1. Acute Pancreatitis Arefe Hedayati

2. Normal Anatomy & Physiology neutralize chyme digestive enzymes hormones

3. Exocrine Function common bile duct ampulla pancreatic duct BODY UNCINATE HEAD TAIL

4. Digestive Enzymes in the Pancreatic Acinar Cell  PROTEOLYTICLIPOLYTIC ENZYMES  ENZYMESLipase  TrypsinogenProphospholipase A2  ChymotrypsinogenCarboxylesterase lipase  Proelastase  Procarboxypeptidase ANUCLEASES  Procarboxypeptidase BDeoxyribonuclease (DNAse)  Ribonuclease (RNAse)  AMYOLYTIC ENZYMES  AmylaseOTHERS  Procolipase  Trypsin inhibitor

5. Acute Pancreatitis Definition  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 Pancreatitis Pathogenesis  acinar cell  injury premature enzyme activation failed protective mechanisms

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

8. Etiology

9. Acute Pancreatitis Associated Conditions  Cholelithiasis  Ethanol abuse  Idiopathic  Medications  Hyperlipidemia  ERCP  Trauma  Pancreas divisum  Hereditary  Hypercalcemia  Viral infections  Mumps  Coxsackievirus  End-stage renal failure  Penetrating peptic ulcer

10. Acute Pancreatitis Causative 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

11. Acute Pancreatitis Pathogenesis  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

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

14. Acute Pancreatitis Differential Diagnosis  Choledocholithiasis  Perforated ulcer  Mesenteric ischemia  Intestinal obstruction  Ectopic pregnancy

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

19. Causes of Increased Pancreatic Enzymes AmylaseLipase Pancreatitis↑↑ Parotitis↑Normal Biliary stone ↑↑ Intestinal injury ↑↑ Tubo-ovarian disease ↑Normal Renal failure ↑↑ Macroamylasemia↑Normal

20. 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

21. Acute Pancreatitis Diagnosis  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. Severity Scoring Systems  Ranson and Glasgow 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

23. Ranson Criteria AT ADMISSION 1.Age > 55 years 2.WBC > 16,000 3.Glucose > 200 4.LDH > 350 IU/L 5.AST > 250 IU/L WITHIN 48 HOURS 1.HCT drop > 10 2.BUN > 5 3.Arterial PO2 < 60 mm Hg 4.Base deficit > 4 mEq/L 5.Serum Ca < 8 6.Fluid sequestration > 6L

24. Ranson Criteria AT ADMISSION 1.Age > 70 years 2.WBC > 18,000 3.Glucose > 220 4.LDH > 400 IU/L 5.AST > 250 IU/L WITHIN 48 HOURS 1.HCT drop > 10 2.BUN > 2 3.Base deficit > 5 mEq/L 4.Serum Ca < 8 5.Fluid sequestration > 4L

25. CT Severity Index appearancenormalenlargedinflamed 1 fluid collection 2 or more collections gradeABCDE score01234 necrosisnone < 33% 33-50% > 50% score0246 scoremorbiditymortality1-24%0% 7-1092%17%

26. Severe Acute Pancreatitis  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

27. Treatment of Mild Pancreatitis  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

28. 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)

29. 1-clinical manifestation 2-lypase/amylase 3-sonography Severity 1-manifestation 2-ranson or APACHE score 3-CT MILDSEVER SUPPORTIVE CARE ICU

30. Antibiotic remission FNA SEPSIS/INFLAM ATION debridmane Supportive care

31. 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.