Biological Effects of Ionizing Radiation Deterministic effects Acute radiation syndrome Lecture IAEA Post Graduate Educational Course Radiation Protection

Biological Effects of Ionizing RadiationBiological Effects of Ionizing RadiationDeterministic effectsDeterministic effects

Acute radiation syndromeAcute radiation syndromeLectureLecture

IAEA Post Graduate Educational Course Radiation Protection and Safe Use of Radiation Sources

IAEA Post Graduate Educational Course in Radiation Protection and Safety of Radiation Sources

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IntroductionIntroduction

Acute radiation syndrome (ARS) - the Acute radiation syndrome (ARS) - the combination of syndromes that combination of syndromes that occur after whole-body irradiationoccur after whole-body irradiation

ARS consists of the signs and ARS consists of the signs and symptomssymptoms

Severity of ARS depends on different Severity of ARS depends on different factorsfactors


ContentContent

Definition of the ARSDefinition of the ARS Stages of ARS (timing, dose Stages of ARS (timing, dose

dependence)dependence) Symptoms and signs for every stageSymptoms and signs for every stage Hematopoietic, gastrointestinal, Hematopoietic, gastrointestinal,

cerebrovascular/nervous syndromescerebrovascular/nervous syndromes Management of ARS Management of ARS


Overview Overview

Radiation Radiation DoseDose, , Gy Gy

SyndromeSyndrome

1-51-5 HematopoieticHematopoietic

6-106-10 GastrointestinalGastrointestinal

>10>10 Cerebrovascular/Cerebrovascular/

Central Nervous SystemCentral Nervous System


Stages of the ARSStages of the ARS

1.1. Initial or prodromalInitial or prodromalSigns and symptoms occur within Signs and symptoms occur within minutes,minutes, hours, or day of exposurehours, or day of exposure

2.2. LatentLatentPPatient feels relatively wellatient feels relatively well

3.3. Manifest illnessManifest illnessLLasting from days to weeks depending asting from days to weeks depending upon magnitude of the dose upon magnitude of the dose

4.4. RecoveryRecoverySigns and sySigns and symmptoms begin to subsideptoms begin to subside


Initial or Prodromal stageInitial or Prodromal stage

Symptoms:Symptoms: FatigueFatigue AnorexiaAnorexia VomitingVomiting DiarrhoeaDiarrhoea Water/electrolyte Water/electrolyte

leakageleakage Cardiocirculatory Cardiocirculatory

dysfunctiondysfunction HyperthermiaHyperthermia Early erythemaEarly erythema

Appearance: Appearance: After high dose After high dose

exposure – within a exposure – within a few hoursfew hours

After low dose After low dose exposure – after 6-12 exposure – after 6-12 hourshours

Lasting:Lasting: 24-48 hours24-48 hours


FatigueFatigue Tiredness – the first sign following radiationTiredness – the first sign following radiation Fatigue may include severe apathy, Fatigue may include severe apathy,

prostration, sleep disorders, day-time prostration, sleep disorders, day-time drowsiness, night-time insomniadrowsiness, night-time insomnia

Exposure in a dose of 1.5 Gy – 30% subjects Exposure in a dose of 1.5 Gy – 30% subjects have the symptomhave the symptom

Exposure in a dose close to Exposure in a dose close to LDLD50/3050/30– 90% – 90% subjects have the symptomsubjects have the symptom

Symptom is not a reliable prognostic Symptom is not a reliable prognostic criterioncriterion


AnorexiaAnorexia

Is a precursor of gastrointestinal distressIs a precursor of gastrointestinal distress Occurs in the first 2 hours after exposureOccurs in the first 2 hours after exposure Is characterized by nausea, accompanied Is characterized by nausea, accompanied

by dry mouth and a metallic taste by dry mouth and a metallic taste Exposure in a dose of 1.5 Gy – 50% Exposure in a dose of 1.5 Gy – 50%

subjects have the symptomsubjects have the symptom Exposure in a dose close to Exposure in a dose close to LDLD50/3050/30– 100% – 100%

subjects have the symptomsubjects have the symptom


VomitingVomiting

Is developed at doses of less than 1 Is developed at doses of less than 1 GyGy

The time to onset, the duration and The time to onset, the duration and multiplicity depend overall on the multiplicity depend overall on the dose receiveddose received

The precursors of vomiting are The precursors of vomiting are ptyalism, tachycardia, mydriasis, ptyalism, tachycardia, mydriasis, retchingretching


DiarrhoeaDiarrhoea

Aetiology is poorly understoodAetiology is poorly understood Is a prodromal sign only at a Is a prodromal sign only at a

supralethal doses supralethal doses After radiotherapy at a dose of 7.5 – After radiotherapy at a dose of 7.5 –

10 Gy to an abdominal field – 10% of 10 Gy to an abdominal field – 10% of the subjects develop early the subjects develop early diarrhoea diarrhoea


Disorders related to Disorders related to cardiocirculatory dysfunctioncardiocirculatory dysfunction

At At supralethal doses - circulatory supralethal doses - circulatory shockshock Reason: inability to maintain blood Reason: inability to maintain blood

pressurepressure At low doses exposure – death could At low doses exposure – death could

be related with myocardial infarction be related with myocardial infarction At a dose about 10 Gy – hypotensionAt a dose about 10 Gy – hypotension

Severity increases with doseSeverity increases with dose


Hyperthermia & Early erythemaHyperthermia & Early erythema

Fever:Fever: At supralethal doses develops earlyAt supralethal doses develops early Is accompanied by sweating, severe headache Is accompanied by sweating, severe headache

Early erythemaEarly erythema One of the signs of the radiation-induced One of the signs of the radiation-induced

inflammatory processinflammatory process Develops at doses of 6 Gy or more (whole-body Develops at doses of 6 Gy or more (whole-body

gamma irradiation)gamma irradiation) Develops at between 4 and 24 hours post-Develops at between 4 and 24 hours post-

exposureexposure May last 2 weeksMay last 2 weeks


Timing of Prodromal stageTiming of Prodromal stage

Dose, GyDose, Gy OnsetOnset DurationDuration

0.5-2.00.5-2.0 None to 6 hrsNone to 6 hrs << 24 hrs 24 hrs

2.0-3.52.0-3.5 2-6 hrs2-6 hrs 12-24 hrs12-24 hrs

3.5-5.53.5-5.5 1-2 hrs1-2 hrs 24+ hrs24+ hrs

>>5.55.5 Min to 1 hrsMin to 1 hrs 48 hrs48 hrs


Latent stageLatent stage

Dose, GyDose, Gy DurationDuration

0.5-2.00.5-2.0 Up to 3 weeksUp to 3 weeks

2.0-3.52.0-3.5 2-3 weeks2-3 weeks

3.5-5.53.5-5.5 1.0-2.5 weeks1.0-2.5 weeks

>>5.55.5 2-4 days2-4 days


Stage of manifest illnessStage of manifest illness

Haematopoietic syndromeHaematopoietic syndrome Gastrointestinal syndromeGastrointestinal syndrome Cardiovascular / Neurovascular Cardiovascular / Neurovascular

syndromesyndrome Associated symptomsAssociated symptoms


Haematopoietic syndromeHaematopoietic syndrome

Hematopoietic syndrome Hematopoietic syndrome characterized bycharacterized by:: deficiencies of WBC, lymphocytes and deficiencies of WBC, lymphocytes and

platelets, platelets, immunodeficiency, immunodeficiency, inincreased infectious complications, creased infectious complications, bleeding, anaemia, and bleeding, anaemia, and impaired wound healingimpaired wound healing


Gastrointestinal syndromeGastrointestinal syndrome

Gastrointestinal syndrome characterized Gastrointestinal syndrome characterized byby:: loss of cells lining intestinal cryptsloss of cells lining intestinal crypts,, loss of mucosal barrier, loss of mucosal barrier, alterations in intestinal motility, alterations in intestinal motility, fluid and electrolyte lossfluid and electrolyte loss,, vomiting and diarrhoea, vomiting and diarrhoea, loss of normal intestinal bacteria, loss of normal intestinal bacteria, sepsis, and sepsis, and damage to the intestinal microcirculationdamage to the intestinal microcirculation


Cerebrovascular/Central Nervous Cerebrovascular/Central Nervous System syndromeSystem syndrome Cerebrovascular/Central Nervous System Cerebrovascular/Central Nervous System

syndrome - primarily associated with syndrome - primarily associated with effects on the vasculature and resultant effects on the vasculature and resultant fluid shiftsfluid shifts

Signs and symptoms includeSigns and symptoms include:: vomiting and diarrhoea within minutes of vomiting and diarrhoea within minutes of

exposure, exposure, confusion, confusion, disorientation, disorientation, cerebral oedema, cerebral oedema, hypotension, and hypotension, and hyperpyrexiahyperpyrexia


Associated symptomsAssociated symptoms

Skin syndromeSkin syndrome loss of epidermis (and possibly dermis) with loss of epidermis (and possibly dermis) with

"radiation burns""radiation burns" Oropharyngeal symptomsOropharyngeal symptoms

lesions of the oral mucosalesions of the oral mucosa Lesions of the lungsLesions of the lungs

disorders of vascular permeability,disorders of vascular permeability, disturbances of the fluid balance, disturbances of the fluid balance, infection, and infection, and inhalation of smoke and radioactive inhalation of smoke and radioactive

substancessubstances


Management of ARSManagement of ARS

Management of severityManagement of severity Prodromal effectsProdromal effects

Time of onset Degree of symptoms Duration of symptoms

Hematological changesHematological changes Lymphocyte counts

Physical dosimetryPhysical dosimetry If available


ARS: ARS: ddose ose lless ess tthan 2 Gy han 2 Gy

Management of ARS (dose <2 Gy):Management of ARS (dose <2 Gy): Close observation and frequent CBC Close observation and frequent CBC

with differentialwith differential Outpatient management may be Outpatient management may be

appropriateappropriate Provide instructions regarding home Provide instructions regarding home

carecare


ARSARS: : dose greater tdose greater than 2 Gyhan 2 Gy

Peculiarities of the Peculiarities of the Hematopoietic Hematopoietic Syndrome:Syndrome: The prodromal phase The prodromal phase The latent phaseThe latent phase A bone marrow depression phaseA bone marrow depression phase The recovery phaseThe recovery phase



Gastrointestinal Syndrome:Gastrointestinal Syndrome: Over 10 Gy - this syndrome is Over 10 Gy - this syndrome is

distinguishable from the hematopoietic distinguishable from the hematopoietic syndrome by the immediate, prompt syndrome by the immediate, prompt and profuse onset of nausea, vomiting and profuse onset of nausea, vomiting and diarrhoea, followed by a short latent and diarrhoea, followed by a short latent periodperiod



Cardiovascular Syndrome:Cardiovascular Syndrome: Over 30 Gy, an extremely high dose, to Over 30 Gy, an extremely high dose, to

the whole-body. Always fatal, there is the whole-body. Always fatal, there is immediate nausea, vomiting, anorexia immediate nausea, vomiting, anorexia and prostration, and irreversible and prostration, and irreversible hypotension; blood pressure will be hypotension; blood pressure will be markedly unstable. markedly unstable.


Acute Radiation Syndrome: Dose Acute Radiation Syndrome: Dose GreaterGreater Than 2 Gy Than 2 Gy

Initial management: Initial management: Treat vTreat vomiting omiting Consider initiating viral prophylaxisConsider initiating viral prophylaxis Consider tissue, blood typingConsider tissue, blood typing Treat traumaTreat trauma Consider prompt consultation with Consider prompt consultation with

hematologist and radiation expertshematologist and radiation experts DDraw blood for chromosome analysisraw blood for chromosome analysis Note areas of erythema and record on body Note areas of erythema and record on body

chart. If possible, take photographschart. If possible, take photographs


Acute Radiation Syndrome: Dose Acute Radiation Syndrome: Dose GreaterGreater Than 2 Gy Than 2 Gy

Priorities of actionsPriorities of actions Supportive careSupportive care Prevention and treatment of infectionsPrevention and treatment of infections Stimulation of hematopoiesisStimulation of hematopoiesis Stem cell transfusionsStem cell transfusions Psychological supportPsychological support Observe carefully for erythema Observe carefully for erythema Consultation with experts Consultation with experts


Probability of radiation injury Probability of radiation injury based on the symptomsbased on the symptomsSymptomSymptom UnlikelyUnlikely ProbableProbable SevereSevere

NauseaNausea -- ++++ ++++++

VomitingVomiting -- ++ ++++++

DiarrheaDiarrhea -- - /+- /+ - /+ to +++- /+ to +++

HyperthermiaHyperthermia -- __ - /+ to +++- /+ to +++

HypotensionHypotension -- __ + to +++ to ++

ErythemaErythema -- __ - /+ to ++- /+ to ++

CNS DysfunctionCNS Dysfunction -- __ - /+ to ++- /+ to ++


SummarySummary

This lecture presented materials about This lecture presented materials about acute radiation syndrome (ARS)acute radiation syndrome (ARS)

The following topics were covered in the The following topics were covered in the lecture: stages of ARS (timing, dose lecture: stages of ARS (timing, dose dependence), symptoms and signs for dependence), symptoms and signs for every stage, hematopoietic, every stage, hematopoietic, gastrointestinal, cardiovascular/nervous gastrointestinal, cardiovascular/nervous syndromes, management of ARS syndromes, management of ARS

Comments are welcomed Comments are welcomed


Where to Get More InformationWhere to Get More Information

Mettler FMettler F..AA.., and Mosely R, and Mosely R..D. Medical D. Medical Effects of Ionising Radiation. Grune & Effects of Ionising Radiation. Grune & Station, Orlando 1985.Station, Orlando 1985.Browne D., Weiss J.F., MacVittie T.J., Pillai Browne D., Weiss J.F., MacVittie T.J., Pillai M.V. Treatment of Radiation Injuries. Ed. M.V. Treatment of Radiation Injuries. Ed. Plenum Press. New-York and London 1990.Plenum Press. New-York and London 1990.IIAEA, AEA, Diagnosis aDiagnosis and treatment of radiation nd treatment of radiation injuries. Safety Reports Series injuries. Safety Reports Series NN2. IAEA 2. IAEA 1998. Vienna.1998. Vienna.

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Biological Effects of Ionizing Radiation Deterministic effects Acute radiation syndrome Lecture IAEA Post Graduate Educational Course Radiation Protection