11.5 Gallstone Disease, Biliary Sepsis & Pancreatitis

2. Gallstone Disease & Biliary Tract Infections

Spectrum of Gallstone Pathology

Gallstones (cholelithiasis) affect 10–15% of the UK adult population (80% cholesterol stones, 15% black pigment stones [haemolysis, cirrhosis], 5% brown pigment stones [biliary stasis/infection]):

• Biliary Colic: Transient impaction of a gallstone in the cystic duct during postprandial gallbladder contraction. Episodic, severe, constant epigastric or right upper quadrant pain radiating to the interscapular region or right shoulder, lasting 1–6 hours, resolving completely. Normal inflammatory markers (WBC, CRP) and normal liver biochemistry.
• Acute Cholecystitis: Persistent cystic duct obstruction resulting in gallbladder distension, inflammation, and secondary bacterial infection (E. coli, Klebsiella, Enterococcus). Constant RUQ pain lasting >6 hours, accompanied by fever, leukocytosis, and elevated CRP.
  • Murphy's Sign: Inspiratory arrest elicited when the examiner's fingers palpate deeply under the right costal margin while the patient takes a deep breath.
  • Ultrasound Findings: Gallbladder wall thickening (>3–4 mm), pericholecystic fluid, gallstones, and sonographic Murphy's sign.
  • Treatment: IV fluids, IV antibiotics (co-amoxiclav), and early laparoscopic cholecystectomy (within 72 hours of admission).
• Choledocholithiasis: Gallstone migration into the common bile duct (CBD). Causes colicky RUQ pain, obstructive jaundice (dark urine, pale stools), pruritus, elevated conjugated bilirubin, ALP, and GGT. Dilated CBD on ultrasound (>6 mm). Diagnosed via MRCP/EUS; managed via therapeutic ERCP sphincterotomy and stone extraction.
• Acute Ascending Cholangitis: Life-threatening bacterial infection of an obstructed biliary tree. Elevated intrabiliary pressure facilitates bacterial translocation into the hepatic circulation, provoking rapid sepsis.
  • Charcot's Triad: (1) Right upper quadrant pain, (2) Jaundice, (3) Spiking fever with rigors. (Present in 50–70% of patients).
  • Reynolds' Pentad: Charcot's triad plus (4) Hypotension (septic shock) and (5) Altered mental status / confusion. Indicates toxic suppurative cholangitis with high mortality.
  • Emergency Management Protocol: Immediate fluid resuscitation, blood cultures, intravenous broad-spectrum antibiotics (piperacillin-tazobactam or meropenem), and urgent emergency biliary decompression via ERCP (sphincterotomy, stone extraction, or biliary stenting) within 24 hours (or within 12 hours if Reynolds' pentad or refractory septic shock).

3. Pancreatitis

Acute Pancreatitis

• Pathophysiology: Premature intracellular activation of pancreatic zymogens (conversion of trypsinogen to trypsin by lysosomal cathepsin B within acinar cells) leads to autodigestion of pancreatic parenchyma, microvascular thrombosis, acinar necrosis, and massive release of pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6), provoking a Systemic Inflammatory Response Syndrome (SIRS).
• Aetiology (Mnemonic GET SMASHED):
  • Gallstones (~45–50% of UK cases; transient impaction at ampulla of Vater)
  • Ethanol (~30–35% of UK cases; toxic alcohol metabolites e.g., fatty acid ethyl esters)
  • Trauma (blunt abdominal trauma transecting pancreas across lumbar spine)
  • Steroids (systemic glucocorticoid therapy)
  • Mumps (and other viruses: Coxsackie B, CMV, EBV, HIV)
  • Autoimmune (Type 1 IgG4-related systemic pancreatitis vs Type 2 idiopathic duct-centric)
  • Scorpion sting (venom of Trinidadian scorpion Tityus trinitatis)
  • Hyperlipidaemia (marked hypertriglyceridaemia: fasting serum triglycerides >11.3 mmol/L or >1000 mg/dL) / Hypercalcaemia (primary hyperparathyroidism; calcium activates intra-acinar trypsinogen)
  • ERCP (post-procedural pancreatitis in 3–5%; mitigated by prophylactic rectal diclofenac/indometacin)
  • Drugs: Azathioprine, 6-mercaptopurine, sodium valproate, thiazide diuretics, didanosine, mesalazine, ACE inhibitors
• Diagnostic Criteria (Revised Atlanta Classification): Requires at least 2 of the following 3 features:
  1. Acute onset of severe, persistent epigastric pain radiating to the back (often eased by leaning forward).
  2. Serum amylase or lipase >=3 times the upper limit of normal (ULN). Serum lipase is more sensitive and specific than amylase (stays elevated 8–14 days vs 3–5 days). Exam caveat: Serum amylase may be falsely normal in hypertriglyceridaemia (lipidaemic interference with optical assay) and chronic alcohol-related acute pancreatitis (acinar exhaustion).
  3. Characteristic imaging features of acute pancreatitis on contrast-enhanced CT (CECT), MRI, or transabdominal ultrasound. (CECT is optimal at 72–96 hours post-symptom onset to assess pancreatic necrosis).
• Severity Scoring — Modified Glasgow (Imrie) Prognostic Criteria:
  • Evaluated within the first 48 hours of admission.
  • Mnemonic PANCREAS:

• Clinical Scoring Interpretation: A score of >=3 points indicates severe acute pancreatitis, identifying patients at high risk of pancreatic necrosis, multi-organ failure, and death; mandates immediate High Dependency / Intensive Care Unit (HDU/ICU) admission.
• Acute Management Principles:
  • Fluid Resuscitation: Goal-directed intravenous balanced crystalloids (Hartmann's solution) at 200–250 mL/h, titrated to urine output (>0.5 mL/kg/h) and normal haematocrit. Avoid fluid overload.
  • Analgesia: Intravenous opioids (fentanyl, morphine).
  • Nutritional Support: Early oral re-feeding (low-fat diet) as soon as pain subsides. If oral intake is not tolerated, enteral tube feeding (nasogastric or nasojejunal) is initiated within 48–72 hours. Enteral feeding maintains gut mucosal barrier integrity and reduces infectious complications compared to parenteral nutrition (TPN).
  • Antibiotics: Prophylactic antibiotics are strictly NOT recommended in sterile acute pancreatitis.
  • Urgent ERCP: Indicated within 24 hours for acute gallstone pancreatitis accompanied by concurrent acute cholangitis or persistent biliary obstruction.
• Local Complications:
  • Pancreatic Pseudocyst: Encapsulated collection of amylase-rich fluid bounded by a non-epithelialized fibrous wall developing >4 weeks post-presentation. Asymptomatic pseudocysts are managed conservatively. Cysts >6 cm, symptomatic, or enlarging are drained endoscopically (cystogastrostomy) or radiologically; intervention should be delayed for at least 6 weeks to permit the fibrous wall to mature.
  • Walled-Off Pancreatic Necrosis (WON): Encapsulated collection of solid and liquid necrosis developing >4 weeks. If necrosis becomes infected (gas on CT or persistent sepsis), manage with the "step-up approach": intravenous antibiotics (meropenem), percutaneous catheter drainage, and minimally invasive retroperitoneal or endoscopic necrosectomy.

Chronic Pancreatitis

• Pathophysiology & Aetiology: Progressive, irreversible fibroinflammatory destruction of the pancreatic parenchyma, causing permanent loss of exocrine and endocrine tissue. Alcohol excess accounts for ~70% of UK cases; other causes include smoking, genetic mutations (PRSS1 cationic trypsinogen gain-of-function, SPINK1 serine protease inhibitor loss-of-function, CFTR cystic fibrosis conductance regulator), hyperparathyroidism, ductal obstruction, and autoimmune pancreatitis (Type 1 IgG4-related).
• Clinical Manifestations:
  • Recurrent or continuous epigastric abdominal pain radiating to the back, exacerbated 15–30 minutes after eating and eased by sitting forward.
  • Pancreatic Exocrine Insufficiency (PEI): Occurs when >90% of pancreatic enzyme secretory capacity is lost. Manifests as maldigestion, steatorrhoea (pale, bulky, foul-smelling, difficult-to-flush stools), weight loss, and fat-soluble vitamin malabsorption (vitamins A, D, E, K).
  • Pancreatic Endocrine Insufficiency: Destruction of islet cells produces secondary pancreatogenic Type 3c diabetes mellitus. Because both insulin-secreting beta cells and glucagon-secreting alpha cells are destroyed, patients experience extreme glycaemic volatility with high susceptibility to severe hypoglycemia.
• Diagnostic Evaluation:
  • Fecal Elastase-1: The most sensitive and specific non-invasive laboratory test for pancreatic exocrine insufficiency. Human elastase-1 passes through the intestine without degradation. A value <200 ug/g stool is diagnostic of exocrine insufficiency (<100 ug/g indicates severe insufficiency). Crucial clinical point: Exogenous porcine enzyme replacement does NOT cross-react with the human ELISA assay, permitting diagnostic testing while on therapy.
  • Abdominal CT / Plain Radiography: Demonstrates pathognomonic pancreatic parenchymal and intraductal calcifications, accompanied by pancreatic duct dilatation and parenchymal atrophy.
• Medical Management:
  • Complete abstinence from alcohol and tobacco.
  • Pancreatic Enzyme Replacement Therapy (PERT, e.g. Creon): Enteric-coated porcine pancreatin capsules (lipase, amylase, protease) taken with all meals and snacks. Co-prescribing a proton pump inhibitor (PPI) elevates duodenal pH, preventing acidic inactivation of porcine lipase and optimizing therapeutic efficacy.
  • Fat-soluble vitamin supplementation (A, D, E, K) with regular bone mineral density surveillance.