Pancreatitis

Article Author:
Nabeeha Mohy-ud-din
Article Editor:
Suzanne Morrissey
Updated:
2/19/2019 4:14:57 PM
PubMed Link:
Pancreatitis

Introduction

Acute pancreatitis is an acute response to injury of the pancreas. Chronic pancreatitis can result in permanent damage to the structure and endocrine and exocrine functions of the pancreas. In the United States, about 200,000 hospital admissions annually are due to acute pancreatitis, and this number has been increasing.[1]

Etiology

The two most common causes of acute pancreatitis in the United States are gallstones (35% to 40% of cases) and alcohol use (30% of cases).[2] However, the causes are extensive and include, but are not limited to, the following: autoimmune pancreatitis, hypertriglyceridemia, post-endoscopic retrograde cholangiopancreatography (ERCP), genetic risk (gain of function mutations in PRSS1, mutations in CFTR and SPINK1 genes), pancreatic duct injury and medications. The drugs most strongly associated with acute pancreatitis are azathioprine, 6-mercaptopurine, didanosine, valproic acid, angiotensin-converting–enzyme inhibitors, and mesalamine. Other rare causes include biliary sludge and microlithiasis, biliary obstruction, hypercalcemia, infections (mumps, coxsackievirus, hepatitis B, cytomegalovirus amongst others), toxins, vascular disease-causing pancreatic ischemia, anatomic abnormalities such as choledochal cysts, and idiopathic causes.

The most recent American College of Gastroenterology guidelines recommend checking the triglyceride level in a patient who has no evidence of gallstones and no history of significant alcohol use.[3]  They recommend that this should be considered the cause if it is greater than 1000 mg/dl. The guidelines also state that for patients older than 40 years of age, consideration of a pancreatic tumor as the cause of pancreatitis should be made. Furthermore, genetic testing can be considered for those younger than 30 years of age if they have a family history of pancreatic disorders and no other cause of pancreatitis is identified.

The most common cause of chronic pancreatitis is ethanol abuse. Smoking is also an important risk factor. There are several other causes which include tropical pancreatitis, idiopathic pancreatitis, ductal obstruction (pancreas divisum, pseudocysts, stones, tumors, and trauma), mutations in cystic fibrosis genes, hereditary pancreatitis and systemic diseases such as systemic lupus erythematosus.

Epidemiology

Acute pancreatitis accounts for about 275 000 hospital admissions annually.[2] Eighty percent of patients admitted with pancreatitis usually have mild disease and can be discharged within a few days. Overall mortality of acute pancreatitis is approximately 2%.[2]  The relapse rate of acute pancreatitis is between 0.6% to 5.6%, and this depends on the etiology of pancreatitis. The relapse rate is highest when pancreatitis is due to alcohol use.[4]

Chronic pancreatitis has an annual incidence rate of 5 to 12 per 100,000 people. The prevalence of chronic pancreatitis is 50 per 100,000 people. The most common age group is 30 to 40 years, and it occurs more in men than women.[5]

Pathophysiology

The pathogenesis of acute pancreatitis can occur by the following mechanisms: pancreatic duct and acinar injury. In acute pancreatitis, digestive enzymes within the pancreas are not secreted properly, and this leads to auto-digestion and inflammation of the pancreas.

Alcohol can cause acute pancreatitis through direct toxicity and immunologic processes.[6] Gallstones can lead to temporary obstruction of the pancreatic duct, and this is also believed to be the mechanism of ERCP-induced pancreatitis.

Chronic pancreatitis can occur by repeated acute attacks which leads to inflammatory infiltrates and fibrosis within the pancreas. Over time, this leads to pancreatic insufficiency.

Histopathology

Histopathological characterization of acute pancreatitis depends on the severity of the disease, specifically the absence or presence of necrosis. The disease can be classified as:

  • Interstitial (or edematous) pancreatitis
  • Hemorrhagic-necrotizing pancreatitis

In acute pancreatitis, the pancreas can be edematous, necrotic and surrounded by fat stranding. In mild pancreatitis, fat necrosis is minimal; whereas, with severe pancreatitis, there are large foci of fat necrosis that have merged. This is associated with parenchymal destruction and focal hemorrhages.

Chronic pancreatitis is characterized by mononuclear infiltrates and fibrosis. There can be calcifications present within the pancreas as well.

History and Physical

Acute pancreatitis most commonly presents with abdominal pain, which usually occurs in the upper abdomen and radiates to the back. It is described as severe and is frequently associated with nausea and vomiting.

In regards to medical history, healthcare providers should ask the patient specifically about the previous history of gallbladder disease, history of hyperlipidemia, and previous episodes of pancreatitis. A detailed social history should be obtained including a history of alcohol use. Clinicians should ask patients about previous procedures such as ERCP, and they should obtain a list of medications that the patient is currently taking. Patients should also be asked about a family history of pancreatic disorders.

The physical examination should begin with the vital signs: pulse, blood pressure, respiratory rate, and temperature. The vital signs can also assess the patient’s hydration status. The presence of jaundice indicates biliary tree obstruction. An abdominal exam should be performed, and this may reveal abdominal tenderness/guarding and decreased bowel sounds if an ileus is present. Grey-Turner sign is present where there is ecchymosis in the flanks. Cullen's sign is present when there is ecchymosis around the umbilicus. These signs can signify pancreatic necrosis leading to blood in the abdomen.[7] A patient with severe pancreatitis may also present with mental status changes.

Chronic pancreatitis can present with abdominal pain, nausea, and vomiting. However, it can also be painless, and patients can present with steatorrhea and weight loss.

Evaluation

Current ACG guidelines recommend that a diagnosis of acute pancreatitis should include at least two of the following: abdominal pain consistent with acute pancreatitis, a serum lipase level at least three times the upper limit of the normal range, and findings of acute pancreatitis on abdominal imaging. These guidelines also state that imaging (including computed tomography scans and/or magnetic resonance imaging (MRI) need not be performed in every patient at the time of diagnosis, but in those whose symptoms fail to resolve or in whom the diagnosis remains in question 2 to 3 days after admission to hospital.[3]

Whenever a patient with acute pancreatitis is admitted to the hospital, an assessment of the initial severity of pancreatitis, including evidence of organ failure (particularly respiratory, cardiovascular or renal compromise) should be made. The recently revised Atlanta classification can be used to classify these patients as mild, moderately severe or severe cases of acute pancreatitis.[8]

Laboratory work ordered on admission should include a complete metabolic panel, complete blood count, serum lipase, lactate, serum triglycerides, and C-reactive protein (CRP) levels. The best assessment of evolvement of acute pancreatitis can be made using a rising blood urea nitrogen (BUN) level or a rising hematocrit level. [9]Systemic inflammatory response syndrome (SIRS) criteria can also be used to assess the clinical status of the patient.[9]

In patients with chronic pancreatitis, amylase/lipase levels can be elevated or normal. Fecal fat, stool elastase, and alpha-1-antitrypsin level can also be checked for these patients. An HbA1c level can provide an estimate of the possible endocrine dysfunction caused by chronic pancreatitis. Other tests including IgG4/ANA levels, genetic testing (CFTR, SPINK1, PRSS1) can be ordered if the patient is young or has a positive family history. Imaging studies including Magnetic resonance cholangiopancreatography (MRCP) or CT scans can be ordered. These imaging studies may reveal pancreatic calcifications, pancreatic ductal obstructions or dilations.

Treatment / Management

The most important step in the management of acute pancreatitis is aggressive fluid resuscitation. Current guidelines define this as 250 to 500ml per hour of isotonic crystalline fluids.[3] However, adjustments can be made if there is a concern for cardiovascular or renal comorbidities. One trial suggested the superiority of Ringer’s lactate as compared with normal saline in reducing inflammatory markers.[10] Fluid requirements should be frequently reassessed, and as stated above BUN and hematocrit levels can be used to assess the hydration status of the patient.

In regards to nutrition in acute pancreatitis, oral feedings can be started immediately if the patient can tolerate them. In severe pancreatitis, enteral feedings are preferred over parenteral feedings as there is decreased risk of infections, surgical interventions, and lower mortality. Analgesia is also an important aspect of management of pancreatitis and can include the use of intravenous (IV) opioids.

For patients with acute pancreatitis and acute cholangitis, a gastroenterology consult should be placed, and an urgent ERCP (within 24 hours) is recommended. For patients who have gallstones within the gallbladder, a cholecystectomy can be performed within the same admission. However, if there is a concern of necrotizing AP, surgery can be delayed until the surrounding inflammation has decreased.

For patients with acute pancreatitis caused by hypertriglyceridemia, current standard therapy involves placing the patient on an insulin drip (this activates lipoprotein lipase). Fibrates can also be prescribed for the patient and consideration for apheresis can be made. It is important to state, that there is no role for antibiotics in acute pancreatitis in the absence of infectious complications.

The treatment for chronic pancreatitis involves pain control, counseling regarding smoking and alcohol cessation and pancreatic enzyme replacement. Most importantly, patients should be encouraged to eat a low-fat diet in small meals. If patients fail medical therapy, surgery and extracorporeal shock wave lithotripsy (ESWL) for duct stones can be recommended.

Differential Diagnosis

The differential diagnosis of acute pancreatitis includes other causes of epigastric abdominal pain such as peptic ulcer disease, choledocholithiasis or cholangitis, cholecystitis, perforated viscus, mesenteric ischemia and intestinal obstruction amongst others. The diagnosis of AP can be differentiated from these conditions based on clinical features and laboratory values. However, when significant doubt exists, a contrast-enhanced abdominal computed tomography (CT) scan can be performed for further evaluation.

Differentials of chronic pancreatitis include acute pancreatitis, pancreatic malignancy, and chronic mesenteric ischemia among others.

Prognosis

Mortality from acute pancreatitis is about 2%.[2] After an episode of acute pancreatitis, endocrine and exocrine insufficiency can develop in about 20% to 30% of patients.[5][10][11] Risk factors for recurrent attacks include the etiology of the first attack, the severity of the initial attack, and the degree of pancreatic structural damage. There are several scoring systems that can stratify the severity of acute pancreatitis: Acute Physiology and Chronic Health Evaluation II (APACHE II), APACHE combined with scoring for obesity (APACHE-O), the Glasgow scoring system, the Harmless Acute Pancreatitis Score (HAPS), PANC 3, the Japanese Severity Score (JSS), Pancreatitis Outcome Prediction (POP), and the Bedside Index for Severity in Acute Pancreatitis (BISAP).[11] These scoring systems are not superior to frequent reassessment by clinicians and have been shown to have a high false-positive rate.

Complications

Complications of acute pancreatitis can be divided into local and systemic. Local complications include the following:

  • Pancreatic pseudocyst
  • Walled-off necrosis
  • Peri-pancreatic fluid collection
  • Acute necrotic collection

Peripancreatic fluid collections usually develop in less than 4 weeks after the initial presentation of pancreatitis whereas a pseudocyst and walled off necrosis more than 4 weeks after the onset of acute pancreatitis.

Systemic complications include the following:

  • Acute respiratory distress syndrome (ARDS)
  • Compartment syndrome
  • Acute kidney injury (AKI)
  • Disseminated intravascular coagulation(DIC)

Chronic pancreatitis has several complications including:

  • Formation of pseudocysts
  • Diabetes
  • Pseudoaneurysms
  • Splenic vein thrombosis
  • Recurrent acute pancreatitis
  • Risk of progression to pancreatic cancer

Deterrence and Patient Education

Patients admitted to hospital with pancreatitis should undergo aggressive counseling regarding the risks of readmission. This should include counseling regarding alcohol and smoking cessation. Dietary and lifestyle modifications including weight reduction, low-fat diet, and regular exercise should also be emphasized.

Pearls and Other Issues

  • Acute pancreatitis is a response to injury to the pancreas and results in inflammation of the pancreas. Chronic pancreatitis results in chronic changes within the pancreas including a mononuclear infiltrate and fibrosis of the pancreas.
  • Abdominal pain is the most common presenting complaint of AP and can occur with nausea and vomiting. Chronic pancreatitis can present with or without abdominal pain, nausea or vomiting. Patients with chronic pancreatitis can present with steatorrhea and weight loss.
  • The diagnosis of AP involves two of the following three: abdominal pain characteristic of pancreatitis, lipase greater than two-thirds of the upper limit of normal and imaging findings of acute pancreatitis. In chronic pancreatitis, patients can have a normal lipase and amylase level. Calcifications within the pancreas can point towards chronic pancreatitis.
  • Early aggressive intravenous hydration is the cornerstone of therapy for acute pancreatitis. Early enteral feeding can also be encouraged, and antibiotics in the absence of infectious complications should be avoided.
  • Complications of AP may be local such as peripancreatic fluid collection, pseudocyst or necrosis. Systemic complications may also occur such as ARDS, AKI, and DIC. Complications of chronic pancreatitis involve pseudocyst formation, diabetes, pseudoaneurysms, splenic vein thrombosis, and recurrent attacks.

Enhancing Healthcare Team Outcomes

The management of acute pancreatitis involves multi-disciplinary teams including hospitalists, gastroenterologists, surgeons, nurses, pharmacists, addiction specialists, and dietitians. The management of acute pancreatitis should involve specific counseling geared toward the etiology of pancreatitis. If a patient is noted to have several readmissions with pancreatitis, and the cause is known to be alcohol abuse, for instance, this should be specifically targeted via intensive counseling by the healthcare team. Before the patient is discharged from the hospital, it may be beneficial for a dietitian to meet with them and recommend dietary changes (such as low-fat diet) to patients with chronic pancreatitis. Medication reconciliation on admission and discharge should be emphasized so any medications that may be the cause of pancreatitis can be changed.


References

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