Acute Effects of Radiation

Acute Radiation Syndrome

Breakdown of one or more body systems as the result of a total body dose of radiation that is extremely high and rapid

Survival/recovery is extremely dependent upon

the dose received by the individual

Is it possible to initiate acute radiation syndrome in diagnostic imaging?

Virtually impossible

sometimes can be done on purpose in radiation therapy

Acute radiation syndrome is linked with

catastrophic events/radiation release from nuclear power plants

Acute radiation syndrome has what effects

DETERMINISTIC EFFECTS

Lethal abberations

-ring, dicentric, anaphase bridging

CANT DIVIDE IN MITOSIS

Mature/differentiated cells

Perform the vital functions of the human body

Differentiated!!

Stem/undifferentiated/progenitor cells

Foundational cells

Do not have specific cell function yet

Law of Bergonie and Tribondeau

The radiosensitivity of cells is directly proportional to their reproductive activity and inversely proportional to their degree of differentiation.

Radiosensitivity directly proportional to reproductive rate

Radiosensitivity inversely proportional to their degree of differentiation

Mature cells are

fully differentiated and more radioresistant

Stem cells are

undifferentiated and more radiosensitive

Non-proliferating cells are more

radioresistant

rapidly proliferating cells are

radiosensitive

Which cell population is most affected by acute radiation syndrome/high doses?

Stem cell populations

Stages of acute radiation syndrome

Prodromal syndrome

Latent period

Manifest illness

Recovery or death

What is a strong indicator of the magnitude of radiation dose?

The amount of time that elapses between the four stages

Prodromal period

The initial manifestation of symptoms after an individual is exposed to a high, acute radiation dose

The effects seen in prodromal period reflect the initial death of a large number of what cells?

Differentiated/mature cells in the affected organ systems

The cells in this population may be the type that die via apoptosis or they may be very rapidly-proliferating cells that die via mitotic death

Radiation dose and prodromal phase relationship

The amount of time that elapses between irradiation and manifestation of prodromal symptoms is INVERSELY proportional to dose

If it only takes minutes for prodromal symptoms to appear

It is likely that the radiation dose was extraordinarily high and fatal

Smaller radiation doses may take

a few hours to a few days to cause prodromal symptoms

Blood marker that may be used to estimate radiation dose in an individual with suspected acute radiation syndrome

As low as 0.5 Gy

Can pull blood samples and assess lymphocytes at this marker/assess dose

Most common universal symptoms of acute radiation syndrome: gastrointestinal

Nausea

Vomiting

Diarrhea

Salivation

Anorexia

Dehydration

Most common universal symptoms of acute radiation syndrome: neuromuscular

Fatigue

Listlessness (not lots of energy)

Sweating

Fever (common side effect of infection)

Headache

Hypotension

Latent period

Enough of the mature cells will survive that the patient can continue to function for awhile

The time period after the initial death of differentiated cells, but before the catastrophic manifestation of stem cell death

False sense of security

How do patients report feeling during the latent period?

Report feeling better or "normal"

Symptoms often disappear or become mild but this is an illusion. The latent period will end and the full illness will begin.

Relationship between radiation dose and the length of the latent period

The amount of time that elapses between the latent period and the manifest illness is INVERSELY PROPORTIONAL to dose

High dose will result in

short latent period

Low dose will result in

Long latent period

In extreme cases, what happens with the latent period

There is no latent period

If there is not enough differentiated cells remaining after the prodromal period to support organ function, the patient will transition directly to manifest illness

Manifest illness

When things get really bad

With the exception of non-proliferating, most cells in the body have a finite lifespan (ex: red blood cell is in body for 120 days)

When the mature cells die, new cells normally ready to replace (stem cells)

If a high radiation dose has destroyed the stem cell population, the full radiation syndrome will manifest once all surviving differentiated cells have reached the end of their lives

Three major acute radiation syndromes

Cerebrovascular syndrome

Gastrointestinal syndrome

Hematopoietic syndrome

Dose threshold for cerebrovascular syndrome to occur

100 Gy

Dose threshold for gastrointestinal syndrome to occur

10 Gy

Dose threshold for hematopoietic syndrome to occur

2.5-5 Gy

Timeline of death for cerebrovascular syndrome

Death is inevitable and swift (24-48 hours)

Symptoms usually begin within minutes!!

Cerebrovascular effects manifest so fast that you never see the gastrointestinal or hematopoietic effects

Central nervous system is what type of system

Non-proliferating

-some cells never undergo mitosis

-cell cycle time can be weeks

-makes CNS very radioresistant

CNS syndrome is possibly caused by extreme damage to

microvasculature rather than CNS themselves, allowing fluid to leak into the brain

Hypothesis

Cerebrovascular symptoms

Vomiting

Diarrhea

Seizures

Coma (almost immediately)

Loss of coordination

Respiratory distress

Hypotension

Timeline of death for gastrointestinal syndrome

Death inevitable, may be prolonged for days (3-10 typically)

Symptoms within minutes or hours!!

Inevitably fatal, no proof of survival over 10 Gy

What is gastrointestinal syndrome caused by?

Death of epithelial lining of GI tract (specifically the small intestine)

Gastrointestinal symptoms

Nausea

Vomiting

Lethargy

Diarrhea

Anorexia

Hypotension

Why is radiation so damaging to the GI tract?

Self-renewing tissue such as that in the GI tract, maintains integrity through a system of stem cells that continually replace the mature, functional cells.

Stem cells with radiation exposure, there are no new cells to replace when they lose functionality!

Measure of cell death is loss of either

reproductive integrity or functionality

What cells of the GI tract does high radiation doses destroy?

The crypt stem cells

Small intestine renewability

Constantly renews itself through a system in which stem cells differentiate into epithelial villi cells

Lifespan of villi cell

3-5 days

When mature villi reach the end of their lifespan, there are no stem cells to differentiate into mature cells to replace them (crypt stem cells are dead)

Death timeline for hematopoietic syndrome

Death is not necessarily inevitable

If it occurs, it can take a month!!

What is hematopoetic syndrome caused by?

Caused by damage to precursor stem cells that form red/white blood cells

When does the latent period end with hematopoietic syndrome?

When the remaining mature blood cells reach the end of their lifetime and cannot be replaced by stem cells in bone marrow

Hematopoietic syndrome symptoms

Nausea

Vomiting

Diarrhea

Fever

Fatigue

Hypotension

Ulceration of mucus membranes (mouth)

Epilation (hair loss)

Petechial hemorrhages (pinpoint)

How does the hematopoetic system renew?

Renews via stem cells in bone marrow

The depletion of progenitor stem cells by radiation eventually reduces the

number of circulating white blood cells, red blood cells, and platelets

lose inability to fight infection, clot, etc.

LD50

Dose required to kill 50% of study population within a specified period of time

LD50/30

Dose required to kill 50% in 30 days

What is LD50/30 generally used for?

Animals because they develop signs of hematopoetic damage earlier

LD 50/60

Dose required to kill 50% in 60 days

What is LD50/60 generally used for?

Humans because they develop signs of hematopoetic damage later

Up to a dose of 2 GY, there is

no lethality

At a dose of 8 Gy, there is

100% of lethality

Between 2 Gy- 8Gy there is a

rapid increase in death with increasing dose

LD 50/60 dose for hematopoietic syndrome in humans

4 Gy

Predominant cause of death in hematopoietic syndrome

Caused by INFECTION

Due to depletion of immune cells

Bone marrow must have time to recover before infection sets in, which makes antibiotic an important component of treatment

Death is much more likely at 5Gy and almost certaintly requires

infection control drugs and procedures

What dose do patients receive in which they benefit from bone marrow transplantation?

8-10 Gy

Below 8 Gy, patient has

a decent chance of survival with careful care

Above 10 Gy, patient

will inevitably die from gastrointestinal syndrome

What is a good indicator of dose received?

The amount of time between exposure and manifestation of prodromal symptoms

Average time to vomiting decreases

as dose increases

Dose may be assessed with lymphocyte count within

48 hours of exposure

Chromosome aberrations in lymphocytes tend to disappear quickly near

LD50

Cutaneous radiation injury

Widespread skin damage seen concurrently with the three acute radiation syndromes

Cutaneous radiation syndrome relationship with duration of latent period

Inversely proportional

High dose: short latent period

Low dose: long latent period

Symptoms of cutaneous radiation injury

Itching

Tingling

Erythema

Epilation (hair loss)

Edema

Desquamation

What does cutaenous radiation injury occur from?

Results from depletion of epithelial stem cells in the BASAL layer of the epidermis

Studies of survivors of high total body radiation doses do not show any remarkable increase in

Stochastic effects like cancer