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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

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 problems rather than ones that develop after a prolonged period.[3][4][5]

The onset and type of symptoms that develop depends on the dose of 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, however these diseases are not included in the term radiation sickness.

## 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]

1. Hematopoietic. This syndrome is marked by a drop in blood cells which results in infections due to low white blood cells, bleeding due to low platelets, and anemia due to low red blood cells.[1]
2. Gastrointestinal. This syndrome typically occurs at exposure doses of 600–1000 rad (6–10 Gy).[1] Nausea, vomiting, loss of appetite, and abdominal pain are usually seen within one to two hours.[1]
3. Neurovascular. This syndrome typically occurs at exposure doses greater than 1000 rad (10 Gy).[1] It presents with neurological symptoms such as dizziness, headache, or decreased level of consciousness with an absence of vomiting.[1]

The prodrome associated with 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) and thus may not be followed by acute radiation sickness.[1]

Phase Symptom Exposure (Gy)
1–2Gy 2–6Gy 6–8Gy 8–30Gy >30Gy
Immediate Nausea and vomiting 5–50% 50–100% 75–100% 90–100% 100%
Time of onset 2–6h 1–2h 10–60 min < 10 min Minutes
Duration < 24h 24–48h < 48h < 48h N/A (patients die in < 48h)
Diarrhea None None to mild (<10%) Heavy (>10%) Heavy (>95%) Heavy (100%)
Time of onset 3–8h 1–3h < 1h < 1h
Headache Slight Mild to moderate (50%) Moderate (80%) Severe (80–90%) Severe (100%)
Time of onset 4–24h 3–4h 1–2h < 1h
Fever None Moderate increase (10-100%) Moderate to severe (100%) Severe (100%) Severe (100%)
Time of onset 1–3h < 1h < 1h < 1h
CNS function No impairment Cognitive impairment 6–20 h Cognitive impairment > 24h Rapid incapacitation Seizures, Tremor, Ataxia, Lethargy
Latent period 28–31 days 7–28 days < 7 days none none
Illness Mild to moderate Leukopenia
Fatigue
Weakness
Moderate to severe Leukopenia
Purpura
Hemorrhage
Infections
Epilation after 3 Gy
Severe leukopenia
High fever
Diarrhea
Vomiting
Dizziness and disorientation
Hypotension
Electrolyte disturbance
Nausea
Vomiting
Severe diarrhea
High fever
Electrolyte disturbance
Shock
N/A (patients die in < 48h)
Mortality Without care 0–5% 5–100% 95–100% 100% 100%
With care 0–5% 5–50% 50–100% 100% 100%
Death 6–8 wks 4–6 wks 2–4 wks 2 days–2 wks 1–2 days

[7]

### Skin changes

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]

### Long term exposure

Longer term exposure to radiation, at doses less than that which produces serious radiation sickness, can induce cancer due to genetic mutations. The probability cancer will develop is a function of 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.

## Cause

Radiation sickness is generally associated with a sudden single large exposure.[10][11]

### External

A schematic diagram showing a rectangle being irradiated by an external source (in red) of radiation (shown in yellow).
A schematic diagram showing a rectangle being irradiated by radioactive contamination (shown in red) which is present on an external surface such as the skin; this emits radiation (shown in yellow) which can enter the animal's body

External exposure is exposure which occurs when the radioactive source (or other radiation source) is outside (and remains outside) the organism which is exposed. Examples of external exposure include:

• A person who places a sealed radioactive source in his pocket
• A space traveller who is irradiated by cosmic rays
• A person who is treated for cancer by either teletherapy or brachytherapy. While in brachytherapy the source is inside the person it is still external exposure because the active part of the source never comes into direct contact with the biological tissues of the person.

One of the key points is that external exposure is often relatively easy to estimate, and the irradiated objects do not become radioactive, except for a case where the radiation is an intense neutron beam which causes activation of the object. It is possible for an object to be contaminated on the outer surfaces; assuming that no radioactivity enters the object it is still a case of external exposure and it is normally the case that decontamination is relatively easy.

#### Nuclear weapons

Person suffering burns from thermal radiation after the United States dropped nuclear bombs on Japan in World War II.

Nuclear warfare and bomb tests are more complex because a person can be irradiated by at least three processes. The first (the major cause of burns) is not caused by ionizing radiation.

Common effects of ionizing radiation on the skin
• Thermal burns from infrared heat radiation
• Beta burns from shallow ionizing beta radiation (this would be from fallout particles; the largest particles in local fallout would be likely to have very high activities because they would be deposited so soon after detonation and it is likely that one such particle upon the skin would be able to cause a localised burn); however, these particles are very weakly penetrating and have a short range.
• Gamma burns from highly penetrating gamma radiation. This would likely cause deep gamma penetration within the body, which would result in uniform whole body irradiation rather than only a surface burn. In cases of whole body gamma irradiation (circa 10 Sv) caused by accidents involving medical product irradiators, some of the human subjects have developed injuries to their skin between the time of irradiation and death.

In the picture to the left, the normal clothing that the woman was wearing would have been unable to attenuate the gamma radiation and it is likely that any such effect was evenly applied to her entire body. Beta burns would be likely all over the body caused by contact with fallout, but thermal burns are often on one side of the body as heat radiation does not penetrate the human body. In addition, the pattern on her clothing has been burnt into the skin. This is because white fabric reflects more infrared light than dark fabric. As a result, the skin close to dark fabric is burned more than the skin covered by white clothing.

There is also the risk of internal radiation poisoning by ingestion of fallout particles.

#### Spaceflight

During spaceflight, particularly flights beyond low Earth orbit, astronauts are exposed to both galactic cosmic radiation (GCR) and possibly solar particle event (SPE) radiation. Evidence indicates past SPE radiation levels which would have been lethal for unprotected astronauts.[12] GCR levels which might lead to acute radiation poisoning are less well understood.[13]

### Internal

Internal exposure occurs when the radioactive material enters the organism, and the radioactive atoms become incorporated into the organism. Below are a series of examples of internal exposure.

• The exposure caused by 40K present within a normal person.
• The exposure to the ingestion of a soluble radioactive substance, such as 89Sr in cows' milk.
• A person who is being treated for cancer by means of an unsealed source radiotherapy method where a radioisotope is used as a drug (usually a liquid or pill). A review of this topic was published in 1999.[14] Because the radioactive material becomes intimately mixed with the affected object it is often difficult to decontaminate the object or person in a case where internal exposure is occurring. While some very insoluble materials such as fission products within a uranium dioxide matrix might never be able to truly become part of an organism, it is normal to consider such particles in the lungs as a form of internal contamination which results in internal exposure. The reasoning is that the particles have entered via an orifice and can not be removed with ease from what the lay person (non biologist) would regard as within the animal. It is important to note that in a strictly topological sense, the contents of the digestive tract and the air within the lungs are outside the body of a mammal (whereas, for instance, the abdominal cavity is topologically inside the mammalian body).
• Boron neutron capture therapy (BNCT) involves injecting a boron-10 tagged chemical that preferentially binds to tumor cells. Neutrons from a nuclear reactor are shaped by a neutron moderator to the neutron energy spectrum suitable for BNCT treatment. The tumor is selectively bombarded with these neutrons. The neutrons quickly slow down in the body to become low energy thermal neutrons. These thermal neutrons are captured by the injected boron-10, forming excited (boron-11) which breaks down into lithium-7 and a helium-4 alpha particle both of these produce closely spaced ionizing radiation.This concept is described as a binary system using two separate components for the therapy of cancer. Each component in itself is relatively harmless to the cells, but when combined together for treatment they produce a highly cytocidal (cytotoxic) effect which is lethal (within a limited range of 5-9 micrometers or approximately one cell diameter). Clinical trials, with promising results, are currently carried out in Finland and Japan.

#### Ingestion and inhalation

When radioactive compounds enter the human body, the effects are different from those resulting from exposure to an external radiation source. Especially in the case of alpha radiation, which normally does not penetrate the skin, the exposure can be much more damaging after ingestion or inhalation. The radiation exposure is normally expressed as a committed effective dose equivalent (CEDE).

## Pathophysiology

A gray (Gy) is a unit of radiation dose absorbed by matter. To gauge biological effects the dose is multiplied by a 'quality factor' which is dependent on the type of ionising radiation. Such measurement of biological effect is called "dose equivalent" and is measured in sievert (Sv). For electron and photon radiation (e.g. gamma), 1 Gy = 1 Sv. For information on the effects of lower doses of radiation, see the article on radiation orders of magnitude.

The corresponding non-SI units are the rad (radiation absorbed dose; 1 rad = 0.01 Gy), and rem (roentgen equivalent mammal/man;[15] 1 rem=0.01 Sv).

Annual limit on intake (ALI) is the derived limit for the amount of radioactive material taken into the body of an adult worker by inhalation or ingestion in a year. ALI is the intake of a given radionuclide in a year that would result in:

• a committed effective dose equivalent of 0.05 Sv (5 rems) for a "reference human body", or
• a committed dose equivalent of 0.5 Sv (50 rems) to any individual organ or tissue,

whatever dose is the smaller.[16]

## 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.

### 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 R/hr 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.

$\text{Dose} \propto t$

### Reduction of incorporation into the human body

Potassium iodide (KI), administered orally immediately after exposure, may be used to protect the thyroid from ingested radioactive iodine in the event of an accident or attack at a nuclear power plant, or the detonation of a nuclear explosive. KI would not be effective against a dirty bomb unless the bomb happened to contain radioactive iodine, and even then it would only help to prevent thyroid cancer.

### Fractionation of dose

It has been found in radiation biology experiments that if a group of cells is irradiated, then as the dose increases, the number of cells which survive decreases. It has also been found that if a population of cells is irradiated, then set aside for a length of time before being irradiated again, the radiation causes less cell death. 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[17] and pefloxacin[18] 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.[19]

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.[20]

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).[21]

## 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 Rontgen 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.

Nevertheless, dangers of radiation were not fully appreciated by scientists until later. In 1945 and 1946, one U.S. scientist and one Canadian scientist died from acute radiation exposure in separate criticality accidents. In both cases, victims were working with large quantities of fissile materials without any shielding or protection.

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.[22] 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").

## Society and culture

### Nuclear reactor accidents

The first known incident of a reactor meltdown occurred in Canada in the NRX Reactor. There was also a fatal core meltdown at SL-1, an experimental U.S. military reactor in Idaho. Large-scale nuclear meltdowns at civilian nuclear power plants include:

Radiation poisoning was a major concern after the Chernobyl disaster. There were 56 direct deaths (47 accident workers, and nine children with thyroid cancer), and it is estimated that there may be roughly 4,000 extra cancer deaths among the approximately 600,000 most highly exposed people.[23][24] Of the 100 million curies (4 exabecquerels) of radioactive material, the short lived radioactive isotopes such as 131I Chernobyl released were initially the most dangerous. Due to their short half-lives of 5 and 8 days they have now decayed, leaving the more long-lived 137Cs (with a half-life of 30.07 years) and 90Sr (with a half-life of 28.78 years) as main dangers.

A number of nuclear submarines have experienced nuclear meltdowns, including Soviet submarine K-431 (10 fatalities), Soviet submarine K-27 (9 fatalities), and Soviet submarine K-19 (8 fatalities).[25]

### Deliberate poisoning

On November 23, 2006, Alexander Litvinenko died from suspected deliberate poisoning with polonium-210.[36][37][38][39][40] In addition, an incident occurred in 1990 at Point Lepreau Nuclear Generating Station where several employees acquired small doses of radiation because of the contamination of a sports drink in the office drink fountain with tritium-contaminated heavy water.[41][42]

## In other animals

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).[43] There is a simple guide for predicting survival/death in mammals, including humans, following the acute effects of inhaling radioactive particles.[44]

## References

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16. ^ NRC: Glossary - Annual limit on intake (ALI)
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22. ^ Carmichael, Ann G. (1991). Medicine: A Treasury of Art and Literature. New York: Harkavy Publishing Service. pp. 376. ISBN 0-88363-991-2.
23. ^ "IAEA Report". In Focus: Chernobyl. Retrieved 2008-05-31.
24. ^ WHO Expert Group (July 2006). Burton Bennett, Michael Repacholi, Zhanat Carr. ed. Health Effects of the Chernobyl Accident and Special Health Care Programmes: Report of the UN Chernobyl Forum Health Expert Group. Geneva: World Health Organization. p. 106. ISBN 9789241594172. "...This total, about 4000 deaths projected over the lifetimes of the some 600,000 persons most affected by the accident, is a small proportion of the total cancer deaths from all causes that can be expected to occur in this population. It must be stressed that this estimate is bounded by large uncertainties"
25. ^ Johnston, Robert (September 23, 2007). "Deadliest radiation accidents and other events causing radiation casualties". Database of Radiological Incidents and Related Events.
26. ^ Samuel Upton Newtan. Nuclear War I and Other Major Nuclear Disasters of the 20th Century 2007, pp. 237–240.
27. ^ Perhaps the Worst, Not the First TIME magazine, May 12, 1986.
28. ^ Benjamin K. Sovacool. A Critical Evaluation of Nuclear Power and Renewable Electricity in Asia, Journal of Contemporary Asia, Vol. 40, No. 3, August 2010, p. 393.
29. ^ Investigation of an accidental Exposure of radiotherapy patients in Panama - International Atomic Energy Agency
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33. ^ Lost Iridium-192 Source
34. ^ The Radiological Accident in Goiania p. 2.
35. ^ a b Pallava Bagla. "Radiation Accident a 'Wake-Up Call' For India's Scientific Community" Science, Vol. 328, 7 May 2010, p. 679.
36. ^ Patterson AJ (2007). "Ushering in the era of nuclear terrorism". Critical Care Medicine 35: 953–4. doi:10.1097/01.CCM.0000257229.97208.76. PMID 17421087.
37. ^ Acton JM, Rogers MB, Zimmerman PD (September 2007). "Beyond the Dirty Bomb: Re-thinking Radiological Terror". Survival 49 (3): 151–168. doi:10.1080/00396330701564760.
38. ^ Sixsmith, Martin (2007). The Litvinenko File: The Life and Death of a Russian Spy. True Crime. p. 14. ISBN 0-312-37668-5.
39. ^ Radiological Terrorism: "Soft Killers" by Morten Bremer Mærli, Bellona Foundation
40. ^ Alex Goldfarb; Marina Litvinenko (2007). Death of a Dissident: The Poisoning of Alexander Litvinenko and the Return of the KGB.. New York: Free Press. ISBN 978-1-4165-5165-2.
41. ^ Meeting with past (Russian)
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