Deterministic effects of radiation Ch 33 Acute Radiation

Deterministic effects of radiation –Ch 33 Acute Radiation Lethality Local Tissue Damage Hematologic Effects Cytogenetic Effects Medical Radiography Program RTMR 284 Winter 2014

Effects of Radiation » Early ~ response within a few hours, days, weeks ~ encountered in diagnostic radiology rarely ~ Deterministic: those that exhibit increasing severity with increasing radiation dose » Late ~ response months or years after irradiation » Pioneers ~ “babes” in the field Medical Radiography Program

Comments » Many pioneers in the field of radiology died early or were diagnosed with cancer and leukemia » Some had to have arms amputated due to radiation exposure Medical Radiography Program

Acute Radiation Lethality » 3 stages of acute radiation lethality ~1. prodromal (period) syndrome ~2. latent period ~3. manifest illness stage Medical Radiography Program

1. Prodromal Syndrome The immediate response = radiation sickness acute clinical symptoms occur within hours & continue for up to a day or two at radiation doses above 100 rad to the whole body - signs & symptoms may appear within minutes to hours after exposure Symptoms nausea, vomiting diarrhea decrease in WBC’s Medical Radiography Program

2. Latent Period » A time of apparent well-being » No sign of radiation sickness ~ can last for only hours (doses over 5000 rad) ~ can last for weeks (doses from 100 -500 rad) Medical Radiography Program

3. Manifest Illness Stage » Actual illness stage, depends on dose » 3 main groups in the manifest illness stage ~ hematologic death ~ gastrointestinal death ~ central nervous system death Medical Radiography Program

Acute Radiation Lethality Review so far: » 3 stages of acute radiation lethality ~ 1. Prodromal syndrome - immediate sickness ~ 2. Latent period - apparent well being ~ 3. Manifest illness stage • hematologic death • gastrointestinal death • central nervous system death Medical Radiography Program

Review of Dose and Symptoms Medical Radiography Program

Hematologic Syndrome Dose range of 2 -10 Gyt (200 -1000 rad) Latent period may be as long as 4 wks Mild symptoms of prodromal stage vomiting, mild diarrhea, malaise, lethargy, fever Characterized by: reduction in numbers of WBC’s, RBC’s, & platelets in circulating blood Recovery begins in 2 -4 wks, takes 6 mo Medical Radiography Program

Gastrointestinal Syndrome » Doses in the range of 10 -50 Gyt (1000 -5000 rad) ~ prodromal symptoms start within hours and last one day ~ latent period of 3 -5 days » Symptoms: ~ loss of appetite ~ lethargic Medical Radiography Program

Gastrointestinal Syndrome cont. Death within 4 -10 days due to severe damage to cells lining intestines. Damaged cells proliferate & stem cells are destroyed (generation time is 3 -5 days) When lining of intestine has no more functional cells, fluids pass across the intestinal membrane & electrolyte balance is destroyed, infection occurs Medical Radiography Program

Question? » When the GI syndrome occurs will the Hematologic syndrome also be present? » Why or Why not? Medical Radiography Program

Answer » Yes the GI syndrome can occur with the Hematologic syndrome – there is enough time and dose for both to occur. Medical Radiography Program

Central Nervous System Syndrome Doses over > 50 Gyt (5000 rad) prodromal symptoms within minutes: nervous, confused, lose vision burning sensation in skin lose consciousness within the first hour Latent period up to 6 -12 hours Manifest Illness - CNS symptoms: prodromal symptoms reappear & : person disoriented, has difficulty breathing lose muscle coordination convulsions, seizures, lapses into a coma & dies Medical Radiography Program

Central Nervous System Syndrome » Cause of death: ~ increased fluid content of the brain ~ causes increased ICP’s and ~ inflammation of blood vessels Medical Radiography Program

Another Question? » When the CNS syndrome occurs, will the GI syndrome or the hematological syndrome occur? » Why or Why not? Medical Radiography Program

Answer » No – you would die from the CNS prior to there being enough time for the hematologic or GI syndromes to appear Medical Radiography Program

Question (yes another one!) » What dose response relationship is used for acute human lethality? » Think…. » Medical Radiography Program

Answer » Nonlinear, threshold Medical Radiography Program

LD 50/60 » The dose to the whole body that will result in death to 50% of the population irradiated within 60 days » For humans the dose is approximately 3. 5 Gyt or 350 rad without clinical support » Max dose from clinical data is 8. 5 Gyt or 850 rad Medical Radiography Program

Mean Survival Time (MST) » As the whole-body dose ’s…The time between exposure & death ’s (2 to 10 Gyt = 60 to 4 days) » MST is dose dependent for hematologic & CNS syndrome » MST is a constant 4 days » for GI syndrome Medical Radiography Program

Local Tissue Damage Higher dose is needed to produce a response when only part of the body is irradiated Vs. the whole body Very important that you cone on babies! Every organ/tissue can be affected by local irradiation effect is cell death atrophy non-function or recovery Medical Radiography Program

How Tissues Respond » Depends on 3 things: ~ the inherent radiosensitivity of the tissue ~ cell proliferation rate ~ maturation level of tissue » Sound familiar? ~ The law of B & T? ? ? Medical Radiography Program

Effects on Skin » Stem cells: basal cells ~ damage to basal cells results in radiation injury » Normal skin has 3 layers ~ epidermis - an outer layer ~ dermis - intermediate layer of connective tissue ~ subcutaneous layer of fat & connective tissue » Other structures ~ hair follicles, sweat glands, sensory receptors Medical Radiography Program

Medical Radiography Program

Atomic Structure of Skin Medical Radiography Program

Skin - Definitions » Erythema ~ reddening of the skin » Desquamation ~ ulceration and denudation of the skin » Clinical tolerance (for radiation therapy) ~ moist desquamation known as clinical tolerance » Atrophy ~ shrinkage, reduction in size Medical Radiography Program

Definitions » Epilation ~ loss of hair » Grenz Rays ~ soft X-rays (10 to 20 k. Vp) --old treatment to skin dz-» SED 50 ~ skin erythema dose ~ dose required to affect 50% of the people irradiated • about 600 rad. Medical Radiography Program

Local Tissues Effected Immediately » Gonads » Bone Marrow » Skin Medical Radiography Program

Gonads » Gametogenesis = development of the gametes or germ cells » They are critical target organs ~ Why? » Extremely sensitive to radiation ~ doses as low as 10 rad can cause a response ~ they produce the germ cells that control fertility & heredity Medical Radiography Program

Ovaries » Stem cells: oogonia » Most radiosensitive phase: oocyte » multiply only in fetal life ~ oocytes remain suspended until puberty » At puberty the follicles rupture ejecting the ovum ~ only 400 -500 used for fertilization ~ ~1 million oocytes in an infant & 400, 000 at puberty Medical Radiography Program

Ovaries » Babies & children are the most radiosensitive & germ cells are radiosensitive ~ CONE & SHIELD » Ovaries least sensitive in 20 -30 yr range ~ 100 m. Gyt 10 rad may delay or suppress menstruation ~ 2 Gyt 200 rad will produce temporary sterility ~ 5 Gyt 500 rad could cause permanent sterility Medical Radiography Program

Ovaries - mutations » 250 to 500 m. Gyt (25 -50 rad) can produce ’s in genetic mutations (animals) ~ Surviving oocytes can repair some genetic damage as they mature ~ Women may want to avoid getting pregnant for several months after ovarian doses 10 rad » Abortion NOT indicated for any diagnostic range dose Medical Radiography Program

Testes Stem cell: spermatogonia Most radiosensitive phase: spermatogonia Continually produced Spermatogonia spermatocyte spermatid spermatozoa or sperm cycle takes 3 -5 weeks Medical Radiography Program

Testes » 100 m Gyt 10 rad can cause reduction in # of sperm » 2 Gyt 200 rad produces temporary sterility ~ starts ~2 months after irradiation ~ WHY? » 5 Gyt 500 rad to testes produces permanent sterility Medical Radiography Program

Hemopoietic System Consists of: » Bone Marrow » Circulating Blood » Lymphoid Tissue (consists of) ~ Lymph nodes ~ Spleen ~ Thymus » Stem cell: ~ all cells of Hemopoietic system develop from the pluripotential stem cell Medical Radiography Program

Comments » On the test DO NOT list Lymph nodes, Spleen, Thymus separately for hemopoietic system ~ They are the lymphoid tissue which is one component of the hemopoietic system. Medical Radiography Program

Hemopoietic System » Main cell types: ~Leukocytes • lymphocytes • granulocytes ~Erythrocytes ~Thrombocytes Medical Radiography Program

Cell Types » Leukocytes - white blood cells - immune system ~ Lymphocytes • large round nucleus - nearly fills the cell • 20 -40% of the leukocytes • manufactured in bone marrow, spleen & thymus ~ Granulocytes • scavengers, destroys microorganisms • larger than erythrocytes • 52 -75% of leukocytes • manufactured in bone marrow Medical Radiography Program

Comments » Lymphocytes and Granulocytes are both Leukocytes » Know where each of the blood cells are manufactured Medical Radiography Program

Radiation Effects » Main radiation effect: ~ decrease the # of blood cells in circulation ~ Late effect: leukemia » Lymphocytes are 1 st cells to be affected • lymphopenia within minutes/hours • slow to recover • immediate response indicates that lymphocytes affected directly & not just precursor cells Medical Radiography Program

Radiation Effects » Granulocytes ~ rapid rise in # (granulocytosis) followed by rapid decrease & slower decrease (granulocytopenia) ~ recovery takes ~ 2 months » Platelets ~ thrombocytopenia (decrease in platelets) occurs slowly due to the longer time for precursor cells to reach maturity ~ minimum level in ~ 30 days & recovery in ~ 2 months Medical Radiography Program

Radiation Effects » Erythrocytes ~ less sensitive than other blood cells ~ very long lifetime in peripheral blood ~ injury noticeable for several weeks ~ total recovery (without intervention) may take 6 months to a year Medical Radiography Program

Cytogenetic Effects » Cytogenetics = the study of the genetic aspects of cells, chromosomes in particular » Radiation-induced chromosome aberrations follow a Nonthreshold relationship » High doses of radiation cause chromosome aberrations ~ Unable to see chromosomal aberrations under a dose of 100 m Gyt 10 rad Medical Radiography Program

Cytogenetic Effects » Cytogenetic damage may occur immediately but may not be seen for awhile ~ takes time for that stem cell to reach maturity ~ it can be months and years before damage can be measured. » Chromosome abnormalities can be seen in circulating lymphocytes even 20 years after a radiation accident… Medical Radiography Program

Karyotype » Karyotype = a chromosome map » Photographs of chromosomes are enlarged » Each chromosome is cut out & matched with its “sister” » Chromosomal damage can be observed at this point Medical Radiography Program

Chromosomal Damage » In an inbred population both chromosomes of the pair will usually be the same ~ in a normal population the two chromosomes will usually contain many different genes » When a chromosome is changed the genetic character transmitted is changes ~ these changes are mutations • most mutations are recessive Medical Radiography Program

Single - Hit » Single-hit chromosome ~a chromosome hit produces a visible derangement of the chromosome ~represents severe damage to the DNA • chromatid deletion, isochromatids, chromatid fragments Medical Radiography Program

Double-hit » Double-hit chromosome ◦ most significant for latent damage ◦ when the chromosome is hit more than once ring chromosomes, dicentric chromosomes, chromatid fragments Medical Radiography Program

Chromosomal Damage Medical Radiography Program

Chromosome Map Medical Radiography Program

Chromosome Aberrations » At very low doses: ~ single-hit aberrations are observed » Doses over ~ 100 rad (1 Gray) ~ multihit aberrations observed more frequently » Single-hit uses a linear, nonthreshold dose-response relationship » Multi-hit uses a nonlinear, nonthreshold relationship Medical Radiography Program

THE END Medical Radiography Program