Cystic fibrosis (CF) is a genetic disease that affects the function of various epithelial organs, including the lung, intestine, biliary system, and pancreas. In the past, CF was typically fatal during adolescence due to severe respiratory infections. However, advancements in antibiotics, drugs that improve mucus clearance from the lungs, correction of pancreatic insufficiency and undernutrition, and the recent FDA approval of drugs such as ivacaftor (Kalydeco) and lumacaftor/ivacaftor (Orkambi) have now extended the lifespan of some patients into their fifth decade or beyond. CF is caused by a mutation in CFTR, which impairs the ability to hydrate and alkalinize the contents of the gut. Specifically in the gastrointestinal system, this can result in intestinal obstruction, duodenal mucosal injury, and damage to the liver, biliary system, and pancreas. Many CF patients experience dysfunction of the endocrine pancreas and require digestive enzyme supplements to ensure adequate nutrient digestion. In some patients with milder mutations, pancreatitis may develop later in life without other classic CF symptoms, likely due to the retention of digestive enzymes in the pancreas. Regardless, improved recognition and treatment of the pulmonary complications of CF mean that gastrointestinal symptoms such as liver failure, reduced bile flow, pancreatitis, obstruction, and maldigestion/malabsorption of nutrients are becoming increasingly important aspects of the disease that must be managed in adults, often by multidisciplinary teams of healthcare professionals.

CCK, which is produced by I cells in the small intestinal epithelium, is released into the interstitial space when specific food components are present in the lumen, particularly free fatty acids and certain amino acids. The release of CCK can occur through direct interaction of fatty acids or amino acids, or both, with the I cells. Additionally, the release of CCK is regulated by two releasing factors that act within the lumen. The first factor, CCK-releasing peptide, is secreted by paracrine cells within the epithelium in response to products of fat and protein digestion. The second factor, monitor peptide, is released by pancreatic acinar cells into pancreatic juice. Neural input can also trigger the release of both CCK-releasing peptide and monitor peptide, which is especially important in initiating pancreatic secretion during the cephalic and gastric phases, preparing the system for digestion as soon as the meal enters the small intestine.

What is the significance of these CCK-releasing factors? Their primary role is to regulate the release of CCK and the availability of pancreatic enzymes, ensuring that the enzymes are matched to the need for digestion in the small intestinal lumen.
Cysticfibrosis(CF)isageneticdiseasethataffectsthefunctionofavarietyofepithelialorgans,includingthelung,intestine,biliarysystem,andpancreas.Previouslythediseasewasalmostuniformlyfatalduringadolescenceasaresultofsevererespiratoryinfections.However,improvedantibiotics,drugsthatimproveclearanceofmucusfromthelungs,correctionofpancreaticinsufficiencyandundernutrition,andrecentUSFoodandDrugAdministration(FDA)approvalofdrugssuchasivacaftor(Kalydeco)andlumacaftor/ivacaftor(Orkambi)nowextendlifeintothefifthdecadeorlaterinsomepatients.CFiscausedbyamutationinCFTR, whichinthegutimpairstheabilitytohydrateandalkalinizetheluminalcontents.IntheGIsystemspecifically,thiscanresultinintestinalobstruction,duodenalmucosalinjury,anddamagetotheliverandbiliarysystemaswellasthepancreas.InmanyCFpatientstheendocrinepancreasisdysfunctional,andtheymustbegivendigestiveenzymesupplementstomaintainadequatenutrientdigestion.Inotherpatientswithmildermutations,pancreatitismaydeveloplaterinlifeintheabsenceofotherclassicCFsymptoms,presumablybecauseofretentionofdigestiveenzymesinthepancreas.Ineithercase,improvedrecognitionandtreatmentofthepulmonarycomplicationsofCFmeanthatGIsymptomssuchasliverfailure,reducedbileflow,pancreatitis,obstruction,andmaldigestion/malabsorptionofnutrientsareacquiringincreasedimportanceasfacetsofthediseasethatmustbemanagedinadults,oftenbymultidisciplinaryteamsofphysiciansandotherhealthcareprofessionals.
CCK is the product of I cells, which are also localized in the small intestinal epithelium. These classic enteroendocrine cells release CCK into the interstitial space when specific food components are present in the lumen, particularly free fatty acids and certain amino acids. Release of CCK may occur following direct interaction of fatty acids or amino acids, or both, with the I cells. Release of CCK is also regulated by two luminally acting releasing factors that can stimulate the I cell. The first of these, CCK-releasing peptide, is secreted by paracrine cells within the epithelium into the small intestinal lumen in response to products of fat •Fig. 30.5 MechanismsresponsibleforcontrollingreleaseofCCKfromduodenalIcells.ACh,acetylcholine;CCK-RP,CCK-releasingpeptide;GRP,gastrin-releasingpeptide.Solidarrowsrepresentstimulatoryeffects,whereasdashedarrowsindicateinhibition.(RedrawnfromBarrettKE.Gastrointestinal Physiology. NewYork:McGraw-Hill;2006.) and protein digestion. The second releasing factor, monitor peptide, is released by pancreatic acinar cells into pancreatic juice. Both CCK-releasing peptide and monitor peptide can also be released in response to neural input, which is particularly important in initiating pancreatic secretion during the cephalic and gastric phases, thereby preparing the system to digest the meal as soon as it enters the small intestine.
What is the significance of these CCK-releasing factors? Their primary role is to match CCK release, as well as the resulting availability of pancreatic enzymes, to the need for these enzymes to digest the meal in the small intestinal lumen (