Acute pancreatitis

Summary

Acute pancreatitis is an inflammatory condition of the pancreas most commonly caused by biliary tract

disease or alcohol abuse. Damage to the pancreas causes local release of digestive proteolytic enzymes
that autodigest pancreatic tissue. Acute pancreatitisusually presents with epigastric pain radiating to the
back, nausea and vomiting, and epigastric tenderness on palpation. The diagnosis is made based on the
clinical presentation, elevated serum pancreatic enzymes, and findings on imaging (CT, MRI, ultrasound)
that suggest acute pancreatitis. Treatment is mostly supportive and includes bowel rest, fluid
resuscitation, and painmedication. Enteral feeding is usually quickly resumed once
the pain and inflammatory markers begin to subside. Interventional procedures may be indicated for the
treatment of underlying conditions, such as ERCP or cholecystectomy in gallstone pancreatitis. Localized
complications of pancreatitis include necrosis, pancreatic pseudocysts, and abscesses. Systemic
complications involve sepsis, ARDS, organ failure, and shock and are associated with a considerable rise
in mortality.

Etiology

 Most common causes

1. Biliary pancreatitis (e.g., gallstones, constriction of the ampulla of Vater) ∼ 40% of

cases 

1. Alcohol-induced (∼ 30% of cases)

1. Idiopathic (∼ 15%–25% of cases)

 Other causes

 Hypertriglyceridemia, hypercalcemia

 Post-ERCP 

 Toxic drugs (e.g., steroids, azathioprine, sulfonamides, furosemide, estrogen, protease

inhibitors, NRTIs)

 Scorpion stings

 Viral infections (e.g., coxsackievirus B, mumps)

 Trauma 

 Autoimmune and rheumatological disorders (e.g., Sjögren's syndrome)

 Pancreas divisum 

 Hereditary (e.g., mutation of the trypsinogen gene, cystic fibrosis)

"I GET SMASHED": I = Idiopathic, G = Gall stones, E = Ethanol, T = Trauma, S = Steroids, M = Mumps, A =

Autoimmune, S = Scorpion poison, H = Hypercalcemia, Hypertriglyceridemia, E = ERCP, D = Drugs.
Pathophysiology

Sequence of events leading to pancreatitis:

1. Intrapancreatic activation of pancreatic enzymes: secondary to pancreatic ductal outflow

obstruction (e.g., gallstones, cystic fibrosis) or direct injury to pancreatic acinar cells (e.g.,
alcohol, drugs)

2. Enzymatic autodigestion of pancreatic parenchyma

3. Attraction of inflammatory cells (neutrophils, macrophages) → release of

inflammatory cytokines → pancreatic inflammation(pancreatitis)

Sequelae of pancreatitis (depending on the severity of pancreatitis)

1. Capillary leakage: Release of inflammatory cytokines and vascular injury by pancreatic

enzymes → vasodilation and increased vascular permeability → shift of fluid from
the intravascular space into the interstitial space (third space loss)
→ hypotension, tachycardia → distributive shock

2. Pancreatic necrosis: Uncorrected hypotension and third space loss → decreased organ

perfusion → multiorgan dysfunction(mainly renal) and pancreatic necrosis 

3. Hypocalcemia: Lipase breaks down peripancreatic and mesenteric fat → release of free fatty

acids that bind calcium → hypocalcemia

Disease progression

 Mild acute pancreatitis: interstitial edema, no necrosis; no local and systemic complications, no

organ failure 

 Moderate acute pancreatitis: associated with local (e.g., necrosis, abscesses, pseudocysts) or

systemic complications, such as temporary organ failure (e.g., kidney failure), which improves
within 48 hours

 Severe pancreatitis: associated with persistent pancreatic failure (> 48 hours), as well as single

or multiple organ failure

Clinical features

 Constant, severe epigastric pain

 Classically radiating towards the back

 Worse after meals and when supine

 Improves on leaning forwards

 Nausea, vomiting

 General physical examination

  Signs of shock: tachycardia, hypotension, oliguria/anuria 

 Possibly jaundice in patients with biliary pancreatitis

 Abdominal examination

 Abdominal tenderness, distention, guarding 

 Ileus  with reduced bowel sounds and tympany on percussion

 Ascites

 Skin changes (rare) 

 Cullen's sign: periumbilical ecchymosis and discoloration (bluish-red) 

 Grey Turner's sign: flank ecchymosis with discoloration 

 Fox's sign: ecchymosis over the inguinal ligament

Diagnostics

Acute pancreatitis is diagnosed based on a typical clinical presentation, with abdominal pain radiating to

the back, and either detection of highly elevated pancreatic enzymes or characteristic findings on
imaging. Serum hematocrit is an easy test that should be conducted to help quickly predict disease
severity.

Laboratory tests

 Tests to confirm clinical diagnosis

 ↑ Serum pancreatic enzymes 

 Lipase: if ≥ 3 x the upper reference range → highly indicative of

acute pancreatitis

 Amylase (nonspecific) 

 The enzyme levels are not directly proportional to severity or prognosis! 

 Tests to assess severity

 Hematocrit (Hct)

 Should be conducted at presentation as well as 12 and 24 hours after

admissions

 ↑ Hct (due to hemoconcentration) indicates third space fluid loss and

inadequate fluid resuscitation

 ↓ Hct indicates the rarer acute hemorrhagic pancreatitis

 WBC count 

 Blood urea nitrogen 

  ↑ CRP  and procalcitonin levels 

 ↑ ALT 

 Tests to determine etiology

 Alkaline phosphatase, bilirubin levels (evidence of gallstone pancreatitis)

 Serum calcium levels

 Serum triglyceride levels (fasting)

Determining calcium values is very important: Hypercalcemia may cause pancreatitis, which may then,

in turn, cause hypocalcemia!

Imaging

 Ultrasound (most useful initial test): indicated in all patients with acute pancreatitis 

 Main purpose: detection of gallstones and/or dilatation of the biliary tract (indicating
biliary origin)

 Signs of pancreatitis

 Indistinct pancreatic margins (edematous swelling)

 Peripancreatic build-up of fluid ; evidence of ascites in some cases

 Evidence of necrosis, abscesses, pancreatic pseudocysts

 CT scan: not routinely indicated 

 Indications

 At admission: only when the diagnosis is in doubt (e.g., not very highly
elevated pancreatic enzymes, non-specific symptoms)

 > 72 hours of symptom onset: if complications such as

necrotizing pancreatitis or pancreatic abscess (e.g.,
persistent feverand leukocytosis, no clinical improvement or evidence of organ
failure > 72 hours of therapy) are suspected 

 Findings

 Enlargement of
the pancreatic parenchyma with edema; indistinct pancreatic margins with
surrounding fat stranding 

 Necrotizing pancreatitis: lack of parenchymal enhancement or presence of air in

the pancreatic tissue

 Pancreatic abscess: circumscribed fluid collection

 MRCP and ERCP
  Indications: suspected biliary or pancreatic duct obstructions

 MRCP is noninvasive but less sensitive than ERCP 

 ERCP can be combined with sphincterotomy and stone extraction; but may

worsen pancreatitis. 

 Conventional x-ray

 Sentinel loop sign: dilatation of a loop of small intestine in the upper abdomen
(duodenum/jejunum) 

 Colon cut off sign: gaseous distention of the ascending and transverse colon that
abruptly terminates at the splenic flexure 

 Evidence of possible complications: pleural effusions, pancreatic calcium stones; helps

rule out intestinal perforation with free air

Treatment

General measures

 Admission to hospital and assessment of disease severity (consider ICU admission)

 Fluid resuscitation: aggressive hydration with crystalloids (e.g., lactated Ringer's

solution , normal saline) 

 Analgesia: IV opioids (e.g., fentanyl)

 Bowel rest (NPO)and IV fluids are recommended until the pain subsides 

 Nasogastric tube insertion: not routinely recommended; indicated in patients with vomiting

and/or significant abdominal distention

 Nutrition 

 Begin enteral feeding (oral/nasogastric/nasojejunal) as soon as the pain subsides 

 Total parenteral nutrition: only in patients who cannot tolerate enteral feeds (e.g., those

with persistent ileus and abdominal pain) 

Drug therapy

 Analgesics: fentanyl or hydromorphone; consider pump administration (patient controlled

analgesia = PCA)

 Antibiotics

 Prophylactic antibiotic therapy is not recommended.

 Antibiotics should only be used in patients with evidence of infected necrosis. 

 Fenofibrates: in hyperlipidemia-induced acute pancreatitis

Procedures/surgery
  Biliary pancreatitis

 Urgent ERCP and sphincterotomy (within 24 hours): in patients with evidence

of choledocholithiasis and/or cholangitis; followed by cholecystectomy

 Cholecystectomy (preferably during same admission once the patient is stabilized; or

within 6 weeks): in all patients with biliary pancreatitis 

The most important therapeutic measure is adequate fluid replacement (minimum of 3–4

liters of crystalloids per day)!

"PANCREAS" - Perfusion (fluid replacement), Analgesia, Nutrition, Clinical (observation), Radiology

(imaging), ERC (endoscopic stone extraction), Antibiotics, Surgery (surgical intervention, if necessary).

Complications

Localized

 Bacterial superinfection of necrotic tissue → fever

 Diagnosis: CT-guided percutaneous drainage + culture of the aspirate

 Treatment: surgical debridement, antibiotics

 High mortality rate; multiple organ failure in ∼ 50% of cases

 Pancreatic pseudocysts

 Pancreatic abscess

 Walled-off infected necrotic tissue or pancreatic pseudocyst; typically develops > 4

weeks after an attack of acute pancreatitis

 Abdominal CT: visible contrast-enhanced abscess capsule with evidence of fluid (pus)

 Ultrasound: complex cystic, fluid collection with irregular walls and septations

 Treatment: cannulation and drainage; necrosectomy if other measures are not effective

 Pleural effusion 

 Abdominal compartment syndrome

 Blood vessel erosion with bleeding 

Systemic

 SIRS, sepsis, DIC

 Pneumonia, respiratory failure, ARDS

 Shock

 Prerenal failure due to volume depletion

  Hypocalcemia

 Pleural effusion, pancreatic ascites

 Paralytic ileus

Prognosis

 Mortality

 In patients without organ failure: < 1%

 In patients with organ failure: ∼ 30% 

 Higher mortality in patients with biliary pancreatitis than in patients with

alcoholic pancreatitis

 Important predictors of severity

 Age > 55

 Gastrointestinal bleeding

 Abnormal hematocrit within 48 hours

 Acute hemorrhagic pancreatitis: ↓ Hct

 Third space fluid loss: ↑ Hct

 Hypocalcemia and/or hyperglycemia

 Inflammatory markers: ↑↑ CRP, ↑ IL-6, ↑ IL-8

 Evidence of shock and/or organ failure

 ↑ AST, ↑ ALT

 ↑ BUN, creatinine

 ↑ LDH

 ABG: pO2 < 60 mmHg, metabolic acidosis with a base deficit > 4 mmol/L

 CT findings: pancreatic edema, peripancreatic fluid collection, and/or necrosis of >

33% of the pancreas

Amylase and lipase, which are used for the diagnosis of pancreatitis, cannot be used to predict the
prognosis!

 Numerous scoring systems exist (e.g, Ranson criteria) for assessing the severity and predicting
the prognosis of acute pancreatitis