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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.

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Week 8c Chapter 36 Early Effects of Radiation

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week 8c chapter 36 early effects of radiation
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
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 radiation3
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
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.
acute radiation syndrome
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
  • 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
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 period10
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
  • Manifest Illness is a dose related period characterized by three separate syndromes.
    • Hematologic Syndrome
    • Gastrointestinal Syndrome
    • Central Nervous System Syndrome
hematologic 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 syndrome13
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 syndrome14
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
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 syndrome16
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 syndrome17
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
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 syndrome19
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 syndrome20
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 syndrome21
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.
ld 50 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.
local tissue irradiation
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 irradiation25
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
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 skin27
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 skin28
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 skin29
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
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 skin31
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 skin32
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 skin33
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 skin34
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.
effects on gonads
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 gonads37
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
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 gonads39
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 gonads40
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 gonads41
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 gonads42
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
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 gonads44
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 gonads45
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
Hematologic Effects
  • The Hemopoietic System consists of:
    • Bone Marrow
    • Circulation Blood
    • Lymphoid Tissue
      • Lymph Nodes
      • Spleen
      • Thymus
hematologic effects47
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 effects48
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 effects49
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 effects50
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 effects51
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 effects52
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
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 effects54
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
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 effects56
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 effects57
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 effects58
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 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
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 aberrations61
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
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
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 translocation64
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
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, non-threshold response.
  • Multi-hit aberrations produce a nonlinear, nonthreshold response.
end of lecture

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