Gastrointestinal Secretions Lecture 4 PDF

Gastrointestinal Secretions Dr Beena Suvarna Building 94 Room 020; Veterinary & Biomedical Sciences Building T: 07 4781 4990 Email: [email protected] Consultation: By Email Appointment jcu.edu.au  Learning objectives Describe the principal functions of secretions in the GI trac...

Gastrointestinal Secretions Dr Beena Suvarna Building 94 Room 020; Veterinary & Biomedical Sciences Building T: 07 4781 4990 Email: [email protected] Consultation: By Email Appointment jcu.edu.au  Learning objectives Describe the principal functions of secretions in the GI tract Identify the types of gland/cell that facilitate these secretions Outline the basic mechanisms in secretion of proteins, ions and water in the GI tract Describe the composition, function and regulation of salivary, gastric, biliary, pancreatic and intestinal secretions jcu.edu.au  GI Secretions 1. FUNCTIONS OF SECRETIONS GI secretions include enzymes and fluids → aid in the liberation of nutrients from food + mucus Facilitates transport of food down the alimentary tract 2. SECRETORY STRUCTURES Cells Simple tubular Compound tubular 3. MECHANISMS OF SECRETIONS How are things getting transported? Exportable proteins Ions & Water Gastric acid jcu.edu.au 1. FUNCTIONS of Secretions PROTEINS Digestion (enzymes) Protection & lubrication (mucin) Antimicrobial (immunoglobulins) IONS (electrolytes such as Na+, K+, Cl-, H+) Maintain acid/base pH → correct for enzymes to function Osmolality (intracellular concentration)→ number of particles dissolve in a fluid Electrochemical gradient→ maintain gradients continually across membranes WATER Solvent (dissolve food particles) Transport (carry food particles) Facilitate chemical reactions and digestion and absorption Osmolality (300 milliosmoles) Consistency jcu.edu.au  pH Mouth: pH 6.4-7.3 Stomach: pH 1.5-4.0 Colon: pH 5.5-7 SI: pH 7-8 jcu.edu.au 2. Secretory Structures Goblet Cells Mucus cells Function in response to local irritation of the epithelium Extrude mucus directly into epithelial surface to act as a lubricant Protects the surfaces from excoriation and digestion Secretory Crypts Crypts of Lieberkuhn (SI) invaginations of the epithelium into submucosa Colonic (intestinal) crypts (LI) Simple Tubular Glands Gastric (can be branched) Compound glands (provide secretions for digestion or emulsification of food) Salivary Brunner’s in SI Pancreatic Liver/Gallbladder jcu.edu.au  Unicellular Goblet cell Types of multicellular exocrine glands classified according to duct type (simple/compound) and the structure of their secretory units (tubular/alveolar/tubuloaveolar) jcu.edu.au  GI Secretions 1. FUNCTIONS OF SECRETIONS 2. SECRETORY STRUCTURES 3. MECHANISMS OF SECRETIONS How are things getting transported? a) Exportable proteins b) Ions & Water c) Gastric acid jcu.edu.au  a) Exportable Proteins Overview of making proteins for secretion (PROTEINS=ENZYMES, MUCIN, LYSOZYME) Material needed to make secretion is transported to the base of cell by the capillaries (diffuse or actively transported) Mitochondria form ATP Energy from ATP and the nutrients are used to synthesise the secretory substance by rough ER (ER with ribosomes) and Golgi apparatus Apical Secretory products transported through ER membrane tubules to vesicles of Golgi apparatus Golgi complex materials are formed into secretory vesicles and stored at apical end of cell. Stored until needed and released by exocytosis jcu.edu.au b) Transport of Ions and Water Passive Membrane Transport Processes Simple diffusion - Nonpolar, hydrophobic molecules e.g., O2, CO2 using concentration gradient Facilitated Diffusion - movement of glucose and some ions into cells using membrane protein Osmosis – simple diffusion of water into and out of cells jcu.edu.au  Active membrane transport Processes Primary active transport- transport of substances (usually ions e.g., Na+, K+) against a conc. gradient, requires ATP for energy jcu.edu.au  Secondary active transport Uses a co-transporter (e.g. AA, Ca2+, H+) across membrane Driven by the energy from ion conc. Gradient generated by active transport (maintained with ATP) Two substances move in the opposite direction and the protein is called Antiporter Two substances move in the same direction (both into the cell) and the protein that transports them is called a Symporter jcu.edu.au  Water Absorption Flow by osmosis (thus largely isotonic secretion) Mostly transcellularly (not paracellularly) In water-permeable epithelium, water follows net trans-epithelial salt flow (osmosis) Transcellularly = the substances travel through the cell, passing through both the apical membrane and basolateral membrane Paracellularly = transfer of substances across an epithelium by passing through the intercellular space between the cells jcu.edu.au  Water Absorption (cont..) SI daily receives → ~ 9.3 L /day (2.3 L ingested & 7.0 L secretions) SI absorbs ~ 8.3 L LI ~ 0.9 L absorbed Only 0.1 litre (100 mL) of water is excreted in the faeces each day jcu.edu.au  Water Absorption (cont..) Principal sites of absorption a. Jejunum b. Ileum c. Proximal colon d. Gallbladder jcu.edu.au  Water absorption (cont..) Principal thing of SI → most of the digestion and absorption occurs Apical membrane: Na+- Glu Transporter/ exchangers (SGLT1) Na+ & Glu enter cytosol H2O follows due to osmosis jcu.edu.au  Ileum and Gallbladder Apical membrane: Uses paired Na+ - H+ & Cl - HCO3- exchangers (moving substances in opposite directions- antiporters) –creating osmotic gradient to drive water absorption Na+ and Cl- enter cytosol In Ileum, can we use Na-Glucose transporter-1? jcu.edu.au  Proximal Colon Similar to Jejunum except Na+ enters cytosol via amiloride-sensitive channels Glucose? jcu.edu.au  Salivary glands: Parotid, Submandibular, Sublingual Parotid gland- Purely serous (ions, enzymes and tiny bit of mucin) Sublingual gland- Mixed- contain mostly mucous cells Submandibular gland- has mix of both jcu.edu.au  SALIVARY GLANDS (cont) Saliva composition Water: 97 - 99.5% Electrolytes: Na, K, Cl-, PO4 -, HCO3- (PO4 -, HCO3- to maintain pH) Enzyme: amylase Proteins: mucins (immobilise bacteria), lysozymes (kill bacteria) & IgA (stops pathogen entering body) Volume: 1500 mL/day Function of Saliva Cleanses mouth Dissolves food chemicals to taste Moistens food to form a bolus Contains enzymes (start to breakdown starch) Regulation of Saliva Secretion Parasympathetic - increases watery (serous) enzyme-rich saliva Sympathetic - increases release of thick mucin (constricts blood vessels, inhibits salivary secretion) jcu.edu.au c) Gastric Acid Secretion GASTRIC GLANDS jcu.edu.au  Gastric Acid Secretion (cont..) Gastric glands produce gastric juice- Volume: 2500 mL/day Cell Types: 1. Mucus neck cells and surface mucous cells – mucin 2. Parietal cells - HCl (denatures protein, activates pepsin, breaks down plant cell walls, kills many bacteria - intrinsic factor (absorption Vitamin B12 in SI) 3. Chief cells (or zymogenic cells) - pepsinogen (inactive form of pepsin) and gastric lipase 4. G cells (enteroendocrine cell)- Gastrin (Stimulates parietal cells to secrete HCl and chief cells to secrete pepsinogen; contracts LOS, increases motility of stomach and relaxes pyloric sphincter) (G-cells- primarily found in the pyloric antrum but can also be found in the duodenum & pancreas) jcu.edu.au  Gastric acid secretion (cont..) Function of Gastric Secretion: Homogenisation→ primary function Sterilisation→ food hygiene, HCL kill bacteria Protection of gastric lining→ of gastric lining-thick alkaline mucous mucin + water = mucous Digestion→ mechanical (three layers of muscle), start with pepsin plus HCL Regulation of GI→ chemoreceptor and stretch receptors increase and decrease activity jcu.edu.au One Cell Model: Gastric Acid Secretion jcu.edu.au Tortora et al. 2015 Regulation of Gastric Acid Secretion (cellular level) What increases (HCl) acid secretion? Three Agonists: M3 Gastrin ------------------- an endocrine hormone (via blood) cholecystokinin Acetylcholine ------------- a neurotransmitter B receptor (vagus nerve) CCKB or CCK2 Histamine ----------------- a paracrine hormone (local effect) H2 Acetylcholine and gastrin stimulate parietal cells to secrete more HCl in the presence of histamine - histamine acts synergistically- enhancing the effects of acetylcholine and gastrin jcu.edu.au Two Cell G Cell ECL ECL: Enterochromaffin-like cell Model: - G cell –gastric glands in stomach gastric acid Sst Sst- Somatostatin (delta cells of Islet of Langerhans control D Cell 3 CCKB + Adapted from Bullock and Mania (2014) Fundamentals of Pharmacology 7th Ed. jcu.edu.au Regulation of Gastric Secretion Last few minutes Three phases of gastric secretion: Last 3-4 hours Cephalic phase 70% gastric juice released Gastric phase Intestinal phase Response to a meal jcu.edu.au  Protection Against Acid Mucosal protection barrier - thick coating of alkaline mucus - compacted cell arrangement (tight junctions) - quick turnover of mucosal cells (~ 5-7 days) Prostaglandin (e.g., E2 ) - stimulate secretion of mucus & HCO3 - inhibit histamine-stimulated acid secretion jcu.edu.au  A matter of balance Protective Destructive factors factors Compacted cells Acid/Pepsin Quick cell Exogenous agents turnover (e.g., NSAIDS) Alkaline mucus Helicobacter Blood supply Pylori jcu.edu.au Destructive Factors: Acid/pepsin Increased acid production can result from: Stress psychological pain-chronic illness Risk factors for stress ulcers Large-surface-area burns Trauma Sepsis Acute respiratory distress syndrome Severe liver failure Major surgical procedures Zollinger-Ellison syndrome (ZE) ZE Gastrinoma (gastrin secreting tumor) In pancreas (~85%) or duodenum Hyper-secretion of acid jcu.edu.au May be malignant or metastasis  Destructive Factors Non-steroidal Anti-inflammatory Drugs 15-20% of NSAID users develop chronic gastric ulcers 5-10% of NSAID users develop chronic duodenal ulcers ulcers Inhibit cyclo-oxygenase COX1 (constitutive) and COX2 (inducible) enzymes Prostaglandin } thinner mucous GI defence Most NSAID’s are acidic mucosal irritant With pre-existing condition Risk of complications (e.g. bleeding) jcu.edu.au Adapted from Bullock and Mania (2014) Fundamentals of Pharmacology 7th Ed. Destructive Factors: Helicobacter pylori Discovered by Warren and Marshall in 1983 Conservative estimates that ~50% of population is infected (28-84%) Guo, Y., Cao, X. S., Guo, G. Y., Zhou, M. G., & Yu, B. (2022). Effect of Helicobacter Pylori Eradication on Human Gastric H. pylori infection is a major risk factor for gastric cancer and Microbiota: A Systematic Review and Meta-Analysis. Frontiers in eradication of H. pylori is recommended as an effective gastric cellular and infection microbiology, 12, 899248 cancer prevention strategy https://doi.org/10.3389/fcimb.2022.899248 jcu.edu.au  Helicobacter pylori Transmitted person to person or from contaminated food & water Gram negative spirally bacteria Secretes urease enzyme that converts urea to ammonia to neutralise the barrier of mucus Chemical irritants are released - cause an Inflammatory immune reaction Inflammatory response creates the ulcer jcu.edu.au Actively penetrate the mucus by: Physically capability to burrow through the mucus layer 5-6 flagella and moves in a spiral manner Releases ammonia (has urease enzyme that converts urea to ammonia) to liquify the barrier of mucus and causes HCL release. Bacteria aggregate at surface of cells OR attach to surface or burrow between cells Symptoms and signs Treatment: PPI-based triple therapy jcu.edu.au SI Intestinal Crypts Epithelium of mucosa Mainly columnar absorptive cells (-release enzymes that digest food and contain microvilli that absorb nutrients in small intestinal chyme) Mucous-mucin secreting goblet cells Between villi are pits leading into SI intestinal glands (crypts of Lieberkuhn) Secrete intestinal juice (carrier fluid for absorption/lysozymes) Duodenal Brunner’s glands submucosal (alkaline mucous-neutralise acid chyme) Volume: 1000 mL/day jcu.edu.au jcu.edu.au Pancreas Pancreatic acini cells secrete enzyme-rich fluid Epithelial cells lining the pancreatic duct (duct cells) release bicarbonate-rich fluid (pH 8)- buffer stomach acid Pancreatic duct (carries pancreatic juice) fuses with bile duct and flows into duodenum Volume: 1500 mL/day Exocrine: 98% Endocrine: 2% (insulin and glucagon) jcu.edu.au  Regulation of Pancreatic Secretion Secretin Presence of HCl in chyme in duodenum → release of Secretin from duodenal S cells into bloodstream→ stimulates pancreatic duct cells → secrete water and HCO3 Cholecystokinin (CCK) Presence of fats & proteins in chyme in duodenum → release of CCK from duodenal I cells → via blood to acini cells → secrete enzymes * CCK also has stimulus to contract gall bladder and relax sphincter of Oddi jcu.edu.au  LIVER/GALLBLADDER Bile Secreted by liver & stored in gallbladder Yellow-green alkaline solution: bile salts, bile pigments, cholesterol, neutral fats, phospholipids & electrolytes Only bile salts & phospholipids aid digestion Emulsifies fat, assists absorption & neutralises chyme Volume: 500 mL/day Regulation of Bile Release CCK released into blood when chyme enters duodenum - Contracts gallbladder & relaxes sphincter of Oddi - Also stimulates formation of pancreatic juice jcu.edu.au  Large Intestine Primary functions of the colon are o to absorb water o to maintain osmolality, or level of solutes, of the blood by excreting and absorbing electrolytes from the chyme o To store faecal material until it can be evacuated by defecation Mucosa is thicker, many goblet cells - mucus Mucus eases passage of faeces & protects intestinal wall jcu.edu.au