**5.7 Cardiovascular system**

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

Patients with RILD typically experience symptoms that mimic cirrhosis, which include abdominal pain, elevated liver enzymes, jaundice, and ascites within four months of radiation exposure. Livers with pre-existing damage typically have earlier onset, with more severe symptoms. Treatment is symptomatic with keen observation of potential veno-occlusive and metabolic disease secondary to a congested liver with decreased function. Careful consideration must be given for medications that are metabolized in the liver, especially chemotherapeutic agents

*(A) and (C) Therapy driven pneumonitis outlining the radiation therapy field while on immune check point inhibition. (B) and (D) Improvement after immunotherapy withdrawal. Courtesy of the Department of* 

All components of the kidney, including structures crucial for filtration, such as cells of the glomerulus, are susceptible to radiation damage. The signs of acute radiation damage are usually seen within 3–18 months, typically mimicking signs of renal failure. These signs include decreased glomerular filtration rate (GFR), increased serum β2-microglobulin, albuminuria, and other markers of poor renal function. Later signs of kidney radiation damage, which include hypertension and eventual renal failure, are often hard to distinguish from other pathological causes. For treatment of these sequelae, the use of hypertension medications such as angiotensin-converting-enzyme inhibitors (ACE) inhibitors are theoretically beneficial. Monitoring of renal function, both short and long term, also remains crucial in the standard of care for these patients [27–29]. In aging patients who are

**10**

**5.6 Renal**

**Figure 2.**

that are also hepatotoxic [25, 26].

*Radiation Oncology, University of Massachusetts Medical School.*

The mechanism of radiation damage to the heart and blood vessels involves immediate cellular damage followed by fibrotic and disorganized repair, leading to reduced function in all cardiac segments including electrical conduction, myocardium, valves, and vascular anatomy. The time period is variable due to differences in size and functional architecture. However, what is clear is that unintended radiation exposure to the heart and blood vessels has a strong association with cardiovascular disease and complications [30–33]. The lack of mitigation and therapeutic strategies in response to radiation of cardiovascular tissues explains why radiation oncologists spend such a large amount of effort to minimize cardiovascular exposure [34].

Generous radiation exposure to the heart can result in acute pericarditis. This diagnosis should always be in the differential in a patient with history of radiation exposure who presents with sharp, radiating chest pain that is relieved when sitting up. Anti-inflammatory medications like aspirin, colchicine and prednisone can offer symptomatic relief, with pericardiocentesis being an option in severe cases. Long term, patients who receive radiation exposure to the heart have a higher risk of heart disease and use of echocardiograms and nuclear stress tests in these patients is recommended if symptoms warrant use. Large blood vessels like the aortic, carotid, and femoral arteries can experience hyperplasia and atherosclerotic change from radiation doses. These changes can result in rupture and fistula formation, necessitating immediate treatment. This usually requires very high doses and prolonged exposure usually not seen in modern radiation therapy [30–33]. With improvements in survival, patients can receive therapy with intentional overlap to previously treated volumes for second malignancies. These patients are vulnerable to vascular injury, including larger arteries and survivorship plans need to include periodic surveillance of vessels to optimize follow up care. **Figure 3** demonstrates cardiac sparing for left-sided breast cancer treatment with breath-hold treatment techniques and optical tracking.

#### **Figure 3.**

*Cardiac sparing with deep inspiration breath-hold (DIBH), (left-free-breathing (FB); right-DIBH). Image courtesy of the Department of Radiation Oncology, University of Massachusetts Medical School.*

#### **5.8 Nervous system**

Since most cells of the nervous system do not typically have a high turnover rate, it would seem reasonable to assume that the nervous system is more resistant to radiation damage than other organs. However, this assumption does not account for the immediate molecular effects of radiation. Regardless of the rate of cell division, all cells will receive damage to membranes, organelles, and other structures within the cell. Cells that do not divide very frequently will have to endure these injuries for long periods of time, leading to eventual clinical manifestations. Damage to nearby vasculature also limits growth and healing of these structures, leading to pronounced long term effects. There are clear reports of radiation damage to the central nervous system sometimes long after the initial radiation exposure [35–38].

Patients who received radiosurgery or hypofractionation techniques are at risk of developing necrosis within six months of receiving therapy. Clinically, these developments can result in focal changes and change in behavior depending on the site of necrosis. Demyelinating syndromes, although rare, are also possible in the peripheral nerves and spinal cord. Often, neurotoxic symptoms are enhanced by chemotherapeutic agents, such as vinblastine, vincristine and cisplatin. Gathering a detailed physical exam, medical history and possible neurological referral may be required for definitive identification of these outcomes. Patients who received radiation therapy for pituitary adenomas or at sites near the optic structures are at risk for visual changes [36, 37]. This is because some structures, such as the lens and optic chasm, are sensitive to radiation exposure due to limited blood supply [15, 39, 40]. Patients treated for breast and head and neck cancers may rarely present with brachial plexopathy. Peripheral lymph nodes for these regions are often within the same field of treatment as the brachial plexus, resulting in unintended exposure to this region [41].

#### **5.9 Endocrine**

The effect of radiation therapy on the endocrine glands varies depending on the gland affected. The timeline for the development of clinical sequelae varies, with some cases even being reported many years after the radiation exposure. The pituitary gland is relatively radiation sensitive and results in panhypopituitary syndrome, requiring supplementation of depleted hormones. Secondary malignancies from un-intentional radiation exposure, while rare, have been reported [42]. Patients who received previous head and neck radiation therapy who now present with headache, vision loss and/or hormonal abnormalities should be carefully examined for the development of pituitary adenomas. The thyroid gland is also sensitive to radiation therapy, resulting in hypothyroid syndromes. Patients who receive radiation therapy to the head and neck often receive surgery that involves dissection of the thyroid gland, exasperating thyroid function loss. The thyroid also has a relatively higher incidence of developing secondary malignancies. This finding has been identified not only in patients receiving radiation therapy, but also victims of the Chernobyl incident [5]. The same care must be given to the parathyroid glands, given the proximity to the thyroid gland, which can present with signs and symptoms of hypoparathyroidism. Radiation exposure to the endocrine pancreas and adrenal glands are less characterized and are thought to be more radiation resistant. However, there are a few cases of injury to these organs associated with radiation exposure [42].

#### **5.10 Reproductive**

The reproductive organs are highly sensitive to radiation damage, with early exposure in pediatric patients leading to severe detriments like sterility and

**13**

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

repeated radiation exposure to the gonads [13, 14, 42].

**6. Pediatrics**

survivorship plans.

**7. Mitigation strategies in planning**

secondary malignancies (see Pediatrics). Since much of the reproductive system depends on hormonal homeostasis, radioactive effects on the endocrine system (see Endocrine) and the subsequent effect on hormone production, such as that on testosterone and estrogen, can drastically affect reproductive function and development depending on the effected hormone and gland. When investigating radiation injury to the reproductive system, it is always important to consider the location of exposure and any endocrine glands involved. Germ cells, such as spermatogonia, are particularly sensitive to radiation damage as they can experience inter-mitotic death. Even mild radiation exposure can lead to a heavy drop in sperm numbers. Mature sperm that receive radiation damage can harbor serious mutations or chromosomal abnormalities, leading to severe birth defects in progeny. Exposure to female reproductive organs can even lead to miscarriage and early menopause. As a result, it usually recommended for patients who receive gonadal exposure practice birth control methods for up to six months after the exposure. Because the ovaries rely on a regular, cyclical production of hormones from the follicles, radiation injury can lead to more pronounced effects on fertility. Mucosal atrophy and drying of female genitalia can cause great discomfort for the patient as well. Thus, fertility treatment and consultation should be considered for patients who received heavy or

Pediatric patients are unique in that many organs and tissues are still developing. As a result, the cells involved are particularly sensitive to radiation damage as the fully developed adult organ can become abnormal or dysfunctional. Pediatric patients who receive radiation therapy are known to have a higher risk of developing growth abnormalities, chronic diseases, secondary malignancies and premature death compared to sibling controls [43]. Children who were treated with radiotherapy in the pelvis for tumors such as rhabdomyosarcoma or germ cell tumors are at high risk for gonadal abnormalities. Given the rapid growth in the musculoskeletal system during puberty, exposure to the spine at an early age can cause drastic changes to the respiratory and cardiovascular system. Radiation exposure to any cartilage or bone not only presents the risk of bone necrosis, but also may affect the fully developed form of such tissue, sometimes resulting in stunted extremity length and increased frequency of fractures. Children treated for Wilms tumors are at high risk of renal abnormalities later in their lifetime to the remaining kidney, therefore attention to detail for renal health as these patients become adults is an important aspect of a survivorship plan. Exposure to the bowel and hepatic structures are known to adversely affect the growth and development of intraabdominal organs. These effects can affect nutritional intake, indirectly causing developmental issues as the child matures [14, 43, 44]. As these patients mature into adulthood, detailed review of a patient's radiation exposure history will play a pivotal role in

As many of the side effects of radiation therapy are difficult to anticipate and manage, a great deal of effort has been put into reducing the amount of non-tumor tissue exposed to radiation. In the early days of radiation, this was difficult simply due to the lack of technology. Now, most radiation oncologists have access to various new tools, such as 4-dimensional conformal avoidance techniques to minimize

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

secondary malignancies (see Pediatrics). Since much of the reproductive system depends on hormonal homeostasis, radioactive effects on the endocrine system (see Endocrine) and the subsequent effect on hormone production, such as that on testosterone and estrogen, can drastically affect reproductive function and development depending on the effected hormone and gland. When investigating radiation injury to the reproductive system, it is always important to consider the location of exposure and any endocrine glands involved. Germ cells, such as spermatogonia, are particularly sensitive to radiation damage as they can experience inter-mitotic death. Even mild radiation exposure can lead to a heavy drop in sperm numbers. Mature sperm that receive radiation damage can harbor serious mutations or chromosomal abnormalities, leading to severe birth defects in progeny. Exposure to female reproductive organs can even lead to miscarriage and early menopause. As a result, it usually recommended for patients who receive gonadal exposure practice birth control methods for up to six months after the exposure. Because the ovaries rely on a regular, cyclical production of hormones from the follicles, radiation injury can lead to more pronounced effects on fertility. Mucosal atrophy and drying of female genitalia can cause great discomfort for the patient as well. Thus, fertility treatment and consultation should be considered for patients who received heavy or repeated radiation exposure to the gonads [13, 14, 42].
