8.2 - Pancreas (Part 1)

LECTURE NOTES

PANCREATIC EMBRYOLOGY

  • Abdominal accessory organ arise as foregut outgrowths

  • Proximal duodenum rotates

  • Ventral and dorsal ducts of the pancreas join together as the proximal duodenum rotates clockwise

  • Bile and pancreatic duts join to drain together at major papilla

PANCREATIC ANATOMY

  • Found otuside the abdomen

  • Four parts of the pancreas: head, neck, body and tail

  • Spleen is at the tip of the tail of the pancreas

PANCREATIC IMAGIN

  • CT scans are the best way to image the scans

  • MRCP - magnetic resonance cholangiopanreatography

    • Helps to see the finer structures within the pancreas more clearly

ENDOCRINE VS EXOCRINE SECRETION

  • Endocrine is only 2% of gland

    • Islets of langerhans

    • Secretes hormones into blood - insulin & glucagon (also somatostain and pancreatic polypeptide)

    • Regulation of blood glucose, metabolism and growth effects

  • Exocrine secretion is the remaining 98%

    • Secretes pancreatic juice to duodenum via MPD/sphincter of Oddi/ampulla

    • Digestive function (covered in this lecture)

PANCREATIC CELL DIFFERENTIATION

  • Acini

    • Produce pancreatic juice

    • Connected to ducts

    • Grape-like shape

    • Secrete pro-enzymes (inactive enzymes)

  • Islets

    • Derived from the branching duct system

    • Lose contact with ducts - become islets

    • Differentiate into alpha and beta cells

  • Pancreatic acinus - with many pancreatic acinar cells

  • Between them is intercellular canaliculi

  • Pancreatic juice secrete gradually join bigger and bigger ducts

COMPOSITION OF ISLETS

  • alpha: form about 15-20% of tissue and secrete glucagon

  • beta - form about 60-70% of islet tissue and secrete insulin

  • delta - form about 5-10% of islet tissue and secrete somatostatin

COMPOSITION OF ACINI

  • Secretory acinar cells - large with apical secretion granules

  • Produce thick, viscous, pure pancreatic jelly

  • Large with secretions around the duct (ducts are small and pale)

  • Acinar cells produce enzyme rich viscous mucinous low volume pure enzymes

  • Altered by high volume watery bicarbonate rich juice which is added to increase the pH and that is done by the duct and centroacinar cells

BICARBONATE SECRETION

  • Bicarbonate produced by duct and centroacinar cells

  • There to neutralise acid chyme from the stomach

    • Prevents damage to duodenal mmucosa

    • Raises pH to optimum range for pancreatic enzymes to work

  • Washes low volume enzyme secretion out of the pancreas into the duodenum

  • Bicarbonate secretion stops when pH is still acidic → main reason is because there are other things that can also help e.g bile and brunners glands secrete alkaline fluds

  • Pancreatic Cabronate Secretion

    • Catalysed by carbonic anhydrase

    • Separation of H+ and HCO3-

    • Sodium moves down gradient by tight junctoin and water follows

    • Chloride and bicarbonate exchange at llumen (Anion exchanger)

    • Na+ and proton exchange at basolateral membrane into bloodstream

    • Exchanges are driven by electrochemical gradient

    • High sodium concentration hgih outside compared to inside

    • High chloride in lumen compared to intracellular

    • Sodium gradient maintained by sodium potassium pump

    • Potassium returns to blood via potassium channel

    • Chloride returns to lumen via chloride channel (cystic fibrosis transmembrane conductance regulator - CFTR)

  • Gastric venous blood is very alkaline

  • Pancreatic venous blood is acidic

ACINAR CELL ENZYME SECRETION

  • Enymes for digestion of fat, protein and carbohydrates

  • Syntehsised and stored in zymogen granules

  • Proteases released as inactive pro-enzymes

    • Protects acini and ducts from auo-digestion

  • Pancreas also contains a trypsin inhibitor to prevent trypsin activation

  • Enzymes only activated in duodenum

  • Blockage of MPD may overload protection (auto digesiton which leads to pancreatitis)

  • Enzyme secretion

    • Duodenal mucosa secretes an enzyme - enterokinase, which converts trypsinogen into trypsin

    • Trypsin then converts all other proteolytic and some lipolytic enzymes

    • Lipase secrted in active form but requires colipase, and it also requires the presence of bile salts for effective action

ALTERED PANCREATIC ENZYME FUNCTION

  • Enzyme production depends on our diet

  • Orlistat increases faecal dat

    • occurs when pancreatic lipase secretion decreased

    • e.g. cystic fibrosis, chronic pancreatitis

PANCREATIC JUICE SECRETION

  • Cephalic phase - reflex resposne to sight/smell/taste of food

  • Gastric phase - stimulation of pancreatic secretion originating from food arriving in the stomach, and same mechanisms involved as for cephalic phase

  • Intestinal phase - hormonally mediated when gastric chyme enters duodenum with both components of pancreatic juice stimulated

CONTROL OF SECRETION

  • viscous components and bicarbonate components are separately controlled

  • controlled in acini by vagus nerve and cholecystokinin

  • Bicarbonate secretion controlled in duct and centroacinar cells by secretin (cAMP)

  • Vagus nerve - acetylcholine as NT - stimulates

  • Mechanisms responsible for controlling cholecystokinin afrom duodenal I cellsL]

    • GRP - gastric releasing peptide that stimulates pancres

    • Produce a monitor peptide which can then stimulate the cell to produce cholecystokinin

    • Taking in fatty acid will stimulate cholecystokinin releasing peptide (CCK-RP)

    • Tryspin has a negative effect on all these mechanisms

  • Acinar fluid is isotonic

  • Secretion of acinar fluids and proteins it contains is stimulated by cholecystokinin

  • Secretin stimulates secretions of water and bicarbonate from cells lining extralobular ducts and secretin-stimulated secretion is richer in bicarbonate cf acinar secretion because of chloride/bicarbonate exchange

  • CCK alone no effect on bicarbonate secretion

  • CCK and secretin increases rate of bicarbonate of secretion significantly

SUMMARY OF A MEAL

  • Food mixed, digested in stomach - acidic ph 2

  • Chyme squirted into the duodenum

  • protons in duodenum increases secretin secretion and increases pancreatic juice secretion

    • this inc combination with bile and Brunner’s gland secretion increases pH to neutral and alkaline

  • Peptides and fat in duodenum cause sharp in cholecystokinin and vagal nerve stimulation which stimulates pancreatic enzyme release

  • Peaks by 30 mins continues until stomach empties

  • CCK potentiates effects of secrtin on aqueous component

  • Necessary as most of duodenum not at low pH