A 64-year-old man develops diarrhea, abdominal pain, nausea, vomiting, and anorexia 3 weeks after starting radiation therapy for prostate cancer. Physical examination shows abdominal tenderness. Sigmoidoscopy reveals hyperemia, edema, erosion, and ulceration of the intestinal mucosa. Stool and serum chemistries are normal. Radiation enteritis is suspected. Which of the following is most likely the primary mechanism responsible for this patient's intestinal changes?

Question

A 64-year-old man develops diarrhea, abdominal pain, nausea, vomiting, and anorexia 3 weeks after starting radiation therapy for prostate cancer.  Physical examination shows abdominal tenderness.  Sigmoidoscopy reveals hyperemia, edema, erosion, and ulceration of the intestinal mucosa.  Stool and serum chemistries are normal.  Radiation enteritis is suspected.  Which of the following is most likely the primary mechanism responsible for this patient's intestinal changes?

Quizplus · Accepted Answer

11ec160b_39fa_c5f7_9249_656cbf076249_MD0001_00 This patient developed signs of acute radiation enteritis (eg, abdominal pain, diarrhea, inflammation and denudation of intestinal mucosa) 3 weeks after starting radiotherapy for prostate cancer. Therapeutic ionizing radiation is commonly used to treat or palliate many types of cancer (eg, prostate, breast) and causes cell damage through 2 primary mechanisms: DNA double-strand breakage: Breakage of both strands is required; single-strand breaks can be repaired by polymerases. Generation of reactive oxygen species: Unstable molecules formed by the ionization of water; oxygen free radicals can cause cellular and DNA damage. Radiation-induced DNA damage impairs mitosis and initiates apoptosis of susceptible cells, including intestinal crypt stem cells and other highly proliferative cells (eg, cancer cells, hematogenous precursors). Cellular damage also induces an immune response characterized by increased expression of proinflammatory cytokines (eg, IL-1, IL-6, tumor necrosis factor-alpha) and migration of leukocytes (eg, neutrophils) to the affected tissue, processes that produce additional reactive oxygen species and contribute to the radiation-induced tissue damage. In the gastrointestinal tract, these changes result in progressive inflammation, edema, and mucosal denudation that decrease the absorptive area. Abdominal pain and diarrhea typically manifest several weeks after radiotherapy is started. In some cases, the effects of radiation exposure can be delayed until years after radiation exposure and present as complications of intestinal fibrosis (eg, strictures, adhesions, bowel obstruction). (Choice B) The ubiquitin-proteasome system has an integral role in maintaining normal cell function by degrading damaged proteins and contributing to cell cycle control. Although proteasome activity normally increases in response to oxidative stress, this system is inhibited by ionizing radiation, potentiating the apoptotic effects of radiotherapy. (Choices C, D, and E) Many chemotherapeutic agents impair essential steps in the DNA and cellular repair processes and can potentiate the effects of ionizing radiation. Although inhibition of DNA polymerase (eg, nucleoside analogues), inhibition of thymidylate synthesis (eg, 5-fluorouracil), and prevention of microtubule assembly (eg, vinblastine) would contribute to the cytotoxic effects of radiation, radiation-induced tissue damage occurs primarily through the generation of free radicals. Educational objective: Ionizing radiation causes cellular and DNA damage primarily through generation of reactive oxygen species, which can trigger progressive inflammation and tissue damage. In the gastrointestinal tract, the acute effects of radiation exposure typically occur several weeks after radiotherapy is initiated and manifest as abdominal pain and diarrhea due to mucosal denudation, inflammation, and edema. __________ References: Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials (http://www.ncbi.nlm.nih.gov/pubmed/25324981)

A 64-Year-Old Man Develops Diarrhea, Abdominal Pain, Nausea, Vomiting, and Anorexia