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March 30, 2010

lipids,gallstones


Lipids are the one class of large biological molecules that does not consist of polymers. The compounds called lipids are grouped together because they share one important trait: They have little or no affinity for water. The hydrophobic behavior of lipids is based on their molecular structure. Although they may have some polar bonds associated with oxygen, lipids consist mostly of hydrocarbons. Smaller than true (polymeric) macromolecules, lipids are a highly varied group in both form and function. Lipids include waxes and certain pigments, but we will focus on the most biologically important types of lipids: fats, phospholipids, and steroids.
Fats
Although fats are not polymers, they are large molecules, and they are assembled from smaller molecules by dehydration reactions. A fat is constructed from two kinds of smaller molecules: glycerol and fatty acids.

The synthesis and structure of a fat, or triacylglycerol. The molecular building blocks of a fat are one molecule of glycerol and three molecules of fatty acids. (a) One water molecule is removed for each fatty acid joined to the glycerol. (b) A fat molecule with three identical fatty acid units. The carbons of the fatty acids are arranged zig–zag to suggest the actual orientations of the four single bonds extending from each carbon.

Glycerol is an alcohol with three carbons, each bearing a hydroxyl group. A fatty acid has a long carbon skeleton, usually 16 or 18 carbon atoms in length. At one end of the fatty acid is a carboxyl group, the functional group that gives these molecules the name fatty acid. Attached to the carboxyl group is a long hydrocarbon chain. The nonpolar C–H bonds in the hydrocarbon chains of fatty acids are the reason fats are hydrophobic. Fats separate from water because the water molecules hydrogen–bond to one another and exclude the fats. A common example of this phenomenon is the separation of vegetable oil (a liquid fat) from the aqueous vinegar solution in a bottle of salad dressing.

In making a fat, three fatty acid molecules each join to glycerol by an ester linkage, a bond between a hydroxyl group and a carboxyl group. The resulting fat, also called a triacylglycerol , thus consists of three fatty acids linked to one glycerol molecule. (Still another name for a fat is triglyceride, a word often found in the list of ingredients on packaged foods.) The fatty acids in a fat can be the same, as in Figure 5.11b, or they can be of two or three different kinds.

These terms refer to the structure of the hydrocarbon chains of the fatty acids. If there are no double bonds between carbon atoms composing the chain, then as many hydrogen atoms as possible are bonded to the carbon skeleton. Such a structure is described as being saturated with hydrogen, so the resulting fatty acid is called a saturated fatty acid. An unsaturated fatty acid has one or more double bonds, formed by the removal of hydrogen atoms from the carbon skeleton. The fatty acid will have a kink in its hydrocarbon chain wherever a cis double bond occurs.

A fat made from saturated fatty acids is called a saturated fat. Most animal fats are saturated: The hydrocarbon chains of their fatty acids—the “tails” of the fat molecules—lack double bonds, and the molecules can pack tightly, side by side. Saturated animal fats—such as lard and butter—are solid at room temperature. In contrast, the fats of plants and fishes are generally unsaturated, meaning that they are built of one or more types of unsaturated fatty acids. Usually liquid at room temperature, plant and fish fats are referred to as oils—olive oil and cod liver oil are examples. The kinks where the cis double bonds are located prevent the molecules from packing together closely enough to solidify at room temperature. The phrase “hydrogenated vegetable oils” on food labels means that unsaturated fats have been synthetically converted to saturated fats by adding hydrogen. Peanut butter, margarine, and many other products are hydrogenated to prevent lipids from separating out in liquid (oil) form.
A diet rich in saturated fats is one of several factors that may contribute to the cardiovascular disease known as atherosclerosis. In this condition, deposits called plaques develop within the walls of blood vessels, causing inward bulges that impede blood flow and reduce the resilience of the vessels. Recent studies have shown that the process of hydrogenating vegetable oils produces not only saturated fats but also unsaturated fats with trans double bonds. These trans fat molecules may contribute more than saturated fats to atherosclerosis and other problems.

Fat has come to have such a negative connotation in our culture that you might wonder whether fats serve any useful purpose. The major function of fats is energy storage. The hydrocarbon chains of fats are similar to gasoline molecules and just as rich in energy. A gram of fat stores more than twice as much energy as a gram of a polysaccharide, such as starch. Because plants are relatively immobile, they can function with bulky energy storage in the form of starch. (Vegetable oils are generally obtained from seeds, where more compact storage is an asset to the plant.) Animals, however, must carry their energy stores with them, so there is an advantage to having a more compact reservoir of fuel—fat. Humans and other mammals stock their long–term food reserves in adipose cells (see Figure 4.6b), which swell and shrink as fat is deposited and withdrawn from storage. In addition to storing energy, adipose tissue also cushions such vital organs as the kidneys, and a layer of fat beneath the skin insulates the body. This subcutaneous layer is especially thick in whales, seals, and most other marine mammals, protecting them from cold ocean water.


The structure of a phospholipid. A phospholipid has a hydrophilic (polar) head and two hydrophobic (nonpolar) tails. Phospholipid diversity is based on differences in the two fatty acids and in the groups attached to the phosphate group of the head. This particular phospholipid, called a phosphatidylcholine, has an attached choline group. The kink in one of its tails is due to a cis double bond. (a) The structural formula follows a common chemical convention of omitting the carbons and attached hydrogens of the hydrocarbon tails. (b) In the space–filling model, black = carbon, gray = hydrogen, red = oxygen, yellow = phosphorus, and blue = nitrogen.

A phospholipid is similar to a fat, but has only two fatty acids attached to glycerol rather than three. The third hydroxyl group of glycerol is joined to a phosphate group, which has a negative electrical charge. Additional small molecules, usually charged or polar, can be linked to the phosphate group to form a variety of phospholipids.

Phospholipids show ambivalent behavior toward water. Their hydrocarbon tails are hydrophobic and are excluded from water. However, the phosphate group and its attachments form a hydrophilic head that has an affinity for water. When phospholipids are added to water, they self–assemble into double–layered aggregates—bilayers—that shield their hydrophobic portions from water.

Steroids
Steroids are lipids characterized by a carbon skeleton consisting of four fused rings.

Different steroids vary in the functional groups attached to this ensemble of rings. One steroid, cholesterol , is a common component of animal cell membranes and is also the precursor from which other steroids are synthesized. Many hormones, including vertebrate sex hormones, are steroids produced from cholesterol. Thus, cholesterol is a crucial molecule in animals, although a high level of it in the blood may contribute to atherosclerosis. Both saturated fats and trans fats exert their negative impact on health by affecting cholesterol levels.

What are gallstones?
Gallstones are small, pebble-like substances that develop in the gallbladder. The gallbladder is a small, pear-shaped sac located below your liver in the right upper abdomen. Gallstones form when liquid stored in the gallbladder hardens into pieces of stone-like material. The liquid—called bile—helps the body digest fats. Bile is made in the liver, then stored in the gallbladder until the body needs it. The gallbladder contracts and pushes the bile into a tube—called the common bile duct—that carries it to the small intestine, where it helps with digestion.

Bile contains water, cholesterol, fats, bile salts, proteins, and bilirubin—a waste product. Bile salts break up fat, and bilirubin gives bile and stool a yellowish-brown color. If the liquid bile contains too much cholesterol, bile salts, or bilirubin, it can harden into gallstones.

The two types of gallstones are cholesterol stones and pigment stones. Cholesterol stones are usually yellow-green and are made primarily of hardened cholesterol. They account for about 80 percent of gallstones. Pigment stones are small, dark stones made of bilirubin. Gallstones can be as small as a grain of sand or as large as a golf ball. The gallbladder can develop just one large stone, hundreds of tiny stones, or a combination of the two.

Gallstones can block the normal flow of bile if they move from the gallbladder and lodge in any of the ducts that carry bile from the liver to the small intestine. The ducts include the hepatic ducts, which carry bile out of the liver cystic duct, which takes bile to and from the gallbladder common bile duct, which takes bile from the cystic and hepatic ducts to the small intestine.

Bile trapped in these ducts can cause inflammation in the gallbladder, the ducts, or in rare cases, the liver. Other ducts open into the common bile duct, including the pancreatic duct, which carries digestive enzymes out of the pancreas. Sometimes gallstones passing through the common bile duct provoke inflammation in the pancreas—called gallstone pancreatitis—an extremely painful and potentially dangerous condition.


If any of the bile ducts remain blocked for a significant period of time, severe damage or infection can occur in the gallbladder, liver, or pancreas. Left untreated, the condition can be fatal. Warning signs of a serious problem are fever, jaundice, and persistent pain.

What causes gallstones?
Scientists believe cholesterol stones form when bile contains too much cholesterol, too much bilirubin, or not enough bile salts, or when the gallbladder does not empty completely or often enough. The reason these imbalances occur is not known.

The cause of pigment stones is not fully understood. The stones tend to develop in people who have liver cirrhosis, biliary tract infections, or hereditary blood disorders—such as sickle cell anaemia—in which the liver makes too much bilirubin.

The mere presence of gallstones may cause more gallstones to develop. Other factors that contribute to the formation of gallstones, particularly cholesterol stones, include

Sex. Women are twice as likely as men to develop gallstones. Excess estrogen from pregnancy, hormone replacement therapy, and birth control pills appears to increase cholesterol levels in bile and decrease gallbladder movement, which can lead to gallstones.

Family history. Gallstones often run in families, pointing to a possible genetic link.

Weight. A large clinical study showed that being even moderately overweight increases the risk for developing gallstones. The most likely reason is that the amount of bile salts in bile is reduced, resulting in more cholesterol. Increased cholesterol reduces gallbladder emptying. Obesity is a major risk factor for gallstones, especially in women.

Diet. Diets high in fat and cholesterol and low in fiber increase the risk of gallstones due to increased cholesterol in the bile and reduced gallbladder emptying.

Rapid weight loss. As the body metabolizes fat during prolonged fasting and rapid weight loss—such as “crash diets”—the liver secretes extra cholesterol into bile, which can cause gallstones. In addition, the gallbladder does not empty properly.

Age. People older than age 60 are more likely to develop gallstones than younger people. As people age, the body tends to secrete more cholesterol into bile.

Ethnicity. American Indians have a genetic predisposition to secrete high levels of cholesterol in bile. In fact, they have the highest rate of gallstones in the United States. The majority of American Indian men have gallstones by age 60.

Cholesterol-lowering drugs. Drugs that lower cholesterol levels in the blood actually increase the amount of cholesterol secreted into bile. In turn, the risk of gallstones increases.

Diabetes. People with diabetes generally have high levels of fatty acids called triglycerides. These fatty acids may increase the risk of gallstones.

Who is at risk for gallstones?

People at risk for gallstones include :
women—especially women who are pregnant, use hormone replacement therapy, or take birth control pills
people over age 60
overweight or obese men and women
people who fast or lose a lot of weight quickly
people with a family history of gallstones
people with diabetes
people who take cholesterol-lowering drugs

What are the symptoms of gallstones?
As gallstones move into the bile ducts and create blockage, pressure increases in the gallbladder and one or more symptoms may occur. Symptoms of blocked bile ducts are often called a gallbladder “attack” because they occur suddenly. Gallbladder attacks often follow fatty meals, and they may occur during the night. A typical attack can causesteady pain in the right upper abdomen that increases rapidly and lasts from 30 minutes to several hours pain in the back between the shoulder blades pain under the right shoulder

Notify your doctor if you think you have experienced a gallbladder attack. Although these attacks often pass as gallstones move, your gallbladder can become infected and rupture if a blockage remains.

People with any of the following symptoms should see a doctor immediately:
prolonged pain—more than 5 hours
nausea and vomiting
fever—even low-grade—or chills
yellowish color of the skin or whites of the eyes
clay-coloured stools

Many people with gallstones have no symptoms; these gallstones are called “silent stones.” They do not interfere with gallbladder, liver, or pancreas function and do not need treatment.

How are gallstones diagnosed?
Frequently, gallstones are discovered during tests for other health conditions. When gallstones are suspected to be the cause of symptoms, the doctor is likely to do an ultrasound exam—the most sensitive and specific test for gallstones. A handheld device, which a technician glides over the abdomen, sends sound waves toward the gallbladder. The sound waves bounce off the gallbladder, liver, and other organs, and their echoes make electrical impulses that create a picture of the gallbladder on a video monitor. If gallstones are present, the sound waves will bounce off them, too, showing their location. Other tests may also be performed.

Computerized tomography (CT) scan. The CT scan is a noninvasive x ray that produces cross-section images of the body. The test may show the gallstones or complications, such as infection and rupture of the gallbladder or bile ducts.

Cholescintigraphy (HIDA scan). The patient is injected with a small amount of nonharmful radioactive material that is absorbed by the gallbladder, which is then stimulated to contract. The test is used to diagnose abnormal contraction of the gallbladder or obstruction of the bile ducts.

Endoscopic retrograde cholangiopancreatography (ERCP). ERCP is used to locate and remove stones in the bile ducts. After lightly sedating you, the doctor inserts an endoscope—a long, flexible, lighted tube with a camera—down the throat and through the stomach and into the small intestine. The endoscope is connected to a computer and video monitor. The doctor guides the endoscope and injects a special dye that helps the bile ducts appear better on the monitor. The endoscope helps the doctor locate the affected bile duct and the gallstone. The stone is captured in a tiny basket and removed with the endoscope.

Blood tests. Blood tests may be performed to look for signs of infection, obstruction, pancreatitis, or jaundice.

Because gallstone symptoms may be similar to those of a heart attack, appendicitis, ulcers, irritable bowel syndrome, hiatal hernia, pancreatitis, and hepatitis, an accurate diagnosis is important.

How are gallstones treated?
Surgery. If you have gallstones without symptoms, you do not require treatment. If you are having frequent gallbladder attacks, your doctor will likely recommend you have your gallbladder removed—an operation called a cholecystectomy. Surgery to remove the gallbladder—a nonessential organ—is one of the most common surgeries performed on adults in the United States.

Nearly all cholecystectomies are performed with laparoscopy. After giving you medication to sedate you, the surgeon makes several tiny incisions in the abdomen and inserts a laparoscope and a miniature video camera. The camera sends a magnified image from inside the body to a video monitor, giving the surgeon a close-up view of the organs and tissues. While watching the monitor, the surgeon uses the instruments to carefully separate the gallbladder from the liver, bile ducts, and other structures. Then the surgeon cuts the cystic duct and removes the gallbladder through one of the small incisions.

Recovery after laparoscopic surgery usually involves only one night in the hospital, and normal activity can be resumed after a few days at home. Because the abdominal muscles are not cut during laparoscopic surgery, patients have less pain and fewer complications than after “open” surgery, which requires a 5- to 8-inch incision across the abdomen.

If tests show the gallbladder has severe inflammation, infection, or scarring from other operations, the surgeon may perform open surgery to remove the gallbladder. In some cases, open surgery is planned; however, sometimes these problems are discovered during the laparoscopy and the surgeon must make a larger incision. Recovery from open surgery usually requires 3 to 5 days in the hospital and several weeks at home. Open surgery is necessary in about 5 percent of gallbladder operations.

The most common complication in gallbladder surgery is injury to the bile ducts. An injured common bile duct can leak bile and cause a painful and potentially dangerous infection. Mild injuries can sometimes be treated nonsurgically. Major injury, however, is more serious and requires additional surgery.

If gallstones are present in the bile ducts, the physician—usually a gastroenterologist—may use ERCP to locate and remove them before or during gallbladder surgery. Occasionally, a person who has had a cholecystectomy is diagnosed with a gallstone in the bile ducts weeks, months, or even years after the surgery. The ERCP procedure is usually successful in removing the stone in these cases.

Nonsurgical Treatment.Nonsurgical approaches are used only in special situations—such as when a patient has a serious medical condition preventing surgery—and only for cholesterol stones. Stones commonly recur within 5 years in patients treated nonsurgically.

Oral dissolution therapy. Drugs made from bile acid are used to dissolve gallstones. The drugs ursodiol (Actigall) and chenodiol (Chenix) work best for small cholesterol stones. Months or years of treatment may be necessary before all the stones dissolve. Both drugs may cause mild diarrhea, and chenodiol may temporarily raise levels of blood cholesterol and the liver enzyme transaminase.

Contact dissolution therapy. This experimental procedure involves injecting a drug directly into the gallbladder to dissolve cholesterol stones. The drug—methyl tert-butyl ether—can dissolve some stones in 1 to 3 days, but it causes irritation and some complications have been reported. The procedure is being tested in symptomatic patients with small stones.

Do people need their gallbladder?
Fortunately, the gallbladder is an organ people can live without. Your liver produces enough bile to digest a normal diet. Once the gallbladder is removed, bile flows out of the liver through the hepatic ducts into the common bile duct and directly into the small intestine, instead of being stored in the gallbladder. Because now the bile flows into the small intestine more often, softer and more frequent stools can occur in about 1 percent of people. These changes are usually temporary, but talk with your health care provider if they persist.

Points to Remember
Gallstones form when bile hardens in the gallbladder.

Gallstones are more common among older adults; women;  people with diabetes; those with a family history of gallstones; people who are overweight, obese, or undergo rapid weight loss; and those taking cholesterol-lowering drugs.

Gallbladder attacks often occur after eating a meal, especially one high in fat.

Symptoms can mimic those of other problems, including a heart attack, so an accurate diagnosis is important.

Gallstones can cause serious problems if they become trapped in the bile ducts.

Laparoscopic surgery to remove the gallbladder is the most common treatment.

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