Acute Pancreatitis — Causes, Assessment and Management

Introduction

Acute pancreatitis is an inflammatory condition of the pancreas caused by premature activation of digestive enzymes (particularly trypsin) within the pancreatic parenchyma. It ranges from a mild, self-limiting illness to a life-threatening condition with multi-organ failure. The two commonest causes in the UK are gallstones and alcohol, together accounting for approximately 75% of cases.

The causes of pancreatitis are a perennial favourite of consultants on ward rounds and surgical examiners. Rather than memorising a flat list, the best approach is to use a mnemonic that prioritises the most clinically relevant causes first. The classic mnemonic is "I GET SMASHED" — though as explained below, some modifications improve its clinical utility.

Aetiology — I GET SMASHED

I — Idiopathic

In approximately 10–15% of cases, no cause is identified despite thorough investigation. Many of these cases may represent undetected microlithiasis (tiny gallstones or biliary sludge), sphincter of Oddi dysfunction, or genetic predisposition.

G — Gallstones

The most common single identifiable cause of acute pancreatitis in the UK (approximately 40–50% of cases). Gallstones cause pancreatitis by transiently obstructing the ampulla of Vater (the common opening of the bile and pancreatic ducts into the duodenum), causing pancreatic duct hypertension and reflux of bile into the pancreatic duct. Importantly, the gallstone is usually passed by the time of hospital presentation — a persistent common bile duct stone (choledocholithiasis) warrants urgent ERCP.

E — Ethanol (Alcohol)

The most common cause overall in western countries, and probably the most common single cause in urban UK populations. Alcohol directly damages acinar cells and promotes premature enzyme activation. It tends to cause recurrent episodes that can progress to chronic pancreatitis. A detailed alcohol history should be taken in all patients.

T — Trauma

Blunt abdominal trauma (e.g., a blow to the epigastrium, bicycle handlebar injury, seatbelt injury in road traffic accidents) can cause direct pancreatic injury. This category also includes operative trauma — post-ERCP pancreatitis is one of the commonest iatrogenic complications of any gastrointestinal endoscopic procedure (occurring in approximately 3–5% of ERCP procedures).

S — Steroids

Corticosteroids are a recognised but relatively rare cause. The mechanism is not fully understood, but may relate to increased pancreatic secretion and viscosity. It is important to ask about steroid use in the drug history.

M — Mumps (and Other Viruses)

Mumps virus has a tropism for glandular tissue, including the pancreas, and can cause pancreatitis (often in conjunction with parotitis and orchitis). Other viral causes include Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis B, and varicella-zoster virus.

A — Autoimmune

Autoimmune pancreatitis (AIP) is an IgG4-related inflammatory condition. It is an important diagnosis not to miss because it responds dramatically to corticosteroids. It can present as obstructive jaundice and a pancreatic mass that mimics pancreatic carcinoma. It may be associated with other autoimmune diseases such as systemic lupus erythematosus (SLE), Sjogren's syndrome, and polyarteritis nodosa (PAN).

S — Scorpion Sting

The venom of Tityus trinitatis (a scorpion found in Trinidad) is a well-documented cause of acute pancreatitis — approximately 50 cases per year are described. This cause is unlikely to be encountered outside tropical regions but is retained in the mnemonic for completeness. It is probably not worth mentioning spontaneously unless specifically asked.

H — Hereditary / Hyperlipidaemia / Hypercalcaemia / Hypothermia

The "H" covers several important causes:

• Hereditary pancreatitis — caused by mutations in the PRSS1 gene (cationic trypsinogen) or the SPINK1 gene. It typically presents in childhood with recurrent episodes progressing to chronic pancreatitis. Cystic fibrosis and alpha-1-antitrypsin deficiency are also associated.
• Hyperlipidaemia (hypertriglyceridaemia) — serum triglycerides above 11 mmol/L are associated with acute pancreatitis. The serum will appear lipaemic (milky) on visual inspection. Importantly, a very high triglyceride level can artefactually lower the measured serum amylase, leading to false-negative amylase results — lipase is a more reliable marker in this context.
• Hypercalcaemia — usually associated with primary hyperparathyroidism. Elevated calcium activates trypsinogen within the pancreatic duct, precipitating pancreatitis.
• Hypothermia — a rare cause, occasionally seen in patients with severe accidental hypothermia.

E — ERCP

Post-ERCP pancreatitis deserves its own entry because it is common and clinically important. It occurs due to trauma to the pancreatic duct orifice at the ampulla of Vater during cannulation. Risk factors for post-ERCP pancreatitis include young age, female sex, normal bilirubin, previous post-ERCP pancreatitis, and difficult cannulation. Rectal indomethacin, given prophylactically at the time of ERCP, substantially reduces this risk.

D — Drugs

A broad range of drugs have been implicated in causing pancreatitis. Classes to be aware of include:

• Thiazide and loop diuretics (e.g., furosemide, bendroflumethiazide)
• Sulfonamide antibiotics
• Azathioprine and 6-mercaptopurine (used in inflammatory bowel disease and transplant immunosuppression)
• Valproic acid (sodium valproate)
• Tetracyclines
• Oestrogens (including the oral contraceptive pill)
• Corticosteroids (also listed above)
• Metronidazole
• ACE inhibitors
• GLP-1 receptor agonists (e.g., exenatide, liraglutide)

A drug should be considered as a cause in any unexplained episode of pancreatitis. Always review the medication list carefully.

Whilst Pregnant

Pregnancy increases the risk of gallstone formation (due to elevated oestrogen and progesterone reducing bile acid cycling and increasing cholesterol saturation), and therefore increases the risk of gallstone pancreatitis. Acute pancreatitis in pregnancy carries significant maternal and foetal risk and should be managed in conjunction with an obstetrician.

Cancer — An Important Addition

Pancreatic carcinoma, ampullary carcinoma, and carcinoma of the stomach or biliary tree can all obstruct the pancreatic duct and precipitate pancreatitis. This is a particularly important cause to consider in older patients presenting with their first episode of pancreatitis with no obvious cause, as pancreatitis may be the presenting feature of an underlying malignancy. Cross-sectional imaging is mandatory in this group.

Clinical Presentation

The classical presentation of acute pancreatitis is:

• Severe epigastric pain — often described as "boring" through to the back. Onset is typically rapid and pain is constant (not colicky). The patient may lean forward to gain relief (the pancreatic position).
• Nausea and vomiting — prominent and often persistent.
• Anorexia.
• Fever — low grade initially; high fever suggests infection (necrosis, abscess).
• Haemodynamic compromise — severe pancreatitis causes massive third-space fluid losses into the retroperitoneum and peritoneal cavity, leading to hypovolaemia and shock.

Two rare but classic signs of severe haemorrhagic pancreatitis are:

• Grey Turner's sign — bruising of the flanks, representing tracking of haemorrhagic fluid through retroperitoneal tissue planes.
• Cullen's sign — periumbilical bruising, representing tracking of haemorrhagic fluid along the falciform ligament.

Both signs take 24–48 hours to develop and indicate severe haemorrhagic pancreatitis with a poor prognosis.

Investigations

• Serum amylase — elevated to more than 3 times the upper limit of normal is diagnostic of pancreatitis in the right clinical context. Note that amylase returns to normal within 3–5 days, so a normal amylase does not exclude pancreatitis in late presentations. Amylase can also be elevated in other conditions (perforated peptic ulcer, ischaemic bowel, ectopic pregnancy, renal failure).
• Serum lipase — remains elevated for longer than amylase (up to 14 days) and is more sensitive and specific for pancreatitis, particularly in hypertriglyceridaemia where amylase may be falsely low. Lipase is the preferred diagnostic marker in many centres.
• LFTs and bilirubin — elevated bilirubin and ALT suggest gallstone pancreatitis. An ALT >150 U/L within 48 hours of presentation has a positive predictive value of approximately 95% for gallstone aetiology.
• CRP — the most important prognostic blood marker. A CRP >150 mg/L at 48 hours indicates severe pancreatitis.
• FBC, U&E, LFTs, bone profile — assess for leucocytosis, renal impairment, hypocalcaemia, and hyperlipidaemia. Hypocalcaemia (saponification of fat) is a marker of severity.
• Blood glucose — hyperglycaemia reflects pancreatic endocrine dysfunction and is a severity marker.
• Ultrasound abdomen — should be performed in all patients within 24 hours to assess for gallstones, biliary dilatation, and any pancreatic abnormality visible on ultrasound.
• CT abdomen and pelvis with contrast (contrast-enhanced CT, CECT) — the gold-standard investigation for assessing severity, identifying necrosis, and diagnosing complications. It should be performed 48–72 hours after onset (delayed to allow the full extent of necrosis to declare itself) and is indicated when severity is uncertain, or if there is clinical deterioration.
• MRCP (magnetic resonance cholangiopancreatography) — useful for assessing the biliary tree non-invasively, particularly to detect persistent choledocholithiasis, without the risks associated with ERCP.

Severity Scoring

Accurate and early severity stratification is essential in pancreatitis. Several validated scoring systems exist.

Glasgow Score — PANCREAS Mnemonic

The modified Glasgow (Imrie) score is the most widely used severity score in UK practice. It is calculated at 48 hours from admission. A score of 3 or more indicates severe pancreatitis. The mnemonic PANCREAS aids recall:

Score ≥3 at 48 hours = severe acute pancreatitis, requiring HDU/ICU-level care.

Ranson's Criteria

Ranson's criteria are an older but widely known severity scoring system. Five criteria are assessed on admission, and six more at 48 hours (making a total of 11 parameters). A score of 3 or more at 48 hours indicates severe disease and significantly increased mortality. The Ranson criteria require 48 hours to complete and have largely been superseded in UK practice by the simpler Glasgow score and by the Bedside Index of Severity in Acute Pancreatitis (BISAP), but they remain frequently examined.

Admission criteria: Age >55; WBC >16 × 10⁹/L; blood glucose >10 mmol/L; serum LDH >350 IU/L; AST >250 IU/L.

48-hour criteria: Haematocrit fall >10%; urea rise >1.8 mmol/L; serum calcium <2 mmol/L; PaO₂ <8 kPa; base deficit >4 mEq/L; estimated fluid sequestration >6 litres.

CT Severity Index (Balthazar Score)

The CT Severity Index (CTSI), based on the Balthazar grading system, combines CT appearances of the pancreas (A–E, scored 0–4) with the degree of pancreatic necrosis (0%, <30%, 30–50%, >50%, scored 0–6). Maximum score is 10. A CTSI of 7–10 is associated with a mortality of up to 17% and a morbidity of 92%. CT is most informative at 72–96 hours from onset.

CRP at 48 Hours

A CRP >150 mg/L at 48 hours is a reliable, simple, single-parameter indicator of severe disease and is used in UK clinical practice alongside the Glasgow score.

Management

General Measures — All Patients

• Nil by mouth (NBM) — initially, to rest the pancreas and prevent further stimulation of exocrine secretion. Early oral feeding (including enteral feeding) is now encouraged as soon as tolerated, as it maintains gut integrity and reduces infectious complications.
• Aggressive IV fluid resuscitation — pancreatitis causes massive third-space losses. Hartmann's solution (or crystalloid) is given at high volume. Close monitoring of fluid balance, urine output (target >0.5 mL/kg/hour), heart rate, and blood pressure is essential.
• Analgesia — adequate pain relief is essential. Patient-controlled analgesia (PCA) with opioids (e.g., morphine or fentanyl) is standard for severe pain. Opioids are not contraindicated in pancreatitis. NSAIDs may be used as adjuncts if renal function permits. Older teaching suggested avoiding morphine because of theoretical effects on the sphincter of Oddi, but this is not supported by clinical evidence.
• Antiemetics — for nausea and vomiting.
• Monitoring — continuous observations, hourly urine output, and regular blood tests (CRP, FBC, U&E, LFTs, calcium, glucose) in severe cases. ICU/HDU monitoring for organ failure.
• Enteral nutrition — nasojejunal (NJ) tube feeding is preferred over total parenteral nutrition (TPN) in severe pancreatitis, as it preserves gut mucosal integrity and reduces infective complications.

Specific Management — Gallstone Pancreatitis

When pancreatitis is caused by gallstones and there is evidence of a persistent common bile duct stone (rising bilirubin, dilated CBD on USS, or clinical cholangitis), urgent ERCP (endoscopic retrograde cholangiopancreatography) with sphincterotomy and stone extraction should be performed within 72 hours. Cholecystectomy should be performed during the same admission or within 2 weeks of discharge to prevent recurrence, as the risk of a further episode of gallstone pancreatitis is high if the gallbladder remains in situ.

Specific Management — Severe and Necrotising Pancreatitis

• HDU or ICU admission for organ support.
• Antibiotics — prophylactic antibiotics are not routinely recommended in severe pancreatitis (their use has not been shown to reduce mortality). However, antibiotics should be given if there is confirmed or suspected infected necrosis, sepsis, or another infective complication.
• Infected pancreatic necrosis — confirmed by CT-guided fine needle aspiration or clinical deterioration with signs of sepsis. Treatment is step-up: initial CT-guided or endoscopic drainage, then minimally invasive surgical debridement (video-assisted retroperitoneal debridement, VARD) if needed, escalating to open necrosectomy only if less invasive approaches fail.
• Pancreatic pseudocysts — large or symptomatic pseudocysts are drained endoscopically (endoscopic ultrasound-guided cystogastrostomy) or percutaneously under radiological guidance.

Complications

Local

• Pancreatic necrosis — areas of non-viable pancreatic parenchyma and peripancreatic fat. Detected on contrast-enhanced CT (areas of non-enhancement). May be sterile or infected; infected necrosis carries significantly higher mortality.
• Acute peripancreatic fluid collections — common in the early phase; many resolve spontaneously.
• Pancreatic pseudocyst — a collection of pancreatic fluid and necrotic debris enclosed by a wall of fibrous or granulation tissue, developing over 4 weeks or more after an episode of acute pancreatitis. Does not have an epithelial lining (hence "pseudo"). Presents as a persistent epigastric mass with ongoing pain. Large pseudocysts (>6 cm) or those causing symptoms should be drained.
• Pancreatic abscess — an intra-abdominal collection of pus adjacent to the pancreas, with little or no necrosis. Requires drainage and antibiotics.

Systemic

• Acute Respiratory Distress Syndrome (ARDS) — inflammatory mediators released in severe pancreatitis cause increased pulmonary capillary permeability and non-cardiogenic pulmonary oedema. Manifests as severe hypoxaemia (PaO₂ <8 kPa) and bilateral infiltrates on CXR. Requires ICU with mechanical ventilation.
• Acute kidney injury (AKI) — due to hypovolaemia, third-space losses, and inflammatory mediator-induced renal vasoconstriction. Fluid resuscitation is the primary treatment; renal replacement therapy (haemofiltration) may be required in severe AKI.
• Disseminated intravascular coagulation (DIC) — coagulation pathway activation by pancreatic proteases leads to widespread intravascular clotting followed by coagulopathy and haemorrhage. Requires haematology input and supportive management.
• Hypocalcaemia — calcium combines with free fatty acids released by lipase (saponification), causing a precipitous fall in ionised calcium. Symptomatic hypocalcaemia (tetany, prolonged QT) requires IV calcium replacement.
• Hyperglycaemia — due to destruction of islets of Langerhans, causing endocrine pancreatic insufficiency. May require insulin therapy.