What can trigger chronic pancreatitis?

The leading cause of chronic pancreatitis is alcohol abuse. According to foreign authors, obtained in recent years, the frequency of alcoholic pancreatitis is from 40 to 95% of all etiological forms of the disease.

Drinking 100 g of alcohol or 2 liters of beer daily for 3-5 years leads to histological changes in the pancreas. Clinically expressed manifestations of chronic pancreatitis develop in women after 10-12 years, and in men - after 17-18 years from the onset of systematic alcohol consumption. There is a linear relationship between the risk of developing pancreatitis and the amount of alcohol consumed daily, starting with a minimum dose of 20 g per day. According to Duibecu et al. (1986), many patients with chronic pancreatitis daily consumed 20 to 80 g of alcohol, and the duration of its use before the onset of symptoms of the disease was 5 years or more.

A certain genetic predisposition is also important in the development of alcoholic pancreatitis. The development of chronic alcoholic pancreatitis is also facilitated by a combination of alcohol abuse and excessive intake of food rich in fats and proteins.

Diseases of the biliary tract and liver

Biliary tract diseases are the cause of chronic pancreatitis in 63% of patients. The main mechanisms of chronic pancreatitis development in biliary tract diseases are:

• the passage of infection from the bile ducts to the pancreas through the common lymphatic pathways;
• difficulty in the outflow of pancreatic secretion and the development of hypertension in the pancreatic ducts with subsequent development of edema in the pancreas. This situation occurs in the presence of stones and a stenotic process in the common bile duct;
• biliary reflux into the pancreatic ducts; in this case, bile acids and other ingredients of bile have a damaging effect on the epithelium of the ducts and the parenchyma of the pancreas and contribute to the development of inflammation in it.

Chronic liver diseases (chronic hepatitis, cirrhosis) contribute significantly to the development of chronic pancreatitis in diseases of the biliary tract. Liver dysfunction in these diseases causes the production of pathologically altered bile containing a large amount of peroxides and free radicals, which, when they enter the pancreatic ducts with bile, initiate protein precipitation, stone formation, and inflammation in the pancreas.

Diseases of the duodenum and large duodenal papilla

The development of chronic pancreatitis is possible with severe and long-standing chronic duodenitis (especially with atrophy of the mucous membrane of the duodenum and deficiency of endogenous secretin). The mechanism of development of chronic pancreatitis with inflammatory-dystrophic lesions of the duodenum corresponds to the main provisions of M. Boger's theory of pathogenesis.

In pathology of the duodenum, the development of chronic pancreatitis is very often associated with reflux of the contents of the duodenum into the pancreatic ducts. Duodenopancreatic reflux occurs when:

• the presence of insufficiency of the large duodenal papilla (hypotension of the sphincter of Oddi);
• development of duodenal stasis, causing an increase in intraduodenal pressure (chronic duodenal obstruction);
• combinations of these two conditions. With hypotension of the sphincter of Oddi, its locking mechanism is disrupted, hypotension of the bile and pancreatic ducts develops, duodenal contents are thrown into them and, as a result, cholecystitis, cholangitis, and pancreatitis develop.

The main causes leading to insufficiency of the large duodenal papilla are the passage of a stone through it, the development of papillitis, and impaired motility of the duodenum.

Chronic duodenal obstruction may be due to mechanical and functional causes. Mechanical factors include annular pancreas, cicatricial stenosis and compression of the duodenojejunal junction by the superior mesenteric vessels (arteriomesenteric compression), cicatricial changes and lymphadenitis in the area of the Treitz ligament, afferent loop syndrome after gastric resection according to Bilroth II or gastroenterostomy, etc.

Motor dysfunction of the duodenum is of great importance in the development of chronic duodenal obstruction: in the early stages, according to the hyperkinetic type, and later, according to the pronounced hypokinetic type.

Chronic pancreatitis is promoted by duodenal diverticula, especially peripapillary ones. When the pancreatic and bile ducts enter the diverticulum cavity, spasm or atony of the sphincter of Oddi and disruption of the outflow of bile and pancreatic secretion due to diverticulitis occur. When the ducts enter the duodenum near the diverticulum, compression of the ducts by the diverticulum may occur.

The development of chronic pancreatitis can be a complication of gastric ulcer and duodenal ulcer - when an ulcer located on the back wall of the stomach or duodenum penetrates into the pancreas.

Alimentary factor

It is known that abundant food intake, especially fatty, spicy, fried food, provokes exacerbation of chronic pancreatitis. Along with this, a significant decrease in the protein content in the diet contributes to a decrease in the secretory function of the pancreas and the development of chronic pancreatitis. Fibrosis and atrophy of the pancreas and its pronounced secretory insufficiency in liver cirrhosis, malabsorption syndrome confirm the large role of protein deficiency in the development of chronic pancreatitis. Polyhypovitaminosis also contributes to the development of chronic pancreatitis. In particular, it has been established that hypovitaminosis A is accompanied by metaplasia and desquamation of the epithelium of the pancreas, obstruction of the ducts and the development of chronic inflammation.

With a deficiency of protein and vitamins, the pancreas becomes significantly more sensitive to the effects of other etiological factors.

Genetically determined disorders of protein metabolism

It is possible to develop chronic pancreatitis associated with genetic disorders of protein metabolism due to excessive excretion of individual amino acids in the urine - cysteine, lysine, arginine, ornithine.

Effect of drugs

In some cases, chronic pancreatitis may be caused by taking (especially long-term) certain medications: cytostatics, estrogens, glucocorticoids, etc. The most common association between recurrent pancreatitis and treatment with glucocorticoids is recorded. The mechanism of chronic pancreatitis development during long-term treatment with glucocorticoids is not precisely known. The role of a significant increase in the viscosity of pancreatic secretion, hyperlipidemia, and intravascular blood coagulation in the vessels of the pancreas is assumed. Cases of chronic pancreatitis development during treatment with sulfonamides, nonsteroidal anti-inflammatory drugs, thiazide diuretics, and cholinesterase inhibitors have been described.

Viral infection

It has been established that some viruses can cause both acute and chronic pancreatitis. The role of hepatitis B virus (it is capable of replicating in pancreatic cells) and the COXSACKIE virus subgroup B is allowed.

Studies have shown the presence of antibodies to the Coxsackie B virus antigen in 1/3 of patients with chronic pancreatitis, more often in individuals with HLA CW2 antigens. Convincing evidence of the role of viruses in the development of chronic pancreatitis is the detection of antibodies to RNA in 20% of patients, which is associated with the replication of RNA-containing viruses.

Circulatory disorder in the pancreas

Changes in the vessels supplying the pancreas (pronounced atherosclerotic changes, thrombosis, embolism, inflammatory changes in systemic vasculitis) can cause the development of chronic pancreatitis. In the pathogenesis of so-called ischemic pancreatitis, ischemia of the pancreas, acidosis, activation of lysosomal enzymes, excessive accumulation of calcium ions in cells, increased intensity of free radical oxidation processes and accumulation of peroxide compounds and free radicals, activation of proteolytic enzymes are important.

Hyperlipoproteinemia

Hyperlipoproteinemia of any genesis (both primary and secondary) can lead to the development of chronic pancreatitis. In hereditary hyperlipidemia, symptoms of pancreatitis appear in childhood. Most often, chronic pancreatitis develops in patients with hyperchylomicronemia (types I and V of hyperlipoproteinemia according to Fredricksen). In the pathogenesis of hyperlipidemic pancreatitis, obstruction of the gland vessels by fat particles, fatty infiltration of acinar cells, the appearance of a large number of cytotoxic free fatty acids formed as a result of intensive hydrolysis of triglycerides under the influence of excess secreted lipase are important.

Hyperparathyroidism

According to modern data, chronic pancreatitis occurs in 10-19% of cases of hyperparathyroidism and its development is caused by excessive secretion of parathyroid hormone and hypercalcemia. An increase in the content of free Ca2 ⁺ in acinar cells stimulates the secretion of enzymes; a high level of calcium in pancreatic secretion promotes the activation of trypsinogen and pancreatic lipase and, consequently, autolysis of the pancreas. In this case, calcium precipitates in an alkaline environment in the form of calcium phosphate, duct stones are formed, and calcification of the gland develops.

Postponed acute pancreatitis

Chronic pancreatitis is often not an independent disease, but only a phase state, a continuation and outcome of acute pancreatitis. The transition from acute pancreatitis to chronic is observed in 10% of patients.

Genetic predisposition

There are data confirming the involvement of genetic factors in the development of chronic pancreatitis. Thus, it has been established that in patients with chronic pancreatitis, compared to healthy individuals, antigens of the HLAA1, B8, B27, CW1 system are detected more often and CW4 and A2 are detected much less often. In patients with detected antipancreatic antibodies, the HLAB15 antigen is detected more often

Idiopathic chronic pancreatitis

Etiological factors of chronic pancreatitis can be determined only in 60-80% of patients. In other cases, it is not possible to identify the etiology of the disease. In this case, we speak of idiopathic chronic pancreatitis.

Diagnosis of chronic pancreatitis according to the Marseille-Rome classification (1989) requires morphological examination of the pancreas and endoscopic retrograde cholangiopancreatography, which is not always available. When making a diagnosis, it is possible to indicate the etiology of the disease.