Radiation-induced intestinal lesions - Causes

Radiation sickness or radiation damage to a number of organs, including the intestines, develops with the use of nuclear weapons (the tragedy in Hiroshima and Nagasaki in 1945), violation of safety regulations and negligence with sources of ionizing radiation (events at the Chernobyl Nuclear Power Plant), irrational administration of large doses of radiation therapy. With local irradiation of the abdominal cavity and pelvic organs, the total dose of which exceeds 40 Gy (4000 rad), pathological changes may develop, mainly in the intestines. Most often, damage to the small and large intestines is combined, although an isolated process in one of these sections of the intestine is often observed.

The first clinical report of intestinal damage after radiotherapy of malignant neoplasms was made in 1917 by K. Franz and J. Orth. As the scope of radiation therapy expanded, the number of reports of its complications increased. In particular, it was noted that irradiation of various pelvic, intraperitoneal and retroperitoneal neoplasms leads to the development of radiation enteritis and colitis in 5-15% of patients. According to D. L Earnest, J. S. Trier (1983), radiation damage to the gastrointestinal tract continues to be one of the main and serious clinical problems.

The mechanism of intestinal damage caused by ionizing radiation primarily depends on its effect on the epithelium of the mucous membrane, which is very sensitive to radiation exposure. Irradiation suppresses cell proliferation in the crypts, which causes characteristic acute disorders. If the radiation dose is small, epithelial cell proliferation is restored fairly quickly, and mucous membrane damage disappears 1-2 weeks after irradiation. The effect of repeated radiation doses depends on the duration of irradiation and the stage of cellular renewal of the crypt epithelium. It has been established that epithelial cells are especially radiosensitive in the G1-postmitotic phase and resistant in the late S-synthetic phase. The duration of intervals between irradiations is of great importance for restoring the regeneration processes of the intestinal mucous membrane epithelium during fractional irradiation.

As can be seen, the development of acute and chronic changes characteristic of radiation enteritis is influenced not only by the total dose of radiation and the method of its application, but also by the time between courses of therapy.

Radiation therapy primarily and most often affects the epithelium. It also affects the mesenchymal tissue, which is most important in the occurrence of remote consequences. For example, the endothelium of the arterioles of the submucosa of the small intestine is very sensitive to the effects of ionizing radiation and responds to high doses with proliferation. Vascular disorders appear 1 week or 1 month after acute damage to the mucous membrane. The vessel wall undergoes fibrinoid changes, which subsequently facilitates vascular thrombosis. Obliterating endarteritis and endophlebitis develop, leading to ischemic disorders of the intestinal wall with subsequent ulceration and necrosis. The introduction of bacteria into necrotic tissue, which increases as the blood supply deteriorates, worsens the patient's condition and aggravates the damage to the intestinal wall.

After massive irradiation, the intestine becomes edematous; fibroblasts are activated, connective tissue undergoes hyalinosis, in the development of which smooth muscle cells also participate. As a result, extensive fibrosis is formed, which can lead to narrowing of the intestine, as well as to destruction of the surface of the mucous membrane. Consequently, ionizing radiation can cause both transient changes in the structure of the mucous membrane and the function of the intestine, as well as thickening, ulceration and fibrosis of the intestine.

In addition to acute and chronic changes, there are subacute and latent changes. Acute changes occur immediately after irradiation and are accompanied by disruption of proliferation and maturation of the epithelium in combination with a decrease in crypt cell mitosis. In the small intestine, there is a characteristic shortening of the villi and a decrease in the thickness of the mucous membrane, as well as its hyperemia, edema, and extensive inflammatory cellular infiltration. Crypt abscesses containing neutrophils, eosinophils, and exfoliated epithelial cells are possible. Ulcers may occur with prolonged or massive irradiation.

Subacute changes appear 2-12 months after radiation therapy. They are quite diverse. During this period, the endothelial cells of the small intestinal arterioles in the submucosal layer may swell, peel off from the basement membrane, and eventually undergo necrosis. Thrombi are found in the lumen of the vessel, and in some cases, their recanalization. Large foamy cells are found in the intima, which, according to some researchers, are considered an important diagnostic sign of radiation damage to blood vessels in humans. The submucosal layer becomes thickened, sclerotic, and often contains large, irregularly shaped fibroblasts. The result of obliterating changes in small arterioles is progressive ischemia. The degree of vascular damage and ischemic fibrosis varies and is not always pronounced, so in the subacute period, intestinal blood circulation is often not significantly impaired, except in cases where irradiation was preceded by diseases affecting the vessels (hypertension, diabetes mellitus, generalized atherosclerosis, or coronary and cardiac insufficiency). Insufficiency of microcirculation due to radiation vasculitis, which is the most dangerous, most often occurs in the sigmoid colon and rectum. Abscesses and fistulas can form in the tissues connecting the colon with the vagina, bladder, and ileum. Intestinal carcinoma is a late and relatively rare manifestation of its radiation damage.

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