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Chronic pancreatitis is heterogeneous, mainly inflammatory, the pancreas disease which is characterized by structural changes of fabric of gland (which remain and, in some cases, progress even after cancellation of an etiological factor), shown gradual development ekzo-and endogenous insufficiency.
Morphologically pancreatitis is provided by focal, segmented or diffusion degenerative or destructive changes of exocrine tissue of pancreas, an atrophy of its ferruterous elements and substitution by their connecting fabric; changes in pro-current system with frequent formation of pseudocysts and calcificats.
It is necessary to specify that so far among internist there is no standard approach to definitions and to treatment of pathogenetic interrelation acute and aggravations chronic pancreatitis. Is accepted by most of researchers that distinctive feature of chronic pancreatitis is preservation and even progressing of morphological and functional changes of a pancreas at elimination of action of an etiological factor.
Frequency of occurrence of chronic pancreatitis, according to numerous researches, varies over a wide range. It depends on different factors: national peculiarities, including dietary; an age range of population (with increase in age the frequency of incidence of chronic pancreatitis increases), etc.
On average, the frequency of detection of chronic pancreatitis makes 0,2-0,6% (on autopsy from 0,04 to 5%). In the USA and Denmark chronic pancreatitis is registered in 3,5-10 cases on 100000 all gospitayolizirovanny. Among gastroenterological diseases the share of pancreatitis makes 5-9%.
AETIOLOGY AND ELEMENTS OF THE PATHOGENY
• Alcohol is the leading etiological factor of chronic pancreatitis in the developed countries, being the reason from 38 to 95% of all pancreatitis (including chronic 25-50%). It is considered that alcohol and its metabolites can directly damage pancreas tissue; besides, ethanol causes release of the pancreatic juice oversaturated by protein-litostatinom with the subsequent sedimentation of the last in channels in the form of small proteinaceous concrements (traffic jams) breaking outflow of a secret. At intensively drinking pancreatitis on opening comes to light in 45-50%. At long (6-18 years) alcohol intake in a dose more than 150 mg/days, chronic pancreatitis develop in 60-70% of cases. At daily alcohol intake in a dose more than 20 grams of pure alcohol / days, alcoholic pancreatitis arises at men through 18, at women - in 11 flyings.
• Cholelithiasis is the reason of 25-40% of pancreatitis (so-called holepankreatit, or biliarnozavisimy chronic pancreatitis). For understanding of a pathogeny of this option of chronic pancreatitis with certain assumptions the theory of "the general channel" according to which small stones can break outflow of a pancreatic secret is accepted and lead to an autovospaleniye of podyozheludochny gland. In foreign literature of ZhKB generally is considered as an etiological factor of acute pancreatitis.
• Idiopathic, the unknown nature, pancreatitis makes not less than 10-40% of all chronic pancreatitis. Usually this look is allocated by process of elimination other possible reasons of pancreatitis. Allocate the juvenile option developing in 15-20 years, proceeding with the expressed pain syndrome, exocrine insufficiency and a diabetes mellitus and senile - after 60 flyings. At the last calcification, a diabetes mellitus, a steatorrhea whereas the pain syndrome is uncharacteristic is often observed. All described below etiological options of chronic pancreatitis "are automatically enlisted" in this group at untimely diagnosis.
More rare reasons of chronic pancreatitis.
• Tropical pancreatitis. It is Rather frequent option of chronic pancreatitis in the countries of a tropical belt. It is considered that arises because of a lack of proteins, microelements antioxidants (copper, zinc, selenium) and reception of some toxic substances. Recently the genetic nature of a disease is discussed.
• Pathology of a sphincter of Oddi (strictures, odditis, etc.). The pathogeny is identical to that at ZhKB.
• Drugs (distinguish Azathioprinum, hypothiazid, furosemide, tetracycline, Sulfasalazinum, estrogen, paracetamol, Cisplatinum, streptocides, corticosteroids, metronidazole from "aggressive" drugs, to NPVP)
• A lipidemia (generally - a gipertriglitseridemiya 1 and 5, it is rare - the 3 and 4 types of a dislipidemiya on Fredriksen's classification). It is considered that at the high level of triglycerides (more than 500 mg/dl, or 5,6 mmol/l) their interaction with a lipase of a pancreas leads to formation of a large amount of the free fatty acids affecting a pancreas. It is shown by attacks of acute pancreatitis with possible synchronization.
• Heredity. This rare species of chronic pancreatitis (usually kaltsifitsiruyushchy), is shown by attacks of acute pancreatitis with the subsequent synchronization, inherited on autosomal dominantly type with an incomplete penetration. It is quite often combined with a hyper aminoaciduria. The pathogeny is not studied.
• Hereditary diseases (mucoviscidosis, hemochromatosis, insufficiency of alfa1-antitrypsin, Shvakhman's syndrome and t of)
• Congenital anomalies of a pancreas: cystous fibrosis of a pancreas, the doubled pancreas (it is observed at 5-7% of the population).
• Ischemia. It can be observed at persons with sharply expressed atherosclerotic damage of an aorta and its branches.
• The pancreatitis for the second time developing later (against) other diseases and states - at a peptic ulcer (an ulcer penetration in gland), at a viral hepatitis In and With, after infectious parotitis (in connection with relationship of amilazprodutsiruyushchy cells of a pancreas and parotid glands), after operations, pancreas injuries, after ERPHG, against diffusion diseases of connecting fabric (in many respects the pathogeny is similar to ischemic pancreatitis), etc.
• A hypercalcemia (with kaltsifitsiruyushchy pancreatitis find a hyperparathyreosis in 1-2%). The pathogeny is connected with ability of calcium to indirectly stimulate secretion of pancreatic enzymes.
• Smoking (recently the offered possible etiological factor of chronic pancreatitis).
Main function of acinar cells of a pancreas:
1) synthesis of predecessors of digestive enzymes or zymogens in an endoplasmic reticulum (trypsinogen, chymotrypsinogen, pro-elastase, pro-carboxypeptidase A and B, A2 phospholipase);
2) their preservation in an inactive type (proferments) in secretory granules and release by means of an exocytosis in intercellular space;
3) a passage of proferments as a part of pancreas juice in a gleam of a duodenum (DPK).
The main mechanism of protection against proteolysis consists in synthesis and movement of inactive forms of enzymes intracellularly and inhibition of proteases a1-antitrypsins and a2-macroglobulins which contain in intercellular space and in a system blood-groove.
Main enzymes of a pancreas
Trypsinogen, the main digestive proferment, contains as a part of pancreas juice in two isoforms - trypsinogen-1 and trypsinogen-2 which ratio at healthy people makes 4:1 respectively. In a gleam of DPK there is a conversion of trypsinogen in trypsin under the influence of enterokinase during which trypsinogen loses trailer peptide - the trypsin active peptide (TAP). Trypsin - key enzyme under the influence of which all other proferments are quickly activated, including also trypsinogen.
First phase of an inflammation of a pancreas
Consists in operation etiological factors, and, the mechanisms explaining their communication with direct development of injury of a pancreas are still unknown. In clinical practice correlative connection between obstruction time (for example concrements) the general bilious channel and weight of chronic pancreatitis is established. At experimental pancreatitis (P) - bandaging of the general bilious channel already during the first hours according to histologic research the necrosis centers in iron are found. Besides, an activation established fact in an acinar cell of trypsinogen lizosomalny hydrolases (cathepsine B) that the main of the reasons of intracellular defeat at the Item is. As a result of interaction of digestive and lizosomalny enzymes there is a destruction of cells of a pancreas. Further enzymes come to intercellular space of a pancreas, retroperitoneal and to an abdominal cavity or a system blood stream where they destroy fabrics as a result of a lipolysis, proteolysis and local self-digestion of fabric.
In the forecast P greatest value has individual character of the general immunoreactivity at the inflammatory answer in a pancreas, namely, balance between about - and antiinflammatory cytokines that is very important for purpose of adequate antiinflammatory therapy.
Actually, the pathogeny of P and its complications is identical to such states as sepsis, a polyinjury, reperfusion of ischemic fabrics and burns when not digestive enzymes of a pancreas, but the cascade of pro-inflammatory cytokines after damage of acinar cells are involved in development of the above-stated states.
The limited inflammation in a pancreas is an initial physiological protective answer, loss of control over which leads to polyclonal activation of cells of immune system and emission of mediators of an inflammation that in turn is followed by development of multiorgan dysfunction in the form of a pulmonary, renal, liver failure, shock.
Thus, development of the complicated forms of pancreatitis begins from a local necrosis and an inflammation of a pancreas with the subsequent forming of pseudocysts and abscesses.