Chédiak Higashi syndrome is the main link in pathogenesis. Chédiak Higashi syndrome was performed by Nurai Soltanova first description

Chédiak-Higashi syndrome is an autosomal recessive disease that manifests itself as partial albinism of the skin and eyes due to improper distribution of melanosomes and poor distribution of pigment, photophobia, recurrent cells, and a tendency to bleed. Due to a violation of phagocytosis in cells of the macrophage and granulocytic series, a decrease in immunity is observed in this disease. A striking sign of the presence of this disease are huge cytoplasmic granules in neutrophils and eosinophils. They are also often found in the cytoplasm of neurons and in circulating lymphocytes.

The main cause of the disease is a mutation of a gene that is responsible for the synthesis of lysosomal proteins, after which a violation of chemotaxis is observed, that is, the cytotoxic activity of lymphocytes is attacked. Also, sick children have a tendency to autophagocytosis.

The disease got its name in honor of two great doctors - the Japanese Higashi and the Cuban Chediak. Who independently studied this disease. It was first mentioned in 1943.

Basically, young children get sick with it, their death often occurs before 10 years of age due to malignant tumors. In infants, the disease can progress rapidly, but with recurrence of infections. During the illness, most patients experience fever, jaundice, hemorrhagic diathesis. The development of this disease does not depend in any way on the sex of the child; both boys and girls are equally at risk. Death usually occurs within 30 months. This disease is very rare, with about 1 in a million healthy people.

The pathogenesis is associated with an abnormality of cell membranes. Almost all clinical manifestations can be associated with abnormal distribution of lysosomal enzymes. The severity and frequency of pyogenic infections depends on the decrease in the activity of oxygen metabolism.

According to how the disease develops, there are 3 forms of the Chédiak-Higashi syndrome:

• Leukopenic - which develops under the action of ionizing radiation of toxins and cytostatics.
• Dysregulatory form.
• Dysfunctional - which occurs with structural defects of membranopathies, phagocytes, fermentopathies ... These defects can be both congenital and acquired.

The main symptoms are:

• Violation of pigmentation in the hair, eyes, as well as in the neck and closed areas of the skin. Hair has unnatural white colorif you look closely at the pupil, you will notice that it has a red tint.
• Pathological nystagmus - involuntary movement eyeballs, the child cannot focus his gaze on one subject.
• Intolerance to bright light - it hurts children to look at too bright light.
• Low immunity - the child is exposed to a large number of viral and bacterial infections.
• The appearance of pustules and papules is a characteristic phenomenon in Chédiak-Higashi disease. Also, ulcers often appear that do not heal for a long time.
• Elevated temperatureaccompanied by chills and fever.
• Itching and swelling.
• There are frequent bouts of vomiting and diarrhea.
• The respiratory system is affected, which is accompanied by bouts of constant coughing and sneezing. If you do not take action in time, there will be clear moist wheezing during inhalation and exhalation.
• Chédiak-Higashi syndrome also affects the urinary system. Its difficulty is often observed. Blood clots and pus can be seen in the urine.
• Anemia - accompanied by pallor of the skin and mucous membranes. A decline in performance is often noted.
• Thrombocytopenia is a clear sign of this disease. Is accompanied by internal or external bleeding due to impaired performance internal organs.
• Often the spleen is enlarged due to dysfunction of phagocytes in the spleen.
• There are also violations mental development due to cerebellar dysfunction and peripheral neuropathy.

Diagnostics

For diagnosis, the results of the patient's examination and clinical data are needed. To obtain them, you need to take blood for conducting general analysis blood. When receiving results, doctors pay most attention to the number and condition of leukocytes (in Chédiaka-Higashi patients, the number of neutrophils is often greatly reduced due to the fact that they are destroyed very quickly in this disease or are defective and cannot fully perform their functions). Doctors also evaluate kidney enzyme levels and protein levels.

More accurate data are obtained after immunological blood tests. There are times when the state of T and B lymphocytes is normal, while others immunodeficiency states have obvious deviations.

The patient must undergo an x-ray. During its passage, doctors look at the condition and work of the heart and lungs. Also, during the X-ray, you can often see the presence of any tumors, which are a clear sign of the patient's illness.

Radiography is often used to make observations and urinary tract, and in particular, the presence of infections in them. For organ diagnostics abdominal spend ultrasound diagnostics... The detection of a heart defect is possible thanks to an echocardiogram.

Electrocardiographic studies are also required, thanks to them you can notice an increase in heart rate. Ultrasound gives a clear picture of the presence of cancer cells in the body.

Prevention

Due to the fact that this syndrome is chronic, it is very difficult to prevent its development, but it is still possible. It is very important at what stage the disease will be diagnosed, since at the first stages it is possible to suppress it. It is necessary to consult a doctor at the first symptoms.

Treatment of Chédiak-Higashi syndrome

The treatment of this disease is complicated by the fact that in each case it proceeds individually, therefore there is no standard approach to its treatment. Periodically prescribe vitamins C, P, PP in large doses. Be sure to observe the light regime, wear sunglasses, closed clothes. For infectious diseases, antibiotics are prescribed wide range... Doctors may prescribe high doses of ascorbic acid. Blood components are transfused.

Surgical intervention is extremely rare. A radical method of treatment may be prescribed - this is allogeneic bone marrow transplantation.

To avoid the appearance of skin tumors, sepsis and lymphoproliferative diseases, patients should avoid contact with mutagens and carcinogens.

Forecast

The prognosis is not very optimistic, since 85% of patients die at the age of 10 years. The main causes of death are infectious diseases and hemorrhagic syndrome.

In 2006, the results of transplants of patients with this disease were published, which had been carried out for over 20 years. 10-15 people had a five-year survival rate, but 2 out of 10 patients who survived were seen neurological disorders in early periodafter transplantation. And in 3 more patients, they appeared within 20 years, after transplantation. In 1 patient, symptoms appeared only at 21 years of age.

Chédiak-Higashi syndrome refers to a genetically determined pathological disease that develops and progresses to childhood. Clinical picture the course of the disease is unfavorable, since patients with the syndrome have a tendency to an increased risk of viral or bacterial infection.

Pathogenesis of Chédiak-Higashi syndrome

Pathogenesis is associated with an abnormality in the structure of cell membranes, a malfunction in the collecting microtubule system and a violation of interaction with lysosomal membranes. Clinical manifestations can be explained by an abnormal distribution of lysosomal enzymes. The frequency and severity of pyogenic infections are affected by a decrease in the activity of oxygen metabolism and intracellular digestion of microbes in phagocytes due to the lag and incomplete release of hydrolytic lysosomal enzymes from giant granules into phagosomes. In patients, the antibody-dependent cytotoxicity of lymphocytes and the activity of natural killer cells decrease. Pathology refers to

What is the danger?

The danger of the syndrome lies in the tendency of the body, under the influence of pathology, to form harmful neoplasms, namely, cancer cells and malignant tumors... Most often, such children die before the age of 10, that is, they do not live up to adolescence. Chédiak-Higashi syndrome is not very common in immunology. It is inherited in an autosomal recessive manner.

The nature of the disease

The disease is hereditary, but it progresses as an autosomal recessive pathology and, as a rule, it is accompanied by a violation of pigmentation, as well as hypersensitivity to various harmful microorganisms due to the incapacitation of neutrophils. They contain abnormal cells with lysosomal enzymes and peroxidase.

After all, Chédiak-Higashi syndrome is a consequence of damage to cell membranes. Such pathogenic formations are found mainly in lymphocytes, erythrocytes, platelets, as well as skin fibroblasts, subsequently, due to active growth, they can cause such serious illnesslike anemia, thrombocytopenia and leukopenia. In the body, there is a large-scale damage to all body tissues, as well as disruption of the work of all vital systems and organs. Disease as a pathological process occurs at the genetic level.

Symptoms of the syndrome

Chédiaki-Higashi syndrome has pronounced and obvious signs that immediately cause concern for the child's health. The first external manifestation of the disease is a pigmentation disorder. It is localized in the iris of the eye, on the hair, closed areas of the skin, and also in the neck. In addition, there is an involuntary movement of the eyeballs, photophobia, expressed by intolerance to bright light, nervous tic and blepharospasm.

What you should pay attention to?

There are situations when all of the above symptoms do not cause anxiety in those close to the child, but it should be borne in mind that the patient is prone to frequent viral and bacterial infections. The action of infections is systemic, that is, all systems and organs in the body are exposed to infection. Quite often, disorders concern urinary and digestive systems, as well as the respiratory system, mucous membranes and skin. The most common pathological process of fungal origin, caused by pathogens such as streptococcus and staphylococcus.

Skin damage

In patients with Chediaki-Higashi syndrome, there is an extensive and widespread skin lesion, which is characterized by the formation of papules and pustules, as well as pathogenic crusts with a yellowish color.

Similar pathologies skin violate the temperature regime of the body, and are also accompanied by swelling and severe itching, the formation of long-lasting ulcers. The defeat of the fungus manifests itself in the form of desquamation, plaque on the mucous membrane, granulomas and fistulas. Chédiaka-Higashi are unpleasant.

Damage to the digestive tract

The defeat of the organs of the gastrointestinal tract causes an increase in dyspepsia, which leads to nausea, vomiting, diarrhea and an increase in body temperature, which is accompanied by severe chills and fever. In this situation, it is necessary to restore as soon as possible water balance in the body. Otherwise, unpredictable and dangerous consequences for the whole organism.

The defeat of the upper respiratory tract of a systemic nature may be accompanied by rhinitis of allergic genesis, difficult to stop sneezing and paroxysmal cough. If not accept necessary measures, wet or dry wheezing may appear and can be heard clearly when listening. Fever and a sharp rise in temperature are also possible.

On genitourinary system the syndrome is reflected in the form of a painful and difficult process of urination, accumulation of purulent discharge, blood impurities in the urine, and in some cases, sepsis.

If Chédiak-Higashi syndrome is accompanied by anemia, it manifests itself with the following symptoms: fatigue and decreased performance, pallor of the skin and mucous membranes. Thrombocytopenia is manifested by internal and external hemorrhages, as well as dysfunction of all organs and systems.

Thus, we can conclude that the syndrome begins to attack the most weakened system, gradually destroying it, while there are signs of the underlying disease.

Diagnostics of the Chédiak-Higashi syndrome

To establish the presence of the syndrome, it is necessary to conduct a thorough and detailed examination. It will allow not only to identify the disease itself, but also the accompanying ailments. Therefore, at the initial stage, it is necessary to find qualified specialist, who will be able to give a correct assessment of all existing complaints. The doctor examines the symptoms and directs the patient for a thorough examination. As a rule, the following laboratory and clinical studies are carried out:

1. General, as well as a biochemical blood test, which allows you to identify the level of leukocytes and erythrocytes. Anemia will be indicated by a lack of red blood cells, while a reduced number of leukocytes will indicate leukopenia.
2. A special blood test for immunodeficiency is also part of the diagnosis. In this case, the ratio of T- and B-lymphocytes is checked. It should be noted that with the syndrome, this indicator may be normal.
3. It will reliably indicate the presence and predominance of cancer cells and pathogenic neoplasms in the body. In addition, ultrasound can detect pathologies of the heart, abdominal cavity and other important organs.
4. X-ray examination of the sternum makes it possible to check the size of the myocardium and pulmonary structures for the presence of parenchyma.
5. An electrocardiogram is able to provide information about heart defects. During the ECG, the path of the electrical impulse and its connection with the myocardial area is visible.

After a complete examination, the attending physician will be able to draw the appropriate conclusions and correctly diagnose, as well as give further recommendations to the patient.

Treatment

Chédiak-Higashi syndrome is genetic disease, therefore, preventive measures and prevention of its development in children's body almost impossible. The clinical outcome depends entirely on the degree of progression of the disease in the initial stages, provided early diagnosis it can be paused. For this reason, a woman needs to take a responsible approach to planning pregnancy. If there were such diseases in the family, they must be reported to the attending physician, as well as special tests to identify genetic diseases.

As for the treatment of pathology, there are no specific schemes. There is no universal medicine that can get rid of pathology forever. Therefore, therapy depends on the individual characteristics of the course of the disease in each case.

Prevention

The therapy is based on careful prevention of secondary infections. This is necessary to prevent immune effects on the body. If the child has already been exposed to viruses or harmful bacteria, a antibacterial therapy... Also, various vitamin complexes and immunostimulants are often prescribed. Unfortunately, Chédiak-Higashi syndrome is most often fatal before the age of 10.

First description The syndrome was first described more than 60 years ago by Beguez-Cesar (1943), three siblings who had major clinical signs neutropenia and abnormal granules in leukocytes. Chediak, a Cuban hematologist, reported another case in 1952, and in 1954, Higashi, a Japanese pediatrician, described a number of cases characterizing changes in myeloperoxidase in neutrophil granules of patients.

Definition Chédiak-Higashi syndrome (named after the Japanese physician Higashi and the Cuban Chédiak) is inherited in an autosomal recessive manner and manifests itself in recurrent infections, partial albinism of the eyes and skin, photophobia, nystagmus, and neutrophils containing giant cytoplasmic granules.

Epidemiology Chédiak-Higashi Syndrome (CHS) is rare, with fewer than 500 cases reported worldwide in the past 20 years. In a nationwide survey in Japan, 15 patients were diagnosed over an 11 year period (2000 -2010), indicating that one or two patients with CHS were diagnosed each year. Chédiak-Higashi Syndrome (CHS) affects all races. Al-Khenaizan suggests that the incidence of CHS may be lower in individuals with darker skinned races. Symptoms of Chédiak-Higashi Syndrome (CHS) usually appear shortly after birth or in children under 5 years of age. The average age of onset is 5.85; However, most patients die before 10 years of age.

Etiology and pathogenesis Chédiak-Higashi syndrome (CHS) is an autosomal recessive immunodeficiency disorder characterized by abnormal intracellular transport of proteins. The gene for Chédiak-Higashi syndrome was described in 1996 as the LYST or CHS 1 gene and is localized at loci 1 q 42 -43. The CHS protein is expressed in the cytoplasm of cells of various tissues and may represent an abnormality in the transport of organelle proteins.

The CHS gene affects the synthesis and / or maintenance of storage / secretion of granules in various cell types. Lysosomes of leukocytes and fibroblasts, dense platelet bodies, azurophilic granules of neutrophils, and melanocyte melanosomes are usually larger and have irregular morphology, indicating a common pathway for the synthesis of organelles responsible for the appearance of changes in patients with CHS. On early stages neutrophilic maturation, normal azurophilic granules coalesce to form megagranules, while, at a later stage (i.e., during the myelocytic stage), normal granules form. Mature neutrophils contain both populations. A similar phenomenon occurs in monocytes. The impaired function in polymorphonuclear leukocytes can be associated with an abnormality in the structure of cell membranes, a violation of the collecting microtubule system and a defect in the interaction of the latter with lysosomal membranes.

The disease often leads to death in childhood as a result of infection or accelerated lymphoma-like conditions; Thus, few patients survive to adulthood. In these patients, progressive neurological dysfunction may be the dominant feature. Neurological involvement manifests itself in a variety of ways, but often includes peripheral neuropathy. The mechanism of peripheral neuropathy in CHS has not been fully elucidated. A link has been established between this syndrome and the axonal and demyelinating type of peripheral neuropathy.

Defective melanization of melanosomes manifests itself in CHS-associated oculocutaneous albinism. In melanocytes, melanosome autophagocytosis occurs. Most patients also undergo an accelerated phase or accelerated reaction, which is a benign lymphohistiocytic melanoma-like infiltration of many organs, which occurs in more than 80% of patients. At this stage, precipitation by viruses occurs, in particular as a result of infection with the Epstein-Barr virus. This can lead to anemia, bleeding, and generalized infections leading to death. Infections most commonly affect the skin, lungs and airways and, as a rule, Staphylococcus aureus, pyogenic streptococcus and other types of pneumococci.

Most of clinical manifestations can be explained by abnormal distribution of lysosomal enzymes. The frequency and severity of pyogenic infections is due to a decrease in the activity of oxygen metabolism and intracellular digestion of microbes in phagocytes due to the delay and inconsistent release of hydrolytic lysosomal enzymes from giant granules into phagosomes. In addition, in patients with reduced activity of natural killer cells, antibody-dependent cytotoxicity of lymphocytes. and

Classification There are 3 forms of the Chédiak-Higashi syndrome: Leukopenic - which develops under the action of ionizing radiation of toxins and cytostatics. Dysregulatory form. Dysfunctional - which occurs with defects in the structure of membranopathies, phagocytes, fermentopathies. These defects can be either congenital or acquired.

Clinic Pigmentation disorders in the hair, eyes, as well as in the neck and closed skin areas. Hair has an unnatural white color, if you look closely at the pupil, you will notice that it has a red tint. Pathological nystagmus is an involuntary movement of the eyeballs, the child cannot focus his gaze on one object. Intolerance to bright light - it hurts children to look at too bright light. Low immunity - the child is prone to a large number of viral and bacterial infections. The appearance of pustules and papules is a characteristic phenomenon in Chédiak-Higashi disease. Also, ulcers often appear that do not heal for a long time. Fever, accompanied by chills and fever.

Clinic The appearance of itching and swelling. There are frequent bouts of vomiting and diarrhea. The respiratory system is affected, which is accompanied by bouts of constant coughing and sneezing. If you do not take action in time, there will be clear moist wheezing during inhalation and exhalation. Chédiak-Higashi syndrome also affects the urinary system. Its difficulty is often observed. Blood clots and pus can be seen in the urine. Anemia - accompanied by pallor of the skin and mucous membranes. A decline in performance is often noted. Thrombocytopenia is a clear sign of this disease. It is accompanied by internal or external bleeding due to impaired functioning of internal organs. Often the spleen is enlarged due to dysfunction of phagocytes in the spleen. There is also mental impairment due to cerebellar dysfunction and peripheral neuropathy.

Diagnostics Diagnostics requires the results of the patient's examination and clinical data. To obtain them, you need to take blood for a general blood test. When receiving results, doctors pay most attention to the number and condition of leukocytes (in Chédiaka-Higashi patients, the number of neutrophils is often greatly reduced due to the fact that they are destroyed very quickly in this disease or are defective and cannot fully perform their functions). More accurate data are obtained after immunological blood tests. There are cases when the state of T and B-lymphocytes is normal, while other immunodeficiency states have obvious deviations.

Prevention Due to the fact that this syndrome is chronic, it is very difficult to prevent its development, but it is still possible. It is very important at what stage the disease will be diagnosed, since at the first stages it is possible to suppress it. It is necessary to consult a doctor at the first symptoms.

The treatment of this disease is complicated by the fact that in each case it proceeds individually, therefore there is no standard approach to its treatment. Periodically appoint vitamins C, PP in large doses. Be sure to observe the light regime, wear sunglasses, closed clothing. For infectious diseases, broad-spectrum antibiotics are prescribed. Doctors may prescribe the application ascorbic acid in large doses. Blood components are transfused. Surgical intervention is extremely rare. A radical method of treatment may be prescribed - this is allogeneic bone marrow transplantation. To avoid the appearance of skin tumors, sepsis and lymphoproliferative diseases, patients should avoid contact with mutagens and carcinogens.

The prognosis is not very optimistic, since 85% of patients die at the age of 10 years. The main causes of death are infectious diseases and hemorrhagic syndrome. In 2006, the results of transplantation of patients with this disease were published, which had been carried out for over 20 years. 10-15 people had a five-year survival rate, but 2 out of 10 patients who survived had neurological disorders in the early period after transplantation. And in 3 more patients, they appeared within 20 years, after transplantation. In 1 patient, symptoms appeared only at 21 years of age.

Studied and described in 1952 by the Cuban physician Chediak and supplemented in 1954 by the Japanese physician Higashi.

Etiopathogenesis of Chédiak-Higashi syndrome.

Due to the violation of enzyme activity, about which very little is known. But what is currently known is that the anomaly has a hereditary and familial nature and is transmitted in an autosomal recessive manner, the same for both sexes. An enzymatic defect is probably caused by a mutation that affects a single gene. The existence of only one normal gene is sufficient to ensure satisfactory enzymatic synthesis. Hematological familial syndrome appears only in heterozygotes in which both genes have been mutated.

Morphological abnormalities of neutrophilic leukocytes and significant neutropenia cause deficiency non-specific protection organism.

Synonyms for Chédiak-Higashi syndrome:

• family hematological syndrome;
• steinbrick-Chedick granulation anomaly;
• chediak-Higashi leukocyte giant granulation syndrome;

Represents a familial hematological abnormality due to enzyme disorders associated with many other abnormalities.

Symptomatology (clinic) of Chédiak-Higashi syndrome.

Eye signs:transparent iris; pupils with a reddish tint; chorioretinitis; photophobia; nystagmus; reduction of lacrimation.

Skin signs: asymmetric, uneven skin hyperpigmentation of the trunk, limbs and face.

Hematological manifestations:leukocyte abnormalities with granulations and intraleukocyte inclusions; normo- and hyperchromic anemia.

Hematological disorders make patients very sensitive to infections (otitis media, lung diseases, skin infections), due to a decrease in the immunobiological activity of blood elements.

Other directly associated clinical signs:ganglion adenopathies; moderate hepatomegaly; significant splenomegaly of the spleen with increased density; excessive sweating.

Diagnostics of the Chédiak-Higashi syndrome.

Hematological studies reveal neutropenia with significant morphological abnormalities of leukocytes. The latter contain many large azurophilic granulations ranging from 2 to 3 microns. The nuclei of neutrophilic leukocytes have an irregular shape and small size.

In the peripheral blood, moderate anemia is found: normo- or hypochromic.

Course and prognosis of Chédiak-Higashi syndrome.

The course is chronic, but fatal, usually up to 10 years of age, due to secondary infections (respiratory, skin, meningeal, etc.).

Treatment of Chédiak-Higashi syndrome.

Though immune defense the organism is insufficient, the appointment of gammaglobulins is useless, since the immunological deficiency is caused, in particular, by a decrease in the nonspecific defense mechanisms of the organism.

Treatment consists in relieving the symptoms of various associated infections.

The type of inheritance is autosomal recessive. Refers to a group of hereditary disorders of the function of phagocytic cells. Clinically, it can be suspected in the first months and years of life in the presence of a clinical picture, as well as relapses of vague fever, frequent infections of the respiratory tract, gastrointestinal tract, skin.

Clinical manifestations are diverse: recurrent infections (acute respiratory infections, bronchitis, pneumonia, otitis media, sinusitis, abscesses). Usually, infectious complications are caused by microbial flora (staphylococcus, Gr-), less often fungal. Approximately 1/3 of patients have hemorrhages, an increase in body temperature in the absence of infection.

Patients have partial albinism of hair, skin, eye color. They have light, translucent skin with fine, dry, blond hair that is ashy, silvery, or leaden in color. The iris is light, pigmentation on the retina, nystagmus is noted. Characterized by universal hyperhidrosis and photophobia.

If the disease proceeds for a long time, then CNS disorders are characteristic: paresis, sensitivity disorders, hypo- and areflexia, cerebellar disorders, SV.

In most children under 10 years of age, an acute (torpid) phase occurs: fever, adenopathy, hepatosplenomegaly, hemorrhagic syndrome - associated with thrombocytopenia and impaired neutrophil function. Most children in this phase die of hemorrhagic syndrome or sepsis. This stage is also called the acceleration stage. It can occur at any age, from newborn to puberty.

Morphologically characterized by lymphohistiocytic infiltration of the liver of the spleen, lymph nodes, thymus with symptoms of hemophagocytosis of varying severity. It should be noted that with this syndrome, the cerebrospinal fluid is necessarily examined, where erythrophagia is also found.

A characteristic feature of the syndrome is the presence of giant peroxidase-positive granules in neutrophils, eosinophils, peripheral blood monocytes and bone marrow, in granulocyte progenitor cells, which contain degenerative vacuoles. Granules appear as a result of the fusion of primary and secondary lysosomes. Despite high level in them, peroxidases, the violation of fusion with phagosomes prevents the completion of phagocytosis, since giant lysosomes are not able to transfer their hydrolytic enzymes to phagosomes of neutrophils containing unintegrated bacteria. This predisposes to bacterial infections. In this disease, the phagocytic activity of neutrophils and melanocytes is normal, and chemotaxis and digestion are reduced. This can lead to the fact that neutrophils can become a "refuge" for bacteria from antibiotics and other phagocytic cells.

The pathogenesis of the syndrome is associated with the presence of cell membrane abnormalities. Therefore, there is an uncontrolled fusion of lysosomes, a violation of neutrophil chemotaxis, a change in platelet function, a decrease in the natural killer activity of lymphocytes, and a decrease in ADCC. Most of the clinical manifestations are due to the abnormal distribution of lysososmal enzymes. Damage to a cell is characterized by a change in the structural and chemical properties, metabolism, structure and functions of the cell, which lead to a disruption to its vital activity.

The cage is an open, self-regulating system. The structure of a normal cell is aimed at the implementation of a certain metabolism, differentiation and specialization. When exposed to a cell, various pathogenic agents can cause the following processes: adaptation, damage, death.

Damage types

1. Partial.

3. Reversible.

4. Irreversible (death). There are 2 types of cell death: necrosis and apoptosis.

Causes of damage

By nature:

1. Physical (temperature fluctuations, mechanical injury, ionizing radiation, electrical shock).

2. Chemical (poisons, medicinal substances, environmental factors).

3. Biological (infectious agents, immune responses, genetic disorders, nutritional imbalances).

By origin:

1. Exogenous and endogenous.

2. Infectious and non-infectious.

The action of damaging factors can be direct and indirect.

The following factors have a direct damaging effect: poisons (potassium cyanide), anoxia, very low pH values, lack of calcium ions, ionizing radiation. With mediated damage, secondary reactions develop, mediators of damage or other intermediary substances are formed. Often, the primary changes in damage remain unknown. The nature of the cell's response to damage depends on its hormonal status, nutritional status, and metabolic needs. The response of a cell to a damaging agent depends on the type, duration of action and the severity of the damaging agent (for example, glucose and table salt in high concentrations can cause cell damage by disrupting electrolyte homeostasis).

Cell pathology is an integrative concept that includes the pathology of cellular ultrastructures and components, mechanisms of structural and functional disorders of cell life, disruption of intercellular interactions and cell cooperation in general pathological processes.

Cell damage mechanisms

1. Damage to the membrane apparatus and cell enzyme systems.

2. Imbalance of ions and fluids in cells.

3. Violation of the energy supply of cellular processes.

4. Violation of the genetic program of the cell and the mechanisms of its implementation.

5. Disorders of intracellular mechanisms of regulation of cell function.

Cell nucleus pathology

The following conditions belong to the pathology of the cell nucleus:

1. Pathology of the nucleus itself (changes in the size and structure of the nucleus, shape, number of nuclei and nucleoli, the appearance of nuclear inclusions).

2. Pathology of the nuclear membrane.

3. Pathology of mitosis.

Nuclear structure changes

Polyploidy - an increase in the number of chromosomes to a multiple of their normal haploid set (23 chromosomes). Thus, with triploidy, the total number of chromosomes is 69, with tetraploidy, 92, etc. In polyploidy, the reproduction process does not reach typical endocytosis. Polyploidy develops with DNA reduplication and the absence of chromosome spiralization.

Polyploid cells are detected:

1. In normally functioning human organs, tissues and cells: in the liver, kidneys, myocardium, epidermis, megakaryocytes, giant trophoblast cells.

2. With aging of the body.

3. With reparative regeneration (liver), with compensatory hypertrophy (myocardium).

4. With tumor growth.

Methods for detecting polyploidy:

1. By the size of the kernel.

2. By increasing the amount of DNA in the interphase nucleus.

3. By increasing the number of chromosomes in the mitatic cell.

Aneuplodia - a change in the form of an incomplete set of chromosomes.

With aneuplodia, there is an increase or decrease in the total number of chromosomes in the genotype of the organism in relation to its normal value. Moreover, the changes do not cover every chromosome in the normal haploid set. Aneuplodia is associated with chromosomal mutations. With aneuplodia, the number of autosomes and the number of sex chromosomes can change. The manifestation of aneuploidy is found in malignant tumors.

Microbodies (peroxisomes)

Peroxisomes are an auxiliary oxidation system in the cell. Changes in microbodies reflect disturbances in the oxidase-catalase activity of cells. If the cell is damaged, the following changes in microbodies can be observed:

1. Primary - "peroxisomal diseases".

2. Secondary - changes in the number and structural components of peroxisomes.

Peroxisomal diseases

1. Akatalasemia. It is characterized by a sharp decrease in catalase activity in the liver and other organs. Clinically manifested by ulceration in the oral cavity.

2. Cerebrohepatorenal syndrome Zellweger. It is characterized by the absence of peroxisomes in hepatocytes. The synthesis of bile acids is impaired.

3. Systemic deficiency of carnitine. It is characterized by a pronounced deficiency of carnitine in various organs and tissues. Clinically manifested by myopathy, impaired liver and brain function.

An increase in the number of peroxisomes occurs with alcohol intoxication. A decrease in the number of peroxisomes is observed during hypoxia, exposure to ionizing radiation. Destruction of the peroxisome matrix occurs during ligation of the hepatic veins, viral hepatitis, ischemic necrosis, hyperlipidemia, hypercholesterolemia, and tumor growth.