Gallstone

A gallstone formed within the gallbladder as a result of changes in bile acid (BA) metabolism and gallbladder function are critical factors in the pathogenesis of gallstones. Gallstones can cause blockage the flow of bile through the bile ducts that can lead to inflammatory causes of  acute cholecystitis. Gallstones are most common among older adults, women, overweight people, etc.
 
A. Symptoms  
A.1. Common symptoms

1. Upper gastrointestinal bleeding if ruptured
There is a report of a 67-year-old gentleman with no significant medical history of note presented with sudden onset of epigastric pain, coffee ground vomiting and passing black tarry stool. The diagnosis of gallstone-induced auto-sphincterotomy was only made, using gastroscope via jejunostomy, when a big gallstone was found in the third part of the duodenum and the papilla was ruptured(1).

2. Right upper quadrant or midline epigastric pain
In a  multicenter study was carried out with patients randomized to either surgery or conservative, expectant treatment to examine optimal treatment and natural history in well-defined groups of symptomatic gallbladder stone disease with pain, episodes only (study group 1) or acute cholecystitis (study group 2). The patients were between 18 and 80 years of age and had right upper quadrant or midline epigastric pain and ultrasonographic evidence of gallbladder stone, with or without acute cholecystitis(2).

3. Abdominal pain
Gallstones are relatively rare in children. At-risk populations include patients suffering from hemolysis syndromes. Regardless of etiology, these patients usually will present with postprandial abdominal pain, and ultrasonography is the mainstay of diagnosis. However, some gallstones are radiopaque and can be visualized on plain abdominal radiography(3).

4. Other symptoms
In the study to evaluated the association between gallstones and abdominal symptoms, comparing two different study designs, researchers at the Maastricht University, showed that Gallstones were associated with mid upper abdominal pain in the screening study, and with mid upper abdominal pain, biliary pain, and colic (each independently) in the clinical study. When these symptoms were absent (and only dyspeptic symptoms or food intolerance was present), gallstones were not more common than expected from the general population prevalence (estimated from the screening study)(4).

5. Etc. 

A.2. Symptoms of severe case, include
1. Fever
2. Nausea and vomiting
3. Prolonged period of pain
4. Jaundice
5. Clay-colored stools
6. Etc.

 

B. Causes and Risk factors
B.1. Causes
 High cholesterol or bilirubin in the bile 
Gallstones are precipitations of oversaturated bile fluid. They can develop in the gallbladder and in the efferent bile ducts; they are very often correlated with diseases of the gallbladder, bile ducts and neighboring organs(5).

B.2. Risk factors
1. hypertriglyceridemia, overweight and insulin resistant
 Patients with hypertriglyceridemia (HTG) - often overweight and insulin resistant - are at risk for gallstone disease(6).

2. Pregnancy and gender
Pregnant women(6b)  and Elder are at higher risk to develop (specially, pigment stones in elder) gallstones(6a)

3. Haemoglobin E beta thalassaemia
in the study to  determine whether this has a genetic basis we compared the bilirubin levels and frequency of gallstones in patients with different alleles of the UGT*1 gene, showed that the UGT*1 genotpe is of importance in the genesis of gallstones in this population of patients(7).


4. Obesity and weight loss
In the study to investigate the relation of obesity and weight loss to the formation of gallstones according to pertinent clinical and research issues, showed that during weight loss, particularly among the obese, an increased risk exists for symptomatic gallstone formation. This acute risk offers the opportunity to investigate the cause of gallstones and possibly to prevent them(8).

5. Diet
Diet with high in saturated fat  and low in fiber increase the risk of gallstones as a result of  increased cholesterol in the bile.

6. Ethnicity
Certain races may be at the increased of the development of gallstone such as American Indians, Mexican  have a genetic predisposition to secrete high levels of cholesterol in bile.

7. Hormone replacement therapy in postmenopausal women and oral contraceptives have also been described to be associated with an increased risk for gallstone disease(8a).

C. Diagnosis
After completing the physical examination and family history, if gallstones are suspected, the tests which your doctor orders include
1. Blood tests
The aim of the blood test is to look for the signs of infection, obstruction, pancreatitis, jaundice, liver enzymes, etc.

2. Ultrasonography 
The aim of the test is to look for the images of the abnormalltyof gallbladder and its surrounding area, including the thickened wall of the gallbladder when there is cholecystitis, pancreatitis, enlarged gallbladder, bile duct obstruction, etc.

3. Computerized tomography (CT) scan
the aim of the CT scan to allow your doctor to visualize the gallbladder and its surrounding area, including gallstones, infection, rupture of gallbladder, etc..

4. Cholescintigraphy (HIDA scan)
The aim of the test is to diagnose the abnormal contraction of the gallbladder with the injection of with a small amount of radioactive material


5. Endoscopic retrograde cholangiopancreatography (ERCP)
With the local anesthesia and the use of a The endoscope, your doctor can visualize the gallstone and remove them if found. 

6. Etc.

D. Complications and Diseases associated with gallstone 
1. Spontaneous cholecystocutaneous fistula
Spontaneous perforation of gallbladder as a complication of biliary stones may lead to a cholecystocutaneous abscess or fistula. The pathophysiology of this condition has been associated with increased pressure in the gallbladder, secondary to biliary obstruction(9).

2. Jaundice
In the study to evaluate 56 patients with obstructive jaundice, the presence or absence of calculi in the gallbladder has been correlated with the cause of the obstruction. Seven of 23 patients with obstruction caused by stone had no calculi in the gallbladder. Twelve of 33 patients with obstruction due to tumor also had gallstones. It was concluded that the presence of calculi in the gallbladder is a poor indicator of the cause of obstructive jaundice(10).

3. Others diseases associated with gallstones
a. In Children
In the review of the risk factors, complications, and outcomes of gallstones at our institution, particularly in those patients who are asymptomatic at the time of initial diagnosis, researchers at the The Hospital for Sick Children, Toronto, showed that at diagnosis, 50.5% of children were asymptomatic; these patients were diagnosed at a mean age of 8.23 years. Compared with symptomatic patients, they were less likely to have a hemolytic anemia but more likely to have other risk factors, including cardiac surgery, leukemia and lymphoma, short bowel syndrome, or exposure to total parenteral nutrition or cephalosporins(11). 

b. In Adult
Gallstones cause various problems besides simple biliary colic and choplecystitis. With chronicity of inflammation caused by gallstone obstruction of the cystic duct, the gallbladder may fuse to the extrahepatic biliary tree, causing Mirizzi syndrome, or fistulize into the intestinal tract, causing so-called gallstone ileus. Stones may pass out of the gallbladder and travel downstream through the common bile duct to obstruct the ampulla of Vater resulting in gallstone pancreatitis, or pass out of the gallbladder inadvertently during surgery, resulting in the syndromes associated with lost gallstones(12).

E. Prevention
1. Vegetable
Vegetable protein may reduce the risk of cholelithiasis(19)

2. A low-fat, low-protein, high-carbohydrate or lowering of glycaemic index and the caloric reduction diet may reduce the risk of formation of gallstone formation(21)

3. Reduce intake of bad fat(23)
In the study of found  that  the type of dietary fat habitually consumed can influence bile composition in humans. In gallbladder, this influence was noted in the presence of more concentrated bile in the olive oil group. However, this was not translated into a modification of cholesterol saturation, which is likely due to the fact that cholesterol gallstones were present by the time the dietary intervention started(22).

4. Nuts
Nuts (tree nuts and peanuts) are nutrient dense foods with complex matrices rich in unsaturated fatty and other bioactive compounds: high-quality vegetable protein, fiber, minerals, tocopherols, phytosterols, and phenolic compounds According to the study by Dr, Ros E nuts are likely to beneficially impact health outcomes. Epidemiologic studies have associated nut consumption with a reduced incidence of coronary heart disease and gallstones in both genders and diabetes in women(20).

5. Wheat bran
There is a study of 10 patients with probable cholesterol gallstones took bran supplements for 4-6 weeks, their gallbladder bile aspirated from the duodenum became less saturated with cholesterol(24).

6. Others
Some researchers suggested that intake of high energy, simple sugar and saturated fat favors gallstone formation. Fiber and moderate consumption of alcohol reduce the risk(25).



F. Treatment
F.1. In conventional medicine perspective
1. Cholecystectomy
No treatment for people who have developed galldtones but with no system, otherwise, surgery to remove the gallbladder may be necessary. Cholecystectomy is the surgical removal of the symptomatic gallbladder. In the sugery, It is the most common method for treating symptomatic gallstones, other surgeries include the  laparoscopic cholecystectomy, and an older more invasive procedure, called open cholecystectomy.

2. Others
a. Some researchers suggested for the treatment of gallstones in patients with normal stonefree bile ducts, new modalities have been developed besides the classical cholecystectomy and the oral litholysis. The interventional procedures (local litholysis, extracorporeal shockwave lithotripsy, combination of shockwave lithotripsy and local litholysis, cholecystostomy and extra- or intracorporeal lithotripsy) do not need a narcosis and can be applied even in high-risk patients. Because the gallbladder itself is not removed, the recurrence rate after all these interventions is rather high. The new operative procedures (laparoscopic cholecystectomy, mini-laparotomy cholecystectomy) are definitive solutions for stone disease, but must be performed mostly in narcosis(13).

b. Today, cholecystectomy was still the most frequent method of treatment for symptomatic cholecystolithiasis (n = 1369) with low morbidity (4.3%) and lethality (0.28%). Probably less than 20% of all cases fulfill the strict selection criteria for extracorporeal shock wave lithotripsy (ESWL). All alternative methods of treatment in which the gallbladder is preserved have an increased risk for gall stone recurrence. Only after the long-term follow-up results of ESWL are known, the recurrence rate can be assessed. In most cases, bile duct stones (n = 417) were removed by endoscopy, if necessary in combination with ESWL (n = 310, stone removal: 95%, lethality: 0.3%). However, in low risk patients with concurrent cholecystolithiasis surgery was still the method of choice (n = 107, stone removal: 96%, lethality: 0/107)(14).

F.2. In herbal medicine perspective
1. Fenugreek seeds and onion
In the study to evaluate the antilithogenic effect of a combination of dietary fenugreek seeds and onion, researchers at the Central Food Technological Research Institute, found that hepatic lipid peroxides were reduced by 19-22% and 39-45% with fenugreek, onion and their combination included in the diet along with the HCD. Increased accumulation of fat in the liver and inflammation of the gallbladder membrane produced by HCD were reduced by fenugreek, onion and their combination. The antilithogenic influence was highest with fenugreek alone, and the presence of onion along with it did not further increase this effect(15).

2. Capsaicin and curcumin
In the study of the efficacy of capsaicin and curcumin in cholesterol gallstones induced by feeding mice a high-cholesterol (0.5%) diet for 10 weeks, found that the capsaicin and curcumin combination did not have an additive influence in reducing the incidence of cholesterol gallstones in mice, their combination nevertheless was more beneficial in enhancing the activity of hepatic antioxidant enzyme ─ glutathione reductase in the lithogenic situation. The antioxidant effects of dietary spice compounds are consistent with the observed reduction in cholesterol gallstones formed under lithogenic condition(16).

3. Garlic and onion
The Central Food Technological Research Institute has reported the study of the health beneficial potential of dietary garlic and onion in reducing the incidence and severity of cholesterol gallstone (CGS)with the induced CGS in mice with a lithogenic diet for 10 weeks, they were maintained on basal diets containing 0.6% dehydrated garlic or 2% dehydrated onion for a further 10 weeks(26). Others suggested that dietary allium spices exerted antilithogenic influence by decreasing the cholesterol hyper-secretion into bile and increasing the bile acid output thus decreasing the formation of lithogenic bile in experimental mice(27).

4. Milk thistle
There is a study indicated that after intake of milk thistle bile duct hyperplasia were significantly decreased in 50,000 ppm males and in all exposed groups of females, and the incidence of mixed inflammatory cell infiltration was significantly decreased in 50,000 ppm males(28).


5. Etc.

F.3. In traditional Chinese perpective
1. Traditional Chinese herbs for nourishing the liver (Yanggan Lidan Granule (YGLDG))
In the study of Eighty guinea pigs randomly divided into four groups, which were normal control group, untreated group, nourishing-liver Chinese drug (NLCD) group and ursodeoxycholic acid (UDCA) group, with 20 guinea pigs in each group, gallstones were induced in the guinea pigs of the latter 3 groups by the feed of diet inducing cholelithiasis with high cholesterol, while the corresponding medicines were used in NLCD group and UDCA group for prevention and treatment for 7 weeks, showed that the [Ca(2+)]i in gallbladder cells is the important factor for contractile function of gallbladder and the information of gallstones. Traditional Chinese herbs for nourishing the liver may significantly increase the [Ca(2+)]i in gallbladder cells to facilitate contraction of the smooth muscle cells of gallbladder and relieve the cholestatis(17).
Other study to explore the effects of Yanggan Lidan Granule (YGLDG), a compound traditional Chinese herbal medicine for nourishing liver and improving choleresis, on the rate of gallstone formation and content of plasma cholecystokinin in guinea pigs with induced cholesterol gallstones. indicated that YGLDG can significantly decrease the rate of gallstone formation in guinea pigs. It may be related to elevating the content of CCK in the plasma(18).

2. Ingredients of Yanggan Lidan Granule (YGLDG) 
a. Bai Shao tonifies liver Yin,
b. Chen Pi,
c. Gao Qi Zi tonifies liver Yin
d. He shou wu tonifies liver Yin
e. Gan Cao
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(10) http://www.ncbi.nlm.nih.gov/pubmed/7434173
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(12) http://www.ncbi.nlm.nih.gov/pubmed/18992599 
(13) http://www.ncbi.nlm.nih.gov/pubmed/2028140
(14) http://www.ncbi.nlm.nih.gov/pubmed/2721300
(15) http://www.ncbi.nlm.nih.gov/pubmed/21756271
(16) http://www.ncbi.nlm.nih.gov/pubmed/21609281
(17) http://www.ncbi.nlm.nih.gov/pubmed/17352876
(18) http://www.ncbi.nlm.nih.gov/pubmed/18405610 
(19) http://www.ncbi.nlm.nih.gov/pubmed/1503808
(20) http://www.ncbi.nlm.nih.gov/pubmed/22254047
(21) http://www.ncbi.nlm.nih.gov/pubmed/14619611
(22) http://www.ncbi.nlm.nih.gov/pubmed/15797676
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(26) http://www.ncbi.nlm.nih.gov/pubmed/20153000
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(28) http://www.ncbi.nlm.nih.gov/pubmed?term=Milk%20thistle%20and%20gallstone