Pancreatitis is a potentially serious disorder characterized by inflammation of the pancreas that may cause autodigestion of the organ by its own enzymes. This disease has two manifestations: acute pancreatitis and chronic pancreatitis[1]

Acute Pancreatitis

Acute pancreatitis is the result of an inflammatory process involving the pancreas caused by the release of activated pancreatic enzymes. In addition to the pancreas, this disorder can also affect surrounding organs, as well as cause a systemic reaction. This form of pancreatitis is generally brief in duration, milder in symptom presentation, and reversible. However, while this form of the disease resolves both clinically and histologically, approximately 15% of patients with acute pancreatitis will develop chronic pancreatitis.[1][2] Acute pancreatitis may present as mild or severe. Milder forms of acute pancreatitis involve only the interstitium of the pancreas, which accounts for 80% of all cases, and has a temperate presentation with fewer complications. However, severe forms involve necrosis of the pancreatic tissue, which occurs in 20% of cases, and results in increased complications and mortality.[1][2]

Chronic Pancreatitis

Chronic pancreatitis develops from chronic inflammation of the pancreas that results in irreversible and progressive histologic changes. This includes fibrosis and ductal strictures, which destroy the pancreas directly, as well as decreased endocrine and exocrine functions, which can negatively affect other body systems. Unlike acute pancreatitis, this form of the disease is characterized by recurrent or persistent symptoms.[1][2]


Acute Pancreatitis

There are an estimated 50,000 to 80,000 cases in the United States each year, and 210,000 hospitalizations as a result. Of these, 80% are mild in nature, while 20% are necrotizing and severe, and approximately 2,000 patients die each year from associated complications. In addition, men are affected more frequently than women.[3][4][5]

Chronic Pancreatitis

Worldwide, there are approximately 1.6 to 23 cases per 100,000 each year. In the United States alone chronic pancreatitis results in over 122,000 outpatient visits and 56,000 hospitalizations each year. Chronic pancreatitis also has a higher prevalence in men than women, and often develops between the ages of 30 and 40. This disease is rare in children.[5][4]

Characteristics/Clinical Presentation

Acute Pancreatitis

Mild Pancreatitis

The primary symptom of acute pancreatitis is abrupt abdominal pain in the mediepigatsrium, often involving the entire upper abdomen that increases in intensity for several hours and can last from days to more than a week. In addition, approximately 50% of patients with acute pancreatitis experience radiating pain in the back and, though rare, some patients may first experience pain in the lower abdomen. While characteristically continuous and boring in nature overall, pain may initially present as mild, dull, and nonspecific, but may increase to profound, sharp, and severe pain in conjunction with systemic symptoms, and result in shock, coma, or death. In addition, onset of pain is typically sudden when secondary to gallstones, but progresses over several days when derived from alcohol consumption. Specific movements can also affect pain; sitting upright and leaning forward may reduce pain, while coughing, vigorous activity, walking, lying supine, and deep breathing may intensify it. Furthermore, pain may be triggered or exacerbated by eating fatty foods or consuming alcohol. Along with pain, the disease also tends to cause nausea, anorexia, and vomiting in 90% of people with pancreatitis.[1][6] Patients also display marked changes in appearance resulting from changes in bodily functions. Generally patients appear acutely ill and sweaty and report feelings of malaise, while about 20% experience upper abdominal distention attributable to gastric distention or displacement of the stomach by a pancreatic inflammatory mass. Grey Turner’s sign and/or Cullen’s sign, or a bluish discoloration to the flanks and umbilicus, may also be noted and are indicative of severe hemorrhagic pancreatitis, while other patients present with jaundice. Vital signs are also affected, with the heart rate increasing to 100-140 beats/min, a shallow and rapid breathing pattern, and an interim high or low blood pressure with significant postural hypotension. Temperature may remain normal initially, but rise to 100° - 101° F, and sensation may also be diminished.[2][6] Palpation reveals apparent abdominal tenderness, typically in the upper quadrants. While there may be mild tenderness in the lower abdomen, the rectum is not sore and the stool is devoid of blood. Along with tenderness, the upper abdominal muscles may be rigid; however, this is rare in the lower abdominal region. In rare cases, severe peritoneal irritation can lead to a rigid and board-like abdomen. Furthermore, auscultation of bowel sounds may reveal hypoactivity, and general muscle weakness may be noted.[2]

Severe Pancreatitis

In addition to these symptoms, a small percentage of cases develop into severe pancreatitis, which can have serious complications. Severe pancreatitis includes the aforementioned signs and symptoms, as well as a systemic inflammatory process with shock, multiorgan failure, and/or local complications. Symptoms of severe pancreatitis development include tachycardia, hypoxia, tachypnea, and changes in mental status.[1][2] Complications that may occur with severe forms of this disease include pancreatic fluid-filled collections (57% of cases), pseudocysts, and necrosis. Fluid-filled collections can enlarge and increase pain, and both the fluid-filled collections and necrotic areas can become infected, resulting in pain, leukocytosis, fever, hypotension, and hypovolemia. Ascites and pleural effusions are also possible, but rare, complications.[1]

Necrotic pancreas

Chronic Pancreatitis

Like acute pancreatitis, the central problem arising from chronic pancreatitis is abdominal pain, although 10 to 15% of patients have no pain and present with malabsorption. This pain is typically located in the epigastric and left upper quadrant with referral into the upper left lumbar region, and is frequently associated with nausea, vomiting, anorexia, constipation, flatulence, and weight loss. When the head of the pancreas is primarily affected, pain typically manifests in the T5-T9 regions; however, when the tail of the pancreas is involved pain tends to be referred to the left shoulder due to its innervation by C3-5. Pain is made worse with eating, and relieved by bringing the knees to the chest or bending forward. However, the frequency and severity of the pain may vary, with some patients experiencing acute attacks lasting only a few hours that become more chronic in nature lasting as long as two weeks and increasingly frequent over time, while others have continuous pain that gradually becomes more intense in due course. Patients with alcohol-related pancreatitis often experience pain 12 to 48 hours after imbibing large quantities of alcohol, while those with gallstone-associated pancreatitis have pain after consuming a large meal. This severe and chronic pain frequently leads to an abuse of opioids, decreased appetite, weight loss, and decreased quality of life, and is also the main reason surgery is performed in people with this disease.[2][1][6] Along with chronic pain, the destruction of pancreatic tissue and the consequential loss of pancreatic function often result in diarrhea and steatorrhea. Steatorrhea, or bulky, oily, and foul-smelling stools, occurs in late stages of the disease when the majority of the ancinar cells have been destroyed and less than 10% of normal lipase levels is being produced, resulting in fat maldigestion. Poor digestions leads to malnutrition due to the excretion of fat in the stool, and can cause patients to lose weight, despite normal appetites and eating habits. Other complications that may arise include the development of large pseudocysts, bleeding from pseudoaneurysms, splenic vein thrombosis, and fistula formation.[1][5] Diabetes mellitus may also develop in later stages of the disease, especially if the pancreas has been surgically removed. Because both beta cells, which produce insulin, and alpha-cells, which produce glucagon, are destroyed, this can result in severe hypoglycemia with the use of insulin for an extended length of time.[1]

Healthy Pancreas
Inflamed Pancreas

Associated Co-morbidities

Acute Pancreatitis

  • Alcoholism
  • 15% of patients with acute pancreatitis develop chronic pancreatitis
  • 5-7% mortality rate for milder forms with inflammation confined to the pancreas
  • 10-50% for severe forms with necrosis and hemorrhage of the gland and a systemic inflammatory response
  • Infection of necrotic pancreatic tissue may occur after 5-7 days 100% mortality for pancreatic infection without extensive surgical debridement or drainage of the infected area
  • Patients with peripancreatic inflammation or one area of fluid collection have a 10 to 15% chance of abscess formation
  • Patients with two or more areas of fluid collection have a 60% incidence of abscess formation
  • Diabetes mellitus (increased risk in alcoholic pancreatitis)
  • Recurrent episodes (increased risk in alcoholic pancreatitis)[2][1]

Chronic Pancreatitis

  • Alcoholism
  • Cystic fibrosis
  • Diabetes mellitus develops in 20-30% of patients within 10-15 years of onset
  • Pancreatic cancer develops in 3% to 4% of patients
  • Chronic disability
  • 70% 10-year survival rate
  • 45% 20-year survival rate
  • 60% mortality rate for patients with alcohol-related chronic pancreatitis who do not cease alcohol intake[1]


Acute Pancreatitis

To alleviate pain, parenteral opiods, such as morphine, are often prescribed. Also, antiemetic drugs, such as prochlorperazine 5-10 mg IV every 6 hours, may be given to patients to minimize vomiting. Parenteral H2 blockers or proton pump inhibitors are given as well.[2]

Severe Pancreatitis

Evidence has shown no beneficial effects of medications aimed at improving the physiological process of severe pancreatitis, including platelet-activating factor inhibitors, somatostatin, and protease inhibitors. In addition, the use of prophylactic antibiotics for severe pancreatitis is currently controversial and under debate. Antibiotic prophylaxis with imipenim (500 mg IV every 8 hours) may be administered to prevent infection of necrotic pancreatic tissue, although its effect on decreasing mortality is unclear.[2]

Chronic Pancreatitis

Non-narcotics analgesia, such as nonsteroidal anti-inflammatory drugs, acetaminophen, and tramadol, are typically used to treat the chronic pain associated with chronic pancreatitis. However, because this disease is progressive, patients may eventually need low doses of mild narcotics, such as codeine 15 to 60 mg/day, or propxyphene 65 to 260 mg/day. Should the pain persist, stronger opiates may be prescribed. Pancreatic enzymes may be taken if maldigestion occurs. There are many pancreatic enzyme preparations available, which differ in composition of enzymes, use of microspheres or microtablets, and the presence or absence of a coating. Despite this, lipase is a key ingredient to mixtures due to the fact that a minimum of 30,000 U lipase per meal is need for adequate digestion of fat and protein in the majority of patients; however, as much as 60,000 to 80,000 U lipase per meal may be given since not all of the lipase will necessarily reach the small intestine when active. Because uncoated enzyme preparations can be denatured by gastric acid, an H2 blocker or proton pump inhibitor, such as 20 mg of omeprazole once daily, is often prescribed in conjunction with pancreatic enzyme therapy to suppress the acid.[4]

Diagnostic Tests/Lab Tests/Lab Values

Acute Pancreatitis

The diagnosis of acute pancreatitis is formulated from patient’s clinical presentation, serum markers, and the absence of other causes that would produce similar symptoms. Because of this, a variety of tests are generally obtained, including a CBC, electrolytes, Ca, Mg, glucose, BUN, creatinine, amylase, and lipase. Other tests include an ECG and abdominal series of the chest, flat, and upright abdomen, as well as a urine dipstick for trypsinogen-2 which has >90% sensitivity and specificity for acute pancreatitis.[2]

Laboratory Tests

Because acute pancreatitis results in the release of pancreatic enzymes from injured ancinar cells, an increase in serum enzymatic levels is key to diagnosing this disorder. The two pancreatic enzymes that become elevated in the serum in the first 24 to 72 hours of an acute pancreatic attack are amylase and lipase. While amylase levels typically rise three times greater than normal within the first two hours of symptom onset, the levels quickly decrease in 36 hours, rendering it useful only if a person seeks medical attention very early on. However, lipase levels increase within 4 to 8 hours of symptom onset, peak around 24 hours, and remain elevated for at least 14 days. Levels of 10 to 140 U/L, or 3 times the normal range, are indicative of acute pancreatitis. In addition, it is important to note that previous episodes on pancreatitis can result in the destruction of ancinar cells, therefore decreasing the amount of enzymes released into serum causing amylase and lipase levels to appear normal. Similarly, patients with pancreatitis caused by hypertrygliceridemia often have a circulating inhibitor present in their serum that masks the presence of elevated amylase until the serum is diluted.[2][1] While elevated lipase and amylase levels are elevated with all causes of acute pancreatitis, including alcohol abuse, an increase in alanine aminotransferase (ALT) levels from the normal 5 to 35 U/L range is present solely when gallstones are the cause of the pancreatitis.[1] Other tests suggestive of acute pancreatitis include hypertriglyceridemia and hypercalcemia, an increase in the white blood cell count to 12,000 – 20,000/ųL, a rise in hematocrit to as high as 50 to 55% due to third space fluid losses, and an increase of bilirubin in 15 to 25% of patients because pancreatic edema compresses the common bile duct.[1][2] Below is a table of laboratory tests most commonly utilized in the diagnosis of pancreatitis:[8]

Serum Markers for Determining Diagnosis and Prognosis in Acute Pancreatitis

Laboratory test Time of onset (hours) Purpose Clinical observation/limitations
Alanine transaminase 12-24 Diagnosis and etiology Associated with gallstone pancreatitis; threefold elevation or greater in the presence of acute pancreatitis has a positive predictive value of 95 percent in diagnosing acute gallstone pancreatitis
Amylase 2-12 Diagnosis Most accurate when at least twice the upper limit of normal; amylase levels and sensitivity decrease with time from onset of symptoms
C-reactive protein 24-28 Predictive of severity Late marker; high levels associated with pancreatic necrosis
Interleukin-6 18-48 Predictive of severity Early indication of severity
Interleukin-8 12-24 Predictive of severity Early indication of severity
Lipase 4-8 Diagnosis increased sensitivity in alcohol-induced pancreatitis; more specific and sensitive than amylase for detecting acute pancreatitis
Phospholipase A2 24 Predictive of severity Associated with development of pancreatic necrosis and pulmonary failure
Procalcitonin 24-36 Predictive of severity Early detection of severity' high concentration in infected necrosis
Trypsinogin activation peptide Within a few hours Diagnosis and predictive of severity Early marker for acute pancreatitis and close correlation to severity

Medical Imaging

CT scans are the standard imaging techniques for detecting acute pancreatitis and are able to accurately identify necrotizing pancreatitis, which provides valuable management and prognostic information. They can also identify fluid collections or pseudocysts when administered in conjunction with IV contrast, and is particularly recommended for severe pancreatitis or the development of complications.[2][1]

CT scan showing 3 cm mass (arrow) in the head of pancreas.

  • An MRI may be used for patients with contraindications for CT with contrast, as this test can also identify the presence of necrosis.
  • Transabdominal ultrasound is used to examine the gallbladder and cystic duct when the presence of gallstones is suspected, which is a leading cause of this disorder[1]
  • Endoscopic Retrograde Cholangiopancreatography (ERCP) can help indentify less common causes of pancreatitis, such as microlithiasis, sphincter of Oddi dysfunction, pancreas divisum, and pancreatic duct strictures. ERCP should be immediately performed on patients at risk for biliary sepsis, severe pancreatitis with biliary obstruction, cholangitis, elevated bilirubin, worsening and persistent jaundice, or signs of worsening pain during an abnormal ultrasound examination. As these patients may require immediate surgical or gastroenterologic intervention.[8]
  • Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive technique that can be used preoperatively to determine which patients may benefit from ERCP. MRCP is as accurate as contrast-enhanced CT in predicting the severity of pancreatitis and identifying pancreatic necrosis, can assess pancreatic and peripancreatic cysts, and useful when ERCP is not possible or is unsuccessful.
  • Endoscopic ultrasonography (EUS) is used to identify stones and tumors, but less frequently than ERCP. Nevertheless, it is useful in obese patients and patients with ileus, and can help determine which patients with acute pancreatitis are the best candidates for therapeutic ERCP.
  • Below is a table comparing the various imaging techniques used for acute pancreatitis:[8]

Comparison of Imaging Techniques for Acute Pancreatitis

Imaging technique Effectiveness
Contrast-enhanced computed tomography 78 percent sensitivity and 86 percent specificity severe acute pancreatitis
Endoscopic ultrsanography 100 percent sensitivity and 9 percent specificity for gallstones
Magnetic resonance cholangiopancreatography 81 to 100 percent sensitivity for detecting common bile duct stones
98 percent negative predictive value and 94 percent positive predictive value for bile duct stones
As accurate as contrast-enhanced computed tomography in predicting severity of pancreatitis and identifying pancreatic necrosis
Magnetic resonance imaging 83 percent sensitivity and 91 percent specificity for severe acute pancreatitis
Transabdominal ultrasonography 87 to 98 percent sensitivity for the detection of gallstones

Screening for Severity

The severity of acute pancreatitis can be determined through collecting the Ranson criteria, which requires gathering data both at admission and 48 hours later. At admission, five signs are documented: age > 55 years, WBC > 16,000/ųL, serum LDH > 350 IU/L, AST > 250 IU/L, and serum glucose > 200 mg/dL. Two days later, five other values are reviewed: hematocrit decrease > 10%, BUN increase > 4 mg/dL, serum calcium < 8 mg/dL, PaO2 < 60 mmHg, and fluid sequestration > 6 L. The risk of mortality increases with the number of positive signs. If less than 3 of the above are positive, the mortality rate is < 5%; if 3-4 are positive, the rate increases to 15-20%.[2] Also on the second day of admission, the severity of the disease is determined by the Acute Physiology and Chronic Health Evaluation score (APACHE II). This predicts the severity of the disease, complications, and chance of death. In patients with a severe form of the disease, they will have an elevated C-reactive protein level, an increase in hematocrit above 44%, and a body mass index greater than 30 (obesity). Knowing this information will determine aggressiveness of care and level of observation during medical management.[1]

Chronic Pancreatitis

Unlike acute pancreatitis, diagnosing chronic pancreatitis is often difficult, especially in the early stages of the disease when little functional or structural changes are present in the pancreas.[1]

Laboratory Tests Because patients with chronic pancreatitis experience significant loss of pancreatic function over time, lipase and amylase are often not elevated in the early stages, rendering these laboratory tests ineffective. Similarly, bilirubin may only be abnormal if there is considerable bile duct compression from a pseudocyst or fibrosis. In addition to these tests, more specialized tests have been developed. These tests either directly measure pancreatic enzymes that are produced by the pancreas, indirectly measure a product from the action of a pancreatic enzyme, or identify the presence of a pancreatic enzyme by-product in the serum or stool; however, these tests are neither well-tolerated nor available everywhere.

Medical Imaging

Unlike laboratory tests, imaging tests are able to identify structural changes within the pancreas. These include strictures, pancreatic stones, lobularity, atrophy, and dilated pancreatic ducts (both large and small). Dilation of large pancreatic ducts, or large duct disease, is generally seen with alcohol use and is associated with functional problems, while dilation of small pancreatic ducts, or small duct disease, is more difficult to diagnose and idiopathic in nature. While several different imaging procedures can accurately illustrate these changes and diagnose this disease, the gold standard is an endoscopic retrograde cholangiopancreatography (ERCP), in which an endoscope and contrast injections are passed into the duodenum while the patient is sedated so that the pancreatic and bile ducts can be visualized on x-ray film. However, there is a 5-10% chance of causing acute pancreatitis just by administering this test.[1][3]

ERCP showing normal pancreatic duct.
ERCP showing proximal dilation of the common bile duct.

Other tests that are used include transabdominal ultrasonography, CT scans, endoscopic ultrasonography (EUS), endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance cholangiopancreatography (MRCP), or MRI.[1] In the late stages of pancreatitis, tests of exocrine function become abnormal, such as the 72-hour stool fat test for steatorrhea , secretin pancreatic function testing, and decreased serum trypsinogen and fecal chymotrypsin levels; however, these tests are less sensitive and proactive at diagnosis this disease as the aforementioned methods.[2] Despite these tests, it is not uncommon for chronic pancreatitis to go undiagnosed for months or even years.[3]


Acute Pancreatitis

The most common cause of acute pancreatitis is gallstones, followed by chronic alcohol consumption, which together account for more than 80% of acute pancreatic cases; however, 10% of cases are idiopathic. Furthermore, multiple genes are currently under investigation, as it is believed that a combination of genetics and environmental conditions may contribute to the development of this disease.[1] While these are the primary factors associated with acute pancreatitis, below is a comprehensive list of all possible causes:

  • Alcohol or methanol abuse (> 100 g/day for > 3 to 5 years)
  • Autoimmune diseases
  • Choleduchal cyst
  • Cystic fibrosis
  • Gallstones
  • Hereditary (familial) pancreatitis (including an autosomal dominant mutation of the cationic trypsinogen gene which causes pancreatitis in 80% of carriers)
  • Hypercalcemia
  • Hyperlipidemia or hypertriglyceridemia (levels over 1000 mg/dl)
  • Hypercalcemia (including hyperparathyroidism)
  • Infection (Coxsackie B virus, cytomegalovirus, mumps)
  • Ischemia from hypotension or atheroembolism
  • Medications (ACE inhibitors, aspariganase, azathiprone, oral estrogens, antibiotics, 2’, 3’-dideoxyinosine, furosemide, 6-mercaptouride, pentamidine, sulfa drugs, valproate, thiazide diuretic, corticosteroids)
  • Neoplasm
  • Pancreatic or periampullary cancer
  • Pancreas divisum
  • Peptic ulcers
  • Post- Endoscopic Retrograde Cholangiopancreatography (ERCP)
  • Postoperative inflammation
  • Post-renal transplant
  • Pregnancy (third trimester)
  • Sphincter of Oddi stenosis
  • Blunt or penetrating trauma (including ischemia/perfusion that occurs during some surgical procedures)
  • Tropical pancreatitis
  • Vasculitis
  • Viral infections
  • Unknown[1][2][6]

These sources trigger an intricate cellular and enzymatic process that manifests as acute pancreatitis. While pancreatic digestive enzymes normally do not become active until they reach the small intestine, pancreatitis causes the unwarranted activation of trypsinogen within ancinar cells of the pancreas, which is then converted into the enzyme trypsin. Large quantities of trypsinogen are converted to trypsin so that the normal regulation and removal of trypsin from the cells cannot adequately maintain the proper balance. Consequently, ancinar cells, vasculature, and tissue are damaged by the enzymes, causing an exaggerated inflammatory response, edema, possible necrosis, and the production of cytokines. Therefore, because trypsin controls the activation of other pancreatic enzymes, the activation of these enzymes creates a buildup and may lead to pancreatic autodigestion.[1][5]

Chronic Pancreatitis

Chronic pancreatitis is primarily caused by chronic alcohol consumption, a history of severe acute pancreatitis, autoimmune sources, hereditary contributions, or idiopathic causes. Of these, the most common source of chronic pancreatitis in Western industrialized nations is alcohol abuse, which accounts for more than 50% of all cases and more than 90% of adult cases. Alcohol-related pancreatitis tends to effect males between the ages of 35 and 45 who have consumed large quantities (150 g or more) of alcohol for 6 years or more, while hereditary pancreatitis is found in patients who have a family history of two or more relatives with the disease, including cystic fibrosis (recent studies found that at least 30% of adult patients with unexplained chronic pancreatitis have mutations in the cystic fibrosis gene). Meanwhile, autoimmune chronic pancreatitis is typically found in the Far East and is associated with an elevated IgG level, diffuse involvement of the pancreas, the presence of a mass in the pancreas, an irregular main pancreatic duct, and the presence of autoantibodies. It is also occasionally linked to other autoimmune diseases such as Sjörgen’s syndrome, ulcerative colitis, and systemic lupus erythematosus.[1][3][6] In addition to these causes, several genetic mutations have been found that are associated with this disease, although the cause and effect of these mutations is still not clearly known. These include the PRSS1 and R122H cationic trypsinogen genes; the PST1/SPINKI pancreatic secretory trypsin inhibitor genes; and the CFTR cystic fibrosis transmembrane conductance regulator gene.[1] The clinical manifestation of chronic pancreatitis is still not fully understood, and the process of its development is explained by several different hypotheses, which are primarily targeted towards alcohol-related chronic pancreatitis. Each of these hypotheses will be explored: The first hypothesis proposes that consuming alcohol results in the release of pancreatic fluid that is high in protein, but low in volume and bicarbonate. These features result in an increase of protein, which creates plugs in the pancreatic ducts and may calcify to form pancreatic stones. When these plugs and stones create a blockage in the ducts, pressure increases and the pancreatic tissue and ducts are damaged, resulting in chronic pain. A second hypothesis suggests that alcohol or one of its metabolites acts as either a toxin on pancreatic tissue directly, or increases the sensitivity of ancinar cells to the effects of pathological stimuli. It also states that alcohol may promote the release of cholecystokinin (CCK), which results in the transcription of inflammatory enzymes when alcohol is present. The third hypothesis explains that repeated episodes of acute pancreatitis result in areas of scar tissue or fibrosis that form during the healing of necrotic tissue, while those who do not have a history of recurrent acute pancreatitis may develop continuous necrosis with gradual scarring over time. Other theories support the role of genetic mutations, particularly mutations of the trypsinogen gene, which results in an increased amount of activated trypsin. While the exact cause is still under investigation, the majority of researchers believe a combination of genetic and environmental factors are responsible for the disease.[1]

Systemic Involvement


Both acute and chronic forms of pancreatitis can create systemic complications. Damage to the pancreas can disrupt normal operation, in particular its endocrine and exocrine functions. Ancinar cells within the pancreas contribute to pancreatic exocrine function by secreting bicarbonate and digestive enzymes into ducts connecting the pancreas to the duodenum at the ampulla of Vater, which joins with bile to help digest food. When these cells are destroyed in the event of pancreatitis, fat maldigestion can occur. Conversely, beta cells within the pancreas serve the endocrine function by secreting insulin and glucagon directly into the blood to help the body regulate glucose, and when these cells are destroyed diabetes mellitus may result.[2][5]

Acute Pancreatitis

Severe Pancreatitis

Some of the pancreatic enzymes and cytokines activated during pancreatitis may enter the peritoneal cavity, causing a chemical burn and third spacing of fluid. However, others enter systemic circulation resulting in an inflammatory response that can lead to multiorgan failure, including renal failure and acute respiratory distress syndrome. This is thought to be caused by phospholipase A2, a pancreatic enzyme, which possibly injures the alveolar membranes of the lungs. In fact, all of these systemic effects are primarily caused by increased capillary permeability and decreased vascular tone.[2]

Drawing of pseudocyst.jpg

Severe pancreatic inflammation and ischemia can result in the leakage of pancreatic fluid and the development of fluid collections and pseudocysts. Pseudocysts contain a liquefied collection of necrotic debris and pancreatic enzymes enclosed by either pancreatic tissue or adjacent tissues. These pseudocysts have the potential to cause inflection, bleeding, or rupture into the peritoneum; can affect the heart, lungs, kidneys, or other organs; and develop in approximately 40% of cases.[2][1][5]

Other specific system affected by acute pancreatitis include:

  • Vascular: Hypotension and shock, pericardial effusion and tamponade
  • Pulmonary: Hypoxia, atelectasis, pneumonia, acute lung injury, pleural effusion
  • Gastrointestinal: GI bleeding, abdominal compartment syndrome
  • Urogenital: Acute renal failure, renal artery or vein thrombosis
  • Metabolic: Hypocalcaemia, hyperglycemia, metabolic acidosis, hypomagnesia
  • Hematologic: Vascular thrombosis, disseminated intravascular coagulation[11]

Death may also occur as a result of systemic involvement with pancreatitis. Death within the first several days of onset is typically the result of cardiovascular instability in conjunction with shock and renal failure, or from respiratory failure with hypoxemia and, occasionally, adult respiratory distress syndrome. Death may also occur in the first few days of the disease from heart failure resulting from an unidentified myocardial depressant factor, though this is seldom. After the first week, death is usually caused by pancreatic infection or rupture of a pseudocyst.[2]

Chronic Pancreatitis

  • As mentioned previously, after several years of inflammation and structural damage, progressive fibrosis can result in decreased endocrine and exocrine functions. The most profound effects chronic pancreatitis can have are maldigestion of fat and decreased insulin and glucagon production. Together, these complications can result in the development of diabetes mellitus.[1]

Medical Management (current best evidence)

Acute Pancreatitis

Mild Pancreatitis

The treatment of mild pancreatitis focuses on maintaining normal pancreatic function while preventing complications in an acute care setting. To achieve this, patients are given analgesics for pain control, intravenous fluids for hydration (6-8 L/day), and parenteral nutrition for 2 to 3 days to allow the pancreas to rest. Should the patient continue to vomit, antiemetic agents are prescribed to alleviate this. If symptoms persist after this time period, a CT scan is obtained to assess for complications. During this initial period of hospitalization, vita signs and urine output are monitored hourly; hematocrit, glucose, and electrolytes are checked every 8 hours; central venous pressure lines or Swan-Ganz catheter measurements are taken every 8 hours if the patient is hemodynamically unstable or if fluid requirements are unclear; and complete blood count, platelet count, coagulation parameters, total protein with albumin, BUN, creatinine, Ca, and Mg are measured daily. Once pain levels are controlled and patients can eat, drink, and take oral analgesics, they are discharged with dietary guidelines. These guidelines consist of a diet of clear liquids for 24 hours, followed by small, low fat meals, with a slow progression of quantity intake as tolerated over several days. Symptoms typically resolve within 2 weeks.[2][1] When pancreatitis is the result of gallstones, a laparoscopic cholecystectomy may be performed before discharge for their removal. However, this surgery may only be performed in the absence of pancreatic fluid collections and other complications and must be postponed until they have resolved. If after six weeks fluid collections still exist, laparoscopic cholecystectomy with fluid drainage may be performed.[1] Endoscopic Retrograde Cholangiopancreatography (ERCP) with endoscopic sphincterotomy may be performed following laparoscopic cholecystectomy if common bile duct stones are found, or for patients who are not surgical candidates.[1]

Severe Pancreatitis

Patients with severe pancreatitis are admitted to the intensive care unit and treated with aggressive intravenous hydration and analgesics for pain control. Unlike mild pancreatitis, these patients usually receive enteral nutrition within 2 to 3 days rather than parenteral nutrition, as this has been shown to decrease complications involving infection. In addition, evidence has shown no beneficial effects of medications aimed at improving the physiological process of severe pancreatitis, including platelet-activating factor inhibitors, somatostatin, and protease inhibitors. Because severe pancreatitis is often associated with complications such as pancreatic fluid collections, pseudocysts, necrosis, bacterial cholagitis, and infected fluid collections and necrotic areas, fluid collections and sequential CT scans are necessary to show improvement. Antibiotic prophylaxis with imipenim can be administered to prevent infection; however, if fluid collections do become infected, they are treated with antibiotics and then drained. Necrotic areas that are not infected should be cautiously observed. Should infection develop, a necroectomy may be performed or the area can be drained percutaneously once the patient is stable.[1][2] When this disease is the result of common bile duct stones, an ERCP with sphincterotomy should be performed early on, as it has been shown to decrease the risk of complications. Surgical procedures should be avoided in patients with severe pancreatitis due to the high death rate when performed within the first few days of onset.[1] The use of prophylactic antibiotics for severe pancreatitis is currently controversial and under debate.

Chronic Pancreatitis

Treatment of chronic pancreatitis emphasizes prevention of additional pancreatic injury, pain relief, nutritional support, and replacement of lost endocrine/exocrine function. To achieve this, alcohol must be completely removed from the diet of those with alcohol-related pancreatitis, and smoking should be avoided, as it has been associated with a greater risk of mortality in people with alcohol-related pancreatitis.[1] The pain associated with this disease can be treated with nonnarcotics in the early phases of the disease with a progression to narcotics as the disease develops and the pain becomes more chronic. However, there is a 10% to 30% risk of addiction for those patients with chronic pancreatitis who are using narcotics for pain relief. In addition to these drugs, high-dose pancreatic enzyme therapy is effective at reducing pain in patients with small duct disease, but not large duct disease, while nerve blocks can also facilitate pain relief. Also, an H2 blocker or proton pump inhibitor may be used to reduce the acid-stimulated release of secretin and, therefore, the circulation of pancreatic enzymes.[1][2] Pain directly associated with pancreatic structural changes or complications may be treated in different ways. To relieve the pain associated with a dominant stricture that is common in more than half of patient with large duct disease, stents and pancreatic duct sphincterotomy are often used; however, long-term management if stents is controversial. When pseudocysts exist as a source of severe pain surgical drainage or surgical removal to prevent pancreatic duct blockage may be employed; however, pain often returns following both of these procedures. A final option that may be performed as a last resort to relieve uncontrollable pain after other methods have proven useless is a pancreatectomy. Patients who undergo this course of action may receive islet cell autotransplantation, which has been successful in a small group of patients, or may require insulin if there is islet cell dysfunction. After this procedure, oral enzyme replacements must also be taken before, during, and after meals to prevent malabsorption and aid in the digestion of food.[1]

Islet autotransplantation.

Patients who develop diabetes mellitus require insulin as well to control their blood sugar, and may be advised to adopt a diet that is low in fat with smaller portions consumed at an increased frequency. In addition, oral pancreatic enzyme supplements are often given with every meal to help patients digest food if the pancreas does not secrete enough enzymes on its own.[3]

Physical Therapy Management (current best evidence)

Acute Pancreatitis

Patients with acute pancreatitis may seek physical therapy treatment with a chief complaint of back pain. Back pain is common in patients with pancreatitis, as the inflammation and scarring associated with this disease can lead to decreased spinal extension, particularly in the thoracolumbar junction. This decrease in motion is difficult to treat even with patient compliance and resolution of inflammation due to the depth of the scarring. This tissue is often difficult to penetrate with mobilization techniques and, therefore, continues to decrease motion. Despite this, pain may be relieved through the use of heat to decrease muscular tension, relaxation techniques, and specific positioning techniques, including leaning forward, sitting up, or lying on the left side in the fetal position. It is important to note that a patient may present to physical therapy prior to a diagnosis of acute pancreatitis with back pain. While acute pancreatitis is associated with gastrointestinal symptoms, including diarrhea, pain after eating, anorexia, and unexplained weight loss, the patient may not recognize the importance or necessity of reporting what they may believe are unrelated symptoms. Therefore physical therapists must thoroughly question patients about all body systems and warning signs. It is also important to know that pancreatitis is frequently associated with diabetes mellitus.  Over 23 million Americans are currently living with diabetes, many of which will seek physical therapy services.  Because of this it is important to be aware of the signs of symptoms of pancreatitis, as patients with diabetes are at an increased risk for this condition.[12] Patients with acute pancreatitis my also need physical therapy services if acute respiratory distress syndrome (ARDS) develops as a complication. Assisted respiration and pulmonary care are critical interventions for these patients. For patients who are receiving acute care and are restricted from eating or drinking in order to let the pancreas rest, even ice chips can stimulate enzymes and increase pain. Therefore, physical therapists must be careful to follow all medical orders and not adhere to patient requests until approved by the nursing or medical staff. Hospitalized patients with acute pancreatitis must also be monitored for signs and symptoms of bleeding, including bruising.[1]

Chronic Pancreatitis

Similar to acute pancreatitis, patients with chronic pancreatitis may present to physical therapy with complaints of pain in the upper thoracic spine or at the thoracolumbar junction, while those with alcohol-related chronic pancreatitis may have symptoms of peripheral neuropathy. Because patients may complain of these seemingly musculoskeletal problems, it is imperative that physical therapists receive a complete history perform a thorough examination to screen for this disease. If this visceral problem is not determined upon initial evaluation, failure to improve with therapeutic intervention necessitates referral. Patients with known pancreatitis or post-pancreatectomy may need physical therapy services such as monitoring vital signs and/or blood glucose levels depending on what complications exist. Physical therapists should also educate these patients about the effects of malabsorption and associated osteoporosis that they may experience.[1]

Differential Diagnosis

Acute Pancreatitis

Disorders presenting with symptoms similar to those of acute pancreatitis includeperforated gastric or duodenal ulcer, mesenteric infarction, medications, strangulating intestinal obstruction, dissecting aneurysm, biliary colic, appendicitis, diverticulitis, inferior wall myocardial infarction, tubo-ovarian abscess, renal failure, salivary gland disease, hematoma of the abdominal muscles or spleen, cholecystitis, vascular occlusions, pneumonia, hypertriglyceridemia, hypercalcemia, infection, post-traumatic injury, pregnancy, and diabetic ketoacidosis.[2][4][8][11]

Chronic Pancreatitis

Patients who do not present with a typical history of alcohol abuse and frequent episodes of acute pancreatitis, pancreatic malignancy must be ruled out as the cause of pain. In addition, chronic pancreatitis may initially be confused with acute pancreatitis because the symptoms are similar, gallstones, and neoplastic or inflammatory masses.[2][4]

Case Reports

Patient Demographics: Sixty-year-old male who was admitted to a hospital in October 2001

Chief Complaints: Abdominal pain and dark urine, which had begun 2 weeks previously

Past Medical History: Left lower extremity lymphedema, Raynauds disease, transient ischemic attacks, ischemic heart disease, left side hydronephrosis, lymph node biopsy in 1999, and chronic smoking

Laboratory Tests/Medical Imaging: Liver function tests, transabdominal ultrasound, ERCP, and a CT scan

Initial Medical Diagnosis: The patient was thought to have pancreatic cancer

Additional Tests: A biopsy was performed on a tumor found in the common bile duct, followed by palliative bypass surgery to decrease symptoms, undergo a gastrojejunostomy, choledochojejunostomy, and a cholecystectomy.These biopsies (pancreas, gallbladder, liver and the lymph node) were reviewed by a histopathologist and a diagnosis of sclerosing retroperitonitis was considered

Patient Symptom Progression: The patient developed a nodular itchy rash, with skin biopsies confirming this

Final Medical Diagnosis: Diagnosis of autoimmune pancreatitis

PT Relevance: This case illustrates how complex pancreatitis can present and how difficult it can be to diagnose, as several organs (pancreas, lymph node, liver, gallbladder, retroperitoneum, pericardium, and skin) can be involved at differed times during the disease process.

Nayar M, Charnley R, Scott J, Haugk B, and Oppong K. Autoimmune Pancreatitis with Multiorgan Involvement. A Case of Pericardial Involvement. Journal of the Pancreas. 2009; 10(5):539-542. (accessed 27 March 2010).[13]

Patient Demographics: 57-year-old male presented

Chief Complaints: Acute epigastric pain, nausea, severe dehydration, and a dry mouth the morning after running a marathon. On the previous day, the patient had not only participated in a marathon, but also visited a sauna, and had inadequate fluid and food consumption during both events.

Physical Examination: The patient as found to have an expanded, hypertympanic and tender abdomen with active peristalsis

Vital Signs: Blood pressure of 165/100 mmHg, heart rate of 81 beats per minute, and a respiratory rate of 24 breaths/min

Laboratory Tests: Elevated glucose, amylase, CPK, and CRP levels

Medical imaging: Transabdominal ultrasonography found free intra-abdominal fluid containing blood and an amylase concentration of 944 U/L. Contrast enhanced CT scan showed that more than 90% of functioning pancreatic tissue was lost. 10 days after admission another CT scan showed necrotic pancreatic tissue and peripancreatic fluid collections

PT Relevance: This case is particularly useful for outpatient physical therapists, because while mechanical, stress, physical stress, or dehydration alone rarely cause damage, the combination of the combination of these factors can lead to pancreatic ischemia and, ultimately, acute pancreatitis.

Mast J, Morak M, Brett B, van Eijck C. Ischemic Acute Necrotizing Pancreatitis in a Marathon Runner. Journal of the Pancreas. 2009; 10(1):53-54. (accessed 27 March 2010).[14]

Patient Demographics: 18-year-old man presented to the emergency room

Chief Complaints: Severe epigastric pain lasting 6 hours. Five hours prior to symptom onset, the patient ingested 7 tablets of 400 mg ibuprofen. He had also been taking ibuprofen as prescribed to treat low back pain for 1 week prior to this incident.

Laboratory Testing: Elevated serum amylase, urinary amylase, lactate dehydrogenase, and leucocytosis levels indicating acute pancreatitis

Medical Imaging: CT scan consistent with mild pancreatitis findings. To rule out the large dose of NSAID ingestion as the direct gastric source of epigastric pain a gastroscopy was performed, which was normal.

PT Relevance: While NSAIDs rarely induce acute pancreatic attacks, they, along with several other drugs, can cause acute pancreatitis. Because many patients seeking physical therapy treatment are also on some form of prescribed or over-the-counter pharmaceutical, it is important ask about medication use and watch for any related side effects. This article provides a list of Class I, II, and III drugs associated with acute pancreatitis that therapists can refer to.

Magill P, Ridgway P, Conlon K, Neary P. A Case of Probable Ibuprofen-Induced Acute Pancreatitis. Journal of the Pancreas. 2006; 7(3):311-314. (accessed 21 March 2010).[15]

Patient Demographics: 16-year-old boy

Chief Complaints: Left paraumbilical, and occasionally epigastric, abdominal pain of moderate intensity. After 3 months of pain, these symptoms subsided. However, 20 days later the patient developed right-sided shoulder and chest pain, as well as dyspnea and sought medical treatment

Initial Medical Diagnosis: A physician misdiagnosed the patient’s problems as musculoskeletal pain

Patient Symptom Progression: As the patient’s symptoms of right-sided shoulder and chest pain and dyspnea persisted, he went to the hospital

Laboratory Tests: Elevated pleural amylase

Medical Imaging: Chest x-rays revealed a massive right-sided hemorrhagic pleural effusion and and abdominal CT scan showing a pancreatic pseudocyst. When the pleural effusion had not completely resolved following 3 weeks of treatment, another CT scan was performed, revealing that the pseudocyst was still present in the pancreas and causing the pleural effusion.

PT Relevance: This is important to note, as pancreatitis symptoms can manifest in many different ways and may be mistaken for pulmonary or musculoskeletal conditions if not tested and screened appropriately.

Namazi M and Mowla A. Massive right-sided hemorrhagic pleural effusion due to pancreatitis; a case report. BMC Pulmonary Medicine. 2004; 4:1. (accessed 21 March 2010).[16]

Patient Demographics: 63-year-old female presented to the emergency department

Chief Complaint: Left flank and back pain persisting over the past 5 days. The patient had no fever, abdominal pain, chest pain, dyspnea, or symptoms related to the urinary system, nor had she suffered from any recent trauma.

Past Medical History: 5 year history of hypertension and type 2 diabetes mellitus that were being regularly treated, but no history of cardiac disease, stroke, renal disease, smoking, or alcohol consumption

Physical Examination: Left flank pain exacerbated with percussion

Laboratory Tests: Elevated C-reactive protein (CRP) levels; however, all other laboratory data, a urinary analysis, and abdominal x-rays were unremarkable

Medical Imaging: Due to the elevated CRP levels and left flank pain ultrasound was performed; however, there were no abnormal findings in the kidneys, spleen, pancreas, or hepatobiliary system. Because of this, a CT was performed which found abnormal fluid collection over the peri-renal space and pancreatic tail as well as necrotic changes and swelling of the pancreatic tail, while serum pancreatic enzymes revealed a normal amylase (90 u/L) and a slightly elevated lipase level (336 u/L)

Medical Diagnosis: Acute pancreatitis

PT Relevance: This case illustrates the fact that while pancreatitis typically manifests as upper abdominal pain, nausea, vomiting, and elevated amylase and lipase levels, patients may present with only one or a few of the typical symptoms. In this case, the only complain was left flank pain, a symptom that many physical therapy patients may present with. Therefore, it is important for physical therapists to investigate whether this pain is musculoskeletal or systemic in nature.

Chen JH, Chern CH, Chen JD, How CK, Wang LM, Lee CH. Left flank pain as the sole manifestation of acute pancreatitis: a report of a case with an initial misdiagnosis. Emerg Med J 2005;22:452-453. (accessed 31 March 2010).[17]


Journal of the Pancreas. (accessed 31 March 2010).[18]

The National Pancreas Foundation. Pancreatitis. (accessed 21 March 2010).[3]

American Pancreatic Association. (accessed 21 March 2010).[19]


  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 1.29 1.30 1.31 1.32 1.33 1.34 1.35 1.36 1.37 1.38 Goodman CC, Fuller KS. Pathology: Implications for the Physical Therapist. 3rd ed. Saint Louis, MO: Saunders; 2009.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 Beers MH, et. al. eds. The Merck Manual of Diagnosis and Therapy. 18th ed. Whitehouse Station, NJ: Merck Research Laboratories; 2006.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 The National Pancreas Foundation. Pancreatitis. (accessed 21 March 2010).
  4. 4.0 4.1 4.2 4.3 4.4 Cleveland Clinic: Center for Continuing Education. Chronic Pancreatitis. (accessed 21 March 2010).
  5. 5.0 5.1 5.2 5.3 5.4 5.5 National Digestive Diseases Information Clearinghouse (NDDIC). Pancreatitis. (accessed 21 March 2010).
  6. 6.0 6.1 6.2 6.3 6.4 Goodman C, Snyder T. Differential Diagnosis for Physical Therapists: Screening for Referral. St. Louis, Missouri: Saunders Elsevier, 2007.
  7. Loyola University Health System. Pancreatic Cancer. (accessed 1 April 2010).
  8. 8.0 8.1 8.2 8.3 Carroll J, Herrick B, Gipson T. Acute Pancreatitis: Diagnosis, Prognosis, and Treatment. Am Fam Physician. 2008 Mar 1;77(5):594. (accessed 21 March 2010).
  9. Nayar M, Charnley R, Scott J, Haugk B, and Oppong K. Autoimmune Pancreatitis with Multiorgan Involvement. A Case of Pericardial Involvement. Journal of the Pancreas. 2009; 10(5):539-542. (accessed 27 March 2010).
  10. Frank a, Morse M, Smith B, Shaffer K. Autoimmune pancreatitis presenting with mass and biliary obstruction. Radiology case reports 2008; 3:189. (accessed 1 April 2010).
  11. 11.0 11.1 The Department of Anaesthesia and Intensive Care. Acute Pancreatitis. (accessed 21 March 2010).
  12. American Diabetes Association. (accessed 11 April 2010).
  13. Nayar M, Charnley R, Scott J, Haugk B, and Oppong K. Autoimmune Pancreatitis with Multiorgan Involvement. A Case of Pericardial Involvement. Journal of the Pancreas. 2009; 10(5):539-542. (accessed 27 March 2010).
  14. Mast J, Morak M, Brett B, van Eijck C. Ischemic Acute Necrotizing Pancreatitis in a Marathon Runner. Journal of the Pancreas. 2009; 10(1):53-54. (accessed 27 March 2010).
  15. Magill P, Ridgway P, Conlon K, Neary P. A Case of Probable Ibuprofen-Induced Acute Pancreatitis. Journal of the Pancreas. 2006; 7(3):311-314. (accessed 21 March 2010).
  16. Namazi M and Mowla A. Massive right-sided hemorrhagic pleural effusion due to pancreatitis; a case report. BMC Pulmonary Medicine. 2004; 4:1. (accessed 21 March 2010).
  17. Chen JH, Chern CH, Chen JD, How CK, Wang LM, Lee CH. Left flank pain as the sole manifestation of acute pancreatitis: a report of a case with an initial misdiagnosis. Emerg Med J 2005;22:452-453. (accessed 31 March 2010).
  18. Journal of the Pancreas. (accessed 31 March 2010).
  19. American Pancreatic Association. (accessed 21 March 2010).