Pancreatic pathophysiology in cystic fibrosis

Abstract

The pancreas is one of the earliest- and most commonly- affected organs in patients with cystic fibrosis (CF). Studying the pathogenesis of pancreatic disease is limited in CF patients due to its early clinical onset, co-morbidities and lack of tissue samples from early phases of disease. In recent years, several new CF animal models have been developed that have advanced our understanding of both CF exocrine and endocrine pancreatic disease. Additionally, these models have helped us better define the influence of pancreatic lesions on CF disease progression in other organs such as the gastrointestinal tract and lung.

Structure-Function Relationships of CFTR in Health and Disease: The Pancreas Story

“…They showed that the site of obstruction ranged from the distal jejunum to the proximal spiral colon, similar to that reported in humans with meconium ileus (59,63). The obstruction in the acini and ducts lead to dilatation which causes epithelial injury and destruction, inflammation, fibrosis and fatty infiltration (30,41,59). Tucker and colleagues reported that acinar plugs developed before mucous metaplasia and found that early acinar plugs are composed of zymogen granules and were distinct from mucus in pancreatic tissue of cystic fibrosis patients (104).…”

“…In addition, MUC6 mucin is the main constituent of the complexes that form in small ducts and cause obstruction (81). Therefore, CF patients carrying mutations in the CFTR gene, showed a lower pH, low flow of secretions and high protein concentration in the pancreas duct secretions, which lead to precipitates in the duct lumina that obstruction and injury (30,117). Meyerholz and his colleagues showed in the CF pig model that the changes (obstruction) could be detected in gestations as early as week 17 (59).…”

“…CFRD has characteristics of both type I and II diabetes and does not belong to either one of the diabetes classes. It is characterized by the loss of functional β cell mass and varying degrees of insulin resistance (Figure 3) (30,62,66). Mutations in CFTR that lead to both a decrease in islet cell mass and dysfunction in the β cell are the cause of CFRD (17,67,86).…”

“…CFTR acts as a selective ion channel involved in chloride, bicarbonate (HCO 3 -), water transport across the apical membranes of epithelial cells in multiple organs including the pancreas that produces alkaline fluid in pancreatic ducts (30,70,117). HCO 3 -is an important ion in the pancreatic juice.…”

Einführung des deutschlandweiten Neugeborenenscreenings für Mukoviszidose

“…Die Folge ist ein progredienter absoluter Insulinmangel, welcher sich in einem Cystic Fibrosis-related Diabetes Mellitus (CFRD) äußert [35]. Die Symptomatik des CFRD potenziert sich durch den gesteigerten Energiebedarf von MukoviszidosePatienten im Rahmen der Malabsorption sowie der rezidivierenden Atemwegsinfektionen.…”