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Conservative Treatment and the Role of Replacement Therapy with Pancreatic Enzymes Heinz F. Hammer Assoc. Prof. of Internal Medicine and Gastroenterology.

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Presentation on theme: "Conservative Treatment and the Role of Replacement Therapy with Pancreatic Enzymes Heinz F. Hammer Assoc. Prof. of Internal Medicine and Gastroenterology."— Presentation transcript:

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 Insufficiency Clinical 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 Pancreatic Maldigestion Loss of parenchyma CP, cystic fibrosis, resection, pancreatic tumours Inhibition or inactivation of secretion obstruction (papillary or head tumours), decreased endogenous stimulation (celiac disease, Crohns, diabetes mellitus) inactivation (ZES) Postcibal asynchrony gastric surgery, short bowel, Crohns, diabetes 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 Calcifications Lankisch MR, Mayo Clin Proc. 2001;76: 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 Lipase Output After a Mixed Meal Keller J et al, Am J Physiol 1997;272:G632-G637 Interdigestive range Cumulative postprandial lipase output 500 – 1000 kU

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

9 Postprandial Duodenal Lipase in Health and Chronic Pancreatitis DiMagno EP et al, N Engl J Med 1977;296: Hours postprandially Lipase, kU/min Health (Secretion) Lipase, U/min CP (Pancreatin Supplementation) cumulative kU Lipase prevent steatorrhoea

10 Digestion of Fat is the Determining Factor in Pancreatic Insufficiency 1.Lipase secretion is lost faster than secretion of other enzymes

11 Chronic Pancreatitis: Alcohol Use and Loss of Function DiMagno et al, N Y Acad Sci 1975;252:200-7 Lipase Trypsin % Maximal Enzyme Output Years Of Alcohol Consumption Malabsorption Threshold

12 Digestion of Fat is the Determining Factor in Pancreatic Insufficiency 1.Lipase secretion is lost faster than secretion of other enzymes 2.In contrast to other enzymes, there is no adequate endogenous substitution for lipase

13 Duodenale Amylase and Starch Malabsorption Layer P et al, Gastroenterology 1986;91:41-48 Duodenal Amylase, % normal Starch malabsorption % Salivary amylase Brush Border Oligosaccharidases

14 Digestion of Fat is the Determining Factor in Pancreatic Insufficiency 1.Lipase secretion is lost faster than secretion of other enzymes 2.In contrast to other enzymes, there is no adequate endogenous substitution for lipase 3.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 1.Lipase secretion is lost faster than secretion of other enzymes 2.In contrast to other enzymes, there is no adequate endogenous substitution for lipase 3.Fast luminal destruction of lipase 4.Fast destruction of lipase in luminal pH < 4.0 in chronic pancreatitis

16 Intraduodenal pH in Chronic Pancreatitis DiMagno EP et al, N Engl J Med 1977;296: 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 Fat Cochrane Database of Systematic Reviews 2009; CD006302

19 Individual dosing (severity of the disease, composition of food, body weight) ~ ( units/g lipase units) digest 1 g of fat Adults: at least ( ) units of lipase per main meal, 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: Pancreatic Enzyme Replacement

20 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 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 Efficacy of Enzyme Replacement Therapy is Influenced by:

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

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

24 Questions Agree 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 and units of lipase per main meal, and units per snack Response to enzyme therapy may be monitored through measurement of fecal elastase


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