Radiation Pathology

Tissues area categorized into two main types; acute responding and chronic responding based only on
the time needed for them to express damage after radiation.

This classification doesn't describe the pathological response of these tissue after radiation but just only
describe the timing of appearance of the radiation induced damage.

As Discussed before; radiation induce a cellular response that may range from division delay, interphase
death or reproductive failure. The last two responses (interphase death & reproductive failure) are
responsible for the loss of cells from the organs that leads to visible morphological changes (Pathological
changes).

It must be noted that;

the pathological changes occurred due to radiation is not Unique..... i.e. the tissue and organ
trauma can't be differentiated from other form of trauma e.g. heat....

Thus the pathological changes can't by any mean define that exposure to irradiation as cause of
tissue or organ injury when a history regard receiving irradiation cannot be provided.

Acute Versus Chronic effect of irradiation on tissue....

Effect of irradiation on any type of tissue (whatever the tissue is acute responding or late responding)
pass through two phases: Acute effects and chronic or late effects

First phase; acute effects

Cause: Whatever the type of the tissue

o Due to depletion of the critical parenchymal cells (target cells) of the tissue.
Timing: it depends on the turnover kinetics of the target cells of the irradiated tissue.
o In acute responding tissue occur very soon after irradiation.
o In late responding tissue occur after long time.
Examples:
o In acute responding tissue
Esophagus esophagitis.
Cause: depletion of the basal cell layer in the mucosa of the esophaus
Timing: it appear within the 1st month after irradiation.
Extent of response; marked
o In late responding tissue
Lung pneumonitis.
Cause: depletion of the type II pneumatocytes of the alveolar epith.
Timing: it appears after 3 months or even more.
 Extent of response; minimal

N.B it must be noted that; these changes may be reversible or irreversible depending on the

1. Radiation dose.
2. The Proliferative potential of the target cells in the irradiated tissue.

Second phase; chronic or late effect

Causes:
o as a result from the irreversible effect caused by the first "acute" phase
It's terned (2ndry chronic effects) secondary to primary acute effects.
it's dependent on the state acute phase injury... thus....
Timing:
o Usually appear sooner and quicker.
o due to depletion of the critical non-parenchymal cells in the stroma, blood vessels
it's termed (1ry chronic effects).
it's independent of the of acute phase injury...thus...
Timing:
o usually appear late "after years" due slow turnover of the critical
non-parenchymal cells.
Extent of response;
o in acute responding tissue: usually minimal.
o in late responding tissue: usually marked.

Healing of irradiated tissue

Types of healing:

1. Regeneration:
a. Def: Replacement of damaged cells by same cell type that present before irradiation
b. Type of acute effect:
Occurs with total or partial reversible early "acute" radiation effects.
c. Result:
Restoration of both the function and morphology of the organ to pre-irradiated
state.
d. Type of late "chronic" irradiation changes
would be of primary chronic type.

2. Repair:
a. Def: Replacement of depleted original cells by a different cell type. Type of acute
b. Type of acute effect:
Occurs with catastrophic irreversible early "acute" radiation effects.
c. Result:
 No restoration of either the function or morphology of the organ to
pre-irradiated state.
d. Type of late "chronic" irradiation changes
would be of secondary chronic type.

NB: it must be noted that the processes of healing is not certain i.e. in case of massive extensive damage,
tissue necrosis would happen without any form of healing.

Which type of healing would occur?

the probability of occurrence of certain type of healing depend on a function of both the dose
and the organ irradiated e.g.
A. acute responding tissue i.e. Organs with active division e.g. small intestine, bone
marrow
a. Low & moderate doses regeneration.
b. High doses repair "irradiation destroy large number of parenchymal cells
making regeneration impossible".
B. late responding tissue e.g. kidney or lung
a. Low doses regeneration.
b. Moderate & high doses repair.

it must be noted again.... time play an important factor in tissue response i.e.

A. acute responding tissue will express more severe acute effect of irradiation early more
than late effects.
B. late responding tissue will express more severe late effect of irradiation than the early
effect.
C. Example: dose of 20 Gy to the chest would express
a. Marked changes in the skin with minimal lung changes within 1st 3-6 months
post-exposure.
b. Minimal changes in skin with marked changes in the lung 1 year or more post-
exposure

Clinical factors influencing the response

A. Doses
a. Diagnosic less than 1 Gy usually delivered to only a portion of patient's body e.e.
diagnostic radiology, fluroscopy, nuclear medicine.
b. Therapy doses
i. Usually range from 40 Gy to 60 Gy.
ii. usually fractionated over a period of 4- 6 weeks.
 iii. fractionated dose is biological less effective than a single dose of same
magnitude.
B. Irradiated target volume
a. irradiation of a part of an organ elect a response similar to irradiation of the whole
organ but the response is localized in irradiated part.
b. this is very important in irradiation of critical organ; as irradiation of the whole organ
may be life threatening but partial irradiation will spear a normal part that can maintain
and compensate and lose in the function.

Genera; organ changes

Acute changes in most organs range from inflammation, edema, hemorrhage, shedding of the
mucosal lining

Chronic changes usually range fibrosis, atropy, ulceration, stricture, stenosis and obstruction; it's
impossible pathologically to differentiate between the primary and secondary chronic changes.

Necrosis results from failure of repair of the damage by any mean and considered as secondary
chronic changes.

Hemopoietic system

Bone marrow;

Bone marrow tissue consist of

A. precursor (stem) cells.

B. material end cells that will pass later to circulation.
C. fat cells.
D. connective tissue stroma

Types of bone marrow

A. Red marrow;
a. it contain large number of stem cells and some fat cell.
b. its responsible for supplying mature functional cells to the circulating blood
c. Sites
i. Adult: ribs. end of long bone, vertebrae, sternum and skull bone.
ii. infants: locate in all bones.
B. Yellow marrow;
a. it contain few number of stem cells with large number of fat cells.

Effect of irradiation on the bone marrow

The primary effect is decrease in the number of stem cells.

 A. Low dose:
a. Slight decrease in number of stem cells.
b. Recovery within few weeks post-exposure.
B. Moderate & High doses
a. Severe depletion of cells in the bone marrow.
b. Recovery would be either
i. Prolonged time for recovery in moderate doses.
ii. Less or no recovery in case of permanent decrease stem cells number and
increase in amount of fat cells and connective tissue stroma

Different response of stem cells

different response of stem cells to irradiation is due to different radio-sensitivity of different stem
populations.

A. Erythroblasts (precursor of RBCs) are the most radiosensitive.

B. Megakaryocytes (precursor of the platelet) is the least radiosensitive.
C. Myelocytes (precursor of WBCs) is the in-betweens in radio-sensitivity.

This is manifested as difference in the time of depression of their counts; (moderate dose)

A. erythroblast decrease first and return to normal after one week.

B. Myelocytes decrease as erythroblast but return to normal within 2-6 weeks.
C. Megakarycotes depression occure 1-2 weeks post-exposure and return toi normal withing 4-6
weeks.

Circulating blood

All cells (differentiated & non-dividing) in the blood are radio-resistant except lymphocytes.

But, the reflect the changes in the bone marrow as the stem cells decrease, there are
corresponding in the circulating cells.

The reflection of bone marrow damage on the circulating blood cells is dependent on two factors;

A. sensitivity of different stem cell lines.

B. the life span of each cell type in the circulating blood. (More significant)
a. RBCS 120 days
b. Granulocytes 24 Hrs.

Sequence of appearance of decrease of Cells count

1. Lymphocytes
a. Low dose of 0.1 Gy slight decrease their count ... rapid recovery.
b. moderate doses level reach zero within days... Recovery within months
2. Neutrophils come next with doses > 0.3 Gy.
 a. Moderate dose fall to lowest level within week..... recovery within one month.
3. Platelet and RBCs with higher doses > 0.5 Gy.
a. low and moderate doses little effect.
b. Higher doses marked depression within 4th week post exposure ... recovery after few
months..
4. In Summary:
a. Diagnostic Radiology:
i. very low doses beyond the range of hazard on the bone marrow.
ii. No hazard even seen the chromosome of circulating lymphocytes.
b. Nuclear medicine: As the radioactive material is passing through blood.
i. chromosomal changes in lymphocytes has been noticed but in small
insignificant amount.
c. Radiation therapy:
i. Bone marrow depression is noticed specially for the WBCs.
ii. Routine CBC is a must in all patient receiving Radiotherapy especially for patien
receiving RTH for large volume.

Skin

Histologically; the skin consist of;

Outer layer: Epidermis

1. basal cell layer (immature, dividing cells)
2. several layer of mature non dividing cells
Inner Connective tissue layer; Dermis
1. Blood vessels
2. fat
3. specialized structures
hair follicles
sebaceous glands
sweet glands

Post-exposure changes

acute changes in the skin following moderate to high dose

o Inflammation, erythema, dry or moist desquamation
o Skin erythema usually occur after 10 Gy.
o There are a term called skin eruthema dose (SED) the dose that induce skin erythema.
Chronic changes
o Moderate doses usually permit healling to occur with regeneration resulting in minimal
chronic changes.
chronic changes ranger from
atrophy, fibrosis
 decreased or increased pigmentation.
ulceration
o High doses
necrosis .
increased incidence of cancer.
specialized structure
o hair follicle are radiosensitive
Moderate dose temporary epilation "alopecia".
High dose permanent epilation.
o sebaceous and sweat glands are relative radio-resistant.
Only high dose glandular atrophy and fibrosis.
In Summary:
o Diagnostic Radiology:
very low doses beyond the range of hazard on the skin.
No hazard even seen the skin expect erythema in hands of poineer workers in
radiology.
o Nuclear medicine: As the radioactive material is passing through blood.
no early or late skin changes have been observed in the hands of works
however continuous exposure to hands of the workers due to repeated
procedure have been noticed .
o Radiation therapy:
Bothe early and chronic changes present in the patient receive RTH especially
during the time of orthovoltage era.
today high energy machine give x-ray beam than have skin spearing leading to
minimal chronic skin changes.
fractionated RTH e.g. 60 gray over 6wks usually produce minimal erythema with
late minimal atrophy however this decrease the ability of the irradiated skin to
withstand trauma of any time in comparison to pre-irradiated state.
Sever necrosis is extremely rare today it may occur only in case of
patient have sensitive skin.
Failure of using proper RTH protocols e.g. failure of using of wedges.
Certain CTH increase the skin sensitivity to RTH e.g. Anthracyclines.

Digestive System

Histologically; the gut mucosa consists

1. basal cell "stem cells" that is continous dividing and radiosensitive, cells of crypts of lieberkuhn..
2. the other layer is non dividing and are relatively radio resistant.

Post-irradiation exposure changes

all Gut withstand moderate dose of RTH with minimal symptoms except small intestine +++, stomch++
 acute changes in the mucosa following moderate dose.
o oral cavity mucositis.
o esophagus esophagitis.
o stomach gastritis.
o intestine entritis.
Chronic changes
o Moderate doses
Chronic changes usually minimal exception .....
o Stomach is more radiosensitive than esophagus Ulceration,
atrophy and fibrosis is evident.
o Small intestine is the most radiosensitive
Atrophy and Shortening of the "villi" due to depletion of
the cells of lieberkuhn "stem cells".
Regeneration usually occur with moderate doses.
o High doses
atrophy, fibrosis and stricture
necrosis .
increased incidence of cancer.
Small intestine
permanent depletion of cells of crypts with minimal recovery.
ulceration, fibrosis, hemorrhage, necrosis is evident.
Large intestine
fibrosis and partial obstruction is common.
In Summary:
o Diagnostic Radiology & Nuclear medicine:.
no early or late changes have been observed.
o Radiation therapy:
Acute changes
o Esophagitis and mucositis is evident after doses of 10 - 20 Gy.
o Stomach nausea & vomiting.
o Small intestine usually diarrhea.
Chronic changes in doses
o Esophagus it's minimal up to 60 - 70 Gy.

Reproductive system - Male

Most tissue of male reproductive system is radio-resistant except the testis

Histologically, the testis is composed of

A. Rapid dividing cells "stem cells" Immature spermatogonia".

 B. Differentiated non dividing cells "mature spermatogonia".

Post-irradiation exposure changes

The damage to testis is due to depletion of the immature dividing spermatogonia leading
eventually to depletion of mature sperm after a while in the testis in a process called Maturation
depletion.

Acute changes: usually non effect on fertility in the early time as the mature spermatogonia is
still viable and it is radio-resistant.

Chronic changes: temporary or permanent infertility "sterility" depending on the dose i.e.
whether it's temporary or permanent depletion of the immature spermatogonia.

High doses 5 - 6 Gy per fraction permanent sterility.

Doses of 2.5 Gy temporary sterility.... recovery within 12 months.

Another potential hazard of testicular irradiation is production of sperm with chromosomal anomalies.
These anomalis may be propagated or eliminated through the many division needed to produce
spermatoza "matter of probability".

In Summary:
o Diagnostic Radiology & Nuclear medicine:... these fields involves
acute low dose for the patients.
chronic low doses for the personnel involved in these diagnostic procedures.
These low doses have no hazard on sterility but they may produce chromosomal
anomalies with mutation in the future generations.
o Radiation therapy:
Acute changes
o usually minimal.
Chronic changes
o sterility can occur if the irradiated target volume include the
testis and they received the full dose.
o moderate dose e.g. scattering irradiation can lead to
chromosomal anomalies that can produce future mutations
Important consideration
o Shielding of the testis is very important
o The patient must be warrant of the possibility of infertility or
chromosmal aberration if the irradiated target volume include
the testis.
o It must be clear that irradiation never cause impotency.

Reproductive system - Female

Histologically, the testis is composed of

A. Rapid dividing cells "stem cells"

a. Follicles
i. Small ..... Most resistant
ii. Intermediate ... Most sensitive
iii. Large mature..... Moderate sensitive
B. Differentiated non dividing cells "stroma".

Unlike the male, the stem cells is not continuously dividing and replacing those lost during menstruation
but the mature ovum is released during ovulation followed either by fertilization or menstruations.

Post-irradiation changes

Acute changes: usually non effect on fertility in the early time as the moderate resistant mature
follicle can release the ovum.

Chronic changes: temporary or permanent infertility "sterility" depending on the dose i.e.
whether it's depletion of the intermediate follicle alone or along with the small follicle.

High doses 5 - 6 Gy per fraction permanent sterility.

Doses of 2.5 Gy temporary sterility.... recovery within 12 months... fertility recur due
to maturate of radio-resistant small follicle.

Another potential hazard of ovarian irradiation is production of ovum with chromosomal anomalies.
These anomalies can result in visible genetic mutation in the offspring.

In Summary:
o Diagnostic Radiology & Nuclear medicine:... these fields involves
acute low dose for the patients.
chronic low doses for the personnel involved in these diagnostic procedures.
These low doses have no hazard on sterility but they may produce chromosomal
anomalies with mutation in the future generations.
Body shielding during work is so important.
o Radiation therapy:
Acute changes
o usually minimal.
Chronic changes
o sterility can occur if the irradiated target volume include the
ovary and they received the full dose.
o moderate dose e.g. scattering irradiation can lead to
chromosomal anomalies that can produce future mutations
Important consideration
 o Shielding of the ovary is very important
o The patient must be warrant of the possibility of infertility or
chromosomal aberration if the irradiated target volume include
the testis.
o It must be clear that irradiation can induce artificial menopause
with marked effects on secondary genitalia and sexual
characteristics.

The lens

Histologically, the lens is composed of

o capsule which contain active dividing cells.

Post-irradiation changes;

There is no mechanism in the lens for removing the damaged cells thus damaged cell accumulate
in the lens increasing its opacification.

o Extent of appearance of acute versus chronic changes depend on the dose and its fractionation.
o Dose
Moderate dose of 2 Gy produce cataract in few individual.
High dose of 7 Gy produce cataract in 100% of the individuals.
o Fractionation:
it must be noted that cataract is most commonly to occur in less fractionated doses
rather than more fractionated doses.

In summary:

Diagnostic Radiology & Nuclear medicine:... these fields involves

o Scattered radiation is considered an occupational hazard especially during
fluoroscopic procedures especially during early days rather today.
Radiation therapy:
o Minimal cataract dose 4 Gy.
o Fractionated dose of 12 Gy will produce cataract in 100% of patients.
o eye shield is very important during RTH of facial lesions.

Cardiovascular system

Blood vessels; occlusion may occur due to main mechanisms:

A. Damaged endothelial cells release factors the stimulate undamaged endothelium to

proliferate.... too many proliferation ... obstruction.
B. Destruction of endothelium induce formation of blood clots that occlude the vessels.
Thus; small vessels are more radiosensitive than large one because they are more susceptible for
occlusion.

These chronic changes is usually manifested as:

o petechial hemorrhages
o telangiectasia
o occlusion leading to chronic ischemia.... ranging from organ atrophy to or necrosis.

Heart

There heart was thought to be radio-resistant however recent research show that the heart can
withstand low and moderate doses without any damage except for function ECG changes. High doses
induce pericarditis or even pancarditis.

In summary:

Diagnostic Radiology & Nuclear medicine:... insignificant effects.

Radiation therapy
o The heart is always included in the fields of irradiation e.g. lymphoma, breast.
o Dose of 40 Gy produce changes in few individuals.
o Shielding of heart must be considered if the total dose exceed 40 Gy.

Bone and Cartilage

Although mature bone and cartilage are radio-resistant but growing bone and cartilage is
moderately radiosensitive.

Histologically; growing bone is composed of..

o dividing immature cells osteoblasts and chondroblasts.

o non dividing mature cells osteocytes, chondrocytes.

Post-irradiation exposure;

Usually it's caused by

A. Damage to both small blood vessels and bone marrow.

B. Depletion of osteoblasts and chondroblasts.

Doses

A. Moderate Doses
a. Temporary inhibition of mitosis and death of proliferating immature cells.
b. Recovery occur with minimal late changes
B. High Doses
a. Permanent inhibition of mitosis and death of the immature cells.
 b. No Recovery
c. Stoppage of bone growth.
d. Alteration of bone shape, size Scoliosis occur late.

In summary

Diagnostic Radiology & Nuclear medicine:... insignificant effects except in case of

administration of bone-seeking radioactive nucleotides.
Radiation therapy
o irradiation of bone in the target volume can result in chornic changes e.g.
scoliosis.
o Fractionated dose of 20 Gy produce changes in the bones of children when their
age is < 2 years.
o However the incidence for occurrence of changes decrease dramatically with
either a) decreasing the dose or b) increasing the age

The liver

For many years the liver was thought to be radio-resistant but recently it was found that the liver
is moderately sensitive

Histologically:

A. Parenchymatous cells; they are radio-resistant however they do retain their capability
for regeneration through mitosis.
B. Blood vessels; they are more sensitive to irradiation than blood vessels thus any
secondary damage to the liver usually due to vascular changes.

Post-irradiation exposure

A. Acute changes
a. low to moderate doses: little observable changes.
b. high doses: hepatomegally and ascitis.
B. Chronic late changes radiation hepatitis
a. 2ndry vascular scelorsis and peri-portal fibrosis.
b. These picture are consistent with veno-occlusive disorder
i. Obstructive jaundice.
ii. Portal hypertension.
iii. Ascitis
iv. very late hepatic cell failure.

In summary

Diagnostic Radiology & Nuclear medicine:... insignificant effects

Radiation therapy
 o irradiation of the liver occur in case of treatment of lymphoma, ovarian mass,
kidney .. etc.
o radiation hepatitis occurs usualy from a dose ranging from 35 - 45 Gy. it's clinical
significance depend on the irradiated target volume.

The respiratory system

Histologically:

A. Basal of the respiratrory mucosa; they are radio-sensitive while the layers are radio-
resistant.
B. Peumoatocytes Type II are radiosensitive.

Post-Irradiation changes; most manifestation of irradiation appear on the lung

A. Acute changes;
a. appear after dose of 10 gray in single shoot.
b. radiation pneumonitis.
B. Chronic changes
a. Moderate dose usually minimal changes.
b. high doses chronic fibrosis.

In summary

Diagnostic Radiology & Nuclear medicine:... insignificant effects

Radiation therapy
o irradiation of 25 Gy to both lungs with standard fractionation produce fibrosis in
8% of individuals.
o in case of 30 GY incidence rise to 50%.

Urinary system

Histologically;

A. The most radiosensitive structure in the kidney is the proximal Convoluted tubule.
B. Bladder: basal layer of the epithelium.

Post-irradiation changes

A. Kidney:
a. Acute changes: acute radiation nephritis even renal failure with loss of the
tubules & little effect on glomeruli.
b. Chronic changes: chronic radiation nephritis with renal atrophy.
B. Bladder:
a. acute changes: usually minimal.
 b. chronic changes: within 6 months after large dose... changes include loss of
the of epithelium, fibrosis and contracture leading to decrease bladder
capacity.

In summary

Diagnostic Radiology & Nuclear medicine:... insignificant effects

Radiation therapy
o irradiation of 26 Gy to both kidney with standard fractionation produce
significant damage.
o dose above 28 Gy have high risk in week 5 to produce fatal radiation nephritis.
o Sparing part of the kidney 1/3 or the kidney minimize the possibility of renal
failure.

Central nervous system

Histologically;

A. The nervous system is composed of non dividing full mature cells... The most radio-
resistant cells in the body.
B. Blood vessels ... moderately radio-sensitive.

Post-irradiation changes threshold of injury usually 20 - 40 Gy.

A. Acute changes: due to loss of glial tissue

low & moderate doses ... minimal.
High doses... myelitis that progess to necrosis.
B. Chronic changes: due to secondary ischemic changes
low and moderate dose: minimal.
high doses: gliosis, it particularly affecting the white matter than the gray
matter.

In summary

Diagnostic Radiology & Nuclear medicine:... insignificant effects

Radiation therapy
o irradiation of 50 Gy to brain with standard fractionation produce significant
necrosis. usually it's hard to distinguish the effect of irradiation from the
effect of the tumor.
o The response of the spinal cord varies according to the dose and the volume of
the irradiated area....
Cervical and thoracic area area more sensitive than lumber.
the incidence of irradiation myelitis increase dramatically after
A) 50 Gy in small volume Or B) 45 Gy in large Volume.
Total body radiation response

The term total body response or irradiation response dictates that:

A. The exposure to irradiation must be acute i.e. in minutes not hours.
B. The area exposed must be total body area or nearly the total area.
C. The radiation source must be X-ray, -rays or neutrons... thus internal irradiation by
radioactive isotopes don't induce full syndrome.

Survival time:

The 1ry effect of acute total body irradiation is shortening of the life span of the organism. The degree of
shortening depend on the dose of exposure.

The survival rime of an organism exposed to total body irradiation is expressed as an average survival
time. Variation in survival time exist among different species and even among animal of the same
species. Thus the idea of using the average eliminates these individual variations.

N.B. if the life span of an organism is reduced to less than 2 months, total body exposure is considered in
that case immediately fatal.

An new ideas has been formulated to accommodate for these variations

A. LD50/30: the lethal dose the is necessary to kill 50% of the a population within 30 days.
B. LD100/6: the lethal dose that is necessary to kill 100% of the population in 6 days

e.g. LD50/30 In....... Human is 2.5-3.0 Gy, Monkey 4.0 Gy. Rabbits 8.0 Gy.
In humans, the date of LD50/30 is taken based on the accidental exposures rather than true experiments.

Dose and survival time

A curve has be made relating the survival time of all mammals exposed to total body irradiation and the
dose. As the dose increase , both the number of survivors and survival time decrease........ e.g.

At a dose of 2.0 Gy small percent of animal dies,.... when the dose increase, the percent increase
until reaching the level of 10 Gy.....

In the range of 10 - 100 Gy, no effect on increasing the dose on number of the survivors i.e
The percent if survivors of 10 Gy is the same as 100 Gy.
But in general the survivors of thes high dose range is very few in
comparison to the ranges < 10 Gy.

Note that: Not all body tissue respond to irradiation with same extent thus its expected that some tissue
will show extensive damage to acute high doe while others would show minimal changes. The most
important changes that take place occurs in Bone marrow, GIT, CNS and these changes are responsible
for the mortalities in the animals.
 Survival time & Dose in Gy
100
90
80
70
60
50
Survival time
40 BM
30 $ GI Syndrome
20 CNS Syndrome
10
0
0 50 100 Dose in Gy

The figure reflect the damage on three different systems that may result in the death of the animal as
the primary cause of death is usually related to such system.

1. At dose of 1 - 10 Gy Death usually due to damage to Bone marrow thus the total body
response in that range is named hemopoietic or bone marrow syndrome.
2. At dose 10 - 100 Gy Death usually due to damage to the GIT and the total body response in
that range is named GIT syndrome.
3. At dose > 100 Gy Death usually due to damage to the CNS thus the total body respose in
that range is named CNS Syndrome.

Important notes on that curve

1) This dose range is not specific for humans but include many species.
2) There is overlap of these syndromes at the higher doses of each Range.... e.g. 6 - 10 Gy some
animal dies from damage to BM while other die from GIT Damage..... Same idea in the range
of 60 - 100 Gy.... thus it can said that the threshold for CNS damage is way less than 100 Gy.

Stage of response

The stage of response of animal to acute total body irradiation can be divided into three stages...
The duration of each stage is dose dependant i.e. "the lower the dose, the longer the duration of any of
these stage" "each may last from a period of weeks to minutes depending of the dose".

A.