1. Acute pancreatitis By: Elias S.

2. Acute pancreatitis An acute inflammatory process of the Pancreas Associated with sever abdominal pain and elevated pancreatic enzymes Incidence US – 79.8/100,000/yr Accounts for >220,000 Hosp. Admissions/yr England – 5.4/100,000/yr Incidence increases with Age The two most common causes: Gall stones Alcoholism 20% - idiopathic

3. Acute pancreatitis cont…. Gallstones 30-60% of AP More in women  ed in small GS,<5mm (Microlithiasis) Only 3-7% of GS P’ts develop AP Alcoholism 15-30% of AP More in men Dose dependant Only 10% of alcoholics develop AP

5. Pathogenesis Inciting event – Not clearly known Alcohol ? Sensitization of acinar cells to CCK-induced premature activation Zymogens ? Toxic metabolites – acetaldehyde Fatty acid ethyl esterase ?Generation of oxidative stress Gallstone ?Obstruction of the ampulla: Blockage of drainage Reflux of bile ?Edema resulting from passage of stone Once began – Similar cascade of events

6. Inappropriate intrapancreatic activation Of trypsinogen to trypsin  trypsin Pancreatic autodigestion Activation of More trypsin Activation of other Enzyme cascades Complements Kallikrine-kinin Coagulation Fibrinolysis Activation of Chemotrypsine Phospholipase Elastase  autodgestion Release of more active enzymes From injured cells More & wide Destruction (vicious cycle)

7. Pathogenesis cont… Chemoattraction,activation & sequestration of neutrophils  release of proinflammatory Cytokines and other mediators (TNF,IL-1,6,8 ; prostaglandins,leukotriens, Bradykinins,Histamine….)  More Damage Systemic response: SIRS (vascular indothelial injury, microvascular thrombosis) Fever, ARDS, circulatory collapse  shock, Renal failure, myocardial depression, DIC Infection (local/systemic) In 30% of p’ts with acute sever pancreatitis Cause: enteric organisms Compromized gut barrier  Bacterial translocation lethal

8. Diagnosis Characteristic abdominal pain Predisposing factor to pancreatitis Elevated serum amylase (>3x ULN) Problems with serum Amylase test Normal:  If delay in taking sample(2-5days)  Hypertriglyceridemia associated pancreatitis  Ch. Pancreatitis  ed in many other conditions:  salivary g., liver, kidney, small int., fallopian tube  Ca of lung, Esophagus, ovary, breast More specific tests: Serum -Lipase, -Trypsinogen-2,Trypsinogen activation P. Imaging modalities – X-ray, Abd.US, EUS, CT, MRI ERCP,MRCP

9. Predicting severity 2 broad categories Edematous (mild): recovery in 5-7 days Necrotizing (sever) : high rate of complications  mortality severity: defined by the presence of local/systemic complications Predicting severity Clinical assesment Scoring systems (Ranson,Glasgow,APACHE II..) Serum markers (CRP) CT scan (CT severity index)

10. Clinical assesement Warning signs Thirst Poor urine output Progressing tachycardia Tachypnea Hypoxemia Agitation, confusion Rising Hct Lack of improvement in symptoms in the 1 st 48 hr Consider ICU admission!

15. Risk factors that adversly affect survival Organ failure CVS: SBP 130/m Pulmonary: P o2 <60 mmhg Renal: oliguria(<50ml/hr) or  ing BUN & Cr GI bleeding Pancreatic necrosis Obesity (BMI>30) Age >70 Hct >44% C-reactive protein >150mg/dl  urinary trypsinogen activation peptide

16. Local complications Pancreatic necrosis Pancreatic fluid collections abscess Pseudocysts Ascitis Pleural effusion

17. Rx General principles of therapy Reversing pancreatic inflammation Correcting underlying predisposing factor Mild pancreatitis: Self-limited; subsides spontaneously in3-7days Supportive care (IV fluids, pain control), NPO Sever pancreatitis: - ICU care Fluid resuscitation: 250-300ml/hr for the 1 st 48hrs Asses O 2 saturation – supplemental O 2  maintain SpO 2 >95% Adequate pain control – IV opiates(Morphine,Meperidine) Nutritional support: Enteral feeding > TPN Preventing infections: three approaches  Enteral feeding – Maintain gut barrier integrity  ? Selective decontamination of the gut  ? Prophylactic antibiotics

18. Prophylactic antibiotics- controversial Initial studies (mid-1970s) failed to show benefit Recent meta-analysis of 8 controlled trials  Reduced mortality An other meta-analysis(4 trials)  Reduced infection & Mortality Subsequent,largest,multicenter, placebo controlled trial (114 p’ts, iv ciprofloxacilllin+metronidazol with placebo) – No benefit! Further doubt on the benefit Selection of resistant organisms Development of fungal infection

19. Experimental agents Gabexate mesilate (proteinase inhibitor) Somatostatine, octreotide Correcting predisposing factor Gallstone pancreatitis Removal of the stones (ERCP) Cholecystectomy (to prevent recurrence)  After recovery, prior to discharge Medication induced – Stop the drug Hypertriglyceridemia Low-fat diet, w’t reduction, Exercise, cessation of alcohol intake Surgery

20. THANK YOU