RAD 255: Chapter 33 & 34

deterministic

• tissue reactions / non-stochastic

• high dose level

• early or late

• severity increases, as the dose increases (dose dependent)

• non-linear threshold

  • ARS

  • local skin damage

  • hematologic depression (decreased WBC)

Stochastic

• probabilistic/random

• low dose (low LET)

  • diagnostic x ray

• late response (somatic/genetic)

• severity DOES NOT increase, as dose increases

• linear non-threshold

  • cancer

  • genetic effects

early effects of radiation exposure

• Acute Radiation Syndrome (ARS)

• local tissue damage

• hematologic depression

Acute Radiation Syndrome (ARS)

• occurs at high-level, whole body exposure

• non-linear threshold

  • hematologic syndrome

  • gastrointestinal syndrome

  • central nervous system syndrome

Four stages of ARS

• prodromal

• latent

• manifest illness

• recovery or death

Dose required to produce the latent stage

1-100 Gy_t

Dose required to produce prodromal stage

≥ 1 Gy_t

Hematologic syndrome

• the reduction in WBC, RBC, & platelets

• Dose required: 2-10 Gy

• mean survival time: 10-60 days

• recovery possible within 6-8 weeks

• cause of death caused by bone marrow destruction

Hematologic syndrome: prodromal period symptoms

mild symptoms within few hours & may last a few days

Hematologic syndrome: manifest illness symptoms

• nausea

• vomiting

• diarrhea

• anemia

• leukopenia

• hemorrhage

• fever

• infection

GI syndrome

• severe GI symptoms

• radiation exposure kills stem cells → electrolyte imbalance → infection (intestinal lining)

• dose required

  • 10-50 Gy

  • GI syndrome can also damage the hematologic syndrome

• mean survival time: 4-10 days

  • stays the same independent of dose

Prodromal period symptoms: GI syndrome

• nausea

• vomiting

• diarrhea

manifest illness symptoms: GI Syndrome

• severe nausea

• vomiting

• diarrhea

• anemia

• leukopenia

• electrolytic imbalance

• lethargy

• fatigue

• shock

CNS syndrome

• Severe impairment of the CNS

• increased intracranial pressure

• inflammatory changes to the blood vessels of the brain

  • meningitis

• dose required ≥ 50 Gy

• mean survival time 0-3 days

• death within a few hours to 2-3 days

  • elevated fluid levels in the brain

prodromal symptoms: CNS

• excessive nervousness

• confusion

• severe nausea

• vomiting

• diarrhea

• loss of vision

• loss of consciousness

• burning sensation of skin

manifest illness symptoms: CNS

• prodromal symptoms +

• disorientation

• shock

• loss of muscle coordination

• difficulty breathing

• edema

• vasculitis

• meningitis

• respiratory distress

• coma

LD 50/60

the dose of radiation to the whole body that will result in death within 60 days to 50% of the population

GI syndrome

mean survival time does not change with increasing dose

kinetic factors affecting radiation induced tissue damage

• cell proliferation

• intrinsic radiosensitivity

• maturation of the cell

• method of administration

• quality of radiation

Erythema

• radiation-induced sunburn-like reddening caused by chromosome damage

• early deterministic response

• Dose required to produce: 2-5 Gy

Desquamation

• ulceration & denudation (removal of the top layer) of the skin caused by chromosome damage

• early deterministic response

• Dose required to produce: 15 Gy

Epilation

• Radiation-induced hair loss due to chromosome damage

• early deterministic response

• Dose required to produce temporary: 3 Gy

• Dose required to produce permanent: 7 Gy

skin effects dose response

non-linear threshold

SED50

localized skin dose of 5 Gy is required to effect 50% of those irradiated

sigmoid type

• non-linear threshold

• high dose fluoroscopy/radiation therapy

atrophy

• the shrinkage of an organ of tissue due to cell death

• partial body radiation

gonadal response

seen at doses as low as 100 mGy

Gametogenesis

the development of germ cells to mature cell

oogonia

female stem cells

oocyte

The most radiosensitive stage during female germ cell development

spermatogonia

The most radiosensitive stage during male germ cell development

spermatocytes & spermatids

the most radioresistant cells in males

pluripotential stem cells

• all cells of the hemopoietic system develop from a single type of stem cell

  • lymphocytes

  • granulocytes

  • erythrocytes

  • thrombocytes (platelets)

Cytogenetics

• the study of the genetics of cells and their chromosomes

• non-threshold

radiation induced chromosomal aberrations

follow a non-threshold dose response relation

during what phase are chromosomes taken from the cell nucleus

metaphase

multi-hit abberations dose response

• non-linear threshold

• 1+ Gy

acentric

• forms a ring

• no centromere

dicentric

• two centromeres

• multi-hit aberrations

isochromatids

• chromosome fragments

• single hit aberrations

dose required to reduce # of spermatozoa

100 mGy

temporarily infertility dose

2 Gy

permanent sterility dose

5 Gy

hemopoietic system

• bone marrow

  • RBC, WBC, cell proliferation

• circulating blood

• response to radiation = decreases the number of pluripotential stem cells

Lymphocytes

• AKA: WBC

• initiate the immune response

• first respond due to radiosensitivity

• lifespan in bone marrow within a few minutes

• slow to recover

• radiosensitive

Lymphopenia

• rapid decrease in lymphocytes (WBC) after radiation exposure

• 250 mGy (whole body exposure)

• caused by chromosome damage

Thrombocytes

• platelets

  • involved in clotting of blood

• recovery within 2 months

• response to radiation 30 days after irradiation

• 5 days in bone marrow

• 1 week in peripheral blood

• responds to radiation 30 days after irradiation

karyotype

• a map of each chromosome paired with its sister chromosome

• evaluated during metaphase

  • to evaluate structural radiation damage

Erythrocytes

• RBC

• transportation agents for oxygen

• response to radiation within a couple of weeks

• recovery within 6 months to a year

• 8 to 10 days in bone marrow

• 4 months in peripheral blood

• responds to radiation after a couple of weeks

• recovers after 6 months to a year

multi-hit abberations

• a single chromosome that sustains more than one hit

  • results in stickiness

  • 1+ Gy

  • non- linear, non-threshold

single hit abbertions

• a single chromosome that sustains just one hit

  • diagnostic x ray

  • low dose radiation

  • linear, non-threshold

Granulocytes

• scavenger-type cells used to fight bacteria

• response to radiation 15-20 days after exposure

• recovery within 2 months

• 8 to 10 days in bone marrow

• a couple of days in the peripheral blood

stickiness

• radiation-induced condition that appears at the site of a severed chromosome

• allows chromatids to join

radiation injury

dependent on the time it takes for the injury to present itself

incidence of radiation response

increases with radiation dose but not severity

late somatic effects

caused by low energy, low LET radiation

why is it difficult to study radiation exposure in humans?

• dose is usually unknown

• frequency of response is very low

results of chronic irradiation of the skin

• skin damage

• radiodermatitis

radiodermatitis

• skin appears cracked or flaky

• very high dose required to produce effect

chromosomal damage

can be seen as an early or late response

Leukemia

late stochastic response to radiation

cataracts

• eye radio sensitivity is age-dependent

• non-linear threshold

  • 2 Gy = Acute

  • 10 Gyt = 100% of the population will have

• 5-30 year latent period

radiation induced life span shortening

• potential risk to radiographers and radiologist

• linear non-threshold

effects of radiation exposure while pregnant

• embryologic effect (birth defects)

• genetic effects

all or nothing time frame

• pre-implantation

  • first two weeks of pregnancy

most radiosensitive time of pregnancy

• first trimester

  • major organogenesis

least radiosensitive trimester of pregnancy

second and third trimester

fetus response to radiation

• spontaneous abortion

• congenital abnormalities

• mental retardation

• childhood malignancy

point mutations

recessive mutations caused by radiation

genetic effects

linear non-threshold dose response

reducing radiation risk in fetuses

• 10-day rule

  • First 10 days after onset of menses is the safest time for imaging.

• patient questioning

• signage

critical dose for humans

6 Gy unless medical intervention

imminent death dose

10 Gy +

late somatic stochastic effects

• life span shortening of RT

• leukemia caused by chromosome damage

• malignant disease

• local tissue damage

late genetic stochastic effects

• single hit aberrations

• congenital malformations

• leukemia

• decreased intelligence

• recessive mutations

early deterministic effects

• erythema

• blood changes

• epilation

• ARS

late deterministic effects

• cataracts

• fibrosis

• organ atrophy

• loss of parenchymal cells

• reduced fertility

• sterility

mean survival time

as whole body dose increases, the average time between exposure & death decreases