Pancreas Physiology PDF

Pancreas Part I - Anatomy, Histology and Physiology Part II – Common Pathologies of the Pancreas BMS 150 Week 13 Overview Anatomy and histology of the pancreas Exocrine functions of the pancreas Digestive enzymes Bicarbonate Regulation of...

Pancreas Part I - Anatomy, Histology and Physiology Part II – Common Pathologies of the Pancreas BMS 150 Week 13 Overview Anatomy and histology of the pancreas Exocrine functions of the pancreas Digestive enzymes Bicarbonate Regulation of pancreatic secretions Pancreas: Anatomy Four Parts: Head and uncinate process Neck Body Tail Ducts: Main pancreatic duct joins the common bile duct at the hepatopancreatic ampulla (Ampulla of Vater) Accessory pancreatic duct drains to the minor duodenal papilla (less important) Transverse plane – L1 25 cm long, 5cm wide, 1-2 cm thick Retro-peritoneal structure Possesses a thin capsule Septa from the capsule divide it into lobes and lobules Pancreatic Arterial Supply Arterial Supply: Head: Pancreaticoduodenal branches of the gastroduodenal artery Superior mesenteric artery Neck, Body, Tail Branches of splenic artery (celiac trunk) supply neck, body and tail Venous Supply: Splenic vein & superior mesenteric vein Moore’s Clinically- Oriented Anatomy Fig. 2.59  Exocrine Pancreas – Histology The exocrine functions of the pancreas are carried out by the acini Compound tubulo-acinar gland system ▪ produces 1200 ml of bicarbonate-rich fluid containing digestive enzymes per day 40-50 acinar cells form a spherical acinus ▪ Most of the cells making up the acinus = acinar cells (pyramidal-shaped columnar epithelial cells) ▪ Acinar cells surround centroacinar cells – the centro-acinar cells line the lumen of the acinus Beginning of the intercalated ducts Intercalated ducts branch from the lumen of the acinus and merge into interlobular ducts Exocrine Pancreas - Histology General function of acinar cells: ▪ Secretion of inactive pancreatic enzymes (zymogens) ▪ Rich RER, lots of granules (filled with zymogens) ▪ CCK major stimulator General function of centroacinar cells: ▪ Secretion of HCO3-rich fluid ▪ Secretin major stimulator Exocrine Pancreas Centroacinar cells and intercalated duct cells can both secrete bicarbonate in response to secretin major contributors to bicarbonate-rich secretions  Secretion of Bicarbonate Ions CO2 diffuses from blood to interior of cell and combines with H2O to form H2CO3 (carbonic anhydrase) which dissociates into HCO3- and H+ HCO3- is actively transported into duct Na+ follows HCO3- into the duct – drawn into the duct via the negative charge of HCO3- ▪ H+ exchanged for Na+ at the basolateral surface of ductule cells Movement of HCO3- and Na+ into ducts creates osmotic pressure causing osmosis of H2O into duct  Phases of Pancreatic Secretion Cephalic ▪ Same nervous signals from brain that cause secretion in stomach also cause acetylcholine release by vagal nerve endings in pancreas ▪ 20% of pancreatic secretion Gastric phase ▪ Nervous stimulation of enzyme secretion (5-10%) Intestinal Phase ▪ After chyme leaves stomach and enters small intestine = lots of pancreatic secretion due to secretin and CCK release → more fluid Cephalic and gastric phase Intestinal phase  Regulation of pancreatic secretion Both neural and hormonal control ▪ cephalic and gastric phases are mostly regulated through nervous system ▪ Intestinal phase is mostly under hormonal control Hormone Source Stimulus Stomach Pancreas Gall Bladder Motility and Secretion Secretin S cells lining Acid Inhibits Stimulates fluid None duodenum entering secretion duodenum (HCO3-) CCK I Cells lining Fat and Inhibits Stimulates - Contraction of duodenum amino acids emptying enzyme the gall bladder entering secretion - Relaxation of the sphincter of duodenum Oddi Regulation of pancreatic secretion Secretin (review) ▪ Released from S cells in mucosa of duodenum and jejunum when acidic chyme (pH 4.5 – 5) reaches the small intestine ▪ Released into bloodstream, causes pancreas to secrete large quantities of bicarbonate-rich fluid ▪ Creates appropriate pH for action of pancreatic enzymes (7.0 to 8.0) Regulation of pancreatic secretion Cholecystokinin (review) ▪ Released from I cells in mucosa of duodenum and jejunum when partially digested proteins and long-chain fatty acids are present in the lumen ▪ Travels through the bloodstream to the pancreas ▪ Stimulates secretion of more pancreatic digestive enzymes by acinar cells  Pancreatic Secretions 2 secretions combine and then flow through long pancreatic duct ▪ Joins the common bile duct to release secretions into the ampulla of Vater ▪ Empties into duodenum through the major duodenal papilla ▪ Major duodenal papilla is surrounded by sphincter of Oddi  FYI – actions of pancreatic proteolytic enzymes Proteolytic Source; Inactive Activated by Action Products Enzyme Form Pepsin Stomach (chief cells); Low pH Cleaves between aromatic and Large Pepsinogen (stomach acid) hydrophobic a.a.s peptides good at collagen digestion (10-15% of protein digestion) Trypsin Pancreas (acinar Entero-kinase Cleaves bonds next to lysine or small cells); Trypsinogen (brush border arginine peptides enzyme in duodenum) Chymo- Pancreas (chymo- Trypsin (in cleaves next to: phenylalanine, small trypsin trypsinogen) duodenum) tyrosine, tryptophan, peptides methionine, asparagine, histidine elastase Pancreas (pro- Trypsin (in cleaves elastin small elastase) duodenum) peptides Carboxy- Pancreas (pro- Trypsin (in cleaves COOH terminal end of single a.a.s peptidase carboxypeptidase) duodenum) peptides A&B A: non-polar and aromatic a.a.s B: basic a.a.s  Pancreatic proteolytic enzymes Review: Endopeptidases: ▪ through hydrolysis, cleave peptide bonds at certain amino acids Example: pepsin cleaves between aromatic and hydrophobic amino acids Endopeptidases include pepsin, trypsin, chymotrypsin, elastase Exopeptidases: ▪ through hydrolysis, cleave peptide bonds at the carboxyterminus Exopeptidases include carboxypeptidases (A + B)  Pancreatic Secretions – controlling trypsin Trypsin inhibitor – prevents pancreatic auto-digestion ▪ Secreted from acinar cells, prevents activation of trypsin inside secretory cell and in ducts of pancreas ▪ Packaged together with other pancreatic enzymes in zymogen granules Trypsin, when it “runs out” of proteins to break down in the duodenum, then hydrolyzes itself in a form of negative feedback ▪ Genetic defects involving either of these processes increase the risk of pancreatitis (more in path later) Pancreatic secretions Review: Pancreatic amylase: ▪ Hydrolyzes alpha 1-4 linkages in amylose (starch) Pancreatic lipase and colipase: ▪ Pancreatic lipase needs fat emulsification (bile salts) as well as colipase in order to cleave triglycerides into 2- monoglyceride and FFAs Can be absorbed by the enterocyte Phospholipase A2 ▪ activated by trypsin, digests phospholipids (FYI – glycerophospholipids) References Junquiera’s Basic Histology: Text and Atlas (13th edition) – pg. 326-329 Guyton’s Medical Physiology – pg. 780-783 Moore’s Clinically-Oriented Anatomy, pages 265 - 268 Robbin’s and Cotran’s Pathologic Basis of Disease, Chapter 19