Digestive System Part II PDF

The Digestive System Part II Chapter 23 p. 874 – 924 Section 23.1 – 23.11 1 Dr. Savory Université d’Ottawa | University of Ottawa...

The Digestive System Part II Chapter 23 p. 874 – 924 Section 23.1 – 23.11 1 Dr. Savory Université d’Ottawa | University of Ottawa Disclosure You may only access and use this PowerPoint presentation for educational purposes. You may not post this presentation or the associated videos online or distribute it without the permission of the author. uottawa.ca 2  SMALL INTESTINE & ITS ACCESSORY ORGANS 3 Accessory Digestive Organs of the Small Intestines Digestion in the small intestine depends on three accessory organs: Liver, gallbladder, and pancreas are accessory organs associated with small intestine ▪ Liver: digestive function is production of bile LIVER ▪ Gallbladder: chief function is storage of bile ▪ Pancreas: supplies most of enzymes needed to digest chyme, as well as PANCREAS bicarbonate to neutralize stomach acid DUODENUM Figure 23.28 Relationship of the liver, gallbladder, and pancreas to the duodenum.  The Liver Gross Anatomy ▪ Largest gland in body; ~3 lbs ▪ Consists of four primary lobes: ▪ anterior view: larger right & smaller left, caudate & quadrate ▪ Gallbladder rests in recess on inferior surface of right lobe Falciform ligament Anterior view ▪ Separates larger right and smaller left lobes ▪ Suspends liver from diaphragm and anterior abdominal wall Round ligament (ligamentum teres) o Remnant of fetal umbilical vein along free edge of falciform ligament Posterior view Lesser omentum anchors liver to stomach Figure 23.23  The Liver Gross Anatomy – Hepatic artery proper and hepatic portal vein enter liver at porta hepatis – Bile leaves liver via left and right hepatic ducts; fuse to form common hepatic duct ▪ Cystic duct fills/drains gallbladder ▪ Bile duct formed by union of common hepatic and cystic ducts Fig. 23.23 Illustration of the posterior view of the liver  The Liver Microscopic Anatomy Liver lobules ▪ Hexagonal sesame-seed-size structural and functional units ▪ plates of hepatocytes (liver cells) that filter and process nutrient-rich blood ▪ Central vein located in longitudinal axis Liver sinusoids ▪ leaky capillaries between hepatic plates ▪ lined with stellate (hepatic) macrophages that remove debris and old RBCs Portal triad in each corner of lobule contains: ▪ Branch of hepatic artery, which supplies O2 ▪ Branch of hepatic portal vein, which brings nutrient-rich blood from intestine ▪ Bile duct which receives bile from bile canaliculi (tiny canals between hepatocytes Figure 23.24c Microscopic anatomy of the liver Three-dimensional representation of a small portion of one liver lobule  The Liver Hepatocytes have large amounts of both rough and smooth ER, Golgi apparatus, peroxisomes and mitochondria allowing them to ▪ Produce 900 ml bile per day ▪ Process bloodborne nutrients – eg: store glucose as glycogen and make plasma proteins ▪ Store fat-soluble vitamins ▪ Perform detoxification – eg: converting ammonia to urea ▪ Excrete bilirubin to the bile ▪ Phagocytize (Stellate macrophages cell) old RBC, leukocytes and some bacteria ▪ Synthesize: - most of the clotting factors - lipoproteins The only digestive function of the liver is the production of bile  The Liver Bile: Composition and enterohepatic circulation Yellow- green alkaline solution containing ▪ Bile salts: cholesterol derivatives and phospholipids that function in fat emulsification & absorption ▪ Bilirubin: main bile pigment from heme of hemoglobin o Bacteria break down in intestine to stercobilin that gives brown color of feces ▪ Cholesterol, triglycerides, phospholipids, and electrolytes ▪ Enterohepatic circulation: recycling mechanism that conserves bile salts ▪ Reabsorbed in ileum (the last part of small intestine) and returned to liver via hepatic portal vein ▪ 95% of secreted bile salts recycled Recycling mechanism that conserves bile salts  The Gallbladder Thin-walled muscular sac on the inferior surface of the liver Stores and concentrates bile by absorbing its water and ions Contains many honeycomb folds that allow it to expand as it fills Muscular contraction → releases bile via the cystic duct, which flows into the common bile duct What are gallstones? http://clinicalgate.com/wp-content/uploads/2015/03/B9780443066849500779_gr21.jpg 12  The Pancreas ▪ Location: mostly retroperitoneal, head encircled by duodenum; tail abuts spleen ▪ Contains endocrine and exocrine parts – Endocrine function: secretion of insulin and glucagon by pancreatic islet cells – Exocrine function: produce pancreatic juice Acini: clusters of secretory cells that produce zymogen granules containing proenzymes Ducts: secrete to duodenum via main pancreatic duct; smaller duct cells produce water and bicarbonate (HCO3-) Figure 23.26  The Pancreas Composition of pancreatic juice 1200–1500 ml/day is produced containing: ▪ Watery, alkaline solution (pH 8) to neutralize acidic chyme coming from stomach ▪ Electrolytes, primarily HCO3− ▪ Digestive enzymes ▪ Proteases (for proteins): secreted in inactive form & require activation. Why? ▪ Amylase (for carbohydrates) ▪ Lipases (for lipids) ▪ Nucleases (for nucleic acids) – Proteases activated in duodenum, where they work ▪ Enteropeptidase (formerly called enterokinase): enzyme bound to apical membrane of duodenal epithelial cells, activates trypsinogen to trypsin ▪ Trypsin in turn can then activate: – More trypsinogen to trypsin – Procarboxypeptidase to carboxypeptidase – Chymotrypsinogen to chymotrypsin  The Pancreas 15 Figure 23.27 Activation of pancreatic proteases in the small intestine.  Bile and Pancreatic Secretion Into the Small Intestine Bile & major pancreatic duct unite in wall of duodenum → hepatopancreatic ampulla and sphincter ▪ which opens into duodenum via major duodenal papilla ▪ Hepatopancreatic sphincter controls entry of bile & pancreatic juice into duodenum ▪ Note: smaller accessory pancreatic duct empties directly into duodenum ▪ Hepatopancreatic sphincter is closed, unless digestion is active ▪ Bile is stored in gallbladder and released to small intestine only with contraction  17 Figure 23.28 Relationship of the liver, gallbladder, and pancreas to the duodenum.  Bile & Pancreatic Secretion into the Small Intestine Regulation of bile and pancreatic secretion – Both regulated by neural and hormonal controls Hormonal include two enterogastrones, cholecystokinin (CCK) and secretin – CCK secretion which is stimulated by protein-rich, fatty chyme: » stimulates acini to secrete enzyme-rich pancreatic juice » contracts gallbladder and relaxes hepatopancreatic sphincter – Secretin secretion stimulated by acidic chyme: » stimulates duct cells to secrete bicarbonate-rich pancreatic juice » weakly stimulates bile secretion Neural include long (vagus nerve) reflexes that weakly stimulate gallbladder contraction and pancreatic secretion during cephalic and gastric phases – Unless digestion occurring, hepatopancreatic sphincter is closed, bile backs up into gallbladder via cystic duct, where it is stored and concentrated until needed  Mechanisms Promoting Secretion and Release of Bile & Pancreatic Juice Chyme entering duodenum causes release of cholecystokinin (CCK – red dots) & secretin (yellow dots) from duodenal enteroendocrine cells. ▪ CCK release stimulated by proteins & fat in chyme ▪ Secretin release stimulated by the acidic chyme Pancreas secretion ▪ CCK induces acinar cells → enzyme rich pancreatic juice CCK & secretin enter ▪ Secretin causes the blood stream secretion by duct cells of HCO3- rich pancreatic juice ▪ Weakly stimulated by the vagus nerve Mechanisms Promoting Secretion and Release of Bile & Pancreatic Juice Bile secretion by the liver ▪ Bile salts returning from the enterohepatic circulation are the most important stimulus ▪ Secretin is a minor stimulus Gallbladder contraction ▪ CCK causes the GB to contract ▪ Vagus nerve→ weak GB contraction during cephalic & gastric phase Hepatopancreatic sphincter relaxation ▪ CCK → HP sphincter to relax ▪ Bile and pancreatic juice enter duodenum 21  Small Intestine The major organ of digestion and absorption ▪ Digestion is completed (with the help of bile and pancreatic enzymes) and virtually all absorption ▪ Extends from pyloric sphincter → ileocecal valve ▪ 7-13 ft during life; ~20 ft in a cadaver ▪ Small diameter of 2.5 - 4 cm (1.0 -1.6 inches) Subdivisions ▪ Duodenum (retroperitoneal) ▪ ~ 25.0 cm (10.0 in) long; curves around head of pancreas ▪ Has the most features ▪ Jejunum ▪ ~ 2.5 m (8 ft); attached posteriorly by mesentery ▪ Ileum ▪ ~3.6 m (12 ft) attached posteriorly by mesentery); joins large intestine at ileocecal valve  Small Intestine Blood supply – Superior mesenteric artery brings oxygenated blood supply – Veins (carrying nutrient-rich blood) drain into superior mesenteric veins, then into hepatic portal vein, and finally into liver Nerve supply – Parasympathetic innervation via vagus nerve, and sympathetic innervation from thoracic splanchnic nerves 23  Small Intestine-Microscopic Anatomy Modifications of small intestine for ABSORPTION ▪ length & other structural modifications → huge surface area ▪ modifications – circular folds, villi, and microvilli - increase surface area 600 to ~200 m2 (size of a tennis court) ▪ Circular folds ▪ Permanent folds of mucosa and submucosa (~1 cm deep) that force chyme to slowly spiral through lumen, allowing more time for nutrient absorption ▪ Villi ▪ Fingerlike projections of mucosa (~1 mm high) with a core that contains dense capillary bed and lymphatic capillary called a lacteal (lymphatic capillary for lipid absorption) for absorption ▪ Microvilli ▪ Cytoplasmic extensions of apical surface of enterocytes that create fuzzy appearance called the brush border ▪ contains membrane-bound enzymes brush border enzymes used for final carbohydrate and protein digestion Figure 23.31 Structural modifications of the small intestine that increase its surface area for digestion and absorption.  Small Intestine Histology of the SI wall ▪ Four tunics: mucosa & submucosa modified for digestion ▪ Epithelium of villi and the tubular intestinal crypts (intestinal glands) between villi consists of five main cell types ▪ ↓ in number along the length of the SI. ▪ Produce intestinal juice - watery mixture of mucus that acts as carrier fluid for chyme  Small Intestine Histology of the SI wall Five major types of cells are found in the villi & crypts ▪ Enterocytes: make up bulk of epithelium ▪ Simple columnar absorptive cells bound by tight junctions with many microvilli ▪ Function Villi: absorb nutrients and electrolytes Crypts: produce intestinal juice, watery mixture of mucus that acts as carrier fluid for chyme ▪ Goblet cells: mucus-secreting cells in epithelia of villi & crypts ▪ Enteroendocrine cells: source of enterogastrones (CCK /secretin) & GIP ▪ Found scattered in villi but some in crypts ▪ Paneth cells: deep in crypts, specialized secretory cells that fortify SI’s defenses. ▪ Secrete antimicrobial agents (defensins & lysozyme) that can destroy bacteria ▪ Stem cells that continuously divide to produce other cell types ▪ Villus epithelium renewed every 2–4 days 27  Small Intestine Histology of the SI wall ▪ Mucosa ▪ MALT protects intestine against microorganisms and includes: ▪ Individual lymphoid follicles & Peyer’s patches (aggregated lymphoid nodules) in lamina propria ▪ numbers in distal part of small intestine. Why? ▪ Lamina propria: large numbers of plasma cells that secrete IgA ▪ Submucosa ▪ areolar tissue ▪ duodenal glands secrete alkaline mucus to neutralize acidic chyme ▪ Muscularis ▪ circular & longitudinal muscle ▪ Most of the duodenum (retroperitoneal) → adventitia ▪ Visceral peritoneum (serosa) covers the external intestinal surface Fig. 20.5  Small Intestine Intestinal juice ▪ 1–2 L secreted daily by the intestinal glands in response to distension or irritation of mucosa ▪ hypertonic or acidic chyme is the major stimulus ▪ Slightly alkaline and isotonic with blood plasma ▪ Consists largely of water but also contains mucus secreted by duodenal glands and goblet cells of mucosa ▪ Absorptive cells synthesize digestive (brush border) enzymes Chyme entering the small intestine contains partially digested carbohydrates and proteins, and largely undigested fats ~3-6 hours to pass through small intestine as nutrients and most of the water is absorbed  Digestive Processes in the Small Intestine Sources of enzymes for digestion ▪ Substances such as bile, bicarbonate, digestive enzymes (not brush border enzymes) are from liver and pancreas ▪ Brush border enzymes bound to plasma membrane perform final digestion of chyme Regulating chyme entry Chyme from stomach contains ▪ partially digested CHO, PRO & undigested fats ▪ usually hypertonic; therefore, delivery must be slow to prevent osmotic loss of H2O from blood ▪ low pH must be adjusted upward ▪ must be mixed with bile & pancreatic juice to continue digestion ▪ Enterogastric reflex & enterogastrones control movement of food into duodenum to regulate duodenal filling  Digestive Processes in the Small Intestine Motility of the Small Intestine Two motility patterns: After a meal: segmentation ▪ Initiated by intrinsic pacemaker cells ▪ alternately contracting/relaxing rings of smooth muscle move chyme back-and-forth (also slowly moving it toward cecum) ▪ Mixes/moves contents toward ileocecal valve ▪ Intensity is altered by long /short reflexes & hormones » Parasympathetic motility; sympathetic Between meals: peristalsis ▪ initiated by in hormone motilin in late intestinal phase ▪ Wave every 90–120 minutes ▪ Each wave starts distal to previous; called migrating motor complex (MMC) ▪ Meal remnants, bacteria & debris are moved toward large intestine ▪ Complete trip from duodenum to ileum: ~2 h https://encrypted- tbn2.gstatic.com/images?q=tbn:ANd9GcSlD5RBdWi4DVQewaFNqVV2Fwr_v5vgszakmv4 VoWtXkEkbHTYW  Ileocecal valve control Ileocecal valve control ▪ ileocecal valve relaxes and admits chyme into large intestine when: Gastroileal reflex enhances force of segmentation in ileum Gastrin increases motility of ileum ▪ Ileocecal valve flaps close when chyme exerts backward pressure Prevents regurgitation into ileum 33  The Large Intestine Absorbs Water and Eliminates Feces Large intestine frames small intestine on three sides, extends from ileocecal valve to anus – Much shorter than small intestine (1.5 m v s 6 m), but ersu about twice the diameter (7 cm) – Major digestive functions: ▪ Absorb most of the remaining water from indigestible food residues – Also absorb metabolites produced by resident bacteria ▪ Store residues temporarily, then eliminate them as semisolid feces (or stool) 34  The Large Intestine (Colon) Gross Anatomy ▪ Walls contain typical 4 layers found in the rest of the GI tract ▪ Has 3 unique features Teniae coli Haustra SMA Epiploic appendages Ileocecal valve Subdivisions of the colon 1. Cecum: first part of large intestine 2. Appendix: masses of lymphoid tissue Appendicitis: acute inflammation of appendix; usually results from a blockage by feces that traps infectious bacteria  The Large Intestine (Colon) Gross Anatomy cont. left colic (splenic) flexure 3. Colon: has 4 regions, ▪ Ascending colon: travels up right side of abdominal cavity to level of right kidney – Ends in right-angle turn - right colic (hepatic) flexure Transverse Descending ▪ Transverse colon: travels across abdominal cavity SMA – Ends in another right-angle turn, left colic (splenic) flexure ▪ Descending colon: travels down left side of abdominal cavity Sigmoid Rectum ▪ Sigmoid colon: S-shaped portion that travels through pelvis Anal Canal External Anal Sphincter 4. Rectum: three transverse folds (rectal valves) stop feces from being passed with gas (flatus)  The Large Intestine (Colon) Gross Anatomy cont. 5. Anal canal: last segment of large intestine external to the abdominopelvic cavity that opens to body exterior at anus Has two sphincters that close the anys except during defection ▪ Internal anal sphincter: Anal Canal smooth muscle ▪ External anal sphincter: skeletal muscle Figure 23.31  The Large Intestine (Colon) Relationship to the peritoneum ▪ Colon is also retroperitoneal, except for its transverse and sigmoid parts ▪ Intraperitoneal regions are anchored to posterior abdominal wall by mesentery sheets called mesocolons ▪ Rectum (sometimes cecum) also retroperitoneal Figure 23.32  The Large Intestine (Colon) Microscopic Anatomy ▪ Like the small intestine, the large is lined with simple columnar epithelium (except anal canal has stratified squamous to withstand abrasion) ▪ Does not contain circular folds, villi, or digestive secretions ▪ contains thicker mucosa made up of simple columnar epithelium except in anal canal, where it becomes stratified squamous epithelium to withstand abrasion ▪ Contains abundant deep crypts with many mucus-producing goblet cells  The Large Intestine (Colon) Microscopic Anatomy cont. ▪ Mucosa of anal canal hangs in long ridges or folds referred to as anal columns ▪ Anal sinuses: recesses located between anal columns; secrete mucus to aid in emptying ▪ Pectinate line: horizontal line that parallels the wavy inferior margins of the anal sinuses – Visceral sensory fibers innervate area superior to this line; relatively insensitive to pain – Somatic nerves innervate inferior to this line, sensitive to pain Figure 23.33 Two superficial venous plexuses of anal canal form hemorrhoids if dilated and inflamed  The Large Intestine (Colon) Bacterial Microbiota (Bacterial flora) ▪ consist of 1000+ different types of bacteria (outnumber our cells 10:1) ▪ enter from small intestine or anus to colonize colon Metabolic functions ▪ Fermentation Ferment indigestible carbohydrates and mucin releasing short-chain fatty acids that can be absorbed Release irritating acids and gases (~500 ml/day) ▪ Vitamin synthesis Synthesize B complex & some vitamin K needed by liver to produce clotting factors ▪ Keep pathogenic bacteria in check – Beneficial bacteria outcompete and suppress (and so outnumber) them – Immune system prevents harmful bacteris from crossing gut epithelium Dendritic cells sample microbial antigens in lumen, then migrate to nearby lymphatic follicles (MALT) to trigger I g A antibody–mediated response  The Large Intestine (Colon) Gut bacteria and health – Mounting evidence supports findings that the types & proportions of gut bacteria can influence: Body weight Susceptibility to various diseases (including diabetes, atherosclerosis, fatty liver disease) Response to various drugs Our moods – Manipulating gut bacteria may become a routine health-care strategy in future https://www.frontiersin.org/files/Articles/336645/fmicb-09-01510-HTML/image_m/fmicb-09-01510-g001.jpg  Digestive Processes of the Large Intestine ▪ Residue remains in large intestine 12–24 hours ▪ No food breakdown occurs except what enteric bacteria digest ▪ Vitamins (made by bacterial flora), H2O & electrolytes (especially Na+ and Cl−) are reclaimed ▪ Major functions of large intestine: propulsion of feces to anus & defecation Motility of the large intestine ▪ Haustral contractions: most contractions of colon, haustra sequentially contract in response to distension Slow segmenting movements, mostly in ascending and transverse colon ▪ Mass movements: long, slow-moving, powerful contractile waves that move feces toward rectum; occur about 3-4X per day Descending colon & sigmoid colon act as storage reservoir Usually occur during/after eating (via gastrocolic reflex) https://classconnection.s3.amazonaws.com/544/flashca rds/666544/png/colon_reflexes1322630368379.png Digestive processes of the Large Intestine Figure 23.35 Defecation reflex  Digestive processes of the Large Intestine Defecation ▪ Mass movements force feces toward rectum ▪ Distension initiates defecation reflex (parasympathetic spinal reflex) Stimulate contraction of sigmoid colon and rectum Relax internal anal sphincter Voluntary control allows contraction/relaxation of external anal sphincter ▪ If defecation delayed, contractions end after few seconds (until reflex triggered again) ▪ During reflex, rectal muscles contract to expel feces, which is assisted by: ▪ Valsalva’s maneuver - Closing of glottis, contraction of diaphragm and abdominal wall muscles cause increased intra-abdominal pressure ▪ Levator ani muscle contracts, causing anal canal to be lifted superiorly and allowing feces to leave body What is diarrhea? Constipation? Physiology of Digestion and Absorption https://cnx.org/resources/a8fd4c3ee096f086722dbad7b844e1d6f ef62b68/2405_Digestive_Process.jpg 46  Physiology of Digestion & Absorption Mechanism of Digestion: Enzymatic Hydrolysis ▪ Digestion: catabolic process that breaks down of ingested macromolecules (polymers) down into → monomers (chemical building blocks) small enough for absorption across the small intestine wall ▪ via enzymes secreted into GI tract from intrinsic and accessory glands, and intestinal brush border enzymes ▪ Enzymes carry out hydrolysis -water is added to break chemical bonds http://images.slideplayer.com/26/8497716/slides/slide_9.jpg ▪ In general, pancreatic (also salivary and gastric) enzymes break down larger polymers into smaller polymers that are eventually broken down into absorbable monomers by (intestinal) brush border enzymes  Physiology of Digestion & Absorption Mechanisms of Absorption ▪ Absorption: moving substances from lumen of gut into body ▪ Tight junctions: molecules pass through rather than between cells Materials enter cell through apical membrane (lumen side) and exit through basolateral membrane (interstitial side) Once in IF, substances (except lipids) diffuse into capillaries (lipids enter lacteals) ▪ Lipid molecules can be absorbed passively through membrane, but other polar molecules are absorbed by active transport ▪ Most nutrients are absorbed before chyme reaches ileum  Processing of Nutrients Carbohydrates Three classes ▪ Mono-, di- and polysaccharides (only monosaccharides can be absorbed) ▪ the principal polysaccharide in human body is glycogen Digestion begins in mouth via salivary amylase (splits starch into oligosaccharides) – Continues working until low stomach pH denatures it ▪ Starch and disaccharides → oligo- and disaccharides – Begins in mouth with salivary amylase – SI: further broken down by pancreatic amylase → lactose, maltose & sucrose ▪ Final breakdown into monosaccharides (glucose, fructose, galactose) by brush border enzymes (glucoamylase, dextrinase, maltase, sucrose) Figure 23.36 Flowchart of digestion and absorption of foodstuffs.  Processing of Nutrients Carbohydrates ▪ Monosaccharides are co- transported across apical membrane of absorptive epithelial cell, mostly by secondary active transport with Na+ ▪ Monosaccharides exit across the basolateral membrane by facilitated diffusion Figure 23.37 Lactose intolerance People with lactose intolerance have deficient amounts of lactase and cannot consume lactose Any lactose eaten remains undigested and creates an osmotic gradient in intestine that prevents water from being absorbed, resulting in diarrhea – can also can pull water from interstitial space into intestinal lumen Bacterial metabolism of undigested solutes produces large amounts of gas, resulting in bloating, flatulence, and cramping pain Treatment: add lactase enzyme “drops” to milk or take a lactase tablet before consuming milk products Intranet.tdmu.edu.ua  Processing of Nutrients Proteins ▪ 3D coiled up chain of amino acids (aa) arranged in a precise sequence ▪ Source of protein: diet, digestive enzymes & from breakdown of mucosal cells ▪ Digestion begins in stomach as pepsinogen is converted to pepsin at p H 1.5–2.5 ▪ Digests proteins into polypeptides (and some amino acid monomers); becomes inactive in high pH of duodenum ▪ Proteins are broken into: ▪ Large polypeptides ▪ Small polypeptides and small peptides ▪ Finally, into amino acid monomers, with some dipeptides and tripeptides http://2012books.lardbucket.org/books/introduction-to-chemistry-general-organic- and-biological/section_21/6d9b4af09c98e66f071eb9560fd984ef.jpg  Processing of Nutrients Proteins Figure 23.36 Flowchart of digestion and absorption of foodstuffs. Pancreatic proteases break down proteins and protein fragments into smaller pieces and some individual amino acids ▪ trypsin & chymotrypsin cleave protein into smaller peptides while carboxypeptidase takes off one aa at a time from end Brush border enzymes ▪ aminopeptidases, carboxypeptidases & dipeptidases break oligopeptides and dipeptides into amino acids  Processing of Nutrients Proteins ▪ AAs are co-transported across apical membrane of absorptive epithelial cell via secondary active transport carriers (Na+ or H+) ▪ Amino acids exit across basolateral membrane via facilitated diffusion  Processing of Nutrients Lipids ▪ Triglycerides: most abundant fats in diet ▪ Need pre-treatment with bile salts that break large fat globules into smaller ones → emulsification ▪ lipid droplets are coated with bile salts & lecithin, forming emulsion droplets (larger surface area → digestive action of lipases) that are water soluble - micelles ▪ Digestion: pancreatic lipases break down fat into monoglyceride plus two free FAs (all are insoluble in H2O) ▪ Micelle formation: products from digestion become coated with bile salts and lecithin ▪ Diffusion: lipid products leave micelles and cross epithelial membrane via https://abdominalkey.com/wp-content/uploads/2016/06/A322953_1_En_7_Fig3_HTML.gif diffusion  Emulsification ▪ Bile salts have both hydrophilic & hydrophobic domains o the hydrophobic part → to the lipids o the hydrophilic part → the surface ▪ The molecules in micelles are clustered together exposing polar ends toward H2O making micelles soluble in water o in this form FA & monoglycerides reach the intestinal epithelial cells  Processing of Nutrients Lipids ▪ Chylomicron formation: lipid products are converted back into TGs and packaged phospholipids, cholesterol, proteins; forming lipoprotein called chylomicron ▪ Chylomicron transport: chylomicrons exit from basolateral membrane via exocytosis ▪ once in the IF they diffuse into lacteals (too large for capillary) ▪ Eventually emptied into venous blood at thoracic duct ▪ Once in blood, chylomicrons are broken into free fatty acids and glycerol by lipoprotein lipase so they can be used by https://ib.bioninja.com.au/_Media/lipid-metabolism_med.jpeg cells ▪ Short-chain fatty acids can diffuse directly into blood 57  Processing of Nutrients Lipids Figure 23.36 Flowchart of digestion and absorption of foodstuffs. 58  Processing of Nutrients Nucleic Acids ▪ coiled up chains of nucleotides linked together in a precise arrangement ▪ Nuclei of ingested cells in food contain DNA and RNA ▪ Pancreatic nucleases hydrolyze nucleic acid to nucleotide monomers ▪ Brush border enzymes, nucleosidases, and phosphatases break nucleotides down into free nitrogenous bases, pentose sugars & phosphate ions ▪ Breakdown products are actively transported by special carriers in epithelium of villi Figure 23.36 Flowchart of digestion and absorption of foodstuffs.  Absorption of Vitamins, Electrolytes, and Water 60  Absorption of Vitamins ▪ In small intestine Fat-soluble vitamins (A, D, E, and K) are carried by micelles; diffuse into absorptive cells Water-soluble vitamins (C and B) are absorbed by diffusion or by passive or active transporters Vitamin B12 (large, charged molecule) binds with IF (produced where?) and is absorbed by endocytosis ▪ In large intestine vitamin K and B vitamins from bacterial metabolism are absorbed  Absorption of Electrolytes ▪ Most ions are transported actively along length of GI Amount in intestine is amount absorbed regardless of nutritional state except for Fe and Ca ▪ Na+ absorption is coupled with active absorption of glucose and amino acids ▪ Cl− is transported actively ▪ K+ diffuses (facilitated) in response http://intranet.tdmu.edu.ua/data/kafedra/internal/normal_phiz/classes _stud/en/stomat/2%20course/5%20Cycle%20Physiology%20of%20d igestion%20system%20and%20kidneys/01%20Digestion%20in%20o to osmotic gradients; lost if water ral%20cavity.%20Digestion%20in%20stomach,%20intestine%20and %20colon.files/image052.jpg absorption is poor ▪ HCO3- actively secreted into the lumen  Absorption of Electrolytes ▪ Fe and Ca2+ : absorption in duodenum is related to need Ionic Fe actively transported into mucosal cells and stored bound to ferritin (local storehouse) Normal state: 10-20% pass into portal blood; most lost with epithelial cells Fe depleted: ↑ uptake and release; transported in blood by transferrin ▪ Ca+ absorption: regulated by vitamin D & parathyroid hormone (PTH) Vitamin D promotes absorption PTH releases Ca2+ from the bone matrix 63  Absorption of Water ▪ ~9 L water, most from GI tract secretions, enter small intestine 95% is absorbed in the small intestine by osmosis Most of rest is absorbed in large intestine leaving ~ 100 ml in feces ▪ Net osmosis occurs if concentration gradient is established by active transport of solutes ▪ Water uptake is coupled with solute uptake  The Digestive System Chapter 23 p. 874 – 924 Section 23.1 – 23.11 1 Dr. Savory Université d’Ottawa | University of Ottawa Disclosure You may only access and use this PowerPoint presentation for educational purposes. You may not post this presentation or the associated videos online or distribute it without the permission of the author. uottawa.ca 2 Objectives 1.1 Summarize the general anatomical features of the digestive system 1.1.1. Differentiate between the components of the alimentary canal and the accessory digestive organ 1.1.2. Describe the relationship between the various digestive organs and the peritoneum 1.1.3. Outline the blood supply serving the main components of the GI tract 1.1.4. Describe the histology of the GI tract wall 1.2 Describe the functional anatomy of the GI tract 1.2.1. Describe the functional anatomy of the mouth, pharynx & esophagus 1.2.2. Describe the functional anatomy of the stomach 1.2.3. Describe the functional anatomy of the liver & gallbladder 1.2.4. Describe the functional anatomy of the pancreas 1.2.5. Describe the macroscopic and microscopic anatomy of the small intestine 1.2.6. Describe the anatomy of the large intestine 3 Objectives cont. 1.3 Describe the region-specific digestive activities of the GI tract and their regulation 1.3.1. List, define and provide examples of the 6 digestive processes 1.3.2. Summarize the basic concepts pertaining to the control of digestive function 1.3.3. Describe the digestive activities associated with the oral cavity and their regulation 1.3.4. Describe the voluntary & involuntary regulation of deglutition; define & indicate some potential causes of heartburn 1.3.5. Describe the digestive functions of the stomach and their regulation 1.3.6. Summarize the digestive roles of the liver and gallbladder & their regulation 1.3.7. Describe the exocrine function of the pancreas and its regulation 1.3.8. Summarize the digestive functions of the small intestine and their regulation 1.3.9. Summarize the chemical digestion of carbohydrates, proteins, lipids & nucleic acids 1.3.10. Outline the processes by which the various nutrient breakdown products are absorbed by the small intestine 1.3.11. Describe the digestive functions (& regulation) of the large intestine 1.3.12. Describe the neural regulation of defecation 4  Functions of the Digestive System o Take in food o Break it down into nutrient molecules o Absorb molecules into the bloodstream o Rid body of any indigestible remains o Nutrient production http://image.slidesharecdn.com/15-140427232211- phpapp02/95/digestive-system-3-638.jpg?cb=1398640996 Synthesis of vitamins by bacteria that live in the intestine o Examples: Vitamin K, biotin (one of vitamins B) and other B vitamins o Production of neurotransmitters, hormones and hormone-like compounds o hormones: gastrin, ghrelin, cholecystokinin, secretin, VIP, motilin, GIP (gastric inhibitory peptide) o neurotransmitters: acetylcholine, serotonin, histamine, nitric oxide 5 Alimentary Canal and Accessory Digestive Organs 6 Gastrointestinal Tract Activities 7 Figure 23.2 GI Tract Activities Peristalsis vs Segmentation 8  Relationship of the Digestive Organs to the Peritoneum Peritoneum Serous membranes of the abdominal cavity that consists of o Visceral peritoneum: membrane on external surface of most digestive organs o Parietal peritoneum: membrane that lines body wall Peritoneal cavity o Fluid-filled space between two peritoneums o Fluid lubricates mobile organs What is peritonitis? 9 Relationship of the Digestive System Organs to the Peritoneum Mesentery: double layer of peritoneum fused together that extends to the organs from the body wall mostly posterior. o Provides support for the organs; holds them in place o Provides support for vessels & nerves supplying the organs o Stores fat Intraperitoneal o organs located within the peritoneum Retroperitoneal o located outside of/posterior to the peritoneum o Includes most of pancreas, duodenum, and parts of large intestine 10  Histology of the Alimentary Canal All digestive organs have the same four basic layers or tunics Mucosa / Submucosa / Muscularis externa / Serosa The alimentary canal extends from mouth to anus Most of the length is made up by the small intestine The walls consist of 4 tissue layers Figure 23.5 11  Histology of the Alimentary Canal 1. Mucosa (lines the lumen) Functions: Secretion: mucus, digestive enzymes, hormones Absorption: end products of digestion Protection: against infectious disease Made up of 3 sublayers: 1. Epithelium Simple columnar epithelium rich in mucus-secreting (Goblet) cells mucus (protects digestive organs from enzymes; eases food passage) may secrete enzymes and hormones (e.g., in stomach and small intestine) 2. Lamina propria loose areolar CT; capillaries for nourishment & absorption lymphoid follicles (part of MALT)- protection 3. Muscularis mucosae smooth muscle that produces local movements of mucosa 12  Histology of the GI tract Wall 2. Submucosa o areolar CT o Blood and lymphatic vessels, lymphoid follicles o submucosal nerve plexus o Abundant in elastic fibers (allows stomach to regain shape after large meal) 3. Muscularis externa o segmentation & peristalsis o inner circular & outer longitudinal layers o sphincters in organ-to organ junctions o myenteric nerve plexus 4. Serosa Visceral peritoneum - outermost protective layer o areolar connective tissue covered with mesothelium o replaced by the fibrous adventitia in the esophagus (adventitia: fibrous connective tissue that “binds” the esophagus to surrounding tissues) Retroperitoneal organs have both an adventitia & serosa o serosa on the side facing the peritoneal cavity & an adventitia on the side against the dorsal body wall 13  Blood Supply: Splanchnic Circulation Arteries that branch off the abdominal aorta to serve the digestive organs o Hepatic, splenic, and left gastric of the celiac trunk (serve the liver, spleen and stomach) o Inferior and superior mesenteric (serve small and large intestine) o Venous return from much of the abdominopelvic region is via inferior vena cava. Venous return from the digestive viscera is indirect via the hepatic portal 20 – 25% of CO circulation. Why? after a meal during exercise 14  Enteric (Gut) Nervous System GI tract has its own NS, referred to as Enteric Nervous System (ENS) ▪ Also called the gut brain; made up of enteric neurons that communicate extensively with each other ▪ major nerve supply to GI tract wall that controls motility Linked to the CNS via: o afferent visceral fibers o motor fibers of the ANS (synapses with neurons in the enteric plexuses) ▪ sympathetic impulses inhibit secretion and motility ▪ parasympathetic impulses stimulate secretion and motility (RESTING & DIGESTING!!) Relationship between the ENS and components of the PNS Nature Reviews Gastroenterology & Hepatology volume 13, pages517–528 (2016) 15  Enteric Nervous System Enteric neurons form two major intrinsic nerve plexuses that control GI tract motility Submucosal nerve plexus contains sensory & motor neurons regulates glands & smooth muscle in mucosa Myenteric nerve plexus located between the circular and longitudinal muscles provides the major nerve supply to GI controls GI tract motility (pacemaker cells and local reflex arcs between enteric neurons) Nature Reviews Gastroenterology & Hepatology volume 13, pages517–528 (2016) 16  Enteric Nervous System ▪ Short reflexes in response to stimuli ▪ Long reflexes in response to stimuli inside inside the GI tract (internal) (internal) or outside (external) the GI tract ▪ Control patterns of segmentation involve CNS centers and autonomic and peristalsis nerves 17  Basic Concepts of Regulating Digestive Activity Three key concepts regulate digestive activity: Neurons (intrinsic and extrinsic) and hormones control digestive activity ▪ Nervous system controls – Intrinsic controls: involve short reflexes (ENS only) – Extrinsic controls: involve long reflexes ▪ Hormonal controls – Hormones from stomach and small intestine stimulate targets (muscles, glands) in same or different organs to affect secretion or contraction Digestive activity is provoked by mechanical & chemical stimuli ▪ Receptors in walls of GI tract organs respond to stretch, changes in osmolarity and pH, the presence of substrate and end products of digestion Effectors of digestive activity are SM and glands ▪ Receptors initiate reflexes that stimulate SM to mix and move lumen contents ▪ Reflexes can also activate or inhibit digestive glands that secrete digestive juices or hormones 18  Functional Anatomy of the Digestive System 19 20  Mouth and Associated Structures Oral (buccal) cavity ▪ Bounded by lips, cheeks, palate & tongue ▪ Oral orifice is the anterior opening ▪ Walls lined with SSE ▪ Beginning of digestion & initiation of swallowing food is chewed & mixed with enzyme- containing saliva Associated organs include: Tongue Salivary glands Teeth 21  Mouth and Associated Structures Lips and cheeks ▪ Lips (labia): composed of fleshy orbicularis oris muscle ▪ Oral vestibule: recess internal to lips and cheeks, external to teeth and gums ▪ Cheeks: composed of buccinator muscles ▪ Oral cavity proper: lies within teeth and gums ▪ Lingual frenulum: attachment to the floor of the mouth ▪ Labial frenulum: median attachment of each lip to gum 22  Mouth and Associated Structures Hard palate: palatine bones and palatine processes of the maxillae – Slightly corrugated to help create friction against the tongue Soft palate: fold formed mostly of skeletal muscle – Uvula projects downward from its free edge – Closes off the nasopharynx during swallowing 23 Uvula  Mouth and Associated Structures Tongue Functions: o Repositioning and mixing food during chewing o Formation of the bolus o Initiation of swallowing, speech, and taste o Intrinsic muscles change the shape of the tongue o Extrinsic muscles alter the tongue’s position Ankyloglossia: congenital condition in which children are born with an extremely short lingual frenulum referred to as “tongue- tied” or “fused tongue” 24  Mouth and Associated Structures Tongue Palatine Tonsils Lingual Tonsils Terminal sulcus marks the division between ▪ Body: anterior 2/3 residing in the oral cavity ▪ Root: posterior third residing in the oropharynx Surface papillae (projections of lamina propria covered with epithelium): 1. Foliate—on the lateral aspects of the posterior tongue 2. Filiform—whitish, give the tongue roughness and provide friction 3. Fungiform—reddish, scattered over the tongue 4. Circumvallate (vallate)—V-shaped row in back of tongue ▪ Circumvallate, foliate and fungiform papilla contain taste buds involved in detecting the elements of taste perception ▪ taste qualities are found in all areas of the tongue, some regions are more sensitive than others 25  Mouth and Associated Structures Salivary Glands Secrete saliva, a fluid that: – Cleanses mouth; dissolves food chemicals for taste and moistens food to compact it into a bolus; begins breakdown of starch via amylase Glands: composed of two types of secretory cells ▪ Serous cells: produce watery secretion, enzymes, ions, bit of mucin ▪ Mucous cells: produce mucus Minor or intrinsic salivary glands (buccal glands and others) located throughout oral mucosa help keep it Sublingual moist (minor source of saliva) (mostly mucous cells) Parotid (mostly serous cells) Most saliva secreted (when we eat or anticipate it) by major or extrinsic salivary glands (paired) Submandibular (mostly serous cells) What is mumps? Figure 23.10a The salivary glands. 26  Mouth and Associated Structures Salivary Glands Composition of saliva – Mostly water (97–99.5%), therefore hypo-osmotic; slightly acidic (pH 6.75 to 7) – Electrolytes: Na+, K+, Cl-, PO43-, HCO3- – Salivary amylase and lingual lipase – Proteins: mucin, lysozyme, and I g A – Metabolic wastes: urea and uric acid Saliva protects against microorganisms because it contains: IgA, lysozyme, defensins Xerostomia: uncomfortably dry mouth caused by too little saliva being made – May lead to difficulty with chewing and swallowing, as well as oral infections – Can be caused by medications, diabetes, H I V/AIDS, and Sjögren’s syndrome (autoimmune disease affecting moisture-producing glands throughout body) 27  Mouth and Associated Structures Salivary Glands Control of salivation ▪ 1500 ml/day can be produced ▪ Minor glands continuously keep mouth moist ▪ Major salivary glands are activated by PNS when: Ingested food stimulates chemo- & mechanoreceptors in mouth, sending signals to: Salivatory nuclei in brain stem that stimulate parasympathetic impulses along fibers in cranial nerves VII (facial nerve) and IX (glossopharyngeal nerve) to glands DO NOT MEMORIZE https://doctorlib.info/physiology/illustrated/illustrated.files/image200.jpg Other stimuli: o Swallowing irritating foods; nausea; smell/sight of food or upset GI can act as 28 stimuli  Mouth and Associated Structures Teeth ▪ lie in sockets (alveoli) in gum-covered margins of mandible & maxilla ▪ Mastication: process of chewing that tears and grinds food into smaller fragments ▪ Deciduous dentition: 20 primary/milk/baby teeth (lost between 6-12 years) ▪ Permanent dentition: 32 deep-lying permanent teeth that develop while the milk teeth roots are resorbed Tooth structure – Each tooth has two major regions: Crown: exposed part above gingiva (gum) Root: portion embedded in jawbone – Connected to crown by neck Teeth are classified according to shape: ▪ Incisors: chisel shaped for cutting ▪ Canines: fanglike teeth that tear or pierce ▪ Premolars (bicuspids): broad crowns with rounded cusps used to grind or crush ▪ Molars: broad crowns, rounded cusps: best grinders 29  Digestive Processes of the Mouth Mouth and its accessory organs are involved in (four of six) digestive processes 1. Ingests 2. Begins mechanical breakdown (via mastication) 3. Initiates propulsion (swallowing) 4. Starts digestion of polysaccharides (via salivary amylase) and lipids (via lingual lipase). Note: breakdown in the stomach but with the enzyme produced in the mouth Mastication (Chewing) – Cheeks and lips hold food between the teeth, tongue mixes food with saliva to soften it, and teeth cut and grind solid foods into smaller morsels production of a bolus (lump) – Partly voluntary and partly reflexive ▪ Pattern and rhythm of continued jaw movements controlled mainly by stretch reflexes and in response to pressure via receptors in cheeks, gums, tongue 30  Digestive Processes of the Mouth Mastication (chewing) Production of bolus (lump) easy to swallow ▪ Mechanical – Closed lips and cheeks – Teeth – Tongue ▪ Chemical enzymatic breakdown of starch by salivary amylase breaking of fats by lingual lipase (in the stomach but with the enzyme produced in the mouth) 31  Pharynx and Esophagus The Pharynx o Allow passage of food, fluids, and air o Food passes from mouth into oropharynx and then into laryngopharynx o Stratified squamous epithelium lining with mucus-producing glands External muscle layers consists of two skeletal muscle layers Inner layer of muscles runs longitudinally Outer pharyngeal constrictors encircle wall of pharynx Fig. 22.5 32  Pharynx and Esophagus Esophagus ▪ Flat muscular tube (~25 cm) that runs from laryngopharynx to stomach ▪ collapsed when not involved in food propulsion ▪ pierces diaphragm at esophageal hiatus to join stomach at cardial orifice which is surrounded by lower esophageal sphincter (also called gastroesophageal, or cardiac, sphincter) Keeps orifice closed when food is not being swallowed Mucus cells on both sides of sphincter help protect esophagus from acid reflux What is heartburn? https://assets.lybrate.com/imgs/tic/enadp/image-of-the-esophagus.jpg 33  Pharynx and Esophagus Esophagus has all four alimentary canal layers o Esophageal mucosa contains SSE that changes to simple columnar epithelium at the stomach o Esophageal glands in submucosa secrete mucus to aid in bolus movement o Muscularis externa: skeletal muscle superiorly; mixed in middle; smooth muscle inferiorly Figure 23.13 o Has adventitia instead of serosa 34  Digestive Processes of the Esophagus Swallowing (deglutition) ▪ Pharynx & esophagus: passage of food from mouth to stomach ▪ Major function of both organs is propulsion that starts with deglutition (swallowing) ▪ Involves the tongue, soft palate, pharynx, esophagus, 22 muscle groups ▪ Occurs in 2 phases: Buccal phase – Voluntary , occurs in the mouth (via the tongue) Pharyngeal - esophageal phase (primarily via the vagus nerve) https://www.christart.com/IMAG – Involuntary ES-art9ab/clipart/1696/jonah- whale.png – Control swallowing center in the medulla & lower pons The passage of food is regulated by: ▪ Two sphincters: upper and lower esophageal sphincters ▪ Peristalsis: (involuntary muscle movements controlled by medulla oblongata) & facilitated by mucus produced by the submucosal glands 35 Swallowing (Deglutition) Fig. 23.14 36  Swallowing (Deglutition) 37 Fig. 23.14 38  Gross Anatomy of the Stomach Stomach is a temporary storage tank that continues breaking down food both physically and chemically o Converts bolus of food to paste- like chyme (bolus + gastric juice) o Empty stomach has ~50 ml volume but can expand to 4 L when distended o When empty, stomach mucosa forms many folds called rugae https://ufhealth.org/sites/default/files /graphics/images/en/19223.jpg 39  Gross Anatomy of the Stomach Major regions of the stomach ▪ Cardial part (cardia): surrounds cardial orifice ▪ Fundus: dome-shaped region beneath diaphragm ▪ Body: midportion ▪ Pyloric part: funnel-shaped region, continuation of body ▪ wider and more superior portion of pyloric region, antrum, narrows into pyloric canal that terminates in pylorus ▪ pylorus is continuous with duodenum through pyloric valve (sphincter controlling stomach emptying) ▪ Greater curvature: convex lateral surface of stomach ▪ Lesser curvature: concave medial surface of stomach 40  Gross Anatomy of the Stomach Mesenteries extend from curvatures & tether stomach to other digestive organs – Lesser omentum: from lesser curvature to liver – Greater omentum: inferiorly from greater curvature over intestine, spleen, and transverse colon; blends with mesocolon, mesentery that anchors large intestine to abdominal wall Contains fat deposits and lymph nodes http://158.132.198.175/lexicon/web/tmp_img/e658fc085647892b03bff66ae90ba292.jpg ANS innervation: Sympathetic fibers via the celiac plexus and parasympathetic via vagus nerve Blood supply: celiac trunk (gastric and splenic branches), veins of hepatic portal system 41  Microscopic Anatomy of the Stomach Four tunics but the muscularis & mucosa are modified ▪ Muscularis externa Three layers of smooth muscle Circular, longitudinal & inner oblique layer allows stomach to churn, mix, move & physically break down food ▪ Mucosa layer is also modified Simple columnar epithelium entirely composed From Visible Body of mucous cells Secrete 2-layer coat of alkaline mucus – Surface layer (viscous, insoluble mucus) traps bicarbonate-rich fluid layer that is beneath it – Dotted with gastric pits, which lead into gastric glands that produce gastric juice 42 Microscopic Anatomy of the Stomach 43  Microscopic Anatomy of the Stomach Types of gland cells Mucous neck cells Secrete thin, acidic mucus of unknown function different from mucus of the surface epithelium Parietal cells ▪ Hydrochloric acid (HCl) denatures protein, activates pepsin, breaks down plant cell walls, and kills many bacteria ▪ Intrinsic factor: Glycoprotein required for absorption of vitamin B12 in small intestine 44  Microscopic Anatomy of the Stomach Types of gland cells Chief cells ▪ Pepsinogen (activated to pepsin by HCl & by pepsin itself (+ve feedback mechanism) ▪ Lipases (digests ~15% of lipids) Enteroendocrine cells Secrete variety of chemical messengers into IF of lamina propria, including ▪ Hormones: – gastrin (needed for HCL secretion; opening of pyloric sphincter, stomach’s motility) – ghrelin (stimulates appetite, gastric motility and opening) – Somatostatin acts both locally and as a hormone ▪ Locally acting paracrine: histamine and serotonin 45  Mechanism of HCl Formation Parietal cells pump H+ (from carbonic acid breakdown) into stomach lumen via H+/K+ ATPase (proton pumps) – As H+ is pumped into stomach lumen, HCO3− is exported back to blood (alkaline tide) in exchange for Cl- (via the Cl− /HCO3− antiporter) Resulting increase of HCO3− in blood leaving stomach is referred to as alkaline tide – Cl− is pumped out to lumen to join with H+, forming HCl 1. H2CO3 → HCO3- + H+ (carbonic acid) 2. H+-K+ ATPase ▪ H+ → the lumen ▪ K+ → the cell (K+ returns to the lumen through membrane channels) − 3. Cl in the interstitial fluid is exchanged for intracellular HCO3−. − 4. Cl diffuses through membrane channels into the lumen 46  Microscopic Anatomy of the Stomach Mucosal barrier protects stomach from its own acid and proteolytic enzymes and is created by 3 factors 1. Thick coating of bicarbonate-rich mucus 2. Tight junctions between epithelial cells Prevent juice seeping underneath tissue 3. Damaged epithelial cells are quickly replaced by division of intestinal stem cells (ISC) Surface cells replaced every 3–6 days 47  Digestive Processes in the Stomach – Holding area for food – Mechanical breakdown of food via the churning action of peristalsis – Digestion of protein HCl denatures proteins, enhancing pepsin mediated enzymatic digestion Milk protein (casein) is broken down by rennin in infants – Results in curdy substance – Absorption of lipid-soluble alcohol and aspirin (but not nutrients) – Only stomach function essential to life is secretion of intrinsic factor for vitamin B12 absorption – B12 needed for red blood cells to mature – Lack of intrinsic factor causes pernicious anemia – Treated with B12 injections – Delivers chyme to small intestine 48  Regulation of Gastric Secretion Gastric mucosa secretes >3 L of gastric juice/day and are regulated by: – Neural mechanisms Vagus nerve stimulation secretion Sympathetic stimulation secretion – Hormonal mechanisms Gastrin stimulates enzyme and HCl secretion Gastrin antagonists are secreted by small intestine – Synergistic effect when ACh, gastrin, histamine all stimulate parietal cell receptors – Drugs that block H2 histamine receptors reduce acid secretion 49  Regulation of Gastric Secretion Gastric secretions are broken down into three phases 1. Cephalic (reflex) phase 2. Gastric phase 3. Intestinal phase 50 https://img.brainkart.com/imagebk20/Wb4qhBU.jpg  Regulation of Gastric Secretion 1. Cephalic phase ▪ Before food reached the stomach (minutes) ▪ reflexes initiated by sensory receptors in the head (sight, smell, taste), or by thought 2. Gastric phase ▪ Lasts 3–4 hours & provides 2/3 of gastric juice Stimulation ▪ stretch receptors – detect distention of stomach initiating neural (both long & short) reflexes ▪ chemical stimuli, partial digested proteins, amino acids, stimulate enteroendocrine (G) cells to secrete gastrin ▪ Gastrin directly (and indirectly via triggering histamine release) stimulates parietal cells to secrete HCl 51  Regulation of Gastric Secretion Gastric phase cont. Stimulation ▪ Buffering action of ingested proteins causes pH to rise, which activates more gastrin secretion ▪ initiates HCl release from parietal cells & activates enzyme secretion ▪ Prods parietal cells to secrete HCl by: 1. Binding to receptors on parietal cells 2. Stimulating enteroendocrine cells to release histamine Inhibition ▪ Low pH (< 2) inhibits gastrin secretion; common between meals ▪ Inhibitory action of sympathetic division overrides vagal (parasympathetic) stimulation during times of fight-or-flight (stress, fear, anxiety) 52  Regulation of Gastric Secretion 3. Intestinal phase ▪ Begins with a brief stimulatory component followed by inhibition Stimulation ▪ Partially digested food enters small intestine, causing a brief release of intestinal (enteric) gastrin ▪ Encourages gastric glands of stomach to continue secretory activities ▪ Stimulatory effect is brief and overridden by inhibitory stimuli as intestine fills Inhibition Four main factors in duodenum cause inhibition of gastric secretions: ▪ Distension of duodenum due to entry of chyme ▪ Presence of acidic / fatty / hypertonic chyme 53  Regulation of Gastric Secretion 3. Intestinal phase cont. Inhibition: protects intestine from being overwhelmed by too much chyme or acidity and is achieved in two ways: ▪ Enterogastric reflex (Neural) Duodenum inhibits acid secretion in stomach by: ENS short reflexes & SNS and vagus nerve long reflexes ▪ Enterogastrones (Hormonal) Duodenal enteroendocrine cells release two important hormones that inhibit gastric secretion: secretin & cholecystokinin (CCK) 54 Neural and Hormonal Mechanisms that Regulate Release of Gastric Juice 55 Regulation of Gastric Motility and Emptying Response of the stomach to filling ▪ Stretches to accommodate incoming food ▪ Two factors cause pressure to remain constant until 1.5 L of food is ingested Receptive relaxation – reflex-mediated relaxation of smooth muscle coordinated by swallowing center of brain stem Gastric accommodation – intrinsic ability of smooth muscle to exhibit stress-relaxation response, which enables https://d45jl3w9libvn.cloudfront.net/jaypee/static/books hollow organs to stretch without increasing /9789386056979/Chapters/images/407-1.jpg tension or contractions 56  Regulation of Gastric Motility and Emptying Gastric Contractile Activity ▪ Peristaltic waves move toward the pylorus at the rate of 3/minute ▪ Contractions: most vigorous & powerful near pylorus region (holds ~ 30 ml of chyme) ▪ Each wave spurts ~3 ml duodenum & rest forced back into stomach ▪ only liquids & small particles are allowed to pass through small pyloric valve Basic electrical rhythm (BER) also called the cyclic slow waves of the stomach ▪ initiated by enteric pacemaker cells (formerly interstitial cells of Cajal) which generate waves of depolarization ( ~3/ min) ▪ pacemaker cells (located between SM layer) connected to the rest of the smooth muscle by gap junctions/ entire much contracts when threshold is met – Same factors that increase gastric secretion also increase contractile activity ▪ Distension and gastrin strengthen the waves of depolarization 57 Regulation of Gastric Motility and Emptying Figure 23.21 Peristaltic waves in the stomach. 58 Regulation of Gastric Motility and Emptying Regulation of gastric emptying – Stomach empties in ~4 hours, but increase in fatty chyme entering duodenum can increase time to 6 hours or more Carbohydrate-rich chyme moves quickly through duodenum – Duodenum can prevent overfilling by controlling how much chyme enters Duodenal receptors respond to stretch and chemical signals Enterogastric reflex & enterogastrones inhibit gastric secretion & duodenal filling Figure 23.22 59 Table 23.1 Hormones and paracrines that act in Digestion 60 61  Nutrition, Metabolism & Energy Balance Pt II Chapter 24 p. 961- 973 (Sections 28.8 -24.11) Chapter 16 p. 630 – 632 (section 16.11- the Pancreas) p. 617 - 621 (Section 16.7 - The Thyroid gland) http://2012books.lardbucket.org/books/an-introduction-to- nutrition/section_14/162d91c78c4bfdaeade6c0c77d0b9ee5.jpg 1 Objectives for Part II 2.4 Describe the metabolic consequences of the two types of Diabetes Mellitus 2.5 List the various hepatic functions associated with metabolism 2.6 List and describe the 4 major types of lipoproteins 2.7 Describe the synthesis of thyroid hormones & its regulation 2.8 List the metabolic processes regulated by thyroid hormones 2.9 Define basal metabolism and total metabolism and identify the factors that influence them 2.10 Discuss the mechanisms of appetite regulation 2.11 Describe and explain the mechanisms of heat exchange 2.12 Explain the mechanisms for the control of body temperature 2 Regulating Blood Glucose Levels https://yegfitness.ca/wp-content/uploads/2021/01/diabetes.jpeg Chapter 16: p. 630 – 634 (The Pancreas and Diabetes Mellitus) 3 Insulin & glucagon from the pancreas regulate blood glucose levels 4  Triangular gland located partially behind stomach Has both exocrine and endocrine cells Acinar cells (exocrine) produce enzyme-rich juice for digestion Pancreatic islets (islets of Langerhans) contain endocrine cells Alpha ( ) cells produce glucagon (hyperglycemic hormone) Beta ( ) cells produce insulin (hypoglycemic hormone) Delta (D) cells secrete somatostatin 5 F cells produce pancreatic polypeptide  Diabetes Mellitus Diabetes mellitus (DM) is a group of metabolic diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. Complex disorders of CHO, fat and protein metabolism https://diabetespharmacist.lexblogplatformthree.com/wp- content/uploads/sites/346/2009/11/diabetes-symptoms21.jpg 6  Diabetes Mellitus Type 1 DM ▪ autoimmune destruction of pancreatic -cell ▪ absolute insulin deficiency (Why?) Type 2 DM ▪ insulin resistance = relative insulin deficiency e.g. interference with insulin binding to target tissue https://medlineplus.gov/images/PX0000QW_PRESENTATION.jpeg 7 Insulin Mechanism of Action 8  Figure 16.18 Consequences of Insulin Deficit (Diabetes Mellitus) o uptake of glucose by peripheral tissue / glucose production (gluconeogenesis) / release of glucose from the liver (glycogenolysis) 9  Type I DM: Metabolic Consequences – When sugars cannot be used as fuel, as in DM, fats are used, causing lipidemia (high levels of fatty acids in blood) – Fatty acid metabolism (lipolysis) results in formation of ketones (ketone bodies) – Ketones are acidic, and their build-up in blood can cause ketoacidosis ▪ Also causes ketonuria – Untreated ketoacidosis causes hyperpnea, disrupted heart activity and O2 transport, and severe depression of nervous system that can possibly lead to coma and death Hyperinsulinism – Excessive insulin secretion ▪ Causes hypoglycemia: low blood glucose levels – Symptoms: anxiety, nervousness, disorientation, unconsciousness, even death – Treatment: sugar ingestion 10  Type 2 Diabetes Mellitus Risk factors: age, obesity, hypertension, physical inactivity, and family history. Consequences of obesity ▪ adipose tissue secrete hormone that decrease insulin sensitivity ▪ increased FFAs/ TGs and cholesterol: ▪ interfere with intracellular insulin signalling ▪ decrease tissue responses to insulin ▪ alter incretin actions ▪ promote inflammation ▪ increase inflammatory cytokines that cause insulin resistance and are toxic to beta cells 11  Hepatocytes carry out ~500 metabolic functions Process nearly every class of nutrient Metabolic Role Play major role in regulating plasma cholesterol levels of the Liver Store vitamins and minerals Metabolize alcohol, drugs, hormones, and bilirubin 12 13 14  Cholesterol Metabolism and Regulation of Blood Cholesterol Levels ▪ Not used as an energy source ▪ Structural basis of bile salts, steroid hormones, and vitamin D ▪ Major component of plasma membranes ▪ 15% is ingested, the rest made in body, primarily by liver ▪ Lost from body when catabolized or secreted in bile salts that are lost in feces 15  Cholesterol Metabolism and Regulation of Blood Cholesterol Levels Types of transport Cholesterol Transport Lipoproteins lipoproteins Transport of exogenous transport water-insoluble HDLs (high-density & de novo cholesterol cholesterol and TGs lipoproteins): highest requires a diversity of through blood protein content lipoproteins complexes Contain signaling LDLs (low-density containing triglycerides, molecules that regulate lipoproteins): highest phospholipids, lipid entry/exit at target cholesterol content cholesterol, and protein cells VLDLs (very low-density All contain triglycerides, lipoproteins): contents phospholipids, are more than half cholesterol, and protein triglycerides, with low The higher the density of proteins percentage of lipids, the Chylomicrons: lower the density transported from; have lowest density and consist almost entirely of triglycerides 16  Composition and Function of Lipoproteins – VLDLs: transport triglycerides from liver to peripheral tissues (mostly adipose) – LDLs: transport cholesterol to peripheral tissues for membranes, storage, or hormone synthesis – HDLs: transport excess cholesterol from peripheral tissues to liver to be broken down and secreted into bile ▪ Also provide cholesterol to steroid-producing organs 17  Factors Regulating Blood Cholesterol levels Blood Levels of Total Cholesterol, LDL, and HDL – Generally, total cholesterol < 200 m g/dl of blood is desirable for adults – More important to look at ratio of lipoproteins transporting cholesterol in blood – High levels of LDL are generally considered bad (associated with atherosclerosis) – High levels of HDL were considered good because it transported cholesterol destined for degradation 18  Factors Regulating Blood Cholesterol levels Factors regulating blood cholesterol levels ▪ The liver produces cholesterol at a basal level regardless of dietary cholesterol intake - restricting dietary cholesterol does not markedly reduce blood cholesterol levels ▪ More important effect is relative amounts of saturated and unsaturated fatty acids ▪ Saturated vs Unsaturated fats ▪ Saturated fatty acids stimulate liver synthesis of cholesterol & inhibit cholesterol excretion from body ▪ Unsaturated fatty acids enhance excretion of cholesterol into bile salts ▪ Trans fats Worse effect on cholesterol levels than saturated fats; increase LDL & reduce HDL ▪ Unsaturated omega-3 fatty acids (found in cold-water fish) have lower proportions of saturated fats and cholesterol ▪ Make platelets less sticky and help prevent spontaneous clotting ▪ Appear to lower blood pressure ▪ Cigarette smoking and stress lower HDL levels ▪ Regular aerobic exercise and estrogens lower LDL and increase HDL levels ▪ Body Shape 19  Factors Regulating Blood Cholesterol levels Body shape ▪ “Apples” (people with upper body and abdominal fat, seen more often in males) tend to have higher levels of cholesterol and LDLs ▪ “Pears” (whose fat is localized in the hips and thighs, more common in females) tend to have lower levels https://www.researchgate.net/profile/Lisa- Sangkum/publication/312162831/figure/fig1/AS:1052594982121472@1627969608751/Apple- 20 and-Pear-Body-types-By-permission-of-Mayo-Foundation-for-Medical-and-Research-All.jpg  The Thyroid gland 21 Chapter 16: pp 617-620 (Section 16.7)  The Thyroid gland Location and Structure Butterfly-shaped gland in anterior neck on the trachea, just inferior to larynx, that consists of: ▪ Isthmus: median mass connecting two lateral lobes ▪ Follicles: hollow sphere of epithelial follicular cells that produce glycoprotein thyroglobulin ▪ Colloid: fluid of follicle lumen containing thyroglobulin & iodine (precursor to thyroid hormone) ▪ Parafollicular cells: produce hormone calcitonin 22 Figure 16.8 The thyroid gland.  Thyroid Hormone o The body’s major metabolic hormone o Found in two forms Tyrosine – Both are iodine-containing amine hormones – T4 (thyroxine): major form that consists of two tyrosine molecules with four bound iodine atoms Most converted to T3 at tissue level – T3 (triiodothyronine): form that has two tyrosine molecules with three bound iodine atoms o TH is lipid soluble https://ljkboerner.files.wordpress.com/2011/03/t3-and-t4.jpg 23  Thyroid hormone TH affects virtually every cell in body Enters target cell and binds to intracellular receptors within nucleus – Triggers transcription of various metabolic gene Effects of thyroid hormone include: – Increases basal metabolic rate and heat production ▪ Referred to as calorigenic effect – Regulates tissue growth and development ▪ Critical for normal skeletal and nervous system development and reproductive capabilities – Maintains blood pressure ▪ Increases adrenergic receptors in blood vessels 24 25  Thyroid hormone Synthesis ▪ T3 and T4 are stored in the follicles lumen until triggered for release by TSH ▪ amounts sufficient for 2-3 months Role of iodine ▪ Iodine - ingested in the form of iodides is necessary for the formation of T3/T4 ▪ Iodide from the GI → the blood and is trapped in the thyroid follicles that actively pump iodide from the blood into the interior of the cells ▪ The rate of iodide trapping is influenced by TSH http://www.fuelrunning.com/repository/nutrition-matters/0020.jpg 26 Thyroid Hormone Synthesis 27  Thyroid Hormone Transport and regulation T4 & T3 transported by thyroxine-binding globulins (TBGs) Both bind to target receptors, but T3 is 10 times more active than T4 Peripheral tissues have enzyme that to convert T4 to T3 (-1 iodine) Negative feedback regulation of TH release ▪ Falling TH levels stimulate release of thyroid-stimulating hormone (TSH) – Rising TH levels provide negative feedback inhibition on TSH – TSH can also be inhibited by GHIH, dopamine, and increased levels of cortisol and iodide Figure 16.7 Regulation of thyroid hormone secretion. 28  Clinical Note Hypersecretion of TH: most common type is Graves’ disease – Autoimmune disease: body makes abnormal antibodies directed against thyroid follicular cells ‒ Antibodies mimic TSH, stimulating TH release ‒ Symptoms include elevated metabolic rate, sweating, rapid and irregular heartbeats, nervousness, and weight loss despite adequate food ▪ Exophthalmos may result: eyes protrude as tissue behind eyes becomes edematous and fibrous Treatments include surgical removal of thyroid or radioactive iodine to destroy active thyroid cells 29  Clinical Note TH hyposecretion in adults can lead to myxedema. Symptoms include low metabolic rate, thick and/or dry skin, puffy eyes, feeling chilled, constipation, edema, mental sluggishness, lethargy Myxedema – If due to lack of iodine, a goiter may develop ↑ synthesize of unusable thyroglobulin causes thyroid to enlarge Congenital hypothyroidism leads to cretinism – Symptoms include intellectual disabilities, short and disproportionately sized body, thick tongue and neck 30  Chapter 24 p.945-957 Energy Balance https://quantum.lk/wp-content/uploads/2019/05/Lipo-Therm-Balance-Weight-Loss.png 31  Energy Balance Energy Balance = energy released from food (intake) must equal total energy output ▪ Energy intake ▪ energy derived from absorbable foods = energy liberated during food oxidation ▪ Energy output ▪ Immediately lost as heat (~60%) https://static1.squarespace.com/static/53c14549e4b055a e0c76a5c7/t/53ceef94e4b0602f13f978c5/1406070676762 ▪ Used to do work (driven by ATP) /calorie-balance.jpg ▪ Stored as fat or glycogen Nearly all energy from food is eventually converted to heat, which cannot be used to do work, but it ▪ warms tissues and blood ▪ helps maintain homeostatic body temperature ▪ allows metabolic reactions to occur efficiently For body weight to remain stable, energy intake must equal energy output - if not, there will be weight gain or loss 32  Energy balance Body mass index (BMI) is a formula used to determine obesity based on a person’s weight relative to height – To calculate: BMI = wt (kg) /height in (m)2 Example: A person is 175 cm tall and has a weight of 70 kg. BMI = 70 = 70 = 70 = 22. 86 ( normal body weight) (1.75) (1.75 X 1.75) 2 3.0625 Body mass (BM) is maintained when energy intake = energy expenditure ▪ Clinically, overweight is defined by a BMI of 25–30 (carries some health risk) ▪ Obesity is a B M I > 30 (with markedly increased health risk) https://www.1mg.com/articles/wp-content/uploads/2018/07/BMI.jpg 33  Obesity Obese people have higher incidence of ▪ diabetes mellitus ▪ hypertension ▪ heart disease / atherosclerosis ▪ cancer ▪ osteoarthritis Current US statistics: ▪ ~ 32% are overweight; an additional 42% are obese ▪ 1 in 10 has diabetes ▪ 19% of children are obese (compared with only 5% 40 years ago) 34  Metabolic Syndrome cluster of five risk factors Presence of these factors can: Double chance of heart disease Increase risk of diabetes five times Five factors seen in metabolic syndrome: ↑ Waist circumference ↑ Blood pressure ↑ Blood glucose ↑ Blood triglycerides ↓ Blood HDL cholesterol Regulation of Food Intake 36  Regulation of Food Intake Current theories focus mainly on neural signals from GI tract, hormones, and blood nutrient levels ▪ To lesser extent, body temperature and psychological factors also play role Areas of hypothalamus release peptides that influence feeding behavior – Arcuate nucleus (ARC) – Lateral Hypothalamic Area (LHA), – Ventromedial Nucleus (VMN) 37  Regulation of Food Intake Hunger- promoting neurons Arcuate nucleus (ARC) – Some ARC neurons release neuropeptide Y (NPY) and agouti-related peptides that enhance appetite These increase appetite by stimulating release of orexins from Lateral hypothalamic area (LHA) neurons Satiety-promoting neurons – Other ARC neurons release pro- opiomelanocortin (POMC) and cocaine- /amphetamine-regulated transcript (CART), which suppress appetite These act on the ventromedial nucleus (VMN), causing it to release CRH (important appetite suppressor) 38  Regulation of Food Intake Feeding behavior and hunger regulated by: – Neural signals from digestive tract – Bloodborne signals related to body energy stores – Hormones – To lesser extent, body temperature and psychological factors Operate through brain thermoreceptors, chemoreceptors, and others Food intake is subject to both https://www.gemhospitals.com/wp-content/uploads/2019/07/45154185_xl- 1024x1024.jpg short- and long-term controls 39  Regulation of Food Intake Short-term regulation of food intake Neural signals from digestive tract ▪ High protein content of meal increases and prolongs afferent vagal signals ▪ Distension sends signals along vagus nerve that suppress hunger center Nutrient signals related to energy stores ▪ Increased nutrient levels in blood depress eating – Rising blood glucose levels – Elevated blood amino acid levels – Blood levels of fatty acids Hormones ▪ Gut hormones (e.g., insulin and CCK) signal satiety and depress hunger ▪ Glucagon and epinephrine released during fasting and stimulate hunger ▪ Ghrelin (Ghr) from stomach is a powerful appetite stimulant. Levels peak prior to mealtime and drop after a meal 40  Regulation of Food Intake Long-term regulation of food intake Leptin ▪ Hormone secreted by fat cells in response to increased body fat mass ‒ If fat mass increases, leptin levels rise; more leptin binds to receptors in ARC that: ▪ Stimulate expression of CART ▪ Suppress release of NPY (most potent appetite stimulant known) – Decreasing release of appetite-enhancing orexins from LHA Decreasing appetite/food intake, eventually promoting weight loss ‒ If fat stores decrease, leptin levels fall, producing opposite effect ▪ Increasing appetite/food intake, eventually promoting weight gain – Rising leptin level causes some weight loss but is no “magic bullet” for obese patients – Obese people have high leptin levels but seem to be resistant to its action (unknown reason) – Consensus: leptin’s main role is to protect against weight loss in times of 41 nutritional deprivation Regulation of Food Intake 42  Regulation of Food Intake Additional factors in regulation of food intake – Temperature: cold activates hunger – Stress: depends on individual – Psychological factors – Adenovirus infections – Sleep deprivation – Composition of gut bacteria 43 Metabolic Rate https://i.ytimg.com/vi/68zJ6jqtgfU/hqdefault.jpg 44  Metabolic Rate ▪ total heat produced by chemical reactions and mechanical work of body Can be measured: ▪ Directly: calorimeter measures heat liberated into water chamber ▪ Indirectly: respirometer measures oxygen consumption (directly proportional to heat production) 45  Basal Metabolic Rate (BMR) BMR: energy body needs to perform its most essential activities ▪ Measured in fasting state (12-hour fast) ▪ reclining position ▪ relaxed mentally & physically ▪ room temperature 20–25 C Not lowest metabolic state, that’s during sleep (skeletal muscles fully relaxed) ▪ Recorded as kilocalories per square http://upload.wikimedia.org/wikipedia/commons/b/b0/Indirect _calorimetry_laboratory_with_canopy_hood.jpg meter of body surface per hour (kcal/m2/h) ▪ Example: 70 kg adult BMR = 66 kcal/h 46  Basal Metabolic Rate (BMR) BMR is influenced by: – Age and gender: BMR decreases with age ▪ Males have disproportionately higher BMR – Body temperature: BMR increases with temperature – Stress: BMR increases with stress – Thyroxine: increases oxygen consumption, cellular respiration, and BMR 47  Clinical Note Hyperthyroidism causes many problems resulting from the high BMR it produces – Body catabolizes stored fats and tissue proteins – Person often loses weight despite increased hunger and food intake – Bones weaken, and muscles, including heart, begin to atrophy Hypothyroidism results in slowed metabolism, obesity, and diminished thought processes 48  Total Metabolic Rate (TMR) Total metabolic rate (TMR) – Rate of energy consumption to fuel all ongoing activities – female whose energy needs are ~ 2002 kcal/day may spend about 1400 kcal supporting vital body activities – Increases with skeletal muscle activity – Even slight increases in muscular work significantly increase T M R and heat production – TMR also increases with food ingestion (food-induced thermogenesis) ▪ Greatest with protein ingestion ▪ Fasting or very low caloric intake depresses TMR Total metabolic rate (TMR) = Total daily energy expenditure (TDEE) Components are ▪ Basal energy expenditure (BMR) ▪ The thermic effect of food (TEF) ▪ Energy expended on physical activity (thermic effect of activity = TEA)