PANCREAS INSUFFICIENCY

Fatty acid or monoglyceride

Polar end of bile acid

Hydroxyl groups of bile acids

Bile acid

Bile acids(Conc. >CMC)Micelles

Lipase

HUMAN PANCREATIC LIPASE

Interfacial enzyme,active in the lipid-water 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

Nucleus

Granular-endoplasmicreticulum

Mitochondria

Esterification

Surfacestabilization

Addition oflipoprotein

Chylomicronformation

Uptake frommicellar solutionFA and MG

Secretion viaintercellular spacesinto 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 from300,000 to 500,000 U/meal

Minimum pancreatic function of 10% of normal is necessary for adequate lipid digestion, correspondingto ± 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→sluggishgallbladder 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 InsufficiencyDiagnosis

• 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 PreparationsNon-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 PreparationsEnteric 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 PreparationGalenic aspects

gelatin capsule

pancreatin

pH dependent enteric coated layer

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)

Lipase Amylase Protease sphere diam.

Microsphere Pancreatic Enzyme Preparations

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 PreparationsCourse of dissolution of enteric oat

0

10

20

30

40

50

60

70

80

90

100

5,0 5.2 5.4 5.6 5.8 6.0

Creon

Creon Forte

Pancrease

Pancrease HL

Panzytrat

• 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 Enzyme PreparationsDosage recommendations

Pancreatic Exocrine InsufficiencyDietary 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 inhibitspancreatic enzymes)

Medium chain triglycerides (C6-C12)(80–120 g/d) in case of insufficiently corrected steatorrhea and weight loss

Therapy of Pancreatic InsufficiencyTreatment 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