Acute pancreatitis etiology, pathophysiology, clinical features, management

Acute Pancreatitis
Etiology, Pathophysiology, Clinical Features, and Management

  1. Introduction
    Acute pancreatitis (AP) is a sudden inflammatory process of the pancreas with variable involvement of regional tissues and remote organ systems. Although most attacks are self-limited, severe AP can progress rapidly to multisystem organ failure and death. Incidence in high-income countries approaches 30–40 per 100,000 population per year, making AP one of the most common gastrointestinal emergencies.

  2. Etiology
    More than 80 % of cases arise from two causes—gallstones and alcohol. Yet over 100 aetiological factors have been identified, which can be remembered by the mnemonic “GET SMASHED”:

• G – Gallstones (35–45 %)
• E – Ethanol (25–35 %)
• T – Trauma (post-operative, blunt, penetrating)
• S – Steroids
• M – Mumps and other infections (Coxsackie, CMV, HIV)
• A – Autoimmune (IgG4-related disease, SLE)
• S – Scorpion sting, Snake bite
• H – Hyperlipidaemia (triglycerides > 11.3 mmol/L), Hypercalcaemia, Hereditary (PRSS1, SPINK1, CFTR)
• E – ERCP / Endoscopic instrumentation (3–5 %)
• D – Drugs (azathioprine, valproate, furosemide, thiazides, HIV-PIs), and also Idiopathic (~10 %)

Risk-modifying factors include smoking, obesity, and certain genetic polymorphisms (e.g., CTRC, CPA1).

  1. Pathophysiology
    3.1 Initiating Events
    Regardless of cause, the fundamental problem is premature intra-pancreatic activation of digestive enzymes, particularly conversion of trypsinogen to trypsin. Mechanisms vary:

• Gallstones: transient obstruction at the ampulla → ductal hypertension and reflux of bile into pancreatic ducts.
• Alcohol: direct acinar toxicity, oxidative stress, and increased permeability of ductules.
• Hypertriglyceridaemia: free fatty acids damage acinar cells.

3.2 Autodigestion and Local Inflammation
Trypsin activates other proenzymes (elastase, phospholipase A₂) leading to destruction of acinar, ductal, and vascular endothelium. Activated phospholipase A₂ generates lysolecithin, which dissolves cell membranes and surfactant, producing fat necrosis. Elastase erodes blood vessels causing haemorrhage.

3.3 Systemic Inflammatory Response
Cytokine and chemokine release (TNF-α, IL-1β, IL-6, IL-8) enters the systemic circulation, triggering:

• Systemic inflammatory response syndrome (SIRS)
• Capillary leak, third-spacing, hypovolaemia
• MODS (ARDS, acute kidney injury, shock)

3.4 Classification of Severity (Revised Atlanta, 2012)
• Mild: no organ failure, no local or systemic complications
• Moderately severe: transient (< 48 h) organ failure or local complications
• Severe: persistent organ failure (≥ 48 h) involving respiratory, cardiovascular, or renal systems

Morphologically:
• Interstitial oedematous pancreatitis (IEP)
• Necrotizing pancreatitis (NP) with sterile or infected necrosis

  1. Clinical Features
    4.1 Symptoms
    • Sudden, severe epigastric pain radiating to the back (“boring”)
    • Nausea and persistent vomiting
    • Pain relief by leaning forward or sitting up

4.2 Signs
• Low-grade fever, tachycardia, hypotension (from third-spacing)
• Abdominal distension, guarding
• Grey-Turner sign (flank ecchymosis) and Cullen sign (periumbilical) – late, severe disease
• Pleural effusion, especially left-sided

4.3 Laboratory Findings
• Serum amylase or lipase ≥ 3× upper limit (lipase more specific)
• Elevated haematocrit (hemoconcentration), CRP > 150 mg/L at 48 h (severity marker)
• Hypocalcaemia (fat saponification)
• Hyperglycaemia, metabolic acidosis
• ALT > 150 U/L in first 48 h suggests gallstone pancreatitis (PPV > 90 %)

4.4 Imaging
• Transabdominal US: gallstones, bile duct dilatation
• Contrast-enhanced CT at ≥ 72 h: oedema vs necrosis, collections, complications
• MRCP/EUS: occult stones, ductal disruptions

4.5 Diagnostic Criteria (need any 2 of 3)
1. Typical abdominal pain
2. Serum lipase/amylase ≥ 3× ULN
3. Imaging consistent with AP

  1. Management
    Principles: Early aggressive supportive care, prevention of complications, treatment of underlying cause.

5.1 Initial Resuscitation
• Fluid therapy: Lactated Ringer’s 5–10 mL/kg/h; aim for MAP > 65 mmHg, urine > 0.5 mL/kg/h, decreasing BUN/haematocrit.
• Oxygen supplementation; consider early ICU if PaO₂ < 60 mmHg or organ failure.
• Analgesia: IV opioids (morphine, fentanyl); patient-controlled analgesia often necessary.

5.2 Nutrition
• Early enteral nutrition (nasogastric or nasojejunal) within 24–48 h reduces infection and mortality.
• Parenteral nutrition reserved for intolerance/refusal of enteral.

5.3 Antibiotics
• Not indicated prophylactically in sterile necrosis.
• Start broad-spectrum (carbapenem, quinolone + metronidazole) only if infected necrosis confirmed (positive cultures, gas on CT) or extrapancreatic infection.

5.4 ERCP / Interventions
• Gallstone pancreatitis + cholangitis or persistent biliary obstruction → urgent ERCP (within 24 h).
• Cholecystectomy during index admission for mild disease; delayed until collections resolve for necrotising disease.
• Percutaneous or endoscopic drainage of symptomatic pseudocysts or walled-off necrosis (WON).
• Step-up approach: percutaneous/endoscopic drainage → video-assisted retroperitoneal debridement if needed. Open necrosectomy now rare.

5.5 Management of Complications
• Respiratory failure: low-tidal-volume ventilation, proning.
• Renal failure: CRRT if volume-overloaded or refractory.
• Pancreatic necrosis hemorrhage: angiographic embolisation.
• Venous thromboembolism prophylaxis essential.

5.6 Severity Stratification Tools
• BISAP (BUN > 25 mg/dL, Impaired mental status, SIRS, Age > 60, Pleural effusion)
• APACHE II, Ranson, Glasgow-Imrie – guide ICU admission.

  1. Prognosis
    Overall case fatality 2–5 %. Mortality rises to 15–20 % in severe AP, highest in infected necrosis and persistent MODS. Predictors of poor outcome: age > 55, obesity (BMI > 30), organ failure > 48 h, infected necrosis, elevated BISAP/APACHE II scores.

  2. Future Directions
    Recent trials are evaluating:
    • Goal-directed fluid resuscitation vs liberal vs restrictive protocols
    • Endoscopic transluminal necrosectomy techniques
    • Immunomodulatory therapies (IL-1 blockers) to temper cytokine storm
    • Probiotics and microbiota modulation

  3. Conclusion
    Acute pancreatitis is a multifaceted disease ranging from mild, self-limiting inflammation to catastrophic necrosis with systemic organ failure. Early diagnosis, prompt resuscitation, careful monitoring, and minimally invasive targeted interventions have significantly improved outcomes. Nevertheless, prevention—through gallstone management, alcohol cessation, lipid control, and judicious drug use—remains the most effective strategy to curb the burden of AP.