☢️Radiobiology Unit 11 – Acute Radiation Syndrome & Effects

What is Acute Radiation Syndrome?

• Acute Radiation Syndrome (ARS) occurs when the body receives a high dose of ionizing radiation over a short period of time
• Ionizing radiation damages cells and tissues by breaking chemical bonds and causing oxidative stress
• The severity of ARS depends on the absorbed dose, type of radiation, and the area of the body exposed
• Radiation exposure can be external (from a source outside the body) or internal (from ingested or inhaled radioactive materials)
• ARS primarily affects rapidly dividing cells in the body such as those in the bone marrow, gastrointestinal tract, and skin
• The onset and progression of symptoms depend on the radiation dose received
  • Mild ARS may present with nausea, vomiting, and fatigue
  • Severe ARS can lead to organ failure, sepsis, and death
• The LD50/60 (lethal dose for 50% of the population within 60 days) for humans is estimated to be 3.5-4.5 Gy

Causes and Types of Radiation Exposure

• Radiation exposure can occur from various sources such as nuclear accidents, occupational hazards, medical procedures, and acts of terrorism
• Types of ionizing radiation include alpha particles, beta particles, gamma rays, and neutrons
  • Alpha particles have a short range but high linear energy transfer (LET)
  • Beta particles have a longer range and lower LET compared to alpha particles
  • Gamma rays and X-rays are highly penetrating and can pass through the body
  • Neutrons have a high LET and can cause significant damage to biological tissues
• The biological effects of radiation depend on the type and energy of the radiation, as well as the dose and dose rate
• Whole-body exposure to high doses of radiation (>1 Gy) can lead to ARS
• Partial-body exposure or localized exposure to high doses can cause acute local radiation injuries (skin burns, tissue necrosis)
• Internal contamination occurs when radioactive materials are ingested, inhaled, or absorbed through wounds
  • Incorporated radionuclides can continue to irradiate tissues and cause long-term health effects

Stages of Acute Radiation Syndrome

• ARS progresses through four distinct stages: prodromal, latent, manifest illness, and recovery or death
• The prodromal stage occurs within hours to days after exposure and is characterized by nausea, vomiting, fatigue, and loss of appetite
  • The severity and onset of symptoms depend on the radiation dose received
  • Higher doses lead to earlier onset and more severe symptoms
• The latent stage follows the prodromal stage and is a period of apparent clinical improvement
  • The duration of the latent stage is inversely proportional to the radiation dose
  • Higher doses result in a shorter latent stage
• The manifest illness stage is characterized by the clinical manifestations of specific organ system damage
  • Hematopoietic syndrome occurs at doses >1 Gy and is due to bone marrow suppression
  • Gastrointestinal syndrome occurs at doses >6 Gy and is due to damage to the intestinal mucosa
  • Neurovascular syndrome occurs at doses >20 Gy and is characterized by neurological symptoms and cardiovascular collapse
• The recovery or death stage depends on the severity of the organ damage and the effectiveness of medical interventions
  • Lower doses (<2 Gy) have a better prognosis with appropriate supportive care
  • Higher doses (>6 Gy) have a poor prognosis even with aggressive treatment

Symptoms and Clinical Manifestations

• The symptoms of ARS vary depending on the radiation dose and the stage of the syndrome
• Prodromal stage symptoms include nausea, vomiting, anorexia, fatigue, and headache
  • The time to onset of vomiting is a useful triage tool to estimate the radiation dose
  • Earlier onset of vomiting indicates a higher radiation dose
• Hematopoietic syndrome is characterized by lymphocyte depletion, neutropenia, thrombocytopenia, and anemia
  • Lymphocyte depletion occurs within 24-48 hours and is a sensitive indicator of radiation exposure
  • Neutropenia increases the risk of infections and sepsis
  • Thrombocytopenia leads to hemorrhage and bleeding complications
  • Anemia develops later due to the longer lifespan of erythrocytes
• Gastrointestinal syndrome presents with abdominal pain, diarrhea, and gastrointestinal bleeding
  • Electrolyte imbalances and dehydration can occur due to fluid loss
  • Bacterial translocation from the damaged intestinal mucosa can lead to sepsis
• Neurovascular syndrome is characterized by confusion, disorientation, ataxia, and seizures
  • Cerebral edema and increased intracranial pressure can occur
  • Cardiovascular collapse and shock may lead to rapid death
• Cutaneous radiation syndrome can occur with localized high-dose exposure
  • Skin erythema, blistering, and ulceration may develop
  • Chronic radiation dermatitis and delayed wound healing can occur

Diagnosis and Assessment

• The diagnosis of ARS is based on a history of radiation exposure, clinical symptoms, and laboratory findings
• Dosimetry is essential to estimate the absorbed radiation dose
  • Physical dosimetry using personal dosimeters (film badges, thermoluminescent dosimeters)
  • Biological dosimetry using chromosomal aberrations in lymphocytes (dicentric assay)
• Serial complete blood counts (CBCs) are used to monitor hematologic parameters
  • Lymphocyte depletion is an early and sensitive marker of radiation exposure
  • Neutrophil and platelet counts are used to assess the severity of bone marrow suppression
• Imaging studies (CT scans, MRI) may be used to assess organ damage and complications
• Bioassays can detect internal contamination with radioactive materials
  • Whole-body counting, urine and fecal analysis, nasal swabs
• Psychological assessment and support are important for managing the mental health impact of radiation incidents

Treatment Approaches

• The treatment of ARS is primarily supportive and depends on the specific organ systems affected
• Fluid and electrolyte replacement is essential to maintain hydration and correct electrolyte imbalances
• Antiemetic medications (ondansetron, granisetron) are used to control nausea and vomiting
• Hematopoietic growth factors (G-CSF, GM-CSF) are used to stimulate bone marrow recovery and reduce the duration of neutropenia
  • Filgrastim (G-CSF) is recommended for exposures >2 Gy or when the absolute neutrophil count (ANC) falls below 500/mm³
• Blood product transfusions (packed red blood cells, platelets) are used to manage anemia and thrombocytopenia
• Antibiotics are used to prevent and treat infections in neutropenic patients
  • Empiric broad-spectrum antibiotics are started at the first sign of fever or infection
  • Antifungal and antiviral prophylaxis may be considered in severe cases
• Stem cell transplantation may be considered for severe bone marrow failure or high-dose exposures (>7 Gy)
• Surgical intervention may be necessary for managing gastrointestinal complications (perforations, obstructions)
• Burn care and wound management are essential for treating cutaneous radiation injuries
• Chelation therapy (DTPA, Prussian blue) may be used for internal contamination with specific radionuclides
• Psychological support and counseling are important for addressing the mental health impact of radiation incidents

Long-Term Effects and Prognosis

• Survivors of ARS are at increased risk for long-term health effects and secondary malignancies
• Chronic radiation syndrome can develop after high-dose exposures and is characterized by persistent fatigue, weakness, and organ dysfunction
• Radiation-induced cancers may develop years to decades after exposure
  • Leukemia has the shortest latency period (2-7 years)
  • Solid tumors have longer latency periods (>10 years)
• Cataract formation is a common late effect of radiation exposure to the lens of the eye
• Infertility and reproductive disorders can occur due to radiation damage to the gonads
• Cardiovascular and cerebrovascular diseases have been reported in atomic bomb survivors and occupationally exposed individuals
• Psychological effects such as anxiety, depression, and post-traumatic stress disorder (PTSD) can persist long after the incident
• The prognosis of ARS depends on the radiation dose, the severity of organ damage, and the effectiveness of medical interventions
  • Lower doses (<2 Gy) have a favorable prognosis with appropriate supportive care
  • Higher doses (>6 Gy) have a poor prognosis even with aggressive treatment
• Long-term follow-up and surveillance are essential for monitoring and managing the delayed health effects in ARS survivors

Prevention and Radiation Safety

• Radiation safety principles aim to minimize the risk of radiation exposure and prevent the occurrence of ARS
• The three basic principles of radiation protection are time, distance, and shielding
  • Minimizing the time spent in radiation areas reduces the total dose received
  • Maintaining a safe distance from radiation sources follows the inverse square law
  • Using appropriate shielding materials (lead, concrete) attenuates radiation exposure
• Occupational radiation safety programs ensure that workers' exposures are kept as low as reasonably achievable (ALARA)
  • Radiation monitoring, dosimetry, and record-keeping are essential components
  • Personal protective equipment (PPE) such as lead aprons and thyroid shields are used in medical settings
• Proper training and education on radiation safety procedures are crucial for all personnel working with radiation sources
• Emergency preparedness and response plans are necessary for managing radiation incidents and minimizing the impact on public health
  • Triage, decontamination, and medical management protocols should be established in advance
  • Risk communication and public education are important for reducing panic and misinformation
• International organizations such as the International Atomic Energy Agency (IAEA) and the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) provide guidance and standards for radiation protection
• Adherence to radiation safety regulations and best practices is essential for preventing the occurrence of ARS and other radiation-related health effects.