conservative treatment and the role of replacement therapy with pancreatic enzymes
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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 Medical University Graz, Austria. Exocrine Pancreatic Insufficiency Clinical Problems. Abdominal pain, steatorrhoea, meteorism - PowerPoint PPT PresentationTRANSCRIPT
Conservative Treatment and the Role of Replacement
Therapy with Pancreatic Enzymes
Heinz F. HammerAssoc. Prof. of Internal Medicine and
GastroenterologyMedical University Graz, Austria
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
Pancreatic MaldigestionPancreatic MaldigestionLoss of parenchyma
CP, cystic fibrosis, resection, pancreatic tumours
Inhibition 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,
diabetes
adaped from Keller & Layer, GUT 2005, 54 (Suppl. 6): vi9-29
Pancreatic Calcifications
Red Flags for Exocrine Pancreatic Insufficiency: Disappearance of Pain and
Appearance of Calcifications Lankisch MR, Mayo Clin Proc. 2001;76:242-51
IJCP .. idiopath. Juvenile, ISCP .. idiopath. senileHP ….. Hereditäre, ACP … alkoholische
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?
Lipase Output After a Mixed MealKeller J et al, Am J Physiol 1997;272:G632-G637
Interdigestive range
0 1 2 3 4 5 60
1000
2000
3000
4000
5000
6000
7000
Lipa
se,
U/m
in
Postprandial h
Lipase
n =14x ± SE
Cumulative postprandial lipase output 500 – 1000 kU
Steatorrhoea and Pancreatic Insufficiency
adapted from Di Magno EP et al. NEJM 1973:288:813
0
1
2
3
4
5
0 1 2 3
Postprandial Duodenal Lipase in Health and Chronic Pancreatitis
DiMagno EP et al, N Engl J Med 1977;296:1318-22
Hours postprandially
Lip
ase,
kU
/min
Health (Secretion)
0
10
20
30
40
0 1 2 3
Lip
ase,
U/m
in
CP (Pancreatin Supplementation)
cumulative 25 - 50 kU Lipase prevent steatorrhoea
Digestion of Fat is the Determining Factor in Pancreatic Insufficiency
1.Lipase secretion is lost faster than secretion of other enzymes
Chronic Pancreatitis: Alcohol Use and Loss of Function
DiMagno et al, N Y Acad Sci 1975;252:200-7
LipaseTrypsin
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25
% M
axim
al E
nzym
e O
utpu
t
Years Of Alcohol Consumption
Malabsorption Threshold
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
Duodenale Amylase and Starch Malabsorption
Layer P et al, Gastroenterology 1986;91:41-48
Duodenal Amylase, % normal
Sta
rch
mal
abso
rptio
n %
Salivary amylaseBrush Border Oligosaccharidases
0
20
40
60
80
100
0 20 40 60 80 100 120
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
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 lipase4.Fast destruction of lipase in luminal pH < 4.0
in chronic pancreatitis
Intraduodenal pH in Chronic Pancreatitis
DiMagno EP et al, N Engl J Med 1977;296:1318-22
pH 4 = irreversible destruction of Lipase
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?
Effect of Pancreatic Enzymes on Fecal Fat
Cochrane Database of Systematic Reviews 2009; CD006302
• 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
Pancreatic Enzyme Replacement
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
• 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:
Pancreatic Enzyme Replacement:Choose the Right Product
100.H07
Acid resistant tablets> 2-3 mm: Postprandial retention,no mixing with food
Acid resistant pH-sensitive microspheres
≤2-3mm:mixing with food in
stomach,
prandialemptying,duodenalliberation
Unprotected enzymes: Irreversible Destruction at pH <4
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
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