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Tufts OpenCourseware
Author: Laurence Scott Bailen, M.D.
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1. Objectives: Acute and Chronic Pancreatitis

  1. Understand the predisposing factors for acute pancreatitis: the most common being gallstones and alcohol use

  2. Understand how these predisposing factors lead to acute pancreatitis

  3. Understand symptoms and potential complications of acute pancreatitis

  4. Understand the most common cause of chronic pancreatitis, alcohol abuse

  5. Understand how alcohol leads to acute and chronic pancreatitis

  6. Understand the similarity in the pathogenesis of alcohol induced pancreatitis and cystic fibrosis induced pancreatitis

2. Anatomy and Physiology

  1. The pancreas sits in the retroperitoneum, with its tail at the spleen and its head surrounded by the duodenal sweep.

  2. The main pancreatic duct emptied into the duodenum through the ampulla of Vater, along with the common bile duct. The common bile duct travels behind or through the pancreas. Thus, diseases of the bile ducts or pancreas can affect each other.

  3. The pancreas has both endocrine and exocrine secretions:

    1. Endocrine hormone secretion from the islets includes insulin, glucagon, somatostatin, and some other peptides.

    2. Exocrine secretion: Pancreatic secretion into ducts is essential to chemical digestion of nutrient macromolecules.

      1. Electrolyte secretion, rich in bicarbonate, neutralizes gastric acid as it enters the duodenum. Bicarbonate secretion is stimulated by secretin.

      2. Enzymes are secreted from clusters a acinar cells, stimulated mainly by cholecystokinin

      3. Cholinergic nerves. Digestive enzymes include proteolytic agents (trypsin, chymotrypsin, elastase, etc.) amylase, and lipases (vs. triglycerides, phospholipids, and cholesterol esters). Enzymes are secreted into the ducts in inactive forms, and are not activated until they reach the lumen of the duodenum. This arrangement prevents the pancreas from digesting itself.

  4. The special relationship of the pancreas with the upper gut permits the pancreas to respond quickly to foodstuffs leaving the stomach. Due to pancreatic venous outflow directly into the portal vein, islet hormones reach the liver in relatively high concentrations and regulate hepatic metabolism of glucose and other foodstuffs.

3. Acute Pancreatitis

3.1. What is it?

When protective mechanisms of the pancreas are overcome (by as yet poorly understood factors), the pancreas begins digesting itself and the surrounding tissues. The resulting inflammation and tissue damage is termed "pancreatitis." Clinically, patients develop upper abdominal pain, often radiating into the back, with nausea, and sometimes with systemic symptoms such as fever and shock.

3.2. Pathology

Pathologically, the pancreas is swollen and edematous. In severe cases, part of the pancreas becomes necrotic and hemorrhagic, often with life-threatening hypotension and other systemic symptoms.

3.3. Predisposing factors in Acute Pancreatitis

The following list of predisposing causes of acute pancreatitis is presented for your interest. Alcohol and gallstones are by far the most important causes:


Chronic alcoholism


Stones in common bile duct


Thiazides, azathioprine, pentamidine, DDI, etc.




Very elevated serum triglycerides (>1000)


Pancreas divisum


Prolonged hypotension, vasculitis, embolic


Viral (mumps), hereditary, cystic fibrosis


Accounts for 10-20% of cases of acute pancreatitis

In the U.S., about half of all cases of acute pancreatitis are related to chronic alcoholism, usually at least 3 or 4 drinks/day x years. There is often chronic pancreatic scarring from alcohol before the first attack of pancreatitis.

About a quarter of attacks of acute pancreatitis are related to common bile duct stones, and many of the rest have traditionally been considered "idiopathic." Some studies show that of this idiopathic group, many have tiny stones or cholesterol crystals in the gallbladder or bile ducts, and treatment directed against this reduces the recurrence of acute pancreatitis. Other studies suggest that many patients with idiopathic pancreatitis actually have undiagnosed cystic fibrosis.

3.4. How do these predisposing factors promote Acute Pancreatitis?

  1. Normally, digestive enzymes in the pancreas are stored and secreted as inactive pro-enzymes. Protease inhibitors such as alpha1-anitrypsin are present as well. Digestive enzymes are not activated until they reach the small bowel. Inactive trypsinogen passes through the pancreatic ducts, and upon reaching the duodenum, it is cleaved by enterokinase to yield active trypsin. Trypsin then in turn activates the other enzymes, as well as more of itself.

  2. Inflammation and edema of acute pancreatitis results from inappropriate activation of pancreatic enzymes within the pancreas, with leakage of these enzymes into the interstitial space . Leaky pancreatic ducts may contribute. It is easy to see how the process can get out of control once it gets started. How the proves gets started remains unclear.

  3. Factors (listed in 2.3) may not initiate pancreatitis by a combination of tow mechanism: stimulation of enzyme synthesis and/or blockage of secretion from the acinar cells. Tying off the pancreatic duct sometimes causes pancreatitis, but usually not. However, when enzyme synthesis is stimulated but release of granules is thwarted, intra-pancreatic enzyme activation and pancreatitis results. For example:

    1. Alcohol stimulates pancreatic secretion, with a significantly increase protein concentration. After years of alcoholism, proteinaceous plugs are often seen in small ducts. Hyperstimulation of secretion + blockage of release from acinar cells may = intracellular activation if enzymes.

    2. Bile duct stones may cause temporary blockage of exit of enzymes granules from acinar cells. Bile salts and other bile components may also activate phospholipases which can cause activation of pancreatic enzymes and set off the inflammatory cascade.

    3. Intracellular calcium is part of the intracellular signaling pathway for enzyme secretion. Perhaps excessive stimulation of these signaling pathways can contribute to inappropriate activation of digestive enzymes.

3.5. Clinical manifestations

  1. Local : release of proteolytic enzymes and lipases may cause inflammation and edema throughout the retroperitoneum. This results in upper abdominal pain, often radiating to the back, often with nausea, vomiting, and fever.

  2. Systemic : activated trypsin activates many other enzymes, resulting in varied systemic complications, e.g., activation of bradykinin (capillary leak and vasodilatation), complement (with leukocyte activation), thrombin (with intravascular coagulation), and phospholipases (with cell membrane damage). The serum amylase is usually elevated. The degree of amylase elevation does not correlate with the severity of pancreatitis.

    1. Circulatory: shock and decreased myocardial contractility and decreased systemic vascular resistance (similar to septic shock). Also with capillary lead throughout body: so-called "third spacing."

    2. Lungs: decreased oxygenation of blood is common, with severe damage to lungs in some (ARDS = adult respiratory distress syndrome). Release of phospholipases may cause degradation of pulmonary surfactant.

    3. Renal: renal failure is partly related to decreased intravascular volume and decreased cardiac output, but also to intrarenal vasoconstriction.

    4. Hyperglycemia: related mostly to increased glucagon.

    5. Hypoglycemia: probably related to increased calcium flux into tissues and acute fall in serum albumin (old explanation that unesterified fatty acids precipitated with calcium, probably is not the reason).

3.6. Treatment

  1. Patients are given nothing by mouth, to "put the pancreas to rest." Nasogastric suction is used in severe pancreatitis with ileus, but is not necessary in milder cases. Large amounts of IV fluid may be necessary to replace intravascular losses due t leaky capillaries. Analgesics such as meperidine are used. Unfortunately, no form of anti-secretory (e.g., somatostatin) or antiprotease treatment has yet been found to be beneficial.

  2. Prognosis can be estimated using clinical and laboratory criteria: so-called "Ranson score." Patients with more severe pancreatitis must be monitored closely for complications and treated aggressively, often in the ICU.

  3. Surgery is occasionally necessary to remove necrotic pancreas or drain a pancreatic abscess or pseudocyst. When gallstones are implicated as the cause of pancreatitis, the bile ducts must be cleared of gallstones.

4. Chronic Pancreatitis

4.1. What is it?

By definition, chronic pancreatitis implies permanent damage with fibrosis and loss of functioning tissue. There may not be much inflammatory infiltrate. Ducts are often narrowed in some areas and dilated in others. About 80% of patients have chronic upper abdominal pain. Malabsorption with diarrhea and/or weight loss may occur.

4.2. Predisposing factors

  1. Alcohol

    1. Cause of approximately 70% of cases

  2. Duct obstruction

    1. Post-traumatic pancreatic duct strictures

    2. Pancreas divisum: embryologic anomaly with impaired drainage of main pancreatic duct

    3. Scarring or obstruction of pancreatic sphincters

    4. Tumors: pancreatic cancer or tumor of ampulla

    5. Cystic fibrosis

  3. Hereditary or familial forms

  4. Idiopathic: 20-30% of chronic pancreatitis has unknown cause

4.3. How do these factors cause Chronic Pancreatitis?

  1. Acute pancreatitis is neither necessary nor sufficient to cause chronic pancreatitis. The two processes are related, but chronic pancreatitis is not just the result of repeated acute pancreatitis. For example, repeated episodes of acute pancreatitis from gallstones do not lead to chronic pancreatitis.

  2. Alcohol is a special case:

    1. Alcohol can cause both acute and chronic pancreatitis. Most individuals presenting with their first attack of alcoholic pancreatitis already have detectable, permanent loss of pancreatic function.

    2. Alcoholic chronic pancreatitis often causes calcification of the pancreatic ducts. Hereditary chronic pancreatitis can do this, but other forms of chromic pancreatitis generally do not.

    3. Alcohol causes increased pancreatic secretion, with a significantly increased protein concentration. Proteinaceous plugs form in small pancreatic ductules early in the progression of alcoholic injury. These plugs can calcify, forming stones in the pancreatic ducts. Duct obstruction leads to atrophy of the acini; with islet secretion preserved until late in the course. Once duct obstruction occurs, destruction of the pancreas can continue even though the original insult (alcohol) stops.

  3. Cystic fibrosis (CF) probably causes pancreatic exocrine failure by a mechanism similar to alcohol. Early in CF there is an increase in protein concentration in pancreatic secretions, with proteinaceous plugging of microscopic ducts, and atrophy of the acini. However, in contrast to alcoholic pancreatitis, there is more pure atrophy of the exocrine pancreas, without pain and inflammatory phenomena.

4.4. Clinical manifestations of Chronic Pancreatitis

  1. Patients present with chronic abdominal pain, diarrhea, or weight loss. Diarrhea occurs late in the course, often as the pancreas becomes "burned out."

  2. Pain is caused by increased pressure behind obstructed ducts, (ductal hypertension). Of by fibrosis of nerves in or around the pancreas. The mechanism is not clear, and may vary from patient to patient.

  3. Symptomatic malabsorption does not occur until pancreatic enzyme secretion is reduced to less than 10% of normal . Loss of pancreatic enzymes causes defects in digestion of all three major nutrients: carbohydrates, e.g., starch (decreased amylase), proteins (decreased trypsin and chymotrypsin), and fats (decreased lipase). In general, a patient can compensate well for the defects in starch and protein digestin. Symptoms are usually related to fat malabsorption.

  4. Fat malabsorption is caused especially by decreased lipase secretion. Non-absorbed fats cause diarrhea (steatorrhea) because they are metabolized to noxious hydroxyl-fatty acids in the colon. Fat malabsorption causes weight loss through wasting of a major portion of caloric intake. The fat soluble vitamins A, D, E, and K may be poorly absorbed, and other nutrients such as calcium may bind to inesterified fatty acids.

  5. Diabetes mellitus is a late phenomenon. Patients are frequently insulin-dependent, and microvascular complications may occur.

4.5. Diagnosis

  1. Based partly on evidence of pancreatic damage on x-ray, Ct, or ultrasound imaging. Diffuse pancreatic calcifications on a plain x-ray of the abdomen are good evidence. Endoscopic retrograde cholangiopancreatography (ERCP) shows characteristic pancreatic ductal changes, but is usually not required.

  2. Alternatively, one can demonstrate fat malabsorption by showing that an excessive percentage of ingested fat passes in the stills (i.e., more than 7% of ingested fat). This is best detected by a 72-hour fecal fat collection. More specific tests can be dome to show that the pancreas fails to secrete enzymes normally.

  3. Serologic tests such as amylase are generally not helpful, as they can be normal in patients with symptomatic chronic pancreatitis. Serum lipase may be more sensitive.

4.6. Treatment of Chronic Pancreatitis

  1. Destruction of pancreatic tissue is irreversible, and the process is usually quite advanced by time of diagnosis. Beyond a certain point, destruction of the pancreas may continue even tough the patient has stopped drinking alcohol.

  2. Chronic pain if often the most difficult problem, often leading to opiate addiction. Some evidence suggests pain can be reduced by high-dose pancreatic supplements, which can suppress pancreatic enzyme secretion, essentially by feedback inhibition. Surgery is sometimes performed, with variable success. Endoscopic decompression of obstructed pancreatic ducts is performed increasingly, but the effectiveness of such treatment remains controversial.

  3. Malabsorption can be reduced by means of oral pancreatic enzyme supplements, with special attention to lipase supplementation. Anti-acid treatment is often given to neutralize acidity in the duodenum. A low-fat diet helps to reduce diarrhea.