Parenchymal Dystrophy, Hyaline-drop & Hydropic Dystrophy

Parenchymatous dystrophies or Parenchymal Dystrophy (cell degenerations) is based on metabolism disorder and structural changes that occur in specialized cells of parenchymatous organs (liver, myocardium, kidneys). Besides, there is a metabolism disorder of membranous and cytoplasmic proteins, which leads to a change in their physical and chemical characteristics. The trigger mechanism is the enzyme deficiency – enzymopathies.

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

Denaturation and coagulation of cytoplasmic proteins Hydration, colliquation of cytoplasm (activation of lysosomal hydrolases)
Hyaline-drop dystrophy Hydropic dystrophy 
Coagulation focal cell necrosis Colliquative focal cell necrosis (ballooning degeneration) 
Coagulation total cell necrosis Colliquative total cell necrosis


Granular dystrophy


Granular dystrophy. The so-called “g dystrophy” is considered as the initial stage of parenchymatous dystrophy by many pathologists in the years since R. Virhov to the present day, as it is characterized by the accumulation of protein granules in the cells of parenchymatous organs.


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).

Granular dystrophy


Hyaline-drop dystrophy

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.


  Changes in the kidneys. The cause of this type of dystrophies in the epithelium of renal tubules is the increase in the permeability of the glomerular filter, which leads to proteinuria. The development of hyaline-drop dystrophy is possible in nephrotic syndrome, glomerulonephritis, paraproteinemic states, amyloidosis, diabetes. Hyaline-drop dystrophy of nephrocytes is based on the deficiency of the vascular-lysosomal system of the epithelium of proximal tubules, which normally reabsorb proteins.   Macroscopically, the appearance of the organ does not have specific features in the dystrophy, it, first of all, depends on the specific characteristics of the primary disease. Microscopic changes are characterized by the accumulation of hyaline   droplets in the epithelium of the renal tubules. This is accompanied by the de structure of mitochondria, endoplasmic reticulum, and brush border. Changes in the liver. The cause of the development of hyaline-drop dystrophy may be infectious diseases (viral hepatitis), intoxications, including alcohol intoxication and intoxication in the case of poisoning (Fig. 2).


Hyaline-drop dystrophy


Macroscopic changes are due to the manifestation of the primary disease. Microscopic changes in hepatocytes are characterized by the appearance of hyaline-like bodies in their cytoplasm, which consists of fibrils of the special protein – alcoholic hyaline. The formation of alcoholic hyaline “Mallory’s hyaline bodies” in the hepatocytes is a morphological substrate of perverted protein synthetic function of the hepatocytes.

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).


Hydropic dystrophy or degeneration


Hydropic dystrophy or degeneration


mechanism of the development of hydropic dystrophy is complex and reflects water and electrolyte imbalance, as well as protein metabolism disorder, leading to the changes in colloid osmotic pressure in the cell. In this case, an important role belongs to the disruption of permeability of the membranes of the cells, accompanied by their lysis, which leads to acidification of the cytoplasm, activation of hydrolytic enzymes with the help of lysosomes, which break the intramolecular bonds with the addition of water.

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

Congenital parenchymatous proteinosis include several distro phones, which are based on the intracellular metabolism disorder of some amino acids as a result of a hereditary deficiency of metabolizing enzymes, which is referred to as hereditary enzymopathy. Congenital parenchymatous proteinosis belong to the so-called “storage diseases”, which include cystinosis, tyrosine sis, phenyl pyruvic oligophrenia (phenylketonuria). Their characteristic is shown in table 3.


Hereditary dystrophies associated with a metabolic disorder of amino acids
Name Enzyme deficiency Localization
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)

Parenchymatous lipidoses – manifest themselves as the accumulation of lipid cells in the cytoplasm: neutral fats, triglycerides, phospholipids, cholesterol.

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.


  The macroscopic changes depend on the stage of fatty degeneration. The liver is enlarged, has flabby consistency, the cut is ocherous or yellow-brown, becomes “clay-colored”; the droplets of fat appear on the edge of the postmortem knife. Figuratively, this liver according to the macroscopic picture is referred to as “goose liver”, which is shown in figure 5.


Parenchymatous fatty degeneration (lipidoses)


Microscopic changes in hepatocytes are characterized by the appearance of fat droplets of different sizes in the cytoplasm. In the case of significant accumulation of lipid inclusions, the nucleus is shifted by the fat droplets to the periph year of the cells, looking like “signet ring cells”.   Fatty liver stained with hematoxylin and eosin is characterized by the appearance of fat inclusions in the hepatocytes in the form of light formations “voids”, because fat having been stained, dissolves in alcohols. Lipid complexes are of different sizes; they may be of focal or disseminated nature, filling almost all the cells of the liver acinus (Fig. 6). To identify the fat inclusions, special histochemical techniques are using Sudan-III and Sudan-black. Having been stained on the fat with Sudan-III, fat droplets in the hepatocytes are discolored to different tones of yellow or yellow-orange (Fig. 7).



Changes in the myocardium: dust-like fatty degeneration develops more frequent, microvesicular hepatic steatosis – less often; the process is localized in the venular link of the microvasculature; this type of dystrophy is based on hy hypoxia or intoxication, triggering the mechanism of decomposition, less often – infiltration. The lack of oxygen leads to the activation of anaerobic glycolysis, a significant decrease in ATP, progressing acidosis, and mitochondrial damage, which results in energy failure.

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.



Carbohydrate degeneration is associated with glycogen metabolism disorder. Main glycogen stores are located in the liver and skeletal muscles. Liver and muscle glycogen is consumed, depending on the needs of the body and it is referred to as unstable glycogen. The glycogen of the nerve cells, aorta, en endothelium, epithelium, endometrium, connective tissue, embryonic tissue, cartilage, and leukocytes is an essential component of cells, and its content is not susceptible to an excursion, so it is referred to as stable glycogen.   Glycogen metabolism disorder manifests itself as glycogen decrease (hypoglycemia) or glycogen increases (hyperglycemia), as well as glycogen appearance in abnormal places. Regulation of carbohydrate metabolism is carried out based on the neuroendocrine system. The main role in the regulation have longed to the hypothalamic area, the pituitary gland (ACTH, TSH, GH), the B- cells of the pancreas (insulin), adrenal glands (glucocorticoids, epinephrine), and the thyroid gland.   In diabetes, the development of which is associated with abnormal B-cells of the pancreas, there is insufficient use of glucose by tissues, increased fasting glucose (hyperglycemia), and its urinary excretion (glucosuria). Glycogen stores in tissues decrease, first of all, in the liver, leading to the infiltration of the hepatocyte with fats and the development of the fatty liver. Glycogen inclusions appear in the hepatocyte nuclei, they become light, “perforated” or “empty”. Infiltration of the tubular epithelium with glycogen (glycogenic infiltration), mostly narrow and distal segments of the nephron, is associated with glycosuria.
Microscopically – the epithelium becomes high, with pale foamy cyto plasma; glycogen granules are visible in the lumen of the tubules, which reflects the state of glycogen synthesis polymerization of glucose. Glomerular affects tion in diabetes manifests itself as diabetic microangiopathy. There is the development of intercapillary glomerulosclerosis.   Hereditary carbohydrate degenerations are pathological processes based on glycogen metabolism disorder. They are also called glycogenosis.   The cause of their development is azymia or deficiency of the enzyme involved in the breakdown of depot glycogen, so they belong to hereditary enzymyopathy or “storage diseases”.   Morphological verification of glycogenosis is only possible if histofermentative methods are used for the reaction.   Hereditary glycogenosis can be divided into 2 groups: – without structural lesion of glycogen. They include Gierke disease (glycogen nosis type 1), Pompe disease (glycogenosis type 2), McArdle’s disease (gly cyanosis type 5), her disease (glycogenosis type 6); – with a structural lesion of glycogen. They include Forbes disease (glycogenosis type 3), Andersen disease (glycogenosis type 4).