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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. Module VIII-b. Types of c ellular d amage. Altered Metabolism& function. repair. Mutation. Cell death. Reproductive cell death. R adiosensitivity of t issues. Bone marrow. Skin. CNS.

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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 Module VIII-b

  2. Types of cellular damage Altered Metabolism& function repair Mutation Cell death Reproductive cell death Module Medical VIII.

  3. Radiosensitivity of tissues Bone marrow Skin CNS • 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 Module Medical VIII.

  4. haematopoietic system Bone marrow Module Medical VIII.

  5. Hierarchical organization of haematopoiesis BFU-E CFU-E red blood cell BFU-MK CFU-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 CFU-TL Thymus T lymphocytes Proliferation Blood Differentiation Bone marrow Module Medical VIII.

  6. 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 Module Medical VIII.

  7. 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 Module Medical VIII.

  8. Irradiated bone marrow Irradiated bone marrow lacks all precursor haematopoietic cells Normal bone marrow Module Medical VIII.

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

  10. 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 Module Medical VIII.

  11. Lymphocyte changes as a function of dose <1 Gy 1-2 Gy Lymphocytes (percent of normal) 2-5 Gy >5-6 Gy Time after exposure (days) Module Medical VIII.

  12. 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 Module Medical VIII.

  13. Erythropoietic effects 1 Gy 3 Gy Erythropoietic response to 1Gy and 3Gy whole body exposure Module Medical VIII.

  14. Leukopoietic effects Normal <1Gy Neutrophils (percent of normal) 1-2 Gy 2-5 Gy >5-6 Gy Time after exposure (days) Smoothed average of neutrophil changes in human cases of accidental radiation exposure as a function of dose Module Medical VIII.

  15. Thrombopoietic effects Normal <1Gy Platelets (percent of normal) 2-5 Gy 1-2 Gy >5-6 Gy Time after exposure (Days) Smoothed average of platelet changes in human cases of accidental radiation exposure as a function of dose Module Medical VIII.

  16. Reproductive cell kinetics and sterility-male Module Medical VIII.

  17. Reproductive cell kinetics and sterility-female Module Medical VIII.

  18. The foetus • Typical effects of radiation on embryo: • Intrauterine growth retardation (IUGR) • Embryonic, foetal, or neonatal death • Congenital malformations Module Medical VIII.

  19. Effects of radiation according to gestational stage Module Medical VIII.

  20. Specific radiation effects on foetus:mental retardation , microcephaly Cases of mental retardation caused by radiation exposure in Hiroshima and Nagasaki. Module Medical VIII.

  21. Considerationsforpregnancytermination • Threshold dose for developmental effects approximately 0.1 Gy • Normal rate of preclinical loss >30%. At 0.1 Gy , increase of 0.1-1% • The foetal absorbed dose > 0,5 Gy at 7-13 weeks: substantial risk of IUGR and CNS damage • 0.25–0.5Gy at 7-13 weeks: parental decision with physician’s guidance Module Medical VIII.

  22. Review points • Cells going through the division phase (M and S) are generally the most sensitive to ionizing radiation Exceptions: lymphocytes and some bone marrow stem cells, which exhibit interphase death • Bone marrow consists of progenitor and stem cells, the most radiosensitive cells in the human body and the most important in controlling infection Module Medical VIII.

  23. Review points • 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

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