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

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 signs and symptoms of the human postirradiation syndrome
The various symptoms making up the human prodromal syndrome
The signs and symptoms of the human postirradiation syndrome
Gastrointestinal symptoms
Neuromuscular symptoms
Anorexia
Nausea
Vomiting
Diarrhea
Intestinal cramps
Salivation
Fluid loss
Dehydration
Weight loss
Easy fatigability
Apathy or listlessness
Sweating
Fever
Headache
Hypotension

9. Symptoms of the prodromal Syndrome
Variation of the prodromal syndrome depends
on the size of the dose
Time of onset
Maximum severity
Duration
Symptoms of the prodromal Syndrome
Neuromuscular
Gastrointestinal
Signs and Symptoms to be Expected at About 50% Lethal Dose
Easy fatigability
Anorexia
Vomiting
Additional Signs to be Expected after Supralethal Doses
Fever
Hypotension
Immediate Diarrhea

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. The Cerebrovascular Syndrome
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
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

15. The Cerebrovascular Syndrome
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

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
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
The precise time schedule varies with the species
In small rodent : 3 – 4 days
In large animal (e.g monkey) : 5 – 10 days

21. The Gastrointestinal Syndrome
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
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
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. Stem-cell Concentration
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”
Species
Anerge
Body Weight, kg
50% Lethal
Total-Body
Irradiation, Gy
Rescue Dose
per kg
× 10 -8
Relative
Hematopoietic
Stem-cell Concentration
Mouse
Rat Rhesus Monkey
Dog
Humans
0.025
0.2
2.8 12 70 7
6.75
5.25
3.7 4 2 3
7.5
17.5 20 10
6.7
7.3
1.1 1
Data from Vriesendorp HM, van Bekkum DW: Susceptibility to total-body irradiation in Broerse JJ, MacVittie T (eds): Response to Total-Body Irradiation in Different Species. Amsterdam, Martinus Nijhoff, 1984.
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!!