Aktuelle Ernährungsmedizin 2003; 28(2): 72-78
DOI: 10.1055/s-2003-37987
Originalbeitrag
© Georg Thieme Verlag Stuttgart · New York

Pathophysiologie der Pankreasinsuffizienz

Pathophysiology of Pancreas InsufficiencyP.  Layer1 , U.  Melle1 , J.  Keller1
  • 1Israelitisches Krankenhaus in Hamburg
Manuskript nach einem Vortrag bei der gemeinsamen Jahrestagung von AKE, DGEM und GESKES Nutrition 2002 in Luzern vom 18. - 20.4.2002
Further Information

Publication History

Publication Date:
20 March 2003 (online)

Zusammenfassung

Die chronische Pankreatitis ist überwiegend ethyltoxischer Genese und tritt mit einer Inzidenz von 3 - 10 Fällen pro 100 000 Einwohnern und Jahr auf, wobei überwiegend Männer betroffen sind. Die Erkrankung wird zunächst meist durch intermittierend auftretende Oberbauchschmerzen symptomatisch, während trotz irreversibler Organdestruktionen aufgrund der großen funktionellen Reservekapazität der Bauchspeicheldrüse Beschwerden der exokrinen und endokrinen Pankreasinsuffizienz oft erst Jahre bis Jahrzehnte später auftreten. Dabei steht dann die Steatorrhö im Vordergrund, da einerseits die Pankreaslipaseaktivität stark eingeschränkt ist und andererseits keine effektiven extrapankreatischen Ersatzsysteme für die Fettverdauung existieren. Die exokrine Pankreasinsuffizienz hat jedoch nicht nur eine verminderte Enzymsekretion, sondern auch eine gestörte Interaktion zwischen gastrointestinaler Motilität, Sekretion und endokriner Funktion zur Folge. Daher sollten neuere Therapieentwicklungen nicht nur die intraluminale Enzymsubstitution, sondern auch die Wiederherstellung einer intakten und koordinierten Verdauungsfunktion zum Ziel haben.

Abstract

Long-term alcohol consumption is the most common cause of chronic pancreatitis. The incidence of the disease is 3 to 10 per 100 000 inhabitants and year, and the majority of patients are men. The disease is primarily characterized by intermittent abdominal pain. Symptoms of exocrine and endocrine pancreatic insufficiency develop years or even decades later, because of the high reserve capacity of the pancreas. During the course of pancreatic exocrine insufficiency, synthesis and intraluminal activity of the pancreatic lipase is impaired rapidly and its luminal digestive action is hardly compensated by nonpancreatic mechanisms. As a consequence, steatorrhea dominates the clinical picture. Pancreatic exocrine insufficiency induces not only decreased enzyme secretion resulting in nutrient malabsorption but also alterations of upper gastrointestinal motor, secretory and endocrine functions. Therefore, not only delivery of enzymes into the intestinal lumen but also restoration of disturbed integration of digestive functions should be a goal of future therapeutic concepts.

Literatur

  • 1 Anagnostides A, Chadwick V S, Selden A C, Maton P N. Sham feeding and pancreatic secretion. Evidence for direct vagal stimulation of enzyme output.  Gastroenterology. 1984;  87 109-114
  • 2 Go V L, Hofmann A F, Summerskill W H. Pancreozymin bioassay in man based on pancreatic enzyme secretion: potency of specific amino acids and other digestive products.  J Clin Invest. 1970;  49 1558-1564
  • 3 DiMagno E P, Malagelada J R, Go V L, Moertel C G. Fate of orally ingested enzymes in pancreatic insufficiency. Comparison of two dosage schedules.  N Engl J Med. 1977;  296 1318-1322
  • 4 Fried M, Erlacher U, Schwizer W. et al . Role of cholecystokinin in the regulation of gastric emptying and pancreatic enzyme secretion in humans. Studies with the cholecystokinin-receptor antagonist loxiglumide.  Gastroenterology. 1991;  101 503-511
  • 5 Holtmann G, Kelly D G, DiMagno E P. Nutrients and cyclical interdigestive pancreatic enzyme secretion in humans.  Gut. 1996;  38 920-924
  • 6 Bozkurt T, Adler G, Koop I, Arnold R. Effect of atropine on intestinal phase of pancreatic secretion in man.  Digestion. 1988;  41 108-115
  • 7 Czako L, Hajnal F, Nemeth J, Takacs T, Lonovics J. Effect of a liquid meal given as a bolus into the jejunum on human pancreatic secretion.  Pancreas. 1999;  18 197-202
  • 8 Katschinski M, Dippel C, Reinshagen M. et al . Induction of the fed pattern of human exocrine pancreatic secretion by nutrients: role of cholecystokinin and neurotensin.  Clin Investig. 1992;  70 902-908
  • 9 Beglinger C, Fried M, Whitehouse I, Jansen J B, Lamers C B, Gyr K. Pancreatic enzyme response to a liquid meal and to hormonal stimulation. Correlation with plasma secretin and cholecystokinin levels.  J Clin Invest. 1985;  75 1471-1476
  • 10 Cantor P, Mortensen P E, Myhre J. et al . The effect of the cholecystokinin receptor antagonist MK-329 on meal-stimulated pancreaticobiliary output in humans.  Gastroenterology. 1992;  102 1742-1751
  • 11 Fried M, Mayer E A, Jansen J B. et al . Temporal relationships of cholecystokinin release, pancreatobiliary secretion, and gastric emptying of a mixed meal.  Gastroenterology. 1988;  95 1344-1350
  • 12 Malagelada J R, Go V L, Summerskill W H. Different gastric, pancreatic, and biliary responses to solid-liquid or homogenized meals.  Dig Dis Sci. 1979;  24 101-110
  • 13 Miller L J, Clain J E, Malagelada J R, Go V L. Control of human postprandial pancreatic exocrine secretion: a function of the gastroduodenal region.  Dig Dis Sci. 1979;  24 150-154
  • 14 Owyang C, Louie D S, Tatum D. Feedback regulation of pancreatic enzyme secretion. Suppression of cholecystokinin release by trypsin.  J Clin Invest. 1986;  77 2042-2047
  • 15 Wisen O, Hellstrom P M, Johansson C. Meal energy density as a determinant of postprandial gastrointestinal adaptation in man.  Scand J Gastroenterol. 1993;  28 737-743
  • 16 Keller J, Runzi M, Goebell H, Layer P. Duodenal and ileal nutrient deliveries regulate human intestinal motor and pancreatic responses to a meal.  Am J Physiol. 1997;  272 G632-G637
  • 17 Horowitz M, Edelbroek M A, Wishart J M, Straathof J W. Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects.  Diabetologia. 1993;  36 857-862
  • 18 Brunner H, Northfield T C, Hofmann A F, Go V L, Summerskill W H. Gastric emptying and secretion of bile acids, cholesterol, and pancreatic enzymes during digestion. Duodenal perfusion studies in healthy subjects.  Mayo Clin Proc. 1974;  49 851-860
  • 19 Dooley C P, Valenzuela J E. Duodenal volume and osmoreceptors in the stimulation of human pancreatic secretion.  Gastroenterology. 1984;  86 23-27
  • 20 Holtmann G, Kelly D G, Sternby B, DiMagno E P. Survival of human pancreatic enzymes during small bowel transit: effect of nutrients, bile acids, and enzymes.  Am J Physiol. 1997;  273 G553-G558
  • 21 Sun W M, Houghton L A, Read N W, Grundy D G, Johnson A G. Effect of meal temperature on gastric emptying of liquids in man.  Gut. 1988;  29 302-305
  • 22 Sun W M, Penagini R, Hebbard G. et al . Effect of drink temperature on antropyloroduodenal motility and gastric electrical activity in humans.  Gut. 1995;  37 329-334
  • 23 McArthur K E, Feldman M. Gastric acid secretion, gastrin release, and gastric emptying in humans as affected by liquid meal temperature.  Am J Clin Nutr. 1989;  49 51-54
  • 24 Boivin M, Lanspa S J, Zinsmeister A R, Go V L, DiMagno E P. Are diets associated with different rates of human interdigestive and postprandial pancreatic enzyme secretion?.  Gastroenterology. 1990;  99 1763-1771
  • 25 Tiscornia O M, Cresta M A, de Lehmann E S, Celener D, Dreiling D A. Effects of sex and age on pancreatic secretion.  Int J Pancreatol. 1986;  1 95-118
  • 26 Laugier R, Bernard J P, Berthezene P, Dupuy P. Changes in pancreatic exocrine secretion with age: pancreatic exocrine secretion does decrease in the elderly.  Digestion. 1991;  50 202-211
  • 27 Fried M, Abramson S, Meyer J H. Passage of salivary amylase through the stomach in humans.  Dig Dis Sci. 1987;  32 1097-1103
  • 28 Hildebrand P, Beglinger C, Gyr K. et al . Effects of a cholecystokinin receptor antagonist on intestinal phase of pancreatic and biliary responses in man.  J Clin Invest. 1990;  85 640-646
  • 29 Dagorn J C, Michel R, Morisset J. Nonparallel courses of intrapancreatic levels of exportable enzymes after a fatty meal.  Proc Soc Exp Biol Med. 1976;  151 608-610
  • 30 Ekelund K, Johansson C. Output of bile and pancreatic enzymes after test meals with different fat content. Influence of body weight on pancreatic enzyme composition.  Acta Physiol Scand. 1980;  110 161-165
  • 31 Maouyo D, Morisset J. Modulation of pancreatic secretion of individual digestive enzymes in octreotide (SMS 201-995)-infused rats.  Pancreas. 1997;  14 47-57
  • 32 Maouyo D, Morisset J. Amazing pancreas: specific regulation of pancreatic secretion of individual digestive enzymes in rats.  Am J Physiol. 1995;  268 E349-E359
  • 33 Maouyo D, Guan D, Rivard N, Morisset J. Modulation of the relationship between amylase and chymotrypsinogen secretion in atropine- and MK329-infused rats.  Pancreas. 1995;  11 330-340
  • 34 Borgström B, Dahlqvist A, Lundh G, Sjövall J. Studies of intestinal digestion and absorption in the human.  J Clin Invest. 1957;  36 1521-1536
  • 35 Layer P, Go V L, DiMagno E P. Fate of pancreatic enzymes during small intestinal aboral transit in humans.  Am J Physiol. 1986;  251 G475-G480
  • 36 Layer P, Jansen J B, Cherian L, Lamers C B, Goebell H. Feedback regulation of human pancreatic secretion. Effects of protease inhibition on duodenal delivery and small intestinal transit of pancreatic enzymes.  Gastroenterology. 1990;  98 1311-1319
  • 37 Layer P, Baumann J, Hellmann C, von der Ohe M, Gröger G, Goebell H. Effect of luminal protease inhibition on prandial nutrient digestion during small intestinal chyme transit.  Pancreas. 1990;  5 718
  • 38 Granger M, Abadie B, Marchis-Mouren G. Limited action of trypsin on porcine pancreatic amylase: characterization of the fragments.  FEBS Lett. 1975;  56 189-193
  • 39 Thiruvengadam R, DiMagno E P. Inactivation of human lipase by proteases.  Am J Physiol. 1988;  255 G476-G481
  • 40 Layer P, Keller J. Pancreatic enzymes: secretion and luminal nutrient digestion in health and disease.  J Clin Gastroenterol. 1999;  28 3-10
  • 41 Layer P, Schlesinger T, Groger G, Goebell H. Modulation of human periodic interdigestive gastrointestinal motor and pancreatic function by the ileum.  Pancreas. 1993;  8 426-432
  • 42 Holgate A M, Read N W. Effect of ileal infusion of intralipid on gastrointestinal transit, ileal flow rate, and carbohydrate absorption in humans after ingestion of a liquid meal.  Gastroenterology. 1985;  88 1005-1011
  • 43 Kolbel C, Layer P, Hotz J, Goebell H. Effect of an acid protected, micro-encapsulated pancreatin preparation on pancreatogenic steatorrhea.  Med Klin. 1986;  81 85-86
  • 44 Layer P, Peschel S, Schlesinger T, Goebell H. Human pancreatic secretion and intestinal motility: effects of ileal nutrient perfusion.  Am J Physiol. 1990;  258 G196-G201
  • 45 Read N W, McFarlane A, Kinsman R I. et al . Effect of infusion of nutrient solutions into the ileum on gastrointestinal transit and plasma levels of neurotensin and enteroglucagon.  Gastroenterology. 1984;  86 274-280
  • 46 Soper N J, Chapman N J, Kelly K A, Brown M L, Phillips S F, Go V L. The „ileal brake” after ileal pouch-anal anastomosis.  Gastroenterology. 1990;  98 111-116
  • 47 Spiller R C, Trotman I F, Adrian T E, Bloom S R, Misiewicz J J, Silk D B. Further characterisation of the „ileal brake” reflex in man - effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.  Gut. 1988;  29 1042-1051
  • 48 Jain N K, Boivin M, Zinsmeister A R, Brown M L, Malagelada J R, DiMagno E P. Effect of ileal perfusion of carbohydrates and amylase inhibitor on gastrointestinal hormones and emptying.  Gastroenterology. 1989;  96 377-387
  • 49 Levitt M D, Hirsh P, Fetzer C A, Sheahan M, Levine A S. H2 excretion after ingestion of complex carbohydrates.  Gastroenterology. 1987;  92 383-389
  • 50 Stephen A M, Haddad A C, Phillips S F. Passage of carbohydrate into the colon. Direct measurements in humans.  Gastroenterology. 1983;  85 589-595
  • 51 Layer P, Groger G, Grandt D, Cherian L. The terminal ileum as a co-regulator of cyclic interdigestive pancreatic secretion in man.  Med Klin. 1993;  88, Suppl 1 15-17
  • 52 Welch I M, Cunningham K M, Read N W. Regulation of gastric emptying by ileal nutrients in humans.  Gastroenterology. 1988;  94 401-404
  • 53 Adrian T E, Ferri G L, Bacarese-Hamilton A J, Fuessl H S, Polak J M, Bloom S R. Human distribution and release of a putative new gut hormone, peptide YY.  Gastroenterology. 1985;  89 1070-1077
  • 54 Keller J, Franke A, Rippel K, Holst J J, Goebell H, Layer P. Termination of digestive pancreatic secretory and intestinal motor responses: importance of GLP-1 and PYY.  Digestion. 1999;  60 383
  • 55 Layer P, Holst J J, Grandt D, Goebell H. Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of gastric acid secretion in humans.  Dig Dis Sci. 1995;  40 1074-1082
  • 56 Layer P, Ohe M, Muller M K, Beglinger C. Effects of somatostatin on the exocrine pancreas.  Scand J Gastroenterol. 1991;  26 129-136
  • 57 Savage A P, Adrian T E, Carolan G, Chatterjee V K, Bloom S R. Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers.  Gut. 1987;  28 166-170
  • 58 Wettergren A, Schjoldager B, Mortensen P E, Myhre J, Christiansen J, Holst J J. Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man.  Dig Dis Sci. 1993;  38 665-673
  • 59 Layer P, DiMagno E P. Early and late onset in idiopathic and alcoholic chronic pancreatitis. Different clinical courses.  Surg Clin North Am. 1999;  79 847-860
  • 60 Lin Y, Tamakoshi A, Hayakawa T, Ogawa M, Ohno Y. Associations of alcohol drinking and nutrient intake with chronic pancreatitis: findings from a case-control study in Japan.  Am J Gastroenterol. 2001;  96 2622-2627
  • 61 DiMagno E P, Malagelada J R, Go V L. Relationship between alcoholism and pancreatic insufficiency.  Ann N Y Acad Sci. 1975;  252 200-207
  • 62 Gullo L, Barbara L, Labo G. Effect of cessation of alcohol use on the course of pancreatic dysfunction in alcoholic pancreatitis.  Gastroenterology. 1988;  95 1063-1068
  • 63 Lin Y, Tamakoshi A, Hayakawa T, Ogawa M, Ohno Y. Cigarette smoking as a risk factor for chronic pancreatitis: a case-control study in Japan. Research Committee on Intractable Pancreatic Diseases.  Pancreas. 2000;  21 109-114
  • 64 Layer P, Yamamoto H, Kalthoff L, Clain J E, Bakken L J, DiMagno E P. The different courses of early- and late-onset idiopathic and alcoholic chronic pancreatitis.  Gastroenterology. 1994;  107 1481-1487
  • 65 Layer P, Keller J, Lankisch A. Pancreatic enzyme replacement therapy.  Curr Gastroenterol Rep. 2001;  3 101-108
  • 66 DiMagno E P, Go V L, Summerskill W H. Relations between pancreatic enzyme outputs and malabsorption in severe pancreatic insufficiency.  N Engl J Med. 1973;  288 813-815
  • 67 Sternby B, Holtmann G, Kelly D, DiMagno E. Effect of gastric or duodenal nutrient infusion on gastric and pancreatic lipase secretion.  Gastroenterology. 1992;  102 292
  • 68 Layer P, Zinsmeister A R, DiMagno E P. Effects of decreasing intraluminal amylase activity on starch digestion and postprandial gastrointestinal function in humans.  Gastroenterology. 1986;  91 41-48
  • 69 Layer P, von der Ohe M, Gröger G, Dicke D, Goebell H. Luminal availability and digestive efficacy of substituted enzymes in pancreatic insufficiency.  Pancreas. 1992;  7 745
  • 70 Layer P, Peschel S, Schlesinger T, Goebell H. Human pancreatic secretion and intestinal motility: effects of ileal nutrient perfusion.  Am J Physiol. 1990;  258 G196-G201
  • 71 Layer P, von der Ohe M, Holst J J. et al . Altered postprandial motility in chronic pancreatitis: role of malabsorption.  Gastroenterology. 1997;  112 1624-1634
  • 72 Caliari S, Benini L, Sembenini C, Gregori B, Carnielli V, Vantini I. Medium-chain triglyceride absorption in patients with pancreatic insufficiency.  Scand J Gastroenterol. 1996;  31 90-94
  • 73 Layer P, Holtmann G. Pancreatic enzymes in chronic pancreatitis.  Int J Pancreatol. 1994;  15 1-11
  • 74 Meyer J H, Lake R. Mismatch of duodenal deliveries of dietary fat and pancreatin from enterically coated microspheres.  Pancreas. 1997;  15 226-235
  • 75 Heijerman H G, Lamers C B, Bakker W. Omeprazole enhances the efficacy of pancreatin (pancrease) in cystic fibrosis.  Ann Intern Med. 1991;  114 200-201
  • 76 Mossner J, Keim V, Niederau C. et al . Guidelines for therapy of chronic pancreatitis. Consensus Conference of the German Society of Digestive and Metabolic Diseases. Halle 21 - 23 November 1996.  Z Gastroenterol. 1996;  36 359-367

Prof. Dr. Peter Layer

Israelitisches Krankenhaus

Orchideenstieg 14

22297 Hamburg

Phone: + 49/40/51125-211

Fax: + 49/40/51125-227

Email: layer@ik-h.de