1. Biological Effects of Ionizing Radiation Deterministic effects Acute radiation syndrome Lecture 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

2. Add module code number and lesson title2 Introduction l Acute radiation syndrome (ARS) - the combination of syndromes that occur after whole-body irradiation l ARS consists of the signs and symptoms l Severity of ARS depends on different factors

3. Add module code number and lesson title3 Content l Definition of the ARS l Stages of ARS (timing, dose dependence) l Symptoms and signs for every stage l Hematopoietic, gastrointestinal, cerebrovascular/nervous syndromes l Management of ARS

4. Add module code number and lesson title4 Overview Radiation Dose, Gy Syndrome 1-5Hematopoietic 6-10Gastrointestinal >10 Cerebrovascular/ Cerebrovascular/ Central Nervous System

5. Add module code number and lesson title5 Stages of the ARS 1. Initial or prodromal Signs and symptoms occur within minutes, hours, or day of exposure 2. Latent Patient feels relatively well 3. Manifest illness Lasting from days to weeks depending upon magnitude of the dose 4. Recovery Signs and symptoms begin to subside

6. Add module code number and lesson title6 Initial or Prodromal stage l Symptoms: n Fatigue n Anorexia n Vomiting n Diarrhoea n Water/electrolyte leakage n Cardiocirculatory dysfunction n Hyperthermia n Early erythema l Appearance: n After high dose exposure – within a few hours n After low dose exposure – after 6-12 hours l Lasting: n 24-48 hours

7. Add module code number and lesson title7 Fatigue l Tiredness – the first sign following radiation l Fatigue may include severe apathy, prostration, sleep disorders, day-time drowsiness, night-time insomnia l Exposure in a dose of 1.5 Gy – 30% subjects have the symptom l Exposure in a dose close to LD 50/30 – 90% subjects have the symptom l Symptom is not a reliable prognostic criterion

8. Add module code number and lesson title8 Anorexia l Is a precursor of gastrointestinal distress l Occurs in the first 2 hours after exposure l Is characterized by nausea, accompanied by dry mouth and a metallic taste l Exposure in a dose of 1.5 Gy – 50% subjects have the symptom l Exposure in a dose close to LD 50/30 – 100% subjects have the symptom

9. Add module code number and lesson title9 Vomiting l Is developed at doses of less than 1 Gy l The time to onset, the duration and multiplicity depend overall on the dose received l The precursors of vomiting are ptyalism, tachycardia, mydriasis, retching

10. Add module code number and lesson title10 Diarrhoea l Aetiology is poorly understood l Is a prodromal sign only at a supralethal doses l After radiotherapy at a dose of 7.5 – 10 Gy to an abdominal field – 10% of the subjects develop early diarrhoea

11. Add module code number and lesson title11 Disorders related to cardiocirculatory dysfunction l At supralethal doses - circulatory shock n Reason: inability to maintain blood pressure l At low doses exposure – death could be related with myocardial infarction l At a dose about 10 Gy – hypotension n Severity increases with dose

12. Add module code number and lesson title12 Hyperthermia & Early erythema l Fever: n At supralethal doses develops early n Is accompanied by sweating, severe headache l Early erythema n One of the signs of the radiation-induced inflammatory process n Develops at doses of 6 Gy or more (whole- body gamma irradiation) n Develops at between 4 and 24 hours post- exposure n May last 2 weeks

13. Add module code number and lesson title13 Timing of Prodromal stage Dose, Gy OnsetDuration 0.5-2.0 None to 6 hrs < 24 hrs 2.0-3.5 2-6 hrs 12-24 hrs 3.5-5.5 1-2 hrs 24+ hrs >5.5 Min to 1 hrs 48 hrs

14. Add module code number and lesson title14 Latent stage Dose, Gy Duration 0.5-2.0 Up to 3 weeks 2.0-3.5 2-3 weeks 3.5-5.5 1.0-2.5 weeks >5.5 2-4 days

15. Add module code number and lesson title15 Stage of manifest illness l Haematopoietic syndrome l Gastrointestinal syndrome l Cardiovascular / Neurovascular syndrome l Associated symptoms

16. Add module code number and lesson title16 Haematopoietic syndrome l Hematopoietic syndrome characterized by: n deficiencies of WBC, lymphocytes and platelets, n immunodeficiency, n increased infectious complications, n bleeding, anaemia, and n impaired wound healing

17. Add module code number and lesson title17 Gastrointestinal syndrome l Gastrointestinal syndrome characterized by: n loss of cells lining intestinal crypts, n loss of mucosal barrier, n alterations in intestinal motility, n fluid and electrolyte loss, n vomiting and diarrhoea, n loss of normal intestinal bacteria, n sepsis, and n damage to the intestinal microcirculation

18. Add module code number and lesson title18 Cerebrovascular/Central Nervous System syndrome l Cerebrovascular/Central Nervous System syndrome - primarily associated with effects on the vasculature and resultant fluid shifts l Signs and symptoms include: n vomiting and diarrhoea within minutes of exposure, n confusion, n disorientation, n cerebral oedema, n hypotension, and n hyperpyrexia

19. Add module code number and lesson title19 Associated symptoms l Skin syndrome n loss of epidermis (and possibly dermis) with "radiation burns" l Oropharyngeal symptoms n lesions of the oral mucosa l Lesions of the lungs n disorders of vascular permeability, n disturbances of the fluid balance, n infection, and n inhalation of smoke and radioactive substances

20. Add module code number and lesson title20 Management of ARS l Management of severity n Prodromal effects sTime of onset sDegree of symptoms sDuration of symptoms n Hematological changes sLymphocyte counts n Physical dosimetry sIf available

21. Add module code number and lesson title21 ARS: dose less than 2 Gy l Management of ARS (dose <2 Gy): n Close observation and frequent CBC with differential n Outpatient management may be appropriate n Provide instructions regarding home care

22. Add module code number and lesson title22 ARS: dose greater than 2 Gy l Peculiarities of the Hematopoietic Syndrome: n The prodromal phase n The latent phase n A bone marrow depression phase n The recovery phase

23. Add module code number and lesson title23 ARS: dose greater than 2 Gy l Gastrointestinal Syndrome: n Over 10 Gy - this syndrome is distinguishable from the hematopoietic syndrome by the immediate, prompt and profuse onset of nausea, vomiting and diarrhoea, followed by a short latent period

24. Add module code number and lesson title24 ARS: dose greater than 2 Gy l Cardiovascular Syndrome: n Over 30 Gy, an extremely high dose, to the whole-body. Always fatal, there is immediate nausea, vomiting, anorexia and prostration, and irreversible hypotension; blood pressure will be markedly unstable.

25. Add module code number and lesson title25 Acute Radiation Syndrome: Dose Greater Than 2 Gy l Initial management: n Treat vomiting n Consider initiating viral prophylaxis n Consider tissue, blood typing n Treat trauma n Consider prompt consultation with hematologist and radiation experts n Draw blood for chromosome analysis n Note areas of erythema and record on body chart. If possible, take photographs

26. Add module code number and lesson title26 Acute Radiation Syndrome: Dose Greater Than 2 Gy l Priorities of actions n Supportive care n Prevention and treatment of infections n Stimulation of hematopoiesis n Stem cell transfusions n Psychological support n Observe carefully for erythema n Consultation with experts

27. Add module code number and lesson title27 Probability of radiation injury based on the symptoms SymptomUnlikelyProbableSevere Nausea-+++++ Vomiting-++++ Diarrhea- - /+ - /+ to +++ Hyperthermia-_ Hypotension-_ + to ++ Erythema-_ - /+ to ++ CNS Dysfunction -_ - /+ to ++

28. Add module code number and lesson title28 Summary l This lecture presented materials about acute radiation syndrome (ARS) l The following topics were covered in the lecture: stages of ARS (timing, dose dependence), symptoms and signs for every stage, hematopoietic, gastrointestinal, cardiovascular/nervous syndromes, management of ARS l Comments are welcomed

29. Add module code number and lesson title29 Where to Get More Information l Mettler F.A., and Mosely R.D. Medical Effects of Ionising Radiation. Grune & Station, Orlando 1985. l Browne D., Weiss J.F., MacVittie T.J., Pillai M.V. Treatment of Radiation Injuries. Ed. Plenum Press. New-York and London 1990. l IAEA, Diagnosis and treatment of radiation injuries. Safety Reports Series N2. IAEA 1998. Vienna.