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RAD 315 RADIOBIOLOGY AND RADIATION PROTECTION
WHOLE BODY RADIATION
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Syndrome Signs and symptoms experienced by irradiated mammal
Total body syndrome Radiation syndrome
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Acute exposure Given in minutes Total body or almost total body
External radiation – penetrating Doses quoted in cGy for x or gamma radiation Lower doses would be needed for same effect if high LET radiation is used
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Survival time Is dependent on dose Expressed as mean survival time
Varies between species Lethal dose: LD x/z is the dose needed to kill x% in z number of days Females are more resistant Very young and very old are more sensitive
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LD50/30 for different species
Human – 300 cGy Monkey Dog Rabbit Rat/mouse Frog Goldfish
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Data Has been established from: Animal experiments
Hiroshima and Nagasaki Marshall Island fallout Nuclear accidents Medical exposure
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Total body exposure After total body exposure, the animal exhibits three main stages of response: Prodromal Latent manifest
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prodromal the early symptoms that occur initially after exposure.
Occurs for minutes to days Nausea, vomiting, diarrhea Severe PRS usually means poor survival
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Latent Occurs for hours to weeks after exposure
No major symptoms (latent)
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Manifest illness Hours to weeks after exposure
Symptoms reflect the systems of the body that has been damaged
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Body systems affected There are three body systems affected:
Bone marrow GI CNS So there are basically three types of death at three different levels, depending on dose Each has its own PRS
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Survival time See graph page 139
Derived from experiments with a variety of species Is dose dependent between 2 – 10 Gy and after 100 Gy Not dose dependent between 10 – 100 Gy There is overlapping of syndromes present after exposure. Table shows PRIMARY cause of death.
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Los Alamos in 1958 Major accidental exposure to an individual
3900 – 4900 cGY from neutrons and gamma rays Immediate shock and loss of consciousness No lymphocytes after 8 hours Dead in 35 hours.
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CNS syndrome Death occurs within hours as a result of neurological and cardiovascular breakdown. Associated dose: > 5,000 cGy PRS : Immediate diarrhea Fever Hypertension Loss of consciousness
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CNS syndrome Manifest symptoms: Disorientation Loss of coordination
Respiratory distress Diarrhea Seizures coma
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CNS syndrome Prognosis: two days at most
Person does not live long enough to get GI and bone marrow symptoms
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GI syndrome Prior to Chernobyl, little was known about GI syndrome
Death occurs in matter of days due to destruction of intestinal mucosa. Associated dose: 1000 cGy Threshold dose: 600cGy (LD100 = 600 to 1000 cGy)
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GI syndrome PRS: N, V, D Manifest Symptoms: Prognosis: about 10 days
Dehydration Weight loss exhaustion Prognosis: about 10 days
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Bone Marrow Syndrome Possible death due to damage of blood forming organs (bone marrow) Associated dose: 250 to 500 cGy PRS: N, V, fatigue
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Bone Marrow Syndrome Manifest symptoms (occurs after about 3 weeks):
Chills Fatigue (RBC) Infection (WBC) Hemorrhage (platelets) Prognosis: possible death in about one month from infection and hemorrhage
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Bone Marrow Syndrome 100 – 300 cGy : bone marrow may recover
400 – 600cGy: few survivors 1000 cGy : no survivors LD50 for humans is taken as cGy Survival can be improved with bone marrow transplants and modern medical care.
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Radiation effects on the embryo and fetus
Classic effects: Lethal effects induced by relatively small doses if before or immediately after implantation in the uterine wall Malformations when irradiated during organ formation Growth disturbances without malformation at all stages of fetal development
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Embryo and fetus Miscellaneous effects on various body structures and functions. Main factors of importance are dose and stage of development
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Fetal development Pre – implantation Major organogenesis Fetal stage
Conception to day 10: all cells highly undifferentiated Major organogenesis Day 10 to 6 weeks : differentiation begins Fetal stage 6 weeks to birth
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Pre - implantation Increased prenatal death
Most sensitive stage to lethal effects If embryo survives, it grows normally in utero and afterwards. Few, if any, abnormalities are produced at this stage In mouse: 5 – 15 cGy can kill fertilized eggs
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Major organogenesis Increased neonatal death Decreased prenatal death
Principle effect is production of congenital structural abnormalities In mouse: 200cGyn can result in 100% abnormalities.
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Major organogenesis Contrary to what is seen in animals, radiation induced malformations of body structures other than CNS are uncommon in humans Why is this so? Animal experiments are controlled and exact, but not with humans Human organogenesis is 1/15 gestation period. In mice it is 1/3. CNS org. takes longer time in humans
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Major organogenesis CNS malformations: Microcephaly Hydrocephaly
Micropthalmia Mental retardation
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Fetal stage A variety of effects have been observed in animals: liver, kidney, bone marrow After fairly high doses: sterility, cancer High doses would be needed to kill the fetus at this period Permanent growth retardation
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Experience in humans Medical exposures during the early part of the last century Survivors in Japan
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generalizations Large doses (>250cGy) before 2-3 weeks, are not very likely to produce severe abnormalities but embryo deaths are likely. 4 – 11 weeks: severe abnormalities of many organs 11 – 16 weeks: Eye, skeletal, genital organ abnormalities
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generalizations 16 – 20 weeks: some CNS abnormalities
After 30 weeks gross structural abnormalities not likely, but there could be functional abnormalities. Hiroshima: 30/1600 mental retardations after exposure at 8 – 15 weeks. This is higher than normal.
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summary Moderate doses of radiation can cause catastrophic effects on the developing embryo and fetus Effects depend on stage, dose and doserate Gestation is divided into: Preimplantation – 0 to 9 days Organogenesis – 10 days to 6 weeks Fetal stage – 6 weeks to term
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summary Principle effects are: Growth retardation
Embryonic, neonatal or fetal death Gross congenital malformation
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summary LD50 is lowest during preimplantation
Peak incidence of malformations occurs when fetus is irradiated during organogenesis Malformations other than CNS is uncommon in humans Data from Japan shows that microcephaly can result from air dose of 10 – 19 R
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summary From medical x-ray exposure: low doses of in utero exposure can lead to an increase in cancer incidence in the first 10 – 15 years of life by a factor of 1.5 – 2 No comparable increase was seen in Japanese survivors MPD to fetus is 0.5 rem per gestation period
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