Mixed Dystrophy (parenchymal and stroma dystrophy)

Mixed dystrophy – is a type of dystrophy, when there is a metabolism disorder both in cells (parenchyma or parenchymal) and in the stroma (connective tissue), as well as in the vascular walls. These dystrophies occur in the disorder of complex proteins of chromo proteins, nucleoproteins, and lipoproteins, as well as minerals.


Hematogenous pigments, hemoglobin derivatives: ferritin, hemosiderin bilirubin are formed in the normal decomposition of red blood cells and hemoglobin, and their number increases in pathology; hematoidin, hematin, porphyrin appear in pathology.

Hemosiderin metabolism disorder – Mixed dystrophy

Hemosiderin metabolism disorder (A type of mixed dystrophy) is Under pathological conditions, excessive formation of hemosiderin leads to the development of hemosiderosis.

In pathology, Macroscopically – organs become brown or rusty-brown. In the microscopic examination, hemosiderin, the pigment-containing iron may be identified by the use of Perls test (formation of Prussian blue), where it takes the form of emerald-blue grains or granules. This reaction makes it possible to distinguish be tween hemosiderin from other “brown” pigments. The essence of the reaction of Prussian Blue is the restoration of ferrous iron to ferric iron. The accumulation of hemosiderin in the tissues is referred to as hemosiderosis: it may be general and local.

1. General hemosiderosis, widespread hemosiderosis is observed in the intravascular degeneration of red blood cells, which is referred to as intravascular hemolysis. The cells absorbing fragments of hemosiderin are referred to as siderophages.

Causes are blood diseases, intoxication with hemolytic poisons, infectious diseases, blood transfusions without matching, Rh-disease, and others. Hemochromatosis is a kind of pathological process that develops in the excessive accumulation of hemosiderin and is characterized by the deposition of iron and damage of organs and tissues. In this case, the function of the organ may be reduced there is atrophy of the parenchyma or sclerosis. This state is close to general hemosiderosis and may be primary (hereditary hemochromatosis) or secondary

Primary hemochromatosis is due to the genetic defect associated with increased iron absorption out of food. Typical manifestations are liver cirrhosis, diabetes mellitus, bronze skin color, constrictive cardiomyopathy with cardiomegaly, mucous and serous membrane lesion, endocrine and exocrine insufficiency.

Secondary hemochromatosis develops with an increase in parenteral administration of iron, such as frequent blood transfusions, an overdose of vitamin C; it can also be a manifestation of Kashin-Beck disease and anemia with erythroid hyperplasia. Liver cirrhosis, pancreas damage with the development of diabetes mellitus are typical for secondary hemochromatosis.

2. Local hemosiderosis is a condition that develops in the extravascular degeneration of red blood cells, which is referred to as extravascular hemolysis, This process develops in foci of hemorrhage and hematomas in the skin. Macroscopically, it may have different sizes, with foci of hemorrhage and brown hemosiderosis

The microscopic picture is characterized by the presence of foci of hemorrhage in the dermis as the presence of red blood cells and siderophages containing hemosiderin pigment accumulation, which is brown (Fig. 20).


Figure 20. Hemosiderosis of the skin. There is hemosiderin pigment accumulation in foci of hemorrhage stained with hematoxylin and eosin. 100-fold.

Foci of hemosiderosis are most frequently found in the area of hemorrhage in hemorrhagic cerebral infarction, traumatic brain injuries of different parts of the brain (Fig. 21)


Figure 21. Hemosiderosis in the area of intracerebral hemorrhage. Perls test (reaction of Prussian blue). 200-fold.

Another example is the development of hemosiderosis in chronic venous congestion in the liver, lungs, and other organs. Its main pathogenetic mechanism can be described as – increased vascular permeability of vascular walls and release of red blood cells outside the bloodstream, the formation of hemosiderin pigment, development of hemosiderosis that is referred to as “brown induration of the lung” or “brown firmness of the lung” (Fig. 22).

Bilirubin metabolism disorder is associated with its formation and excretion, what leads to an abnormally large amount of bilirubin in the blood (hyper- bilirubinemia), icteric discoloration of the skin, sclerae, mucous and serous membranes, internal organs; this symptom (a sign of the disease) is referred to as jaundice.


Figure 22. Brown induration of the lung: The accumulation of emerald-blue hemosiderin in the alveolar lumens and interstitial tissue of the lung, Perls test (reaction of Prussian blue) 400-fold.

According to the pathology mechanism of jaundice development, there are 3 types:

  1. Cythemolytic icterus is characterized by an increased amount of bilirubin due to increased destruction of red blood cells. It may be observed in intoxication with hemolytic poisons, infections, blood transfusions without matching, sepsis, malaria, autoimmune and isoimmune diseases (hemolytic disease of the newborn).
  2. Hepatocellular jaundice occurs in the injury of hepatocytes. In this case, there is disturbed absorption of bilirubin, its conjugation with glucuronic acid, and excretion. It develops in acute and chronic hepatitis, liver cirrhosis, drug-induced hepatocyte injury, auto-intoxication, pregnancy, hemorrhagic syndrome.
  3. Obstructive jaundice develops in obstructed bile flow and bile duct patency (Fig. 23). For example: in cholelithiasis, tumors of the liver and gallbladder or bile ducts, metastases in hepatico-pancreatic area, obstructed bile flow is possible in the presence of parasites (giardiasis, hydatid disease), liver cirrhosis.


Figure 23. Cholestasis in the liver (obstructive jaundice). Stained with hematoxylin and eosin. 100-fold

Possible localization of gallstones in different parts of the bile ducts is shown in figure 24. Localization of gallstones in the lumen of the small intestine is also possible in the case of their penetration through the bile ducts, or the development of such complications as perforation of the gallbladder with the large gallstones, which may lead to the development of peritonitis.


Figure 24. Possible localization of gallstones in the bile ducts

  1. gallbladder,
  2. intrahepatic bile ducts,
  3. common bile duct
  4. pancreas,
  5. the small intestine


Under conditions of pathology, such pigment, as – hematoid, hematin, and porphyrin may be formed in hemoglobin decomposition.

Hematoidin is a pigment that does not contain iron, has the form of rhomboid plates. It is formed intracellularly in red blood cells and hemoglobin decomposition, but unlike hemosiderin, it can be found among the necrotic masses in the case of cell death. Hematoidin accumulation can be observed in old hematomas, scars of infarctions. Its localization is also possible in the central parts of hemorrhage – away from living tissues.

Hematin is the hydroxide of heme and formed by the hydrolysis of oxyhemoglobin. It has the form of dark brown or black rhomboid crystals or granules, produces birefringence in polarized light (anisotropic), contains iron, but in a bound state. Detectable in the tissues porphyrins include – malarial pigment, hemin, and formalin pigment. Histological characteristics of these pigments are identical.

  1. the malarial pigment is derived from the prosthetic part of hemoglobin under the influence of malaria parasites in red blood cells. Iron storage disease develops in malaria.
  2. hematin may be found in gastric erosions and ulcers, where it appears to have been caused by the influence of enzymes of gastric juice and chlorohydric acid on hemoglobin, wherein the defect area becomes brown-black.
  3. formalin pigment appears in tissues during their fixing in formaldehyde, It takes the form of brown granules; it is considered a derivative from hematin.

Porphyrins are precursors of the prosthetic part of hemoglobin having hemes and tetrapyrrole ring, but being iron-free. It is detected with the help of histo-fluorescence. Normally, the pigment is found in blood, urine, tissues, it has the ability to increase the sensitivity of the body, especially the skin to the light, Porphyrins are antagonists of melanin.

Porphyria is a genetic disorder characterized by a disturbance in porphyrin metabolism. It may be in the blood – erythropoietic porphyria, in the urine porphyrinuria. There is increased sensitivity to ultraviolet rays – photophobia, erythema, dermatitis.

There are congenital and acquired forms of porphyria.

  1. Acquired porphyria may develop in intoxications (lead, barbiturates), avitaminosis (pellagra), pernicious anemia and some liver diseases.
  2. Congenital porphyria occurs as a rare hereditary disease in disturbance of the porphyrin synthesis in liver cells and erythroblasts.



Proteinogenic pigments are associated with the metabolism disorder or metabolism dystrophy of tyrosine. They include melanin, the pigment of the granules of enterochromaffin cells (carcinoids); adrenochrome – oxidation product of adrenaline.

Melanin – In mixed Dystrophy, it is characterized by the brown pigment, which is accounted for the dark color of eyes, hair, and skin. The synthesis of melanin occurs in the cells called melanocytes. The cells phagocytizing melanin, are called melanophages, Disturbance of melanin synthesis can be associated with its increased amount – melanosis, decreased amount – hypomelanosis, its absence – albinism or vitiligo. Xeroderma pigmentosum is a common congenital melanosis. Local melanosis (hyperpigmentation) is mainly represented by nevi.

The pigment of the granules of enterochromaffin cells is localized in the different parts of the gastrointestinal tract, in tumors – carcinoids and is a tryptophan derivative; it may be detected in histochemical reaction – argentaffin reaction, chromaffin reaction. Pigment formation is related to the synthesis of serotonin and melatonin.

Adrenochrome – oxidation product of adrenaline occurs in the form of granules in the cells of the adrenal medulla (Adrenal Medulla Dystrophy). It gives a typical chromaffin reaction, which is based on the ability to discolor with chromic acid to dark-brown and restore dichromate.



Lipogenic pigments are lipofuscin – A Mixed Dystrophy which is characterized by the pigment of deficiency of vitamin E, ceroid, lipochrome.

The pigments “hemofuscin” and the pigment of deficiency of vitamin E are believed to be derivatives of lipofuscin, its sub-types. They are accumulated in parenchymal cells and formed in chronic diseases, tumors, aging, that is why these pigments are called “aging pigments”. Ceroid is detected in mesenchymal cells. Lipochrome is a source of vitamin “A” and refers to carotenoids, colored hydrocarbons.

Lipofuscin is an insoluble pigment consisting of polymers of lipids and phospholipids in combination with proteins. It is believed to be formed as a result of lipid peroxidation. Normally, lipofuscin is responsible for the energy supply of the cells in the case of oxygen deficiency, lipofuscin is accumulated this process is referred to as lipofuscinosis. The basis of the excessive formation of lipofuscin is damage to the Golgi apparatus. Lipofuscinosis may be primary and secondary’

Primary (hereditary) lipofuscinosis is characterized by the selective accumulation of the pigment in the cells of a particular organ or system. It occurs mainly in diseases related to the central nervous system, and pigment accumulation of lipofuscin in neurons (Tay-Sachs disease, Jansky- Bielschowsky disease, and others).

Secondary lipofuscinosis may develop in parenchymal organs as age-related changes in old age, in exhaustion, severe chronic infectious and non-infectious dis cases, tumors leading to deep metabolism disorder, and the development of cachexia, as well as in drug abuse, deficiency of vitamin E and others.

Macroscopic changes are characterized by the atrophy of the internal organs, and the pathological process is referred to as “brown atrophy. Organs are reduced in size, become brown due to the accumulation of lipofuscin pigment in the parenchyma of internal organs.

So, in brown atrophy of the heart, macroscopically, the organ is reduced in volume and size, indurated, the myocardium becomes brown due to the ac cumulation of lipofuscin pigment in cardiomyocytes: the heart cavity is reduced in volume (Fig. 25).


Figure 25. Brown myocardial atrophy. The heart is reduced in size, the myocardium becomes brown, dull due to the ac- cumulation of lipofuscin pigment.


Microscopic changes are characterized by the accumulation of brown lipofuscin granules in the perinuclear area of golden-brown cells, such as cardiomyocytes and hepatocytes (Fig. 26).


Figure 26. Brown atrophy of the liver. Lipofuscin granules in the cytoplasm of golden brown hepatocytes Stained with hematoxylin and eosin. 200-fold




In metabolism disorder or metabolism/mixed dystrophy, it is characterized by nucleoproteins and excessive formation of uric acid, its salts may be deposited in the tissues, the joints in gout resulting in deformation called “gouty tophi”; as well as in urolithiasis, uric acid infarct in the newborn.

Both urolithiasis and gout are associated with the metabolism disorder of purines and manifest themselves as the development of lithiasis, the formation of urates in the kidneys and urinary tracts.

Uric acid infarct occurs in newborns who have lived for at least 2 days and manifests itself as sodium and ammonium acid urate deposits in the renal collecting tubules (Fig. 27).


Figure 27. The deformation of the joints of the fingers in gout.