Gallbladder Motility Change in Late Pregnancy and after Delivery

Article information

Korean J Intern Med. 1997;12(1):16-20
Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, Korea
Address reprint requests to: Joon Soo Hahm, M.D. Department of Internal Medicine, Hanyang University Hospital, #17 Heangdang-dong, Sungdong-ku Seou 133-792, Korea

Abstract

Objectives

The incidence of gallstone disease has increased recently in Korea and there seems to be an increased prevalence of gallstones when in association with pregnancy. Although the pathogenesis is incompletely defined, an altered motility of the gallbladder may contribute to the increased risk of gallstones during pregnancy.

Methods

We measured gallbladder volume using real-time ultrasonography to find out the mechanism for the changes of gallbladder motility during late pregnancy. Eighteen pregnant women took the gallbladder ultrasonography during their last trimester of pregnancy and after delivery: gallbladder volume and ejection fraction were calculated in each patient.

Results

Fasting gallbladder volumes increased significantly in the last trimester of pregnancy (25.28± 14.26ml) compared with postpartum (17.44±5.82ml) (p<0.05). Gallbladder volumes measured after fatty meals showed more increment in pregnant women (10.13±7.19ml) than in those after delivery (4.34±3.36ml) (p<0.005). A significantly reduced gallbladder ejection fraction was found in the pregnant group (60.56± 18.80%) compared with those after delivery (77.48± 13.37%) (p<0.005).

Conclusion

Gallbladder motility in late pregnancy shows significant impairment compared with that in postpartum. Thus, we suggest that gallbladder hypomotility may occur during late pregnancy, and this impairment of gallbladder motility may play an important role in gallstone formation.

INTRODUCTION

Cholesterol cholelithiasis has been reported to be twofold to threefold more common among women than men1) This difference between men and women begins during puberty and is present throughout the childbearing age2). The increased incidence of cholelithiasis is believed to be related to pregnancy3,4). The cause of gallstone formation in pregnant women has been explained by these two mechanisms : supersaturation of cholesterol in bile and gallbladder hypomotility during pregnancy5,6) Studies of gallbladder motility in pregnant women have been limited due to the radiation hazard and invasiveness of the radiologic procedure. At present, the real-time ultrasonography can provide the measurements of gallbladder volume and ejection fraction easily and safely7,8).

With such backgrounds, we have evaluated the motor functions of the gallbladder in eighteen women during their third trimester of pregnancy and after delivery, and we tried to show that pregnancy itself can alter the gallbladder motility. In addition, we reviewed the effects of the reduced gallbladder motility during pregnancy on the formation of gallstones.

MATERIALS AND METHODS

1. Materials

Eighteen pregnant women in their third trimester of pregnancy (10 primipara, 8 multipara) were selected for ultrasonographic evaluation. They varied in age from 25 to 37 (mean=29.33±3.11). None of the subjects had a history of gastrointestinal, gallbladder, liver or endocrine disease.

2. Methods

Ultrasonography was performed during the third trimester of pregnancy and between 30 to 60 days after delivery. Measurement of gallbladder volume was performed by one sonographer using a 3.5 MHz convex probe. The real-time ultrasonography was conducted 5 times with an interval of 5 minu-tes, after overnight fasting, to obtain the average volume of the gallbladder, and it was again conducted 5 times with an interval of 5 minutes, 30 minutes after fatty meals which were blended with were boiled rice, egg, beef and contained 750kcal with 32% of fat.

The volume of the gallbladder was calculated by obtaining the width/height/length with the realtime ultrasonography and multiplying the dimensions using the ellipsoid method9) (Fig. 1). These fasting and postprandial volumes of the gallbladder were substituted into the formula to calculate the ejection fraction (EF) of the gallbladder10) (Fig. 2).

Fig. 1.

Ellipsoid method for calculating gallbladder volume from the longitudinal and transverse ultrasound images.

Fig. 2.

Equation for calculating ejection fraction of gallbladder in response to a fatty meal.

Results are expressed as mean ± S.D. The data were statistically analyzed using Student’s t-test with the level of p value at 0.05 or less.

RESULTS

1. Comparison of gallbladder volume between pregnancy and after pregnancy

The average fasting volume of the gallbladder during pregnancy (25.28± 14.26ml) was significantly higher than after delivery (17.44±5.82ml) (p<0.05) (Fig. 3). The average gallbladder volume after feeding during pregnancy (10.13±7.19ml) was also significantly higher than after delivery (4.34+3.36ml) (p<0.005) (Fig. 4).

Fig. 3.

The changes in fasting gallbladder volume during pregnancy and after delivery. The fasting gallbladder volume significantly decreased after delivery (p<0.05).

Fig. 4.

The changes in postprandial gallbladder volume during pregnancy and after delivery. The difference of gallbladder volume was significant and the changes in gallbladder volume are similar to those of fasting gallbladder volume (p<0.005).

2. Comparison of gallbladder ejection fraction

The average ejection fraction of the gallbladder was 60.56± 18.80% during pregnancy and 77.48± 13.37% after delivery. This finding means significant reduction of ejection fraction during pregnancy (p<0.005) (Fig. 5).

Fig. 5.

Ejection fraction changes during pregnancy and after delivery. The ejection fraction of gallbladder significantly increased after delivery (p<0.005).

3. Biliary sludge

Biliary sludge was found in two women during pregnancy, but the sludge disappeared after delivery. No gallstones were found among the eighteen pregnant women.

DISCUSSION

The common gastrointestinal symptoms during pregnancy are heartburn, indigestion and constipation11,12). These symptoms were often associated with alterations in both gastrointestinal and biliary motility. It has been well known that gallstone diseases are more common in women than in men14) and this difference between men and women begins during puberty2,14). In other words, increased incidence of gallstone disease in women is present throughout their childbearing years and is more remarkable by pregnancy24). Several recent reports also indicated an increased prevalence of gallstones during pregnancy. Valdivieso reported that gallstones were detected in 12.2% of the puerperal women14) and the high incidence of gallstone during pregnancy does not result in an accumulative prevalence14). In our study, no subject had gallstones.

The tendency of increasing cholesterol saturation15) in bile and gallbladder dysmotility during pregnancy are appropriate to the gallstone formation6). The cholesterol saturation of gallbladder bile increased during the second and third trimester in a previous study6), but the decreased cholesterol saturation, while inhibiting gallbladder emptying15), showed little correlation between gallbladder dysmotility during pregnancy and cholesterol saturation of bile. Many studies for gallbladder motility revealed increased gallbladder volume and decreased ejection fraction during pregnancy6,7,16), while some investigators reported no significant change in ejection fraction during pregnancy17). The majority of the previous studies were performed with the design of comparing subjects’ gallbladder motility with controls’. In this study, we tried to reduce the possible bias of control selection by evaluating gallbladder motility during pregnancy and post delivery in the same subjects.

In Ylöstalo’s study, fasting gallbladder volume was 14±0.8ml in nonpregnant controls, and 31.6± 2.0ml in women in the third trimester of normal pregnancy18), while the volume was 25.28± 14.26ml in our study, suggesting that gallbladder enlargement and incomplete evacuation of bile from the gallbladder may be one of pathogenetic significance during pregnancy.

Increased gallbladder volume during fasting is due to a combination of decreased water absorption by the gallbladder mucosa8,19,20), diminished tone of the gallbladder smooth muscle7,21). It is also partially due to proliferation of the gallbladder wall muscle16) caused mainly by the high concentration of progesterone7). The bile concentrates about 10 times by water absorption from gallbladder mucosa in normal subjects, and the water absorption decreased by estradiol in animal study18).

The main factor responsible for gallbladder contraction after a meal is cholecystokinin22). A recent study demonstrated that the secretion of cholecystokinin in the response to food intake was enhaced during pregnancy23), but there was no significant change in the total amount of cholecystokinin. There was no or little correlation between gallbladder volume and cholecystokinin concentration17) and the gallbladder volume is mainly controlled by smooth muscle relaxation due to elevated serum progesterone level24). Everson et al. demonstrated the linear increase of gallbladder volume correlated directly with serum progesterone in the first two-thirds trimester of pregnancy16), while Braverman found significantly increased gallbladder volume in second and third trimester but no changes during first trimester7). Both of the studies revealed the largest gallbladder volume during the third trimester of pregnancy. For this reason, we selected subjects in their third trimester for measuring gallbladder volume in this study.

In Everson’s study, the gallbladder volumes returned toward normal in two weeks postpartum16). In our study, the gallbladder volume was diminished after delivery (25.28ml→17.44ml fasting, 10.13ml→4.34ml after feeding), and the ejection fraction was increased after delivery (60.56→77.48%).

In some studies, the risk of gallstone is directly related to the number of pregnancies13). However, there was no significant difference in gallbladder motility between primipara and multipara in our study. A recent study suggests that the hypomotility of gallbladder in pregnancy induces gallbladder sludge formation. The sludge formation was thought to be temporarilly related to the pregnancy25), because of its tendency to resolve spontaneously postpartum26). In our study, the biliary sludge was observed in two subjects and the sludge disappeared after delivery.

The real time ultrasonogram and the ellipsoid method were used to measure the volume of the gallbladder. While the examinees would inevitably be exposed to radiation or subject to invasive examinations in tests such as cholecystogram or radioisotope scan8), the real-time ultrasonography can measure the volume and ejection fraction of gallbladder comparatively easily and precisely without using any complex devices27). In addition, this new test method features outstanding reducibility and therefore, it is thought of as a useful method to estimate the motor function of the gallbladder28). The original method for gallbladder volume using ultrasonography was the sum of cylinders method developed by Everson29), but it was rather time-consuming30). However, Dodds et al. proposed the use of the simple ellipsoid method9), and they reported an excellent correlation with the sum of cylinders method30). In the present study, we were able to confirm the good reproducibility of the ellipsoid method comparing the sum of cylinders method.

In summary, gallbladder motility in late pregnancy shows significant impairment compared with that in postpartum. Thus, we suggest that gallbladder hypomotility may occur during late pregnancy and this impairment of gallbladder motility may play an important role in gallstone formation.

References

1. Bennion LJ, Grundy SM. Risk factors for the development of cholelithiasis in man. N Engl J med 1978;299:1161–1167.
2. Friedman G, Kannel WB, Dawber TR. The epidemiology of gallbladder disease: Observations in the Framingham study. J Chron Dis 1966;19:273–293.
3. GREPCO-Rome group for the Epidemiology and prevention of cholelithiasis. Prevalences of gallstone disease in Italian adult female population. Am J Epidemiol 1984;119:796–805.
4. Barbara L, Sama C, Morselli AM, Tavoni F, Rusticali AG, Festi D, Sapio C. A population study on the prevalence of gallstone disease: the Sirmione study. Hepatology 1987;7:913–917.
5. Potter M. G. Observations of gallbladder and bile during pregnancy at term. JAMA 1938;106:1070–1074.
6. Kern F, Everson GT, DeMark B, McKinley C, Showalter R, Erfling W, Braveman D. Biliary lipids, bile acids and gallbladder function in the human female. J Clin Invest 1981;68:1229–1242.
7. Braverman D, Michael L, Fred K. Effects of pregnancy and contraceptive steroids on gallbladde function. N Engl J Med 1980;302:362–364.
8. Kirshnamurthy GT, Bobba VR, Kingston E. Radionuclide ejection fraction: A technique for quantitative analysis of motor function of the human gallbladder. Gastroenterology 1981;80:482–490.
9. Dodds WJ, Groh W, Darweesh R. Sonograhic measurement of gallbladder volume. AJR 1985;145:1009–1011.
10. Festi D, Frabboni R, Bazzoli F. Gallbladder motility in cholesterol gallstone disease. Gastroenterology 1990;89:1779–1785.
11. Hart DM. Heartburn in pregnancy. J Int Med Res 1978;6(suppl):1–5.
12. Hey VM, Cowely DJ, Ostick DG. Proceedings. Gastroesophageal reflux in late pregnancy. Gut 1975;16:403–404.
13. Scragg RK, McMichael AJ, Seamark RF. Oral contraceptives, hregnancy and endogenous estrogen in gallstone disease-a case control study. BMJ 1984;288:1795–1799.
14. Valdivieso V, Covarrubias C, Siegel F, Cruz F. Pregnancy and cholelithiasis: Pathogenesis and natural course of gallstones diagnosed in early puerperium. Hepatology 1993;17:1–4.
15. Pauletzki JG, Xu QW, Shaffer EA. Inhibition of gallbladder emptying decreased cholesterol saturation in bile in the Richardson ground squirrel. Hepatology 1995;22:325–331.
16. Everson GT, Mckinley C, Lawson M, Johnson M, Kern F. Gallbladder function in the human female effect of the ovulation cycle, pregnancy, and con traceptive steroid. Gastroenterology 1982;82:711–719.
17. Radberg G, Asztely M, Cantor P, Rehfeld JF, Jarnfeldt A, Svanvik J. Gastric and gallbladder emptying in relation to the secretion of cholecystokinin after a meal in late pregnancy. Digestion 1989;42:174–180.
18. Ylöstalo P, Kirkinen P, Heikkinen J. Gallbaldder volume and serum bile acids in cholestasis of pregnancy. Br J Obstet Gynecol 1982;89:59–61.
19. Reyes H, Kern F Jr. Effect of pregnancy on bile flow and biliary lipids in the hamster. Gastroenterology 1979;76:144–150.
20. Radberg G, Svanvik J. Influence of pregnancy, oophorectomy and contraceptive steroids on gall bladder concentrating function and hepatic bile flow in the cat. Gut 1986;27:10–14.
21. Cohen S. The sluggish gallbladder of pregnancy. N Engl J Med 1980;302:397–398.
22. Manton P, Selden A, Fritzpatrick M, Chadwick V. Defective gallbladder emptying and cholecystokinin release in celiac disease. Gastroenterology 1985;88:391–396.
23. Radberg G, Rehfeld J, Cantor P, Jarnfelt A, Samsioe G, Asztely M, Svanvik J. Cholecystokinin secretion in pregnancy. Scand J Gastroent 1987;22:687–690.
24. Fisher R, Robert G, Grabowski C, Cohen S. Inhibition of lower esophageal sphincter circular muscle by female sex hormones. Am J Physiol 1978;234:243–247.
25. Maringhinl A, Marceno MP, Lanzarone F. Sludge and stones in gallbladder after pregnancy. J He patol 1987;5:218–223.
26. Maringhinl A, Ciambra M, Baccelliere P. Sludge, stones and pregnancy. Gastroenterology 1988;95:1160–1161.
27. Krook P, Allen F, Bush W. Comparison of real-time cholecystography and oral cholecystography. Radiology 1980;132:145–148.
28. Mackie CR, Baxter JN, Grime JS. Gallbladder emptying in normal subject-A database for clinica cholescintigraphy. Gut 1987;28:137–141.
29. Everson GT, Braverman DZ, Johnson ML. A critical evaluation of real-time ultrasonography for the study of gallbladder volume and contraction. Gastroenterology 1981;79:40–46.
30. Keshavarzian A, Dunne M, Iber FL. Gallbladder volume and emptying in insulin-requiring male diabetics. Dig Dis Sci 1987;32:824–828.

Article information Continued

Fig. 1.

Ellipsoid method for calculating gallbladder volume from the longitudinal and transverse ultrasound images.

Fig. 2.

Equation for calculating ejection fraction of gallbladder in response to a fatty meal.

Fig. 3.

The changes in fasting gallbladder volume during pregnancy and after delivery. The fasting gallbladder volume significantly decreased after delivery (p<0.05).

Fig. 4.

The changes in postprandial gallbladder volume during pregnancy and after delivery. The difference of gallbladder volume was significant and the changes in gallbladder volume are similar to those of fasting gallbladder volume (p<0.005).

Fig. 5.

Ejection fraction changes during pregnancy and after delivery. The ejection fraction of gallbladder significantly increased after delivery (p<0.005).