Whole Body Irradiation
 Experience with bomb and powerplant
incidents.
 Experimental exposure of animals
 Refers to complete irradiation of body
– Particulate radiation (except neutrons) and
internal emitters are not usually uniform
 Survival figures usually expressed as in
lethality assays i.e. LDx/y
Whole Body Radiation Syndromes
 Stages of response
– Prodromal Stage
– Latent Stage
– Manifest Illness Stage
 Following the manifest illness stage the
patient either recovers or dies.
– Long term health issues may remain
Total Body Irradiation Syndromes
 Prodromal Stage
– Initial reaction to irradiation –
 immediate response
– Characterized by
 Nausea
 Vomiting
 Diarhea
– Lasts from a few minutes to few days
– Happens at low doses but increases with dose
Total Body Irradiation Syndromes
 Latent Stage
– Characterized by apparent lack of signs
– Changes are occurring at the cellular level
– Patient has false sense of well being
– Lasts for a few days to a week or so
Total Body Irradiation Syndromes
 Manifest illness stage
– Time during which clinical illness is evident.
– Depending on the dose received this stage may
last from a few minutes to several weeks
– Signs are referable to the type of syndrome
being manifest.
– Ends in recovery or death
Total Body Irradiation Syndromes
 Bone marrow Syndrome
– Occurs at doses of 2-10 Gray.
– The LD50/60 is in the 4-6 Gy range
– The prodromal stage is characterized by
nausea
 Cause of the nausea is not well understood.
 The latent period can be from a few days to 3 weeks
– Manifest illness is due to signs of bone marrow
stem cell depletion.
Total Body Irradiation Syndromes
 Bone marrow depletion leads to a drop in
circulating platelets and white blood cells.
– Allows increase in infections and hemorrhage
– Blunts response to new environmental antigens
– With supportive care the patient may recover
 If sufficient stem cells remain recovery may be
spontaneous
 Bone marrow transplants may improve survival
Total Body Irradiation Syndromes
 GI syndrome
– Occurs at doses above 8-10 gray
 This dose is equal to 4-5 time D0
 Prodromal signs begin a few hours after exposure
and last a day or so.
 Latent period generally last 3-4 days
– Less with higher exposures
 Manifest illness stage lasts a few days
– Diarhea returns and systemic infections ensue
Total Body Irradiation Syndromes
 GI syndrome
 Signs are d/t combination of Bone Marrow syndrome
and GI irradiation
 In GI tract there is a loss of the intestinal villi which
absorb nutrients and fluid from the bowel
– The villi also form a barrier between the blood and bacteria
in the gut lumen.
– Fluid from the body is lost into the bowel lumen
 Intensive medical therapy effective only at lower
dose range
 Above 10 gray death is virtually certain by 14 days
Total Body Irradiation Syndromes
 GI syndrome
– Even if patient survives the GI disease there is
still the effects of the bone marrow depletion to
deal with.
– Signs and effects will be seen even with just
irradiation of the abdomen but bone marrow
depletions would not occur so LD is higher
Total Body Irradiation Syndromes
 Central Nervous System Syndrome
– Can occur with just irradiation of the CNS or
with whole body irradiation
– Occurs at doses of 60-100 Gy.
– Prodromal phase as usual but with nervousness
and hyperesthesia
– Latent period lasts for a few hours
– Manifest illness stage lasts up to a day and
consists of severe diarrhea and convulsions
Total Body Irradiation Syndromes
 Central Nervous System Syndrome
– Death invariably occurs in 2-3 days
– Signs are probably related to brain edema or
dysfunction of critical cells in the CNS
– There are few microscopic changes seen
– Bone marrow and GI syndromes do not have
time to be manifest
– At doses above 100 Gy death can be immediate
Irradiation of Embryo and Fetus
 The embryo arises from the fertilized ovum
– Ovum is the “parent” cell of the entire body
 The term embryo refers the morula of cells
present in the uterus prior to implantation
– Does not have attachment to the uterine wall
– Does not have a blood supply
 Essentially a rapidly dividing ball of stem
cells
Irradiation of Embryo and Fetus
 After 5-6 generations the division early
differentiation begins to occur
– Irradiation of the embryo can kill a single cell
which gives rise to entire cell lines or organs
– For irradiation at this stage even very low dose
result in a high incidence of fetal loss.
– If the embryo survives then there are few
consequences of the irradiation
 Remaining cells make up for loss
Irradiation of Embryo and Fetus
 Following implantation in the uterine wall the
embryo is considered to be a fetus.
 Following implantation there is a period of
rapid differentiation and development of the
major organ systems.
– This is called the period of organogensis
– Begins at about 2 weeks and lasts to 42 days in
humans.
Irradiation of Embryo and Fetus
 Irradiation during this time can cause growth
delay in the fetus
 During this time the organs develop at
different times.
– For each organ there are intense bursts of
growth – nearly constant mitosis
 Very radiation sensitive
 Irradiation during one of these bursts can destroy or
severely damage the developing organ system
Irradiation of Embryo and Fetus
 The central nervous system is a special
case
– Developing constantly not only during
organogensis but throughout gestation and
often beyond.
– Doses of 1 Gy have been shown to result in a
reduction in cognition
 In humans CNS development lasts up to about 12
years of age.
Irradiation of Embryo and Fetus
 Period of fetal growth
– Begins following the period of organogensis
– Lasts throughout rest of gestation
– All of the major organ systems are present and
enlarging
– Eyes are part of CNS and severe ocular effects
are expected following irradiation.
– Humans are particularly sensitive due to the
advanced CNS development.
Irradiation of Embryo and Fetus
 Other effects
– Mutation induction >>> cancer
– May not be seen for years after birth
 Single cells may require years to grow to noticeable
size.
– Ovum and spermatigonia may have mutations
which can be passed on to subsequent
generations
Irradiation of Embryo and Fetus
 Dose limiting tissue for radiation workers
– 500 millirem for duration of pregnancy
– Fetal monitors often required if radiation in area
 Accidental exposure of pregnant women not
generally at risk is a problem.
– Mother may feel no ill effects
– Damage to fetus may still be significant
Irradiation of Embryo and Fetus
 One of few instances where diagnostic xrays are considered a hazard.
– Abdominal radiograhs in pregnant women could
result in a dose of 1-3 cGy to the fetus.
– Ultrasound is generally used except in cases of
emergency.
Effects of Moderate (0.5-1.0 Gy)
Whole Body Irradiation
 Immunologic effects
– As always, severity of effect increases w/ dose
– Macrophages and other white blood cells in the
spleen, liver and circulating blood are an
important part of the bodies immune system
– Macrophages are resistant but their stem cells
are not
 Many white blood cells are short lived
 Major function is destruction of infective microbes
Effects of Moderate (0.5-1.0 Gy)
Whole Body Irradiation
 White blood cell (wbc’s) effects
– WBC’s engulf and destroy microbes which get
into the blood stream.
 There is a constant shower of these from the gut,
skin, eyes, lungs etc.
 If the influx of microbes is to great the wbc’s can be
overwhelmed.
 Following irradiation there is a decrease in wbc
numbers
 There may also be a decrease in functional capability
Effects of Moderate (0.5-1.0 Gy)
Whole Body Irradiation
 Cytokines and other chemicals in the body
that attack microbes are products of wbc’s
and their levels or activity may also be
affected.
Effects of Moderate (0.5-1.0 Gy)
Whole Body Irradiation
 Humoral defense mechanism (antibodies)
effects.
 Plasma cells (derived from lymphocytes)
produce antibodies
– Antibodies are derived from immunologically
sensitized cells.
– They attach to foriegn protiens and microbes
– Attract macrophages to engulf and destroy
foreign material.
Antibody Production Effects
 Plasma cells must first be “sensitized”
– Requires a few days between sensitization and
the onset of antibody production.
 Once antibodies begin to attack foreign materials the
macrophages will eliminate it relatively quickly.
– Long lived lymphocytes and plasma cells
“remember” the foreign agent so a second
response occurs more quickly and vigorously
Antibody Production Effects
 Phases of antibody stimulation
– Preinduction
 Recognition of foreign protien
– Induction period
 Antibody production mechanisms are set in place
– Production period
 Large amounts of antibodies released into circulation
Antibody Production Effects
 Preinduction period
– Circulating lymphocytes detect the foreign
protiens, this takes 1-4 hours
– Sensitized lympocytes divide and migrate out of
the blood stream into the tissues.
– Once in tissues they mature into plasma cells.
– Due to cell division, this stage is highly
radiosensitive and irradiation at this time results
in severe blunting of antibody response
– Low wbc #’s d/t prior irradiation has same effect
Antibody Production Effects
 Induction period
– Plasma cells differentiate from the sensitized
lymphocytes
– Antibody production mechanisms initiated
– Moderately radiosensitive period
– Irradiation at this time delays response but
antibody levels will reach normal levels.
Antibody Production Effects
 Production period
– Antibody production occurs and high levels
– Plasma cells are resistant FPM cells
– The phase is highly radiation resistant
 Some studies have suggested that moderate
irradiation during this period may actually increase
production of antibodies.
– Because the induction phase is skipped in a
secondary response there is little response
blunting.
Antibody Production Effects
 If antibody response is blunted then foreign
cell killing by radioresistant macrophages
and neutrophils can still occur but is less
efficient and takes longer.
Carcinogenisis
 It has been shown that radiation is a
relatively potent carcinogen
 This is a cumulative effect
– Increased dose increases the effect.
– The effect is not mitigated by dose rate as it is
associated with non-repairable DNA damage.
 Since chromosomal effects are associated
with cell reproduction it may take years for
them to manifest in slowly dividing cells.
Carcinogenisis
 The effect is a stochastic effect
– Increased dose increases probability
– But, the creation of a cancer is all or none effect
 Effect is to increase the incidence in synch
with the natural background occurrence.
 Seen in post radiation therapy patients but
oncology patients have higher incidence of
second cancers anyway.