1. Deterministic effects of radiation –Ch33
Acute Radiation Lethality RTMR 284 Winter 2013
Local Tissue Damage
Hematologic Effects
Cytogenetic Effects

2. Effects of Radiation Early response within a few hours, days, weeks
encountered in diagnostic radiology rarely
Deterministic: those that exhibit increasing severity with increasing radiation dose
Late
response months or years after irradiation
Pioneers
“babes” in the field

3. Comments
Many pioneers in the field of radiology died early or were diagnosed with cancer and leukemia
Some had to have arms
amputated due to
radiation exposure

4. Acute Radiation Lethality
3 stages of acute radiation lethality
1. prodromal (period) syndrome
2. latent period
3. manifest illness stage
ACUTE RADIATION LETHALITY = the events following high-level radiation exposure that lead to death within days or weeks
DEATH is the worst human response to radiation exposure, but no cases of death following diagnostic x-ray exposure have been recorded. the doses are not high enough.
It has been said that:
diagnostic x-ray beams are not intense enough or large enough to cause death.
they only result in partial body exposure which is less effective than whole-body exposure.
IS THIS TRUE? (what about babies..?)
at chernobyl, in 1986, 30 people died of acute radiation syndrome. no one died or was seriously irradiated at the three mile island meltdown in 1979

5. 1. Prodromal Syndrome The immediate response = radiation sickness
acute clinical symptoms occur within hours & continue for up to a day or two
at radiation doses above 100 rad to the whole body - signs & symptoms may appear within minutes to hours after exposure
Symptoms
nausea, vomiting
diarrhea
decrease in WBC’s

6. 2. Latent Period A time of apparent well-being
No sign of radiation sickness
can last for only hours (doses over 5000 rad)
can last for weeks (doses from rad)

7. 3. Manifest Illness Stage
Actual illness stage, depends on dose
3 main groups in the manifest illness stage
hematologic death
gastrointestinal death
central nervous system death

8. Acute Radiation Lethality Review so far:
3 stages of acute radiation lethality
1. Prodromal syndrome - immediate sickness
2. Latent period - apparent well being
3. Manifest illness stage
hematologic death
gastrointestinal death
central nervous system death

9. Review of Dose and Symptoms

10. Hematologic Syndrome Dose range of 2-10 Gyt (200-1000 rad)
Latent period may be as long as 4 wks
Mild symptoms of prodromal stage
vomiting, mild diarrhea, malaise, lethargy, fever
Characterized by:
reduction in numbers of WBC’s, RBC’s, & platelets in circulating blood
Recovery begins in 2-4 wks, takes 6 mo

11. Gastrointestinal Syndrome
Doses in the range of Gyt ( rad)
prodromal symptoms start within hours and last one day
latent period of 3-5 days
Symptoms:
loss of appetite
lethargic

12. Gastrointestinal Syndrome cont.
Death within 4-10 days due to severe damage to cells lining intestines.
Damaged cells proliferate & stem cells are destroyed (generation time is 3-5 days)
When lining of intestine has no more functional cells, fluids pass across the intestinal membrane & electrolyte balance is destroyed, infection occurs

13. Question?
When the GI syndrome occurs will the Hematologic syndrome also be present?
Why or Why not?
Think…..
What is the dose range for the GI syndrome? The Hematologic syndrome?
What else do you need to know?

14. Answer
Yes the GI syndrome can occur with the Hematologic syndrome – there is enough time and dose for both to occur.

15. Central Nervous System Syndrome
Doses over > 50 Gyt (5000 rad)
prodromal symptoms within minutes:
nervous, confused, lose vision
burning sensation in skin
lose consciousness within the first hour
Latent period up to 6-12 hours
Manifest Illness - CNS symptoms:
prodromal symptoms reappear & :
person disoriented, has difficulty breathing
lose muscle coordination
convulsions, seizures, lapses into a coma & dies

16. Central Nervous System Syndrome
Cause of death:
increased fluid content of the brain
causes increased ICP’s and
inflammation of blood vessels

17. Another Question?
When the CNS syndrome occurs, will the GI syndrome or the hematological syndrome occur?
Why or Why not?
***Q when the CNS syndrome is occurring will the Hematologic syndrome or the GI syndrome also be occurring?
Think…..
What is the dose range for the GI syndrome? The Hematologic syndrome?
What else do you need to know? Time range of symptoms?
NO - not enough time for the symptoms to develop.
**at radiation doses sufficiently high enough to produce CNS effects, the person always dies within a few days of exposure.

18. Answer
No – you would die from the CNS prior to there being enough time for the hematologic or GI syndromes to appear

19. Question (yes another one!)
What dose response relationship is used for acute human lethality?
Think….

20. Answer
Nonlinear, threshold

21. LD 50/60
The dose to the whole body that will result in death to 50% of the population irradiated within 60 days
For humans the dose is approximately 3.5 Gyt or 350 rad without clinical support
Max dose from clinical data is
8.5 Gyt or 850 rad

22. Mean Survival Time (MST)
As the whole-body dose ’s…The time between exposure & death ’s (2 to 10 Gyt = 60 to 4 days)
MST is dose dependent for hematologic & CNS syndrome
MST is a constant 4 days
for GI syndrome

23. VERY IMPORTANT THAT YOU CONE ON SMALL BABIES
Local Tissue Damage
Higher dose is needed to produce a response when only part of the body is irradiated Vs. the whole body
Very important that you cone on babies!
Every organ/tissue can be affected by local irradiation
effect is cell death  atrophy  non-function or recovery
a higher dose is needed to produce a response when only part of the body is irradiated versus the whole body. WHY?
VERY IMPORTANT THAT YOU CONE ON SMALL BABIES
-every organ and tissue in the body can be affected by local irradiation
effect: cell death - resulting in shrinkage, or atrophy of the tissue or organ.
this can lead to a total non-function of that tissue or organ, or recovery may occur
-how the tissue responds is dependent upon 3 things:
1. their radiosensitivity
2. cell proliferation (LAW OF B AND T)
3. maturation

24. How Tissues Respond Depends on 3 things:
the inherent radiosensitivity of the tissue
cell proliferation rate
maturation level of tissue
Sound familiar?
The law of B & T???

25. Effects on Skin Stem cells: basal cells Normal skin has 3 layers
damage to basal cells results in radiation injury
Normal skin has 3 layers
epidermis - an outer layer
dermis - intermediate layer of connective tissue
subcutaneous layer of fat & connective tissue
Other structures
hair follicles, sweat glands, sensory receptors
the epidermis, has several layers of cells, the lowest layer is the basal cells. basal cells are the stem cells. as they mature they migrate to the surface of the epidermis then are replaced and the cycle repeats
-it is damage to these basal cells that results in the earliest response/manifestation of radiation injury to the skin

27. Atomic Structure of Skin

28. Skin - Definitions Erythema Desquamation
reddening of the skin
Desquamation
ulceration and denudation of the skin
Clinical tolerance (for radiation therapy)
moist desquamation known as clinical tolerance
Atrophy
shrinkage, reduction in size

29. Definitions Epilation loss of hair Grenz Rays
soft X-rays (10 to 20 kVp) --old treatment to skin dz--
SED 50
skin erythema dose
dose required to affect 50% of the people irradiated
about 600rad.

30. Local Tissues Effected Immediately
Gonads
Bone Marrow
Skin

31. Gonads Gametogenesis = development of the gametes or germ cells
They are critical target organs
Why?
Extremely sensitive to radiation
doses as low as 10 rad can cause a response
they produce the germ cells that control fertility & heredity

32. Ovaries Stem cells: oogonia Most radiosensitive phase: oocyte
multiply only in fetal life
oocytes remain suspended until puberty
At puberty the follicles rupture ejecting the ovum
only used for fertilization
~1 million oocytes in an infant & 400,000 at puberty

33. Ovaries
Babies & children are the most radiosensitive & germ cells are radiosensitive
CONE & SHIELD
Ovaries least sensitive in yr range
100 mGyt 10 rad may delay or suppress menstruation
2 Gyt 200 rad will produce temporary sterility
5 Gyt 500 rad could cause permanent sterility

34. Ovaries - mutations
250 to 500 mGyt (25-50 rad) can produce ’s in genetic mutations (animals)
Surviving oocytes can repair some genetic damage as they mature
Women may want to avoid getting pregnant for several months after ovarian doses  10 rad
Abortion NOT indicated for any diagnostic range dose

35. Testes Stem cell: spermatogonia
Most radiosensitive phase: spermatogonia
Continually produced
Spermatogonia  spermatocyte  spermatid  spermatozoa or sperm
cycle takes 3-5 weeks

36. Testes 100 m Gyt 10 rad can cause reduction in # of sperm
2 Gyt 200 rad produces temporary sterility
starts ~2 months after irradiation
WHY?
5 Gyt 500 rad to testes produces permanent sterility

37. Hemopoietic System Consists of:
Bone Marrow
Circulating Blood
Lymphoid Tissue (consists of)
Lymph nodes
Spleen
Thymus
Stem cell:
all cells of Hemopoietic system develop from the pluripotential stem cell

38. Comments
On the test DO NOT list Lymph nodes, Spleen, Thymus separately for hemopoietic system
They are the lymphoid tissue which is one component of the hemopoietic system.

39. Hemopoietic System Leukocytes lymphocytes granulocytes Erythrocytes
Main cell types:
Leukocytes
lymphocytes
granulocytes
Erythrocytes
Thrombocytes

40. Cell Types Leukocytes - white blood cells - immune system
Lymphocytes
large round nucleus - nearly fills the cell
20-40% of the leukocytes
manufactured in bone marrow, spleen & thymus
Granulocytes
scavengers, destroys microorganisms
larger than erythrocytes
52-75% of leukocytes
manufactured in bone marrow

41. Comments Lymphocytes and Granulocytes are both Leukocytes
Know where each of the blood cells are manufactured

42. Radiation Effects lymphopenia within minutes/hours slow to recover
Main radiation effect:
decrease the # of blood cells in circulation
Late effect: leukemia
Lymphocytes are 1st cells to be affected
lymphopenia within minutes/hours
slow to recover
immediate response indicates that lymphocytes affected directly & not just precursor cells

43. Radiation Effects Granulocytes
rapid rise in # (granulocytosis) followed by rapid decrease & slower decrease (granulocytopenia)
recovery takes ~ 2 months
Platelets
thrombocytopenia (decrease in platelets) occurs slowly due to the longer time for precursor cells to reach maturity
minimum level in ~ 30 days & recovery in ~ 2 months

44. Radiation Effects Erythrocytes less sensitive than other blood cells
very long lifetime in peripheral blood
injury not noticeable for several weeks
total recovery (without intervention) may take 6 months to a year

45. Cytogenetic Effects
Cytogenetics = the study of the genetic aspects of cells, chromosomes in particular
Radiation-induced chromosome aberrations follow a Nonthreshold relationship
High doses of radiation cause chromosome aberrations
Unable to see chromosomal aberrations under a dose of 100 m Gyt 10 rad

46. Cytogenetic Effects
Cytogenetic damage may occur immediately but may not be seen for awhile
takes time for that stem cell to reach maturity
it can be months and years before damage can be measured.
Chromosome abnormalities can be seen in circulating lymphocytes even 20 years after a radiation accident…

47. Karyotype Karyotype = a chromosome map
Photographs of chromosomes are enlarged
Each chromosome is cut out & matched with its “sister”
Chromosomal damage can be observed at this point

48. Chromosomal Damage
In an inbred population both chromosomes of the pair will usually be the same
in a normal population the two chromosomes will usually contain many different genes
When a chromosome is changed the genetic character transmitted is changes
these changes are mutations
most mutations are recessive

49. Single - Hit Single-hit chromosome
a chromosome hit produces a visible derangement of the chromosome
represents severe damage to the DNA
chromatid deletion, isochromatids, chromatid fragments

50. Double-hit Double-hit chromosome most significant for latent damage
when the chromosome is hit more than once
ring chromosomes, dicentric chromosomes, chromatid fragments

51. Chromosomal Damage

52. Chromosome Map

53. Chromosome Aberrations
At very low doses:
single-hit aberrations are observed
Doses over ~ 100 rad (1 Gray)
multihit aberrations observed more frequently
Single-hit uses a
linear, nonthreshold
dose-response relationship
Multi-hit uses a
nonlinear, nonthreshold
relationship

54. THE END