Radiation proctitis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rekha, M.D., Mahshid Mir, M.D. [2]

Overview

The exact pathogenesis of radiation proctitis is not fully understood however it is thought that acute radiation proctitis is due to direct damage of the lining (epithelium) of the colon. Chronic radiation proctitis occurs in part because of damage to the blood vessels which supply the colon and results in full-thickness ischemia and fibrotic changes and ultimately the colon is therefore deprived of oxygen and necessary nutrients.

Pathophysiology

Pathogenesis

  • Acute radiation proctitis is due to direct damage of the lining (epithelium) of the colon. [1]
  • Chronic radiation proctitis occurs in part because of damage to the blood vessels which supply the colon and results in full-thickness ischemia and fibrotic changes and ultimately the colon is therefore deprived of oxygen and necessary nutrients.[2]
  • Ionizing radiation primarily damages DNA leading to the apoptosis of targeted tumor cells, however inadvertently intestinal crypt stem cells in the radiation field get also affected resulting in crypt involution, mucosal injury, and exposure of the underlying lamina propria to luminal bacteria and activation of acute inflammatory response.
  • Secondary to significant production of enzymes and reactive oxygen metabolites by these inflammatory cells, further degradation of the extracellular matrix and injury to mucosal and submucosal tissue ensures, causing further damage to the bowel wall.
  • After the cessation of radiation exposure, intestinal crypt cells regenerate and the mucosal surface is repopulated with epithelium with the resolution of acute inflammatory response.
  • However, progressive exposure causes ulceration followed by progressive fibrosis and the development of chronic inflammatory changes associated with chronic symptoms.
  • Endothelial damage causes arterial sclerosis with obliterative endarteritis of small vessels, leading to chronic ischemia and associated fibrosis.
  • These changes can lead to ulcers, bleeding, stenosis, strictures, fistulas, and bleeding.

Gross Pathology

On gross pathology, rectal mucosa in acute radiation proctitis appears edematous, erythematous (beefy red), and may have ulceration or sloughing however the intestines are pale, non compliant with telangiectasias, and may have strictures, ulcerations, fistulas, or heavy bleeding in case of chronic radiation proctitis.[3]

Microscopic Pathology

On microscopic histopathological analysis, there is a loss or distortion of the microvillus architecture with hyperemia, edema, and ulceration in acute radiation proctitis. However progressive mucosal atrophy, chronic mucosal ischemia, focal distortion and destruction of small arteries and arterioles with intimal fibrosis and new vessel formation can be seen in case of chronic radiation proctitis.[3]

References

  1. Babb RR. Radiation proctitis: a review. Am J Gastroenterol. 1996 Jul;91(7):1309-11. Review. PMID 8677984
  2. Wu XR, Liu XL, Katz S, Shen B (2015). "Pathogenesis, diagnosis, and management of ulcerative proctitis, chronic radiation proctopathy, and diversion proctitis". Inflamm Bowel Dis. 21 (3): 703–15. doi:10.1097/MIB.0000000000000227. PMID 25687266.
  3. 3.0 3.1 Tagkalidis PP, Tjandra JJ (2001). "Chronic radiation proctitis". ANZ J Surg. 71 (4): 230–7. PMID 11355732.

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