AcutePancreatitis：急性胰腺炎

1、Acute Pancreatitis,Rajeev Jain, M.D. December 15, 2003,Normal Anatomy & Physiology,neutralize chyme digestive enzymes hormones,Exocrine Function,pancreatic duct,common bile duct,ampulla,pancreatic enzymes,TAIL,BODY,HEAD,UNCINATE,Enzyme Secretion,pancreatic duct,duodenum,acinus,microscopic view of pa

2、ncreatic acini,Enzyme Secretion,Hormonal CCK gastrin,Neural acetylcholine VIP GRP,Secretin (hormonal),H2O bicarbonate,Digestive Enzymes in the Pancreatic Acinar Cell,PROTEOLYTICLIPOLYTIC ENZYMES ENZYMESLipase TrypsinogenProphospholipase A2 ChymotrypsinogenCarboxylesterase lipase Proelastase Procarbo

3、xypeptidase ANUCLEASES Procarboxypeptidase BDeoxyribonuclease (DNAse) Ribonuclease (RNAse) AMYOLYTIC ENZYMES AmylaseOTHERS Procolipase Trypsin inhibitor,Normal Enzyme Activation,trypsinogen,trypsin,chymotrypsin elastase phospholipase carboxypeptidase,enterokinase,chymotrypsinogen proelastase prophos

4、pholipase procarboxypeptidase,duodenal lumen,Exocrine Stimulation,The more proximal the nutrient infusionthe greater the pancreatic stimulation (dog studies) stomach maximal stimulation duodenum intermediate stimulation jejunum minimal / negligible stimulation Elemental formulas tend to cause less s

5、timulation than standard intact formulas intact protein oligopeptides free amino acids Intravenous nutrients (even lipids) do not appear to stimulate the pancreas,Protective Measures,COMPARTMENTALIZATION - digestive enzymes are contained within zymogen granules in acinar cells REMOTE ACTIVATION - di

6、gestive 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,Acute PancreatitisDefinition,Acute inflammat

7、ory 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,Acute PancreatitisEtiology,Cholelithiasis Ethanol abuse Idiopathic Medications Hyperlipidemia ERCP Trauma,Pancreas

8、divisum Hereditary Hypercalcemia Viral infections Mumps Coxsackievirus End-stage renal failure Penetrating peptic ulcer,Acute PancreatitisAssociated Conditions,Acute PancreatitisCausative Drugs,AIDS therapy: didanosine, pentamidine Anti-inflammatory: sulindac, salicylates Antimicrobials: metronidazo

9、le, sulfonamides, tetracycline, nitrofurantoin Diuretics: furosemide, thiazides IBD: sulfasalazine, mesalamine Immunosuppressives: azathioprine, 6-mercaptopurine Neuropsychiatric: valproic acid Other: calcium, estrogen, tamoxifen, ACE-I,Adjusted ORs for Pancreatitis,Freeman et al. Gastrointest Endos

10、c. 97.,Pancreas divisum,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,failed protectivemecha

11、nisms,acinar cell injury,Acute PancreatitisPathogenesis,autodigestion of pancreatic tissue,release ofenzymes into the circulation,activation of white blood cells,localcomplications,local vascular insufficiency,premature enzyme activation,distantorgan failure,Acute PancreatitisPathogenesis,STAGE 1: P

12、ancreatic Injury Edema Inflammation STAGE 2: Local Effects Retroperitoneal edema Ileus STAGE 3: Systemic Complications Hypotension/shock Metabolic disturbances Sepsis/organ failure,SEVERITY Mild Severe,Acute PancreatitisPathogenesis,Abdominal pain Epigastric Radiates to the back Worse in supine posi

13、tion Nausea and vomiting Fever,Acute PancreatitisClinical Presentation,Acute PancreatitisDifferential Diagnosis,Choledocholithiasis Perforated ulcer Mesenteric ischemia Intestinal obstruction Ectopic pregnancy,Symptoms Abdominal pain Laboratory Elevated amylase or lipase 3x upper limits of normal Ra

14、diology Abnormal sonogram or CT,Acute PancreatitisDiagnosis,Causes of IncreasedPancreatic Enzymes,Acute PancreatitisDiagnosis,EtOH: history Gallstones: abnormal LFTs & sonographic evidence of cholelithiasis Hyperlipidemia: lipemic serum, Tri1,000 Hypercalcemia: elevated Ca Trauma: history Medication

15、s: history, temporal association,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 A

16、djacent viscera: ileus, obstruction, perforation Cardiovascular: hypotension Pulmonary: pleural effusions, ARDS Renal: acute tubular necrosis Hematologic: disseminated intravascular coag. Metabolic: hypocalcemia, hyperglycemia,Acute PancreatitisTime Course,ER presentation,cytokine release,organ fail

17、ure,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?,Severity Scoring Systems,Ranson and Glasgow Criteria (1974)

18、 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

19、 hours Computed Tomography Severity Index much better diagnostic and predictive tool optimally useful at 48-96 hours after symptom onset,Ranson CriteriaAlcoholic Pancreatitis,AT ADMISSION Age 55 years WBC 16,000 Glucose 200 LDH 350 IU/L AST 250 IU/L,WITHIN 48 HOURS HCT drop 10 BUN 5 Arterial PO2 4 m

20、Eq/L Serum Ca 6L,Number,Mortality,2 1%,3-4 16%,5-6 40%,7-8 100%,Glasgow CriteriaNon-alcoholic Pancreatitis,WBC 15,000 Glucose 180 BUN 16 Arterial PO2 600 U/L AST or ALT 200 U/L,CT Severity Index,Balthazar et al. Radiology 1990.,Severe Acute Pancreatitis,Scoring systems 3 Ranson criteria 8 APACHE II

21、points 5 CT points Organ failure shock (SBP 2.0 mg/dl) Local complications fluid collections pseudocysts necrosis (mortality 15% if sterile, 30-35% if infected) abscess,Goals of Treatment,Limit systemic injury support and resuscitation effective decrease pancreatic secretion ineffective / harmful? i

22、nhibit inflammatory mediators ineffective inhibit circulating trypsin ineffective (too late) removing gallstones mostly ineffective Prevent necrosis how? Prevent infection antibiotics (imipenem and ciprofloxacin) probably effective in necrotic pancreatitis prevent colonic bacterial translocation rem

23、oving gallstones variably effective,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-fr

24、ee (off IV narcotics) amylase & lipase not very useful here,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 derangement

25、s (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),Role of ERCP,Gallstone pancreatitis Cholangitis Obstructive jaundice Recurrent acute pancre

26、atitis Structural abnormalities Neoplasm Bile sampling for microlithiasis Sphincterotomy in patients not suitable for cholecystectomy,Nutrition in Acute Pancreatitis,Metabolic stress catabolism & hypermetabolism seen in 2/3 of patients similar to septic state (volume depletion may be a major early f

27、actor in the above derangements) Altered substrate metabolism increased cortisol & catecholamines increased glucagon to insulin ratio insulin resistance Micronutrient alterations calcium, magnesium, potassium, etc,Systemic Changes in Acute Pancreatitis,Hyperdynamic Increased cardiac output Decreased

28、 systemic vascular resistance Increased oxygen consumption Hypermetabolism Increased resting energy expenditure Catabolism Increased proteolysis of skeletal muscle,Reduced Oral Intake in Acute Pancreatitis,Abdominal pain with food aversion Nausea and vomiting Gastric atony Ileus Partial duodenal obs

29、truction,Factors Differentiating Mild from Severe Pancreatitis,TPN in Acute Pancreatitis,delay until volume repleted & electrolytes corrected check triglycerides first goal 400 lipids are OK to use (possible exception of sepsis) monitor glucose levels carefully can see insulin insufficiency and resi

30、stance may need to limit calories at first separate insulin drip may be needed,TPN in Acute Pancreatitis,Benefit or harm? early uncontrolled studies suggested benefit two retrospective studies (70s & 80s) showed no benefit with TPN in pancreatitis 1987 randomized study of early TPN vs. IVF alone sho

31、wed more sepsis, longer stays, & no fewer complications with TPN When to use TPN? jejunal access is unavailable ileus prevents enteral feeding patients in whom TEN clearly exacerbates pancreatitis,Enteral Nutrition in Acute Pancreatitis,studies late 80s patients who received jejunal feeding tubes at the time of surgery, did well with earlypost-op enteral support 1991 randomized study of early TPN vs. early TEN post-op show