**5. Organ specific injury**

A common theme in radiation injury is the ability of the tissue or organ to respond to cell death and self-regenerate. These aspects vary among organs and thus the clinical presentation and treatment is different depending on the organ involved. Injuries and treatment protocols for specific organs are as follows:

#### **5.1 Hematopoietic system**

As previously discussed, damage to the hematopoietic system typically results from injury to progenitor cells, which can lead to hematopoietic crisis and infection. Fortunately, with the exception of whole-body exposure, the hematopoietic system is generally able to recover from radiation damage due to migration of stem cells from outside the site of exposure. Patients who are also receiving chemotherapy or taking medications that may result in immunosuppressed states should be carefully assessed. In the case of total body irradiation, an immediate decrease in circulating lymphocytes can be expected with subsequent defects in immune response. Symptomatic treatment, including blood infusions and antibiotics as needed, with isolation are crucial in these situations [13, 14]. Use of bone marrow transplants to replenish depleted progenitor cells has a theoretical survival benefit opportunity in total body irradiation patients, but to date has not been embraced as standard practice and often only applied to those most severely affected. The risk of graft-vs-host disease makes this approach controversial, especially in the setting of an emergency unrelated allogeneic transplant [6].

#### **5.2 Skin**

The skin is often the most direct site of radiation injury, as the epidermis covers all other organs and is susceptible to radiation damage. The dermal stem cells are the most susceptible component of the skin, as these are the actively dividing cells

**7**

*Radiation Injury and Emergency Medicine DOI: http://dx.doi.org/10.5772/intechopen.95262*

behind this phenomenon is unknown [15].

and contain less local immunity.

**5.3 Gastrointestinal system**

that replace other cells in the rest of the organ. Early symptoms of exposure typically involve erythema and swelling as vasodilation and the recruitment of inflammatory components localize to the area. These symptoms typically resolve within a month. Late term effects include decreased wound healing capacity with increased fibrosis and ulceration. Interestingly, the skin will appear to be more vascularized with more prominent vasculature. However, this is due to thinning of the epidermis, which causes veins to appear more prominent. Proper wound care is the standard treatment for these manifestations, with surgical debridement as needed. Particular concern must be paid for patients with medical conditions that are prone to fibrosis, such as those with dermatitis, lupus, and scleroderma. Skin infections, such as cellulitis, are particularly dangerous given the immunosuppressive effects of radiation therapy. Lastly, an interesting phenomenon occurs in some patients where previously irradiated skin can become erythemic and fibrotic several years later in response to certain medications like antibiotics and chemotherapy. The mechanism

In the past, skin involvement from radiation therapy that could not be treated with topical ointments was relatively rare. However, with the increasing use of hypofractionation (radiation therapy with greater amounts of dose per treatment), these findings are becoming more common [16]. Thus, radiation damage to the skin is likely to become more prominent in the future as therapy becomes more compressed with higher doses delivered in a shorter period of time. Patients with a history of radiation therapy and significant skin sequalae should be carefully observed for more serious developments as injuries in treated tissues heal less well

Like the skin, the gastrointestinal system is composed of mucosal cells with multiple layers underneath that are constantly replaced over time. Unfortunately, the rate at which some of these cells are replaced is higher than that of the skin, leading to more immediate and sometimes more severe clinical manifestations. Cells of the gastric and small bowel tend to have the highest rate of replacement, leading to very early nausea if these regions were exposed. Exposure to mucosal cells in the upper gastrointestinal system (mouth, esophagus, salivary glands) tend to present with clinical symptoms around two weeks after exposure due to a longer replacement rate. Damage to these cells tends to present with more localized pain and swelling. Exposure to the salivary glands can result not only with localized pain, but also xerostomia (dryness of mouth) and ageusia (loss of taste). Saliva can become more acidic which can further injure normal tissue and alter the environment of the oral cavity. Regardless of these manifestations, patients should be advised to maintain adequate nutrition and dental hygiene, as this practice helps mitigate the complications of an immunocompromised state. Symptomatic treatment of localized pain is also advised and considered standard of care as bone exposure can be a serious consequence of mucosal denudation [14]. **Figure 1** represents modern head/neck radiation therapy treatment plan through the oral cavity demonstrating sparing of the parotid tissue with intensity modulation. Farther along the digestive tract, the expected symptoms can be predicted based on the location of the tumor. Radiation exposure to the gastric mucosa during treatment of gastric tumors can result in near immediate nausea given the daily replacement the gastric mucosa. Treatment of esophageal tumors, which are now more commonly in the lower third of the esophagus, present with a timeline of symptoms

similar to head and neck tumors (approximately two weeks after exposure). Tumors in this region typically cause dysphagia and anorexia. Treatment initially tends to relieve patient symptoms, but later patients may return thinking the tumor

#### *Radiation Injury and Emergency Medicine DOI: http://dx.doi.org/10.5772/intechopen.95262*

*Trauma and Emergency Surgery - The Role of Damage Control Surgery*

poietic and mesenchymal transplant remains under investigation.

**4. Subacute and late toxicity**

to investigate a potential long-term effect.

**5. Organ specific injury**

**5.1 Hematopoietic system**

unrelated allogeneic transplant [6].

radioprotectors are expected to be approved as the need to protect against radiation toxicity increases. Although many compounds have been and are in development, no others to date are actively used in clinical practice and the role of both hemato-

The subacute and/or late effects of radiation toxicity, by nature, are less visible and harder to identify for most emergency and primary care physicians. Often, these effects take many years to develop and are often mistaken as sequelae from another disease. However, they are nevertheless important to identify and address. A common misconception is that the degree to which a patient suffers from acute symptoms is proportional to severity of the long-term response. Unfortunately, patients who experience little to no acute sequela can experience serious long-term sequela, and vice versa. While both children and adults can experience the effects of late radiation toxicity, children are susceptible as they have a much longer period for these clinical manifestations to develop [13]. Unlike acute toxicity effects, anticipating long term effects is much more difficult. This technique relies heavily not only on a physician's knowledge of potential long-term effects, but also their willingness

A common theme in radiation injury is the ability of the tissue or organ to respond to cell death and self-regenerate. These aspects vary among organs and thus the clinical presentation and treatment is different depending on the organ involved. Injuries and treatment protocols for specific organs are as follows:

As previously discussed, damage to the hematopoietic system typically results from injury to progenitor cells, which can lead to hematopoietic crisis and infection. Fortunately, with the exception of whole-body exposure, the hematopoietic system is generally able to recover from radiation damage due to migration of stem cells from outside the site of exposure. Patients who are also receiving chemotherapy or taking medications that may result in immunosuppressed states should be carefully assessed. In the case of total body irradiation, an immediate decrease in circulating lymphocytes can be expected with subsequent defects in immune response. Symptomatic treatment, including blood infusions and antibiotics as needed, with isolation are crucial in these situations [13, 14]. Use of bone marrow transplants to replenish depleted progenitor cells has a theoretical survival benefit opportunity in total body irradiation patients, but to date has not been embraced as standard practice and often only applied to those most severely affected. The risk of graft-vs-host disease makes this approach controversial, especially in the setting of an emergency

The skin is often the most direct site of radiation injury, as the epidermis covers all other organs and is susceptible to radiation damage. The dermal stem cells are the most susceptible component of the skin, as these are the actively dividing cells

**6**

**5.2 Skin**

that replace other cells in the rest of the organ. Early symptoms of exposure typically involve erythema and swelling as vasodilation and the recruitment of inflammatory components localize to the area. These symptoms typically resolve within a month. Late term effects include decreased wound healing capacity with increased fibrosis and ulceration. Interestingly, the skin will appear to be more vascularized with more prominent vasculature. However, this is due to thinning of the epidermis, which causes veins to appear more prominent. Proper wound care is the standard treatment for these manifestations, with surgical debridement as needed. Particular concern must be paid for patients with medical conditions that are prone to fibrosis, such as those with dermatitis, lupus, and scleroderma. Skin infections, such as cellulitis, are particularly dangerous given the immunosuppressive effects of radiation therapy. Lastly, an interesting phenomenon occurs in some patients where previously irradiated skin can become erythemic and fibrotic several years later in response to certain medications like antibiotics and chemotherapy. The mechanism behind this phenomenon is unknown [15].

In the past, skin involvement from radiation therapy that could not be treated with topical ointments was relatively rare. However, with the increasing use of hypofractionation (radiation therapy with greater amounts of dose per treatment), these findings are becoming more common [16]. Thus, radiation damage to the skin is likely to become more prominent in the future as therapy becomes more compressed with higher doses delivered in a shorter period of time. Patients with a history of radiation therapy and significant skin sequalae should be carefully observed for more serious developments as injuries in treated tissues heal less well and contain less local immunity.

## **5.3 Gastrointestinal system**

Like the skin, the gastrointestinal system is composed of mucosal cells with multiple layers underneath that are constantly replaced over time. Unfortunately, the rate at which some of these cells are replaced is higher than that of the skin, leading to more immediate and sometimes more severe clinical manifestations. Cells of the gastric and small bowel tend to have the highest rate of replacement, leading to very early nausea if these regions were exposed. Exposure to mucosal cells in the upper gastrointestinal system (mouth, esophagus, salivary glands) tend to present with clinical symptoms around two weeks after exposure due to a longer replacement rate. Damage to these cells tends to present with more localized pain and swelling. Exposure to the salivary glands can result not only with localized pain, but also xerostomia (dryness of mouth) and ageusia (loss of taste). Saliva can become more acidic which can further injure normal tissue and alter the environment of the oral cavity. Regardless of these manifestations, patients should be advised to maintain adequate nutrition and dental hygiene, as this practice helps mitigate the complications of an immunocompromised state. Symptomatic treatment of localized pain is also advised and considered standard of care as bone exposure can be a serious consequence of mucosal denudation [14]. **Figure 1** represents modern head/neck radiation therapy treatment plan through the oral cavity demonstrating sparing of the parotid tissue with intensity modulation.

Farther along the digestive tract, the expected symptoms can be predicted based on the location of the tumor. Radiation exposure to the gastric mucosa during treatment of gastric tumors can result in near immediate nausea given the daily replacement the gastric mucosa. Treatment of esophageal tumors, which are now more commonly in the lower third of the esophagus, present with a timeline of symptoms similar to head and neck tumors (approximately two weeks after exposure). Tumors in this region typically cause dysphagia and anorexia. Treatment initially tends to relieve patient symptoms, but later patients may return thinking the tumor

#### **Figure 1.**

*Parotid sparing. Image courtesy of the Department of Radiation Oncology, University of Massachusetts Medical School.*

has returned when in reality these symptoms are due to swelling from the therapy. Like head and neck tumors, patients should be advised to continue maintaining adequate hydration and nutrition [13, 14].

Symptoms from radiation exposure in the small and large bowel are more complex and require more in-depth patient history and laboratory tests. The small bowel absorbs much of the nutrients from food. Damaging the microvilli of the mucosal surface, which are vital for nutrient absorption, can result in severe malabsorption regardless of a patient's appetite. These findings can be confirmed by stool tests. Patients will often present to the emergency room with diarrhea, steatorrhea, bloating and general abdominal pain a few days after radiation exposure. The large bowel plays an important role in absorption of water, and exposure of large portions of this organ may compromise this function. Patients may complain of increased defecation frequency, which can lead to dehydration and electrolyte abnormalities that can be confirmed through electrolyte panels. To make matters more difficult, abdominal organs are prone to forming adhesions after surgical interventions, which disrupts blood flow to portions of the bowel that are exacerbated after concurrent radiation therapy. Anticipation of these issues through a careful patient history are vital to preventing severe complications from occurring [13, 14, 17].

Late effects of radiation also depend on location of the exposure. The mucosal cells of the oral cavity should theoretically recover like that of typical skin cells, but the combination of a tight space and harsh oral environment prone to infection and necrosis makes healing difficult. Thus, fibrosis and ulceration over a long period of time are possible. Acute effects of radiation typically damage mucosa of the gums and affect the pH of the saliva, facilitating microbial growth. These changes can lead to long-term problems with dental hygiene and patients should modify their dental habits accordingly through increased tooth brushing and fluoride mouthwash [13, 14]. Motility issues are also becoming more common, especially since patients who receive radiation therapy are now living longer. Dysphagia appears to be due to edema surrounding constrictor muscles, and physical therapy

**9**

**5.5 Liver**

*Radiation Injury and Emergency Medicine DOI: http://dx.doi.org/10.5772/intechopen.95262*

parenchyma outside of the field of radiation [20].

with improvement seen after withdrawal of the immunotherapy.

placement of therapy in close approximation to disease.

Radiation injury to the liver, also known as radiation-induced liver disease (RILD), is unique in that it is often during the healing process that tissue function undergoes disorganized repair, including injury to the reticulum network, and limits the vascular relationship to the hepatocyte. While acute damage to hepatocytes affects liver function, as the cells divide during repair they tend to become disorganized, particularly if the structural reticulum of the liver is damaged. Increased distance between the hepatocytes and the blood supply leads to decreased liver function. This phenomenon explains why the state of the liver before exposure to radiation also plays an important role in this process. For example, a cirrhotic liver due to heavy alcoholic use or hepatitis will likely have pre-existing disorganized architecture, making this liver more susceptible to radiation damage. This includes veno-occlusive disease which also separates vascular anatomy from the hepatocyte. For these reasons, imaging studies such as magnetic resonance imaging before the delivery of radiation are obtained for evaluation of anatomy and function [25]. Disorganized repair can lead to migration of infusional therapies including radiolabeled therapy as the vascular anatomy can be disrupted and limit efficacy in spite of

**5.4 Lung**

to encourage lymph drainage offers symptomatic treatment [18]. Gastric emptying issues due fibrosis at the gastric antrum and regions in the bowel where surgery was performed are also possible years after treatment. Atrophy of the pancreas many years after radiation exposure is also known to happen, although the clinical relevance of this is unknown [13, 14]. Symptoms can mimic malabsorption syndrome.

The main mechanism of radiation injury in the lungs is the generation of free oxygen and nitrogen radicals which damage the lung parenchyma with irregular repair of type I and II pneumocytes along the delicate reticulin network of pulmonary parenchyma. This oxidative damage causes disorganized repair and replacement of these cells associated with late fibrosis, impairs the ability for the lungs to oxygenate the blood. Pneumocyte damage also leads to recruitment of proinflammatory modulators that recruit immune cells to the region, leading to fibrosis and further depleting oxygenation capacity [19]. Furthermore, the radiation-driven production of nitric oxide has been suggested as a possible cause of damage to lung

Complicating this situation is that many chemotherapeutic agents given with radiation therapy, such as bleomycin, also causes pulmonary fibrosis. The results of these sequelae are the development of pneumonitis up to two to six months after exposure. If asymptomatic, careful observation is standard of care. If symptomatic, the patient usually presents with occasional bouts of cough and dyspnea. Treatment with corticosteroids, supplementary oxygen, and prophylactic antibiotics are recommended in this situation. Once the pneumonitis resolves, fibrosis typically marks the site of radiation injury and can result in limited ventilation requiring long term use of supplemental oxygen. Given these findings, it is important to note that these patients tend to be at higher risk of developing chronic pulmonary disease compared to those who were unexposed [13, 21–24]. Pulmonary rehabilitation is an important aspect to survivorship care and optimizing respiratory health is important to each patient as the rehabilitate from therapy. **Figure 2** represents changes in lung parenchyma associated with immunotherapy and low dose radiation therapy

to encourage lymph drainage offers symptomatic treatment [18]. Gastric emptying issues due fibrosis at the gastric antrum and regions in the bowel where surgery was performed are also possible years after treatment. Atrophy of the pancreas many years after radiation exposure is also known to happen, although the clinical relevance of this is unknown [13, 14]. Symptoms can mimic malabsorption syndrome.

### **5.4 Lung**

*Trauma and Emergency Surgery - The Role of Damage Control Surgery*

has returned when in reality these symptoms are due to swelling from the therapy. Like head and neck tumors, patients should be advised to continue maintaining

*Parotid sparing. Image courtesy of the Department of Radiation Oncology, University of Massachusetts* 

Symptoms from radiation exposure in the small and large bowel are more complex and require more in-depth patient history and laboratory tests. The small bowel absorbs much of the nutrients from food. Damaging the microvilli of the mucosal surface, which are vital for nutrient absorption, can result in severe malabsorption regardless of a patient's appetite. These findings can be confirmed by stool tests. Patients will often present to the emergency room with diarrhea, steatorrhea, bloating and general abdominal pain a few days after radiation exposure. The large bowel plays an important role in absorption of water, and exposure of large portions of this organ may compromise this function. Patients may complain of increased defecation frequency, which can lead to dehydration and electrolyte abnormalities that can be confirmed through electrolyte panels. To make matters more difficult, abdominal organs are prone to forming adhesions after surgical interventions, which disrupts blood flow to portions of the bowel that are exacerbated after concurrent radiation therapy. Anticipation of these issues through a careful patient history are vital to preventing severe complications from occurring [13, 14, 17]. Late effects of radiation also depend on location of the exposure. The mucosal cells of the oral cavity should theoretically recover like that of typical skin cells, but the combination of a tight space and harsh oral environment prone to infection and necrosis makes healing difficult. Thus, fibrosis and ulceration over a long period of time are possible. Acute effects of radiation typically damage mucosa of the gums and affect the pH of the saliva, facilitating microbial growth. These changes can lead to long-term problems with dental hygiene and patients should modify their dental habits accordingly through increased tooth brushing and fluoride mouthwash [13, 14]. Motility issues are also becoming more common, especially since patients who receive radiation therapy are now living longer. Dysphagia appears to be due to edema surrounding constrictor muscles, and physical therapy

adequate hydration and nutrition [13, 14].

**Figure 1.**

*Medical School.*

**8**

The main mechanism of radiation injury in the lungs is the generation of free oxygen and nitrogen radicals which damage the lung parenchyma with irregular repair of type I and II pneumocytes along the delicate reticulin network of pulmonary parenchyma. This oxidative damage causes disorganized repair and replacement of these cells associated with late fibrosis, impairs the ability for the lungs to oxygenate the blood. Pneumocyte damage also leads to recruitment of proinflammatory modulators that recruit immune cells to the region, leading to fibrosis and further depleting oxygenation capacity [19]. Furthermore, the radiation-driven production of nitric oxide has been suggested as a possible cause of damage to lung parenchyma outside of the field of radiation [20].

Complicating this situation is that many chemotherapeutic agents given with radiation therapy, such as bleomycin, also causes pulmonary fibrosis. The results of these sequelae are the development of pneumonitis up to two to six months after exposure. If asymptomatic, careful observation is standard of care. If symptomatic, the patient usually presents with occasional bouts of cough and dyspnea. Treatment with corticosteroids, supplementary oxygen, and prophylactic antibiotics are recommended in this situation. Once the pneumonitis resolves, fibrosis typically marks the site of radiation injury and can result in limited ventilation requiring long term use of supplemental oxygen. Given these findings, it is important to note that these patients tend to be at higher risk of developing chronic pulmonary disease compared to those who were unexposed [13, 21–24]. Pulmonary rehabilitation is an important aspect to survivorship care and optimizing respiratory health is important to each patient as the rehabilitate from therapy. **Figure 2** represents changes in lung parenchyma associated with immunotherapy and low dose radiation therapy with improvement seen after withdrawal of the immunotherapy.
