The exact mechanism of pancreatic fibrosis has not yet been elucidated. We have proposed the following three classifications related to the pathogenesis of pancreatic fibrosis: predominantly perilobular sclerosis in chronic alcoholic pancreatitis, predominantly intralobular sclerosis in alcoholic dependence syndrome, and mixed intralobular and perilob-ular sclerosis in both obstructive pancreatitis and chronic alcoholism. To examine the development of pancreatic fibrosis, periacinar collagenization at the initial stage of periacinar fibrosis was investigated in patients with chronic alcoholism by electron microscope. Myofibroblasts were found around acini at the initial stage of periacinar fibrosis, and were accompanied by numerous fine filaments 8-15 nm in diameter. In the acinar cells at the initial stage of periacinar fibrosis, various changes in zymogen granules (ZG), lysosomes and lipid droplets were augmented. Mucin-like medium-dense materials were also found in dilated rough endoplasmic reticulum (RER). The contents of ZG and RER occasionally leaked out. The above-mentioned electron-microscopic findings reveal that myofibroblasts play an important role at the initial stage of periacinar collagenization, and that the intracellular transport blockage of protein represented by abnormalities of ZG, ER and lysosomes may contribute to the development of periacinar collagenization. In another of our studies, prolyl hydroxylase was demonstrated in acinar cells immunohistochemically. Furthermore, the intracytoplasmic filaments in close proximity to the degenerative zymogen granules, lysosomes or basal lamina were also been investigated, and were found to be caused by alcohol-enhanced metabolic injury to the acinar cells. It may be confirmed in the near future that the acinar cells themselves participate in periacinar collagenization. Furthermore, our subsequent investigations suggest that the distribution of myofibroblasts in the periacinar and perilobular areas will provide a valuable clue to resolving the mechanism of the three different types of pancreatic fibrosis related to pathogenesis.
Copyright © 2007 S. Karger AG, Basel
Pancreatic fibrosis is one of the representative histopathologic findings in cases of chronic pancreatitis. According to Martin's classification, there are three types: predominantly intralobular sclerosis, predominantly perilobular sclerosis, and mixed intralobular and perilobular sclerosis . We have proposed that this classification is related to the pathogenesis of pancreatic fibrosis. Our previous studies showed that (a) predominantly perilobular sclerosis was found in patients with chronic alcoholic pancreatitis, (b) predominantly intralobular sclerosis mainly in patients with alcoholic dependence syndrome or chronic alcoholism, and (c) mixed intralobular and perilobular sclerosis in both obstructive pancreatitis patients  and chronic alcoholism patients [3, 4]. Several other investigators have also discussed the pathogenesis and development of pancreatic fibrosis from a pathological point of view [5-9]. However, the mechanism of human pancreatic fibrosis remains unclear, especially in chronic alcoholism.
To investigate the mechanism of intralobular sclerosis, we focused on the myofibroblasts around the acini as periacinar mesenchymal cells [10, 11]. At that time, the existence of myofibroblasts in the pancreas was not generally acknowledged. The term 'myofibroblast' was introduced by Majno et al. to define the contractile spindle cells in granulation tissue , and the electron-microscopic characteristics of both fibroblasts and smooth muscle cells were demonstrated in this cell by Gabbiani et al. [13-15]. Nowadays, it is well known that myofibroblasts play an important role not only in healing, but also in colla-genization, which is followed in many organs by fibrosis [16-18]. The role of myofibroblasts in fibrosis has been clarified not only by morphology, but also by biochemistry [19-21]. Many investigators, including Gabbiani and colleagues, have clarified myofibroblast differentiation, the transformation from fibroblasts to proto- or differentiated myofibroblasts with biological changes in variant EDA fibronectin and TGF-P, the synthesis of a-smooth muscle actin (a-SMA) and stimulation of collagen type I production [22, 23]. Myofibroblasts have been observed in many normal tissues, such as the terminal alveoli of the lungs, the interstitium of the renal cortex and the duodenal villi [18, 24, 25].
In this chapter, electron-microscopic changes in both mesenchymal cells neighboring the acini and zymogen granules at the initial stage of intralobular, or periacinar, fibrosis are briefly reviewed based on previous and current reports by ourselves and others.
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Alcoholism is something that can't be formed in easy terms. Alcoholism as a whole refers to the circumstance whereby there's an obsession in man to keep ingesting beverages with alcohol content which is injurious to health. The circumstance of alcoholism doesn't let the person addicted have any command over ingestion despite being cognizant of the damaging consequences ensuing from it.