Gallbladder Pathophysiology

Cholelithiasis (Gallstones)

Pathophysiology

Gallstones form when bile components precipitate out of solution. The two major types are cholesterol stones (80%) and pigment stones (20%). Cholesterol stones form when bile is supersaturated with cholesterol relative to bile salts and lecithin (lithogenic bile), combined with reduced gallbladder motility and crystal nucleation. Black pigment stones form from excess unconjugated bilirubin (hemolytic states); brown pigment stones form from bacterial enzymatic deconjugation of bilirubin in infected bile.

Risk Factors

🧠 Mnemonic — 4 F's + additionalFat · Female · Fertile (pregnancy) · Forty (age >40) — PLUS: Fair (Native American/Hispanic), Family history, Rapid weight loss, OCPs/estrogen, Ileal disease (Crohn's, ileal resection), TPN, diabetes, hemolytic anemia

Stone Types

Type	Composition	Appearance	Association
Cholesterol	>50% cholesterol	Large, solitary, pale yellow, may float on X-ray	Obesity, OCP, pregnancy, rapid weight loss, Crohn's
Black pigment	Calcium bilirubinate	Small, multiple, radio-opaque	Hemolysis (sickle cell, spherocytosis), cirrhosis, total parenteral nutrition
Brown pigment	Calcium bilirubinate + fatty acids	Soft, brown, radio-lucent	Biliary stasis + infection (E. coli, Klebsiella)

🏥 ClinicalMost gallstones (80%) are asymptomatic. Biliary colic: episodic RUQ pain radiating to right shoulder, post-fatty meal, lasting 1–6 hours, with nausea/vomiting. RUQ ultrasound is the imaging of choice (sensitivity >95%). Asymptomatic gallstones generally do not require cholecystectomy unless in high-risk populations (porcelain gallbladder, Native American heritage, transplant candidates).

Cholecystitis

Acute Calculous Cholecystitis

Gallstone impaction in the cystic duct → bile accumulation → increased intraluminal pressure → gallbladder wall ischemia → inflammation and possible secondary bacterial infection. 90–95% of acute cholecystitis cases are calculous.

Clinical Presentation

Feature	Details
Pain	Persistent RUQ or epigastric pain (>6 hours), unlike biliary colic
Murphy's sign	Inspiratory arrest during deep RUQ palpation (pathognomonic)
Fever/leukocytosis	Low-grade fever, WBC 12,000–15,000
Labs	Mild elevation of bilirubin, alkaline phosphatase, ALT/AST; WBC elevated
Imaging	U/S: gallstones + gallbladder wall thickening (>3mm), pericholecystic fluid, sonographic Murphy's sign

Complications of Cholecystitis

Gangrenous cholecystitis: full-thickness necrosis; higher surgical risk
Emphysematous cholecystitis: gas-forming organisms (Clostridium, E. coli); diabetics; CT: gas in wall
Gallbladder perforation: pericholecystic abscess or bile peritonitis
Mirizzi syndrome: external compression of common bile duct by stone in cystic duct/gallbladder neck

Acalculous Cholecystitis

Gallbladder inflammation without stones; occurs in critically ill patients (ICU, trauma, major surgery, burns, TPN, sepsis). Mechanism: bile stasis + ischemia + mucosal injury. Higher risk of gangrene and perforation. Diagnosis: HIDA scan (if ultrasound non-diagnostic). Treatment: percutaneous cholecystostomy in unstable patients.

🎯 Boards PearlTreatment of acute cholecystitis: NPO, IV fluids, analgesics, IV antibiotics (ceftriaxone + metronidazole, or piperacillin-tazobactam), and early laparoscopic cholecystectomy within 72 hours (preferred over delayed surgery). Delayed cholecystectomy (4–6 weeks) is reserved for high surgical risk patients.

Choledocholithiasis

Stones in the common bile duct (CBD). May be primary (formed in CBD) or secondary (migrated from gallbladder). Causes obstructive jaundice, biliary colic, and can lead to cholangitis or gallstone pancreatitis.

Feature	Detail
Symptoms	Jaundice, RUQ pain, acholic stools, dark urine, pruritus
Labs	Elevated direct bilirubin, elevated alkaline phosphatase, mildly elevated AST/ALT
Imaging	Ultrasound (dilated CBD >6mm), MRCP (definitive non-invasive), ERCP (diagnostic + therapeutic)
Treatment	ERCP with sphincterotomy and stone extraction; followed by laparoscopic cholecystectomy

🏥 Clinical NoteCBD dilation threshold: >6mm after cholecystectomy; >8mm before age 60 or in patients with intact gallbladder. MRCP is preferred over CT for CBD stone detection (no radiation, better sensitivity for soft tissue). ERCP is reserved for cases requiring intervention.

Ascending (Acute) Cholangitis

Pathophysiology

Biliary obstruction (most often from CBD stones) → increased intraluminal pressure → biliary-venous reflux → bacteremia. Common organisms: E. coli (most common), Klebsiella, Enterococcus, anaerobes.

Charcot's Triad & Reynolds' Pentad

Charcot's Triad (classic)	Reynolds' Pentad (severe/suppurative)
Fever + chills	Fever + chills
Jaundice	Jaundice
RUQ pain	RUQ pain
—	Altered mental status
—	Hypotension (septic shock)

Management

IV fluid resuscitation, NPO, IV antibiotics (coverage for gram-negatives and anaerobes)
Urgent biliary decompression: ERCP (preferred), or percutaneous transhepatic cholangiography (PTC)
Blood cultures before antibiotics
ICU admission for Reynolds' pentad

🎯 Boards PearlAscending cholangitis is a surgical/GI emergency. Reynolds' pentad = suppurative cholangitis with septic shock — mortality up to 50% without prompt decompression. Don't delay ERCP waiting for broad workup. Charcot's triad is only present in ~50–70% of cases.

Biliary Disease Comparison

Condition	Pain Duration	Fever	Jaundice	Key Finding	Treatment
Biliary colic	1–6 hours	No	No	Gallstones on U/S	Elective cholecystectomy
Acute cholecystitis	>6 hours	Yes (low-grade)	Mild (5–10%)	Murphy's sign, wall thickening	Antibiotics + early cholecystectomy
Choledocholithiasis	Variable	No (unless cholangitis)	Yes (direct)	CBD dilation, direct hyperbilirubinemia	ERCP + later cholecystectomy
Ascending cholangitis	Constant	Yes (high, rigors)	Yes	Charcot's triad	Emergent ERCP + IV antibiotics
Gallstone pancreatitis	Epigastric/back	Variable	Mild	Elevated lipase, dilated CBD	Supportive + ERCP if obstruction