Pancreas - Endocrine System

Exocrine & Endocrine gland of the human body

1. Pancreas Endocrine & Exocrine Pancreas Insulin & Glucagon BreadWinnerzAssociation

2. The Pancreas: Is a soft, lobulated organ that stretches obliquely across the posterior abdominal wall in the epigastric region . Situated behind stomach & extends from the duodenum to the spleen . Has both exocrine & endocrine functions. The endocrine pancreas is composed of the islets of Langerhans. Contains several hormone-producing cells. Produces hormones which play key roles in carbohydrate metabolism. Dysfunction causes diabetes mellitus . The exocrine pancreas contains acini , which secretes pancreatic juice into the duodenum through the pancreatic ducts . Disorders causes maldigestion of fat & steatorrhea (fatty stools). Dysfunction results from inflammation (acute/chronic pancreatitis), neoplasm ( pancreatic carcinoma), or duct obstruction by stones or abnormally viscid mucus (cystic fibrosis ). Both exocrine & endocrine pancreatic dysfunction occur together in some patients. BreadWinnerzAssociation

3. Surface Marking: Lies across the transpyloric plane. The head lies below & to the right. The neck lies on the plane. The body & tail lie above & to the left. The transpyloric plane passes through the tips of the 9 th costal cartilages on the 2 sides -i.e., the point where the lateral margin of the rectus abdominis ( linea semilunaris ) crosses the costal margin. It lies at the level of L1 vertebrae body. The plane passes through the pylorus of stomach, the duodenojejunal junction, the neck of pancreas, & the hila of kidneys. BreadWinnerzAssociation

4. Illustration 1.1: Arrangement of peritoneum BreadWinnerzAssociation

5. Vasculature: Blood supply: Arteries: Supplied by splenic & the superior and inferior pancreaticoduodenal arteries. Veins: Corresponding veins drain into the portal system. Lymph drainage: Lymph nodes are situated along the arteries that supply the gland. Ultimately drain into the celiac & the superior mesenteric lymph nodes. Nerve supply: Sympathetic & parasympathetic (vagal) nerve fibers. BreadWinnerzAssociation

6. Anatomy- Exocrine Pancreas: Is a solid organ. Lies transversely across posterior abdominal wall deep within epigastrium. (retroperitoneal organ) Firmly fixed in front of the abdominal aorta & 1 st and 2 nd lumbar vertebrae. Normally, is abt 15cm long, although it weighs <110g . Divided into 4 parts: head, including uncinate process; neck; body; & tail. The head lies in the curved space btw 1 st , 2 nd & 3 rd portions of duodenum. The uncinate process is the portion of the head that extends to the left behind the superior mesenteric vessels. The neck is the constricted part and connects the head & the body. The body is situated horizontally in the retroperitoneal space. The tail extend towards the hilum of the spleen. BreadWinnerzAssociation

7. Illustration 1.2 Reproduced, with permission, from Way LW [editor]: Current Surgical Diagnosis & Treatment, 10th ed. Originally published by Appleton & Lange. Copyright © 1998 by The McGraw-Hill Companies, Inc. BreadWinnerzAssociation

8. (cont’d) The exocrine pancreas is drained by a major central duct called duct of Wirsung . This duct runs the length of the gland. D uct normally is about 3-4mm in diameter. Pancreatic duct enters the duodenum at the major duodenal papilla alongside the common bile duct. The sphincter of Oddi surrounds both ducts. In abt one third of individuals, the duct of Wirsung & the common bile duct join to form a common channel before terminating at the ampulla of Vater at about the middle portion of second part of duodenum. The accessory pancreatic duct, ( duct of Santorini ), runs from the head & body of the gland to enter the duodenum abt 2cm proximal to the duodenal papilla . BreadWinnerzAssociation

9. Anatomy- Endocrine Pancreas: Endocrine pancreas is composed of nests of cells called the islets of Langerhans . There are more than 1 million islets in the human pancreas, many of which contain several hundred cells. The endocrine pancreas has great reserve capacity; >70% of the B cells must be lost before dysfunction occurs. The islets are much more vascularized than the exocrine pancreatic tissues. Blood flow is thought to proceed from the center of the islet to the periphery, thereby allowing insulin produced by the central B cells to inhibit glucagon release by peripheral A cells . BreadWinnerzAssociation

10. (cont’d) Cell Type Proportion Hormone(s) A cells <20% of the islet cells Glucagon, proglucagon, glucagon-like peptides (GLP) B cells 80% of the islet cells Insulin, proinsulin, C-peptide, amylin, GABA D cells Few in number Somatostatin PP cells (a.k.a. F cells) In islets in posterior lobe of head of pancreas Pancreatic polypeptide There are 4 cell types within the islets, each of which produces a different major secretory product. Blood from the islets then drains into the hepatic portal vein. Thus, secretory products pass directly into the liver before proceeding into systemic circulation. BreadWinnerzAssociation

11. Illustration 1.3 Schematic representation of a normal rat (right) & human (left) islet showing the topographic relationships of the major cell types. BreadWinnerzAssociation

12. Physiology: Pancreatic Juice & Enzymes BreadWinnerzAssociation

13. Pancreatic juice: (exocrine) Abt 1.5L of pancreatic juice is secreted each day. Pancreatic juice contains water, ions, & a variety of proteins. The principal ions are HCO₃⁻ , Cl ⁻, Na⁺, & K⁺. Of these, HCO ₃⁻ is particularly important. The alkaline nature of pancreatic juice plays a major role in neutralizing the gastric acid entering the duodenum with ingested food ( chyme ) from the stomach. Pancreatic enzymes aid in the intraluminal phase of digestion & absorption of fats, carbs, & proteins. The rest are plasma proteins, mucoproteins , & trypsin inhibitors. BreadWinnerzAssociation

14. Pancreatic enzymes: Secreted in active form(s): Secreted as inactive proenzymes: (zymogens) Lipase Trypsinogen Amylase Chymotrypsinogen Deoxyribonuclease Proelastase Ribonuclease Procarboxypeptidase Phospholipase A2 BreadWinnerzAssociation Activation of zymogens within the acinar cell might otherwise lead to acute pancreatitis & pancreatic autodigestion.

15. Secretion of Pancreatic Juice: Secretion is controlled primarily by: Secretin & Cholecystokinin (CCK); both produced by specialized enteroendocrine cells of the duodenal mucosa. Also controlled in part by a reflex mechanism: Ach released by the vagus nerve acts like CCK on acinar cells to cause discharge of zymogen granules. BreadWinnerzAssociation Hormone Trigger for release Target cell(s) Action(s) Secretin Gastric acid Products of protein digestion in duodenum Pancreatic duct cells Cause an outpouring of very alkaline pancreatic juice CCK Products of protein & fat digestion in the duodenum Acinar cells Release of enzymes from zymogen granules.

16. Physiology: Insulin BreadWinnerzAssociation

17. Insulin Synthesis: Insulin plays a major role in fuel homeostasis-it plays an important role in storing the excess energy. Insulin is a protein composed of 2 peptide chains ( α & β chains), connected by 2 disulfide bonds. Preproinsulin is synthesized in the ribosomes & enters the endoplasmic reticulum of B cells. From here, it is cleaved by microsomal enzymes to form proinsulin. Transported to the Golgi apparatus, packaged into secretory vesicles . In the secretory vesicles, proinsulin is cleaved at two sites to form insulin & the biologically inactive C peptide fragment. Liver catabolizes ~50% of insulin BreadWinnerzAssociation

18. Insulin Secretion: Glucose is the primary physiologic stimulant of insulin release. Other factors such as amino acids ingested with a meal or vagal stimulation can cause insulin release . Amino acids strongly potentiate the glucose stimulus for insulin secretion. Glucose enters B cells via glucose transporter proteins (GLUT 2). ATP formed via glucose metabolism inhibits K⁺ efflux from the B cell . ( ATP-sensitive potassium channels ) Depolarization occurs; allowing Ca⁺⁺ to enter-through voltage-gated calcium channels. This triggers exocytosis of insulin-containing granules. BreadWinnerzAssociation

19. BreadWinnerzAssociation Illustration 1.4 Glucose-stimulated insulin release

20. Factors & Conditions That Increase/Decrease Insulin Secretion Increase Insulin Secretion: Decrease Insulin Secretion: Increased blood glucose Decreased blood glucose Increased blood free fatty acids Fasting Increased blood amino acids Somatostatin Gastrointestinal hormones (gastrin, CCK, secretin, GIP) Α -Adrenergic activity Leptin Glucagon, growth hormone, cortisol Parasympathetic stimulation; Ach Β -Adrenergic stimulation Insulin resistance; obesity Sulfonylurea drugs (glyburide, tolbutamide) BreadWinnerzAssociation

21. Mechanism of Action: Insulin exerts its effects by binding to insulin receptors present on the surfaces of target cells (liver, muscle, & fat). Binding of insulin to its receptor (e.g. of an enzyme-linked receptor ) causes: activation of a tyrosine kinase region a utophosphorylation of the receptor . ( ß -subunit) This amplifies downstream signaling molecules, ultimately leading to the biologic effects of insulin; Translocation of GLUT 4 glucose transporter to the plasma membranes of muscle & fat cells. BreadWinnerzAssociation

22. Insulin Effects: Insulin promotes fuel storage (anabolism) & prevents catabolism . Increase glucose uptake in abt 80% of the body’s cells; esp. muscle & fat cells but not neurons in brain . In liver; insulin stimulates glycogen synthesis & storage. Insulin inhibits hepatic glucose output by inhibiting gluconeogenesis & glycogenolysis. Also promotes formation of fatty acid precursors. Insulin stimulates lipogenesis, leading to the increased synthesis of VLDLs ; increasing fat stored. Insulin stimulates glucose uptake both in muscle & fat by causing the rapid translocation of GLUT-4 to the surface of these cells. In muscle, insulin causes glycogen & protein synthesis and inhibits glycogen catabolism. BreadWinnerzAssociation

23. Illustration 1.5 BreadWinnerzAssociation The receptor tyrosine kinase activity begins a cascade of cell phosphorylation that increases/decreases the activity of the enzymes, including insulin receptor substrates (IRS), that mediate the effects on glucose, fat, & protein metabolism.

24. BreadWinnerzAssociation Physiology: Glucagon

25. Glucagon Synthesis: Is produced by the proteolytic processing of proglucagon. Apart from pancreas, proglucagon is also expressed in the intestine & brain. Pancreatic glucagon opposes the effects of insulin. Circulatory half-life is 3-6 min. Glucagon is metabolized in liver (25%) & kidneys. BreadWinnerzAssociation

26. Regulation of Secretion: Glucagon secretion is inhibited by glucose. Fatty acids & ketones inhibit glucagon secretion. GABA (from B cells) is also thought to inhibit glucagon release. Catecholamines & cortisol stimulate glucagon release. BreadWinnerzAssociation

27. Mechanism of Action: Glucagon binds to a glucagon receptor present on hepatocytes. This promotes interaction with a stimulatory G protein , which in turn activates adenylyl cyclase. CAMp , generated by adenylyl cyclase, activates protein kinase regulator protein , Which activates protein kinase, Which activates phosphorylase b kinase , Which converts phosphorylase-b into phosphorylase-a , Which promotes degradation of glycogen into glucose-1-phosphate . Which is then dephosphorylated; & the glucose released from hepatocytes. BreadWinnerzAssociation

28. Effects: Glucagon affects metabolism by its actions in the liver & elsewhere. It counters the effects of insulin by acting in a catabolic fashion to maintain serum glucose levels. It stimulates hepatic glucose output. It stimulates glycogenolysis & gluconeogenesis. Also stimulates fatty acid oxidation & ketogenesis ; providing an alternative fuel that can be used by the brain when glucose is not available. BreadWinnerzAssociation

29. The End! Halleluyah! BreadWinnerzAssociation