Transcript Week 8 B Chapter 36 Early Effects of Radiation Exposure

Week 8c Chapter 36 Early Effects
of Radiation
• In the 1920’s & 1930’s if was not
uncommon for radiologic technologist to
get hematologic exams weekly.
• Blood work was used to monitor the
worker for over exposure before
dosimeters were available.
• In the 1960’s blood work was done
quarterly and dosimeters were worn.
Early Effects of Radiation
• In humans, a response to radiation that
occurs within months of the exposure is
called Early Effects.
• Death is the most devastating human
response to radiation. No deaths
immediately after diagnostic radiography
have ever been reported.
Early Effects of Radiation
• Many of the pioneers in radiology died
from long term effects of exposure.
• Diagnostic x-ray beams always result in
partial body exposure, which is much less
effective at producing a response than
whole body exposure.
Major Lethal Exposures in Humans
• 1945 Atomic Bombs in WW2
• 1979 Three Mile Island Nuclear Power
Plant Accident killed one person.
• 1986 Chernobyl Russia nuclear reactor
melt down killed 30 people (official)
500,000 reported.
• Military accidents have also killed humans.
Early Effects
Death
Whole Body
200 rad/ 2GyT
Hematolic
Depression
Whole Body
25 rad/
0.25 GyT
Skin Erythema
Small Field
200 rad/ 2GyT
Epilation
Small Field
300 rad/ 3GyT
Early Effects
Chromosome
aberration
Whole Body
5 rad
Gonadal
Dysfunction
Local Tissue
10 rad
Acute Radiation Syndrome
• 1. Prodormal period: acute symptoms
within hours of exposure.
• 2. Latent period: time free of any visible
effects.
• 3. Manifest illness:
– Hematologic syndrome
– Gastrointestinal syndrome
– Central Nervous System Syndrome
• 4. Recovery or Death
Prodromal Period
• Prodromal period may last for a few hours
or a couple of days.
• Symptoms include nausea, vomiting and
diarrhea.
• Severity of symptoms are dose related.
• For extremely high exposure it is hard to
distinguish Prodromal from manifest
illness
Latent Period
• After prodormal radiation sickness there is
a period of apparent well-being called the
Latent Period.
• With very high exposure, it may last only a
few hours. For lower exposures, it may
last for weeks.
• May be mistakenly thought to be recovery
from moderate exposure.
Latent Period
• Biologic and physiologic changes are
occurring even though they give no
indication of the response yet to follow.
• Responses are extremely variable relative
to dose.
• High exposure will skip the latent period
while low exposure may not have the
Prodromal period.
Manifest Illness
• Manifest Illness is a dose related period
characterized by three separate
syndromes.
– Hematologic Syndrome
– Gastrointestinal Syndrome
– Central Nervous System Syndrome
Hematologic Syndrome
• The hematologic syndrome is produced
with exposures of 200 to 1000 rads.
• The prodormal period will be rather mild
lasting for a few hours to a couple of days.
The latent period may last for a month.
Hematologic Syndrome
• There are no obvious signs of illness,
although the number of cells in the
peripheral blood is declining.
• Manifest illness is characterized by
vomiting, mild diarrhea, malaise, lethargy
and fever. All types of blood cells are
depleted.
Hematologic Syndrome
• If the patient recovers, recovery will begin
in two to four weeks.
• If the exposure is severe, the cell depletion
will continue until the body no longer has
any defense from infection.
• Just before death, infections and
dehydration will be pronounced.
Gastrointestinal Syndrome
• After radiation exposures of 1000 to 5000
rads, the GI syndrome occurs.
• The Prodromal symptoms of vomiting and
diarrhea occur within hours and may last
for days.
• A latent period of 3 to 5 days follows with
no apparent symptoms.
Gastrointestinal Syndrome
• The manifest illness phase begins with a
second wave of nausea and vomiting
followed by diarrhea.
• Patient my loose appetite and become
lethargic. Diarrhea increases to watery
and then bloody stools.
• Death occur occurs in 4 to 10 days.
Gastrointestinal Syndrome
• Intestinal cells are normally rapidly
proliferating. Radiation kills the stem cells
stopping repopulation.
• At the level of exposure for GI syndrome,
hematologic damage also occurs but the
response is slower so the patient dies
before the manifest symptoms occur.
Central Nervous System Syndrome
• CNS Syndrome occurs with exposures
greater than 5000 rads.
• A series of signs and symptoms occur that
leads to death in a matter of hours to 3
days.
• First is nausea and vomiting minutes after
exposure
Central Nervous System Syndrome
• Within the first hour.
– The person will become extremely nervous
and confused.
– Complain of burning sensation in the skin.
– Loss of vision and consciousness.
• A latent period of about 12 hours follows
with the symptoms subsiding.
Central Nervous System Syndrome
• Manifest illness begins with the prodromal
signs returning with increased intensity.
• Person becomes:
– Disoriented;
– Looses muscle coordination
– Difficulty breathing
Central Nervous System Syndrome
• Person experiences:
– Loss of equilibrium
– Convulsive seizures
– Ataxia
– Lethargy
– Coma followed by death.
• The ultimate cause of death is increased
fluid content of the brain.
LD50/60
• The LD50/60 is the dose of whole body
radiation necessary to kill 50% of the
population in 60 days.
• For humans the lethal dose is 350 rads.
With medical support, humans can survive
850 rads.
LD50/60 of Various Species
Pig
250 rad
Human
350 rad
Monkey
475 rad
Gerbil
1050 rad
Armadillo
2000 rad
Cockroach
10,000 rad
Local Tissue Irradiation
• When only a localized area is irradiated,
higher dose is required to produce a
response.
• Every organ and part of the body can be
affected by partial body irradiation. The
affects of cell death is shrinkage or
reduction in size of the tissue or organ.
This is called atrophy.
Local Tissue Irradiation
• If the dose is high enough, any tissue will
have immediate response.
• Tissue types that are commonly affected
immediately are:
– Skin
– Gonads
– Bone Marrow
Effects on Skin
• The skin is the tissue that we have the
most experience.
• Normal skin consists of three layers:
– An outer layer (epidermis)
– An intermediate layer of connective tissue
(dermis)
– A subcutaneous layer of fat and connective
tissue.
Effects on Skin
• Additional accessory structures of the skin
include:
– Hair follicles
– Sweat glands
– Sensory Receptors
• All skin layers and accessory structures
participate in the response to irradiation.
Effects on Skin
• Like intestinal cells, skin cells have a
continuous cell renewal but at a much
slower rate.
• The epidermis consists of several layers of
cells with the inner most being basal cells.
• Basal cells are stem cells that as the
mature migrate to the surface.
Effects on Skin
• One of the common responses of the skin
during radiation therapy is a Erythema or
a sun burn like reddening of the skin
followed in a couple of weeks by
desquamation or ulceration and
denudation of the skin.
Skin Reaction to High Exposure
• These are serial
photographs on a
patient that had
multiple long
fluoroscopic
examination.
• Last image is after
skin graphs.
Effects on Skin
• Many of the pioneers of radiography
including Roentgen suffered from
radiation induced skin burns.
• Patients were exposed for up to 30 minute
exposures so burns were common
• Low level exposures do not cause
Erythema.
Effects on Skin
• Intermediate exposures depend upon the
individual’s radiosensitivity, the dose rate
and the size of the area of exposure.
• High exposure will cause a response for
all people.
• The Skin Erythema Dose 50 would be a
dose causing Erythema half the time.
Effects on Skin
• Another skin response is hair loss or epilation.
• For many years soft rays (10 to 20 kVp) called
Genz rays were used to treat many skin
diseases such as ring worms.
• Tinea Capitis or ring worm in the scalp was
successfully treated with Genz rays.
• Often the hair would fall out for months.
Effects on Skin
• Today the exposure of the skin is currently
receiving more close attention because of
high dose fluoroscopy.
• During interventional fluoroscopy, the
patient may receive 20 R/ minute so
hazards do exist.
Skin Responses to High Dose
Fluoroscopy
Transient
200 Rad
Erythema
Main Erythema 600 Rad
Onset Hours
Temporary
Epilation
Permanent
Epilation
300 Rad
Onset 3 weeks
700 Rad
Onset 3 weeks
Moist
Desquamation
1500 Rad
Onset 4 weeks
Onset 10 days
Effects on Gonads
• Human gonads are critically important target
organs because they are particularly sensitive to
radiation.
• Responses to exposures as low as 10 rads have
been observed.
• Since these organs produce germ cells that
control fertility and heredity, their response is
well studied.
Effects on Gonads
• Cells from the testes and ovaries respond
to radiation differently due to differences in
the progression from stem cells to mature
cells.
• Germ cells are produced by both ovaries
and testes but they develop at different
rates and at different times.
Effects on Female Gonads
• During the late fetal life, many primordial
follicles grow to encapsulate the oogonia,
which become oocytes.
• These follicles remain suspended state of
growth until puberty.
Effects on Female Gonads
• At puberty, the follicles rupture with
regularity, ejecting a mature germ cell
called the ovum.
• There will be only about 400 to 500 such
ova available for fertilization during the
next 30 to 40 years.
• Radiation effect on the ovaries are age
dependent.
Effects on Female Gonads
• During fetal life and into early childhood,
the ovaries are especially radiosensitive.
• They decline in sensitivity reaching a
minimum between 20 and 30 years old.
• After age 30, they increase in
radiosensitivity with age.
Effects on Female Gonads
• The most radiosensitive cell during female
germ cell development is the oocyte in a
mature follicle.
• Doses as low as 10 rads have resulted in
a delay or suppression of menses.
• 200 Rads produce pronounced infertility.
Effects on Female Gonads
• 500 rad will result in permanent sterility.
• Doses of 25 to 50 rad are associated with
measurable increases in genetic mutation.
Effects on Male Gonads
• The testes like the ovaries will atrophy with
high doses of radiation.
• The earliest stage of cell development is
the time of greatest radiosensitivity.
• Therefore effects will not be apparent for 3
to 5 weeks.
Effects on Male Gonads
• Exposures of 10 rad have resulted in a
reduction of sperm.
• 200 rad will produce temporary sterility.
• 500 rad produces permanent sterility.
Effects on Male Gonads
• After an exposure of 10 rad, the male
patient should refrain from procreation for
two to four months so the irradiated cells
have matured and disappeared.
• There will still be a possibility of genetic
damage.
Hematologic Effects
• The Hemopoietic System consists of:
– Bone Marrow
– Circulation Blood
– Lymphoid Tissue
• Lymph Nodes
• Spleen
• Thymus
Hematologic Effects
• All tissue develop from the same stem cell
called a pluripotential stem cell.
• Although the spleen and thymus produce
one type of leukocyte, the lymphocyte,
most circulating lymphocytes are produced
in the bone marrow.
Hematologic Effects
• In children, bone marrow is rather evenly
distributed through out the skeleton.
• In adults, the active bone marrow is limited
to the flat bones and the ends of long
bones.
Hematologic Effects
• From a single pluripotential stem cell, a
number of cells are produced.
– Lymphocytes used in the immune response.
– Granulocytes scavenger cells used to fight
bacteria.
– Thrombocytes or Platelets
– Erythrocytes Red blood cells that carry
oxygen.
Hematologic Effects
• The principle response to irradiation is a
depletion of all types of blood cells. Lethal
exposure to the stem cells and other
precursor cells cause the depletion.
• Lymphocytes are the first cells to be
affected. Almost immediately the numbers
are reduced directly by the exposure.
Hematologic Effects
• Lymphopenia is the result and they are
very slow to recover.
• Granulocytes experience a rapid increase
followed by a rapid decrease and then a
gradual decrease. Recovery will take 2
months.
• Thrombocytes depletion is slower and
recover in 2 months.
Hematologic Effects
• Erythrocytes are less sensitive than the
other blood cells.
• Blood cell injury is dependent upon the
mature life time of the cell and the time it
takes to produce the mature cells.
• Lymphocytes and Spermatogonia cells are
the most radiosensitive cells in the body.
Cytogenetic Effects
• Cytogenetics is the study of genetics of
the cell and in particular, cell
chromosomes.
• Radiation induced chromosome
aberrations follow a nonthreshold dose
response relationship.
Cytogenetic Effects
• Attempts to measure chromosome
aberrations in patients after diagnostic
x-rays examinations have been largely
unsuccessful.
• High dose fluoroscopy have shown
radiation induced chromosome aberrations
soon after exposure.
Cytogenesis Effects
• High doses of radiation without question
cause chromosome aberration.
• Low doses of less than 5 rad can also
cause damage but technically they cannot
be observed.
• Even more difficult is the identification of
chromosome damage and latent illness or
disease.
Cytogenetic Effects
• When the body is irradiated, all cells can
suffer Cytogenetic damage.
• Such damage is an early response
because if the cell survives, the damage
will be manifested in the next mitosis.
• Lymphocytes are often used for
cytogenetic analysis.
Cytogenetic Effects
• Chromosome damage
takes three forms.
• Chromatid Deletion or a
severing of a portion of
the chromatid from a
single hit.
• When the chromosome is
hit twice, it may form a
ring or dysenteric
aberration.
Cytogenetic Effects
• Another form of
chromosome damage
from multiple hits of the
chromosome is called
Reciprocal
Translocation.
• In Dysenteric Aberrations,
genetic material is lost.
With Reciprocal
Translocation, it is mixed
up.
Chromosome Radiation
Aberrations
• Chromosome DNA Aberrations result from
– Single hit Chromosome Aberrations
– Multi-Hit Chromosome Aberrations
– Reciprocal Translocations
• A chromosome hit represents severe
damage to the DNA
Single Hit Aberrations
• If a single hit happens
during the G1 phase, it will
fracture the chromatid
called chromatid
deletion. During the S
phase, the remaining
chromatid and the
missing fragment is
replicated.
• At the metaphase there
will be two sister
chromatids with missing
material and two acentric
fragments.
Single Hit Aberrations
• If it happens in the G2
phase, the chance
that ionizing radiation
will pass through the
sister chromatid is
low.
• Usually the radiation
produces a deletion of
only one arm.
Multi-Hit Chromosome Aberration
• A single chromosome can
sustain more than one hit.
• In the G1 phase a ring
chromosome is produced
if the two hits are on the
same chromosome.
• Dicentrics are produced
when adjacent
chromosome each suffer
one hit and recombine.
Reciprocal Translocation
• The multi-hit
chromosome aberration
represents rather severe
damage to the cell.
• The acentric fragment is
either lost or attracted to
one of the daughter cells.
• Consequently one or both
daughter cell may be
missing considerable
genetic material.
Reciprocal Translocation
• In reciprocal
translations result in
no loss of genetic
material but simply a
rearrangement of the
material into an
incorrect sequence.
Kinetic of Chromosome Aberrations
• At very low doses, only
single hit aberrations
occur.
• When the radiation dose
exceeds 100 rad, the
frequency of multi-hit
aberrations increase.
• Single hit aberration
follow a linear, nonthreshold response.
• Multi-hit aberrations
produce a nonlinear,
nonthreshold response.
End of Lecture
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