Acute radiation syndrome
Acute radiation syndrome (6, pp. 93 – 101) is a clinical condition occurring when the entire body or large parts of it have been exposed to a dose of ionising radiation equal to 1 Gy or more (9). The most frequent cause will be external irradiation, but one case resulting from internal contamination is also known: Alexander Litvinenko developed acute radiation syndrome after having been poisoned with polonium mixed into a cup of tea (10).
Acute radiation syndrome is a well-defined disease entity that develops through multiple clinical stages in a dynamic process. The disease manifests itself initially through so-called prodromal symptoms, mainly nausea and vomiting, as well as stomach pains, diarrhoea and other symptoms. The prodromal symptoms are reversible, and are assumed to be caused by an excitation of the autonomic nervous system (7). The time that elapses before onset of the prodromal symptoms and their degree of severity reflect the radiation dose received. In the exercise scenario described above, it was assumed that in the two persons who had been exposed to the largest radiation doses, the prodromal symptoms would have appeared within approximately one hour.
eIt is assumed that radioactive radiation may affect all organs in the body (11), but the clinical consequences are likely to be greatest in the most radiation-sensitive organ systems, such as the bone marrow and the digestive tract. The time elapsing before the onset of symptoms depends on the dose rate and the radiation dose. In the exercise scenario described above, it was calculated that symptoms of bone marrow failure with granulocytopenia (infection) and thrombocytopenia (haemorrhage) would have appeeared in the two most heavily irradiated patients approximately 10 – 14 days after the radiation incident.
Mature lymphocytes are among those cells in the body that are most sensitive to radiation. After even moderate radiation doses, a reduced lymphocyte count in the blood can be detected within 1 – 2 days. This phenomenon is primarily used as a factor for estimating the radiation dose received during the acute stage (Figure 1) (12). After radiation doses in excess of approximately 2 – 3 Gy, symptoms of bone marrow failure can commonly be observed. Animal studies have shown that rapidly initiated treatment with granulocyte-colony stimulating factor that stimulates the remaining haematopoietic stem cells reduces the fall in neutrophil granulocytes and shortens the time in granulocytopenia after exposure to radiation. This is consequently regarded as the standard treatment in the case of acute radiation syndrome (13).
Allogeneic haematopoietic stem cell transplantation is considered in cases where the bone marrow is unlikely to regenerate spontaneously and other organ systems are not affected to a life-threatening degree (14). After radiation doses exceeding approximately 5 Gy, symptoms from other organ systems in addition to the bone marrow will also appear, primarily from the digestive tract, followed by the skin, the central nervous system and other organs (7). With the exception of drugs that stimulate the bone marrow, only supportive treatment is relevant, including empirical antibiotic treatment, prophylactic transfusions of thrombocytes to prevent haemorrhaging, monitoring of the fluid and electrolyte balance, and use of antiemetics for nausea, vomiting and similar.
It has been shown that if one or more organ systems in addition to the haematopoietic system are affected, the patient’s condition will be significantly exacerbated (15), and in many cases a terminal stage with multiple organ failure will develop, similar to that seen, for example, in multiple-traumatised patients. At the time, this observation gave rise to a change in notions about the pathophysiological mechanisms involved in acute radiation syndrome. Previously, each organ system was considered in isolation, whereas it has now become clear that acute radiation syndrome is a manifestation of a generalised process involving interplay between several affected organs, mediated by cytokines and other signal molecules (16). As of today, no established course of treatment that has an effect on the mechanism behind multiple organ failure is available.