by Richard Mitchell, MD, PhD

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    00:01 Hello there. This talk is going to be Cholelithiasis, stones in the gallbladder.

    00:08 Gallstones in the gallbladder looks like this. There can be one, there can be many and they become symptomatic when they obstruct the outflow from the gallbladder.

    00:20 Let's look at the epidemiology. So, it's a relatively common entity, about 10% to 15% of the adult population will have gallstones.

    00:29 I know that I have three gallstones. Three gallstones.

    00:33 The Native American population in the United States has a very high prevalence, as high as 70 or 75%.

    00:41 The vast majority of these, 80% or so are completely asymptomatic.

    00:46 Nevertheless, they can cause in excess of about $6 billion per year in medical costs.

    00:53 They occur more typically in women than in men. So, about a three to one ratio.

    00:59 Typically manifest if they're going to manifest over the age of 40 and the vast majority of these are also cholesterol stones.

    01:09 So, we're getting a precipitation, a nucleation of cholesterol and cholesterol esters to form the majority of the stones.

    01:18 As I just said, cholesterol stones are the most common, 80% of the stones. They look as you see there.

    01:26 They often have kind of a crystalline yellow brown color. They tend to be round and/or faceted.

    01:33 So, they have kind of flat surfaces. They're associated with a family history, so, this may clearly have to do with the kind of biliary contents that you are secreting and storing within the gallbladder.

    01:49 They're associated with obesity. They're associated with increased estrogen and this probably has to do with increased cholesterol within the bile and decreased bile salt.

    02:00 They may be associated with rapid weight loss, for example, after bariatric surgery.

    02:05 They're associated with diabetes and dyslipidemia.

    02:08 Remember that it's more common in women and more common over the age of 40.

    02:12 So, there is kind of a mnemonic that fat, female, fecund, usually, in childbearing years, and family history.

    02:26 10% of gallstones are going to be black or pigmented stones.

    02:30 And these are formed of calcium bilirubinate.

    02:34 They are associated with excessive bilirubin secretion and may also be associated with abnormal enterohepatic circulation, so, they're associated with cirrhosis, Crohn's disease, hemolytic anemias in particular in patients who get recurrent transfusions will be very prone to these pigmented stones and they occur more frequently with advancing age.

    03:01 Brown pigment stones as shown here are a combination of unconjugated bilirubin, calcium soaps, cholesterol and mucin. They're overall about 10% of the total.

    03:11 They're typically associated with infections, either bacterial or parasitic.

    03:16 More common in the Asian population and instead of forming within the gallbladder, will form in the bile ducts.

    03:25 There's also biliary sludge. So, you don't necessarily have to form a discrete stone.

    03:30 You can have just kind of a muddy sludge of material.

    03:36 This is a mixture of calcium bilirubinates, cholesterol, microcrystals, mucin, and it can have the same effect.

    03:44 The sludge can limit egress of bile out of the gallbladder into the biliary tree and into the common bile duct.

    03:54 And that may be associated with fasting, total parenteral nutrition and pregnancy.

    04:02 The pathophysiology of stones. So, bile is collected.

    04:07 It's a combination of conjugated bilirubin. It is mucin.

    04:13 It's a variety of things and it's accumulated within the gallbladder to then be ejected after a meal down the common bile duct and into the duodenum.

    04:24 This is showing you the various constituents that are there.

    04:28 And if they are in an appropriate balance of salts, acids, cholesterol, bilirubin, then, it tends to remain in a liquid form that is easily ejected out the cystic duct, common bile duct, and into the duodenum.

    04:43 However, if we have excess of one or another of the constituents, that may lead to a physical chemical crystallization and the formation of stones or sludge.

    04:55 And again, the two major constituents of bile are going to be cholesterols and bilirubin.

    05:01 With that crystallization, we form actual stones or sludge but stones are what I'm going to be talking about here.

    05:09 And the gallstones then, depending on their constituents, can look as you see, cholesterol which tend to be yellow golden brown and faceted.

    05:21 The black pigments stones tend to be quite irregular and very dark and the brown pigment stones as you see.

    05:28 Again, the pathophysiology associated with the cholesterol stones.

    05:31 It's cholesterol supersaturation of the bile. It may be associated with bile or gallbladder hypomotility.

    05:37 So, there's a relative stasis that allows the constituents to sit there longer and not be ejected.

    05:43 And therefore, nucleate and crystallize.

    05:48 The pathophysiology associated with the black pigment stones is an overproduction of bilirubin, typically, associated with hemolysis. And there may be a decrease in the enterohepatic cycling.

    06:00 So, we're not getting the normal constituents within the bile and that decreased enterohepatic cycling is occurring with cirrhosis.

    06:11 And then, the brown pigment stones associated with bacterial or parasitic infections often are due to an overproduction of mucin with inflammatory cell recruitment and in that case, we may have elevated enterohepatic recirculation of the bilirubin that contributes to the formation of the stone in that setting.

    06:31 Again, we, when we get a stone, there has been an abnormal accumulation of one of the components that are normally present within the liquid bile. The clinical presentation, recall, again, that the vast majority of patients with gallstones will be completely asymptomatic.

    06:49 If you are going to be symptomatic, it's because of the movement of the stone into either the cystic duct or into the common bile duct. And the pain is relatively severe.

    07:00 It's a constant dull right upper quadrant pain. It will last for hours. It's usually associated with meals.

    07:08 So, after you eat and the gallbladder is trying to squeeze its contents out, the stone gets stuck in one of the cystic or common bile ducts and with that then, you get the pain associated with the dilation there. It may radiate to the epigastrium.

    07:24 It may radiate to the right shoulder. It can radiate to the back.

    07:28 There may be associated nausea and vomiting with any visceral pain. Those are common associated features.

    07:35 And notably, there will not be peritoneal signs.

    07:40 In other words, you don't have peritonitis. You don't have tenderness, rebound guarding.

    07:46 So, making the diagnosis. It's largely based on clinical grounds.

    07:49 But then, on physical exam, you will have mild right upper quadrant tenderness, no peritoneal signs, so, no rebound, no guarding, no abdominal tenderness.

    08:02 The ultrasound is going to be your best friend in making this diagnosis.

    08:05 It's not invasive. It's easy to perform and will be specific for detecting stones about 95% of the time.

    08:13 You can see the stones as an echo lucent area. And you can see exactly where they are, whether they're in the gallbladder proper, or stuck in one of the ducts, cystic duct or the common bile duct.

    08:27 How do we manage this? So, there are a variety of ways.

    08:30 Basically, you'd like to prevent them from forming in the first place.

    08:34 So, changing the diet, losing weight, etc.

    08:37 Medical management. You can administer certain oral agents that will solubilize the crystalline stone that has accumulated.

    08:48 It takes a while but is effective in a subset of patients.

    08:54 Clearly, you want to provide analgesia for patients who are having the acute symptoms of a bile stone and getting pain.

    09:05 You may also give spasmolytics that will cause relaxation of the smooth muscle and anti-nausea medications.

    09:14 We want to do surgery if we identify stones that have been symptomatic, usually, we remove the gallbladder.

    09:23 The consequence of that is that the patient can't really eat fatty foods very easily after that because they don't have any mechanism to store the bile and bile salts necessary to solubilize fat in a fatty meal.

    09:35 But patient otherwise does quite well. It's important that we identify and remove gallbladders that have a predilection to stone formation because a significant portion of patients with gallstones will have associated inflammation, eventually, cholangiocarcinoma.

    09:54 So, incidentally or just as a point of fact, 85% of gallbladder cancers are associated with gallstones.

    10:02 Although only half a percent of patients who have gallstones will have the cancer.

    10:08 Still, you don't wanna have that risk.

    10:12 With that, we've concluded our talk on Cholelithiasis.

    About the Lecture

    The lecture Cholelithiasis by Richard Mitchell, MD, PhD is from the course Disorders of the Biliary Tract.

    Included Quiz Questions

    1. ...cholesterol.
    2. ...calcium.
    3. ...phosphate.
    4. ...bilirubin.
    5. ...bile acid.
    1. Estrogen
    2. Obesity
    3. Family history
    4. Cirrhosis
    5. Ulcerative colitis
    1. Bacterial infection
    2. Cholesterol supersaturation of bile
    3. Gallbladder hypomotility
    4. Overproduction of bilirubin
    5. Underproduction of bilirubin
    1. 80%
    2. 50%
    3. 30%
    4. 15%
    5. 5%
    1. Ultrasound
    2. CT abdomen
    3. MRI abdomen
    4. CT thorax with contrast
    5. Abdominal X-ray

    Author of lecture Cholelithiasis

     Richard Mitchell, MD, PhD

    Richard Mitchell, MD, PhD

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