Transcript BIOLOGICAL EFFECTS OF IONIZING RADIATION ON TISSUES

BIOLOGICAL EFFECTS
OF IONIZING RADIATION
ON TISSUES, ORGANS
AND SYSTEMS
Types of cellular damage
Norma
Mutation
repair
Interphase
cell death
Mitotic
cell death
Changes of
metabolism
& function
Radiosensitivity of tissues
Bone marrow
Highly
radiosensitive
•Lymphoid tissue
•Bone marrow
•Gastrointestinal
epithelium
•Gonads
•Embryonic tissues
Skin
Moderately
radiosensitive
•Skin
•Vascular endothelium
•Lung
•Kidney
•Liver
•Lens (eye)
CNS
Least
radiosensitive
•Central nervous
system (CNS)
•Muscle
•Bone and cartilage
•Connective tissue
Relative radiosensitivity of various organs
based on parenchymal hypoplasia
Organs
Relative radio
sensitivity
Lymphoid organs; bone marrow,
testes & ovaries; small
intestines
Embryonic tissue
High
Destruction of parenchymal cells, especially
the vegetative or differentiating cells
Fairly high
Destruction of vegetable and differentiating
cells of the stratified epithelium
Skin; cornea & lens of eyes;
gastrointestinal organs: cavity,
esophagus, stomach, rectum
Growing cartilage; the
vasculature; growing bones
Mature cartilage or bone; lungs;
kidneys; liver; pancreas;
adrenal gland; pituitary gland
Muscle; brain; spinal cord
Chief mechanism of parenchymal
hypoplasia
Medium
Destruction of proliferating chondroblasts or
osteoblasts; damage to the endothelium;
destruction of connective tissue cells &
chondroblasts or osteoblasts
Fairly low
Hypoplasia secondary damage to the fine
vasculature and connective tissue elements
Low
Hypoplasia secondary damage to the fine
vasculature and connective tissue elements,
with little contribution by the direct effects on
parenchymal tissues
Haematopoietic system
Bone marrow
Hierarchical organization
of haematopoiesis
BFU-E
BFU-MK
CFU-GEMM
CFU-GM
CFU-E
CFU-MK
CFU-M
CFU-G
red blood cell
platelets
monocytes
neutrophils
CFU-Ba
Stem cell
basophils
CFU-Eo
CFU-L
eosinophils
CFU-BL
B lymphocytes
Thymus
CFU-TL
Proliferation Bone marrow Differentiation
T lymphocytes
Blood
Bone marrow kinetics
Normal physiological situation
Resting
Proliferating
stem cells compartment:
stem cell and
progenitors
Differentiating
compartment:
precursors
Mature Blood
cells
exit
differentiation
activation
proliferation,
differentiation
Stem cells: immature cells with autorenewal capability
Progenitors: primitive cells, high proliferative potential
Mature cells: no proliferative capability
Effects of radiation
on haematopoiesis
Resting
stem cells
I
R
R
A
D
I
A
T
I
O
N
activation
Proliferating
compartment:
stem cell and
progenitors
Differentiating
compartment:
precursors
proliferation,
differentiation
differentiation
Block of
proliferation,
cell death
Mature
cells
Blood
Depletion by absence of renewal
Depletion of
proliferating
compartment
BLOOD APLASIA
Effect of radiation
on bone marrow
Normal bone marrow
Irradiated bone marrow
lacks all precursor
haematopoietic cells
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
Transit time
Relative
Number of Cells
Changes after irradiation
Time
After Irradiation
1 hour
1 day
2 days
3 days
4 1/4 days
5 days
Erythrocytes changes
as a function of dose
1 Gy
3 Gy
Leukocytes changes
as a function of dose
Normal
<1Gy
1-2 Gy
2-5 Gy
>5-6 Gy
Time after exposure, days
Thrombocytes changes
as a function of dose
Normal
<1Gy
2-5 Gy
1-2 Gy
>5-6 Gy
Time after exposure, days
Effects of radiation
on lymphatic tissue
A
B
Normal monkey
lymph node
C
Lymphoid cells depleted
in cortex of canine lymph node
Germinal centre of normal
monkey lymph node
D
Germinal centre of irradiated
human lymph node
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
Lymphocytes changes
as a function of dose
<1 Gy
1-2 Gy
2-5 Gy
>5-6 Gy
Time after exposure, days
Effect of radiation on
gastrointestinal tract
Irradiated
gastrointestinal
mucosa
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
Reproductive cell kinetics and
sterility – male
Reproductive cell kinetics and
sterility – female
Human skin structure
Penetration of radiation
through skin stuctures
Alpha radiation is absorbed in
superficial layers of dead cells
within the stratum corneum
Beta radiation damages epithelial
basal stratum. High energy ßradiation may affect vascular layer
of derma, with lesion like thermal
burn
Gamma
radiation
damages
underlying tissues and organs
Effect of radiation on skin
Normal
Irradiated
Pulmonary effects
Irradiated lung tissue
Pulmonary fibrosis
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
Lecture is ended
THANKS FOR ATTENTION
In lecture materials
of the International Atomic Energy Agency (IAEA),
kindly given by doctor Elena Buglova, were used