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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 7  |  Issue : 4  |  Page : 121-125

Correlation of gallstone disease with iron deficiency anemia


Department of General Surgery, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India

Date of Web Publication29-Oct-2018

Correspondence Address:
Dr. Sumanth Bille
26/23, 2nd Main, KGS Layout, Vijayanagar, Bengaluru - 560 040, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ais.ais_3_18

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  Abstract 


Association between gallstone disease and iron deficiency anemia is not uncommon. The objective of this study was to assess correlation between gallstone formation and iron deficiency anemia in patients presenting with gallstone disease.
Materials and Methods: A total of 60 patients' sonological evidence of gallstone were included in the study. Serum ferritin and serum iron levels were estimated. Gallstone patients were divided into anemic and non-anemic groups and compared with each other. Data were analyzed with descriptive statistical principles.
Patients and Methods: Chi-square test or Fisher's exact test , Yates correction, independent t-test or Mann–Whitney U test.
Results: There was significant association between serum iron and hemoglobin levels in patients with gallstone disease. This study suggests that iron deficiency leading to anemia plays a significant role in super saturation of bile, leading to stone formation in the gall bladder.
Conclusions: Low serum iron and ferritin levels were found to be statistically significant in gallstone patients. Significant correlation found between iron deficiency and gallstone disease. Iron deficiency and low serum ferritin are probably independent risk factors operating for the causation of gallstones.

Keywords: Gall bladder, gallstones, iron deficiency anemia, serum cholesterol, serum iron, serum ferritin


How to cite this article:
Babu RG, Bille S. Correlation of gallstone disease with iron deficiency anemia. Arch Int Surg 2017;7:121-5

How to cite this URL:
Babu RG, Bille S. Correlation of gallstone disease with iron deficiency anemia. Arch Int Surg [serial online] 2017 [cited 2018 Nov 18];7:121-5. Available from: http://www.archintsurg.org/text.asp?2017/7/4/121/244412




  Introduction Top


Cholelithiasis is one of the common diseases affecting mankind and the prevalence of calculous cholecystitis is increasing in South India. The prevalence of gallbladder stones varies widely in different parts of the world. In India it is estimated to be around 4%, whereas in western world it is 10%.[1]

Gallstones may occur as one large stone or hundreds of tiny stones almost in any combination. Cholesterol and calcium bilirubinate are the two main substances involved in gallstone formation. Gallstones derived from bile consist of mixture of cholesterol, bilirubin with, or without calcium. Based on their chemical composition, gallstones found in the gallbladder are classified as cholesterol, pigmented, or mixed stones.[2]

Four factors which explain gallstones are supersaturation of secreted bile, concentration of bile in gallbladder, crystal nucleation, and gallbladder dysmotility. Recent studies have identified the role of trace elements (iron, calcium, zinc, and copper) and defective pH in formation of gallstones.[3] Iron deficiency was found to be a new parameter in aetiology of gallstones.[3],[4],[5],[6]

Iron deficiency has been shown to alter the activity of several hepatic enzymes, leading to increased gallbladder cholesterol saturation and promotion of cholesterol crystal formation.[7],[8] Iron acts as a coenzyme for nitric oxide synthetase (NOS), which synthesizes nitric oxide (NO) important for the maintenance of gallbladder tone and normal relaxation.[9],[10] Alteration of motility of the gallbladder and  Sphincter of Oddi More Details leading to biliary stasis results in cholesterol crystal formation, which has been reported with iron deficiency.[11]

The objective of our study was to assess correlation between gallstone formation and iron deficiency anemia in patients presenting with gallstone disease.


  Patients and Methods Top


Prospective study was conducted on patients presenting with cholelithiasis admitted to various surgical units. All patients with sonological evidence of gallbladder stones formed subjects for the study. A total of 60 patients fulfilling the criteria were included in the study. Inclusion criteria included patients diagnosed with gallstone disease admitted in various surgical wards and confirmed by ultrasonography, both male and female patients: patients satisfying the above conditions and willing to give consent and participate in the study. Exclusion criteria included patients who opt out of study and not giving consent for the study, patients diagnosed with cirrhosis of liver on ultrasound scan, patients with gallstone diseases due to hemolytic anemias, patients diagnosed clinically with Crohn's disease, and cystic fibrosis.

Serum ferritin, serum cholesterol, serum iron along with other routine investigations were estimated in all 60 patients. Patients with gallstones were diagnosed with iron deficiency anemia based on hemoglobin levels, serum iron, and serum ferritin levels. Adult male with hemoglobin level <13 and adult female with <12 are diagnosed as anaemic. Normal serum ferritin levels in adult male average is 100 μg/L (15–200 μg/L) and in female average is 30 μg/L (12–150 μg/L). Normal serum iron levels in adult male is 60–160 μg/dL, and in female 35–145 μg/dL. Gallstone patients were divided into anaemic and non-anaemic groups and compared with each other. Data were analyzed with descriptive statistical principles.


  Results Top


Age incidence

Mean age of subjects was 42.58 ± 14.5 years, range was 21–77 years and median age was 41.5 years. Majority of subjects were in the age group 21–30 years [Table 1] and [Figure 1].
Table 1: Age distribution of subjects with gallstone disease

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Figure 1: Bar diagram showing age distribution of subjects with gallstone disease

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Sex distribution

In the study majority, i.e. 78.3% were females and 21.7% were males [Table 2] and [Figure 2].
Table 2: Gender distribution of subjects with gallstone disease

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Figure 2: Pie diagram showing gender distribution of subjects with gallstone disease

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Mean serum iron levels with respect to gender and iron deficiency

Among females mean serum iron in subjects with iron deficiency was 21.7 ± 6.3 and among males was 44.8 ± 5.

Among females mean serum iron in subjects without iron deficiency was 87.6 ± 22.6 and among males was 104.8 ± 24.8 [Table 3] and [Figure 3].
Table 3: Mean serum iron levels with respect to gender and iron deficiency

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Figure 3: Bar diagram showing mean serum iron levels with respect to gender and iron deficiency

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Distribution of serum iron according to anemia

Most of the patients with gallstone have serum iron level less than normal, and are anaemic. This association between low serum iron with anemia and gallstone disease was statistically significant in our study, P value of 0.003 [Table 4] and [Figure 4].
Table 4: Association between anaemia and Serum iron levels in gallstone patients

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Figure 4: Bar diagram showing association between anemia and serum iron levels

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Mean serum cholesterol levels with respect to iron deficiency anemia

Mean serum cholesterol among those with iron deficiency was 159 ± 53.8 mg/dL and among those without iron deficiency was 167.8 ± 44.2 mg/dL. There was no significant difference in mean serum cholesterol between iron deficiency and no deficiency, P value of 0.524. There is no effect of anemia on serum cholesterol [Table 5], [Figure 5] and [Figure 6]. Among females, 14.9% had raised serum cholesterol. Among males 7.7% had raised cholesterol.
Table 5: Mean serum cholesterol levels with respect to iron deficiency anaemia

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Figure 5: Bar diagram showing association between serum cholesterol levels and gender

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Figure 6: Bar diagram showing mean serum cholesterol levels with respect to iron deficiency anemia

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Association between serum ferritin levels and gender in gallstone patients

Among females, 19.1% had decreased serum ferritin and among males 23.1% had decreased serum ferritin. There was no significant association between serum ferritin and gender, P value of 0.754 [Table 6] and [Figure 7].
Table 6: Association between serum ferritin levels and gender in gallstone patients

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Figure 7: Bar diagram showing association between serum ferritin levels and gender

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Association between serum ferritin levels and anaemia in gallstone patients

There was significant association between low serum ferritin with anemia and gallstone disease in our study, P value of 0.004 [Table 7] and [Figure 8].
Table 7: Association between serum ferritin levels and anaemia in gallstone patients

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Figure 8: Bar diagram showing association between serum ferritin levels and anemia

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  Discussion Top


Majority of the subjects were in the age group of 20–50 years. In the series of Ghosh et al. and Shenoy et al. the highest incidence was found in the age group of 41–50 years.[12],[13] Tyagi et al. showed higher incidence in 30–40 years.[14] In Prasad et al. study majority of cases were in the age range of 20–40 years.[3]

In the study, majority i.e. 78.3% were females and 21.7% were males. In Kumar et al. study 80% were females and 20% were males. Similar sex preponderance was noted by Tamhankar et al. and Ganey et al.[15],[16]

This study suggests that iron deficiency plays a significant role in supersaturation of bile, leading to stone formation in the gall bladder. In study conducted by Prasad et al. 78% of the patients with gallstones had the value of serum iron less than normal. Most of the patients with gallstones have serum iron levels less than normal.[3]

In a study by Kannan et al. showed that the gallbladder bile cholesterol level was significantly higher in anaemic patients due to low serum iron as compared to that of non-anaemic patients with normal serum iron levels leading to gallstone formation.[4] In a study by Kumar et al., found that low serum iron levels lead to bile supersaturation with respect to cholesterol, which leads to gallstone formation.[6]

There was no significant association between iron deficiency anemia and serum cholesterol in patients with gallstone disease. In study by Prasad et al. found that there is no effect of iron deficiency anemia on serum cholesterol which is similar to our study.[3] In a study by Kannan et al., no statistically significant difference in serum cholesterol values of iron deficient and non-iron deficient groups, which is similar to our study.[4] In a study by Athar Parvez et al., there was no significant variation in the serum cholesterol of the two groups.[5] But in Halgaonkar et al. study, serum cholesterol levels were found to be raised in the majority of the patients.[2]

There was significant association between serum ferritin and hemoglobin levels in patients with gallstone disease. In Prasad et al. study, 74% of patients with gallstones have normal value of serum ferritin; in this 48% are anaemic. Serum ferritin cannot be taken as a sole diagnostic tool in the diagnosis of iron deficiency anemia as its value can vary due to other causes such as iron therapy, hepatocellular disease, and inflammations (since cholecystitis is an inflammatory condition, this could be the reason for the high level of serum ferritin).[3] In the study by Athar Parvez et al. correlation between low serum ferritin and increase in cholesterol level in bile was established. This result gives impression that in reference to serum cholesterol, deficiency of serum ferritin will lead to increase in saturation of biliary cholesterol which may enhance gallstone formation.[5]

There was no significant association between serum ferritin and gender. In Prasad et al. study, the number of females having normal serum ferritin levels (in both case and control groups) was more.[3]


  Conclusion Top


To conclude, there was significant correlation found between iron deficiency and gallstone disease. Iron deficiency and low serum ferritin are probably independent risk factors operating for the causation of gallstones. Prevention of iron deficiency anemia also prevents the possible development of gallstones in a healthy person.

Financial support and sponsorship

Nutrition Community Department of Ministry of Health and Medical Education.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Tandon R. Diseases of gall bladder and biliary tract. In: Shah SN, editor. API Textbook of Medicine. 9th ed, Mumbai: API Publications; 2012. p. 911.  Back to cited text no. 1
    
2.
Halgaonkar P, Verma R, Bhadre R, Unadkat P, Vaja C, Unadkat P. Study to establish the clinical correlation between chemical constituents of gallstones and serum biochemical parameters. Int J Sci Stud. 2016;4:97-102.  Back to cited text no. 2
    
3.
Prasad PC, Gupta S, Kaushik N. To study iron levels in patients of gallbladder stone disease and to compare with healthy individuals. Ind J Surg. 2015;77:19-22.  Back to cited text no. 3
    
4.
Kannan R, Ramalakshmi V, Reddy AV, Srivishnu S. Analysis of biliary cholesterol levels in iron deficient patients operated for gallstone disease. J Evid Based Med Healthc. 2017;4: 401-04.  Back to cited text no. 4
    
5.
Parvez A, Singh G, Chaubey D, Thakur S, Suparna, PN. “Can serum ferritin be a marker for lithogenic bile and gallstones? A prospective study”. Int J Curr Res. 2017;9:44933-37.  Back to cited text no. 5
    
6.
Kumar M, Goyal BB, Mahajan M, Singh S. Role of iron deficiency in formation of gall stones. Ind J Surg. 2006;68:80-3.  Back to cited text no. 6
    
7.
Swartz-Basile DA, Goldblatt MI, Blaser C, Decker PA, Ahrendt SA, Sarna SK. Iron deficiency diminishes gallbladder neuronal nitric oxide synthase. J Surg Res. 2000;90:26-31.  Back to cited text no. 7
    
8.
Kumar Muneesh, Goyal BB, Mahajan M, Singh S. Role of iron deficiency in the formation of gall stones. Ind J Surg.2006;68: 80-83.  Back to cited text no. 8
    
9.
Hamid H. Sarhan, Mahdi S. Hamed, Salim J. Khalaf. Relationship between iron deficiency and gall stones formation. Tikrit Med J. 2009;15:119-23.  Back to cited text no. 9
    
10.
Johnston SM, Murray KP, Martin SA, Fox-Talbot K, Lipsett PA, Lillemoe KD. Iron deficiency enhances cholesterol gallstone formation. Surgery. 1997;122:354-61;discussion 361-2.  Back to cited text no. 10
    
11.
Deborah A. Swartz-Basile, Matthew I. Goldblatt, Cindy Blaser, Philip A. Decker, Steven A. Ahrendt, Sushil K. Sarna. Iron deficiency diminishes gallbladder neuronal nitric oxide synthase. J Med Res. 2000;90;26-31.  Back to cited text no. 11
    
12.
Ghosh SK, Das KN, Bose D, Raj B, Sadhu BN, Roy D. Aetiopathogenisis of chronic cholecystitis in Gangetic West Bengal-A study of 300 cases. Ind J Surg. 1995;57:313-16.  Back to cited text no. 12
    
13.
Shenoy UAK, Nayak MN, Shenoy MG, Mohan K, Shivananda PG. Cholelithiasis in Manipal. Ind J Med Res. 1982;76:454-57.  Back to cited text no. 13
    
14.
Tyagi SP, Tyagi N, Maheshwari V, Ashraf SM, Sahoo P. Morphological changes in diseased gallbladder: A study of 415 cholecystectomies at Aligarh. J Ind Med Assoc. 1992;90:178-81.  Back to cited text no. 14
    
15.
Tamahankar AP, Nigam K, Houghton PW. The fate of gallstones: Traditional practice questioned. Ann R Coll Surg Engl. 2003;85:102-04.  Back to cited text no. 15
    
16.
Ganey JB, Johnson PA Jr, Prillaman PE, McSwain GR. Cholecystectomy: Clinical experience with a large series. Am J Surg. 1986;151:352-57.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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