Epidemiology and Etiology
Epidemiology
- Incidence:
- United States: 40–50 cases per 100,000 adults
- Worldwide: 5–80 per 100,000 adults
- Men > women
- Men: likely due to alcohol
- Women: related to biliary tract disease
- Mortality is approximately 5%, overall:
- Necrotizing pancreatitis: 17%
- Interstitial pancreatitis: 3%
Etiology
- Biliary tract disease:
- Approximately 40% of cases
- Caused by biliary obstruction due to a stone
- Alcohol use:
- Approximately 30% of cases
- Often an exacerbation of chronic pancreatitis
- Usually seen with habitual consumption over 5–15 years, but may be seen after a binge
- Endoscopic retrograde cholangiopancreatography (ERCP):
- Can cause accidental lodging of stone into the sphincter of Oddi
- Increased risk in sphincter of Oddi dysfunction
- Abdominal trauma:
- More often in penetrating injuries
- Blunt trauma may lead to ductal injury
- Drugs:
- Azathioprine
- Sulfonamides
- Tetracycline
- Valproic acid
- Estrogens
- Thiazide and loop diuretics
- Corticosteroids
- Octreotide
- Pentamidine
- Idiopathic:
- Approximately 10%–30% of cases
- Occult microlithiasis may be responsible.
- Less common causes:
- Infections:
- Mumps
- Hepatitis
- Cytomegalovirus
- Coxsackievirus
- Salmonella
- Parasites
- Genetic predispositions (e.g., CFTR mutation, as in cystic fibrosis)
- Hypercalcemia
- Hypertriglyceridemia
- Tumors
- Toxins:
- Organophosphates
- Scorpion bite
- Vascular or ischemic
- Autoimmune pancreatitis (IgG4)
- Developmental:
- Pancreatic ductus divisum: failure of the dorsal and ventral pancreatic ducts to fuse
- Annular pancreas: a band of pancreatic tissue surrounds the 2nd part of the duodenum
- Sphincter of Oddi dysfunction
- Infections:
Pathophysiology
Normal pancreatic function
- The pancreas has endocrine (insulin) and exocrine (digestive enzymes) functions.
- Digestive enzymes made in acinar cells → stored as zymogens (inactive form) → released in the pancreatic duct and small intestine → activation by trypsin
- Protective mechanisms against organ injury (autodigestion) include:
- Negative feedback mechanism (↑ trypsin in duodenum → ↓ cholecystokinin (CCK) and secretin → ↓ pancreatic secretion)
- Zymogens are controlled with protease inhibitors.
- ↓ Acinar cell pH and calcium concentrations → prevent premature activation of trypsin
- Anything that disrupts the homeostasis of normal pancreatic function can cause acute pancreatitis.
Acute pancreatitis pathogenesis
- Initiated through acinar cell injury from:
- Biliary obstruction → increased pancreatic duct pressure → acinar cell injury
- Direct injury (e.g., toxins, alcohol)
- Changes in acinar cell pH and calcium concentrations → allows intrapancreatic activation of trypsin → activation of zymogens → autodigestion
- Inhibited secretion on zymogens into the pancreatic ducts → exocytosis into the interstitium → not fully understood, but believed to lead to attraction of inflammatory cells
- Inflammatory cells arrive → cytokine release → pancreatic inflammation
- Cytokine release and vascular injury from enzymes → vasodilation and vascular permeability → fluid shifting to the interstitial space (3rd spacing) → decreased perfusion and hypotension → can result in:
- Shock
- Acute renal failure
- Pancreatic necrosis
Acute pancreatitis
Image by Lecturio.
Hematoxylin and eosin (H&E) stain of necrotic pancreatitis (eosinophilic area without architecture: necrosis), surrounded by basophilic inflammatory cells and normal fat cells
Image: “Tryptic fat tissue necrosis in severe pancreatitis” by Patho. License: CC BY-SA 3.0.
Clinical Presentation
Symptoms
- Acute abdominal pain:
- Epigastric
- Dull and steady
- Sudden onset, increasing in severity
- Radiation to the back (approximately 50% of patients)
- Nausea and vomiting
- Anorexia
- Diarrhea
- Low-grade fever
Physical examination
- General:
- Tachycardia
- Abdominal tenderness
- Abdominal distention
- Diminished bowel sounds → ileus
- Evidence of severe disease:
- Fever
- Hypotension
- Tachypnea and crackles
- Pale and diaphoretic
- Signs of an underlying cause:
- Hepatomegaly → alcoholic pancreatitis
- Scleral icterus or jaundice → choledocholithiasis
- Muscle spasms → hypocalcemia
- Xanthomas → hypertriglyceridemia
- Warning signs of retroperitoneal bleeding in severe, necrotizing pancreatitis:
- Cullen’s sign: bluish discoloration around the umbilicus due to blood in the peritoneum
- Grey-Turner’s sign: reddish-brown discoloration on the flanks due to blood in the retroperitoneum or pancreatic exudates
Cullen’s sign, signaling blood in the peritoneum
Image: “Cullen’s sign” by Herbert L. Fred, MD. License: CC BY 2.0.
Grey-Turner’s sign due to hemorrhagic pancreatitis
Image: by Herbert L. Fred, MD and Hendrik A. van Dijk. License: CC BY 2.0.
Diagnosis
Diagnostic criteria
The diagnosis of acute pancreatitis requires at least 2 of the following:
- Acute onset of epigastric abdominal pain
- Serum amylase or lipase > 3 times the upper limit of normal
- Characteristic findings on imaging
Laboratory evaluation
- ↑ Serum amylase
- ↑ Serum lipase: more specific for pancreatitis
- Hepatic function tests:
- Alanine transaminase (ALT) > 150 U/L and ↑ bilirubin → pancreatitis secondary to gallstones
- Maybe be ↑ with heavy alcohol use
- Basic metabolic panel:
- Calcium:
- ↑ Calcium → may be a potential cause of pancreatitis
- ↓ Calcium → frequently seen, and should be corrected
- Electrolyte imbalances can occur due to 3rd spacing of fluids
- ↑ Blood urea nitrogen (BUN) → severe disease
- Calcium:
- Lactate dehydrogenase (LDH): ↑ in severe disease
- Complete blood count:
- ↑ Hematocrit → severe disease
- ↑ WBCs → inflammation
- C-reactive protein (CRP): > 150 mg/L at 48 hours → risk of severe pancreatitis and organ failure
- Triglycerides: ↑ in hypertriglyceridemia
- Immunoglobulin G4 (IgG4): may be checked if autoimmune pancreatitis is suspected
- Arterial blood gas:
- Should be done if the patient is tachypneic
- Can evaluate oxygenation and acid-base status
Milky plasma seen in a patient with hypertriglyceridemia: If seen, milky plasma should be considered as a potential cause of acute pancreatitis.
Image: “Milky plasma” by the Department of Emergency and Critical Care Medicine, Ohta Nishinouchi Hospital, 2-5-20 Nishinouchi, Koriyama, Fukushima, 963-8558, Japan. License: CC BY 2.0.Imaging
Imaging may not be required if the 1st 2 diagnostic criteria are met, but can be used for evaluating the underlying cause and complications:
- Computed tomography (CT):
- Normal in 30% of cases
- Potential findings:
- Inflammatory changes of the pancreas
- Necrosis, fluid collections, or pseudocysts can be seen later in the course.
- Abdominal ultrasound (US):
- Can be done if gallstone pancreatitis is suspected
- Potential findings:
- Gallstones
- Common bile duct (CBD) dilation
- Pancreatic edema
- Peripancreatic fluid
- Magnetic resonance cholangiopancreatogram (MRCP):
- Can evaluate the biliary system
- Findings:
- Choledocholithiasis
- Biliary dilation
- Pancreatic edema
- Pancreatic necrosis or pseudocysts
- Chest radiograph:
- For patients with pulmonary symptoms (dyspnea, tachypnea, hypoxia)
- Potential findings:
- Pleural effusions
- Basal atelectasis
- Diffuse, patchy infiltrates indicating acute respiratory distress syndrome (ARDS)
- Abdominal radiograph:
- Limited role
- “Sentinel loop” finding (short segment of ileus near the pancreatic inflammation)
A CT scan showing changes in the pancreas, which appears enlarged and edematous
Image: “A computed tomography scan” by the Department of Surgery, Helsingborg Hospital, 25187 Helsingborg, Sweden. License: CC BY 3.0.
A tiny CBD stone is revealed using US. Such stones should be considered a potential etiology in a patient presenting with acute pancreatitis.
Image: “F2” by the Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung 81362, Taiwan. License: CC BY 2.0, edited by Lecturio.
Acute pancreatitis on CT scan, showing edema around the pancreas
Image: “Arterial phase contrast CT showing an acute pancreatitis” by Benoît Bédat et al. License: CC BY 4.0.
Prognosis evaluation
Identifying the severity of acute pancreatitis is helpful in order to ensure the patient is treated appropriately:
- Ranson’s criteria (see table):
- Widely used
- The biggest disadvantage is that it takes 48 hours to complete the assessment.
- Bedside index of severity in acute pancreatitis (BISAP) score (see table):
- Simple
- Calculated during the 1st 24 hours
- APACHE II score:
- Evaluates age, temperature, mean arterial pressure, heart rate, respiratory rate, blood gas results, WBC count, electrolytes, creatinine, Glasgow coma score (GCS), and other health conditions
- Very cumbersome and complex
| Present on admission | At 48 hours after admission |
|---|---|
| Age > 55 years | Decrease in hematocrit > 10% |
| WBC > 16,000/μL | Increase in BUN by > 8 mg/dL |
| Blood glucose > 200 mg/dL | Serum Ca < 8 mg/dL |
| Serum LDH > 350 IU/L | PaO2 < 60 mm Hg |
| Aspartate transaminase (AST) > 250 IU/L | Base deficit > 4 mEq/L |
| Estimated fluid sequestration > 6 L |
3‒5: 10%‒20% mortality rate, must be admitted to ICU
> 5: Increased risk of systemic complications and mortality
Definitions:
- PaO2 is the partial pressure of oxygen in arterial blood.
- Base deficit indicates excess acid in the blood.
| BUN | > 25 mg/dL |
|---|---|
| Impaired mental status | GCS < 15 |
| Systemic inflammatory response syndrome (SIRS) | Evidence of SIRS |
| Age | > 60 years |
| Pleural effusion | Positive finding on imaging |
3‒5 points: higher mortality (> 15%)
Management
Acute management
- Basic treatment:
- Aggressive intravenous fluid (IVF) resuscitation
- Fluid intake and output monitoring
- Close vital sign monitoring
- Address electrolyte imbalances
- Medications:
- Analgesics (typically opioids)
- Antiemetics
- Initial bowel rest
- Early nutritional support:
- Can be started as early as 24 hours, if pain is decreasing
- Is associated with ↓ morbidity compared to delayed or no nutrition
- Mild acute pancreatitis:
- Can be treated on a general medical ward
- May begin low-residue, low-fat diet as soon as tolerated
- Severe acute pancreatitis:
- Intensive care setting is preferred.
- May require enteral nutrition if the patient cannot tolerate oral intake: Start within 72 hours.
Treating the etiology
- Gallstones
- ERCP:
- Can perform sphincterotomy and stone extraction
- Indicated for choledocholithiasis or evidence of cholangitis
- Cholecystectomy:
- Surgical removal of the gallbladder
- Performed after recovery from pancreatitis
- ERCP:
- Hypertriglyceridemia:
- Goal triglyceride level is < 500 mg/dL.
- Intravenous (IV) insulin:
- Requires close glucose monitoring
- May need a concurrent dextrose infusion to prevent hypoglycemia
- Apheresis:
- Should be considered in patients with SIRS, hypocalcemia, and multi-organ dysfunction
- May not be available at all hospitals
- Alcohol:
- Patient education
- Abstinence
Complications
Infected pancreatic necrosis or abscess
- Consider if patients continue to have a fever or increasing leukocytosis
- ⅓ of patients with pancreatic necrosis will develop infection.
- Causative organisms:
- E. coli
- Pseudomonas
- Klebsiella
- Enterococcus
- Treatment:
- Antibiotics:
- Carbapenems
- Fluoroquinolones with metronidazole
- Cefepime or ceftazidime with metronidazole
- Image-guided aspiration and drainage
- Surgical necrosectomy (debridement of pancreatic necrosis) if less-invasive measures are not successful
- Antibiotics:
Abdominal CT scan showing the initial area of patchy necrosis around the head of the pancreas
Image: “Abdominal CT scan” by Francesco Fontana. License: CC BY 4.0.
CT scans in a patient who developed infected pancreatic necrosis.
Image: “CT scan” by Roberto Rasslan et al. License: CC BY 4.0.
A: Extensive pancreatic necrosis with a large amount of gas is seen in the body and tail of the pancreas.
B: After 60 days of follow-up, a small decrease in the collection of gas is noted.
C: Four months after hospital discharge: atrophy of pancreatic parenchyma.
Pseudocyst
- An encapsulated collection of fluid with a well-defined inflammatory wall
- Occurs several weeks after the onset of pancreatitis
- Most are asymptomatic, but some may have abdominal pain, early satiety, or jaundice.
- Diagnosis is made with US, CT, or magnetic resonance imaging (MRI)
- Treatment:
- Observation:
- For those with minimal or no symptoms
- Most will reduce in size or resolve
- Drainage:
- For those who are symptomatic or develop infection
- Requires the wall of the pseudocyst to mature, which may take weeks
- Observation:
Acute pancreatitis repeatedly occurred 1 month after the 1st operation, and a pancreatic pseudocyst developed at the same site. Enhanced CT showed a cyst with a diameter of 29 mm in the body of the pancreas.
Image: “Pancreatic pseudocyst” by the Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556 Japan. License: CC BY 4.0.
Abdominal compartment syndrome
- Sustained intra-abdominal pressure with organ failure
- Due to significant tissue edema and fluid resuscitation
- Presentation:
- Tense, distended, painful abdomen
- Progressive oliguria
- Hemodynamic instability
- Pulmonary decompensation
- Diagnosis is made by measuring the intra-abdominal pressure.
- Treatment:
- Hemodynamic support
- Pain control
- Surgical decompression
Pseudoaneurysm
- Results from the erosion of the gastroduodenal or splenic artery into a pseudocyst
- Rare, but life threatening
- Presents with unexplained gastrointestinal bleeding and anemia
- Angiography for diagnosis and embolization
CT scan of the abdomen with IV contrast showing a contrast-enhanced mass (solid arrow) at the splenic artery (branching from the superior mesenteric artery) compatible with a splenic artery pseudoaneurysm. Hemoretroperitoneum and hemoperitoneum were demonstrated (hollow arrows).
Image: “CT scan of the abdomen” by the Accident and Emergency Department, Ruttonjee Hospital, Wanchai, Hong Kong. License: CC BY 4.0.
Contrast-enhanced CT scan of the abdomen reveals a 5 × 6 × 7 cm complex cystic mass in the region of the uncinate process of the pancreatic head with an enhancing capsule and a small hyperdensity consistent with pseudoaneurysm of a peripancreatic vessel with active bleeding into the pancreatic pseudocyst.
Image: “Contrast-enhanced CT scan” by Rohan Mandaliya. License: CC BY 2.0.
Splanchnic venous thrombosis
- Thrombosis of the splenic, portal, or superior mesenteric veins
- Splanchnic venous thrombosis is, many times, found incidentally on imaging.
- Treatment:
- Treat the underlying pancreatitis.
- Anticoagulation if compromising hepatic function or bowel perfusion
Acute respiratory distress syndrome (ARDS)
- Respiratory failure with widespread alveolar damage and inflammation of the lungs:
- Mediated by cytokines and inflammatory cells
- Caused by systemic inflammation from acute pancreatitis
- Mortality rate of 30%–40%
- Chest radiograph will show diffuse, bilateral opacities.
- Treatment:
- Oxygen supplementation:
- High-flow nasal cannula
- Mechanical ventilation
- Conservative fluid management
- Oxygen supplementation:
Differential Diagnosis
- Acute cholecystitis: inflammation of the gallbladder resulting from sustained gallstone impaction of the cystic duct. Patients present with colicky, upper abdominal pain, nausea, and vomiting. Inflammation of the gallbladder and gallstones are seen on US or CT. Amylase and lipase are usually not elevated, which differentiates acute cholecystitis from acute pancreatitis. Treatment includes IVF, antibiotics, and cholecystectomy.
- Perforated peptic ulcer disease: complete erosion of an ulcer through the wall of the stomach or duodenum. Patients present with severe epigastric pain, tachycardia, and abdominal rigidity. Lipase and amylase may be elevated, but not to the degree seen in acute pancreatitis. Diagnosis relies on imaging, which will show extraluminal gas. Patients require antibiotics and emergency surgery for repair.
- Acute mesenteric ischemia: tissue injury caused when perfusion fails to meet the demands of the intestines, usually due to an embolism or thrombosis. Patients have periumbilical pain out of proportion to the exam. Computed tomography with angiography is used to detect vessel stenosis or occlusion. Lipase can be elevated, but not to the degree seen in acute pancreatitis. Acute ischemia requires revascularization and resection of the infarcted bowel.
- Pancreatic cancer: a neoplasm of the pancreas. Symptom onset is more insidious, and patients may have unrelenting epigastric pain, weight loss, and jaundice. The diagnosis is confirmed with imaging. The history, exam, and imaging will differentiate pancreatic cancer from acute pancreatitis. Treatment is usually aggressive because tumors are usually found late, and includes chemotherapy, radiation, and surgery. Prognosis for survival is generally poor.
References
- Tang, J.C.F., & Markus, J.T. (2019). Acute pancreatitis. In Anand, B.S. (Ed.), Medscape. Retrieved November 8, 2020, from https://emedicine.medscape.com/article/181364-overview
- Vege, S.S. (2019). Clinical manifestations and diagnosis of acute pancreatitis. In Grover, S. (Ed.), UpToDate. Retrieved November 8, 2020, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-acute-pancreatitis
- Vege, S.S. (2019). Etiology of acute pancreatitis. In Grover, S. (Ed.), Uptodate. Retrieved November 9, 2020, from https://www.uptodate.com/contents/etiology-of-acute-pancreatitis
- Vege, S.S. (2019). Management of acute pancreatitis. In Grover, S. (Ed.), Uptodate. Retrieved November 9, 2020, from https://www.uptodate.com/contents/management-of-acute-pancreatitis
- Vege, S.S. (2019). Pathogenesis of acute pancreatitis. In Grover, S. (Ed.), Uptodate. Retrieved November 9, 2020, from https://www.uptodate.com/contents/pathogenesis-of-acute-pancreatitis
- Bartel, M. (2020). Acute pancreatitis. [online] MD Professional Version. https://www.msdmanuals.com/professional/gastrointestinal-disorders/pancreatitis/acute-pancreatitis
