Parenchymatous protein dystrophy (proteinosis) –
Parenchymatous protein dystrophy is morphologically characterized by the appearance of protein granules in the cell cytoplasm. However, the appearance of protein granules may be of a physiological nature, as a manifestation of compensatory and adaptive reaction, without changing its physical and chemical characteristics and be the result of the physiological activity of cells.
Parenchymatous protein dystrophy includes granular dystrophy, hyaline-drop dystrophy, hydropic dystrophy, and keratinization. Morphogenesis of parenchymatous protein dystrophy occurs as denaturation and coagulation, or as hydration and colliquation of cytoplasmic proteins that are presented in a table which is given below.
Morphogenesis of parenchymatous protein dystrophy
However, this stage may be both manifestations of functional overstrain of cellular structures or manifestation of physiological processes, but if the cause led to the functional overstrain is not eliminated, there is an excessive accumulation of protein granules with the change in the characteristics of the protein, leading to dysfunction and failure of specific characteristics of the cells.
Macroscopically – the internal organs increase in volume and size, become dull (cloudy), which gave occasion to call granular dystrophy “dull or cloudy dystrophy”.
Microscopic changes are characterized by the accumulation of protein granules in the cytoplasm of the cells of parenchymatous organs. Thus, in granular dystrophy, there is an accumulation of protein granules in the cytoplasm of the cells of the renal tubules; the epithelium becomes swollen; the lumen of tubules is reduced (Fig. 1).
Hyaline-drop dystrophy – large hyaline-like protein granules appear in the cytoplasm coalescing and filling the cytoplasm of the cell, if this occurs, there is a destruction of ultrastructural elements. In some cases, hyaline-drop dystrophy results in focal coagulation necrosis. This type of dystrophies often develops in kidney cells; it is rarely found in the liver and very rarely localized in cardiomyocytes. The resulting changes in the cells reflect the deficiency of the vacuolar lysosomal system and are irreversible.
The outcome of hyaline-drop dystrophy is adverse, irreversible. The disease results in the development of necrosis, later, the development of sclerosis or fibrosis of the organ is possible. The functional significance – it depends on the localization and the prevalence of the process, on morphological and functional characteristics. For example, the appearance of protein (proteinuria) and cylinders (cylindric) in the urine, loss of plasma proteins (hypoproteinemia), electrolyte imbalance, damage of hepatocytes leading to liver dysfunction are associated with hyaline-drop dystrophy of the epithelium of the renal tubules.
Hydropic dystrophy or degeneration
Hydropic dystrophy or degeneration is characterized by the appearance of the vacuoles in the cell, which are filled with cytoplasmic fluid. This type of dystrophy is most often localized in the epithelium of the skin and renal tubules, hepatocytes, muscle and nerve cells, adrenal cortex cells.
The causes of hydropic dystrophy are different. They are rupture of the membranes or ultrastructure of the cell, which leads to hyperfiltration. This may be in viral and bacterial infections, intoxications, or be a manifestation of the physiological activity of cells, in particular, of the ganglion cells of the central and peripheral nervous system. Macroscopically – the appearance of organs and tissues is little changed; to diagnose the process is possible only with the help of microscopic examination.
The microscopic changes cells are increased in volume, the cytoplasm is filled with vacuoles of different sizes, containing a clear liquid. The nucleus is shifted to the periphery, sometimes, the nucleus substance is contracted. Pro regression of the process leads to the disintegration of ultrastructure and cell filling with water vacuoles. The cell filled with a liquid looks like a balloon or it turns into a huge vacuole, which, in the fact, is the morphological expression of focal colliquative necrosis, and this type of dystrophy is called ballooning degeneration. Changes in the liver in ballooning degeneration are characterized by the disturbance of the structure of the liver tissue, and the pattern of liver acini is traded with difficulty due to severe degenerative changes of hepatocytes, which is characterized by the development of hydropic and vacuolar degeneration of the liver cells. In the cytoplasm of hepatocytes, the formation of large vacuoles is indicated that fill the entire surface of the cell, nuclei of the cells are shifted to the periphery; they have indistinct contours. In most cells of liver acini, there are hepatocytes in the state of necrobiosis changes with lyses of nucleus substance, which is characterized by the development of focal necrosis (Fig. 3, 4).
The outcome is adverse. The disease results in tissue necrosis and organ dysfunction.
Keratinization “hyperkeratinization” is characterized by excessive formation of horny substance in the squamous epithelium and is referred to as hyperkeratosis, ichthyosis, or leukoplakia – when the formation of the horny substance occurs in the abnormal place. For example, in the mucous membranes of the oral cavity, esophagus, uterine cervix; in chronic inflammation, hypoxia miosis, or in neoplastic processes, for example – in the formation of “chancroid corpuscles” in squamous cell cancer. The process of keratinization may be local or widespread in nature. Morphological manifestations depend on the localization and prevalence of the process.
Macroscopically – mucous membranes become pearl-pink in leukoplakia, there is an increased seal and shine of mucosa. Microscopic changes are characterized by the appearance of keratinized cells, there is an increase in the number of keratinized layers of the epithelium, or concentric structures, or the formation of «chancroid corpuscles» in squamous cell cancer.
The causes are a developmental disorder of the skin, chronic inflamed too, viral infection, vitamin deficiency diseases, tumors, and others. Outcome – at first, the process may be reversible and result in tissue repair; if there is process progression, it may result in the death of tissue. Functional significance – depends on the degree, prevalence, and localization of the process. Prolonged leukoplakia may cause the development of cancer, congenital ichthyosis in severe form, which is generally fatal.
Congenital parenchymatous proteinosis
|Cystinosis||Unknown||The liver, kidneys, eyes, spleen, bone marrow, lymph nodes, skin.|
|Tyrosinosis||Tyrosine aminotransferase use or oxidase, or phenyl pyruvic acid||The liver, kidneys, bones.|
|Phenyl Pyruvic oligophrenia||Phenylalanine-4 hydroxylase||The nervous system, muscles, skin, blood, and urine|
Parenchymatous fatty degeneration (lipidoses)
The causes: the most frequent cause of lipidoses is a condition referred to as hyperlipidemia. The development of lipidoses is possible in intoxication with hepatotropic poisons, hypoxia of any origin, alimentary diseases caused by pro twin or vitamin deficiency, as well as in congenital enzymopathy. Among the mechanisms of the development of parenchymatous lipidoses, lipid there are infiltration and decomposition. The most frequent localization of lipidoses is in the liver and the myocardium, less often – in the kidneys.
An example of alimentary obesity is kwashiorkor a disease that is based on chronic protein deficiency in the carbohydrate diet. There are 3 stages of fatty degeneration (types) depending on the size of lipid granules in the hepatocytes: dust-like dystrophy, microvesicular and macrovesicular hepatic steatosis.
Having been stained with hematoxylin and eosin, fat dissolves in alcohol, and cells appear in the form of «honeycomb», nuclei are shifted to the periphery. Having been stained with a special color on the fat Sudan-3, fat inclusions are discolored to different tones of yellow-orange, are of different sizes, sometimes filling the entire cell cytoplasm.
Changes in the liver: the cause of fatty liver is the excessive intake of fatty acids in hepatocytes or their increased synthesis affected by toxic substances that block the oxidation of fatty acids and lipoprotein synthesis in hepatocytes; the insufficient intake of amino acids in the liver acini needed for the synthesis of phospholipids and lipoproteins. For example, in alcoholism, diabetes, intoxications with hepatotropic poisons, avitaminosis, gastrointestinal diseases, and other causes.
Macroscopic changes: the heart is enlarged, has flabby consistency, the cavities of atria and ventricles are stretched; there is endocardial yellow-whitish striation, which is referred to as a “tiger heart”. Microscopic changes, in the cardiomyocytes, are in the form of pulverized
accumulation of fat inclusions stained with Sudan-3 in yellow-orange (Fig. 8).
The outcome of dust-like dystrophy and microvesicular hepatic steatosis may be reversible; structural damage leading to focal necrosis of the cells and the irreversible process occurs in macrovesicular hepatic steatosis. The outcome and prognosis of fatty degeneration depend on its degree, localization of the process, and functional significance of the organ. There is atrophy of cells and their replacement by connective tissue in fatty degeneration.
The group of inherited lipidoses includes «systemic lipidoses» arising from hereditary deficiency of enzymes involved in the metabolism of certain lipids. Therefore, they are hereditary enzymopathies or «storage diseases». Con genital parenchymatous lipidoses are characterized by systemic primary accumulation and deposition of lipids in the cells with their subsequent damage. They are characterized by the appearance of one or another type of lipidosis in the cytoplasm of cells, which is of great diagnostic importance. They include cerebroside lipidoses (Gaucher disease), gangliosidosis (Tay-Sachs disease, Sandhoff’s disease), and sphingolipidoses (Niemann-Pick disease).
Parenchymatous carbohydrate degradation
Parenchymatous carbohydrate degradation – in this type of dystrophies, carbohydrates can only be identified with the use of histochemical reactions. To reveal polysaccharides, glycosaminoglycans, and glycoproteins, Schick test or Hotchkiss-McManus PAS reaction, toluidine, or methylene blue necessarily with enzymatic control are used. Histochemical methods are described in the special manuals devoted to histological techniques [1, 2].
Carbohydrates are divided into polysaccharides, of which only glycogen can be revealed in animal tissues; glycosaminoglycans (mucopolysaccharides) and glycoproteins, which main representatives are mucins and mucoids. Mucins are the basis of mucus produced by the epithelium of the mucous membranes and glands, mucoid is the part of many types of tissue.
Parenchymatous carbohydrate degradation may be associated with glycogen or glycoprotein metabolism disorder.
Carbohydrate degeneration is associated with glycogen metabolism disorder (unstable glycogen), which is located in the liver and skeletal muscles and consumed according to the body’s needs.
Glycogen, which is a component of the cell structures, is referred to as stable glycogen.
Carbohydrate degeneration associated with glycoprotein metabolism disorder in the cells and ground substance is referred to as mucous degenerations in the case when there is an accumulation of mucins and mucoid leading to the formation of mucoid substance (pseudomucins). These substances may thicken and become colloids, then, it is a case of
“mucous or colloid degeneration”.
The microscopic changes are characterized by the accumulation of mu covid (colloid) in the cell cytoplasm, the nuclei are shifted to the periphery, the cell is signet ring-shaped, so the cells are called “signet ring cells”, and since this type of dystrophy occurs in stomach cancer, it is referred to as “signet ring cell carcinoma” or “mucinous carcinoma” or “colloid carcinoma” of the stomach (Fig. 9).
Excessive production of mucus in the tissues may occur in inflammation, endocrine dysfunction, or neoplastic processes, such as mucinous carcinoma of the stomach, which is referred to as a “signet ring cell carcinoma” according to the shape of tumor cells.