biological effects of ionizing radiation deterministic effects radiation injury of gastrointestinal...

Biological Effects of Ionizing RadiationBiological Effects of Ionizing Radiation Deterministic effectsDeterministic effects

Radiation injury of Radiation injury of

Gastrointestinal tract Gastrointestinal tract LectureLecture

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

Damage of gastrointestinal tract by Damage of gastrointestinal tract by ionizing radiation – one of the typical ionizing radiation – one of the typical consequence of whole body exposureconsequence of whole body exposure

Development of damage had different Development of damage had different stagesstages

Symptoms of gastrointestinal syndrome Symptoms of gastrointestinal syndrome could help for diagnosis and treatmentcould help for diagnosis and treatment


ContentContent

Structure of gastrointestinal systemStructure of gastrointestinal system Gastrointestinal syndromeGastrointestinal syndrome Pathophysiology of gastrointestinal syndromePathophysiology of gastrointestinal syndrome Phases and symptoms of gastrointestinal Phases and symptoms of gastrointestinal

syndromesyndrome Differential organ response in gastrointestinal Differential organ response in gastrointestinal

syndromesyndrome Radiation-induced diarrhoeaRadiation-induced diarrhoea Diagnosis and treatment of gastrointestinal Diagnosis and treatment of gastrointestinal

syndromesyndrome


OverviewOverview


Gastrointestinal syndromeGastrointestinal syndrome

Phases of GIT injury after exposure:Phases of GIT injury after exposure: ProdromalProdromal Manifest Manifest

SymptomsSymptoms NauseaNausea VomitingVomiting AnorexiaAnorexia DiarrhoeaDiarrhoea


Pathophysiology of Pathophysiology of gastrointestinal syndromegastrointestinal syndrome

Depletion of the epithelian cells Depletion of the epithelian cells lining the lumen of the lining the lumen of the gastrointestinal tractgastrointestinal tract

Intestinal bacteria gain free access to Intestinal bacteria gain free access to the bodythe body

Hemorrhage through the denuded Hemorrhage through the denuded areasareas

Loss of absorptive capacityLoss of absorptive capacity


Phases and symptoms of GISPhases and symptoms of GIS

PhasePhase SymptomsSymptoms Time of onsetTime of onset

ProdromalProdromal Nausea, vomiting, Nausea, vomiting, diarrhoeadiarrhoea

Immediate – hoursImmediate – hours

SubacuteSubacute Vomiting, Vomiting, diarrhoeadiarrhoea

Hours – daysHours – days

AcuteAcute Diarrhoea, Diarrhoea, toxaemia, toxaemia,

septicaemiasepticaemia

Days – weeksDays – weeks

ChronicChronic Fibrosis, bleeding, Fibrosis, bleeding, fistulasfistulas

Months - yearsMonths - years


Differential organ responses in Differential organ responses in GISGIS

Parts of GIT could be exposed Parts of GIT could be exposed during radiotherapyduring radiotherapy

Segmental difference in Segmental difference in radiosensitivity of GIT existsradiosensitivity of GIT exists

Radiosensitivity order of different Radiosensitivity order of different parts of the GIT: parts of the GIT: duodenum, duodenum, jejunum, ileum, oesophagus, jejunum, ileum, oesophagus, stomach, colonstomach, colon,, and rectum and rectum


OesophagusOesophagus

May be irradiated by radiotherapy of May be irradiated by radiotherapy of oesophagus itself or lungoesophagus itself or lung

Symptoms:Symptoms: Denudation of the mucosaDenudation of the mucosa Burning sensationsBurning sensations Difficulty in swallowingDifficulty in swallowing Changes in motilityChanges in motility Loss of mucosal barrierLoss of mucosal barrier Increased possibility of infectionIncreased possibility of infection


StomachStomach

Symptoms of radiation injury:Symptoms of radiation injury: decreased gastric motility, decreased gastric motility, emptying and decreased fluid outputemptying and decreased fluid output nauseanausea dyspepsiadyspepsia gastritisgastritis


Small intestineSmall intestine

Most sensitive part of the GITMost sensitive part of the GIT Has a Has a high proliferative activity high proliferative activity

which results in damage within a which results in damage within a short time after exposureshort time after exposure

Exposure in dose 0.01 Gy may Exposure in dose 0.01 Gy may increase the apoptotic yieldincrease the apoptotic yield


Colon and rectumColon and rectum

Main symptom – diarrhoeaMain symptom – diarrhoea Diarrhoea may arise from Diarrhoea may arise from small small

intestinal dysfunction, colo-rectal intestinal dysfunction, colo-rectal dysfunction and/or bothdysfunction and/or both

Colon has strong compensatory Colon has strong compensatory function and adaptive capacityfunction and adaptive capacity


Radiation-induced diarrhoea – Radiation-induced diarrhoea – multifactorial naturemultifactorial nature

Effects on intestinal fluid and electrolyte Effects on intestinal fluid and electrolyte transporttransport

Effects of exposure:Effects of exposure: increased basal chloride secretionincreased basal chloride secretion release of mediators from cells of the release of mediators from cells of the

epithelium, surrounding tissue or from nervesepithelium, surrounding tissue or from nerves

Later effects:Later effects: reduced stem cell activity and capacity to reduced stem cell activity and capacity to

replace the epitheliumreplace the epithelium


Radiation-induced diarrhoeaRadiation-induced diarrhoea

Was investigated in experimentsWas investigated in experiments Observations:Observations:

Changes in motor activity, which can lead to:Changes in motor activity, which can lead to: Change in absorption of some nutrients Abdominal cramping Associated pain

Changes in motor activity are likely to be related Changes in motor activity are likely to be related with altered neuronal activitywith altered neuronal activity

Modifications in colon’s motor activity can Modifications in colon’s motor activity can contribute to contribute to altered transit, altered transit, mmalabsorption alabsorption and diarrhoeaand diarrhoea


Radiation-induced diarrhoeaRadiation-induced diarrhoea

One of the reason - dysfunction of One of the reason - dysfunction of regularity mechanismsregularity mechanisms

Ionizing radiation influences Ionizing radiation influences the the synthesis, metabolism, release and synthesis, metabolism, release and actions of regulatory mediators actions of regulatory mediators ((hormones, neurotransmitters or hormones, neurotransmitters or paracrine agentsparacrine agents))


Diagnosis of gastrointestinal Diagnosis of gastrointestinal damage - clinical observationdamage - clinical observation

Main aspect – clinical observationMain aspect – clinical observation Important observations:Important observations:

Description of the diarrhoea:Description of the diarrhoea: Time of onset, Duration, and Severity

Characteristics of diarrhoea may Characteristics of diarrhoea may indicate the prognosisindicate the prognosis


Diagnosis of gastrointestinal Diagnosis of gastrointestinal damage - other diagnostic methodsdamage - other diagnostic methods Estimation of rEstimation of radiation-induced adiation-induced

gastrointestinal dysfunction by standard gastrointestinal dysfunction by standard functional testfunctional tests:s: intestinal permeability (sucrose/lactulose ratio for the intestinal permeability (sucrose/lactulose ratio for the

proximal intestine; lactulose/mannitol ratio for the distal proximal intestine; lactulose/mannitol ratio for the distal intestine), intestine),

intestinal transit time and bile acid or vitamin B12 intestinal transit time and bile acid or vitamin B12 absorptionabsorption

MMeasurement of some gastrointestinal easurement of some gastrointestinal regulatory peptides as site-specific markersregulatory peptides as site-specific markers

MMeasurement of certain easurement of certain inflammatory inflammatory mediators in stool samples, gut lavage or mediators in stool samples, gut lavage or biopsy materialbiopsy material


Treatment of gastrointestinal Treatment of gastrointestinal damagedamage

Purpose - Purpose - correction of altered intestinal correction of altered intestinal physiological functionsphysiological functions

Treatment - Treatment - antiemetics, antispasmodics, antiemetics, antispasmodics, antibiotics as well as anti-inflammatory antibiotics as well as anti-inflammatory agents (mainly steroids) agents (mainly steroids)

Purpose - Purpose - to promote the restoration of to promote the restoration of the epithelium and/or the surrounding the epithelium and/or the surrounding tissuetissue

Treatment – use of growth factorsTreatment – use of growth factors


SummarySummary

This lecture presented materials about This lecture presented materials about radiation injury of gastrointestinal tractradiation injury of gastrointestinal tract

The following topics were covered in the The following topics were covered in the lecture: lecture: structure of gastrointestinal system; structure of gastrointestinal system; gastrointestinal syndrome (pathophysiology, gastrointestinal syndrome (pathophysiology, phases and symptoms, differential organ phases and symptoms, differential organ response); radiation-induced diarrhoea; response); radiation-induced diarrhoea; diagnosis and treatment of gastrointestinal diagnosis and treatment of gastrointestinal syndrome.syndrome.

Comments are welcomedComments are welcomed


Where to Get More InformationWhere to Get More Information

Gunter-Smith PJ. Effect of ionising Gunter-Smith PJ. Effect of ionising radiation on gastrointestinal physiology. radiation on gastrointestinal physiology. ConardConard RA,RA, Walker RI, eds. Military Walker RI, eds. Military Radiobiology, Orlando: Academic Press, Radiobiology, Orlando: Academic Press, 1987: 135-151.1987: 135-151.

Barber J, James RD, Radiation effects on Barber J, James RD, Radiation effects on the human gastrointestinal tract. Potten CS, the human gastrointestinal tract. Potten CS, Hendry JH, eds. Radiation and Gut. Hendry JH, eds. Radiation and Gut. Amsterdam: Elsevier, 1995; 231-52.Amsterdam: Elsevier, 1995; 231-52.

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