Effects of cholestyramine on gallbladder and gastric emptying in obese and lean subjects

Abstract. Gallbladder stasis is frequent in obese subjects and may contribute to their increased risk for gallstone formation. The bile salt sequestrant cholestyramine acutely enhances postprandial gallbladder emptying in lean subjects, through dis-inhibition of a negative feedback between intraluminal bile salts and CCK release. In this study the effect of cholestyramine on both gallbladder and gastric antrum dynamics were studied by realtime ultrasonography in 12 obese and 15 lean subjects. For the acute study, on different days, subjects ingested a liquid meal (two egg yolks plus water 200 mL, 50 kJ) or a meal with 4g cholestyramine. Gallbladder emptying was impaired in obese patients who had significantly larger fasting gallbladder volume (39.4 ± 6.9 vs. 21.6 ± l.7mL, P <0.02), larger residual volume (12.3 ± 1.8 vs. 4.0 ± 0.5ml, P < 0.0006) and slower emptying time ( T /2: 33 ± 2 vs. 21 ± 2 min, P < 0.05) than lean subjects. Integrated antral emptying was also less in obese than lean subjects (5521 ± 578 vs. 7908 ± 491 % 120min^-1, P <0.02). Cholestyramine enhanced postprandial gallbladder emptying in both obese and lean subjects. Gastric emptying was delayed with cholestyramine in lean but not obese subjects. For the chronic study, after 1 month therapy with cholestyramine (4 g every 2 days), the motility tests were repeated in nine obese subjects. Gallbladder and gastric responses to a test meal, with or without cholestyramine, were preserved. We conclude that both gallbladder and antral emptying of a liquid test meal are impaired in obese subjects. Gallbladder emptying improves after acute administration of a low dose cholestyramine with test meal. This effect is sustained after 1 month treatment with a low dose of cholestyramine and does not interfere with gastric emptying of obese patients. Cholestyramine may improve gallbladder hypomotility in obese people.     

Sonographic study of postprandial gallbladder emptying and common bile duct changes in patients with diabetes or cholelithiasis

The aim of our study was to evaluate postprandial emptying of the gallbladder and common bile duct (CBD) in 20 patients with gallstones and in 20 diabetic patients with or without autonomic neuropathy. Gallbladder fasting volume was significantly increased in patients with multiple stones. Diabetics with autonomic neuropathy showed a decreased gallbladder emptying rate. CBD size did not show any significant change in all groups examined.     

Changes of gallbladder and gastric dynamics in patients with acute hepatitis A

Transient alterations of gallbladder morphology and dynamics have been reported in patients with during acute hepatitis A. The presence of dyspepsia also suggests involvement of gastric motility. During a 60-day follow-up, we investigated gallbladder and gastric motility in relation to dyspepsia in acute viral hepatitis A patients. Twenty patients were assessed at referral (day 0) and at days 7, 21, 42 and 60 and compared with 20 healthy volunteers. Gallbladder morphology and motility and gastric motility were assessed in the fasting and postprandial period by functional ultrasonography using a liquid test meal. Dyspeptic symptoms were scored. At day 0, fasting gallbladder volume was 5.9 +/- 1.3 mL, 32.6 +/- 4.6 mL, and 21.5 +/- 1.9 mL (mean +/- SE) in patients with gallbladder sludge (n = 7), without sludge (n = 13) and controls, respectively (P < 0.05 in sludge vs. no sludge and controls; P < 0.05 in no sludge vs. controls, ANOVA). Small fasting gallbladder volume in patients with sludge increased and sludge disappeared within 7 days. At day 0, patients with sludge also had increased thickness of fasting gallbladder wall and increased serum transaminase levels compared with patients without sludge and controls. Gallbladder contraction was similar in patients and controls. However, patients had delayed gastric emptying, which positively correlated with dyspepsia score. Gallbladder morphological changes observed in the acute phase of hepatitis A are transient and are associated with hepatocellular damage. Gastric emptying is delayed during the first week of disease and is associated with dyspeptic symptoms.     

Three-dimensional sonographic evaluation of gallbladder contractility: comparison with cholescintigraphy

PURPOSE: To compare three-dimensional sonography (3D US) with quantitative cholescintigraphy for assessing gallbladder contractility. METHODS: Gallbladder radioactivity was assessed in 35 patients with suspected gallbladder disease using a gamma camera 5, 30, 60, and 90 minutes after technetium 99m (Tc-99m) DISIDA injection and 30 and 60 minutes after ingestion of a high-fat meal. Immediate gallbladder images were obtained via 3D US. Gallbladder radioactivity at 120 minutes after injection of Tc-99m DISIDA was defined as 100%, and gallbladder contractility was calculated. Gallbladder volume on 3D US was calculated using a dedicated software. Pearson correlation analysis and simple linear regression analysis were used. RESULTS: The mean gallbladder volume on 3D US was 25.3 ml after fasting and 6.6 ml after a high-fat meal. The mean gallbladder contractility index was 77.7% on cholescintigraphy (range, 18-99) and 73.4 on 3D US (range, 16.7-97.3). A linear correlation between cholescintigraphy and 3D US contractility indices was observed. The r value on Pearson analysis was 0.92 and R(2) of the coefficient of determination was 0.85. The difference in measured contractility between the 2 methods ranged from +21.5% to -15.0% (mean +/- SD, 4.4 +/- 8.7%). CONCLUSIONS: 3D US is a reliable and easy method for clinical measurement of the volume of the gallbladder and its contractility.     

Fetal gallbladder growth and development during gestation.

This study sought to establish normal dimensions of the fetal gallbladder throughout pregnancy. The gallbladders in 300 normal fetuses between 15 and 40 weeks of gestation were measured prospectively for length, anteroposterior dimension, and transverse dimension. The gallbladder length, anteroposterior diameter, and transverse diameter have a linear relationship with gestational age between 15 weeks and 30 weeks of gestation, after which a plateau is observed. Calculated gallbladder area, volume, and sagittal perimeter have similar rates of growth in utero. The normative dimensions we have established for the fetal gallbladder throughout pregnancy can be expected to serve as a basis against which aberrant growth can be evaluated prenatally.     

Evaluation of gallbladder volume and emptying with a novel three-dimensional ultrasound system: Comparison with the sum-of-cylinders and the ellipsoid methods

To overcome the geometrical limitations of current methods to calculate gallbladder volume from two-dimensional sonographic images, we evaluated the accuracy and precision of a novel three-dimensional ultrasound system (3D). In vitro accuracy of 3D volumetry (10 mL to 55 mL) was 98.1 ± 7.1% (mean ± SD) with a mean difference of 0.7 mL between the measured and the true volume (p < 0.003). Compared with the sum-of-cylinders (SC) and the ellipsoid (EL) methods, 3D was characterized by a significantly smaller systematic bias and closer limits of agreement with the true volume. The variation coefficient was smallest with 3D (2.4%, p < 0.02) and largest with EL (4.2%). In vivo, gallbladder volumes were on average 1.4 mL (9%) smaller with 3D than with SC (p < 0.0001) and 2.4 mL (14%) larger with EL than with SC (p < 0.0001). 3D ultrasonography accurately measures gallbladder volume and emptying. © 1996 John Wiley & Sons, Inc.     

胆囊穿孔11例超声诊断分析

目的 分析胆囊穿孔的超声诊断价值。方法 使用Acuson 128 XP和HP HX（超声诊断仪,探头频率3.5MHz,患者取仰卧位及左侧卧位。结果 11例均见胆囊结石声像,胆囊壁连续中断3例,胆囊周围局限性积液7例,超声符合率63．7％（7／11）,超声漏诊4例,漏诊率36．3％（4／11）,所有病例均经手术证实。结论 超声对胆囊穿孔的诊断具有较大价值。     

Sonographic measurements of normal gallbladder sizes in children

PURPOSE: Our goal was to establish the range of sonographic measurements of normal gallbladders in children. METHODS: Six hundred ten children aged 0-16 years (male:female ratio, 1.5:1) with normal clinical and laboratory findings were included in this study. The sonographic parameters were the length, width, and calculated volume of the gallbladder, and the clinical parameters were the age, height, weight, and body surface area of the children. Statistical significance was determined through correlation and regression analyses. RESULTS: The length of the gallbladder showed significant positive correlations with age (r = 0.65), height (r = 0.67), weight (r = 0.63), and body surface area (r = 0.65; p < 0.01). The calculated volume of the gallbladder also showed moderate correlations with age (r = 0.53), height (r = 0.55), weight (r = 0.61), and body surface area (r = 0.57; p < 0.01). The gallbladder width showed modest but significant correlations with age (r = 0.48), height (r = 0.53), weight (r = 0.53), and body surface area (r = 0.55; p < 0.01). The highest correlation coefficients were found between the gallbladder length and subject age (r = 0.65; p < 0.01) and between the gallbladder length and subject height (r = 0.67; p < 0.01). For all correlations, statistical significance remained after regression analysis (p < 0.01). CONCLUSIONS: Values for the size of the normal pediatric gallbladder are defined and will be helpful in the diagnosis of gallbladder abnormalities.     

Role of the gastric phase in fat-induced gallbladder contraction and cholecystokinin secretion in humans

The present study was undertaken to investigate the role of the gastric phase of fat-induced gallbladder contraction and endogenous cholecystokinin (CCK) secretion in humans. Gallbladder emptying, measured by cholescintigraphy, and endogenous CCK secretion, measured by radioimmunoassay, were studied in healthy subjects after both intragastric and intra-intestinal administration of corn oil. In addition, patients with partial gastrectomy were investigated to study the effect of accelerated gastric emptying. In the healthy subjects, intragastric administration of fat resulted in a significantly (P less than 0.05) later increase in plasma CCK levels (20 +/- 2 min) compared to intraintestinal fat (5 +/- 1 min). Similarly, the onset of gallbladder emptying was significantly (P less than 0.05) delayed after intragastric fat (20 +/- 2 min) compared to intestinal fat (10 +/- 1 min). In the healthy subjects the integrated plasma CCK response to intragastric fat was significantly (P less than 0.005-P less than 0.01) reduced from 10 to 30 min. In the patients with partial gastrectomy the rise in plasma CCK (10 +/- 1 min) and the onset of gallbladder emptying (15 +/- 2 min) were in the same range after intra-intestinal and intragastric fat. No significant differences in plasma CCK levels, integrated CCK response or gallbladder emptying were found in the patients according to the site of fat application. It is concluded that endogenous CCK secretion and gallbladder emptying in response to intragastric fat are significantly delayed in healthy subjects but not in patients with partial gastrectomy, in whom gastric emptying is accelerated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of rectal distension on gallbladder emptying and circulating gut hormones

BACKGROUND: Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility. MATERIALS AND METHODS: Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal. RESULTS: Rectal distension enhanced maximum gallbladder emptying from 66 +/- 7% to 78 +/- 5% (P < 0.05). Distension tended to increase integrated plasma PYY from 77 +/- 30 pM min to 128 +/- 40 pM min in the first hour after the meal (P = 0.08) and it suppressed integrated plasma PP from 1133 +/- 248 pM min to 269 +/- 284 pM min in the second hour (P < 0.05). Integrated plasma CCK concentrations were not significantly affected. CONCLUSION: Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients.     

Impaired gallbladder and gastric motility and pathological gastro-oesophageal reflux in gallstone patients

Impaired gallbladder motility is common in gallstone patients and might be associated with other gastrointestinal defects. Twenty patients with small stones in an opacified gallbladder at oral cholecystography and 20 healthy subjects homogeneous for sex, age and body size were studied by ultrasonography to assess gallbladder and gastric emptying simultaneously in response to a standard liquid meal (120 kcal, 11 g fat, 200 mL). The same subjects underwent ambulatory 24-h gastro-oesophageal pH monitoring. Dyspeptic symptoms were specifically investigated using a questionnaire. Gallstone patients had a significantly larger fasting (P < 0.05) and residual (P < 0.005) gallbladder volume with slower (P < 0.05) and less complete (anova , 0.001 < P < 0.05) gastric emptying than healthy control subjects. The speed of antral emptying was significantly correlated with the speed of gallbladder emptying (n = 40, r = + 0.31, P < 0.05). Pathological gastro-oesophageal reflux was present in 75% and 15% of patients and control subjects respectively (P < 0.05). Overall, 95% of gallstone patients had abnormal pH profiles resulting from pathological gastro-oesophageal reflux and/or prolonged gastric alkalinization. The speed of post-prandial antral emptying was significantly correlated with the duration of the longest gastro-oesophageal reflux episode (r = + 0.30, P < 0.03) and duodeno-gastric reflux episode (r = + 0.80, P < 0.02). Best predictors for gastric alkalinization were the following indices of gallbladder function: large fasting volume (P = 0.03), large ejection volume (P = 0.009) and slower emptying (P = 0.032). Gallbladder and gastric motility were similar in patients with (n = 12) and without (n = 8) dyspeptic symptoms. Pathological gastro-oesophageal reflux was found in 83% of dyspeptic patients and in 25% of patients without dyspepsia (P < 0.01). When reflux was present, it was significantly less in asymptomatic than in dyspeptic patients [time at pH < 4, median (range): 6.4% (3.2–22.6%) vs. 47.8% (2.1–87%), P < 0.05]. This study shows that a subgroup of gallstone patients with small—mainly asymptomatic—stones have impaired gallbladder and gastric motility as well as abnormal gastro-oesophageal pH-profiles. These findings point to the existence of multiple functional defects of the upper gastrointestinal tract in gallstone disease.     

Effects of gastrointestinal hormones on fasting gallbladder storage patterns in man

Gallbladder storage and emptying patterns were studied in fasting normal subjects by a duodenal perfusion technique using indocyanine green as a biliary marker. Fasting gallbladder storage patterns were very variable but a more uniform biliary output with net storage of about 40% of the biliary marker was observed during a simulated interprandial state (2--4 h after meals) produced by a low dose intravenous infusion of secretin and caerulein. With this background hormonal stimulation, infusion of bovine pancreatic polypeptide to achieve physiological interprandial levels promoted further gallbladder storage of bile. Bovine pancreatic polypeptide produced storage by a major effect on the gallbladder rather than on the liver, common bile duct or sphincter of Oddi since a reduction of biliary output was not observed during bovine pancreatic polypeptide infusion in cholecystectomized subjects. Bovine pancreatic polypeptide had a separate effect on the pancreas, reducing trypsin output in both normal and cholecystectomized subjects.     

Ultrasonic evaluation of gallbladder emptying with ceruletide: comparison to oral cholecystography with fatty meal

Assessment of gallbladder function is required prior to nonsurgical treatment of gallstones. In order to develop a practical and reproducible method of evaluation, gallbladder emptying was studied by ultrasound (US) in 55 gallstone patients after intramuscular administration of ceruletide (0.3 g/kg). In 27 of these subjects, the US procedure was compared to oral cholecystography (OCG) with fatty meal. Maximal percent gallbladder contraction was reached 30 min after ceruletide in all patients. Maximal percent contractions were 47.5±27.7 during US with ceruletide and 33.9±16.3 during OCG with fatty meal (p = 0.03). A significant linear relationship was found between the results obtained with the two different procedures (r=0.57; p = 0.002). Serial US determinations of gallbladder emptying were performed in 16 patients. Individual variation was below 20% in 11 subjects, and in five subjects it ranged between 20 and 40%. Minor, self-limiting side effects were observed in 13 patients. US determination of gallbladder emptying after ceruletide appears to be a practical and reliable method to assess gallbladder function.     

Effect of sildenafil citrate on postprandial gallbladder motility

OBJECTIVE: Sildenafil stimulates the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway through inhibition of type 5 phosphodiesterase. NO-cGMP pathway causes smooth muscle relaxation. The aim of this study is to evaluate the effects of sildenafil on gallbladder motility. METHODS: Twenty healthy male volunteers (21-35 years old) participated in this randomized, double blind, crossover, and placebo-controlled study. Oral sildenafil (50 mg) or placebo was randomly dispensed to each volunteer on two consecutive days. After the sildenafil or placebo, a special meal with a high fat content was administered. Gallbladder volume was measured using sonography preprandially and at 5, 15, 30, 60, 120 and 180 minutes postprandially. RESULTS: Sildenafil showed an inhibitory effect on gallbladder contraction in healthy volunteers that began at 30 minutes. Gallbladder volumes showed significant differences at 30 minutes following the test meal (approximately 50-60 min after the sildenafil intake), between placebo (15.4 +/- 5.1 mL) and the sildenafil groups (19.3 +/- 6.1 mL) (P < 0.05). In addition, gallbladder volume was significantly higher during the refilling phase in the sildenafil group (P < 0.05 at 180 min). Maximal contraction was achieved at 60 minutes in each group. CONCLUSIONS: Sildenafil constituted a significant inhibitory effect on gallbladder discharge in healthy individuals when compared with placebo group. Because of this inhibitory effect, sildenafil consumption for long periods may potentiate risks of gallbladder disorders and gallstone formation resulting from disturbed gallbladder motility.     

三维超声测量胆囊体积的探讨

目的　评价三维超声测量胆囊体积的准确性。方法　用二维、三维超声测量不同充盈度的离体猪胆囊和 80例成人脂餐前后胆囊的体积 ,比较二维、三维超声的准确性。结果　三维超声测量不规则形离体、成人胆囊体积的准确性分别为 10 4.7%和 97.9%。结论　三维超声测量不规则胆囊体积较二维超声准确     

In vitro and in vivo accuracy of sonographic gallbladder volume determinations

To assess gallbladder function, sonographic gallbladder volume determinations have been used with increasing frequency. This study presents a modified and automated procedure for gallbladder volume determinations using Simpson's rule of integration, Simpson's method. This method is a standard option in the data systems of many sonographic instruments. Simpson's method was validated in vitro and in vivo, and it was compared with the sum-of-cylinders method for gallbladder volume determinations. In vitro assessment indicated that the two methods were equally accurate, with Simpson's method being more precise. The absolute deviation was independent of the size of the volume and of the shape of the gallbladder. In vivo Simpson's method was validated on 11 patients with cholecystitis. The gallbladder volumes (mean 65 mL; Range 20 mL to 130 mL) measured by sonography differed from the aspirated volumes by 1.5 mL (SD 10.4 mL). Thus Simpson's method is an accurate, precise, and fast method for sonographic gallbladder volume determination. © 1993 John Wiley & Sons, Inc.     

Effects of a novel cholecystokinin (CCK) receptor antagonist, MK-329, on gallbladder contraction and gastric emptying in humans. Implications for the physiology of CCK.

To explore the physiology of cholecystokinin (CCK) in humans, we investigated the effect on gallbladder contraction and gastric emptying of a recently developed CCK receptor antagonist, MK-329. In a double-blind, four-period crossover study eight subjects received single doses of 0.5, 2, or 10 mg MK-329, or placebo, followed by an intravenous infusion of CCK-8 (30 pmol/kg.h). In placebo-treated subjects gallbladder volumes decreased on average to 43% of initial volumes after 2 h of CCK infusion. MK-329 caused a dose-dependent inhibition of CCK-stimulated gallbladder contraction with 10 mg producing complete blockade (P less than 0.01, cf. placebo). Gallbladder contraction and gastric emptying rates after a mixed meal were then measured in a two-period crossover study. Subjects received placebo or 10 mg of MK-329 2 h before eating. Gastric emptying of both solids and liquids was measured simultaneously by gamma scintigraphy. In placebo-treated subjects plasma CCK levels increased postprandially to 2.3 pM, gallbladder volumes decreased 68.4 +/- 3.8% (SE), and the times for 50% emptying of liquids and solids from the stomach were 58 +/- 10 and 128 +/- 8 min, respectively. In MK-329-treated subjects there was a marked elevation in peak CCK levels to 13.8 pM (P less than 0.01, cf. placebo), and gallbladder contraction was completely inhibited. Solid and liquid emptying rates were unaffected. These findings demonstrate that (a) MK-329 is a potent, orally active antagonist of CCK in humans, and (b) CCK is the major regulator of postprandial gallbladder contraction. These data also support the concept of negative feedback regulation of CCK secretion and suggest that mechanisms other than CCK play a dominant role in the regulation of postprandial gastric emptying rates.     

Gallbladder wall thickening secondary to focal lymphatic obstruction

Gallbladder wall thickening (3 mm or greater) has been described as a sign of acute or chronic inflammatory disease of the gallbladder. However, gallbladder wall thickening is a nonspecific finding in contracted, postprandial gallbladders and in cases of hypoproteinemia, elevated portal venous pressure, congestive heart failure, multiple myeloma, and hepatitis. This report describes the case of a patient who had a markedly thickened gallbladder wall secondary to focal obstruction of gallbladder lymphatic drainage by malignant lymphoma in the portal lymph nodes.     

慢性胆囊炎与胆结石形成关系的超声研究

目的 探讨慢性胆囊炎与胆结石形成的关系.方法 慢性胆囊炎、胆结石患者及正常人各20例采用超声法进行脂餐前后胆囊容积及排空率的测定.结果 结石组较对照组脂餐前、餐后各期胆囊容积增大,排空率降低(P＜0.05).慢性胆囊炎组餐后胆容积及排空率与对照组无显著性差异(P＞0.05),但空腹容积显著增大(P＜0.05).结论 慢性胆囊炎患者存在胆囊运动功能异常,这种异常可能是胆囊结石形成的原因之一.     

Sodium transport in the diseased human gallbladder and the effects of indomethacin

1. Sodium ion (Na+) transport, a principal function of the gallbladder epithelium, was studied by measuring the flux of 22Na across isolated, inflamed human gallbladder mucosa maintained in a modified 'Ussing' flux chamber. Tissue was obtained from cholecystectomy specimens in symptomatic patients with cholelithiasis. 2. In 30 gallbladders studied, 57% had a net Na+ flux from mucosa to serosa (Na+ absorption), while 23% had a net Na+ flux from serosa to mucosa (Na+ secretion). The remaining 20% showed no overall net Na+ flux. 3. Indomethacin added to the serosal fluid reversed the direction of net Na+ flux in secreting gallbladders and caused an absorption of Na+. In Na+-absorbing gallbladders, indomethacin caused a slight reduction in Na+ absorption. No change in Na+ flux was induced in gallbladders with no initial net Na+ flux. 4. These results demonstrate that instead of absorbing Na+, some inflamed human gallbladders may secrete Na+. As this secretion can be reversed to the more usual absorption by indomethacin, it is likely that this secretion is mediated by prostaglandins.