Acute Pancreatitis

Acute pancreatitis is an inflammatory condition of the pancreas, most often triggered by gallstones or alcohol consumption. It typically presents with sudden and severe epigastric pain radiating to the back, accompanied by nausea, vomiting, and epigastric tenderness on palpation. Diagnosis is confirmed by elevated serum lipase or amylase levels (≥ 3× the upper limit of normal) and/or characteristic findings on imaging, such as contrast-enhanced abdominal CT.

Severity and prognosis are assessed using clinical scoring systems like the Ranson criteria and APACHE II. Initial treatment focuses on supportive care, including fluid resuscitation, pain management, antiemetics, and early enteral nutrition as tolerated. Identifying and addressing the underlying cause is crucial to prevent recurrence (e.g., cholecystectomy for biliary pancreatitis or lipid-lowering therapy for hypertriglyceridemia-induced pancreatitis).

Complications can be local or systemic:

• Localized complications include necrotizing pancreatitis (with the risk of infection), pancreatic pseudocysts, and walled-off necrosis.
• Systemic complications include sepsis, acute respiratory distress syndrome (ARDS), organ failure, and shock.

Complications significantly contribute to the morbidity and mortality associated with acute pancreatitis.

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Etiology of Acute Pancreatitis

Most Common Causes:

1. Biliary Pancreatitis: Responsible for approximately 40% of cases, primarily due to gallstones.
2. Alcohol-Induced Pancreatitis: Accounts for around 20% of cases.
3. Idiopathic Pancreatitis: Comprises about 25% of cases with no identifiable cause.

Other Causes:

• Hypertriglyceridemia-Induced Pancreatitis: Triggered by severe hypertriglyceridemia (>1,000 mg/dL).
• Hypercalcemia
• Post-ERCP (Endoscopic Retrograde Cholangiopancreatography)
• Drug-Induced Pancreatitis:
  • Steroids
  • Azathioprine
  • Sulfonamides
  • Loop and thiazide diuretics
  • Estrogen
  • Protease inhibitors
  • NRTIs (nucleoside reverse transcriptase inhibitors)
  • Anticonvulsants (e.g., valproate)
  • Metronidazole
• Scorpion Stings
• Viral Infections: Such as coxsackievirus B and mumps.
• Trauma: Particularly in pediatric cases.
• Autoimmune and Rheumatological Disorders: E.g., Sjögren syndrome.
• Pancreas Divisum
• Hereditary Causes: E.g., PRSS1 gene mutation or cystic fibrosis.
• Cholesterol Embolism

Mnemonic: “I GET SMASHED”
The following mnemonic outlines the key causes of acute pancreatitis:

• I – Idiopathic
• G – Gallstones
• E – Ethanol (alcohol)
• T – Trauma
• S – Steroids
• M – Mumps (and other viral infections)
• A – Autoimmune disorders
• S – Scorpion venom
• H – Hypercalcemia and Hypertriglyceridemia
• E – ERCP
• D – Drugs

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Pathophysiology of Acute Pancreatitis

Sequence of Events

1. Intrapancreatic Activation of Enzymes
   • Triggered by pancreatic ductal outflow obstruction (e.g., gallstones, cystic fibrosis) or direct injury to acinar cells (e.g., alcohol, drugs).
   • Leads to increased proteolytic and lipolytic enzyme activity, causing destruction of pancreatic parenchyma.
2. Inflammatory Cascade
   • Recruitment of inflammatory cells (neutrophils, macrophages) → release of proinflammatory cytokines.
   • Results in localized pancreatic inflammation, manifesting as acute pancreatitis.

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Sequelae of Pancreatitis

1. Capillary Leakage and Fluid Redistribution
   • Inflammatory cytokines and pancreatic enzymes cause vascular injury, leading to:
     • Vasodilation and increased vascular permeability → Fluid shifts from the intravascular to the interstitial space (third-spacing).
   • Clinical manifestations include:
     • Hypotension
     • Tachycardia
     • Warm, flushed skin
   • Can progress to distributive shock or, in severe cases, hypovolemic shock due to extensive fluid loss.
2. Pancreatic Necrosis and Organ Dysfunction
   • Persistent hypotension and third-spacing impair end-organ perfusion.
   • Consequences include:
     • Pancreatic necrosis
     • Multiorgan dysfunction, particularly renal failure.
3. Hypocalcemia
   • Lipase activity breaks down peripancreatic and mesenteric fat, releasing free fatty acids.
   • These free fatty acids bind calcium, forming insoluble complexes (fatty saponification).
   • Results in hypocalcemia, a hallmark biochemical feature in severe pancreatitis.

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Clinical Features of Acute Pancreatitis

Symptoms

• Severe, constant epigastric pain:
  • Typically radiates to the back.
  • Worsens after meals and in the supine position.
  • Improves with leaning forward.
• Nausea and vomiting
• Fever
• Pulmonary symptoms (if complications arise):
  • Chest pain
  • Dyspnea

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Examination Findings

General Findings:

• Signs of shock:
  • Tachycardia
  • Hypotension
  • Oliguria or anuria
• Jaundice (in cases of biliary pancreatitis)

Abdominal Examination:

• Tenderness, distention, and guarding
• Ileus:
  • Reduced bowel sounds
  • Tympany on percussion
• Ascites

Skin Changes (Rare):

• Cullen Sign: Bluish-red ecchymosis and discoloration around the umbilicus.
• Grey Turner Sign: Ecchymosis with discoloration over the flanks.
• Fox Sign: Ecchymosis over the inguinal ligament.

Pulmonary Examination:

• Signs of pleural effusion or acute respiratory distress syndrome (ARDS).

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Diagnosis of Acute Pancreatitis

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Diagnostic Criteria

A diagnosis of acute pancreatitis is made when two out of the following three criteria are met:

1. Characteristic abdominal pain: Severe, constant, and epigastric, often radiating to the back.
2. Elevated serum pancreatic enzymes: Lipase or amylase levels ≥ 3× the upper limit of normal (ULN).
3. Imaging findings: Characteristic features of acute pancreatitis on cross-sectional imaging, such as abdominal ultrasound or contrast-enhanced CT (CECT).

Diagnostic Approach

1. Laboratory Studies

• For Diagnosis: Serum lipase and/or amylase levels.
• For Severity Assessment:
  • Complete blood count (CBC)
  • Basic metabolic panel (BMP)
  • Arterial blood gases (ABG)
  • Lactate dehydrogenase (LDH)
  • Inflammatory markers (e.g., CRP)
  • Serum calcium
• For Etiological Evaluation:
  • Liver function tests (LFTs)
  • Serum/plasma triglyceride levels

2. Imaging

• Abdominal Ultrasound: First-line imaging to detect gallstones and assess for biliary pancreatitis.
• Contrast-Enhanced CT (CECT): Reserved for cases with diagnostic uncertainty or to evaluate complications, such as necrosis, particularly 5–7 days after symptom onset.
• MRCP (Magnetic Resonance Cholangiopancreatography): Used to identify biliary obstruction or stones in suspected biliary pancreatitis.

3. Severity Assessment

• Calculate severity scores (e.g., Ranson criteria, APACHE II) to estimate prognosis and guide management.

Additional Considerations

• Simultaneously perform tests to confirm the diagnosis, assess severity, and exclude other causes of acute abdominal pain.
• Acute pancreatitis is a medical emergency; fluid resuscitation should be initiated immediately upon clinical suspicion.

Read More on Diagnosis of Acute Pancreatitis

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Management

Initial Management of Acute Pancreatitis

The initial management for all etiologies of acute pancreatitis follows a similar approach and should be initiated promptly.

Goal-Directed IV Fluid Therapy

• Fluids: Crystalloids, such as lactated Ringer’s solution (LR), are the preferred choice.
• Timing: IV fluid resuscitation is most impactful in the first 12–24 hours, as it significantly affects clinical outcomes.

Supportive Therapy

1. Analgesics:
   • NSAIDs (e.g., ketorolac, diclofenac, ibuprofen) as first-line.
   • Opioids (e.g., hydromorphone, morphine) may be used for more severe pain.
2. Antiemetics: Use agents like ondansetron or metoclopramide to control nausea and vomiting.
3. Electrolyte Repletion: Monitor and correct electrolyte imbalances. Prophylactic antibiotics: Not recommended routinely. Use only in the presence of infected necrosis.

Nutrition

• Early Oral Feeding: Begin a low-fat, solid diet as soon as tolerated, ideally within 24 hours.
• Enteral Tube Feeding (nasogastric or nasojejunal): Preferred if the patient cannot tolerate oral intake.
• Parenteral Nutrition: Reserved for patients who cannot tolerate enteral feeding, such as those with persistent paralytic ileus.
• Bowel Rest: No longer routinely recommended. Early enteral nutrition should be initiated as tolerated.

Management of Underlying Causes

1. Biliary Pancreatitis
   • Therapeutic ERCP: Indicated in cases of biliary pancreatitis associated with cholangitis or persistent common bile duct (CBD) obstruction. Perform within 24 hours if cholangitis is present.
   • Cholecystectomy: Indicated for all patients with biliary pancreatitis to prevent recurrence. Consider for those with recurrent, unclear etiology.
2. Hypertriglyceridemia-Induced Pancreatitis
   • Treatment: Initiate measures to rapidly reduce triglyceride levels, including:
     • Insulin therapy
     • Plasmapheresis and hemofiltration
   • Long-term Management: Start lipid-lowering therapy (e.g., fibrates) as soon as tolerated. Address lifestyle and dietary changes, and evaluate for familial hypertriglyceridemia.
3. Alcohol-Induced Pancreatitis
   • Electrolyte Repletion: Correct magnesium and phosphorus deficiencies.
   • Vitamin Supplementation: Administer thiamine and pyridoxine.
   • Alcohol Use Disorder: Provide counseling and support for alcohol use disorder.

The “PANCREAS” Approach

1. P – Perfusion (fluid replacement)
2. A – Analgesia (pain management)
3. N – Nutrition (early enteral feeding)
4. C – Clinical (observation and supportive care)
5. R – Radiology (imaging for diagnosis and complications)
6. E – ERCP (for biliary issues)
7. A – Antibiotics (if infection is present)
8. S – Surgery (surgical intervention if necessary)

This comprehensive approach ensures the best possible outcome for patients with acute pancreatitis across various etiologies.

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Acute Pancreatitis During Pregnancy

Epidemiology

• Incidence: 1 in 1,000 to 10,000 pregnancies.
• Risk Factors: More commonly affects multiparous individuals (75%).
• Timing:
  • Third trimester: 50% of cases.
  • Early postpartum period: 38% of cases.
  • First and second trimesters: 12% of cases.

Etiology

• Most commonly caused by gallstones, heavy alcohol use, and familial hypertriglyceridemia.
• Physiologic Changes During Pregnancy:
  • Progesterone: Increases pressure on the sphincter of Oddi, leading to bile stasis.
  • Estrogen: Alters bile composition, making it more lithogenic (prone to stone formation).

Clinical Features

• Same as nonpregnant individuals (see Clinical Features section).

Diagnostics

• CBC: May show pregnancy-related physiological changes (e.g., mild leukocytosis).
• Serum Amylase and Lipase: If levels are more than 3 times greater than normal, acute pancreatitis is likely.
• Imaging:
  • Abdominal ultrasound or MRI are preferred modalities to identify choledocholithiasis or complications such as hemorrhage, edema, or pseudocysts.

Treatment

• Management: Identical to nonpregnant individuals (see Treatment of Acute Pancreatitis section).
• Analgesics: Use caution in choosing medications during pregnancy; consult “Overview of analgesics to avoid during pregnancy” for further details.

Complications

• Pregnancy-related complications:
  • Increased risk of preterm labor, premature birth, and fetal death.
• General complications of acute pancreatitis: Can occur as in nonpregnant patients (e.g., multi-organ failure, pancreatic necrosis).

This approach ensures appropriate management of acute pancreatitis during pregnancy, balancing maternal and fetal health.

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Differential Diagnoses of Acute Pancreatitis

Intestinal Manifestations

1. Acute Peritonitis: Inflammation of the peritoneum, often caused by perforation of an abdominal organ.
2. Appendicitis: Inflammation of the appendix, often presenting with right lower quadrant pain.
3. Acute Mesenteric Ischemia: Reduced blood flow to the intestines, leading to ischemia and potential infarction.
4. Acute Cholecystitis: Inflammation of the gallbladder, typically due to gallstones, presenting with right upper quadrant pain.
5. Acute Cholangitis: Inflammation of the bile duct, often due to biliary obstruction, causing fever, jaundice, and abdominal pain.
6. Peptic Ulcer Disease: Ulceration of the stomach or duodenum, often presenting with epigastric pain.
7. Biliary Colic: Pain due to gallstones temporarily obstructing the bile duct, causing intermittent pain.
8. Abdominal Aortic Aneurysm: Rupture or dissection of the abdominal aorta can cause sudden, severe abdominal pain.

Extraintestinal Manifestations

1. Myocardial Infarction: Chest pain radiating to the abdomen, sometimes mimicking acute pancreatitis, especially in elderly or diabetic patients.
2. Bacterial Pneumonia: Lung infections can present with upper abdominal pain due to referred pain or diaphragmatic irritation.

These conditions should be considered in the differential diagnosis when evaluating a patient with suspected acute pancreatitis, especially when the presentation is atypical or the diagnosis is uncertain.

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Comparison table between acute and chronic pancreatitis:

Aspect	Acute Pancreatitis	Chronic Pancreatitis
Definition	Acute inflammation of the pancreas with potentially reversible damage	Progressive, irreversible inflammation leading to permanent pancreatic damage
Onset	Sudden	Gradual, with recurrent episodes
Etiology	Common causes:	Common causes:
	– Gallstones (biliary pancreatitis)	– Chronic heavy alcohol use (60–70%)
	– Alcohol use	– Idiopathic (20–30%)
	– Idiopathic	– Pancreatic ductal obstruction (<10%)
	Less common causes:	– Tobacco use
	– Severe hypertriglyceridemia (>1,000 mg/dL)	Less common causes:
	– Hypercalcemia	– Severe hypertriglyceridemia
	– Post-ERCP	– Pancreas divisum
	– Drugs (e.g., thiazide diuretics)	– Autoimmune pancreatitis
	– Trauma (especially in children)	– Hereditary pancreatitis
	– Autoimmune or rheumatologic disorders
Pathophysiology	– Enzyme activation within the pancreas → autodigestion and inflammation	– Repeated inflammation → fibrosis and loss of pancreatic function (exocrine and endocrine)
	– Inflammatory cytokines attract neutrophils and macrophages
	– Possible necrosis, fat saponification, or systemic inflammation
Clinical Presentation	Main symptoms:	Main symptoms:
	– Severe epigastric pain, radiating to the back	– Persistent epigastric pain radiating to the back
	– Nausea, vomiting	– Pain worsens after eating, relieved by leaning forward
	– Fever	– Malabsorption, steatorrhea, weight loss
	Other features:	Other features:
	– Shock (tachycardia, hypotension)	– Pancreatic diabetes
	– Cullen, Grey Turner, and Fox signs	– Symptoms manifest late in disease progression
Laboratory Findings	– ↑ Lipase (specific)	– Normal or slightly ↑ lipase and amylase
	– ↑ Amylase (nonspecific)	– ↓ Fecal elastase-1 confirms steatorrhea due to pancreatic insufficiency
	– ↓ Calcium (in severe cases)
Imaging	– Ultrasound: Pancreatic edema, peripancreatic fluid, pseudocysts, cholelithiasis	– CT or ultrasound: Pancreatic calcifications, ductal abnormalities, and atrophy
	– CT: Pancreatic enlargement, fat stranding	– ERCP/MRCP: Chain-of-lakes appearance, ductal dilations
	– X-ray: Sentinel loop, colon cut-off sign
Treatment	Initial management:	Management strategies:
	– Fluid resuscitation with crystalloids	– Avoid alcohol, smoking
	– Pain control with NSAIDs or opioids	– Pancreatic enzyme replacement
	– Enteral feeding as early as tolerated	– Pain management: celiac ganglion block or endoscopic interventions
	– ERCP for biliary pancreatitis	– Surgery for complications (e.g., cancer or intractable pain)
	– Antibiotics only for infected necrosis
Complications	Localized:	Localized:
	– Pancreatic pseudocysts, abscess, necrosis	– Pancreatic pseudocysts
	– Bacterial superinfection	– Splenic vein or portal vein thrombosis
	– Fistula formation	Systemic:
	Systemic:	– Exocrine insufficiency: maldigestion, steatorrhea, vitamin deficiencies
	– SIRS, sepsis, DIC	– Endocrine insufficiency: diabetes
	– ARDS, pneumonia, respiratory failure
	– Shock
Prognosis	– Mortality < 1% without organ failure, ∼30% with organ failure	– Progressive disease with risk of pancreatic insufficiency and long-term complications
	– Dependent on severity and promptness of treatment

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Localized Complications:

1. Necrotizing Pancreatitis:
   • Definition: Necrosis of pancreatic and peripancreatic tissue.
   • Clinical Features: Fever, persistent tachycardia, and insufficient symptomatic improvement over several days.
   • Diagnostics: Nonenhancing areas of pancreatic parenchyma on CECT abdomen.
   • Treatment: Conservative management for sterile necrotizing pancreatitis, encouraging enteral nutrition and providing supplemental nutritional support.
2. Infected Necrotizing Pancreatitis:
   • Definition: Bacterial superinfection of necrotic pancreatic parenchyma.
   • Clinical Features: Similar to necrotizing pancreatitis, but with signs of infection.
   • Diagnostics:
     • Persistent or worsening leukocytosis, bacteremia, increasing inflammatory markers.
     • CECT abdomen showing gas within the pancreas or peripancreatic tissue or fluid collections.
     • Fine-needle aspiration of necrotic areas is not routinely recommended.
   • Treatment:
     • Broad-spectrum empiric antibiotics (e.g., carbapenems) for 2–4 weeks.
     • Drainage of infected material if clinical deterioration or persistence of symptoms occurs despite antibiotics.
   • Prognosis: High mortality rate (30%).
3. Walled-Off Necrosis (Pancreatic Abscess):
   • Definition: An encapsulated collection of sterile necrotic material, usually occurring >4 weeks after necrotizing pancreatitis.
   • Diagnostics: CT abdomen with IV contrast showing an encapsulated heterogeneous collection containing fluid and debris.
   • Treatment: Symptomatic walled-off necrosis is managed with percutaneous drainage or transmural endoscopic necrosectomy.
4. Other Localized Complications:
   • Pancreatic pseudocyst
   • Abdominal compartment syndrome
   • Pancreatic hemorrhage (blood vessel erosion with bleeding)

Systemic Complications:

1. Shock: Can be associated with severe pancreatitis.
2. SIRS, Sepsis, DIC: Systemic inflammatory response syndrome and disseminated intravascular coagulation due to infection or organ dysfunction.
3. Pneumonia, Respiratory Failure, ARDS: Respiratory complications due to inflammation or infection.
4. Pleural Effusion: Fluid accumulation in the pleural cavity.
5. Prerenal Failure: Due to volume depletion, leading to kidney dysfunction.
6. Hypocalcemia: Often caused by saponification of fat during pancreatitis.
7. Paralytic Ileus: Bowel dysfunction often seen in severe pancreatitis.
8. Pancreatic Ascites: Accumulation of fluid in the abdomen due to pancreatic leakage.

These complications vary in severity and may require various forms of intervention, including supportive care, antibiotic therapy, drainage, and surgical interventions. The selection listed above represents the most important complications, but it is not exhaustive.

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Prognosis of Acute Pancreatitis:

• Mortality:
  • In patients without organ failure: Mortality is less than 1%.
  • In patients with organ failure: Mortality is approximately 30%.
  • Higher mortality is observed in patients with biliary pancreatitis compared to those with alcohol-induced pancreatitis.
• Risk Factors for Severe Disease:
  • Specific risk factors for severe disease are discussed in the section on “Severity scores for acute pancreatitis.