Radiation sickness

Introduction to radiation sickness Acute radiation sickness (acuteradiation) is a systemic disease caused by high dose (>1Gy) ionizing radiation in a short period of time. Acute radiation sickness may occur in both external and internal irradiation, but external radiation is the main cause. The rays causing acute radiation sickness caused by external irradiation include gamma rays, neutrons, and X-rays. Radioactive workers should strictly abide by the operating procedures and protective regulations to reduce unnecessary exposure. Shielding should be placed between the source and the staff according to the nature of the radiation; the operation should be proficient, shorten the time of contact with the source; try to increase the source The distance between to reduce the dose of radiation should be strictly pre-employment physical examination, active tuberculosis, diabetes, glomerulonephritis, endocrine and blood system diseases, all of which are contraindications to exposure to radiation, regular physical examination, establish personal health And dose file data, when using the radioactive source should set the target to prevent accidents. basic knowledge The proportion of illness: 0.0325% Susceptible people: no special people Mode of infection: non-infectious Complications: Intussusception Intestinal obstruction

Cause of radiation sickness

(1) Nuclear war

Exposure and shielding personnel at nuclear explosions below 101 kt, shielded personnel at the time of explosion above 101 kt, persons who have passed and stayed in the severely contaminated area, exposed to early nuclear radiation or radioactive contamination, a large number of acute radiation sickness The main factor of the wounded.

(two) usually

1. Nuclear radiation accident

There are currently more than 430 nuclear power plants in operation around the world, and new nuclear power plants are still increasing. There have been several accidents since the 1950s, the largest of which was the Chernobyl nuclear power plant accident in 1986, more than 200 accidents. There are 29 cases of acute radiation sickness, and various types of radiation sources are widely used in various fields of production and medical treatment. Due to improper use or storage, various types of radiation accidents have occurred hundreds of times. Since the 1960s, China has also There have been many incidents of radiation sources, and many people have suffered casualties.

2, medical accidents

Medical applications of radionuclides and radiation devices may also cause medical accidents. For example, accidents involving the use of excessive radionuclide treatment in foreign countries have resulted in acute radiation death caused by internal radiation, and there have been cases where patients suffer from radiation device failure. An accident of excessive exposure.

3. Therapeutic irradiation

High doses of radiation to patients due to treatment needs can cause therapeutic acute radiation sickness, such as high-dose (>6Gy) whole body irradiation or systemic lymph node irradiation before bone marrow transplantation, as a pre-treatment before bone marrow transplantation.

Hematopoietic damage is a characteristic of bone marrow-type radiation sickness. It runs through the whole process of the disease. The bone marrow shows a decrease in cell division index, sinusoidal expansion, congestion, followed by bone marrow necrosis, hematopoietic cell reduction, sinusoidal oozing and Rupture, hemorrhage, blood cell reduction, redness is earlier than granulocyte, initially the immature cells are reduced, and the mature cells are also reduced. The degree of bone marrow changes is related to the dose of irradiation. The small dose of radiation, the blood cells are only slightly reduced, and the bleeding is not obvious. In large doses, hematopoietic cells are severely deficient, and completely disappear. Only fat cells, reticular cells and plasma cells, lymphocytes can be relatively increased. Others such as tissue basophils, osteoclasts, and osteoblasts also increase. Severe bleeding, severely inhibited bone marrow. If the bone marrow is destroyed, if there are enough hematopoietic stem cells to rebuild the blood, the recovery of bone marrow hematopoiesis can begin in the third week after irradiation, and the obvious regeneration is restored after 4-5. Week, if the dose is large, the hematopoietic function often cannot be recovered by itself.

The changes of lymphocytes (mainly spleen and lymph nodes) are similar to those of bone marrow. They are also caused by cell division inhibition, cell necrosis, reduction and hemorrhage. The development is faster than bone marrow and recovery is earlier than bone marrow, but it takes longer to recover completely. time.

With the development of hematopoietic organ diseases, the clinical process of bone marrow-type radiation sickness has obvious stages, which can be divided into initial stage, pseudo-healing period, extreme period and recovery period, especially medium and severe stage.

Radiation disease prevention

Radioactive workers should strictly abide by the operating procedures and protective regulations to reduce unnecessary exposure. Shielding should be placed between the source and the staff according to the nature of the radiation; the operation should be proficient, shorten the time of contact with the source; try to increase the source The distance between to reduce the dose of radiation should be strictly pre-employment physical examination, active tuberculosis, diabetes, glomerulonephritis, endocrine and blood system diseases, all of which are contraindications to exposure to radiation, regular physical examination, establish personal health And dose file data, when using the radioactive source should set the target to prevent accidents.

Several major radiation protectants

1. Mercaptoethylamine (MEA)

Cysteamine is one of the earliest thiol-containing protective agents. It is a decarboxylated derivative of cysteine and a component of coenzyme A. Intraperitoneal injection of mice 10 to 15 minutes before lethal dose of gamma rays can improve survival. The rate of 80%, intravenous administration of patients with clinical radiotherapy can reduce the radiation response, but this drug has a short effective period of protection, high toxicity, poor oral effect, and instability in the air.

2, cystamine (cystamine)

Cystamine is an oxide of cystamine, which can be reduced to cystamine in vivo. Its protective effect is better than that of cysteamine, and it can be taken orally. It is chemically stable. Oral administration of cystamine hydrochloride before irradiation can reduce radiation response and improve Peripheral blood leukocytes.

Usage: Oral administration of 1g of cystamine hydrochloride 1 hour before irradiation, the side effect is a certain stimulating effect on the gastric mucosa, gastrointestinal patients are hanged.

3. Aminoethyl isothiourea (AET)

Aminoethyl isothiourea is also an early researcher. It is a derivative of cysteamine sulfhydryl substituted by thiol. It has a long protective effect, can be taken orally, is chemically stable, and has good preventive effects, such as dogs. Before the 5Gy -ray irradiation, AET hydrobromide 125mg/kg was injected intravenously, and the survival rate was 90%. All the control animals died, but the side effects of oral administration or injection were large (nausea, vomiting, diarrhea, skin flushing, etc.). Limit its use.

4. Aminopropylaminoethyl thiophosphate monosodium salt (WR-2721)

WR-2721 is a better protective effect in the protective agent. This is the sulfur-based thiosulfate salt of MEA, and the propylamine group is substituted for a derivative of a hydrogen atom on the amino group of MEA. Above MEA and AET, the effective time is about 3 hours. For example, the beagle is subjected to a mixture of neutron and gamma rays in the nuclear reactor for 2.5, 3.3, 5.5, and 150 mg/kg intravenously for the first 30 minutes of 6.5 Gy, which can increase the survival rate by 100%. 100%, 80% and 60%, the mice are effective orally, but the large animals have poor oral effects, and the oral doses that reach the effective blood concentration are too large, and the animals are difficult to tolerate the toxicity of the drugs.

Oral administration of 200mg/kg is a human tolerable and protective dose. Because WR-2721 is selectively distributed in normal tissues, it is less distributed in solid tumor tissues lacking blood vessels. It can be used for radiation therapy to protect normal. Tissue to enhance the radiotherapy effect on tumors.

Notable after WR-2721 is WR-3689, which has one more methyl group than WR-2721 (replaces one H on the propylamino group), and its protective potency is comparable to that of WR-2721, and even reports It is considered that over WR-2721, its therapeutic index (LD50/lowest effective dose of the drug) is 13.6, while WR-2721 is 12.0, which is listed as an alternative drug to WR-2721.

5, estrogen

Natural steroid hormones (such as estradiol) or synthetic non-steroidal hormones (such as diethylstilbestrol, diethylstilbestrol, etc.) show a certain degree of radiation protection in animal experiments, and before and after administration All have effects, such as the dog is injected with estriol 10mg 36 hours before 2.6 ~ 2.8Gy irradiation, improve the survival rate of 67%; intramuscular injection of 10mg 6 hours after irradiation, can still improve the survival rate of 60%, such as before, after the photo Two injections of 10mg can improve the survival rate by 70%, which is better than single administration. It can be used clinically in patients with tumor radiotherapy to reduce the leukopenia caused by radiotherapy. The disadvantage is that it has female activity and has certain side effects when applied. Estradiol oil suspension injection, preventive use, intramuscular injection 10mg within 6 days before irradiation or immediately before treatment, treatment use, intramuscular injection 10mg within 1 day after irradiation, combined with pre-illumination, or with other drugs Use, can improve the efficacy, gynecological tumors, aplastic anemia, liver disease and juvenile patients hanged.

The principle of action of radiation protectants

1. Participate in radiation chemical reactions

Radiation chemical reactions in the early stage of radiation biology include free radical generation, free radical chemical reactions, biological macromolecular damage, etc. Since the radiation protective agent participates in the above-mentioned radiation chemical reaction, it may provide protection to the target molecule, thereby reducing its damage, such as protection. The agent directly absorbs energy, alleviates the action of O2, provides hydrogen atoms to promote the repair of damaged molecules, and protects the protective agent from the target molecule or cell binding complex. It is generally believed that the thiol-containing radiation protective agent may have this effect. These drugs are usually only effective before use.

2. Intervention biochemical-physiological response

Some chemical protective agents can interfere with cell metabolism, or participate in neurohumoral regulation mechanisms, altering their biochemical and physiological states, thereby reducing damage and promoting repair, such as reducing cell metabolic rate to reduce cell radiation sensitivity; delay or Promote cell proliferation and differentiation.

Radiation complications Complications, intussusception, intestinal obstruction

Infection is a serious complication of acute radiation sickness, and often becomes the main cause of death. Severe patients or large doses of abdominal radiation can cause complications such as intussusception and intestinal obstruction.

Symptoms of radiation sickness Common symptoms Loss of appetite, dizziness, dyspepsia, nausea, fever, lethargy, small intestine crisis

Initial symptoms

The initial symptoms exhibited by the patient within 1-2 days after exposure are useful for judging the condition.

1. There may be nausea and loss of appetite at the beginning of the procedure, the dose may be greater than 1Gy; those with vomiting may be greater than 2Gy. If multiple vomiting occurs, it may be greater than 4Gy. If you have vomiting and diarrhea very early, you may be exposed to more than 6Gy.

2. Multiple vomiting occurs within a few hours after the operation, and severe diarrhea occurs very quickly, but those with no neurological symptoms may be considered as intestinal radiation sickness.

3. Frequent vomiting, disorientation, loss of ataxia, limb tremor, and increased muscle tone within 1 hour after treatment can be basically diagnosed as brain-type radiation sickness. If a convulsion occurs in the absence of a traumatic factor, it can be confirmed as a brain-type radiation sickness.

Pay attention to the comprehensive analysis of the initial symptoms, but also exclude psychological factors.

Initial symptoms of acute radiation sickness

Bone marrow type

Mild: hours to 1 day or not obvious >1 fatigue, discomfort, slightly poor appetite.

Moderate: 3 ~ 5h1 ~ 2 dizziness, fatigue, loss of appetite, nausea and vomiting, white blood cells rise after a brief rise.

Severe: 20min ~ 2h1 ~ 3 times vomiting, may have diarrhea, white blood cells increased significantly after a brief increase.

Extremely severe: Immediately or 2 to 3 times vomiting within 1 hour, diarrhea, mild abdominal pain, a sudden drop in white blood cells after a brief rise.

Intestinal type: frequent vomiting, severe diarrhea, abdominal pain, and elevated hemoglobin in immediate or tens of minutes.

Brain type: immediate frequent vomiting, diarrhea, disorientation, shock, ataxia, increased muscle tone, convulsions.

Radiation sickness check

1. Peripheral blood

(1) The change rule of white blood cells indicates the development stage of the disease. During the whole disease course, there are seven stages of changes in the number of white blood cells in the peripheral blood. According to the process of white blood cell changes, the development of the disease can be predicted.

1, increase; 2, decline; 3, setbacks; 4, the lowest value; 5, recovery; 6, excessive increase; 7, return to normal.

(2) The speed and minimum value of leukocyte decline can reflect the severity of the disease.

Reference data of leukocyte changes in patients with acute bone marrow type acute radiation

Index reduction speed (×10 ⁹ /L·d) 7d value after exposure (×10 ⁹ /L) 10d value after exposure (×109/L) <1×10 ⁹ /L Time (after d) Minimum value ( ×10 ⁹ /L) The lowest value time (after d).

Mild 4.5 4.0 >3.0.

Moderate <0.25 3.5 3.0 20~32 1.0~3.0 35~45.

Severity 0.25 ~ 0.6 2.5 2.0 8 ~ 20 < 1.0 25 ~ 35.

Extremely severe >0.6 1.5 1.0 <8 <0.5 <21.

(3) Those with granulocyte/lymphocyte ratio inversion are moderate or above, and those who do not appear are generally mild.

(4) In addition to the quantitative changes, white blood cells also have morphological changes, neutrophils visible nuclear, plasma vacuoles, cytoplasmic poisoning particles, excessive nuclear lobes, large cells or large nuclei, and nuclear spines, nuclear solid Contraction, nuclear dissolution, etc., lymphocytes can be seen in nuclear chromatin condensation, nuclear pyknosis, nuclear fragmentation, nuclear lobulation or binuclear, atypical lymphocytes can be seen during recovery.

The morphological changes of platelets can be seen as disappearance of pseudopods, vacuolar degeneration, reduction of dense bodies (5-HT organelles), dissolution of particles, etc., and giant or abnormal platelets can be seen during recovery.

Erythrocytes also have morphological changes, such as uneven cell size, heterotypic and multi-staining cells, and red blood cells can be seen in the peripheral blood during recovery.

2, bone marrow examination

(1) Bone marrow cell division index: Early detection of bone marrow cell division index (number of dividing cells / 1000 bone marrow nucleated cells) is also helpful in judging the condition. The normal male bone marrow cell division index averages 8.8 (6.3 to 10.0 ). The degree of decrease of bone marrow cell division index on the 4th day after exposure to 0.53Gy was significantly correlated with the dose of radiation. It is generally believed that the bone marrow cell division index of 1-3 days after irradiation is still higher than 1.8, which may be mild radiation sickness; Those who are 1.80.9 may be moderate; those who fall to 0.80.2 may be severe; those who fall to 0 are extremely severe.

(2) Bone marrow: In the course of the disease, the bone marrow can be examined once a week. The bone marrow is basically normal and mild radiation sickness. After 20 to 30 days after irradiation, severe bone marrow suppression occurs, but the degree is mild, but moderate. The "severe bone marrow suppression" phenomenon was severe in 15 to 25 days after irradiation, and it was extremely severe within 10 days after irradiation.

3, biochemical examination

(1) Increased blood and urine amylase content: normal human blood amylase content is 40-180u, the parotid gland is irradiated, blood, urine amylase content can be significantly increased, and the degree of increase is related to the dose of radiation, Cherno The serious injury to the Bailey nuclear power plant accident increased to 10 to 100 times normal after 36 to 48 hours after irradiation.

(2) Increased urinary amino acid excretion: the emission of certain amino acids in the urine increased after irradiation, and the more obvious ones were proline, cystine and tryptophan.

Taurine is a metabolite of sulfhydryl compounds (such as cysteine, glutathione, etc.) in the body. It is one of the amino acids excreted in the urine of normal people. After irradiation, the amount of urine discharged can be several times higher than the normal value. The discharge is most frequently 1 to 4 days after the irradiation, and is related to the irradiation dose within a certain range.

(3) Increased creatine output and increased creatine creatinine ratio: creatine is synthesized in the liver, converted to creatine phosphate in the muscle, most of which is excreted by the urine, and a small part is dehydrated to creatinine and excreted by the urine. The amount of excretion increased and the creatinine output was relatively constant, so the creatine/creatinine ratio increased.

(4) Excretion of catabolic products of urinary DNA: such as deoxycytidine (CdR) and -aminoisobutyric acid (BAIBA), the amount of excretion increased after irradiation.

Diagnosis of radiation sickness

diagnosis

Clinical diagnosis is the continuation of early classification, and the two are inseparable. The purpose is to complete the final diagnosis based on the dose of radiation, the development of the disease and various laboratory indicators.

(1) Physical dose and biological dose determination

Correct measurement of the dose of the patient's exposure is the main basis for judging the condition. When conditions permit, the physical dose and the biological dose can be separately determined, and the two can complement each other to obtain a more accurate value.

1, physical dose determination

It is necessary to know in detail the radiation field at the time of the accident, the geometric position of the person and the source, the presence or absence of shielding, and the changes in the movement and time of the person, such as the patient wearing a personal dosimeter to understand the position of the wearer, and collecting the patients carry-on Watch ruby and some medicines, the former uses thermoluminescence method, the latter uses electron spin resonance spectroscopy to determine the dose to be irradiated. When there is neutron irradiation, the metal objects carried by the patient and the patient's hair should be collected. Biological products such as urine samples and blood are used to measure the activation of neutrons, to understand the neutron dose, to perform 24Na activation measurement when necessary, to perform human body model simulation irradiation measurement, and then to analyze and calculate the conclusion.

2, biological dosimetry

Using some sensitive radiation biological effects indicators in the body to reflect the dose of the patient's exposure, said biological dosimetry, it is now recognized that the lymphocyte chromosome aberration rate is a suitable biological dosimeter, which is a function of the dose, especially suitable for 0.25 ~ 5Gy dose range, but the measurement method is more complicated, and it needs to be carried out in a special laboratory. The types of distortion commonly used for biological dosimetry are fragment, double mitochondria and centromere ring within 24 hours after irradiation ( At the latest, no more than 6 to 8 weeks, the blood was collected in vitro for 48 to 72 hours to observe the chromosome aberration rate of lymphocytes.

Recently, some people have used the micronucleus rate of lymphocytes as a method for biological dosimetry. The lymphocyte micronucleus is a circular or elliptical body that is free from the cytoplasm. The structure and staining are similar to those of the main nucleus. 3, the source may be a fragment of the chromosome, the measurement method is similar to the chromosome aberration rate, and the observation analysis is easier than the chromosome aberration rate. In the dose range of 0.2-5 Gy, the micronucleus rate is linear with the dose.

(two) clinical experience

Initial and extreme major clinical manifestations, as well as their timing and severity, can be used as a basis for diagnosis.

Differential diagnosis

Hematopoietic system changes should be differentiated from chronic benzene poisoning, thrombocytopenia, iron deficiency anemia and infection, certain diseases (hepatitis, hypersplenism, etc.), hematological changes caused by certain drugs and chemicals, and hematopoietic inhibition Most of them can be recovered after detachment from radiation. After detachment from radiation and active treatment, the hematopoietic inhibition of long-term unhealed needs to consider the possibility of (or combining) other causes. Clinical symptoms should be associated with neurasthenia, inner ear vertigo, and menopausal syndrome. In the identification of diseases, radioactive cataract should be differentiated from cataracts such as complication (retinal pigmentosa, high myopia, etc.), senile, congenital and systemic metabolism.

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