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Гастроэнтерология (анг,рус)

Short theoretic material

Chronic pancreatitis is a disease process characterized by irreversible damage to the pancreas as distinct from the reversible changes noted in acute pancreatitis. The condition is best defined by the presence of histologic abnormalities, including chronic inflammation, fibrosis, and progressive destruction of both exocrine and eventually endocrine tissue. A number of etiologies may result in chronic pancreatitis, but all may ultimately lead to irreversible morphologic damage to the pancreas, and these etiologies may produce the cardinal complications of chronic pancreatitis such as abdominal pain, steatorrhea, and diabetes mellitus.

The events that initiate the inflammatory process in the pancreas are still not well understood. Current experimental and clinical observations have shown that alcohol has a direct toxic effect on the pancreas. While patients with alcohol-induced pancreatitis generally consume large amounts of alcohol, some consume very little, as little as 50 g/d. Prolonged consumption of socially acceptable amounts of alcohol is compatible with the development of chronic pancreatitis. Findings of extensive pancreatic fibrosis in patients who died during their first attack of clinical acute alcohol-induced pancreatitis support the concept that such patients already have chronic pancreatitis.

The biochemical and molecular mechanisms that may be important to the pathogenesis of chronic pancreatitis continue to be explored. Overexpression of fibroblasts and growth factors in tissue in patients with chronic pancreatitis has been reported. High levels of transforming growth factor and its receptor protein epidermal growth factor have been documented in patients with chronic pancreatitis. It is yet to be determined whether these observations are truly relevant in the pathogenesis of chronic pancreatitis.

Etiologic Considerations

Among adults in the United States, alcoholism is the most common cause of clinically apparent chronic pancreatitis, while cystic fibrosis is the most frequent cause in children. In up to 25% of adults in the United States with chronic pancreatitis, the cause is not known. That is, they are labeled as idiopathic chronic pancreatitis. Recent investigations have indicated that up to 15% of patients with idiopathic pancreatitis may have pancreatitis due to genetic defects (Table 1).

Table 1 Chronic Pancreatitis and Pancreatic Exocrine Insufficiency:

TIGAR-O Classification System

1. Toxic-metabolic 

- Alcoholic

- Tobacco smoking

- Hypercalcemia

- Hyperlipidemia

- Chronic renal failure

- Medications—phenacetin abuse

- Toxins—organotin compounds (e.g., DBTC)

2. Idiopathic

- Early onset

- Late onset

- Tropical

3. Genetic

- Hereditary pancreatitis

- Cationic trypsinogen

- CFTR mutations

- SPINK1 mutations

4. Autoimmune

- Isolated autoimmune CP

- Autoimmune CP associated with

- Sjögren's syndrome

- Inflammatory bowel disease

- Primary biliary cirrhosis

5. Recurrent and severe acute pancreatitis

- Postnecrotic (severe acute pancreatitis) 

- Recurrent acute pancreatitis

- Vascular diseases/ischemia

- Postirradiation

6. Obstructive  

- Pancreas divisum

- Sphincter of Oddi disorders (controversial)

- Duct obstruction (e.g., tumor)

- Preampullary duodenal wall cysts

- Posttraumatic pancreatic duct scars

 

Whitcomb and associates studied several large families with hereditary chronic pancreatitis and were able to identify a genetic defect that affects the gene encoding for trypsinogen. Several additional defects of this gene have also been described. The defect allows trypsinogen to be resistant to the effect of trypsin inhibitor, become spontaneously activated, and to remain activated. It is hypothesized that this continual activation of digestive enzymes within the gland leads to acute injury and, finally, chronic pancreatitis. This group of investigators has also reported that a second form of hereditary chronic pancreatitis tends to present later, has a female predominance, and frequently leads to chronic pancreatitis.

 

 

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