1. Presented by: Ahmad Pourhosseini

2. pancreatic duct common bile duct ampulla pancreatic enzymes TAIL BODY HEAD UNCINATE

3. PROTEOLYTICLIPOLYTIC ENZYMES ENZYMESLipase ENZYMESLipase TrypsinogenProphospholipase A2 ChymotrypsinogenCarboxylesterase lipase Proelastase Procarboxypeptidase ANUCLEASES Procarboxypeptidase BDeoxyribonuclease (DNAse) Ribonuclease (RNAse) AMYOLYTIC ENZYMES AmylaseOTHERS Procolipase Trypsin inhibitor

4. COMPARTMENTALIZATION - digestive enzymes are contained within zymogen granules in acinar cells REMOTE ACTIVATION - digestive enzymes are secreted as inactive proenzymes within the pancreas PROTEASE INHIBITORS – trypsin inhibitor is secreted along with the proenzymes to suppress any premature enzyme activation AUTO “SHUT-OFF” – trypsin destroys trypsin in high concentrations

5. Acute inflammatory process involving the pancreas Usually painful and self-limited Isolated event or a recurring illness Pancreatic function and morphology return to normal after (or between) attacks

7. Cholelithiasis Ethanol abuse Idiopathic Medications Hyperlipidemia ERCP Trauma Pancreas divisum Hereditary Hypercalcemia Viral infections Mumps Coxsackievirus End-stage renal failure Penetrating peptic ulcer

8. AIDS therapy: didanosine, pentamidine Anti-inflammatory: sulindac, salicylates Antimicrobials: metronidazole, sulfonamides, tetracycline, nitrofurantoin Diuretics: furosemide, thiazides IBD: sulfasalazine, mesalamine Immunosuppressives: azathioprine, 6-mercaptopurine Neuropsychiatric: valproic acid Other: calcium, estrogen, tamoxifen, ACE-I

10. Autosomal dominant with 80% phenotypic penetrance Recurrent acute pancreatitis, chronic pancreatitis, and 50-fold increased risk of pancreatic cancer Mutation in cationic trypsinogen gene (R122H) Other genetic defects CFTR SPINK1

11. failed protective mechanisms acinar cell injury premature enzyme activation

12. autodigestion of pancreatic tissue release of enzymes into the circulation activation of white blood cells local complications local vascular insufficiency premature enzyme activation distant organ failure

13. STAGE 1: Pancreatic Injury Edema Inflammation STAGE 2: Local Effects Retroperitoneal edema Ileus STAGE 3: Systemic Complications Hypotension/shock Metabolic disturbances Sepsis/organ failure SEVERITYMildSevere

15. Abdominal pain Epigastric Radiates to the back Worse in supine position Nausea and vomiting Fever Acute Pancreatitis Clinical Presentation

16. Choledocholithiasis Perforated ulcer Mesenteric ischemia Intestinal obstruction Ectopic pregnancy

17. Symptoms Abdominal pain Laboratory Elevated amylase or lipase > 3x upper limits of normal Radiology Abnormal sonogram or CT Acute Pancreatitis Diagnosis

18. Grey Turner sign - flank discoloration due to retroperitoneal bleed in pt. with pancreatic necrosis (rare) Cullen’s sign - periumbilical discoloration (rare)

19. Grey Turner sign Cullen’s sign

20. AmylaseLipasePancreatitis↑↑ Parotitis↑Normal Biliary stone ↑↑ Intestinal injury ↑↑ Tubo-ovarian disease ↑Normal Renal failure ↑↑ Macroamylasemia↑Normal

21. EtOH: history Gallstones: abnormal LFTs & sonographic evidence of cholelithiasis Hyperlipidemia: lipemic serum, Tri>1,000 Hypercalcemia: elevated Ca Trauma: history Medications: history, temporal association

22. Acute Pancreatitis Clinical Manifestations PANCREATICPERIPANCREATICSYSTEMIC Mild: edema, inflammation, fat necrosis Severe: phlegmon, necrosis, hemorrhage, infection, abscess, fluid collections Retroperitoneum, perirenal spaces, mesocolon, omentum, and mediastinum Adjacent viscera: ileus, obstruction, perforation Cardiovascular: hypotension Pulmonary: pleural effusions, ARDS Renal: acute tubular necrosis Hematologic: disseminated intravascular coag. Metabolic: hypocalcemia, hyperglycemia

23. ER presentationcytokine releaseorgan failure

24. Why are they needed? appropriate patient triage & therapy compare results of studies of the impact of therapy When are they needed? optimally, within first 24 hours (damage control must begin early) Which is best?

25. Ranson Criteria (1974) based on clinical & laboratory parameters scored in first 24-48 hours of admission poor positive predictors (better negative predictors) APACHE Scoring System can yield a score in first 24 hours APACHE II suffers from poor positive predictive value APACHE III is better at mortality prediction at > 24 hours Computed Tomography Severity Index much better diagnostic and predictive tool optimally useful at 48-96 hours after symptom onset

26. Number Mortality <21% 3-416%5-640%7-8100%

28. appearancenormalenlargedinflamed 1 fluid collection 2 or more collections gradeABCDE score01234 necrosisnone < 33% 33-50% > 50% score0246 scoremorbiditymortality1-24%0% 7-1092%17% Balthazar et al. Radiology 1990.

29. Scoring systems  3 Ranson criteria  8 APACHE II points  5 CT points Organ failure shock (SBP < 90 mmHg) pulmonary edema / ARDS (PaO 2 < 60 mmHg) renal failure (Cr > 2.0 mg/dl) Local complications fluid collections  pseudocysts necrosis (mortality 15% if sterile, 30-35% if infected) abscess

31. Pancreatic rest Supportive care fluid resuscitation – watch BP and urine output pain control NG tubes and H 2 blockers or PPIs are usually not helpful Refeeding (usually 3 to 7 days) bowel sounds present patient is hungry nearly pain-free (off IV narcotics) amylase & lipase not very useful here

32. Pancreatic rest & supportive care fluid resuscitation* – may require 5-10 liters/day careful pulmonary & renal monitoring – ICU maintain hematocrit of 26-30% pain control – PCA pump correct electrolyte derangements (K +, Ca ++, Mg ++ ) Rule-out necrosis contrasted CT scan at 48-72 hours prophylactic antibiotics if present surgical debridement if infected Nutritional support may be NPO for weeks TPN vs. enteral support (TEN)

33. Abdominal pain with food aversion Nausea and vomiting Gastric atony Ileus Partial duodenal obstruction

34. ParameterMildPancreatitisSeverePancreatitisAdmissions80%20% Pancreatic necrosis NoYes Oral diet within 5 days 80%0% Morbidity8%38% Mortality3%27%

35. Acute pancreatitis is a self-limited disease in which most cases are mild. Gallstones and alcohol are the leading causes of acute pancreatitis. In mild pancreatitis, nutritional support is usually not required In severe pancreatitis, nutritional support will likely be required with the enteral route preferred over TPN because of both safety and cost.