly in the lymph nodes. In this case, the reticular fibers turn into massive dense cords, the cellular elements between them atrophy and disappear.
The process consists of the deposition along the reticular fibers of first liquid and then compacting protein, which merges with the fibers into a homogeneous mass. In the lymph nodes, this is most often observed with atrophy, chronic inflammation, and tuberculosis. In this case, the collagen fibers swell and merge into homogeneous strands. Cells atrophy.
General hyalinosis
This process becomes especially important when hyaline is deposited in the walls of blood vessels. It appears in the intima and perivascular tissue of small arteries and capillaries. Narrowing or complete obliteration of the vessel occurs due to thickening and homogenization of the wall. The media atrophies and is replaced by hyalinous masses.
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MINISTRY OF AGRICULTURE OF THE RUSSIAN FEDERATION
Federal State Budgetary Educational Institution of Higher Professional Education "Yakut State Agricultural Academy"
Faculty of Veterinary Medicine
Test
Topic: Dystrophy
Completed by: 4th year student
Andreev P.V.
Checked by: Tomashevskaya E.P.
Yakutsk, 2014.
General concepts about dystrophy
Dystrophy - (from the Greek dys - disorder, trophe - nutrition) - qualitative changes in the chemical composition, physicochemical properties and morphological appearance of cells and tissues of the body associated with metabolic disorders. Changes in metabolism and cell structure, reflecting the adaptive variability of the organism, are not related to dystrophic processes.
Etiology. Disruption of metabolic processes, leading to structural changes in tissues, is observed under the influence of many external and internal factors (biologically inadequate feeding, various conditions of keeping and exploitation of animals, mechanical, physical, chemical and biological effects, infections, intoxication, disorders of blood and lymph circulation, lesions endocrine glands and nervous system, genetic pathology, etc.). Pathogenic factors act on organs and tissues either directly or reflexively through the neurohumoral system, which regulates metabolic processes. The nature of dystrophic processes depends on the strength, duration and frequency of exposure to a particular pathogenic stimulus on the body, as well as the reactive state of the body and the type of damaged tissue. Essentially, dystrophic changes are noted in all diseases, but in some cases they arise primarily and determine the nature of the disease, and in others they represent a nonspecific or secondary pathological process accompanying the disease.
Pathogenesis. Modern research methods (histochemical, electron microscopic, autoradiographic, biochemical, etc.) have shown that the basis of any dystrophic process is a violation of enzymatic reactions (enzymopathy) in the exchange (synthesis and breakdown) of substances with damage (alteration) to the structure and functions of the cell - tissue systems of the body. At the same time, metabolic products accumulate in the tissues (changed both quantitatively and qualitatively), physiological regeneration (restoration of living matter primarily at the molecular and ultrastructural levels of its organization) and the functions of one or another organ, as well as the vital activity of the organism as a whole, are disrupted.
Classification of dystrophies
Dystrophy is distinguished by origin, pathogenesis and prevalence of the process. By origin there are acquired and congenital, by pathogenesis decomposition, infiltration, transformation, and altered synthesis, and by the prevalence of the process local and general.
The mechanism of development and the essence of changes in different dystrophies are not the same.
According to the mechanism of the process of dystrophic changes, they distinguish: decomposition; infiltration; transformation and altered or perverted synthesis.
Decomposition (from Latin decompositio - restructuring) is a change in ultrastructures, macromolecules and complex (protein-fat-carbohydrate and mineral) compounds of cellular and tissue systems. The immediate causes of this restructuring are an imbalance of nutrients, metabolites and metabolic products, hypoxia and intoxication, changes in temperature (fever, colds), disturbances in acid-base balance (acidosis, less commonly alkalosis), redox and electrolyte potential of cells and tissues.
As a result of changes in the basic parameters of cell-tissue systems (pH, state of the ATP system, etc.), complex biological compounds of cellular organelles and macromolecules either change or break down into simpler compounds that become available for histochemical examination. Free proteins are hydrolyzed with the participation of lysosome enzymes or denatured. In this case, along with primary damage to ultrastructures, secondary processes may occur (for example, the formation of complex compounds such as amyloid, hyaline, etc.).
Pathological infiltration (from the Latin infiltratio - impregnation) is characterized by deposition and accumulation (deposition) in cells and tissues of metabolic products (proteins, lipids, carbohydrates, etc.) and substances carried through the blood and lymph flow (“storage diseases”).
Transformation (from Latin transformatio - transformation) is the process of chemical conversion of compounds into others, for example fats and carbohydrates into proteins or proteins and carbohydrates into fats, increased synthesis of glycogen from glucose, etc., with excessive accumulation of newly formed compounds.
Altered synthesis of any compounds is expressed in increased or decreased formation of them with accumulation or depletion and loss in tissues, for example, glycogen, fat, calcium, etc. (“deficiency diseases”). “Perverted” (pathological) synthesis is possible with the appearance and accumulation in tissues of compounds that are not characteristic of them under normal metabolic conditions, for example, the synthesis of an unusual amyloid protein, glycogen in the epithelium of the kidneys, keratin in the epithelium of the lacrimal gland, pathological pigments, etc.
Specified pathogenetic mechanisms dystrophies can appear simultaneously or sequentially as the process develops.
Morphologically, dystrophies are manifested primarily by disturbances in the structure of ultrastructures of cells and tissues. Under physiological conditions, the restructuring of cell organelles and intercellular substance is combined with the processes of their restoration, and in dystrophies, regeneration at the molecular and ultrastructural levels is disrupted (molecular morphogenesis). In many dystrophies, inclusions, grains, drops or crystals of various chemical natures are found in cells and tissues, which under normal conditions do not occur or their number increases compared to the norm.
In other cases, on the contrary, in cells and tissues the amount of their inherent compounds decreases until they completely disappear (glycogen, fat, minerals, etc.).
In both cases, cells and tissues lose their characteristic fine structure (muscle tissue - transverse striations, glandular cells - polarity, connective tissue - fibrillar structure, etc.), and in severe cases, discomplexation of cellular tissues is observed elements (for example, the beam structure of the liver is disrupted).
Macroscopic changes. With dystrophies, the color, size, shape, consistency and pattern of organs change. The change in the appearance of the organ served as the basis for calling this process degeneration, or degeneration - a term that does not reflect the essence of dystrophic changes.
Functional significance of dystrophies. It consists in a violation of the basic functions of the organ (for example, the synthesis of protein, carbohydrates, lipoproteins in hepatosis, proteinuria in nephrosis, weakening of cardiac activity in myocardial dystrophy, etc.). After eliminating the cause that caused the development of the dystrophic process, metabolism in cells, tissues and the whole organism, as a rule, is normalized, as a result of which the organ acquires functional usefulness and normal appearance. However, severe dystrophic changes are irreversible, that is, the growing disproportion between the increased disintegration of one’s own structures and insufficient restoration ends in their necrosis.
articular dystrophy dog uric acid
PROTEIN DYSTROPHY (dysproteinosis)
Protein dystrophies are structural and functional tissue disorders associated with changes in the chemical composition, physicochemical properties and structural organization of proteins. They occur when there is an imbalance between the synthesis and breakdown of proteins in cells and tissues as a result of protein or amino acid deficiency, when substances foreign to the body enter the tissue, as well as from pathological protein synthesis. Protein metabolism disorders in the body are varied. They may have local or general (systemic) distribution. Based on localization, disorders of protein metabolism are distinguished in cells (cellular, or parenchymal, dysproteinoses), in the intercellular substance (extracellular, or stromal-vascular, dysproteinoses), or simultaneously in cells and intercellular substance (mixed dysproteinoses).
CELLular (parenchymatous) dysproteinoses
Granular dystrophy, or cloudy swelling, is a violation of the colloidal properties and ultrastructural organization of cells with the identification of protein in the form of grains. This is the most common type of protein dystrophy.
Causes: infectious and invasive diseases, inadequate feeding and intoxication, blood and lymph circulation disorders and other pathogenic factors.
The pathogenesis is complex. The leading mechanism is decomposition, which is based on insufficiency of the ATP system associated with hypoxia and the effect of toxic substances on oxidative phosphorylation enzymes (enzymopathy). As a result of this, the redox potential of cells decreases, underoxidized and acidic (acidosis), and less often alkaline (alkalosis) metabolic products accumulate, and oncotic-osmotic pressure and membrane permeability increase. Disorders of electrolyte and water metabolism are accompanied by swelling of cell proteins, a violation of the degree of dispersion of colloidal particles and stability colloidal systems, especially in mitochondria. At the same time, the activity of hydrolytic enzymes of lysosomes increases. Hydrolases break intramolecular bonds by attaching water molecules, causing rearrangement of complex compounds and macromolecules. The adsorption of any toxic substances in lipoprotein and glycoprotein complexes also causes their restructuring and disintegration. The released protein, and then other components of complex compounds (fat, etc.) become larger, and being in an isoelectric state, they coagulate with the appearance of grains. In this case, the synthesis of cytoplasmic protein (molecular morphogenesis) may be disrupted, as was shown using labeled atoms (S.V. Anichkov, 1961).
Along with decomposition, the appearance of granularity is also associated with the pathological transformation of carbohydrates and fats into proteins, infiltration and resorption of proteins foreign to the body (paraproteins) brought by the bloodstream (dysproteinemia).
Histological signs of granular dystrophy are most pronounced in the liver, kidneys, myocardium, and also in skeletal muscles (therefore it is also called parenchymal). An uneven increase in the volume of epithelial cells and muscle fibers compressing the capillaries, swelling and turbidity of the cytoplasm, smoothness and disappearance of the fine structure (brush border) are noted. glandular epithelium, transverse striations in muscle tissue, etc.), the appearance and accumulation of fine acidophilic grains of protein nature in the cytoplasm. In this case, the boundaries of cells and the outlines of nuclei are difficult to distinguish. Sometimes the cytoplasm takes on a foamy appearance, and some cells separate from the basement membrane and from each other (discomplexation). Under the influence of a weak solution of acetic acid or alkali, the cytoplasm becomes clear and the nucleus becomes visible again.
Along with solubility in weak acids and alkalis, the presence of protein in grains is determined by histochemical methods, as well as using an electron microscope.
Electron microscopically, granular dystrophy is characterized by swelling and rounding of mitochondria, expansion of the cisterns and tubules of the cytoplasmic reticulum. Mitochondria enlarge, their membranes stretch, stratify, the ridges unevenly thicken and shorten, the structural proteins of mitochondria dissolve with clearing of the matrix and the appearance of transparent vacuoles (vacuolization of mitochondria) or swell and enlarge. The protein-synthesizing apparatus of the cell (polysomes, ribosomes) also disintegrates.
Macroscopically, the affected organs are enlarged in volume, have a flabby consistency, are anemic, when cut, the tissue bulges beyond the capsule, the cut surface is dull, the liver and kidneys are grayish-brown in color with a smoothed pattern, and the muscle tissue (myocardium, skeletal muscles) resembles meat scalded with boiling water.
The clinical significance of granular dystrophy is that the functions of the affected organs are disrupted and may change qualitatively (heart weakness in infectious diseases, albuminuria in kidney damage, etc.).
The outcome depends on many reasons. Granular dystrophy is a reversible process, but if its causes are not eliminated, then at the height of development it can turn into a more severe pathological process - hydropic, hyaline-droplet, fatty and other types of dystrophies resulting in cell necrosis (the so-called acidophilic degeneration, balloon degeneration or coagulative necrosis).
Differential diagnosis. Granular dystrophy must be distinguished from the physiological synthesis of proteins in a cell with the accumulation of protein granules associated with the normal functioning of the body (for example, the formation of secretion granules in a glandular organ) or the physiological resorption of protein by the cell (for example, in renal tubules proximal segment). This intravital process differs from postmortem changes in organs (cadaveric dullness) by a clearly expressed increase in the size of cells and organs, as well as the unevenness of pathological lesions.
Hyaline droplet dystrophy (from the Greek hyalos - glassy, transparent) is an intracellular dysproteinosis, characterized by the appearance of transparent oxyphilic protein droplets in the cytoplasm.
Causes: acute and chronic infections, intoxication and poisoning (sublimate, chromium salts, uranium, etc.); in addition, dystrophy can be the result of allergic processes after preliminary sensitization with proteins. It is also noted in chronic catarrhs of the gastrointestinal tract, bladder, actinomyomas and tumors.
The pathogenesis of hyaline-droplet dystrophy is that, under pathological conditions, deep denaturation of cytoplasmic lipoproteins occurs with the loss of a coarse dispersed phase due to the loss of hydrophilic properties by the protein. In other cases, resorption and pathological infiltration of the cell by coarsely dispersed proteins foreign to the body - paraproteins coming from the blood - are possible.
Macroscopically, hyaline droplet dystrophy is not diagnosed.
Histological changes occur in glandular organs (liver, etc.), tumors, muscle tissue, as well as in foci of chronic inflammation, but especially often in the epithelium of kidney tubules. In this case, more or less homogeneous, translucent protein droplets are visible in the cytoplasm, stained with acidic dyes (for example, eosin). As droplets accumulate and merge with each other, they can completely fill the cell. The most severe changes occur with glomerulonephritis and protein nephrosis in the epithelium of convoluted tubules. Similar changes occur in the epithelium of the adrenal glands and bronchi. In chronically inflamed tissues, mainly in plasma cells, so-called Roussel's, or fuchsinophilic, bodies are found in the form of large homogeneous, sometimes layered hyaline balls, which are intensely stained with fuchsin and, after cell disintegration, lie freely in the tissue. Electron microscopy reveals the appearance of hyaline drops and vacuoles in the cytoplasm, swelling and disintegration of mitochondria, disappearance of polysomes and ribosomes, rupture of network cisterns, etc.
The clinical significance of hyaline droplet dystrophy is that it reflects severe organ failure, in particular the kidneys.
Exodus. Due to the irreversible denaturation of plasma protein, hyaline droplet dystrophy results in necrosis.
Hydropic (dropsy, vacuolar) dystrophy is a violation of the protein-water-electrolyte metabolism of the cell with the release of water inside the cells.
Causes: infectious diseases (foot and mouth disease, smallpox, viral hepatitis, etc.), inflammatory infiltration of tissues, physical, chemical and acute toxic effects causing hypoxia and the development of edema, metabolic diseases (protein deficiency, salt starvation, hypovitaminosis, such as pellagra, and etc.), as well as chronic intoxication and exhaustion (chronic gastroenteritis, colitis, etc.).
Pathogenesis. As a result of a decrease in oxidative processes, a lack of energy and the accumulation of under-oxidized metabolic products, bound water is not only released and retained in the cell (intracellular water), but also enters the cell from the tissue fluid (extracellular water) due to an increase in colloid-osmotic pressure and impaired permeability cell membranes. In this case, potassium ions leave the cell, while sodium ions intensively penetrate into it due to disruption of osmosis processes associated with the “ion pump”. The biochemical essence of dystrophies is the activation of hydrolytic enzymes of lysosomes (esterases, glucosidases, peptidases, etc.), which break intramolecular bonds by adding water, causing hydrolysis of proteins and other compounds.
Histological changes are often found in epithelial tissue skin, liver, kidneys, adrenal glands, in nerve cells, muscle fibers and leukocytes. They show signs of granular degeneration, partial cytolysis with the formation of vacuoles in the cytoplasm (vacuolar dystrophy) filled with fluid containing protein and enzymes. Sometimes the protein of the cytoplasmic fluid coagulates under the influence of calcium salts. Further dissolution of the cytoplasm and an increase in the amount of water in it cause more pronounced intracellular edema, the development of which can lead to karyocytolysis. At the same time, the cell enlarges, the nucleus and cytoplasm dissolve, only its shell remains. The cell takes on the appearance of a balloon (balloon dystrophy). Electron microscopy reveals the expansion and rupture of cisterns and tubules, swelling and lysis of mitochondria, ribosomes and other organelles, as well as the dissolution of the main plasma.
Macroscopically, organs and tissues change little, with the exception of their swelling and pallor. Vacuolar dystrophy is determined only under a microscope.
The clinical significance of hydropic dystrophy is that the functions of the affected organ decrease.
Exodus. Vacuolar dystrophy is reversible provided that there is no complete dissolution of the cell cytoplasm. While maintaining the nucleus and part of the cytoplasm, normalization of water-protein and electrolyte metabolism leads to cell restoration. With significant destruction of organelles with the development of severe edema (balloon dystrophy), irreversible changes occur (liquation necrosis).
Differential diagnosis. Vacuolar dystrophy must be distinguished from fatty dystrophy using histochemical methods for determining fat, since during the production of histological preparations using solvents (alcohol, ether, xylene, chloroform), fatty substances are extracted and vacuoles also appear in their place.
Horny dystrophy or pathological organization is excessive (hyperkeratosis) or qualitatively impaired (parakeratosis, hypokeratosis) formation of horny substance. Keratin is stained pink by eosin, and yellow by picrofuchsin according to Van Gieson. It has osmiophilicity and high electron density.
Causes: metabolic disorders in the body - protein, mineral (lack of zinc, calcium, phosphorus) or vitamin deficiency (hypovitaminosis A, especially in birds, cattle and pigs, pellagra, etc.); infectious diseases associated with skin inflammation (dermatophytoses, scabies, scab, etc.); physical and chemical irritant effects on mucous membranes and skin; chronic inflammation of the mucous membranes; sometimes hereditary diseases (ichthyosis - the formation of horny layers on the skin, reminiscent fish scales or turtle shell). Excessive horn formation is observed in warts, cancroid (cancer-like tumor) and dermoid cysts.
The pathogenesis of horny dystrophy is associated with excessive or impaired synthesis of kerotene in the epidermis of the skin and in the keratinized epithelium of the mucous membranes. Formation of horny substance in mucous membranes digestive tract, upper respiratory tract and genital organs is accompanied by the replacement of glandular epithelium with keratinizing squamous stratified epithelium.
Parakeratosis (from the Greek para - about, keratos - horny substance) is expressed in the loss of the ability of epidermal cells to produce keratohyalin.
Histologically, parakeratosis reveals thickening of the epidermis as a result of hyperplasia of cells of the Malpighian layer and excessive accumulation of horny substance. In mucous membranes of the skin type and in the epidermis of the skin, papillary thickening of the epidermis is possible due to hyperplasia of the layer of styloid cells and elongation of the styloid processes. Such lesions are called acanthosis (from the Greek akantha - thorn, needle).
With para- and hypokeratosis, atrophy of the granular layer is pronounced, the stratum corneum is loose, with discomplexed cells having rod-shaped nuclei (incomplete keratinization).
Macroscopically, in places of pathological keratinization (widespread or local), the skin is thickened, with excessive growth of the stratum corneum. It loses its elasticity, becomes rough and hard, and dry thickening and calluses form. With parakeratosis, the stratum corneum is thickened, loose, with increased desquamation of horny scales, and sometimes hair loss. In adult animals, especially dairy cows, abnormal growth of the hoof horn is noted, which loses its glaze and cracks.
With leukoplakia (from the Greek leukos - white, plax, axos - slab), foci of keratinized epithelium of varying sizes form on the mucous membranes in the form of raised strands and gray-whitish plaques.
The clinical significance of pathological keratinization is associated with the development infectious complications. Leukoplakia can become a source of development of epithelial tumors (papillomas, less commonly cancer).
The outcome of horny dystrophy depends on the course of the underlying disease. When the cause of pathological keratinization is eliminated, the damaged tissue can be restored. Newborn animals suffering from ichthyosis usually die on the first day of life.
EXTRACELLULAR (STROMAL-VASCULAR) DYSPROTEINOSES
These are disorders of protein metabolism in the intercellular substance. Their essence lies in the pathological synthesis of proteins by cells of mesenchymal origin, in the disorganization (decay) of the main substance and fibrous structures with an increase in vascular-tissue permeability and the accumulation of blood and lymph proteins, as well as metabolic products, in the intercellular substance of the connective tissue.
These processes can be local or widespread. These include mucoid swelling, fibrinoid swelling (fibrinoid), hyalinosis and amyloidosis.
Mucoid swelling is the initial stage of disorganization of connective tissue (stroma of organs, blood vessels), which is characterized by impaired communication with proteins and redistribution of acidic glycosaminoglycans (hyaluronic, chondroitinsulfuric acids, etc.).
Causes: oxygen starvation, intoxication, some metabolic diseases (hypovitaminosis C, E, K) and endocrine system (myxedema), acute allergic and chronic diseases connective tissue and blood vessels (“collagen diseases”, rheumatism, atherosclerosis, etc.), in the development of which hemolytic group A streptococcus plays an etiological role, as well as infectious diseases (edema disease of piglets, erysipelas of pigs, etc.).
The pathogenesis of changes in mucoid swelling lies in the disruption of the synthesis of intercellular substance or in its superficial disintegration under the influence of hyaluronidase of exogenous (hemolytic streptococcus, etc.) or endogenous origin, as well as in conditions of increasing tissue hypoxia with the development of environmental acidosis. This leads to depolymerization of the protein-polysaccharide complex and the accumulation of released acidic glycosaminoglycans (especially hyaluronic and chondroitinsulfuric acids), which, having hydrophilic properties, cause an increase in tissue and vascular permeability, serous swelling of the tissue with its impregnation with plasma proteins (albumin, globulins and glycoproteins).
Microscopically, mucoid swelling of connective tissue is determined by basophilia and metachromasia of fibers and ground substance (for example, toluidine blue stains acidic glycosaminoglycans red, picrofuchsin does not color red, but yellow-orange).
The essence of metachromasia (from the Greek meta - change, chromasia - coloring) is the ability of glycosaminoglycans to cause polymerization of the dye. And if the dye as a monomer is blue, as a dimer or trimer it is violet, then as a polymer it is red (tautomerism). Changes in the molecular structure of collagen fibers are accompanied by their swelling, an unevenly expressed increase in volume and blurring of contours and structure, disintegration, and changes in the interstitial substance are accompanied by an accumulation of T-lymphocytes and histiocytes. Macroscopically, the organ remains unchanged, but the supporting-trophic and barrier functions of the connective tissue are disrupted.
Exodus. Complete restoration of damaged structures or transition to fibrinoid swelling is possible.
Fibrinoid swelling is a deep disorganization of the connective tissue of the stroma of organs and vessels, characterized by increased depolymerization of protein-polysaccharide complexes of the main substance and fibrillar structures with a sharp increase in vascular-tissue permeability. Due to plasmorrhagia, the connective tissue is saturated with blood proteins (albumin, globulins, glycoproteins, fibrinogen). As a result of precipitation or chemical interaction of these compounds, a chemically complex, heterogeneous substance is formed - fibrinoid, which includes proteins and polysaccharides of disintegrating collagen fibers, the main substance and blood plasma, as well as cellular nucleoproteins.
Causes: the same allergic, infectious factors, neurotrophic disorders that cause mucoid swelling, but act with greater strength or duration. As a local process, fibrinoid swelling is observed in areas of chronic inflammation.
Pathogenesis. Fibrinoid changes, being the subsequent stage of mucoid swelling, develop if the process of disorganization of the connective tissue deepens, disintegration occurs not only of the main substance, but also of collagen and other fibrillar structures, depolymerization of glycosaminoglycans, disintegrating collagen fibers and impregnation of them with plasma proteins, including including coarsely dispersed protein - fibrinogen, which is an obligatory component of fibrinoid.
In this case, fibrillogenesis is disrupted, especially the biosynthesis of acid glycosaminoglycans in mesenchymal cells, and proliferation of T-lymphocytes and histiocytes is also observed. Chemical interaction and polymerization of the breakdown products of the main substance, collagen and plasma proteins are accompanied by the formation of unusual protein-polysaccharide complexes of fibrinoid.
Histological changes occur in two stages: fibrinoid swelling and fibrinoid necrosis. With fibrinoid swelling, disintegration of the main substance, swelling and partial disintegration of collagen and elastic fibers, plasmorrhagia with impregnation of the connective tissue with albumin, plasma globulins and fibrinogen, which is detected by histochemical and immunofluorescent methods, are noted. Collagen, forming dense insoluble compounds with fibrinogen and other substances, changes its tinctorial properties: it becomes eosino-, pyronino- and argyrophilic, picrofuchsin turns yellow, and the PIC reaction is sharply positive. The process ends with complete destruction of connective tissue with the development of fibrinoid necrosis. In this case, the tissue takes on the appearance of a granular-clumpy or amorphous mass, which includes breakdown products of collagen fibers, ground substance and plasma proteins. With complete depolymerization of free glycosaminoglycans, metachromasia is usually not expressed. Around the necrotic masses, productive inflammation develops with the formation of nonspecific granulomas consisting of T-lymphocytes and macrophages.
Macroscopically, fibrinoid changes in connective tissue are subtle and can be detected under a microscope.
The clinical significance of fibrinoid swelling arises from the disruption or shutdown of the function of the affected organ.
The outcome is related to the course of the underlying disease in which this process develops. Fibrinoid masses can be resorbed and replaced by connective tissue that undergoes sclerosis or hyalinosis.
Hyalinosis (from the Greek hyalos - transparent, glassy), or hyaline dystrophy, is a peculiar physicochemical transformation of connective tissue due to the formation of a complex protein - hyaline, similar in morphological characteristics to the main substance of cartilage. Hyaline gives tissues a special physical state: they become homogeneous, translucent and denser. The composition of hyaline includes glycosaminoglycans and proteins of connective tissue, blood plasma (albumin, globulins, fibrinogen), as well as lipids and calcium salts. Electron microscopy data indicate that hyaline contains a type of fibrillar protein (fibrin). Hyaline is resistant to acids, alkalis, and enzymes, is intensely stained with acidic dyes (eosin, acid fuchsin or picrofuchsin) in red or yellow, and gives a CHIC-positive reaction.
Causes. Hyalinosis develops as a result of various pathological processes: plasma impregnation, mucoid and fibrinoid swelling of connective tissue. The physiological prototype of hyalinosis is aging.
Systemic hyalinosis of blood vessels and connective tissue is observed in collagen diseases, arteriosclerosis, infectious and toxic diseases, chronic inflammation, diseases associated with protein metabolism disorders, especially in highly productive cows and pigs. Severe vascular hyalinosis occurs in chronic glomerulonephritis, especially in dogs.
Along with this, local hyalinosis (sclerosis) occurs in newly formed connective (scar) tissue.
Pathogenesis. An important role in the occurrence and development of systemic hyalinosis is played by tissue hypoxia, damage to the endothelium and the basal layer of the vascular wall, disturbances in the synthesis and structure of reticular, collagen, elastic fibers and the basic substance of connective tissue. In this case, an increase in vascular and tissue permeability occurs, the tissue is impregnated with plasma proteins, their adsorption with the formation of complex protein compounds, precipitation and compaction of protein masses.
Immunological mechanisms are also involved in the development of hyalinosis, since it has been proven that hyaline masses have some properties of antigen-antibody immune complexes.
Histologically, hyaline is found in the intercellular substance of connective tissue. Systemic hyalinosis of the walls of blood vessels and connective tissue is manifested by the formation of hyaline in the ground substance of the intima and perivascular connective tissue of arteries and capillaries. Ultimately, a homogeneous dense protein mass is formed, stained with acidic dyes. Although hyaline is an indifferent substance, its accumulation is accompanied by thickening of the vessel wall, displacement of the media by the hyaline mass with narrowing of the lumen, up to its complete closure (obliteration) in small vessels. Necrotization of tissues exposed to hyalinosis may be accompanied by their calcification, ruptures of the vessel wall with the occurrence of hemorrhages and thrombosis. In glandular organs, connective tissue hyalinosis is accompanied by thickening of the basal membranes of the glands, compression of the glandular epithelium, followed by its atrophy. Local hyalinosis occurs in foci of chronic inflammation, in newly formed connective tissue (connective tissue capsules and old scars). In this case, the collagen fibers swell, merge into homogeneous tissues, and the cells atrophy.
Macroscopically, organs and tissues affected by hyalinosis to a weak degree do not have noticeably pronounced changes; the process is detected only under a microscope. With pronounced hyalinosis, the vessels lose their elasticity, and the affected organs become pale and dense. When calcium salts precipitate into the hyaline masses, they become even more compact.
The functional significance of hyalinosis depends on its degree and prevalence. Systemic hyalinosis causes dysfunction of organs, especially their vessels, with the development of atrophy, ruptures and other serious consequences. Local hyalinosis may not cause significant functional changes.
The outcome is different. It has been established that hyaline masses can loosen and dissolve or mucus, for example, in scars, in the so-called keloids. However, in most cases, widespread hyalinosis manifests itself as an irreversible process.
Differential diagnosis. Pathological hyalinosis should be distinguished from physiological hyalinosis, which manifests itself in the process of involution and normal aging of tissues (for example, involution of the corpus luteum, vessels of the uterus, mammary gland, etc.). In this case, hyalinosis of the uterus and mammary gland is reversible due to increased organ function. Externally, hyalinosis is similar to the hyaline-like transformation of dead tissue, secretion products (for example, the formation of hyaline casts in nephrosis-nephritis, hyaline blood clots, hyalinization of fibrin, etc.).
Amyloidosis (amloid dystrophy) is characterized by the pathological synthesis of a peculiar fibrillar protein (preamyloid) in the cells of the reticuloendothelial system with the subsequent formation of amyloid complex glycoprotein. R. Virchow (1859) mistook this glycoprotein for a starch-like compound (amylum - starch) due to its characteristic blue coloring with iodine and sulfuric acid. Due to the strength of chemical bonds, amyloid is resistant to acids, alkalis, enzymes, and resists decay. Acidic glycosaminoglycans (chondroitin sulfate) with varying degrees of polymerization give amyloid the property of metachromasia, which distinguishes it from hyaline and other proteins. Amyloid stains pink-red with gentian and cresyl violet against a violet tissue background. Jodgrün also stains amyloid red and Congo red a brownish-brown color. Congo red, introduced into the blood, is able to accumulate in amyloid mass in vivo, which is used for intravital diagnostics amyloidosis. Amyloid masses give a CHIC-positive reaction. The chemical composition of amyloid can vary. Due to this, some colorful amyloid reactions (eg metachromasia) are lost (paramyloid).
Causes of systemic amyloidosis: inflammatory, suppurative, necrotic processes of any origin and intoxication. In these cases, amyloidosis develops as a complication of the disease (secondary or typical amyloidosis) caused by the breakdown of tissue protein (for example, in tuberculosis, malignant tumors, nonspecific inflammatory processes with suppuration, etc.). Secondary amyloidosis is observed in lactating highly productive cows, birds, fur-bearing animals, horses (“hay sickness”), etc. The causes of atypical primary (idiopathic) and senile amyloidosis characteristic of humans are unknown. Genetic amyloidosis is a hereditary enzymopathy or anomaly (mutation) in the genetic apparatus of RPE cells. In experiments on laboratory animals, amyloidosis can be caused parenteral administration foreign protein (casein), as well as by creating foci of chronic suppuration. Due to prolonged parenteral administration of a foreign protein, amyloidosis develops in horses - producers of immune sera.
Causes of local amyloidosis: chronic inflammatory processes with stagnation of blood and lymph.
The pathogenesis of amyloidosis is complex.
According to the theory of disproteinosis (K. Apitz, E. Randerath, 1947), amyloid arises on the basis of impaired protein synthesis with the appearance of paraproteins or paraglobulins in the blood and the development of dysproteinemia and hypergamma-globulinemia. These products of the coarse protein fraction of blood plasma, released through the endothelial barrier, primarily in the spleen, liver and kidneys, combine with acidic glycosaminoglycans, which are released under the influence of plasma proteins and tissue hyaluronidases, and form amyloid.
According to the theory of autoimmunity (Loeschke, Letterer, 1962) crucial in the formation of amyloid have altered reactivity of the body and autoimmune processes. In many processes complicated by amyloidosis, decay products of tissues, leukocytes, and bacteria with antigenic properties accumulate. It is possible that disturbances in reactions in the immune system, associated with an excess of antigen and a lack of antibodies, lead to the appearance in the blood of precipitins specific to tissue proteins and the fixation of the protein complex at the sites of antibody formation (Letterer). This theory has retained its significance for experimental and secondary amyloidosis. It does not explain the mechanism of development of idiopathic, genetic and senile amyloidosis.
The theory of cellular local genesis (G. Teilum, 1962) considers amyloid as a product of protein synthesis by cells of the mesenchymal system with perverted metabolism (“mesenchymal disease”). It is confirmed by the selectivity of damage to this system and the intracellular formation of preamyloid fibrils by cells of a mesenchymal nature.
A new mutational theory of amyloidosis is being put forward (E. Benditt, N. Eriksen, 1977; V.V. Serov, I.A. Shamov, 1977), which can become universal for understanding the pathogenesis of all its known forms, taking into account the diversity of factors causing mutation. According to this theory, mutating cells are not recognized by the immunocompetent system and are not eliminated, since amyloid fibrils are extremely weak antigens. The emerging reaction of amyloid resorption (amyloidoclasia) at the very beginning of its formation is insufficient and is quickly suppressed. Immunological tolerance (tolerance) of the body to amyloid and the irreversible development of amyloidosis occur. The mutation theory explains the closeness of amyloidosis to tumor processes.
Histological and macroscopic changes depend on the cause of formation, the relationship to various connective tissue cells and the location of the amyloid.
In general typical amyloidosis, most common in farm animals, amyloid falls along the reticular fibers of vascular and glandular membranes and into the perireticular spaces of parenchymal organs (perireticular or parenchymal amyloidosis). The liver, spleen, kidneys, less often the adrenal glands, the pituitary gland, the lining of the intestinal glands, the intima of capillaries and arterioles are affected. In connective tissue cells, preamyloid fibrils accumulate, ribosomes disappear, mitochondria (giant mitochondria), as well as the lamellar Golgi complex, hypertrophy (A. Policar, M. Bessi, 1970).
The accumulation of amyloid in tissue is accompanied by atrophy and death of the parenchymal elements of the organ.
Liver amyloidosis is characterized by the formation of amyloid in the surrounding sinusoidal space (space of Disse) between stellate reticuloendotheliocytes and liver cells (Fig. 8). Amyloid is also noted in the walls of interlobular capillaries and arterioles. As amyloid substance accumulates, the liver increases in size, becomes pale brown in color, denser, and in horses has a flabby consistency. In horses, it can reach a weight of 16-33 kg, while about 10% of cases end in liver rupture due to the melting of the stroma (A.P. Gindin, 1959), bruises appear, which often end in fatal hemorrhage into the abdominal cavity.
Amyloidosis of the spleen manifests itself in two forms: follicular and diffuse. In the first case, amyloid is deposited in the reticular tissue of the follicles, starting from their periphery. The reticular and lymphoid tissues of the follicles atrophy and are replaced by amyloid masses. Macroscopically, amyloid-modified follicles on a section look like translucent grains that resemble grains of boiled sago (“sago spleen”). In the second case, amyloid falls out more or less evenly throughout the reticular stroma of the organ and under the endothelium of the sinuses. With diffuse amyloidosis, the spleen is enlarged in size, dense in consistency, and in horses, doughy; the cut surface is smooth, light red-brown, reminiscent of raw ham (“greasy” or “ham” spleen). In horses, organ rupture and hemorrhage are possible.
In the kidneys, amyloid is deposited primarily in the mesangium and behind the endothelium of the capillary loops and glomerular arterioles, as well as in the reticular stroma of the cortex and medulla, in the walls of arterioles and small arteries, and less often in the basal layer under the tubular epithelium. The renal glomeruli gradually atrophy, the tubular epithelium, in addition, undergoes granular and hyaline-droplet degeneration.
As amyloid accumulates, the kidneys increase in size and become pale brown, waxy, and dry. With isolated damage to the renal glomeruli, they look like grayish-red specks.
In other organs (adrenal glands, pituitary gland, intestines), amyloid is deposited in the reticular stroma and the basal layer of blood vessels and glands. Due to the fact that organs with amyloidosis acquire a waxy or greasy appearance, the Hungarian pathologist K. Rokitansky in 1844 described these changes under the name sebaceous disease.
Primary atypical amyloidosis with systemic damage adventitia of medium and large vessels, myocardium, striated and smooth muscles, gastrointestinal tract, lungs, nerves, skin in farm animals is a relatively rare phenomenon. It is noted in connective tissue diseases of infectious-allergic origin (rheumatism, etc. ), viral plasmacytosis, etc. In this case, amyloid is found mainly in the walls of capillaries and arteries, near the plasma membranes of fibroblasts and collagen fibers (pericollagen amyloidosis). This amyloid does not always give rise to a metachromasia reaction (paramyloid) and shows a tendency to develop cell proliferative reactions with the formation of nodular growths.
Rare atypical forms of amyloidosis include local amyloidosis with the deposition of amyloid masses into the connective tissue and into the wall of blood vessels in an isolated area of the organ. It is found in the alveoli of the lungs in chronic pneumonia, in the mucous membrane of the nasal cavity in horses, in prostate gland in old animals (dogs, etc.), in the central nervous system at the site of dystrophically changed and dead nerve cells, as well as in the mucous membranes of other organs.
The functional significance of amyloidosis is associated with the development of atrophy and death of parenchymal cells and progressive organ failure (liver, kidney), disorder of blood and lymph circulation and the possibility of organ rupture (particularly in horses), sometimes accompanied by fatal bleeding.
The outcome of general amyloidosis is usually unfavorable. However, there is experimental, clinical and pathomorphological evidence that amyloid masses can be resolved with the participation of giant cells if the cause of its formation is eliminated (M. N. Nikiforov, A. I. Strukov, B. I. Migunov, 1971). In animals, amyloidosis is an irreversible process.
Mixed dysproteinoses are metabolic disorders of complex proteins: chromoproteins (endogenous pigments), nucleoproteins, glycoproteins and lipoproteins. They are manifested by structural changes both in cells and in the intercellular substance.
Pathology of pigmentation. All organs and tissues have a certain color, which depends on the presence of colored compounds (pigments) in them. They are deposited in tissues in soluble, granular or crystalline form. Some of them are formed in the body itself (endogenous pigments) and are associated with certain types of metabolism (proteins, fats, etc.), others enter the body from the outside (exogenous pigments).
Endogenous pigments are usually divided into three groups: pigments arising from the breakdown of hemoglobin - hemoglobinogenic pigments; derivatives of the amino acids tyrosine and tryptophan - proteinogenic, tyrosine tryptophan pigments; associated with fat metabolism - lipidogenic pigments.
Disturbances in the normal pigmentation of organs and tissues are manifested by increased formation of pigments in tissues, their deposition in unusual places, insufficient formation with partial or complete depigmentation of normal organs. Color change is one of the important indicators of the state of the internal environment of the body and often has diagnostic value.
Hemoglobinogenic pigments are formed as a result of the physiological and pathological breakdown of red blood cells, which contain the high molecular weight chromoprotein hemoglobin, which gives the blood a specific color. As a result of physiological death, part of the erythrocytes (about 1/30 of their number daily) is split by intravascular hemolysis with the splitting off of hemoglobin and absorption of it, erythrocyte fragments or the entire cell (erythrophagy) by macrophages of the mononuclear-macrophage system (MMC). In these cells, enzymatic (hydrolytic) breakdown of hemoglobin occurs with the formation of pigments: ferritin, hemosiderin, bilirubin, etc.
Ferritin is a reserve iron protein. It contains approximately 23% iron, which in the form of oxide hydrate forms a complex compound with the phosphate groups of a specific protein (apoferritin). It is formed from dietary iron in the intestinal mucosa and pancreas and during the breakdown of red blood cells and hemoglobin in the spleen, liver, bone marrow and lymph nodes. In these organs it is detected by a histochemical reaction to Prussian blue. Crystals of pure ferritin are found in the liver, kidneys and other parenchymal organs and MMS cells.
Since ferritin has a vasoparalytic effect, an increase in its concentration in the blood (ferritinemia) contributes to the development of irreversible shock and collapse. Excessive accumulation of ferritin in MMC cells is accompanied by the formation of large pigment granules of hemosiderin, which includes ferritin.
Hemosiderin (from the Greek haima - blood, sideros - iron) is normally formed during the breakdown of hemoglobin or red blood cells in the MMC cells of the spleen, as well as in small quantities in the bone marrow, partly in the lymph nodes.
In physicochemical terms, hemosiderin is a compound of colloidal ferric hydroxide with proteins, glycoproteins and cell lipids. It is deposited in the cytoplasm in the form of amorphous, golden-yellow or brown grains that strongly refract light. During the disintegration of pigmented cells, it can be localized extracellularly. The presence of iron distinguishes hemosiderin from other pigments similar to it. In the histochemical Perls reaction, hemosiderin combines with potassium iron sulfide (yellow blood salt) in the presence of hydrochloric acid with the formation of iron sulfide ("Prussian blue"), Sudan black reveals the lipid components in it, and the CHIC reaction reveals the carbohydrate components. The pigment is soluble in acids, insoluble in alkalis, alcohol and ether; does not discolor under by the action of hydrogen peroxide; turns black from ammonium sulfide, and upon subsequent processing according to the Perls method gives a reaction with a blue color (Turnboulian blue).
With an increase in intravascular hemolysis, the formation and concentration of dissolved hemoglobin in the blood increases (hemoglobinemia), it is excreted in the urine (hemoglobinuria), the synthesis and accumulation of pigment in the cells of the mononuclear-macrophage system of the kidneys, lungs and other organs increases, where normally he is absent. In addition, the pigment is found in the epithelial cells of the excretory organs, where ferritin also accumulates, especially in the parenchymal cells of the liver.
Organ, or local, hemosiderosis, caused by extravascular (extravascular) hemolysis, is observed with hemorrhages. Fragments of erythrocytes and whole cells are captured by leukocytes, histiocytes, reticular, endothelial and epithelial cells (siderophages), in which hemosiderin is synthesized, which gives the organs or its parts a brownish-rusty color (for example, the lungs in chronic congestive hyperemia with the development of brown induration or in hemorrhagic infarctions ). In the body, siderophages can migrate and accumulate in other organs, especially often in regional lymph nodes. In large hemorrhages at the periphery of the lesion, hemosiderin is noted in living cells, and in the center of it, hematoidin is detected among dead cells.
Hematoidin is formed by the breakdown of red blood cells and hemoglobin intracellularly, and is usually not found in dissolved form. But at high concentrations in old foci of hemorrhages (in bruises, hematomas, infarctions in the stage of organization, etc.), after cell death (among the necrotic masses of the central areas of hemorrhages, as well as during the breakdown of blood outside the body), it falls out in the form of rhombic or needle-shaped crystals forming peculiar figures of stars, panicles, sheaves, etc., less often angular grains or amorphous lumps of golden yellow color, giving, together with hemosiderin, a corresponding color to these foci. In the form of amorphous granules or lumps, it is also found inside hepatocytes, stellate reticuloendotheliocytes, and especially in the epithelium of the urinary tubules with impaired function or its excessive formation. Hematoidin is based on a protoporphyrated heme ring associated with proteins, but unlike hemosiderin, it lacks iron. The pigment dissolves in alkalis and gives a positive Gmelin reaction (the appearance of a green, then blue or purple color under the influence of concentrated nitric and sulfuric acids). Its detection has diagnostic value. Chemically, hematoidin is identical to bilirubin.
Bilirubin is formed as a result of the destruction of red blood cells and hemoglobin in the cells of the mononuclear-macrophage system of the liver, spleen, bone marrow and lymph nodes. During decay, the heme protoporphyrin ring loses iron hydroxide and turns into biliverdin, and when it is reversibly reduced, bilirubin is formed. The pigment has the same chemical properties as hematoidin. Easily oxidized, it gives the Gmelin reaction. In the blood, bilirubin is combined with plasma proteins, but can be deposited in the cytoplasm of cells and tissues in the form of small grains or yellowish-green crystals. In its pure form, it is isolated in the form of reddish and yellowish crystals. Its metabolism is closely connected with the hematopoietic organs, with the blood, the plasma of which normally contains 0.3-0.6 mg% of it, and with the liver, from where it is released in a water-soluble form into the duodenum as part of bile. Part of the pigment from the large intestine again enters the blood and liver, and part is converted in the intestine into stercobelin and excreted from the body. In addition, it is excreted from the blood in the urine in the form of urobilin.
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