Progressive inflammation of the pancreas, that results in structural damage, which leads to impairment of exocrine & endocrine function.
1. Alcohol abuse:
There is considerable variation in individual sensitivity to the toxicity of alcohol; so it is difficult to define a "safe" level of consumption. Only 5-10% of alcoholics develop chronic pancreatitis, suggesting that other factors may be important in the pathogenesis of the disease, as very high protein or fat diets, genetic predisposition and cigarette smoking.
Alcohol abuse was previously reported to account for 70-80% of cases of chronic pancreatitis, but these high percentages likely overestimate the contribution of alcohol.
2. Cigarette smoking:
An association between cigarette smoking and both acute and chronic pancreatitis has been reported.
3. Ductal obstruction:
Obstruction of the pancreatic duct from strictures secondary to trauma, pseudocysts, calcific stones, or tumors can lead to chronic pancreatitis.
Sphincter of Oddi dysfunction has also been associated with chronic pancreatitis in a small subset of patients.
It is controversial whether pancreas divisum . (pancreas divisum is a common anatomic variant which occurs in 7% of individuals due to failure of the embryologically derived dorsal and ventral pancreas to fuse, resulting in separate pancreatic ductal systems) may cause chronic pancreatitis by producing a relative obstruction to flow at the minor papilla..
In the management of patients with pancreas divisum, minor papillotomy will be of benefit in patients with pain and chronic pancreatitis, but endoscopic stenting should not be performed, as it may cause permanent damage to the pancreatic ducts, resulting in chronic pancreatitis.
4. Tropical pancreatitis:
A condition of unknown etiology that is seen commonly in south India and other parts of the tropics, where it is the most common cause of chronic pancreatitis. Children are commonly affected, and often die in early adulthood from endocrine and exocrine dysfunction. The cassava fruit had been implicated as an etiologic factor in this disorder, although it is no longer thought to be related. Mutations in the serine protease inhibitor SPINK1 have been identified in some patients.
5. Systemic disease:
Cystic fibrosis, SLE, hyperparathyroidism and hypertriglyceridemia may cause chronic pancreatitis.
6. Hereditary pancreatitis:
This accounts for a small percent of cases. It is transmitted as an autosomal dominant trait. The majority of affected individuals develop symptoms before the age of 20, and often before the age of 5. Hereditary pancreatitis is associated with a marked increased risk of pancreatic adenocarcinoma.
7. Idiopathic pancreatitis:
The majority of cases of chronic pancreatitis that are not related to alcohol abuse are idiopathic.
The pathogenesis of chronic pancreatitis is incompletely understood. The following explanations have been proposed:
1. Protein ductal plugs:
Increased secretion of pancreatic proteins causes protein plugs to form within pancreatic ducts. These plugs may act as a nidus for calcification, leading to stone formation within the duct system. The net result is the formation of ductal epithelial lesions which scar and obstruct the ducts, thereby causing inflammatory changes and cell loss. The formation of plugs within some but not all of the ducts explains the patchy nature of this disease.
Ischemia has been proposed as another factor in the pathogenesis of chronic pancreatitis. However, it is more likely that ischemia is important in exacerbating rather than initiating disease. ductal hypertension increased the resistance to blood flow within the pancreas. Vascular perfusion decreased further following secretory stimuli. Pancreatic interstitial pressure may rise to a greater degree in patients with chronic pancreatitis than in normal individuals due to the inelasticity of the gland. This theory explains why ductal decompression improves chronic pancreatitis.
Patients with chronic pancreatitis are frequently nutritionally depleted, particularly with regard to antioxidants. An imbalance between a decrease in antioxidants and an increased demand for them in "stressed cells" may lead to elevations in free radical formation, which is in turn associated with lipid peroxidation and cellular impairment. Controlled trials are needed to define the role of antioxidant therapy.
4. Autoimmune disorders:
Chronic pancreatitis has been found in association with other autoimmune diseases such as Sjögren's syndrome, primary biliary cirrhosis, and renal tubular acidosis. A serum autoantibody to a pancreatic antigen was found in 30% of patients with idiopathic chronic pancreatitis, 27% in patients with Sjögren's syndrome, and in 7% of patients with chronic alcoholic pancreatitis.