Unit2/Obj1 Radiation Responses

Differentiate between acute effects from radiation, late effects from radiation, and genetic effects from radiation exposure

Early effects of radiation are produced by high dose, late effects of radiation exposure are the result of low doses delivered over a long period. The principal late effects of low dose radiation over long periods consist of radiation induced malignancy and genetic effects. Human responses to radiation fall into two types, early or late, high or low dose, and deterministic or stochastic. An early effect is a radiation response in humans within a few days to months due to a substantial dose. These early effects are described as deterministic and they exhibit increasing severity with increasing radiation dose, also there is usually a dose threshold. Genetic effects are late effects.

List the three general syndromes and the doses relevant to each

-CNS death requires radiation doses in excess of 5000 rads and results in death within hours Hematologic and GI death follow lower exposures and require a longer time for death to occur -Gastrointestinal 1000-5000 rads -Hematopoietic 100/200-1000 rads

Differentiate between and describe the prodromal, latent, and manifest stages of the total body syndromes

-Prodromal-directly after exposure, usually greater than 100 rads, known as radiation sickness, NVD *appears within min to hours, may last hours to days, severity is dose related, with very high doses becomes difficult to separate prodromal from manifest -Latent- patient appears to have recovered, no symptoms, duration is shorter as dose is higher *apparent well being, extends from hours to weeks -Manifest- syndrome (stage) with various signs and symptoms, dependent upon dose. *seems as though it is the second onslaught of the prodromal stage, often worse where the syndrome manifests itself

Differentiate between relative and absolute risk and give examples of each

-Relative risk is calculated when a population's radiation dose is not known, it is computed by comparing the number of persons in the exposed population showing a given late effect with the number in an unexposed population who show the same late effect. A relative risk of 1 indicates no risk at all (there is the same incidence in the unexposed population as in the nonexposed population). The relative risk for radiation induced late effects of particular importance observed in humans is range of 1-2. (1.5 indicates freq of late response is 50% higher in irradiated pop than in nonirradiated pop). Relative risk= Observed cases/expected cases. - If at least 2 different dose levels are known then it may be possible to determine absolute risk factor. The absolute risk consists of units of cases/population/dose. To determine absolute risk a linear dose response relationship must be assumed.

Describe late effects of radiation- cataracts

Early physicists in the 40s and 50s developing the cyclotron had to receive high doses of radiation to the lens of the eye because they had to look directly into the beam. Several hundred cases were reported. Radiation induced cataracts occur on the posterior pole of the lens. Due to the data several conclusions can be drawn. The radiosensitivity of the lens of the eye is age-dependent. As the age of the individual increases the radiation effect becomes greater and the latent period becomes shorter. Latent periods ranging from 5-30 years have been observed and the average latent period is approx 15 years. High LET radiation has a high RBE for the production of cataracts. The dose response relationship for radiation induced cataracts is nonlinear-threshold. Moderate doses of 2Gray and 7Gray fo sho!

Describe the three stages of fetal development, pre-implantation, major organogenesis, and fetal stage

-Within 2 weeks of fertilization the most pronounced effect of high radiation dose is prenatal death which manifests as a spontaneous abortion. The first 2 weeks may be of least concern because the response is all or nothing. 0-9, sperm and egg is distal third of fallopian tube, implants in posterior wall of uterus. Death is likely, all or nothing, chance of interaction is small due to size. 5-10rads, spontaneous abortion rate 6%, if congenital abnormalities occur at this stage and cell survives it will be exencephaly -During major organogenesis (2-10wks) two effects may occur, skeletal and organ abnormalities early on and congenital abnormalities of the CNS if preg carried to term. If the congenital abnormalities are severe enough the result will be neonatal death. Effects are rare at diagnostic levels and undetectable at doses less than 10rads. Occurs with doses as low as 25radsDuring this period a dose of 10 rad is expected to increase the incidence of congenital abnormalities by 1% above natural incidences. Microcephaly, hydrocephaly, eye deformities, and mental retardation is associated with radiation during this period. -Fetal stage, differentiation is complete. Post 6-12wks/after first trimester irradiation in utero has been associated with childhood malignancy, mental retardation, radiation exposure in utero dose retard the growth and development of the newborn. Damage if induced will be later in

Epidemiology

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List the three conditions that must be met to have total body radiation syndrome

1. Acute dose- must happen within minutes, not fractionated 2. Near whole body exposure 3. External source of radiation that penetrate, xray, gamma, neutron Need whole body, external dose, of acute radiation

Differentiate between stochastic and non-stochastic (deterministic) effects, threshold and nonthreshold radiation

Deterministic radiation responses usually follow high dose exposure and an early response. Radiation skin burns represent a deterministic response. Stochastic responses are cancer, leukemia, or genetic effects. Such responses usually follow low radiation exposure and appear as a late response. Every radiation dose-response relationship has 2 characterisitics, it is either linear or nonlinear, and it is either threshold or nonthreshold. Linear infers that the response is directly proportionate to the dose. When radiation is doubled response to it is doubled. In a nonthreshold dose response relationship, any dose, regardless of size, is expected to produce a response. Dose response relationships that intercept the dose axis at some value greater than 0 are threshold. As doses below the threshold no response is expected.

Define and describe LD 50/30

Dose of radiation to the whole body that causes 50% of irradiated subjects to die within 30 days. Percentage that die as a function of radiation dose.

Describe late effects of radiation- lung cancer

Known that radiation exposure from radon in miners contributed to incidence of lung cancer in miners. One of the decay products of uranium is radon and this radionuclide is a gas that emanates through the rock to produce a high concentration in air. When breathed radon can be deposited in the lung, where it undergoes an addtl successive series of decay to a stable isotope of lead. During these decays alpha particles are also released resulting in a high local dose. To date more than 4000 uranium miners have been observed and they have received estimated doses to lung tissue as high as 3000 rad, on this basis, the relative risk was approx 8:1.

Describe late effects of radiation- leukemia

Populations who have exhibited an elevated incidence of leukemia after radiation exposure include the atomic bomb survivors, american radiologists, and radiotherapy patients, and children irradiated in utero. Radiation induced leukemia follows a linear nonthreshold dose response relationship. It is considered to have a latent period of 4-7 years and an at risk period of approx 20 years. 3:1 relative risk for atomic bomb survivors. Early rads whose doses were exceeding 100rad/year currently american rads do not exhibit elevated incidence of leukemia. Patients with ankylosing spondylitis received radiation therapy treatment with doses to the bone marrow in the spinal cord of 100-4000rads. Relative risk was 10:1. Several studies discuss a link of leukemia to background radiation, whose levels can increase with altitude and latitude.

List the three general effects to the embryo and fetus from radiation

Prenatal death, congenital abnormalities, neonatal death. Before pregnancy the concern is interrupted fertility, during pregnancy the concern is directed to possible congenital effects in newborns, and postpregnancy concerns are related to suspected genetic effects.

Describe thoroughly the CNS syndrome

Radiation dose in excess of approx 5000 rads. Ultimate cause of death in CNS syndrome is elevated fluid content of the brain. Series of signs occur that lead to death within a matter of hours to days. First severe NV begin within a few min of exposure. During initial onset patient may become nervous and confused, may describe burning in the skin, may lose vision, and even can lose consciousness within first hour. latent period next may be up to 12hrs, then manifest period in which prodromal symptoms return and are more severe. Person is disoriented, loses muscle coordination, has difficulty breathing, may go into convulsive seizures, experiences loss of equilibrium, ataxia, and lethargy. Lapses into a coma and dies. Characterized by extreme intracranial pressure, inflammatory changes in the blood vessels of the brain (vasculitis), and inflammation of the meninges (meningitis). At these doses damage to all other organs are equally severe. The classic radiation induced changes in the GI tract and the hematologic system cannot occur because there is insufficient time between exposure and death for them to occur.

Describe thoroughly the Hematologic (bone marrow) syndrome

Radiation doses in the range of 200-1000 rads. Characterized by a reduction in white and red cells, and platelets. Mild prodromal appear in hours and may persist for days, latent period that follows can extend as long as 4 weeks and pt feels well although the number of cells in the peripheral blood declines during this time. The stem cells die. The manifest period is characterized by possible vomiting, mild diarrhea, malaise, lethargy and fever. Reduction in blood cells remains unchecked until the body's defense against infection is nil. Just before death dehydration and hemorrhage may be pronounced. Death occurs because of generalized infection, electrolyte imbalance, and dehydration because of destruction of stem cells.

Describe thoroughly the GI syndrome

Radiation doses of 1000-5000 rads. Prodromal NV occur within hours of exposure and persist for hours to as long as a day. A latent period of 3-5 days follows (no symptoms) then manifest illness period begins with second wave of NV followed by diarrhea. Victim loses appetite, may become lethargic. Diarrhea persists and becomes more severe leading to loose watery and bloody stools because can't absorb nutrients. The rapid progression of these symptoms lead to death in 4-10 days. GI death primarily occurs principally because of severe damage to the cells lining the intestines which are normally in a rapid state of proliferation continuously being replaced by new cells every 3-5 days. Since radiation exposure kills the most sensitive stem cells this is what controls the length of time until death. When intestinal lining is completely denuded of functional cells, fluids pass uncontrollably across the intestinal membrane, electrolyte balance is destroyed, and conditions promote infection. Hematologic effects don't have enough time to take full effect before the GI syndrome will cause death.

Describe late effects of radiation- lifespan shortening

Radiation induced lifespan shortening is nonspecific, that is, no characteristic diseases are associated with it, and it does not include late malignant effects.Due to radiation causing cancer. Biggest myth according to Darlene.

Describe late effects of radiation- bone cancer

Radium watch dial painters and patients treated with radium salts for a variety of illnesses have contributed to data of radiation causing bone cancer. Radium watch dial painters licked the end of paintbrushes thus ingesting radium salts, where it metabolized much like calcium and deposited in the bone, they received doses of up to 50K rads, overall relative risk of 122:1. Arthritis to tuberculosis were often treated w radium.

Describe the total body radiation syndromes in relation to dose

Result of acute radiation is lifespan shortening, as dose increases lifespan shorteneing decreases. Hematologic- 200-1000 rads Gastrointestinal- 1000-5000 Central Nervous System- >5000 rads

List the ways radiation effects the embryo or fetus

The effects of radiation in utero are time related and dose related. They include prenatal death, neonatal death, congenital abnormalities, malignancy induction, general impairment of growth, genetic effects, and mental retardation. Prevent preimplantation-kills cells making fetal nonviable, damages the cells creating abnormalities. The reason radiation effects embryos so much is because they are highly undifferentiated and highly mitotic.

Define radiation syndrome

The sequence of events that follow high-level radiation exposure leading to death within days or weeks. There are 3 separate syndromes that are dose related and follow a distinct course of response. 3 stages.

Differentiate between sigmoid, linear, linear-quadratic, and supralinear risk assessment curves

These are shapes of Nonlinear curves that say different things -A sigmoid curve says that at low doses of insult the risk is minimal and at high doses the change in risk is minimal but there is an area in between that is very susceptible to risk. -Linear curve is a straight line that says with similar changes in insult there will be similar changes in effect, they are directly proportional. -Linear Quadratic curve says that at low insult the amount of risk is low and then when you reach an inflection point where any increase in insult will exponentially increase the risk. -Supralinear curve says that at low doses the risk is relatively high and then an inflection point is reached where any increase in insult will result in minimal change in the risk effect.

Describe late effects of radiation- thyroid cancer

Thyroid cancer has been shown to develop in three groups of patients whose thyroid glands were irradiated in childhood. These children were treated for enlarged thymus glands. After 500 rad treatment the thymus would shrink, 20 yrs later nodules and thyroid cancer began to develop in these patients.

Describe late effects of radiation- breast cancer

Tuberculosis patients data from the 60's. They were treated by inducing a pneumothorax in affected lung under fluoro and then they received multiple treatments with several hundred fluoro exams. relative risk in those patients 10:1. Also data has come from patients treated with postpartum mastitis. Doses ranged from 75-1000rad. The relative risk in that population was 3:1. Latent period 10-40years

Describe late effects of radiation- skin cancer

Usually begin with development of radiodermatitis, and radiation induced skin cancer follows a threshold dose response relationship. It has been concluded through studies of radiation therapy patients that it has a latent period of 5-10 years. When the dose delivered to the skin was in the range of 500-2000 rads the relative risk of developing skin cancer was 4:1, if the doses were higher the risks increased to 14:1 and 27:1