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Etiology of Acute Pancreatitis

There are many conditions implicated as causative factors in the pathogenesis of acute pancreatitis (Table CAUSES OF ACUTE PANCREATITIS).

Etiology of Acute PancreatitisAlcoholism and biliary tract disease

The two most common etiologic factors associated with pancreatitis are alcoholism and biliary tract disease (gallstones). These two factors account for 75% to 85% of all cases. In countries in which the incidence of alcoholism and excessive alcohol use is high, such as the United States, Australia, and South Africa, alcohol is the etiologic factor in more than 50% of patients. In contrast, in countries in which alcoholism is less prevalent, such as Britain and Israel, biliary tract disease is the most common cause of acute pancreatitis. The mortality of gallstone-associated pancreatitis is approximately 8% during the first attack and 1% during subsequent attacks. Chronic pancreatitis with pancreatic insufficiency rarely, if ever, occurs, even after multiple episodes of pancreatitis associated with gallstones.

There is a well-documented association between excessive alcohol consumption and pancreatitis. In most patients, the disease recurs many times, leading to chronic pancreatitis with irreversible functional and structural damage of the organ. Even though the mortality is considerably less than that of gallstone disease-associated pancreatitis, all the complications of acute pancreatitis may develop during the acute attacks.

TABLE. CAUSES OF ACUTE PANCREATITIS
Alcohol abuse (acute and chronic alcoholism)
Gallstones (biliary tract disease)
Surgery (abdominal, cardiac, cardiopulmonary bypass, thoracic)
Trauma
Endoscopic retrograde cholangiopancreatography
Infections (viral, Mycoplasma, Salmonella, Cryptosporidium, Mycobacterium)
Metabolic disorders (hypertriglyceridemia, pregnancy, hypercalcemia-hyperparathyroidism
Vasculitis
Drugs
Anatomic abnormalities in the area of the ampulla of Vater with possible obstruction
(Crohn’s disease, duodenal diverticulum, annular pancreas, pancreas divisum, choledochal cyst, sphincter of Oddi dysfunction)
Penetrating peptic ulcer
Hereditary factors
Miscellaneous (scorpion bite, parasites obstructing the pancreatic duct [Ascaris, fluke], severe systemic hypotension, cholesterol embolization, Reye’s syndrome, fulminant hepatitis, refeeding in eating disorders)
Renal failure
Renal transplantation

Postoperative pancreatitis is infrequent but has a high mortality. It occurs after cardiopulmonary bypass, thoracic, and abdominal surgical procedures. Operations on and near the pancreas such as gastrectomy, biliary tract surgery, and splenectomy are involved in most of the cases.

Endoscopic retrograde pancreatography. Pancreatitis may occur in less than 1% of cases after endoscopic retrograde pancreatography. However, hyperamylasemia is common after endoscopic retrograde cholangiopancreatography.

Blunt abdominal trauma is the most common cause of pancreatitis in children and young adults.

Some metabolic disorders are implicated as causes of pancreatitis.

Hypertriglyceridemia may precede and cause pancreatitis. Patients with some lipoprotein abnormalities, especially Frederickson type I, type intravenous, and type V hyperlipoproteinemia, are at increased risk of development of pancreatitis. An abrupt increase in serum triglycerides to greater than 2,000 mg/dL can precipitate a bout of acute pancreatitis. This can occur in patients with underlying hypertriglyceridemia who ingest either large amounts of lipid and moderate amounts of alcohol or large amounts of alcohol or who use birth control pills. Serum amylase may be normal in lipemic serum. Dilutions should be requested to ascertain the correct level of serum amylase.

Hypercalcemia from any cause can lead to acute pancreatitis. Causes of hypercalcemia include hyperparathyroidism, parathyroid adenoma or carcinoma, myeloma, excessive doses of vitamin D, familial hypocalciuric hypercalcemia, and hypercalcemia in patients receiving total parenteral nutrition or using calcium carbonate-containing antacids. Acute pancreatic necrosis is frequent during hyperparathyroid crisis. Increased concentrations of calcium ions in pancreatic secretion and pancreatic tissue might promote activation of trypsinogen, initiating the proteolytic cascade.

Organ transplantation

Pancreatitis may complicate renal and liver transplantation.

Pregnancy

Women in whom acute fatty liver of pregnancy develops in the third trimester may also develop acute pancreatitis. However, 90% of instances of pancreatitis during pregnancy are associated with gallstones.

Infections

Viral agents, including mumps, hepatitis B, and Coxsackie virus group B, and some bacteria (e.g., Mycoplasma pneumoniae) have been implicated as causes for acute pancreatitis. Opportunistic protozoan, bacterial, and fungal pathogens, which may involve the pancreas include Cryptosporidium, cytomegalovirus, Legionella pneumophila, and Salmonella species, Mycobacterium avium, and tuberculosis.

Connective tissue diseases

Pancreatitis may occur in patients with some connective tissue diseases, such as systemic lupus erythematosus (systemic lupus erythematosus), especially those complicated with vasculitis.

Vasculitis, present in other disorders such as Henoch-Schönlein purpura, thrombocytopenic purpura, and necrotizing angiitis, may also be implicated as a cause of acute pancreatitis.

Drugs have been associated with the development of pancreatitis in some patients. Table DRUGS ASSOCIATED WITH PANCREATITIS lists the drugs in two groups: those for which there is a definite association and those for which the association is probable.

Anatomic abnormalities

Pancreatitis has been reported in patients with a number of anatomic abnormalities in the vicinity of the ampulla of Vater, possibly associated with its obstruction, such as duodenal Crohn’s disease, duodenal diverticula, choledochocele, choledochal cysts, duodenal intussusception, and sphincter of Oddi dysfunction.

Pancreas divisum is a special condition that may lead to recurrent bouts of pancreatitis. Pancreas divisum results when the ducts of the embryologic ventral and dorsal parts of the pancreas fail to fuse. Wirsung’s duct, which normally drains the entire pancreas, only drains the uncinate process in these patients. The rest of the pancreas is drained by the duct of Santorini through the minor papilla. In many of the patients with pancreas divisum and recurrent pancreatitis, the minor papilla has been found to be stenotic and may be implicated as the predisposing condition for the development of pancreatitis.

TABLE. DRUGS ASSOCIATED WITH PANCREATITIS
Definitely Associated Probably Associated
Sulfonamides Ethacrynic acid
Estrogens (oral contraceptives) Chlorthalidone
Tetracyclines Methyldopa
Azathioprine l-Asparaginase
Mercaptopurine Procainamide hydrochloride
Furosemide Corticosteroids
Thiazides Nonsteroidal antiinflammatory drugs
Valproic acid Isoniazid
Ethanol Nitrofurantoin
Methanol Rifampin
Organophosphate insecticides Metronidazole
Pentamidine Erythromycin
Angiotensin-converting enzyme inhibitors
DDI
DDI, 2’,3’-dideoxyinosine; Angiotensin-converting enzyme, angiotensin converting enzyme.

Duodenal ulcer

Penetration of a duodenal ulcer into the pancreas may result in local pancreatic inflammation. Even though there may be an elevation of serum amylase, extensive pancreatitis usually does not develop.

Hereditary pancreatitis in an autosomal dominant transmission pattern has been described in a number of families. Symptoms usually appear between the ages of 5 and 15 years and progress to chronic pancreatitis. There may be an increased incidence of pancreatic adenocarcinoma in these families.

Miscellaneous

There are numerous other reported causes of pancreatitis including scorpion bite by Tityus trinitatis found in the West Indies and pancreatic duct obstruction by parasites such as flukes (Clonorchis sinensis) and worms (ascaris). Systemic hypotension, cholesterol embolization, Reye’s syndrome, and fulminant hepatic failure may also be associated with acute pancreatitis. Refeeding pancreatitis may occur in patients with eating disorders such as anorexia nervosa and bulimia.

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