ACUTE PANCREATITIS DR BHUMIKA SAMBYAL ACUTE PANCREATITIS Acute
ACUTE PANCREATITIS DR. BHUMIKA SAMBYAL
ACUTE PANCREATITIS Acute pancreatitis is defined as sudden inflammation of the pancreas which is reversible. It has 2 forms MILD: often successfully treated with conservative measures, such as fasting and aggressive intravenous fluid rehydration. SEVERE: require admission to the intensive care unit or even surgery to deal with complications of the disease process.
ANATOMY OF PANCREAS
ANATOMY AND PHYSIOLOGY Pancreas is a retroperitoneal organ approx 12 -15 cm long. Lacks a capsule Lies transversely and obliquely on posterior abdominal wall behind the stomach along L 1 L 2. 4 parts: Head(IVC &L Ren V) neck(portal v) body tail • Dual organ • EXOCRINE-98%-secretes bicarbonate rich fliud (which has enzymesamylase, lipase, trypsinogen) through main pancreatic duct Which joins CBD at ampulla of vater and drain into duodenum which activates digestion • ENDOCRINE 2%-Islet of langerhans which is made up of 4 types of cells wich secrete GLUCAGON, INSULIN, SOMATOSTA TIN & PANCREATIC POLYPEPTIDE
Pathogenesis The two types of pancreatitis are mild pancreatitis and severe pancreatitis, which are separated based on whether their predominant response to cell injury is inflammation or necrosis, respectively. In mild pancreatitis there is inflammation and edema of the pancreas. In severe pancreatitis there additional features of necrosis and secondary injury to extrapancreatic organs. Both types share a common mechanism of abnormal inhibition of secretion of zymogens and inappropriate activation of pancreatic zymogens inside the pancreas, most notably trypsinogen. Normally, trypsinogen is activated to trypsin in the duodenum where it assists in the digestion of proteins. During an acute pancreatitis episode there is colocalization of lysosomal enzymes, specifically cathepsin, with trypsinogen. Cathepsin activates trypsinogen to trypsin leading to further activation of other molecules of trypsinogen and immediate pancreatic cell death according to either the necrosis or apoptosis mechanism (or a mix between the two). The balance between these two processes is mediated by caspases which regulate apoptosis and have important anti-necrosis functions during pancreatitis: preventing trypsinogen activation, preventing ATP depletion through inhibiting poly. ADP-ribose polymerase, and by inhibiting the inhibitors of apoptosis (IAPs). If, however, the caspases are depleted due to either chronic ethanol exposure or through a severe insult then necrosis can predominate. As part of the initial injury there is an extensive inflammatory response due to pancreatic cells synthesizing and secreting inflammatory mediators: primarily TNF-alpha and IL-1. A hallmark of acute pancreatitis is a manifestation of the inflammatory response, namely the recruitment of neutrophils to the pancreas. The inflammatory response leads to the secondary manifestations of pancreatitis: hypovolemia from capillary permeability, acute respiratory distress syndrome, disseminated intravascular coagulations, renal failure, cardiovascular failure, and gastrointestinal hemorrhage.
Symptoms and signs The most common symptoms and signs include: 1. severe epigastric pain radiating to the back in 50% cases 2. nausea 3. vomiting 4. loss of appetite 5. fever 6. chills (shivering) 7. Hemodynamic instability, including shock, tachycardia 8. respiratory distress 9. peritonitis 10. Hiccough
Signs which are less common, and indicate severe disease, include: • • Grey-Turner's sign (hemorrhagic discoloration of the flanks) Cullen's sign (hemorrhagic discoloration of the umbilicus) Pleural effusions (fluid in the bases of the pleural cavity) Grünwald sign (appearance of ecchymosis, large bruise, around the umbilicus due to local toxic lesion of the vessels) Körte's sign (pain or resistance in the zone where the head of pancreas is located (in epigastrium, 6– 7 cm above the umbilicus)) Kamenchik's sign (pain with pressure under the xiphoid process) Mayo-Robson's sign (pain while pressing at the top of the angle lateral to the Erector spinae muscles and below the left 12 th rib (left costovertebral angle (CVA) Mayo-Robson's point - a point on border of inner 2/3 with the external 1/3 of the line that represents the bisection of the left upper abdominal quadrant, where tenderness on pressure exists in disease of the pancreas. At this point the tail of pancreas is projected on the abdominal wall
Most common causes 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. Alcohol-western countries Gallstones-eastern IDIOPATHIC Metabolic disorders: hypercalcemia(secretory block- causing activation of proteases , accumulation of proteins), hypertryglyceridemia Post-ERCP Abdominal trauma Penetrating ulcers Carcinoma of the head of pancreas, and other cancer Drugs: diuretics (e. g. , thiazides, furosemide), gliptins e. g. , vildagliptin, (galvus) sitagliptin(januvia), saxagliptin, linagliptin, (DDP 4 inhibitors)tetracycline, sulfonamides, estrogens, azathioprine and mercaptopurine, pentamidine, salicylates, steroids Infections: mumps, viral hepatitis, coxsackie B virus, cytomegalovirus, Mycoplasma pneumoniae, Ascaris Structural abnormalities: choledochocele, pancreas divisum Radiation X-ray Autoimmune pancreatitis(TYPE I-Ig 4 related&TYPE 2)
Less common causes 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Scorpion venom Chinese liver fluke Ischemia from bypass surgery Fat necrosis Pregnancy Infections other than mumps, including varicella zoster Repeated marathon running Hyperparathyroidism Drugs: , Valproic acid, Cystic fibrosis Anorexia or bulimia Familial Long common duct Codeine phosphate reaction
Differential diagnosis 1. Perforated peptic ulcer 2. Biliary colic 3. Acute cholecystitis 4. Pneumonia 5. Pleuritic pain 6. Myocardial infarction 7. Peritonitis 8. Macroamylasemia 9. Mesentric ischemia 10. Chronic pancreatitis 11. Irritable bowel syndrome
Diagnosis Acute pancreatitis is diagnosed clinically but requires CT evaluation to differentiate mild acute pancreatitis from severe necrotic pancreatitis. 1. Blood Investigations - Full blood count, Renal function tests, Liver Function, serum calcium, serum amylase and lipase, Arterial blood gas, PT 2. Imaging – a)CHEST RADIOGRAPHY-pleural effusion, basal atelectasis b)USG abdomen-detection of gall bladder stones c)CT scan-Triple phase
Labs 1. Elevated serum amylase and lipase levels, in combination with severe abdominal pain, often trigger the initial diagnosis of acute pancreatitis. 2. S. Amylase-normal in 10% cases(depleted acinar cell mass). rises 2 -12 hours after attack, normalizes after 3 -6 days. 3. Serum lipase rises 4 to 8 hours from the onset of symptoms and normalizes within 7 to 14 days after treatment. 4. Reasons for false positive elevated serum amylase include salivary gland disease (elevated salivary amylase), bowel obstruction, infarction, cholecystitis, and a perforated ulcer. 5. If the lipase level is about 2. 5 to 3 times that of amylase, it is an indication of pancreatitis due to alcohol, can also rise because of cholecystitis, intestinal ulcers, pancreatic and gastric tumors, celiac disease, drugs(furosemide, steroids, OCPs , valproic acid), HIV, renal failure 6. Decreased serum calcium, hypoalbumenemia 7. Hyperglycemia, Glycosuria 8. Thrombocytopenia, ^PT and APTT
HYPOCALCEMIA IN PANCREATITIS • Caused primarily by precipitation of calcium soaps in abdominal cavity, but glucagon stimulated calcitonin release and decreased PTH secretion may play a role. When pancreas are damaged, free fatty acids are generated by the action of pancreatic lipase. Insoluble calcium salts are present in the pancreas , and the free fatty acids avidly chelate the salts, resulting in calcium deposition in retroperitoneum. In addition, hypoalbuminemia can result in decreased total calcium levels.
Computed tomography CT is an important common initial assessment tool for acute pancreatitis. Imaging is indicated during the initial presentation if: 1. the diagnosis of acute pancreatitis is uncertain 2. there is abdominal distension and tenderness, fever >102, or leukocytosis 3. there is a Ranson score > 3 or APACHE score > 8 4. there is no improvement after 72 hours of conservative medical therapy 5. there has been an acute change in status: mental, fever, pain, or shock CT is recommended as a delayed assessment tool in the following situations: 1. To determine therapeutic response after surgery or interventional radiologic procedure 2. Before discharge in patients with severe acute pancreatitis 3. CT abdomen should not be performed before the first 12 hours of onset of symptoms as early CT (<12 hours) may result in equivocal or normal findings.
COMPUTED TOMOGRAPHY Axial CT in a patient with acute exudative pancreatitis showing extensive fluid collections surrounding the pancreas.
Magnetic resonance imaging While computed tomography is considered the gold standard in diagnostic imaging for acute pancreatitis, magnetic resonance imaging (MRI) has become increasingly valuable as a tool. 1. Visualization of the of pancreatic fluid collections and necrotized debris. 2. In patients with an allergy to CT's contrast material, 3. Greater sensitivity to hemorrhage, vascular complications, pseudoaneurysms, and venous thrombosis. 4. Another advantage - utilization of magnetic resonance cholangiopancreatography (MRCP) sequences. MRCP provides useful information regarding the etiology of acute pancreatitis, i. e. , the presence of tiny biliary stones (choledocholithiasis or cholelithiasis) and duct anomalies.
Prognostic indices In predicting the prognosis, there are several scoring indices that have been used as predictors of survival. RANSONS criteria APACHE II (Acute Physiology and Chronic Health Evaluation) indices. CT SEVERITY INDEX(balthazar scoring system) BISAP’S SCORE GLASGOW CRITERIA
Ranson Score Ranson criteria is a clinical prediction rule for predicting the severity of acute pancreatitis. It was introduced in 1974 At admission 1. 2. 3. 4. 5. age in years > 55 years white blood cell count > 16000 cells/mm 3 blood glucose > 10 mmol/L (> 200 mg/d. L) serum AST > 250 IU/L serum LDH > 350 IU/L At 48 hours 1. 2. 3. 4. 5. 6. Calcium (serum calcium < 2. 0 mmol/L (< 8. 0 mg/d. L) Hematocrit fall >10 mmol/l Oxygen (hypoxemia PO 2 < 60 mm. Hg) BUN increased by 1. 8 or more mmol/L (5 or more mg/d. L) after IV fluid hydration Base deficit (negative base excess) > 4 m. Eq/L Sequestration of fluids > 6 L
Ranson's score 1. Interpretation: If the score ≥ 3, severe pancreatitis likely. If the score < 3, severe pancreatitis is unlikely Or APACHE "Acute Physiology And Chronic Health Evaluation" (APACHE II) score > 8 points predicts 11% to 18% mortality. 1. 2. 3. 4. 5. 6. 7. Hemorrhagic peritoneal fluid Obesity Indicators of organ failure Hypotension (SBP <90 mm. HG) or tachycardia > 130 beat/min PO 2 <60 mm. Hg Oliguria (<50 m. L/h) or increasing BUN and creatinine Serum calcium < 1. 90 mmol/L (<8. 0 mg/d. L) or serum albumin <33 g/L (<3. 2. g/d. L)>
Balthazar scoring(ct severity index) Balthazar Grade • • Balthazar Grade Points Grade A Grade B Grade C Grade D Grade E Appearance on CT Normal CT Focal or diffuse enlargement of the pancreas Pancreatic gland abnormalities and peripancreatic inflammation Fluid collection in a single location Two or more fluid collections and / or gas bubbles in or adjacent to pancreas Necrosis Score Necrosis Percentage • No necrosis • 0 to 30% necrosis • 30 to 50% necrosis • Over 50% necrosis CT Grade Points 0 points 2 points 4 points 6 points 0 points 1 point 2 points 3 points 4 points
Glasgow criteria The Glasgow criteria is valid for both gallstone and alcohol induced pancreatitis, whereas the Ranson score is only for alcohol induced pancreatitis. If a patient scores 3 or more it indicates severe pancreatitis. It is scored through the mnemonic, PANCREAS: P - Pa. O 2 <8 k. Pa A - Age >55 year old N - Neutrophilia - WBC >15 x 10(9)/L C - Calcium <2 mmol/L R - Renal function, Urea >16 mmol/L E - Enzymes: LDH >600 iu/L; AST >200 iu/L A - Albumin <32 g/L (serum) S - Sugar: blood glucose >10 mmol/L
BISAP Score Predicts mortality risk in pancreatitis with fewer variables than Ranson's criteria. Data should be taken from the first 24 hours of the patient's evaluation. • BUN >25 mg/d. L (8. 9 mmol/L) • Abnormal mental status with a Glasgow coma score <15 • Evidence of SIRS (systemic inflammatory response syndrome) • Patient age >60 years old • Imaging study reveals pleural effusion Patients with a score of zero had a mortality of less than one percent, whereas patients with a score of five had a mortality rate of 22 percent.
Treatment Initial management of a patient with acute pancreatitis consists of supportive care with OYXGEN, fluid resuscitation, pain control, and nutritional support, correction of electrolyte imbalances(hypo kalemia and calcemia), SUPPORTIVE MEASURES(ANTIEMETICS) Fluid replacement • Aggressive hydration at a rate of 5 to 10 m. L/kg per hour of isotonic crystalloid solution (e. g. , normal saline or lactated Ringer’s solution) to all patients with acute pancreatitis, unless cardiovascular, renal, or other related comorbid factors preclude aggressive fluid replacement. In patients with severe volume depletion that manifests as hypotension and tachycardia, more rapid repletion with 20 m. L/kg of intravenous fluid given over 30 minutes followed by 3 m. L/kg/hour for 8 to 12 hours. • Fluid requirements should be reassessed at frequent intervals in the first six hours of admission and for the next 24 to 48 hours. The rate of fluid resuscitation should be adjusted based on clinical assessment, hematocrit and blood urea nitrogen (BUN) values. • Some evidence that fluid resuscitation with lactated Ringer’s solution may reduce the incidence of Systemic Inflammatory Response Syndrome (SIRS) as compared with normal saline.
• Pain control • Abdominal pain is often the predominant symptom in patients with acute pancreatitis and should be treated with analgesics. • Opioids are safe and effective. Adequate pain control requires the use of intravenous opiates, usually in the form of a patient-controlled analgesia pump. • Hydromorphone or fentanyl (intravenous) may be used for pain relief in acute pancreatitis. Fentanyl is being increasingly used due to its better safety profile, especially in renal impairment. As with other opiates, fentanyl can depress respiratory function. It can be given both as a bolus as well as constant infusion. • Meperidine has been historically favored over morphine because of the belief that morphine caused an increase in sphincter of Oddi pressure. However, no clinical studies suggest that morphine can aggravate or cause pancreatitis or cholecystitis. In addition, meperidine has a short half-life and repeated doses can lead to accumulation of the metabolite normeperidine, which causes neuromuscular side effects and, rarely, seizures
• Bowel rest • In the management of acute pancreatitis, the treatment is to stop feeding the patient, giving him or her nothing by mouth, giving intravenous fluids to prevent dehydration, and sufficient pain control. As the pancreas is stimulated to secrete enzymes by the presence of food in the stomach, having no food pass through the system allows the pancreas to rest. Approximately 75% of relapses occur within 48 hours of oral refeeding. • In mild form , oral feeding can be started when pain and anorexia settle. • Nutritional support • ENTERAL FEEDING-Recently, there has been a shift in the management paradigm from TPN (total parenteral nutrition) to early, post-pyloric enteral feeding (in which a feeding tube is endoscopically or radiographically introduced to the jejunum). The advantage of enteral feeding is that it is more physiological, prevents gut mucosal atrophy, and is free from the side effects of TPN (such as fungemia). The additional advantages of post-pyloric feeding are the inverse relationship of pancreatic exocrine secretions and distance of nutrient delivery from the pylorus, as well as reduced risk of aspiration • TPN- to be initiated when compicated or severe pancreatitis suspected and patient cannot meet his caloric requirement. • POST SURGERY-place feeding jejunostomy.
Antibiotics-(E. COLI &Pseudomo A) sensitive to 3 rd gen cephalosporins, BROAD spe. carbapenems, quinolones and metronidazole. Indicacted in c/o infected necrosis, multiorgan failure, FNAC proven sepsis of collections • Up to 20 percent of patients with acute pancreatitis develop an extrapancreatic infection (e. g. , bloodstream infections, pneumonia, and urinary tract infections). Extrapancreatic infections are associated with an increase in mortality. When an infection is suspected, antibiotics should be started while the source of the infection is being determined. However, if cultures are
• Carbapenems • An early randomized controlled trial of imipenem 0. 5 gram intravenously every eight hours for two weeks showed a reduction in from pancreatic sepsis from 30% to 12%. • A subsequent randomized controlled trial that used meropenem 1 gram intravenously every 8 hours for 7 to 21 days, • Cephalosporins-CEFTAZIDIME(1 gm I/V)8 -12 HRLY) &CEFOTAXIM • Quinolones-ciprofloxacin ANTIFUNGAL THERAPY-Fluconazole therapy decreases the emergence of resistant fungi SELECTIVE DECONTAMINATION OF THE GUT- 4 days A)Polymyxin E, B)Amphotericin B, C)Tobramycin, D)I/V CEFOTAXIM LEXIPAFANT- Platelet activating factor antagonist-reduces systemic response. PROTEASE INHIBITOR-Gabexate mesylate-2. 4 gm/dayx 7 days, Nafemostat mesylate(new)(DIC)
• ERCP • Early ERCP (endoscopic retrograde cholangiopancreatography), performed within 24 to 72 hours of presentation, is known to reduce morbidity and mortality. The indications for early ERCP are: • Clinical deterioration or lack of improvement after 24 hours • Detection of common bile duct stones or dilated intrahepatic or extrahepatic ducts on abdominal CT • The disadvantages of ERCP are: • ERCP precipitates pancreatitis, and can introduce infection to sterile pancreas
SURGERY GALLSTONES-cholecystectomy to be performed on index admission if STABLE • INFECTION diagnosed by: • Gas bubbles on CT scan (present in 20 to 50% of infected necrosis) • Positive bacterial culture on FNA (fine needle aspiration, usually CT or US guided) 1. ACUTE FLIUD COLLECTIONS-Resolve spontaneously 2. STERILE PANCREATIC NECROSIS-mostly nonoperative unless clinical deterioration 3. Infected necrosis • Minimally invasive management - necrosectomy through small incision in skin (left flank) • • • or stomach Conventional management - necrosectomy with simple drainage Closed management - necrosectomy with closed continuous postoperative lavage Open management - necrosectomy with planned staged reoperations at definite intervals (up to 20+ reoperations in some cases 4. PSEUDOCYSTS-treated only if symptomatic-internal surgical drainage(cystogastrostomy, cystodudenostomy, R en ycystojejunostomy), E ndoscopic(transmural and transpapillary) and percutaneous drainage. 5. PANCREATIC ASCITES OR PANCREATIC PLEURAL FISTULA-ERCP with distal
• Complications can be systemic or loco regional. • Systemic complications • Metabolic Hypocalcemia, hyperglycemia, hypertriglyceridemia • Respiratory Hypoxemia, atelectasis, Effusion, pneumonitis, Severe acute respiratory syndrome (SARS) Renal artery or vein thrombosis Renal failure • Circulatory. Gastrointestinal • hemorrhage, gastricvarices, obstruction • Arrhythmias Hypovolemia and shock myocardial infarct Pericardial effusion vascular thrombosis • Hepatobiliary Jaundice Portal vein thrombosis Neurologic Psychosis or encephalopathy (confusion, delusion and coma) Cerebral Embolism • Hematologic
1. PANCREATIC PSEUDOCYST, -4 -6 weeks after attack(wall of fibrous tissue around collection which lacks an epithelial lining)drained in c/opain, bleeding, infection or>7 cm in size 2. PANCREATIC PERIPANCREATIC FLUID COLLECTIONS, 3. PANCREATIC NECROSIS-sterile or infected after 2 -4 weeks(step up technique better-necrosectomy follows percutaneous drainage+ antibiotics) 4. pancreatic ABSCESS(circumscribed intraabdominal collection of pus close to pancreas without necrosis PHYSIOLOGY 5. hemorrhage from splenic artery, vein 6. Thrombosis of splenic and superior mesentric vein
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