Food-induced pancreatic secretion

The stimulatory effect of feeding on pancreatic exocrine function has been divided into three phases: the cephalic phase; the gastric phase; the intestinal phase. Following the cephalic phase there is strong vagal stimulation when food enters the mouth, is chewed and swallowed, and further vagal stimulation when food enters the stomach. The movement of food plus gastric secretions through the pylorus into the duodenum results in the maximal stimulation of pancreatic secretion mediated by humoral secretion of cholecystokinin and secretin; the combined stimulation being fortified by cholinergic excitation⁽Reference O'Keefe⁹⁾.

Enteral feeding-stimulated pancreatic secretin

The stimulatory effect of polymeric and ‘elemental’ enteral diets on pancreatic secretion has been examined with diets either being administered orally or infused at the site of the ampulla of Vater with intestinal contents being aspirated 200 mm distally⁽Reference O'Keefe, Lee, Anderson, Gennings, Abou-Assi, Clore, Heuman and Chey¹⁰⁾. The secretory response to oral ingestion of the polymeric diet was found to be similar to that of the infused diet. However, pancreatic secretion was found to be reduced by 50% in response to ingestion of a predigested elemental diet (l-amino acid N source, 6% energy only derived from fat). It is clear from these basic physiological studies that patients receiving post-pyloric intraduodenal feeding should receive a polymeric enteral diet, the pancreatic secretory response being entirely adequate to result in assimilation of nutrients from the diet.

Inhibition of pancreatic secretion

In 1984 two research groups (one of which was the author's group) independently described an important humorally-mediated braking mechanism whereby jejunal transit and motility is inhibited by the infusion of nutrients in the terminal ileum⁽Reference Spiller, Trotman, Higgins, Ghatei, Grimble, Lee, Bloom, Misiewicz and Silk^11, Reference Read, McFarlane and Kinsman¹²⁾. This mechanism was termed the ‘ileal brake’ and the hormones enteroglucagon, neurotensin and peptide YY were thought to mediate the braking effects. Later studies have also implicated glucagon-like peptide-1⁽Reference Van Citters and Lin¹³⁾. Importantly, later studies of the ileal brake have shown that stimulated pancreatic secretion can be inhibited by the infusion of unabsorbed nutrients into the ileum⁽Reference Keller, Runzi, Goebell and Layer^14, Reference Layer and Host¹⁵⁾ and that the inhibitory action is mediated via the release of peptide YY and glucagon-like peptide-1⁽Reference Wen, Phillips, Sarr, Kost and Holst¹⁶⁾. These very important studies led to an investigation of the effect of the site of jejunal feeding on stimulated pancreatic secretion⁽Reference Vu, van der Veek, Frolich, Souverijn, Biemond, Lamers and Masclee¹⁷⁾. Normal subjects received a polymeric enteral diet infused either at the ligament of trietz (proximal jejunum) or 600 mm distally (mid jejunum). Proximal jejunal feeding was found to provide a strong stimulus for lipase, trypsin, amylase and bilirubin secretions. In contrast, feeding at 600 mm down the jejunum was found to have no significant effects on basal secretion rates⁽Reference Wen, Phillips, Sarr, Kost and Holst¹⁶⁾. Subsequently, it has been confirmed in healthy volunteers that there is no significant pancreatic secretory response to the infusion of a predigested diet at distances of 400–1200 mm from the ligament of trietz⁽Reference Kaushik, Pietraszewski, Hoist and O'Keefe¹⁸⁾. This lack of stimulatory exocrine pancreatic response has been shown to occur in association with elevated peptide YY and glucagon-like peptide-1 responses⁽Reference Kaushik, Pietraszewski, Hoist and O'Keefe¹⁸⁾, indicating that the ileal brake is activated during intra-jejunal nutrient infusion. The same research group has developed a technique for measuring trypsin synthetic rates⁽Reference O'Keefe, Lee, Li, Zhou, Stoll and Dang¹⁹⁾ and using this technique have shown that inhibition of pancreatic secretion is the result of inhibition of trypsin synthesis⁽Reference Zhou, Kiswardy and Kaushik²⁰⁾.

Predigested and polymeric diets during jejunal enteral feeding

For the reasons discussed, post-pyloric duodenal feeding techniques are not the optimum means of overcoming the problems of complications that occur with intragastric enteral nutrition. Properly-sited access beyond the ligament of trietz is the way forward in those difficult cases; certainly, initially and in the short term nasojejunal enteral-tube feeding is the technique of choice. In patients with normal small intestinal motility nasojejunal tubes, once they are correctly positioned, will be moved in a caudad direction by the phase III migrating motor complex⁽Reference Silk, Payne-James, Grimble and Silk¹⁾. It must be assumed therefore that in most patients the diet will be infused approximately 300–400 mm distal to the ligament of trietz. Infusion of polymeric diet at this site will activate the ileal brake, causing release of peptide YY and glucagon-like peptide-1. In turn this response will result in an inhibition of exocrine pancreatic enzyme synthesis and secretion, which is likely to have a most deleterious effect on the digestion and absorption of nutrients from the polymeric diet. Although the evidence points to the fact that the intrajejunal infusion of predigested diets also fails to elicit a pancreatic exocrine secretory response⁽Reference Kaushik, Pietraszewski, Hoist and O'Keefe¹⁸⁾, near optimum absorption of nutrients can occur from suitably-formulated diets in the absence of pancreatic enzymes⁽Reference Silk, Payne-James, Grimble and Silk¹⁾.

On the basis of the evidence discussed it is concluded that properly-formulated predigested enteral feeds are the diets of choice for patients undergoing post-ligament of trietz intrajejunal enteral feeding.