Acute Radiation Syndrome (ARS) - PDF

## MRD441: RADIATION BIOLOGY AND SAFETY ### Acute Radiation Syndrome ARS, or radiation sickness, occurs in humans after whole-body reception of large doses of ionizing radiation delivered over a short period of time. Data from epidemiologic studies of human populations exposed to doses of ionizing...

## MRD441: RADIATION BIOLOGY AND SAFETY ### Acute Radiation Syndrome ARS, or radiation sickness, occurs in humans after whole-body reception of large doses of ionizing radiation delivered over a short period of time. Data from epidemiologic studies of human populations exposed to doses of ionizing radiation sufficient to cause this syndrome have been obtained from: - Atomic bomb survivors of Hiroshima and Nagasaki, - The Marshall Islanders who were subjected to high levels of fallout during an atomic bomb test in 1954, - Nuclear radiation accident victims such as those injured in the 1986 Chernobyl disaster, and - Radiation therapy patients. Early radiation responses are described as deterministic. Deterministic radiation responses are those that exhibit increasing severity with increasing radiation dose. Furthermore, there is usually a dose threshold. ### ARS manifests itself in four major response stages: - Prodromal (initial stage) - Latent period - Manifest illness - Recovery The chart shows a graph of radiation exposure versus time. The graph is divided into four sections: 1. Prodromal syndrome 2. Latent period 3. Manifest illness 4. Recovery or death. The graph shows that the prodromal syndrome starts immediately after radiation exposure. The latent period starts a short time after that, and the manifest illness begins at the end of the latent period. The recovery period starts at the end of the manifest illness stage. ### **Prodromal Stage** It occurs within hours after a whole-body absorbed dose of 1 Gy (100 rads) or more. The severity of the symptoms is dose-related; the higher the dose, the more severe the symptoms. The length of time involved for this stage to run its course may be hours or a few days. **LD<sub>50<sup>** The LD₅₀ is the dose necessary to kill 50% of the exposed population. The LD_50/60 is the dose necessary to kill 50% of the exposed population in 60 days. ### **Latent Period** It occurs for about 1 week, during which no visible symptoms occur. Actually, it is during this period that either recovery or lethal effects begin. Toward the end of the first week, the next stage commences. ### **Manifest Illness Stage** It is the period when symptoms that affect: - The hematopoietic, - Gastrointestinal, and - Cerebrovascular systems become visible. In severe high-dose cases, emaciated human beings eventually die. ### **Repair and Recovery** Because cells contain a repair mechanism inherent in their biochemistry (repair enzymes), repair and recovery may occur when cells are exposed to sublethal doses of ionizing radiation. After irradiation, surviving cells begin to repopulate. This permits an organ that has sustained functional damage as a result of radiation exposure to regain some or most of its functional ability. However, the amount of functional damage sustained determines the organ’s potential for recovery. If both oxygenated and hypoxic cells receive a comparable dose of low-LET radiation, the oxygenated cells are more severely damaged but those that survive repair themselves and recover from the injury. Even though they are less severely damaged, the hypoxic cells do not repair and recover as efficiently. Research has shown that repeated radiation injuries have a cumulative effect. Hence a percentage (about 10%) of the radiation-induced damage is irreparable, whereas the remaining 90% may be repaired over time. When the processes of repair and repopulation work together, they aid in healing the body from radiation injury and promote recovery. ### **Syndrome is the medical term that means a collection of symptoms.** ARS is a collection of symptoms associated with high-level radiation exposure. Three separate dose-related syndromes occur as part of the total-body syndrome: - Hematopoietic Syndrome - Gastrointestinal Syndrome - Cerebrovascular Syndrome ### **Hematopoietic Syndrome** The hematopoietic form of ARS, or “bone marrow syndrome,” occurs when human beings receive whole-body doses of ionizing radiation ranging from 2.5 to 5 Gy (250 to 500 rads). The hematopoietic system manufactures the corpuscular elements of the blood and is the most radiosensitive vital organ system in humans. Radiation exposure causes the number of: - Red Cells - White Cells - Platelets In the circulating blood to decrease. Dose levels that cause this syndrome also may damage cells in other organ systems, causing the affected organ or organ system to fail. The patient initially experiences mild symptoms of the prodromal syndrome, which appear in a matter of a few hours and may persist for several days. The diagram shows a long bone, cross sectioned. The diagram shows three different areas: 1. Spongy bone (contains red marrow) 2. Compact bone 3 Yellow marrow. Surrounding the bone, there is a blood vessels network inside of the bone marrow. Inside the bone marrow there is a blood stem cell, red blood cells, white blood cells, and platelets. ### **Bone Marrow Failure Syndromes** - Idiopathic Aplastic Anemia - Paroxysmal Nocturnal Hemoglobinuria (PNH) - Myelodysplastic Syndrome (MDS) - Constitutional (Congenital/ Inherited) Aplastic Anemia The diagram shows four microscopic slides. The first slide shows a peripheral blood sample showing pancytopenia, the second slide shows a peripheral blood sample showing normal peripheral blood and red blood cells, the third slide shows fatty bone marrow in aplastic anemia, and the fourth slide shows normal cellular bone marrow. For example, radiation doses ranging from 2.5 to 5 Gy (250 to 5000 rads) produce a decrease in the number of bone marrow stem cells. When the cells of the lymphatic system are damaged, the body loses some of its ability to combat infection. Because the number of platelets also decreases with loss of bone marrow function, the body loses a corresponding amount of its blood-clotting ability. This makes the body more susceptible to hemorrhage. For persons affected with hematopoietic syndrome, survival time shortens as the radiation dose increases. When death occurs, it is a consequence of bone marrow destruction. Death may occur 6 to 8 weeks after irradiation in some sensitive human subjects who receive a whole-body dose exceeding 2 Gy (200 rads). As the whole-body dose increases from 2.5 to 5 Gy (250 to 500 rads), irradiated individuals die sooner. If the radiation exposure is not lethal, perhaps in the range of 1 to 2 Gy (100 to 200 rads), bone marrow cells will eventually repopulate to a level adequate to support life in most individuals. Many of these people recover 3 weeks to 6 months after irradiation. | Syndrome | Dose | Prodromal Stage | Latent Stage | Manifest Illness Stage | Recovery | |---|---|---|---|---|---| | Hematopoietic (Bone marrow) | 2.5-5 Gy | Symptoms are anorexia, nausea and vomiting. - Onset occurs 1 hour to 2 days after exposure. - Stage lasts for minutes to days. | - Stem cells in bone marrow are dying, although patient may appear and feel well. - Stage lasts 1 to 6 weeks. | - Symptoms are anorexia, fever, and malaise. - Drop in all blood cell counts occurs for several weeks. - Primary cause of death is infection and hemorrhage. - Survival decreases with increasing dose. - Most deaths occur within 1-2 months after exposure. | In most cases, bone marrow cells will begin to repopulate the marrow. - There should be full recovery for a large percentage of individuals from a few weeks up to two years after exposure. - The LD_50/60 is about 2.5 to 5 Gy (250 to 500 rads). | ### **Gastrointestinal Syndrome** In human beings the gastrointestinal form of ARS appears at a threshold dose of approximately 6 Gy (600 rads) and peaks after a dose of 10 Gy (1000 rads). Without medical support to sustain life, exposed persons receiving doses of 6 to 10 Gy (600 to 1000 rads) may die 3 to 10 days after being exposed. Even if medical support is provided, the exposed person will live only a few days longer. Survival time does not change with dose in this syndrome. A few hours after the dose required to cause the gastrointestinal syndrome has been received, the prodromal stage occurs. This is followed by a latent period, which lasts as long as 5 days. During this time the symptoms disappear. The manifest illness stage follows this period of false calm. Again, the human subject experiences severe nausea, vomiting, and diarrhoea. Other symptoms are discussed later. Death occurs primarily because of catastrophic damage to the epithelial cells that line the gastrointestinal tract. Such severe damage to these cells results in the death of the exposed person within 3 to 10 days of irradiation, as a result of infection, fluid loss, or electrolytic imbalance. ### **Mechanism of Action** The small intestine is the most severely affected part of the gastrointestinal tract. Because epithelial cells function as an essential biologic barrier, their breakdown leaves the body vulnerable to infection (mostly from its own intestinal bacteria), dehydration, and severe diarrhoea. Some epithelial cells regenerate before death occurs. However, because of the large number of epithelial cells damaged by the radiation, death may occur before cell regeneration is accomplished. The workers and firefighters at Chernobyl are examples of humans who died as a result of gastrointestinal syndrome. The diagram shows a small intestine, cross sectioned. The diagram is divided into two parts: 1. The small intestine, which shows the duodenum, jejunum, and ileum. 2. A closer look of the small intestine. The small intestine has crypts, villi, lamina propria, and lymphatic nodes. Inside of each villus, there are stem cells, goblet cell, enterocytes, lacteal, and inflammatory cells. | Syndrome | Dose | Prodromal Stage | Latent Stage | Manifest Illness Stage | Recovery | |---|---|---|---|---|---| | Gastrointestinal (GI) | 10 Gy (5-12Gy) | - Symptoms are anorexia, severe nausea, vomiting, cramps, and diarrhoea. - Onset occurs within a few hours after exposure. - Stage lasts about 2 days. | Stem cells in bone marrow and cells lining GI tract are dying, although patient may appear and feel well. - Stage lasts less than 1 week. | Symptoms are malaise, anorexia, severe diarrhoea, fever, dehydration, and electrolyte imbalance. - Death is due to infection, dehydration, and | The LD₁₀₀ is about 10 Gy (1000 rads). | ### **Cerebrovascular Syndrome** The cerebrovascular form of the ARS results when the central nervous system and cardiovascular system receive doses of 100 Gy (10000 rads) or more of ionizing radiation. A dose of this magnitude can cause death within a few hours to 2 or 3 days after exposure. After irradiation the prodromal stage begins. Symptoms discussed later. A latent period lasting up to 12 hours follows. During this time, symptoms lessen or disappear. After the latent period the manifest illness stage occurs. During this period the prodromal syndrome recurs with increased severity, and other symptoms appear. The diagram shows three diagrams of the brain: 1. The cerebrovascular system, showing cerebral veins, cerebral arteries, and cerebral ventricles. 2. A closer view of the neurovascular unit, showing an astrocyte end-foot, pericyte, neuron, lumen, basal lamina endothelial cells, and a tight junction. 3. A closer view of the blood-brain barrier, showing tight junction, blood vessel lumen, and brain parenchyma. ### **Mechanism of Action** Damaged blood vessels and permeable capillaries permit fluid to leak into the brain, causing an increase in fluid content. This creates an increase in intracranial pressure, leading to more tissue damage. The final result of this damage is failure of the central nervous and cardiovascular systems, which causes death in a matter of minutes. Because the gastrointestinal and hematopoietic systems are more radiosensitive than the central nervous system, they also are severely damaged and fail to function after a dose of this magnitude. However, because death occurs quickly, the consequences of the failure of these two systems are not demonstrated. | Syndrome | Dose | Prodromal Stage | Latent Stage | Manifest Illness Stage | Recovery | |---|---|---|---|---|---| | Cardiovascular (CV)/ Central Nervous System (CNS) | 100Gy Total body dose of X-Rays or total Neurons | Symptoms are extreme nervousness and confusion; severe nausea, vomiting, and watery diarrhoea; loss of consciousness; and burning sensations of the skin. - Onset occurs within minutes of exposure. | Patient may return to partial functionality. - Stage may last for hours but often is less. | Symptoms are return of watery diarrhoea, convulsions, and coma. - Onset occurs 5 to 6 hours after exposure. - Death occurs within 24-48 hours of exposure. | No recovery is expected. | The diagram shows a graph of mean survival time in days versus radiation dose in rad. The graph is divided into five sections: 1. Not lethal 2. Hematologic death 3. Gastrointestinal death 4. Central nervous system death 5. 10 to the power of 5 rad.