GI System Secretion & Digestion PDF

Secretion in the GI system. Digestion and Absorption in the GI tract Konstantinos Ekmektzoglou MD, PhD, FEBGH Assistant Professor School of Medicine European University Cyprus November 2024 Secretion in the GI system  Main GI Secretions Digestive enzymes Mucus ✓In res...

Secretion in the GI system. Digestion and Absorption in the GI tract Konstantinos Ekmektzoglou MD, PhD, FEBGH Assistant Professor School of Medicine European University Cyprus November 2024 Secretion in the GI system  Main GI Secretions Digestive enzymes Mucus ✓In response to the presence of food in the GI tract ✓Precise amount needed for proper digestion  Anatomical Types of Glands 1. single-cell mucous glands = mucous cells = goblet cells billions extrude mucus directly onto the epithelial surface -> lubricant -> protects from excoriation and digestion 2. pits -> invaginations of the epithelium into the submucosa crypts of Lieberkühn (small intestine) -> secretory cells 3. Tubular glands stomach and upper duodenum (e.g. oxyntic gland) 4. complex glands (salivary glands, pancreas, and liver) secretions for digestion or emulsification millions of acini lined with secreting glandular cells  Stimulation of Alimentary Tract Glands Contact of Food with the Epithelium Local effect ENS stimulation (tactile stimulation, chemical irritation, distention) Both mucous cells and glands Regulation of Glandular Secretion by Hormones Stomach and intestine Regulate volume and character of secretion  Stimulation of Alimentary Tract Glands Autonomic Stimulation of Secretion Parasympathetic Stimulation Increases Glandular Secretion Glossopharyngeal and vagus (upper GI + pancreas) Sympathetic Stimulation sympathetic stimulation alone usually slightly increases secretion if parasympathetic or hormonal stimulation -> copious secretion by the glands sympathetic stimulation reduces the secretion vasoconstrictive reduction of the blood supply  The role of mucus thick secretion: water - electrolytes - several glycoproteins, which themselves excellent lubricant and protectant for the GI wall adhere tightly to the food and spread as a thin film over the surfaces coats the wall of the gut -> prevents actual contact of food particles with the mucosa low resistance for slippage -> particles slide along the epithelium facilitates feces formation resistant to digestion by enzymes glycoproteins -> amphoteric properties buffering both acids or alkalies  Secretion of Saliva Glands of salivation –Parotid –Submandibular –Sublingual –Buccal Saliva protein secretions –Serous secretion (ptyalin) –Mucous secretion (mucin) Secretion of Saliva Large amounts of K+ and HCO-3 Secretion occurs in 2 stages Saliva concentrations Na+ = 15mEq/L Cl- = 15mEq/L K+ = 30mEq/L HCO-3 = 50-70mEq/L  Esophageal Secretion Main Simple mucous Esophageal glands Body provide lubrication for swallowing prevents excoriation by entering food Proximal and protect from acidic gastric juices Compound Distal mucous glands Esophageal End  Gastric Secretion Oxyntic glands Tubular glands Body and fundus HCl – pespinogen - intrinsic factor – mucus Pyloric glands Tubular glands Antrum Gastrin - mucus Oxyntic Gland mucus HCl and pepsinogen pepsinogen Hydrochloric Acid Secretion ✓ Produced in the canaliculi villi ✓ pH = 0,8 ✓ 1500 cal / liter of gastric juice ✓ hydrogen-potassium pump (H+-K+ ATPase)  Hydrochloric Acid Secretion 1 4 Final Secretion 2 Water 3 HCL: 150 - 160 mEq/L 3 KCL: 15 mEq/L small amount of NaCl 5 6  Gastric Secretion Stimulation Chief cell Pepsinogen Parasympathetic Ach Parietal cell HCL stimulation Mucous cell Mucus Pepsinogen -> secreted in inactive form When in contact with HCL -> pepsin Pepsin Highly proteolytic enzyme Active in pH 1,8-3,5  Intrinsic Factor (IF) Secretion Intrinsic Factor essential for vitB12 absorption in ileum secreted by the parietal cells Chronic gastritis reduced parietal cell volume Achlorhydria (lack of stomach acid secretion) Lack of IF -> reduced vitB12 absorption -> reduced bone marrow stimulation -> pernicious anemia  Pyloric Gland – Mucus Secretion Surface mucous cells Alkaline viscid mucus Stomach protection Lubrication of food transport  Pyloric Gland – Gastrin Secretion Gastrin produced by the G cells in the pyloric gland Main stimulator of HCL secretion by the parietal cells Direct effect -> stimulation of parietal cells to secrete HCL Indirect effect -> stimulation of ECL cells (also in the oxyntic gland -> secrete histamine -> stimulate parietal cells to secrete HCL Phases of Gastric Secretion 30% of gastric secretion before food enters the stomach sight, smell, thought, taste the greater the appetite -> the more intense Neurogenic signals ->cerebral cortex and in the appetite centers of the amygdala and hypothalamus. 60% of gastric secretion When food enters the stomach long vago-vagal reflexes: stomach -> brain -> stomach local enteric reflexes gastrin – histamine mechanism initiation 10% of gastric secretion when food in duodenum small amounts of gastrin released by the duodenal mucosa HCL secretion by the parietal cells  Inhibition of Gastric Secretion Entero-gastric reflex Intestinal hormones presence of food in the small presence of acid, fat, protein, transmitted through MNS, hyperosmotic or hypo-osmotic sympathetic and vagus nerves fluids, irritating factor inhibits stomach secretion secretin Initiated by: gastric inhibitory peptide small bowel distension vasoactive intestinal polypeptide presence of acid in the upper intestine Somatostatin presence of protein breakdown All 4 inhibit gastric secretion products irritation of the mucosa  Secretion of Small Intestine Brunner’s Glands Crypts of Lieberkühn proximal duodenum Between villi, entire small intestine alkaline mucus Goblet cells -> mucus irritating stimuli in duodenum Enterocytes vagal stimulation Secrete and absorb water and electrolytes secretin 1,8 l/d bicarbonate ions Facilitate absorption from chyme protect duodenal wall by highly acidic gastric juice  Secretion of the Colon Mucous cells protect intestinal wall against excoriation provide adherent medium for holding fecal matter together protect intestinal wall from bacterial activity provide barrier to keep acids formed in the feces away from mucosa Digestion and Absorption in the GI tract What and why do we need to digest? Hydrolysis as a Common Digestion Procedure  Digestion of Carbohydrates Sucrose disaccharide Lactose disaccharide Starches polysaccharides  Digestion of Carbohydrates in the Mouth and Stomach Ptyalin (α-amylase ) secreted by parotid glands in saliva hydrolyzes starch -> maltose (disaccharide) + small glucose polymers (3-9 molecules) 5% of starches become hydrolyzed in the mouth Hydrolysis continues in the stomach body and fundus 1 hour gastric acid blocks salivary amylase Non-active if pH saliva amylase As in contact with enterocytes 15-30min all carb0hydrates digested Lactose -> galactose + glucose Sucrose -> fructose + glucose to maltose + glucose polymers Maltose -> multiple glucose molecules Monosaccharides water soluble immediate absorption by portal blood glucose > 80% galactose ~ 10% fructose ~ 10% Digestion of Proteins  Digestion of Proteins in the Stomach Pepsin Active at pH 2-3; inactive >5 Gastric pH 2-3 ->favorable for pepsin activity hydrolysis the peptide linkages between amino acids proteoses, peptones, polypeptides initiates protein digestion 10-20 % of total protein digestion Digest collagen albuminoid protein affected little by other enzymes major constituent of intercellular connective tissue of meats If achlorydria meats may be poorly digested  Digestion of Proteins in the Small Intestine Pancreatic Proteolytic Enzymes Intestinal Epithelial Peptidases Duodenum, upper jejunum brush border (microvilli) Trypsin -> small polypeptides Aminopolypeptidase Chymotrypsin -> small polypeptides Dipeptidases Carboxypolypeptidase larger polypeptides -> tripeptides/dipeptides/amino Cleaves individual amino acids from acids carboxyl end of polypetides easily transported to the interior of the enterocyte Proelastase -> elastase cytosol peptidases -> split remaining linkages between amino acids Elastin fibers Within minutes -> single amino acids Absorbed into the blood. Final result dipeptides tripeptides  Digestion of Fats - Emulsification Fat Emulsification break of fat globules into small sizes attackable by lipase duodenum under the influence of bile bile salts + lecithin (phospholipid) Polar parts highly soluble in water and remaining portions highly soluble in fat fat-soluble portions dissolve in the surface fat layer, polar portions project polar projections soluble in watery fluids -> decreases fat tension -> soluble broken up into many tiny particles -> increase of total fat surface area the average diameter < 1 micrometer -> 1000-fold increase in total surface  Digestion of Fats – Micelles Formation TG hydrolysis -> reversible process Bile salts Remove rapidly monoglycerides and FFA from the vicinity of the digesting fat High concentration in water -> form micelles small spherical, cylindrical globules (3-6 nm) sterol nucleus -> fat-soluble polar group -> water-soluble. sterol nucleus + fat digestate -> fat globule in the middle of a micelle polar groups project outward cover the surface of the micelle negatively charged -> micelle dissolves in the water transport medium for monoglycerides and FFA till absorbed  Anatomical Basis of Absorption 1,5 l ingested liquids + 7 l secretions = 8,5 l juice to be absorbed/day 7 l absorbed by small intestine Folds of Kerckring Villi 1000-fold increase of Brush border absorptive surface on each epithelial cell on each villus 1000 microvilli  Absorption in the Small Intestine Carbohydrates – fat – amino acids – ions – water Water Transported by diffusion Usual laws of osmosis Vice versa Isosmotic chyme Absorption of Ions - Sodium Sodium active transport into paracellular spaces Energy -> adenosine triphosphatase (ATP) enzymes Part absorbed along with chloride ions negatively charged chloride ions passively “dragged” co-transported through the brush border membrane sodium-glucose co-transporter sodium amino acid co-transporters sodium-hydrogen exchanger Osmotic movement of water  Absorption of Ions – Chloride and Bicarbonate Ions Chloride Ions Bicarbonate Ions Duodenum and Jejunum (large amounts In the upper part of the small intestine during pancreatic secretion) rapid absorption by diffusion Indirect absorption sodium ions are absorbed -> H+ secreted move along this electrical gradient H+ + HCO3- = H2CO3 following the sodium ions H2CO3 -> H2O + CO2 H2O -> chyme but the carbon dioxide is Ileum and colon CO2 -> absorbed in the blood / expired brush border membrane chloride- bicarbonate exchanger  Absorption of Nutrients - Carbohydrates Glucose transport Two stages active sodium co-transport First: active sodium transport through the basolateral membranes of the intestinal epithelial cells in the blood Secondary active transport Decrease of sodium inside the cells causes -> sodium from GI lumen through the brush border to the cell interiors Sodium ion combines with a transport protein transport protein combines glucose Sodium and glucose molecule are transported together Diffusion through the cell’s basolateral membrane into the para-cellular space and into the blood  Absorption of Nutrients - Proteins Dipeptides – tripeptides - free amino acids sodium co-transport mechanism peptide or amino acid molecules bind in the cell’s microvillus membrane with a specific transport protein that requires sodium binding sodium ion moves to the interior of the cell and pulls the amino acid or peptide along with it few amino acids: special membrane transport proteins -> facilitated diffusion  Absorption of Nutrients - Fats Micelles -> surfaces of the microvilli of the cell brush border monoglycerides and fatty acids diffuse out of the micelles into the interior of the epithelial cells -> lipids are soluble in the epithelial cell membrane taken up by the cell’s smooth endoplasmic reticulum form triglycerides ->released as chylomicrons -> flow upward through the thoracic lymph duct and empty into the circulating blood Small quantities of short- and medium-chain FA absorbed directly into the portal blood Bile micelles still in chyme to continue their “ferrying” function Abundance of bile micelles: 97% of fat absorbed Absence of bile micelles: 40-50% of fat absorbed