PANCREAS INSUFFICIENCY
Lipase
Micelles
Bile acids
(Conc. >CMC)
Fatty acid or monoglyceride
Polar end of bile acid
Hydroxyl groups of bile acids
Bile acid
HUMAN PANCREATIC LIPASE
Interfacial enzyme,active in the lipidwater interface
Dependent on clean interface for
lipolysis
Colipase binds to lipase in presence of
bile salts
Lipase is specific for primary esterbond
Lipase is rapidly and irreversibly
inactivated at pH<4
Chylomicron Formation and Secretion
FA and MG
Uptake from
micellar solution
Mitochondria
Esterification
Granularendoplasmicreticulum
Surface
stabilization
Chylomicron
formation
Addition of
lipoprotein
Nucleus
Secretion via
intercellular spaces
into lacteals
Golgi material
Pancreatic Exocrine Function
 Normal post-prandial pancreatic secretion is ±70% of
maximal secretory capacity or 4–5 times the basal rate
 Post-prandial secretion lasts for about 4 hours
 Total intraduodenal lipase output varies from
300,000 to 500,000 U/meal
 Minimum pancreatic function of 10% of normal is
necessary for adequate lipid digestion, corresponding
to ± 30,000–50,000 U lipase in the duodenum
 Amount of lipase, to be added to meals, varies
depending upon degree in insufficiency and degree of
gastric/duodenal denaturation
Pancreatic Exocrine Insufficiency
Steatorrhea (mild:7–10 g/d; moderate:
10–20 g/d; severe: >20 g/d)
Bile salt precipitation due to low duodenal
pH (bicarbonate deficiency)→increased
fecal bile salt loss
Impaired CCK and GIP release→sluggish
gallbladder emptying
Malabsorption of lipid-soluble
vitamins,cholesterol
SYMPTOMATOLOGY OF EXOCRINE
PANCREATIC INSUFFICIENCY
 Steatorrhea and creatorrhea causes
 -Abdominal complaints
bloating,pain,cramps
urgency,diarrhea,foul smelling stools
 -Generalised symptoms
-
weight loss
fatigue,loss of energy
sympoms related to vitamin deficiencies
-
-
Exocrine Pancreatic Insufficiency
Diagnosis
• Suspicion because of associated medical condition and:


clinical history of steatorrhea
weight loss
• Laboratory tests



fat balance test (not specific)
non-invasive pancreatic function test
• fecal elastase, fecal chymotrypsin, PABA test
invasive direct pancreatic function test (gold standard)
• secretin test
Indications for Pancreatic Enzyme
Therapy
 Exocrine pancreatic insufficiency causing
– any moderate / severe steatorrhea
– any steatorrhea with weight loss
– chronic / watery diarrhea
– dyspeptic symptoms
 Unrelenting pain in chronic pancreatitis
(inhibition of pancreatic secretory drive by
negative feedback) (non-enteric coated
preparations)
Pancreatic Enzyme Preparations
Non-Enteric Coated Preparations
Pancreatin powder / granulate
 blends well with food
 unpalatable
 denaturation in acid / peptic milieu
 hyperuricosuria
Pancreatin tablet / capsule
 inadequate dispersion into the meal
 neutral taste
 denaturation in acid / peptic milieu
Pancreatic Enzyme Preparations
Enteric Coated Preparations
Enteric-coated tablet / capsule (dissolving at pH >5)
 prolonged gastric retention causing de-synchronisation
 failed or delayed dissolution when duodenal pH is low
(lack of bicarbonate)
Enteric-coated microspheres (dissolving at pH >5)
 premature gastric dissolution when pH >5 during early
phase of meal
 delayed gastric emptying of particles >1.4 mm
 failed or delayed dissolution when duodenal pH is low
Enteric Coated Mini-Doses Preparation
Galenic aspects
gelatin capsule
pH dependent enteric coated layer
pancreatin
Microsphere Pancreatic Enzyme Preparations
Lipase
Amylase
Protease sphere diam.
Creon
8,000
9,000
450
1.4 (1.2–1.7)
Pancrease
5,000
2,900
330
2.0 (1.7–2.2)
Panzytrat
25,000
22,500
1,250
2.0
Creon forte
25,000
18,000
1,000
1.4 (1.2–1.8)
 microspheres larger than 1.4 mm empty more
slowly than solid phase of the meal
 release of enzymes from microspheres is slow,
depending upon pH and ionic strength of medium
Pancreatic Enzyme Preparations
Course of dissolution of enteric oat
100
90
80
70
60
50
40
30
20
10
0
Creon
Creon Forte
Pancrease
Pancrease HL
Panzytrat
5,0
5.2
5.4
5.6
5.8
6.0
Pancreatic Enzyme Preparations
Dosage recommendations
• Enzyme supplementation during all meals
• Main meal: 25.000 to 75.000 FIP units lipase of EC preparation
• In-between snacks: 5.000 to 25.000 FIP lipase of EC preparation
• Dosage should be adjusted for individual patient
• Addition of H2-receptor blocker or protonpump inhibitor
Pancreatic Exocrine Insufficiency
Dietary recommendations
 Abstinence from alcohol
 In principle NO limitation of fat content of food
(<60 g/d) (unpalatable; risk of deficit of essential
fatty acids e.g. linoleic acid) except therapy failure
 Frequent small meals
 Reduction in fiber content (fiber inhibits
pancreatic enzymes)
 Medium chain triglycerides (C6-C12)
(80–120 g/d) in case of insufficiently corrected
steatorrhea and weight loss
Therapy of Pancreatic Insufficiency
Treatment failure
• Acid related
– inactivation of lipase
– precipitation of bile salts
– enteric coat dissolves too distally
• Related to the use of medication
– too low dose
– noncompliance
– incorrect timing or mode of ingestion
• False diagnosis or concomitant disease
– celiac disease
– bacterial overgrowth