功能性消化不良患者胆囊排空及激素水平的研究

目的研究胆囊排空及血浆胃肠激素水平变化在功能性消化不良(FD)发病机制中的作用.方法采用放射性核素序列成像和放免技术检测20例健康志愿者(对照组)和32例功能性消化不良患者(FD组)空腹及餐后胆囊排空指数和血浆胃动素(MTL)、胆囊收缩素(CCK)、血管活性肠肽(VIP)和生长抑素(SS)水平.结果FD组空腹及餐后胆囊排空指数均明显低于对照组,差异有非常显著性(P＜0.001);FD组空腹及餐后血浆MTL值均低于对照组,差异有非常显著性(P＜0.001),MTL值与胆囊排空指数呈正相关(r空腹=0.82,P＜0.01,r餐后=0.94,P＜0.01);FD组空腹血浆CCK值与对照组比较,差异无显著性(P＞0.05),餐后差异有非常显著性(P＜0.001),CCK值与胆囊排空指数呈显著正相关(r=0.97,P＜0.01);FD组空腹与餐后血浆VIP值均高于对照组,差异有非常显著性(P＜0.001),VIP值与胆囊排空指数呈负相关(r空腹=-0.81,P＜0.01,r餐后=-0.47,P＜0.01);FD组空腹及餐后血浆SS值与对照组相比,差异无显著性(P＞0.05).结论(1)FD患者存在空腹及餐后胆囊排空下降,血浆促胃肠动力激素(MTL、CCK)水平下降和抑制胃肠动力激素(VIP)水平升高,可能是其病因和发病机制之一;(2)放射性核素胆囊序列成像无创、安全,可作定量分析及动态观察,值得推广应用.     

Gallbladder emptying response to sham feeding in humans

Cholescintigraphy, using 99mTc-HIDA, was employed to determine the gallbladder emptying response to sham feeding of a steak and potato meal, and to compare it with the emptying responses to direct cholinergic stimulation by bethanechol and to ingestion of the test meal. The maximal cumulative gallbladder emptying response to sham feeding was 44.1% + 10.1%, which was not significantly different from the response to bethanechol. Cholinergic blockade with atropine eliminated the emptying response to sham feeding. Also, sham feeding did not stimulate gallbladder emptying in patients with vagotomy. This study suggests that intact vagus nerves and cholinergic pathways are required in order for the gallbladder to respond to sham feeding. The precise mechanism for this effect has not been elucidated.     

Ovarian function and gastrointestinal motor activity

Gastrointestinal disorders are strictly related to the ovary function. In fact, it is noted that the prevalence of visceral pain disorders such as irritable bowel syndrome, gastroesophageal reflux disease, gallbladder and biliary tract diseases are significantly higher in women. Furthermore, symptom such as nausea, vomiting, abdominal pain, distension, satiety, bloating, diarrhoa or constipation, frequently appears in relation with pregnancy, luteal phase of the menstrual cycle or perimenopausal and menopausal states. Further support for the contribution of ovarian steroids to functional gastrointestinal disorders comes from studies demonstrating that pharmacological ovariectomy reduces abdominal pain symptoms. Therefore, addressing the influence of sex and sex hormones in the modulation of visceral pain appears critical to develop new strategies of diagnosis and therapy sex-directed for gastro-intestinal disorders.     

Gallbladder volume and emptying in insulin-requiring male diabetics

Gallbladder function was evaluated in 27 healthy male volunteers and 47 male insulin-requiring diabetics from a diabetic clinic. Three groups of patients were studied: 18 patients without neuropathy or retinopathy (A); 17 patients with evidence of peripheral neuropathy (B); and 12 patients with evidence of peripheral and autonomic neuropathy (C). Eleven patients complained of gastrointestinal symptoms (three in group B, eight in group C). Thirty minutes after a standard breakfast, fasting gallbladder volumes and gallbladder emptying rates were measured using a real-time mechanical sector ultrasound scanner. Fasting gallbladder volume in diabetic patients was similar to controls (24.9 +/- 2.7 N; 28.9 +/- 3.9 A; 23.7 +/- 2.2 B; 16.7 +/- 3.4 C ml mean +/- SEM). Postprandial gallbladder emptying was not significantly different in any groups (47.4 +/- 5.1% N; 43.2 +/- 7.7% A; 50.7 +/- 7.7% B; 46.8 +/- 11.1% C). Seven diabetics and two controls had poor gallbladder emptying. One screened patient had cholecystectomy, three patients had stones, and two had sludge with a thickened gallbladder wall for a total of 12.5% gallbladder disease. These data suggest that gallbladder dysfunction in male insulin-requiring diabetics is rare.     

Gallbladder function and gastric liquid emptying in achalasia

Because of evidence that the abnormalities in achalasia are not restricted to the distal esophagus, we investigated gallbladder function by cholescintigraphy in the steady state and in response to CCK and the scintigraphic gastric emptying of a liquid caloric meal in 10 individuals with achalasia and 10 normal controls. No abnormalities were found during the filling phase of the gallbladder but seven of the 10 patients showed a 50% reduction in the ejection fraction (39.4%±30.4 vs 80.3±8.3 of controls, mean±sd,P=0.007) and a slower than normal ejection phase (9.1%/min±6.6 vs 18.1±4.5,P=0.02. In eight of the 10 patients, gastric liquid emptying was accelerated with a T1/2 of 41.5 min±15.4 vs 74.7 min±11.5 in the controls (P=0.007). It is concluded that in some achalasia patients extraesophageal functional abnormalities of the gastrointestinal tract may be found. Whether these findings are promoted by degenerative changes of extraesophageal nerve fibers as well as their clinical significance require further investigations.This paper was presented as abstract at the American Gastroenterological Association Meeting, San Antonio, Texas, in May 1990.     

Cephalic stimulation of gastrointestinal secretory and motor responses in humans.

The present study was designed (a) to investigate the cephalic phase of gastropancreatic secretion, antroduodenal motility, and regulatory peptide release in six healthy young men and (b) to assess its regulation by the cholinergic system and endogenous cholecystokinin. Sham feeding performed for 15 minutes induced a concurrent stimulation of gastropancreatic secretion, antroduodenal motility, and pancreatic polypeptide release that lasted for 30 minutes. Reappearance of interdigestive phases III was retarded in the post-sham-fed state. Atropine abolished secretory, motor, and pancreatic polypeptide responses to sham feeding and enhanced gastrin release. The cholecystokinin receptor antagonist loxiglumide did not attenuate pancreatic enzyme response but diminished antral motor response by 72% (P less than 0.05) and release of pancreatic polypeptide by 91% (P less than 0.05); it enhanced gastrin release and abolished retardation of reappearance of phase III with sham feeding. It is concluded that (a) there is a distinct cephalic phase of gastropancreatic secretion, antroduodenal motility, and pancreatic polypeptide release in humans that is primarily under cholinergic control and that (b) endogenous cholecystokinin is involved in antral motor, gastrin, and pancreatic polypeptide responses to sham feeding.     

Gallbladder emptying stimuli in obese and normal-weight subjects.

Gallbladder stasis may be an important factor in the pathogenesis of cholesterol-gallstone formation in some individuals. We investigated gallbladder function in a group of nondieting, gallstone-free, healthy subjects with normal (22 +/- 1 kg/m2) and high (36 +/- 1 kg/m2) body mass indexes. Fasting gallbladder volume (28.2 +/- 4.4 ml) and residual volume after maximal emptying (8.4 +/- 2.3 ml) in high-body-mass index subjects were not significantly different from those of normal-body-mass index subjects (20.5 +/- 2.5 ml and 4.2 +/- 1.3 ml, respectively). The percentage of gallbladder emptying (71% +/- 5%) and the rate of gallbladder emptying (-1.9 +/- 0.3 x 10(-2) min-1) in high-body-mass index subjects in response to a maximal emptying stimulus was similar to the percentage of emptying (78% +/- 6%) and rate of emptying (-2.3 +/- 0.6 x 10(-2) min-1) in normal-body-mass index subjects. A liquid meal containing less than 1 gm fat, 14 gm protein and 6 gm carbohydrate resulted in both a decreased rate of gallbladder emptying and an increased residual gallbladder emptying and an increased residual gallbladder volume in both groups. The addition of 10 or 20 gm (but not 4 gm) of fat to the liquid meal restored gallbladder emptying to the maximal-stimulus level. These results demonstrate that gallbladder emptying in response to a single liquid meal stimulus is not altered in obesity and that dose-response relationships to fat are similar in obese and normal-weight individuals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gallbladder emptying in patients with primary achalasia.

Being more evident that primary achalasia is not confined to the esophagus and that it may involve other organs in the digestive tract, gallbladder emptying was ultrasonographically evaluated in 10 patients affected with primary achalasia and in 10 controls. An intravenous cerulein infusion was used to induce gallbladder contraction. Eight out of 10 achalasic patients had a lower gallbladder emptying, and 6 out of 10 had a markedly delayed gallbladder emptying compared with the controls. Achalasic patients, taken as a whole, showed a significantly lower and delayed mean gallbladder emptying when compared with the controls. Such a finding confirms the possible extra-esophageal extension of primary achalasia. In this study, the hypothesis of impaired cholinergic gallbladder innervation in primary achalasia is discussed.     

Gallbladder emptying in patients with primary sclerosing cholangitis

AIM： To assess gallbladder emptying and its association with cholecystitis and abdominal pain in patients with primary sclerosing cholangitis （PSC）. METHODS： Twenty patients with PSC and ten healthy subjects were investigated. Gallbladder fasting volume, ejection fraction and residual volume after ingestion of a test meal were compared in patients with PSC and healthy controls using magnetic resonance imaging. Symptoms, thickness and contrast enhancement of the gallbladder wall and the presence of cystic duct strictures were also assessed. RESULTS： Median fasting gallbladder volume in patients with PSC [67 （19-348） mL] was twice that in healthy controls [32 （16-55） mL] （P 〈 0.05）. The median postprandial gallbladder volume in patients with PSC was significantly larger than that in healthy controls （P 〈 0.05）. There was no difference in ejection fraction, gallbladder emptying volume or mean thickness of the gallbladder wall between PSC patients and controls. Contrast enhancement of the gallbladder wall in PSC patients was higher than that in controls; （69% ± 32%） and （42% ± 21%） （P 〈 0.05）. No significant association was found between the gallbladder volumes and occurrence of abdominal pain in patients and controls.CONCLUSION： Patients with PSC have increased fasting gallbladder volume. Gallbladder Mucosal dysfunction secondary to chronic cholecystitis, may be a possible mechanism for increased gallbladder.     

Gallbladder and gastric emptying: relationship to cholecystokininemia in diabetics

Background: Impaired gastrointestinal and gallbladder motility, as a complication of long-lasting diabetes mellitus, has been ascribed to the possible development of autonomic neuropathy, although the intervention of hormonal factors may not completely be excluded. In this regard, cholecystokinin (CCK), a gut hormone known to regulate pancreatic exocrine secretion, gallbladder contraction, and bowel motility in response to a meal, is impaired in patients with diabetes mellitus. This prompted us to evaluate the relationship between the plasma levels of CCK and gallbladder and gastric emptying in neuropathy-free diabetic patients treated with insulin (group A) or with oral hypoglycemic agents (group B) under basal conditions and in response to a standard test meal. Methods: Plasma CCK was measured by radioimmunoassay. Gastric and gallbladder emptying were evaluated ultrasonographically. Results: Plasma CCK levels were significantly lower in both groups of diabetics than in healthy controls during a fast and in response to a standard meal. However, meal ingestion was able to evoke a pattern of CCK response in both groups of diabetic patients similar to that seen in controls. Fasting gallbladder volume was higher in patients with diabetes than in controls, whereas the percentage of emptying was lower in patients of both groups. Gastric final emptying time was significantly longer in both groups of diabetics than in controls. Conclusion: This study shows that patients with diabetes have lower plasma levels of CCK, which may explain their relatively hypotonic gallbladder and reduced gastric motility.     

胆汁反流性胃炎患者胆囊排空功能研究

目的研究胆汁反流性胃炎（ＢＲＧ）患者胆囊（ＧＢ）排空功能及其与胆汁反流的关系．方法采用随机、双盲和对照的方法，应用实时超声检查研究了３２例ＢＲＧ患者和２６例健康对照者的空腹ＧＢ容量（ＦＧＶ）和餐后ＧＢ排空功能．结果ＦＧＶ（ｃｍ３，ｘ±ｓｘ）ＢＲＧ患者（２３５±１５）明显大于对照组（１９７±１３，Ｐ＜００１）．餐后１５ｍｉｎＧＢ排出量（ＧＥＦ）ＢＲＧ患者即显著减少（Ｐ＜００１），餐后４５ｍｉｎ减少达最大（４５３％ｖｓ７０３％）．最大ＧＥＦＢＲＧ患者（６５４％）明显少于对照组（８０２％，Ｐ＜００１）．ＧＢ排空速度ＢＲＧ患者显著慢于对照组（Ｐ＜００１）．结论ＢＲＧ患者ＧＢ排空明显不良，可能系ＧＢ收缩无力和（或）Ｏｄｄｉ括约肌松弛不良所致；餐后ＧＥＦ减少与ＦＧＶ增多有关，从而使消化间期排入肠道的胆汁增多，当同时存在胃肠运动功能紊乱时即可反流入胃     

Gallbladder emptying and somatostatin and cholecystokinin plasma levels in celiac disease

OBJECTIVE: Gallbladder hypomotility in celiac disease has been attributed to decreased cholecystokinin secretion. The possible influence of somatostatin, which inhibits gallbladder motility, however, has never been evaluated. In this study gallbladder emptying and cholecystokinin and somatostatin plasma levels were evaluated in response to a fatty meal in patients with celiac disease at diagnosis and after long-term gluten-free diet and in controls. METHODS: Gallbladder volume and plasma levels of cholecystokinin and somatostatin were measured by ultrasonography and radioimmunoassay, respectively, at 0 time and 30, 60, 75, and 90 min after an oral fatty meal (227 kcal, 45% fat) in 10 celiac patients at diagnosis and after 18 months of successful gluten-free diet and in 10 healthy subjects. The pattern of gallbladder emptying was evaluated by mixed factorial analysis of variance and the curve fitting by multiple regression analysis. RESULTS: Patients at diagnosis had significantly greater fasting gallbladder volume and higher somatostatin plasma levels than controls (25.7 +/- SD 9.7 ml vs 16.8 +/- 7.0 ml, p = 0.021 and 9.3 +/- 4.6 vs 4.8 +/- 3.4 pmol/L, p = 0.023, respectively), significantly lower fatty meal-induced gallbladder ejection fraction (55 +/- 11.2% vs 76 +/- 7.2%, p = 0.005), and cholecystokinin peak and smaller area under the cholecystokinin secretion curve (3.1 +/- 2.3 pmol/L vs 10.5 +/- 6.9 pmol/L, p = 0.028 and 157 +/- 142 pmol/L/90 min vs 453 +/- 229 pmol/L/90 min, p = 0.028, respectively). The two groups had a similar emptying pattern (p = 0.8913) expressed by a significant quadratic term of the emptying function (p = 0.0001). The mean overall emptying volume was significantly greater in patients than in controls (p = 0.0007). Gluten-free diet normalized these findings. CONCLUSIONS: In patients at diagnosis, elevated somatostatin levels were associated with increased gallbladder fasting volume, whereas decreased cholecystokinin secretion was responsible for the reduced gallbladder emptying. Gluten-free diet reversed these abnormalities.     

Upper gastrointestinal motor activity in patients with slow-transit constipation

Recent evidence indicates that patients complaining of severe chronic idiopathic constipation may have motor abnormalities not limited to the colon. We studied by manometric means gastric and small bowel motility in a homogeneous group of patients with chronic idiopathic constipation ie, the slow transit type. Twenty-one patients were recruited for the study and compared to 33 healthy subjects. Manometric examination was carried out for about 5 hr fasting and 1 hr after a standard meal. Analysis of the manometric tracings revealed during fasting no abnormalities in number and configuration of migrating motor complex with respect to controls. However, in 70% of patients motor abnormalities were detected, represented by bursts of nonpropagated contractions and discrete clustered contractions. After feeding, the patient group displayed a significantly shorter antral motor response to the meal with respect to controls; moreover, intestinal bursts of nonpropagated contractions were found in 19% of patients, and 14% of them had an early return of the activity fronts. We conclude that patients with slow transit constipation frequently display motor abnormalities of the upper gut. These findings further strengthen the concept that this condition may represent a panenteric disorder.     

Gallbladder contraction and its relationship to interdigestive duodenal motor activity in normal human subjects

Gallbladder volume and interdigestive gastric and duodenal motor activity were evaluated simultaneously in 12 normal subjects. After overnight fasting, gallbladder volume was monitored every 4 min in each subject by means of real-time ultrasonography, and gastroduodenal motor activity was measured by means of a probe consisting of three polyvinyl catheters with one side opening for each catheter, placed 15 cm apart and constantly perfused with deionized water. Real-time ultrasonography and intestinal manometry were performed by different investigators and continued until at least two consecutive spontaneous phase III activities of migrating motor complexes were observed. The results show a cyclic variation of gallbladder volume, which reached its minimum value before the end of phase II in the proximal duodenum and its maximum in early phase II, 25 min after the beginning of phase III. These results suggest that there is a relationship between the cyclic gallbladder volume changes, which occur during fasting in humans, and with the various phases of duodenal migrating motor complex.     

Measurement of gastric emptying rate in humans

Simultaneous measurements of the gastric emptying rate of the solid and liquid phase of a dual-isotope-labeled test meal were made using a gamma camera and a simple scintillation detector, similar to that used in a hand-held probe. A simple scanning apparatus, similar to that used in a hand-held scintillation probe, was compared with simultaneous measurements made by a gamma camera in 16 healthy males. A dual-labeled test meal was utilized to measure liquid and solid emptying simultaneously. Anterior and posterior scans were taken at intervals up to 120 min using both a gamma camera and the scintillation probe. Good relative agreement between the methods was obtained both for solid-phase (correlation range 0.92-0.99, mean 0.97) and for liquid-phase data (correlation range 0.93-0.99, mean 0.97). For solid emptying data regression line slopes varied from 0.75 to 1.03 (mean 0.84). Liquid emptying data indicated that slopes ranged from 0.71 to 1.06 (mean 0.87). These results suggested that an estimate of the gamma measurement could be obtained by multiplying the scintillation measurement by a factor of 0.84 for the solid phase and 0.87 for the liquid phase. Correlation between repeat studies was 0.97 and 0.96 for solids and liquids, respectively. The application of a hand-held probe technique provides a noninvasive and inexpensive method for accurately assessing solid- and liquid-phase gastric emptying from the human stomach that correlates well with the use of a gamma camera, within the range of gastric emptying rate in the normal individuals in this study.     

Cholinergic effects on gallbladder emptying in humans

The role of cholinergic mechanisms in the control of gallbladder emptying has not been defined. In this report a scintigraphic technique using 2,6-dimethylphenylcarbamoylmethyl iminodiacetic acid labeled with technetium 99m to visualize the gallbladder and its emptying and diethylenetriamine pentaacetic acid labeled with indium 111 to visualize the stomach and its emptying was used to study 43 normal subjects and 18 patients with vagotomies. Direct cholinergic stimulation with bethanechol induced significant gallbladder emptying. Cholinergic blockade with atropine sulfate decreased the gallbladder emptying responses to a liquid meal, a solid meal, and the infusion of cholecystokinin-octapeptide. In patients with vagotomies, gallbladder emptying was decreased despite accelerated gastric emptying of an ingested liquid meal. The gallbladder emptying response to cholecystokinin-octapeptide was augmented in patients who had undergone vagotomy. These studies suggest that cholinergic receptors may be important in the regulation of human gallbladder emptying.     

Duodenal osmolality drives gallbladder emptying in humans

The effect of duodenal osmoreceptor stimulation on gallbladder motility was evaluated in 18 normal subjects during intraduodenal infusion of 280, 560 and 840 mosmlliters NaCl solutions. Gallbladder emptying was found to be dose-dependent between 560 and 840 mosm/liter (P<0.01 vs basal volume). The effect of duodenal infusion of hypertonic saline on gallbladder emptying was prevented by atropine and partially antagonized by naloxone,indicating that cholinergic and endorphinergic pathways may be involved in regulating this reflex. Since proglumide, a cholecystokinin (CCK) antagonist, did not affect gallbladder emptying induced by hypertonic saline, it seems likely that CCK is not released by increasing duodenal osmolality. A significant reduction in gallbladder volume was obtained when hyperosmolar saline was delivered into the duodenum, whereas no emptying was seen when infused into the gastric antrum or the jejunum, suggesting that osmoreceptors that activate gallbladder emptying are located only in the duodenum. Additionally, all subjects manifested central symptoms (nausea or vomiting) during duodenal infusion of hypertonic saline,suggesting that central mechanisms might be activated by a change in duodenal osmolality. Our data indicate that the osmolality of duodenal contents might regulate gallbladder motility by neural atropine- and naloxone-sensitive pathways.