radiation injury

see also:

• ionising radiation
• oncology
• radiation emergencies
• polonium poisoning
• tardigraves repair ionising radiation damage by substantially increasing DNA repair proteins which allows them to survive radiation levels 1000x greater than humans can survive ¹⁾

• bone marrow suppression results from exposures > 1Sv (Sievert)
• 0.25Sv is the lowest dose to cause detectable effects on lymphocyte count 
• 1Sv causes nausea & fatigue, mild haemopoietic syndrome in 50% of exposed
• 2Sv causes nausea, loss of body hair & possible death from haempoietic syndrome
• 3Sv whole body acute exposure results in:
  • prodromal phase lasting 2 days:
    • transient rise in neutrophils
    • fall in neutrophil & lymphocyte counts
  • latent phase from D2-20:
    • moderate neutropenia, lymphopenia, falling platelets & Hb
  • acute illness - bone marrow depression phase D20-40:
    • severe neutropenia, lymphopenia, thrombocytopenia & falling Hb
    • risk of death mainly due to secondary infection, bleeding, poor wound healing
  • recovery phase or death D40-60:
    • return of cell counts to normal
• 4Sv causes death in 50% of those exposed
• 6Sv causes death in most people exposed

• loss of crypt intestinal stem cells & mucosal barrier occurs due to exposures > 10Sv
  • however, the stem cells normally produce billions of daughter cells each day and these can de-differentiate back into stem cells if the patient can be kept alive for a week and there is no ongoing radiation injury ²⁾
• fluid & electrolyte loss, sepsis, probable death within 2wks

• microvascular injury due to exposures > 20Sv
• LOC a few minutes after exposure, brain damage then certain death within days

• treat life-threatening injuries
• survey for radiological contamination and decontaminate
• consider decorporation of absorbed or ingested radiological contaminants
• supportive care in reverse isolation
• 5-HT3 antagonists for vomiting (eg. metoclopramide, ondansetron)
• early consultation with haematologists & health physicists re:
  • dosimetry & prognosis
  • use of colony stimulating factors (CSFs)
  • stem cell transfusion
  • other Rx options
• prevention & Rx of infections
• observe carefully for erythema, hair loss, skin injury - if possible, take photographs
• psychological support
• Ix:
  • FBE then absolute lymphocyte counts 6hrly for 48hrs to assess radiation dose, & degree of injury
  • urinalysis to establish baseline
  • swabs from body orifices to assess possibility of internal radioactive contamination
  • wound dressing or wound swabs to determine if wounds are contaminated
  • 24hr urine x 4 days & faeces x 4 days as excreta may contain evidence of internal contamination
• RSP follow up:
  • collection of personal data for entry into DHS emergency database, including charts detailing areas of significant contamination
  • assist with psychological counseling to put risks in perspective

• Burns occur at exposures above 10Sv (erythema at lower doses)
• eg. an 8hr exposure to a piece of radioactive metal placed in a pocket caused initial erythema & blistering with evolving spreading necrosis which by 2mths had necrosed approx. 30cm diameter region of the thigh requiring amputation of the limb.

• may be apparent 2wks or so after exposures > 3Sv

• 300mSv to testes causes temporary sterility in men
• 3Sv to ovaries induces permanent sterility on women
• presumed risk of induction of severe genetic effects in offspring based on animal studies is 8-10 in a million per mSv exposure

• see also: neoplasia / cancer / tumours
• the natural risk of dying from cancer is 1 in 4
• the additional risk of dying from cancer due to radiation exposure is ~ 5/100,000ths per mSv exposure
• atomic bomb data in Japan for solid cancers:
  • approx. linear increase in rate of cancers with colon dose such that a 0.75Sv colon dose caused a 20-40% increase in cancer rate, while a 2Sv exposure caused a 40-100% increase in rate (ie. double the normal rate of cancer)
• examples of chronic exposure or late effects of acute exposure:
  • XS X-ray ⇒ skin cancer
  • ingestion luminous paints containing radium (alpha) ⇒ stomach cancer;
  • surface beta-ray seems to only cause skin burns & hair loss;
  • ingested Sr90 (beta) in fallout ⇒ replaces Ca in bones ⇒ insidious!!
  • fast neutrons ⇒ eye cataracts as high RBE;

• Measurement of cellular radiation effects is based on the “survival curve” which shows the % of cells still able to multiply (on a log scale) vs radiation dose (Gy) on linear scale;
• For most radiations, there is an initial “shoulder” on the curve where little damage is caused, as an accumulation of sub-lethal damage is necessary before an observable effect is seen, but once past this there is a relatively straight steep slope of rapidly reducing survival with increased dose.
• The slope depends on the RBE & thus on:
  • LET:
    • av. amount of energy deposited per micron of track;
    • This is important as the greater the no. of ionisations grouped closely together, the more likely to initiate a lethal chain of biological events & the less likely cellular repair mechanisms will act effectively;
    • Depends on type of particle & energy of particle;
  • OER:
    • ratio of doses to reduce survival to same level in anoxic vs normal conditions;
    • presence of oxygen enhances ionisation damage by binding to freshly severed ends of molecular structures thus preventing them from rejoining;
  • Presence of other radio-sensitisers & radio-protectors;
  • Time allowed for repair & recovery:
    • If some hours are allowed to elapse to allow cells to repair, the shoulder must again be passed.

• As cell function not related to mitosis & division is relatively insensitive to radiation requiring large doses to produce these other cell functions, the typical radiation effect on tissues arises from inhibition of cell division.
• Thus, tissues whose cells are continuously undergoing controlled division to maintain integrity are therefore the first tissues to show effects of radiation:
  • skin, GIT, bone marrow, immune system, malignant tumours;
• The initial effect is a reduction in cell numbers as the supply of new cells falls, this leads via homeostatic feedback mechanisms to a build up of the population stem-cells & to an increase in rate of cell division. If successful, the depleted population is restored, often with a temporary hyperplasia or overshooot.
• There may be an inflammatory response which may result in fibrosis;
• If the cell population falls below a critical level (eg. 8 Gy to bone marrow or 12Gy to GIT), the tissue can lose its functional effectiveness which may result in death of the individual;
• If the limit of tolerance is reached, there is an accumulation of permanent irreparable damage (eg. 18Gy);
• Cells that are long-lived & not dividing (eg. adult liver, thyroid, long-lived lymphocytes) show little effect after doses of several grays, but damage has been done & becomes apparent when the cells are stimulated to divide, even after long periods of time.
• Damage to gonads may lead to infertility due to impairment of germ cell division. Mutations also occur & the rate is proportional to dose, & thus, there is no “safe” level of background irradiation;
• Mutations in somatic cells may lead to tumours;

• Following a substantial dose, there is a latent period of hours or days before histologic evidence of tissue damage is seen.
• Early changes in skin include dilatation of blood vessels, & other signs of acute inflammation reflecting tissue injury;
• With a single dose of 15Gy, mitotic activity of basal cells arrested causing loss of epidermis & epilation. The walls of the dermal vessels are infiltrated with fibrin, later concentric proliferation of fibrous tissue is seen (endarteritis obliterans), followed by replacement with hyaline collagen. Large bizarre fibrocytic nuclei are present in dermal CT.
• With repeated doses, the dermal collagen becomes very dense with tendency to necrosis even years after exposure. Persistent melanin pigmentation & vasc.dilatation noted;

• radiation exposure to a pregnant woman:
  • prior to implantation (ie. 1st 9 days post-conception) will result either in embryonic loss or complete recovery
  • 15-50 days post-conception (ie. organogenesis phase) causes risk of:
    • neuropathology (peak incidence if exposure 1st half of this time period)
    • growth retardation
    • miscarriage
    • fetal malformations
    • carcinogenesis - increased risk of childhood cancer is thought to be 4-6 per 10,000 children per cGy exposure
    • thus max. allowable occupational radiation exposure to pregnant women is 0.5milliSievert/month
  • > 50 days post-conception:
    • as for 15-50 days BUT:
      • minimal risk of malformations & miscarriage
      • lower risk of neuropathology
      • similar risk of carcinogenesis & growth retardation