Summary
Human acute pancreatitis results from an autodigestive process frequently associated with alcohol abuse, gall stone disease and shock. Peripancreatic fat necrosis was identified as one of the earliest visible lesions, whereas acinar cell necrosis and haemorrhage were regarded as secondary changes. To examine the alterations in acinar cells in more detail, their enzyme content and fine structural features were studied immunocytochemically using antisera against α-amylase, lipase, trypsin, chymotrypsin and pancreatic stone protein, and electronmicroscopically in pancreatic tissues from patients with severe acute pancreatitis. Peripheral acinar cells in the immediate vicinity of fat necrosis were found to be heavily degranulated, while acinar cells at some distance of necrosis fully retained their enzyme content. Other frequent changes of the acinar cells included cuboidal transformation, loss of microvilli, increased occurrence of autophagosomes, and formation of enlarged acinar lumina. As there was no apparent cell membrane leakage or rupture of duct lumina, it is concluded that the acinar cells adjacent to fat necrosis release their granules by undirected basolateral extrusion. The findings thus suggest that one of the basic defects in acute pancreatitis is the uncontrolled release of enzymes from peripheral acinar cells into the interstitial space which, in turn, presumably by the action of lipase, leads to autodigestive fat necrosis.
Similar content being viewed by others
References
Adler G, Rohr G, Kern HF (1982) Alteration of membrane fusion as a cause of acute pancreatitis in the rat. Dig Dis Sci 27:993–1002
Aho HJ, Nevalainen TJ, Havia VT, Heinonen RJ, Aho AJ (1982) Human acute pancreatitis. A light and electron microscopic study. Acta path microbiol immunol scand Sect A 90:367–373
Aho HJ, Putzke H-P, Nevalainen TJ, Löbel D, Pelliniemi LJ, Dumller W, Suonpää AK, Tessenow W (1983) Immunohistochemical localization of trypsinogen and trypsin in acute and chronic pancreatitis. Digestion 27:21–28
Baggenstoss AH (1973) Pathology of pancreatitis. In: Gambill EE (ed) Pancreatitis. CV Mosby, St Louis, p 179–212
Becker V (1973) Bauchspeicheldrüse (Inselapparat ausgenommen). In: Doerr W, Seifert G, Uehlinger E (eds) Spezielle pathologjsche Anatomie, Bd 6. Springer, Berlin Heidelberg New York
Becker V (1981) Acute pancreatitis: Pathological anatomy and pathogenesis. World J Surg 5:303–313
Bendayan M, Roth J, Perrelet A, Orci L (1980) Quantitative immunocytochemical localization of pancreatic secretory proteins in subcellular compartments of the rat acinar cell. J Histochem Cytochem 28:149–160
Chiari H (1906) Über die Beziehungen zwischen dem Pankreas und der Fettgewebsnekrose. Zbl Pathol 17:798–799
Creutzfeldt W, Schmidt H (1970) Aetiology and pathogenesis of pancreatitis (current concepts). Scand J Gastroenterol 5 (Suppl 6):47–62
Doerr W (1964) Pathogenese der akuten und chronischen Pankreatitis. Verh Dtsch Ges Inn Med 70:718–758
Dürr GH-K (1979) Acute pancreatitis. In: Howat HT, Sarles H (eds) The exocrine pancreas. Saunders, London Philadelphia Toronto, p 352–401
Foulis AK (1980) Histological evidence of initiating factors in acute necrotising pancreatitisin man. J Clin Pathol 33:1125–1131
Greenbaum LM, Hirshkowitz A (1961) Endogenous cathepsin activation of trypsinogen in extracts of dog pancreas. Proc Soc Exp Biol Med 107:74–76
Gyr K, Heitz PU, Beglinger C (1984) Pancreatitis. In: Klöppel G, Heitz PU (eds) Pancreatic Pathology. Churchill Livingstone, Edinbourgh London Melbourne New York, pp 44–72
Helin H, Mero M, Markkula H, Helin M (1980) Pancreatic acinar ultrastructure in human acute pancreatitis. Virchows Arch [Path Anat] 387:259–270
Kern HF (1986) Fine structure of the human exocrine pancreas. In: Go VLW, DiMagno E, Lebenthal E, Brooks FP, Gardner J, Scheele G (eds) The exocrine pancreas: Biology, pathobiology and diseases. Raven Press, New York, pp 9–19
Kern HF, Ferner H (1971) Die Feinstruktur des exokrinen Pankreas beim Menschen. Z Zellforsc 113:322–343
Klöppel G, von Gerkan R, Dreyer T (1984) Pathomorphology of acute pancreatitis. Analysis of 367 autopsy cases and 3 surgical specimens. In: Gyr KE, Singer MV, Sarles H (eds) Pancreatitis - concepts and classification, pp 29–35 Excerpta Medica, Amsterdam New York Oxford
Kraehenbühl JP, Racine L, Jamieson JD (1977) Immunocytochemical localization of secretory proteins in bovine pancreatic exocrine ceils. J Cell Biol 72:406–423
Lampel M, Kern HF (1977) Acute interstitial pancreatitis in the rat induced by excessive doses of pancreatic secretagogue. Virchows Arch [Pathol Anat] 373:97–117
Nevalainen TJ, Aho HJ, Eskola JU, Suonpää AK (1983) Immunohistochemical localization of phospholipase A2 in human pancreas in acute and chronic pancreatitis. Acta Pathol Microbiol Immunol Scand [Sect A] 91:97–102
Opie EL (1901) The aetiology of acute haemorrhagic pancreatitis. Johns Hopkins Hospital Bull 12:182–188
Scheele GA, Adler G, Kern HF (1984) Role of lysosomes in the development of acute pancreatitis. In: Gyr KE, Singer MV, Sarles H (eds) Pancreatitis - Concepts and classification. Excerpta Medica, Amsterdam New York Oxford, pp 17–23
Schmitz-Moormann P (1981) Comparative radiological and morphological study of the human pancreas. IV. Acute necrotizing pancreatitis in man. Pathol Res Pract 171:325–335
Schmitz-Moormann P, Wedel R v, Agricola B, Himmelmann GW (1978) Studies of lipase induced fat necrosis in rats. Pathol Res Pract 163:93–108
Steer ML, Meldolesi J, Figarella C (1984) Pancreatitis. The role of lysosomes. Digest Dis Sci 29:934–938
Wanke M (1976) Pathogenese und morphologisches Bild akuter Pankreaserkrankungen. In: Forell MM (ed) Handbuch der Innerern Medizin, Band III, Teil 6: Pankreas, 5th edn. Springer, Berlin
Watanabe O, Baccino FM, Steer ML, Meldolesi J (1984) Supramaximal caerulein stimulation and ultrastructure of rat pancreatic acinar cell: early morphological changes during development of experimental pancreatitis. Am J Physiol 246:457–467
Author information
Authors and Affiliations
Additional information
Dedicated to Prof. Dr. G. Seifert on the occasion of his 65th birthday
Rights and permissions
About this article
Cite this article
Klöppel, G., Dreyer, T., Willemer, S. et al. Human acute pancreatitis: Its pathogenesis in the light of immunocytochemical and ultrastructural findings in acinar cells. Vichows Archiv A Pathol Anat 409, 791–803 (1986). https://doi.org/10.1007/BF00710764
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00710764