Introduction
Background
Chronic pancreatitis is characterized by progressive pancreatic damage that eventually leads to impairment of both exocrine and endocrine functions of the pancreas. The most common cause of chronic pancreatitis in Western societies is alcohol abuse. Understanding of the pathogenesis of chronic pancreatitis has improved primarily because of advances in the understanding of the mechanisms responsible for development of pancreatic fibrosis after repeated acute attacks of pancreatic necroinflammation. The pancreatic stellate cells are considered to be the key cells in fibrogenesis, particularly when they are activated by toxic factors such as alcohol, its metabolites, or oxidant stress or by cytokines released during pancreatic necroinflammation.1,2
Chronic pancreatitis. Plain abdominal radiograph shows calcification in the pancreas associated with osteomalacia secondary to malabsorption. Note the pseudofracture in the right 11th rib (arrow).
Chronic pancreatitis. Nonenhanced axial CT scan through the pancreas shows granular calcification in the pancreas, associated with a 4-cm pseudocyst to the right of the head of the pancreas.
Research has focused on the genetic factors that may predispose to chronic pancreatitis. Genes regulating trypsinogen activation/inactivation and cystic fibrosis transmembrane conductance regulator function have received particular attention. Mutations in these genes are now increasingly being recognized for their potential "disease modifier" role in distinct forms of chronic pancreatitis, including alcoholic, tropical, and idiopathic pancreatitis.
Imaging plays an important role in the diagnosis and management of chronic pancreatitis. Treatment of uncomplicated chronic pancreatitis is usually symptomatic and directed toward the relief of pain, malabsorption, and diabetes. Minimally invasive therapy and surgery are generally reserved for complications such as pseudocysts, abscess, and malignancy.3 Acute pancreatitis and chronic pancreatitis are assumed to be different disease processes, and most cases of acute pancreatitis do not result in chronic disease.
For excellent patient education resources, visit eMedicine's Liver, Gallbladder, and Pancreas Center. Also, see eMedicine's patient education article, Pancreatitis.
Pathophysiology
Causes of chronic pancreatitis
The main causes of chronic pancreatitis include the following:
- Alcoholism: Changes appear to develop slowly and may develop after excessive alcohol consumption for 10 years or more. Alcoholism is associated with chronic pancreatitis in 70% of patients.4
- Cholelithiasis: Cholelithiasis is a common cause of acute pancreatitis, but it probably is associated with chronic pancreatitis in 20-25% of patients.5
- Idiopathic: Etiology is idiopathic in 20% of patients.4
- Drug use: Usually, drug-induced pancreatitis is an acute process and does not evolve into a chronic form.
- Hereditary causes: Hereditary pancreatitis is an autosomal dominant disorder. Symptoms usually appear in the patient's first decade of life and eventually lead to both exocrine and endocrine pancreatic dysfunction.
- Autoimmune disease: Autoimmune pancreatitis is a rare condition that is often seen in patients with primary sclerosing cholangitis.
- Congenital causes: A congenital abnormality of fusion, pancreas divisum, can cause chronic pancreatitis
- Cystic fibrosis: This disease is associated with pancreatic atrophy and chronic pancreatitis
- Other conditions: Hyperlipidemia, hyperparathyroidism, and uremia can cause chronic pancreatitis.
Categories of chronic pancreatitis
Chronic pancreatitis can be classified into 3 categories:
- Chronic calcifying pancreatitis
- Chronic obstructive pancreatitis
- Chronic inflammatory pancreatitis
Chronic calcifying pancreatitis
Chronic calcifying pancreatitis is invariably related to alcoholism. The earliest finding is precipitation of proteinaceous material in the pancreatic ducts that forms protein plugs that subsequently calcify. The ducts and lobules are initially involved in a random manner, and they are surrounded by normal parenchymal tissue. However, as the disease progresses, these normal areas become more diffuse. The pancreatic ductal epithelium undergoes atrophy, hyperplasia, and metaplasia at the site of the protein plugs. Many of the small pancreatic ductules dilate, while others are obliterated by fibrosis.
The main pancreatic duct shows a chain-of-lakes appearance due to alternating stenoses and dilatation. In approximately 50% of patients with chronic calcific pancreatitis, the pancreatic parenchyma contains cysts of varying sizes (several millimeters to 5 cm). These cysts are lined by cuboidal epithelium and contain pancreatic enzymes. Peripancreatic fibrosis is usually a late finding that involves the portal and/or splenic veins. Peripancreatic fibrosis causes stenosis or occlusion of retroperitoneal lymph channels. Ascites may complicate chronic calcific pancreatitis as a result of portal hypertension or lymphatic obstruction in 1-2% patients.
Chronic obstructive pancreatitis
In chronic obstructive pancreatitis, the prominent histologic changes are periductal fibrosis and subsequent ductal dilatation. These changes are much more focal than those in the other forms, and in most patients, the changes involve only the portion of the pancreas in which ductal drainage is impaired. Diffuse changes may occur, in which the main pancreatic duct or ampulla is obstructed. Although protein inspissation may occur, histologic changes in the ductal mucosa are less common, and calcification is unusual. Moreover, the pancreatic duct is dilated, and the pancreas is normal in size, atrophic, or focally and/or globally enlarged. A variety of factors are implicated in chronic obstructive pancreatitis; these include ductal obstruction due to ampullary stenosis, inflammatory or neoplastic causes, surgical ductal ligation, and fibrosis due to a pseudocyst as a complication of an episode of acute pancreatitis.
Chronic inflammatory pancreatitis
Chronic inflammatory pancreatitis is rare and can affect elderly persons without a previous history of alcohol excess.
Autoimmune pancreatitis
Autoimmune-related chronic pancreatitis is a distinct clinical entity, which may present with signs of acute or chronic pancreatitis, sometimes associated with cholestatic jaundice. On imaging, it may appear as diffuse (duct destructive) or pseudotumoral lesions. These 2 aspects are probably different clinical forms of chronic autoimmune pancreatitis.6
Some autoimmune diseases are associated with chronic autoimmune pancreatitis, but not consistently. One such disease involves a bile disorder that is very similar to primary sclerosing cholangitis but is responsive to corticosteroid treatment. Pancreatitis may be associated with Crohn disease and ulcerative colitis and thus provides justification to investigate patients with idiopathic pancreatitis for underlying inflammatory bowel disease. Chronic autoimmune pancreatitis must always be considered in patients with a pancreatic mass that is atypical for carcinoma on imaging or clinical findings. Corticosteroid therapy for 4 weeks in patients with pancreatic adenocarcinoma is probably less harmful than pancreatectomy (or chemotherapy) in patients with chronic autoimmune pancreatitis.
Diagnosis depends on clinical and radiologic findings. The diagnostic value of serologic markers and, especially, autoantibodies must still be clarified.6
Frequency
United States
The incidence of chronic pancreatitis is 4 per 100,000 population in the West.4
Alcoholism is responsible for 70% of the cases of pancreatitis in the United States.
International
The exact frequency of chronic pancreatitis is unknown.
Mortality/Morbidity
Morbidity associated with chronic pancreatitis can be related to surgical approaches that are occasionally attempted to control intractable pain (see Intervention).
- Morbidity also results from surgical management of pseudocysts.
- In patients with chronic pancreatitis and in nonaffected family members, the incidence of pancreatic adenocarcinoma is increased.
Race
A form of calcific pancreatitis occurs in children and young adults in southern India and other developing countries; this form is termed nutritional or tropical pancreatitis.
Sex
A slight male preponderance exists.
Age
- Any age group can be affected, but chronic pancreatitis is unusual in children younger than 10 years. Most patients are aged 40-50 years.
- Nutritional or tropical pancreatitis affects children and young adults in southern India and other developing countries.
Anatomy
An understanding of pancreatic anatomy is important in delineating the cross-sectional anatomy of the pancreas and the causation of pain in pancreatic disease. The pancreas varies in shape and lies in the anterior pararenal space. The head of the pancreas lies within the curve of the duodenal loop, and the inferior vena cava and right renal vessels lie posteriorly. The common bile duct receives the main pancreatic duct as it passes through the pancreatic head and then drains into the duodenum at the ampulla.The gastroduodenal artery may be seen anteriorly at the pancreatic head and neck. The head of the pancreas is the most bulbous part of the gland, which then narrows to the neck. The union of the superior mesenteric and splenic veins, which forms the portal vein posteriorly, marks the anatomic position of the pancreatic neck. The pylorus lies anteriorly. The lesser sac lies anterior to the pancreas, whereas the splenic vein runs along its posterosuperior surface. The tail of the pancreas is related to the spleen, left adrenal gland, and upper pole of the left kidney.
Sonograms of the pancreas typically demonstrate a homogeneous echo pattern, and the pancreas is more echogenic than the liver. The pancreatic head measures 2.5-3.5 cm; the body, 1.75-2.5 cm; and the tail, 1.5-3.5 cm. The size of the pancreas varies considerably; therefore, reliance on size alone can lead to diagnostic errors. Generally, the size of the gland decreases with patient age, while echogenicity increases. The pancreas is more echogenic than the liver in 52% of young adults and equally echogenic in 48%. With the use of modern ultrasonographic machines, the main pancreatic duct can be identified in 85% of patients. On sonograms, the normal duct diameter is 1.3 mm ± 0.3. In patients with gallstones, the average diameter is 1.4 mm.
The typical criteria for pancreatic size on CT scans are the following: the head is 23 mm; neck, 19 mm; body, 20 mm; and tail, 15 mm. By using optimal CT techniques, the pancreatic duct can be identified in just more than 50% of the patients. Normally, the pancreatic diameters demonstrated on CT scans vary from 2-4 mm, but the effect of pixel averaging on normal pancreatic duct measurements is significant and can make such measurements unreliable. Errors of 1 or 2 mm may occur.
In most patients, a normal pancreatic duct is seen on images obtained with T2-weighted short-tau inversion recovery MRI sequences and magnetic resonance cholangiopancreatography (MRCP).
Presentation
Signs and symptoms
The most common presentation of chronic pancreatitis, irrespective of its etiology, is abdominal pain. Pain can be episodic, lasting hours to days, or it can persist for months or even years. The pain is characteristically steady in the epigastrium, and it frequently radiates to the back.
Most patients lose weight during the course of the disease. This weight loss may be related to malabsorption due to pancreatic exocrine deficiency or related to the fear of eating, because food intake exacerbates the pain. On occasion, the disease process can be painless, and patients may present with steatorrhea, weight loss, or diabetes mellitus.
Complications
Chronic pancreatitis is a relapsing condition that presents with abdominal pain. As the disease progresses, the frequency and duration of episodes of abdominal pain increase. Consequently, narcotic addiction is a common problem because of the intractable pain. Weight loss and malabsorption are also common.
Complications of chronic pancreatitis include pseudocyst and fistula formation, pseudoaneurysms of large arteries close to the pancreas, stenosis of the common bile duct, and splenic and/or portal venous obstruction.
Diabetes can develop in 58% of patients with chronic calcific pancreatitis.4 Diabetes tends to be brittle in these patients, probably because of the lack of both insulin and glucagon. However, patients with diabetes associated with chronic pancreatitis are less prone to complications such as retinopathy, nephropathy, atherosclerosis, and ketoacidosis than are patients with primary diabetes. On the other hand, neuropathy and myopathy can occur in one third of patients with chronic pancreatitis–associated diabetes. However, the exact etiology of neuropathy and myopathy in these patients is controversial, because these conditions occur with alcohol abuse in the absence of pancreatitis.
Preferred Examination
Plain radiographs show pancreatic calcification in 25-59% of patients. This feature is pathognomonic for chronic pancreatitis. Gastrointestinal (GI) tract barium testing still has a place in the management of chronic pancreatitis. First, some patients with chronic pancreatitis present with atypical abdominal complaints, and initially, barium studies may be ordered. Second, complications from chronic pancreatitis may cause obvious changes in the GI tract.
Ultrasonography is the first modality to be used in patients presenting with upper abdominal pain, although the direct diagnosis of chronic pancreatitis is not always possible. Sonography can help in determining the cause of chronic pancreatitis (eg, alcoholic liver disease, calculus disease) and in assessing the complications of the disease (eg, pseudocysts, ascites, splenic/portal venous obstruction).
Magnetic resonance imaging (MRI), particularly MR cholangiopancreatography (MRCP), is a noninvasive technique. MRI provides excellent images that may show the changes in the diseased pancreas and the complications of chronic pancreatitis. The use of secretin with MRCP can demonstrate pancreatic exocrine reserve, as well as a "santorinocele" (ie, a dilated Santorini duct seen in pancreas divisum).
CT is excellent for imaging of the retroperitoneum, and it is useful in differentiating chronic pancreatitis from pancreatic carcinoma. Cholangiopancreatography is the most sensitive imaging modality; it is used to show the ductal anatomy directly and when intervention (eg, stricture dilatation, stent placement) is being considered. Angiography is reserved for patients with suspected complications resulting from chronic pancreatitis.
Optical coherence tomography
Optical coherence tomography (OCT) allows high-resolution imaging of tissue microstructures by using a probe inserted into the main pancreatic duct (MPD) through an endoscopic retrograde cholangiopancreatography (ERCP) catheter. Perkins conducted a prospective study to assess the capacity of OCT to differentiate between noncancerous and cancerous lesions in patients with MPD segmental strictures investigated by endoscopic ultrasonography (EUS), with fine-needle aspiration cytology if necessary, and ERCP, followed by brush cytology and OCT scanning.7 OCT identified 3-layer architecture in all cases with normal MPD or chronic pancreatitis; in all the neoplastic lesions, the 3-layer architecture was totally subverted, with heterogeneous backscattering of the signal. OCT was 100% accurate in detecting cancer tissue, compared with 66.7% for brush cytology. OCT is therefore feasible with ERCP in cases of MPD segmental stricture and superior to brushcytology in distinguishing noncancerous from cancerous lesions.
Limitations of Techniques
On anteroposterior radiographs, the spine may mask small punctate calcifications; therefore, the acquisition of additional oblique or lateral imaging may be indicated.
On sonograms, the pancreas may appear normal even in the presence of advanced disease. In patients who are obese, excessive intraperitoneal gas may obscure the pancreas. Gas overlying the pancreas also can make visualization of the pancreas difficult.
Differential Diagnoses
Pancreas Divisum
Pancreas, adenocarcinoma with extrapancreatic
spread
Pancreas, Mucinous Cystic Neoplasm
Pancreas, Serous Cystadenoma
Pancreatitis, Acute
More on Pancreatitis, Chronic |
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References
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Further Reading
Related eMedicine topics
Pancreatitis Chronic (from Gastroenterology)
Pancreatitis (from Emergency Medicine)
Pancreatitis and Pancreatic Pseudocyst
Autoimmune Pancreatitis
Pancreatitis, Acute
Clinical guidelines
The Role of Endoscopy in Patients With Chronic Pancreatitis
Operative Treatment for Chronic Pancreatitis
Clinical trials
Role of Antioxidants Supplementation in Chronic Pancreatitis
The Incretin Effect in Patients With Chronic Pancreatitis
Keywords
chronic pancreatitis, pancreatitis, pancreas, chronic calcifying pancreatitis, chronic obstructive pancreatitis, chronic inflammatory pancreatitis, pancreatic dysfunction, alcoholic pancreatitis, calcific pancreatitis, obstructive pancreatitis, inflammatory pancreatitis, pancreatic pseudotumor, autoimmune pancreatitis.
