Ch 23- Digestive System, Part 2 • Small intestine • Pancreas • Liver -Hepatic portal system • Gall bladder -Bile • Large Intestine • Chemical digestion and absorption Junction of stomach and small intestine Small Intestine • Major function- responsible for 90% of absorption and also important for digestion • Divided into three regions – Duodenum- ‘mixing bowl’ – Jejunum- chemical digestion/absorption – Ileum- protection from large intestine Layers of the small intestine Plica Unique to the small intestine is the presence of plica (plicae circulares). Plica are permanent folds of the mucosa and submucosa. One plica One villus On the plica, you will see villi-Present only in small intestine -Crypts spaced between them -Do not confuse with ‘mircovilli’ Plica and villi Each plica supports a forest of villi. Each villus is covered with simple columnar epithelium. These epithelial cells have microvilli. Phew! Villus and enzymes of the brush microvilli border cells Brush border cell The lamina propria of each villus contains a lacteal, nerves and blood vessels Regional Features of the Small Intestine • Duodenum- site of chyme entry, where it is blasted with HCO3- (and other things) – Along duodenum, pH of chyme changes from 1-2 to 7-8 – Mucus glands of mucosa – Also, Brunner’s glands (submucosal glands) • Jejunum- first half has numerous plicae and villi, but they decrease in number en route to ileum – Brush border enzymes • Ileum - lack plicae, contain masses of lymphoid tissue..why?? Duodenum Villi Crypts Plica Brunner’s Glands (submucosal glands) Jejunum- Panorama Ileum Goblet Cells Crypts Peyer’s Patches What organs secrete into the small intestine? Liver Gall bladder Anatomy of the pancreas -An accessory structure of the small intestine Pancreas • Where have you seen the pancreas before? • Primarily an exocrine gland (99% of cells) • Composed of a series of ductules that are surrounded by secretory cells, acinar cells Acinar Cells • Cuboidal epithelial cells that form pancreatic acini • Pancreatic juice produced by acinar cells • Alkaline mixture of enzymes, water, and ions • Over 1200 ml of ‘juice’ produced each day! • Travels in pancreatic duct, joins the common bile duct Enzymes produced by the pancreas • • • • Pancreatic alpha-amylase Pancreatic lipase Nucleases Four inactive proteolytic enzymes – Not activated until they reach the small intestine Proteolytic Enzymes • Inactive trypsinogen converted to active trypsin by enteropeptidase (enterokinase) • Trypsin then converts other proenzymes into their active forms – Chymotrypsin – Carboxypeptidase Inactive 1 proteases released from acinar cells 2 3 6 trypsinogen 4 enteropeptidase Brush border cells 5 Inactive protease active protease Trypsin is now active, and will activate other proteases: Chymotrypsin Carboxypeptidase Liver • Largest visceral organ, 3 lb • Surrounded by fibrous capsule • Has numerous lobes, with numerous lobules – Cells are called hepatocyes • Receives ~25% of total cardiac output!! • Blood flow to and from the liver is unique Hepatic Portal System • Liver receives 1/3 of blood via hepatic artery (not shown) • 2/3 from hepatic portal vein • This major vein drains capillaries from: esophagus, stomach, small and large intestine and THEN heads to liver •Venous blood from liver dumps directly into inferior vena cava Any guesses as to a major function of the liver? Hepatic Portal System -The portal venous blood contains all of the products of digestion absorbed from the GI tract. -Thus all nutrients are processed/viewed in the liver (by hepatocytes) before being released back into the central veins. Liver • Each lobe divided into lobules • Cells of the liver are hepatocytes – Arranged as a single layer of cells, stacked – Divided by sinusoids – Blood flows through sinusoids, past Kupffer cells (resident macrophage) Kupffer bacteria RBCs Liver lobules Blood is flowing towards center Hepatocytes arranged into ‘walls’. Walls radiate outward from a central point. The central area contains a single, central vein. Liver lobules- Portal Triads 1 mm Portal Triad Central Vein Major functions of the liver • Metabolic regulation • Hematological regulation • Bile production (its only true digestive function) Metabolic Regulation • Hepatocytes regulate the composition of the blood and blood nutrients • They do this by selectively secreting and absorbing molecules from the blood • What molecules? Carbs, lipids, amino acids, waste products, vitamins, minerals and drugs Portal triad Metabolic regulation • Hepatocytes adjust the contents of the blood by selective absorption and secretion – Remove/store excess nutrients – Correct deficiencies • Hepatocytes are able to take in and/or release large molecules with ease, partly because the nearby capillaries are so leaky! hepatocytes A big ol’ leaky capillary, a sinusoidal capillary What role does the liver play in amino acid metabolism? • Removes excess amino acids from the bloodstream or releases stored amino acids that are deficient • Besides maintenance/growth, what might these amino acids be used for? Alanine, valine, leucine, proline, etc, etc. What role does the liver play in lipid metabolism? • Regulates circulating levels of triglycerides, fatty acids, and cholesterol • If levels decline, lipid stores are broken down and released • ALSO, we will return to Bile in 3 minutes, an important player in lipid breakdown What role does the liver play in carbohydrate metabolism? • Blood glucose levels are kept at or near 90 mg/dl • If blood glucose levels rise, glucose is stored in liver as ______? • If glucose levels drop, glycogen reserves in the liver are broken down and glucose is released into blood Other metabolic functions of the liver • Removal of waste products – Ammonia is converted to urea • Vitamin storage – The fat soluble ones! • Mineral storage • Drug inactivation Hematological regulation • Synthesis of plasma proteins (think albumins, etc.) • Removal of hormones (like a giant sponge, the liver takes NE, epi, thyroid hormones, steroid hormones, etc. ‘out of the game’) • Removal of antibodies • Removal (or storage) of toxins • Phagocytosis (Kupffer cells chomp up RBCs and are APCs!) • Production of bile (1 liter/day) Kupffer RBCs Hepatocytes produce bile • Bile is made and then secreted into channels called bile canaliculi • Canaliculi merge to join the bile ducts at each of the triads triad What is bile? • Bile is an alkaline solution containing: water, electrolytes, bilirubin, phospholipids, triglycerides, cholesterol, and lipids known as bile salts • Function of bile (bile salts): emulsify fats for digestion – Bile salts are not enzymes, they merely help to bust up large fat droplets into smaller fat droplets. – Why is this important? Gall Bladder • Major functions: –Bile storage –Bile concentration, modification Gall bladder receives bile from liver via the cystic duct What regulates release of bile? • When chyme enters the small intestine, CCK is released • CCK relaxes sphincter (sphincter of Oddi) and triggers muscle contractions that squeeze the gall bladder and send bile out, into duodenum • How clever that CCK secretion increases when chyme is high in fats! • Interesting note: CCK also slows stomach movement (release of food to duodenum) – What does this tell you about a high fat meal? Review of Digestion at Small Intestine • Chyme enters duodenum from stomach • Gets blasted with HCO3-, enzymes and bile – Which enzymes? Where from? Are all enzymes active upon arrival? Which ones are? Which ones are not? • Segmentation provides mechanical digestion • Bile salts surround fats, increasing lipase effectiveness • ABSORBPTION of nutrients!! • Once most absorption done, two waves of peristalsis push left-overs into large intestines. Each wave takes ~2 hours. Animation-Recap The last part..large intestine • General functions – Reabsorption of water – Absorption of vitamins made by bacteria – Compaction and storage of fecal material Anatomy of the large intestine The large intestine is comprised of sections: 1. Cecum and appendix 2. Colon (ascending, transverse, descending, sigmoid) 3. Rectum, leads to anal canal and anal canal NoteLarge diameter Thin walls Histology of the Large Intestine • Colon- Simple columnar with goblet cells • Rectum- the anal canal is stratified squamous • So, as you move from colon to out: epithelium changes from columnar (with goblet cells) stratified squamous keratinized stratified squamous. • Mucosa does not produce enzymes • No villi Site ofVitamins, bile, and some H2O absorption A word about bacterial flora Most bacteria are DOA (dead on arrival) at the large intestine, but some survive and comprise the bacterial flora Over 700 species! Functions? Chemical Digestion and Absorption • Virtually all nutrients from the diet are absorbed into blood (or lymph vessels) across the mucosa of the small intestine. • Much of this absorption happens via cotransport or diffusion across the apical membrane of intestinal epithelial cells (the brush border cells), aka eneterocytes Chemical digestion and absorption Part 1 & 2 First steps of mechanical and chemical digestion Part 3 Final steps of chemical digestion and absorption Recall polymers and monomers Hydrolysis • Hydrolysis is breaking of a bond ‘with water’ or the addition of water • Digestive enzymes hydrolyze one specific substrate ABCDase A-B-C-D + H2O A-B-H + OH-C-D Absorption • Carbohydrates- simple, hexose sugars will be absorbed • Proteins- di or tripeptides are typically absorbed, also amino acids • Fats- Fatty acids and monoglycerides are absorbed (and then converted immediately back to triglycerides) Carbohydrates • Sucrase catalyzes the cleavage of the bond between (glucose-fructose) in sucrose • Lactase catalyzes the cleavage of the bond between (glucose-galactose) in lactose • Maltase catalyzes the cleavage of the bond between (glucose-glucose) in maltose Where do we find these three enzymes? • Enzymes are transmembrane (or at least membrane-associated) proteins • Function at the microvilli of enterocytes (brush border cells) • Apical surface Sucrase Maltase Lactase brush border cells Disaccharides in intestinal lumen interact with brush border enzymes, and the enzymatic products are absorbed Sucrose Hexose sugars Sucrase Maltose Hexose sugars Maltase Lactose Lactase brush border cells Hexose sugars When brush border epithelial cells fail to make lactase…. Lactose is not digested or absorbed. Bacteria ferment lactose Gas, diarrhea, etc. Sucrase Maltase Lactase Absorption of Carbs • Monosaccharides (glucose and galactose) are into epithelial cell membranes via cotransport (along with Na+) • Fructose moves in via facilitated diffusion • All monosacs. pass through basal membrane of cell (toward capillary) by facilitated diffusion Co-transport • A special type of passive transport • Moves more than one molecule at same time, with molecules moving in same direction • Doesn’t directly require ATP, but cell expends ATP to maintain homeostasis • Cotransport can function despite an opposing concentration gradient – Example- glucose/Na+ co-transporter Absorbed nutrients can enter a capillary or a lacteal Sucrose Maltose Hexose sugars L U M E N Animation-absorption Carbs and peptides enter capillaries. Fats enter lacteals. Capillary Lacteal Protein Digestion • Effects of mastication (mechanical digestion) • Effects of pH on protein structure • What enzymes are first involved? • Where are they found? • What enzymes are at brush border? • At brush border, trypsinogen is converted to trypsin by enterokinase • Trypsin then activates: chymotrypsin, elastase and carboxypepsidase • Dipeptidases at brush border! trypsinogen trypsin enterokinase Activates pancreatic peptidases. Trypsin activates pancreatic proteases. Dipeptidases are membrane enzymes. Dipeptidases! Absorption of proteins • Amino acids are absorbed by – Facilitated diffusion – Cotransport • Once inside the cell they transported out via: – Facilitated diffusion diffusion Hepatic portal! Digestion of lipids • What enzymes are involved? • Where are they found? Lipid Digestion and Absorption • First with lipases – Break down triglycerides to free fatty acids or monoglycerides • Form micelles with bile salts • Micelles diffuse across the columnar cells • Inside cells, free fatty acids are re-attached to monogylcerides, forming triglycerides (TGs) again • TGs coated with phospholipids and proteins form chylomicrons Chylomicrons • Transported out of the columnar cells via exocytosis • Enter lacteal…..so, when and where will chylomicrons actually reach the blood? diffusion chylomicron Lacteal Vitamin absorption • The small intestine absorbs dietary vitamins, and the large intestine absorbs some of the K and B vitamins made by resident bacteria • Fat soluble (A, D, E, and K) – Enter mixed with micelles • Water soluble (B vitamins and vit. C) – All by diffusion except Vit. B12, which requires intrinic factor from stomach to be absorbed Ion Absorption • • • • Most transported along conc. gradients Na+ the more eaten, the more absorbed Calcium regulated by vitamin D and PTH Most anions move by diffusion Ion and Vitamin Absorption Water Absorption • Cells cannot actively absorb or secrete H2O • All water moves via passive transport, down its concentration gradient • As intestinal cells absorb nutrients and ions, their concentration falls in the lumen, and increases in cells, thus water moves into cells. •The small intestine and large intestine are key in water reabsorption