Acute Radiation Syndrome (ARS) (sometimes known as radiation toxicity or radiation sickness) is an acute illness caused by irradiation of the entire body (or most of the body) by a high dose of penetrating radiation in a very short period of time (usually a matter of minutes). The major cause of this syndrome is depletion of immature parenchymal stem cells in specific tissues.Examples of people who suffered from ARS are the survivors of the Hiroshima and Nagasaki atomic bombs, the firefighters that first responded after the Chernobyl Nuclear Power Plant event in 1986, and some unintentional exposures to sterilization irradiators.

1. ACUTE RADIATION
SYNDROME
Presented by
Dr. Rahul Srivastava
Professor
Rama Dental College Hospital
& Research Centre Kanpur

2. Acute radiation syndrome (ARS)
Acute radiation syndrome (ARS), sometimes known
as radiation toxicity or radiation sickness, is an
acute illness caused by irradiation of the entire
body (or most of the body) with a high dose of
radiation over a very short period of time (usually a
matter of minutes).

3. The signs and symptoms of ARS are related to the
type of radiation and the absorbed dose of
radiation.
The threshold whole-body dose for ARS in adults is
approximately 1 Gy (100 rad); lower doses are not
expected to cause clinically apparent ARS.
A whole-body dose of 4.5 Gy is lethal to 50 percent
of exposed persons (LD50) and a dose of ≥10 Gy is
typically associated with 100 percent mortality.

4. Pathophysiology of ARS
Among cells, sensitivity to radiation varies
according to cell cycle length. The rate at which a
cell replicates and divides is an important
determinant of radiosensitivity.
During mitosis, when genetic material is most
exposed, cells are most vulnerable to the effects of
radiation.

5. Spermatogonia are easily damaged by ionizing
radiation.
Lymphocytes, erythroblasts and other
hematopoietic cells are also fairly radiosensitive,
as are the cells of the gastrointestinal tract.
Muscle, bone and collagen-producing cells are less
mitotically active and therefore among the least
sensitive to the effects of radiation.

6. Phases of ARS
Each ARS syndrome follows a predictable course
that can be divided into four clinical phases (or
stages):
Prodromal Phase.
Latent Phase.
Manifest Illness.
Recovery or Death.

7. A- Prodromal Phase
Nausea and vomiting are hallmarks of the
prodromal phase. Time to vomiting can range from
minutes to days following exposure.
More rapid onset suggests a higher absorbed dose.

8. In addition, other nonspecific health effects include
fever, headache, parotitis, abdominal cramping,
skin erythema, conjunctivitis and hypotension.
Symptoms typically last no more than 48 hours.

9. B- Latent Phase
Patients experience apparent clinical improvement
for a few hours or even up to a few weeks
postexposure as adverse health effects abate.
By this time, however, the reservoir of pluripotent
stem cells – whose function is to replace cells lost
through natural attrition – has been significantly
and critically depleted.

10. Adverse health effects associated with cellular loss
gradually appear, heralding the next phase of ARS.
The extent of the latent period is also dose-related.
It extends from hours or days at supralethal
exposures (greater than approximately 5 Gy) to a
few weeks at sublethal exposures (less than 2 Gy).

11. C- Manifest Illness
Adverse health effects that characterize the various
syndromes become apparent during the manifest
illness phase.
Their severity is influenced by such factors as the
magnitude of the absorbed dose, the overall body
volume irradiated, concomitant infection, trauma,
or dermal injury, underlying health status and age.

12. The manifest illness phase can last from days to
months.
D- Recovery or Death
The recovery process – generally slow – will last for
several weeks to years. High quality supportive care
can extend the lives of radiation exposure victims.
Very high dose radiation exposure will cause death
within days; at lower lethal levels of exposure,
patients may die within weeks or months.

13. Classic Syndromes of ARS
DOSE (GY) MANIFESTATION
1 to 2 Prodromal Symptoms
2 to 4 Mild hematopoietic
symptoms
4 to 7 Severe hematopoietic
symptoms.
7 to 15 Gastrointestinal symptoms
50 C.V.S. & C.N.S symptoms.

14. Prodromal Symptoms
The individual may develop:
Anorexia.
Nausea.
Vomiting.
Diarrhea.
Weakness.
Fatigue.

15. These early symptoms constitute the prodromal
period of the acute radiation syndrome.
Their cause is not clear but probably involves the
autonomic nervous system.

16. 1- Hematopoietic Syndrome
Whole-body exposures of 2 to 7 Gy cause injury to
the hematopoietic stem cells of the bone marrow
and spleen.
The rapidly dividing hematopoietic stem cells and
progenitor cells of the bone marrow are highly
sensitive to the effects of ionizing radiation.

17. As a consequence, doses in this range cause a
rapid and profound fall in the numbers of
circulating granulocytes, platelets, and finally
erythrocytes.
The mature circulating granulocytes, platelets,
and erythrocytes themselves are very
radioresistant, however, because they are
nonreplicating cells.

18. The differential changes in the blood count do not
all appear at the same time. Rather, the rate of fall
in the circulating levels of a cell depends on the life
span of that cell in the peripheral blood.
Granulocytes, with short lives in circulation, fall off
in a matter of days, whereas red blood cells, with
their long lives in circulation, fall off only slowly.

19. Clinical signs of the hematopoietic syndrome:
Infection (due to lymphopenia & granulocytopenia).
Hemorrhage (due to thrombocytopenia).
Anemia (due to erythrocyte depletion).
When death results from the hematopoietic syndrome,
it usually occurs 10 to 30 days after irradiation.

20. 2- Gastrointestinal Syndrome
Whole-body exposures in the range of 7 to 15 Gy
cause extensive damage to the gastrointestinal
system.
This damage, in addition to the hematopoietic
damage, causes signs and symptoms called the
gastrointestinasl syndrome.

21. Individuals exposed in this range may experience
the prodromal stage within a few hours of exposure.
Such exposure, however, causes considerable injury
to the rapidly proliferating basal epithelial cells of
the intestinal villi and leads to a loss of the
epithelial layer of the intestinal mucosa.

22. The turnover time for cells lining the small
intestine is normally 3 to 5 days.
Because of the denuded mucosal surface, plasma
and electrolytes are lost; efficient intestinal
absorption cannot occur.
Ulceration also occurs, with hemorrhaging of the
intestines.

23. All these changes are responsible for the diarrhea,
dehydration and loss of weight that are observed.
Endogenous intestinal bacteria readily invade the
denuded surface, producing septicemia.
At about the time that developing damage to the
gastrointestinal system reaches a maximum, the
effect of bone marrow depression is just beginning
to be manifested.

24. By the end of 24 hours, the number of circulating
lymphocytes falls to a very low level followed by
decreases in the number of granulocytes and then
of platelets.
The result is a marked lowering of the body's
defense against bacterial infection and a decrease
in effectiveness of the clotting mechanism.

25. The combined effects on these stem cell systems
cause death within 2 weeks from a combination of
factors.

26. 4- Cardiovascular and Central Nervous System
Syndrome
Exposures in excess of 50 Gy usually cause death
in 1 to 2 days.
Collapse of the circulatory system with a
precipitous fall in blood pressure in the hours
preceding death.

27. Intermittent stupor, incoordination, disorientation,
and convulsions suggestive of extensive damage to
the nervous system.
These symptoms result from radiation induced
damage to the neurons and fine vasculature of the
brain.

28. The syndrome is irreversible and the clinical course
may run from only a few minutes to about 48 hours
before death occurs.
The cardiovascular and central nervous system
syndromes have such a rapid course that the
irradiated individual dies before the effects of
damage to the bone marrow and gastrointestinal
system can develop.

29. Diagnosis
If a patient received more than 0.05 Gy (5 rads) and
three or four CBCs are taken within 8 to 12 hours
of the exposure, a quick estimate of the dose can be
made.
If these initial blood counts are not taken, the dose
can still be estimated by using CBC results over the
first few days.

30. It would be best to have radiation dosimetrists
conduct the dose assessment, if possible.
If a patient is known to have been or suspected of
having been exposed to a large radiation dose,
draw blood for CBC analysis with special attention
to the lymphocyte count, every 2 to 3 hours during
the first 8 hours after exposure (and every 4 to 6
hours for the next 2 days).

31. Observe the patient during this time for symptoms
and consult with radiation experts before ruling
out ARS.
Other indications are bleeding, epilation or white
blood count (WBC) and platelet counts abnormally
low a few days or weeks after unexplained nausea
and vomiting.
Again, consider CBC and chromosome analysis and
consultation with radiation experts to confirm
diagnosis.

32. Management of Acute Radiation Syndrome
Goals of medical management:
Obtaining a history and physical examination.
Removal of external contamination.
Dose estimation.
Supportive care (including psychological support
of the patient and family).
Symptomatic treatment.
Replacement of fluids and electrolytes.

33. Antibiotics are indicated when infection threatens
or the granulocyte count falls.
Fluid and electrolyte replacement is used as
necessary.
Whole blood transfusions are used to treat
anemia.
Platelets may be administered to arrest
thrombocytopenia.

34. Bone marrow grafts are indicated between
identical twins because there is no risk for graft-
versus-host disease.
Patients also receive such grafts when exposed to
8 to l0 Gy for treatment of leukemia.

35. References
Donnelly E. H et al Acute Radiation Syndrome:
Assessment and Management Southern Medical
Journal 2010;103:541-44.
White and Pharoah. Radiation Biology Oral
Radiology: Principles and Interpretation 5th edition
Mosby Publisher 2004;25-45.