Pancreatitis

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

Causes

• gallstones and alcohol abuse (the most common causes collectively accounting for 70% of all cases)

• hypertriglyceridemia (fasting triglycerides >1000 mg/dL)

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

• 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)

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

• smoking, obesity, and diabetes are associated with acute pancreatitis

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.

(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:

  • characteristic upper abdominal pain

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

  • characteristic findings on abdominal imaging (by CT, MRI or ultrasound)

• A history to establish the cause of pancreatitis should include:

  • review of medications

  • detailed history of alcohol use

  • prior history of gallstone disease, abdominal surgeries, hypertriglyceridemia and hypercalcemia

  • family history of pancreatitis

• Laboratory evaluation should include complete blood count, serum liver tests, serum calcium and triglyceride levels.

• Imaging: Abdominal ultrasound should be performed to evaluate for gallstones. When a clear etiology is not apparent, endoscopic ultrasound and magnetic resonance cholangiopancreatography should be considered for evaluation of pancreatic ducts, smaller gallstones (that could be missed on ultrasound), and tumors.

• Acute pancreatitis is generally classified into two types based on imaging findings (Atlanta classification):

  • Interstitial edematous pancreatitis: acute inflammation of pancreatic parenchyma and peripancreatic tissues, without findings of peripancreatic necrosis.

  • Necrotizing pancreatitis: acute inflammation associated with pancreatic parenchymal or peripancreatic necrosis

• 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

Management

General:

• Start early with small fluid boluses (e.g., 10 mL/kg) in hypovolemic patients or no bolus if euvolemic. All patients should receive maintenance fluids at 1.5 mL/kg/hr, in addition to electrolyte replacement. Fluid resuscitation should then be modified as needed based on patient’s volume status.

• Provide analgesia and antiemetics if required.

• Patients should be monitored for the first 24-72 hours for development of moderate-to-severe pancreatitis (O2 saturation, serum glucose and electrolytes, urine output).

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 (choledocholithiasis) 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. ERCP is also indicated in the absence of cholangitis if choledocholithiasis is present.

Prevention of recurrence:

• Laparoscopic cholecystectomy of acute pancreatitis is necessary within 4 weeks when the etiology for pancreatitis is thought to be secondary to gallstones. 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, including end-organ failure (e.g., acute kidney or lung injury), that may be associated with SIRS response. Important local complications include

Pancreatic fluid collections (PFCs) are important local complications:

• PFCs can be divided into 4 sub-types based on the revised Atlanta classification:

  • Acute Peripancreatic Fluid Collection (APFC)

  • Pancreatic Pseudocyst

  • Acute Necrotic Collection (ANC)

  • Walled Off Necrosis (WON)

• PFCs can cause persistent pain, become infected, and cause other complications including obstruction of GI tract or biliary tree. If infection is suspected (e.g., rising white count, fever, gas within collection), empiric antibiotics should be initiated without aspiration and culture.

• Most PFCs spontaneously resolve, but in some instances, drainage may be indicated (rapidly enlarging pseudocysts, sepsis/SIRS refractory to conservative management, gastric/duodenal outlet obstruction, biliary tract obstruction, ongoing systemic illness, refractory pain, and anorexia/weight loss lasting >8 weeks after initial onset). Drainage can be performed endoscopically or percutaneously, both of which are preferred to surgical management when possible.

• Endoscopic drainage generally occurs transmurally, and thus can be limited based on location of the collections in relation to the stomach wall. Waiting for maturation of the collection wall prior to endoscopic drainage is recommended to reduce risk of adverse events (peritonitis).

Other complications of acute pancreatitis include splanchnic vein thrombosis, pseudoaneurysm, and abdominal compartment syndrome.

Chronic Pancreatitis

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

Causes

Common causes include:

• chronic or prolonged alcohol consumption (> 80 g/day for 6-12 years)

• smoking

• autoimmune pancreatitis

• genetic factors (cystic fibrosis transmembrane conductance regulator [CFTR], serine protease inhibitor Kazal type1 [SPINK1], or chymotrypsin C [CTRC], cationic trypsinogen [PRSS1] mutations)

• 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 pancreatitis with epigastric pain, but it tends to be chronic, relapsing, or remitting.

• However, some patients do not have a previous diagnosis of acute pancreatitis (50%) or pain (30%).

• Other common features of chronic pancreatitis include symptoms of exocrine insufficiency (steatorrhea, sarcopenia, weight loss and deficiencies in fat soluble vitamins and nutrients) and endocrine insufficiency (diabetes secondary to islet cell depletion and hypoinsulinemia).

Diagnosis

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

(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.

• Medical pain management consists of acetaminophen, nonsteroidal anti-inflammatory drugs, low-potency opioids as needed (limit use as able), and neuromodulators (e.g., gabapentoids) if required.

• An integrated approach addressing biophysical and psychosocial determinants of pain is recommended.

  

  (Source: Chronic Pancreatitis. N Engl J Med 2022.)

• 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 often require insulin.

• Patients with pancreatic duct stones or strictures may benefit from endoscopic procedures (e.g., lithotripsy, stone removal, stenting). Endoscopic intervention may also be required for complications like pseudocysts and pancreatic ascites.

• Surgical interventions for chronic pancreatitis include pancreatic resection (standard pancreaticoduodenectomy and its variants or distal pancreatectomy), drainage of an obstructed duct (longitudinal pancreaticojejunostomy and its variants), or a combination of both (Frey procedure) and total pancreatectomy with or without autologous islet-cell transplantation. These should be considered if medical and endoscopic strategies fail.

• Pancreatic cancer is a complication of chronic pancreatitis, but there is currently no effective early detection strategy.

Complications

Complications include pseudocysts, bile-duct stricture, duodenal stricture, splanchnic venous thromboses, pancreatic cancer, weight loss, osteoporosis, and diabetes mellitus.