Presentation on theme: "Conservative Treatment"— Presentation transcript:
1Conservative Treatment and the Role of Replacement Therapy with Pancreatic EnzymesHeinz F. HammerAssoc. Prof. of Internal Medicine and GastroenterologyMedical University Graz, Austria
2Exocrine Pancreatic Insufficiency Clinical Problems Abdominal pain, steatorrhoea, meteorismWeight loss - malnutritionDeficiency of fat soluble vitamins (esp. Vit D)Diabetes mellitusObstructionBiliaryduodenalDisease related complicationspancreatic carcinoma
3Pancreatic Maldigestion Loss of parenchymaCP, cystic fibrosis, resection, pancreatic tumoursInhibition or inactivation of secretionobstruction (papillary or head tumours),decreased endogenous stimulation (celiac disease, Crohn’s, diabetes mellitus)inactivation (ZES)Postcibal asynchrony gastric surgery, short bowel, Crohn’s, diabetesadaped from Keller & Layer, GUT 2005, 54 (Suppl. 6): vi9-29
5Red Flags for Exocrine Pancreatic Insufficiency: Disappearance of Pain and Appearance of Calcifications Lankisch MR, Mayo Clin Proc. 2001;76:242-51IJCP .. idiopath. Juvenile, ISCP .. idiopath. senileHP ….. Hereditäre, ACP … alkoholische
6Enzyme Replacement Therapy Pancreatic physiology: what do you need to know about pancreatic secretion in order to understand enzyme replacement therapyTreatmentWhich dosage?Are all products the same?
7Lipase Output After a Mixed Meal Keller J et al, Am J Physiol 1997;272:G632-G637 Cumulative postprandial lipase output 500 – 1000 kUl1234561000200030004000500060007000Lipase, U/minPostprandial hLipasen =14 x ± SEJK from my group could show that the duration of the pancreatic postprandial response, defined by the return of secretion into the id range, correlates quite well with the duration of the motor response, i.e., the fed patternInterdigestive range
8Steatorrhoea and Pancreatic Insufficiency adapted from Di Magno EP et al. NEJM 1973:288:813
9Postprandial Duodenal Lipase in Health and Chronic Pancreatitis DiMagno EP et al, N Engl J Med 1977;296:Lipase, U/minCP (Pancreatin Supplementation)Health (Secretion)cumulative kU Lipase prevent steatorrhoeaLipase, kU/min4 - 6 fold increase over fasting secretion for the duration of the digestive periodWhich components cause stimulation? For one, protein and their breakdown productsHours postprandially
10Digestion of Fat is the Determining Factor in Pancreatic Insufficiency Lipase secretion is lost faster than secretion of other enzymes
11Chronic Pancreatitis: Alcohol Use and Loss of Function DiMagno et al, N Y Acad Sci 1975;252:200-7 10203040506070809010051525% Maximal Enzyme OutputYears Of Alcohol ConsumptionMalabsorption ThresholdLipaseTrypsinWhich could be corrected by supplementing enzymesThis suggested that intraileal nutrients might play a role, e.g. a shift of balance between stimul duod nutr and inhibit ileal nutrient.
12Digestion of Fat is the Determining Factor in Pancreatic Insufficiency Lipase secretion is lost faster than secretion of other enzymesIn contrast to other enzymes, there is no adequate endogenous substitution for lipase
13Duodenale Amylase and Starch Malabsorption Layer P et al, Gastroenterology 1986;91:41-48 10080Salivary amylaseBrush Border Oligosaccharidases60Starch malabsorption %402020406080100120Duodenal Amylase, % normal
14Digestion of Fat is the Determining Factor in Pancreatic Insufficiency Lipase secretion is lost faster than secretion of other enzymesIn contrast to other enzymes, there is no adequate endogenous substitution for lipaseFast luminal destruction of lipase (Layer P et al, Am J Physiol 1986;251:G475)Lipase: < 5% reach the ileumTrypsin: 20% reach the ileumAmylase: >35% reach the ileum
15Digestion of Fat is the Determining Factor in Pancreatic Insufficiency Lipase secretion is lost faster than secretion of other enzymesIn contrast to other enzymes, there is no adequate endogenous substitution for lipaseFast luminal destruction of lipaseFast destruction of lipase in luminal pH < 4.0 in chronic pancreatitis
16Intraduodenal pH in Chronic Pancreatitis DiMagno EP et al, N Engl J Med 1977;296:1318-22 pH 4 = irreversible destruction of Lipase
17Enzyme Replacement Therapy Pancreatic physiology: what do you need to know about pancreatic secretion in order to understand enzyme replacement therapyTreatmentWhich dosage?Are all products the same?
18Effect of Pancreatic Enzymes on Fecal Fat Cochrane Database of Systematic Reviews 2009; CD006302
19Pancreatic Enzyme Replacement Individual dosing (severity of the disease, composition of food, body weight)~ ( units/g lipase units) digest 1 g of fatAdults: at least ( ) units of lipase per main meal, units per snackAdministrationwith every meal or snackin individual portions during the meal, or short time after startingLayer, P. et al Current Gastroenterological Reports, 2001, 3:
20Pancreatic Enzyme Replacement Response to enzyme therapy may be monitored throughan assessment of symptoms or,more objectively, through 72-hour stool weight quantification, or even better72-hour stool fat quantification
21Efficacy of Enzyme Replacement Therapy is Influenced by: Denaturation of enzymes (lipase!) by gastric acidImproper timing of enzymesCoexisting small-intestinal mucosal diseaseRapid intestinal transitNoncomplianceAlternate diagnosis (eg. pancreatic cancer)Effects of diabetes:disturbance of motility, stasis,bacterial overgrowth,impairment of mucosal regeneration and villus function
22Pancreatic Enzyme Replacement: Choose the Right Product Unprotected enzymes: Irreversible Destruction at pH <4Acid resistant pH-sensitive microspheres ≤2-3mm: mixing with food in stomach,prandial emptying, duodenal liberationAcid resistant tablets > 2-3 mm: Postprandial retention, no mixing with food
23Chronic Pancreatitis and Exocrine Pancreatic Insufficiency Decreasing insulin andglucagon secretionIncreasing need of lipaseSteatorrhoeaIncreasing calcificationsAbnormal fecal elastaseDecreasing painRemaining parenchymaYears to decades
24Questions 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 developEnzyme replacement therapy needs to replace 10 % of normal postprandial lipase output in order to prevent steatorrhoeaDigestion of protein is the determining factor in pancreatic insufficiencyAdults should receive between and units of lipase per main meal, and units per snackResponse to enzyme therapy may be monitored through measurement of fecal elastase