Acute radiation syndrome

Acute radiation syndrome
Classification and external resources
A Japanese girl recovering from the effects of radiation sickness
ICD-10	T66
ICD-9	990
MedlinePlus	000026
eMedicine	article/834015
MeSH	D011832

Radiation sickness redirects here. This can refer to any of the detrimental health effects of radiation, notably radiation-induced cancers which are not acute radiation syndrome.

Acute radiation syndrome (ARS), also known as radiation poisoning, radiation sickness or radiation toxicity, is a constellation of health effects which occur within several months of exposure to high amounts of ionizing radiation.^[1][2] The term generally refers to acute medical problems rather than ones that develop after a prolonged period.^[3][4][5]

The onset and type of symptoms depends on the radiation exposure. Relatively smaller doses result in gastrointestinal effects such as nausea and vomiting and symptoms related to falling blood counts such as infection and bleeding. Relatively larger doses can result in neurological effects and rapid death. Treatment of acute radiation syndrome is generally supportive with blood transfusions and antibiotics.^[1]

Chronic radiation syndrome has been reported among workers in the Soviet nuclear program due to long term exposures to radiation levels lower than what is required to induce acute sickness.^[6] It may manifest with low blood cell counts and neurological problems.^[6] Radiation exposure can also increase the probability of developing some other diseases, mainly different types of cancers. These diseases are sometimes referred to as radiation sickness, but they are never included in the term acute radiation syndrome.

Signs and symptoms

Classically acute radiation syndrome is divided into three main presentations: hematopoietic, gastrointestinal and neurological/vascular. These symptoms may or may not be preceded by a prodrome.^[1] The speed of onset of symptoms is related to radiation exposure, with greater doses resulting in a shorter delay in symptom onset.^[1]. These presentations presume whole-body exposure and many of them are markers which are not valid if the entire body has not been exposed. Each syndrome requires that the tissue showing the syndome itself be exposed. The hematopoetic syndrome requires exposure of the areas of bone marrow actively forming blood elements (i.e., the pelvis and sternum in adults). The neurovascular symptoms require exposure of the brain. The gastrointestinal syndrome is not seen if the stomach and intestines are not exposed to radiation.

1. Hematopoietic. This syndrome is marked by a drop in the number of blood cells, called aplastic anemia. This may result in infections due to low white blood cells, bleeding due to low platelets, and anemia due to low red blood cells.^[1] These changes can be detected by blood tests after receiving a whole-body acute dose as low as 0.25 Gy, though they might never be felt by the patient if the dose is below 1 Gy.
2. Gastrointestinal. This syndrome often follows absorbed doses of 6–30 Gy (600–3000 rad).^[1] Nausea, vomiting, loss of appetite, and abdominal pain are usually seen within two hours. Vomiting in this time-frame is a marker for whole body exposures that are in the fatal range above 4 Gy. Without exotic treatment such as bone marrow transplant, death with this dose is common.^[1] The death is generally more due to infection than gastrointestinal dysfunction.
3. Neurovascular. This syndrome typically occurs at absorbed doses greater than 30 Gy (3000 rad), though it may occur at 10 Gy (1000 rad).^[1] It presents with neurological symptoms such as dizziness, headache, or decreased level of consciousness, occurring within minutes to a few hours, and with an absence of vomiting. It is invariably fatal.^[1]

The prodrome (early symptoms) of ARS typically includes nausea and vomiting, headaches, fatigue, fever and short period of skin reddening.^[1] These symptoms may occur at radiation doses as low as 35 rad (0.35 Gy). These symptoms are common to many illnesses and may not, by themselves, indicate acute radiation sickness.^[1]

^[7]

Skin changes

Common effects of ionizing radiation on the skin

In a nuclear explosion, ARS may be accompanied by flash burns, as pictured above, due to thermal radiation

Cutaneous radiation syndrome (CRS) refers to the skin symptoms of radiation exposure.^[5] Within a few hours after irradiation, a transient and inconsistent redness (associated with itching) can occur. Then, a latent phase may occur and last from a few days up to several weeks, when intense reddening, blistering, and ulceration of the irradiated site are visible. In most cases, healing occurs by regenerative means; however, very large skin doses can cause permanent hair loss, damaged sebaceous and sweat glands, atrophy, fibrosis, decreased or increased skin pigmentation, and ulceration or necrosis of the exposed tissue.^[5] Notably, as seen at Chernobyl, when skin is irradiated with high energy beta particles, moist desquamation and similar early effects can heal, only to be followed by the collapse of the dermal vascular system after two months, resulting in the loss of the full thickness of the exposed skin.^[8] This effect had been demonstrated previously with pig skin using high energy beta sources at the Churchil Hospital Research Institute, in Oxford. ^[9]

Cancer

Any exposure to ionizing radiation, even at doses too low to produce any symptoms of radiation sickness, can induce cancer due to genetic mutations. Survivors of acute radiation syndrome face an increased risk of cancer for the remainder of their lives. The probability cancer will develop is a function of effective radiation dose. In radiation-induced cancer the disease, the speed at which the condition advances, the prognosis, the degree of pain, and every other feature of the disease are not functions of the radiation dose to which the person is exposed.

For information on the effects of lower doses of radiation, see the article on radiation orders of magnitude.

Cause

Radiation sickness is caused by exposure to a large dose of ionizing radiation (>~0.1 Gy) over a short period of time. (>~0.1 Gy/h) This might be the result of a nuclear explosion, a criticality accident, a radiotherapy accident as in Therac-25, a solar flare during interplanetary travel, escape of radioactive waste as in the Goiania accident, human error in a nuclear reactor, or other possibilities. Acute radiation sickness due to ingestion of radioactive material is possible, but rare. Examples include the Alexander Litvinenko poisoning and Leide das Neves Ferreira.

Alpha and beta radiation have low penetrating power and are unlikely to affect vital internal organs from outside the body. Any type of ionizing radiation can cause burns, but alpha and beta radiation can only do so if radioactive contamination or nuclear fallout is deposited on the individual's skin or clothing. Gamma and neutron radiation can travel much further distances and penetrate the body easily, so whole-body irradiation generally causes ARS before skin effects are evident. Local gamma irradiation can cause skin effects without any sickness. In the early twentieth century, radiographers would commonly calibrate their machines by irradiating their own hand and measuring the time to onset of erythema.

Spaceflight

During spaceflight, particularly flights beyond low Earth orbit, astronauts are exposed to both galactic cosmic radiation (GCR) and solar particle event (SPE) radiation. Evidence indicates past SPE radiation levels which would have been lethal for unprotected astronauts.^[10] GCR levels which might lead to acute radiation poisoning are less well understood.^[11]

Quantities and Units

The most commonly used predictor of acute radiation symptoms is the whole-body absorbed dose. Several related quantities, such as the equivalent dose, effective dose, and committed dose, are used to gauge long-term stochastic biological effects such as cancer incidence, but they are not designed to evaluate acute radiation syndrome.^[12] To help avoid confusion between these quantities, absorbed dose is measured in units of gray (Gy) or rad, while the others are measured in sievert (Sv) or rem. 1 rad = 0.01 Gy^[13]

In most of the acute exposure scenarios that lead to radiation sickness, the bulk of the radiation is external whole-body gamma, in which case the absorbed, equivalent and effective doses are all equal. There are exceptions, such as the Therac-25 accidents and the Cecil Kelley accident, where the absorbed doses in Gy or rad are the only useful quantities.

Radiotherapy treatments are typically prescribed in terms of the local absorbed dose, which might be 60 Gy or higher. Although such a dose is lethal to the local tissues (as intended), it is not lethal to the patient. The dose to the targeted tissue mass must be averaged over the entire body mass, most of which receives negligible radiation, to arrive at a whole-body absorbed dose that can be compared to the table above.

Diagnosis

Diagnosis is typically made based on a history of significant radiation exposure and suitable clinical findings.^[1] An absolute lymphocyte count can give a rough estimate of radiation exposure.^[1] Time from exposure to vomiting can also give estimates of exposure levels if they are less than 1000 rad.^[1]

Prevention

The best prevention for radiation sickness is to minimize the exposure dose or to reduce the dose rate.

Distance

Increasing distance from the radiation source reduces the dose according to the inverse-square law for a point source. Distance can sometimes be effectively increased by means as simple as handling a source with forceps rather than fingers. This could reduce erythema to the fingers, but the extra few cm distance from the body will give little protection from acute radiation syndrome.

Time

The longer that humans are subjected to radiation the larger the dose will be. The advice in the nuclear war manual entitled "Nuclear War Survival Skills" published by Cresson Kearny in the U.S. was that if one needed to leave the shelter then this should be done as rapidly as possible to minimize exposure.

In chapter 12 he states that "Quickly putting or dumping wastes outside is not hazardous once fallout is no longer being deposited. For example, assume the shelter is in an area of heavy fallout and the dose rate outside is 400 [ roentgen (R) per hour ] enough to give a potentially fatal dose in about an hour to a person exposed in the open. If a person needs to be exposed for only 10 seconds to dump a bucket, in this 1/360th of an hour he will receive a dose of only about 1 R. Under war conditions, an additional 1-R dose is of little concern."

In peacetime, radiation workers are taught to work as quickly as possible when performing a task which exposes them to radiation. For instance, the recovery of a lost radiography source should be done as quickly as possible.

Shielding

Matter attenuates radiation in most cases, so placing any mass (e.g. dirt, sandbags, vehicles) between humans and the source will reduce the radiation dose.

Reduction of incorporation into the human body

Where radioactive contamination is present, a gas mask, dust mask, or good hygiene practices may offer protection, depending on the nature of the contaminant. Potassium iodide (KI) tablets can reduce the risk of cancer in some situations, but they do not prevent acute radiation syndrome.

Fractionation of dose

If an intentional dose is broken up into a number of smaller doses, with time allowed for recovery between irradiations, the same total dose causes less cell death. Even without interruptions, a reduction in dose rate below 0.1 Gy/h also tends to reduce cell death.^[12] This technique is routinely used in radiotherapy.

The human body contains many types of cells and a human can be killed by the loss of a single type of cells in a vital organ. For many short term radiation deaths (3 days to 30 days), the loss of two important types of cells that are constantly being regenerated causes death. The loss of cells forming blood cells (bone marrow) and the cells in the digestive system (microvilli which form part of the wall of the intestines) is fatal.

Management

Treatment is supportive with the use of antibiotics, blood products, colony stimulating factors, and stem cell transplant as clinically indicated.^[1] Symptomatic measures may also be employed.^[1]

Antimicrobials

There is a direct relationship between the degree of the neutropenia that emerges after exposure to radiation and the increased risk of developing infection. Since there are no controlled studies of therapeutic intervention in humans, most of the current recommendations are based on animal research.

The treatment of established or suspected infection following exposure to radiation (characterized by neutropenia and fever) is similar to the one used for other febrile neutropenic patients. However, important differences between the two conditions exist. Individuals that develop neutropenia after exposure to radiation are also susceptible to irradiation damage in other tissues, such as the gastrointestinal tract, lungs and central nervous system. These patients may require therapeutic interventions not needed in other types of neutropenic patients. The response of irradiated animals to antimicrobial therapy can be unpredictable, as was evident in experimental studies where metronidazole^[14] and pefloxacin^[15] therapies were detrimental.

Antimicrobials that reduce the number of the strict anaerobic component of the gut flora (i.e., metronidazole) generally should not be given because they may enhance systemic infection by aerobic or facultative bacteria, thus facilitating mortality after irradiation.^[16]

An empirical regimen of antimicrobials should be chosen based on the pattern of bacterial susceptibility and nosocomial infections in the effected area and medical center and the degree of neutropenia. Broad-spectrum empirical therapy (see below for choices) with high doses of one or more antibiotics should be initiated at the onset of fever. These antimicrobials should be directed at the eradication of Gram-negative aerobic bacilli ( i.e. Enterobacteriace, Pseudomonas ) that account for more than three-fourths of the isolates causing sepsis. Because aerobic and facultative Gram-positive bacteria (mostly alpha-hemolytic streptococci) cause sepsis in about a quarter of the victims, coverage for these organisms may also be needed.^[17]

A standardized management plane of febrile, neutropenic patients must be devised in each institution or agency. Empirical regimens must contain antibiotics broadly active against Gram-negative aerobic bacteria (quinolones: i.e. ciprofloxacin, levofloxacin, a third- or fourth-generation cephalosporin with pseudomonal coverage: e.g. cefepime, ceftazidime, or an aminoglycoside: i.e. gentamicin, amikacin).^[18]

History

Although radiation was discovered in late 19th century, the dangers of radioactivity and of radiation were not immediately recognized. Acute effects of radiation were first observed in the use of X-rays when Wilhelm Röntgen intentionally subjected his fingers to X-rays in 1895. He published his observations concerning the burns that developed, though he attributed them to ozone rather than to X-rays. His injuries healed later.

The genetic effects of radiation, including the effects on cancer risk, were recognized much later. In 1927 Hermann Joseph Muller published research showing genetic effects, and in 1946 was awarded the Nobel prize for his findings.

Before the biological effects of radiation were known, many physicians and corporations had begun marketing radioactive substances as patent medicine and radioactive quackery. Examples were radium enema treatments, and radium-containing waters to be drunk as tonics. Marie Curie spoke out against this sort of treatment, warning that the effects of radiation on the human body were not well understood. Curie later died of aplastic anemia caused by radiation poisoning. Eben Byers, a famous American socialite, died of multiple cancers (but not acute radiation syndrome) in 1932 after consuming large quantities of radium over several years; his death drew public attention to dangers of radiation. By the 1930s, after a number of cases of bone necrosis and death in enthusiasts, radium-containing medical products had nearly vanished from the market.

In the United States, the experience of the so-called Radium Girls, where thousands^{[citation needed]} of radium-dial painters contracted oral cancers (but no cases of acute radiation syndrome^[19]), popularized the warnings of occupational health associated with radiation hazards. Robley D. Evans, at MIT, developed the first standard for permissible body burden of radium, a key step in the establishment of nuclear medicine as a field of study. With the development of nuclear reactors and nuclear weapons in the 1940s, heightened scientific attention was given to the study of all manner of radiation effects.

The atomic bombings of Hiroshima and Nagasaki resulted in a large number of incidents of radiation poisoning, allowing for greater insight into its symptoms and dangers. Red Cross Hospital Surgeon, Dr. Terufumi Sasaki led intensive research into the Syndrome in the weeks and months following the Hiroshima bombings. Dr Sasaki and his team were able to monitor the effects of radiation in patients of varying proximities to the blast itself, leading to the establishment of three recorded stages of the syndrome. Within 25-30 days of the explosion, the Red Cross surgeon noticed a sharp drop in white blood cell count and established this drop, along with symptoms of fever, as prognostic standards for Acute Radiation Syndrome.^[20] Actress Midori Naka, who was present during the atomic bombing of Hiroshima, was the first incident of radiation poisoning to be extensively studied. Her death on August 24, 1945 was the first death ever to be officially certified as a result of radiation poisoning (or "Atomic bomb disease").

Incidents

Between 1944 and 2000, there occurred 417 accidents causing about 3000 cases of acute radiation syndrome, of which 127 were fatal.^[21] (The two deliberate bombings are not included.) The detailed accounting is difficult because of confounding factors. ARS may be accompanied by conventional injuries such as steam burns, or may occur in someone with a pre-existing condition undergoing radiotherapy. There may be multiple causes for death, and the contribution from radiation may be unclear. Some documents may incorrectly refer to radiation-induced cancers as radiation poisoning, or may count all overexposed individuals as survivors without mentioning if they had any symptoms of ARS. The table below attempts to catalog only cases of ARS. Many of these incidents involved additional fatalities from other causes which are excluded from this table.

In other animals

Thousands of scientific experiments have been performed to study acute radiation syndrome in animals. They were not televised.

An episode of MythBusters exposed several types of insects to a cobalt-60 source at the Pacific Northwest National Laboratory facility, to test the myth that cockroaches would be the sole survivors of a nuclear blast. At 100 Gy, 70% of the cockroaches were dead after 30 days, as were 40% of the flour beetles. At 1000 Gy, all of the cockroaches were dead after 30 days, whereas 10% of the flour beetles survived (thus "busting" the myth).^[37] There is a simple guide for predicting survival/death in mammals, including humans, following the acute effects of inhaling radioactive particles.^[38]

See also

Wikimedia Commons has media related to: Radiation health effects

• Hibakusha – Japanese atomic bomb survivors
• List of civilian nuclear accidents
• List of military nuclear accidents
• Biological effects of ionizing radiation
• Radium Girls
• Orders of magnitude (radiation)
• CBLB502
• Ex-Rad

References

Further reading

• Michihiko Hachiya, Hiroshima Diary (Chapel Hill: University of North Carolina, 1955), ISBN 0-8078-4547-7.
• John Hersey, Hiroshima (New York: Vintage, 1946, 1985 new chapter), ISBN 0-679-72103-7.
• Ibuse Masuji, Black Rain (1969) ISBN 0-87011-364-X
• Ernest J. Sternglass, Secret Fallout: low-level radiation from Hiroshima to Three-Mile Island (1981) ISBN 0-07-061242-0 (online)
• Norman Solomon, Harvey Wasserman Killing Our Own: The Disaster of America's Experience with Atomic Radiation, 1945–1982, New York: Dell, 1982. ISBN 0-385-28537-X, ISBN 0-385-28536-1, ISBN 0-440-04567-3 (online)

External links

• The Center for Disease Control's fact sheet on Acute Radiation Syndrome
• List of radiation accidents and other events causing radiation casualties
• The criticality accident in Sarov, International Atomic Energy Agency, 2001 — well documented account of the biological effects of a criticality accident
• Armed Forces Radiobiology Research Institute
• This article incorporates public domain material from websites or documents of the Armed Forces Radiobiology Research Institute and the Center for Disease Control and Prevention