Immunogenetic aspects in pathogenesis of acute pancreatitis

Acute pancreatitis is characterized by essential decrease of the activity of the complement C1-C5 system components which is more marked under destructive form of the disease. The increased consumption of the components of the complement may be determined by forming immune complexes under interaction of the antibodies with structural and secretory components of the pancreas and direct proteolytic conversion under influence of trypsin. The revealed associations with HLA I antigens suggest the presence of genetic determination of the changes in the complement system. It may be also possible that components of the complement system, in particular C4 which is immune product of the HLA class III region, exert regulating influence on humoral immune reactions in acute pancreatitis.     

急性胰腺炎发病机制的研究进展

急性胰腺炎(AP)是胰腺的炎症性疾病,其发病机制除与胰蛋白酶原异常激活相关外,还与钙超载、线粒体功能障碍、自噬受损和内质网应激相关,发病机制尚未完全阐明。目前尚无有效治疗AP的方案,难以防止胰腺功能的丧失。深入了解AP的病理生理机制有助于找到潜在的治疗靶点。因而,本文旨在对AP发病机制做一综述,为治疗提供更多的研究方向。     

线粒体损伤在急性胰腺炎发病机制中的作用

急性胰腺炎(AP)是一种严重的炎症性疾病,其发病机制尚未完全阐明,因此临床上缺乏特异性的治疗方案。越来越多的研究表明线粒体损伤在AP的发病机制中处于中心地位。目前认为,线粒体损伤与钙超载、细胞内ATP耗竭、线粒体膜通透性改变、自噬受损等关系密切,这些病理变化共同参与AP的发生发展。此外,线粒体对腺泡细胞死亡途径的调控也在AP中发挥着重要作用。笔者就AP中线粒体损伤的病理机制研究进展作一综述。     

Pathological anatomy and pathogenesis of acute pancreatitis

Acute pancreatitis involves autodigestion of the pancreas by its own secretions. The anatomical signal is tryptic necrosis. The so-called edematous pancreatitis cannot be compared with acute tryptic pancreatitis as it is caused by swelling of the pancreas, with pancreatic juice in the parenchyma, but no necrosis occurs. The severity of acute pancreatitis is determined by the state of preservation of the pancreatic capsule. Three stages may exist: (a) the gland is enlarged with solitary areas of necrosis and the capsule is preserved; (b) confluent necrosis with necrosis of the lipid tissue occurs, but the capsule is preserved; and (c) necrosis extends into surrounding areas, especially into the omental bursa and the retroperitoneum, and the capsule is destroyed. Peritonitis, ileus, and pleural effusion may represent regional extension of acute pancreatitis. Shock is the most dangerous complication and is the most frequent cause of death.

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Résumé La pancréatite aigüe implique une autodigestion du pancréas par ses propres sécrétions avec, au point de vue anatomique, une nécrose tryptique. La soidisant pancréatite oedémateuse ne peut être comparée à la pancréatite aigüe tryptique: elle est causée par un simple oedème du pancréas avec suffusion de suc pancréatique dans le parenchyme, mais sans nécrose. La gravité de la pancréatite aigüe dépend de l'intégrité de la capsule pancréatique, avec trois stades possibles: (1) gonflement de la glande avec zones isolées de nécrose mais capsule intacte, (2) nécroses confluentes et nécrose du tissu graisseux, mais capsule toujours intacte, (3) nécrose s'étendant aux tissus péripancréatiques, en particulier l'arrière cavité des épiploons et les tissus rétropéritonéaux, avec capsule détruite. La péritonite, l'iléus, l'épanchement pleural peuvent être des signes d'extension régionale. Le choc est la complication la plus dangereuse et la cause la plus fréquente de décès.

     

Etiology and pathogenesis of acute pancreatitis]

The pathogenesis of acute pancreatitis is based on the following principles: 1. Biliary. In biliary pancreatitis there is a causal relationship between the induction of acute pancreatitis and the migration of gallstones. The basic pathomechanism seems to be a combination of an increase in permeability and pressure in the ductal system. 2. Intraacinar. Caerulein-pancreatitis is a well established experimental model which reflects the intracellular/interstitial type of activation. Basolateral secretion of pancreatic enzymes into the interstitial space represents the initial event. Intracellular activation of trypsin by the fusion of zymogen-granules and lysosomes has been advocated as an alternative mechanism. 3. Alcohol. The acute alcohol pancreatitis comprises a combined pathogenesis. Obstruction and reflux as well as the cytotoxic effect of alcohol seem to be the main principles. 4. Disturbance of pancreatic microcirculation. Ischemia of the pancreas seems to play a key role in the transition from pancreatic edema to necrosis. Improvement of capillary perfusion by isovolemic hemodilution with dextran 60 has been shown to be an efficient therapeutic tool.     

细胞信号通路在重症急性胰腺炎发病机制中的研究进展

重症急性胰腺炎是一种预后凶险的疾病,常导致全身炎性介质反应综合征及多器官功能衰竭.重症急性胰腺炎全身炎性介质反应的基础是由许多细胞因子通过细胞信号通路介导构成的复杂的炎性介质反应网络.本文通过综合分析和归纳近年来国内外有关文献,就细胞信号通路在重症急性胰腺炎发病机制中的研究现状作一综述.     

The pathogenesis of pulmonary edema in acute pancreatitis.

Acute pulmonary edema appeared 3 or more days after the onset of acute pancreatitis in 7 patients, an approximate incidence of 8%. The severity of pancreatitis in these patients was characterized by massive requirements for intravenous colloid and by marked hypocalcemia. In addition, at least 5 of the 7 patients had very high serum levels of triglycerides at the time of hospital admission. Hemodynamic studies during pulmonary edema showed normal central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance. Cardiac index was appropriately elevated. Respiratory treatment, consisting of endotracheal intubation and controlled ventilation with PEEP, was successful in allowing reversal of the pulmonary injury and recovery of respiratory function within 1-2 weeks in all cases. Two patients died later from pancreatic abscesses. The findings indicate that a distinct form of pulmonary injury may occur in acute pancreatitis, characterized by loss of integrity of the alveolar-capilllary membrane, leading to pulmonary edema. The mechanism of injury is not known but may be caused by circulating free fatty acids, phospholipase A, or vasoactive substances. The pulmonary membrane lesion appears to heal during the period of intensive respiratory support.     

细胞凋亡在实验性急性胰腺炎发病中的作用

目的　探讨细胞凋亡在急性胰腺炎发病机制中的作用 ,了解川芎嗪在AP中对细胞凋亡的影响。方法　实验动物随机分为 3组 :( 1)AP组 ;( 2 )对照组 ;( 3 )治疗组。通过病理评分和TUNEL法检测 3组胰腺组织的病理形态和胰腺细胞的凋亡指数。结果　胰腺炎早期以细胞凋亡为主 ,病变程度轻 ;晚期以细胞坏死为主 ,病变程度重 ;诱导细胞凋亡有利于减轻胰腺炎病情。结论　通过诱导细胞凋亡可以减轻胰腺炎的病变程度 ,但具有一定的时间性     

高脂血症性重症急性胰腺炎病因及发病机制研究概况

高脂血症能够诱发和加重重症急性胰腺炎的胰腺损伤,一直是临床研究的焦点,其发病机制尚未完全阐明.在众多学说中,游离脂肪酸的毒性作用、胰蛋白酶原活化加速、胰腺微循环障碍一直是占主导地位的理论.近年来,关于肠道细菌移位、胰腺腺泡内钙超载等理论也受到了关注和重视.本文将对高脂血症性重症急性胰腺炎的病因及发病机制的研究概况进行概述.