Acute Pancreatitis

1. Aetiology

• Acute pancreatitis is caused by the premature activation of pancreatic enzymes within the pancreas, resulting in autodigestion of pancreatic tissue and surrounding structures.
• This leads to inflammation, oedema, haemorrhage, and in severe cases, necrosis. Common aetiologies include:

1.1 Gallstones

• Gallstones obstructing the common bile duct or the ampulla of Vater increase pancreatic ductal pressure and trigger enzyme activation.

1.2 Alcohol

• Chronic alcohol consumption (>100g/day for >3–5 years) leads to protein plug formation in small ductules, resulting in duct obstruction and intrapancreatic enzyme activation.
• Binge drinking can also directly stimulate enzyme release.

1.3 Other Causes

• Mechanical/Structural: ERCP (5–15% post-procedure), trauma, pancreatic or periampullary tumours, sphincter of Oddi dysfunction, pancreas divisum.
• Metabolic: Hypertriglyceridaemia, hypercalcaemia (including in hyperparathyroidism).
• Drugs: Azathioprine, diuretics (e.g. frusemide), tetracyclines, sodium valproate, steroids, sulphonamides, isoniazid, ACE inhibitors.
• Infectious: Mumps, coxsackie B virus, cytomegalovirus.
• Other: Autoimmune pancreatitis, pregnancy, post-transplantation, scorpion venom, ischaemia.

Mnemonic: GET SMASHED — Gallstones, Ethanol, Trauma, Steroids, Mumps, Autoimmune, Scorpion sting, Hyperlipidaemia/hypercalcaemia, ERCP/embolism, Drugs.

2. Epidemiology

• Incidence in the UK: up to 80 per 100,000 people annually.
• The condition is increasing in incidence, likely due to higher alcohol consumption and improved diagnostic tools.
• Mortality rate: ~5–10%.
  • Early deaths (first 2 weeks): linked to multiorgan failure.
  • Late deaths: due to septic complications, especially infected necrosis.

3. Pathophysiology

• Enzyme-mediated autodigestion starts with premature activation of trypsinogen to trypsin within acinar cells.
• Activated enzymes (trypsin, elastase, phospholipase A2) digest pancreatic parenchyma, fat, and vasculature.
• Fat necrosis causes saponification and may lead to hypocalcaemia.
• Inflammatory cytokines enter systemic circulation, producing systemic inflammatory response syndrome (SIRS), leading to capillary leak, third-spacing, hypotension, ARDS, renal failure, and DIC.
• Local effects include oedema, necrosis, haemorrhage, and formation of fluid collections or pseudocysts.

4. Risk Factors

• Chronic alcohol consumption.
• Gallstones or biliary sludge.
• Previous ERCP procedures.
• Hypertriglyceridaemia or hypercalcaemia.
• Certain medications (see Section 1.3).
• Family history or genetic predisposition (e.g. CFTR mutations).
• Obesity (BMI >30 increases severity risk).
• Smoking.

5. Signs and Symptoms

5.1 Symptoms

• Severe epigastric or central abdominal pain, often radiating to the back.
• Pain may improve when sitting forward; worsens with coughing or movement.
• Nausea and vomiting are common.
• Sudden onset in gallstone-related pancreatitis; gradual in alcohol-related cases.

5.2 Signs

• Tachycardia, tachypnoea, hypotension.
• Fever typically develops within hours.
• Reduced consciousness in severe cases.
• Abdominal tenderness and guarding; sometimes generalised peritonitis.
• Cullen’s sign: Periumbilical bruising.
• Grey-Turner’s sign: Flank bruising.
• Distended abdomen, hypoactive bowel sounds.
• Pleural effusions or basal crackles may occur due to systemic inflammation.

6. Investigations

6.1 Initial Blood Tests

• Serum amylase: Typically >3x normal but may fall after 48 hours.
• Serum lipase: More sensitive and specific; remains elevated longer.
• FBC, U&E, LFTs, glucose, calcium, magnesium, coagulation screen, CRP, arterial blood gases.

6.2 Imaging

• Abdominal ultrasound: First-line for gallstone detection.
• CT abdomen (with contrast): Best for evaluating necrosis, fluid collections, and complications.
• MRI/MRCP: Useful for ductal anomalies or subtle complications.
• Erect chest X-ray: Rules out perforation; may show pleural effusion.
• Abdominal X-ray: Sentinel loop, loss of psoas shadow (retroperitoneal oedema).

6.3 Specialised Investigations

• Endoscopic ultrasound (EUS): High sensitivity for microlithiasis and biliary sludge.
• ERCP: Indicated in gallstone pancreatitis with biliary obstruction or cholangitis.
• Fasting lipids and calcium: During recovery to identify metabolic triggers.
• Viral serology and genetic testing: If aetiology remains unclear after initial workup.

7. Immediate Management

7.1 Supportive Measures

• Fluid resuscitation: Large-volume IV crystalloid (e.g. Hartmann’s), guided by urine output (>0.5 mL/kg/h), BP, lactate, and haematocrit.
• Nil by mouth initially; consider nasogastric or nasojejunal feeding within 72 hours if unable to eat.
• Analgesia: Opiates (e.g. morphine or pethidine) as needed; morphine is not contraindicated.
• Monitoring: Hourly vitals, strict fluid balance, daily bloods (FBC, U&E, glucose, amylase, CRP), ABGs.
• Urinary catheterisation to monitor output.

7.2 Risk Stratification

• Modified Glasgow Score (PANCREAS): ≥3 factors within 48h = severe disease.
• Ranson’s criteria: Used for alcohol-related cases.
• CRP >150 mg/L at 36h suggests severe disease.
• BISAP and APACHE II scores may also aid risk assessment.

7.3 Critical Care

• Admit to ITU/HDU if:
  • Organ dysfunction
  • Persistent SIRS
  • Hypoxia
  • Rising haematocrit or lactate

7.4 Gallstone Pancreatitis

• ERCP with sphincterotomy within 72h if obstructive jaundice or cholangitis present.
• Cholecystectomy after recovery in all surgically fit patients to prevent recurrence.

7.5 Infection Control

• Antibiotics not used prophylactically.
• Initiate broad-spectrum antibiotics (e.g. meropenem) only if infection of necrotic tissue is suspected.
• Fine-needle aspiration of necrosis may be needed for microbiology.
• Necrosectomy (surgical, endoscopic, or radiological) for infected necrosis.

8. Long-Term Management

• Alcohol cessation support and counselling.
• Lipid-lowering therapy if hypertriglyceridaemia-induced.
• Pancreatic enzyme supplementation if exocrine insufficiency develops.
• Diabetes screening and management, particularly if significant pancreatic necrosis occurred.
• Surveillance for recurrent episodes or progression to chronic pancreatitis.
• Genetic counselling if hereditary cause suspected.

9. Complications

9.1 Early

• Shock (hypovolaemic or distributive)
• Acute respiratory distress syndrome (ARDS)
• Renal failure
• Disseminated intravascular coagulation (DIC)
• Hypocalcaemia, hypomagnesaemia, hyperglycaemia
• Pancreatic ascites

9.2 Late

• Pancreatic necrosis: May become infected.
• Pancreatic pseudocyst: Occurs in ~40%, may resolve or require drainage.
• Pancreatic abscess: Often due to E. coli; presents with fever and pain.
• Haemorrhage: Enzymatic erosion of vessels (e.g. splenic artery).
• Fistulae: May involve GI tract or skin.
• Venous thrombosis: Including splenic or portal vein thrombosis.
• Chronic pancreatitis: From recurrent episodes.

Chronic Pancreatitis

1. Aetiology

• Chronic pancreatitis is characterised by progressive inflammatory and fibrotic destruction of the pancreatic parenchyma, often following repeated episodes of acute pancreatitis.
• It leads to irreversible loss of both exocrine and endocrine function.

1.1 Common Causes

• Alcohol abuse: Accounts for approximately 80% of cases in the Western world.
• Smoking: A recognised independent risk factor that also synergistically worsens alcohol-related disease.

1.2 Less Common and Rare Causes

• Obstructive causes: Pancreatic ductal obstruction from strictures, stones, or tumours.
• Metabolic: Hypertriglyceridaemia, hypercalcaemia (including from hyperparathyroidism).
• Genetic:
  • CFTR gene mutations: Seen in cystic fibrosis and implicated in idiopathic cases.
  • SPINK1 mutations: Observed in a subset of tropical and childhood pancreatitis; reduces inhibition of trypsin.
  • PRSS1 (cationic trypsinogen) mutations: Autosomal dominant inheritance; highly penetrant familial pancreatitis.
• Autoimmune: Steroid-responsive autoimmune pancreatitis with IgG4 association.
• Idiopathic: Diagnosis of exclusion; incidence declining with better diagnostic tools.

2. Epidemiology

• Incidence in industrialised nations: 3.5–10 per 100,000 people annually.
• Male predominance: Male-to-female ratio ~4:1.
• Typically affects adults in the 4th to 5th decades of life.
• Associated with increased morbidity and a 10-year mortality rate of up to 33%.

3. Pathophysiology

• Repeated pancreatic injury leads to progressive fibrosis, calcification, and ductal distortion.
• Exocrine insufficiency results when enzyme output drops below ~10% of normal.
• Endocrine dysfunction arises from destruction of islet cells, leading to diabetes.
• Chronic inflammation and oxidative stress are associated with increased risk of pancreatic adenocarcinoma.

4. Risk Factors

• Chronic alcohol consumption.
• Smoking (independent and synergistic with alcohol).
• Family history of pancreatitis.
• Genetic mutations (CFTR, SPINK1, PRSS1).
• Autoimmune conditions (e.g. IgG4-related disease).
• Recurrent acute pancreatitis.
• Pancreatic duct obstruction (e.g. tumour, stone).
• Hypertriglyceridaemia and hypercalcaemia.

5. Signs and Symptoms

5.1 History

• Epigastric pain: Persistent or intermittent; often radiates to the back and may improve with leaning forward or applying heat.
• Maldigestion and steatorrhoea: Pale, bulky, foul-smelling stools due to fat malabsorption.
• Weight loss: Due to malabsorption and pain-related anorexia.
• Diabetes mellitus: Late finding; symptoms include polyuria, polydipsia, and fatigue.
• Relapsing symptoms: Recurrent pain episodes, worsening over time.

5.2 Examination

• May be unremarkable, especially between attacks.
• Skin changes: Erythema ab igne from chronic heat application.
• Signs of malnutrition: Muscle wasting, vitamin deficiency signs.
• Abdominal mass: May suggest pseudocyst formation.
• Jaundice: If biliary obstruction is present.

6. Investigations

6.1 Laboratory Tests

• Serum amylase and lipase: Typically normal or mildly elevated; not useful for diagnosis.
• LFTs: Elevated bilirubin, ALP, GGT if biliary involvement.
• Serum calcium and triglycerides: To identify metabolic causes.
• Fasting glucose or OGTT: To assess endocrine function.
• Faecal elastase: <200 µg/g indicates exocrine insufficiency.
• Vitamin levels: Particularly fat-soluble (A, D, E, K).

6.2 Imaging

• Abdominal ultrasound: Initial test for biliary disease and pseudocysts.
• CT scan: Best for detecting pancreatic calcifications, pseudocysts, and ductal changes.
• MRCP: Non-invasive imaging of the pancreatic ducts and biliary tree.
• AXR: May show speckled calcifications.
• ERCP: Reserved for ductal interventions or diagnostic uncertainty.
• Endoscopic ultrasound (EUS): Highly sensitive for ductal changes and useful for biopsy of suspicious lesions.

7. Immediate Management

7.1 General Principles

• Abstain from alcohol and smoking: Core to halting disease progression.
• Treat underlying causes: Correct metabolic derangements and manage ductal obstructions.

7.2 Pain Management

• Stepwise approach: Start with paracetamol, escalate to weak then strong opioids.
• Avoid long-term opioid dependence.
• Adjuvant measures:
  • Coeliac plexus block.
  • Antioxidant therapy.
  • Pancreatic enzyme supplements (to reduce feedback stimulation of the pancreas).
  • Endoscopic duct drainage or stone extraction.
  • Surgical drainage or resection in selected cases.

8. Long-Term Management

8.1 Exocrine Insufficiency

• Pancreatic enzyme replacement therapy (PERT):
  • e.g. Creon®, 25,000–50,000 U lipase per meal.
  • May require proton pump inhibitors to enhance efficacy.
• Nutritional support:
  • Regular diet with adequate fat content.
  • Avoid strict fat restriction; treat steatorrhoea with enzymes.
  • Monitor and supplement fat-soluble vitamins (A, D, E, K).

8.2 Endocrine Insufficiency

• Diabetes management:
  • Often requires insulin.
  • Monitor closely due to increased hypoglycaemia risk (from glucagon deficiency).
  • Avoid overly aggressive glucose targets in patients with poor compliance or ongoing alcohol use.

8.3 Nutrition

• Frequent, small meals.
• Alcohol abstinence is mandatory.
• Monitor for deficiencies and treat accordingly.
• Consider medium-chain triglycerides (MCT) if malabsorption is severe, though may worsen diarrhoea.

8.4 Monitoring

• Regular follow-up for:
  • Nutritional status.
  • Glycaemic control.
  • Screening for pancreatic cancer (particularly in older patients and smokers).

9. Complications

• Pseudocysts: Can cause pain, infection, rupture, or bleeding; may require drainage.
• Pancreatic ductal stones: May obstruct outflow and worsen symptoms.
• Biliary obstruction: Can lead to jaundice or cholangitis.
• Diabetes mellitus: Endocrine insufficiency.
• Pancreatic cancer: Increased lifetime risk, especially with persistent inflammation and smoking.
• Splenic vein thrombosis: May lead to gastric varices.
• Local aneurysm formation: Due to enzymatic vessel wall damage.
• Malnutrition and fat-soluble vitamin deficiency.

Pancreatic Tumours

1. Aetiology

• Pancreatic tumours encompass a range of neoplasms, of which ductal adenocarcinoma is by far the most common, accounting for over 90% of cases.
• Tumours can also arise from endocrine cells (neuroendocrine tumours) or cystic precursors (e.g. mucinous cystadenocarcinoma, intraductal papillary mucinous neoplasm).

1.1 Pancreatic Adenocarcinoma

• Arises from ductal epithelial cells.
• Often preceded by PanIN (pancreatic intraepithelial neoplasia) lesions.
• Typically located:
  • Head of pancreas: ~60%
  • Body: ~25%
  • Tail: ~15%
• Early metastasis and late presentation are typical.

1.2 Other Pancreatic Tumours

• Cystadenocarcinoma: Arises from mucinous cystadenomas; slow-growing, better prognosis.
• Intraductal Papillary Mucinous Tumours (IPMNs): Mucin-secreting tumours usually in the tail; may cause recurrent pancreatitis.
• Pancreatic Neuroendocrine Tumours (PNETs): Rare, may be functioning (e.g. insulinoma, gastrinoma) or non-functioning.

2. Epidemiology

• Pancreatic cancer accounts for ~3% of all cancers in the UK.
• Incidence: ~9 per 100,000/year; lifetime risk ~1 in 74.
• Most common in men, with a male-to-female ratio of 2:1.
• Peak age: 55–75 years, but median presentation ~70 years.
• 95% of pancreatic cancers are ductal adenocarcinomas.
• The incidence has remained stable since the late 1990s in the UK.

3. Pathophysiology

• Invasive ductal carcinoma develops from PanIN lesions via genetic mutations, commonly in KRAS2, p16, and TP53.
• Tumours induce a dense fibrotic stroma (desmoplasia), contributing to local invasion and resistance to therapy.
• Obstruction of the biliary tree is common with head lesions, while splenic vein thrombosis and diabetes are more frequent with body and tail tumours.
• Neuroendocrine tumours can secrete hormones (e.g. insulin, gastrin), leading to systemic syndromes.

4. Risk Factors

• Smoking: Up to 30% of cases.
• Chronic pancreatitis
• Age: Strongest non-modifiable risk factor.
• Obesity and high-fat, high-meat diets
• Type 2 diabetes mellitus: Both a risk factor and potential result.
• Family history and genetic syndromes:
  • BRCA2
  • Peutz–Jeghers syndrome
  • PALB2 mutations
  • FAMMM (familial atypical multiple mole melanoma)

5. Signs and Symptoms

5.1 Common Clinical Features

• Epigastric pain, often radiating to the back.
• Weight loss
• Anorexia
• Obstructive jaundice (painless, with pale stools and dark urine) — most common in head of pancreas tumours.
• Diabetes mellitus: New-onset or worsening; may precede diagnosis.

5.2 Specific Signs

• Courvoisier’s sign: Palpable, non-tender gallbladder in jaundiced patients — suggests malignancy.
• Splenic vein thrombosis (in body/tail tumours): Can lead to gastric varices and GI bleeding.
• Migratory thrombophlebitis (Trousseau’s syndrome): Seen in ~10% — recurrent thrombosis in different veins.
• Pancreatic exocrine insufficiency: Steatorrhoea, weight loss, malnutrition.
• Palpable epigastric mass or hepatomegaly (with liver metastases).

6. Investigations

6.1 Laboratory Tests

• Liver function tests: Cholestatic pattern (raised bilirubin, ALP, GGT) if biliary obstruction.
• Tumour marker CA 19-9: Not diagnostic but useful for monitoring progression/response.
• FBC, glucose, coagulation, renal profile: For staging and treatment planning.

6.2 Imaging

• CT (helical/contrast-enhanced): First-line imaging to evaluate tumour, staging, and resectability.
• MRCP: Non-invasive assessment of biliary and pancreatic ducts.
• Ultrasound: May identify dilated ducts or mass; useful for initial jaundice workup.
• ERCP: Diagnostic and therapeutic in obstructive jaundice; may allow stent placement.
• EUS with FNA: Endoscopic ultrasound with fine-needle aspiration — best for tissue diagnosis.
• PET scan: Occasionally used in selected cases for staging.

7. Immediate Management

7.1 Symptomatic Relief

• Pain management:
  • Opioid analgesics (e.g. morphine) should not be withheld due to concerns about dependence.
  • Coeliac plexus block: Surgical or percutaneous; effective for refractory pain.
• Relief of jaundice:
  • Endoscopic stent placement via ERCP.
  • Surgical biliary bypass if ERCP fails.
  • Cholestyramine or phenobarbitone for pruritus if stenting not feasible.
• Nutritional support: High-calorie diet, pancreatic enzyme replacement if insufficiency present.

7.2 Pancreatic Insufficiency

• PERT (pancreatic enzyme replacement therapy) with meals.
• Fat-soluble vitamin supplementation as needed.

8. Long-Term Management

8.1 Curative Treatment (if eligible)

• Surgical resection:
  • Whipple procedure (pancreaticoduodenectomy): For resectable head tumours.
  • Distal pancreatectomy: For body/tail lesions.
  • Only ~20% of patients present with resectable disease.
• Adjuvant chemotherapy (e.g. gemcitabine-based regimens) is standard post-op.
• Radiotherapy may be used in some settings, though evidence is mixed.
• Surveillance imaging is used post-treatment.

8.2 Palliative Care

• Most patients require palliative treatment only:
  • Pain management
  • Nutritional support
  • Jaundice management
  • Psychological support
• Referral to palliative care is essential early in the disease course.

8.3 Treatment of Other Pancreatic Tumours

• Cystadenocarcinoma:
  • Presents with mass effect; diagnosed on CT/MRI.
  • Treated with surgical resection; excellent prognosis if resected early.
• Intraductal Papillary Mucinous Neoplasm (IPMN):
  • Causes mucin overproduction and pancreatitis.
  • “Fish-eye” papilla may be seen on ERCP.
  • Resected surgically; prognosis good if benign.
• Neuroendocrine Tumours:
  • Functioning tumours cause endocrine syndromes.
  • Non-functioning tumours present with mass effect.
  • Treated with surgery, somatostatin analogues (e.g. octreotide), or targeted therapies.

9. Complications

• Metastases: Liver, peritoneum, lung, bones.
• Malabsorption: Due to exocrine insufficiency.
• Diabetes mellitus
• Thrombosis: Deep vein thrombosis, splenic vein thrombosis, Trousseau’s syndrome.
• Gastric varices: From splenic vein involvement.
• Haemorrhage: From local invasion of vessels.
• Pancreatitis: From ductal obstruction by tumour.
• Psychological distress and poor quality of life due to pain and advanced disease.