Gastrointestinal physiology

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Gilbert Wade
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2 Gastrointestinal physiology

3 General principal of gastrointestinal function

5 Characteristic of the GI wall Mucosa: Epithelium; varies at different part of GI Lamina propria; connective tissue Glands, lymph node, capillaries Muscularis mucosa; mucosal fold and ridges Submucosa: connective tissue Glands, large nerve trunks, blood vessels Muscularis externa: mix & propel content of the lumen Inner circular layer Outer longitudinal layer Serosa: connective tissue covered by squamous mesothelial cells

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7 Microvillus Villi Crypt

9 Control of contractile and secretory activities of the GI Neural control Central nervous system Enteric nervous system Hormones

10 Neural control of GI function The Enteric nervous system (ENS)* Myenteric (Auerbach's) plexus: motor neuron Submucosal (Meissner's) plexus: secretory Neurotransmitters on ENS: Excitatory: Ach Inhibitory: VIP, NO

12 Autonomic control of GI tract Parasympathetic innervation Cranial (vagus n) Sacral (S 2 -S 4 ): pelvic n

13 - Sympathetic innervation (T5 - L2) : celiac and mesenteric ganglions

15 Hormonal control of GI Cholecystokinin: I cells Secretin: s cells Gastric inhibitory peptide (GIP) *

17 Types of GI movements: Propulsive movement-peristalsis Myenteric plexus is necessary for peristalsis Directional movement of peristalsis wave toward the anus: Law of the gut Receptive relaxation Mixing movement

18 Peristaltic motilility

19 Segmental contraction

20 Clinical note Paralytic ileus is a temporary cessation of gut motility that is most commonly caused by abdominal surgery. Other common causes that result in an ileus are infection or infl ammation in the abdominal cavity (e.g., appendicitis), electrolyte abnormalities (e.g., hypokalemia), and drug ingestion (e.g., narcotics). Signs and symptoms of paralytic ileus include nausea and vomiting, abdominal distension, and absent bowel sounds.

22 Propulsion and mixing of food in the alimentary tract Chapter 63

23 Mastication (chewing) Swallowing* Ingestion of food Voluntary (oral) stage of swallowing Pharyngeal stage of swallowing: reflexive Trachea is closed, esophagus is opened, fast peristaltic wave start Respiration is inhibited by swallowing center in medulla CN: 5, 9,10,12 involved in this stage Esophageal stage of swallowing* Primary peristalsis: initiated by swallowing Secondary peristalsis: elicited by distention Controlled by Swallowing center (vagus n), ENS

24 Receptive relaxation of the stomach Function of the lower esophageal sphincter Basal tone: vagal cholinergic fiber Relaxation of LES by inhibitory effect of NO & VIP Ashalasia: defect in LES relaxation Gastroesophageal reflux

26 Motor function of the stomach Anatomic subdivision of stomach* Storage function of the stomach: vagovagal reflex Mixing and propulsion of food in the stomach The basic electrical rhythm of the stomach(3/min) Fed and fasted state: migrating myoelectric complex (MMC): 75-90min Vagal impulse motilin Chyme Hunger contractions

27 Physiological anatomy of the stomach

28 Emptying of the stomach The pyloric pump Role of the pylorus in controlling stomach emptying

29 Regulation of stomach emptying The gastric factors that affect emptying Effect of food volume Effect of hormone Gastrin The duodenal factors that inhibit stomach emptying Inhibitory effect of entrogastric nervous reflexes from the duodenum: Osm, PH, Distention Hormonal feedback from duodenum : role of fat and CCK, Secretin, GIP

30 Movement of small intestine Mixing contraction: segmentation Contraction of circular muscle (alternative site) Fr: 12-8/min Propulsive movements Short range progressive contraction in circular muscle Fr: less than segmentation Important for absorption (codeine, caster oil) Control of peristalsis by ENS Nervous and hormone modulation MMC: housekeeper of the SI

31 Movement caused by the muscularis mucosa ileocecal valve: pressure in cecum inhibits ileal peristalsis and excite the sphincter*

33 Movement of the colon Anatomic subdivision of large intestine Teniae coli Innervation of colon: vagus n. Pelvic n. Int & Ext anal sphincter Mixing movement Haustrations Propulsive movements mass movements: 3/day Initiation of mass movements by gastrocolic and deodenocolic reflexes

35 Defecation: reflex and voluntary action Defecation reflexes: Filling rectum relaxation of Int sphincter and contraction of Ext ones. Integration center in Sacral region and modulated by higher center

37 Secretory function of the alimentary tract Chapter 64

38 General principles of alimentary tract secretion Mechanism of stimulation of the alimentary tract glands Effect of contact of food with the epithelium Autonomic stimulation of secretion Parasympathetic, sympathetic Hormonal regulation of secretion

39 Basic mechanism of secretion by glandular cells Secretion of organic substances Water and electrolyte secretion

40 Secretion of saliva Structure of salivary glands: Parotid, submandibular, sublingual glands Characteristic of saliva: Mucosal secretion (mucin): submandibular, sublingual Serousal secretion (ptyalin); Parotid, submandibular, sublingual Buccal glands; mucous ph: 6-7 Secretion rate:1ml/min/gr of gland, 1.5 L/day Secretion of lingual lipase

41 Microscopic structure of salivary gland secretion of primary saliva in the end piece (acini)

42 Secretion of water and electrolytes

43 Nervous regulation of salivary secretion* Parasympathetic: long-lasting secretion VIP, Ach Increase blood flow, metabolism and growth Sympathetic: transient secretion Function of saliva for oral hygiene Flow Proteolytic enzyme Abs

44 Major secretion: Gastric secretion Hydrochloric acid: activate pepsin; low ph is necessary for pepsin action Pepsin: digestion of protein Intrinsic factor: bind to Vit B 12 Mucous & bicarbonate: protection Endocrine secretion: Gastrin; promote secretion of HCL and pepsinogen

45 Structure of gastric mucosa A: Oxyntic glandular region B: Pyloric glandular region Columnar epithelial cell: mucous and HCO3 - Parietal (oxyntic) cells: HCL & intrinsic factor Chief or peptic cells: pepsinogen ECL-cells: histamine D-cells: Somatostatin Mucous neck cell (in B) G-cells (in B): gastrin

47 Basic mechanism of hydrochloric acid secretion ph: 0.8 Isotonic

48 Neural and hormonal regulation of gastric secretion Basic factors that regulate gastric secretion: Stimulators: Ach, Gastrin, Histamine Inhibitors: Somatostatin, prostaglandins (E&I)

49 Control of gastric HCL secretion

50 Protection of the gastric surface epithelium and neutralization of acid in the duodenum

51 ... Break down of gastric barrier: salicylate, ethanol Role of prostaglandins in maintaining mucosal integrity: Inhibit acid secretion, increase mucosal blood flow, modify local inflammatory response Helicobacter pylori (H. Pylori)

52 Peptic ulcer Drug used in peptic ulcer: Cimetidine; H2-Blocker Omeprazol; inhibitor of H+-K pump Proglumide: CCk-B receptor antagonist Misoprostol: PG analog

53 Secretion and activation of pepsinogen Pepsin: Digest 20% of protein ph:3 Inactivate in duodenal ph

54 Phases of gastric secretion Cephalic phase* Gastric phase Intestinal phase

56 Inhibition of gastric secretion by poststomach intestinal factors: Stimuli: low ph, digestion product of fat and protein, hypertonicity - Mechanism : Vagovagal and enteric reflexes that inhibited HCL secretion Secretin, CCK, GIP, inhibited parietal cells

57 Pancreatic secretion Exocrine juice: Isotonic Aqueous (HCO3) & enzymatic component Structure of exocrine portion of pancreas

58 Location of transport processes involved in pancreatic secretion

59 Pancreatic digestive enzyme : Trypsin Chymotrypsin Carboxypolypeptidase digestion of proteins Elastase Pancreatic lipase Cholesterol esterase Phospholipase digestion of lipids Pancreatic amylase digestion of carbohydrate

60 Regulation of pancreatic secretion Basic stimulants Ach. Secretin. Cholecystokinin Secretin.secretion of bicarbonate Ach & Cholecystokinin secretion of digestive enzyme

61 Function of the liver Regulates metabolism of CHO, lipid and protein Synthesizes all major plasma protein Storing vitamins and iron Degrading hormones Inactivating and excreting drugs and toxins Major rout for cholesterol excretion

63 Bile secretion Produced by hepatocytes Composition of bile : Bile acid, cholesterol, phospholipids, bile pigment Primary secretion stimulated by CCK Ductular aqueous secretion stimulated by Secretin Storage concentration of bile in the gallbladder CCK stimulates gallbladder emptying

64 Bile pigments: Bilirubin formed after degradation of RBC in RES Bilirubin bind to albumin traveled in blood Hepatocytes take-up Bilirubin from blood Conjugation of Bilirubin with glucoronides Bilirubin glucoronides secreted in bile Convert to urobilinogen by colonic bacteria

65 Structure of biliary tract

66 Gallbladder emptying

67 Gallstones: Cholesterol G: supersaturation of bile by cholesterol Bile pigment G: Ca 2+ salt of uncojugated bilirubin

68 Small and large intestines Microscopic view *

70 Secretion of small intestine Brunner's glands secrete Mucus Crypts of lieberkühn secrete digestive juice Goblet cells: mucous secretion Enterocyte : water and electrolytes secretion Secretion of digestive enzyme in the small intestine Peptidase, sucrase, maltase, isomaltase, intestinal lipase

71 Regulation of small intestine secretion Local stimuli Hormonal regulation: CCK, Secretin

72 Secretion of large intestine Mucus secretion:hco3 - Diarrhea caused by secretion of water and electrolyte in response to irritation

74 Digestion and absorption in the GI tract Chapter 65

75 Digestion of various foods 3 main group of nutrients: Carbohydrates (CHO) Proteins lipids Hydrolysis: basic process of digestion

76 Digestion of carbohydrate Dietary source of CHO Polysaccharides: Starch: amylopectin, amylose (plant source) Glycogen (animal source) Disaccharides: sucrose, lactose, Monosaccharides: glucose

77 Digestion of carbohydrate Digestion of CHO in the mouth and duodenum : Salivary α-amylase (ptyalin) Pancreatic α-amylase : maltose, maltotriose, dextrines

78 Digestion of CHO in the small intestine Digestion of disaccharides and small glucose polymers by epithelial enzymes Oligosaccharidases: Lactase, Sucrase, α-dextrinase Glucose, fructose, galactose

79 Basic principal of GI absorption Anatomical basis of absorption Absorptive surface of the small intestinal mucosa-villi Basic mechanism of absorption: Active transport, Diffusion, Facilitated transport, Solvent drag

81 Absorption of carbohydrates Duodenum and jejunum At apical membrane Glucose & galactose: Na/Glucose transporter (SGLT1) Fructose: facilitated transport; glucose transporter (GLUT2) At basolateral membrane Facilitated transport (GLUT 5) 6-10% starch escape adsorption in SI (carbon source for colonic bacteria)

82 Digestion of proteins Proteins sources Proteins of diet ( All of them absorbed) Digestive secretion of GI Exfoliate epithelial cells Colonic bacteria protein in feces Colonic mucus protein

83 Digestion of proteins in the stomach HCL and pepsin (~15%) Digestion of proteins by pancreatic enzyme (50%) Enteropeptidase Trypsinogen Trypsin proenzyme Trypsinogen Chymotrypsinogen Procarboxypeptidase Proelastase small peptide active enzyme Trypsin Chymotrypsin Carboxypeptidase Elastase

84 Digestion of peptides by peptidase in the SI: Entrocyte brush border enzymes: ( peptide 4 or more aa) Aminopeptidase Dipeptidase Tripeptidase Digestion continues in the cytosol of duodenal and jejunal epithelial cells: (di or tripeptides) Single amino acids

85 Absorption of proteins Absorption of intact proteins and large peptides by M cells Absorption of small peptide: (jejunum>ileum) Secondary active transport; with H + Role of luminal Na/H + exchanger Cleavage of small peptide in the enterocyte Absorption of single aa in BL membrane Absorption of amino acids: (ileum > jejunum) By aa-transporter (Na-dependent/independent) By diffusion

86 Defect in amino acids absorption Hartnup's disease: defective renal & intestinal transport of neutral aa Cystinuria Prolinuria Non of them results in protein malnutrition (why?)

87 Digestion of fats Fats of diet: TG, sterols, phospholipids, vitamins Chemical formula of some common lipids:

88 Digestion of fats Lingual lipase Gastric lipase 15% of fat digestion occur in stomach FFA reach duodenum.cck release stimulate: 1. Flow of bile by contraction of GB and relaxation of Oddi sphincter 2. Secretion of pancreatic enzymes

89 Absorption of lipid digestion product Most of fat absorption in midjejunum The function of micelles in lipid absorption Diffuse among the microvilli..saturate an unstirred layer with fat digestion products* Transport of lipids across brush border membrane; simple diffusion ***************************************************** Complete absence of : Bile acids.absorption of 50% lipids Pancreatic lipase all lipids are poorly absorbed

90 Handling of lipids inside the intestinal entrocyte Cytosolic lipid transport Resynthesis of lipids in the SER Chylomicron formation and transport Entrance of chylomicron to lacteal Direct absorption of fatty acids into the portal blood Absorption of bile acids in the terminal ileum

91 Absorption in the small intestine Absorption of water: isosmotic absorption

92 Fluid balance in GI

93 Absorption of ions: Active transport of sodium: Na/glucose, Na/amino acid cotransporter in SI Na-H exchanger in SI Parallel Na-H and CL-HCO3 exchangers in ileum and proximal colon Aldosterone greatly enhances Na absorption

94 Absorption in the large intestine Absorption and secretion of electrolytes and water Maximum absorption capacity of the large intestine: 8 liter Bacterial action in the colon

95 Physiological regulation of salt and Endocrine control: water absorption Increase net absorption of salt and water Aldosterone, Glucocorticoids, Opiods, Somatostatin Neural regulation: Parasympathetic Diminishes absorptive flux and enhance secretion Sympathetic Enhance net absorption Diabetic diarrhea due to autonomic neuropathy

96 Absorption of others ions Calcium: actively absorbed by all segments Action of Vit D Iron: Calbindin (CaBP) Ca 2+ ATPase / Na + -Ca 2+ exchanger at basolateral membrane Heme iron is taken up by facilitated transport Iron split from heme by hemeoxygenase Absorption of water soluble vitamins: Facilitated transport (folic acid, Vit B2), diffusion( Vit B6), co-transport with Na + (Vit C) Cobalamin (Vit B12) binds to IF in the small intestine before endocytosis by enterocytes in the ileum

97 With best wishes for you!

Gastrointestinal Anatomy and Physiology. Bio 219 Napa Valley College Dr. Adam Ross

Gastrointestinal Anatomy and Physiology Bio 219 Napa Valley College Dr. Adam Ross Functions of digestive system Digestion Breakdown of food (chemically) using enzymes, acid, and water Absorption Nutrients,