ACUTE PANCREATITIS Etiology "I GET SMASHED": I = Idiopathic, G = Gall stones(most common, biliary pancreatitis) , E=Ethanol, T = Trauma, S = Steroids, M = Mumps, A = Autoimmune and rheumatological disordes (e.g. Sjôgren syndrome), S = Scorpion poison, H= Hypercalcemia, Hypertriglyceridemia, E = ERCP, D = Drugs.(steroids azathioprine sulfonamides furosemide estrogen protease inhibitors NRTIs) Pathophysiology(video osmosis) Sequence of events leading to pancreatitis: 1. Intrapancreatic activation of pancreatic enzymes: secondary to pancreatic ductal outflow obstruction (e.g., gallstones, cystic fibrosis) or direct injury to pancreatic acinar cells (e.g., alcohol, drugs) Alcohol can also be responsible for blocked ducts by increasing zymogen secretion (elevating pancreatic juice’s viscosity) and decreasing of fluid secretion in the interstitial tissu, that leads to membrane trafficking, fusing of zymogens and autodigestion 2. Enzymatic autodigestion of pancreatic parenchyma 3. Attraction of inflammatory cells (neutrophils, macrophages) → release of inflammatory cytokines → pancreatic inflammation (pancreatitis) Sequelae of pancreatitis (depending on the severity of pancreatitis) 1. Capillary leakage: Release of inflammatory cytokines and vascular injury by pancreatic enzymes → vasodilation and increased vascular permeability → shift of fluid from the intravascular space into the interstitial space (third space loss) → hypotension, tachycardia → distributive shock 2. Pancreatic necrosis: Uncorrected hypotension and third space loss → decreased organ perfusion → multiorgan dysfunction (mainly renal) and pancreatic necrosis 3. Hypocalcemia: Lipase breaks down peripancreatic and mesenteric fat → release of free fatty acids that bind calcium → hypocalcemia Disease progression Mild acute pancreatitis: interstitial edema, no necrosis; no local and systemic complications, no organ failure Moderate acute pancreatitis: associated with local (e.g., necrosis, abscesses, pseudocysts) or systemic complications, such as temporary organ failure (e.g., kidney failure), which improves within 48 hours Severe pancreatitis: associated with persistent pancreatic failure (> 48 hours), as well as single or multiple organ failure Clinical features Constant, severe epigastric pain o Classically radiating towards the back o Worse after meals and when supine o Improves on leaning forwards o Nausea, vomiting General physical examination o Signs of shock: tachycardia, hypotension, oliguria/anuria o Possibly jaundice in patients with biliary pancreatitis Abdominal examination Abdominal tenderness, distention, guarding o As the pancreas is a retroperitoneal organ, abdominal guarding does not present with the typical hard rigidity seen in inflammation of intraperitoneal organs. Instead, the abdomen is distended and elastic on palpation. o Ileus with reduced bowel sounds and tympany on percussion o Ascites o Skin changes (rare) Circulating pancreatic enzymes cause swelling of the subcutaneous tissue and localized hemorrhages. These signs, though nonspecific, suggest retroperitoneal bleeding and are associated with a poor prognosis. Cullen's sign: periumbilical ecchymosis and discoloration (bluish-red) Grey Turner's sign: flank ecchymosis with discoloration Fox's sign: ecchymosis over the inguinal ligament Diagnostics Acute pancreatitis is diagnosed based on a typical clinical presentation, with abdominal pain radiating to the back, and either detection of highly elevated pancreatic enzymes or characteristic findings on imaging. Serum hematocrit is an easy test that should be conducted to help quickly predict disease severity. Laboratory tests Tests to confirm clinical diagnosis ↑ Serum pancreatic enzymes o Lipase: if ≥ 3 x the upper reference range → highly indicative of acute pancreatitis Amylase (nonspecific) The enzyme levels are not directly proportional to severity or prognosis! Tests to assess severity Hematocrit (Hct) o Should be conducted at presentation as well as 12 and 24 hours after admissions ↑ Hct (due to hemoconcentration) indicates third space fluid loss and inadequate fluid resuscitation ↓ Hct indicates the rarer acute hemorrhagic pancreatitis o WBC count Leukocytosis is an indicator of severe pancreatitis. o Blood urea nitrogen o ↑ CRP and procalcitonin levels Procalcitonin levels help determine if a rise in CRP is due to necrosis caused by bacterial pancreatitis, as procalcitonin typically indicates bacterial infection, whereas CRP may be elevated in either sterile or bacterial pancreatitis. ↑ ALT o Tests to determine etiology o Alkaline phosphatase, bilirubin levels (evidence of gallstone pancreatitis) o Serum calcium levels o Serum triglyceride levels (fasting) Determining calcium values is very important: Hypercalcemia may cause pancreatitis, which may then, in turn, cause hypocalcemia! Imaging Ultrasound (most useful initial test): indicated in all patients with acute pancreatitis o Main purpose: detection of gallstones and/or dilatation of the biliary tract (indicating biliary origin) o Signs of pancreatitis Indistinct pancreatic margins (edematous swelling) Peripancreatic build-up of fluid ; evidence of ascites in some cases Evidence of necrosis, abscesses, pancreatic pseudocysts CT scan: not routinely indicated Indications o At admission: only when the diagnosis is in doubt (e.g., not very highly elevated pancreatic enzymes, non-specific symptoms) > 72 hours of symptom onset: if complications such as necrotizing pancreatitis or pancreatic abscess (e.g., persistent fever and leukocytosis, no clinical improvement or evidence of organ failure > 72 hours of therapy) are suspected Pancreatic necrosis or abscess takes time to develop and therefore, a CT scan done on the first day of symptom onset will not delineate the necrotic and/or infected pancreatric parenchyma and will not alter the treatment. o Findings Enlargement of the pancreatic parenchyma with edema; indistinct pancreatic margins with surrounding fat stranding Necrotizing pancreatitis: lack of parenchymal enhancement or presence of air in the pancreatic tissue Pancreatic abscess: circumscribed fluid collection Balthazar score : MRCP and ERCP o Indications: suspected biliary or pancreatic duct obstructions o MRCP is noninvasive but less sensitive than ERCP o ERCP can be combined with sphincterotomy and stone extraction; but may worsen pancreatitis. Conventional x-ray o Sentinel loop sign: dilatation of a loop of small intestine in the upper abdomen (duodenum/jejunum) dilatation of a loop of small intestine due to a functional ileus near an inflamed process. o Colon cut off sign: gaseous distention of the ascending and transverse colon that abruptly terminates at the splenic flexure o Evidence of possible complications: pleural effusions, pancreatic calcium stones; helps rule out intestinal perforation with free air Treatment General measures Admission to hospital and assessment of disease severity (consider ICU admission) Fluid resuscitation: aggressive hydration with crystalloids (e.g., lactated Ringer's solution , normal saline) Analgesia: IV opioids (e.g., fentanyl) Bowel rest (NPO)and IV fluids are recommended until the pain subsides Nasogastric tube insertion: not routinely recommended; indicated in patients with vomiting and/or significant abdominal distention Nutrition o Begin enteral feeding (oral/nasogastric/nasojejunal) as soon as the pain subsides o Total parenteral nutrition: only in patients who cannot tolerate enteral feeds (e.g., those with persistent ileus and abdominal pain) Drug therapy Analgesics: fentanyl or hydromorphone; consider pump administration (patient controlled analgesia = PCA) Antibiotics o Prophylactic antibiotic therapy is not recommended. o Antibiotics should only be used in patients with evidence of infected necrosis. Fenofibrates: in hyperlipidemia-induced acute pancreatitis Procedures/surgery Biliary pancreatitis o Urgent ERCP and sphincterotomy (within 24 hours): in patients with evidence of choledocholithiasis and/or cholangitis; followed by cholecystectomy o Cholecystectomy (preferably during same admission once the patient is stabilized; or within 6 weeks): in all patients with biliary pancreatitis The most important therapeutic measure is adequate fluid replacement (minimum of 3–4 liters of crystalloids per day)! Cours du prof : Pancreatite A B C cholecystectomie au cours de la meme hospitalisation, Pancreatite D ou E chirurgie reportée à 2 ou 3 mois après refroidissement "PANCREAS" - Perfusion (fluid replacement), Analgesia, Nutrition, Clinical (observation), Radiology (imaging), ERCP (endoscopic stone extraction), Antibiotics, Surgery (surgical intervention, if necessary). Complications Localized Bacterial superinfection of necrotic tissue → fever o Diagnosis: CT-guided percutaneous drainage + culture of the aspirate o Treatment: surgical debridement, antibiotics o High mortality rate; multiple organ failure in ∼ 50% of cases Pancreatic pseudocysts Pancreatic abscess o Walled-off infected necrotic tissue or pancreatic pseudocyst; typically develops > 4 weeks after an attack of acute pancreatitis o Abdominal CT: visible contrast-enhanced abscess capsule with evidence of fluid (pus) o Ultrasound: complex cystic, fluid collection with irregular walls and septations o Treatment: cannulation and drainage; necrosectomy if other measures are not effective Pleural effusion Abdominal compartment syndrome Blood vessel erosion with bleeding Systemic SIRS, sepsis, DIC Pneumonia, respiratory failure, ARDS Shock Prerenal failure due to volume depletion Hypocalcemia Pleural effusion, pancreatic ascites Paralytic ileus Prognosis Mortality o In patients without organ failure: < 1% o In patients with organ failure: ∼ 30% o Higher mortality in patients with biliary pancreatitis than in patients with alcoholic pancreatitis Important predictors of severity o Age > 55 o Gastrointestinal bleeding o Abnormal hematocrit within 48 hours Acute hemorrhagic pancreatitis: ↓ Hct Third space fluid loss: ↑ Hct o Hypocalcemia and/or hyperglycemia o Inflammatory markers: ↑↑ CRP, ↑ IL-6, ↑ IL-8 o Evidence of shock and/or organ failure ↑ AST, ↑ ALT ↑ BUN, creatinine ↑ LDH ABG: pO2 < 60 mmHg, metabolic acidosis with a base deficit > 4 mmol/L o CT findings: pancreatic edema, peripancreatic fluid collection, and/or necrosis of > 33% of the pancreas Amylase and lipase, which are used for the diagnosis of pancreatitis, cannot be used to predict the prognosis! Numerous scoring systems exist (e.g, Ranson criteria) for assessing the severity and predicting the prognosis of acute pancreatitis 1. Cite 11 étiologies 2. Physiopathologie : Events leading to pancreatitis, sequelae of pancreatitis, disease progression 3. Clinical features, physical examination, abdominal examination(4) 4. Laboratory findings : tests to confirm the dg, tests to assess severity, tests to determine etiology 5. Imaging : Ultrasound’s findinds, CT :when to perform, findings, Balthazar score, MRCP ERCP, X-ray 6. Treatment : General measures, drug therapy, surgery 7. Complications : localized, systemic 8. Prognosis : predictors of severity