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Conservative Treatment and the Role of Replacement Therapy with Pancreatic Enzymes

Conservative Treatment and the Role of Replacement Therapy with Pancreatic Enzymes Heinz F. Hammer Assoc. Prof. of Internal Medicine and Gastroenterology Medical University Graz, Austria. Exocrine Pancreatic Insufficiency Clinical Problems. Abdominal pain, steatorrhoea, meteorism

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Conservative Treatment and the Role of Replacement Therapy with Pancreatic Enzymes

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  1. Conservative Treatment and the Role of Replacement Therapy with Pancreatic Enzymes Heinz F. Hammer Assoc. Prof. of Internal Medicine and Gastroenterology Medical University Graz, Austria

  2. Exocrine Pancreatic InsufficiencyClinical Problems • Abdominal pain, steatorrhoea, meteorism • Weight loss - malnutrition • Deficiency of fat soluble vitamins (esp. Vit D) • Diabetes mellitus • Obstruction • Biliary • duodenal • Disease related complications • pancreatic carcinoma

  3. Loss of parenchyma CP, cystic fibrosis, resection, pancreatic tumours Inhibition or inactivation of secretion obstruction (papillary or head tumours), decreased endogenous stimulation (celiac disease, Crohn’s, diabetes mellitus) inactivation (ZES) • Postcibal asynchronygastric surgery, short bowel, Crohn’s, diabetes Pancreatic Maldigestion adaped from Keller & Layer, GUT 2005, 54 (Suppl. 6): vi9-29

  4. Pancreatic Calcifications

  5. Red Flags for Exocrine Pancreatic Insufficiency: Disappearance of Pain and Appearance of CalcificationsLankisch MR, Mayo Clin Proc. 2001;76:242-51 IJCP .. idiopath. Juvenile, ISCP .. idiopath. senile HP ….. Hereditäre, ACP … alkoholische

  6. Enzyme Replacement Therapy • Pancreatic physiology: what do you need to know about pancreatic secretion in order to understand enzyme replacement therapy • Treatment • Which dosage? • Are all products the same?

  7. 7000 6000 l Lipase 5000 l l l 4000 l n =14x ± SE l l Lipase, U/min l l l 3000 l l l 2000 l l l l l l l l l Interdigestive range l 1000 l l l 0 0 1 2 3 4 5 6 Postprandial h Lipase Output After a Mixed MealKeller J et al, Am J Physiol 1997;272:G632-G637 Cumulative postprandial lipase output 500 – 1000 kU

  8. Steatorrhoea and Pancreatic Insufficiencyadapted from Di Magno EP et al. NEJM 1973:288:813

  9. CP (Pancreatin Supplementation) Lipase, U/min Postprandial Duodenal Lipase in Health and Chronic PancreatitisDiMagno EP et al, N Engl J Med 1977;296:1318-22 Health (Secretion) cumulative 25 - 50 kU Lipase prevent steatorrhoea Lipase, kU/min Hours postprandially

  10. Digestion of Fat is the Determining Factor in Pancreatic Insufficiency Lipase secretion is lost faster than secretion of other enzymes

  11. 100 90 80 70 60 % Maximal Enzyme Output 50 40 Trypsin Lipase 30 20 Malabsorption Threshold 10 0 0 5 10 15 20 25 Years Of Alcohol Consumption Chronic Pancreatitis: Alcohol Use and Loss of FunctionDiMagno et al, N Y Acad Sci 1975;252:200-7

  12. Digestion of Fat is the Determining Factor in Pancreatic Insufficiency Lipase secretion is lost faster than secretion of other enzymes In contrast to other enzymes, there is no adequate endogenous substitution for lipase

  13. Duodenale Amylase and Starch MalabsorptionLayer P et al, Gastroenterology 1986;91:41-48 100 80 Salivary amylase Brush Border Oligosaccharidases 60 Starch malabsorption % 40 20 0 0 20 40 60 80 100 120 Duodenal Amylase, % normal

  14. Digestion of Fat is the Determining Factor in Pancreatic Insufficiency • Lipase secretion is lost faster than secretion of other enzymes • In contrast to other enzymes, there is no adequate endogenous substitution for lipase • Fast luminal destruction of lipase (Layer P et al, Am J Physiol 1986;251:G475) • Lipase: < 5% reach the ileum • Trypsin: 20% reach the ileum • Amylase: >35% reach the ileum

  15. Digestion of Fat is the Determining Factor in Pancreatic Insufficiency Lipase secretion is lost faster than secretion of other enzymes In contrast to other enzymes, there is no adequate endogenous substitution for lipase Fast luminal destruction of lipase Fast destruction of lipase in luminal pH < 4.0 in chronic pancreatitis

  16. Intraduodenal pH in Chronic PancreatitisDiMagno EP et al, N Engl J Med 1977;296:1318-22 pH 4 = irreversible destruction of Lipase

  17. Enzyme Replacement Therapy • Pancreatic physiology: what do you need to know about pancreatic secretion in order to understand enzyme replacement therapy • Treatment • Which dosage? • Are all products the same?

  18. Effect of Pancreatic Enzymes on Fecal FatCochrane Database of Systematic Reviews 2009; CD006302

  19. Pancreatic Enzyme Replacement • Individual dosing (severity of the disease, composition of food, body weight) • ~ 2.000 (1000 - 4000 units/g lipase units) digest 1 g of fat • Adults: at least 40 000 (20 000-75 000) units of lipase per main meal, 10 000-25 000 units per snack • Administration • with every meal or snack • in individual portions during the meal, or short time after starting Layer, P. et al Current Gastroenterological Reports, 2001, 3: 101-108

  20. Pancreatic Enzyme Replacement • Response to enzyme therapy may be monitored through • an assessment of symptoms or, • more objectively, through 72-hour stool weight quantification, or even better • 72-hour stool fat quantification

  21. Efficacy of Enzyme Replacement Therapy is Influenced by: • Denaturation of enzymes (lipase!) by gastric acid • Improper timing of enzymes • Coexisting small-intestinal mucosal disease • Rapid intestinal transit • Noncompliance • Alternate diagnosis (eg. pancreatic cancer) • Effects of diabetes: • disturbance of motility, stasis, • bacterial overgrowth, • impairment of mucosal regeneration and villus function

  22. Unprotected enzymes: Irreversible Destruction at pH <4 Acid resistant pH-sensitive microspheres≤2-3mm:mixing with food in stomach, prandialemptying,duodenalliberation Acid resistant tablets> 2-3 mm:Postprandial retention,no mixing with food Pancreatic Enzyme Replacement: Choose the Right Product

  23. Chronic Pancreatitis and Exocrine Pancreatic Insufficiency Decreasing insulin and glucagon secretion Increasing need of lipase Steatorrhoea Increasing calcifications Abnormal fecal elastase Decreasing pain Remaining parenchyma Years to decades

  24. QuestionsAgree or Disagree? • Pancreatic calcifications indicate that exocrine pancreatic insufficiency is likely to be present. • Appearance of pain in chronic pancreatitis should make you suspicious of pancreatic insufficiency to develop • Enzyme replacement therapy needs to replace 10 % of normal postprandial lipase output in order to prevent steatorrhoea • Digestion of protein is the determining factor in pancreatic insufficiency • Adults should receive between 20 000 and 75 000 units of lipase per main meal, and 10 000-25 000 units per snack • Response to enzyme therapy may be monitored through measurement of fecal elastase

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