1. Biological Effects of Ionizing Radiation Deterministic effects Radiation injury of Gastrointestinal tract 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 Damage of gastrointestinal tract by ionizing radiation – one of the typical consequence of whole body exposure l Development of damage had different stages l Symptoms of gastrointestinal syndrome could help for diagnosis and treatment

3. Add module code number and lesson title3 Content l Structure of gastrointestinal system l Gastrointestinal syndrome l Pathophysiology of gastrointestinal syndrome l Phases and symptoms of gastrointestinal syndrome l Differential organ response in gastrointestinal syndrome l Radiation-induced diarrhoea l Diagnosis and treatment of gastrointestinal syndrome

4. Add module code number and lesson title4 Overview

5. 5 Gastrointestinal syndrome l Phases of GIT injury after exposure: n Prodromal n Manifest l Symptoms n Nausea n Vomiting n Anorexia n Diarrhoea

6. Add module code number and lesson title6 Pathophysiology of gastrointestinal syndrome l Depletion of the epithelian cells lining the lumen of the gastrointestinal tract l Intestinal bacteria gain free access to the body l Hemorrhage through the denuded areas l Loss of absorptive capacity

7. Add module code number and lesson title7 Phases and symptoms of GIS PhaseSymptoms Time of onset Prodromal Nausea, vomiting, diarrhoea Immediate – hours Subacute Vomiting, diarrhoea Hours – days Acute Diarrhoea, toxaemia, septicaemia Days – weeks Chronic Fibrosis, bleeding, fistulas Months - years

8. Add module code number and lesson title8 Differential organ responses in GIS l Parts of GIT could be exposed during radiotherapy l Segmental difference in radiosensitivity of GIT exists l Radiosensitivity order of different parts of the GIT: duodenum, jejunum, ileum, oesophagus, stomach, colon, and rectum

9. Add module code number and lesson title9 Oesophagus l May be irradiated by radiotherapy of oesophagus itself or lung l Symptoms: n Denudation of the mucosa n Burning sensations n Difficulty in swallowing n Changes in motility n Loss of mucosal barrier n Increased possibility of infection

10. Add module code number and lesson title10 Stomach l Symptoms of radiation injury: n decreased gastric motility, n emptying and decreased fluid output n nausea n dyspepsia n gastritis

11. Add module code number and lesson title11 Small intestine l Most sensitive part of the GIT l Has a high proliferative activity which results in damage within a short time after exposure l Exposure in dose 0.01 Gy may increase the apoptotic yield

12. Add module code number and lesson title12 Colon and rectum l Main symptom – diarrhoea l Diarrhoea may arise from small intestinal dysfunction, colo-rectal dysfunction and/or both l Colon has strong compensatory function and adaptive capacity

13. Add module code number and lesson title13 Radiation-induced diarrhoea – multifactorial nature l Effects on intestinal fluid and electrolyte transport l Effects of exposure: n increased basal chloride secretion n release of mediators from cells of the epithelium, surrounding tissue or from nerves l Later effects: n reduced stem cell activity and capacity to replace the epithelium

14. Add module code number and lesson title14 Radiation-induced diarrhoea l Was investigated in experiments l Observations: n Changes in motor activity, which can lead to: sChange in absorption of some nutrients sAbdominal cramping sAssociated pain n Changes in motor activity are likely to be related with altered neuronal activity l Modifications in colon’s motor activity can contribute to altered transit, malabsorption and diarrhoea

15. Add module code number and lesson title15 Radiation-induced diarrhoea l One of the reason - dysfunction of regularity mechanisms l Ionizing radiation influences the synthesis, metabolism, release and actions of regulatory mediators (hormones, neurotransmitters or paracrine agents)

16. Add module code number and lesson title16 Diagnosis of gastrointestinal damage - clinical observation l Main aspect – clinical observation l Important observations: n Description of the diarrhoea: s Time of onset, s Duration, and sSeverity l Characteristics of diarrhoea may indicate the prognosis

17. Add module code number and lesson title17 Diagnosis of gastrointestinal damage - other diagnostic methods l Estimation of radiation-induced gastrointestinal dysfunction by standard functional tests: n intestinal permeability (sucrose/lactulose ratio for the proximal intestine; lactulose/mannitol ratio for the distal intestine), n intestinal transit time and bile acid or vitamin B12 absorption l Measurement of some gastrointestinal regulatory peptides as site-specific markers l Measurement of certain inflammatory mediators in stool samples, gut lavage or biopsy material

18. Add module code number and lesson title18 Treatment of gastrointestinal damage l Purpose - correction of altered intestinal physiological functions l Treatment - antiemetics, antispasmodics, antibiotics as well as anti-inflammatory agents (mainly steroids) l Purpose - to promote the restoration of the epithelium and/or the surrounding tissue l Treatment – use of growth factors

19. Add module code number and lesson title19 Summary l This lecture presented materials about radiation injury of gastrointestinal tract l The following topics were covered in the lecture: structure of gastrointestinal system; gastrointestinal syndrome (pathophysiology, phases and symptoms, differential organ response); radiation-induced diarrhoea; diagnosis and treatment of gastrointestinal syndrome. l Comments are welcomed

20. Add module code number and lesson title20 Where to Get More Information l Gunter-Smith PJ. Effect of ionising radiation on gastrointestinal physiology. Conard RA, Walker RI, eds. Military Radiobiology, Orlando: Academic Press, 1987: 135-151. l Barber J, James RD, Radiation effects on the human gastrointestinal tract. Potten CS, Hendry JH, eds. Radiation and Gut. Amsterdam: Elsevier, 1995; 231-52.