Acute radiation syndrome (ARS) or acute radiation sickness is an acute illness caused by irradiation of the entire body (or most of the body) by a high dose 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. Classically, acute radiation syndrome is subdivided into three sub-syndromes: the hematopoietic syndrome, the gastrointestinal syndrome, the cerebrovascular syndrome others include : pulmonary syndrome, cutaneous radiation injury radiation-induced multi organ dysfunction (failure) syndrome.

1. ACUTE RADIATION SYNDROME
PRESENTER: DR. MONICA P

2. • Acute radiation syndrome (ARS) or acute radiation sickness is an acute illness
caused by irradiation of the entire body (or most of the body) by a high dose
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.
• The signs and symptoms are the consequences of severe radiation damage to
specific tissues of specific organs (mono-organ involvement) although many
tissues can be damaged (multi-organ involvement).
• The first description of acute radiation syndrome was made by De-Coursey after
atomic bomb explosions in Japan during World War II in 1945.

3. • The accidental exposure to ionizing
radiation can be:
o Whole body irradiation
o Surface contact
o Ingestion or
o Inhalation of radioactive material
• ARS depends on two factors mainly :
o Absorbed dose (Gy)
o Rate of dose

4. • Factors affecting ARS are:
 Type of radiation : Alpha, Beta, Gamma, Neutrons
 Type of exposure : Contamination and irradiation
 Contamination may be internal or external
 Radiation dose
 Duration of exposure
 Tissue radio sensitivity

5. • The required conditions for ARS are:
o Radiation dose must be large ( > 0.7Gy or 70rads)
 Mild symptoms may be observed with low doses as low as 0.3Gy
o The dose usually must be external (source of radiation is outside the patient’s
body)
 Radioactive materials deposited inside the body have produced some ARS
effects only in extremely rare cases.
o The radiation must be penetrating (so that it can reach the internal organs to
cause damage)
 High energy X-rays, Gamma rays and Neutrons are penetrating radiations.

6. o The entire body or significant portion of it must have received the dose
 Most radiation injuries are local, frequently involving the hands, and these local
injuries seldom cause classical sign of ARS.
o The dose must have been delivered in a short time (usually within a matter of
minutes)
 Fractionated dose are often used in radiation therapy. These are large doses delivered
in small daily amount over a period of time.
 Fractionated doses are less effective at inducing ARS than a single dose of the same
magnitude.

7. Threshold dose Lethal dose
• It depends on dose delivery mode:
o Fractionation increases threshold
dose in most cases significantly
o Single high dose is most effective
o Decreasing the dose rate increases
threshold in most cases
• It is an expression of the percent
lethal dose as a function of time
• Dose which could cause death to
50% of the population in 30days
It may differ in different persons Its value is about 2-3Gy for humans
for whole body irradiation
Criteria of dose:
 <1Gy LOW DOSE
 1-10Gy MODERATE DOSE
 >10Gy HIGH DOSE
• Dosage :

8. • Data on the various forms of acute radiation syndrome in human population
have been obtained by studies of:
 Atomic bomb survivors of Hiroshima and Nagasaki
 The Marshall islanders who were accidentally exposed to high levels of fallout
during an atomic bomb test in 1954
 Nuclear radiation accident victims – examples : Chernobyl accident and
Tokaimura accident in Japan
 Medical exposure : Radiation therapy patients, prenatal X-ray exposures
 Occupational exposures : uranium miners, radium dial painters(1920’s). Nuclear
dockyard workers scientific researches, nuclear material enrichment and
processing workers, diagnostic and therapeutic radiation workers.
• From these studies, the pattern of events that follows after total body exposure to
a dose of ionizing radiation has been well documented.

9. EARLY LETHAL EFFECTS
• Early radiation lethality means death occurs within a few weeks after exposure to a
specific high intensity radiation.
• The early radiation responses are described as deterministic.
• These deterministic radiation responses exhibit increasing severity with increasing
radiation dose.
• There are four clinical phases in the development of radiation sickness:
1. Prodromal syndrome
2. Latent period
3. Manifest illness
4. Recovery or death

10. • Classically, acute radiation syndrome is subdivided into three sub-syndromes:
 the hematopoietic syndrome,
 the gastrointestinal syndrome and
 the cerebrovascular syndrome
• others include :
 pulmonary syndrome
 cutaneous radiation injury
 radiation-induced multi organ dysfunction (failure) syndrome

11. • THE PRODROMAL RADIATION SYNDROME :
o initial phase of acute illness
o the various symptoms in this phase vary with respect to time of onset, maximum
severity, duration and depending on the size of the dose.
o With the doses of a few tens of Gray, all exposed individuals are expected to show
all phases of the syndrome within 5 to 15min of exposure.
o Reaction might reach a maximum by about 30min and persist for a few days,
gradually diminishing in intensity until they merge with either cerebrovascular
syndrome or gastrointestinal syndrome in lower dose.

12. • In prodromal radiation syndrome, signs and symptoms are mainly divided into :
1. Gastrointestinal symptoms - anorexia, nausea, vomiting, diarrhoea, intestinal cramps,
salivation, fluid loss, dehydration, and weight loss
2. Neuromuscular symptoms - easy fatigability, apathy or listlessness, sweating, fever,
headache and hypotension

13. • The symptoms occur at normal dose, LD50 and supra lethal dose.
• LD50 is the dose necessary to kill 50% of the exposed population.
Normal dose LD50 Supra lethal dose
Neuromuscular
symptoms
• Easy fatigability
• Apathy
• Sweating
• Fever
• Headache
• Hypotension
• Easy fatigability • Fever
• Hypotension
Gastrointestinal
symptoms
• Anorexia
• Nausea
• Vomiting
• Diarrhoea
• Intestinal cramps
• Salivation
• Fluid loss
• Dehydration
• Weight loss
• Anorexia
• Nausea
• Vomiting
• Immediate diarrhoea

14. • LATENT PERIOD :
o During this period, no visible symptoms are found because, in this period either
recovery or lethal effects begin.
o The duration of latent period is inversely proportional to the dose, and may last a
few hours for high exposures or as long as 2 or more weeks for lower exposures.
o Absence of latent phase implies - progressive worsening from prodromal
syndrome directly into the manifest illness phase. (this is seen in very high dose
exposures)
o Towards the end of the week, the next stage begins.

15. • MANIFEST ILLNESS :
o Also known as Critical phase
o It is the third phase of ARS, where the symptoms that affect the hematopoietic,
gastrointestinal and cerebrovascular systems become visible.
o In severe high-dose cases (2-6Gy), emaciated human beings eventually die within a
few days.

16. • REPAIR AND RECOVERY :
o When cells are exposed to sub lethal doses of ionizing radiation,
Because of repair mechanism in the cells by repair enzymes
Repair and recovery may occur.

17. o After irradiation, surviving cells begin to repopulate.
o Repopulation allows an organ that has sustained functional damage as a result of
radiation exposure to regain some or most of its functional ability.
o However, the amount of functional damage sustained determines the organ’s
potential for recovery.
• Research has shown that repeated radiation injuries have a cumulative effect. Hence
a percentage of about 10% of the radiation-induced damage is irreparable, whereas
the remaining 90% may be repaired over time. When the processes of repair and
repopulation work together, they help in healing the body from radiation injury and
promote recovery.

18. • According to Medical Treatment Protocols for Radiation Accident
(METREPOL) , syndromes of ARS are in following sequence:
 Haematopoietic syndrome
 Cutaneous syndrome
 Gastrointestinal syndrome
 Cerebrovascular syndrome

19. HEMATOPOIETIC SYNDROME
 It occurs at exposure to dose range of : 2.5Gy to 5Gy
 It is also known as Bone marrow syndrome
 The hematopoietic system manufactures the corpuscular elements of the blood
and is the most radiosensitive vital organ system in humans.

20.  Radiation exposure causes the decrease
in number of RBCs, WBCs and
platelets in the circulating blood.
 Dose levels that cause this syndrome
also may damage cells in other organ
systems, causing the affected organ or
organ system to fail.
 The patient initially experiences mild
symptoms of the prodromal syndrome,
which appear in a matter of a few hours
and may persist for several days.

21. Prodromal phase
symptoms
Latent phase Manifest illness phase Recovery
• Anorexia
• Nausea
• Vomiting
In this phase, stem
cells in bone
marrow are dying
• Anorexia
• Fever (neutropenic
fevers)
• Malaise
• Infections
• Bleeding
• Petechial haemorrhages
• In most cases, bone
marrow cells begins
to repopulate the
marrow
Onset occurs 1hr to
2days after
exposure
Patient may appear
and feel well
usually except for
fatigue and
weakness
Here there is drop in all blood
cell counts, occurs for several
weeks
Full recovery is seen for
a large percentage of
individuals from a few
weeks up to 2 years after
exposure
Lasts for minutes to
days
Lasts for 1 week to
6weeks
Primary cause of death :
Infection and Haemorrhage
Survival decreases with
increasing dose
Most death occurs within 1-
2months after exposure
The LD 50/60 is about
2.5Gy to 5Gy

22. Medical management of hematopoietic syndrome :
• Granulocyte macrophage stimulating factor (GM-CSF) – Sargramostim
(Leukine)
• Granulocyte colony stimulating factor (G-CSF) – Filgastrim (Neupogen)
• Interleukin series (IL 1-16)
• Platelet support
• Thrombopoietin
• Erythropoietin
• Antibiotics
• Bone marrow transplant

23. CUTANEOUS RADIATION SYNDROME
 The concept of Cutaneous radiation syndrome (CRS) was introduced in
recent years to describe the complex pathological syndrome that results from
acute radiation exposure to the skin
 It can occur at doses of 2Gy (may also be seen in absence of ARS)

24.  Sources of CRS :
 Contact with unsecured radiation sources
from food irradiators
 Radiotherapy equipment
 Well depth gauges
 Overexposure to X-rays from fluoroscopy
units.

25.  ARS usually will be accompanied by some skin damage
 It is also possible to receive a damaging dose to the skin without symptoms of
ARS especially with acute exposures to beta radiation or X-rays.
 Sometimes this occurs when radioactive materials contaminate a patient’s skin or
clothes.

26. Prodromal stage Latent stage Manifest illness stage Third wave of
erythema
Other effects
• Occurs within
hours of
exposure
• Characterized
by
o Early
erythema(first
wave of
erythema)
o Heat sensations
o Itching that
defines the
exposure area
• Duration – 1 to 2
days
• Occurs within 1-2
days post exposure
• No injury is evident
• Depending on the
part of the body:
larger the dose,
shorter is the latent
period
• Skin of face, chest,
neck have short
latent stage than the
skin of the palms of
the hands or soles of
the feet.
• Occurs within days
to weeks post
exposure
• The basal layer is
repopulated
through
proliferation of
surviving
clonogenic cells.
• It begins with:
o Erythema (second
wave )
o Sense of heat
o Slight edema
o Often
accompanied by
hyperpigmentation
o Dry desquamation
o Ulceration
o necrosis
• Occurs within 10-
16weeks post
exposure
• Seen especially
after beta exposure
• The patient
experiences:
o Late erythema
o Injury to blood
vessels
o Edema
o Increasing pain
o A distinct bluish
color of the skin is
observed
o Epilation may
subside but new
ulcers, dermal
necrosis and
dermal atrophy
may develop.
• Temporary hair loss
(2-6Gy)
• Sterility (males-
~4Gy ; females
>6.25Gy)
• Cataractogenesis
(>2Gy damages the
anterior epithelial
cells in eye)
• Fatal pneumonitis
(acute lung
exposure)
• Nephritis (>20Gy)
• Increased
cardiovascular
disease prevalence

28. • When the Basal cell
layer of skin is damaged
by radiation
INFLAMMATION
ERYTHEMA
DRY/MOIST
DESQUAMATION
Mechanism of action in CRS :
Hair follicles may be
damaged
EPILATION
Latent phase may occur and last
for a few days up to several weeks
and then the following are visible
TRANSIENT AND
INCONSISTENT
ERYTHEMA
OCCURS
ASSOCIATED
WITH ITCHING
Within few hours
after irradiation
INTENSE REDDENING
BLISTERING
ULCERATION OF THE
IRRADIATED SITE

29. • Medical management of CRS :
o Anti-inflammatory
o Glucocorticoids
o Antihistamines

30. GASTROINTESTINAL SYNDROME
 In human beings, the gastrointestinal form of ARS appears at a threshold dose of
approximately 6Gy and peaks after a dose of 10Gy
 Without medical support to sustain life, exposed persons receiving doses of 6 – 10Gy
may die 3 to 10 days post exposure.
 Even if medical support is provided, the exposed
person will live only a few days longer.
 Survival time dose not change with dose
in this syndrome.

31. Prodromal stage Latent period Manifest illness Recovery
• Occurs a few hours
after the dose required
to cause this syndrome
has been received
• Stem cells in bone
marrow and cells
lining GI tract are
dying
• But patient appears
and fell well
• Here, the patient again experiences
symptoms.
• Death occurs primarily because of
catastrophic damage to the epithelial cells
that line the GIT
• The LD 100
is about
10Gy
• Anorexia
• Severe nausea
• Vomiting
• Cramps
• diarrhoea
• Malaise
• Severe diarrhoea
• Fever
• Malabsorption  malnutrition
• Electrolyte imbalance  dehydration, ARF,
cardiovascular collapse
• GI bleed  anaemia
• Sepsis
• Paralytic ileus
• Death is because of infection(septicaemia),
combined with hematopoietic syndrome,
fluid loss or electrolyte imbalance
• Lasts about 2days Lasts for < 1week Death occurs within 3-12 days of exposure

32. Mechanism of action:
• The small intestine is the most severely affected part of the GI tract.
• Because epithelial cells function as an essential biologic barrier, their breakdown
leaves the body vulnerable to infection (mostly from its own intestinal bacteria),
haemorrhage occurs through denuded areas, loss of absorptive capacity causes
dehydration and severe diarrhoea.
• Some epithelial cells regenerate before death occurs.
• However, because of the large number of epithelial cells damaged by the radiation,
death may occur before cell regeneration is accomplished.
• The workers and firefighters at Chernobyl are examples of humans who died as a
result of Gastrointestinal syndrome.

33. • Medical management of gastrointestinal syndrome:
o Antibiotics
o Sucralfate and prostaglandin
o Cytokine G-CSF
o Immunoglobulins (IgG)

34. CEREBROVASCULAR SYNDROME
• The cerebrovascular form of the ARS results when the central nervous system and
cardiovascular system receive doses of 100Gy or more of ionizing radiation.
• A dose of this magnitude can cause death within a few hours to 2 or 3 days after the
exposure.

35. Prodromal stage Latent stage Manifest illness stage Recovery
• Symptoms:
• Extreme
nervousness
• Confusion
• Severe nausea &
vomiting
• Watery diarrhoea
• Loss of
consciousness
• Burning sensations
of the skin
• Patient may return
to partial
functionality.
• Symptoms:
• Return of watery diarrhoea,
convulsions and coma.
• Death occurs within 24-
48hours of exposure.
No recovery is
expected.
Onset occurs within
minutes of exposure.
Lasts for minutes to
hours.
Lasts for hours but
often is less.
Onset occurs 5-6hours after
exposure.

36. Severe nausea and
vomiting (within
matter of minutes)
Disorientation
Loss of co-ordination
of muscular
movements
Respiratory distress
Diarrhea
Convulsive seizures
Coma
Death
Chronology of events occurring :

37. Mechanism of action of cerebrovascular syndrome
Damaged blood vessels and permeable capillaries permit fluid to
leak into the brain, causing an increase in fluid content.
This creates an increase in Intracranial pressure (ICT)
It causes more tissue damage
The final result of this damage is failure of CNS and CVS
And causes death in a matter of minutes

38. • Medical management :
• Glucocorticoids
• Electrolyte compensation
• Mannitol

39. PULMONARY SYNDROME
• In recent years, a few individuals exposed to 8Gy or more and who survived
haematopoietic syndrome as a result of intensive treatment with antibiotics,
blood transfusions and haematopoietic growth factors, died much later at
130days after irradiation with inflammatory pneumonitis.

41. Summary

42. Specific organ systems and related damage :

43. Examples :
1. Former Russian spy, Alexander Litvinenko , is the first known
victim to be poisoned with Polonium-210 and to die from the
resulting radiation sickness.
• He died on Nov 23, 3 weeks after he fell ill in London.
• The symptoms he had were characteristic to haematopoietic
syndrome: hair loss, erythema, and death caused by loss of
circulating blood elements.
2. The first person to die of the ARS was a 26yrs old male involved in
a criticality accident at Los Alamos in March 1945.
• He was exposed total body to a mixture of neutrons and gamma
rays , estimated dose being 6.35Sv.
• His right hand received 200Gy, and left hand received 30Gy
• He died on day 24 with WBCs close to zero.

44. 3. In 1964, a 38yrs old man working in a Uranium-235 recovery plant was
involved in an accidental nuclear excursion.
• He received total body dose of 88Gy (22Gy neutrons and 66Gy gamma rays)
• He had developed symptoms within minutes: abdominal cramps, headache,
vomiting and bloody diarrhoeal stools
• 24hrs later, he was comfortable but restless
• On 2nd day, he was disoriented, restless, fatigued, apprehensive, short of
breath, impaired vision
• 6hrs before his death, he was disoriented
• Died after 49hrs after exposure.

45. TRIAGE
• Following an event in which several individuals are exposed to radiation, an
immediate need is to know what doses are involved.
• The possibilities are:
o Average time to emesis decreases with increasing dose.
o The decline in the lymphocyte count allows an estimate to be made of the total
body radiation exposure.
o If a cytogenetic laboratory is available, the best method to assess radiation
exposure is to measure the incidence of chromosomal aberrations in peripheral
lymphocytes stimulated to divide in vitro. Doses of >0.2Gy can be accurately
assessed. At high doses, as lymphocytes disappear, this technique is not
possible to use.

46. Assessment of bio-dosimetry methods for radiological incident :
1. Haematological bio dosimetry
2. Cytogenetic bio dosimetry
3. DNA damage assays
4. Emerging methods- “omic” assays
5. Bio-physically based dosimetry

47. Haematological bio-dosimetry
• Lymphocyte depletion kinetic assay
• Ratio of neutrophils to lymphocytes

48. Cytogenetic bio-dosimetry
• Dicentric chromosome assay
• Premature chromosome condensation assay
DNA damage assays
• Gamma-H2AX foci assay
• Cytokinesis block micronucleus assay (CBMN)

49. Emerging methods- “omic” assays
• Gene expression biomarkers
• MicroRNA expression
• Protein biomarkers
• Metabolic biomarkers
Bio-physically based dosimetry
• Electron paramagnetic resonance
• Optically stimulated luminescence (OSL)

52. Radiation Emergency Assistance Center
• Radiation Emergency Assistance Center/Training Site (REAC/TS) is a
Medical Science Division of the Oak Ridge Institute for Science and
Education, operated on behalf of US Department of Energy.
• It provides 24hr direct or consultative assistance with medical and health
physics problems associated with radiation accidents in local, national and
international incidents.
• The resources of REAC/TS consist of expertise in cytogenetics for dose
assessments, calculation of doses from internally deposited radionuclides,
and laboratory facilities that include total body counting capabilities.
• Website: www.orau.gov/reacts

53. CONCLUSION
 prodromal symptoms varies in time
of onset, severity and duration
 At dose close to LD50, principal
symptoms of prodromal syndrome:
anorexia, nausea, vomiting and easy
fatigability.
 Immediate diarrhoea, fever or
hypotension : indicates supra-lethal
exposure

54. Syndrome Cerebrovascular Gastrointestinal Haematopoietic Pulmonary
Total body
exposure
About 100Gy of
gamma rays
About 10Gy 2.5 to 5Gy 8Gy or more
Death occurs in: 24-48hrs 7-10days 3 or more weeks
later
130days (in those
who survived
haematopoietic
syndrome)
Cause of death Changes in
permeability of
small blood vessels
in the brain
following damage
to the
microvasculature
Depopulation of
the epithelial
lining of the GI
tract
Lack of circulating
blood elements
Inflammatory
pneumonitis
These syndromes may be complicated by damage to the skin from high local doses.

56.  The LD50 for humans is estimated to be between 3 and 4Gy for young adults
without medical interventions. It may be less for very young or very old .
 The LD50 may be raised to 7Gy by the use of antibiotics, as in Chernobyl
case.
 Intense counter measures including antibiotics, infusions, and haematopoietic
growth factors may increase the LD50 for the haematopoietic syndrome to as
much as 8 to 9Gy.
 Worldwide, about 400 individuals have suffered from the ARS.