Pancreas is an accessory organ of digestion known to have dual functions in the endocrine and exocrine systems. It is necessary for the hydrolysis of macromolecules including proteins, carbohydrates, and fats (in combination with bile from the common bile duct). The pancreas has a main pancreatic duct running through the length of it, an accessory duct, and many various cell types. The ducts can become blocked, or they can be genetically deformed. During constant inflammation, scarring and fibrosis of the ducts lead to permanent damage to many structures, impairing its secretory functions.

Chronic pancreatitis is a progressive inflammatory disease of the pancreas that affects both functions of the pancreas. For example, when the exocrine function is affected, patients will present with pancreatic insufficiency, steatorrhea, and weight loss. Pancreatic insufficiency results when greater than 90% of the organ is damaged. The incidence depends on the severity of disease and can be as high as 85% in severe chronic pancreatitis. On the other hand, impairment of the endocrine function of the pancreas will eventually result in pancreatogenic diabetes (Type 3c diabetes). Chronic pancreatitis is unlike acute pancreatitis. The latter presents with acute onset abdominal pain radiating to the back. Patients with chronic pancreatitis may be asymptomatic for long periods of time. At other times, they may also have unrelenting abdominal pain with breakthrough pain requiring hospitalization. This disease process varies from acute pancreatitis in another way, in other words, histologically. The types of inflammatory cells present are different. Acute pancreatitis has a predominance of neutrophils, while chronic pancreatitis has more mononuclear infiltrates.

The pathogenesis of chronic pancreatitis seems to involve genetic factors and environmental factors. Studies have identified pancreatitis susceptibility genes associated with loss of function mutations. There are two main theories on the pathogenesis of chronic pancreatic disease. One theory is that of impaired bicarbonate secretion which cannot respond to the increased secretion of pancreatic proteins. These abundant proteins subsequently combine to form plugs within the lobules and ducts. This leads to calcification and stone formation. The other theory involves intraparenchymal activation of digestive enzymes within the pancreatic gland (possibly due to genetics or external influences such as alcohol). One recent study proposes that alcohol diminishes the cell's ability to respond to calcium signaling. This alters the feedback mechanism and promotes a cycle leading to cell death. Histopathology will reveal a marked increase in the connective tissue around the lobules and ducts. The acini architecture is often distorted and fibrosis is common in the later stages. Plus of precipitated protein may also be seen in the ducts. The distortion of the ductal system can lead to "chain of lakes' appearance on the CT scan. Chronic pancreatitis can present with prolonged abdominal pain with intermittent pain-free periods, weight loss, and relief of abdominal pain when leaning forward. However, in some cases, patients can be asymptomatic. Glucose intolerance or pancreatic diabetes is another finding later in the disease process. The goal of treatment is to decrease abdominal pain and improve malabsorption. Pain is secondary to inflammation, neuropathic mechanisms, and blocked ducts. Eating small, frequent low-fat meals is generally recommended along with replacement of fat-soluble vitamins and pancreatic enzymes. In cases where pain relief is not achieved with enzyme replacement treatment and dietary modification, non-opioid regimens should be utilized (TCA, NSAIDs, pregabalin) initially before starting a trial of opioids. Studies regarding the benefit of antioxidants are unconfirmed. New studies show some benefit of using medium-chain triglycerides. Surgery should be considered in patients who fail medical therapy and continue to have pain. The patient's behavior has to be modified to prevent exacerbation of the disorder. Patients must cease alcohol and discontinue smoking. Inpatient care is often required for patients with chronic pain and anorexia. These patients often require narcotics and nutritional supplementation. Pancreatic enzymes are usually taken with a meal and help lower the pain. However, the benefits of pancreatic enzymes still remain questionable.

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Mariko Wilson

Managing Editor

Pancreatic Disorders & Therapy

Mail ID: pdt@longdomjournal.org