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GALLSTONES (CHOLELITHIASIS) AND ACUTE CALCULOUS CHOLECYSTITIS

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PART 1: CLASSIFICATION OF GALLSTONES

Three Main Types:

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PART 2: ETIOPATHOGENESIS OF GALLSTONES

Cholesterol Stone Formation - Three Steps:

• Cholesterol is insoluble in water and secreted from the canalicular membrane in phospholipid vesicles
• When bile is supersaturated with cholesterol and/or bile acid concentrations are low, unstable unilamellar phospholipid vesicles form
• Factors increasing cholesterol secretion: obesity, high-calorie diet, oral contraceptives, oestrogens (increase hepatic lipoprotein receptors and stimulate hepatic cholesterol synthesis)
• Factors depleting bile acid pool: ileal disease (Crohn's), ileal resection, cholestyramine

• Cholesterol monohydrate crystals nucleate from multilamellar vesicles
• Nucleating factors include mucus, glycoproteins, and infection

• Abnormal gallbladder emptying aids aggregation of nucleated crystals
• This is why removing stones without removing the gallbladder leads to recurrence

Risk Factors (The "5 F's" mnemonic expanded):

• Fat - obesity, metabolic syndrome, hyperlipidaemia
• Female - higher prevalence due to oestrogen exposure
• Fertile - pregnancy increases biliary cholesterol secretion
• Forty - increasing age; predominantly middle to older age
• Fair - Northern Europeans, North/South Americans, Native Americans (Pima, Hopi, Navajo tribes up to 75%)
• Additional: oral contraceptives, rapid weight reduction, gallbladder stasis, inborn bile acid metabolism disorders, total parenteral nutrition, vagotomy

Pigment Stone Pathogenesis:

• Black stones: Unconjugated bilirubin increases due to haemolysis → precipitates as bilirubin polymer in concentrated supersaturated bile
• Brown stones: Bacterial β-glucuronidase (from E. coli, Bacteroides) deconjugates bilirubin glucuronide → insoluble unconjugated bilirubinate precipitates in infected stagnant bile in ducts

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PART 3: CLINICAL FEATURES OF GALLSTONES

• Prophylactic cholecystectomy generally NOT indicated
• 20-year follow-up: only 18% develop biliary pain; mean yearly probability is 2% in first 5 years, declining to 0.5% by years 10-20

• Right upper quadrant (RUQ) or epigastric pain, radiating to the back or right shoulder tip
• Pain is typically dull, continuous, and severe (not truly "colicky") - lasts minutes to hours
• Associated nausea, vomiting, anorexia
• Pain often starts at night (wakes the patient)
• Relieved when stone slips back into the gallbladder body
• Dyspepsia, flatulence, fatty food intolerance (less specific symptoms)

• Acute cholecystitis: fever, positive Murphy's sign, RUQ mass (omental wall-off)
• Empyema of gallbladder: high fever, rigors, severely ill patient
• Gangrene and perforation: peritonitis
• Choledocholithiasis: obstructive jaundice (dark urine, pale stools, pruritus)
• Cholangitis: Charcot's triad (RUQ pain + fever/rigors + jaundice); Reynolds' pentad adds shock + confusion
• Pancreatitis: epigastric pain radiating to the back, elevated amylase/lipase

• Peptic ulcer disease / gastritis
• Acute pancreatitis
• Hepatitis (acute)
• Right-sided renal colic
• Myocardial infarction (inferior MI can mimic biliary pain)
• Irritable bowel syndrome
• Hiatus hernia / GORD
• Appendicitis (atypical)

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PART 4: INVESTIGATIONS FOR GALLSTONES

Bloods:

• FBC - leucocytosis in cholecystitis (WBC >18,000/mm³ indicates moderate severity by Tokyo Guidelines)
• LFTs - elevated ALP, GGT, conjugated bilirubin if CBD involvement; transaminases elevated in hepatitis/pancreatitis
• Serum amylase/lipase - if pancreatitis suspected
• CRP - inflammatory marker to assess severity
• PT/INR - may be prolonged if jaundiced (Vitamin K deficiency)
• Serum albumin - marker of nutritional status

Imaging:

• Sonographic Murphy's sign
• Gallbladder wall thickening >4mm
• Pericholecystic fluid
• Distended gallbladder with gallstones

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PART 5: ACUTE CALCULOUS CHOLECYSTITIS

Pathogenesis:

1. Stone impaction in the cystic duct or gallbladder neck → outflow obstruction
2. Chemical inflammation - mucosal phospholipases hydrolyze luminal lecithins to toxic lysolecithins → disrupts the protective glycoprotein mucus layer → bile salts exert direct detergent action on mucosa
3. Prostaglandin release from distended gallbladder wall → mucosal and mural inflammation
4. Distension and raised intraluminal pressure → compromised mucosal blood flow
5. Bacterial superinfection (later phase) - bacteria from: E. coli, Klebsiella, Enterococcus, Bacteroides, Clostridium
6. Progression → gangrenous cholecystitis → perforation → empyema/peritonitis

Clinical Features:

• Onset: Progressive RUQ or epigastric pain lasting >6 hours (distinguishes it from biliary colic)
• Fever: Low-grade initially; high fever suggests gangrenous cholecystitis or empyema
• Nausea and vomiting
• Anorexia, tachycardia, sweating

• Murphy's sign (pathognomonic) - RUQ tenderness exacerbated during inspiration when palpating the right subcostal region; the patient catches their breath
• RUQ tenderness and guarding - tenderness, voluntary guarding
• Palpable mass - inflamed gallbladder walled off by omentum
• Jaundice (in ~20%) - due to CBD compression by periductal inflammation (Mirizzi syndrome) or concurrent choledocholithiasis

Complications:

• Empyema of the gallbladder - pus filling the lumen; high fever, rigors, very tender mass
• Gangrenous cholecystitis - wall necrosis; gas-forming organisms → emphysematous cholecystitis
• Perforation - generalised biliary peritonitis or localised pericholecystic abscess
• Fistula - cholecystoduodenal, cholecystocolic, or cholecystogastric
• Gallstone ileus - large stone erodes into duodenum, causes small bowel obstruction at ileocaecal valve
• Mirizzi syndrome - stone in cystic duct compresses common hepatic duct

Tokyo Guidelines 2018 - Severity Grading:

• Elevated WBC >18,000/mm³
• Palpable tender mass in RUQ
• Duration of symptoms >72 hours
• Marked local inflammation (gangrenous/emphysematous cholecystitis, pericholecystic abscess)

• Cardiovascular: hypotension requiring dopamine ≥5 μg/kg/min or any epinephrine
• Neurological: decreased level of consciousness
• Respiratory: PaO₂/FiO₂ ratio <300
• Renal: oliguria; creatinine >2.0 mg/dL
• Hepatic: PT-INR >1.5
• Haematological: platelets <100,000/mm³

Management of Acute Calculous Cholecystitis:

1. Nil by mouth + IV fluid resuscitation until pain resolves
2. Analgesia - NSAIDs (diclofenac IM/IV reduces intraluminal pressure via prostaglandin inhibition), opioids (pethidine preferred over morphine to avoid Oddi spasm)
3. IV Antibiotics - as cystic duct is blocked, serum concentration matters more than biliary concentration:
   • Mild-moderate: cefazolin, cefuroxime, cefoxitin, or ciprofloxacin
   • Severe: piperacillin-tazobactam or 3rd-generation cephalosporin + metronidazole
   • Add anaerobic cover if gangrenous/emphysematous cholecystitis suspected
4. Monitoring: temperature, pulse, WBC, CRP

• USG to confirm (first-line)
• If jaundiced: MRCP to exclude choledocholithiasis
• If complicated: CT scan

• Laparoscopic cholecystectomy is the gold standard (higher conversion rate in acute vs. elective but still preferred)
• Tokyo Guidelines algorithm: Grade I → early laparoscopic cholecystectomy; Grade II → early LC if experienced surgeon available, otherwise conservative + delayed LC; Grade III → ICU stabilisation first, then LC when stable or cholecystostomy as bridge
• Percutaneous cholecystostomy - for Grade III patients unfit for surgery; tube drainage of gallbladder as a temporising measure

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OBSTRUCTIVE JAUNDICE

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DEFINITION

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ETIOLOGY / CAUSES

Malignant (Painless, Progressive):

• Carcinoma of the head of pancreas (most common malignant cause)
• Cholangiocarcinoma (Klatskin tumour at hilum)
• Carcinoma of the gallbladder
• Ampullary carcinoma
• Metastatic disease compressing the biliary system

Benign (often Painful, Fluctuating):

• Choledocholithiasis (most common cause overall - painful, fluctuating)
• Primary or secondary sclerosing cholangitis
• Benign biliary strictures (post-operative, post-inflammatory)
• Choledochal cyst
• Parasites (Clonorchis sinensis, Ascaris)
• Haemobilia
• Pancreatic pseudocysts
• Chronic pancreatitis (pseudotumoral)
• Duodenal diverticulum / ampullary scarring

Congenital:

• Biliary atresia
• Caroli's disease

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CLINICAL FEATURES

Symptoms:

• Jaundice - yellow discolouration of skin, sclerae, mucous membranes
• Dark urine (conjugated bilirubin - water soluble, excreted in urine → "Coca-Cola urine")
• Pale/clay-coloured stools (absence of stercobilinogen)
• Pruritus - due to bile salt deposition in skin; often severe
• Fatigue
• Abdominal pain - RUQ colicky pain in stones; epigastric pain in pancreatic cancer
• Weight loss, anorexia - suggests malignancy
• Fever and rigors - suggests cholangitis (Charcot's triad: pain + fever + jaundice)

Signs:

• Icteric sclerae, jaundiced skin
• Scratch marks (pruritus)
• Palpable, non-tender gallbladder (Courvoisier's sign) → malignant obstruction
• Hepatomegaly
• Splenomegaly in portal hypertension
• Cachexia, Virchow's node (left supraclavicular lymph node) - in GI malignancy
• Hepatic flap/asterixis if hepatic failure developing

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DIFFERENTIAL DIAGNOSIS

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INVESTIGATIONS

Blood Tests:

Imaging Investigations:

1. Ultrasound (US) - FIRST LINE:
   • Detects biliary duct dilation; establishes level of obstruction in ~67% of cases
   • Sensitivity for CBD stones only 21-63% (poor for distal stones)
   • Shows liver parenchyma, gallbladder, hepatic/pancreatic masses
2. MRCP (Magnetic Resonance Cholangiopancreatography):
   • Non-invasive test of choice for biliary anatomy
   • Sensitivity 95% for biliary obstruction; best for CBD stones
   • Differentiates strictures but distinguishing benign vs malignant can be challenging
   • No therapeutic capability
3. CT abdomen/pelvis:
   • Excellent for pancreatic tumours >2cm, staging of malignancy
   • Identifies vascular involvement, lymphadenopathy, metastases
   • Less sensitive than MRCP for CBD stones
4. EUS (Endoscopic Ultrasound):
   • Best for distal CBD, ampullary region, pancreatic head
   • Enables fine-needle aspiration (FNA): sensitivity 84-91%, specificity 71-100%
   • Can identify vascular invasion and lymph node metastases
5. ERCP (Endoscopic Retrograde Cholangiopancreatography):
   • Primarily therapeutic (not just diagnostic)
   • Cannulation successful in >90% cases
   • Enables: sphincterotomy, stone extraction, balloon sweep, stent placement, brush cytology
   • Complications: pancreatitis, cholangitis, bleeding, perforation
6. Percutaneous Transhepatic Cholangiography (PTC):
   • Used when ERCP fails or inaccessible anatomy
   • Allows external biliary drainage, internal stenting
7. Liver biopsy:
   • Reserved for suspected parenchymal disease
   • Contraindicated if PT prolonged and unresponsive to Vitamin K, or platelets <50,000/mm³

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MANAGEMENT OF OBSTRUCTIVE JAUNDICE

General Preoperative Preparation:

1. Correction of coagulation:
   • IV Vitamin K₁ 20 mg → rapid normalisation of PT within 12-24 hours (if liver synthetic function intact)
   • Good response = post-hepatic obstruction (favourable surgical risk)
   • Poor response = hepatocellular disease
2. Renal protection:
   • Jaundiced patients at high risk of hepatorenal syndrome
   • Aggressive IV fluid hydration pre- and post-operatively
   • Monitor urine output; consider mannitol infusion
   • Avoid nephrotoxic drugs
3. Nutritional support - correct malnutrition, hypoalbuminaemia
4. Antibiotics - treat concurrent cholangitis with broad-spectrum cover

Surgical mortality in jaundiced patients: ~20%; recognised risk factors:

• Old age
• Malnutrition
• Ongoing biliary infection
• Malignancy
• High serum urea (renal impairment)

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Definitive Management Based on Cause:

A. Choledocholithiasis (CBD stones):

• ERCP + endoscopic sphincterotomy + stone extraction (first-line)
• Basket or balloon retrieval of stones
• Lithotripsy for large stones
• Followed by laparoscopic cholecystectomy for the gallbladder

B. Malignant Obstruction (Pancreatic/Bile Duct Cancer):

• Pancreaticoduodenectomy (Whipple's procedure) for periampullary/pancreatic head tumours
• Preoperative biliary drainage: controversial - not proven to reduce operative mortality; however, needed if neoadjuvant chemotherapy is planned

• Biliary decompression/palliation:
  • ERCP + stenting (first-line for distal obstruction)
    • Plastic stents: cheap but occlude every 3-4 months (biofilm formation); patency ~43 days
    • Self-expanding metallic stents (SEMS): wider bore, patency ~125 days; preferred for >6 months survival
    • Covered SEMS (cSEMS): prevent tumour ingrowth, removable; meta-analysis shows fewer adverse events vs uncovered SEMS
  • Percutaneous transhepatic drainage (when ERCP fails)
  • Surgical bypass (hepaticojejunostomy or choledochojejunostomy) if endoscopic approach not possible
• Only 25-30% of liver volume needs to be drained for jaundice resolution
  • Right hepatic duct drains 50-55% of liver
  • Left hepatic duct drains 30-35%
  • Caudate lobe drains 10%

C. Benign Biliary Strictures (Bismuth Classification):

• Endoscopic treatment: serial large-bore plastic stents exchanged every 3-4 months; success 74-90%, recurrence up to 30% at 2 years
• Surgical hepaticojejunostomy (Roux-en-Y) for failed endoscopic treatment

D. Sclerosing Cholangitis:

• Ursodeoxycholic acid (medically)
• Dominant strictures: ERCP dilation + stenting
• Liver transplantation for end-stage disease

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Summary Algorithm for Obstructive Jaundice:

Jaundice suspected
      ↓
Blood tests (LFTs, bilirubin fractions, ALP, transaminases, PT)
      ↓
Ultrasound abdomen (1st line)
      ↓
Biliary dilation?
   YES                          NO
    ↓                            ↓
MRCP/CT/EUS              Consider hepatic/pre-hepatic cause
    ↓
Cause identified?
   Stones → ERCP + extraction    Malignancy → Resectable? → Whipple's
                                             → Non-resectable → ERCP stent / PTC
   Benign stricture → ERCP or surgical bypass

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• Bailey and Love's Short Practice of Surgery, 28th Edition - Chapters on Gallstones, Acute Cholecystitis
• Robbins, Cotran & Kumar Pathologic Basis of Disease - Gallbladder pathology
• Sleisenger and Fordtran's Gastrointestinal and Liver Disease - Acute Cholecystitis, Obstructive Jaundice
• Current Surgical Therapy, 14th Edition - Obstructive Jaundice evaluation and endoscopic management
• Pye's Surgical Handicraft, 22nd Edition - Management of obstructive jaundice, preoperative preparation