Gallbladder disease in cystic fibrosis

L'Heureux, P R; Isenberg, J. Nevin; Sharp, H L; Wj, Warwick

doi:10.2214/ajr.128.6.953

Cited by 33 publications

(15 citation statements)

References 1 publication

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“…The role ofCFTR in the gallbladder, generally thought ofas salt-absorptive epithelium, is less clear. Clinically, > 40% ofCF patients have signs ofgallbladder disease ( 15 ), and CF patients at all levels of pancreatic function have decreased bile acid and water output from the gallbladder (36), suggesting a primary defect may be present. In addition, a cAMP-stimulated apical CP-conductance has been described in the gallbladder ofmammals and amphibians, and is associated with inhibition of fluid and salt absorption (37,38).…”

Section: Discussionmentioning

confidence: 99%

“…A similar blockage, distal intestinal obstruction, occurs in > 20% of adult patients ( 11). CF patients also face an increased incidence of liver disease characterized by focal biliary cirrhosis (12,13), and an increased incidence of gallbladder disease compared with the normal population ( 14,15). Other gastrointestinal disturbances include dilation of the duodenal Brunner's glands ( 16) and small bowel changes evident by radiographic studies ( 17).…”

Section: Introductionmentioning

confidence: 99%

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Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ hybridization.

Strong¹,

Boehm²,

Collins³

1994

J. Clin. Invest.

253

165

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We have used in situ hybridization to localize expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in the human gastrointestinal tract and associated organs. The stomach exhibits a low level of CFTR expression throughout gastric mucosa. In the small intestine, expression is relatively high in the mucosal epithelium, with a decreasing gradient of expression along the crypt to tip axis. The cells of the Brunner's glands express high levels of CFTR mRNA. In addition, there is a small subpopulation of highly positive cells scattered along the epithelium in the duodenum and jejunum, but not in the ileum. These cells do not represent endocrine cells, as determined by lack of colocalization with an endocrine-specific marker. The distribution of CFTR mRNA in the colon is similar to the small intestine, with highest level of expression in the epithelial cells at the base of the crypts. In the pancreas, CFIR is expressed at high levels in the small, intercalated ducts and at lower levels in the interlobular ducts. CFI'R transcripts are expressed at uniformly high levels in the epithelium of the gallbladder. Throughout the gastrointestinal tract, CFTR expression is increased in mucosal epithelial cells that are near lymph nodules. (J. Clin. Invest. 1994. 93:347-354.)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ hybridization.

Strong¹,

Boehm²,

Collins³

1994

J. Clin. Invest.

253

165

View full text Add to dashboard Cite

show abstract

“…Defective HCO 3 Ϫ secretion may permit the juxtaepithelial mucus layer to undergo a pH-dependent phase shift to the gel state that has been associated with the nucleation of cholesterol crystals from saturated bile (53). Indirect evidence for this hypothesis is the observation that gallstone risk is increased 10-fold among patients with cystic fibrosis (24) and reported links between CFTR and mucus hypersecretion during gallstone formation (51). Future studies in cholesterol-fed prairie dogs will determine the role of altered gallbladder HCO 3 Ϫ secretion during the formation of gallstones.…”

Section: Discussionmentioning

confidence: 99%

Electrogenic bicarbonate secretion by prairie dog gallbladder

Moser¹,

Gangopadhyay²,

Bradbury³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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.-Pathological rates of gallbladder salt and water transport may promote the formation of cholesterol gallstones. Because prairie dogs are widely used as a model of this event, we characterized gallbladder ion transport in animals fed control chow by using electrophysiology, ion substitution, pharmacology, isotopic fluxes, impedance analysis, and molecular biology. In contrast to the electroneutral properties of rabbit and Necturus gallbladders, prairie dog gallbladders generated significant short-circuit current (I sc; 171 Ϯ 21 A/cm 2 ) and lumen-negative potential difference (Ϫ10.1 Ϯ 1.2 mV) under basal conditions. Unidirectional radioisotopic fluxes demonstrated electroneutral NaCl absorption, whereas the residual net ion flux corresponded to I sc. In response to 2 M forskolin, Isc exceeded 270 A/cm 2 , and impedance estimates of the apical membrane resistance decreased from 200 ⍀ ⅐ cm 2 to 13 ⍀ ⅐ cm 2 . The forskolin-induced Isc was dependent on extracellular HCO 3 Ϫ and was blocked by serosal 4,4Ј-dinitrostilben-2,2Ј-disulfonic acid (DNDS) and acetazolamide, whereas serosal bumetanide and Cl Ϫ ion substitution had little effect. Serosal trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chroman and Ba 2ϩ reduced Isc, consistent with the inhibition of cAMP-dependent K ϩ channels. Immunoprecipitation and confocal microscopy localized cystic fibrosis transmembrane conductance regulator protein (CFTR) to the apical membrane and subapical vesicles. Consistent with serosal DNDS sensitivity, pancreatic sodium-bicarbonate cotransporter protein pNBC1 expression was localized to the basolateral membrane. We conclude that prairie dog gallbladders secrete bicarbonate through cAMP-dependent apical CFTR anion channels. Basolateral HCO 3 Ϫ entry is mediated by DNDS-sensitive pNBC1, and the driving force for apical anion secretion is provided by K ϩ channel activation.disease; ion transport; cystic fibrosis conductance membrane regulator; sodium-bicarbonate symporters ALTHOUGH GALLBLADDER DISEASE is the most frequent indication for abdominal surgery in the United States (19), the factors that confer susceptibility to gallstones remain poorly understood. Prairie dogs have been widely studied as an experimental model of human cholelithiasis due to their unique propensity for developing gallstones on high-cholesterol chow (7). Prior studies in cholesterol-fed prairie dogs (4) have demonstrated that gallbladder salt and water transport are altered before gallstones form, a phenomenon that may cause cholesterol to precipitate in the gallbladder lumen. The potential for targeting gallbladder ion transport as a strategy for preventing cholelithiasis is underscored by data showing that amiloride inhibits the formation of gallstones in cholesterol-fed prairie dogs (56).To use the prairie dog as a model to investigate this event, we performed a detailed characterization of gallbladder ion transport in animals fed control chow. Classic studies in Necturus and rabbit gallbladders established the paradigm for electr...

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“…Despite the abnormal size, the gallbladder functions adequately. Cholelithiasis, usually with cholesterol stones, occurs in up to 12% of patients [85]. These can cause cholecystitis.…”

Section: Other Gastrointestinal Manifestationsmentioning

confidence: 99%

Cystic fibrosis

Bye¹,

Ewig²,

Quittell

1994

Lung

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While the care of cystic fibrosis (CF) patients has been mainly the province of pediatricians, great improvements in the therapy and life span of CF patients often results in their transition to care by adult physicians. In this review of CF, we begin with an overview of the epidemiology and genetics of the disease, with a discussion of the recently found ion abnormalities that lead to the clinical manifestations. This is followed by a discussion of the pathophysiology. Methods of diagnosis, ranging from the gold standard, the sweat test, to recent advances based on a greater understanding of the genetics of the disease are reviewed. This is followed by a discussion of therapy primarily geared to the treatment of the respiratory complications, as they are the most common lethal factors of the disease. We point out controversies where they exist. Newer forms of therapy such as lung transplantation are discussed, and we finish with a discussion about future therapeutic modalities, some of which are being approved as the paper is in print.

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Gallbladder disease in cystic fibrosis

Cited by 33 publications

References 1 publication

Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ hybridization.

Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ hybridization.

Electrogenic bicarbonate secretion by prairie dog gallbladder

Cystic fibrosis

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