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Gastroenterology - Pancreatitis - Fast Facts | NEJM Resident 360

The pancreas has both endocrine (secretion of hormones such as insulin and glucagon) and exocrine (secretion of digestive enzymes such as lipase) functions. In this section, we focus on the exocrine function of the pancreas. Acute or chronic pancreatitis is characterized by inflammation of the pancreas with necrosis caused by release of activated pancreatic enzymes. Acute pancreatitis is one of the most common gastrointestinal conditions that require hospitalization; milder cases are often treated in the outpatient setting.

The pathophysiology of pancreatitis is thought to involve activation of pancreatic acinar digestive enzymes in the pancreas itself rather than in the duodenum. Trypsinogen is a proenzyme that is activated to trypsin in the duodenum by the action of enterokinase. Trypsin subsequently activates the other pancreatic proenzymes. Pancreatitis develops when early trypsinogen activation occurs within the pancreas itself and leads to acute inflammation and acinar cell injury.

Acute Pancreatitis

The most common causes of acute pancreatitis are gallstones and alcohol abuse. Collectively, they account for 70% of all cases. Additional causes of acute pancreatitis include:

• hypertriglyceridemia (fasting triglycerides >1000 mg/dL)

• drugs (including azathioprine, 6-mercaptopurine, sodium valproate, and angiotensin-converting–enzyme inhibitor)

• autoimmune pancreatitis (e.g., IgG4-related disease)

• blunt abdominal trauma with injury to the pancreatic duct

• bile and pancreatic duct obstruction from tumors

• idiopathic pancreatitis (no underlying cause is identified in a large proportion of cases not attributable to alcohol or gallstone disease)

• obesity and type 2 diabetes are recognized risk factors

• post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis occurs in 1 to 3% of patients undergoing this procedure

Clinical Features

Patients typically present with epigastric pain of gradual onset that radiates to the back and can be associated with nausea, vomiting, and fever. In the most severe cases, a patient with acute pancreatitis can also present with acute respiratory distress. Classic signs of acute pancreatitis include the Cullen sign of abdominal distention with periumbilical ecchymosis and Grey Turner sign with flank ecchymosis. These discolorations are a result of liberated pancreatic enzymes causing fat necrosis, inflammation, and bleeding. At its most extreme, acute pancreatitis may be associated with systemic inflammatory response syndrome (SIRS), a serious generalized inflammatory response that is frequently complicated by shock, acute kidney and lung injury, and multiple organ system dysfunction.

Cullen sign (panel A) and Grey Turner sign (panel B)
(Source: Cullen’s and Grey Turner’s Signs in Acute Pancreatitis. N Engl J Med 2015.)

Diagnosis

A diagnosis of acute pancreatitis requires two of the following three criteria:

1. upper abdominal pain

2. serum amylase and/or lipase levels >3 times the upper limit of normal

3. characteristic findings on abdominal imaging (by CT, MRI, or ultrasound [US])

Episodes of acute pancreatitis can be further classified as mild, moderate, or severe.

• mild acute pancreatitis: no organ failure or local or systemic complications; usually self-limiting (<7 days)

• moderate acute pancreatitis: associated with transient organ failure or local complications lasting <48 hours

• severe acute pancreatitis: persistent organ failure for >48 hours; associated with high morbidity and mortality

The following table describes three scoring systems used to assess severity of acute pancreatitis and predict mortality:

Management

General:

• Start early aggressive intravenous (IV) hydration in first 12–24 hours at a rate of at least 250–500 mL/hr in addition to electrolyte replacement.

• Provide analgesia and antiemetics if required.

Mild pancreatitis:

• Commence oral intake after nausea and vomiting have resolved and if patient does not have ileus. Low-fat solid diet has been shown to be as safe as clear fluids.

Severe acute pancreatitis:

• Consider early intensive care management.

• Commence enteral feeding within 48 hours if possible; may require nasogastric delivery.

Suspected cholangitis or infection:

• This is the only indication for antibiotics. Routine use of prophylactic antibiotics is not recommended.

Suspected acute cholangitis secondary to bile duct obstruction from a gallstone or tumor:

• Emergency endoscopic retrograde cholangiopancreatography (ERCP) is recommended within 24 hours with the goal of removing the obstruction, performing a sphincterotomy, and stenting the common bile duct.

Prevention of recurrence:

• Laparoscopic cholecystectomy of acute pancreatitis is necessary within 4 weeks. For severe pancreatitis, delay to >6 weeks to allow for resolution of inflammatory changes.

Complications:

Moderate and severe acute pancreatitis can be associated with many local and systemic complications. Some important local complications include:

• Pancreatic necrosis or phlegmon develops in 15%–20% of all cases and usually presents with persistent pain and lack of clinical improvement on days 3 to 5. Supportive care is usually adequate for sterile necrosis. However, if infection is suspected, empiric antibiotics may be initiated. CT-guided fine-needle aspiration can be used for gram stain, culture, or both. Surgical debridement may be required if refractory to antibiotics.

• Pancreatic abscess is a circumscribed intra-abdominal collection of pus. The treatment is surgical drainage and antibiotics.

• Pancreatic pseudocyst typically presents >4 weeks after acute pancreatitis. It is a collection of fluid, debris, and pancreatic enzymes enclosed by a wall of fibrous tissue or granulation tissue. The majority of pseudocysts spontaneously resolve, but larger or expanding cysts may require endoscopic or surgical drainage to prevent infection, enlargement, rupture, or hemorrhage.

• End-organ failure (such as acute kidney or lung injury) is associated with SIRS response.

Chronic Pancreatitis

Chronic pancreatitis is a slow, irreversible process with inflammation and fibrosis with eventual reduction of exocrine and endocrine pancreatic function. Common causes include:

• chronic or prolonged alcohol consumption (4–5 standard drinks per day for >5 years)

• autoimmune pancreatitis

• genetic factors

• long-term pancreatic duct obstruction

• idiopathic (no cause can be identified)

Clinical Features

Some features of chronic pancreatitis are similar to features of acute pancreatitis. Patients present with recurrent acute epigastric pain, but it tends to be chronic, relapsing, or remitting. Other common features of chronic pancreatitis include symptoms of exocrine insufficiency (steatorrhea and weight loss) and endocrine insufficiency (diabetes secondary to islet cell depletion and hypoinsulinemia).

Diagnosis

Diagnosis of chronic pancreatitis is based on CT or MRI demonstrating signs of calcifications, dilated ducts, and pancreatic atrophy.

Extensive pancreatic calcifications on computer tomography scan

(Source: Calcified Pancreatitis Associated with Alcohol Use. N Engl J Med 2017.)

Functional studies to document exocrine insufficiency include:

• secretin testing: used to stimulate pancreatic exocrine secretion; pancreatic juices are collected via a duodenal tube placed endoscopically; bicarbonate concentration and amylase concentration are analyzed

• fecal elastase concentration: <200 µg/g of stool suggests advanced chronic pancreatitis

• serum trypsin concentration: <20 mg/dL is associated with advanced chronic pancreatitis

Management

• Treatment of the underlying cause (alcohol cessation, cholecystectomy) is required. Smoking is a known risk factor, and cessation is advised.

• Pain management consists of acetaminophen, anti-inflammatories, low-potency opioids as needed, and adjuncts such as gabapentoids if required.

• For pancreatic enzyme insufficiency, fat-soluble vitamin supplementation, calcium supplementation, and pancreatic enzyme replacement therapy are required. Pancreatic enzyme replacement therapy (lipase/protease/amylase) at mealtimes should be titrated to response (steatorrhea improvement, weight gain, vitamin levels).

• Patients with pancreatogenic diabetes may often require insulin.

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