Gallstones and biliary obstruction

Spectrum of Gallstone Disease & Biliary Pathologies

Gallstone disease (cholelithiasis) is exceptionally prevalent in Australia, affecting approximately 15% to 20% of the adult population. While up to 80% of individuals with gallstones remain asymptomatic throughout life, symptomatic presentations span a wide spectrum from self-limiting colic to life-threatening suppurative cholangitis and necrotizing pancreatitis.

Pathogenesis of Gallstone Formation

Gallstones are classified into three biochemical categories:

1. Cholesterol Stones (80% to 85% in Western nations): Arise when hepatic cholesterol secretion supersaturates bile relative to solubilizing bile salts and phospholipids (lecithin), promoting cholesterol monohydrate crystal nucleation and hypomotility of the gallbladder. Risk factors correspond to the classic mnemonic (Female, Forty, Fertile, Fat, Family history, Rapid weight loss).
2. Black Pigment Stones (~10% to 15%): Small, hard, radiopaque stones composed of calcium bilirubinate, resulting from chronic unconjugated hyperbilirubinaemia in patients with chronic haemolysis (hereditary spherocytosis, sickle cell disease, thalassaemia major), liver cirrhosis, or ileal resection.
3. Brown Pigment Stones (< 5%): Soft, greasy, radiolucent stones formed within the intrahepatic or extrahepatic bile ducts secondary to chronic biliary stasis and bacterial infection (Escherichia coli, Klebsiella) producing bacterial beta-glucuronidase, which hydrolyzes conjugated bilirubin into insoluble unconjugated bilirubin.

Clinical Entities of Gallstone Disease

• Biliary Colic:
  • Mechanism: Transient impaction of a gallstone within the neck of the gallbladder (Hartmann's pouch) or cystic duct during postprandial gallbladder contraction (stimulated by cholecystokinin release following a fatty meal). As the gallbladder relaxes, the calculus falls back into the fundus, relieving the obstruction.
  • Clinical Presentation: Episodic, severe, constant dull or cramping ache in the right upper quadrant (RUQ) or epigastrium that radiates around the right costal margin to the right infrascapular region or back. Pain builds to a plateau over 15 to 30 minutes and resolves completely within 4 to 6 hours (typically lasting 1 to 5 hours).
  • Discriminative Features: The patient is afebrile; full blood count (white cells, neutrophils) and C-reactive protein are strictly normal; liver function tests (LFTs) are entirely normal; abdominal palpation reveals mild RUQ tenderness without peritoneal signs (Murphy sign is negative).
  • Investigation & Treatment: Transabdominal ultrasound confirms cholelithiasis (mobile, echogenic foci with posterior acoustic shadowing). Definitive management is an elective outpatient laparoscopic cholecystectomy. For acute pain, parenteral NSAIDs (e.g., indomethacin or diclofenac) are superior to opioids as they inhibit prostaglandin-mediated gallbladder contractility and reduce progression to cholecystitis.
• Acute Cholecystitis:
  • Mechanism: Persistent, non-resolving calculus obstruction of the cystic duct leads to intraluminal distension, mucosal ischaemia, chemical inflammation mediated by lysolecithin, and secondary bacterial colonization in 50% to 75% of cases (E. coli, Klebsiella, Enterococcus).
  • Clinical Presentation: Continuous, severe, sharp RUQ or epigastric pain lasting longer than 6 hours, accompanied by anorexia, nausea, repeated vomiting, low-grade to moderate fever ($> 38^\circ\text{C}$), and tachycardia.
  • Physical Examination: Positive Murphy Sign—the examiner places fingers under the right costal margin at the mid-clavicular line and asks the patient to inhale deeply; as the descending liver drives the inflamed gallbladder against the examiner's fingers, the patient experiences an abrupt, sharp catch of pain and arrests inspiration. (Crucially, palpation under the left costal margin does not arrest inspiration).
  • Diagnostic Findings: Marked leukocytosis with left shift, elevated CRP; LFTs are usually normal, though a mild reactive transaminitis or minor alkaline phosphatase elevation may occur.
  • Ultrasound Criteria (First-Line): Demonstrates cholelithiasis, thickened gallbladder wall ($> 3\text{ mm}$), pericholecystic fluid halo, gallbladder distension (long axis $> 8\text{ cm}$, transverse $> 4\text{ cm}$), and a sonographic Murphy sign (focal maximal tenderness directly over the sonographically visualized gallbladder).
• Gallstone pancreatitis: In mild disease, perform cholecystectomy during the same admission when appropriate to prevent recurrence. Severe disease or collections may warrant delay. Cholangitis or ongoing biliary obstruction can require urgent ERCP; routine early ERCP is not indicated for all gallstone pancreatitis.
  • Unfit / Critically Ill Patients: In elderly, septic, or severely comorbid patients with acalculous cholecystitis or severe cholecystitis unfit for general anaesthesia, percutaneous transhepatic cholecystostomy (PTC) tube drainage under ultrasound guidance provides immediate decompression and source control.

Choledocholithiasis & Acute Ascending Cholangitis

Choledocholithiasis occurs when a gallstone migrates from the gallbladder through the cystic duct into the common bile duct (CBD), or less commonly, forms de novo within the duct (primary choledocholithiasis).

Clinical and Biochemical Profile

• Presentation: Intermittent biliary colic associated with obstructive jaundice (dark tea-coloured urine due to water-soluble conjugated bilirubinuria, pale clay-coloured acholic stools due to lack of stercobilin, and generalized pruritus caused by bile salt deposition in skin).
• Biochemical Pattern: Obstructive / Cholestatic LFT Derangement: Early marked elevations in alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), accompanied by elevated total and conjugated (direct) bilirubin. Serum transaminases (ALT, AST) are normal or demonstrate a transient, acute spike ($> 500-1000\text{ U/L}$) during acute stone passage, mimicking acute viral or toxic hepatitis before settling into a typical cholestatic pattern.
• Diagnostic Risk Stratification:
  • High Risk: Presence of ascending cholangitis, visible CBD stone on transabdominal ultrasound, or total bilirubin $> 68\ \mu\text{mol/L}$ ($> 4\text{ mg/dL}$) with dilated CBD on ultrasound ($> 6\text{ mm}$, or $> 8\text{ mm}$ in post-cholecystectomy patients). Patients proceed directly to therapeutic Endoscopic Retrograde Cholangiopancreatography (ERCP).
  • Intermediate Risk: Abnormal LFTs, age $> 55$, or dilated CBD without a visible calculus on ultrasound. Because transabdominal ultrasound has a poor sensitivity for distal CBD stones (~50% due to overlying duodenal gas), intermediate-risk patients must undergo non-invasive Magnetic Resonance Cholangiopancreatography (MRCP) or Endoscopic Ultrasound (EUS) to confirm stone presence prior to any invasive ERCP, avoiding unnecessary ERCP-related pancreatitis.
  • Low Risk: Normal LFTs, non-dilated duct on ultrasound. Proceed directly to laparoscopic cholecystectomy with intraoperative cholangiogram (IOC).

Primary references (checked 7 October 2026): ASGE cholangitis guidance.