Pancreas

Severity based on Modified Glasgow Criteria: (mnemonic: PANCREAS) PaO2 Age >55 Neutrophilia: WBC>15x10'9/L Calcium Renal function Urea>16mmol/L Enzymes LDH>600 iU/L, AST >200iU/L Albumin Sugar glucose >10mmol/L In mild pancreatitis there is inflammation and oedema of the pancreas. In severe pancreatitis there are additional features of necrosis and secondary injury to extrapancreatic organs. 

Causes:(mnemonic: GET SMASHED) Gallstones:  blocking the bile duct, causing back pressure in the main pancreatic duct, causing periductal necrosis Ethanol Trauma Steroids Mumps Autoimmune (PAN) Scorpion venom Hyperlipidaemia, hypercalcaemia, hypothermia ERCP and Emboli Drugs +Pregnancy and neoplasia

Pathology: -self-perpetuating pancreatic inflammation by enzyme-mediated autodigestion-oedema and fluid shifts causing hypovolemia, as extracellular fluid is trapped in gut, peritoneum and retroperitoneum (worse with vomiting)-Mechanism: abnormal inhibition of secretion of zymogens and inappropriate activation of pancreatic zymogens inside the pancreas, most notably 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 -Caspases regulate apoptosis and have anti-necrosis functions, but if they are depleted due to either chronic ethanol exposure or through a severe insult then necrosis can predominate.

Early complications: shock, systemic inflammatory response syndrome (SIRS) Hypovolemia Metabolic: hypocalcaemia, hyperglycaemia Disseminated intravascular coagulation (DIC) Renal dysfunction due to hypovolaemia, intravascular coagulation, dehydration Respiratory complications : Pleural effusion, Pulmonary oedema, Consolidation, ARDS

Late complications: Pancreatic necrosis (triples mortality risk) Infected necrosis : almost always fatal without intervention Acute fluid collections (30-50% of severe cases) Acute pseudo-cyst:contains pancreatic juice in a wall of fibrous or granulation tissue Pancreatic abscess Pancreatic ascites: pseudo-cyst collapses into the peritoneal cavity or major pancreatic duct breaks down and releases pancreatic juices into the peritoneal cavity Acute cholecystitis (10% of severe cases)

Symptoms: severe upper abdominal pain of sudden/gradual onset with vomiting. Pain is central or epigastric and penetrates to the back. (may be relieved with sitting forward) Pain tends to decrease steadily over 72 hours. Signs check temperature to exclude hypothermia; mild pyrexia is more common. Probable tachycardia with the patient unwell and dehydrated. Jaundice  Epigastric or generalised abdominal tenderness, often with rigidity. Bowel sounds are usually present in the early phase. Paralytic ileus, causing absent bowel sounds can last for >4 days and is a useful marker of disease severity. In severe cases: gross hypotension (shock), pyrexia, tachypnoea, acute ascites, pleural effusions, periumbilical bruising (Cullen's sign) or flanks (Grey Turner's sign). Hypoxaemia is characteristic of acute pancreatitis.

Investigations: serum amylase (>1000u/ml or 3x of upper limit): levels start falling in 24-48hrs raised serum lipase (specific to pancreas) FBC, U&E, glucose (hyperglycaemic) and CRP : CRP>150 indicates severe disease, may be reduced in drug-induced cases ABG: monitor O2 and acid-base levels Raised bilirubin and/or serum aminotransferase suggest gallstones. Hypocalcaemia is relatively common. Abdominal X-ray: excludes some other causes (eg, intestinal obstruction and perforation) and may show calcification. CXR may show elevation of one hemidiaphragh m, infiltrates ± acute respiratory distress syndrome (ARDS) or pleural effusions in severe cases. CT scan with contrast enhancement may be diagnostic where clinical and biochemical results are equivocal on admission. CT after four days can help in the assessment of complications. Contrast-enhanced CT scanning can identify pancreatic swelling, fluid collection and change in density of gland.  Ultrasound: The pancreas is poorly visualised in 25-50% of cases. Ultrasound can show a swollen pancreas, dilated common bile duct and free peritoneal fluid.It is useful to detect the presence of gallstones. MRI may reveal acute abdominal wall oedema which may be a supplementary indicator of severity

Most pancreatic malignancies are exocrine.Exocrine tumours: Infiltrating ductal adenocarcinomas account for 90% of pancreatic cancers.The majority arise in the head (2/3), neck or uncinate process. 90% of periampullary malignancies arise from the pancreas and the remaining 10% from the distal common bile duct, the ampulla of Vater and the duodenum. Endocrine tumours: Pancreatic endocrine tumours (PETs) are classified as neuroendocrine tumours (NETs). PETs arise from amine precursor uptake and decarboxylation (APUD) stem cells PETs can be divided into functional (exhibit a distinct clinical syndrome due to hormone hypersecretion) and non-functional tumours. The majority of PETs are non-functional.Insulinomas and gastrinomas are equally common and account for more than half of all clinically apparent PETs.  Other functional ones: Vasoactive intestinal polypeptide-secreting tumours (VIPomas),glucagonomas, somatostatinomas. Non-functional tumours account for 14-48% of all recognised PETs.

Presentation: Abdominal pain: typically located in the epigastric region, radiating through to the back. Can present as simple back pain. Back pain is typically dull and worse when supine and eased by sitting forward. Jaundice: obstructive jaundice causes dark urine, pale stools and pruritus. Acute pancreatitis: pancreatic cancer should be considered in the differential diagnosis of any elderly patient presenting for the first time with acute pancreatitis, particularly in the absence of known precipitating factors such as gallstones or alcohol abuse. Unexplained weight loss, anorexia. Steatorrhoea due to malabsorption. Epigastric mass (late). Courvoisier's sign ( palpable gallbladder + painless jaundice) occurs in less than 25% of patients. Compression of the duodenum or the stomach may cause gastric outlet obstruction or delayed gastric emptying, leading to nausea and vomiting. Haematemesis, melaena or iron-deficiency anaemia. Patients presenting with rapid weight loss, persistent back pain, ascites, an epigastric mass or enlarged supraclavicular node (Virchow's node) are likely to have advanced disease.

Endocrine tumours (secretory effects) Insulinoma: confusion, sweating, dizziness, weakness, unconsciousness; fasting hypoglycaemia and relief of hypoglycaemic symptoms with eating or after glucose administration,palpitations, weakness, trembling, tachycardia, and irritability. Gastrinoma: Zollinger-Ellison syndrome of severe peptic ulceration and diarrhoea, GORD and dyspepsia. Glucagonoma: necrolytic migratory erythema, weight loss, diabetes mellitus, stomatitis, diarrhoea. VIPoma: profuse watery diarrhoea with marked hypokalaemia (faecal potassium loss), and achlorhydria (deficiency of hydrochloric acid in the stomach), weakness, hypotension, lethargy and weight loss. Abdominal cramps and nausea are common and flushing episodes may occur. Somatostatinoma: cholelithiasis, weight loss, diarrhoea and steatorrhoea, diabetes mellitus., postprandial fullness, relative biliary stasis with gallbladder calculi and symptoms of biliary colic.

Location:More than two thirds occur in the head of the pancreas and classically present with painless, progressive, obstructive jaundice. Tumours in the body and tail of the pancreas generally occur in patients presenting with nonspecific pain and weight loss and are much less likely to cause obstructive signs and symptoms

pancreatitis

Pancreatic cancer