Acute Radiation Syndrome

Acute Radiation Syndrome

Three Types of ARS

the Bone Marrow Syndrome

the Gastrointestinal Syndrome

the Cardiovascular and Central Nervous System Syndrome

The Stages of ARS

ARS Diagnosis

Treatment of ARS

Cytokine Therapy

Transfusion and Stem cell transplantation

General Care

Recent Researches

Acute Radiation Syndrome

Acute Radiation Syndrome, also known as radiation sickness or radiation toxicity, refers to a severe condition that results when the whole body or most parts of the body is exposed to a high dosage of penetrating radiation over a very short period of time. The syndrome manifests a constellation of clinical symptoms including nausea, vomiting, diarrhea, fever, change in blood count, and a total collapse of the gastro intestinal and Central nervous system. The full spectrum of symptoms is known to occur at radiation levels in the range of .7GY to 10 GY. However, even exposure in the range of .3 GY triggers mild symptoms. [CDC] The most striking examples of people who survived ARS are from the nuclear bomb explosions at Hiroshima and Nagasaki as well as the Chernobyl nuclear power plant accident. With radioactive materials being increasingly used in research facilities, medical community needs to be prepared for the treatment of ARS. A brief overview of ARS including its different types, stages, diagnosis and treatment would provide better insight into the topic.

Three Types of ARS

There are three different types of ARS namely the hematopoietic, gastrointestinal, and cerebrovascular syndromes.

The Bone Marrow Syndrome

The Hematopoietic symptoms usually occur at radiation levels exceeding 1 GY though minor symptoms occur at much lower levels. (.3 GY). Radiation levels above 2 GY directly affect the mitotic function of cells, resulting in depletion of bone marrow cells. Bone marrow hypoplasia leads to increased risk for infections, hemorrhage and poor wound healing which ultimately lead to death. It is known that radiation mostly affects cells that are actively dividing while cells, which are mitotically inactive are found to be radiation resistant. Lymphopenia, or the rapid decline in lymphocyte count is one of the distinct markers of acute radiation syndrome. For very high levels of radiation exposure, up to 50% decline in lymphocyte count within the first 24 hours, followed by further significant decline in the next 24 hours have been clinically documented. [Waselenko et.al, (2004)] Variations in other blood counts are also noted. For instance, in cases where the radiation exposure is less than 5 GY there is a noted increase or an 'abortive rise' in granulocytes before the count starts to decline. Other blood components are also affected. Blood platelet levels for instance decline from the normal range of above (100-150) x 109 cells/liters to a very low count of (0-50) x 109 cells/liter within 15 to 16 days of exposure. [Health and Human Services, 2010]

The Gastrointestinal Syndrome

The gastrointestinal syndrome occurs when the radiation levels exceed 10 GY but in some cases GI symptoms are observed even at radiation levels of around 6 GY. [CDC] High levels of ionizing radiation cause irreparable damage to the GI tract leading to fatal consequences. Typically, the gastrointestinal crypts and mucosal barrier are destroyed which affects the ion exchange process leading to dehydration and mal nutrition due to mal absorption. Besides the usual symptoms of nausea and vomiting, dehydration, bowel obstruction, electrolyte imbalance and anemia are other common symptoms of Gastrointestinal Syndrome. Intestinal bleeding, sepsis and acute kidney failure are the other severe effects of GI syndrome. Compared to the Hematopoietic syndrome, the prognosis for gastrointestinal syndrome is very weak and in most cases death will result in 2 weeks. [Waselenko et.al, (2004)]

The Cardiovascular and Central Nervous System Syndrome

The cardiovascular (CV) and the central nervous system (CNS) are the most resistant to radiation. The full symptoms of CV and CNS syndrome manifest when the radiation levels exceed 50 GY but the general symptoms occur even at an exposure level greater than 20 GY. [CDC] The usual symptoms in the prodromal phase include confusion, disorientation, loss of gait and seizures. Acute Meningitis, increased fluid accumulation in the cranium, cerebral anoxia, circulatory complications, respiratory distress and cardiovascular shock are the severe symptoms of very high levels of radiation exposure. [Waselenko et.al, (2004)] This syndrome is the most severe form and is mostly fatal with death occurring within 3 days. [CDC]

The Stages of ARS

Four different stages of ARS are commonly observed. These include the Pro-Dromal stage, Latent stage, Manifest Illness Stage and Death or recovery. The Prodromal stage is the first and is usually referred to as the NVD stage as it is usually characterized by the standard symptoms of Nausea, Vomiting and Diarrhea. These symptoms may last for a few minutes but can persist intermittently over a few days. The Latent stage or the 'silent stage' follows the Prodromal period and in general, the patient feels significantly healthy and might be asymptomatic for a few days or even weeks. Next is the 'Manifest illness Stage' when the patient experiences symptoms related to the specific form of the ARS. These symptoms may last for a short period of time to several months. The last phase is the recovery stage where in the patient recovers from the radiation illness. This recovery period may vary and would be anywhere between a few weeks to two years depending on the severity of the exposure and the condition of the patient. Patients who do not show signs of recovery within few months after the exposure usually die. [CDC]

ARS Diagnosis

Diagnosis is not very simple as there is no symptom that could be used to uniquely identify acute radiation syndrome. Further, in most cases where the exposure level was mild prodromal symptoms do not manifest immediately (might even take a few days) presenting additional difficulties in diagnosis. In general, complete blood count taken several times within the first 12 hours of exposure could be very useful in the estimate of initial exposure. Individual dosimetry information must be ascertained to have an accurate appraisal of the level of radiation exposure. The time of onset of first vomiting, the lymphocyte depletion rates (assessed from the CBC) and chromosomal aberration studies are the three important variables that are useful in calculating the exposure dosage levels. In particular, the chromosome-aberration cytogenetic bioassay is considered the benchmark for radiation estimation and is used as the main diagnostic tool for patients suspected to have received very high dosage of radiation. Pronounced epilation along with unexplained vomiting and nausea may also be considered as important symptoms in the diagnosis of ARS. [CDC]

Treatment of ARS

Cytokine Therapy

ARS can produce a multitude of symptoms based on the degree of radiation exposure. Studies have reported a systemic inflammatory response to radiation. Control of inflammatory response is important in the treatment of patients with radiation exposure as otherwise it can lead to adverse metabolic responses. Stimulation of hematopoiesis using growth factors is vital. Cytokine therapy with granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) is vital. It is indicated that CSF therapy should be continued until the neutrophil count is atleast 1.0 x 109 cells/L . [Waselenko et.al, (2004)]

Transfusion and Stem cell transplantation

Erythrocyte and platelet transfusion maybe necessary in cases with severe bone marrow damage. Before transfusion these products are Leukoreduced to limit the immunosuppressive effects of transfusion. Stem cell transplantation may be necessary particularly for patients with radiation exposure levels exceeding 7 to 10 GY. Stem cell transplantation helps in total hematopoietic recovery. [Waselenko et.al, (2004)]

General Care

Since the immune system is very weak due to the depleted Lymphocyte counts, the patients are at an increased risk for opportunistic infections. So it is necessary to provide a prophylactic general care involving antibiotic, antiviral and anti-fungal agents. Antiemetic (to control nausea and vomiting) and anti-diarrheal agents drugs should be suitably administered. [Waselenko et.al, (2004)] Also, providing psychological support to the patient and the family members is also crucial as the news of radiation exposure and the consequences can be alarming. Psychological counseling could help to alleviate the distress and calm the patient.

Recent Researches

Jacob et.al (2010) reported that ARS affects multiple organs besides the well-documented effects on hematopoietic and gastrointestinal systems. ARS causes multiple organ damage. For instance, the patients affected in the radiation accidents at Nesvizh (Belarus) and Tokaimura (japan) exhibited different symptom pathology with the liver and kidney being the main organs affected. Animal studies have reported a significant increase in proinflammatory cytokines, which trigger a powerful and systemic inflammatory response. A recent study on radiation-exposed rats found that Ghrelin, a human gastrointestinal hormone could be useful to control the inflammatory response and limit organ damage. In particular, the researchers found that Ghrelin administration significantly reduced myeloperoxidase activities in the lungs, gut and kidneys and improved the survival rates to up to 69% in the rats with radiation combined injury. [Jacob et.al 2010]

Another recent study by Christ et.al (2008) reported the protective effect of dietary antioxidants on hematopoietic cells. The results from this animal study indicated higher peripheral blood leukocyte, bone marrow…