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Pancreas is a large gland Involved in the digestive process but located outside the GI tract Composed of both exocrine and endocrine functions 15-25 cm in length 60-100 gram in weight 2 M. Zaharna Clin. Chem. 2009 Two functionally different tissues: o Endocrine (hormone releasing) • The smaller component • consists of islet of langerhans – 4 cell types • Secrete 4 hormones • Insulin, glucagon, gastrin & somatostatin o Exocrine (enzyme secreting) • The larger component • secrets 1.5 – 2 L/day, rich in digestive enzymes • has alkaline pH due to its content of NaHCO3 • Produced by pancreatic acinar cells 3 M. Zaharna Clin. Chem. 2009 4 M. Zaharna Clin. Chem. 2009 Completes the job of breaking down food using digestive enzymes of pancreas o Protein → trypsin, chymotrypsin o Carbohydrates → amylase o Fats → lipase, lecithinase Secretes hormones that affect the level of sugar in the blood. o Insulin, glucagon Produces chemicals that neutralize stomach acids that pass from the stomach into the small intestine o NaHCO3 Most of the pancreatic action is under the hormonal control of secretin and Cholecystokinin 5 M. Zaharna Clin. Chem. 2009 The major disorders of the pancreas are: o Endocrine pancreas: • Diabetes Mellitus (DM) • Islet Cell Tumors o Exocrine pancreas: • Acute pancreatitis & chronic pancreatitis • Pancreatic cancer • Cystic fibrosis 6 M. Zaharna Clin. Chem. 2009 Tumors of the pancreatic islets are rare in comparison with tumors of the exocrine pancreas. Islet cell tumors of the pancreas affect endocrine capability o If tumor occurs in beta cells → hyperinsulinism → low blood sugar o Alpha cell tumors → ↑ glucagon → DM 7 M. Zaharna Clin. Chem. 2009 Inflammation of the pancreas The exocrine pancreas produces a variety of enzymes, such as proteases, lipases, and saccharidases. These enzymes start auto-digestion of the pancreas which causes the pain and complications of pancreatitis. About 80% of cases are associated with cholelithiasis and alcoholism. Associated with raised levels of pancreatic enzymes (amylase and lipase) in blood and urine. 8 M. Zaharna Clin. Chem. 2009 Marked elevation of the serum amylase during the first 24 hours, followed within 7296 hours by a rising serum lipase. Hypocalcemia 9 M. Zaharna Clin. Chem. 2009 Carcinoma of the pancreas refers to carcinoma of the exocrine pancreas Almost always arising from ductal epithelial cells (adenocarcinoma). Presentation often occurs as a result of metastases rather than as a direct effect of the primary tumor. 10 M. Zaharna Clin. Chem. 2009 Tumor markers, include: o carcinoembryonic antigen (CEA), o CA 19-9, o and CA 125, All are associated with pancreatic cancer but are nonspecific and can be elevated in conditions other than malignancies 11 M. Zaharna Clin. Chem. 2009 Cystic fibrosis is an inherited, autosomal recessive disease that affects nearly all exocrine glands in the body. The disease is characterized by: o chronic obstructive pulmonary disease, o pancreatic insufficiency, o and abnormally high sweat electrolytes. The disease causes the exocrine glands to become obstructed by viscous material. The blockage leads to cellular damage within the tissue. Pancreatic insufficiency leads to poor digestion and poor growth pattern with a deficiency of fat-soluble vitamins. 12 M. Zaharna Clin. Chem. 2009 CF is caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR). This gene is required to regulate the components of sweat, digestive juices, and mucus. The diagnosis of cystic fibrosis is made by clinical symptoms and positive sweat chloride test. People with cystic fibrosis have unusually large amounts of chloride in their sweat when compared to reference ranges of healthy individuals. The sweat is collected on sterile gauze over a period of a few minutes and later analyzed for the amount of chloride present. Genetic analysis can be used to counsel families for gene carrier status. 13 M. Zaharna Clin. Chem. 2009 Detection of malabsorption o Fecal fat test • Distinguish between pancreatic dysfunction and intestinal malabsorption o D-xylose absorption test • A pentose sugar which does not require pancreatic enzymes for absorption 14 M. Zaharna Clin. Chem. 2009 Measuring exocrine function o Secretin, chymotrypsin, trypsin, cholecystokinin Measuring endocrine function o gastrin, insulin, glucose 15 M. Zaharna Clin. Chem. 2009 A 38-year-old man entered the emergency department with the complaint of severe, mid abdominal pain of 6 hours' duration. The patient had a 15-year history of alcoholism He had last been hospitalized for acute alcoholism 3 months ago, at which time he had relatively minor abnormalities of liver function. On this admission, his blood pressure was 80/40 mm Hg; 16 M. Zaharna Clin. Chem. 2009 Serum amylase 640 units (3.5-260 units) Calcium 4.0 mEq/L (4.5-5.5 mEq/L) Blood urea nitrogen 32 mg/dL (8-25 mg/dL) White blood cell count 16,500 Hemoglobin 12 g/dL 1. What is the probable disease? • Acute pancreatitis 17 M. Zaharna Clin. Chem. 2009 2. What is the cause for the low serum calcium? o 3. Enzymatic fat necrosis and digestion, which result in free fatty acids in abdominal adipose tissue. The fatty acids then bind calcium as they form fatty acid salts. What is the cause for the increased blood urea nitrogen? o Shock, resulting in prerenal azotemia 18 M. Zaharna Clin. Chem. 2009