Chapter 18 part 6: Gallbladder

Question 1

Congenital anomalies of the gallbladder

Answer 1

• can be congenitally absent or exist in aberrant locations (embedded in hepatic substance)
• other variants include folded fundus (phrygian cap) or duplicated or bilobed gallbladder
• agenesisi of common or hepatic bile ducts or hypoplastic narrowing of biliary channels

Question 2

Cholelithiasis (gallstones)

Answer 2

• 95% of biliary tract disease attributed to this
• 90% are cholesterol stones with remainder being pigmented (bilirubin calcium salts); vast majority remain asymptomatic for decades

Question 3

Risk factors for cholesterol gallstones

Answer 3

• related to increased hepatic cholesterol uptake or synthesis or increased biliary cholesterol secretion
• Native Americans (75% in Hopi, Navajo and Pima groups)
• Industrialized countries
• increasing age, female more than males
• Estrogenic influences, including oral contraception and pregnancy
• Obesity, metabolic syndromes, hypercholestrolemia, and rapid weight loss
• Gallbladder stasis, like in spinal cord injury
• Heritable conditions related to hepatic biliary transport (common variants of adenosine triphosphate [ATP]-binding cassette sterol transported encoded by ABCG8 gene

Question 4

Pathogenesis of Cholesterol stones

Answer 4

-When cholesterol concentration exceed solubilizing capacity of bile salts (supersaturation), cholesterol nucleates into solid cholesterol monohydrate crystals

Question 5

Four conditions that contribute to cholesterol stone formation

Answer 5

1) Bile must be supersaturated with cholesterol
2) Gallbladder hypomotility promotes crystal nucleation
3) Cholesterol nucleation in bile is accelerated by microprecipitates of calcium salts (inorganic or bilirubin salts)
4) Mucus hypersecretion in gallbladder traps the cyrstals permitting aggregation into stones

Question 6

Pathogenesis of pigment stones

Answer 6

• form in setting of unconjugated bilirubin (most commonly due to chronic hemolytic conditions) and precipitation of calcium bilirubin salts
• In underdeveloped countries, pigmented stones are often formed bc biliary infections (with E. Coli, Ascaris lumbricoides, or O. sinensis) promote bilirubin glucuronide deconjugation

Question 7

Morphology of cholesterol stones

Answer 7

• arise exclusively in gallbladder and are classically hard and pale yellow
• bilirubin salts can impart a black color
• when composed mostly of cholesterol, they are radiolucent; calcium carbonate deposition in 10-20% of stones is sufficient to render them radiopaque
• single stones are ovoid; multiple stones are faceted

Question 8

Morphology of pigmented stones

Answer 8

• can be black (sterile gallbladder bile) or brown (with infection)
• Both are soft and usually multiple and most are radiopaque

Question 9

Clinical features of gallstones

Answer 9

• 70-80% asymptomatic in life
• become symptomatic at a rate of 1-4% per year with risk diminishing with time
• S/S: spasmodic, colicky pain, due to passing stones in bile ducts (smaller stones more commonly cause symptoms than large stones)
• Associated gallbladder inflammation (cholecystitis) generates right upper-abdominal pain

Question 10

Severe complications of gallstones

Answer 10

• Empyema, perforation, fistulas, biliary tree inflammation (cholangitis), obstructive cholestasis or pancreatitis and erosion of gallstone into adjacent bowel (gallstone ileus)
• Clear mucinous secretions in obstructed gallbladder distend the gallbladder (mucocele)
• also increased risk for gallbladder carcinoma

Question 11

Cholecystitis

Answer 11

• Can be acute or chronic

- Acute divided into acute calculous colecystitis (WITH gallstones) and acute acalculus cholecystitis

Question 12

Acute cholecystitis

Answer 12

• acute inflammation of gallbladder precipitated most frequently by gallstone obstruction
• 10% of cases without gallstone obstruction usually occur in severely ill patients

Question 13

Acute calculus cholecystitis

Answer 13

• with gallstones
• initiated by chemical irritation of gallbladder by retained bile acids; subsequent release of inlammatory mediators (lysolecithin, prostaglandins) and gallbladder develops dysmotility
• In severe cases, distention and increased luminal pressures compromise mucosal blood flow causing ischemia; bacterial contamination can be late complication

Question 14

Acute acalculous cholecystitis

Answer 14

• results from ischemia due to diminished flow in end-arterial cystic artery circulation
• occurs in setting of sepsis with hypotension and multiorgan failure, immunosuppression, major trauma or burns, DM, or infections

Question 15

Morphology of acute cholecystitis

Answer 15

• enlarged, tense, bright red to blotchy green-black gallbladder with serosal fibrinous exudate
• Luminal contents range from turbid to purulent
• In severe cases, gallbladder is transformed into green-black necrotic organ (gangrenous cholecystitis) with multiple perforations
• In milder cases only gallbladder wall edema and hyperemia

Question 16

Clinical features of acute cholecystitis

Answer 16

-may be mild and intermittent or may be a surgical emergency
S/S: RUQ or epigastric pain, fever, anorexia, tachycardia, diaphoresis, and nausea and vomiting
-jaundice suggests common bile duct obstruction

Question 17

Cholecystitis prognosis

Answer 17

• Slef limited attacks subside over several days
• 25% develop more severe symptoms and require surgical intervention
• In severely ill paients with acalculus cholecystitis, symptoms may not be evident due to comorbid conditions and mortality rate is higher

Question 18

Chronic cholecystitis

Answer 18

• consequence of repeated bouts of acute cholecystitis but often develops without antecedent attacks
• although gallstones are usually present (90%), they may not play a role in initiating inflammation
• Rather chronic bile supersaturation with cholesterol permits cholesterol suffusion of gallbladder wall and initiation of inflammation and gallbladder dysmotility
• Pt. populations and symptoms are same as for acute cholecystitis

Question 19

Morphology of chronic cholecystitis

Answer 19

• contracted gallbladders (from fibrosis), normal size or enlarged (from obstruction)
• wall is variably thickened and gray-white
• mucosa is generally preserved but may be atrophied
• cholesterol-laden macrophages in lamina propria (cholesterolosis) and gallstones frequent
• Variable inflammation with occasional mucosal outpouchings (Rokitansky-Aschoff sinuses)
• Rarely see mural dystrophic calcifications (porcelain gallbladder) or a fibrosed, nodular gallbladder with marked histiocytic inflammation (xanthogranulomatous cholecystitis)

Question 20

Clinical features of chronic cholecystitis

Answer 20

• Recurrent attacks of steady or colicky epigastric or RUQ pain
• Complications: same as for acute including bacterial superinfection, gallbladder perforation and abscess formation or peritonitis and formation of biliary-enteric fistulas

Question 21

Carcinoma of the gallbladder

Answer 21

• slightly more common in women, age over 70
• gallstones coexist in 95% of US patients
• chronic gallbladder inflammation (with or without stones) is critical risk factor)
• Gallstones less common precursor in Asian populations where pyogeniic and parasitic diseases dominate as causes
• Gallbladder cancers harbor recurrent molecular alterations; ERBB2 (Her-2/neu) is overexpressed in 30-60% of cases and mutations of chromatin remodeling genes (PBRM1 and MLL3) occur in 25%

Question 22

Morphology of gallbladder carcinoma

Answer 22

• tumors may be INFILTRATING with diffuse gallbladder thickening and induration, or EXOPHYTIC–growing into lumen as irregular, cauliflower-like mass
• Most gallbladder carcinomas are adenocarcinomas
• Histo varies from papillary to infiltrating and can range from moderately differentiated to undifferentiated
• Rarely there are squamous, adenosquamous, carcinoid or mesenchymal variants
• spread by local invasion of liver, extension to cystic duct and portohepatic lymph nodes and metastatic seeding of peritoneum, viscera and lungs

Question 23

Clinical features of gallbladder carcinoma

Answer 23

• S/S: insiduous and indistinguishable from those caused by cholelithasis
• Tumors usually unresectable when discovered