Pancreatic function test


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Pancreatic function test

  1. 1. PANCREATIC FUNCTION TEST Dr. Gangadhar Chatterjee Dept. of Biochemistry
  2. 2. Pancreas Gland with both exocrine and endocrine functions  6-10 inch in length  60-100 gram in weight 
  3. 3. Location: Retro-peritoneum, 2nd lumbar vertebral level  Extends in an oblique, transverse position  Parts of pancreas: head, neck, body and tail 
  4. 4. Histology-Exocrine Pancreas 2 major components – Acinar cells and Ducts  They constitute 80% to 90% of the pancreatic mass  20 to 40 acinar cells coalesce into a unit called the acinus  Acinar cells secrete the digestive enzymes  Centroacinar cell (2nd cell type in the acinus) is responsible for fluid and electrolyte secretion by the pancreas 
  5. 5. Histology-Exocrine Pancreas Ductular system - network of conduits that carry the exocrine secretions into the duodenum  Acinus  small intercalated ducts  interlobular duct  pancreatic duct  Interlobular ducts contribute to fluid and electrolyte secretion along with the centroacinar cells 
  6. 6. Histology-Endocrine Pancreas Accounts for only 2% of the pancreatic mass  Nests of cells - islets of Langerhans  Four major cell types  Alpha (A) cells secrete glucagon  Beta (B) cells secrete insulin  Delta (D) cells secrete somatostatin  F cells secrete pancreatic polypeptide 
  7. 7. Histology-Endocrine Pancreas B cells are centrally located within the islet and constitute 70% of the islet mass  PP, A, and D cells are located at the periphery of the islet 
  8. 8. Physiology – Exocrine Pancreas Secretion of water and electrolytes originates in the centroacinar and intercalated duct cells  Pancreatic enzymes originate in the acinar cells  Final product is a colorless, odorless, and isosmotic alkaline fluid that contains digestive enzymes (amylase, lipase, and trypsinogen) 
  9. 9. Physiology – Exocrine Pancreas 500 to 800 ml pancreatic fluid secreted per day  Alkaline pH results from secreted bicarbonate which serves to neutralize gastric acid and regulate the pH of the intestine  Enzymes digest carbohydrates, proteins, and fats 
  10. 10. Bicarbonate Secretion     Centroacinar cells and ductular epithelium secrete 20 mmol of bicarbonate per liter in the basal state Fluid (pH from 7.6 to 9.0) acts as a vehicle to carry inactive proteolytic enzymes to the duodenal lumen Sodium and potassium concentrations are constant and equal those of plasma Chloride secretion varies inversely with bicarbonate secretion
  11. 11. Bicarbonate Secretion Bicarbonate is formed from carbonic acid by the enzyme carbonic anhydrase  Major stimulants  Secretin, Cholecystokinin, Gastrin, Acetylcholine  Major inhibitors Atropine, Somatostatin, Pancreatic polypeptide and Glucagon  Secretin - released from the duodenal mucosa in response to a duodenal luminal pH < 4.5
  12. 12. Enzyme Secretion  Acinar cells secrete isozymes   Major stimulants    amylases, lipases, and proteases Cholecystokinin, Acetylcholine, Secretin, VIP Synthesized in the endoplasmic reticulum of the acinar cells and are packaged in the zymogen granules Released from the acinar cells into the lumen of the acinus and then transported into the duodenal lumen, where the enzymes are activated.
  13. 13. Enzymes  Amylase     only digestive enzyme secreted by the pancreas in an active form functions optimally at a pH of 7 hydrolyzes starch and glycogen to glucose, maltose, maltotriose, and dextrins Lipase   function optimally at a pH of 7 to 9 emulsify and hydrolyze fat in the presence of bile salts
  14. 14. Enzymes of Pancreas  Proteases      essential for protein digestion secreted as proenzymes and require activation for proteolytic activity duodenal enzyme, enterokinase, converts trypsinogen to trypsin Trypsin, in turn, activates chymotrypsin, elastase, carboxypeptidase, and phospholipase Within the pancreas, enzyme activation is prevented by an antiproteolytic enzyme secreted by the acinar cells
  15. 15. Pancreatic Function Tests Everything you eagerly waiting for….
  16. 16. Why pancreatic function tests ? Pancreatic function tests should be performed if:  Diagnosis of CP is suspected and  Imaging tests normal or inconclusive
  17. 17. Indications for pancreatic function tests  Characterization of pancreatic function in suspected pancreatic disease  Differential diagnosis in malabsorption  Assessment of adequacy of pancreatic enzyme replacement therapy
  18. 18. Pediatric disorder of exocrine pancreas
  19. 19. Etiology of pancreatitis
  20. 20. Pancreatic function test DIRECT TEST     Secretin stimulation test Lundh standardized meal test Fecal enzyme assays Chymotrypsin Elastase-1 Serum enzyme assays INDIRECT TEST Fat absorption test C13-MTG test Flurescein dilauryl test  BT-PABA Test  Pancreatic Schilling test 
  21. 21. Secretin stimulation test  requires the passage of a triple lumen tube  distal opening usually is placed near the angle of Treitz by fluoroscopic guidance. second duodenal tube is used for the infusion of a nonabsorbable marker, such as polyethylene glycol or bromsulphalein  The marker substance is introduced at a known concentration and rate. 
  22. 22. If volume and bicarbonate production are to be measured, pure secretin from the Karolinska Institute in Sweden should be used (usual dose is 0.5 to 1.0 CU per kg of body weight per hour).  The usual dose of CCK is 50 microg per kg of body weight per hour administered by continuous infusion.  Duodenal juice is collected by gravity drainage in iced tubes at 15-minute intervals for 11/2 hours after the stimulants are given. 
  23. 23. Drawbacks of Secretin test (1) (2) (3) The length of the procedure, the necessity for nasogastric intubation, which frequently is poorly tolerated by the patient and radiation exposure during placement of the tube. Nevertheless with careful attention SST has more than 90% accuracy in differentiating normal and abnormal pancreatic function
  24. 24. Rapid Endoscopic PFT  Standard endoscopy under sedation  IV secretin (0.2 microgr/kg)  Endoscopic fluid collection (0, 15, 30, 45 and 60 min)  Fluid analysis for bicarbonate conc Conwell et al 2003; Stevens et al. 2006
  25. 25. Standard vs Endoscopic PFT
  26. 26. Rapid Endoscopic PFT - 2  Standard endoscopy under sedation  Endoscopic fluid collection for 10 min  IV secretin (1 CU/kg)  Fluid analysis for bicarb and enzyme conc Raimondo M et al 2003; Clin Gastroenterol Hepatol
  27. 27. LUNDH Test  stimulus to pancreatic secretion is a standardized liquid meal ingested by the patient after a tube has been passed into the duodenum.  effect of the stimulant (food) on enzyme and bicarbonate secretion is measured directly in the aspirated duodenal juice.  After single lumen duodenal intubation patient drinks a 300-ml liquid meal
  28. 28. (5 percent protein, 6 percent fat and 15percent carbohydrate), and duodenal contents are aspirated at 15-minute intervals for two hours.  accuracy of 75 percent to 90 percent, depending on the type of disease present  As a marker is not used, only enzyme concentrations rather than enzyme output can be determined.  The secretin test has stood the test of time. nonabsorbable markers enable quantitation, made the test reasonably reproducible and sensitive for quantitation of pancreatic exocrine function.
  29. 29. Fecal Enzyme Assays Suitable for pediatric patients  Measurement of CHYMOTRYPSINthough less variable not used in adults  Falsely low result because of - voluminous stool ( 300g/day) - inadequate food intake - partial gastrectomy or mucosal disease - obstruction in bile duct Falsely normal result in mild pancreatic insufficiency as high as 50% 
  30. 30. Fecal Elastase-1  - - - - Advantages: Does not degrade during passage through gut conc. In feces is five to six fold than that of pancreatic juice Measured by commercial ELISA using two monoclonal antibody of human enzyme. In children with CF, discriminates between with and without pancreatic insufficiency
  31. 31. Chymotripsin Elastase 10 day intraindividual Variation, mean CV 30% 15% Loss of activity, 7 days at 4degree cel. 17% 2.5% Overall diagnostic sensitivity 64% 93% Overall diagnostic specificity 89% 93%
  32. 32. Serum Enzyme Assays Serum amylase and lipase concentrations can be measured easily, but values do not correspond with the amount of pancreatic exocrine function.  Trypsin, difficult to measure in serum due to presence of inhibitors, recently a radioimmunoassay for serum trypsin developed.  In summary, serum enzyme levels do not appear to be useful in diagnosing exocrine insufficiency. 
  33. 33. Indirect Tests of Pancreatic Exocrine Function  Fat Absorption Triglyceride absorption can be quantitated by radioactive-labeled triglyceride tests. Initially, triolein, a triglyceride composed of glycerol and three molecules of the long-chain fatty acid oleate, was labeled with iodine 131 .
  34. 34. Advantages:  breath test appears to be about as sensitive and specific as the measurement of stool fat in the diagnosis of fat malabsorption.  time requirement of only 6 hours instead of 72 hours accuracy of the two-part tests in a large population still needs to be determined before it can be recommended as a routine method for detecting pancreatic insufficiency.
  35. 35. BT-PABA Test & Pancreolauryl test Obsolete now a days  N-benzoyl-N-tyrosyl para-aminobenzoic acid (BT-PABA) is the combination of paraaminobenzoic acid (PABA) and a chymotrypsin-sensitive dipeptide.  Flurescein dilaurate is hydrolyzed by cholesterol esterse  Not became popular due to several drawbacks of interfering substances, defective renal and liver function, gastric acidity etc. 
  36. 36. Invasive tests are the „Goldstandard“, but are they necessary?
  37. 37. ‘ It is important to recognize that biochemical tests have a limited clinical application in the diagnosis of pancreatic diseases because of complexity of the invasive tests or the inadequate sensitivity and specificity for mild and moderate pancreatic disease of noninvasive tests. Of greater importance are the imaging procedure...................... the future, it may therefore be possible to confidently diagnose pancreatic insufficiency with the use of imaging technique alone’ - TIETZ
  38. 38. THANK YOU