Lecture 13

Cholecystitis

{ ‫ ﺗﺠﺮع ذ ﱠل اﻟﺠﮭﻞ طﻮال ﺣﯿﺎﺗ ِﮫ‬..ً‫} وﻣﻦ ﻟﻢ ﯾﺬق ﻣ ّﺮ اﻟﺘﻌﻠﱡ ِﻢ ﺳﺎﻋﺔ‬

Red: Important. Grey: Extra Notes Doctors Notes will be in text boxes

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Objectives:
— Compare the various types of gallstones, how they are formed, what the risk factors for
their development are, and what complications they can cause.
— Recognize the predisposing factors of cholecystitis and the different types of
cholecystitis.
— Understand the pathogenesis of acute and chronic cholecystitis
References:
Lecture Slides & Robbins.

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General information (you can find theses in physiology and hematology lectures)
A. Bile salts/acids (~67%)

1) Hepatic product of CH metabolism

2) Water soluble

3) Detergent action renders CH soluble in bile.

B. Phospholipid (22%)

Mainly lecithin, Hydrophobic, Solubilizes CH in bile

C. Protein (4.5%), free CH (4%), conjugated bilirubin (0.3%)

— In extravascular hemolytic anemia (EHA; e.g., hereditary spherocytosis,

sickle cell disease), there is an increase in UCB (unconjugated bilirubin)

(macrophage destruction of spherocytes/sickle cells) and a corresponding

increase in the uptake and conjugation of UCB to conjugated bilirubin (CB) in

the liver. In the gallbladder, some of the CB is converted back to UCB, which

combines with calcium to form calcium bilirubinate stones.

D. Water, electrolytes, bicarbonate

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 Disorders of the Gallbladder:

Cholelithiasis (Gallstones):

Majority of gallstones (>80%) are "silent," and most

individuals remain free of biliary pain or stone
complications for decades.

There are two main types of gallstones:

Cholesterol stones Pigment stones

About 80%, containing more than 50% of 20%, containing bilirubin
crystalline cholesterol monohydrate. calcium salts.
Note: Cholesterol stones contain calcium, but
not as much as pigment stones.
Definition

Multiple black pigment stone

(black stones indicate sterile
gallbladder)
Multiple pale yellow oval cholesterol
stone

Demography: northern Europeans, North and Demography: Asians more than

South Americans, Native Americans, Mexican Westerners, rural more than
Prevalence and Risk Factors

Americans (Industrial countries; the people urban

have cholesterol rich diet) § Chronic hemolytic syndromes
§ Advancing age § Female gender § Biliary infection
§ Pregnancy § Gallbladder stasis § Gastrointestinal disorders:
ileal disease (e.g., Crohn
§ Female sex hormones
disease), ileal resection or
§ Oral contraceptives
bypass, cystic fibrosis with
§ Obesity and metabolic syndrome
pancreatic insufficiency
§ Rapid weight reduction
§ Inborn disorders of bile acid metabolism
§ Hyperlipidemia syndromes

Cholesterol stones are yellow in Always keep in mind that anything related to hormonal
color and radiolucent. imbalance, weight problems or metabolism abnormality, can be a
Pigment stones are radiopaque. cause of cholesterol stones.

Chronic hemolytic syndromes = increased unconjugated bilirubin level in plasma.

Remember that patients coming from villages are more prone to pigment stones that to cholesterol.
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 Cholesterol stones Pigment stones
§ Cholesterol is rendered soluble in bile by § Pathogenesis of pigment stones is
aggregation with water-soluble bile salts based on the presence of
and water-insoluble lecithins, both of which unconjugated bilirubin in the
act as detergents. biliary tract (which is poorly
§ When cholesterol concentrations exceed the soluble in water) and precipitation
solubilizing capacity of bile (supersaturation), of calcium bilirubin salts.
cholesterol can no longer remain dispersed § Thus, infection of the biliary tract, as
and nucleates into solid cholesterol with Escherichia coli or Ascaris
monohydrate crystals. (Simply; 1- the lumbricoides or by the liver fluke
cholesterol increase 2- cholesterol will not Opisthorchis sinensis, increases the
be soluble 3- cholesterol precipitate and likelihood of pigment stone
form stones.) formation.
Chronic hemolytic conditions also
Pathogenesis

Cholesterol gallstone formation involves four §

simultaneous defects: promote formation of unconjugated
bilirubin in the biliary tree.
1- Supersaturation of bile with cholesterol is
the result of hepatocellular hypersecretion
of cholesterol.
2- Gallbladder hypomotility ensues. It
promotes nucleation typically around a
calcium salt crystal nidus1.
3- Cholesterol nucleation in bile is accelerated.
4- Mucus hypersecretion in the gallbladder
traps the crystals, permitting their
aggregation into stones.
5- Prolonged fasting, pregnancy, rapid weight
loss, total parenteral nutrition, and spinal Black stones are harder
cord injury also promote stone formation.

Arise exclusively in the gallbladder and are Black and brown.

composed of cholesterol ranging from 100% pure § "Black" pigment stones are found in
(which is rare) down to around 50%. sterile gallbladder.
§ Pale yellow, round to ovoid to faceted, and § "Brown" pigment stones are found in
have a finely granular, hard external surface. infected intrahepatic or extrahepatic
Morphology

§ Stones composed largely of cholesterol are bile ducts.

radiolucent; only 10% to 20% of cholesterol § Both are soft and usually multiple.
stones are radio-opaque (because of the small § Brown stone are greasy.
amount of calcium.) § Because of calcium carbonates and
phosphates, approximately 50% to
75% of black stones are radio-
opaque (High percentage radio-
opaque because it contains high
amount concentrations).

1
The point of origin or focus of a disease process.
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Cholesterolosis:

An incidental finding, is cholesterolosis. Cholesterol hypersecretion by the liver

promotes excessive accumulation of cholesterol esters within the lamina propria of
the gallbladder. The mucosal surface is studded with minute yellow flecks,
producing the "strawberry gallbladder”

Under microscope:
infiltration of lamina propria by foamy
histiocytes.
Grossly:
Velvet green and in between is yellow flecks
which will produce strawberry gallbladder
appearance.

Clinical Features:

§ 70% to 80% of patients remain asymptomatic throughout their lives.

§ Symptoms: spasmodic or "colicky" upper quadrant pain, which tends to be
excruciating (very painful).
§ It usually follows a fatty meal which forces a stone against the gall bladder
outlet leading to increased pressure in the gall bladder causing pain. Pain is
localized to right upper quadrant or epigastrium that may radiate to the right
shoulder or the back
§ It is usually due to obstruction of bile ducts by passing stones.
Once the stone get passed the bile ducts to the intestine, the pain will stop.
Complications:

§ Obstructive cholestasis. § Pancreatitis. § Perforation. § Fistulas.

§ Inflammation of the biliary tree (cholangitis) § Empyema (pus accumulation).

§ The larger the calculi the less likely they are to enter the cystic or common ducts
to produce obstruction; it is the very small stones, or “gravel,” that are more
dangerous.
§ Occasionally a large stone may erode directly into an adjacent loop of small
bowel, generating intestinal obstruction (“gallstone ileus” or Bouveret
syndrome).
§ Gallstones are associated with an increased risk of gallbladder carcinoma.

Large calculi can be dangerous sometimes, by blocking the bile ducts which will result in a
swollen gall bladder, and this may lead to an acute on chronic cholecystitis.

Acute pancreatitis is the most dangerous one. 6

Cholecystitis:
Inflammation of the gallbladder may be acute, chronic, or acute superimposed on
chronic. It almost always occurs in association with gallstones.
Acute Cholecystitis:

Acute calculous cholecystitis Acute acalculous cholecystitis

An acute inflammation of the gallbladder, Occurs in the absence of gallstones, generally

precipitated 90% of the time by in severely ill patients.
Definition

obstruction of the neck or cystic duct.

o It is the primary complication of Is acute cholecystitis always caused by
gallstones and the most common stones?
reason for emergency No.
cholecystectomy.
Progressive right upper quadrant or Tend to be more insidious, since symptoms are
epigastric pain, frequently associated obscured by the underlying conditions
with mild fever, anorexia, tachycardia, precipitating the attacks.
Clinical Features

sweating, and nausea and vomiting. The § A higher proportion of patients have no
upper abdomen is tender. Most patients symptoms referable to the gallbladder.
are free of jaundice
May appear with remarkable suddenness § The incidence of gangrene and perforation
and constitute an acute surgical is much higher than in calculous
emergency or may present with mild cholecystitis. (Because it’s masked by other
symptoms that resolve without medical conditions, it is often detected late when the
complication has already occurred)
intervention.
Just like the symptoms in
acute pancreatitis.
Results from chemical irritation and Most cases of occur in the following
inflammation of the obstructed circumstances:
gallbladder. These events occur in the (1)Severe burns. (2)Multisystem organ failure.
Pathogenesis

absence of bacterial infection; only later in (3)Sepsis. (4)The postpartum state.

the course may bacterial contamination
(5) The postoperative state after major,
develop.
nonbiliary surgery.
(6) Severe trauma (motor vehicle accidents,
Acute calculous is aseptic,
just a chemical irritation. war injuries).
(7) Prolonged intravenous hyperalimentation.

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Morphology: Under the microscope, can someone knows if it’s caused by stones or not? No

§ In acute cholecystitis, the gallbladder is usually enlarged and tense, and bright
red to green-black. The serosal covering is frequently layered by fibrin and, in
severe cases, by exudate.
§ There are no morphologic differences between acute acalculous and calculous
cholecystitis, except for the absence of macroscopic stones in the former.
§ In calculous cholecystitis, an obstructing stone is usually present in the neck of
the gallbladder or the cystic duct.
§ The gallbladder lumen is filled with a cloudy or turbid bile that may contain
fibrin and frank pus, as well as hemorrhage. When the contained exudate is
virtually pure pus, the condition is referred to as empyema of the gallbladder.
§ In mild cases, the gallbladder wall is thickened, edematous, and hyperemic.
§ In more severe cases, it is transformed into a green-black necrotic organ,
termed gangrenous cholecystitis, with small-to-large perforations.
Chronic Cholecystitis:

May be a sequel to repeated bouts of mild to severe acute cholecystitis, but in many instances, it
develops in the apparent absence of antecedent attacks. It is associated with cholelithiasis in
over 90% of cases.
§ The symptoms of calculous chronic cholecystitis are similar to those of the acute form
and range from biliary colic to indolent right upper quadrant pain and epigastric
Features
Clinical

distress. A sense of fullness, specially when they eat butter.

§ Patients often have intolerance to fatty food, belching and postprandial epigastric
distress, sometimes include nausea and vomiting.

§ The morphologic changes in chronic cholecystitis are extremely variable and

sometimes minimal. Gall bladder may be contracted (fibrosis), normal in size or
Morphology

enlarged (from obstruction). The wall is variably thickened. Stones are frequent.
§ On histology, the degree of inflammation is variable. Outpouchings of the mucosal
epithelium through the wall (Rokitansky-Aschoff sinuses) may be quite prominent.
§ Finally, an atrophic, chronically obstructed gallbladder may contain only clear
secretions, a condition known as hydrops of the gallbladder

§ Rarely, extensive dystrophic calcification within the gallbladder wall may yield a
Rare conditions

porcelain gallbladder (hard gallbladder), notable for a markedly increased incidence

of associated cancer.
§ Xanthogranulomatous cholecystitis is also a rare condition in which the gallbladder is
shrunken, nodular, fibrosed and chronically inflamed with abundant lipid filled
macrophages.

Under microscope:
Acute cholecystitis: proliferation of fibroblasts.
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Chronic cholecystitis: thickening of the muscularis propria
 On histology, we can see lymphocytes.
Porcelain bladder on x-rays will
appear as bright white.

Xantho- means yellow, and in

xanthogranulomatous cholecystitis
you can see foamy histiocytes.

Hydrops of the gall bladder is very

rare.

If the epithelium penetrates the wall,

Rokitansky-Aschoff sinuses (outpouchings of the it means either cancer or
mucosal epithelium through the muscular wall of diverticulum.
the gallbladder) may be seen in chronic cholecystis

Acute on chronic cholecystitis is a chronic cholecystitis and on it is a proliferation (acute).

Complications of Acute & Chronic Cholecystitis:

1- Bacterial superinfection with cholangitis or sepsis.

2- GB perforation & local abscess formation.

3- GB rupture with diffuse peritonitis.

4- Biliary enteric (cholecystenteric) fistula with drainage of bile into adjacent

organs, and potentially gallstone-induced intestinal obstruction (ileus).

5- Aggravation of pre-existing medical illness, with cardiac, pulmonary, renal,

or liver decompensation.

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 Check Your Understanding
MCQs:

1. A 47-year-old woman presents with a 3-month history of vague upper

abdominal pain after fatty meals, some abdominal distension, and frequent
indigestion. Physical examination shows an obese woman (BMI = 30 kg/m2)
with right upper quadrant tenderness. An ultrasound examination discloses
multiple echogenic objects in the gallbladder. Which of the following
metabolic changes is most likely associated with the formation of gallstones
in this patient?
A. Increased hepatic cholesterol secretion
B. Decreased serum albumin
C. Increased bilirubin uptake by the liver
D. Increased hepatic calcium secretion

2. For the patient described in Question 1, which of the following is a common

complication?
A. Bile peritonitis
B. Chronic passive congestion of the liver
C. Confluent hepatic necrosis
D. Extrahepatic biliary obstruction

3. A 45-year-old, mildly obese woman presents with a 1-week history of upper

abdominal pain, fever, shaking chills, and occasional vomiting. Physical
examination shows severe right upper quadrant tenderness. An ultrasound
examination of the abdomen reveals a normal-appearing liver and bile duct
and thickening of the wall of the gallbladder. Which of the following is the
most likely diagnosis?
A. Acute cholecystitis
B. Acute pancreatitis
C. Adenocarcinoma of the gallbladder
D. Adenocarcinoma of the pancreas

4. Patient presents to the hospital with a long history of intolerance to fatty

food, saying they get a sense of fullness specially after they eat butter.
Histological findings include Rokitansky-Aschoff sinuses. What is most
likely the diagnosis?
A. Acute cholecystitis
B. Chronic cholecystitis 1:A 2:D 3:A 4:B
C. Adenocarcinoma of the gallbladder * 1,2,3 from 434.

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5. A patient presented to the ER with progressive upper right abdominal pain,
tachycardia, sweating and nausea. His temperature was 37.8 ° C, upon
abdominal examination his upper abdomen is tender. After several
investigations, it was discovered that he has multiple gallstones. What is
most likely the diagnosis?
A. Acute calculous cholecystitis
B. Acute acalculous cholecystitis
C. Chronic Cholecystitis

6. A strawberry gallbladder appearance is a feature of?

A. Acute calculous cholecystitis
B. Acute acalculous cholecystitis
C. Chronic Cholecystitis
D. Cholesterolosis

7. Presence of unconjugated bilirubin in the biliary tract indicates which of the

following?
A. Pigment stones
B. Cholesterol stones
C. Chronic Cholecystitis
D. Cholesterolosis

8. A woman presented to the hospital with cholesterol stones, which of the

following could be the precipitating factor?
A. Chronic hemolytic syndromes
B. Biliary infection
C. Oral contraceptives
D. Ileal disease

9. The incidence of gangrene and perforation of the gallbladder is much higher

in?
A. Acute calculous cholecystitis
B. Acute acalculous cholecystitis
C. Chronic Cholecystitis
D. Cholesterolosis

10. Which of the following is not a complication of cholecystitis?

A. Bacterial superinfection with cholangitis or sepsis.
B. Alzheimer
C. GB perforation & local abscess formation.
D. GB rupture with diffuse peritonitis
5:A 6:D 7:A 8:C 9:B 10:B

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