THE BILIARY TRACT

Lecture 30

CHOLELITHIASIS

Gall bladder Stores & Concentrates BileThe commonest location of impaction of a gallstone is Hartmann’s pouch

Hartmann's pouch is an out-pouching of the wall of the gallbladder at the junction of the neck of the gallbladder and the cystic duct.

The main function of the gallbladder is to store and concentrate the bile secreted by the liver and then deliver it into the intestine for digestion and absorption of fat. The concentrating ability of the gallbladder is due to its absorptive mucosal surface that has numerous folds.

Normally, the liver secretes approximately 500 ml of bile per day and the gallbladder concentrates it 5-10 times. The motility, concentration and relaxation of the gallbladder are under the influence of a peptide hormone, cholecystokinin, released from neuroendocrine cells of the duodenum and jejunum.

Cholesterol,Bile Pigments,Calcium Salts

CHOL, GALL Liver secretes 400-800 ml bile per day

Lecithin

Cholelithiasis*Presence of stones in the gallbladder is

referred to as cholelithiasis (from the Greek chol- (bile) + lith- (stone) + iasis- (process).

3% to 4% in Asian countries

Gallbladder (cholecyst, or biliary vesicle, bile bladder)

GALL means BILE or Chol

They are usually formed in the gallbladder, but sometimes may develop within extrahepatic biliary passages, and rarely in the larger intrahepatic bile duct (Pigment stones).

CHOLELITHIASIS (GALLSTONES) Epidemiology

• Gallstones afflict (badly affect)10% to 20% of adult populations in developed countries.

• It is estimated that more than 20 million persons in the United States have gallstones, totaling some

25 to 50 tons in weight!

Over 95% of biliary tract disease is attributable to cholelithiasis (gallstones).

*TYPES OF GALLSTONES

1.Cholesterol stones 20%

2.Pigment stones (Black & Brown) 5%

3.Mixed stones 75%

I. PURE GALLSTONES: Cholesterol stones, Pigment stones, Calcium Stones

II. MIXED GALLSTONES III. COMBINED gallstones ( shell different & nucleus

different).

*Pathogenesis or Lithogenesis• Bile formation is the only significant pathway for

elimination of excess cholesterol from the body, either as free cholesterol or as bile salts. Cholesterol is rendered water-soluble by aggregation with bile salts and lecithins (Phospholipids).

• When cholesterol concentrations exceed the solubilizing capacity of bile (supersaturation), cholesterol can no longer remain dispersed and crystallizes out of solution.

CHOLESTEROL STONES:

Cholesterol gallstone formation involves four simultaneous conditions:

(1) Supersaturation: The bile must be supersaturated with cholesterol;

(2) Hypomotility (Stasis): Hypomotility of the gallbladder promotes nucleation;

(3) Nucleation: Cholesterol nucleation in the bile is accelerated;

(4) Accretion: Hypersecretion of mucus in the gallbladder traps the nucleated crystals, leading to their aggregation into stones (Accretion).

Accretion within the gallbladder mucous layer.

Schematic pathogenesis of gallstone formation. (HMG- CoAR = hydroxy methyl glutaryl-coenzyme A reductase; 7α-OHase = cholesterol 7 α-OHase hydroxylase;

MDR3 = multidrug resistance- associated protein 3).

Cholesterol Stones:Imbalance between bile salts, lecithin & cholesterol allows cholesterol to precipitate out of solution and form stones.

Pigment Stones: Occur due to excess of circulating pigments (e.g., Hemolytic anemia.

The four contributing factors for cholelithiasis: supersaturation, gallbladder hypomotility, crystal nucleation, and accretion within the gallbladder mucous layer.

A micelle is an aggregate of surfactant molecules dispersed in a liquid colloid

1

2 3

4

Cholesterol is essentially insoluble in water and can be solublised by another lipid. Normally, cholesterol and phospholipids (lecithin) are secreted into bile as ‘bilayered vesicles’ but are converted into ‘mixed miscelles’ by addition of bile acids, the third constituent. If there is excess of cholesterol compared to the other two constituents, unstable cholesterol-rich vesicles remain behind which aggregate and form cholesterol crystals.

When cholesterol concentrations exceed the solubilizing capacity of bile (supersaturation), cholesterol can no longer remain dispersed and crystallizes out of solution.

Pathogenesis – Pigment Stones• Formation of PIGMENT stones is more likely in

the presence of UNCONJUGATED BILIRUBIN in the biliary tree, as occurs in hemolytic anemias and infections of the biliary tract.

• The precipitates are primarily insoluble calcium bilirubinate salts.

The risk factors most commonly associated with the development of

cholesterol stones are:

1. ↑Age and Sex-F. 2. Environmental Factors. 3. Acquired Disorders. 4. Hereditary Factors.

Recently, mutation in CYP7A1 gene has been found that results in deficiency of enzyme, cholesterol 7-hydroxylase, which has a role in bile acid synthesis. This mutation is associated with hypercholesterolaemia and gallstones.

Deficiency of dietary fibre content is linked to higher prevalence of gallstones. A moderate consumption of alcohol, however, seems to protect against gallstones

These factors cause enhanced activity of enzyme, HMG-CoA reductase, that normally regulates cholesterol synthesis and its hepatic uptake.

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Any condition in which gallbladder motility is reduced predisposes to gallstones, such as pregnancy, rapid weight loss, and spinal cord injury. In most cases, however, gallbladder hypomotility is present without obvious cause.

Up to 80% of people with gallstones, however, have no

identifiable risk factors other than AGE and

GENDER.

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Morphology – Cholesterol Stones• Cholesterol stones arise exclusively in the

gallbladder and consist of 50% to 100% cholesterol.

• Pure cholesterol stones are pale yellow; increasing proportions of calcium carbonate, phosphates, and bilirubin (Mixed Stones) impart gray-white to black discoloration .

Pure gallstones, Mixed gallstones and Combined gallstones.

Morphology – Cholesterol Stones• They are Large, ovoid and firm; they can occur

singly, but most often there are several, with faceted surfaces resulting from their apposition.

• Most (80%) cholesterol stones are radiolucent, although as many as 20% may have sufficient calcium carbonate to be radiopaque.

Morphology - Pigment Stones• Pigment stones may arise ANYWHERE in the biliary

tree and are classified into BLACK & BROWN stones. • In general, BLACK pigment stones are found in

sterile gallbladder bile, while BROWN stones are found in infected intrahepatic or extrahepatic ducts.

• The stones contain calcium salts of unconjugated bilirubin and lesser amounts of other calcium salts, mucin glycoproteins, and cholesterol.

• Black stones are usually small in size, fragile to the touch, and numerous.

Morphology – Brown stones• Brown stones tend to be single or few in number

and to have a soft, greasy, soaplike consistency that results from the presence of retained fatty acid salts released by the action of bacterial phospholipases on biliary lecithins.

• Because of calcium carbonates and phosphates, 50% to 75% of black stones are radiopaque.

• Brown stones, which contain calcium soaps, are radiolucent.

Mutation in MDR3 gene has been found that causes defect in phospholipid secretion from bile (↓Lecithin), resulting in cholesterol supersaturation of bile and cholesterol gallstone formation.

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Black & Brown

RUQ

Murphysign

Clinical features

• The vast majority of gallstones

(>80%) are “silent,” and most individuals remain free of biliary pain or other

complications for decades.

Symptoms Symptoms commonly begin to appear once

the stones reach a certain size

(>8 mm). Symptomatic gallstone disease appears only when complications develop.

PAIN

Pain- Biliary Colic• The patients with gallstones develop symptoms due

to cholecystitis which include typical biliary colic precipitated by fatty meal, nausea, vomiting, fever along with leucocytosis and high serum bilirubin.

Pain during inspiration with examiner’s hand on the GB location.

A cholescintigraphy scan, also known as: Hepatobiliary Iminodiacetic Acid HIDA, a nuclear imaging procedure to evaluate the health and function of the gallbladder. A radioactive tracer is injected through any accessible vein, then allowed to circulate to the liver, where it is excreted into the biliary system and stored by the gallbladder and biliary system.[1]

In the absence of disease, the gallbladder is visualized within 1 hour of the injection of the radioactive tracer. If the gallbladder is not visualized within 4 hours after the injection, this indicates either cholecystitis or cystic duct obstruction. Cholescintigraphy for acute cholecystitis has sensitivity of 97%, specificity of 94%

URSODEOXYCHOLIC ACID

(Hepexa- M)

1. Cholecystitis 2. Choledochlithiasis 3. Mucocele (Hydrops) 4. Biliary Fistula 5. Gallstone ileus 6. GB Cancer

Intestinal Obstruction

Or Hydrops GB

Inflam of BD

Pus

The invasion of GAS-FORMING ORGANISMS, notably clostridia and coliforms, may cause an acute “emphysematous” cholecystitis.

"Is there any reward for good, other than good?"