Chapter 36 Early Effects of Radiation

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Chapter 36 Early Effects of Radiation

• In the 1920s 1930s 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 1960s blood work was done quarterly and
  dosimeters were worn.

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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.

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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.

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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.

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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
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Early Effects
Chromosome aberration Whole Body 5 rad
Gonadal Dysfunction Local Tissue 10 rad
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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

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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

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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.

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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.

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Manifest Illness

• Manifest Illness is a dose related period
  characterized by three separate syndromes.
• Hematologic Syndrome
• Gastrointestinal Syndrome
• Central Nervous System Syndrome

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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.

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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.

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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.

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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.

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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.

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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.

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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

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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.

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Central Nervous System Syndrome

• Manifest illness begins with the prodromal signs
  returning with increased intensity.
• Person becomes
• Disoriented
• Looses muscle coordination
• Difficulty breathing

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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.

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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.

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LD50/60 of Various Species
Pig 250 rad
Human 350 rad
Monkey 475 rad
Gerbil 1050 rad
Armadillo 2000 rad
Cockroach 10,000 rad
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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 or the
  tissue or organ. This is called atrophy.

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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

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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.

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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.

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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.

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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.

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Skin Reaction to High Exposure

• These are serial photographs on a patient that
  had multiple long fluoroscopic examination.
• Last image is after skin graphs.

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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.

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Effects on Skin

• Intermediate exposures depend upon the
  individuals 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.

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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.

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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.

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Skin Responses to High Dose Fluoroscopy
Transient Erythema 200 Rad Onset Hours
Main Erythema 600 Rad Onset 10 days
Temporary Epilation 300 Rad Onset 3 weeks
Permanent Epilation 700 Rad Onset 3 weeks
Moist Desquamation 1500 Rad Onset 4 weeks
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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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Hematologic Effects

• The Hemopoietic System consists of
• Bone Marrow
• Circulation Blood
• Lymphoid Tissue
• Lymph Nodes
• Spleen
• Thymus

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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.

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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.

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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.

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Hematologic Effects

• The principle response to irradiation is a
  depletion of all times 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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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

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Single Hit Aberrations

• If a single hit happens during the G1 phase 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.

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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.

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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.

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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.

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Reciprocal Translocation

• In reciprocal translations result in no loss of
  genetic material but simply a rearrangement of
  the material into an incorrect sequence.

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Kinetics 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,
  non-threshold response.
• Multi-hit aberrations produce a nonlinear,
  nonthreshold response.

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End of Lecture