1.4.3.2 Exogenous Factors

1.4.3.2 Exogenous Factors

GOALS

1. To review the basic concepts relating to radioactive compounds.
2. To understand the biologic effects of exposure to radioactive compounds.
3. To review some historical radiation disasters and epidemics
4. To understand the potential scenarios of a major radiation exposure today.
5. To review basic assessment and management of patients with radioactive exposures.

BASIC CONCEPTS OF RADIOACTIVE COMPOUNDS

A. The Atom

An atom consists of a nucleus and orbiting electrons. The nucleus contains most of the mass of the atom. It is comprised of neutrons, which confer a binding affinity, and protons, which contain repulsive or coulombic forces.

As the number of protons in a given element increases, so does the repulsive force generated. The number of neutrons required to balance this effect increases. Sometimes the neutrons are not able to compensate adequately with binding forces. It is at this point that a substance is considered unstable.

To increase stability, the atom, or parent compound releases some energy and/or mass, to form a daughter compound, and decay products. The energy imparted to these decay products can be measured as radioactivity. This process occurs at a certain frequency or disintegrations per second and can be referred to in Curies (Ci).There are numerous decay products that can be formed.

B. Definitions

1. Radiation: energy given off by atoms in form of particles or electromagnetic rays.

2. Non-ionizing radiation: radiation that gives off enough energy to make atoms vibrate, however not enough energy to remove electrons (ex: radio waves, visible light, microwaves)

3. Ionizing radiation: radiation that has enough energy to remove electrons from atoms which convert to ions in form of particles or rays (particles, g-rays, x-rays).

a. Types of ionizing radiation
i. a-particles: subatomic fragments consisting of 2 protons and 2 neutron that are ejected by the nuclei of some unstable atoms. Results in the ejection of a positively charged heavy particle identical to a helium nucleus. The parent atom has a large atomic number (83 or higher) and becomes another element since 2 protons are lost.
(a). Examples of a-emitters include: americium-241, plutonium-236, uranium-238, radon-222.
(b). External exposure not considered hazardous – because of their large mass they travel slowly and can only penetrate <0.1 mm tissue. The outer layer of skin or a piece of paper can stop them. Once they have lost their energy they pick up 2 electrons and become a helium atom.
©. Inhaled or ingested a-particles cause biologic damage increasing the risk of cancer, particularly lung cancer. Most common inhalational exposure for people is from Radon. Radon-222 is a decay product of Uranium-238, it is a gas with a half-life of 3.8 days, meaning that it emits a-particles at a high rate.
ii. b-particles: subatomic fragments that are ejected from the nucleus of an atom with a negative charge. Equivalent to electrons except that they are nuclear in origin rather than from the valence shell. Occurs when the ration of neutrons to protons in the nucleus is too high. Theory is that an excess neutron is converted to a proton and electron. The proton remains in the nucleus and the electron is ejected. Results in an increase of nuclear protons by one, converting the atom to another element.
(a). Examples of b-emitters include: Iodine-131, Strontium-90, Carbon-14 and Cesium-137 (although g-rays from Cs are more hazardous).
(b). External exposure to b-particles can cause local burns. Given their small size, b-particles can penetrate skin and soft tissue by a few centimeters.
©. Internal exposure to b-particles is of much greater concern because of their small size and their increased ability to cause tissue damage at the molecular level.
iii. g-rays (gamma): electromagnetic energy otherwise known as a photon. Most energetic wave in the electromagnetic spectrum. Very short wavelength photon that has no mass or charge. High energy waves that travel at the speed of light. g-ray emission often occurs when an unstable nucleus of a radioactive atom gives off a b-particle, but still contains too much energy, therefore releases photons.
(a). Examples of g-emitters include: Cobalt-60, Cesium-137, and Technicium-99.
(b). External and internal exposures are of equal concern since g-rays can penetrate through the entire body. They are hazardous because they transfer energy to electrons, which then interact with tissue at the molecular level to form destructive ions. The will not make the patient radioactive, however, because they are pure electromagnetic energy.
iv. x-rays: another form of electromagnetic energy that is formed when an unstable nucleus captures one of its valence electrons (known as electron capture)and releases a neutrino. The higher valence shells give up electrons to fill the orbital vacancy and energy is released in a short wavelength burst called an x-ray. X-rays behave in a similar manner to g-rays, but they have a lower energy and are therefore less destructive.

C. Measuring Radiation

1. Radioactive contamination can be quickly detected with Geiger counters.

2. Rads (radiation absorbed dose):. A measure of the energy deposited in tissue by ionizing radiation, or the units used to measure the dose of radiation absorbed by a gram of tissue.

3. Gray (Gy): This is the international unit of measurement and is replacing the rad terminology. 1 Gy =100 rad

4. Rem (radiation equivalent in man or Roentgen equivalent in man): conventional unit of measurement of the effective dose

5. Sievert: 100 rem; international unit of measurement of effective dose

6. Gray = sievert when dealing with gamma rays and beta particles.

7. Effective dose: measured in sieverts; the dose at which an effect occurs in man; used to assess the probability of an effect occurring in a population as the dose is increased

8. Radioactive Decay: atoms are unstable if the protons and neutrons that make up the nucleus are unbalanced causing an excess of energy. The atom will then attempt to stabilize by throwing off excess energy in the form of particles or electromagnetic rays. As the nucleus emits radiation, it undergoes a sequence of transformations called radioactive decay to form different radionuclides until the forces in the nucleus are finally balanced. If the atom gives off neutrons, it will become a different isotope of the atom, whereas if the atom gives off protons, it will be transformed into another element altogether. The total number of nucleons (protons + neutrons) is conserved. Therefore neutrons are sometimes converted to protons and vice versa, but this process gives off energy. The parent compound will therefore have a higher mass than the decay product. For example Uranium-238 is unstable and starts a decay chain that eventually leads to the stable nuclide Lead-206. This occurs over time (Uranium-238 has a half-life of 4.5 billion years, whereas radioactive iodine is short-lived; cesium, strontium, and cobalt also have half-lives of many years)

D. Biological Effects

1. The biological effects of radiation relate to the ability of these particles to confer tissue damage. Radiation type and dose, duration of exposure, patient age, and where the decay process or products localize in the body are important factors in determining the extent of injury. Generally a decay product imparts its energy to the surrounding tissue. Depending on the mass and speed of the decay product, either direct cellular damage occurs, or a cascade of free-radical damage occurs as electrons are expelled from the atoms of the tissue.

2. Biological Damage occurs with the splitting of covalent bonds, formation of free radicals and the interaction of free radicals with oxygen, forming HO·. Cells with high oxygen content are more susceptible to g-radiation.

3. Radiation Damage occurs when DNA injury in the cellular nucleus leads to cell dysfunction. Generally speaking. younger patients are more susceptible to radiation damage since their cells are dividing more rapidly. This is especially true of the thyroid gland which avidly sequesters radioactive Iodine.

4. Clinical symptoms develop when:
a. a large number of cells die
b. cells essential for survival die

5. Rapidly dividing cells are most sensitive to radiation (i.e., intestinal mucosal cells and bone marrow cells)

E. Types of Radiation Exposure

1. Localized Exposure
a. From direct handling
b. Development of radiation burns (look like thermal burns); erythema, desquamation, blistering, appear over a period of days
c. Extent of localized injury is dependent on extent of penetration of radiation

2. Whole Body Exposure
a. Effect of whole body exposure to gamma rays or x-rays is dependent on dose
i. > 2 grays
haematopoietic syndrome from bone marrow depression (anaemia, thrombocytopenia, leukopenia); Lymphocyte counts at 48 hours are prognostic: less than 300 cells/m3 has a poor outcome, greater than 1200 cells/m3 at 48 hours has a good prognosis. Hemorrhage and infection are sequelae of this syndrome and can present 1-3 weeks after the exposure. (a). maximal leukopenia and thrombocytopenia occurs several weeks after exposure – hemorrhage and infection can be major problems at this time (b). if the bone marrow is not completely eradicated; recovery will begin ©. unfortunately, even if the haematopoietic syndrome is treated, death usually follows due to radiation pneumonitis, denudation of the alimentary tract, hepatic and renal dysfunction.

ii. 10-30 grays
gastrointestinal syndrome (death of intestinal mucosal cells);

  • rapid onset of nausea, vomiting, diarrhoea (the earlier the onset, the greater the radiation dose)
  • followed by a latent period
  • recurrent GI symptoms
  • sloughing causes fluid and electrolyte disturbances
  • and predisposes to bacteraemia from gastrointestinal flora
  • death

iii. > 30 grays
cardiovascular collapse and central nervous system damage with symptoms of lethargy, tremor, seizure, ataxia and death in 24-72 hours

iv. Patients may also have dermal burns, corneal injury, and blast injuries if the exposure was secondary to an explosion or very high radiation dose.

b. Long term sequelae of radiation exposure relates to the chance event of chromosomal injury. The common pathway is the inability of the affected cells to repair faulty DNA. This may lead to uncontrolled replication of a surviving abnormal cell, resulting in neoplasm. It may also lead to inhibition of normal cell replication with subsequent sterility, cataracts, or alterations in the genetic material that will be donated to offspring.

For example*: Ra=Radium Rn=Radon He= Helium= an alpha particle

226Ra
222 Rn + 4He + g88 86 2c. Radium accumulates in bone. Therefore, any local uptake of radium in bone can potentially lead to localized decay products in bone. Historically, radium was used to paint the glowing numbers of watch dials. Radium watch dial workers employed before 1930 had a high incidence of bone cancer and leukaemias thought to be related to their occupational exposure.

222Rn
218Po + 4He + 86 84 2a. The daughter product, radon, is formed in an excited, unstable or (high energy) state. This extra energy is released as a gamma (g) ray which has no mass but whose energy can cause tissue damage. Lung cancer in miners is correlated to dose-dependent exposure to inhaled radon. Radon gas is inhaled in the lung.

*Superscript is the mass number= protons + neutron=nucleons.
Subscript is the atomic number from the periodic table = number of protons.
Usually alpha particles (helium nuclei) are harmless because they are big particles. As they collide with another mass, in this instance our skin, they slow to a stop, so penetration is limited.
Protective clothing may prevent particles from reaching the skin. Alpha particles are dangerous only if produced by decay of an incorporated parent compound after ingestion, inhalation, or dermal absorption from damaged skin.


F. Minimizing Effects of Radiation Exposure

1. Get far away from the radioactive source as quickly as possible!

2. Absorbed dose is proportional to time

3. Absorbed dose is proportional to distance - the Inverse square law applies here: the dose of radiation drops off proportionally to the square of the distance of the source.

4. Shielding with lead provides protection from small radioactive sources

HISTORICAL RADIATION USES AND DISASTERS

A. Atomic Bomb Survivors

1. Hiroshima (8/6/45) Uranium-235 and Nagasaki, Japan (8/9/45) Plutonium-239 A-bombs
a. 64,000 killed immediately by the blast, thermal effects and release of gamma and neutron radiation
b. survivors ↑ risk for stomach, colon, liver, lung, breast, thyroid, bladder cancers; leukaemias

2. Irradiation treatment for Tinea Capitis (Ringworm) 1905 - 1960
a. > 10,000 children irradiated (x-ray) in U.S. and Israel to treat tinea capitis
b. Associated with skin and thyroid cancers; rarely fatal

3. Irradiation treatment for Ankylosing Spondylitis 1935 – 1954
a. 14,000 men irradiated (x-ray) in Great Britain and Ireland to treat ankylosing spondylitis
b. Significant increase in development of leukaemia and solid tumours

4. Chernobyl Disaster 4/2686
a. Reactor core blown apart releasing Iodine-131
i. of the radionuclides or isotopes available for release in a nuclear reactor accident I131 is most significant due to huge reactor core load and high volatility
ii. uptake rapid from GI (ingestion of contaminated milk and vegetables) and lung; (radioactive cloud released)
iii. incorporation into thyroid is complete within 48 hours; once made into thyroid hormone it slowly decays, releasing beta and gamma radiation
b. 30 power plant employees and firemen died within weeks
c. Significant increase in thyroid cancer in survivors
i. Incidence of childhood thyroid cancers dramatically increased in the Ukraine after the Chernobyl Disaster
d. In the event of a nuclear incident, one can prophylactically block uptake into the thyroid with KI tablets 100 mg iodide for 7-14 days, unless exposure persists.

SPECIFIC RADIONUCLIDES

A. Radon[Rn222]: gas released from decay of U238 which goes through 4 steps to form Ra226 which eventually decays to form Rn222; releases a particles, so only a problem if inhaled or ingested; acceptable home level < 4 picocurie/L. Associated with lung cancer as found in uranium miners; actual carcinogen appears to be the daughter compounds (plutonium Po214,218) which are solids and deposit in airways; much higher risk in smokers; Clinton, NJ has very high radon levels since it and most of New England is on the Reading Prong.

B. Strontium90: product found in nuclear fallout; similar to calcium (an alkaline earth metal) and subsequently deposits in bone.

C. Thorium [Th232]: historically this was used as Thorotrast - a contrast agent for radiologic procedures; associated with liver cancer; alpha emitter.

D. Cesium [Cs137]: gamma emitter; second largest radiation accident ever (after Chernobyl) was in Goiania, Brazil: a medical unit was stolen and sold to a junkyard and opened because the material within glowed blue in the dark. Within 5 days, several patients had gastrointestinal symptoms and four later died. Prussian blue therapy was given to 37 patients.

E. Uranium [U238 mostly]: Produces several daughter compounds including: radon, radium-226, and thorium-230. Because of long half-life, U238 itself has very little radioactivity. It is mainly used for nuclear plant fuel (410 power plants in world). Ironically, acute uranium toxicity is related to the chemical effects on the kidney, specifically acute tubular necrosis. Chronic exposure results in lung or bone cancer from the daughter compounds.

F. Radium [Ra226,228]: Watch dial painters in 1920’s, mostly women, licked brushed to make tip fine and developed osteogenic sarcoma; Some said that they painted their teeth to make them glow for fun; a-emitter; similar metabolism as calcium.

POTENTIAL SCENARIOS OF A RADIATION DISASTER TODAY

A. Dispersal of radioactive substances without the use of explosives
1. Metallic devices such as radiotherapy machines and industrial radiographic devices have large amounts of radioactivity – person must be very close or handle these devices for serious exposure to occur
2. These devices should be easily detected at checkpoints because they are metal

B. Dispersal of radioactive substances with the use of explosives
1. Explosives or “dirty bomb” would disperse substances to a large # of people – probably a few city blocks
2. Material would be solid or powder
3. Effect is primarily psychological, as patients and area are easily decontaminated

C. Attacks on nuclear reactors
1. Commercial nuclear power plants
a. Reactor core is encased in a stainless steel vessel within a concrete building
b. In the case of an unplanned reaction, the reactor is designed to stop the reaction
c. Reactor coolant system contains some radioactivity that would be released if the coolant system is damaged (radioactive iodine and noble gases)
2. Small experimental reactors in university nuclear engineering departments
a. Minimal security; in densely populated areas
b. Small amounts of radioactive material, but good targets for terrorists
3. “spent” fuel rods
a. Stored in less secure facilities
b. Solid; difficult to expose a large population

D. Detonation of nuclear weapons
1. Less likely to be used by terrorists – require expertise
2. Cause destruction by air blast, radiation and fireball (flashes and flame burns)

BASIC ASSESSMENT AND MANAGEMENT OF RADIATION EXPOSURES

1. Prophylactic Drugs Against Radiation Exposure
a. Amifostine: FDA-approved for some patients undergoing radiation therapy; has serious side
b. Androstenediol: evaluated only in animals
c. Bone marrow transplant has not been helpful

2. Internal Contamination
a. Occurs through inhalation, ingestion, wounds/burns in the skin
b. Effective treatment depends on the radionuclide involved
c. Detonation of a nuclear weapon would most likely require treatment with potassium iodide or iodate to prevent accumulation of radioiodine in the thyroid – must be taken shortly before exposure or within several hours after exposure

3. External Contamination
a. Contaminated skin and clothing is not a medical emergency – removal of clothing eliminates 90% of contamination
i. Medical personnel should wear protective clothing and gloves
ii. Respirators are only needed at the site by rescue personnel – not needed in the hospital
iii. Decontamination is accomplished by removing clothing and using soap and water – be careful not to abrade skin
iv. All contaminated materials should be placed in labeled plastic bags

4. Contaminated Burns and Wounds
a. A wound that is contaminated should be copiously irrigated with saline
b. Excision is reserved for long-lived radionuclides (especially alpha-emitting)
i. b burns should be treated with early excision and skin grafting; g ray burns should be allowed to demarcate since these deeper rays produce more damage
c. If a patient has received more than 1 gray of total body radiation – the wound should be closed as soon as possible so it does not become a portal for infection

5. General Management
a. Preparation
i. Emergency planning
ii. Clarification of command and control issues
iii. Specification of organizational responsibility
iv. Development of notification criteria and communications systems
v. Assessment of the type and quantity of equipment required
vi. Specification of the levels of protective actions that will be taken under certain circumstances
b. Management during the crisis
i. FBI is the lead federal agency and is in charge of activities undertaken to ensure that there is no further threat and to establish control over the site of the attack as a crime scene
c. Management of the consequences
i. FEMA (Federal Emergency Management Agency) is the lead federal agency
ii. Means prevention of further damage, protection of the public, decontamination and disposal of radioactive material
(a). Access to the site must be controlled
(b). People must be directed to stay indoors
©. Contaminated clothing must be removed
d). Respiratory protection must be provided
(e). Potassium iodide should be given if the dose to the thyroid is > 100 rem
(f). Certain food should be restricted if contamination expected

6. Early Management
a. People who are injured and contaminated should be taken to the hospital and decontaminated there
b. Those who are uninjured should be evaluated for contamination at the scene
c. Ambulance staff should wear gowns and gloves and appropriately dispose of the victim’s clothing
d. Any person who reports nausea, vomiting, diarrhea should be taken to the hospital for evaluation of whole body exposure
e. Decontaminate with copious irrigation – skin can be cleaned with bleach first
f. Chelators can be used for appropriate metals; Ca-DTPA (diethylenediaminepentaacetic acid) has been used for the actinide series (transuranics plutonium, neptunium, americium)
g. Aluminum antacids may reduce absorption of strontium
h. Prussian blue should be considered for caesium, thallium, and rubidium exposures.
i. Contact authorities about management, specifically the Radiation Emergency Assistance Center/Training Site (REAC/TS) of Oak Ridge, Tennessee. (423)-576-1004 or (423) 525-7885, to speak with a specialist in radiation injury.

BIBLIOGRAPHY

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