Pancreas 2008

PANCREAS MARIA TERESITA ANDAL-GAMUTAN, MD,FPCP,FPSG,FPSDE

PANCREAS Exocrine – acinus and draining ducts Endocrine – islet of langerhans Pancreatic exocrine secretion • 1500 – 3000 ml isosmotic alkaline(pH>8) fluid per day • 20 enzymes and zymogens • to effect the major digestive activity of GIT • provide an optimal pH for the function of these enzymes

REGULATION OF PANCREATIC SECRETION Gastric acid  secretin  p. juice rich in H2O & elect. Long chain FA, essential AA & gastric acid CCK  enzyme-rich secretion Gastrin weak stimulus for p. enzyme output Bile  pancreatic secretion Somatostatin --/pancreatic secretion Water & electrolyte secretion bicarbonate - helps neutralize gastric acid and - creates the appropriate pH for the activity of the pancreatic enzymes

PANCREAS Enzyme secretion secretes amylolytic, lipolytic, and proteolytic enzymes Autoprotection packaging of proteases in precursor form synthesis of protease inhibitors

TESTS USEFUL IN THE DIAGNOSIS OF PANCREATIC DISEASES Pancreatic enzymes  amylase  lipase trypsinogen pancreatic polypeptide Pancreatic structure  radiologic and radionuclide tests pancreatic biopsy with US or CT guidance Exocrine pancreatic function  direct stimulation – secretin  indirect stimulation – nutrients followed by assays of proteolytic, lipolytic and amylolytic enzymes  intraluminal digestion products – undigested meat, fibers, stool fat  measurement of fecal pancreatic enzymes - elastase

ACUTE PANCREATITIS Incidence: varies, depends on cause, e.g., alcohol, gallstones Common Causes of Acute Pancreatitis Alcohol ingestion Biliary tract disease(gallstone) Hypertriglyceridemia Postoperative state ERCP Trauma  Drugs Sphincter of Oddi dysfunction

CAUSES OF ACUTE PANCREATITIS Drugs for which association is definite  Azathioprine, 6-mercaptopurine  Sulfonamides  Thiazide diuretics  Furosemide  Estrogen (oral contraceptives)  Tetracycline  Valproic acid  Pentamidine  Dideoxyinosine

CAUSES OF ACUTE PANCREATITIS Drugs for which association is probable  Acetaminophen  Nitrofurantoin  Methyldopa  Erythromycin  Salicylates  Metronidazole  NSAIDS  ACE inhibitors

Uncommon CAUSES OF ACUTE PANCREATITIS  Vascular causes and vasculitis  Connective tissue disorders and thrombotic thrombocytopenic purpura  Cancer of the pancreas  Hypercalcemia  Periampullary diverticulum  Pancreas divisum  Heridetary pancreatitis  Cystic fibrosis  Renal failure

Uncommon CAUSES OF ACUTE PANCREATITIS Vascular causes and vasculitis Vascular Ischemic hypoperfusion state (after cardiac surgery) Atherosclerotic emboli Aneurysm of celiac axis/ hepatic artery Connective tissue disorders with vasculitis SLE Necrotizing angiitis Thrombotic, throbocytopenic purpura Penetrating peptic ulcer Obstruction of the ampulla of Vater Regional enteritis Duodenal diverticulum

RARE CAUSES OF ACUTE PANCREATITIS Infections  Mumps  Viral hepatitis  Other viral infections(coxsackievirus, echovirus, cytomegalvirus)  Ascariasis  Mycoplasma, Campylobacter, Mycobacterium avium complex, other bacteria Autoimmune (e. g., Sjogren,s syndrome

CAUSES OF ACUTE PANCREATITIS

Causes to be considered in patients having recurrent bouts of acute pancreatitis without an obvious cause

Occult disease of the biliary tree or pancreatic ducts, especially occult gallstones (microlithiasis, sludge)  Drugs  Hypertriglyceridemia  Pancreas divisum  Pancreatic cancer  Sphincter of Oddi dysfunction  Cystic fibrosis  Truly idiopathic

PATHOGENESIS Drugs: hypersensitivity reaction or generation of a toxic metabolite Autodigestion theory: proteolytic enzymes are activated in the pancreas rather than in the intestinal lumen

Pathogenesis Activation of Pancreatic Enzymes 3 Phases

7. Intrapancreatic digestive enzymes activation and acinar cell injury - consequence of zymogen activation 9. Activation , chemoattraction and sequestration of neutrophils in the pancreas resulting in intrapancreatic inflammatory reaction of variable severity 3. Effects of activated proteolytic enzymes and mediators released by inflamed pancreas, on distant organs

CLINICAL FEATURES Abdominal pain Nausea, vomiting, abdominal distension Physical examination Distressed and anxious Low grade fever Tachycardia Hypotension Shock: retroperitoneal burn formation & releases of kinin peptides systemic effects of proteolytic & lipolytic enzymes Jaundice Erythematous skin nodules Pulmonary findings

LABORATORY DATA Amylase Lipase Trypsin Leukocytosis Hemoconcentration Hyperglycemia Hypocalcemia Hyperbilirubinemia Alk. Phos, ALT, AST LDH >500U/dL – poor prognosis Hypoalbuminemia Hypertriglyceridemia Hypoxemia

DIAGNOSIS Any severe abdominal or back pain Nausea, emesis Fever, tachycardia, abnormal abdominal findings Elevated amylase and or lipase

DIFFERENTIAL DIAGNOSIS 3. Perforated viscus 4. Acute cholecystitis and biliary colic 5. Acute intestinal obstruction 6. Mesenteric vascular occlusion 7. Renal colic 8. Myocardial infarction 9. Dissecting aortic aneurysm 10.Connective tissue disorders with vasculitis 11.Pneumonia 12.Diabetic ketoacidosis

Factors that Adversely Affect the Survival in Acute Pancreatitis Ranson/Imrie criteria At admission or diagnosis Age >55 years Leukocytosis>16,000/uL Hyperglycemia Serum LDH>400IU/L Serum AST>250IU/L During initial 48 h Fall in hematocrit by >10% Fluid deficit of >4000ml Hypocalcemia(<8 mg/dL Hypoxemia (PO2<60mmHg) Increase in BUN to > 1.8mmol/L after IV administration Hypoalbunemia Acute physiology and chronic health evaluation (APACHE II) score >12 Hemorrhagic peritoneal fluid Obesity(BMI>29)

RISK FACTORS THAT ADVERSELY AFFECT SURVIVAL IN ACUTE PANCREATITIS 1. Organ Failure a. Cardiovascular hypotension(BP < 90mmHg) or tachycardia>130 beats/min b. Pulmonary: Po2<60mmHg c. Renal: oliguria(<50ml/h) or increasing BUN, creatinine c. Gastrointestinal bleeding

RISK FACTORS THAT ADVERSELY AFFECT SURVIVAL IN ACUTE PANCREATITIS 3. Organ failure 4. Pancreatic necrosis SEVERITY INDEX IN ACUTE PANCREATITIS Points Grade of acute pancreatitis G. Normal pancreas 0 H. Pancreatic enlargement 1 I. Inflammation compared with p.& peripancreatic fat 2 J. One peripancreatic fluid collection 3 K. Two or more fluid collections 4 Degree of pancreatic necrosis M. No necrosis 0 N. Necrosis of one-third of pancreas 2 O. Necrosis of one-half of pancreas 4 P. Necrosis of more than one-half of pancreas 6 ----------------------------------------------------------------------------------------------3-6 scores --- negligible 7-10 --- 92% morbidity rate & 17% mortality rate Presence of necrosis – morbidity >20% With out necrosis - morbidity<10%, negligible mortality rate

RISK FACTORS THAT ADVERSELY AFFECT SURVIVAL IN ACUTE PANCREATITIS 4. 5. 6. 7. 8. 9.

Organ failure Pancreatic necrosis Obesity(BMI > 29); age > 70 Hemoconcentration(hematocrit > 44%) C-Reactive protein> 150mg/L Trypsinogen activation peptide a. >3 Ranson criteria (not fully utilizable until 48 h) b. Apache II score >8 (cumbersome

COMPLICATIONS OF ACUTE PANCREATITIS Local Pancreatic ascites Necrosis Disruption of main pancreatic duct Sterile Leaking pseudocyst Infected Involvement of contiguous organs by Pancreatic fluid collections necrotizing pancreatitis Pancreatic abscess Massive Intraperitoneal hemorrhage Pancreatic pseudocyst Thrombosis of blood vessels Pain (splenic, & portal vein) Rupture Bowel Infarction Hemorrhage Obstructive jaundice Infection Obstruction of GIT(stomach, duodenum, colon)

SYSTEMIC COMPLICATIONS OF ACUTE PANCREATITIS Pulmonary Renal Pleural effusion Oliguria Atelectasis Azotemia Mediastinal abscess RAT and /or RVT Pneumonitis Acute tubular necrosis ARDS Metabolic Cardiovascular Hyperglycemia Hypotension Hypertriglyceridemia Hypovolemia Hypocalcemia Hypoalbunemia Encephalopathy Sudden death Sudden blindness(Purtscher’s retinopathy NSSTTC like MI Central nervous system Pericardial effusion Psychosis Hematologic Fat emboli DIC Fat necrosis Gastrointestinal hemorrhage Subcutaneous tissues(erythematous nodules) PUD Erosive gastritis Bone Hemorrhagic pancreatic necrosis w Miscellaneous(mediastinum, pleura, erosion into major blood vessel nervous system) Portal vein thrombosis, variceal hemorrhage

TREATMENT Conventional Measures 4. Analgesics for pain 5. Intravenous fluids and colloids to maintain normal intravascular volume 7. No oral alimentation 8. Nasogastric suction to decrease gastrin release from the stomach and prevent gastric contents from entering duodenum Prophylactic antibiotics in severe pancreatitis

Infected pancreatic necrosis  diffuse infection of an acutely inflamed, necrotic pancreas  occurring in the first 1-2 weeks after the onset of acute pancreatitis  should be treated by surgical debridement Pancreatic abscess  ill-defined , liquid collection of pus that evolves over a longer period, often 4-6 weeks Pseudocyst  collections of tissue, fluid, debris, pancreatic enzymes and blood  develop over a period of 1-4 weeks after the onset of acute pancreatitis

Pancreatic ascites  due to disruption of the main pancreatic duct, often by an internal fistula between the duct and the peritoneal cavity or a leaking pseudocyst  elevated serum amylase level in whom the ascites fluid has both increased level albumin & markedly elevated level of amylase  ERCP  Treatment: nasogastric suction& parenteral alimentation paracentesis long acting somatostatin analogue octreotide

CHRONIC PANCREATITIS Chronic inflammatory disease of the pancreas  acute inflammation in a previously injured pancreas or as a chronic damage with persistent pain or malabsorption Pathophysiology Alcohol-induced – precipitation of protein (inspissated enzymes) in the ducts duct dilatation, diffuse atrophy of acinar cells, fibrosis & calcification Direct toxic effects on the pancreas

CAUSES Alcohol, chronic alcoholism Idiopathic pancreatitis Cystic fibrosis Hypertriglyceridemia Severe protein-calorie malnutrition w/ hypoalbuminemia Pancreatic and duodenal neoplasm Pancreatic resection Gastric surgery Gastrinoma Hereditary pancreatitis Traumatic pancreatitis Abdominal radiotherapy Hemochromatosis Enterokinase deficiency

CLINICAL FEATURES Symptoms identical to acute pancreatitis Pain may be continuous, intermittent or absent Weight loss Abnormal stools, malabsorption

DIAGNOSIS Amylase and lipase – not elevated Classic triad > pancreatic calcification ---< 1/3rd > steatorrhea > diabetes mellitus Intubation test – secretin stimulation test Cobalamin malabsorption – pancreatic enzymes Marked excretion of fecal fat – p. enzymes Decreased serum trypsinogen level Radiographic hallmark – calcification Sonography, CT, ERCP

COMPLICATIONS Cobalamin malabsorption Effusions – pleural, pericardial, or peritoneal space GI bleeding – peptic ulceration, gastiritis, pseudocyst eroding to duodenum, esophageal varices Cholangitis Subcutaneous fat necrosis Bone pain Pancreatic cancer Addiction to narcotics

TREATMENT Directed to two major problems Pain Malabsorption PAIN abstinence: alcohol & fatty meals use of narcotics pancreatic enzymes surgery MALABSORPTION pancreatic enzyme replacement supportive measures

PANCREATIC CANCER 90% moderately differentiated mucinous adenocarcinoma derived from pancreatic duct epithelium 5% islet cell origin More common in men than in women Risk factors: cigarette smoking, alcohol consumption gallstones, animal fat-rich diet, DM, chronic pancreatitis Clinical manifestations are related to compression or invasion of the adjacent vital structures jaundice, pruritus, abd. pain, wt. loss Diagnosis No single laboratory test Ultrasound and CTscan ERCP  Management Surgery Palliative management