Gall Stones

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Stones in the gallbladder and bile duct system (cholelithiasis)} are the most common cause of disease affecting the biliary tree.

Stones form from the constituents of bile, the main components being variable proportions of cholesterol, calcium salts (phosphates, carbonates),and bilirubin (in the form of calcium bilirubinate).

Although it is recognized that most stones have several constituents, two main types of stone have been defined according to the major constituent of each: cholesterol stones (80% of all stones) and pigment stones (20% of all stones).

Cholesterol stones are predisposed by changes in cholesterol solubility in bile.
Cholesterol stones occur in 20% of women and 8% of men, usually causing no problems. They form when bile becomes supersaturated with cholesterol, there being insufficient bile salts to keep the cholesterol in solution. In most cases the reasons for these changes are unclear.

The main risk factors associated with cholesterol stone formation are:
Decreased bile acids in bile, caused by oestrogen or excessive loss from gut due to malabsorption in   Crohn's disease or cystic fibrosis.
Increased cholesterol in bile caused by obesity, female sex, increasing age.

Stones are round, faceted and can be 0.5-3 cm in size, but are typically large. Biochemical
analysis reveals over 50% cholesterol composition, with lesser amounts of calcium salts so, strictly,
most such stones are of mixed composition.

Cholesterolosis of the gallbladder occurs when the sub-mucosa of the gallbladder is focally infiltrated by macrophages laden with cholesterol. This condition is frequently associated with the development of cholesterol stones and is believed to be predisposed by the same conditions that cause decreased solubility of cholesterol in bile.
Understanding of the pathogenesis of cholesterol stone formation has led to medical treatment
of stones by oral therapy with bile salts to dissolve stones.

In cholesterolosis the accumulation of lipid is seen in mucosal folds as a fine, yellow stippling.
Pigment stones are predisposed by increased hepatic secretion of bilirubin
Several clinical situations are associated with the development of pigment stones
which are largely composed of calcium bilirubinate, with lesser amounts
of other calcium salts and mucoproteins.
It is easy to understand why patients with abnormal red-cell breakdown, generating large
amounts of conjugated bilirubin, develop pigment stones, but the association of pigment
stones with cirrhosis, chronic biliary infections, and ileal resections is not understood.
Stones are irregular in shape. They measure up to 1cm, being typically smaller than cholesterol stones.

Blockage of the main bile ducts causes obstructive jaundice
Gallstones may obstruct the biliary tract and predispose to development of carcinoma of the gallbladder
Over 70% of gallstones remain clinically silent.
Stones impacted in the cystic duct predispose to inflammation of the gallbladder
(cholecystitis),} which may be acute or chronic, and those forming in the bile ducts
(choledocholithiasis) predispose to obstructive jaundice, cholangitis and acute pancreatitis.

Gallstones may cause acute cholecystitis

Acute inflammation of the gallbladder causes pain in the right upper quadrant of the abdomen.
The affected gallbladder is enlarged, red and oedematous and, histologically,
there is acute inflammation of the wall.
Most cases are associated with gallstones.
Inflammation is precipitated by the chemical effects of concentrated bile, but secondary
infection may develop. Complications of acute cholecystitis include perforation into
the abdomen (causing biliary peritonitis).
Chronic cholecystitis is associated with the presence of gallstones
Chronic cholecystitis is caused by the chronic effects of gall-stones. There is
thickening and fibrosis of the wall, with variable chronic inflammatory infiltration of mucosa and sub-mucosa.

The pathogenesis of chronic cholecystitis is probably multifactorial. As many gallbladders
that have been removed show muscle thickening and fibrosis without inflammatory changes,
it may be more appropriate to call such cases obstructive cholecystopathy. Other cases
have associated chronic inflammation and these may truly be called chronic cholecystitis.
Development of disease has been related to contractile abnormalities of the gallbladder
(stimulated by the presence of stones), to direct chemical injury to the mucosa by bile,
or to the effects of repeated episodes of acute cholecystitis.
Secondary changes include extensive calcification of the wall of the gallbladder
(porcelain gallbladder) and development of a mucocele of the gallbladder.

In chronic cholecystitis there is thickening of the gallbladder wall. Histologically this
is due to muscular hypertrophy, sub-mucosal fibrosis, and chronic inflammation. Outpouches
of mucosa into the wall form small cystic spaces termed 'Aschoff-Rokitansky sinuses'. In this example,
stones are seen in the fundus, and the mucosa in inflamed.
Mucocele of the gallbladder is caused by obstruction of the cystic duct by stones.
The bile is resorbed and the epithelium changes type to a mucin-secreting pattern, filling
the gallbladder with clear mucus (emptied from this specimen).
The mucosal surface is smooth and the wall is thinned.

Over 70% of gallstones remain clinically silent.
The main clinical complications of cholelithiasis arise from obstruction of the cystic duct or common bile duct by a stone.
The presence of stones in the biliary tract leads to muscle hypertrophy and thickening of the wall of the gall-bladder(obstructive cholecystopathy). Stones impacted in the cystic duct predispose to
inflammation of the gallbladder(cholecystitis),which may be acute or chronic, and those forming in the bile ducts(choledocholithiasis)predispose to obstructive jaundice, cholangitis and acute pancreatitis.

Stones in the gallbladder predispose to the development of carcinoma of the gallbladder.
Inflammation is precipitated by the chemical effects of concentrated bile in the gallbladder, but secondary infection may develop with enteric organisms such as
Escherichia coli. Primary bacterial infection of the gallbladder, e.g. with Salmonella, is rare.

Acute cholecystitis can occur in critically ill patients in the absence of gallstones, when septicaemic spread of infection is postulated.

Complications of acute cholecystitis include perforation into the abdomen (causing
biliary peritonitis), and secondary infection which, in severe cases, may cause empyema of the gallbladder,filling the lumen with pus.
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Revised: 02-11-2014.