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BIOLOGICAL EFFECTS OF IONIZING RADIATION ON T I SSUE S , ORGANS AND SYSTEMS

BIOLOGICAL EFFECTS OF IONIZING RADIATION ON T I SSUE S , ORGANS AND SYSTEMS. Types of c ellular d amage. Norma. Mutation. repair. Changes of m etabolism & function. Interphase cell death. Mitotic cell death. R adiosensitivity of t issues. Bone marrow. CNS. Skin.

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BIOLOGICAL EFFECTS OF IONIZING RADIATION ON T I SSUE S , ORGANS AND SYSTEMS

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  1. BIOLOGICAL EFFECTS OF IONIZING RADIATION ON TISSUES,ORGANS AND SYSTEMS

  2. Types of cellular damage Norma Mutation repair Changes of metabolism & function Interphase cell death Mitotic cell death

  3. Radiosensitivity of tissues Bone marrow CNS Skin • Highlyradiosensitive • Lymphoid tissue • Bone marrow • Gastrointestinal epithelium • Gonads • Embryonic tissues • Moderately radiosensitive • Skin • Vascular endothelium • Lung • Kidney • Liver • Lens (eye) • Leastradiosensitive • Central nervous system (CNS) • Muscle • Bone and cartilage • Connective tissue

  4. Relative radiosensitivity of various organs based on parenchymal hypoplasia

  5. Haematopoietic system Bone marrow

  6. Hierarchical organization of haematopoiesis BFU-E CFU-E red blood cell CFU-MK BFU-MK platelets CFU-GEMM CFU-M CFU-GM monocytes CFU-G neutrophils CFU-Ba Stem cell basophils CFU-Eo CFU-L eosinophils CFU-BL B lymphocytes Thymus CFU-TL T lymphocytes Proliferation Blood Differentiation Bone marrow

  7. Bone marrow kinetics Normal physiological situation Resting stem cells Proliferating compartment: stem cell and progenitors Differentiating compartment: precursors Mature cells Blood exit differentiation activation proliferation, differentiation Stem cells:immature cells with autorenewal capability Progenitors:primitive cells, high proliferative potential Mature cells:no proliferative capability

  8. Effects of radiation on haematopoiesis Proliferating compartment: stem cell and progenitors Differentiating compartment: precursors Mature cells Blood Resting stem cells activation IRRADIATION proliferation, differentiation differentiation Block of proliferation, cell death Depletion by absence of renewal Depletion of proliferating compartment BLOOD APLASIA

  9. Effect of radiation on bone marrow Irradiated bone marrow lacks all precursor haematopoietic cells Normal bone marrow

  10. Model of blood renewal system Cell pools in normal steady state Stem cell Dividing & maturing Maturing only Blood ? 2 days 1 day 1 day 1 day Time After Irradiation Transit time Changes after irradiation 1 hour 1 day 2 days Relative Number of Cells 3 days 4 1/4 days 5 days

  11. Erythrocyteschanges as a function of dose 1 Gy 3 Gy

  12. Leukocytes changes as a function of dose Normal <1Gy Neutrophils,percent of normal 1-2 Gy 2-5 Gy >5-6 Gy Time after exposure,days

  13. Thrombocyteschanges as a function of dose Normal <1Gy Platelets,percent of normal 2-5 Gy 1-2 Gy >5-6 Gy Time after exposure,days

  14. Effects of radiation on lymphatic tissue A B Normal monkey lymph node Germinal centre of normal monkey lymph node C D Lymphoid cells depleted in cortex of canine lymph node Germinal centre of irradiated human lymph node

  15. Early changes in peripheral blood lymphocyte counts 0.25-1.0 Gy 1.0-2.0 Gy 2-4 Gy 4-6 Gy >6 Gy

  16. Lymphocyteschanges as a function of dose <1 Gy Lymphocytes,percent of normal 1-2 Gy 2-5 Gy >5-6 Gy Time after exposure,days

  17. Effect of radiation on gastrointestinal tract Irradiated gastrointestinal mucosa

  18. Pathogenesis of the gastrointestinal syndrome • Depletion of the epithelial cells lining lumen of gastrointestinal tract • Intestinal bacteria gain free access to body • Haemorrhage through denuded areas • Loss of absorptive capacity

  19. Reproductive cell kinetics and sterility–male

  20. Reproductive cell kinetics and sterility–female

  21. Human skin structure

  22. Penetration of radiation through skin stuctures Alpha radiationis absorbed in superficial layers of dead cells within the stratum corneum Beta radiationdamages epithelial basal stratum. High energy ß-radiation may affect vascular layer of derma, with lesion like thermal burn Gamma radiationdamages underlying tissues and organs

  23. Effect of radiation on skin Irradiated Normal

  24. Pulmonary effects Pulmonary fibrosis Irradiated lung tissue

  25. Summary of lecture • Bone marrow consists of progenitor and stem cells, the most radiosensitive cells in the human body and the most important in controlling infection • Doses in tens of gray produce central nervous system syndrome, causing death before appearance of the haematopoietic or gastrointestinal syndromes • The latter syndromes may occur after doses of as low as 2.5 and 8 Gy, respectively. Lesions in the brain are usually caused by damage to the vascular endothelium • Lung lesions do not usually appear at radiation doses less than 10 Gy. Significant concern in partial-body irradiation and in radiation therapy

  26. Lecture is ended THANKS FOR ATTENTION In lecture materials of the International Atomic EnergyAgency (IAEA), kindly given by doctor Elena Buglova, were used

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