Acute Effects of Total-body Irradiation

1. Acute Effects of Total-body Irradiation Radiobiology for the Radiologist, chapter 8, pg 112 - 122

2. Introduction • The effect of ionization on whole organism • Data collection • Animal experiment • Experiences in radiotherapy • Studies of the Japanese survivors of Hiroshima and Nagasaki • The victims of the limited number of accidents at nuclear installations, e.g. Chernobyl

3. Early Lethal Effects

4. Early Lethal Effects • Early radiation lethality • Death occurring within a few weeks that can be attributed to a specific high-intensity exposure to radiation • Prodromal radiation syndrome • Soon after irradiation • Early symptoms appear • Last for a period of time

5. Three distinct modes of death can be identified • At very high doses (>100 Gy) • Death occurs 24 – 48 hours after exposure • Appears to result from neurologic and cardiovascular breakdown • Cerebrovascular syndrome • At intermediate doses (5 – 10 Gy) • Death occurs in a matter of days • Associated with extensive bloody diarrhea and destruction of the GI mucosa • Gastrointestinal syndrome • At low doses (2.5 – 5 Gy) • Death occurs several weeks after exposure • Caused by effects on the blood-forming organs • Bone-marrow death, or hematopoietic syndrome

6. Early Lethal Effects • The exact cause of death • Cerebrovascular syndrome : unclear • GI and hematopoietic syndrome • Caused by the depletion of the stem cells of a critical self-renewal tissue • The difference in the dose level and the time scale between GI and hematopoetic syndrome • Variations in the population kinetics of two cell-renewal systems • Differences in the amount of the damage that can be tolerated in these system

7. The Prodromal Radiation Syndrome

8. The various symptoms making up the human prodromal syndrome The signs and symptoms of the human postirradiation syndrome

9. Variation of the prodromal syndrome depends • on the size of the dose • Time of onset • Maximum severity • Duration

10. The Prodromal Radiation Syndrome • Typical course of prodromal syndrome with doses of a few tens of grays • within 5 to 15 minutes of exposure • show all phases of the syndrome • About 30 mins • Reaction reaches maximum and persist for a few days • Following few days • reaction persisted • Until the prodromal symptoms merge with fatal vascular or GI syndromes • Reaction diminished in intensity

11. The Prodromal Radiation Syndrome • A severe prodromal response • indicates a poor clinical prognosis • Portends a prolonged period of acute hematologic aplasia e.g. fatal infection, anemia, and hemorrhage

12. The Cerebrovascular Syndrome

13. The Cerebrovascular Syndrome • Doses of irradiation • A total-body dose on the order of 100 Gy of γ-rays • Corresponding less of neutrons • Results in death in a matter of hours • All organs systems are seriously damaged • GI and hematopoietic syndrome do not have time to be expressed • Course • Disorientation • Loss of coordination of • muscular movement • Respiratory distress • Diarrhea • Convulsive seizures • Coma • Severe • nausea & vomiting  Death

14. Case 1 38 y/o ♂, working in a uranium-235 recovery plant Involved in an accidental nuclear excursion Total body dose estimated to be about 88 Gy 22 Gy of neutrons 66 Gy of γ-rays Clinical manifestations Immediately Abdominal cramps, headache, Vomiting, Incontinent of bloody diarrhea 2nd day Comfortable but restless 3rd day Condition deteriorated Restless, fatigued, apprehensive, short of breath and impair of vision Blood pressure could be maintained with great difficult 6 hours before his death Disorientation, BP could not be maintained He died 49 hours after accident The Cerebrovascular Syndrome

15. Case 2 Nuclear criticality accident at Los Alamos in 1958 A worker received a total-body dose Neutron : 39 Gy γ-radiation : 49 Gy Part of his body : >120 Gy Clinical manifestations Immediately Shock and unconscious within a few minutes After 8 hours Circulating blood : no lymphocyte were found Complete urinary shutdown The patient died 35 hours after the accident The Cerebrovascular Syndrome

16. The Cerebrovascular Syndrome • The exact and immediate cause of death in what is unknown • It has been suggested that the immediate cause of death • An increase in the fluid content of the brain owing to the leakage from small vessels • Resulting in a build-up of pressure within the bony confines of the skull

17. The Gastrointestinal Syndrome

18. The Gastrointestinal Syndrome • Doses of irradiation • A total-body exposure > 10 Gy of γ-rays • Culminating in death some days later (usually between 3 – 10 days) • The characteristic course • Nausea • Vomiting • Prolong diarrhea • Loss appeptite • Sluggish • lethargic • prolong diarrhea • Dehydration • Loss of weight • Death • (in a few days)

19. The Gastrointestinal Syndrome • Prolonged diarrhea (extending for several days) is regarded as a bad sign • Indicates that dose received has been more than 10 Gy • No record of a human survived a dose in excess of 10 Gy The classic self-renewal tissue.

20. The Gastrointestinal Syndrome Mechanism • The precise time schedule varies with the species • In small rodent : 3 – 4 days • In large animal (e.g monkey) : 5 – 10 days • Sterilized dividing cell • Does not affected the • differentiated & • functioning cells • The surface of the villi • is sloughed off • No replacement cells • produced • Radiation • exposure • > 10 Gy • Villi begin to • shorten & shrink • Surface lining of the intestine is • completely denuded villi

21. Case 1 In 1946, 32 y/o /♂, admitted to hospital one hour of a radiation accident Total body exposure range from 11 to 20 Gy Clinical manifestations Few hours Vomiting, BT & HR ↑, PE : WNL 6th day Sign of severe paralytic ileus 7th day Liquid stools with occult blood 9th day Circulating collapse Death The Gastrointestinal Syndrome • Autopsy • Macroscopically • Mucosal surface of edematous & erythematous • Covered by a membrane exudate • Microscopically • Complete erosion of the epithelium • Mass of bacteria in exudate

22. The Hematopoietic Syndrome

23. The Hematopoietic Syndrome • Total-body exposure to 3 – 8 Gy • The peak incidence of human death • 30 days after exposure (continue up to 60 days) • Mechanism Diminished the supply of mature RBC, WBC, & platelet Total body exposure to 3 – 8 Gy Sterilized mitotically active precursor cells Circulating cell die off The effect of the radiation became apparent

24. The Hematopoietic Syndrome • 3 weeks later • Chill, Fatigue • Petechial hemorrhage in • the skin • Ulceration of the mouth Clinical manifestations • Prodromal syndrome • Nausea • Vomiting • Death • Caused by • infection Total-body exposure to LD50 • Depression of granulocytes • Infection & fever • Depression of platelet • Hemorrhage, anemia

25. Mean Lethal Dose and Bone-Marrow Transplants

26. Table 8.2. The Fifty Percent Lethal Doses for Various Species from Mouse to Human and the Relation between Body Weight and the Number of Cells that Need to be Transplanted for a Bone Marrow “Rescue” • Large species are more susceptible to hematopoietic damage than small • species • In human, bone marrow cells / kg 10 times less than mouse • Lower concentration of hematopoietic stem cells

27. Treatment of Radiation Accident Victims Exposed to Dose Close to the LD50/60

28. Treatment of Radiation Accident Victims Exposed to Dose Close to the LD50/60 • Radiation exposure < 4 – 5 Gy • The patient be watched carefully • Only treated in response to specific symptoms • Antibiotics for and infection • Fresh platelets for local hemorrhage • Blood transfusion should not be given prophylactically • Delay the regeneration of blood-forming organs

29. Treatment of Radiation Accident Victims Exposed to Dose Close to the LD50/60 • Radiation exposure > 5 Gy • Death from the hematopoietic syndrome 3 –4 weeks later is a real possibility • Isolation and barrier nursing • Antibiotics • LD 50 can be raised by a factor of about 2 in animal experiment • Avoid physical trauma and bleeding

30. Use of bone marrow transplantation to treated the patient with total body exposure • The area of most discussion and disagreement • The window of dose within which a bone-marrow transplant is useful is very small Illustrating the narrow window of dose over which bone-marrow transplant might be useful following total-body irradiation

31. The End Thanks!!