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Small intestinal mucosa changes, including epithelial cell proliferative activity, of children receiving total
1Department of Pediatrics, Children's Hospital of Buffalo, New York 14222.
Insights
Total parenteral nutrition (TPN) in children shows minimal effects on small intestine histology and enzyme activity in the short term. Long-term TPN, however, leads to reduced cell proliferation and mild villus atrophy, indicating a slower onset of these effects compared to animal models.
Area of Science:
- Pediatric Gastroenterology
- Cell Biology
- Nutritional Science
Background:
- Total parenteral nutrition (TPN) is a life-sustaining therapy for children with intestinal failure.
- The long-term impact of TPN on pediatric small intestinal histology and cellular function remains incompletely understood.
- Previous studies in animal models suggest TPN can induce intestinal hypoplasia.
Purpose of the Study:
- To investigate the effects of short-term and long-term TPN on small intestinal histology, disaccharidase activity, and DNA synthesis in pediatric patients.
- To compare these effects in children receiving TPN with age-matched healthy controls.
- To assess whether TPN induces similar hypoplastic changes in the pediatric small intestine as observed in animal studies.
Main Methods:
- Analysis of small intestinal biopsies from children receiving TPN (short-term and long-term) and healthy controls.
- Measurement of disaccharidase activities (lactase, sucrase, palatinase) in biopsy samples.
- Quantification of [3H]thymidine incorporation into DNA to assess cell proliferation.
- Histological examination for villus atrophy.
Main Results:
- Short-term TPN (1 month) showed no statistically significant differences in disaccharidase activities compared to controls.
- Long-term TPN (> 9 months) was associated with focal mild villus atrophy and decreased disaccharidase activity in some patients.
- Long-term TPN significantly reduced thymidine incorporation into DNA, indicating decreased cell proliferation (P < 0.001).
Conclusions:
- In children, significant histological and functional changes in the small intestine due to TPN, such as villus atrophy and reduced cell proliferation, require longer durations of therapy compared to animal models.
- While TPN is essential, careful monitoring for potential long-term effects on intestinal integrity and function is warranted in pediatric patients.
- The findings suggest a slower adaptive response or a more resilient intestinal mucosa in children compared to animals exposed to TPN.
Abstract:
We examined the small intestinal histology disaccharidase activities as well as the incorporation of [3H]thymidine into DNA of biopsies maintained in organ culture from seven children (ages 9 months to 5 years) receiving total parenteral nutrition (TPN). Three children suffered from inflammatory bowel disease and received TPN for one month (short term). Four required long-term TPN (> 9 months) for short-bowel syndrome. DNA was extracted from the samples following serial precipitation with perchloric acid. Results were compared to those from 22 age-matched children investigated for abdominal pain or chronic diarrhea. Short-term TPN resulted in slightly lower lactase, sucrase, and palatinase activities that were not statistically different from controls. Long-term TPN resulted in focal mild villus atrophy and a decrease in disaccharidase activity in two patients. Biopsies from long-term TPN patients incorporated less thymidine compared to those of controls (P < 0.001) when data was expressed per total biopsy (3.6 +/- 1.1 vs. 8.4 +/- 1.1 fmol) or per milligram of tissue (1.0 +/- 0.12 vs 2.7 +/- 0.7 fmol). The above data are in general agreement with the hypoplastic effect of TPN in animals. However, in children, much longer periods of TPN are required to realize the changes.