What causes chronic pancreatitis?

Chronic pancreatitis in children, as in adults, has a polyetiological nature and is the main form of pancreatic pathology. In children, the leading etiological cause is considered to be diseases of the duodenum (41.8%), biliary tract (41.3%), less often - intestinal pathology, pancreatic developmental anomalies, abdominal trauma. Concomitant factors: bacterial and viral infections (hepatitis, enterovirus, cytomegalovirus, herpes, mycoplasma infections, infectious mononucleosis, epidemic mumps, salmonellosis, sepsis, etc.) and helminthiases (opisthorchiasis, strongyloidiasis, giardiasis, etc.). Systemic diseases of connective tissue, respiratory diseases, endocrine organs (hyperlipidemia, most often types I and V; hyperparathyroidism, hypercalcemia, hypothyroidism), chronic renal failure and other conditions can contribute to the development of pancreatitis. The toxic effect of some drugs on acinar tissue has been proven, leading to the development of drug-induced pancreatitis (glucocorticosteroids, sulfonamides, cytostatics, furosemide, metronidazole, NSAIDs, etc.). Irreversible changes in the pancreas can occur as a result of drinking alcoholic beverages and other toxic substances.

Genetic and congenital factors can also cause the development of pronounced morphological changes in the pancreas in hereditary pancreatitis, cystic fibrosis, Shwachman-Diamond syndrome, and isolated deficiency of pancreatic enzymes.

The frequency of hereditary pancreatitis among other etiologic forms is from 3 to 5%, inheritance occurs according to the autosomal dominant type. The development of the disease is caused by a gene mutation of pancreatic enzymes (trypsinogen and trypsin). Mutation of the cationic trypsinogen gene R117H leads to loss of control over the activation of proteolytic enzymes in the pancreas. As a rule, clinical symptoms of hereditary pancreatitis are formed at 3-5 years, the disease is characterized by the severity of pain and dyspeptic syndrome. With age, the frequency of relapses increases, severe pancreatic insufficiency develops. Ultrasound examination diagnoses calcifying pancreatitis.

Allergic diseases, food sensitization, consumption of food products containing xenobiotics and various additives that adversely affect the pancreas play a major role in the etiology of chronic pancreatitis. If the cause of pancreatitis cannot be determined, idiopathic pancreatitis is diagnosed. Some researchers distinguish an autoimmune variant of pancreatitis, including primary.

In most children, chronic pancreatitis develops secondarily (86%); as a primary disease, it occurs much less frequently - in 14% of patients.

Pathogenesis of chronic pancreatitis

To understand the mechanism of development of the pathological process in the pancreas, all factors should be divided into 2 groups. The first are factors that cause difficulty in the outflow of pancreatic juice and lead to ductal hypertension. The second are factors that contribute to direct primary damage to the acinar cells of the gland. Identification of the leading etiologic factor is necessary for the justified appointment of therapeutic measures.

The main link in the mechanism of development of most forms of chronic pancreatitis is the activation of pancreatic enzymes in the ducts and parenchyma of the gland. In the cascade of pathological reactions, a special place belongs to proteolytic enzymes (trypsin, chymotrypsin, etc.) and, less often, lipolytic enzymes (phospholipase A). The process of autolysis leads to edema, destruction of acinar cells, infiltration. In case of recurrence, it leads to sclerosis and fibrosis of the gland with the development of secretory insufficiency. Due to powerful inhibitory systems, the pathological process in the gland can be limited to interstitial edema without the development of necrosis, which is more often observed in childhood. Chronic pancreatitis in children is often the outcome of previously suffered acute pancreatitis.

The transition to chronic forms can be subclinical, subsequently leading to complications (cysts, changes in the ductal system, etc.).

Inflammatory mediators also play an important role in the genesis of chronic pancreatitis. Anti-inflammatory cytokines include interleukins 1, 6, 8, tumor necrosis factor, platelet aggregation factor. At the same time, cytokine production does not depend on the cause of pancreatitis. Activation of cytokine reactions has a damaging effect on pancreatic acinocytes.

Pathological process in the pancreas can begin as a result of deficiency of gastrointestinal hormones and biologically active substances. A decrease in the number of hormone-producing cells synthesizing secretin, cholecystokinin, pancreozymin, serotonin in diseases of the duodenum with impaired motility and development of atrophic processes in the mucous membrane has been proven. Disturbance of metabolism and deposition of intestinal hormones leads to dystrophic changes in the gland, difficulty in the outflow of pancreatic secretion, impaired motility of the duodenum, decreased pressure in it and dysfunction of the sphincter apparatus. Under these conditions, atrophy of acinar cells and their replacement with connective tissue occurs.