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What are the main components of bile?

-bile acids



-immunoglobulin A and M





What are the main roles of bile acids and phospholipids?

-solubilization of cholesterol



Describe bile

The volume of hepatic bile secretion is estimated to be between 500 and 600 ml per day.

It is a complex lipid--rich micellar solution that is isoosmotic with plasma and composed primarily of water, inorganic electrolytes, and organic solutes such as bile acids, phospholipids (mostly phosphatidylcholine), cholesterol, and bile pigments.

Bile acids are travel down the biliary tree and are stored in the gallbladder. Following a meal, the gallbladder contracts and empties its content into the duodenum


What are the main types of gallstones?

-pure and mixed cholesterol stones

-pigmented black and brown stones


Describe cholesterol stones

these are the most frequent type of stone, yellowish-white in color 

         - Monohydrate cholesterol crystals

         - Matrix of mucin glycoprotein

         - Calcium salts  of  unconjugated  bilirubin

         - Only occasionally seen by x-ray



Describe pigmented brown stones

   - Calcium salts and deconjugated bilirubin , cytoeskeleton of bacteria

   - Frequent in patient with previous surgery, infection, and patients with duodenal diverticula


Describe pigmented black stones

seen more in patients with liver disease, hemolysis, older age,total parenteral nutrition and are small and very hard

   - Pure calcium bilirubinate, calcium copper, mucin glycoprotein


What things are likely to cause a supersaturated cholesterol bile?

-estrogens and progesterone (aka women) by Increased cholesterol uptake (Increased lipoprotein receptors B and E) (estrogen) and preventing conversion of ACAT to cholesterol ester for storage (Progesterone)- (Inhibitor of AcoA CAT Decreased conversion of cholesterol to cholesteryl ester stores)

-Age by preventing/decreasing the production of bile acids (Age related decreased in 7 alfa hydroxylase)

-Obesity by promoting formation of free cholesterol from acetate via HMG CoA reductase

-marked weight reduction/starvation


What are the three main parts of the Pathophysiology of Cholesterol Stone Formation?

•Cholesterol Supersaturation

•Accelerated Nucleation

•Gallbladder Hypomotility


What is this showing?

Abetalipoproteinemia-The small bowel mucosa shows the characteristic clear enterocytes (due to lipid accumulation).


What is abetalioproteinemia?

Abetalipoproteinemia, or Bassen-Kornzweig syndrome, is a rare autosomal recessive disorder that interferes with the normal absorption of fat and fat-soluble vitamins from food. It is caused by a mutation in microsomal triglyceride transfer protein resulting in deficiencies in the apolipoproteins B-48 and B-100, which are used in the synthesis and exportation of chylomicrons and VLDL respectively. It is not to be confused with familial dysbetalipoproteinemia.


How does abetalipoproteinemia present?

The signs and symptoms of abetalipoproteinemia appear in the first few months of life (because pancreatic lipase is not active in this period). They can include failure to gain weight and grow at the expected rate (failure to thrive); diarrhea; abnormal star-shaped red blood cells (acanthocytosis); and fatty, foul-smelling stools (steatorrhea). The stool may contain large chunks of fat and/or blood. Other features of this disorder may develop later in childhood and often impair the function of the nervous system. They can include poor muscle coordination, difficulty with balance and movement (ataxia), and progressive degeneration of the retina (the light-sensitive layer in the posterior eye) that can progress to near-blindness (due to deficiency of vitamin A, retinol).[3] Adults in their thirties or forties may have increasing difficulty with balance and walking. Many of the signs and symptoms of abetalipoproteinemia result from a severe vitamin deficiency, especially vitamin E deficiency, which typically results in eye problems with degeneration of the spinocerebellar and dorsal column tracts.



NOTE: Cholesterol molecules are virtually insoluble in water. Bile acids, because of their unique amphiphatic properties, are able to solubilize cholesterol and phospholipid


What is the Cholesterol Saturation Index (CSI)? 

the ratio of the amount of cholesterol in a given bile sample to the maximal cholesterol micellar-holding capacity of that sample.

in vitro, Bile that has a CSI greater than 1 is considered supersaturated


Even two people with the same CSI may or may not form cholesterol stones. What are some factors that promote stone formation?

The gallbladder mucosa concentrates bile and secretes mucin glycoprotein, both of which increase cholesterol crystal formation. Changes in the composition of bile, including high cholesterol saturation, increased biliary calcium salts, and an increased deoxycholate content all enhance cholesterol crystallization.

Delayed gallbladder emptying also promote stone formation


Patient with gall-stones have a delay in gallbladder emptying

Not eating or getting nutrition via an IV is assoicated with cholesterol stones b/c normally food in the duodenum increases the pH enough to cause CCK release which cause gallbladder contraction and spincter of Oddi relaxation to allow bile to enter the blood


The following factors have been described as possible risk factors for gall-stones formation:                           

1) Defective acidification of gallbladder bile: > pH causes increased risk of precipitation of calcium salts

2) Gallbladder stasis: Can produce increase of mucin and interfere with mechanical emptying

3) allbaladder hypomotility and mucin hypersecretion

4) Decreased response to CCK

5) Increased intestinal conversion to deoxycholate


What things promote black pigment stone formation?

   - Hemolysis

   - Advancing age

   - Long term TPN

   - Cirrhosis


Cholesterol gallstones develop when bile contains too much cholesterol and not enough bile salts. Besides a high concentration of cholesterol, two other factors are important in causing gallstones. The first is how often and how well the gallbladder contracts; incomplete and infrequent emptying of the gallbladder may cause the bile to become overconcentrated and contribute to gallstone formation. This can be caused by high resistance to the flow of bile out of the gallbladder due to the complicated internal geometry of the cystic duct. The second factor is the presence of proteins in the liver and bile that either promote or inhibit cholesterol crystallization into gallstones. In addition, increased levels of the hormone estrogen, as a result of pregnancy or hormone therapy, or the use of combined (estrogen-containing) forms of hormonal contraception, may increase cholesterol levels in bile and also decrease gallbladder movement, resulting in gallstone formation.

Cholesterol stones vary from light yellow to dark green or brown or chalk white and are oval, usually solitary, between 2 and 3 cm long, each often having a tiny, dark, central spot. To be classified as such, they must be at least 80% cholesterol by weight (or 70%, according to the Japanese- classification system). Between 35% and 90% of stones are cholesterol stones


Bilirubin ("pigment", "black pigment") stones are small, dark (often appearing black), and usually numerous. They are composed primarily of bilirubin (insoluble bilirubin pigment polymer) and calcium (calcium phosphate) salts that are found in bile. They contain less than 20% of cholesterol (or 30%, according to the Japanese-classification system). Between 2% and 30% of stones are bilirubin stones


What are the clinical risk factors for black pigment gallstone disease?

-decreases in bilirubin solubilizers (chronic liver disease, age)

-increases in bilirubin secretion (chronic hemolysis, TPN, chronic liver disease, Crohn's disease, age)

Gallbladder stasis


Mixed ("Brown Pigment") stones typically contain 20–80% cholesterol (or 30–70%, according to the Japanese- classification system). Other common constituents are calcium carbonate, palmitate phosphate, bilirubin and other bile pigments (calcium bilirubinate, calcium palmitate and calcium stearate). Because of their calcium content, they are often radiographically visible.

They typically arise secondary to infection of the biliary tract which results in the release of β-glucuronidase (by injured hepatocytes and bacteria) which hydrolyzes bilirubin glucuronides and increases the amount of unconjugated bilirubin in bile. Between 4% and 20% of stones are mixed


What are the risk factors for formation of brown stones?

–Infection, primary biliary, prior surgery

–Decreasing biliary secretory IgA

–High activity of B-glucuronidase


What is biliary colic?

Biliary colic, also known as a gallbladder attack, is when pain occurs due to a gallstone temporarily blocking the bile duct. Typically the pain is in the right upper part of the abdomen and it can radiate to the shoulder. Pain usually lasts from one to a few hours. Often it occurs after eating a heavy meal or during the night.Repeated attacks are common


What is acute chlecystitis?

Cholecystitis is inflammation of the gallbladder due to stone blockage. Symptoms include right upper abdominal pain, nausea, vomiting, and occasionally fever. Often gallbladder attacks (biliary colic) precede acute cholecystitis. The pain, however, lasts longer than a typical gallbladder attack. Without appropriate treatment, recurrent episodes of cholecystitis are common.

Complications of acute cholecystitis include gallstone pancreatitis, common bile duct stones, or inflammation of the common bile duct


What is choledocholithiasis?

Common bile duct stone, also known as choledocholithiasis, is the presence of gallstones in the common bile duct (thus choledocho- + lithiasis). This condition causes jaundice and liver cell damage, and requires treatment by cholecystectomy and/or ERCP


How does choledochlolithiasis present?

Murphy's sign is commonly negative on physical examination in choledocholithiasis, helping to distinguish it from cholecystitis. Jaundice of the skin or eyes is an important physical finding in biliary obstruction. Jaundice and/or clay-colored stool may raise suspicion of choledocholithiasis or even gallstone pancreatitis. If the above symptoms coincide with fever and chills, the diagnosis of ascending cholangitis may also be considered.

Greater than 70% of people with gallstones are asymptomatic and are found incidentally on ultrasound. Studies have shown that 10% of those people will develop symptoms within five years of diagnosis and 20% within 20 years


What is ascending cholangitis?

Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is an infection of the bile duct (cholangitis), usually caused by bacteria ascending from its junction with the duodenum. It tends to occur if the bile duct is already partially obstructed by gallstones


What is cholestasis?

Cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system that can occur from a gallstone or malignancy, and metabolic types of cholestasis which are disturbances in bile formation that can occur because of genetic defects or acquired as a side effect of many medications.


How does biliary pancreatitis occur?

Reflux of bile into the pain panreatic duct in the presence of a gallstone can activate pacnreatic enzymes