Acute radiation syndrome

1. ACUTE EFFECTS OF TOTAL BODY IRRADIATION
Dr Kiran Kumar BR

2. • “Acute Radiation Syndrome (ARS) 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”- CDC

3. Radiation Sickness
• Accidental exposure to Ionizing
radiation
• whole body irradiation
• surface contact
• ingestion or
• inhalation of radioactive material
• Dependent on two factors:
• Absorbed dose (Gy)
• Rate of dose

4. TIMINGS OF EVENTS OF RADIATION
RESPONSE
10-6
10
-12
10-9
10-15
10-3
1 second
1 hour
1 day
1 year
100 years
1 ms
10
0
109
106
103
Energy deposition
Excitation/ionization
Initial particle tracks
Radical formation
PHYSICAL INTERACTIONS
PHYSICO-CHEMICAL INTERACTIONS
BIOLOGICAL RESPONSE
MEDICAL EFFECTS
Diffusion, chemical reactions
Initial DNA damage
DNA breaks / base damage
Repair processes
Damage fixation
Cell killing
Promotion/completion
Teratogenesis
Cancer
Hereditary defects
Proliferation of "damaged" cells
Mutations/transformations/aberrations
TIME(sec)

5. Factors affecting ARS
• Type of radiation eg Alpha,beta, Gamma, neutrons.
• Type of Exposure : Contamination & Irradiation ,
• Contamination may be internal contamination or external contamination
• Radiation Dose
• Duration of exposure
• Tissue radiosensitivity

6. The required conditions for Acute Radiation
Syndrome (ARS) are
• The radiation dose must be large (i.e., greater than 0.7 Gray (Gy) or
70 rads).
• Mild symptoms may be observed with doses as low as 0.3 Gy or 30
rads.
• The dose usually must be external ( i.e., the source of radiation is
outside of the patient’s body).
• Radioactive materials deposited inside the body have produced
some ARS effects only in extremely rare cases.
• The radiation must be penetrating (i.e., able to reach the internal
organs).
• High energy X-rays, gamma rays, and neutrons are penetrating
radiations.

7. • The entire body (or a 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 signs
of ARS.
• The dose must have been delivered in a short time (usually a
matter of minutes).
• Fractionated doses are often used in radiation therapy.
These are large total doses delivered in small daily amounts
over a period of time. Fractionated doses are less effective
at inducing ARS than a single dose of the same magnitude.

8. Dosage ;
• Threshold Dose : Depend on dose delivery mode:
• single high dose most effective
• fractionation increases threshold dose in most cases
significantly
• decreasing the dose rate increases threshold in most cases
• Threshold may differ in different persons
• Criteria of dose
• < 1 Gy: LOW DOSE
• 1-10 Gy: MODERATE DOSE
• > 10 Gy: HIGH DOSE
Lethal Dose
• It is an expression of the per cent lethal dose as a
function of time.
• It means: “Dose which would cause death to 50%
of the population in 30 days”.
• Its value is about 2-3 Gy for humans for whole body
irradiation

9. Sources of Data on Human Exposures
• Atomic bomb denonation and fall-out –survivors and there off springs
• Medical Exposures- such as patients receiving radiation therapy, prenatal X-ray
exposures
• Occupational Exposures- uranium miners, radium dial painters (1920’s), nuclear
dockyard workers, scientific researchers, nuclear material enrichment and
processing workers, diagnostic and therapeutic radiation workers.

11. Whole Body Exposure
ABSORBED DOSE (Gy) SYNDROME OR TISSUE
INVOLVED
SYMPTOMS
1-10 Bone Marrow syndrome Leucopenia,
thrombopenia,
hemorrhage, infections
10-50 GastroIntestinal
Syndrome
Diarrhoea, fever,
electrolytic imbalance
>50 Central Nervous
syndrome
Cramps, tremor, ataxia,
lethargy, impaired vision,
coma

12. Phases of Radiation Injury
Dose
(Gy)
Prodromal
Phase
Manifest Phase
Prognosis without
Supportive Care
0.5–1.0 Mild Modest decline in blood counts Survival
1.0–2.0 Mild–moderate Some bone marrow damage Survival >90%
2.0–3.5 Moderate
Moderate–severe bone marrow
damage
Probable survival
3.5–5.5 Severe
Severe bone marrow damage;
modest GI damage
Death within 3.5–6
wk (50% of victims)
5.5–7.5 Severe
Pancytopenia and moderate GI
damage
Death probable
within 2–3 wk
7.5–10.0 Severe
Severe GI and bone marrow
damage
Death probable
within 2 wk
10 Severe
Severe GI damage, radiation-
induced lung injury, altered mental
status; at higher doses (>20.0 Gy),
cardiovascular collapse, fever,
shock
Death within 2 wk
Ann Intern Med. 2004;140:1037–1051.

13. Phases of Radiation Sickness
• Prodromal Phase (N-V-D stage):
• Initial appearance of symptoms (nausea, vomiting, fatigue,
diarrhea, shock, ataxia, disorientation, etc.)
• Within a few hours and up to a week
• Latent Phase:
• Complete lack of illness/ symptoms for 1-4weeks
• Manifest illness/ Critical Phase:
• A relapse into severe symptomatology (GI, hematopoetic and
CNS syndromes)
• In extremely high doses (2-6 Gy), death within a few days.
• Recovery or death

14. Prodromal Syndrome
• Depends on size of dose
• Symptoms vary with respect to time of onset, maximum severity,
duration of exposure.
• Severe prodromal phase means poorer outcomes.
• Symptoms can be gastro intestinal nausea, vomiting, intestinal
cramps, diarrhea or neuro muscular such as easy fatigability, fever,
head ache and hypotension.
• At 50% Lethal dose gastrointestinal symptoms are commin while at
supra lethal dose neuromuscular symptoms prevail.

15. Hematopoietic Syndrome
• LD 50 -2.5-5 Gy , death , if it occurs, is a result of
radiation damage to hematopoietic system.
• Occurs upon irradiation of bone marrow inflicting
irreversible damage to the proliferative capacity of the
spleen and bone marrow
• Prodormal Phase nausea, vomiting and anorexia within
a few hours at the higher dose levels, or after 6 to 12
hours at the lower dose levels. Lasts 24 to 48 hours.
• Latent Phase : can last upto one month, depending on
dose received. Usually asymptomatic except for fatigue
and weakness.
• Manifestation : usually after 3 weeks, infections,
neutropenic fevers, bleeding, petechial hemorrhages.

16. • The number of circulating granulocytes, platelets and erythrocytes
decreases rapidly.
• Death occurs unless the bone marrow begins to regenerate.
Infections is an important cause of death.
• Peak incidence of deaths from HPS occurs 30 days after exposure,
although deaths continue till 60 days.

18. Typical hematologic course and clinical stages after sublethal (~3 Gy) exposure to total-body
irradiation

19. Gastrointestinal syndrome
• Lethal dose 50 7-15 Gy
• immediate, prompt and profuse onset of nausea,
vomiting and diarrhea, followed by a short latent
period.
• Death occurs due to destruction of intestinal villi ,
basal epithelial cells.
• The surface gets rapidly infected; combined with
Hematopoietic syndrome, septicemia and death
occur invariably

21. • Dose of radiation in magnitude of 10Gy sterilizes large population of
dividing cells in the crypts
• Vili and differentiated cells are not affected in a dose of this order
• As the vili get sloughed off, no replacement cells produced in the
crypt, consequently intestine is denuded of vili.
• GI mucosa becomes increasingly atrophic, Plasma and electrolytes are
lost into the intestines, hemorrhages and ulcerations occur, resulting
in marked dehydration and vascular effects

22. Manifestation
• Malabsorption--- Malnutrition
• Fluid and elctrolye imbalance--- Dehydration, ARF,
cardiovascular collapse
• GI bleed --- Anaemia
• Sepsis
• Paralytic Illeus

23. • Death in humans usually after 9-10 days following irradiation.
• All individuals who receives a dose large enough for gastrointestinal
to result in death have already received far more than enough
radiation to result in hematopoetic death.

24. Cardiovascular Syndrome
• >30 Gy
• Always fatal, there is immediate nausea,
vomiting, anorexia and prostration, and
irreversible hypotension; blood pressure will
be markedly unstable.
• Within hours after exposure, the victim will
be listless, drowsy, tremulous, convulsive,
and ataxic.
• Death most likely will occur within a matter
of days.

25. CNS syndrome
• > 50 Gy
• Increased pressure in the confining cranial
vault as the result of increased fluid content
caused by edema, vasculitis, and meningitis
• Uncoordinated movements, disorientation
and convulsions
• Due to damage to the neurons and brain
vasculature
• Death occurs in 1-2 days.

26. • Chronology of events:
• Severe nausea vomiting with matterof minutes
• Disorientation, loss of co-ordination of muscular movements,
• Respiratory distress, diarrhea, convulsive seizures,coma and death

27. Cutaneous Radiation Syndrome
(CRS)
Atrophy and necrosis of
skin layers results in a
complete disintegration
of the dermal vascular
system

28. • Radiation injury to skin caused by non penetrating beta particles or
low energy photons. Injury may b also seen in absence of ARS.
• Can occur at doses of 2Gy
• Sources : contact with unsecured radiation sources from food
irradiators, radiotherapy equipment, or well depth gauges. In
addition, cases of CRI have occurred in people who were overexposed
to x-radiation from fluoroscopy units.
• Symptoms include tingling to itching
• Signs : erythema, epilation, edema, dry desquamation to wet
desquamation, ulceration and necrosis as dose increased.

29. • Prodromal stage (within hours of exposure)—This stage is
characterized by early erythema (first wave of erythema), heat
sensations, and itching that define the exposure area. The duration of
this stage is from 1 to 2 days.
• Latent stage (1–2 days postexposure)—No injury is evident.
Depending on the body part, the larger the dose, the shorter this
period will last. The skin of the face, chest, and neck will have a
shorter latent stage than the skin of the palms of the hands or the
soles of the feet.

30. • Manifest illness stage (days to weeks postexposure)—The basal layer
is repopulated through proliferation of surviving clonogenic cells. This
stage begins with erythema (second wave), a sense of heat, and slight
edema, which are often accompanied by increased pigmentation. The
symptoms that follow vary from dry desquamation or ulceration to
necrosis, depending on the severity of the CRI .
• Third wave of erythema (10–16 weeks postexposure, especially after
beta exposure)—The exposed person experiences late erythema,
injury to blood vessels, edema, and increasing pain. A distinct bluish
color of the skin can be observed. Epilation may subside, but new
ulcers, dermal necrosis, and dermal atrophy (and thinning of the
dermis layer) are possible.

31. Other effects
• Temporary hair loss (2-6 Gy)
• Sterility (Males ~ 4 Gy; Females >6.25 Gy)
• Cataractogenesis (doses > 2Gy damage anterior epithelial cells in eye)
• Fatal pneumonitis (acute lung exposure)
• Nephritis (> 20 Gy)
• Increased Cardiovascular disease prevalence

32. SPECIFIC ORGAN SYSTEMS
& RELATED DAMAGE
HIGH RS MIDDLE RS LOW RS
•Bone Marrow
•Spleen
•Thymus
•Lymphatic nodes
•Gonads
•Eye lens
•Lymphocytes
•Skin
•Mesoderm organs
(liver, heart,
lungs…)
•Muscle
•Bones
•Nervous system