Biological Effects of Ionizing Radiation Deterministic effects Part No...., Module No....Lesson No. Part title IAEA Post Graduate Educational Course in Radiation Protection and Safety of Radiation Sources Biological Effects of Ionizing Radiation Deterministic effects Part III: Biological Effects of Ionizing Radiation Module III.2: Deterministic effects Lesson III.2.1: Deterministic effects: overview Learning objectives: Upon completion of this lesson, the students will be able to: describe effects of radiation on human define deterministic health effects give an examples of deterministic health effects describe time of occurrence and threshold of occurrence for deterministic health effects explain general dose-response curve and variation in person’s sensitivity describe acute and chronic damage of the tissue due to ionizing radiation explain influencing factors on person’s radiation sensitivity. Activity: lecture Duration: 1 hour Materials and equipment needed: none References: UNSCEAR, Sources and Effects of Ionizing Radiation, 2000 Report to the General Assembly with Scientific Annexes, United Nations, New York (2000). IAEA REGIONAL BASIC PROFESSIONAL TRAINING COURSE ON RADIATION PROTECTION. September-October, 1997. Germany, Training materials. IAEA Training Course at IPSN. Medical Emergencies in Case of Radiological Accidents. November 1998. Training materials. Deterministic effects: overview Lecture IAEA Post Graduate Educational Course Radiation Protection and Safe Use of Radiation Sources IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Part No...., Module No....Lesson No. Part title Introduction Types of health effects of radiation: Deterministic Stochastic Data on deterministic health effects ere collected from observation of: the side effects of radiotherapy the effects on the early radiologists the effects amongst survivors of the atomic bombs at Hiroshima and Nagasaki in Japan the consequences of severe accidents. Lecture notes: There are two types of health effects which could be caused due to radiation influencing on human. These effects are: deterministic and stochastic. Data on deterministic effects in man has been collected from observations of the side effects of radiotherapy; from effects on the early radiologists; from the effects amongst survivors of the atomic bombs at Hiroshima and Nagasaki in Japan; and from the consequences of severe accidents, some in the nuclear industry and some involving radiographic sources. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Part No...., Module No....Lesson No. Part title Content Effects of radiation on human Deterministic health effects: definition, description, examples, time of occurrence, threshold of occurrence General dose-response curve Variation in person’s sensitivity Acute and chronic damage of the tissue due to ionizing radiation Influencing factors on person’s radiation sensitivity Influence of dose rate Lecture notes: The following topics are covered in the lesson: Effects of radiation on human Deterministic health effects: definition, description, examples, time of occurrence, threshold of occurrence General dose-response curve Variation in person’s sensitivity Acute and chronic damage of the tissue due to ionizing radiation Influencing factors on person’s radiation sensitivity Influence of dose rate. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Part No...., Module No....Lesson No. Part title Overview Deterministic health effects: Mechanism of development Typical features Examples of deterministic health effects: Acute radiation syndrome Skin burns Sterility Hypothyroidism Cataract Lecture notes: If cellular damage occurs as a result of radiation that is not adequately repaired, it may prevent the cell from surviving or reproducing, as one of the possible consequences. Most organs or tissues of the body are unaffected by the loss of a few cells; but if- the number lost is sufficiently large, there will be observable harm, reflecting the loss of tissue function. The probability of causing such harm will be zero at small radiation doses; but above some level of dose, called the threshold dose, the probability will increase rapidly with dose to 100%. Above the threshold the severity of harm will also increase with dose. Effects such as this, previously called nonstochastic, are now called deterministic. A deterministic effect has a threshold of dose, and the severity of the effect is dose related. Examples of deterministic health effects are the following: acute radiation syndrome, skin burns, sterility, hypothyroidism, cataract. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Radiation Causes Ionisation Of: Part No...., Module No....Lesson No. Part title Radiation Causes Ionisation Of: ATOMS which will affect MOLECULES which may affect CELLS TISSUES ORGANS THE WHOLE BODY Lecture notes: Whether the source of radiation is natural or man made, whether it is small dose of radiation or large, there will be some biological effects. Although we tend to think of biological effects in terms of the effect of radiation on living cells, in actuality, ionising radiation, by definition, interacts only with atoms by a process called ionisation. Thus, all biological damage effects begin with the consequence of radiation interactions with the atoms forming the cells. As a result, radiation effects on human proceed from the lowest to the highest level as noted in this slide. Module 26 IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Ionising Radiation and Human Cellular Level Part No...., Module No....Lesson No. Part title Ionising Radiation and Human Cellular Level Normal repair of damage Cell dies from damage Lecture notes: The target for all health effects of ionising radiation is the genome of the cell, the DNA (deoxyribonucleic) molecule. Even a single hit by a particle or a photon can cause a break in the DNA molecule. If it is a break in one strand of the DNA only (a single strand break) it will most probably be perfectly repaired with no consequences for health. If, however, both DNA strands are broken close to each other, which is also possible after a single hit, repair mechanisms are likely to fail and the genome may be changed. Cells, like a human body, have tremendous ability to repair damage. As a result not all radiation effects are irreversible. In many instances, the cells are able to completely repair any damage and function normally. In some case, however, the damage is severe enough that the cell dies. In other instances, the cell is damaged but it still able to reproduce. The daughter cell, however, may be lacking some critical life sustaining components, and they die. Finally, the cell may be affected in such a way that it does not die but is simply mutated. The mutated cell reproduces and thus perpetuates the mutation. This could be the beginning of the malignant tumour. Generally, cells are most sensitive to radiation when they are dividing, so that the most radiosensitive tissues are the blood, the intestinal wall, the skin, and the fetus. Conversely, the most radioresistant tissues are muscle, nerves, and the adult brain, where cell reproduction is minimal. No repair or non-identical repair before reproduction Daughter cells die Module 26 IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Deterministic Health Effects: Definition Part No...., Module No....Lesson No. Part title Deterministic Health Effects: Definition A radiation effect for which generally a threshold level of dose exists above which the severity of the effect is greater for a higher dose. The level of the threshold dose is characteristic of the particular health effect but may also depend, to a limited extent, on the exposed individual. The term non-stochastic effect is used in some older publications, but is now superseded Lecture notes: Definition of deterministic effects, used in the IAEA documents, is presented at the slide. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Deterministic Health Effects Part No...., Module No....Lesson No. Part title Deterministic Health Effects A cell that has been hit may destroy itself or may be destroyed while dividing Cell killing is not equal to health effect Only massive cell killing leads to health effects Massive cell killing can occur only after high doses These are called deterministic effects Lecture notes: The function of most organs and tissues of the body is unaffected by the loss of small numbers of cells, or sometimes even of substantial number. However, if the number of cells lost in a tissue is large enough and the cells are important enough, there will be observable harm, reflected in a loss of tissue function. The probability of causing such harm is zero at small doses of radiation, but above some level of dose (the threshold) it increases to unity (100%). Above the threshold, the severity of the harm also increases with dose. This type of effect is called deterministic, because it is sure to occur if the dose is large enough and is higher than threshold. If the loss of cells can be compensated by the repopulation, the effect will be relatively short-lived. Examples of deterministic effects are radiation burns; induction of temporary or permanent sterility in the testes and ovaries; depression of the effectiveness of the blood forming system, leading to a decrease in the number of a blood cells; cataract. A special case of the deterministic effect is the acute radiation sickness resulting from acute whole body irradiation. Photo Two views of the right hand of a pioneer medical radiologist. The first injury to this radiologist was seen in 1899, namely 3 years after the discovery of X-rays was announced. The hand was amputated in 1932 and death from cancer occurred in 1933. Module 26 IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Deterministic Health Effects (Cont’d) Part No...., Module No....Lesson No. Part title Deterministic Health Effects (Cont’d) Early appearance (days to weeks, excl. cataract) Existence of dose threshold, specific for particular effect Below dose thresholds - no effect Above threshold the severity depends on level of radiation dose Lecture notes: A deterministic effect generally shows up within a short time after exposure (”early effects”), but this is not always true. Cataract, for example, is a typical deterministic effect appearing only after several years. That is why the term ”early effects” can not be used as a synonym . For each deterministic effect there is a threshold dose, below which the effect does not appear. This threshold shows only limited variation between individuals. If people of varying susceptibility are exposed to radiation, the threshold in a given tissue for deterministic effects of sufficient severity to be observable will be reached with the lower doses in the more sensitive individuals. The thresholds are generally quite high. Deterministic effects are not seen after exposure to low doses. Once the threshold has been exceeded, however, the effect is certain (”deterministic”) and is rapidly getting worse with increased radiation dose. Threshold dose depends on the organ, dose rate, medical treatment and other factors. Module 26 IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Deterministic Health Effects (Cont’d) Part No...., Module No....Lesson No. Part title Deterministic Health Effects (Cont’d) Some deterministic effects have characteristics that distinguish them from similar effects due to other causes, which may help to identify the affected individuals The occurrence of the initial event has sometimes been detected by the unexpected appearance of deterministic effects Need specialized treatment Lecture notes: If the exposure is caused by a certain identified event, it will usually be possible to identify the affected individuals. Some deterministic effects have characteristics that distinguish them from similar effects due to other causes, which may help to identify the affected individuals. The occurrence of the exposure has indeed sometimes been detected by the unexpected appearance of deterministic effects. Module 26 IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Part No...., Module No....Lesson No. Part title Typical dose effect relationships for deterministic effects expressed in a population Lecture notes: Graphically, the dose response curve can be represented by a sigmoid form, starting after a threshold and then rising steeply, soon reaching 100% response. For healthy individuals, the probability of causing harm will be zero at doses up to some hundreds, or sometimes thousands, of millisieverts, depending on the tissue. The frequency of the effect will increase steeply to unity (100X) above some level of dose called the threshold. The plot on linear axes of the probability of harm against dose is sigmoid. Above the threshold, the severity of the harm will increase with dose, reflecting the number of cells damaged, and usually with dose rate because a protracted dose will cause the damage to cells to be spread out in time, allowing for more effective repair or repopulation. Whole body irradiation can cause the death of the individual if the dose is high enough. When considering a population, the term LD50/60 is used to express the lethality of the radiation. It is a way of saying that half of the exposed population have a probability of dying from the radiation within a period of 60 days after exposure. In addition to the loss of functional cells in a tissue or organ, damage to supporting blood vessels may also occur, leading to secondary tissue damage due to lack of oxygen and cellular nutrients. There may also be some replacement of functional tissue by fibrous tissue causing a reduction in organ function. The clinical findings depend on the specific function of the irradiated tissue. For example, radiation-induced opacity may occur in the lens of the eye, sometimes leading to visual impairment (cataract), and, if the gonads are irradiated, there may be a temporary or permanent loss of fertility. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Part No...., Module No....Lesson No. Part title Dose-effect Relationships: variation in person’s sensitivity Lecture notes: It’s known that is could be some variation in person sensitivity to radiation. Variation in sensitivities among exposed individuals in dose-effect relationship is presented at the slide. The LD50 for humans (i.e. the dose that would be lethal to 50% of the population) is 3 to 4 Gy (300 to 400 rads) for young adults without medical intervention. It may be less for the young or the old. IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Deterministic Health Effects: time of occurrence: Part No...., Module No....Lesson No. Part title Deterministic Health Effects: time of occurrence: Deterministic health effects could occur: Hours-weeks after exposure ARS, skin burns, sterility Months-years after exposure Cataract Occurrence is connected with radiation damage of the tissue: Acute Chronic Lecture notes: All organs develop an acute response after high radiation doses which is always followed by a late, chronic response, however, the relative importance of acute or chronic normal tissue damage differs between organs. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Acute damage of the tissue Part No...., Module No....Lesson No. Part title Acute damage of the tissue Occurs early, within days or weeks after radiation exposure The main clinical sign – inflammation The main structural feature – hypoplasia Latency depends on cell turnover kinetics of the tissue Spontaneous recovery occurs from surviving stem cells Severity can be most effectively reduced by increased dose protraction Lecture notes: The prominent features of acute damage of the tissue are: It occurs early, within days or weeks after radiation exposure. The main clinical sign is inflammation. The main structural feature is hypoplasia due to decreased supply of new cells in tissues with rapid cell turnover, i.e. bone marrow and epithelia. Latency depends on cell turnover kinetics of the tissue ( 2 weeks in oral mucosa, 4-8 weeks in skin), not on dose. Spontaneous recovery occurs from surviving stem cells. Severity can be most effectively reduced by increased dose protraction. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Chronic damage of the tissue Part No...., Module No....Lesson No. Part title Chronic damage of the tissue Occurs late, after many months and may be progressive over years The main clinical sign – fibrosis The main structural feature – atrophy No fixed latency but continuous progression, no recovery Severity is most effectively reduced by decrease of dose per fraction Lecture notes: The prominent features of chronic damage of the tissue are: It occurs late, after many months and may be progressive over years. The main clinical sign is fibrosis. The main structural feature is atrophy due to decreased vascular density in the connective tissue and starvation of the dependent tissue-specific (parenchymal) cells, particularly in tissues with slow cell turnover (lung, central nervous system, kidney). There is no fixed latency but continuous progression, no recovery. Severity is most effectively reduced by decrease of dose per fraction. The risk of chronic damage of the tissue is the main limitation of dose (and thus chance of cure) in cancer radiotherapy. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Deterministic Health Effects: Threshold of Occurrence Part No...., Module No....Lesson No. Part title Deterministic Health Effects: Threshold of Occurrence Organ or tissue Dose in less than 2 days, Gy Deterministic effects Type of effect Time of occurrence Whole body (bone marrow) 1 Death 1 – 2 months Skin 3 Erythema 1 – 3 weeks Thyroid 5 Hypothyroidism 1st – several years Lens of the eye 2 Cataract 6 months - several years Gonads Permanent sterility weeks Foetus 0.1 Teratogenesis - Lecture notes: The organs of the body have different sensitivities to radiation, therefore, dose thresholds for deterministic health effects are also different. A typical deterministic effect of radiation exposure is radiation sickness. It occurs after acute whole body doses of penetrating radiation of not less than one sievert. The first signs of exposure appear after a latency time of one or two hours and consist of malaise, nausea and possibly vomiting. The prognosis can be greatly improved by high standard hospital care, but if the dose to the bone marrow has been more than 6-8 Sv, death usually follows after a few weeks. Doses of this magnitude are seen only in serious accidents, often in connection with strong radiation sources in wrong hands. It is extremely unlikely that a population exposed to fallout from a nuclear accident would get such high doses except possibly in the close vicinity of the reactor. No member of the public got radiation sickness after the Chernobyl accident. It appeared only in emergency workers working at the accident site. 28 of them died of the disease. The radiation sickness may be further complicated by high doses to certain organs. In an accident, exposure is often highly inhomogeneous, in which case severe organ damage is possible in spite of a moderate bone marrow dose. In the Chernobyl accident response, the situation for exposed emergency workers was worsened by severe radiation damage to the skin. In case of a prolonged dose of several Sv, a chronic form of bone marrow depression may develop. The skin is especially sensitive to beta rays. A high local dose causes reddening of the skin after a few hours. Two weeks later hair of the skin falls off. Epilation of all hair is usually observed after a life threatening whole body dose of a few Sv. High local doses to the skin may damage and occlude the blood vessels of the skin, and ulcers and necrosis may develop. Such type of a damage can be very painful and invalidising, and amputation may be the only solution. Module 26 IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Acute Radiation Syndrome Part No...., Module No....Lesson No. Part title Acute Radiation Syndrome Most notable deterministic health effect of ionizing exposure Signs and symptoms are not specific for radiation injury but collectively highly characteristic for ARS Combination of symptoms occurring hours to week after exposure Extent and severity of symptoms are determined by: Total radiation dose received Dose rate Exposed part of the body (whole body or local irradiation) Lecture notes: One of the most notable and serious example of deterministic effects is acute radiation syndrome (ARS). General description of it is presented at the slide. All detail information is presented in separate lectures. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Influencing factors on radiation sensitivity Part No...., Module No....Lesson No. Part title Influencing factors on radiation sensitivity The sensitivity to radiation of different organs and their consequences for the individual person vary very much between organs It depends on: the fraction of the organ irradiated (the volume effect) the overall exposure time (the time factor) the dose rate or dose per fraction (the fractionation effect) Lecture notes: The sensitivity to radiation of different organs and their consequences for the individual person vary very much between organs. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Part No...., Module No....Lesson No. Part title Influence of dose rate When the radiation dose rate is reduced from about 1 Gy/min to 0.3 Gy/h there is a reduction in the cell killing from a given dose As the dose rate is reduced, the slope of the survival curve becomes shallower In some cell lines an inverse dose-rate effect is evident Lecture notes: Dose rate has a profound influence on both the threshold dose itself and the severity of the effect. Quite high doses can be tolerated, if received during a long time, allowing cell division to compensate for radiation induced cell loss. When the radiation dose rate is reduced from about 1 Gy/min to 0.3 Gy/h there is a reduction in the cell killing from a given dose because sublethal damage repair occurs during the protracted exposure. As the dose rate is reduced, the slope of the survival curve becomes shallower (Do increases), and the shoulder tends to disappear. In some cell lines an inoerse dose-rate effect is evident (ie, reducing the dose rate increases the proportion of cells killed) owing to the accumulation of cells in G2, which is a sensitive phase of the cycle. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Part No...., Module No....Lesson No. Part title Summary This lecture presented overview of deterministic health effects The following topics were covered in the lecture: effects of radiation on human, deterministic health effects: definition, description, examples, time of occurrence, threshold of occurrence, general dose-response curve, variation in person’s sensitivity, acute and chronic damage of the tissue due to ionizing radiation, influencing factors on person’s radiation sensitivity, influence of dose rate Comments are welcomed Let’s summarize the main subjects we did cover in this session. This lecture presented overview of deterministic health effects. We did cover the topics describing effects of radiation on human, deterministic health effects: definition, description, examples, time of occurrence, threshold of occurrence, general dose-response curve, variation in person’s sensitivity, acute and chronic damage of the tissue due to ionizing radiation, influencing factors on person’s radiation sensitivity, influence of dose rate. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources
Where to Get More Information Part No...., Module No....Lesson No. Part title Where to Get More Information UNSCEAR, Sources and Effects of Ionizing Radiation, 2000 Report to the General Assembly with Scientific Annexes, United Nations, New York (2000) Lectures describing specific examples of deterministic health effects Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources