Acute Pancreatitis

1. Acute Pancreatitis Presented by: Ahmad Pourhosseini

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

3. Digestive Enzymes in the Pancreatic Acinar Cell PROTEOLYTIC LIPOLYTIC ENZYMES ENZYMES Lipase Trypsinogen Prophospholipase A2 Chymotrypsinogen Carboxylesterase lipase Proelastase Procarboxypeptidase A NUCLEASES Procarboxypeptidase B Deoxyribonuclease (DNAse) Ribonuclease (RNAse) AMYOLYTIC ENZYMES Amylase OTHERS Procolipase Trypsin inhibitor

4. Protective Measures • 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 PancreatitisDefinition • 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

6. Acute PancreatitisEtiology

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

8. Acute PancreatitisCausative Drugs • 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

9. Pancreas divisum

10. Hereditary Pancreatitis • 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. prematureenzyme activation Acute PancreatitisPathogenesis acinar cell injury failed protectivemechanisms

12. Acute PancreatitisPathogenesis premature enzyme activation autodigestion of pancreatic tissue local vascular insufficiency activation of white blood cells release ofenzymes into the circulation localcomplications distantorgan failure

13. Acute PancreatitisPathogenesis • STAGE 1: Pancreatic Injury • Edema • Inflammation • STAGE 2: Local Effects • Retroperitoneal edema • Ileus • STAGE 3: Systemic Complications • Hypotension/shock • Metabolic disturbances • Sepsis/organ failure SEVERITY Mild Severe

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

16. Acute PancreatitisDifferential Diagnosis • Choledocholithiasis • Perforated ulcer • Mesenteric ischemia • Intestinal obstruction • Ectopic pregnancy

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

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. Causes of IncreasedPancreatic Enzymes

21. Acute PancreatitisDiagnosis • 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 PancreatitisClinical Manifestations PANCREATIC PERIPANCREATIC SYSTEMIC 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. Acute PancreatitisTime Course ER presentation cytokine release organ failure

24. Predictors of Severity • 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. Severity Scoring Systems • 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. Ranson CriteriaCriteria for acute pancreatitis not due to gallstones Number <2 1% 3-4 16% 5-6 40% 7-8 100% Mortality

27. Ranson Criteria Criteria for acute gallstone pancreatitis

28. CT Severity Index Balthazar et al. Radiology 1990.

29. Severe Acute Pancreatitis • Scoring systems •  3 Ranson criteria •  8 APACHE II points •  5 CT points • Organ failure • shock (SBP < 90 mmHg) • pulmonary edema / ARDS (PaO2 < 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. Treatment of Mild Pancreatitis • Pancreatic rest • Supportive care • fluid resuscitation – watch BP and urine output • pain control • NG tubes and H2 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. Treatment of Severe Pancreatitis • 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. Reduced Oral Intake in Acute Pancreatitis • Abdominal pain with food aversion • Nausea and vomiting • Gastric atony • Ileus • Partial duodenal obstruction

34. Factors Differentiating Mild from Severe Pancreatitis

35. Conclusions • 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.

36. Thank u for your attention