Physiology of Digestion and Absorption 1

1. Physiology of Digestion and Absorption 1 Professor John Peters E-mail: j.a.peters@dundee.ac.uk

2. Learning Objectives • After this lecture students should be able to: • Describe the nature of the chyme • List the hormones released from the duodenal mucosa • Relate function to basic structure/cell type on drawings of the pancreas • Compare salivary and pancreatic secretion - primary and modified secondary secretion • List the composition of pancreatic secretion • Indicate briefly how pancreatic enzymes are activated • Describe the importance of bicarbonate • State the importance of bile in fat digestion • Describe briefly the hormonal controls of biliary and pancreatic secretions in the cephalic, gastric and intestinal phases of digestion

3. The Small Intestine • Major site for digestion and absorption Approx. 6 m long, 3.5 cm diameter (longer when relaxed - after death) 3 parts • Duodenum – approx. 25 cm • Jejunum – approx. 2.5 m • Ileum – approx. 3 m • Receives • chyme from stomach • pancreatic juice from pancreas • bile from gall bladder • Secretes intestinal juice • Moves remaining residues to the large intestine

4. Secretions of the Small Intestine (1) • Duodenum secretes (into the blood) various peptide hormones from endocrine cells within the mucosa: • Gastrin – from D cells of gastric antrum (mainly) and duodenum • Cholecystokinin (CCK) – from I cells of duodenum and jejunum • Secretin – from S cells of duodenum • Motilin – from M cells of duodenum and jejunum • Glucose-dependent (or glucagon-like) insulinotropic peptide (GIP) – an incretin from K cells of duodenum and jejunum [note activity is potentiated by gliptins (e.g.sitagliptin) used in treatment of type 2 diabetes mellitus] • Glucagon-like peptide-1 (GLP-1) – an incretin from L cells of small and large intestine [note activity mimicked by extenatide and potentiated by gliptins (e.g.sitagliptin), both used in treatment of type 2 diabetes mellitus] • All act on G-protein coupled receptors

5. Secretions of the Small Intestine (2) Succus (juice) entericus (of the intestine) – approximately 2 litre secreted per day - composition varies throughout small intestine • Control mechanisms include • Distension/irritation, gastrin, CCK, secretin, parasympathetic nerve activity (all enhance), sympathetic nerve activity (decreases) • Secretion contains • mucus – for protection/lubrication (from goblet cells) • aqueous salt - for enzymatic digestion (mostly from the crypts) • no digestive enzymes Secretion involves Na+/K+ ATPase Na+/K+/2Cl- co-tranporter Chloride channel (CFTR) Nb. Excessive activity causes secretory diarrhoea (as in cholera)

6. Mixing and Propulsion of Chyme (1) 1. Segmentation (mixing) • “chopping” moves chyme back and forth – very vigorous after a meal (little / none between meals) • Alternating contraction and relaxation of segments of circular muscle • Initiated by small intestine pacemaker cells causing the BER which is continuous. At threshold activates segmentation which in the duodenum is primarily due to distension by entering chyme • Segmentation in the empty ileum is triggered by gastrin from the stomach (gastroileal reflex) • Duodenum has frequent segmentation contractions (12 per min), ileum has fewer (9 per min)  net movement is aboral

7. Mixing and Propulsion of Chyme (2) • Movement is slow - takes 3-5 hrs - allows time for absorption • Strength of segmentation enhanced and decreased by parasympathetic and sympathetic activity, respectively 2. Peristalsis Two activities occur in the interdigestive, or fasting, state • A few localised contractions • The migrating motor complex (MMC) • Occurs between meals every 90 – 120 minutes • Strong peristaltic contraction passing length of the intestine (stomach  ileocaecal valve) • Clears small intestine of undigested debris, mucus and sloughed epithelial cells between meals – ‘housekeeper function’ • Inhibited by feeding and vagal activity • Triggered by motilin, suppressed by gastrin and CCK Nb. Macrolide antibiotics (e.g. erythromycin) mimic the action of motilin and may cause unpleasant G.I. disturbances

8. Pancreatic Secretions • Endocrine – insulin and glucagon – secreted to blood • Exocrine – digestive enzymes (acinar cells), aqueous NaHCO3- solution (duct cells) – secreted to the duodenum collectively as pancreatic juice

9. Pancreatic Enzymes • Can completely digest food in the absence of all other of enzymes Acinar cells Enzymes stored in zymogen granules Duodenum Enterokinase(mucosal cells) Proteases Trypsinogen Trypsinogen Trypsin Autocatalysis Chymotrypsinogen Chymotrypsinogen Chymotrypsin + + + Procarboxypeptidase Procarboxypeptidase Carboxypeptidase Amylases Inactive enzyme Pancreatic amylase Pancreatic amylase Lipases Active enzyme Pancreatic lipase Pancreatic lipase

10. Secretion of the Pancreatic Duct Cells • Duct cells secrete 1 – 2 litre of alkaline (HCO3- -rich) fluid into the duodenum per day • Neutralises acidic chyme entering the duodenum • Provides optimum pH for pancreatic enzyme function • Protects the mucosa from erosion by acid Secretion involves Na+/K+ ATPase K+ Na+/H+ exchanger Ductule HCO3- Na+ HCO3- Na+ K+/H+ ATPase H2CO3 Cl- Cl- Cl-/HCO3- exchanger H+ Carbonic anhydrase K+ Chloride channel (CFTR)* CO2 + H2O CO2 Na+, H2O Na+, H2O *Nb. Patients with cystic fibrosis have reduced fluid secretion

11. Control of Pancreatic Secretion • Three phases: • Cephalic – mediated by the vagal stimulation of mainly the acinar cells (20% total secretion) • Gastric – gastric distension evokes a vagovagal reflex resulting in parasympathetic stimulation of acinar and duct cells (5-10% total secretion) • Intestinal(see below; 70-80% of total secretion) Acid in duodenal lumen Fat and protein in duodenal lumen  Secretin release from S cells  CCK release from I cells Neutralizes Digests Secretin carried by blood CCK carried by blood Pancreatic duct cells Pancreatic acinar cells  Secretion of aqueous NaHCO3 solution into duodenal lumen  Secretion of digestive enzymes into duodenal lumen

12. The Biliary System • Comprises liver, gall bladder and associated ducts

13. Bile • Produced continuously by the liver 0.6 – 1.2 litre per day • Between meals • Stored and concentrated in gall bladder (sphincter of Oddi closed) • During a meal • Chyme in duodenum stimulates gall bladder smooth muscle to contract • Sphincter of Oddi opens • Bile spurts into duodenum via cystic and common bile ducts • Bile composition • Secretion of bile duct cells • Secretion of hepatocytes Secretions mix in the ducts Bile participates in the digestion and absorption of fats

14. Integrative Activity of Secretin Acid in duodenal lumen  Secretin release from S cells Secretin carried by blood Neutralizes Pancreatic duct cells Hepatocytes and duct cells  Gastric secretion  Gastric emptying  Secretion of aqueous NaHCO3 solution into duodenal lumen  Secretion NaHCO3 – rich bile into duodenal lumen

15. Integrative Activity of CCK Fat and protein in duodenal lumen  CCK release from I cells CCK carried by blood Efficient Digestion Pancreatic acinar cells Gall bladder and sphincter of Oddi  Gastric secretion  Gastric emptying  Secretion of digestive enzymes into duodenal lumen Contraction of Gall bladder Relaxation of sphincer of Oddi