Although the very end of the 19th century witnessed the discovery of radioactivity by Henri Becquerel, the realization that radioactivity is associated with adverse health effects remained elusive until the early 20th century. [1,2] Pierre Curie was among the first to recognize that radiation exposure might have adverse effects on biological tissue, noting that carrying glass vials of radioactive substances in his pocket resulted in sores appearing on the adjacent skin in the days and weeks afterwards.  Nevertheless, it would be as many as several decades into the 20th century before the extent of the dangers of ionizing radiation came to be appreciated.  The success of the Manhattan Project and the decimation of the cities of Hiroshima and Nagasaki in 1945 have ushered in a nuclear era with which comes the danger of exposure to substantial doses of radiation through a variety of means, including, but not limited to, nuclear warfare, nuclear reactor accidents, and incidents during radiotherapy sessions. [1,3-5]
The effects of exposure to ionizing radiation are dependent both on the particular type of radiation, as well as the total whole-body dose absorbed and the dose rate. [5-7] Acute radiation syndrome (ARS), or acute radiation sickness, occurs as a result of the absorption of a high whole-body dose of ionizing radiation over a time period on the time scale of minutes. [1,6,7] The development of ARS as the condition progresses in the time following initial exposure to radiation is generally decomposed into three distinct phases: [1,7]
Initial or prodromal phase
Here, we briefly outline how ARS is typically manifested at each of its three phases of development across whole-body exposure levels ranging from a mild 1-2 Gray (Gy) to lethal levels in excess of 8 Gy.
The primary symptoms of ARS associated with the prodromal phase include vomiting, diarrhea, headaches, and fever. Bouts of vomiting afflict up to 50% of patients with mild exposures and up to 90% of those exposed to moderate levels of radiation, whereas patients exposed to 4 Gy or more will invariably begin vomiting within an hour after being exposed.  In the patients exhibiting this symptom, the time to onset of vomiting decreases with increasing absorbed whole-body dose of ionizing radiation, ranging from 2 hours for mild doses to a matter of minutes for lethal doses. [1,7] ARS patients may also experience headaches, the severity and percent of incidence of which increases with increasing exposure levels.  A fraction of patients exposed to moderate radiation levels may experience a heightened body temperature, while individuals exposed to radiation in excess of 4 Gy will generally develop high fevers in the hours following exposure.  Diarrhea as well as loss of consciousness are also common in individuals who have been exposed to lethal radiation doses.  Treatment of patients with mild exposures in general entails outpatient observation, while patients exposed to radiation levels in the range of 2-8 Gy (mild to very severe exposures) will require hospitalization and specialized treatment. [1,7] Unfortunately, palliative care is generally the only option for individuals exposed to 8 Gy or more of ionizing radiation. 
The symptoms associated with the prodromal phase of ARS, as described above, are summarized in Table 1.
|Table 1: Summary of prodromal phase ARS symptoms depending on whole-body exposure levels. |
As the condition progresses into the latent phase, levels of lymphocytes and granulocytes decrease dramatically, with larger decreases associated with greater exposure levels. [1,7] This decrease in the levels of these cells, which are types of white blood cells and, as such, a key component of the immune system, opens up the organism to a much greater risk of infection. [1,7] Diarrhea commonly appears within a week of exposure in the case of exposure levels in excess of 6 Gy.  Moderate depilation is also observed for exposures up to 6 Gy, while exposures greater than 6 Gy will generally result in complete depilation well within two weeks post-exposure.  The duration of the latency period before the onset of these symptoms decreases with increasing exposure levels, ranging from approximately one month for mild exposures to the complete absence of a latency period in the case of lethal exposure doses. 
The symptoms associated with the latent phase of ARS, as described above, are summarized in Table 2.
|Table 2: Summary of latent phase ARS symptoms depending on whole-body exposure levels. |
The onset of the final, critical phase symptoms of ARS is dependent on the exposure dose, with symptoms taking over a month to manifest themselves for mild doses, but can take less than 3 days for lethal doses in excess of 8 Gy.  Persisting low lymphocyte levels are coupled with dose-dependent decreases in platelet levels, thereby contributing to progressively more severe clinical manifestations of ARS.  As expected, increasing radiation dosage not only leads to greater lethality levels, but also to a faster onset of lethality from the time of exposure in those patients that unfortunately do pass away as a consequence of ARS. [1,7]
The dose-dependent symptoms associated with the critical phase of ARS, as described above, are summarized in Table 3.
|Table 3: Summary of critical phase ARS symptoms depending on whole-body exposure levels. |
© Bojan Milic. The author grants permission to copy, distribute and display this work in unaltered form, with attribution to the author, for noncommercial purposes only. All other rights, including commercial rights, are reserved to the author.
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