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Pathology of Gallbladder Flashcards

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1
Q

Front

A

Back

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2
Q

What are the three main objectives for understanding gall bladder pathology outlined in this lecture?

A
  1. Types, etiopathogenesis, macroscopy and complications of cholelithiasis. 2. Types, pathogenesis, morphology and complications of cholecystitis. 3. Brief description on gall bladder carcinoma.
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3
Q

What percentage of adult populations in developed countries are affected by cholelithiasis (gall stones)?

A

10% to 20%.

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4
Q

Are the majority of gallstones symptomatic or asymptomatic?

A

The majority of gallstones (>80%) are asymptomatic or “silent”.

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5
Q

What are the two main types of gall stones?

A
  1. Cholesterol stones. 2. Pigment stones.
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6
Q

What is the primary composition of cholesterol stones, and what percentage of gallstones do they represent?

A

Cholesterol stones are composed of crystalline cholesterol monohydrate and represent the majority (90%) of gallstones.

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7
Q

What is the primary composition of pigment stones?

A

Pigment stones are composed of unconjugated bilirubin and inorganic calcium salts.

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8
Q

List three demographic or lifestyle risk factors for cholesterol stones.

A

Any three from: Northern Europeans, North and South Americans, Native Americans, Mexican Americans (demography); Advancing age; Female sex hormones (female gender, oral contraceptives, pregnancy); Obesity and metabolic syndrome; Rapid weight reduction.

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9
Q

List three physiological or medical condition risk factors for cholesterol stones.

A

Any three from: Gallbladder stasis; Inborn disorders of bile acid metabolism; Hyperlipidemia syndromes.

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10
Q

List two demographic risk factors for pigment stones.

A

Asians more than Westerners; rural more than urban.

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11
Q

List three medical condition risk factors for pigment stones.

A

Chronic hemolytic anemias; Biliary infection; Gastrointestinal disorders (ileal disease e.g., Crohn disease, ileal resection or bypass, cystic fibrosis with pancreatic insufficiency).

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12
Q

What is the fundamental condition related to bile composition that leads to cholesterol stone formation?

A

When cholesterol concentrations exceed the solubilizing capacity of bile (supersaturation), cholesterol can no longer remain dispersed and nucleates into solid cholesterol monohydrate crystals.

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13
Q

What are the four conditions that appear to contribute to the formation of cholesterol gallstones?

A

(1) Supersaturation of bile with cholesterol; (2) Hypomotility of the gallbladder; (3) Accelerated cholesterol crystal nucleation; (4) Hyper-secretion of mucus in the gallbladder.

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14
Q

What type of disorders are associated with the pathogenesis of pigment stones?

A

Disorders associated with elevated levels of unconjugated bilirubin.

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15
Q

List three conditions that can lead to elevated levels of unconjugated bilirubin, contributing to pigment stone formation.

A

Chronic hemolytic anemia, severe ileal dysfunction or bypass, and bacterial contamination of the biliary tree (e.g., Escherichia coli, Ascaris lumbricoides, or the liver fluke C. sinensis).

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16
Q

What is the enzymatic mechanism by which bacterial contamination contributes to pigment stone formation?

A

Bacterial contamination leads to the release of microbial β-glucuronidases, which cause hydrolysis of bilirubin glucuronides (to unconjugated bilirubin).

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17
Q

How does chronic hemolytic anemia contribute to elevated unconjugated bilirubin levels?

A

Increased breakdown of red blood cells produces excess unconjugated bilirubin.

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18
Q

Which enzyme, introduced by pathogens like E. coli, Ascaris lumbricoides, or C. sinensis, is critical for pigment stone formation through deconjugation?

A

β-glucuronidase.

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19
Q

How does ileal dysfunction or bypass contribute to pigment stone formation?

A

Impaired bile acid reabsorption in the ileum reduces the bile acid pool. Since bile acids normally solubilize bilirubin, their deficiency promotes bilirubin precipitation. Altered enterohepatic circulation may also increase biliary calcium concentration.

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20
Q

How do biliary stasis and infection (e.g., from parasitic infections) contribute to pigment stone aggregation?

A

Parasitic infections can cause mechanical obstruction or inflammation, leading to bile stasis. This allows time for bacterial overgrowth, β-glucuronidase activity, and stone aggregation.

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21
Q

Where are cholesterol stones exclusively found?

A

Exclusively in the gallbladder.

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22
Q

Describe the typical macroscopic appearance (color, shape, number) of cholesterol stones.

A

Pale yellow, round to ovoid, multiple, several cm.

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23
Q

What causes the gray white to black discoloration sometimes seen in cholesterol stones?

A

Varying proportions of calcium bilirubin.

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24
Q

Describe the external surface and cut section appearance of cholesterol stones.

A

External surface: Finely granular, hard, facetted. Cut section: Radiating crystalline (radial/spoked-wheel pattern).

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25
Where are black pigment stones typically found?
In sterile gallbladder bile.
26
Describe the typical size, number, and texture of black pigment stones.
Size: Less than 1.5 cm in diameter. Number: Large number of stones. Texture: Crumble to the touch, spiculated and molded.
27
What is the radiopacity of black pigment stones?
50% to 75% Radiopaque (due to calcium carbonate/phosphates).
28
What is the main composition of black pigment stones?
Oxidized polymers of the unconjugated bilirubin, calcium carbonate, calcium phosphate, mucin glycoprotein, cholesterol monohydrate crystals.
29
Where are brown pigment stones typically found?
Found in infected bile (Intrahepatic or extra hepatic ducts).
30
Describe the typical texture and radiopacity of brown pigment stones.
Texture: Laminated and soft, soap like or greasy. Radiopacity: Radiolucent (calcium soaps).
31
What is the main composition of brown pigment stones?
Unconjugated bilirubin + mucin glycoprotein + Cholesterol + calcium salts.
32
What are the two main complications of gall stones mentioned on page 12?
Acute/chronic cholecystitis and Pancreatitis.
33
What is cholecystitis?
Inflammation of the gallbladder.
34
What are the three types of cholecystitis listed?
1. Acute, 2. Chronic, 3. Acute on chronic.
35
Cholecystitis is almost always in association with what condition?
Gallstones.
36
What are the two types of acute cholecystitis, and their relative prevalence?
1. Acute calculous cholecystitis (90%) and 2. Acute acalculous cholecystitis (10%).
37
What precipitates acute calculous cholecystitis?
Obstruction of the neck or cystic duct (by a gallstone).
38
In what patient population does acute acalculous cholecystitis typically occur, and is it associated with gallstones?
It occurs in severely ill patients and is not associated with gallstones.
39
What is the initial pathogenic event in acute calculous cholecystitis after stone obstruction?
Chemical irritation and inflammation of a gallbladder obstructed by stones, with mucosal phospholipases hydrolyzing luminal lecithins to toxic lysolecithins.
40
How does the disruption of the protective mucus layer contribute to acute calculous cholecystitis?
It exposes the mucosal epithelium to the direct detergent action of bile salts.
41
What role do prostaglandins play in the pathogenesis of acute calculous cholecystitis?
Prostaglandins released within the wall of the distended gallbladder contribute to mucosal and mural inflammation; distention and increased intraluminal pressure compromise blood flow to the mucosa.
42
Is bacterial infection an initial event in acute calculous cholecystitis?
No, these events initially occur in the absence of bacterial infection, but later in the course bacterial infection may be superimposed and exacerbate the inflammatory process.
43
What is the primary proposed cause of acute acalculous cholecystitis?
Ischemia, because the cystic artery is an end artery without collateral circulation.
44
List two contributing factors to acute acalculous cholecystitis.
A. Inflammation and edema of the wall (compromising blood flow). B. Gallbladder stasis due to accumulation of microcrystals of cholesterol (biliary sludge), viscous bile, and mucus.
45
List three risk factors for acute acalculous cholecystitis.
Any three from: (1) sepsis with hypotension and multisystem organ failure; (2) immunosuppression; (3) major trauma and burns; (4) diabetes mellitus; (5) infections.
46
Describe the typical macroscopic appearance of the gallbladder in acute cholecystitis.
The gallbladder is usually enlarged and tense, and it may assume a bright red or blotchy, violaceous to green-black discoloration.
47
What is often found covering the serosa in acute cholecystitis?
The serosa is frequently covered by a fibrinous exudate that may be fibrinopurulent in severe cases.
48
Is there a specific morphologic difference between acute acalculous and calculous cholecystitis visible macroscopically?
There are no specific morphologic differences between acute acalculous and calculous cholecystitis, save the absence of stones in the acalculous form.
49
In calculous cholecystitis, what is typically found in the gallbladder lumen besides stones?
The gallbladder lumen contains one or more stones and is filled with cloudy or turbid bile mixed with fibrin, pus, and hemorrhage.
50
What is gallbladder empyema?
A condition in acute cholecystitis where the exudate is virtually pure pus.
51
What is gangrenous cholecystitis?
In severe cases of acute cholecystitis, the gallbladder is transformed into a green-black necrotic organ.
52
What causes acute "emphysematous" cholecystitis?
The invasion of gas-forming organisms, notably clostridia and coliforms.
53
What are the early microscopic changes seen in acute cholecystitis?
Edema, congestion, and mucosal erosion.
54
Are neutrophils typically abundant in the early stages of acute cholecystitis?
Neutrophils are typically sparse, unless there is superimposed infection.
55
List three complications of acute/chronic cholecystitis.
Any three from: Cholangitis, Perforation/abscess formation, Diffuse peritonitis, Gangrene, Septicemia, Biliary enteric fistula, Pancreatitis, Aggravation of preexisting medical illness.
56
What is a biliary enteric fistula and what can it lead to?
An abnormal connection between the biliary system and the intestines. It can lead to entry of gallstones into intestines causing intestinal obstruction (Gall stone Ileus), or entry of air and bacteria into the biliary tree causing cholangitis.
57
What are the common clinical features of acute cholecystitis?
Progressive right upper quadrant or epigastric pain, mild fever, anorexia, tachycardia, sweating, nausea, and vomiting.
58
What is a common laboratory finding in acute cholecystitis?
Mild to moderate leucocytosis.
59
How might the onset of pain differ between acute calculous and acute acalculous cholecystitis?
Acute calculous cholecystitis often presents with previous episodes of pain and acute onset pain. Acute acalculous cholecystitis is often more insidious and occurs in severely ill patients.
60
How can chronic cholecystitis develop?
It 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.
61
What percentage of chronic cholecystitis cases are associated with cholelithiasis?
More than 90% of cases.
62
How does supersaturation of bile contribute to chronic cholecystitis?
Supersaturation of bile predisposes to both chronic inflammation and, in most instances, stone formation.
63
What microorganisms are commonly cultured from the bile in about one-third of chronic cholecystitis cases?
Usually E. coli and enterococci.
64
Describe the macroscopic appearance of the serosa and lumen in chronic calculous cholecystitis.
Serosa: Glistening, fibrous adhesions - Gray-white appearance. Lumen: Clear, green-yellow, mucoid bile - Usually contains stones.
65
What is the typical state of the mucosa and gallbladder wall in chronic calculous cholecystitis macroscopically?
Mucosa: Usually preserved. Gall bladder wall: Markedly thickened.
66
What inflammatory cells are typically seen in the mucosa during microscopic examination of chronic cholecystitis?
Lymphocytes, plasma cells, macrophages.
67
What are Rokitansky-Aschoff sinuses, seen microscopically in chronic cholecystitis?
Outpouchings of the mucosal epithelium through the wall, which may be quite prominent.
68
What changes occur in the gallbladder wall and subserosa microscopically in chronic cholecystitis?
Wall: Thickened. Subserosa: Fibrosis.
69
List three sequelae of chronic cholecystitis.
Any three from: Pancreatitis, Dystrophic calcification ("Porcelain gallbladder"), Xanthogranulomatous cholecystitis, Hydrops of the gallbladder, Hyalinizing cholecystitis, Increased risk of cancer.
70
What is a "Porcelain gallbladder"?
A rare sequela of chronic cholecystitis characterized by dystrophic calcification of the gallbladder wall.
71
Describe Xanthogranulomatous cholecystitis.
A shrunken, nodular gallbladder with a massively thickened wall, a sequela of chronic cholecystitis.
72
What is hydrops of the gallbladder?
An atrophic gallbladder with clear secretions due to chronic obstruction, a sequela of chronic cholecystitis.
73
What is hyalinizing cholecystitis, and what risk does it carry?
Complete replacement of the gallbladder wall and mucosa by dense fibrosis, with or without calcification. It carries an increased risk of cancer.
74
What is the significance of carcinoma of the gallbladder in relation to biliary tract malignancies?
It is the most common malignancy of the extrahepatic biliary tract.
75
What is the gender predilection and peak age for gallbladder carcinoma?
Gender: Women > Men. Peak age: Seventh decade.
76
At what stage is gallbladder carcinoma typically discovered, and what is the mean 5-year survival rate?
Discovery: Usually at an advanced stage. Mean 5-year survival rate: About 5% to 12% despite surgical intervention.
77
What is the most important risk factor for gallbladder carcinoma, and in what percentage of cases is it present?
Gallstones (cholelithiasis) - Important; present in 95%.
78
List two other risk factors for gallbladder carcinoma besides gallstones.
Pyogenic infections and Parasitic diseases.
79
Outline the proposed pathogenesis sequence for gallbladder carcinoma.
Irritation and trauma -> Chronic inflammation -> Carcinogenic derivatives of bile acids -> Gall bladder carcinoma.

Pathology GI (4 decks)

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