Pancreatic Function Lecture 19

The Pancreas 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

Types of Tissues Two functionally different tissues: Endocrine (hormone releasing) The smaller component consists of islet of langerhans – 4 cell types Secrete 4 hormones Insulin, glucagon, ghrelin & somatostatin 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

Somatostatin Epsilon cells producing ghrelin Glucagon Insulin

Functions Completes the job of breaking down food using digestive enzymes of pancreas Protein → trypsin, chymotrypsin Carbohydrates → amylase Fats → lipase, lecithinase Secretes hormones that affect the level of sugar in the blood. Insulin, glucagon Produces chemicals that neutralize stomach acids that pass from the stomach into the small intestine NaHCO3 Most of the pancreatic action is under the hormonal control of secretin and Cholecystokinin Lecithin is any of a group of yellow-brownish fatty substances occurring in animal and plant tissues, and in egg yolk, composed of phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides, and phospholipids (e.g., phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol). However, lecithin is sometimes used as a synonym for pure phosphatidylcholine Secetin: digestive hormone secreted by the wall of the upper part of the small intestine (the duodenum). Its secretion is stimulated when acid from the stomach or digested protein bathes the mucous tissue of the duodenum.

Pancreatic disorders The major disorders of the pancreas are: Endocrine pancreas: Diabetes Mellitus (DM) Islet Cell Tumors Exocrine pancreas: Acute pancreatitis & chronic pancreatitis Pancreatic cancer Cystic fibrosis

Islet Cell Tumors Tumors of the pancreatic islets are rare in comparison with tumors of the exocrine pancreas. Islet cell tumors of the pancreas affect endocrine capability If tumor occurs in beta cells → hyperinsulinism → low blood sugar Alpha cell tumors → ↑ glucagon → DM

Pancreatitis 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.  cholelithiasis: involves the presence of gallstones  ethanol administration which induced pancreatic hypoxia and oxidative stress

Laboratory Findings Marked elevation of the serum amylase during the first 24 hours, followed within 72-96 hours by a rising serum lipase. Hypocalcemia Hypocalcemia: Free fatty acids chelate calcium

Pancreatic Cancer 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.

Laboratory Finding Tumor markers, include: carcinoembryonic antigen (CEA), CA 19-9, and CA 125, All are associated with pancreatic cancer but are nonspecific and can be elevated in conditions other than malignancies CA 19-9: carbohydrate antigen 19-9 CA 19-9 can be elevated in many types of gastrointestinal cancer, such as colorectal cancer, esophageal cancer and hepatocellular carcinoma. Apart from cancer, elevated levels may also occur in pancreatitis, cirrhosis, and diseases of the bile ducts.

Cystic Fibrosis Cystic fibrosis is an inherited, autosomal recessive disease that affects nearly all exocrine glands in the body. The disease is characterized by: chronic obstructive pulmonary disease, pancreatic insufficiency, 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. CF is caused by a mutation in the gene, cystic fibrosis transmembrane conductance regulator (CFTR). The product of this gene is a chloride ion channel important in creating sweat, digestive juices and mucus

Cystic Fibrosis 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.

Other Tests Detection of malabsorption Fecal fat test Indicates either pancreatic dysfunction or intestinal malabsorption D-xylose absorption test A pentose sugar which does not require pancreatic enzymes for absorption In normal individuals, a 25 g oral dose of D-xylose will be absorbed and excreted in the urine at approximately 4.5 g in 5 hours. A positive qualitative fecal fat test indicates that fat is likely not being absorbed normally and that the person may have impaired digestion or malabsorption.

Other Tests Measuring exocrine function Measuring endocrine function Secretin, chymotrypsin, trypsin, cholecystokinin Measuring endocrine function insulin, glucose This hormone, which is very similar to cholecystokinin, is secreted in large amounts by the stomach in response to gastric distention and irritation. In addition to stimulating acid secretion by the parietal cell, gastrin stimulates pancreatic acinar cells to secrete digestive enzymes.

Case Study 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;

What is the probable disease? Acute pancreatitis 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 What is the probable disease? Acute pancreatitis 8 mg/dl

What is the cause for the low serum calcium? 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? Shock, resulting in prerenal azotemia