What is the role of meconium ileus in the pathogenesis of cystic fibrosis (CF)?

Updated: Oct 22, 2019
  • Author: Girish D Sharma, MD, FCCP, FAAP; Chief Editor: Kenan Haver, MD  more...
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Answer

The meconium of fetuses with cystic fibrosis and meconium ileus has increased viscosity and decreased water content compared with those of healthy controls. The developmental sequence of mucin secretion in the fetal intestine is not fully understood, although the CFTR ion channel defect possibly leads to dehydration of intraluminal contents.

Meconium in patients with meconium ileus also has higher protein and lower carbohydrate concentration than that in control populations. Albumin is the major protein in the meconium of infants with meconium ileus, and is present in concentrations 5-10 times higher than normal. [9] In addition, there is a significant increase in the liver's production of intraluminal glutamyltranspeptidase (GGTP) and 5'-nucleotidase, which enters the meconium and promotes meconium ileus.

The addition of albumin to normal meconium makes it viscid; the addition of pancreatic protease liquefies the viscid mass. This led to the belief that pancreatic insufficiency played a central role in the pathogenesis of meconium ileus, although pancreatic insufficiency is not the sole cause of abnormal meconium in meconium ileus. In 1988, however, Lands et al reported 2 infants with cystic fibrosis and meconium ileus, aged 9 and 11 months, who displayed no clinical evidence of pancreatic insufficiency. [10]

In the murine model of cystic fibrosis, developed in 1992, newborn mice had severe intestinal obstruction at birth with minimal pulmonary or pancreatic involvement. These animal studies support the concept that meconium ileus may occur in patients with sufficient pancreatic activity. The lack of concordance between meconium ileus and severity of pancreatic disease suggests that intraluminal intestinal factors contribute to meconium ileus development.

Abnormal intestinal motility may also contribute to meconium ileus development. Some patients with cystic fibrosis have prolonged small intestinal transit times. Diseases other than cystic fibrosis in which there is abnormal gut motility (eg, Hirschsprung disease, chronic intestinal pseudo-obstruction) have been associated with meconium ileus–like disease, suggesting that decreased peristalsis may allow increased resorption of water, thus favoring meconium ileus development.


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