Methods of strategic management in China. Specific features of the Chinese management model. What Western Managers Can Learn from Eastern Colleagues

Iron-deficiency anemia;

2. B12 deficiency anemia;

3. Folate deficiency anemia;

4. Anemia due to protein deficiency;

5. Anemia due to scurvy;

6. Unspecified anemia caused by poor diet;

7. Anemia due to enzyme deficiency;

8. Thalassemia (alpha thalassemia, beta thalassemia, delta beta thalassemia);

9. Hereditary persistence of fetal hemoglobin;

11. Hereditary spherocytosis (Minkowski-Choffard anemia);

14. Drug-induced non-autoimmune hemolytic anemia;

15. Hemolytic-uremic syndrome;

16. Paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli disease);

17. Acquired pure red cell aplasia (erythroblastopenia);

18. Constitutional or drug-induced aplastic anemia;

19. Idiopathic aplastic anemia;

20. Acute posthemorrhagic anemia (after acute blood loss);

21. Anemia due to neoplasms;

22. Anemia in chronic somatic diseases;

23. Sideroblastic anemia (hereditary or secondary);

24. Congenital dyserythropoietic anemia;

25. Acute myeloblastic undifferentiated leukemia;

26. Acute myeloblastic leukemia without maturation;

27. Acute myeloid leukemia with maturation;

28. Acute promyelocytic leukemia;

29. Acute myelomonoblastic leukemia;

30. Acute monoblastic leukemia;

31. Acute erythroblastic leukemia;

32. Acute megakaryoblastic leukemia;

33. Acute lymphoblastic T-cell leukemia;

34. Acute lymphoblastic B-cell leukemia;

35. Acute panmyeloid leukemia;

36. Letterer-Siwe disease;

37. Myelodysplastic syndrome;

38. Chronic myeloid leukemia;

39. Chronic erythromyelosis;

40. Chronic monocytic leukemia;

41. Chronic megakaryocytic leukemia;

43. Mast cell leukemia;

44. Macrophage leukemia;

45. Chronic lymphocytic leukemia;

46. ​​Hairy cell leukemia;

48. Sézary's disease (skin lymphocytoma);

49. Mycosis fungoides;

50. Burkitt's lymphosarcoma;

51. Lennert's lymphoma;

52. Malignant histiocytosis;

53. Malignant mast cell tumor;

54. True histiocytic lymphoma;

56. Hodgkin's disease (lymphogranulomatosis);

57. Non-Hodgkin's lymphomas;

58. Multiple myeloma (generalized plasmacytoma);

59. Waldenström's macroglobulinemia;

60. Alpha heavy chain disease;

61. Gamma heavy chain disease;

62. Disseminated intravascular coagulation (DIC syndrome);

63. Hemorrhagic disease of newborns;

64. Deficiency of K-vitamin-dependent blood clotting factors;

65. Coagulation factor I deficiency and dysfibrinogenemia;

66. Deficiency of clotting factor II;

67. Deficiency of coagulation factor V;

68. Deficiency of blood coagulation factor VII (hereditary hypoproconvertinemia);

69. Hereditary deficiency of blood clotting factor VIII (von Willebrand disease);

70. Hereditary deficiency of blood clotting factor IX (Christamas disease, hemophilia B);

71. Hereditary deficiency of blood clotting factor X (Stewart-Prower disease);

72. Hereditary deficiency of blood clotting factor XI (hemophilia C);

73. Deficiency of blood coagulation factor XII (Hageman defect);

74. Deficiency of clotting factor XIII;

75. Deficiency of plasma components of the kallikrein-kinin system;

76. Antithrombin III deficiency;

77. Hereditary hemorrhagic telangiectasia (Rendu-Osler disease);

78. Glanzmann's thrombasthenia;

79. Bernard-Soulier syndrome;

80. Wiskott-Aldrich syndrome;

81. Chediak-Higashi syndrome;

83. Hegglin's syndrome;

84. Kasabach-Merritt syndrome;

85. Hemorrhagic vasculitis (Scheinlein-Henoch disease);

86. Ehlers-Danlos syndrome;

87. Gasser syndrome;

88. Allergic purpura;

89. Idiopathic thrombocytopenic purpura (Werlhof's disease);

90. Fake bleeding (Munchausen syndrome);

92. Functional disorders of polymorphonuclear neutrophils;

95. Familial erythrocytosis;

96. Essential thrombocytosis;

97. Hemophagocytic lymphohistiocytosis;

98. Hemophagocytic syndrome caused by infection;

99. Cytostatic disease.

Blood disease - types

1. Anemia (conditions in which the hemoglobin level is below normal);

2. Hemorrhagic diathesis or pathology of the hemostatic system (blood clotting disorders);

3. Hemoblastoses (various tumor diseases of their blood cells, bone marrow or lymph nodes);

4. Other blood diseases (diseases that do not relate to hemorrhagic diathesis, anemia, or hemoblastosis).

Anemia

1. Anemia due to impaired synthesis of hemoglobin or red blood cells;

2. Hemolytic anemia associated with increased breakdown of hemoglobin or red blood cells;

3. Hemorrhagic anemia associated with blood loss.

Anemia due to blood loss is divided into two types:

• Acute posthemorrhagic anemia - occurs after a rapid, simultaneous loss of more than 400 ml of blood;
• Chronic posthemorrhagic anemia - occurs as a result of prolonged, constant blood loss due to small but constant bleeding (for example, with heavy menstruation, bleeding from a stomach ulcer, etc.).

Anemia caused by impaired hemoglobin synthesis or red blood cell formation is divided into the following types:

1. Aplastic anemia:

• Red cell aplasia (constitutional, drug-induced, etc.);
• Partial red cell aplasia;
• Blackfan-Diamond anemia;
• Fanconi anemia.

2. Congenital dyserythropoietic anemia.

3. Myelodysplastic syndrome.

4. Deficiency anemias:

• Iron-deficiency anemia;
• Folate deficiency anemia;
• B12 deficiency anemia;
• Anemia due to scurvy;
• Anemia due to insufficient protein in the diet (kwashiorkor);
• Anemia due to a lack of amino acids (orotaciduric anemia);
• Anemia due to a lack of copper, zinc and molybdenum.

5. Anemia due to impaired hemoglobin synthesis:

• Porphyrias – sideroachristic anemias (Kelly-Paterson syndrome, Plummer-Vinson syndrome).

6. Anemia of chronic diseases (with renal failure, cancer, etc.).

7. Anemia with increased consumption of hemoglobin and other substances:

As you can see, the spectrum of anemia caused by impaired hemoglobin synthesis and the formation of red blood cells is very wide. However, in practice, most of these anemias are rare or very rare. And in everyday life, people most often encounter various variants of deficiency anemia, such as iron deficiency, B12 deficiency, folate deficiency, etc. These anemias, as the name implies, are formed due to an insufficient amount of substances necessary for the formation of hemoglobin and red blood cells. The second most common form of anemia associated with impaired synthesis of hemoglobin and red blood cells is the form that develops in severe chronic diseases.

1. Anemia caused by a defect in the shape of red blood cells:

• Hereditary spherocytosis (Minkowski-Schaffar disease);
• Hereditary elliptocytosis;
• Hereditary stomatocytosis;
• Hereditary acanthocytosis.

2. Anemia caused by deficiency of erythrocyte enzymes:

• Anemia due to glucose-6-phosphate dehydrogenase deficiency;
• Anemia due to disorders of glutathione metabolism;
• Anemia due to disorders of nucleotide metabolism;
• Anemia due to hexokinase deficiency;
• Anemia due to pyruvate kinase deficiency;
• Anemia due to triosephosphate isomerase deficiency.

3. Anemia caused by a defective hemoglobin structure:

• Sickle cell anemia.

4. Anemia caused by defective alpha and beta chains of the globin protein, which is part of hemoglobin:

• Thalassemia (alpha, beta, delta thalassemia);
• Delta-beta thalassemia;
• Hereditary persistence of fetal hemoglobin.

Acquired hemolytic anemias are divided into the following types:

1. Hemolytic anemia caused by the destruction of red blood cells by antibodies:

• Anemia after blood transfusion or blood substitutes;
• Autoimmune hemolytic anemia (AIHA).

2. Hemolytic anemia caused by mechanical destruction of red blood cells:

• Marching hemoglobinuria (occurs after a long march);
• Anemia due to pathology of small and medium vessels;
• Thrombotic thrombocytopenic purpura;
• Hemolytic-uremic syndrome;
• Paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli disease).

• Anemia due to malaria;
• Anemia due to lead poisoning, etc.

4. Anemia caused by poisoning with hemolytic poisons.

5. Anemia caused by a large number or increased activity of cells from the group of mononuclear phagocytes:

• Anemia in acute infectious disease;
• Anemia with an enlarged spleen.

As you can see, hemolytic anemias are even less common in everyday life than those associated with impaired hemoglobin or red blood cell synthesis. However, these types of anemia have a more malignant course and are often less responsive to therapy.

Hemoblastoses (oncological blood diseases, blood cancer)

• Lymphoblastic T- or B-cell;
• Myeloblastic;
• Monoblastic;
• Myelomonoblastic;
• Promyelocytic;
• Erythromyeloblastic;
• Megakaryoblastic;
• Plasmablastic;
• Macrophagic;
• Undifferentiated;
• Panmyeloid leukemia;
• Acute myelofibrosis.

Chronic leukemia is divided into the following types:

1. Lymphoproliferative chronic leukemias:

• Lymphocytic leukemia;
• Hairy cell leukemia;
• T-cell leukemia;
• Sezary's disease;
• Letterer-Siwe disease;
• Paraproteinemias (myeloma, Waldenström's macroglobulinemia, light and heavy chain disease).

2. Myeloproliferative leukemias:

• Myelocytic leukemia;
• Neutrophilic leukemia;
• Basophilic leukemia;
• Eosinophilic leukemia;
• Erythremia;
• Megakaryocytic;
• Mast cell;
• Subleukemic myelosis;
• Myelosclerosis;
• Essential thrombocythemia.

3. Monocytoproliferative leukemias:

• Monocytic leukemia;
• Myelomonocytic leukemia;
• Histiocytosis X.

4. Other chronic leukemias:

• Malignant mast cell tumor;
• True histiocytic lymphoma;
• Malignant histiocytosis.

All types of acute and chronic leukemia develop from cells present in the bone marrow and at different stages of maturation. Acute leukemias have a higher degree of malignancy compared to chronic ones, and therefore are less treatable and have a more negative prognosis for life and health.

1. Follicular lymphoma:

• Mixed large cell and small cell with split nuclei;
• Large cell.

2. Diffuse lymphoma:

• Small cell;
• Small cell with split nuclei;
• Mixed small cell and large cell;
• Reticulosarcoma;
• Immunoblastic;
• Lymphoblastic;
• Burkitt's tumor.

3. Peripheral and cutaneous T-cell lymphomas:

• Sezary's disease;
• Mycosis fungoides;
• Lennert's lymphoma;
• Peripheral T-cell lymphoma.

4. Other lymphomas:

Hemorrhagic diathesis (blood clotting diseases)

1. Disseminated intravascular coagulation syndrome (DIC syndrome).

2. Thrombocytopenia (the number of platelets in the blood is below normal):

• Idiopathic thrombocytopenic purpura (Werlhof's disease);
• Alloimmune purpura of newborns;
• Transimmune purpura of newborns;
• Heteroimmune thrombocytopenia;
• Allergic vasculitis;
• Evans syndrome;
• Vascular pseudohemophilia.

3. Thrombocytopathies (platelets have a defective structure and inferior functional activity):

• Hermansky-Pudlak disease;
• TAR syndrome;
• May-Hegglin syndrome;
• Wiskott-Aldrich disease;
• Glanzmann's thrombasthenia;
• Bernard-Soulier syndrome;
• Chediak-Higashi syndrome;
• Von Willebrand's disease.

4. Blood clotting disorders against the background of vascular pathology and insufficiency of the coagulation link of the coagulation process:

• Rendu-Osler-Weber disease;
• Louis-Bar syndrome (ataxia-telangiectasia);
• Hemangiomas;
• Kasabach-Merritt syndrome;
• Ehlers-Danlos syndrome;
• Gasser syndrome;
• Hemorrhagic vasculitis (Scheinlein-Henoch disease);
• Thrombotic thrombocytopenic purpura.

5. Blood clotting disorders caused by disorders of the kinin-kallikrein system:

• Fletcher's defect;
• Williams defect;
• Fitzgerald defect;
• Phlojac defect.

6. Acquired coagulopathies (pathology of blood clotting against the background of disorders of the coagulation component of coagulation):

• Afibrinogenemia;
• Consumptive coagulopathy;
• Fibrinolytic bleeding;
• Fibrinolytic purpura;
• Lightning purpura;
• Hemorrhagic disease of the newborn;
• Deficiency of K-vitamin-dependent factors;
• Coagulation disorders after taking anticoagulants and fibrinolytics.

7. Hereditary coagulopathies (blood clotting disorders caused by a deficiency of coagulation factors):

• Fibrinogen deficiency;
• Deficiency of clotting factor II (prothrombin);
• Deficiency of coagulation factor V (labile);
• Factor VII deficiency;
• Factor VIII deficiency (hemophilia A);
• Coagulation factor IX deficiency (Christmas disease, hemophilia B);
• Coagulation factor X deficiency (Stuart-Prower);
• Factor XI deficiency (hemophilia C);
• Coagulation factor XII deficiency (Hageman disease);
• Deficiency of coagulation factor XIII (fibrin-stabilizing);
• Thromboplastin precursor deficiency;
• AC globulin deficiency;
• Proaccelerin deficiency;
• Vascular hemophilia;
• Dysfibrinogenemia (congenital);
• Hypoproconvertinemia;
• Ovren's disease;
• Increased antithrombin content;
• Increased levels of anti-VIIIa, anti-IXa, anti-Xa, anti-XIa (anti-clotting factors).

Other blood diseases

1. Agranulocytosis (lack of neutrophils, basophils and eosinophils in the blood);

2. Functional disorders of the activity of band neutrophils;

3. Eosinophilia (increased number of eosinophils in the blood);

5. Familial erythrocytosis (increased number of red blood cells);

6. Essential thrombocytosis (increased number of blood platelets);

7. Secondary polycythemia (increase in the number of all blood cells);

8. Leukopenia (reduced number of leukocytes in the blood);

9. Cytostatic disease (a disease associated with taking cytostatic drugs).

Blood diseases - symptoms

• Weakness;
• Fatigue;
• Dizziness;
• Dyspnea;
• Heartbeat;
• Decreased appetite;
• Increased body temperature, which lasts almost constantly;
• Frequent and long-term infectious and inflammatory processes;
• Itchy skin;
• Perversion of taste and smell (a person begins to like specific smells and tastes);
• Bone pain (with leukemia);
• Bleeding such as petechiae, bruises, etc.;
• Constant bleeding from the mucous membranes of the nose, mouth and gastrointestinal tract;
• Pain in the left or right hypochondrium;
• Low performance.

This list of symptoms of blood diseases is very brief, but it allows you to navigate the most typical clinical manifestations of blood system pathology. If a person experiences any of the above symptoms, they should consult a doctor for a detailed examination.

Blood disease syndromes

• Anemic syndrome;
• Hemorrhagic syndrome;
• Necrotizing ulcerative syndrome;
• Intoxication syndrome;
• Ossalgic syndrome;
• Protein pathology syndrome;
• Sideropenic syndrome;
• Plethoric syndrome;
• Jaundice syndrome;
• Lymphadenopathy syndrome;
• Hepato-splenomegaly syndrome;
• Blood loss syndrome;
• Fever syndrome;
• Hematological syndrome;
• Bone marrow syndrome;
• Enteropathy syndrome;
• Arthropathy syndrome.

The listed syndromes develop against the background of various blood diseases, some of them are characteristic only of a narrow range of pathologies with a similar development mechanism, while others, on the contrary, occur in almost any blood disease.

Anemic syndrome

• Paleness of the skin and mucous membranes;
• Dry and flaky or moist skin;
• Dry, brittle hair and nails;
• Bleeding from mucous membranes - gums, stomach, intestines, etc.;
• Dizziness;
• Unsteady gait;
• Darkening in the eyes;
• Noise in ears;
• Fatigue;
• Drowsiness;
• Shortness of breath when walking;
• Heartbeat.

In severe cases of anemia, a person may experience pasty legs, perversion of taste (like inedible things, such as chalk), a burning sensation in the tongue or its bright crimson color, as well as choking when swallowing pieces of food.

Hemorrhagic syndrome

• Bleeding gums and prolonged bleeding during tooth extraction and injury to the oral mucosa;
• Feeling of discomfort in the stomach area;
• Black chair;
• red blood cells or blood in the urine;
• Uterine bleeding;
• Bleeding from injection punctures;
• Bruises and pinpoint hemorrhages on the skin;
• Headache;
• Pain and swelling of the joints;
• Inability to actively move due to pain caused by hemorrhages in the muscles and joints.

Hemorrhagic syndrome develops with the following blood diseases:

1. Thrombocytopenic purpura;

2. Von Willebrand's disease;

3. Rendu-Osler disease;

4. Glanzmann's disease;

5. Hemophilia A, B and C;

6. Hemorrhagic vasculitis;

9. Aplastic anemia;

10. Taking large doses of anticoagulants.

Necrotizing ulcerative syndrome

• Pain in the oral mucosa;
• Bleeding from the gums;
• Inability to eat due to pain in the mouth;
• Increased body temperature;
• Chills;
• Bad breath;
• Discharge and discomfort in the vagina;
• Pain in the anus;
• Difficulty defecating.

Ulcerative-necrotic syndrome develops with hemoblastoses, aplastic anemia, as well as radiation and cytostatic diseases.

Intoxication syndrome

• General weakness;
• Fever with chills;
• Prolonged persistent increase in body temperature;
• Malaise;
• Reduced ability to work;
• Pain in the oral mucosa;
• Symptoms of a common respiratory disease of the upper respiratory tract.

Intoxication syndrome develops with hemoblastoses, hematosarcomas (Hodgkin's disease, lymphosarcoma) and cytostatic disease.

Ossalgic syndrome

Protein pathology syndrome

• Headache;
• Deterioration of memory and attention;
• Drowsiness;
• Pain and numbness in the legs and arms;
• Bleeding of the mucous membranes of the nose, gums and tongue;
• Hypertension;
• Retinopathy (impaired functioning of the eyes);
• Kidney failure (in later stages of disease);
• Dysfunction of the heart, tongue, joints, salivary glands and skin.

Protein pathology syndrome develops in myeloma and Waldenström's disease.

Sideropenic syndrome

• Perversion of the sense of smell (a person likes the smells of exhaust fumes, washed concrete floors, etc.);
• Perversion of taste (a person likes the taste of chalk, lime, charcoal, dry cereals, etc.);
• Difficulty swallowing food;
• Muscle weakness;
• Pale and dry skin;
• Seizures in the corners of the mouth;
• Thin, brittle, concave nails with transverse striations;
• Thin, brittle and dry hair.

Sideropenic syndrome develops in Werlhof and Randu-Osler diseases.

Plethoric syndrome

The syndrome develops with erythremia and Vaquez disease.

Jaundice syndrome

Lymphadenopathy syndrome

• Enlargement and pain of various lymph nodes;
• Intoxication phenomena (fever, headache, drowsiness, etc.);
• Sweating;
• Weakness;
• Strong weight loss;
• Pain in the area of ​​an enlarged lymph node due to compression of nearby organs;
• Fistulas with discharge of purulent contents.

The syndrome develops in chronic lymphocytic leukemia, lymphogranulomatosis, lymphosarcoma, acute lymphoblastic leukemia and infectious mononucleosis.

Hepato-splenomegaly syndrome

• Feeling of heaviness in the upper abdomen;
• Pain in the upper abdomen;
• Increased abdominal volume;
• Weakness;
• Reduced performance;
• Jaundice (at a late stage of the disease).

The syndrome develops in infectious mononucleosis, hereditary microspherocytosis, autoimmune hemolytic anemia, sickle cell and B12 deficiency anemia, thalassemia, thrombocytopenia, acute leukemia, chronic lympho- and myeloid leukemia, subleukemic myelosis, as well as erythremia and Waldenström's disease.

Blood loss syndrome

The syndrome develops with hemoblastoses, hemorrhagic diathesis and aplastic anemia.

Fever syndrome

Hematological and bone marrow syndromes

Enteropathy syndrome

Arthropathy syndrome

• Swelling and thickening of the affected joint;
• Pain in the affected joint;
• Osteoporosis.

Tests for blood diseases (blood parameters)

1. General blood test with determination of such parameters as:

• Total number of leukocytes, erythrocytes and platelets;
• Leukoformula count (percentage of basophils, eosinophils, band and segmented neutrophils, monocytes and lymphocytes in 100 counted cells);
• Blood hemoglobin concentration;
• Study of the shape, size, color and other qualitative characteristics of red blood cells.

2. Counting the number of reticulocytes.

3. Platelet count.

5. Duke bleeding time.

6. Coagulogram with determination of such parameters as:

• The amount of fibrinogen;
• Prothrombin index (PTI);
• International normalized ratio (INR);
• Activated partial thromboplastin time (aPTT);
• Kaolin time;
• Thrombin time (TV).

7. Determination of the concentration of coagulation factors.

8. Myelogram - taking bone marrow using a puncture, followed by preparing a smear and counting the number of different cellular elements, as well as their percentage per 300 cells.

Identifying Some Common Blood Disorders

Infectious blood diseases

Viral blood disease

Chronic blood pathology

Hereditary (genetic) blood diseases

Systemic blood diseases

Autoimmune blood diseases

• Autoimmune hemolytic anemia;
• Drug-induced hemolysis;
• Hemolytic disease of newborns;
• Hemolysis after blood transfusion;
• Idiopathic autoimmune thrombocytopenic purpura;
• Autoimmune neutropenia.

Blood disease - causes

Treatment of blood diseases

Prevention of blood diseases

• Identification and treatment of diseases accompanied by bleeding;
• Timely treatment of helminthic infestations;
• Timely treatment of infectious diseases;
• Good nutrition and vitamin intake;
• Avoidance of ionizing radiation;
• Avoiding contact with harmful chemicals (paints, heavy metals, benzene, etc.);
• Avoiding stress;
• Prevention of hypothermia and overheating.

Common blood diseases, their treatment and prevention - video

Blood diseases: description, signs and symptoms, course and consequences, diagnosis and treatment - video

Blood diseases (anemia, hemorrhagic syndrome, hemoblastosis): causes, signs and symptoms, diagnosis and treatment - video

Polycythemia (polycythemia), increased level of hemoglobin in the blood: causes and symptoms of the disease, diagnosis and treatment - video

What are pathological blood cells

One of the main causes of pathological changes in red blood cells, in addition to blood loss, toxins, hemolysins, etc., is a disruption of the normal activity of the bone marrow.

In some diseases, with increased reactivity of the body, increased activity of the bone marrow occurs - hyperfunction; Instead of dead mature red blood cells, young cells enter the bloodstream - red blood cell regeneration occurs.

The regenerative ability of the bone marrow is judged by the presence of polychromatophilic erythrocytes, reticulocytes and normoblasts in the smear. In a number of diseases of the hematopoietic system, erythrocytes with Jolly bodies and erythrocytes with Cabot rings are found in the peripheral blood.

Degenerative forms of erythrocytes include anisocytes, poikilocytes, and erythrocytes with basophilic granularity.

Red blood cells are hyperchromic, so-called. megalocytes and megaloblasts, belong to the so-called. embryonic form of hematopoiesis. Four cells can often be found in the bloodstream indicating regeneration and degeneration at the same time.

With various blood diseases, red blood cells change their shape, size, and color. The appearance of red blood cells of various sizes in the blood is called anisocytosis.

Red blood cells that are smaller than normal are called microcytes, and those that are larger than normal are called macrocytes. Red blood cells can take on a wide variety of shapes: flasks, pears, gymnastic weights, crescents; such elements are called poikilocytes Anisocytosis and poikilocytosis occur in pernicious anemia and hemolytic jaundice.

In a stained blood sample, anemic red blood cells are found that are weaker colored than normal in hypochromic anemia. In hyperchromic anemia, red blood cells are found that are brighter colored than normal. In case of anemia, blood loss, when there is a large consumption of red blood cells, the blood flow, due to increased activity of the bone marrow, is replenished with not quite mature forms of red blood cells, which have the ability to be stained with both acidic and alkaline dyes, as a result of which they have a grayish-violet color.

Such red blood cells are called polychromatophils, and the ability to stain this way is called polychromasia.

With Addison-Birmer anemia, red blood cells may be found in the protoplasm of which remains of the nucleus are still preserved in the form of loops, rings, stained purple according to Romanovsky, the so-called Cabot rings, or single small fragments of the nucleus in the form of dots - Jolly bodies, stained cherry -Red color.

Degenerative forms include red blood cells with basophilic granularity. These are small grains in the red blood cell that turn bluish. Basophilic granularity in the erythrocyte is clearly visible when stained according to E. Freifeld.

Reticulocytes. In a blood sample stained with diamond-cresyl blue, you can see red blood cells with a thin blue mesh or granularity throughout the cell or only in the center. This mesh is called reticular, or reticular, granulofilamentous substance (substantia granulofilamentosa). Red blood cells with this substance are called reticulocytes.

Reticulocytes are young, immature red blood cells that appear in the blood during increased bone marrow activity. To count reticulocytes, you can use an eyepiece with a piece of paper with a square hole cut into it. 1000 red blood cells and the number of simultaneously detected reticulocytes are counted in different places of the preparation. In normal blood there are 2-4 reticulocytes per 1000 red blood cells.

Differences between absolute and relative lymphocytosis in a blood test

A few years ago, I wrote about the differences between viral and bacterial infections based on a general blood test, and which cells become more and less numerous during various infections. The article has gained some popularity, but needs some clarification.

Even at school they teach that the number of leukocytes should be from 4 to 9 billion (× 10 9) per liter of blood. Depending on their functions, leukocytes are divided into several types, therefore the leukocyte formula (ratio different types leukocytes) normally in an adult looks like this:

• neutrophils (total 48-78%):
  • young (metamyelocytes) - 0%,
  • stab - 1-6%,
  • segmented - 47-72%,
• eosinophils - 1-5%,
• basophils - 0-1%,
• lymphocytes - 18-40% (according to other standards 19-37%),
• monocytes - 3-11%.

For example, a general blood test revealed 45% lymphocytes. Is it dangerous or not? Should we sound the alarm and look for a list of diseases in which the number of lymphocytes in the blood increases? We’ll talk about this today, because in some cases such deviations in blood tests are pathological, while in others they do not pose a danger.

Stages of normal hematopoiesis

Let's look at the results of a general (clinical) blood test of a 19-year-old guy with type 1 diabetes. The analysis was done in early February 2015 in the Invitro laboratory:

Analysis, the indicators of which are discussed in this article

In the analysis, indicators that differ from normal values ​​are highlighted in red. Now in laboratory research the word “ norm" is used less frequently, it is replaced by " reference values" or " reference interval" This is done so as not to confuse people, because depending on the diagnostic method used, the same value can be either normal or abnormal. Reference values ​​are selected in such a way that they correspond to the test results of 97-99% of healthy people.

Let's look at the analysis results highlighted in red.

Hematocrit

Hematocrit - proportion of blood volume accounted for by formed blood elements(erythrocytes, platelets and platelets). Since there are many more red blood cells (for example, the number of red blood cells in a unit of blood exceeds the number of white blood cells by a thousand times), the hematocrit actually shows what part of the blood volume (in%) is occupied by red blood cells. In this case, the hematocrit is at the lower limit of normal, and other indicators of red blood cells are normal, so a slightly reduced hematocrit can be considered a variant of the norm.

Lymphocytes

The above blood test shows 45.6% lymphocytes. This is slightly higher than normal values ​​(18-40% or 19-37%) and is called relative lymphocytosis. It would seem that this is a pathology? But let's count how many lymphocytes are contained in a unit of blood and compare them with the normal absolute values ​​of their number (cells).

The number (absolute value) of lymphocytes in the blood is: (4.69 × 10 9 × 45.6%) / 100 = 2.14 × 10 9 /l. We see this figure at the bottom of the analysis; reference values ​​are indicated nearby: 1.00-4.80. Our result of 2.14 can be considered good, because it is almost in the middle between the minimum (1.00) and maximum (4.80) level.

So, we have relative lymphocytosis (45.6% greater than 37% and 40%), but no absolute lymphocytosis (2.14 less than 4.8). In this case, relative lymphocytosis can be considered a normal variant.

Neutrophils

The total number of neutrophils is calculated as the sum of young (normally 0%), band (1-6%) and segmented neutrophils (47-72%), with a total of 48-78%.

Stages of granulocyte development

In the blood test under consideration, the total number of neutrophils is 42.5%. We see that the relative (%) content of neutrophils is below normal.

Let's calculate the absolute number of neutrophils in a unit of blood:

There is some confusion regarding the proper absolute number of lymphocyte cells.

1) Data from the literature.

2) Reference values ​​for the number of cells from the analysis of the Invitro laboratory (see blood test):

3) Since the above figures do not coincide (1.8 and 2.04), let’s try to calculate the limits of normal cell number values ​​ourselves.

• The minimum acceptable number of neutrophils is the minimum of neutrophils (48%) of the normal minimum of leukocytes (4 × 10 9 / L), that is, 1.92 × 10 9 / L.
• Maximum permissible quantity neutrophils are 78% of the normal maximum of leukocytes (9 × 10 9 / L), that is, 7.02 × 10 9 / L.

The patient's analysis showed 1.99 × 10 9 neutrophils, which in principle corresponds to normal cell numbers. A neutrophil level below 1.5 × 10 9 /l is considered clearly pathological (called neutropenia). A level between 1.5 × 10 9 /L and 1.9 × 10 9 /L is considered intermediate between normal and pathological.

Should we panic if the absolute neutrophil count is near the lower limit of the absolute normal? No. With diabetes (and also with alcoholism), a slightly reduced level of neutrophils is quite possible. To make sure that fears are unfounded, you need to check the level of young forms: normally young neutrophils (metamyelocytes) are 0% and band neutrophils are from 1 to 6%. The commentary to the analysis (does not fit in the figure and is cropped to the right) states:

A blood test using a hematology analyzer did not reveal any pathological cells. The number of band neutrophils does not exceed 6%.

For the same person, the indicators of a general blood test are quite stable: if there are no serious health problems, then the results of tests done at intervals of six months to a year will be very similar. The subject had similar blood test results several months ago.

Thus, the considered blood test, taking into account diabetes mellitus, stability of results, the absence of pathological forms of cells and the absence of an increased level of young forms of neutrophils, can be considered almost normal. But if doubts arise, you need to observe the patient further and order a repeat general blood test (if an automatic hematology analyzer is not able to identify all types of pathological cells, then the analysis should be additionally examined under a microscope manually, just in case). In the most difficult cases, when the situation worsens, a bone marrow puncture (usually from the sternum) is taken to study hematopoiesis.

Reference data for neutrophils and lymphocytes

The main function of neutrophils is to fight bacteria through phagocytosis (absorption) and subsequent digestion. Dead neutrophils make up a significant part of the pus during inflammation. Neutrophils are " ordinary soldiers» in the fight against infection:

• there are a lot of them (every day about 100 g of neutrophils are formed in the body and enter the bloodstream, this number increases several times during purulent infections);
• they do not live long - they circulate in the blood for a short time (12-14 hours), after which they enter the tissues and live for several more days (up to 8 days);
• many neutrophils are released with biological secretions - sputum, mucus;
• The complete development cycle of a neutrophil to a mature cell takes 2 weeks.

The normal content of neutrophils in the blood of an adult is:

• young (metamyelocytes) neutrophils - 0%,
• stab neutrophils - 1-6%,
• segmented neutrophils - 47-72%,
• Total neutrophils - 48-78%.

Leukocytes containing specific granules in the cytoplasm are classified as granulocytes. Granulocytes are neutrophils, eosinophils, basophils.

Agranulocytosis is a sharp decrease in the number of granulocytes in the blood until they disappear (less than 1 × 10 9 / l leukocytes and less than 0.75 × 10 9 / l granulocytes).

Close to the concept of agranulocytosis is the concept of neutropenia ( decreased number of neutrophils- below 1.5 × 10 9 /l). Comparing the criteria for agranulocytosis and neutropenia, one can guess that only severe neutropenia will lead to agranulocytosis. To give a conclusion " agranulocytosis", a moderately reduced level of neutrophils is not enough.

Causes of a reduced number of neutrophils (neutropenia):

1. severe bacterial infections,
2. viral infections (neutrophils do not fight viruses. Cells affected by the virus are destroyed by certain types of lymphocytes),
3. suppression of hematopoiesis in the bone marrow (aplastic anemia - sharp inhibition or cessation of growth and maturation of all blood cells in the bone marrow),
4. autoimmune diseases ( systemic lupus erythematosus, rheumatoid arthritis and etc.),
5. redistribution of neutrophils in organs ( splenomegaly- enlarged spleen)
6. tumors of the hematopoietic system:
   • chronic lymphocytic leukemia (a malignant tumor in which the formation of atypical mature lymphocytes occurs and their accumulation in the blood, bone marrow, lymph nodes, liver and spleen. At the same time, the formation of all other blood cells is inhibited, especially those with a short life cycle - neutrophils);
   • acute leukemia (a bone marrow tumor in which a mutation of a hematopoietic stem cell occurs and its uncontrolled reproduction without maturation into mature forms of cells. Both the common stem cell-precursor of all blood cells and later varieties of precursor cells in individual blood sprouts can be affected. The bone marrow is filled with immature blast cells, which displace and suppress normal hematopoiesis);
7. deficiencies of iron and some vitamins ( cyanocobalamin, folic acid),
8. effect of drugs ( cytostatics, immunosuppressants, sulfonamides and etc.)
9. genetic factors.

An increase in the number of neutrophils in the blood (above 78% or more than 5.8 × 10 9 / L) is called neutrophilia ( neutrophilia, neutrophilic leukocytosis).

4 mechanisms of neutrophilia (neutrophilia):

1. increased neutrophil formation:
   • bacterial infections,
   • inflammation and tissue necrosis ( burns, myocardial infarction),
   • chronic myeloid leukemia ( a malignant bone marrow tumor in which there is an uncontrolled formation of immature and mature granulocytes - neutrophils, eosinophils and basophils, displacing healthy cells),
   • treatment of malignant tumors (for example, with radiation therapy),
   • poisoning (exogenous origin - lead, snake venom, endogenous origin - uremia, gout, ketoacidosis),
2. active migration (early exit) of neutrophils from the bone marrow into the blood,
3. redistribution of neutrophils from the parietal population (near blood vessels) into the circulating blood: during stress, intense muscular work.
4. slowing down the release of neutrophils from the blood into tissues (this is how glucocorticoid hormones act, which inhibit the mobility of neutrophils and limit their ability to penetrate from the blood into the site of inflammation).

Purulent bacterial infections are characterized by:

• development of leukocytosis - an increase in the total number of leukocytes (above 9 × 10 9 / l) mainly due to neutrophilia- increase in the number of neutrophils;
• shift of the leukocyte formula to the left - increase in the number of young [ young + stab] forms of neutrophils. The appearance of young neutrophils (metamyelocytes) in the blood is a sign of a severe infection and evidence that the bone marrow is working under great strain. The more young forms (especially young ones), the greater the stress on the immune system;
• the appearance of toxic granularity and other degenerative changes in neutrophils ( Dele bodies, cytoplasmic vacuoles, pathological changes in the nucleus). Contrary to the established name, these changes are not caused by “ toxic effect» bacteria on neutrophils, and a violation of cell maturation in the bone marrow. The maturation of neutrophils is disrupted due to a sharp acceleration due to excessive stimulation of the immune system by cytokines, therefore, for example, toxic granularity of neutrophils appears in large quantities during the disintegration of tumor tissue under the influence of radiation therapy. In other words, the bone marrow prepares young “soldiers” to the limit of their capabilities and sends them “into battle” ahead of schedule.

Drawing from the site bono-esse.ru

Lymphocytes are the second most numerous white blood cells and come in different subtypes.

Brief classification of lymphocytes

Unlike neutrophils, the “soldiers,” lymphocytes can be classified as “officers.” Lymphocytes “train” longer (depending on the functions they perform, they are formed and multiply in the bone marrow, lymph nodes, spleen) and are highly specialized cells ( antigen recognition, initiation and implementation of cellular and humoral immunity, regulation of the formation and activity of cells of the immune system). Lymphocytes are able to leave the blood into the tissues, then into the lymph and with its current return back to the blood.

To decipher a general blood test, you need to have an idea of ​​the following:

• 30% of all peripheral blood lymphocytes are short-lived forms (4 days). These are the majority of B lymphocytes and T suppressor cells.
• 70% of lymphocytes are long-lived (170 days = almost 6 months). These are other types of lymphocytes.

Of course, with the complete cessation of hematopoiesis, the level of granulocytes in the blood first drops, which becomes noticeable precisely in the number neutrophils, because the eosinophils and basophils in the blood and normally very little. A little later, the level of red blood cells (live up to 4 months) and lymphocytes (up to 6 months) begins to decrease. For this reason, bone marrow damage is detected by severe infectious complications, which are very difficult to treat.

Since the development of neutrophils is disrupted earlier than other cells (neutropenia - less than 1.5 × 10 9 / L), blood tests most often reveal relative lymphocytosis (more than 37%), and not absolute lymphocytosis (more than 3.0 × 10 9 / L).

Reasons for an increased level of lymphocytes (lymphocytosis) - more than 3.0 × 10 9 /l:

• viral infections,
• some bacterial infections ( tuberculosis, syphilis, whooping cough, leptospirosis, brucellosis, yersiniosis),
• autoimmune connective tissue diseases ( rheumatism, systemic lupus erythematosus, rheumatoid arthritis),
• malignant tumors,
• side effects of drugs,
• poisoning,
• some other reasons.

Reasons for a reduced level of lymphocytes (lymphocytopenia) - less than 1.2 × 10 9 / l (according to less strict standards 1.0 × 10 9 / l):

• aplastic anemia,
• HIV infection (primarily affects a type of T lymphocyte called T helper cells),
• malignant tumors in the terminal (last) phase,
• some forms of tuberculosis,
• acute infections,
• acute radiation sickness,
• chronic renal failure (CRF) in the last stage,
• excess glucocorticoids.

/ Patfizo / Belova L. A / Pathology of red blood

PATHOLOGY OF RED BLOOD

Blood is a complex, constantly changing internal environment of the body. Blood carries oxygen, carbon dioxide, nutrients, hormones, and tissue metabolic products. It plays a vital role in maintaining oncotic and osmotic pressure; acid-base balance. In other words, blood takes a vital part in respiration, metabolism, ensuring the processes of secretion and excretion, immunological defense of the body, and, along with the central nervous system, acts as an integrative system that unites the body into a single whole. Blood consists of a liquid part with proteins, organic and inorganic compounds dissolved in it; and cellular elements. The liquid part of the blood is constantly exchanged due to the entry of lymph and tissue fluid into it. The ratio of cellular elements and the liquid part of the blood, determined by hematocrit, is 44-48%. During pathological processes, a natural change occurs in the quantitative and qualitative composition of cells and blood plasma. These changes are an extremely important pathogenetic aspect of many pathological processes, and in addition act as important diagnostic symptoms of a particular disease. Today's lecture is devoted to pathological changes in the red blood of polycythemia.

A N E M I Z Normally, the peripheral blood contains 4.5-5.0 x 10 12 in men; in women, 4.0-4.5 x 10 12 erythrocytes per 1 liter, needles/l of hemoglobin. Moreover, the hemoglobin content in women is also somewhat less than men. Anemia, or anemia, is a condition characterized by a decrease in the number of red blood cells or a decrease in the hemoglobin content in (unit volume) blood. (Explain) A feature of true anemia is an absolute decrease in the number of red blood cells and hemoglobin in the body. Hydremia should be distinguished from true anemia, i.e. blood thinning due to the abundant influx of tissue fluid, observed in patients during the period of swelling. At the same time, as a result of blood dilution, the number of red blood cells and hemoglobin per unit volume decreases, but their total number in the body remains normal. It may be the other way around. With true anemia (a decrease in the total number of red blood cells and hemoglobin in the body), due to blood thickening caused by fluid loss, the amount of hemoglobin and red blood cells per unit volume of blood may remain normal or even increased. Depending on the functional state of the bone marrow, its ability to regenerate and compensate for the anemic state, the following types of anemia are distinguished: regenerative, hyporegenerative anemia. Most anemias are regenerative. They are accompanied by a compensatory increase in erythropoiesis in the hematopoietic apparatus. In this case, hematopoiesis occurs due to the formation of normal red blood cells. At the same time, the proliferation of erythro-normoblastic elements increases, the accelerated transformation of normoblasts into erythrocytes and their increased leaching into the blood. As a result, the blood is replenished with young forms of red blood cells - reticulocytes. Hyporegenerative anemia is a form in which the compensatory capabilities of the bone marrow are depleted and the number of newly emerging red blood cells decreases. In the peripheral blood, the number of young forms of erythrocytes decreases. If reticulocytes practically disappear from the blood, they speak of an aregenerative form of anemia. Most often, these forms of anemia arise due to damage to the red bone marrow - with intoxication, radiation injuries, replacement of red bone marrow with yellow ( for leukemia). In order to determine the nature of anemia based on the regenerative capacity of the bone marrow, it is necessary to calculate the number of reticulocytes per cubic mm. Normally, the number of reticulocytes ranges between 1.0x.0x10 11 per liter. If the number of reticulocytes in a patient is within these limits, then they speak of a regenerative or normogenerative type of anemia; if the number of reticulocytes is less than 100 thousand, then this is a hyporegenerative type. Based on the level of color index, anemia is divided into normochromic, hypo- and hyperchromic. Let me remind you that the color indicator reflects the hemoglobin saturation of an individual red blood cell. The color indicator is normal if it ranges from 0.9 to 1.1. If the CP is less than 0.9, then the anemia is hypochromic and this means that the red blood cells are undersaturated with hemoglobin. If the CP is more than 1.1, then they speak of hyperchromic anemia, accompanied by an increase in hemoglobinization of red blood cells. The color indicator is calculated by the doctor at the time of reading the general blood test of the patient and therefore you need to have a good idea of ​​how this is done. And so the CP is the ratio of the hemoglobin concentration by the number of red blood cells. However, if you use absolute numbers - a million - red blood cells and hemoglobin, then this turns out to be inconvenient for oral recalculation. Therefore, they use relative -% values. To calculate the color indicator, 5000 is taken as 100% of red blood cells for both men and women. 166.7 g/l is taken as 100% of hemoglobin. Let's calculate the CP as an example - red blood cells 4.1x10, hemoglobin 120.0 g/l.% therefore 1-20%. Thus, in order to convert the number of red blood cells from absolute numbers to relative ones, you need to multiply the number of red blood cells in millions by 20%. 4.1x20=82%. Let's convert hemoglobin from g/l to % normal.

120.0 - X X= 100 x 120.0 = 0.6 x 120.0 = 72% 166.7 Let’s create the general equation CPU = heme.=120x0.6= 72 =0.87 er. 4.1x20 82 Thus, in this case we can talk about hypochromic anemia.

PATHOGENESIS AND ETIOLOGY OF ANEMIA. According to etiopathogenesis, all anemias are divided into 3 large groups.

I.Anemia caused by blood loss - POSTHEMORAGIC. II. Anemia associated with disruption of the formation of red blood cells. III.Anemia associated with increased destruction of red blood cells. Each of these large pathogenetic groups is divided into subgroups. I. Posthemorrhagic anemia is divided into 2 subgroups: I. Acute. 2. Chronic. The causes of acute blood loss are various injuries accompanied by damage to blood vessels or bleeding from internal organs. Most often from CCT, lungs, kidneys, etc. The pathogenesis of acute blood loss consists of two groups of circumstances: 1. With blood loss, a rapid decrease in the volume of circulating blood occurs, which leads to a drop in blood pressure and other circulatory disorders that lead to circulatory type hypoxia . 2. At a certain stage of posthemorrhagic anemia, there is a decrease in the oxygen capacity of the blood associated with a decrease in the number of red blood cells and hemoglobin in it and the development of anemic type hypoxia. The more pronounced the disturbances are, the greater the rate of blood loss. The blood picture after acute posthemorrhagic blood loss depends on the time elapsed after the blood loss and the stage compensation of the volume of circulating fluid. Let me remind you of the stages of compensation of bcc - 1. The release of deposited erythrocyte masses into the vascular bed occurs immediately after blood loss. 2. The stage of hydremia - the entry of interstitial fluid into the vascular bed develops after approximately 1 day and continues for 3-4 days. 3. Stage of stimulation of bone marrow hemorrhage. How the main indicators characterizing the state of red blood change at various stages. (Think for yourself). This is homework. Let me remind you of the main indicators: hematactic number, number of red blood cells, hemoglobin concentration, CP, and reticulocyte count. Chronic, posthemorrhagic anemia. Develops after small but prolonged or repeated blood loss. Most often observed with chronic bleeding from the gastrointestinal tract with peptic ulcers, cancer, hemorrhoids and ulcerative colitis, as well as with renal and uterine bleeding. Often the source of blood loss is so insignificant , which remains unclear. To imagine how small blood losses can contribute to significant anemia, it is enough to provide the following data: the daily amount of iron necessary for reparative processes in the bone marrow and maintaining hemoglobin balance is

5 mg. And it must be said that it is not always easy for the body to extract these 5 mg from environment So this is the amount of iron contained in 10 ml of blood. Consequently, the daily loss of 2-3 teaspoons of blood not only deprives the body of its daily need for iron, but also, over time, leads to a significant depletion of the body’s “iron fund,” resulting in the development of severe iron deficiency anemia. Since chronic anemia is characterized by slow blood loss, there is practically no change in the central nervous system and, consequently, hemodynamic disorders. The blood picture with CPH anemia changes in two phases. In the first phase, mainly the formation of hemoglobin and its disruption of red blood cells are disrupted. Therefore, the blood picture here is as follows: hypochromic anemia with a sharp decrease in CP to 0.6-0.4. The number of reticulocytes is near the lower limit of normal, those. regenerative anemia, while in the blood there are also degenerative forms of erythrocytes, macro and microcytes, anisocytosis and poikilocytosis. The number of platelets is normal or slightly reduced. The number of leukocytes is slightly reduced (if there are no additional circumstances causing leukocytosis). The next phase is characterized by a disruption in the formation of red blood cells themselves. At the same time, their blood quantity decreases, but the CP increases and approaches normal. The consequence of the inhibition of hematopoiesis is a decrease in the number of reticulocytes, i.e. anemia becomes hyporegenerative, all degenerative forms of erythrocytes are noted in the blood.

ANEMIA ASSOCIATED WITH DISTURBANCES IN RED CYTE FORMATION Anemias developing as a result of disturbances in the process of blood formation can be divided according to pathogenesis into: 1.Anemias developing as a result of a deficiency of substances necessary for the formation of erythrocytes. 2. Anemia developing as a result of damage to the red bone marrow (ionizing radiation, intoxication). 3. Anemia caused by the presence of a genetic defect in the hematopoietic system.

4. Metaplastic anemia developing as a result of the displacement of the blood germ - yellow during its malignant degeneration (leukemia).

1.gr.a) IRON DEFICIENCY ANEMIA. The group of iron deficiency anemia combines numerous anemic syndromes, the main pathogenetic factor of which is a lack of iron in the body (sideropenia, hyposiderosis). The reasons leading to a lack of iron in the body can be due to: 1. Lack of iron in food. 2. Impaired absorption of iron in the gastrointestinal tract. 3. Excessive loss of iron. 4.Increasing the body's need for iron. 5. Impaired utilization of bone marrow Fe. Impaired intake of iron develops, for example, when the acidity of the gastric juice decreases (hydrochloric acid is necessary for iron in an easily digestible form), as well as as a result of impaired absorption of iron in the intestine during enteritis, intestinal resections and hypovitaminosis - C, etc. Excessive loss of iron from the body is associated most often with chronic bleeding, including menstrual bleeding. Iron can be lost later with increased sweating among workers in hot industries in the tropics. An increased need for iron under physiological conditions occurs during periods of rapid growth in childhood and adolescence, and in women during pregnancy and lactation. Pathological conditions accompanied by an increase in iron requirements include chronic infections (tuberculosis), intoxication (azotemia), hypovitaminosis, endocrine disorders (hypothyroidism), and malignant neoplasms.

Iron deficiency anemia is divided into primary - sensory, and secondary - symptomatic. Primary anemias include early (youthful) chlorosis that occurs in girls during puberty (pale sickness), and late chlorosis that also occurs in women during menopause. Symptomatic iron deficiency anemia occurs against the background of any disease: chronic enteritis, nephritis, connection with gastric resection, chronic blood loss, infections. Picture of blood. The most characteristic feature of the blood picture in chlorosis and symptomatic anemia is hypochromia

A sharp decrease in hemoglobin in red blood cells with a slight decrease in the number of red blood cells themselves. In severe cases, hemoglobin decreases by 100/l, but the number of red blood cells rarely decreases below. Thus, the CP is reduced to 0.5-0.6 and even lower. There are many degenerative forms of red blood cells, mainly microcytes. The number of reticulocytes is usually reduced.

B 12 (FOLIUM) - DEFICIENCY ANEMIA. The classic form of B12 deficiency anemia is the so-called malignant or pernicious anemia of Adison-Biermer. The disease is characterized by a triad of syndromes - dysfunction of the digestive tract, damage to the nervous and hematopoietic systems. In 1929, Castle showed the importance of a special hematopoietic substance in hematopoiesis. This substance enters the body as a result of the interaction of an “external factor” that enters the body with food and an “intrinsic factor” produced by the gastric mucosa. The resulting substance is absorbed and deposited in the liver. It was later found that " external factor Kasla" is vitamin B12 - cyanocobilamine. The internal factor necessary for the absorption of vitamin B12 is a gastromucoprotein contained in normal gastric juice and the mucous membrane of the fundic part of the stomach. In patients with Adison Birmer anemia, gastromucoprotein is absent in the gastric juice. Normally, vitamin B12 after penetration plasma combines with globulin into the bloodstream and is deposited in the liver in the form of a B12-protein complex. Vitamin B12 and folic acid are involved in the metabolism of cell nuclei, they are necessary for the synthesis of so-called thymonucleic acids, in particular folinic acid. With a lack of folinic acid, the bone marrow is impaired synthesis of DNA and RNA in the nuclei of cells of the erythrocyte series. And the mitotic processes in them are disrupted. A megaloblastic type of hematopoiesis occurs in the bone marrow. The final cell of the megaloblastic series is a large cell resembling previously embryonic blood cells. Cells of the megaloblastic series contain a large amount of hemoglobin i.e. their volume is much larger than that of a red blood cell. But in general, these cells perform their function of delivering oxygen to tissues much worse than ordinary red blood cells. This is due to several circumstances. Firstly, due to their large diameter, megalocytes do not enter small capillaries. Secondly, the large diameter and spherical shape complicate the process of oxygenation in the lungs and oxygen release in the tissues. Finally, since these cells contain nuclei, they themselves consume much more a large number of energy than erythrocytes. The megaloblastic type of hematopoiesis is characterized by a much lower intensity of cell division processes. If the pronormoblast, in the process of maturation, makes 3 divisions, resulting in the formation of 8 erythrocytes, then the promegaloblast makes only one division and forms 2 megalocytes. In addition, during maturation, many cells of the megaloblastic series disintegrate, due to this, the accumulation of free hemoglobin and its breakdown products occurs in the blood plasma (and these products, let me remind you, are toxic to the body). Thus, despite the forced restructuring of hematopoiesis to the megaloblastic type of hematopoiesis, the processes of hematopoiesis do not have time in conditions of vitamin B12 deficiency, compensate for the processes of destruction of blood cells, resulting in the development of anemia. The question of the etiology and early links in the pathogenesis of Adison Birmer's disease has not yet been resolved. It is assumed that it is associated with either congenital deficiency of the glandular apparatus

fundus part of the stomach, which manifests itself with age in the form of premature involution of these glands producing gastromucoprotein. Either with autoimmune processes caused by the formation of autoantibodies to gastromucoprotein, or the complex of gastromucoprotein and vitamin B12. B12 deficiency anemia can develop in other types of pathology except for Adison-Birmer disease accompanied by vitamin B12 deficiency. Vitamin deficiency can be caused by elementary deficiency, diseases of the stomach and intestines accompanied by impaired absorption processes, including helminthases, in particular, infection by the broad tapeworm (in which, due to some circumstances, the expression hypovitaminosis arises). A relative lack of vitamin can also occur in physiological conditions accompanied by an increased need for vit. B12 - in childhood, pregnancy, as well as in some diseases, in particular chronic disease. infections.

The processes of bone marrow hematopoiesis and the blood picture in all forms of vitamin B12 deficiency change approximately in the same way. There is a transition to the megaloblastic type of hematopoiesis, as a result of which megalocytes and megaloblasts (immature cells of the megalocytic series) are found in the peripheral blood. The detection of megalocytes and megaloblasts is a pathognomonic sign of B12 deficiency anemia. Due to the fact that megalocytes are large in volume and therefore contain much more hemoglobin than ordinary red blood cells, the color indicator for anemia of this type is greater than one, that is, hyperchromic anemia. Regenerative processes in the bone marrow are sharply reduced. There are few reticulocytes in the blood, which means the anemia is hyporegenerative or, in severe cases, aregenerative in nature. In conclusion, I will say that half a century ago, Adison Birmer’s disease was considered a very serious and completely untreatable disease in 100% of cases ending in the death of the patient. Only at the end of the 20s of the twentieth century they began to somehow treat it with raw liver of various animals - containing large quantities of vit. AT 12. Currently, after receiving medications Vit. B12 treatment of this disease is not a big problem. An exception to this is the so-called B12 achrestic anemia, in contrast to Adison Biermer's disease, this disease has no symptoms of damage to the gastrointestinal tract and nervous system. With achrestic anemia, the intake of vit. B12 into the body is not disturbed; its content in the blood plasma remains normal or elevated. The pathogenesis of anemia in this case is associated with a violation of the ability of the bone marrow to utilize B12 and use it in hematopoietic processes. Iron-deficiency anemias can also occur according to the achrestic type, the peculiarity of which is a high iron content in the blood plasma. However, this iron, due to certain hereditary defects in enzymatic systems, cannot be utilized and used for the synthesis of hemoglobin.

HEMOLYTIC ANEMIA. Hemolytic anemia includes a number of anemic conditions that occur with increased breakdown of red blood cells. According to pathogenesis, hemolytic anemia can be divided into three groups: 1. Anemia in which hemolysis of red blood cells is caused by the synthesis of pathological red blood cells in the bone marrow. This group of diseases includes sickle cell anemia, thalasemia or Mediterranean anemia, hereditary spherocytosis, hemoglobinosis and many other hereditary diseases. 2. The second group of hemolytic anemia is caused by an increase in the activity of the organs responsible for the destruction of red blood cells. The red blood cells can be completely normal. Normally, old red blood cells are destroyed in the reticuloendothelial organs, mainly to a lesser extent in the lymph nodes and liver. The spleen is figuratively called the cemetery of red blood cells. So if this cemetery (active cemetery) works more actively, more red blood cells are destroyed than necessary and anemia occurs. Hemolytic activity of the spleen, for example, in splenomegaly, some chronic diseases. infectious diseases, etc.

3. The third pathogenetic group of hemolytic anemia develops as a result of exposure to erythrocytes by pathogenic factors that normally do not affect them. For example, hemolytic poisons: phosphorus, arsenic hydrogen, saponins, viper venom, etc.; anti-erythrocyte antibodies - foreign during transfusion of incompatible blood, maternal in case of Rh incompatibility, or autoantibodies in pathology of the immunocompetent system. In addition, hemolysis can be a consequence of an injection process - a classic example of which is malaria. Any type of hemolytic anemia is accompanied by the release of a large amount of hemoglobin into the blood from destroyed red blood cells and the accumulation of its breakdown products in the blood, in particular bilirubin. Therefore, hemolytic anemia in most cases is accompanied by hemolytic jaundice with all its adverse manifestations. The blood picture in hemolytic anemia can be very diverse depending on the type of disease and its stage. In most cases, anemia is of the regenerative type, the normoblastic type of hematopoiesis.

ERYTHROCYTOSIS Erythrocytosis is called an increase in the number of red blood cells in the blood above 5.0 * 10 12 per liter. Erythrocytoses are distinguished between absolute and relative. With absolute red blood cells, the total number of red blood cells in the body increases. With relative red blood cells, the total number of red blood cells does not increase, but due to blood thickening there is an increase the number of red blood cells per unit volume of blood. The cause of absolute erythrocytosis is a compensatory increase in the formation of red blood cells in the bone marrow under conditions of chronic hypoxia. This is observed in people living in the mountains and with diseases leading to hypoxia. Especially in chronic conditions. lung diseases. Pathogenetic significance of erythrocytosis. An increase in the number of red blood cells increases the oxygen capacity of the blood and has some adaptive significance. But at the same time, the viscosity of the blood increases, which means the load on the heart increases and microcirculation processes worsen - these are negative phenomena. And with a high degree of erythrocytosis, these negative signs clearly outweigh the positive ones.

ERYTHREMIA (Vaquez's disease) Erythremia, unlike erythrocytosis, is a malignant disease of a tumor nature. With tumor-like growth of the red blood cell. Erythremia in this case is of a hyperregenerative nature. An increase in the number of red blood cells leads to an increase in blood viscosity and a sharp disruption of hemodynamics. Naturally, erythrocytosis in this case has no adaptive significance and is entirely a pathological phenomenon.

Cell pathology

A cell is an elementary living system that has the ability to exchange with the environment. The structure of the cells of the human body ensures that they perform a specialized function and “preserve themselves,” i.e., maintaining the cell pool. Cell organelles, having certain morphological characteristics, provide the main manifestations of cell life. Associated with them are respiration and energy reserves (mitochondria), protein synthesis (ribosomes, granular cytoplasmic reticulum), accumulation and transport of lipids and glycogen, detoxification function (smooth cytoplasmic reticulum), synthesis of products and their secretion (lamellar complex), intracellular digestion and protective function (lysosomes). The activity of cell ultrastructures is strictly coordinated, and coordination in the production of a specific product by the cell is subject to the law of the “intracellular conveyor”. According to the principle of autoregulation, it carries out the relationship between the structural components of the cell and the metabolic processes occurring in it.

The functions of organelles are not strictly determined, since they can participate in various intracellular processes. The metaplasmic formations of the cell are more specialized, performing particular functions: tonofibrils, performing the supporting function of the cell; myofibrils, which contract the cell and promote its movement; microvilli, brush border, involved in absorption processes; desmosomes that provide cell contacts, etc. However, not a single cell function is the result of the activity of one organelle or one metaplasmic formation. Every functional manifestation of a cell is the result of the joint work of all interconnected components. It is therefore clear that structural changes in a cell, reflecting disturbances in its function, cannot be understood without taking into account possible changes in each of its two main parts - the nucleus and cytoplasm, its organelles, metaplasmic formations and inclusions. From violations of the elementary structures of the cell and their functions to the pathology of the cell as an elementary self-regulating living system and to the pathology of cellular cooperations united by a final function - this is the path to understanding the pathology of the cell - the structural basis of human pathology.

Therefore, cell pathology is an ambiguous concept. Firstly, this is the pathology of specialized cell ultrastructures, it is represented not only by fairly stereotypical changes in one or another ultrastructure in response to various influences, but also by such specific changes in ultrastructures that we can talk about chromosomal diseases and “diseases” of receptors, lysosomal, mitochondrial, peroxisomal and other “diseases” of the cell. Secondly, cell pathology is changes in its components and ultrastructures in cause-and-effect relationships. In this case, we are talking about identifying general patterns of cell damage and its response to damage. These may include: reception of pathogenic information by the cell and response to damage, disturbances in the permeability of cell membranes and the circulation of intracellular fluid; disorders of cell metabolism, cell death (necrosis), cellular dysplasia and metaplasia, hypertrophy and atrophy, pathology of cell movement, its nucleus and genetic apparatus, etc.

Pathology of the cell nucleus

Morphologically, it manifests itself in changes in the structure, size, shape and number of nuclei and nucleoli, in the appearance of various nuclear inclusions and changes in the nuclear envelope. A special form of nuclear pathology is the pathology of mitosis; The development of chromosomal syndromes and chromosomal diseases is associated with pathology of nuclear chromosomes.

Structure and size of nuclei

The structure and size of the nucleus (we are talking about an interphase, intermitotic nucleus) depend primarily on ploidy, in particular on the DNA content in the nucleus, and on the functional state of the nucleus. Tetraploid nuclei have a larger diameter than diploid ones, while octoploid ones have a larger diameter than tetraploid ones.

Most cells contain diploid nuclei. In proliferating cells, during the period of DNA synthesis (S-phase), the DNA content in the nucleus doubles; in the postmitotic period, on the contrary, it decreases. If, after DNA synthesis, normal mitosis does not occur in a diploid cell, then tetraploid nuclei appear. Polyploidy occurs - a multiple increase in the number of sets of chromosomes in cell nuclei, or a state of ploidy from tetraploidy and higher.

Polyploid cells are identified in various ways: by nuclear size, by an increased amount of DNA in the interphase nucleus, or by an increase in the number of chromosomes in a mitotic cell. They are found in normally functioning human tissues. An increase in the number of polyploid nuclei in many organs is observed in old age. Polyploidy is especially clearly represented during reparative regeneration (liver), compensatory (regenerative) hypertrophy (myocardium), and tumor growth.

Another type of change in the structure and size of the cell nucleus occurs with aneuploidy, which is understood as changes in the form of an incomplete set of chromosomes. Aneuploidy is associated with chromosomal mutations. Its manifestations (hypertetraploid, pseudoploid, “approximately” diploid or triploid nuclei) are often found in malignant tumors.

The sizes of nuclei and nuclear structures, regardless of ploidy, are determined to a large extent by the functional state of the cell. In this regard, it should be remembered that the processes constantly occurring in the interphase nucleus are multidirectional: firstly, this is the replication of genetic material in the S-neriod (“semi-conservative” DNA synthesis); secondly, the formation of RNA during transcription, the transport of RNA from the nucleus to the cytoplasm through nuclear pores to perform a specific cell function and for DNA replication.

The functional state of the nucleus is reflected in the nature and distribution of its chromatin. In the outer parts of the diploid nuclei of normal tissues, condensed (compact) chromatin is found - heterochromatin, in its remaining parts - non-condensed (loose) chromatin - euchromatin. Hetero- and euchromatin reflect different states of nuclear activity; the first of them is considered “low-active” or “inactive”, the second is considered “quite active”. Since the nucleus can transition from a state of relatively functional rest to a state of high functional activity and back, the morphological picture of chromatin distribution, represented by hetero- and euchromatin, cannot be considered static. “Heterochromatinization” or “euchromatinization” of nuclei is possible, the mechanisms of which have not been sufficiently studied. The interpretation of the nature and distribution of chromatin in the nucleus is also ambiguous.

For example, chromatin margination, i.e. its location under the nuclear envelope, is interpreted both as a sign of nuclear activity and as a manifestation of its damage. However, condensation of euchromatic structures (nuclear wall hyperchromatosis), reflecting inactivation of active transcription sites, is considered a pathological phenomenon, as a harbinger of cell death. Pathological changes in the nucleus also include its dysfunctional (toxic) swelling, which occurs with various cell damage. In this case, a change occurs in the colloid-osmotic state of the nucleus and cytoplasm due to inhibition of the transport of substances through the cell membrane.

Shape of kernels and their number

Changes in the shape of the nucleus are an essential diagnostic feature: deformation of the nuclei by cytoplasmic inclusions during dystrophic processes, polymorphism of the nuclei during inflammation (granulomatosis) and tumor growth (cellular atypia).

The shape of the nucleus can also change due to the formation of multiple protrusions of the nucleus into the cytoplasm (Fig. 3), which is caused by an increase in the nuclear surface and indicates the synthetic activity of the nucleus in relation to nucleic acids and proteins.

Changes in the number of nuclei in a cell can be represented by multinucleation, the appearance of a “nucleus satellite,” and nuclear absence. Multinucleation is possible with cell fusion. These are, for example, giant multinucleated cells of foreign bodies and Pirogov-Langhans, formed by the fusion of epithelioid cells (see Fig. 72). But the formation of multinucleated cells is also possible in case of mitotic disorders - division of the nucleus without subsequent division of the cytoplasm, which is observed after irradiation or the introduction of cytostatics, as well as during malignant growth.

“Satellites of the nucleus,” karyomeres (small nuclei), are small nucleus-like formations with the corresponding structure and their own shell, which are located in the cytoplasm near the unchanged nucleus. The cause of their formation is considered to be chromosomal mutations. These are karyomers in malignant tumor cells in the presence of a large number of pathological mitotic figures.

Non-nuclearity in relation to the functional assessment of the cell is ambiguous. Nuclear-free cellular structures are known that are quite viable (erythrocytes, platelets). In pathological conditions, the viability of parts of the cytoplasm separated from the cell can be observed. But nuclear absence may also indicate the death of the nucleus, which is manifested by karyopyknosis, karyorrhexis and karyolysis (see Necrosis).

Structure and size of nucleoli

Changes in the nucleoli are of significant importance in the morphofunctional assessment of the state of the cell, since the processes of transcription and transformation of ribosomal RNA (r-RNA) are associated with the nucleoli. The size and structure of the nucleoli in most cases correlate with the amount of cellular protein synthesis detected by biochemical methods. The size of the nucleoli also depends on the function and type of cells.

An increase in the size and number of nucleoli indicates an increase in their functional activity. The newly formed ribosomal RNA in the nucleolus is transported into the cytoplasm and, probably, through the pores of the inner nuclear membrane. Intensive protein synthesis in such cases is confirmed by an increase in the number of ribosomes in the endoplasmic reticulum.

Hypergranular nucleoli with a predominance of granules over fibrillar substance may reflect a different functional state of both the nucleoli and the cell. The presence of such nucleoli with a well-defined lacunar system and sharp basophilia of the cytoplasm indicates both increased r-RNA synthesis and transmission. Such “hyperfunctional nucleoli” are found in young plasma cells, active fibroblasts, hepatocytes, and in many tumor cells. The same hypergranulated nucleoli with mild basophilia of the cytoplasm may reflect a violation of transmission (transport of granules) during the ongoing synthesis of r-RNA. They are found in tumor cells characterized by a large nucleus and slight cytoplasmic basophilia.

Loosening (dissociation) of nucleoli, reflecting their hypogranulation, may be a consequence of the “eruption” of r-RNA into the cytoplasm or inhibition of nucleolar transcription. Disorganization (segregation) of nucleoli usually reflects the complete and rapid cessation of nucleolar transcription: the nucleus decreases in size, pronounced condensation of nucleolar chromatin is observed, and separation of granules and protein filaments occurs. These changes occur during energy deficiency of the cell.

Nuclear inclusions

Nuclear inclusions are divided into three groups:

1. nuclear cytoplasmic

2. true nuclear

3. nuclear virus-related.

Nuclear cytoplasmic inclusions are parts of the cytoplasm in the nucleus delimited by a shell. They can contain all the constituent parts of the cell (organelles, pigment, glycogen, fat droplets, etc.). Their appearance in most cases is associated with a violation of mitotic division.

True nuclear inclusions are considered to be those located inside the nucleus (karyoplasm) and corresponding to substances found in the cytoplasm [protein, glycogen, lipids, etc.]. In most cases, these substances penetrate from the cytoplasm into the nucleus through intact or damaged pores of the nuclear envelope or through a destroyed nuclear envelope. It is also possible that these substances enter the nucleus during mitosis. These are, for example, inclusions of glycogen in the nuclei of the liver in diabetes mellitus (“nuclear glycogen”, “holey, empty, nuclei”).

Virus-related nuclear inclusions (so-called nuclear inclusion bodies) are controversial. Firstly, these are nuclear inclusions in the karyoplasm of the crystal lattice of the virus, and secondly, inclusions of protein particles that arise during the intranuclear reproduction of the virus; thirdly, nuclear inclusions as a manifestation of a reaction to damage to the cytoplasm by the virus (“reactive inclusions”).

Nuclear envelope

The nuclear envelope performs a number of functions, violations of which can serve as the basis for the development of cell pathology.

The role of the nuclear envelope in maintaining the shape and size of the nucleus is evidenced by the formation of intranuclear tubular systems extending from the inner nuclear membrane, inclusions in the perinuclear zone [myocardial hypertrophy, pulmonary fibrosis, systemic vasculitis, sarcoidosis, liver tumors, dermatomyositis].

The nuclear envelope as a site of DNA attachment to facilitate replication and transcription is evidenced by the fact that the nuclear envelope contains structures modulated by chromatin and in turn responsible for the orientation and structure of chromatin. It has been shown that the functional activity of DNA is associated with its distribution during cell division and with the degree of condensation in interphase, and damage to the membrane can cause changes in such areas of distribution and cause pathological changes in the cell.

The established correlation between changes in the structure of the nuclear envelope, the module of its pores, and the release of RNA into the cytoplasm speaks in favor of the function of the nuclear envelope as a physical barrier and modulator of nucleocytoplasmic metabolism. Control by the nuclear envelope of RNA transport into the cytoplasm can have a significant impact on cell homeostasis under pathological conditions. The participation of the nuclear envelope in the synthesis of membranes does not have reliable evidence, although it is believed that this role is possible, since the membranes of the nuclear envelope directly pass into the endoplasmic reticulum of the cytoplasm. The possible influence of nuclear envelope enzymes on nuclear function is evidenced by the presence of various detoxification enzymes in the nuclear envelope, a. also substances that provide “hormonal control” (adenylate cyclase, insulin receptors, etc.).

Pathology of mitosis

Mitosis occupies a special place in the life cycle of a cell. With its help, cell reproduction is carried out, and hence the transfer of their hereditary properties. The preparation of cells for mitosis consists of a number of sequential processes: DNA reproduction, doubling of cell mass, synthesis of protein components of chromosomes and the mitotic apparatus, doubling of the cell center, accumulation of energy for cytotomy. In the process of mitotic division, as is known, there are 4 main phases: prophase, metaphase, anaphase and telophase.

With pathology of mitosis, any of these phases can suffer. Guided by this, a classification of the pathology of mitosis was created [Alov I. A., 1972], according to which the following types of pathology of mitosis are distinguished:

I. Damage to chromosomes:

1. delay of cells in prophase;

2. violation of spiralization and despiralization of chromosomes;

3. chromosome fragmentation;

4. formation of bridges between chromosomes in anaphase;

5. early separation of sister chromatids;

6. kinetochore damage.

II. Damage to the mitotic apparatus:

1. delayed development of mitosis in metaphase;

2. dispersal of chromosomes in metaphase;

3. three-group metaphase;

4. hollow metaphase;

5. multipolar mitoses;

6. asymmetric mitoses;

7. monocentric mitoses;

8. K-mitoses.

III. Violation of cytotomy:

1. premature cytotomy;

2. delay of cytotomy;

3. absence of cytotomy.

The pathology of mitosis can be caused by various effects on the cell: ultraviolet and ionizing radiation, high temperature, chemicals, including carcinogens and mitotic poisons, etc. The number of pathological mitoses during tissue malignancy is high.

Chromosomal aberrations and chromosomal diseases

Chromosomal aberrations.

Chromosome aberrations mean changes in the structure of chromosomes caused by their breaks, followed by redistribution, loss or doubling of genetic material. They reflect various types of chromosome abnormalities. In humans, among the most common chromosomal aberrations, manifested by the development of deep pathology, are anomalies relating to the number and structure of chromosomes. Abnormalities in the number of chromosomes can be expressed by the absence of one of a pair of homologous chromosomes (monosomy) or the appearance of an additional, third chromosome (trisomy). The total number of chromosomes in the karyotype in these cases differs from the modal number and is equal to 45 or 47. Polyploidy and aneuploidy are less important for the development of chromosomal syndromes. Violations of the structure of chromosomes with an overall normal number in the karyotype include various types of their “breakage”: translokady (exchange of segments between two non-homologous chromosomes), deletion (loss of a part of a chromosome), fragmentation, ring chromosomes, etc.

Chromosomal aberrations, disturbing the balance of hereditary factors, are the cause of various deviations in the structure and functioning of the body, manifested in so-called chromosomal diseases.

Chromosomal diseases.

They are divided into those associated with abnormalities of somatic chromosomes (autosomes) and those associated with abnormalities of sex chromosomes (Barr bodies). In this case, the nature of the chromosomal abnormality is taken into account - a violation of the number of individual chromosomes, the number of chromosome sets or the structure of chromosomes. These criteria make it possible to identify complete or mosaic clinical forms of chromosomal diseases.

Chromosomal diseases caused by disturbances in the number of individual chromosomes (trisomy and monosomy) can affect both autosomes and sex chromosomes.

Autosomal monosomies (any chromosomes other than the X and Y chromosomes) are incompatible with life. Autosomal trisomies are quite common in human pathology. Most often they are represented by Patau syndrome (13th pair of chromosomes) and Edwards syndrome (18th pair), as well as Down disease (21st pair). Chromosomal syndromes with trisomies of other autosomal pairs are much less common. Monosomy of the sex X chromosome (genotype XO) is the basis of Shereshevsky-Turner syndrome, trisomy of the sex chromosomes (genotype XXY) is the basis of Kleinfelter syndrome. Abnormalities in the number of chromosomes in the form of tetra- or triploidy can be represented by both complete and mosaic forms of chromosomal diseases.

Chromosome structure disorders constitute the largest group of chromosomal syndromes (more than 700 types), which, however, can be associated not only with chromosomal abnormalities, but also with other etiological factors.

All forms of chromosomal diseases are characterized by a multiplicity of manifestations in the form of congenital malformations, and their formation begins at the stage of histogenesis and continues in organogenesis, which explains the similarity of clinical manifestations in various forms of chromosomal diseases.

Pathology of the cytoplasm

Membrane changes and cell pathology

Cell membranes are known to consist of a bilayer of phospholipids, on both sides of which are located a variety of membrane proteins. On the outer surface of the membrane, protein molecules carry polysaccharide components (glycocalyx), which contain numerous cell surface antigens. They play an important role in the formation of cell junctions.

Changes in cell membranes.

Among them, the following are distinguished [Avtsyn A.P., Shakhlamov V.A., 1979]: excessive vesicle formation (“minus membrane”); increase in the surface of the plasmalemma of cells with membranes of micropinocytotic vesicles (“plus membrane”); increased microclasmatosis and clasmatosis (“minus membrane”); formation of cytoplasmic processes from the cell plasmalemma; formation of bubbles on the cell surface; thickening of membrane layers; formation of micropores; the formation of myelin-like structures from the plasmalemma and organelle membranes; fusion of dissimilar cell membranes; local destruction of membranes - “gaps” in the plasmalemma; “darning” of locally destroyed plasmalemma with membranes of micropinocytotic vesicles.

Pathology of cell membranes can be caused by disturbances in membrane transport, changes in membrane permeability, changes in cell communication and their “recognition”, changes in membrane mobility and cell shape, disturbances in the synthesis and exchange of membranes.

Membrane transport disorders.

The process of membrane transport involves the transport of ions and other substrates against a concentration gradient. Transport can be active, in which case it requires ATP and the “mobility” of transport proteins in the membrane, or passive through various diffusion and metabolic processes. Active transport is also a function of epithelial barriers. Disturbances in membrane transport leading to cell pathology are well observed during ischemia, which leads to primary changes in mitochondria. In mitochondria, the efficiency of oxidative phosphorylation sharply decreases, they swell, initially the permeability of their inner membrane increases, and then the damage becomes total and irreversible.

Ischemic damage to mitochondria leads to the failure of the sodium-potassium ATP pump, the gradual accumulation of sodium in the cell and the loss of potassium. Violation of sodium-potassium metabolism leads to the displacement of calcium from mitochondria. As a result, the level of ionized calcium in the cytoplasm increases and its binding to calmodulin increases. A number of cellular changes are associated with an increase in the content of calcium-calmodulin complexes: divergence of cell junctions, absorption of calcium by mitochondria, changes in microtubules and microfilaments, activation of phospholipases. The endoplasmic reticulum accumulates water and ions, which results in the expansion of its tubules and cisterns and the development of hydropic dystrophy. Increased glycolysis is accompanied by glycogen depletion, lactate accumulation and a decrease in cellular pH. These changes are associated with disruption of chromatin structure and a decrease in RNA synthesis. Irreversible ischemic cell damage is associated with hydrolysis of membranes, especially membrane lipids, under the action of phospholipases. Disturbances of lysosomal membranes also occur with the release of hydrolases.

Changes in membrane permeability.

Control of membrane permeability involves maintaining the structure of both the phospholipid bilayer of the membrane with the necessary exchange and resynthesis, and the corresponding protein channels. An important role in the implementation of this control belongs to the glycocalyx and the interaction of membrane proteins with the cytoskeleton, as well as hormones that interact with membrane receptors. Permeability changes may be severe (irreversible) or superficial. The most studied model for changes in membrane permeability is damage by heavy metals (mercury, uranium). Heavy metals, interacting with sulfhydryl groups of membrane proteins, change their conformation and sharply increase the permeability of the membrane to sodium, potassium, chlorine, calcium and magnesium, which leads to rapid swelling of cells and disintegration of their cytoskeleton. Similar changes in membranes are observed when they are damaged by complement (“hypersensitivity diseases”). Gaps form in the membranes, which reduces their resistance and dramatically increases permeability.

Changes in cell communication and “recognition”. Cell communication and recognition of “friends” and “foes” is a necessary property of cellular cooperation. Cellular “communication” and “recognition” primarily imply differences in the outer surfaces of the plasma membrane and the membranes of intracellular organelles. Of particular interest in this regard is the glycocalyx of membranes with surface antigens - markers of a certain cell type.

Changes in cellular “communication” and “recognition” occur during those pathological processes (inflammation, regeneration, tumor growth) in which surface antigens can change, and the differences may concern both the type of antigen and its “availability” from the extracellular space. It has been shown that when antigens characteristic of a given cell type disappear, “embryonic” and abnormal (for example, carcinoembryonic) antigens may appear; changes in membrane glycolipids make it more accessible to antibodies.

Cell communication is also determined by the state of cell junctions, which can be damaged in various pathological processes and diseases. In cancer cells, for example, a correlation was found between changes in cell junctions and disruption of intercellular connections; abnormal cellular connections are found in tumors.

Changes in membrane mobility and cell shape. There are two types of changes associated with impaired membrane mobility: protrusion of the membrane outward - exotropia and into the cytoplasm - esotropia. In exotropia, the membrane protrudes into the extracellular space to form a membrane-enclosed cytoplasmic structure. With esotropia, a cavity surrounded by a membrane appears. Changes in cell shape are associated not only with exo- and esotropia, but also with simplification of the cell surface (loss of small podocyte processes in nephrotic syndrome).

Disturbances in the synthesis and exchange of membranes. It is possible to enhance the synthesis of membranes (when exposed to a number of chemical substances per cell) or its weakening (decreased synthesis of enterocyte brush border membranes when membrane enzymes are inhibited). It is equally possible to increase membrane turnover (with stimulation of autophagocytosis) or weaken it (with lysosomal diseases).

Endoplasmic reticulum

Changes in the granular endoplasmic reticulum and ribosomes

The functions of the granular endoplasmic reticulum and ribosomes are closely coupled, so the morphological manifestations of their disorders usually affect both organelles.

Changes in the granular endoplasmic reticulum and ribosomes can be represented by hyperplasia and atrophy, structural simplification, disaggregation (dissociation) of ribosomes and polysomes, and the formation of abnormal ribosomal-lamellar complexes.

Hyperplasia of the granular endoplasmic reticulum and ribosomes, i.e., an increase in their number, is optically manifested by increased basophilia of the cytoplasm, which reflects the volumetric density of ribosomes and is an indicator of the intensity of protein synthesis in the cell. In such cases, electron microscopy can be used to judge the coupling of protein synthesis and excretion or the absence of such coupling. In intensively secreting and excreting protein cells (for example, in active fibroblasts), the cisterns of the granular endoplasmic reticulum are expanded and contain little electron-dense material: hyperplasia of both membrane-bound and free ribosomes forming polysomes is noted; the lamellar complex (Golgi complex), involved in the excretion of synthesized protein, is well developed. In intensively secreting protein cells with impaired protein excretion, flocculent electron-dense material accumulates in hyperplastic dilated cisterns of the endoplasmic reticulum with an abundance of ribosomes and polysomes, and sometimes crystallizes; The Golgi complex in such cases is poorly developed.

1) at the level of interaction of biologically active substances (hormones, neurotransmitters, etc.) with cell receptors. Changes in the sensitivity, number and (or) conformation of receptor molecules, its biochemical composition or lipid environment in the membrane can significantly modify the nature of the cellular response to a regulatory stimulus. Thus, the accumulation of toxic products of SPOL in myocardial cells during ischemia causes a change in the physicochemical composition of their membranes, including the cytolemma, which is accompanied by a disruption of the heart’s response to neurotransmitters of the autonomic nervous system: norepinephrine and acetylcholine, as well as other biologically active substances;

2) at the level of cellular, so-called second messengers (messengers) of nervous influences: cyclic nucleotides - adenosine monophosphate (cAMP), guanosine monophosphate (cGMP), formed in response to the action of “first messengers” - hormones and neurotransmitters.
An example is the disruption of the formation of membrane potential in cardiomyocytes when excess cAMP accumulates in them, which is, in particular, one of the possible causes of the development of cardiac arrhythmias;

3) at the level of metabolic reactions regulated by cyclic nucleotides or other intracellular factors. Thus, disruption of the process of activation of cellular enzymes can significantly change the intensity of metabolic reactions and, as a result, lead to disruption of cell functioning.

Types of cell damage:

Dystrophies:

The main mechanisms of dystrophies are:

The main types of cellular dystrophies, depending on the predominantly disturbed type of metabolism, include:
protein (dysproteinoses);
fat (lipidoses);
carbohydrates;
pigmented;
mineral.

Dysproteinoses:

With granular dystrophy, protein granules (grains) appear in the cytoplasm. They are formed as a result of its infiltration (penetration) from the intercellular fluid, transformation of carbohydrates and fats into proteins, and disintegration (decomposition) of cytoplasmic lipoproteins and membranes. One of the main common causes of granular dystrophy is a violation of the energy supply of cells.

Hyaline dystrophy is characterized by the accumulation of protein hyaline-like acidophilic inclusions (“drops”) in the cytoplasm. At the same time, signs of destruction of cellular organelles are revealed. Signs of hyaline dystrophy are observed in conditions that cause increased permeability of cell membranes.

Lipidoses:

Carbohydrate dystrophies:

“Polysaccharide” dystrophies manifest themselves:
1) a decrease in their content in the cell (for example, glycogen in diabetes mellitus);
2) their absence or significant decrease (aglycogenosis);
3) accumulation of their excess (glycogen infiltration of cells, glycogenosis).
The cause of carbohydrate dystrophies is most often endocrinopathies (for example, insulin deficiency) or enzymopathies (the absence or low activity of enzymes involved in the processes of synthesis and breakdown of carbohydrates).
Carbohydrate dystrophies associated with impaired metabolism of glycoproteins are usually characterized by the accumulation of mucins and mucoids, which have a mucous consistency. In this regard, they are called mucous dystrophies. They are most often caused by endocrine disorders (for example, insufficient production or low activity of thyroid hormones), as well as the direct damaging effect of pathogenic factors on cells.

Pigmentary dystrophies (dyspigmentosis):

Depending on the biochemical structure, endogenous cellular pigments are divided as follows:
1) hemoglobinogenic (ferritin, hemosiderin, bilirubin, hematoidin, hematin, porphyrin);
2) proteinogenic, tyrosinogenic (melanin, adrenochrome, pigments of ochronosis and enterochromaffin cells);
3) lipidogenic, lipoproteinogenic (lipofuscin, hemofuscin, ceroid, lipochromes).
All dyspigmentoses are divided into several groups depending on their origin, mechanism of development, biochemical structure of the pigment, manifestations and prevalence.

Types of dyspigmentosis

According to the development mechanism:
1. Caused by defects in enzymes (enzymopathies) of pigment metabolism and (or) changes in their activity.
2. Associated with changes in the content and (or) activity of enzymes transporting pigments through cell membranes.
3. Caused by damage to cell membranes.
4. Caused by the accumulation of excess pigments in cells that have the property of phagocytosis.

According to the biochemical structure of the pigment:
1. Hemoglobinogenic, “iron dependent”.
2. Proteinogenic, tyrosinogenic.
3. Lipidogenic, lipoproteinogenic.

By manifestation:
1. The appearance in the cell of a pigment that is not normally present in it.
2. Accumulation of excess pigment that is normally produced in the cell.
3. Decrease in the amount of pigment produced normally in the cell.

By prevalence:
1. Local (regional).
2. General (common).

Hemoglobinogenic dyspigmentosis includes hemosiderosis, hemochromatosis, hemomelanosis, porphyria, and accumulation of excess direct bilirubin in hepatocytes. Most hemoglobinogenic pigments are products of hemoglobin catabolism. Some of them (ferritin, hemosiderin) are formed with the participation of iron absorbed in the intestine.

Some hemoglobinogenic dyspigmentosis is the result of fermentopathy. These include, in particular, primary hemochromatosis and porphyria.

Primary hemochromatosis is a disease caused by a genetic defect (transmitted in an autosomal dominant manner) of a group of enzymes involved in the processes of iron transport from the intestinal cavity. At the same time, excess iron enters the blood, which accumulates in the form of ferritin and hemosiderin in the cells of various tissues and organs (liver, myocardium, skin, endocrine glands, salivary glands, etc.). Similar changes are observed in secondary hemochromatosis. It is the result of either an acquired deficiency of enzymes that ensure the metabolism of dietary iron (during alcoholism, intoxication), or an increased intake of iron into the body with food or iron-containing medications, or a consequence of excessive hemolysis of red blood cells.

Porphyria is characterized by the accumulation of uroporphyrinogen I, porphobilin, and porphyrinogens in cells. One of the common causes of porphyria is a deficiency or low kinetic activity of porphyrin metabolic enzymes (in particular, uroporphyrinogen - III - cosynthetase) of a hereditary or acquired nature.

Most other types of hemoglobinogenic dyspigmentosis (hemosiderosis, hemomelanosis) are a consequence of excessive accumulation of pigments in cells due to increased hemolysis of erythrocytes of various origins (infections, intoxications, blood transfusions of a different group, Rh conflict, etc.).

Proteinogenic (tyrosinogenic) dyspigmentosis is manifested by an increase or decrease in tissue pigmentation (local or general) by products of tyrosine metabolism.
Increased pigmentation is often a consequence of an excess of melanin in cells (melanosis, from the Greek melas - dark, black). It is observed in cases of adrenal insufficiency caused by a decrease in their mass, for example, with tuberculous or tumor lesions, with pituitary adenoma, hyperthyroidism, and ovarian tumors. It is believed that excess melanin in cells is the result of its increased synthesis from tyrosine instead of adrenaline. The process of melanin formation is potentiated by ACTH, the level of which is increased under conditions of adrenaline deficiency in the blood.

The accumulation of ochronosis pigment (from the Greek ochros - yellow, yellowish) in cells is observed in primary (hereditary) fermentopathy, characterized by a deficiency of enzymes for the metabolism of tyrosine and phenylalanine. In this case, hyperpigmentation is local or widespread. The pigment accumulates in the cells of the tissues of the nose, ears, sclera, trachea, bronchi, tendons, cartilage, etc.

Weakening of tissue pigmentation or absence of pigment in their cells (albinism, from Latin albus - white) can also be of primary or secondary origin. With albinism, melanin is absent in the cells of the skin, iris, and hair. The reason for this is most often the hereditary absence of the enzyme tyrosinase in the cells. In the case of a local decrease in pigmentation, for example, skin (leukoderma, vitiligo), a secondary disorder of melanin metabolism is of significant importance due to neuroendocrine disorders of its regulation (with hypoinsulinism, decreased levels of parathyroid hormones), due to the formation of antibodies to melanin or as a result of increased destruction of melanocytes during inflammation or tissue necrosis.

Lipidogenic dyspigmentosis, most often characterized by an increase in the amount of lipid or lipoprotein pigments in cells (lipofuscin, hemofuscin, lipochromes, ceroid). All these pigments are very similar in basic physical and biochemical properties. In humans, there are usually various variants of local lipofuscinosis of hereditary (less often) or acquired (more often) origin.

It is believed that the main causes of acquired lipofuscinosis are tissue hypoxia, deficiency in the body of vitamins, protein, individual species lipids. Most often it develops in old and senile age, in people with chronic “metabolic” diseases.
Hereditary and congenital lipofuscinoses are characterized by the accumulation of excess lipofuscin in cells, usually combined with enzymopathies (i.e., these lipofuscinoses are a variant of storage diseases - thesaurisosis). Examples of these diseases can be neuronal lipofuscinosis (deposition of excess lipofuscin in neurons, which is combined with a decrease in intelligence, vision, hearing, and the development of seizures), hepatic lipofuscinosis, combined with disorders of bilirubin metabolism caused by hereditary defects in the transport enzymes of glucuronidation of bile pigments.

Mineral dystrophies:

Mineral dystrophies are characterized by the accumulation of excess content in cells of molecular or ionized fractions of cations (for example, calcinosis, siderosis, copper deposits in hepatocerebral dystrophy) or a decrease in their content.

One of the most common types of cellular mineral dystrophies in humans is calcification - the accumulation (“deposition”) of excess calcium salts in cells. Calcinosis can be general or local in nature. In the “territory” of the cell, calcium salts accumulate to the greatest extent in mitochondria, lysosomes (phagolysosomes), and in the tubules of the sarcoplasmic reticulum. The main cause of cellular calcification is a change in the physicochemical properties of the cell hyaloplasm (for example, intracellular alkalosis), combined with calcium absorption. The most commonly observed calcification of myocardial cells, epithelium of the renal tubules, lungs, gastric mucosa, and arterial walls.

Dystrophies also include thesaurismosis (from the Greek thesauriso - accumulation, absorption, filling). They are characterized by the accumulation of excess of various substances in cells, which is accompanied by a violation of their structure and function, as well as the intensity and nature of metabolic and plastic processes in them.

Almost all thesaurismoses are the result of hereditary pathology of enzymes, transmitted, as a rule, in an autosomal recessive manner. Inherited changes in the genetic program cause defects in enzymes (lysosomal, membrane-bound, free). The consequence of this is a metabolic disorder in the cell, causing the accumulation in it of products of incomplete or abnormal breakdown of substrates.

Depending on the biochemical structure of the substances accumulated in cells, thesaurismoses are divided into lipid (lipidoses), glycogen (glycogenoses), amino acid, nucleoprotein, mucopolysaccharide, mucolipid. The most common types of thesaurismosis are lipid and glycogen.

Dysplasia:

The causes of dysplasia are factors of a physical, chemical or biological nature that damage the genome of the cell. In this case, the genetic program of the cells or the mechanisms for its implementation are disrupted. This is what causes changes that are persistent and, as a rule, inherited from cell to cell, in contrast to dystrophies, which are often temporary, reversible and can be eliminated when the action of the causative factor ceases.

The main mechanism of dysplasia is a disorder of the differentiation process, which consists in the formation of structural and functional specialization of the cell. Cellular differentiation is determined mainly by a genetic program. However, the implementation of this program largely depends on the complex interactions of the nucleus and cytoplasm, the microenvironment of the cell, the influence of biologically active substances on it and many other factors. That is why, even with the same change in the genome of different cells, the manifestations of dysplasia can be “various in nature.”

Dysplasia is manifested by changes in the size and shape of cells, their nuclei and other organelles, the number and structure of chromosomes. As a rule, cells are enlarged in size, have an irregular, bizarre shape (“monster cells”), and the ratio of various organelles in them is disproportionate. Often, various inclusions and signs of degenerative processes are found in such cells.

Examples of cellular dysplasia include the formation of megaloblasts in the bone marrow with pernicious anemia, sickle-shaped red blood cells in the presence of pathological hemoglobin, large neurons - “monsters” with damage to the cerebral cortex (tuberculous sclerosis), multinucleated giant cells with a bizarre arrangement of chromatin in neurofibromatosis (disease Recklinhausen). Cellular dysplasia is one of the manifestations of atypia of tumor cells.

Typical disorders of subcellular structures and components:

Damage to a cell is characterized by a greater or lesser disruption of the structure of the function of all its components. However, under the influence of various pathogenic factors, signs of damage to some of them may predominate.

Core is the “carrier” of the cell’s genetic program. Damage to the nucleus is combined with a change in its size and shape, the number of nucleoli in it, condensation of chromatin along the periphery of the nucleus (chromatin margination), disruption of double-circuit or ruptures of the nuclear membrane, its fusion with a strip of chromatin margination, the appearance of inclusions, satellites of the nucleus, etc.

Mitochondria. These organelles are involved in many intracellular processes. The main ones are oxidation associated with phosphorylation, leading to the formation of ATP and regulation of the intracellular content of calcium (mitochondria have a high calcium capacity), potassium, and hydrogen ions.

Under the influence of pathogenic factors, there is a change in the total number of mitochondria, as well as the structure of individual organelles. A decrease in the number of mitochondria in relation to the total mass of the cell, in particular in the liver, is observed during prolonged fasting, after irradiation of the body, and in diabetes mellitus.

Changes in individual mitochondria that are stereotypical for the action of most damaging factors are a decrease or increase in their size and a change in shape. Many pathogenic effects on the cell (hypoxia, endo- and exogenous toxic agents, including medications in case of their overdose, ionizing radiation, changes in osmotic pressure) are accompanied by swelling and vacuolization of mitochondria, which can lead to rupture of their membranes, fragmentation and homogenization of cristae. There is often a loss of granular structure and homogenization of cristae, loss of granular structure and homogenization of the matrix of organelles, loss of double-circuitry of their outer membrane, and deposits of organic (myelin, lipids, glycogen) and inorganic (most often calcium salts) compounds in the matrix. Violation of the structure of mitochondria leads to a significant suppression of the process of respiration in them and the formation of ATP, as well as to an imbalance of ions (Ca2+, K+, H+) inside the cell.

Lysosomes. Normally, lysosome enzymes ensure the renewal of cell structures during aging or damage, as well as the destruction of foreign agents during the process of phagocytosis.
Under pathogenic influences, the release and activation of lysosome enzymes can lead to “self-digestion” (autolysis) of the cell. The increased release of lysosomal hydrolases into the cytoplasm may be due to mechanical rupture of their membrane or a significant increase in the permeability (“labilization”) of the latter.

This is a consequence of the accumulation of hydrogen ions in the cells (intracellular acidosis), exposure to SPOL products, toxins and other agents. In humans and animals, primary, hereditary dysfunctions of lysosomes (so-called lysosomal diseases) are also often detected. They are characterized by a deficiency and (or) decreased activity of lysosomal enzymes. This is usually accompanied by the accumulation in the cell of excess substances that are normally metabolized with the participation of lysosome enzymes. Specified forms lysosomal enzymopathies are a type of thesaurismosis - storage diseases, which include, as already indicated, glycogenosis, gangliosidosis, some hepatoses (accompanied by the accumulation of lipofuscin and, as a rule, direct bilirubin in hepatocytes), etc.

Ribosomes. These organelles are necessary for the implementation of the genetic program of cells. With their participation, protein synthesis occurs based on reading information from mRNA. Therefore, about 40% of the mass of ribosomes is RNA. Under the influence of damaging factors, destruction of groups of ribosomal subunits (polysomes), usually consisting of several ribosomes - “monomers”, is observed; reduction in the number of ribosomes, separation of organelles from intracellular membranes. These changes are accompanied by a decrease in the intensity of protein synthesis in the cell.

Endoplasmic reticulum. Performs the functions of accumulation and distribution of various substances in the cell (in particular, calcium ions in myocytes), and also participates in the inactivation of chemical agents. When damaged, there is an expansion of the network tubules, up to the formation of large vacuoles and cisterns due to the accumulation of fluid in them, focal destruction of the membranes of the network tubules, and their fragmentation. Changes in the structure of the endoplasmic reticulum may be accompanied by the development of cellular dystrophies, disruption of the propagation of the excitation impulse, the contractile function of muscle cells, and the processes of neutralization of cytotoxic factors (poisons, metabolites, free radicals, etc.).

Peroxisomes (microbodies). Topographically closely related to the endoplasmic reticulum. Microbodies contain various oxidases involved in the oxidation of higher fatty acids, carbohydrates, amino acids and other (including cytotoxic) substrates for the breakdown of hydrogen peroxide, various reducing components of the respiratory chain. When cells are damaged of various origins, an increase (under conditions of alcohol intoxication, viral aggression) or a decrease (under hypoxia, exposure to ionizing radiation) in the number of peroxisomes can be observed. Primary dysfunctions of peroxisomes of hereditary origin (“peroxisomal diseases”) are also known. They are characterized by metabolic disorders as a result of either a deficiency and (or) defect of certain peroxisomal enzymes, most often catalase, or the absence of microbodies in the cell.

Golgi complex. Plays a significant role in the processes of transport of substances in cells with high metabolic and secretory activity, especially in the endocrine glands and cells that produce mucus. This complex also synthesizes a number of substances (polysaccharides, proteins), activates enzymes, and deposits various compounds. With its participation, lysosomes are “generated”. Damage to the Golgi complex is accompanied by structural changes similar to those in the endoplasmic reticulum. In this case, the removal of waste products from the cell and the inactivation of toxic compounds in it are disrupted, which can lead to a breakdown of its function as a whole.

Microtubules, microfilaments, intermediate filaments(cytokeratins, neurofilaments, glial filaments). They make up the “skeleton” of the cell and ensure the performance of its supporting, transport, contractile, and motor functions. Damage to the cytoskeleton can disrupt the flow of secretory granules or fluids, the implementation of phagocytosis, mitotic cell division, and the ordered movement of cilia (for example, the epithelium of the respiratory tract or the “tail” of the sperm, which is the equivalent of a cilium).

Hyaloplasma(cytoplasmic matrix). It is a liquid, slightly viscous internal environment of the cell. The main components of hyaloplasm are intracellular fluid, various structures: organelles, metaplasmic formations and inclusions. The effect of damaging factors on the cell can cause a decrease or increase in the fluid content in the hyaloplasm, proteolysis or coagulation of protein, and the formation of “inclusions” that are not found normally.

A change in the state of the hyaloplasm, in turn, significantly affects the metabolic processes occurring in it, due to the fact that many enzymes (for example, glycolysis) are located in the cell matrix; on the function of organelles; on the processes of perception of regulatory and other influences on the cell.

Intravital study of cells showed that the hyaloplasm exhibits ordered circulation of intracellular fluid, as well as rhythmic movements of organelles. It has been suggested that fluids of different compositions may circulate in different regions of the cell and its organelles. When cells are damaged, the orderly circulation of cytoplasmic fluid may be disrupted. An example of discirculatory disorders can be changes in the speed of transport of neurotransmitters along the axons of neurons, slowing down the migration of phagocytes (due to the slow movement of hyaloplasm in pseudopodia), the development of so-called “partial” edema in cells (for example, edema of the nucleus, mitochondria, myofibrils, etc.).

Plasmolemma. Normally performs protective, barrier, contact, information, transport functions. When the cell is damaged, these functions of the plasmalemma suffer to a greater or lesser extent. This is due to significant changes in its permeability (usually an increase), integrity, number and sensitivity of receptor structures, transmembrane “channels” and other deviations.

Damage to an individual cell (including its individual components) can disrupt intercellular interactions (“communication”) and “cooperation.” This is based on a change in the properties and (or) structure of the plasma membrane, as well as the receptor formations located in it and on it, surface antigens, and intercellular junctions; deviation from the norm of the “set” and properties of metabolites, including biologically active ones (mediators and modulators of “communication”). This can potentiate the degree and scale of disorders in an already damaged cell, as well as cause alteration of other, intact cells.

The set of changes in subcellular structures and their functions, cells as a whole, as well as disruption of their interaction and cooperation underlie the development of typical pathological processes, standard forms pathologies of organs and physiological systems, specific diseases and painful conditions.

Necrosis and apoptosis:

Necrosis(from the Greek necros - dead) is the death of cells, accompanied by the irreversible cessation of their vital functions. Necrosis is often the final stage of dystrophy, dysplasia, and also a consequence of the direct action of damaging factors of significant force. The changes that precede necrosis are called necrobiosis or pathobiosis.

Most dead cells undergo autolysis, i.e. self-destruction of structures. The main mechanism of autolysis is the hydrolysis of cell components and intercellular substance under the influence of lysosome enzymes. This is facilitated by the development of acidosis in damaged cells. Free radicals also take part in the autolysis process. One of the arguments is the fact of intensification of free radical and lipid peroxide reactions in damaged tissues during inflammation, at certain stages of infarction, tumor growth and other pathological processes.

Other cells - phagocytes, as well as microorganisms - can also take part in the process of lysis of damaged cells. In this regard, in contrast to the autolytic mechanism, the latter is called heterolytic. Thus, the lysis of necrotic cells (necrolysis) can be achieved by auto- and heterolytic processes, in which enzymes and other factors of both dead cells and living cells in contact with them take part.

Apoptosis(from the Greek aro - absence, denial of something, ptosis - fall) is a genetically programmed process of cessation of vital activity and death of a cell or group of cells in a living organism. In this case, the dead cell does not undergo autolysis, but is usually absorbed and destroyed by a phagocyte. The process of apoptosis is observed during pathological tissue hypertrophy, inflammation, tumor growth; its frequency increases as the body ages.

Manifestations of cell damage:

Under the influence of uncouplers of the oxidation and phosphorylation processes, the coupling of these processes is reduced or blocked and the efficiency of biological oxidation decreases. A high concentration in the blood of one of the hormones of the adrenal cortex - aldosterone - causes the accumulation of excess sodium ions in various cells. On the other hand, the effect of damaging agents on certain types of cells causes changes specific to them (the cells). For example, the influence of various (chemical, biological, physical) pathogenic factors on muscle cells is accompanied by the development of contracture of their myofibrils, on neurons - by the formation of the so-called damage potential, on red blood cells - by hemolysis and the release of hemoglobin from them.

Cell damage is always accompanied by a complex of nonspecific, stereotypical, standard changes in them. They are detected by the action of various agents. Common nonspecific manifestations of cell alteration include acidosis, excessive activation of free radical and peroxide reactions, denaturation of protein molecules, increased permeability of cell membranes, imbalance of ions and liquids, changes in membrane potential parameters, and increased sorption properties of cells.

Identification of a complex of specific and nonspecific changes in the cells of organs and tissues makes it possible to judge the nature and strength of the action of the pathogenic factor, the degree of damage, as well as the effectiveness of medicinal and non-medicinal agents used for treatment. For example, by changes in the activity of the MB isoenzyme creatine phosphokinase, specific for myocarditis cells, in the blood plasma and the myoglobin content in comparison with the dynamics of the level of potassium ions (emerging from damaged cardiocytes), changes in the ECG, and indicators of contractile function of various parts of the myocardium, one can judge the degree and scale of damage heart during his heart attack.

Disturbances in the functioning of the human body under various extreme conditions and diseases are always, in one way or another, associated with changes in the functioning of cells. A cell is a structural and functional unit of tissues and organs. The processes that underlie the energetic and plastic support of tissue structures and functions take place in it. Under the influence of unfavorable environmental factors, disruption of cell functioning can become persistent and be caused by their damage. Pathology always begins with damage, when adaptive capabilities become untenable. Any pathological process occurs with a greater or lesser degree and scale of cell damage, which is expressed in a certain disruption of their structure and functions. Based on this, cell damage is understood as such changes in its structure, metabolism, physicochemical properties and functions that lead to disruption of its vital functions and which persist after removal of the damaging agent. However, taking into account that the body, as a system, is a collection of elements and connections between them, the nature of the disease must be considered from two perspectives - structural-metabolic and informational, since it is associated both with damage to the cells themselves, their executive cellular apparatus, and and with violation information processes- signaling, reception and intercellular connections, i.e. with dysregulation, and according to the terminology of G.N. Kryzhanovsky with dysregulatory pathology. At the same time, despite the diversity of pathogenic factors acting on cells, they respond with fundamentally the same type of reactions, which are based on tissue mechanisms of cellular alteration. Thus, damage should be considered as a typical pathological process, the basis of which is a violation of intracellular homeostasis, the structure of the cell’s integrity, as well as its functional ability.

Moving on to specific aspects of the pathophysiology of damage, based on the teachings of the founder of cellular pathology R. Virchow, taking into account the “priority of damage to elements over communication disorder,” we will first consider typical violations intracellular homeostasis, pathochemical and pathophysiological aspects of cell damage and its executive apparatus.

Causes of cell dysfunction and damage

The immediate cause of cell dysfunction is changes in its environment, while cell damage is caused by the action of damaging agents on it. Cell damage, the essence of which is disturbances of intracellular homeostasis, can be the result of direct (direct) or indirect, due to disruption of intercellular interaction, constancy of the internal environment of the body itself (hypoxia, acidosis, alkalosis, hypoglycemia, hyperkalemia, increased content of metabolic end products in the body), exposure to many pathogenic factors, which are divided into three main groups: physical, chemical and biological.

Among physical factors, the most common causes of cell damage are the following:

Mechanical influences: they cause disruption of the structure of the plasmalemma and membranes of subcellular formations;

Temperature factor: increased temperature of the environment in which the cell is located, up to 45-50°C or more, can lead to denaturation of proteins, nucleic acids, decomposition of lipoprotein complexes, increased permeability of cell membranes and other changes. A significant decrease in temperature can cause a significant slowdown or irreversible cessation of metabolic processes in the cell, crystallization of intracellular fluid and rupture of membranes;

Changes in osmotic pressure in the cell: the accumulation in it of products of incomplete oxidation of organic substrates, as well as excess ions, is accompanied by the flow of liquid into the cell along the osmotic pressure gradient, its swelling and stretching (up to rupture) of its plasmalemma and organelle membranes. A decrease in intracellular osmotic pressure or an increase in it in the extracellular environment leads to the loss of fluid by the cell, its wrinkling (pyknosis) and often to death;

Exposure to ionizing radiation, which causes the formation of free radicals and activation of peroxide free radical processes, the products of which damage membranes and denature cell enzymes;

Gravitational, electromagnetic factors.

Cell damage is often caused by chemical factors. These include a variety of substances of exogenous and endogenous origin: acids, alkalis, salts of heavy metals, poisons of plant and animal origin, products of impaired metabolism. Thus, cyanides inhibit the activity of cytochrome oxidase. Ethanol and its metabolites inhibit many cellular enzymes. Substances containing arsenic salts inhibit pyruvate oxidase. Incorrect use medicines can also cause cell damage. For example, an overdose of strophanthin causes a significant suppression of the activity of K + - Na + -ATPase of the sarcolemma of myocardial cells, which leads to an imbalance in the intracellular content of ions and fluid.

It is important that cell damage can be caused by both excess and deficiency of the same factor. For example, excess oxygen in tissues activates the process of lipid peroxidation (LPO), the products of which damage enzymes and cell membranes. On the other hand, a decrease in oxygen content causes a disruption of oxidative processes, a decrease in the formation of ATP and, as a consequence, a breakdown in cell functions.

Cell damage is often caused by factors of immune and allergic processes. They can be caused, in particular, by the similarity of antigens, for example, between microbes and body cells.

Damage may also result from the formation of antibodies or the influence of T lymphocytes acting against unchanged body cells due to a mutation in the genome of B or T lymphocytes of the immune system.

An important role in maintaining metabolic processes in the cell is played by substances entering it from the endings of neurons, in particular, neurotransmitters, trophogens, and neuropeptides. The reduction or cessation of their transport causes metabolic disorders in cells, disruption of their vital functions and the development of pathological conditions called neurodystrophies.

Except the above factors, cell damage is often caused by significantly increased function of organs and tissues. For example, with prolonged excessive physical activity, heart failure may develop as a result of disruption of the functioning of cardiomyocytes.

Cell damage can be the result of not only pathogenic factors, but also a consequence of genetically programmed processes. An example is the death of the epidermis, intestinal epithelium, red blood cells and other cells as a result of their aging process. The mechanisms of cell aging and death include gradual irreversible changes in the structure of membranes, enzymes, nucleic acids, depletion of substrates for metabolic reactions, and a decrease in cell resistance to pathogenic influences.

Based on their origin, all causative factors of cell damage are divided into: exogenous and endogenous; infectious and non-infectious origin.

Common mechanisms of cell damage

Depending on the speed of development and severity of the main manifestations, cell damage can be acute or chronic. Depending on the degree of disruption of intracellular homeostasis, the damage can be reversible or irreversible.

There are two pathogenetic variants of cell damage.

Violent option. It develops when an initially healthy cell is exposed to physical, chemical and biological factors, the intensity of which exceeds the usual disturbing influences to which the cell is adapted. The most sensitive to this type of damage are functionally low-active cells that have low power of their own homeostatic mechanisms.

Cytopathic variant. It occurs as a result of a primary violation of the protective-compensatory homeostatic mechanisms of the cell. In this case, the factor that triggers the pathogenetic mechanisms of damage are disturbing stimuli natural to the cell, which under these conditions become damaging. The cytopathic variant includes all types of cell damage due to the absence of any necessary components (hypoxic, during starvation, hypovitaminosis, neurotrophic, with antioxidant deficiency, with genetic defects, etc.). The most sensitive to cytopathic damage are those cells whose intensity of disturbances, and, consequently, whose functional activity in natural conditions is very high (neurons, myocardiocytes).

At the cellular level, damaging factors “turn on” several pathogenetic links. These include:

Disorder of the processes of energy supply to cells;

Damage to membranes and enzyme systems;

Imbalance of ions and liquid;

Violation of the genetic program and/or its implementation;

Disorder of the mechanisms regulating cell function.

Violation of energy supply processes occurring in cells is often the initial and leading mechanism of their alteration. Energy supply can be disrupted at the stages of ATP synthesis, its delivery and use.

Disruption of energy supply processes, in turn, can become one of the factors of dysfunction of the membrane apparatus of cells, their enzyme systems (ATPase actomyosin, K + - Na + - dependent ATPase of the plasmalemma, Mg 2+ -dependent ATPase of the “calcium pump” of the sarcoplasmic reticulum etc.), ion and fluid balance, decrease in membrane potential, as well as cell regulation mechanisms.

Damage to membranes and enzymes plays a significant role in the disruption of cell functioning, as well as the transition of reversible changes in it to irreversible ones. This is due to the fact that the basic properties of a cell largely depend on the state of its membranes and the enzymes associated with them.

One of the most important mechanisms of damage to membranes and enzymes is the intensification of peroxidation of their components. Formed in large quantities oxygen radicals (superoxide and hydroxyl radical) and lipids cause: 1) changes in the physicochemical properties of membrane lipids, which causes a violation of the conformation of their lipoprotein complexes and, in connection with this, a decrease in the activity of proteins and enzyme systems that provide the reception of humoral effects, transmembrane transport of ions and molecules, structural integrity of membranes; 2) changes in the physicochemical properties of protein micelles that perform structural and enzymatic functions in the cell; 3) the formation of structural defects in the membrane - the so-called. the simplest channels (clusters) due to the introduction of LPO products into them. These processes, in turn, cause disruption of processes important for the life of cells - excitability, generation and conduction of nerve impulses, metabolism, perception and implementation of regulatory influences, intercellular interaction, etc.

Normally, the composition and state of membranes is modified not only by free radical and lipid peroxide processes, but also by membrane-bound, free (solubilized) and lysosomal enzymes: lipases, phospholipases, proteases. Under the influence of pathogenic factors, their activity or content in the hyaloplasm of the cell may increase (in particular, due to the development of acidosis, which increases the release of enzymes from lysosomes and their subsequent activation, the penetration of calcium ions into the cell). In this regard, glycerophospholipids and membrane proteins, as well as cell enzymes, undergo intensive hydrolysis. This is accompanied by a significant increase in membrane permeability and a decrease in the kinetic properties of enzymes.

As a result of the action of hydrolases (mainly lipases and phospholipases), free fatty acids and lysophospholipids accumulate in the cell, in particular glycerophospholipids: phosphatidylcholine, phosphatidyl-ethanolamine, phosphatidylserine. They are called amphiphilic compounds due to their ability to penetrate and fix in both hydrophobic and hydrophilic environments of cell membranes (amphi means “both”, “two”). The accumulation of amphiphiles in large quantities in membranes, which, like an excess of lipid hydroperoxides, leads to the formation of clusters and microfractures in them. Damage to cell membranes and enzymes is one of the main causes of significant disruption of cell functioning and often leads to their death.

Imbalance of ions and fluid in the cell. As a rule, a violation of transmembrane distribution, as well as the intracellular content and ratio of various ions, develops after or simultaneously with disorders of energy supply and is combined with signs of damage to cell membranes and enzymes. As a result, the membrane permeability for many ions changes significantly. This applies to the greatest extent to potassium, sodium, calcium, magnesium, chlorine, that is, ions that take part in such vital processes as excitation, its conduction, electromechanical coupling, etc.

The consequence of an imbalance of ions is a change in the resting and action membrane potential, as well as a disruption in the conduction of the excitation impulse. These changes are important because they are often one of the important signs of the presence and nature of cell damage. An example is changes in the electrocardiogram when myocardial cells are damaged, and electroencephalogram when the structure and functions of brain neurons are disrupted.

Disturbances in the intracellular ion content cause changes in cell volume due to fluid imbalance. This can be manifested by cell hyperhydration. For example, an increase in the content of sodium and calcium ions in damaged cells is accompanied by an increase in osmotic pressure in them. As a result, water accumulates in the cells. At the same time, the cells swell, their volume increases, which is accompanied by an increase in stretching, often micro-tears of the cytolemma and organelle membranes. On the contrary, cell dehydration (for example, in some infectious diseases that cause water loss) is characterized by the release of fluid and proteins dissolved in it (including enzymes), as well as other organic and inorganic water-soluble compounds. Intracellular dehydration is often combined with nuclear shrinkage, breakdown of mitochondria and other organelles.

One of the significant mechanisms of cell dysfunction is damage to the genetic program and/or mechanisms for its implementation. The main processes leading to changes in the genetic information of a cell are mutations, derepression of pathogenic genes (for example, oncogenes), suppression of the activity of vital genes (for example, regulating the synthesis of enzymes) or the introduction of a fragment of foreign DNA into the genome (for example, the DNA of an oncogenic virus, an abnormal region DNA of another cell). In addition to changes in the genetic program, an important mechanism of cell dysfunction is violation of the implementation of this program mainly during the process of cell division during mitosis or meiosis.

An important mechanism of cell damage is disorder of regulation of intracellular processes. This may be the result of disturbances developing at one or more levels of regulatory mechanisms:

At the level of interaction of biologically active substances (hormones, neurotransmitters, etc.) with cell receptors;

At the cellular level, so-called. “second messengers” (messengers) of nervous influences: cyclic nucleotides - adenosine monophosphate (cAMP) and guanosine monophosphate (cGMP), formed in response to the action of “first messengers” - hormones and neurotransmitters. An example is the disruption of the formation of membrane potential in cardiomyocytes due to the accumulation of cAMP in them, which is, in particular, one of the possible causes of the development of cardiac arrhythmias;

At the level of metabolic reactions regulated by cyclic nucleotides or other intracellular factors. Thus, disruption of the process of activation of cellular enzymes can significantly change the intensity of metabolic reactions and, as a result, lead to disruption of cell functioning.

Having considered the pathochemical aspects of cell damage, it is necessary not to forget that the problem of cellular damage also has another, very important side - the informational aspect of the problem of cell damage. Communication between cells, the signals they exchange can also be sources of disease.

In most cases, cells in the body are controlled by chemical regulatory signals, namely hormones, mediators, antibodies, substrates, and ions. The lack or absence of a particular signal, as well as an excess, can prevent the inclusion of certain adaptive programs or contribute to their excessively intense, and possibly abnormally long functioning, which leads to certain pathological consequences. A special case is the fairly common situation when a cell mistakenly mistakes one signal for another - the so-called mimicry of bioregulators, leading to serious regulatory disorders. Examples of diseases caused by signaling pathology include: parkinsonism, kwashiorkor, insulin-dependent diabetes mellitus (pathology caused by signal deficiency), von Basedow's disease, Cushing's syndrome, obesity (pathology caused by signal excess). The pathogenicity of excess substrates is especially clearly visible in the example of obesity.

In some cases, even with adequate signaling, the cell is not able to respond properly if it is “blind and deaf” in relation to this signal. This is precisely the situation that is created in the absence or deficiency of receptors corresponding to any bioregulator. In particular, an example of such a pathology is familial hereditary hypercholesterolemia, the pathogenesis of which is associated with a defect in the receptor protein responsible for the recognition by cells of the vascular wall and some other tissues and organs of the protein component of low and very low density lipoproteins - apoprotein B, as well as the insulin-resistant form of sugar diabetes

However, even with adequate signaling and correct recognition of signals by cellular receptors, cells are not able to implement proper adaptation programs if there is no transfer of information from surface membrane receptors into the cell. According to modern concepts, the mechanisms that mediate intracellular signal transmission to the cell genome are diverse. Of particular importance are the pathways of post-receptor signaling in the cell through the G-protein system (guanosine triphosphate-binding proteins). These transmitter proteins occupy a key position in the exchange of information between receptors located on the surface of cell membranes and the intracellular regulatory apparatus, because they are able to integrate signals perceived by several different receptors, and in response to a specific receptor-mediated signal can include many different effector programs, bringing into play a network of various intracellular modulators, mediators, such as cAMP and cGMP.

Inadequate use by a cell of its adaptive capabilities in a number of hereditary and acquired diseases can be the result of malfunctions not only of post-receptor information mechanisms, but also a defect in genetic programs and/or mechanisms for their implementation (as a result of damage by DNA mutations, the occurrence of chromosomal abnormalities). Because of this, they are either not implemented or produce an inadequate or inappropriate result for the situation.

Main manifestations of cell damage

Dystrophies. Dystrophies (dys - disorder, disorder, trophe - nutrition) are understood as metabolic disorders in cells and tissues, accompanied by disorders of their functions, plastic manifestations, as well as structural changes leading to disruption of their vital functions.

The main mechanisms of dystrophies are:

Synthesis of abnormal substances in the cell, for example, the amyloid protein-polysaccharide complex;

Excessive transformation of some compounds into others, for example, fats and carbohydrates into proteins, carbohydrates into fats;

Decomposition (phanerosis), for example, of protein-lipid membrane complexes;

Infiltration of cells and intercellular substance with organic and inorganic compounds, for example, cholesterol and its esters of arterial walls in atherosclerosis.

The main cellular dystrophies include protein (dysproteinoses), fatty (lipidoses), carbohydrate and mineral.

Dysplasia(dys - disorder, disorder, plaseo-form) are a disruption of the process of cell development, manifested by a persistent change in their structure and function, which leads to a disorder in their vital functions.

The cause of dysplasia is damage to the cell genome. This is what causes changes that are persistent and, as a rule, inherited from cell to cell, in contrast to dystrophies, which are often temporary, reversible and can be eliminated when the action of the causative factor ceases.

The main mechanism of dysplasia is a disorder of the differentiation process, which consists in the formation of structural and functional specialization of the cell. Structural signs of dysplasia are changes in the size and shape of cells, their nuclei and other organelles, the number and structure of chromosomes. As a rule, cells are enlarged in size, have an irregular, bizarre shape (“monster cells”), and the ratio of various organelles in them is disproportionate. Often, various inclusions and signs of degenerative processes are found in such cells. Examples of cell dysplasia include the formation of megaloblasts in the bone marrow in pernicious anemia, sickle-shaped erythrocytes in hemoglobin pathology, and multinucleated giant cells with a bizarre arrangement of chromatin in Recklinghausen neurofibromatosis. Cellular dysplasia is one of the manifestations of atypia of tumor cells.

Changes in the structure and functions of cellular organelles upon cell damage. Cell damage is characterized by greater or lesser disruption of the structure and function of all its components. However, under the influence of various pathogenic factors, signs of damage to certain organelles may predominate.

Under the influence of pathogenic factors, there is a decrease in the number of mitochondria in relation to the total mass of the cell. Changes in individual mitochondria that are stereotypical for the action of most damaging factors are a decrease or increase in their size and shape. Many pathogenic effects on the cell (hypoxia, endo- and exogenous toxic agents, including drugs in case of overdose, ionizing radiation, changes in osmotic pressure) are accompanied by swelling and vacuolization of mitochondria, which can lead to rupture of their membrane, fragmentation and homogenization of cristae. Violation of the structure of mitochondria leads to a significant suppression of the process of respiration in them and the formation of ATP, as well as to an imbalance of ions inside the cell.

Under pathogenic influences, the release and activation of lysosome enzymes can lead to “self-digestion” (autolysis) of the cell.

Under the influence of damaging factors, destruction of groups of ribosomal subunits (polysomes), a decrease in the number of ribosomes, and separation of organelles from intracellular membranes are observed. These changes are accompanied by a decrease in the intensity of the protein synthesis process in the cell.

Damage to the endoplasmic reticulum and Golgi apparatus is accompanied by expansion of the reticulum tubules, up to the formation of large vacuoles and cisterns due to the accumulation of fluid in them. There is focal destruction of the membranes of the network tubules and their fragmentation.

Damage to the nucleus is combined with a change in its shape, condensation of chromatin along the periphery of the nucleus (chromatin margination), disruption of double-circuiting or rupture of the nuclear envelope.

The effect of damaging factors on the cell can cause a decrease or increase in the fluid content in the cytoplasm, proteolysis or coagulation of protein, and the formation of “inclusions” that are not found normally. A change in the state of the cytoplasm, in turn, significantly affects the metabolic processes occurring in it, due to the fact that many enzymes (for example, glycolysis) are located in the cell matrix, the function of organelles, and the processes of perception of regulatory and other influences on the cell.

Necrosis and autolysis. Necrosis (gr. necros - dead) is the death of cells and tissues, accompanied by the irreversible cessation of their vital functions. Necrosis is often the final stage of dystrophy, dysplasia, and also a consequence of the direct action of damaging factors of significant force. The changes that precede necrosis are called necrobiosis or pathobiosis. According to I.V. Davydovsky necrobiosis is the process of cell death. Examples of pathobiosis include processes of tissue necrosis in neurotrophic disorders as a result of tissue denervation due to prolonged venous hyperemia or ischemia. Necrobiotic processes also occur normally, being the final stage of the life cycle of many cells. Most dead cells undergo autolysis, i.e. self-destruction of structures. The main mechanism of autolysis is the hydrolysis of cell components and intercellular substance under the influence of lysosome enzymes. This is facilitated by the development of acidosis in damaged cells.

Other cells - phagocytes, as well as microorganisms - can also take part in the process of lysis of damaged cells. In contrast to the autolytic mechanism, the latter is called heterolytic. Thus, the lysis of necrotic cells (necrolysis) can be achieved by auto- and heterolytic processes, in which enzymes and other factors of both dead cells and living cells in contact with them take part.

Specific and nonspecific changes in cell damage. Any damage to a cell causes a complex of specific and nonspecific changes in it.

Under specific understand changes in the properties of cells that are characteristic of a given factor when it acts on various cells, or characteristic only of a given type of cell when exposed to damaging agents of various types. Thus, the effect of mechanical factors on any cell is accompanied by a violation of the integrity of its membranes. Under the influence of uncouplers of the process of oxidation and phosphorylation, the coupling of these processes is reduced or blocked. A high concentration in the blood of one of the hormones of the adrenal cortex, aldosterone, causes the accumulation of excess sodium ions in various cells. On the other hand, the effect of damaging agents on certain types of cells causes changes specific to them. For example, the influence of various pathogenic factors on muscle cells is accompanied by the development of myofibril contracture, on neurons - by the formation of the so-called damage potential, on red blood cells - by hemolysis and the release of hemoglobin from them.

Damage is always accompanied by a complex and nonspecific, stereotypical changes in cells. They are observed in various types cells under the influence of various agents. Common nonspecific manifestations of cell alterations include acidosis, excessive activation of free radical and peroxide reactions, denaturation of protein molecules, increased permeability of cell membranes, and increased sorption properties of cells.

Identification of a complex of specific and nonspecific changes in the cells of organs and tissues makes it possible to judge the nature and strength of the action of the pathogenic factor, the degree of damage, as well as the effectiveness of medicinal and non-medicinal agents used for treatment.

Damage compensation mechanisms

The effect of pathogenic factors on a cell and the development of damage is accompanied by activation or inclusion of reactions aimed at eliminating or reducing the degree of damage and its consequences. The complex of these reactions ensures the cell’s adaptation to the changed conditions of its life. The main adaptive mechanisms include reactions of compensation, restoration and replacement of lost or damaged structures and impaired functions, protection of cells from the action of pathogenic agents, as well as a regulatory decrease in their functional activity. The entire complex of such reactions can be divided into two groups: intracellular and extracellular (intercellular).

The main intracellular mechanisms of compensation for damage include the following.

Compensation for disturbances in the process of energy supply to cells. One of the ways to compensate for disturbances in energy metabolism due to damage to mitochondria is to intensify the process of glycolysis. A certain contribution to the compensation of disturbances in the energy supply of intracellular processes during damage is made by the activation of transport enzymes and the utilization of ATP energy (adenine nucleotide transferase, creatine phosphokinase, ATPase), as well as a decrease in the functional activity of the cell. The latter helps reduce ATP consumption.

Protecting cell membranes and enzymes. One of the mechanisms for protecting cell membranes and enzymes is the limitation of free radical reactions and lipid peroxidation processes by antioxidant defense enzymes (superoxide dismutase, catalase, glutathione peroxidase). Another mechanism for protecting membranes and enzymes from damaging effects, in particular lysosome enzymes, may be the activation of cell buffer systems. This causes a decrease in the degree of intracellular acidosis and, as a consequence, excessive hydrolytic activity of lysosomal enzymes. An important role in protecting cell membranes and enzymes from damage is played by microsomal enzymes, which ensure the physicochemical transformation of pathogenic agents through their oxidation, reduction, demethylation, etc.

Compensation for ion and liquid imbalance. Compensation for the imbalance of ion content in the cell can be achieved by activating the energy supply mechanisms of ion “pumps”, as well as protecting membranes and enzymes involved in ion transport. The action of buffer systems plays a certain role in reducing the degree of ion imbalance. Activation of intracellular buffer systems (carbonate, phosphate, protein) can help restore optimal ratios of K + , Na + and Ca ++ ions. A decrease in the degree of ion imbalance, in turn, may be accompanied by a normalization of intracellular fluid content.

Elimination of violations in the genetic program of cells. Damage to a section of DNA can be detected and repaired with the participation of DNA repair enzymes. These enzymes detect and remove the altered section of DNA (endonucleases and restriction enzymes), synthesize a normal nucleic acid fragment to replace the deleted one (DNA polymerases), and insert this newly synthesized fragment in place of the deleted one (ligases). In addition to these complex enzyme systems for DNA repair, the cell contains enzymes that eliminate “small-scale” biochemical changes in the genome. These include demethylases, which remove methyl groups, and ligases, which eliminate breaks in DNA chains caused by ionizing radiation or free radicals.

Compensation for disorders of intracellular metabolic processes caused by impaired regulatory functions of cells. This includes: a change in the number of receptors for hormones, neurotransmitters and other physiologically active substances on the cell surface, as well as the sensitivity of the receptors to these substances. The number of receptors can change due to the fact that their molecules are able to sink into the membrane or cytoplasm of the cell and rise to its surface. The nature and severity of the response to them largely depends on the number and sensitivity of receptors that perceive regulatory stimuli.

Excess or deficiency of hormones and neurotransmitters or their effects can also be compensated at the level of second messengers - cyclic nucleotides. It is known that the ratio of cAMP and cGMP changes not only as a result of the action of extracellular regulatory stimuli, but also intracellular factors, in particular, phosphodiesterases and calcium ions. Violation of the implementation of regulatory influences on the cell can also be compensated at the level of intracellular metabolic processes, since many of them occur on the basis of regulation of the metabolic rate by the amount of the enzyme reaction product (the principle of positive or negative feedback).

Decreased functional activity of cells. As a result of a decrease in the functional activity of cells, a decrease in the consumption of energy and substrates necessary for the implementation of plastic processes is ensured. As a result, the degree and scale of cell damage due to the action of the pathogenic factor are significantly reduced, and after the cessation of its action, a more intense and complete restoration of cellular structures and their functions is observed. The main mechanisms that provide a temporary decrease in cell function include a decrease in efferent impulses from nerve centers, a decrease in the number or sensitivity of receptors on the cell surface, and intracellular regulatory suppression of metabolic reactions.

Adaptation of cells under conditions of damage occurs not only at the metabolic and functional levels. Long-term repeated or significant damage causes significant structural changes in the cell, which have adaptive significance. They are achieved through the processes of regeneration, hypertrophy, hyperplasia, hypotrophy (see section “Structural basis of compensation”).

Regeneration(regeneratio - revival; restoration) means the replacement of cells and/or its individual structural elements in replacement of those that are dead, damaged or have completed their life cycle. Regeneration of structures is accompanied by restoration of their functions. There are so-called cellular and intracellular forms of regeneration. The first is characterized by cell reproduction through mitosis or amitosis. Intracellular regeneration is manifested by the restoration of organelles - mitochondria, nucleus, endoplasmic reticulum and others instead
damaged or dead.

Hypertrophy(hyper - excessively, increase; trophe - nourish) is an increase in the volume and mass of structural elements, in particular cells. Hypertrophy of intact cell organelles compensates for the disruption or insufficiency of the functions of its damaged elements.

Hyperplasia(hyper - excessively; plaseo - form) is characterized by an increase in the number of structural elements, in particular, organelles in the cell. Often in the same cell signs of both hyperplasia and hypertrophy are observed. Both processes provide not only compensation for the structural defect, but also the possibility of increased cell functioning.

Intercellular (extracellular) mechanisms of interaction and adaptation of cells when they are damaged. Within tissues and organs, cells are not separated. They interact with each other by exchanging metabolites, physiologically active substances, and ions. In turn, the interaction of tissue cells and organs in the body as a whole is ensured by the functioning of the lymph and blood circulation systems, endocrine, nervous and immune influences.

Characteristic feature intercellular (extracellular) adaptation mechanisms is that they are implemented mainly with the participation of cells that were not directly exposed to the pathogenic factor (for example, hyperfunction of cardiomyocytes outside the necrosis zone during myocardial infarction).

Based on the level and scale, such reactions in case of cell damage can be divided into organ-tissue, intrasystem, and intersystem. An example of an adaptive reaction at the organ-tissue level is the activation of the function of undamaged liver or kidney cells when the cells of a part of the organ are damaged. This reduces the load on cells exposed to pathogenic effects and helps reduce the degree of their damage. Intrasystemic reactions include constriction of arterioles when the work of the heart decreases (for example, during myocardial infarction), which ensures and prevents (or reduces the degree of) damage to their cells.

The involvement of several physiological systems in adaptive reactions is observed, for example, during general hypoxia. At the same time, the work of the respiratory, circulatory, blood and tissue metabolism systems is activated, which reduces the lack of oxygen and metabolic substrates in tissues, increases their utilization and thereby reduces the degree of damage to their cells (see section “Hypoxia”).

Activation of intracellular and intercellular adaptation mechanisms during damage, as a rule, prevents cell death, ensures their functions and helps eliminate the consequences of the pathogenic factor. In this case, we talk about reversible changes in cells. If the strength of the pathogenic agent is great and/or the protective and adaptive ones are insufficient, irreversible damage to the cells develops and they die.

Task No. 1

Two micropreparations were proposed for study: 1) onion skin and 2) mosquito wing.

1. When working with which of these drugs will a magnifying glass be used?

2. When studying which of these two objects will a microscope be used?

Task No. 2

For execution practical work Temporary and permanent medications have been proposed.

1. How do you distinguish a temporary drug from a permanent one?

2. Why is it better to use a temporary microslide to study some objects?

Task No. 3

In the field of view, when studying the “Hair Cross” preparation (hair contains a large amount of dark brown pigment), the following formations are visible at low magnification: thick dark brown stripes arranged crosswise, dark-colored bubbles of different diameters, long thread-like formations with clear edges, but colorless.

1. Where in the field of view are the artifacts presented?

2. What is the object of study on this drug?

Task No. 4

Three types of cells are considered: onion skin cells, a bacterial cell, and a frog skin epithelial cell.

1. Which of the listed cells can already be clearly seen with a microscope magnification (7x8)?

2. Which cells can be seen only with magnification (7x40) and immersion?

Problem #5

Based on the proposed poem:

“They peeled the skin off the onion -

Thin, colorless,

Put the peel

On a glass slide,

The microscope was installed

The drug is on the table..."

1. About the preparation of what drug we're talking about(temporary or permanent)?

2. What important points not noted here in the preparation of the drug?

Problem #6

The permanent preparation was studied at low magnification, but when switched to high magnification, the object is not visible, even with correction with macro- and micrometric screws and sufficient lighting.

1. What could this be connected with?

2. How to fix this error?

Problem No. 7

The specimen is placed on the stage of a microscope that has a mirror at the base of the tripod arm. There is weak artificial light in the audience. The object is clearly visible at low magnification, but when you try to view it with a x40 lens magnification, the object is not visible in the field of view, a dark spot is visible.

1. What could be causing the appearance of a dark spot?

2. How to fix the error?

Problem No. 8

The test specimen was damaged: the slide and cover glass were broken.

1. How could this happen?

2. What rules must be followed when microscopying?

Problem No. 9

The total magnification of the microscope during operation is 280 in one case, and 900 in the other.

1. What lenses and eyepieces were used in the first and second cases?

2. What objects do they allow to study?

Lesson No. 2. BIOLOGY OF THE EUKARYOTIC CELL. STRUCTURAL COMPONENTS OF THE CYTOPLASMA

Task No. 1

It is known that vertebrates have red blood, and some invertebrates (cephalopods) have blue blood.

1. The presence of what microelements determines the red color of blood in animals?

2. What is the reason for the blue color of blood in mollusks?

Task No. 2

Wheat grains and sunflower seeds are rich in organic matter.

1. Why is the quality of flour related to its gluten content?

2. What organic substances are found in sunflower seeds?

Task No. 3

Waxy lipofuscinoses of neurons can manifest as at different ages(childhood, adolescence, adulthood), belong to true storage diseases associated with dysfunction of membrane organelles containing a large number of hydrolytic enzymes. Symptoms include signs of damage to the central nervous system with brain atrophy, and convulsive seizures. The diagnosis is made by electron microscopy - pathological inclusions are found in these organelles of the cells of many tissues.

1. The functioning of which neuron organelle is impaired?

2. What signs did you use to identify this?

Task No. 4

The patient was diagnosed with a rare glycoprotein accumulation disease associated with a deficiency of hydrolases that break down polysaccharide bonds. These anomalies are characterized by neurological disorders and a variety of somatic manifestations. Fucosidosis and mannosidosis most often lead to death in childhood, while aspartylglucosaminuria manifests itself as a storage disease with a late onset, severe mental retardation and a longer course.

1. The functioning of which cell organelle is impaired?

2. By what signs can this be detected?

Problem #5

During pathological processes, the number of lysosomes usually increases in cells. Based on this, the idea arose that lysosomes can play an active role in cell death. However, it is known that when the lysosome membrane ruptures, the incoming hydrolases lose their activity, because the cytoplasm has a slightly alkaline environment.

1. What role do lysosomes play in this case, based on the functional role of this organelle in the cell?

2. Which cell organelle performs the function of lysosome synthesis?

Problem #6

A hereditary disease has been identified that is associated with defects in the functioning of the cell organelle, leading to disturbances in energy functions in cells - disruption of tissue respiration and synthesis of specific proteins. This disease is transmitted only through the maternal line to children of both sexes.

1. In which organelle did the changes occur?

2. Why is this disease transmitted only through the maternal line?

Problem No. 7

Typically, if cellular pathology is associated with the absence of peroxisomes in liver and kidney cells, then the organism with such a disease is not viable.

1. How to explain this fact based on the functional role of this organelle in the cell?

2. What is the reason for the non-viability of the organism in this case?

Problem No. 8

In winter hibernating marmots and hibernating bats, the number of mitochondria in cardiac muscle cells is sharply reduced.

1. What is the reason for this phenomenon?

2. What other animals are characterized by this phenomenon?

Lesson No. 3. CORE, ITS STRUCTURAL COMPONENTS. CELL REPRODUCTION

Task No. 1

The nucleus of the egg and the nucleus of the sperm have an equal number of chromosomes, but the volume of the cytoplasm and the number of cytoplasmic organelles in the egg are greater than in the sperm.

1. Is the DNA content in these cells the same?

2. Will the number of organelles increase after the fusion of an egg with a sperm?

Task No. 2

Genes that should have been activated in the G2 period remained inactive.

1. What changes in the cell will this lead to?

2. Will this affect the progress of mitosis?

Task No. 3

A binuclear cell with diploid nuclei (2n=46) has entered mitosis.

1. What amount of hereditary material will a cell have in metaphase during the formation of a single division spindle?

2. How much hereditary material will the daughter nuclei have at the end of mitosis?

Task No. 4

After fertilization, a zygote 46XX was formed, from which the female body should be formed. However, during the first mitotic division (fragmentation) of this zygote into two blastomeres, the sister chromatids of one of the X chromosomes, having separated from each other, did not separate to the 2 poles, but both moved to one pole. The chromatids of the other X chromosome separated normally. All subsequent mitotic cell divisions during embryogenesis occurred without disruption of the mitosis mechanism.

2. What might be the phenotypic characteristics of this organism?

Problem #5

After fertilization, a 46XY zygote was formed, from which a male organism should be formed. However, during the first mitotic division (fragmentation) of this zygote into two blastomeres, the sister chromatids of the Y chromosome did not separate and this entire self-duplicated (replicated) metaphase chromosome moved to one of the poles of the daughter cells (blastomeres). The segregation of the X chromosome chromatids occurred normally. All subsequent mitotic cell divisions during embryogenesis occurred without disruption of the mitosis mechanism.

1. What will be the chromosomal set of cells of the individual developing from this zygote?

2. What phenotype might this individual have?

3. What factors could lead to this mutation?

Problem #6

When a cell divides by mitosis, one of the two new cells formed does not have a nucleolus.

1. What is the structure of the nucleolus?

2. What can this phenomenon lead to?

Problem No. 7

The number of nuclear pores is constantly changing.

1. What is the structure of a nuclear pore?

2. What is the reason for the change in the number of pores in the nuclear envelope?

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