Radiation sickness

Radiation sickness. Acute radiation sickness is an independent disease that develops as a result of the death of predominantly dividing cells of the body under the influence of short-term (up to several days) exposure to significant areas of the body of ionizing radiation. The cause of acute radiation sickness can be both an accident and total irradiation of the body with a therapeutic purpose - for bone marrow transplantation, in the treatment of multiple tumors.

In the pathogenesis of acute radiation sickness, the decisive role is played by cell death in immediate lesions. There are no significant primary changes in organs and systems not directly exposed to radiation. Under the influence of ionizing radiation, first of all, fissile cells that are in the mitotic cycle die, but unlike the effect of most cytostatics (except for myelosan, which acts at the level of stem cells), dying cells die, and lymphocytes die. Lymphopenia is one of the earliest and most important signs of acute radiation injury. The body's fibroblasts are highly resistant to the effects of radiation. After irradiation, they begin a rapid growth, which in the centers of significant lesions contributes to the development of severe sclerosis. The most important features of acute radiation sickness include a strict dependence of its manifestations on the absorbed dose of ionizing radiation.

The clinical picture of acute radiation sickness is very diverse; It depends on the dose of irradiation and the terms that passed after irradiation. In its development, the disease passes through several stages. In the first hours after irradiation, a primary reaction (vomiting, fever, headache immediately after irradiation) appears. A few days (the earlier, the higher the dose of radiation), the bone marrow is being devastated, in the blood - agranulocytosis, thrombocytopenia. There are a variety of infectious processes, stomatitis, hemorrhages. Between the primary reaction and the height of the disease at doses less than 500-600 rad, the period of external well-being is marked-the latent period. The division of acute radiation sickness into periods of primary reaction, latent, midsection and recovery is inaccurate: purely external manifestations of the disease do not determine the true position.

When the victim is close to the radiation source, the reduction in the radiation dose absorbed throughout the human body is very significant. The part of the body facing the source is irradiated substantially more than its opposite side. The unevenness of irradiation can be caused by the presence of radioactive particles of low energies, which have a small penetrating ability and cause predominantly damage to the skin, subcutaneous tissue, mucous membranes, but not bone marrow and internal organs.

It is expedient to distinguish four stages of acute radiation sickness: mild, moderate, severe and extremely severe. "The cases of relatively uniform irradiation in a dose of 100 to 200 rad, to the average from 200 to 400 rad, to the heavy one from 400 to 600 rad, and to the extremely severe radiation above 600 rad are cases of light irradiation in a dose of less than 100 rad. Radiation trauma.The basis for the division of radiation by severity is a clear therapeutic principle.The radiation injury without the development of the disease does not require special medical observation in the hospital.With an easy degree of patients are usually hospitalized, but no special treatment is given, and only in rare cases, The development of a short agranulocytosis with all infectious complications and consequences requiring antibacterial therapy, with an average severity of agranulocytosis and deep thrombocytopenia are observed in almost all patients, treatment in a well-equipped hospital, isolation, carrying out powerful antibiotic therapy during the period of hematopoiesis depression In severe cases, along with bone marrow damage, there is a picture of radiation stomatitis, radiation damage to the gastrointestinal tract. Such patients should be hospitalized only in a highly specialized hematological and surgical hospital, where there is experience in managing such patients.

With uneven irradiation, it is not at all easy to identify the severity of the disease, focusing only on dose loads. However, the task is simplified if we proceed from the therapeutic criteria: radiation injury without the development of the disease - there is no need for special observation; Easy - hospitalization mainly for observation; Average - all victims require treatment in a conventional multidisciplinary hospital; Severe - requires the assistance of a specialized hospital (in terms of hematologic lesions or deep cutaneous or intestinal lesions); Extremely difficult - in modern conditions the forecast is hopeless. The dose is rarely established physically, as a rule, it is done with the help of biological dosimetry. The special system of biological dosimetry developed in our country allows at present not only to accurately determine the fact of overexposure, but also reliably (within the described degrees of severity of acute radiation sickness) to determine the radiation doses absorbed in specific areas of the human body. This provision is valid for cases of direct, that is, during the immediate after the irradiation of the day, the receipt of the victim for examination. However, even after several years after irradiation, it is possible not only to confirm this fact, but also to establish an approximate radiation dose for chromosomal analysis of peripheral blood lymphocytes and bone marrow lymphocytes.

The clinical picture of the primary reaction depends on the radiation dose; It is different for different degrees of gravity. Repeat vomit is mainly determined by irradiation of the chest and abdomen. Irradiation of the lower half of the body, even very extensive and heavy, is usually not accompanied by significant signs of a primary reaction. Within the next hours after irradiation, neutrophilic leukocytosis is observed in patients without noticeable rejuvenation of the formula. It appears to be due to the mobilization of a primarily vascular granulocyte reserve. The height of this leukocytosis, in the development of which can play an important role and emotional component, is not clearly related to the dose of irradiation. During the first 3 days in patients, there was a decrease in the level of lymphocytes in the blood, caused, apparently, by the interphase death of these cells. This indicator has a dose dependence after 48-72 hours after irradiation.

After the end of the primary reaction, there is a gradual decrease in the level of leukocytes, platelets and reticulocytes in the blood. Lymphocytes remain close to the level of their initial fall. The leukocyte curve and, in general, the curves of platelets and reticulocytes that are similar to it characterize the regular, and not random, changes in the level of these cells in the blood (a blood test is done daily). Following the initial increase in the level of leukocytes, a gradual decrease in the level of leukocytes develops, associated with the expenditure of a bone marrow granulocyte reserve, consisting mainly of mature, radiation-resistant cells - rod-shaped and segmented neutrophils. Time to reach the minimum levels, and these levels themselves in the initial decrease in leukocytes have a dose dependence (see Table 10). Thus, if the dose of irradiation is not established in the early days of the disease, it can be determined with sufficient accuracy for treatment after 1 to 1.5 weeks. At radiation doses higher than 500-600 rad to the bone marrow, the initial decrease is accompanied by a period of agranulocytosis, deep thrombocytopenia. At lower doses, after a primary fall, a certain increase in white blood cells, platelets and reticulocytes will be noted. In some cases, white blood cells can reach normal levels. Then again comes leuko- and thrombocytopenia. So, agranulocytosis and thrombocytopenia when the bone marrow is irradiated at doses more than 200 rad will occur earlier, the larger the dose, but not earlier than the end of the first week, during which the marrow granulocyte reserve is spent and the platelets "live out".

The period of agranulocytosis and thrombocytopenia in its clinical manifestations is identical to that of other forms of cytostatic disease. In the absence of blood transfusions, hemorrhagic syndrome in acute radiation sickness is not expressed if the period of deep thrombocytopenia does not exceed 1.5-2 weeks. The depth of cytopenia and the severity of infectious complications with radiation dose are not strictly related. The way out of agranulocytosis comes earlier, the earlier it began, ie, the higher the dose.

The period of agranupocytosis is completed by the final restoration of the level of leukocytes and platelets. Recurrence of deep cytopenia in acute radiation sickness is not observed. The exit from agranulocytosis is usually rapid - within 1 to 3 days. Often, it is preceded by a 1-2-day rise in the platelet count. If in the period of agranulocytosis there was a high body temperature, sometimes its fall by 1 day outstrips the rise in the level of leukocytes. By the time of exit from agranupocytosis, the level of reticulocytes also increases, often significantly exceeding the normal-reparative-reticulocytosis. However, it is at this time (after 1 -1,5 months) that the level of red blood cells reaches its minimum value. The defeat of other organs and systems in acute radiation sickness in part resembles a hematologic syndrome, although the timing of their development is different. When the oral mucosa is irradiated at a dose above 500 rad, the so-called oral syndrome develops: swelling of the oral mucosa in the first hours after irradiation, a short period of edema relaxation and its reinforcement, beginning from the 3rd-4th day; Dry mouth, violation of salivation, the appearance of a viscous, provoking vomiting saliva; Development of ulcers on the mucous membrane of the mouth. All these changes are caused by local radiation damage, they are primary. Their occurrence usually precedes agranulocytosis, which can aggravate the infection of oral lesions. Oral syndrome proceeds wavyly with a gradual weakening of the severity of relapses, sometimes delaying for 1.5-2 months. Starting from the 2nd week after the lesion at irradiation doses less than 500 rad, the swelling of the mucous membrane of the mouth is replaced by the appearance of densely seated whitish raids on the gums - hyperkeratosis, outwardly reminiscent of thrush. In contrast, these attacks are not removed; In the differentiation helps and microscopic analysis of the impression from the plaque, which does not detect the mycelium of the fungus. Ulcerative stomatitis develops when the mucous membrane of the mouth is irradiated in a dose higher than 1000 rad. Its duration is about 1-1.5 months.

Mucosal repair is almost always complete; Only when the salivary glands are irradiated at a dose higher than 1000 rad, the persistent deactivation of salivation is possible.

At radiation doses above 300-500 rad in the intestinal region, signs of radiation enteritis may develop. When irradiated to 500 rad, a slight bloating is observed at the 3rd-4th week after irradiation, an unresolved stump-like stupa, an increase in the temperature of the thallet to the febrile digits. The time of appearance of these signs is determined by the dose: the higher the dose, the earlier the intestinal syndrome will appear. At higher doses, a picture of severe enteritis develops: diarrhea, hyperthermia, abdominal pain, swelling, splashing and rumbling, tenderness in the ileocecal region. Intestinal syndrome can be characterized by a lesion of the large intestine (in particular, a straight line with the appearance of characteristic tenesmus), radiation gastritis, radiation esophagitis. The time of formation of radiation gastritis and esophagitis occurs at the beginning of the second month of the disease, when bone marrow lesion is usually already eliminated.

Still later (in 3-4 months) radiation hepatitis develops. Its clinical characteristics differ in some features: jaundice occurs without a prodrome, bilirubinemia is low, the level of aminotransferases is increased (within 200-250 units), the skin itching is expressed. For several months the process passes many "waves" with a gradual decrease in gravity. "Waves" are characterized by increased itching, a certain rise in the level of bilirubin and a pronounced activity of serum enzymes. Immediate prognosis for hepatic lesions should be considered good, although no specific medications have been found so far (prednisolone worsens the course of hepatitis). In the future, the process can progress and after many years leads the patient to death from cirrhosis of the liver.

A typical manifestation of acute radiation sickness is the damage to the skin and its appendages. Hair loss is one of the most striking external signs of the disease, although it least affects its course. The hair of different parts of the body have different radiosensitivity: the most resistant hair on the legs, the most sensitive on the scalp, on the face, but the eyebrows belong to a group of very resistant. The final (without restoration) hair loss on the head occurs with a single dose of irradiation above 700 rad.

The skin also has an unequal radiosensitivity of different regions. The most sensitive areas of axillary cavities, inguinal folds, ulnar folds, neck. The zones of the back, the extensor surfaces of the upper and lower extremities are substantially more resistant.

Defeat of the skin - radiation dermatitis - passes the corresponding phases of development: primary erythema, edema, secondary erythema, development of blisters and ulcers, epithelization. Between the primary erythema, which develops at a dose of skin irradiation above 800 rad, and the appearance of secondary erythema, a certain period passes, which is shorter, the higher the dose, -a peculiar latent period for skin lesions. It should be emphasized that the latent period itself in the defeat of specific tissues should not coincide with the latent period of lesion of other tissues.

In other words, a period when the total external well-being of the victim is noted can not be noted at irradiation doses above 400 rad for uniform irradiation; It is practically not observed in uneven irradiations, when the bone marrow is irradiated at a dose of more than 300-400 rad. Secondary erythema may result in skin peeling, mild atrophy, pigmentation without compromising the integrity of the covers if the radiation dose does not exceed 1600 rad. At higher doses (starting at a dose of 1600 rad), bubbles appear. At doses above 2500 rad, the primary erythema is replaced by swelling of the skin, which after a week passes necrosis or bubbles filled with serous fluid appear on its background.

The prognosis of skin lesions can not be considered sufficiently definite: it depends on the severity of not only the skin changes, but also on the skin vessels, large arterial trunks. Affected vessels undergo progressive sclerotic changes for many years, and previously well-healed skin radial ulcers after a long period can cause repeated necrosis, lead to limb amputation, etc. Outside vascular lesions, secondary erythema results in the development of pigmentation at the site of the radiation "burn" often With compaction of subcutaneous tissue. At this point the skin is usually atrophic, easily vulnerable, prone to the formation of secondary ulcers. In the places of the blisters after their healing, knotty skin scars with multiple angiectasias on the atrophic skin are formed. Apparently, these scars are not prone to cancer degeneration.

The diagnosis of acute radiation sickness at the present time presents no difficulties. The characteristic picture of the primary reaction, its temporal characteristics of changes in the levels of lymphocytes, leukocytes, platelets make the diagnosis not only error-free, but also accurate with respect to the severity of the process. Chromosomal analysis of cells, bone marrow and blood lymphocytes allows us to clarify the dose and severity of the lesion immediately after irradiation and retrospectively, months and years after irradiation. When a given area of ​​the bone marrow is irradiated at a dose of more than 500 rad, the frequency of cells with chromosomal abnormalities is practically equal to 100%, at a dose of 250 radians - about 50%.

Treatment of acute radiation sickness strictly corresponds to its manifestations. Treatment of the primary reaction is symptomatic: vomiting is stopped with the use of antiemetic drugs, the introduction of hypertonic solutions (with indomitable vomiting), with dehydration, the introduction of plasma substitutes is necessary.

For the prevention of exogenous infections, patients are isolated and created aseptic conditions (boxes, ultraviolet air sterilization, use of bactericidal solutions). Treatment of bacterial complications should be urgent. Before identifying the causative agent of infection, the so-called empiric therapy with broad-spectrum antibiotics is performed according to one of the following schemes.

1. Penicillin - 20 000 000 units / day, streptomycin - 1 r / day.

2. Kanamycin-1 g / day, ampicillin -4 g / day.

3. Ceporin - 3 g / day, gentamicin -160 mg / day.

4. Rifadine (benefemycin) - 450 mg orally per day, lincomycin - 2 g / day.

Daily doses of antibiotics (except for rifadine) are administered / in 2-3 times per day. When sowing the infectious agent, antibiotic therapy becomes directed.

Treatment of necrotic enteropathy: complete hunger before the elimination of its clinical manifestations (usually about 1-1.5 weeks), drink only water (but not juices!); If necessary, prolonged fasting, parenteral nutrition; Careful care for the mucous membrane of the mouth (rinsing); Intestinal sterilization (kanamycin -2 g, polymyxin M - up to 1 g, ristomycin - 1.51, nystatin - 10,000,000-20,000,000 units / day). To combat thrombocytopenic hemorrhagic syndrome, transfusions of platelets obtained from one donor are necessary. It should be warned once again about the inexpediency of transfusion of erythromass in acute radiation sickness, if there is no clear indication for this in the form of severe anemia and the respiratory, cardiac failure caused by it. In other words, at a hemoglobin level above 83 g / l (8.3g%) without signs of acute blood loss, it is not necessary to transfuse erythromass, as this can further aggravate radiation damage to the liver, increase fibrinolysis, and provoke severe bleeding.

Forecast. After the elimination of all severe manifestations of acute radiation sickness (bone marrow, intestinal, oral syndromes, skin lesions), the patients recover. With mild and moderate lesions, convalescence is usually complete, although moderate asthenia may persist for many years. After a severe illness, severe asthenia persists for a long time. In addition, such patients are threatened by the development of cataracts. Its appearance is caused by a dose of exposure to the eyes of more than 300 rad. At a dose of about 700 rad, severe retinal lesions develop, hemorrhages on the fundus, an increase in intraocular pressure, possibly with subsequent loss of vision in the affected eye.

After acute radiation sickness, changes in the blood picture are not strictly constant: in some cases, stable moderate leukopenia and moderate thrombocytopenia are observed, in other cases this is not. Increased propensity to infectious diseases in such patients is not found. The appearance of gross changes in blood-expressed cytopenia or, conversely, leukocytosis - always indicates the development of a new pathological process (aplastic anemia as an independent disease, leukemia, etc.). Are not subject to any relapse changes in the intestine and oral cavity. Chronic radiation sickness is a disease caused by repeated exposures of the body in small doses, in total exceeding 100 rad. The development of the disease is determined not only by the total dose, but also by its power, i.e., the duration of irradiation, during which the dose of radiation in the body has been absorbed. In the conditions of a well-organized radiological service, there are currently no new cases of chronic radiation sickness in our country. Poor control of radiation sources, violation of safety precautions in work with X-ray therapeutic devices in the past led to the occurrence of cases of chronic radiation sickness.

The clinical picture of the disease is determined primarily by asthenic syndrome and moderate cytopenic changes in the blood. By themselves, changes in blood are not a source of danger for patients, although they reduce work capacity. The pathogenesis of the asthenic syndrome remains unclear. As for cytopenia, at its base lie, apparently, not only the reduction of the hematopoietic base, but also the redistribution mechanisms, since these. Patients in response to infection, the introduction of prednisone develops distinct leukocytosis.

There is no pathogenic treatment of chronic radiation sickness. Symptomatic therapy is aimed at eliminating or reducing asthenic syndrome.

Forecast. Actually chronic radiation sickness does not pose a danger to the life of patients, its symptoms do not tend to progress, but at the same time complete recovery does not appear. Chronic radiation sickness is not a continuation of acute, although residual phenomena of acute form and resemble in part the form of chronic.

In chronic radiation sickness, tumors often occur - hemoblastoses and cancer. With well-planned medical examination, thorough oncological examination once a year and a blood test 2 times a year, it is possible to prevent the development of advanced forms of cancer, and the life expectancy of such patients is approaching normal.

Along with acute and chronic radiation sickness, it is possible to identify a subacute form resulting from multiple repeated irradiations in medium doses for several months, when the total dose within a relatively short period reaches more than 500-600 rad. According to the clinical picture, this disease resembles acute radiation sickness.

Treatment of subacute form has not been developed, since such cases do not occur at the present time. The main role is played, apparently, by replacement therapy with blood components in severe aplasia and antibacterial therapy in infectious diseases.