Acute pancreatitis

Contents

Pathophysiology

The initiating event is premature intracellular activation of digestive zymogens (principally trypsinogen → trypsin) within pancreatic acinar cells, rather than in the duodenal lumen.

Consequences:

  • Trypsin activates other proenzymes: elastase (destroys connective tissue and vessel walls), phospholipase A₂ (disrupts cell membranes, degrades surfactant → ARDS), lipase (peripancreatic fat necrosis → saponification)
  • Acinar cell necrosis → local inflammation and oedema
  • Release of cytokines (TNF-α, IL-1, IL-6, IL-8) → systemic inflammatory response syndrome (SIRS)
  • SIRS → capillary leak, third spacing, hypovolaemia, MODS

The severity of systemic complications is driven by the extent of systemic inflammation, not simply the extent of local pancreatic necrosis.

Calcium signalling plays a central role in acinar cell injury: pathological persistent intracellular Ca²⁺ elevation activates premature intracellular trypsinogen.

Aetiology

Cause Approximate proportion
Gallstones (including microlithiasis) ~40%
Alcohol ~30%
Idiopathic ~15–20%
Hypertriglyceridaemia (>10 mmol/L) ~1–5%
Hypercalcaemia Uncommon
Drugs (valproate, azathioprine, furosemide, didanosine, GLP-1 agonists) Uncommon
Post-ERCP 2–5% of procedures
Autoimmune pancreatitis Uncommon
Trauma, pancreatic tumour, anatomical anomalies Uncommon

Severity Classification

Revised Atlanta Classification (2012)

Based on persistent organ failure (>48h) and local complications:

Category Definition
Mild No organ failure, no local/systemic complications; resolves within 1 week
Moderately severe Transient organ failure (<48h) OR local/systemic complications without persistent OD
Severe Persistent organ failure ≥48h (single or multi-organ)

Organ failure: respiratory (PaO₂/FiO₂ <300), renal (creatinine ≥170 µmol/L), cardiovascular (SBP <90 despite resuscitation).

Severe acute pancreatitis = ~20% of all cases; mortality ~20–40%.

BISAP Score (Bedside Index of Severity in Acute Pancreatitis)

Criterion Score
BUN >25 mg/dL (urea >8.9 mmol/L) 1
Impaired mental status (GCS <15) 1
SIRS (≥2 criteria) 1
Age >60 years 1
Pleural effusion on imaging 1

Score ≥3: significantly increased risk of severe disease and in-hospital mortality.

CT Severity Index (Balthazar, CTSI)

Assigns points for pancreatic inflammation grade (A–E) and percentage necrosis. Score 0–10; CTSI ≥7 = severe disease. CT is not required at presentation; perform at 72h if clinical deterioration or diagnosis in doubt.

Management — Acute Phase

Fluid Resuscitation

Hypovolaemia from third-spacing and vomiting is a key driver of early morbidity (pancreatic ischaemia from microvascular constriction worsens necrosis). Early aggressive resuscitation is important.

Fluid choice: Ringer's lactate (Hartmann's) is preferred over 0.9% NaCl:

  • 0.9% NaCl → hyperchloraemic acidosis and may activate trypsinogen (acidic environment)
  • Ringer's lactate associated with less SIRS in small RCTs and pathophysiologically more appropriate
  • WATERFALL trial (Cuéllar-Monterrubio et al, NEJM 2022): aggressive (250 mL/h Ringer's until specific targets) vs moderate resuscitation (1.5 mL/kg/h); no improvement in moderate-severe pancreatitis with aggressive strategy; aggressive group had more fluid overload. Supports moderate, goal-directed resuscitation over aggressive bolusing.

Targets: HR <100/min, MAP ≥65 mmHg, UO >0.5 mL/kg/h, haematocrit 35–44% (haemoconcentration predicts necrosis).

Analgesia

  • Regular paracetamol; NSAID with caution (renal effects)
  • Opioids as needed (morphine, fentanyl); no evidence that morphine worsens pancreatitis by increasing sphincter of Oddi tone — this is an historical concern
  • Consider patient-controlled analgesia or epidural in severe cases

Monitoring in ICU

  • Fluid balance, weight, haematocrit, CRP (rises for first 48–72h; peak at 48h >150 mg/L predicts severity)
  • Daily U&E, creatinine, LFTs, calcium, glucose
  • Regular abdominal examination; signs of developing abdominal compartment syndrome
  • CT at 72h if not improving (best assessment of necrosis extent — earlier CT underestimates)

Nutrition

Early enteral nutrition (EN) is strongly recommended — within 24–72h of admission in predicted moderate-severe or severe pancreatitis.

Evidence base:

  • Multiple RCTs and meta-analyses consistently show EN reduces infectious complications, organ failure, surgical intervention, and hospital stay compared with parenteral nutrition (PN) or nil by mouth
  • Mechanism: maintains gut mucosal integrity, prevents bacterial translocation, preserves gut immune function
  • Route: nasogastric (NG) is equivalent to nasojejunal (NJ) in most patients (PYTHON trial, NEJM 2010: NG equivalent to NJ in safety and efficacy in predicted severe pancreatitis); only use NJ if NG not tolerated
  • In practice: start EN at a low rate (20–30 mL/h) and advance as tolerated; add PN only if EN is insufficient or not achievable

Total parenteral nutrition (TPN): reserved for when EN is not achievable (persistent ileus, bowel obstruction, post-surgical limitations). Associated with more infectious complications than EN.

ERCP in Acute Pancreatitis

Indications

ERCP is NOT indicated for predicted severe acute pancreatitis alone, even when caused by gallstones.

ERCP IS indicated for gallstone pancreatitis WITH:

  • Concurrent cholangitis (Charcot's triad: fever, jaundice, RUQ pain; Reynold's pentad if severe: plus hypotension and confusion) — urgent ERCP within 24h
  • Persistent common bile duct obstruction without resolution

PYTHON trial (NEJM 2010): urgent (within 24h) ERCP vs conservative management in predicted severe gallstone pancreatitis without cholangitis → no reduction in complications or mortality; ERCP conferred no benefit without cholangitis.

Conclusion: reserve ERCP for cholangitis or persistent CBD obstruction, not simply for gallstone pancreatitis severity.

Necrotising Pancreatitis

Classification of local complications (Revised Atlanta 2012)

Lesion Timing Features
Acute peripancreatic fluid collection (APFC) First 4 weeks No wall; acute; usually resolves
Pancreatic pseudocyst >4 weeks Walled-off fluid collection; no necrosis
Acute necrotic collection (ANC) First 4 weeks Heterogeneous; necrosis within pancreas/peripancreatic tissue
Walled-off necrosis (WON) >4 weeks Mature walled encapsulation of necrosis

Infected Necrosis

  • Develops in 30–40% of those with necrotising pancreatitis (typically >2–4 weeks)
  • Most common late cause of death in acute pancreatitis
  • Organisms: often gut-derived gram-negatives, enterococci; also gram-positives and fungi
  • Diagnosis: clinical (fever, rising inflammatory markers, deterioration) ± CT (gas within necrosis = pathognomonic); fine needle aspiration (FNA) if uncertain
  • Antibiotics are NOT recommended prophylactically in necrotising pancreatitis (multiple RCTs show no benefit; promote resistance and fungal superinfection)
  • Antibiotics only if infected necrosis is confirmed or strongly suspected; use broad-spectrum agents that penetrate necrosis (carbapenems have good penetration)

Step-Up Approach (PANTER Trial)

PANTER trial (van Santvoort et al, NEJM 2010): step-up approach vs primary open necrosectomy for infected necrotising pancreatitis.

Step-up approach:

  1. Antibiotics (carbapenems for penetration)
  2. Percutaneous or endoscopic drainage (CT-guided, ultrasound-guided, or endoscopic via stomach/duodenum into WON)
  3. If drainage insufficient: video-assisted retroperitoneal debridement (VARD) or endoscopic necrosectomy (minimal access)
  4. Open surgery only as last resort

Result: step-up approach reduced new-onset multi-organ failure, pancreatic fistula, hernia, and mortality vs immediate open surgery. Has become standard of care.

Timing of intervention: delay until WON is mature (≥4 weeks from onset) whenever possible — necrotic tissue demarcates and is more amenable to drainage; mortality of early surgery is high.

Complications

Complication Notes
ARDS Phospholipase A₂ → surfactant destruction; 15–20% of severe AP
AKI Third-spacing, hypovolaemia, cytokine-mediated
Hypocalcaemia Fat saponification (calcium binds fatty acids); also hypoalbuminaemia
Hyperglycaemia Islet cell destruction; requires insulin
Splenic vein thrombosis Local inflammation → left-sided portal hypertension; gastric varices
Pseudoaneurysm Splenic, gastroduodenal, or other arteries; risk of life-threatening haemorrhage
Pleural effusions Inflammatory; left-sided more common; large effusions may need drainage
Abdominal compartment syndrome Aggressive fluid resuscitation + ileus → raised IAP

Viva Questions

1. Describe the pathophysiology of acute pancreatitis and explain why some patients develop MODS while others don't.

Acute pancreatitis begins with premature intracellular activation of trypsinogen to trypsin within acinar cells, rather than in the duodenal lumen where it belongs. Active trypsin activates other zymogens — elastase (destroys connective tissue), phospholipase A₂ (disrupts cell membranes and degrades surfactant, causing ARDS), and lipase (peripancreatic fat necrosis). Acinar cell injury triggers local inflammation. In most patients, this is contained by pancreatic anti-proteases and the immune system. In a minority, the inflammatory response escapes local containment — high cytokine levels (TNF-α, IL-1, IL-6) produce systemic SIRS, capillary leak, third-spacing, and ultimately MODS. The severity of systemic complications depends on the magnitude of systemic inflammation, not simply the extent of local necrosis — a patient can have extensive necrosis without MODS, or severe MODS with only mild local changes. This is why severity prediction is imprecise early in the disease course, and why resuscitation (addressing the systemic inflammatory state) is the foundation of treatment.

2. What fluid should you use to resuscitate acute pancreatitis and how aggressive should you be?

Ringer's lactate (Hartmann's) is the preferred crystalloid for acute pancreatitis. Normal saline (0.9% NaCl) causes hyperchloraemic acidosis and may activate trypsinogen in an acidic environment; Ringer's lactate is more physiologically neutral. Pathophysiologically, fluid is required to correct hypovolaemia from vomiting and third-spacing, and to maintain pancreatic microcirculation — ischaemia worsens acinar injury. However, aggressive hyperresuscitation is not beneficial: the WATERFALL trial showed aggressive IV fluid resuscitation did not reduce the rate of moderate-to-severe pancreatitis compared with moderate resuscitation and increased fluid overload. Current guidance supports moderate, goal-directed resuscitation targeting HR <100 bpm, MAP ≥65 mmHg, and urine output >0.5 mL/kg/h, rather than fixed aggressive protocols. Haematocrit >44% (haemoconcentration) predicts pancreatic necrosis — normalisation is a useful target. Reassess fluid needs frequently and avoid cumulative fluid overload, which raises abdominal compartment pressure and worsens outcomes.

3. When is ERCP indicated in gallstone pancreatitis and why is it not indicated for severe pancreatitis alone?

ERCP is indicated in gallstone pancreatitis with concurrent biliary obstruction causing cholangitis — urgent ERCP within 24 hours is recommended to relieve obstruction and control sepsis. It is also indicated if there is persistent common bile duct obstruction without clinical resolution. It is NOT indicated simply because pancreatitis is predicted to be severe. The PYTHON trial showed that urgent ERCP in predicted severe gallstone pancreatitis without cholangitis conferred no benefit over conservative management in terms of complications or mortality. In severe gallstone pancreatitis, the impacted stone has usually passed or become dislodged by the time ERCP would be performed, and the dominant pathology is established systemic inflammation rather than ongoing biliary obstruction. Performing ERCP carries procedure-related risks (post-ERCP pancreatitis, perforation, bleeding) without benefit in this context. Cholecystectomy should be planned after recovery to prevent recurrence, ideally during the same admission for mild-moderate pancreatitis.

4. A patient with confirmed infected necrotising pancreatitis at week 4 is haemodynamically stable. What is the management approach?

Infected pancreatic necrosis requires intervention, but the approach has shifted from early open surgery to a step-up strategy (PANTER trial). Step one: broad-spectrum antibiotics that penetrate pancreatic necrosis — carbapenems (meropenem) have good tissue penetration and should cover gram-negative and gram-positive organisms; add antifungal cover (fluconazole or anidulafungin) if fungal superinfection is suspected. Step two: minimally invasive drainage — percutaneous CT-guided drainage or endoscopic transmural drainage via a lumenapposing metal stent (LAMS) through the stomach or duodenal wall into the walled-off necrosis. If drainage alone is insufficient (persistent sepsis, non-resolving collections): step three: video-assisted retroperitoneal debridement (VARD) or endoscopic necrosectomy under direct visualisation. Open surgery is a last resort. The key principle is that intervention should be deferred until the necrosis is walled off and mature (≥4 weeks from onset), as early surgery on immature necrosis carries very high mortality. With this patient at week 4 and haemodynamically stable, a step-up approach beginning with drainage is appropriate.