1 duodenum The response of the duodenum to food (continued) Preparing for more digestion (involves - pancreas, liver and gallbladder) Signaling back to the stomach – Regulating release of food, – Stopping (eventually) gastric secretions Continuing digestion Beginning absorption in the small intestine

2 Readings – Digestive 4 McKinley, O’Loughlin, and Bidle, Anatomy and Physiology An integrative Approach, p Overview of the Digestive System – Small intestine

Objectives Describe how the duodenum regulates the functions of the stomach. Review the stimulants, receptors and the effects that are involved in the signaling between the duodenum and the stomach. Describe the enterogastric reflex. Describe the stimulants, receptors and the effects that relate to signaling between the duodenum and the pancreas, liver, and gall bladder. Understand the different roles of CCK, secretin, GIP, VIP and serotonin as they relate to function of the stomach and small intestine. Review and describe the methods to increase absorption in the intestines. Compare the 5 major epithelial cell types in the intestine

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What happens to chyme (food and acid) in the duodenum and small intestine Pancreas releases digestive enzymes Liver – synthesizes bile for lipid absorption Gallbladder releases bile Digestion continues Absorption of building blocks through enterocytes Water added and reabsorbed Undigested material remains and is eliminated 5 Digestion and absorption are important here!

Out of Stomach & Into the Intestine Gastro- duodenal junction Plicae circulares = Examine the structure of the intestines: length and lumen characteristics

7 Food enters the duodenum – What happens? 2 Jobs : 1. Duodenum signals the stomach to regulate work – want regulated release of contents … cause duodenum is toooo small & needs time to neutralize chyme. 2. Must promote digestion and absorption – Neutralize acidic chyme – Signal pancreas, liver, and gallbladder to make and release fluids, muscle walls contract, sphincters open the duodenum is the ‘cockpit’ of the GI system

Intestinal Phase (food into the duodenum) Why does the duodenum talk back to the stomach? The duodenum is smaller and it receives large volumes of very acidic chyme. – Regulate gastric motility (muscle contractions) in stomach – squirts into duodenum – Allows time to import HCO 3 - and buffer the stomach acid – Need to raise the pH to ~7.0 … the pH optimum for digestive enzymes – Eventually regulates/turn off the stomach cell secretions (by parietal and chief cells)

9 Stimulants: – Bulk = food (slightly digested) stretches the lumen – Chemicals: pH of chyme is low (due to stomach HCl) Nutrients: lipids, proteins & carbohydrates Receptors in duodenum respond to food – Mechanoreceptors (stretch) receptors sense bulk – Chemoreceptors - sense pH – Enteroendocrine cells - sense nutrients Intestinal Phase – talkin’ to the stomach Receptors (mechano- and chemo-) Regulate myenteric plexus so … Regulate stomach cell secretion (parietal and chief cells) Regulate stomach muscle contraction (gastric motility) Enteroendocrine cells sense Nutrients and/or low pH and release: CCK & GIP (lipids, peptides and carbohydrates); Secretin (low pH) Regulate stomach cell secretion (parietal and chief cells) Regulate stomach muscle contraction (gastric motility) effects: CCK = cholecystokinin; GIP =gastric inhibitory peptide

Cells: Mucous Parietal Chief Myenteric and Submucosal plexus’ Muscle contraction mucous HCl pepsinogen Intestinal phase … Note inhibition - gastric functions! Duodenal stretch receptors chemoreceptors mostly an intrinsic – reflex response Stimuli: distention lowered pH Lipids & carbo- hydrates Decreased pH CCK GIP Secretin X X Stimuli: Enterogastric reflex X

11 Food enters the duodenum – What else happens? Duodenum signals the stomach to regulate and then stop work Must regulate gastric motility - inhibitory – Allows slow release of foods into the duodenum Allows duodenum time to recruit digestive enzymes Allows duodenum time to recruit HCO 3 - to buffer stomach acid Must promote digestion and absorption (need digestive enzymes & bile)

12 What controls functions of the small intestine and related accessory glands? Stimulate the pancreas to release water, enzymes, and HCO 3 - (bicarbonate) Stimulate the liver to make bile Help release bile and pancreatic fluids Regulate duodenal motility (peristalsis) alsosignal Signals that turn down the stomach also signal the intestine to upregulate – digestion and absorption

13 Response and effect Response and effect – CCK – CCK released – zymogens synthesized and secreted by pancreas – relaxes hepato-pancreatic sphincter – stimulates contraction of gall bladder – bile released Intestinal Phase (food into the duodenum) Stimulants: – lipids & peptides Receptors: – Enteroendocrine cells making CCK =cholecystokinin

14 Stimulants: pH – Chemicals: low pH Receptors: – Enteroendocrine cells making Secretin Responseand effects Response and effects – Secretin is released from duct cells – Accelerated release of water and HCO 3 - from the pancreas – neutralizes stomach pH – Increases secretion of bile from the liver – Gastric motility regulated so food enters duodenum in ‘squirts’ Intestinal Phase (food into the duodenum)

15 Stimulants: – lipids & carbohydrates (glucose) Receptors: – Enteroendocrine cells making GIP = glucose–dependent insulinotropic peptide Response and effects Response and effects – GIP released – insulin released from the pancreas when glucose causes hyperosmolarity – Duodenal glands more active – more buffer made – More glucose used by skeletal muscle Intestinal Phase (food into the duodenum)

16 Stimulants: – lipids and carbohydrates Receptors: – Enteroendocrine cells making VIP = vasoactive intestinal peptide Response and effects Response and effects – VIP released by enteroendocrine cells in the duodenum – Duodenal glands more active – more buffer made – Intestinal capillaries more dilated – helps with absorption Intestinal Phase (food into the duodenum)

17 Summary: stomach and duodenum signaling

5. Intestinal phase - summary 18 Stimuli Pathways Effects Neural, endocrine, and paracrine pathways : - Intrinsic and Extrinsic neural pathways – afferent via the vagus nerve into the CNS activate parasympathetic outflow - Endocrine – CCK, secretin, GIP, and VIP - Paracrine – CCK and others Mechanical – distension of smooth muscle wall Chemical – protons (H+), osmolarity changes, nutrients from food Motor – -regulation of gastric emptying and timed release of chyme -peristalsis - less in stomach and more in small intestine -gallbladder contraction and relaxation of sphincter of Oddi (bile release) Secretory - regulation of gastric cell secretion - increased pancreatic secretion, Brunner gland secretion of mucus and HCO bile secreted

19 Small intestine: structure and functions duodenum jejunum ileum

20 Food enters the duodenum – What happens? Duodenum signals the stomach to regulate then stop work Duodenum – jobs to do: – Neutralize stomach acid – Signal for new digestive enzymes to continue digestion process – Signal for bile from the gallbladder – Continues digestion of foods and – Begins absorption process

21 How do you optimize absorption? Breakdown large foods into the building blocks – Complex carbohydrates to monosaccharides – Proteins to small peptides and amino acids – Large fats to cholesterol, fatty acids and monoglycerides Increase surface area for more absorption

22 Structure - Function: Increase surface area – increase absorption 2-3 fold  10 fold  fold  Mucosal folds = plicae VilliEpithelial cellsMicrovilli Increases in surface area increase absorption by 400 to 900 times! MORE MEMBRANE = MORE CHANNELS = MORE ABSORPTION Four methods: (1) length, (2) plicae, (3) villi, (4) microvilli

23 1. Mucosa = Plicae and villi – Epithelium – simple columnar with microvilli – Lamina propria (CT) – Muscularis mucosa 2. Submucosa (CT) Plicae, no glands 3. Muscularis externa – Inner circular – Outer longitudinal 4. Serosa -- (Adventitia only at anus) 4 Layers of the Intestinal System

24 Ileum in situ The ileum has folds = plicae circulares that are visible in the gross specimen. Compare and contrast these with rugae in the stomach.

25 Small intestine - Structure Ileum plicae - submucosa included in the fold (with the muscularis mucosa) plicae are visible In contrast – villi only include the epithelium and lamina propria so …the muscularis mucosa and submucosa are not included in the villus. villi Higher mag.

26 Villi structure Simple columnar epithelium Lamina propria – capillaries – lacteals

27 Intestinal villi (V) Simple epithelium: – enterocytes = columnar absorptive cells with microvilli – goblet cells (ratio varies with location) Core = lamina propria (LP) = connective tissue Blood vessels Lacteals (lymphatic) Glands or crypts of Lieberkühn (C) LUMENLUMEN c LP V V

28 Villus – higher magnification (microvilli)

29 Microvilli ( per cell) 1. Increase surface area and create more sites for channels and absorption. 2. Also contain disaccharidases and dipeptidases What do microvilli do?

30 lumen 1. Enterocyte = absorption Lamina propria 2. Goblet cell 5 Intestinal Cells 4. Paneth cell 3. Enteroendocrine cell 5. Stem cells differentiate into the other 4 types

31 5 Cells 5 Cells of the intestine Enterocyte = absorptive cell, microvilli on the apical surface, dipeptidases and disaccharidases in the glycocalyx, pass building blocks to the lamina propria and the blood vessels of the portal system Goblet cell – secretes mucous to protect the surface from chemical damage (pH and enzymes) or shear stress Paneth cells – ‘guardians of the gut cell hatchery’; regulate bacterial flora of the gut with lysozymes, lactoferrins, and antibodies Enteroendocrine cells – sense chemical changes in the intestinal lumen and secrete signaling molecules to cause changes in the gut, eg. gastrin stimulates parietal cells to make HCl. Stem cells – can differentiate into any of the other 4 types

32 Cells in the crypt of Lieberkühn Paneth cells (P) have intensely eosinophilic granules and secrete antimicrobial peptides into the lumen (L) Enteroendocrine (E) cells secrete their signaling molecules into the surrounding CT. Goblet cells (G) secrete mucous into the lumen. Gland Lumen LP (intestinal gland)

33 Intestine - Structures – Plicae – Villi, glands – Microvilli Cells: – Enterocyte – Goblet cell – Enteroendocrine – Paneth cell – Stem cell Review

34 Summary Stimulants – bulk, chemicals, nutrients. Receptors –mechano- and chemo-receptors & enteroendocrine cells. Signals to the stomach regulate its function – & then make it stop. Signals to the pancreas, liver, and gallbladder to release chemicals to promote digestion. Signals to the intestinal muscles to promote peristalsis and segmentation. Structural changes - increases surface area to improve absorption.

For those who want more - Serotonin is a very important molecule in the gut. You will here a lot about serotonin and its receptor and their involvement in Crohn’s disease and inflammatory bowel disease. 35

36 Stimulants: Receptors: – Enteroendocrine cells making Serotonin Response Response – Serotonin – Serotonin released Effects: Effects: – Peristalsis – muscle contraction in small intestine – Intestinal secretion – Intestinal capillaries more dilated – helps with absorption Intestinal Phase (food into the duodenum) Serotonin Serotonin = 5-HT

Serotonin is an important activator of gastrointestinal reflexes Most of the 5-HT in the bowel is synthesized by an enteroendocrine cell called the enterochromaffin (EC) cells. 95% of serotonin in the body is in the gut 5-HT released from EC cells can initiate reflex responses such as intestinal secretion, peristalsis, and vasodilation, and when released in large amounts, it causes nausea and vomiting. The actions of 5-HT are terminated by reuptake involving the same serotonin-selective reuptake transporter (SERT) that is found in the CNS.

5-HT signaling in the gut SERT 50 µm 5-HT 50 µm At Rest 5-HT Receptors EC Cell Lamina Propria Afferent nerve SERT Lumen Epithelial Cell 5-HT StimulationRecovery capillary Platelet