injuries poisoning
Radiation Exposure and Contamination
Pathophysiology of Radiation Exposure and Contamination
Ionizing radiation can damage DNA, RNA, and proteins directly, but more often, the damage to these molecules is indirect, caused by highly reactive free radicals generated by radiation’s interaction with intracellular water molecules. Large doses of radiation can cause cell death, and lower doses may interfere with endogenous molecular repair systems, homeostasis, and cellular proliferation. Damage to these and other cellular components can result in progressive tissue hypoplasia, atrophy, and eventually fibrosis. However, it is now clear that cell killing alone cannot explain many tissue reactions because those reactions also depend on complex events, including inflammatory, chronic oxidative, and immune reactions, as well as damage to the vasculature and the extracellular matrix. In general, early reactions, such as in the skin and gastrointestinal tract, involve killing of the stem/early progenitor cells that supply the mature functional cells in the tissue, as well as inflammatory reactions. On the other hand, late reactions (eg, in the lung, kidneys, and brain) involve complex and dynamic interactions between multiple cell types in the tissues and organs and include infiltrating immune cells, production of cytokines and growth factors, often in persistent, cyclic cascades, and chronic oxidative stress. Biologic response to radiation varies with Tissue radiosensitivity Dose Dose rate Duration of exposure Degree of inflammatory response The age of the patient Comorbidities Presence of genetic DNA repair defect disorders (eg, Ataxia-Telangiectasia , Bloom syndrome, Cells and tissues differ in their radiosensitivity. In general, cells that are undifferentiated and those that have high mitotic rates (eg, stem cells, cancer cells) are particularly vulnerable to radiation. Because radiation preferentially depletes rapidly dividing stem cells over the more resistant mature cells, there is typically a latent period between radiation exposure and overt radiation injury. Injury does not manifest until a significant fraction of the mature cells die of natural senescence and, due to loss of stem cells, are not replaced. Cellular sensitivitiesin approximate descending order from most to least sensitive are Lymphoid cells Germ cells Proliferating bone marrow cells Intestinal epithelial cells Epidermal stem cells Hepatic cells Epithelium of lung alveoli and biliary passages Kidney epithelial cells Endothelial cells (pleura and peritoneum) Connective tissue cells Bone cells Muscle, brain, and spinal cord cells The severity of radiation injury depends on the dose and the length of time over which it is delivered. A high, single, rapid dose is more damaging than the same dose given over weeks or months. Dose-response also depends on the fraction of the body exposed. Significant illness is certain, and death is possible, after a whole-body dose>4.5 Gy is delivered over a short time interval (minutes to hours); however, 10s of Gy can be well tolerated when delivered over a long period to a small area of tissue (eg, for cancer therapy). Other factors can increase the sensitivity to radiation injury. Children are more susceptible to radiation injury because they have a higher rate of cellular proliferation. People who are homozygous for the Ataxia-Telangiectasia gene exhibit greatly increased sensitivity to radiation injury. Disorders such as connective tissue disorders and diabetes may increase sensitivity to radiation injury. Some medications and chemotherapeutic agents (eg, actinomycin D, Radiation-induced genetic damage to somatic cells may result in malignant transformation, while in-utero exposure can lead to teratogenic effects, and damage to germ cells raises the theoretical possibility of transmissible genetic defects. Protracted whole-body exposure to 0.5 Gy is estimated to increase an average adult’s lifetime risk of cancer mortality from approximately 22% to about 24.5%, an 11% relative risk increase but only a 2.5% absolute risk increase. The chance of developing cancer due to commonly encountered doses (ie, from background radiation and typical imaging tests [see Risks of Medical Radiation ]) is much less and may be zero. Estimates of increased risk of radiation-induced cancer as a result of the typically low doses experienced by people in the vicinity of reactor incidents such as Fukushima have been made by extrapolating downward from known effects of much higher doses. The very small resultant theoretical effect is multiplied by a large population to give what may appear to be a concerning number of additional cancer deaths. The validity of such extrapolations cannot be confirmed because the hypothesized increase in risk is too small to be detected in epidemiologic studies, and the possibility that there is no increased cancer risk due to this exposure cannot be excluded. Children are more susceptible because they have a higher number of future cell divisions and a longer life span during which cancer may manifest. CT of the abdomen done in a 1-year-old child is estimated to increase the child's estimated lifetime absolute risk of developing cancer by about 0.1%. Radionuclides that are incorporated into specific tissues are potentially carcinogenic at those sites (eg, the Chernobyl reactor accident resulted in substantial radioactive iodine uptake due to consumption of contaminated milk, and subsequent excess thyroid cancers occurred among exposed children). The fetus is exceptionally susceptible to high-dose radiation injury. However, at doses<100 mGy, teratogenic effects are unlikely. The fetal risk from radiation at doses typical of imaging tests that pregnant women are likely to undergo is very small compared with the overall risk of birth defects (2 to 6 % observable at birth) and the potential diagnostic benefit of the examination. The increased risk of developing cancer as a result of in-utero radiation exposure is about the same as that from radiation exposure of children which is about 2 to 3 times the adult risk of 5%/Sv. The potential risks from radiation exposure mandate giving careful consideration to the need for (or alternatives to) imaging tests involving radiation, optimizing the radiation exposure for body habitus and the clinical question being asked, as well as attention to the use of proper radiation protection procedures, especially in children and pregnant women. Damage to reproductive cells has been shown to cause birth anomalies in progeny of severely irradiated animals. However, hereditary effects have not been found in children of radiation-exposed humans, including the children of Japanese atomic bomb survivors or the children of cancer survivors treated with radiotherapy. The average dose to the ovaries was ~ 0.5 Gy and to the testes 1.2 Gy. 1.Balter S, Hopewell JW, Miller DL, et al: Fluoroscopically guided interventional procedures: A review of radiation effects on patients' skin and hair.Radiology254(2):326-341, 2010. doi:10.1148/radiol.2542082312 