Small bowel mucosal dysfunction in patients with cystic fibrosis

doi:10.1016/S0022-3476(76)80984-5

The Journal of Pediatrics

Volume 88, Issue 2, February 1976, Pages 213-216

https://doi.org/10.1016/S0022-3476(76)80984-5 Get rights and content

Jejunal biopsies were obtained from 37 children with cystic fibrosis, 16 with gluten-induced enteropathy, and 18 control subjects for the following studies: (1) disaccharidase activity, (2) L-ALA-L-Phe hydrolase activity, and (3) intestinal uptake of three ¹⁴C-labeled amino acids. Values were significantly reduced in the three determinations in patients with gluten-induced enteropathy as compared to control subjects. Lactase and L-ALA-L-Phe hydrolase activities were significantly reduced (p<0.01) in CF patients as compared to control subjects. Definite hypolactasia was also observed in 23% of the children with CF. Uptake of lysine was normal in CF patients whereas that of phenylalanine and cycloleucine was reduced as compared to control subjects. This study suggests an intestinal component to the malabsorption of patients with CF.

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Cited by (38)

Digestive system dysfunction in cystic fibrosis: Challenges for nutrition therapy
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Citation Excerpt :
In CF, the activity of these brush border digestive enzymes varies according to specific enzymes [74–77]. Maltase and sucrase activity in CF seem unaffected [77], but lactase activity can be lower in CF mucosa [74,76,77]. The quantity of lactase in CF may also be suppressed, depending on the genotype [78].
Cystic fibrosis can affect food digestion and nutrient absorption. The underlying mutation of the cystic fibrosis trans-membrane regulator gene depletes functional cystic fibrosis trans-membrane regulator on the surface of epithelial cells lining the digestive tract and associated organs, where Cl⁻ secretion and subsequently secretion of water and other ions are impaired. This alters pH and dehydrates secretions that precipitate and obstruct the lumen, causing inflammation and the eventual degradation of the pancreas, liver, gallbladder and intestine. Associated conditions include exocrine pancreatic insufficiency, impaired bicarbonate and bile acid secretion and aberrant mucus formation, commonly leading to maldigestion and malabsorption, particularly of fat and fat-soluble vitamins. Pancreatic enzyme replacement therapy is used to address this insufficiency. The susceptibility of pancreatic lipase to acidic and enzymatic inactivation and decreased bile availability often impedes its efficacy. Brush border digestive enzyme activity and intestinal uptake of certain disaccharides and amino acids await clarification. Other complications that may contribute to maldigestion/malabsorption include small intestine bacterial overgrowth, enteric circular muscle dysfunction, abnormal intestinal mucus, and intestinal inflammation. However, there is some evidence that gastric digestive enzymes, colonic microflora, correction of fatty acid abnormalities using dietary n − 3 polyunsaturated fatty acid supplementation and emerging intestinal biomarkers can complement nutrition management in cystic fibrosis.
Hereditary, Familial, and Genetic Disorders of the Pancreas and Pancreatic Disorders in Childhood
2010, Sleisenger and Fordtran’s Gastrointestinal and Liver Disease- 2 Volume Set: Pathophysiology, Diagnosis, Management, Expert Consult Premium Edition - Enhanced Online Features and Print
10 Growth failure in gastrointestinal diseases
1992, Bailliere's Clinical Endocrinology and Metabolism
Fecal fat concentration
1985, Gastroenterology
Enhanced glucose absorption in the jejunum of patients with cystic fibrosis
1985, Gastroenterology
After oral d-xylose ingestion, cystic fibrosis patients have significantly higher blood levels of xylose than controls. The aim of this study was to examine whether nutrient absorption at the mucosal level is altered in cystic fibrosis. Steady-state perfusion experiments using isotonic test solutions were performed in 11 healthy controls and 10 cystic fibrosis patients. Net d-glucose absorption was higher in cystic fibrosis when the perfusate contained a glucose concentration of ≤ 50 mM. Kinetic analysis by three different methods, including Lineweaver-Burk analysis, revealed a lower apparent K_m as well as a lower apparent V_max in cystic fibrosis as compared with healthy controls (33.9 mM and 52.5 mmol/20 cm · h vs. 81.8 mM and 68.3 mmol/20 cm · h, respectively, p < 0.01). Absorption of d-fructose and glycine demonstrated a tendency for increased net absorption in cystic fibrosis but the results were not significantly different. l-Xylose absorption and electrolyte movement were not altered in cystic fibrosis. Among several possible mechanisms investigated, a decrease in the apparent K_m for glucose absorption would be consistent with a decrease in diffusion barriers overlying the jejunal mucosa in cystic fibrosis. Using an electrical method, the unstirred water layer thickness was significantly decreased in cystic fibrosis (546 ± 41 μm in cystic fibrosis vs. 780 ± 110 μm in controls, p < 0.05). A decrease in the mucosal surface area in the cystic fibrosis group or an intrinsic defect in the mucosal glucose transport system could account for differences in the apparent V_max values. We suggest, however, that enhanced absorption in cystic fibrosis is most likely due to a decrease in intestinal diffusion barriers possibly due to abnormal mucus overlying the intestinal mucosa.
Inhibition of Na<sup>+</sup>-coupled solute transport by calcium in brush border membrane vesicles
1984, Life Sciences
Intracellular Ca⁺⁺ is known to influence Na⁺ flux in luminal membranes. Abnormally elevated Ca⁺⁺ levels in some cells is believed to be the primary pathophysiologic defect in cystic fibrosis (CF). This in turn is thought to alter Na⁺ transport which accounts for certain clinical manifestations of this disease. Two Na⁺-dependent intestinal transport mechanisms have been reported to be suppressed or missing in CF. To examine whether alterations in cell Ca⁺⁺ may account for these findings, studies were performed to examine the influence of Ca⁺⁺ on Na⁺-solute co-transport across intestinal luminal membranes. Purified brush border membrane vesicles prepared from rat small bowel were preincubated in either Ca⁺⁺-free buffer or buffer containing 2.5 mM CaCl₂. Ca⁺⁺ loaded vesicles showed marked inhibition of Na⁺ co-transport of taurocholic acid, taurochenodeoxycholic acid, glucose and valine when compared to controls. The uptake of Na⁺ was also significantly reduced by intravesicular Ca⁺⁺. These data demonstrate that intravesicular Ca⁺⁺ inhibits Na⁺-coupled solute transport as well as Na⁺ influx across intestinal brush border membranes. These data suggest that intracellular Ca⁺⁺ may suppress Na⁺-dependent solute absorption in the intestine. Results presented here further support the theory that elevated intracellular Ca⁺⁺ may account for intestinal malabsorption and other altered transport phenomena reported in CF.

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¹

Supported by the Canadian Cystic Fibrosis Foundation, by the Medical Research Council of Canada (Grant: MA-3320), and by the Foundation Justine Lacoste-Beaubien.

Presented in part at the combined meeting of the American Pediatric Society and the Society for Pediatric Research, San Francisco, May 1973.

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Original articleSmall bowel mucosal dysfunction in patients with cystic fibrosis1

Lancet

J Pediatr

J Pediatr

Anal Biochem

J Biol Chem

Gastroenterology

Lancet

Am J Clin Nutr

Gastroenterology

Biochim Biophys Acta

Biochim Biophys Acta

J Pediatr

Malabsorption of bile acids in children with cystic fibrosis

N Engl J Med

Malabsorption of crystalline vitamin B12 in cystic fibrosis

N Engl J Med

Cystic fibrosis of the pancreas: intestinal absorption of fat and fatty acid labeled with I131

Pediatrics

Lactase deficiency in patients with cystic fibrosis

Pediatrics

Original article
Small bowel mucosal dysfunction in patients with cystic fibrosis1

Malabsorption of crystalline vitamin B₁₂ in cystic fibrosis

Cystic fibrosis of the pancreas: intestinal absorption of fat and fatty acid labeled with I¹³¹