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Indian Journal of Surgery, Vol. 68, No. 2, March-April, 2006, pp. 80-83 Original Article Role of iron deficiency in the formation of gall stones Kumar Muneesh, Goyal BB, Mahajan M, Singh S Departments of Surgery, Govt. Medical College and Guru Nanak Dev Hospital, Amritsar, Punjab Code Number: is06021 Abstract Background : The old axiom that a typical gall stone sufferer is a fat, fertile, female of fifty, is only partially true, as the disease is found in women soon after their first delivery and also in underweight and thin people. So while searching for other parameters, iron deficiency was found to be a new parameter of interest in the aetiology of gall stones.Aims : The study was aimed at establishing the role of iron deficiency in the supersaturation of bile with cholesterol and thus formation of gallstones. Setting and Design : 50 patients suffering from Cholelithiasis were divided into two groups. Group A consisted of patients with normal serum iron levels (non-anaemic) and group B, of patients with less than normal serum iron (anaemic). Serum cholesterol and gall bladder bile cholesterol of both the groups were studied and compared. Materials and Methods: 50 patients of Cholelithiasis, confirmed by Ultrasonography (USG) were divided into anaemic and non-anaemic groups, based on serum iron levels. Serum cholesterol and gall bladder bile cholesterol of both the groups were estimated. Statistical Analysis Used : Students' t-test. The p-value <0.05 was considered significant. Results : Total serum cholesterol was not different in gall stone formers from that of the general population.Gall bladder bile cholesterol was significantly higher in anaemic, than in non-anaemic individuals. Conclusion : Low serum iron levels lead to bile supersaturation with respect to cholesterol, which leads to gallstone formation. Keywords: Iron deficiency, gallstones, biliary cholesterol The old axiom, that a typical gall stone sufferer is a fat, fertile, female of fifty, is only partially true, as the disease has been found in women soon after their first delivery and also in underweight and thin people. So while searching the literature for different factors, Iron deficiency was found to be new and interesting aetiological factor in the formation of gall stones. Gallstones may produce symptoms, or may remain asymptomatic. Over half the cases are asymptomatic, usually detected by abdominal ultrasound. Today the incidence of gallstone disease has increased considerably with the invention of ultrasonography.[1] Three conditions must be met to permit the formation of cholesterol gallstones.
Iron deficiency has been shown to alter the activity of several hepatic enzymes,[2] leading to increased gall bladder bile cholesterol saturation and promotion of cholesterol crystal formation.[3] Iron acts as a coenzyme for nitric oxide synthetase (NOS),[4] which synthesizes nitric oxide (NO)[5] and that is important for the maintenance of basal gall bladder tone and normal relaxation. It was found that iron deficiency resulted in altered motility of gall bladder and sphincter of Oddi (SO), leading to biliary stasis and thus increased cholesterol crystal formation in the gall bladder bile.[6] Materials and Methods The study was conducted over a period of one and half years, from February 2003- July 2004. The study protocol was approved by the review board of our institute for ethical research. It was a retrospective analysis. The patients were selected, based only on the USG confirmation of their gall stones, irrespective of their age, sex, physique, parity, etc. Only those patients were included, whose serum as well as bile could be procured for analysis. Patients who underwent laparoscopic Cholecystectomy were excluded, as their bile could not be procured. Patients who underwent open Cholecystectomy, but whose bile sample was not available for analysis, were also excluded from the study. Patients with empyaema gall bladder were also excluded. All the patients, who were included in the study were given a serial number 1 to 50, in the order of their admission to the surgery department for Cholecystectomy. Thus their bile and serum samples were also labeled 1 to 50 accordingly. The numbered samples were sent to the Biochemistry department for analysis. All the numbered samples with less than normal serum iron (n=23) were put in the anaemic group, B and all the samples with normal serum iron (n=27) were put in the non anaemic group, Group A. Serum iron was estimated by Ferrozine kit method for determination of iron. This kit was procured from CREST BIOSYSTEMS. The normal reference values supplied with the kit, for males (60-160 μg/dl) and for females (35-145 g/dl), were used to label the patients as anaemic and non-anaemic i.e. males with serum iron < 60 g/dl and females with serum iron < 35 μg/dl were labeled as anaemic. During the operation for open cholecystectomy, bile was aspirated with an aspiration needle mounted on a sterilized syringe. The aspiration needle was passed obliquely into the fundus of gall bladder and as much of bile as possible, was withdrawn from the gall bladder. Bile was kept in a sterile labeled container and carried to the Biochemistry Department for analysis. Serum cholesterol and gall bladder bile cholesterol of all the patients were estimated. Bile was first subjected to the Folch method to extract lipids and then the cholesterol contents were estimated as for serum cholesterol. In the Folch method, lipids from bile were extracted by using water, Methanol and Chloroform mixture in the ratio of 3:4:8 v/v and from the extracted lipids, cholesterol was estimated by Enzopak kit, based on the cholesterol oxidase/peroxidase method. The enzymes used only the cholesterol as substrate and hence Bilirubin is automatically eliminated, from the procedure of cholesterol estimation. Statistical analysis Data amongst the two groups were subjected to statistical analysis using students′t-test. The P -value < 0.05 was considered significant. Results Out of the total 50 patients, 40 (80%) were females and 10 (20%) were males. The majority of patients 31 (62%) presented with all the three symptoms of cholelithiasis i.e. pain in the right upper quadrant, nausea/vomiting and flatulent dyspepsia. Pain was the most consistent symptom present in 49 (98%) patients. 31 (77.5%) out of the total female patients were multipara. 40 (80%) patients had body mass index (BMI) more than normal and 10 (20%) had normal or decreased BMI. Normal BMI means values between 19.1-24.9 i.e. < 25. Serum total cholesterol of gall stone formers was not different from that of the general population. There were no significant variations in the serum cholesterol contents of both the groups ( P =0.367, t=0.91). Also, there was no significant variation of the above parameter in the male and female patients ( P =0.082, t=1.77). The gall bladder bile cholesterol was significantly higher in the anaemic individuals, as compared to that of the non-anaemic ones ( P < 0.0001, t=4.53). Discussion The present study was conducted on the randomly selected individuals of the Punjabi population, suffering from gall stone formation, to decipher the facts on the current divided opinion available in literature regarding the aetiology of gall stone formation and the role of iron deficiency anaemia in gall stone formation. Out of the 50 gall stone patients included in the present study, 40 (80%) were females, and 10 (20%) were males, supporting the age old axiom that gall stone formation is most common in the female population. The increased prevalence of gall stone formation in females could be attributed to the fact, that anaemia is more common in females than males, as 22 (55%) females were observed to be anaemic, as compared to 1 (10%) male [Table - 1]. This male to female ratio of 1:4 observed in the present study was different from that of Pima Indians (1:17)[7] and Pakistanis (1:3).[8] This sex-related difference showing more prevalence of cholelithiasis in females could be linked to pregnancy and female sex hormones and also to iron deficiency anaemia now. All the forty females, both anaemic (n=22) and non-anaemic (n=18) included in the present study, were further sub classified on the basis of parity [Table - 2]. In both the non anaemic and anaemic groups of female gall stone formers, the number of multipara females (n=12 and n=19 respectively) suffering from gall stones was more than that of primipara (n=4 and n=2 respectively) and nullipara (n=2 and n=1), respectively, hence suggesting, that parity plays a significant role in gall stone formation. More the number of babies delivered, more is the probability of a female suffering from gall stone formation. It could probably be attributed to advancing anaemia with increase in number of deliveries. The percentage of multipara female patients was more in the anaemic 19 (86.5%) group than in the non anaemic 12 (66.7%) group, again reinforcing the fact that anaemia contributes to gall stone formation. Different workers suggested differently about the serum cholesterol levels vis a vis cholelithiasis.[9] All non anaemic gall stone sufferers (n=27) had a high average serum iron content of 91 ± 35 microg/dl, as compared to anaemic ones (n=23), where average serum iron was 26 ± 9.5 μg/dl. The corresponding values for serum cholesterol were observed to be 183 18336 ± 36 mg% and 172 ± 49 mg% and that for gall bladder bile cholesterol were 0.70 ± 0.37 g% and 1.2 ± 0.41 g%, respectively [Table - 3]. There was no significant variation ( P =0.367) in the serum cholesterol of the two groups, whereas gall bladder bile cholesterol was significantly increased ( P < 0.0001) in the anaemic, than in the non anaemic group, thus suggesting that anaemia may be contributing to the super saturation of gall bladder bile with respect to cholesterol independent of serum cholesterol levels [Table - 3]. Probably anaemia, obesity and sex hormones are independent risk factors operating for the causation of gallstones and if present together, they produce synergistic effects. The scope of this study can be further advanced in the field of enzymes controlling gall bladder tone, motility and relaxation and cofactors affecting these enzymes Conclusion Low serum iron levels lead to bile supersaturation with respect to cholesterol, which leads to gallstone formation.References
Copyright 2006 - Indian Journal of Surgery The following images related to this document are available:Photo images[is06021t1.jpg] [is06021t3.jpg] [is06021t2.jpg] |
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