Long-term consequences of the action of ionizing radiation. Long-term effects of irradiation. The effect of laser radiation on the body

There are two types of effect of exposure to ionizing radiation on the body: somatic and genetic. With a somatic effect, the consequences are manifested directly in the irradiated person, with a genetic effect, in his offspring. Somatic effects may be early or delayed. Early ones occur in the period from several minutes to 30-60 days after irradiation. These include redness and peeling of the skin, clouding of the lens of the eye, damage to the hematopoietic system, radiation sickness, death. Long-term somatic effects appear several months or years after irradiation in the form of persistent skin changes, malignant neoplasms, decreased immunity, and reduced life expectancy.

When studying the effect of radiation on the body, the following features were revealed:
The high efficiency of the absorbed energy, even small amounts of it, can cause profound biological changes in the body.
The presence of a latent (incubation) period for the manifestation of the action of ionizing radiation.
Action from small doses can be summed up or accumulated.
Genetic effect - effect on offspring.
Various organs of a living organism have their own sensitivity to radiation.
Not every organism (human) as a whole reacts equally to radiation.
Irradiation depends on the frequency of exposure. With the same dose of radiation, the harmful effects will be the less, the more fractionally it is received in time.

Ionizing radiation can affect the body with both external (especially X-ray and gamma radiation) and internal (especially alpha particles) radiation. Internal exposure occurs when sources enter the body through the lungs, skin and digestive organs. ionizing radiation. Internal irradiation is more dangerous than external irradiation, since the IRS that got inside expose unprotected internal organs to continuous irradiation.

Under the action of ionizing radiation, water, which is an integral part of the human body, is split and ions with different charges are formed. The resulting free radicals and oxidants interact with molecules organic matter tissue, oxidizing and destroying it. Metabolism is disturbed. There are changes in the composition of the blood - the level of erythrocytes, leukocytes, platelets and neutrophils decreases. Damage to the hematopoietic organs destroys the human immune system and leads to infectious complications.

Local lesions are characterized by radiation burns of the skin and mucous membranes. With severe burns, edema, blisters are formed, tissue death (necrosis) is possible.

Lethal absorbed doses for individual parts of the body are as follows:
head - 20 Gr;
lower abdomen - 50 Gr;
rib cage-100 Gr;
limbs - 200 Gr.

When exposed to doses 100-1000 times the lethal dose, a person can die during exposure ("death under the beam").

Biological disorders depending on the total absorbed dose of radiation are presented in (Table 3.4).

Depending on the type of ionizing radiation, there may be different protection measures: reducing the exposure time, increasing the distance to sources of ionizing radiation, fencing sources of ionizing radiation, sealing sources of ionizing radiation, equipment and arrangement of protective equipment, organization of dosimetric control, hygiene and sanitation measures.

In Russia, based on the recommendations of the International Commission on Radiation Protection, the method of protecting the population by rationing is used. The developed radiation safety standards take into account three categories of exposed persons:
A - personnel, i.e. persons permanently or temporarily working with sources of ionizing radiation;

B - a limited part of the population, i.e. persons who are not directly involved in work with sources of ionizing radiation, but due to the conditions of residence or placement of workplaces, may be exposed to ionizing radiation;

B is the entire population.

Table 3.4 Biological disturbances during single (up to 4 days) irradiation of the whole human body

The maximum allowable dose is highest value individual equivalent dose per year, which, with uniform exposure for 50 years, will not cause adverse changes in the state of health of personnel detected by modern methods.

Table 3.5 - Maximum permissible radiation doses

natural springs give a total annual dose of approximately 200 mrem (space - up to 30 mrem, soil - up to 38 mrem, radioactive elements in human tissues - up to 37 mrem, radon gas - up to 80 mrem and other sources).

Artificial sources add an annual equivalent dose of approximately 150-200 mrem (medical devices and research - 100-150 mrem, TV viewing - 1-3 mrem, coal-fired power plant - up to 6 mrem, test results nuclear weapons- up to 3 mrem and other sources).

World Organization Healthcare (WHO), the maximum permissible (safe) equivalent dose of radiation for an inhabitant of the planet is defined as 35 rem, subject to its uniform accumulation over 70 years of life.
Protection against ionizing radiation

Alpha rays can be protected by:
increasing the distance to IRS, because alpha particles have a short range;
use of overalls and special footwear, tk. the penetrating power of alpha particles is low;
exclusion of sources of alpha particles from entering food, water, air and through mucous membranes, i.e. the use of gas masks, masks, glasses, etc.

As protection against beta radiation, use:
fences (screens), taking into account the fact that an aluminum sheet with a thickness of several millimeters completely absorbs the flow of beta particles;
methods and methods that exclude the ingress of beta-radiation sources into the body.

Protection against X-rays and gamma radiation must be organized taking into account the fact that these types of radiation are characterized by high penetrating power. The following measures are most effective (usually used in combination):
increasing the distance to the radiation source;
reducing the time spent in the danger zone;
shielding of the radiation source by materials with high density(lead, iron, concrete, etc.);
the use of protective structures (anti-radiation shelters, basements, etc.) for the population;
use of personal protective equipment for respiratory organs, skin and mucous membranes;
dosimetric control of the environment and food.

When using various types of protective structures, it should be taken into account that the exposure dose rate of ionizing radiation is reduced in accordance with the value of the attenuation coefficient (Kosl). Some values ​​of Kosl are given in (Table 3.5).

For the population of the country, in case of declaring a radiation hazard, there are the following recommendations.
SHELTER IN HOUSES. It is important to know that the walls wooden house weaken ionizing radiation by 2 times, and brick - by 10 times. Cellars and basements of houses weaken the radiation dose from 7 to 100 or more times (Table 3.6).
TO TAKE PROTECTION MEASURES AGAINST RADIOACTIVE SUBSTANCES WITH AIR INTO THE APARTMENT (HOUSE):
close the windows, seal the frames and doorways.
MAKE A STOCK OF DRINKING WATER:
draw water into closed containers, prepare the simplest sanitary products (for example, soap solutions for hand treatment), turn off the taps.
CARRY OUT EMERGENCY IODINE PREVENTION (as soon as possible, but only after special notification!). Iodine prophylaxis consists in taking stable iodine preparations: potassium iodide or a water-alcohol solution of iodine. This achieves 100% protection against the accumulation of radioactive iodine in the thyroid gland.
Water-alcohol solution of iodine should be taken after meals 3 times a day for 7 days:
- children under 2 years old - 1-2 drops of 5% tincture per 100 ml of milk or nutrient mixture;
- children over 2 years old and adults - 3-5 drops per glass of milk or water.

Apply tincture of iodine in the form of a grid to the surface of the hands once a day for 7 days.

Table 3.6 - Average values ​​of radiation dose attenuation coefficient

Start preparing for a possible evacuation

Prepare documents and money, essentials, pack medicines, a minimum of linen and clothes. Gather a supply of canned food. All items should be packed in plastic bags.

Try to follow the following rules:
take canned foods;
do not drink water from open sources;
avoid long-term movements on the contaminated territory, especially on a dusty road or grass, do not go to the forest, do not swim;
when entering the premises from the street, take off your shoes and outerwear.

In the case of movement in open areas, use improvised means of protection:
respiratory organs: cover your mouth and nose with a gauze bandage moistened with water, a handkerchief, a towel or any part of clothing;
skin and hairline: cover with any items of clothing, hats, scarves, capes, gloves.

PLEASE PAY YOUR ATTENTION!

Drinking alcohol during this period - the period of maximum stress - can affect the correctness of the decision.

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Chronic radiation sickness, long-term effects of ionizing radiation

Introduction

radiation sickness radiation

Currently, this is a rare disease that occurs mainly when emergency situations at nuclear power plants during emissions of harmful substances into the atmosphere, at nuclear submarines and some facilities strategic purpose. Radiation protection includes collective and individual protective equipment, strict observance of the rules of conduct on the territory of the contaminated area, protection of food and water from contamination with radioactive elements, dosimetric control and determination of the level of contamination of the area.

Neglect of the safety rules of human interaction, his scientific and technological achievements with nature and the environment leads to the formation of various dangers and the possibility of causing damage to one's health. The occurrence of any emergency or man-made disaster is caused by a combination of objective and subjective factors that open the way for radiation sickness, as an unpredictable presentation of horrific consequences for health and social conditions of human existence on Earth.

1. The concept of chronic radiation sickness

Chronic radiation sickness. This is a general disease of the body, which develops as a result of prolonged exposure to ionizing radiation in relatively small, but exceeding the permissible levels, doses. Damage to various organs and systems is characteristic.

In accordance with the modern classification, chronic radiation sickness can be caused by: a) exposure to general external radiation or radioactive isotopes with their uniform distribution in the body; b) the action of isotopes with selective deposition or local external exposure. There are three periods in the development of chronic radiation sickness: 1) the period of formation, or chronic radiation sickness proper; 2) recovery period; 3) the period of consequences and outcomes of radiation sickness.

The first period, or the period of formation of the pathological process, is approximately 1-3 years - the time required for the formation, under adverse working conditions, of the clinical syndrome of radiation sickness with its characteristic manifestations.

According to the severity of the latter, 4 degrees of severity are distinguished: I - mild, II - medium, III - severe and IV - extremely severe. All 4 degrees are only different phases of a single pathological process. The second period, or the recovery period, is usually determined 1–3 years after the cessation of irradiation or with a sharp decrease in its intensity.

During this period, one can clearly establish the degree of severity of primary destructive changes and form a definite opinion about the possibility of recovery processes. The disease can result in a complete restoration of health, restoration with a defect, stabilization of previous changes or deterioration.

2. Pathological and clinical picture

Pathological picture. In chronic radiation sickness, structural changes occur in the endocrine glands, central and peripheral nervous systems, and the gastrointestinal tract. The organs that primarily realize the energy of ionizing radiation suffer the most. Microscopic examination reveals disorders in the hematopoietic organs. In the lymph nodes, changes are found in the central part of the follicles, in the bone marrow - aplasia phenomena.

Morphologically in the blood initial stages diseases, the compatibility of the processes of destruction and regeneration is noted. With continued irradiation, there is a violation and perversion of regeneration, a delay in differentiation and maturation of cells. In a number of organs signs of atrophy, perversion of regeneration processes are revealed. A feature of the impact of ionizing radiation is its oncogenic orientation as a result of mutagenic action and general suppression of the body's immune reactivity.

clinical picture. Chronic radiation sickness is characterized by the slow development of individual symptoms and syndromes, the peculiarity of symptoms and a tendency to progression. The leading symptoms are changes in the nervous system, hematopoietic apparatus, cardiovascular and endocrine systems, gastrointestinal tract, liver, kidneys; metabolic disturbance occurs. The effects depend on the total dose of radiation, the nature of the distribution of the absorbed dose and the sensitivity of the organism.

Chronic radiation sickness caused by general exposure occurs in persons exposed to ionizing radiation for 3-5 years and receiving single and total doses exceeding the maximum allowable. One of the early manifestations of this form is non-specific reactions of vegetative-vascular disorders occurring against the background of a functional change in the central nervous system with obligatory changes in the blood. Patients complain of general malaise, headache, irritability, bleeding gums, etc. However, during this period, all complaints are transient, and the symptoms are quickly reversible. In the future, if this stage is not diagnosed and the patient continues to work under the influence of ionizing radiation, the formation of the disease occurs, passing through all stages of its development. Only dynamic monitoring of persons with signs of individual symptoms, suspicious for the presence of radiation sickness, allows us to establish their clinical nature and cause.

With the further development of the process, symptoms of general asthenization of the body, metabolic disorders and various neurotrophic disorders appear and progress. There may be symptoms of inhibition of the secretory and motor functions of the stomach and intestines, a decrease in the function of the endocrine glands (especially the sex), trophic disorders of the skin (reduced elasticity, dryness, keratinization) and nails. The body's resistance is sharply reduced, which contributes to the emergence of various infectious complications. A feature is the possibility of developing leukemia and malignant neoplasms.

Depending on the severity of the disease and the clinical course, there are four degrees of severity of chronic radiation sickness.

Chronic radiation sickness I (mild) degree is characterized by early development functional reversible disorders of a nonspecific nature. According to the manifestation of individual syndromes, the disease at this stage differs little from the preclinical period. However, as the disease develops, symptoms of various disorders of nervous regulation are noted. The clinical picture consists of vegetative-vascular disorders, initial asthenic manifestations and changes in the peripheral blood. The main complaints are general weakness, malaise, headaches, decreased performance, loss of appetite, sleep disturbance. An objective examination attracts attention: emotional lability, persistent red dermographism, trembling of the fingers of outstretched hands, instability in the Romberg position, lability of the pulse. One of the permanent symptoms is a functional disorder of the gastrointestinal tract in the form of dyspeptic symptoms, intestinal and biliary dyskinesia, chronic gastritis with a decrease in the secretory and motor functions of the stomach. Bleeding at this stage is negligible. There is a violation of the function of the endocrine glands - the genital and thyroid glands: in men, impotence is noted, in women - a violation of the ovarian-menstrual function. Hematological parameters are characterized by lability. First of all, the content of leukocytes decreases. When examining the bone marrow, signs of irritation of the red hematopoietic germ and the white one (a slight increase in the number of immature cells of the myeloid series), as well as an increase in the number of plasma cells, are revealed. The disease has a favorable course, complete clinical recovery is possible.

Chronic radiation sickness II (medium) degree is manifested by the further development of asthenovegetative disorders and vascular dystonia, inhibition of the function of the hematopoietic apparatus and the severity of hemorrhagic phenomena. As the disease progresses, patients have a pronounced asthenic syndrome, accompanied by headaches, dizziness, increased excitability and emotional lability, memory loss, weakening of sexual feelings and potency. Trophic disorders become more pronounced: dermatitis, hair loss, nail changes. Short-term loss of consciousness, attacks of paroxysmal tachycardia, chills and metabolic disorders are possible. From the side of cardio-vascular system persistent hypotension with a predominant decrease in pressure, expansion of the boundaries of the heart, muffled heart tones are noted. Bleeding increases, which is due to both an increase in the permeability of the vascular walls and changes in the blood (a decrease in its coagulability). There are hemorrhages in the skin and mucous membranes, stomatitis, multiple skin petechiae, nosebleeds. It turns out that the motility of the stomach is disturbed with a decrease in secretion, the enzymatic activity of the pancreas and intestines is changed; possible liver toxicity. The greatest changes in this degree of chronic radiation sickness appear in the blood. Observed a sharp decline the level of leukocytes (up to 2.0 * 103 / l and below), and leukopenia is persistent. Signs of toxic granularity and degenerative changes in neutrophils, thrombocytopenia become more pronounced. In the bone marrow, hypoplasia of all types of hematopoiesis is noted. The disease is persistent.

Chronic radiation sickness III (severe) degree is characterized by severe, sometimes irreversible, changes in the body with a complete loss of tissue regenerative capacity. There are dystrophic disorders in various organs and systems. The clinical picture is progressive. The disease can take a long time, complications such as infection, trauma, intoxication can join. The leading symptoms of this form of the disease are severe lesions of the nervous system and deep inhibition of all types of hematopoiesis. Patients are sharply asthenic, complain of significant general weakness, adynamia, constant headache, which is accompanied by bouts of dizziness, nausea or vomiting. There are persistent insomnia, frequent bleeding; reduced memory. Often there are signs of diffuse brain damage of the type of disseminated encephalomyelitis with changes in the motor, reflex and sensitive areas. There are multiple hemorrhages, ulcerative necrotic processes on the mucous membranes. At the site of hemorrhages - brown pigmentation of the skin. Massive hair loss occurs, complete baldness occurs. Teeth loose and fall out. Necrotic changes can also be observed on the tonsils and in the larynx. Patients' complaints of shortness of breath, palpitations and dull pains in the region of the heart are objectively confirmed upon examination. The boundaries of the heart are expanded, muffled tones are heard. On the ECG - deep dystrophic changes in the heart muscle. The appetite is sharply reduced, which is combined with dyspeptic disorders and hemorrhagic phenomena. Deep metabolic changes, disturbances in the endocrine system (in the adrenal glands, pituitary gland, gonads, thyroid gland) are determined. In biochemical blood tests, a decrease in all indicators of metabolic processes is detected. Deep disorders of the hematopoietic apparatus due to a sharp hypoplasia of the bone marrow attract attention. The number of leukocytes in the peripheral blood drops sharply. Lymphocytes are sometimes not detected. Significantly reduced platelet count. All white blood cells are degeneratively changed. The results of the study of the bone marrow indicate a sharp depletion of its cellular elements, a delay in the normal maturation of bone marrow elements, and cell breakdown.

It is noted that the addition of other diseases to this pathological process, especially inflammatory ones, leads to a rapid progression of changes in the bone marrow. This, in turn, causes a sharp weakening of the body's resistance and creates conditions for the onset of severe sepsis.

In chronic radiation sickness IV degree, there is a rapid and steady increase in all painful symptoms. The prognosis is unfavorable (fatal outcome).

3. Diagnosis

It is very difficult to diagnose chronic radiation sickness, especially at an early stage. None of the symptoms detected in this period is specific.

Symptoms of vegetovascular dystonia, asthenia phenomena, arterial hypotension, decreased gastric secretion - all this can be due to a number of different reasons that are not related to the effects of ionizing radiation.

When making a diagnosis, great importance should be given to the sanitary and hygienic characteristics of working conditions and the professional history of the subject.

Of particular value are the data of dynamic observations and the results of dosimetry, as well as the quantitative determination of radioactive substances in body secretions: not only in urine and feces, but also in saliva, sputum, and gastric juice.

4. Treatment

Patients with chronic radiation sickness should undergo complex treatment depending on the severity of the disease.

In case of early manifestations of the disease, a sparing regimen and general strengthening measures are prescribed: exposure to air, therapeutic exercises, good nutrition, vitaminization. Physical methods of treatment are widely used: water procedures, galvanic collar, galvanic vocal therapy. From sedatives, bromine is prescribed, as well as calcium glycerophosphate, phytin, phosphrene, pantocrine, ginseng, etc. If the hematopoietic apparatus is affected, agents that stimulate hematopoiesis are indicated. For shallow and unstable hematopoietic disorders, vitamin B12 is prescribed in combination with sodium nucleinate or leukogen. Vitamins B12 are recommended to be administered intramuscularly at 100-300 mcg for 10 days. In the future, symptomatic therapy is carried out.

In case of radiation sickness II (medium) degree, especially during the period of exacerbation, treatment in a hospital is recommended. In addition to general strengthening and symptomatic agents, leukopoiesis stimulants (vitamin B12, tezan, pentoxyl, sodium nucleinate), antihemorrhagic drugs ( ascorbic acid in large doses, vitamins B6, P, K; calcium preparations, serotonin), anabolic hormones (nerobol), etc. If infectious complications join, antibiotics are administered.

At severe forms radiation sickness treatment should be persistent and long. The main attention is paid to the fight against the hypoplastic state of hematopoiesis (multiple blood transfusions, bone marrow transplantation), infectious complications, trophic and metabolic disorders (hormonal drugs, vitamins, blood substitutes), etc. An extremely difficult task is the excretion of radioactive incorporated substances from the body. So, in the presence of uranium fragments in the body, alkalis, diuretics and adsorbents are used. Special diets are also recommended: alkaline - with the incorporation of uranium, magnesium - with the incorporation of strontium. To bind and accelerate the excretion of isotopes, complexones (tetacin-calcium, pentacin) are prescribed.

5. Long-term effects of ionizing radiation

Somatic and stochastic effects that manifest themselves over a long time (several months or years) after a single or as a result of chronic exposure.

Include:

1.changes in the reproductive system

2.sclerotic processes

3.radiation cataract

4.immune diseases

5. radiocarcinogenesis

6.Shortened life span

7.genetic and teratogenic effects

It is customary to distinguish between two types of long-term consequences - somatic, developing in the exposed individuals themselves, and genetic - hereditary diseases that develop in the offspring of exposed parents. Somatic long-term effects include, first of all, a reduction in life expectancy, malignant neoplasms and cataracts. In addition, long-term effects of irradiation are noted in the skin, connective tissue, blood vessels of the kidneys and lungs in the form of thickening and atrophy of the irradiated areas, loss of elasticity and other morphofunctional disorders leading to fibrosis and sclerosis, which develop as a result of a complex of processes, including a decrease in the number of cells, and fibroblast dysfunction.

It should be borne in mind that the division into somatic and genetic consequences is very arbitrary, because in fact the nature of the damage depends on which cells were exposed to radiation, i.e. in which cells this damage occurred - in somatic or germinal. In both cases, the genetic apparatus is damaged, and, consequently, the resulting damage can be inherited. In the first case, they are inherited within tissues given organism, uniting in the concept of somatic mutagenesis, and in the second - also in the form of various mutations, but in the offspring of irradiated individuals.

Conclusion

Having read enough literature on this topic, I can conclude that such an occupational disease as chronic radiation sickness entails sad consequences. And it is very important to know the measures to prevent, treat and eliminate this disease.

List of used literature

1. Guskova A.K., Baisogolov B.D., Radiation sickness of a person (Essays), 1971.

2. Kireev P.M., Radiation sickness, M., 1960.

3. Moskalev Yu.I. Long-term effects of ionizing radiation - M., "Medicine", 1991

4. Romantsev E.F. and etc. - Molecular mechanisms radiation sickness. M., "Medicine", 1984.

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UDK 612.017.1:612.014.482

Yu.A. Sennikova, L.V. Grishina, E.L. Gelfgat, N.Yu. Soloviev,

S.V. Kiselev, S.V. Krysov, S.V. Sennikov, V.A. Kozlov

LONG-TERM CONSEQUENCES OF THE INFLUENCE OF SMALL DOSES OF RADIATION ON THE HUMAN IMMUNE SYSTEM

State Research Institute of Clinical Immunology SB RAMS, Novosibirsk

We studied the frequency of occurrence of the main immunopathological syndromes and the state of the immune system, in particular, the subpopulation structure and proliferative activity of peripheral blood mononuclear cells in residents of the Uglovsky district. Altai Territory living in the territory affected by nuclear tests at the Semipalatinsk test site. An increase in the frequency of infectious, autoimmune, allergic, hematological and oncological syndromes was found among residents of the Uglovsky district in comparison with the population of Siberia. In persons exposed to radiation, changes in the subpopulation structure and functional properties of immunocompetent peripheral blood cells were found. Revealed a significant increase in serum concentrations of cytokines IL-1, IL-2, IL-4, IL-6, IL-10, TNF-a, INF-y. The most significant deviations in the immune system were found in residents of settlements exposed to greater radiation exposure. The possible role of immune disorders in the formation of immunopathological syndromes in persons exposed to ionizing radiation is discussed.

Keywords Keywords: ionizing radiation, immune system, cytokines, CD markers

The problem of the consequences of radiation exposure to the health of the population of the Altai Territory as a result of the activities of the Semipalatinsk test site has acquired in Lately special relevance. The excess of mortality and prevalence of diseases among the irradiated population of the Altai Territory over the spontaneous level was established. The "dose-effect" dependence for a number of diseases has been determined. In response to extreme exposure to radiation, diverse pathological processes develop that affect various systems and organs of a person. The immune system is highly sensitive to the effects of ionizing radiation. The impact of ionizing radiation is accompanied by the development of a number of changes in the immune system at the cellular and subcellular level, and the emerging defects underlie the pathogenesis of a number of diseases. The consequences of exposure to ionizing radiation on the body include an increase in oncological diseases, an increase in the frequency of allergic diseases, and an increase in the number of chronic inflammatory diseases of various localization. The pathogenesis of all these diseases involves the immune system, which is one of the main targets of the negative effects of ionizing radiation on the body.

The purpose of this work was to study the long-term consequences of radiation exposure

tvia in small doses on the state of the human immune system.

Methodology

The studies were carried out in the Uglovsky district of the Altai Territory, which was exposed to radiation as a result of nuclear weapons testing at the Semipalatinsk test site. Persons who were directly in this territory in the period 1949-1962 were examined. and living in the following settlements: Poplar - effective equivalent dose of radiation (EED) 157.1 cSv, conventionally designated by us as the 1st zone; With. Belenky and s. Na-umovka - EED 121.6 and 122.8 cSv, respectively, taken for the 2nd zone; With. Laptev Log - EED 63.3 cSv, taken for the 3rd zone. The age of these individuals at the time of the survey was 49-80 years. As a comparison group (with the exception of the prevalence of the main immunopathological syndromes), we used conditionally survey data. healthy donors aged 23-40 living in Novosibirsk.

The prevalence of the main immunopathological syndromes (IPS) was studied during the examination of 132 residents of the Uglovsky district. The automated system for assessing the individual risk of immunopathological conditions - "ASIRIS", developed at the State Research Institute of CI SB RAMS, was used, which allows, by processing on a personal computer, to

the results of the survey to determine for each individual of the surveyed group a quantitative measure of the severity of a particular immunopathological syndrome. As a control, the results of a survey of 595 people were used.

Residents of different regions of Siberia of the corresponding age. The proposed ASI-RIS system makes it possible to identify 5 main types of immunopathological syndromes: infectious, allergic, autoimmune, hematological, and oncological. With the help of the ASIRIS system, various forms of immunopathological syndromes were identified, including definite and probable ones, which indicate a formed pathological syndrome according to the totality of anamnestic signs; in the case of a certain form of pathological syndrome, the information is confirmed by the diagnosis. Prenosological and small forms indicate the presence of a number of symptoms that, taken together, do not reflect the full clinical picture of the pathological syndrome.

Peripheral blood mononuclear cells (PBMCs) were isolated as standard by centrifugation of heparinized venous blood in a ficoll-urographin density gradient (p=1.082) (ficoll - Pharmacia Fine Chemicl, Sweden, urographin - Schering, Germany) at 1500 rpm. within 40 minutes. The cells collected from the interphase were placed in siliconized tubes with 6 ml of RPMI-1640 medium with 1% fetal bovine serum (FBS). Cells were washed with this medium 3 times by resuspension and subsequent centrifugation at 1000 rpm. within 10 minutes.

Cultivation of PC MNCs was carried out in 24-well flat-bottomed plates (Costar, USA). 1 ml of complete culture medium (RPMI-1640 supplemented with 10% FTS, 100 µg/ml gentamicin, 2 mmol/l L-glutamine, 5*10-5 mol/l mercaptoethanol, 20 mmol/l HEPES containing 1 million cells Concanavalin A (Sigma, USA) at a concentration of 10 μg/mL was used to stimulate PBMNCs.Cultivation time was 48 hours at 37°C in a humid atmosphere with 5% CO2.Before collecting the conditioned medium, the cells were pelleted by centrifugation in tablets at 1000 rpm for 10 minutes The collected samples were stored at a temperature of -20 ° C until the content of cytokines in them was determined.

The subpopulation structure of immunocompetent peripheral blood cells was studied by flow cytometry using monoclonal antibodies. Immunophenotyping of peripheral blood cells was carried out on a flow cytofluo-

FACSCalibur meter (Becton Dickinson, USA) in the CellQuest program (Becton Dickinson, USA). Monoclonal antibodies labeled with fluorescent labels - phycoerythrin or fluorescein isothiocyanate - were used to determine the expression of CD3, CD4, CD8, CD16, CD20 antigens (MedBioSpektr, Russia).

The proliferative activity of peripheral blood mononuclear cells was determined by the standard method. The isolated PC MNCs were cultured in a volume of 150 µl in round-bottom 96-well plates (Costar, USA) at a final concentration of 0.15*106 cells per well. To stimulate the proliferative response of MNCs, concanavalin A was used at a final concentration of 10 µg/mL. The intensity of proliferation was assessed after 72 hours by the incorporation of 3H-thymidine into the nucleoprotein fractions of cells. 3H-thymidine was added at a rate of 1 µCi/well 6 hours before the end of cultivation; cells were deposited on filters using a Cell Harvester device (Flow Laboratories, UK). The radioactivity of the experimental material was calculated in an SL-30 liquid scintillation counter (Intertechnic, France). The results are presented as average counts (pulses/min.) from three identical cultures.

The concentration of cytokines was determined by the electrochemiluminescent method using the ORIGEN-Analyser (IGEN Inc., USA) according to the method described earlier. Polyclonal and monoclonal antibodies were purchased from R&D Systems (UK). Calibration curves were constructed using recombinant human cytokines TNF-a, IL-1R, IL-6, IL-2, IL-4, IL-10 (R&D Systems, UK) and IFNy (Thomae-Biberach/Riss, Germany).

For statistical testing of hypotheses about the significance of differences between data groups, non-parametric tests of Mann-Whitney, Kolmogorov-Smirnov, the criterion of the table 2 * 2 were used, since the studied samples did not follow a normal distribution. Data are presented as mean and standard error of the mean (M±m) and as median (Me) and range of quartiles.

results

As a result of the studies carried out using the ASIRIS system, it was found that various forms of IPS were detected in 95.3% of the examined, which is significantly higher in comparison with the standard developed for the population of Siberia (79.6%) (Fig. 1A). The frequency of detection of certain and probable immunopathological syndromes (58.7%) in residents of the Uglovsky district is

was significantly higher than in the control group (p<0,001). В дальнейшем анализировали частоту встречаемости только определенных и вероятных иммунопатологических синдромов, для которых можно говорить уже о сформированной иммунопатологии.

An analysis of the structure of immunopathological syndromes in residents of the Uglovsky district revealed a significant increase in the incidence of all forms of IPS in comparison with the control, with the highest values ​​being determined for autoimmune (36.3%) and infectious (23.2%) syndromes (Fig. 1C).

On the whole, it can be concluded that individuals who were directly affected by the nuclear explosion of August 1949 have an increase in the frequency of infectious, autoimmune, allergic, hematological and oncological syndromes in comparison with the population of Siberia. This fact may indicate the presence of defects in the immune system in the examined group.

Analysis of the subpopulation structure of immunocompetent peripheral blood cells in the examined groups revealed an increase in the content of cells with the CE3+ phenotype with an increase in the dose of radiation exposure (Fig. 2). No statistically significant changes in the content of the T-helper subpopulation (SE4+) were found in all three studied zones. The content of cells expressing SE8 is reduced in the inhabitants of the 1st zone in comparison with the content of these cells in the inhabitants of the 2nd zone. Differences in the content of CD8+ cells in persons living in the 3rd zone were not revealed.

groups.

Thus, the results obtained indicate changes in the subpopulation structure of immunocompetent cells in the long term in individuals exposed to low doses of radiation. The most significant changes were found in the content of CD3+ and CD16+ cells, the number of which increases with increasing dose of radiation exposure, and CD20+ cells, for which there is a tendency to decrease.

The functional properties of lymphocytes were assessed by the proliferative activity of PK MNCs and their ability to produce immunoregulatory cytokines in vitro (TNF-a, IL-2, and IL-4). It has been established that the proliferative activity of PC MNCs in response to a mitogen (concanavalin A) increases with an increase in the dose of radiation exposure, and the differences in the indicator are significant between all zones (Fig. 3). The highest values ​​of concanavalin A-induced proliferative activity were registered in residents of the 1st zone (maximum EED). It should be noted that it is almost impossible to select a control group for the examined contingent of exposed individuals whose age is over 49 years, but if the indicators of the proliferative activity of PC MNCs in the examined are compared with the group of conditionally healthy donors (average age 25-30 years), they turn out to be significantly above (data not shown)

6єз IPS All forms and groups defined + probable. donozol.+small sips IPS IPS

■ exposed to low doses of radiation □ monitoring

I exposed to low doses of radiation □ control

Rice. 1. The prevalence of immunopathological syndromes (IPS) in individuals exposed to low doses of radiation:

A - general characteristics of the prevalence of IPS;

B - structure of the IPS.

Note: *** - there is a statistically significant difference with the control group p<0,001.

Table 1

Spontaneous and mitogen-induced production of cytokines by peripheral blood mononuclear cells of persons exposed to low doses of radiation (M±m)

Cytokine production, ig/ml 1st zone (n=28) 2nd zone (n=29) 3rd zone (n=24)

TNF-a spontaneous 215.0±156.34 643.7±494.55 1155.0±471.80

TNF-a stimulated 7132.1±1078.44 6218.6±957.93 7049.7±1483.2

IL-4 spontaneous 2399.5±455.97 913.5±164.67 606.3±182.85

IL-4 stimulated 4119.9±894.95 1434.3±294.82 552.6±162.51

IL-2 spontaneous 218.1±137.1 231.6±91.57 603.8±99.2

IL-2 stimulated 265.9±153.27 129.7±46.78 559.9±131.55

sya). The obtained results testify to changes in the functional state of PC MNCs. This fact is also reflected in the change in the ability of immunocompetent cells to produce the main immunoregulatory cytokines. Thus, in all the examined groups, conca-navalin A stimulated MNCs of SC to the most powerful production of TNF-a (Table 1) - 6218.6-7132.1 pg/ml, several tens of times higher than in the group of conditionally healthy donors (199.0 pg/ml). These data are consistent with the data obtained earlier, which showed that in residents of the Uglovsky district, with an increase in EED, the number of individuals with positive expression of mRNA of pro-inflammatory cytokines, including TNF-a, in intact PB MNCs increases. Since TNF-α is a marker of inflammation, the ability of cells to overproduce it in response to a stimulating factor is undoubtedly a predisposition to the chronicity of inflammatory processes.

When evaluating the production of cytokines by T-helpers of the 1st (Tx1) and 2nd (Tx2) types in the PB MNC culture, a different picture is observed (Table 1). It was shown that PB MNCs of the studied individuals do not respond to mitogen stimulation with the production of Tx1 and Tx2 cytokines, which are necessary for the formation of a full-fledged humoral and cellular immune response. These changes in the functional properties of immunocompetent cells can lead to a pronounced inflammatory response due to increased production of TNF-a to antigenic stimuli and to the formation of an inferior humoral and cellular immune response, since stimulation of the production of Tx1 and Tx2 cytokines in response to a mitogen is not recorded.

In the study of the serum level of cytokines, the most pronounced changes were found for the pro-inflammatory mediator IL-1R (Table 2). The content of other pro-inflammatory cytokines - IL-6 and TNF-a - was also increased in the blood serum in all subjects.

ZІІІЇEЇїZE;

CD3+ CD4+ CD8+ CD20+ CD16+

Rice. Fig. 2. Subpopulation structure of immunocompetent peripheral blood cells of residents of the Uglovsky district (M±m).

^ - statistically significant difference between the studied groups at * - p<0,05; ** - р<0,01; *** - р<0,001.

□ spontaneous □ stimulated

Rice. 3. Spontaneous and mitogen-induced proliferative activity of peripheral blood mononuclear cells in residents of the Uglovsky district (M±m).

The difference with the control group is statistically significant: ** - p<0,01; *** - р<0,001. ^ - статистически достоверное различие между группами при р<0,05.

groups (Table 2). At the same time, in people exposed to greater radiation exposure (zone 1), the concentration of TNF-a in the blood serum was the lowest (median 19.6 pg/ml). Conversely, in the group exposed to less radiation exposure (3rd zone), the concentration of TNF-a was the highest (median 1437.4 pg/ml). The decrease in serum concentrations of TNF-a in the inhabitants of the 1st zone coincides with the data on the spontaneous production of TNF-a MNCs of PC in culture (table 1), which was minimal in the inhabitants of the 1st zone. The serum level of IL-6 in residents in all three zones significantly exceeded normal values, but only slightly. Our results are consistent with the data on an increase in the expression level of IL-1R, TNF-a, and IL-6 mRNA in intact PB MNCs, previously obtained in the same group of patients.

Another group of important mediators that have been studied and on which the development of an immune response, predominantly of a cellular or humoral type, largely depends, are cytokines produced by Tx1 and Tx2 cells. Normally, there is a certain balance in the production of these cytokines, which ensures the functioning of various parts of the immune system. A change in the profile of produced cytokines indicates the activation of the immune system and, with stable changes, may indicate the formation of immunopathological conditions.

When analyzing the content of cytokines produced by Tx1, it was shown that the concentration of IL-2 in the blood serum of the surveyed residents of the Uglovsky district was significantly higher in comparison with the control group (Table 2). In persons from settlements with different EED, changes in the content of IL-2 in the blood serum

are of a similar nature. The level of IFN-y (table 2) in the blood serum of residents of the Altai Territory was significantly increased in the 1st, 2nd zones and in the aggregate of groups as a whole in comparison with the group of apparently healthy donors.

The study of the content of IL-4 (table 2) in the blood serum of residents of the Uglovsky district of the Altai Territory found an increase in the concentration of cytokine in the entire group of patients. In the study of the content of IL-4 in the blood serum of people living in certain settlements, in the 1st and 3rd zones, a significant increase in the indicator was revealed. In the 2nd zone, the median value is lower than in healthy donors, but a large range of quartiles indicates an increased level of IL-2 in a significant percentage of the subjects. The content of IL-10 in the blood serum of residents of the Altai Territory exposed to radiation, both in general and separately in settlements, is significantly increased, which is similar to the nature of the changes detected for other studied cytokines (Table 2).

Conclusion

Thus, against the background of an increased prevalence of immunopathological syndromes, we revealed a number of changes in the quantitative and functional properties of immunocompetent cells in the examined patients. In persons exposed to radiation, there is an increased proliferative activity of mononuclear cells and the production of TNF-a in response to the mitogen, while the production of cytokines Tx1 and Tx2 (IL-2 and IL-4) remains practically unchanged or even decreases after an activating stimulus.

In the blood serum of persons exposed to radiation, an increase in the content of pro-inflammatory cytokines IL-1p,

table 2

Cytokines, pg/ml Healthy donors (n=17) 1st zone (n=38) 2nd zone (n=36) 3rd zone (n=31) 1st, 2nd, 3rd zones (n=105)

IL-1r 7.6 (20.7)*** 2449.1 (29851.5)*** 1338.2 (5078.9)*** 786.2 (6479.6)** 1204.6 ( 9785.6)***

TNF-a 21.5 (38.5) 19.6 (243.9)* 1043.9 (11467.8)*** 1437.4 (5029.7)*** 280.5 (3270.5) ***

IL-6 5.7 (59.6) 9 5 (85.9)* 16.4 (108.2)* 36.2 (1193.7)* 6.6 (91.8)*

IL-2 5.8 (19.4) 119 (316.6)* 171 (21)* 220.5 (40)* 180 (107)*

IFN-y 0 (19) 18.9 (423.3)*** 16.9 (570.4)* 0 (172.2) 12.1 (332.6)**

IL-4 6.7 (37.5) 42.7 (371.7)* 1.3 (581.1)* 57 5 (308.5)* 35.0 (391.3)*

IL-10 14.3 (58.7) 130.5 (46)*** 191.0 (204.0)*** 250.0 (47.5)*** 178.0 (118)** *

Note: *** - there is a significant difference with the group of apparently healthy donors p<0,001, ** - р<0,01; * р<0,05. Данные представлены в виде: медиана (размах квартилей)

IL-6 and TNF-a, with the most significant changes found for IL-1r. An increase in the content of cytokines produced by both Tx1 (IL-2 and IFN-γ) and Tx2 (IL-4, IL-10) was also revealed, which indicates the activation of the immune system. This increase is not as pronounced as for pro-inflammatory cytokines and, to a certain extent, may be a consequence of an increase in pro-inflammatory mediators, a high level of which leads to a change in the balance of cytokines and its establishment at a different, higher level. On the other hand, an increased level of Tx1 and Tx2 type cytokines in the blood serum of residents of the Uglovsky district is accompanied by an increase in the frequency of occurrence of such immunopathological syndromes as infectious, allergic, autoimmune, in the formation of which both cellular and humoral immunity mechanisms are involved, which are precisely regulated by the cytokines we studied.

It can be concluded that the residents of all the surveyed settlements exposed to radiation as a result of the activities of the Semipalatinsk test site showed changes in both quantitative and functional parameters of immunocompetent peripheral blood cells, and the most significant deviations were found in residents of the settlement with the maximum EED value. The revealed changes in the subpopulation structure and functional properties of immunocompetent cells and the level of cytokines, of course, underlie the recorded increase in the incidence of immunopathological syndromes and indicate profound changes in the immune system.

The distant consequence of low radiation doses influence on the human immune system

J.A. Sennikova, L.V. Grishina, E.L. gelfgat,

N. Yu. Solovyeva, S.V. Kisselev, S.V. krysov,

S.V. Sennikov, V.A. Kozlov

The prevalence of primary immunopathologic syndromes and immune system status (subpopulation structure, proliferation activity of PBMC, cytokine production) in the population of the Altai region, which exposed to nucleic testing of Semipalatinsk Test Site were studied. We discovered that preva-

lence of infection, autoimmune, allergic, haemato-logic and oncologic syndromes in the investigation population were increased in comparison with the siberian population. The modifications of subpopulation structure and functional properties of peripheral blood immunocompetent cells were found in the persons exposed to radiation influence. We are determined significant increase serum levels of IL-i, -2, -4, -6, -10, TNF-a, IFN-y. These modifications positively correlate with the value of radiation dose. The possible role of immune disorders in the immunopathologic syndromes formed in the persons, which are exposed to low dose rate radiation.

Literature

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2. The immune system of the population subjected to radiation exposure in the wake of a nuclear explosion / Ya.N. Shoikhet, V.A. Kozlov, V.I. Konenkov and others - Barnaul. - 2000. - 179 p.

3. Kozlov V.A. Expression of the genes of the main mediators of the immune and hematopoietic systems in individuals exposed to radiation exposure / V.A. Kozlov, L.V. Guskova, Yu.A. Sennikova // Bulletin of the scientific program "Semipalatinsk test site - Altai". - 1995.

- No. 2. - S. 58-64.

4. Radiation impact on the population of the Altai Territory of nuclear tests at the Semipalatinsk test site / Ya.N. Shoikhet, V.I. Kiselev, V.M. Loborev and others - Barnaul. - 1999. - 345 p.

5. Sharetsky A.N. Influence of low doses of ionizing radiation on thymus-dependent humoral immune response and polyclonal activation of B-lymphocytes / A.N. Sharetsky, B.P. Surinov, M.R. Abramova // Radiation. biology. Radioecology. - 2000. - T. 40.- No. 2. - S. 168-172.

6. Dainiak N. Hematologic consequences of exposure to ionizing radiation // Exp. Hematol. - 2002. - Vol. thirty.

7. Modification of immune response by low dose radiation: role of apoptosis / B. Shankar, S. Premachandran, S.D. Bharambe et al. // Immunology Lett. - 1999. - Vol. 68. - P. 237-245.

8. Quantitative analysis of human immunoregulatory cytokines by electrochemiluminescence method / S.V. Sennikov, S.V. Krysov, T.V. Injelevskaya et al. // J. Immun. methods. - 2003. - Vol. 275. - No. 1-2. - P. 81-88.

Types of ionizing radiation and their effect on a living organism. It is impossible to imagine the 21st century without modern and constantly improved nuclear weapons, large nuclear power facilities scattered throughout the globe and many complex industrial facilities using various radioactive substances in the technological process. All this predetermined the appearance and then the increase in the intensity of such a negative environmental factor as ionizing radiation, which poses a significant threat to human life and requires reliable measures to ensure the radiation safety of workers and the public.
Ionizing radiation is a phenomenon associated with radioactivity. Radioactivity is the spontaneous transformation of the nuclei of atoms of one element into another, accompanied by the emission of ionizing radiation.
Depending on the half-life1, short-lived isotopes are distinguished, the half-lives of which are calculated in fractions of a second, minutes, hours, days, and long-lived isotopes, the half-lives of which range from several months to billions of years.
When ionizing radiation interacts with matter, the atoms of the medium are ionized. Possessing a relatively large mass and charge, a-particles have an insignificant ionizing ability: their path length in air is 2.5 cm, in biological tissue - 31 microns, in aluminum - 16 microns. At the same time, os-particles are characterized by a high specific ionization density of biological tissue. For P-particles, the path length in air is 17.8 m, in water - 2.6 cm, and in aluminum - 9.8 mm. The specific ionization density created by P-particles is approximately 1000 times less than for oc-particles of the same energy. X-ray and y-radiation have a high penetrating power, and their path in air reaches hundreds of meters.
The degree, depth and form of radiation injuries that develop among biological objects when exposed to ionizing radiation, primarily depend on the amount of absorbed radiation energy. To characterize this indicator, the concept of absorbed dose is used, i.e., the radiation energy absorbed per unit mass of the irradiated substance.
To characterize the dose by the ionization effect caused in the air, the so-called exposure dose of X-ray and y radiation is used, expressed as the total electric charge of ions of the same sign formed in a unit volume of air under electronic equilibrium conditions.
The absorbed and exposure doses of radiation, referred to a unit of time, are called the absorbed and exposure dose rates.
To assess the biological effect of ionizing radiation, along with the absorbed dose, the concept of biological equivalent dose is also used.
Ionizing radiation is a unique environmental phenomenon, the effects of which on the body, at first glance, are completely non-equivalent to the amount of absorbed energy. At present, there is a widespread hypothesis about the possibility of the existence of chain reactions that enhance the primary effect of ionizing radiation.
The processes of interaction of ionizing radiation with the substance of the cell, as a result of which ionized and excited atoms and molecules are formed, are the first stage in the development of radiation injury. Ionized and excited atoms and molecules interact with each other for 10-6 s, giving rise to chemically active centers (free radicals, ions, radical ions, etc.).
Then there are reactions of chemically active substances with various biological structures, in which both destruction and the formation of new compounds unusual for the irradiated organism are noted.
At the next stages of the development of radiation injury, metabolic disorders in biological systems are manifested with a change in the corresponding functions.
However, it should be emphasized that the final effect of irradiation is the result not only of the primary irradiation of cells, but also of subsequent recovery processes. This reduction is thought to be related to enzymatic reactions and is driven by energy metabolism. It is believed that this phenomenon is based on the activity of systems that, under normal conditions, regulate the natural mutation process.
If we take morphological changes as a criterion for sensitivity to ionizing radiation, then the cells and tissues of the human body can be arranged in the following order according to the degree of sensitivity increase:
nervous tissue;
cartilage and bone tissue;
muscle;
connective tissue;
thyroid;
digestive glands;
lungs;
leather;
mucous membranes;
sex glands;
lymphoid tissue, bone marrow.
The effect of exposure to sources of ionizing radiation on the body depends on a number of reasons, the main of which are considered to be the level of absorbed doses, exposure time and dose rate, the volume of tissues and organs, and the type of radiation.
The level of absorbed doses is one of the main factors determining the possibility of the body's response to radiation exposure. A single irradiation of a dog with γ-radiation at a dose of 4-5 Gy1 (400-500 rad) causes acute radiation sickness in it; a single irradiation with a dose of 0.5 Gy (50 rad) leads only to a temporary decrease in the number of lymphocytes and neutrophils in the blood.
The time factor in the prediction of the possible consequences of irradiation occupies an important place in connection with the recovery processes developing after radiation damage in tissues and organs.
Diseases caused by the action of ionizing radiation. The most important biological reactions of the human body to the action of ionizing radiation are conditionally divided into two groups. The first includes acute lesions, the second - long-term consequences, which, in turn, are divided into somatic and genetic effects.
Acute lesions. In the case of simultaneous total irradiation of a person with a significant dose or its distribution for a short time, the effect of irradiation is observed already on the first day, and the degree of damage depends on the magnitude of the absorbed dose.
When a person is irradiated with a dose of less than 100 rem, as a rule, only mild reactions of the body are noted, manifested in a change in the blood formula, some autonomic functions.
At radiation doses of more than 100 rem, acute radiation sickness develops, the severity of which depends on the radiation dose. The first degree of radiation sickness (mild) occurs at doses of 100-200 rem, the second (moderate) - at doses of 200-300 rem, the third (severe) - at doses of 300-500 rem and the fourth (extremely severe) - at doses of more than 500 rem.
Single exposure doses of 500-600 rem in the absence of medical care are considered absolutely lethal.
Another form of acute radiation injury manifests itself in the form of radiation burns. Depending on the absorbed dose of ionizing radiation, there are reactions of I degree (at a dose of up to 500 rem), II (up to 800 rem), III (up to 1200 rem) and IV degree (at a dose above 1200 rem), manifested in different forms: from hair loss, peeling and light skin pigmentation (I burn degree) to ulcerative necrotic lesions and the formation of long-term non-healing trophic ulcers (IV degree of radiation injury).
With prolonged repeated external or internal exposure of a person in small doses, but exceeding the permissible values, the development of chronic radiation sickness is possible.
Long-term consequences. Long-term consequences of a somatic nature include a variety of biological effects, among which the most significant are leukemia, malignant neoplasms, cataracts of the lens of the eye and a reduction in life expectancy.
Leukemia is a relatively rare disease. Most radiobiologists believe that the probability of developing leukemia is 1-2 cases per year per 1 million population when the entire population is exposed to a dose of 1 rem.
Malignant neoplasms. The first cases of the development of malignant neoplasms from exposure to ionizing radiation were described as early as the beginning of the 20th century. These were cases of hand skin cancer among X-ray workers.
Information about the possibility of developing malignant neoplasms in humans is still descriptive, despite the fact that some quantitative characteristics have been obtained in a number of experimental studies on animals. Therefore, it is not possible to accurately indicate the minimum doses that have a blastomogenic effect.
The development of cataracts has been observed in survivors of the atomic bombings of Hiroshima and Nagasaki; physicists who worked on cyclotrons; in patients whose eyes were exposed to irradiation for therapeutic purposes. The single-stage cataractogenic dose of ionizing radiation, according to most researchers, is about 200 rem. The latent period before the appearance of the first signs of the development of the lesion is usually from 2 to 7 years.
The reduction in life expectancy as a result of exposure to ionizing radiation on the body was found in animal experiments (it is assumed that this phenomenon is due to the acceleration of the aging process and an increase in susceptibility to infections). The life span of animals irradiated with doses close to lethal is reduced by 25~50% compared to the control group. At lower doses, the life span of animals is reduced by 2-4% for every 100 rem.
Reliable data on the reduction of human life with long-term chronic exposure to low doses has not yet been received.
According to most radiobiologists, the reduction in human life expectancy with total irradiation is in the range of 1-15 days per 1 rem.
Regulation of exposure and principles of radiation safety. Since January 1, 2000, exposure of people in the Russian Federation is regulated by Radiation Safety Standards (NRB)-9b, Hygienic Standards (GN) 2.6.1.054-96.
The main dose exposure limits and permissible levels are established for the following categories of exposed persons:
personnel - persons working with man-made sources (group A) or who, due to working conditions, are in the sphere of their influence (group B);
the population, including persons from the staff, outside the scope and conditions of their production activities.
Three classes of standards are provided for the indicated categories of exposed persons:
basic dose limits (maximum allowable dose - for category A, dose limit - for category B);
permissible levels (permissible dose rate, permissible flux density, permissible content of radionuclides in a critical organ, etc.);
control levels (doses and levels) set by the administration of the institution in agreement with the State Sanitary and Epidemiological Supervision at a level below the permissible level.
The main dose limits are set for three groups of critical organs.
Critical organ - an organ, tissue, part of the body or the whole body, the irradiation of which causes the greatest damage to the health of a given person or his offspring. The division into groups of critical organs is based on the Bergonier-Tribondeaux law of radiosensitivity, according to which the most sensitive to ionizing radiation are the least differentiated tissues characterized by intensive cell reproduction.
The first group of critical organs includes the gonads, the red bone marrow, and the whole body if the body is irradiated with uniform radiation. To the second group - all internal organs, endocrine glands (with the exception of the gonads), nervous and muscle tissue and other organs that do not belong to the first and third groups.
To the third group - skin, bones, forearms and hands, ankles and feet.
In NRB-96, the effective dose is used as the main dose limits, which is determined by the product of the equivalent dose in an organ by the appropriate weighted coefficient for a given organ or tissue. The effective dose is used as a measure of the risk of long-term effects of human exposure. The effective dose for personnel is equal to 20 mSv per year for any subsequent 5 years, but not more than 50 mSv per year; for the population - 1 mSv per year for any subsequent 5 years, but not more than 5 mSv per year.
For the second and third groups of critical organs, the equivalent dose in the organ, respectively, is:
for personnel - 150 and 300 mSv;
for a person from the population - 15 and 50 mSv.
For personnel group B, the effective and equivalent doses in the body should not exceed 1/4 of the value for personnel (group A).
The main dose limits for exposure of personnel and the public are set without taking into account doses from natural and medical sources of ionizing radiation, as well as doses resulting from radiation accidents. The regulation of these types of exposure is carried out by special restrictions and conditions.
In addition to exposure dose limits, NRB-96 establishes permissible levels of dose rate for external irradiation of the whole body from man-made sources, as well as permissible levels of general radioactive contamination of work surfaces, skin, overalls and personal protective equipment.
Compliance with the established exposure standards and ensuring the radiation safety of personnel are predetermined by a complex of diverse protective measures that depend on the specific conditions of work with sources of ionizing radiation, and primarily on the type (closed or open) of the radiation source.
Protective measures to ensure radiation safety when using sealed sources are based on knowledge of the laws of propagation of ionizing radiation and the nature of their interaction with matter.
The main ones are the following:
the external exposure dose is proportional to the radiation intensity and exposure time;
the intensity of radiation from a point source is proportional to the number of quanta or particles that arise in it per unit time, and is inversely proportional to the square of the distance;
radiation intensity can be reduced with the help of screens.
From these patterns follow the basic principles of ensuring radiation safety:
reducing the power of sources to minimum values ​​("protection by quantity");
reducing the time of work with sources ("time protection");
increasing the distance from sources to workers ("protection by distance");
shielding of radiation sources with materials that absorb ionizing radiation ("shield protection").
Hygienic requirements for the protection of personnel from internal retraining when using open sources of ionizing radiation are determined by the complexity of the operations performed during the work. However, the main principles of protection remain unchanged. These include:
use of the principles of protection applied when working with sealed radiation sources;
sealing of production equipment to isolate processes that can be sources of radioactive substances entering the environment;
planning activities;
the use of sanitary devices and equipment, the use of protective materials;
use of personal protective equipment and sanitization of personnel;
compliance with the rules of personal hygiene.

Based on the materials of the book - "Life Safety" Edited by prof. E. A. Arustamova.

Chronic radiation sickness is a consequence of repeated exposure to small doses. The pathogenesis of disorders and the clinic essentially do not differ from those in an acute disease, however, the dynamics of the development of the disease and the severity of individual signs differ.

There are three degrees of severity of chronic radiation sickness. In case of a disease of the first degree, the disturbances are of the nature of functional reversible disorders on the part of the most sensitive systems. Sometimes the patient's health may be satisfactory, but a blood test reveals signs of the disease - moderate unstable leukopenia and thrombocytopenia.

The disease of the second degree is characterized by more pronounced changes in the nervous and hematopoietic systems, as well as the presence of hemoeragic syndrome and a decrease in immunity. There is persistent leukopenia and lymphopenia, the number of platelets is also reduced.

The disease of the third degree is characterized by severe irreversible changes in the organs, deep tissue degeneration. Signs of organic damage are expressed in the nervous system. The function of the pituitary and adrenal glands is depleted. Hematopoiesis is sharply suppressed, vascular tone is lowered, and their wall permeability is sharply increased. The mucous membranes are affected by ulcerative necrotic process. Infectious complications and inflammatory processes are also necrotic.

Chronic radiation sickness of any severity leads to early degenerative lesions of all tissues, premature aging.

The biological effect of low doses of radiation is assessed differently in relation to the population as a whole and in relation to an individual. There are such minimal levels of exposure that do not significantly affect the incidence of the population. This determines the permissible doses of radiation in the workplace. The background (natural) radiation is also estimated. There is evidence that certain minimum levels of radioactive radiation are a necessary component of the environment, below which, under artificially created conditions, living organisms develop worse. In this sense, we can talk about the threshold of influence.

Otherwise, the biological significance of low doses of radiation for a single individual is estimated. One quantum of energy is enough for a mutation, and the consequences of a single mutation can be dramatic for the body, especially in cases where there is a weakness in reparative enzyme systems or a lack of natural antioxidants. In this sense, no radiation can be considered absolutely harmless to humans.

It is also known that low doses of radiation that do not cause visible functional and morphological disorders in the early stages can cause pathological changes in the body in the long term, in particular, increase the incidence of neoplasms. It is difficult to quantify them against the background of spontaneous cancer incidence.

The experiments describe a new phenomenon, which consists in the fact that cells that received a small dose of radiation that did not cause any visible pathological changes die prematurely, and this ability is inherited in several generations. This suggests premature aging and the transmission of this property by inheritance.

Hypoxia. Types, characteristics, compensation mechanisms. Changes in blood oxygenation parameters during hypoxia (hypoxic, respiratory, circulatory, tissue, hemic). Mechanisms of resistance to hypoxia in childhood. Consequences of hypoxia.

Hypoxia, or oxygen starvation- a typical pathological process that develops as a result of insufficient supply of oxygen to tissues or a violation of its use by tissues.

Types of hypoxia

The classification given below is based on the causes and mechanisms of the development of oxygen starvation. There are the following types of hypoxia: hypoxic, respiratory, hemic, circulatory, tissue and mixed.

Hypoxic or exogenous hypoxia develops with a decrease in the partial pressure of oxygen in the inhaled air. The most typical example of hypoxic hypoxia is mountain sickness. Its manifestations depend on the height of the rise. In the experiment, hypoxic hypoxia is simulated using a pressure chamber, as well as using respiratory mixtures poor in oxygen.

Respiratory, or respiratory, hypoxia occurs as a result of a violation of external respiration, in particular a violation of pulmonary ventilation, blood supply to the lungs or diffusion of oxygen in them, in which the oxygenation of arterial blood is disturbed (see section XX - "Pathological physiology of external respiration").

Blood, or hemic, hypoxia occurs in connection with disorders in the blood system, in particular with a decrease in its oxygen capacity. Hemic hypoxia is subdivided into anemic and hypoxia due to inactivation of hemoglobin. Anemia as a cause of hypoxia is described in section XVIII ("Pathological physiology of the blood system").

Under pathological conditions, the formation of such hemoglobin compounds that cannot perform a respiratory function is possible. This is carboxyhemoglobin - a compound of hemoglobin with carbon monoxide (CO). The affinity of hemoglobin for CO is 300 times higher than for oxygen, which causes the high toxicity of carbon monoxide: poisoning occurs at negligible concentrations of CO in the air. In this case, not only hemoglobin is inactivated, but also iron-containing respiratory enzymes. In case of poisoning with nitrates, aniline, methemoglobin is formed, in which ferric iron does not attach oxygen.

Circulatory hypoxia develops with local and general circulatory disorders, and it is possible to distinguish ischemic and congestive forms in it.

If hemodynamic disorders develop in the vessels of the systemic circulation, oxygen saturation in the lungs may be normal, but delivery to tissues may suffer. With hemodynamic disorders in the system of a small circle, arterial blood oxygenation suffers.

Circulatory hypoxia can be caused not only by absolute, but also by relative circulatory insufficiency, when the tissue demand for oxygen exceeds its delivery. Such a condition can occur, for example, in the heart muscle during emotional stress, accompanied by the release of adrenaline, the action of which, although it causes the expansion of the coronary arteries, at the same time significantly increases the myocardial oxygen demand.

This type of hypoxia includes oxygen starvation of tissues as a result of impaired microcirculation, which, as you know, is a capillary blood and lymph flow, as well as transport through the capillary network and cell membranes.

tissue hypoxia- violations in the oxygen utilization system. With this type of hypoxia, biological oxidation suffers against the background of a sufficient supply of oxygen to the tissues. The causes of tissue hypoxia are a decrease in the number or activity of respiratory enzymes, uncoupling of oxidation and phosphorylation.

A classic example of tissue hypoxia, in which respiratory enzymes are inactivated, in particular cytochrome oxidase, the final enzyme of the respiratory chain, is cyanide poisoning. Alcohol and some drugs (ether, urethane) in large doses inhibit dehydrogenases.

A decrease in the synthesis of respiratory enzymes occurs with beriberi. Riboflavin and nicotinic acid are especially important - the first is a cofactor of flavin enzymes, the second is part of NAD-dependent dehydrogenases.

When oxidation and phosphorylation are uncoupled, the efficiency of biological oxidation decreases, energy is dissipated in the form of free heat, and the resynthesis of macroergic compounds decreases. Energy starvation and metabolic shifts are similar to those that occur during oxygen starvation.

In the occurrence of tissue hypoxia, the activation of peroxide free radical oxidation, in which organic substances undergo non-enzymatic oxidation by molecular oxygen, may be important. Lipid peroxidation (LPO) causes destabilization of mitochondrial and lysosome membranes. Activation of free radical oxidation and, consequently, tissue hypoxia are observed under the action of ionizing radiation, hyperoxia, and also with a deficiency of natural antioxidants that are involved in the reduction of free radicals or in the elimination of hydrogen peroxide. These are tocopherols, rutin, ubiquinone, ascorbic acid, glutathione, serotonin, catalase, cholesterol, and some steroid hormones.

The individual types of oxygen starvation listed above are rare, their various combinations are more often observed. For example, chronic hypoxia of any origin is usually complicated by damage to respiratory enzymes and the addition of oxygen deficiency of a tissue nature. This gave grounds to distinguish the sixth type of hypoxia - mixed hypoxia.

There is also hypoxia of the load, which develops against the background of sufficient or even increased supply of tissues with oxygen. However, increased organ function and a greatly increased oxygen demand can lead to inadequate oxygen supply and the development of metabolic disorders characteristic of true oxygen deficiency. Excessive loads in sports, intensive muscular work can serve as an example. This type of hypoxia is a trigger for the development of fatigue.

Pathogenesis

Like any other pathological process, hypoxia develops in two stages - compensation and decompensation. First, due to the inclusion of compensatory-adaptive reactions, it is possible to maintain a normal supply of oxygen to tissues despite the violation of its delivery. With the depletion of adaptive mechanisms, the stage of decompensation or oxygen starvation itself develops.

Compensatory-adaptive reactions during hypoxia develop in transport systems and in the oxygen utilization system. In addition, there are mechanisms of "struggle for oxygen" and mechanisms of adaptation to conditions of reduced tissue respiration.

An increase in pulmonary ventilation occurs as a result of reflex excitation of the respiratory center by impulses from the chemoreceptors of the vascular bed, mainly the carotid sinus and aortic zones, which usually respond to changes in the chemical composition of the blood and, first of all, to the accumulation of carbon dioxide (hypercapnia) and hydrogen ions.

In the case of hypoxic hypoxia, for example, when climbing to a height in the mountains, stimulation of chemoreceptors occurs directly in response to a decrease in oxygen tension in the blood, since pCO2 in the blood is also reduced. Hyperventilation is undoubtedly a positive reaction of the body to altitude, but it also has negative consequences, since it is complicated by the excretion of carbon dioxide, the development of hypocapnia and respiratory (gas) alkalosis. If we take into account the effect of carbon dioxide on the cerebral and coronary circulation, the regulation of the tone of the respiratory and vasomotor centers, the acid-base state, the dissociation of oxyhemoglobin, then it becomes clear what important indicators can be violated during hypocapnia. All this means that when considering the pathogenesis of mountain sickness, hypocapnia should be given the same importance as hypoxia.

An increase in blood circulation is aimed at mobilizing the means of delivering oxygen to tissues (hyperfunction of the heart, an increase in blood flow velocity, opening of non-functioning capillary vessels). An equally important characteristic of blood circulation under conditions of hypoxia is the redistribution of blood towards the predominant blood supply to vital organs and the maintenance of optimal blood flow in the lungs, heart, and brain due to a decrease in blood supply to the skin, spleen, muscles, and intestines. The presence in the body of a kind of oxygen topography and its dynamic fluctuations is an important adaptive mechanism during hypoxia. These changes in blood circulation are regulated by reflex and hormonal mechanisms, as well as tissue products of altered metabolism, which have a vasodilating effect.

An increase in the number of red blood cells and hemoglobin increases the oxygen capacity of the blood. The release of blood from the depot can provide an emergency, but short-term adaptation to hypoxia. With longer hypoxia, erythropoiesis in the bone marrow is enhanced, as evidenced by the appearance of reticulocytes in the blood, an increase in the number of mitoses in erythronormoblasts, and bone marrow hyperplasia. Stimulators of hematopoiesis are erythropoietins of the kidneys, as well as the breakdown products of erythrocytes, which occurs during hypoxia.

Changes in the dissociation curve of oxyhemoglobin. During hypoxia, the ability of the hemoglobin A molecule to attach oxygen in the lungs and give it to the tissues increases. Several possible variants of this device are shown in Fig. 17.1. The shift of the dissociation curve in the region of upper inflection to the left indicates an increase in the ability of Hb to absorb oxygen at a lower partial pressure of it in the inhaled air. Arterial blood may be more oxygenated than usual, which increases the arteriovenous difference. A shift to the right in the region of lower inflection indicates a decrease in the affinity of Hb for oxygen at low values ​​of pO2, i.e., in tissues. In this case, tissues can receive more oxygen from the blood.

There is evidence of an increase in the blood content of fetal hemoglobin, which has a higher affinity for oxygen.

Mechanisms of long-term adaptation to hypoxia. The adaptive changes described above develop in the most reactive systems of the body responsible for oxygen transport and distribution. However, emergency hyperfunction of external respiration and blood circulation cannot provide a stable and long-term adaptation to hypoxia, as it requires increased oxygen consumption for its implementation, is accompanied by an increase in the intensity of the functioning of structures (IFS) and increased protein breakdown. Emergency hyperfunction requires, over time, structural and energy reinforcement, which ensures not just survival, but the possibility of active physical and mental work during prolonged hypoxia.

At present, this aspect attracts the most attention of researchers. The subject of study are mountain and diving animals, indigenous people of high mountain regions, as well as experimental animals with compensatory adaptations for hypoxia developed over several generations. It has been established that in the systems responsible for oxygen transport, the phenomena of hypertrophy and hyperplasia develop - the mass of the respiratory muscles, pulmonary alveoli, myocardium, neurons of the respiratory center increases; the blood supply to these organs increases due to an increase in the number of functioning capillary vessels and their hypertrophy (increase in diameter and length). This leads to the normalization of the intensity of functioning of structures (IFS). Bone marrow hyperplasia can also be considered as a plastic support for the hyperfunction of the blood system.

Data have been obtained that with prolonged acclimatization to high-altitude hypoxia, the conditions for oxygen diffusion from the alveolar air into the blood improve due to an increase in the permeability of the pulmonary capillary membranes, the content of myoglobin increases, which is not only an additional oxygen capacity, but also has the ability to stimulate the process of diffusion of O2 in a cage (Fig. 17.2). Of great interest are adaptive changes in the oxygen utilization system. The following is fundamentally possible here:

strengthening the ability of tissue enzymes to utilize oxygen, maintain a sufficiently high level of oxidative processes and carry out normal ATP synthesis despite hypoxemia;

more efficient use of the energy of oxidative processes (in particular, an increase in the intensity of oxidative phosphorylation due to a greater association of this process with oxidation has been established in the brain tissue);

strengthening the processes of anoxic energy release with the help of glycolysis (the latter is activated by the breakdown products of ATP, and also due to the weakening of the inhibitory effect of ATP on the key enzymes of glycolysis).

There is an assumption that in the process of long-term adaptation to hypoxia, qualitative changes occur in the final enzyme of the respiratory chain - cytochrome oxidase, and possibly other respiratory enzymes, as a result of which their affinity for oxygen increases. Data have appeared on the possibility of accelerating the very process of oxidation in mitochondria (M. N. Kondrashova).

Another mechanism of adaptation to hypoxia is to increase the number of respiratory enzymes and the power of the mitochondrial system by increasing the number of mitochondria.

The sequence of these phenomena is shown in fig. 17.3. The initial link is the inhibition of the oxidation and oxidative resynthesis of adenosine triphosphoric acid with a lack of oxygen, as a result of which the number of macroergs in the cell decreases and, accordingly, the number of their decay products increases. The [ADP]x[F]/[ATP] ratio, referred to as the phosphorylation potential, increases. This shift is a stimulus for the cell's genetic apparatus, the activation of which leads to an increase in the synthesis of nucleic acids and proteins in the mitochondrial system. The mass of mitochondria increases, which means an increase in the number of respiratory chains. In this way, the ability of the cell to produce energy in spite of the lack of oxygen in the incoming blood is restored or increased.

The described processes occur mainly in organs with the most intense adaptive hyperfunction during hypoxia, i.e., those responsible for oxygen transport (lungs, heart, respiratory muscles, bone marrow erythroblastic germ), as well as those most suffering from oxygen deficiency (cerebral cortex, neurons respiratory center). In the same organs, the synthesis of structural proteins increases, leading to the phenomena of hyperplasia and hypertrophy. Thus, the long-term hyperfunction of oxygen transport and utilization systems receives plastic and energy support (F. 3. Meyerson). This fundamental change at the cellular level changes the nature of the adaptation process during hypoxia. Wasteful hyperfunction of external respiration, heart and hematopoiesis becomes superfluous. Sustainable and economical adaptation develops.

An increase in the resistance of tissues to hypoxia is facilitated by the activation of the hypothalamic-pituitary system and the adrenal cortex. Glycocorticoids activate some enzymes of the respiratory chain, stabilize lysosome membranes.

With different types of hypoxia, the ratio between the described adaptive reactions may be different. So, for example, with respiratory and circulatory hypoxia, the possibilities of adaptation in the system of external respiration and blood circulation are limited. In tissue hypoxia, adaptive phenomena in the oxygen transport system are ineffective.

Pathological disorders in hypoxia. Disorders characteristic of hypoxia develop with insufficiency or depletion of adaptive mechanisms.

Redox processes, as is known, are a mechanism for obtaining the energy necessary for all life processes. The conservation of this energy occurs in phosphorus compounds containing macroergic bonds. Biochemical studies during hypoxia revealed a decrease in the content of these compounds in tissues. Thus, the lack of oxygen leads to energy starvation of tissues, which underlies all disorders during hypoxia.

With a lack of O 2, metabolic disorders and the accumulation of products of incomplete oxidation occur, many of which are toxic. In the liver and muscles, for example, the amount of glycogen decreases, and the resulting glucose is not completely oxidized. Lactic acid, which accumulates in this case, can change the acid-base state towards acidosis. Fat metabolism also occurs with the accumulation of intermediate products - acetone, acetoacetic and β-hydroxybutyric acids (ketone bodies). The appearance of products of lipid peroxidation (LPO) is one of the most important factors of hypoxic cell damage. Their neutralization occurs by means of natural antioxidant protection, the mechanisms of which we strive to reproduce artificially in order to correct hypoxic conditions at the tissue level. Accumulate intermediate products of protein metabolism. The content of ammonia increases, the content of glutamine decreases, the exchange of phosphoproteins and phospholipids is disturbed, a negative nitrogen balance is established. Synthetic processes are reduced. Changes in electrolyte metabolism are a violation of the active transport of ions through biological membranes, a decrease in the amount of intracellular potassium. The important role of calcium ions, the accumulation of which in the cytoplasm of cells is considered one of the main links in hypoxic cell damage, has been proven by the positive effect of calcium channel blockers. Metabolic disorders during hypoxia should also include a violation of the synthesis of mediators of the nervous system.

Structural disturbances in the cell during hypoxia arise as a result of the biochemical changes described above. Thus, a shift in pH to the acid side and other metabolic disorders damage the membranes of lysosomes, from where active proteolytic enzymes come out. Their destructive effect on the cell, in particular on mitochondria, is enhanced against the background of macroerg deficiency, which makes cellular structures even more vulnerable. Ultrastructural disorders are expressed in hyperchromatosis and disintegration of the nucleus, swelling and degradation of mitochondria, the safety of which predetermines the reversibility of hypoxic damage to the cell.

It was mentioned above that the basis of long-term adaptation to hypoxia is the structurally provided hyperfunction of the oxygen transport and utilization systems, and this, in turn, is due to the activation of the genetic apparatus. In differentiated cells, especially in the cerebral cortex and neurons of the respiratory center, this process can end in exhaustion.

The sensitivity of different tissues to a lack of oxygen is not the same and depends on the following factors:

1. metabolic rate, i.e. tissue oxygen needs;

2. the power of its glycolytic system, i.e., the ability to produce energy without the participation of oxygen;

3. energy reserves in the form of macroergic compounds;

4. the potential of the genetic apparatus to provide plastic fixation of hyperfunction.