Lecture 20 - Therapeutic and Accidental Total Body Irradiation

ONCOL 335 - Radiobiology. University of Alberta

what two categories can radiation exposure be divided into

1. whole body exposure

2. localized radiation exposure

two categories of tissues radiation can have effects on

1. somatic tissues

2. germ tissues

two categories of radiation effects

1. acute effects

2. late effects

what is acute radiation syndrome (ARS)

a collection of health effects which present within 24 hours of exposure to high amounts of radiation

where did we get initial data on ARS from?

1. demon core

2. atomic bombs

3. chernobyl

what are hibakusha?

survivors of the atomic bombings of Hiroshima and Nagasaki in 1945 who were exposed to the bomb's radiation and suffered from physical and psychological effects, including cancer and other long-term health issues.

what comission was founded to study hibakusha, and who started it?

the atomic bomb casualty comission was founded by Dr. Terufumi Sasaki

what did the atomic bomb casuallty commission become?

the Radiation Effects Research Foundation

What is the LD_50/60 for young healthy adults without medical attention?

4.5 Gy

nobody has ever survived ___ Gy

10 Gy

Examples of ARS in history (don’t need to memorize all)

1. Atomic Bombs

2. Demon core

3. Chernobyl

4. Goiania incident

5. Fukushima

what is a criticality accident?

an uncontrolled nuclear chain reaction that occurs with the unintentional assembly of a critical mass

difference between critical reaction and accident

critical reaction occurs within reactor cores and test environments, accidents occur when same reation is acheived unintentionally and in an unsafe environment

what does the top sphere represent

a sphere of fissile material that is too small to cause self-sustaining chain reaction

• neutrons can escape too easily

what does the middle sphere represent

by increasing the mass of the sphere, the reaction is made self sustaining, neutrons can hit other atoms

what does the bottom sphere represent

the original sphere is surrounded with a neutron reflector to increase the efficiency of reactions to allow reaction to become self-sustaining

What happened in the Harry Daghlian Demon Core incident?

Harry Daghlian accidentally dropped a neutron reflector (tungsten carbide) brick onto the plutonium pit during a criticality experiment, causing a brief critical reaction and exposure to lethal radiation. He died 25 days later from radiation poisoning.

how much dose did Daghlian receive?

5.1 Sv of neutron radiation

what was the Litvinenko case

The Litvinenko case involved the poisoning of Alexander Litvinenko, a former Russian FSB agent, who was fatally poisoned with polonium-210 in 2006 in London. Litvinenko died after ingesting the radioactive substance

what radioactive isotope was Alexander Litvinenko exposed to?

Po-210

• alpha emitter = high LET

what are stochastic effects?

all or nothing random radiation effects

stochastic effects occurance is a probabilty of …

dose

examples of stochastic effects

cancers, inheritable mutations

deterministic effects

effects that severity increase as a function of dose

do deterministic effects have a threshold?

yes

examples of deterministic effects

organ failure, fibrosis, cataracts

is ARS (and other early radiation responses) a deterministic effect?

yes

• they have a threshold

what is a syndrome?

a set of medical signs and symptoms that correlate with eachother

what are the three ARS syndromes?

1. hematopoietic syndrome

2. gastrointestinal syndrome

3. cerebrovascular syndrome

at what doses does CV syndrome happen at?

very high doses

will CV syndrome cause you to develop the other two syndromes

theoretically yes, but it will kill you before the onset of the other syndromes

what are the four stages of ARS?

1. prodromal (initial) stage

2. latent stage

3. manifest illness

4. death or recovery

how does the length of the prodromal stage vary with dose?

the higher the dose, the quicker you will develop the symptoms

if you are exposed to 40 Gy, when will the prodromal stage begin

5-15 minutes after exposure

two categories of prodromal symptoms

1. neuromuscular

2. GI

3 neuromuscular prodromal symptoms

1. fatigability

2. fever

3. hypotension

4 GI prodromal symptoms

1. anorexia

2. nausea

3. vomiting

4. immediate diarrhea

what are the three causes of the prodromal stage of ARS?

1. immediate cell membrane damage

2. inflammatory eleemnts of cell destruction

3. neurologic mediation by Parasympathetic nervous symptom

what is the latent stage of ARS

the stage after the prodromal stage where the patient may become symptom free

how is the latent stage related to dose?

the higher the dose, the shorter the latent stage

if a patient does not experience a latent stage, what do we know about the dose of radiation they received?

it was very high

what what dose to lymphocyte counts drop at

0.5 Gy

what does the Law of Bergonie and Tribondeau state?

radiosensitivty of cells is higher in cells that are less differentiated and faster at proliferating

what are the two exceptions to the Law of Bergonie and Tribondeau?

1. lymphocytes

   • highly differentirated, but the most sensitive cell

2. oocytes

   • non-proliferating, but sensitive

what stem cell line is more radiosensitive, the lymphoid or myeloid lineage?

the lymhpoid lineage

6 radiosensitive cells/tissue

1. cells of red bone marrow

2. epithelial cells of GI and lung

3. epithelial cells of lens

4. germ cells of testis and ovaries

5. endothelial cells (vasculature)

6. salivary glands

If you receive higher doses, which ARS syndrome will you die of?

CV syndrome

if you received a low dose, which ARS syndrome could you potentially die of?

Hematopoietic syndrome

above what dose will progression to death stage of ARS be the quickest

above 8 Gy

what is the caveat to ARS data?

all of the data that has been collected is for healthy young adult males (like soldiers).

• limited data in older people, babies, or even females

clinicians should not expect a specific dose or dose range for ARS syndromes to occur at

which ARS syndrome do we know the least about?

CV syndrome

what dose will cause CV syndrome death within 24-48 hrs

greater than 100 Gy of gamma radiation

symptoms of CV syndrome

nausea and vomiting within minutes —> disorientation, loss of muscle coordination, breathing problems, seizures, coma, death

what indicent resulted in a person dying from CV syndrome?

Rhode Island Criticality Accident

what was the rhode island criticality accident

a worker at a uranium 235 recovery plant was exposed to 88 Gy of neutrons (22 of them were neutrons).

• died 49 H after

which ARS syndrome did Daghlian die of after his demon core exposure?

GI syndrome

• died of sepsis in 24 days

what dose will cause GI syndrome death in 7-10 days?

10 Gy of gamma rays

symptoms of GI syndrome

nausea, vomiting, prolonged diarrhea, lethargy, lack of appetite

if person has prolonged diarrhea after exposure, how much dose did they receive?

more than 10 Gy

describe how GI syndrome causes death

GI syndrome leads to death primarily due to damage to the intestinal lining, resulting in severe dehydration and sepsis from gut bacteria entering the bloodstream. The rapid loss of intestinal function hinders nutrient absorption and fluid balance, contributing to mortality.

if patients have GI syndrome get bone marrow transplant, will they survive?

no, they will die of GI syndrome

• treatment of hematopoeitic syndrome has not effect

if we looked at the GI tract of a patient who died of GI syndrome, what would we see?

complete erosion of jejunum and ileum, and system is full of bacteria

• sepsis often occurs

if death occurs after 2.5-5 Gy, what syndrome caused it?

hematopoietic syndrome

what happens in hematopoietic syndrome

mitortic stem-cell precursors of RBC, WBC, and platelets are killed

why is the onset of hematopoietic syndrome delayed by weeks?

syndrome is only displayed when mature cells are depleted below a threshold

when will a patient diet of hematopoietic syndrome

30-60 days

who are more sensitive to hematopoietic syndrome?

older people, children, and men (compared to women)

early symptoms of hematopoeitic syndrome

chills, fatigue, loss of hair, petechial hemorrages of skin

late symptoms of hematopoietic syndrome

anemia, impaired immune function

why is there a spike in neutrophil numbers after irradiation?

neturophil spike is often due to infection

why does the RBC not drop?

RBC have life spand of 120 days, they wont be affected as much

why do we see a drop in platelets at 10 days

Platelets have a shorter lifespan of about 7-10 days, leading to a drop in numbers after irradiation.

what cells do we often use as a measure of how much radiation a person got?

lymphocytes

the larger the dose, what happens to lymphocytes

lymphocyte count drops

why can skin effects occur in the absence of ARS?

lower energy photons only deposit dose to surface of bodye

examples of cutaneous radiation injury

severity of ARS is a function of ____

dose

time of latent period is ______ to dose

inversely proportional

again, what cells do we look at to classifiy exposure?

lymphocytes

what is another thing we can look at to classift exposure?

the probability of vomiting

2 methods to confirm radiation exposure

1. lymphocyte count

2. vomiting time

treatment plan of radiation exposure

1. supportive care

2. gut decontamination

3. bone marrow transplant

4. radiation mitigators

examples of supportive care for radiation exposure

electrolyte/fluid replacement, isolation, antibiotics

what is sucralfate used for?

sticks to gut lining, forming a barrier to protect agaisnt sepsis

• reduces radiation ulcers as well

what are the four uses of Therapeutric total body irradiation?

1. leukemia

2. lymphoma

3. myeloma

4. stem cell transplants

who was the first person to describe TBI?

Friedrich Dessauer in 1905

what cancers was TBI found most effective on?

hematopoeitic and lymphoid stem cells

how was TBI used for transplant surgeries?

was used for immunosupression before the surgery

• now we just use drugs

what is graft vs. host disease

a complication that arises when newly transplanted donor cells attack reciepient’s body

TBI definition

irradiation of entire body

leukemia defintiion

group of cancers that begin in bone marrow and result in abnormal WBCs

lymphoma definition

any group of blood cell tumor that develops from lymphatic cells

multiple myeloma defintiion

cancer of plasma cells

HSCT definition

hematopoietic stem cell transplant: transplant stem cells derived from bone marrow, peripheral blood, or umbilical cord

most common type of lymphoma

non-hodgkins

what percent of diagnosed cncers are hematologic malignancies in adults?

10%

what percent of diagnosed cncers are hematologic malignancies in children?

40%

4 main subtypes of leukemia

1. acute lymphocytic

2. acute myelogenous

3. chronic lymphocytic

4. chronic myelogenous

myelogenous meaning

arising from hematopoietic stem cells

lymphocytic meanin

arising from other cells in the bone marrow