PANCREAS INSUFFICIENCY

Fatty acid or monoglyceridePolar end of bile acidHydroxyl groups of bile acidsBile 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

NucleusNucleus

Granular-Granular-endoplasmicreticulumendoplasmicreticulum

MitochondriaMitochondria

EsterificationEsterificationSurfaceSurfacestabilizationstabilizationAddition ofAddition oflipoproteinlipoprotein

ChylomicronChylomicronformationformation

Uptake fromUptake frommicellar solutionmicellar solutionFA and MGFA and MG

Secretion viaSecretion viaintercellular spacesintercellular spacesinto lactealsinto lacteals

Golgi materialGolgi 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, 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→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 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 PreparationsPancreatin powder / granulate blends well with food unpalatable denaturation in acid / peptic milieu hyperuricosuriaPancreatin tablet / capsule inadequate dispersion into the meal neutral taste denaturation in acid / peptic milieu

Pancreatic Enzyme PreparationsEnteric Coated PreparationsEnteric-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 2.0Creon 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

0102030405060708090

100

5,0 5.2 5.4 5.6 5.8 6.0

CreonCreon FortePancreasePancrease HLPanzytrat

• 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 inhibits

pancreatic 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