![]() ![]() The ongoing fibrosis in chronic RE may lead to stricture formation and mechanical small bowel obstruction. Chronic RE presents after 6 months following radiotherapy and is due to vasculitis and chronic fibrosis. Acute RE usually manifest within 10 days and its pathological features include oedema of the bowel wall, mucositis, ulceration, perforation, necrosis of small bowel, or death within days. Radiation enteritis can occur within days or many years following treatment. The risk factors of RE include age above 60 years, smoking, diabetes mellitus, hypertension, connective tissue disorders, HIV status, previous abdominal surgery, hypo-albuminemia and concurrent administration of chemotherapy with radiotherapy. The most common side effects of radiotherapy to abdominal or pelvic organs is radiation enteropathy/radiation enteritis (RE). Paneth cells provide the link between the innate immunity and adaptive immunity of the in the gut, and ultimately of the entire body. Additionally, Paneth cells monitor and regulate the microbiota in the lumen of the small intestine. The Lgr5 + ISCs use lactate which is produced in the adjacent Paneth cells for their energy production. The other roles of the Paneth cells in the small intestine are to protect, nourish, and regulate proliferation and differentiation of the Lgr5 + ISCs. The process of de-differentiation and replacement of the Lgr5 + ISCs is normally led by the reserve ISCs and Paneth cells, and the other intestinal epithelial cells (IECs) only get activated by the Paneth cells that have also been irreversibly damaged. The reserve ISCs, Paneth cells, enterocytes, goblet cells, and enteroendocrine can de-differentiate to replace Lgr5 + ISCs if they are irreversibly damaged, for instance following ionizing radiation. Compared to Lgr5 + ISCs, the reserve ISCs are usually quiescent and thus more resistant to damage due to ionizing radiation. The other ISCs are found higher up starting from around position 4 (reserve ISCs) along the crypt-villous axis. The Lgr5 + ISCs in a normal small intestine are found intermingled with the Paneth cells in a 1:1 ratio. The ISCs which are found at the base of the intestinal crypt are known as the leucine-rich repeat-containing G-protein-coupled receptor 5 ISCs (Lgr5 + ISCs). The intestinal stem cells (ISCs) are arranged in tiers with the most actively cycling ISCs and therefore the most sensitive to ionizing radiation being found at the base of the crypt of Lieberkühn (intestinal crypt). The effect of ionizing radiation on the intestinal stem cells and its derivatives, and the knowledge can be used to develop effective treatment of radiation enteritis is discussed. This article reviews the anatomy of the epithelium of the small intestine and the intestinal epithelial cells including the Paneth cells. Paneth cells can also de-differentiate and replace irreversibly damaged intestinal stem cells. ![]() The other roles of the Paneth cells are protection and nourishment of the intestinal stem cells, and control of the gut microbiota. Paneth cells regulate the proliferation and differentiation of the intestinal stem cells. Severe acute and chronic radiation enteritis result from the damage to the crypt-based intestinal stem cells and their derivatives, which include the Paneth cells. Advances in the management of cancer has not led to an improvement in the treatment of radiation enteritis as the available preventative or treatment options are still ineffective. High-dose ionizing radiation can affect all the layers of the small intestine leading to weakening of its structural integrity, dysbiosis, malabsorption, and derangement of the innate immunity. The onset of radiation enteritis may delay the completion of treatment or lead to life-threatening conditions such as bowel perforation or obstruction. Radiotherapy is used in the management of around half of patients who have abdominal and pelvic malignancies and 70% of the treated patients will develop radiation enteritis. Cancer is the leading cause of death in adults and majority of cancers involve abdominal and pelvic organs. ![]()
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