Abstract
Hirschsprung's disease-associated enterocolitis (HE) is a life-threatening septic complication of Hirschsprung's disease (HD), leading to bacterial translocation (BT) and sepsis. Many factors, such as intestinal stasis, HD-related inherited immune disorders and abnormal mucosal secretion have been implicated in its pathogenesis. To investigate the effect of intestinal stasis as an independent factor in the pathogenesis of HE intestinal lesions and its systematic effects. The rectal ganglion cells of 46 Wistar rats were chemically ablated through local benzalkonium chloride (BAC) injection, in order to create a HD model (megacolon rats) that does not carry the possible genetic burden of HD. The animals were sacrificed either on the 20th or 25th day after ablation and were examined for histopathological changes on the wall of the small intestine, presence of bacterial translocation in body organs, body biometrics, and white blood cell count (WBC) and hemoglobin concentration. The results were compared to control animals. In the megacolon rats, severe damage on the small intestine as well as BT proportional to the extent of the intestinal damage and to the time elapsed after ablation was observed. Significant effects on the WBCs, hemoglobin concentration and biometric parameters were also observed. In megacolon rats, intestinal stasis can lead by itself to a full-blown HE. The HE lesions that promote BT are present even in regions distant from the aganglionic bowel and are proportional to the time elapsed under the influence of intestinal stasis. Systematic effects such as growth retardation are also produced.
Highlights
Hirschsprung’s disease (HD) is a congenital disease characterized by a lack of ganglion cells in a segment of the terminal bowel, causing functional obstruction and distension of the proximal bowel.[1,2] In 6–26% of HD cases, Hirschsprung’s enterocolitis (HE) can develop, which is accompanied by considerable morbidity.[2,3] The pathogenesis of Hirschsprung’s disease-associated enterocolitis (HE) appears complex and is not completely understood.[4]
The HE lesions that promote bacterial translocation (BT) are present even in regions distant from the aganglionic bowel and are proportional to the time elapsed under the influence of intestinal stasis
In order to exclude the confounding factors present in genetic HD animal models, we used a chemical model of HD instead of a genetic model and we investigated the effects of intestinal stasis on the intestinal wall, which is not adjacent to the aganglionic segment and not directly affected by the alterations in the mucosa caused by induced aganglionosis
Summary
Hirschsprung’s disease (HD) is a congenital disease characterized by a lack of ganglion cells in a segment of the terminal bowel (aganglionosis), causing functional obstruction and distension of the proximal bowel (megacolon).[1,2] In 6–26% of HD cases, Hirschsprung’s enterocolitis (HE) can develop, which is accompanied by considerable morbidity.[2,3] The pathogenesis of HE appears complex and is not completely understood.[4] It presents with both gastrointestinal (GI) and generalized symptoms ranging from fever and diarrhea to bloodstained stools and septic shock, while in chronic cases it affects somatic growth.[5,6,7]. Hirschsprung’s disease-associated enterocolitis (HE) is a life-threatening septic complication of Hirschsprung’s disease (HD), leading to bacterial translocation (BT) and sepsis. Many factors, such as intestinal stasis, HD-related inherited immune disorders and abnormal mucosal secretion have been implicated in its pathogenesis
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