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Progesteroneand gallbladder stone

Dr Sanjay Agrawal
Wednesday, October 18, 2017, 08:00 Hrs  [IST]

The gallbladder is only a storage organ and bile is formed in the liver. It comprises cholesterol, bile acids, electrolytes, phospholipids and bilirubin. Bile salts from blood into bile is essential for the generation of bile flow and to solubilise cholesterol in bile. The most common problems are gallstones which form in the liver, gallbladder and the bile duct.

Gallstones are solid lumps that develop when the stored bile crystallizes. They comprise cholesterol stones, which make up over 80%, caused by an excess of cholesterol in bile and insufficient bile salts, and pigment stones, made principally of bilirubin and calcium salts, caused by an excess of bilirubin in bile.  Most are less than an inch in diameter, but they can be as small as a grain of sand or as large as a golf ball. Most gallstones are composed mainly of cholesterol. The rest known as pigment stones are made of calcium salts and bilirubin, a breakdown product of red blood cells. Gallstones cause problems when they block any of the ducts carrying bile from the liver or gallbladder (or digestive enzymes from the pancreas) to the small intestine.

Cholesterol stones form when liquid bile in the gallbladder contains more cholesterol than the bile salts can dissolve. 17(beta)-glucuronides of oestradiol and oestradiol-17-D-glucuronide are known to induce cholestasis, or malfunctioning of the liver, causing inhibition of bile flow. Most studies blame progesterone as cholestasis occurs during pregnancy. Cholesterol stones may also develop if the gallbladder doesn't contract and empty as it should. Pigment stones are associated with certain medical conditions, including liver disease, some types of anemia, and infection of the bile ducts.

Women at greater risk
Ratio of women to men with gallbladder problems is about 80% women to 20% men, or 4:1. It's the effect of female hormones. Estrogen increases cholesterol in the bile, and progesterone slows the emptying of the gallbladder. That may explain why the risk for women, relative to men, decreases with age. Before age of 40, women are diagnosed with gallstones almost three times more often than men are (pregnancy, for example, increases the risk), but at age 60, their risk is just slightly greater. Estrogen therapy increases the risk, especially when taken as a pill rather than a patch. Oral contraceptive pills also increase the risk slightly, but only in the first decade of use.

Women are also at increased risk of developing chronic acalculous cholecystitis and sphincter of Oddi dysfunction. Problems in the gallbladder stem from insufficient bile production, toxins, slow flow of bile, an excess of cholesterol in the bile (which causes stones to form), infections, poor choice of foods, excess oestrogen, contraceptive pills and HRT, certain blood disorders. Obesity is another risk factor, because bodies with more fat produce more estrogen. Paradoxically, rapid weight loss also increases the risk, because very low-calorie diets interfere with bile production and therefore cause more crystallization of cholesterol. Gallstones are so common after weight-loss surgery that patients are often advised to have their gallbladders removed at the same time. Gallstones are also more likely to occur in people with diabetes or any condition that decreases gallbladder contractions or intestinal motility, such as a spinal cord injury. Finally, there's some evidence for genetic vulnerability to gallstone formation.

Most people who have gallstones don't know about it. Their gallstones stay silent and may only be discovered incidentally, through an ultrasound or CT scan performed for other reasons.

If insufficient taurine is eaten in the diet, the liver cannot make bile. Taurine is not found in vegetables, only in meat. The body can convert it from the amino acid cysteine, but if stressed or insufficient cysteine is eaten, taurine will be low. Taurine is essential for the heart and eyes, cholesterol excretion, heart disease and blood sugar control. Symptoms arise mainly when stones pass through a bile duct or obstruct it, causing biliary colic - better known as a gallbladder attack. These attacks occur when the gallbladder contracts (usually in response to a fatty meal) and presses the stones so as to block the gallbladder duct.
The main symptom is pain, usually in the right upper or middle abdomen (just below the rib cage), which builds to greatest intensity within an hour and can persist up to several hours. It can be either sharp or knife like or a deep ache; sometimes it radiates to the back or the right shoulder. There may also be nausea and vomiting. The pain subsides as the gallbladder relaxes.

A stone lodged in a duct can also cause more serious problems, including acute cholecystitis (inflammation of the gallbladder), pancreatitis (inflammation of the pancreas), or cholangitis (inflammation of the bile ducts in the liver). Any of these conditions can cause severe pain and other symptoms, including jaundice, high fever, chills, and vomiting. Treatment usually requires intravenous antibiotics and often surgical removal of the stone.

If you think have a gallbladder attack, your clinician will probably order several blood tests and an abdominal ultrasound (after you fast for at least eight hours). Ultrasound is particularly helpful in diagnosing acute cholecystitis because it also picks up any thickening of the gallbladder wall and indicates the presence of fluid, which may suggest inflammation. Other diagnostic techniques include cholescintigraphy, a radioactive injection used to view a possible blockage of the cystic duct; MRI of the bile ducts; endoscopic ultrasonography, which introduces an ultrasound device through the mouth, esophagus, and stomach to the duodenum (the first section of the small intestine) to get images of the area; and endoscopic retrograde cholangiopancreatography, which uses a scope inserted through the mouth to the duodenum to view the biliary ducts.

Gallstones should be treated only if they cause symptoms. For recurrent gallbladder attacks, the most effective treatment is surgical removal of the gallbladder, or cholecystectomy. In the past, the standard procedure was surgery requiring a five-inch incision and a hospital stay of up to a week. This approach has largely been replaced by laparoscopic cholecystectomy, in which the gallbladder is removed with instruments inserted through small incisions in the skin. This procedure requires only an overnight hospital stay and a week of recovery at home. However, there's a slight risk of injuring the bile ducts, and in  5% to 10% of cases, the surgeon may have to switch to an open surgery with a larger incision because of complications. You can easily live without a gallbladder. The liver produces enough bile for normal digestion. When the gallbladder is removed, bile simply flows directly into the small intestine through the common bile duct. When no food is present, loose stools may result, but you can treat that with a bile acid-binding medication like cholestyramine.

Medical options
If you don't want to undergo surgery and your gallstones are small, one option is to take ursodeoxycholic acid, under medical supervision a naturally occurring bile acid that helps dissolve cholesterol stones when taken by mouth two to four times a day. It's also used to prevent the formation of gallstones in people who are losing weight quickly. Ursodeoxycholic acid, dissolves only those gallstones made of cholesterol, and it may take several months before it has an effect. Drug therapy is occasionally combined with lithotripsy, in which sound waves from outside the body are used to break gallstones into pieces that dissolve more easily or are small enough to safely pass through the bile duct. Unfortunately, stones are likely to recur after medical treatment.

Risk reducingfactors
There's no proven way to prevent gallstones, but research suggests some possibilities. Eat three well-balanced meals daily, maintain a normal weight, and get regular exercise (at least 30 minutes a day most days of the week). Several studies have linked moderate alcohol consumption to a lower risk for symptom-causing gallstones. It also found that women with more fiber in their diets and those who ate several 1-ounce servings of nuts per week were less likely to need gallbladder surgery. Avoiding fatty foods won't prevent or get rid of gallstones, but it may reduce the frequency of attacks.

(Author is a pharmaceutical consultant)


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