BIOLOGICAL EFFECTS OF IONIZING RADIATION ON TISSUES, ORGANS AND SYSTEMS

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BIOLOGICAL EFFECTS OF IONIZING RADIATION ON
TISSUES, ORGANS AND SYSTEMS
Module VIII-b
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Types of cellular damage
Altered Metabolism function
repair
Mutation
Cell death
Reproductive cell death
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Radiosensitivity of tissues
Bone marrow
Skin
CNS

• Moderately radiosensitive
• Skin
• Vascular endothelium
• Lung
• Kidney
• Liver
• Lens (eye)

• Highly radiosensitive
• Lymphoid tissue
• Bone marrow
• Gastrointestinal epithelium
• Gonads
• Embryonic tissues

• Least radiosensitive
• Central nervous system (CNS)
• Muscle
• Bone and cartilage
• Connective tissue

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haematopoietic system
Bone marrow
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Hierarchical organization of haematopoiesis
BFU-E
CFU-E
red blood cell
CFU-MK
BFU-MK
platelets
CFU-GEMM
CFU-M
monocytes
CFU-GM
CFU-G
neutrophils
CFU-Ba
Stem cell
basophils
CFU-Eo
eosinophils
CFU-L
CFU-BL
B lymphocytes
CFU-TL
Thymus
T lymphocytes
Proliferation
Blood
Differentiation
Bone marrow
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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
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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
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Irradiated bone marrow
Irradiated bone marrow lacks all precursor
haematopoietic cells
Normal bone marrow
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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
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Early changes in peripheral blood lymphocyte
counts
0.25-1.0 Gy
1.0-2.0 Gy
2-4 Gy
4-6 Gy
gt6 Gy
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Lymphocyte changes as a function of dose
lt1 Gy
1-2 Gy
Lymphocytes (per cent of normal)
2-5 Gy
gt5-6 Gy
Time after exposure (days)
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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
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Erythropoietic effects
1 Gy
3 Gy
Erythropoietic response to 1Gy and 3Gy whole body
exposure
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Leukopoietic effects
Normal
lt1Gy
Neutrophils (per cent of normal)
1-2 Gy
2-5 Gy
gt5-6 Gy
Time after exposure (days)
Smoothed average of neutrophil changes in human
cases of accidental radiation exposure as a
function of dose
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Thrombopoietic effects
Normal
lt1Gy
Platelets (per cent of normal)
1-2 Gy
2-5 Gy
gt5-6 Gy
Time after exposure (Days)
Smoothed average of platelet changes in human
cases of accidental radiation exposure as a
function of dose
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Reproductive cell kinetics and sterility - male
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Reproductive cell kinetics and sterility - female
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The foetus

• Typical effects of radiation on embryo
• Intrauterine growth retardation (IUGR)
• Embryonic, foetal, or neonatal death
• Congenital malformations

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Effects of radiation according to gestational
stage
Gestational age Stage Radiogenic effects
0-9 days Preimplantation All or none
10 days- 6 weeks Organogenesis Congenital anomalies, growth retardation
6 weeks- 40 weeks foetal Growth retardation, microcephly, mental retardation
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Specific radiation effects on foetusmental
retardation , microcephaly
Cases of mental retardation caused by radiation
exposure in Hiroshima and Nagasaki.
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Considerations for pregnancy termination

• Threshold dose for developmental effects
  approximately 0.1 Gy
• Normal rate of preclinical loss gt30. At 0.1 Gy
  , increase of 0.1-1
• The foetal absorbed dose gt 0,5 Gy at 7-13 weeks
  substantial risk of IUGR and CNS damage
• 0.250.5 Gy at 7-13 weeks parental decision
  with physicians guidance

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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

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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