Secretory Functions of the Alimentary Tract

Secretory Functions in the Alimentary Tract Lecture Outline I. General principles of alimentary tract secretions II. Secretion of saliva III. Gastric secretion IV. Pancreatic secretion V. Bile secretion by the liver VI. Intestinal secretions 1 Secretory Functions in the Alimentary Tract Objectives 1...

Secretory Functions in the Alimentary Tract Lecture Outline I. General principles of alimentary tract secretions II. Secretion of saliva III. Gastric secretion IV. Pancreatic secretion V. Bile secretion by the liver VI. Intestinal secretions 1 Secretory Functions in the Alimentary Tract Objectives 1. Identify the two main secretions of the alimentary tract; explain the functions of mucus. 2. Explain the stimuli for secretion throughout the GI tract 3. List the function of gastrin, secretin, CCK, GIP, and somatostatin 4. Describe the production of saliva from a compound gland 5. Identify the three primary saliva glands and their products 6. Explain the cells and products of oxyntic and pyloric glands 7. Identify the implication of NSAIDS and the mucus-bicarbonate barrier 8. Describe HCL production and inhibition 9. Explain the development of pernicious anemia 10. Identify the phases of digestion 11. Identify the components of the exocrine pancreas and identify the activation of zymogens 12. Describe bicarbonate production and the “alkaline tide” 13. Explain movement of digestive fluids through the biliary tree 14. Identify the function and components of bile and enterohepatic circulation 15. Explain the formation of gallstones 16. Compare the secretions of the small and large intestines 17. identify the sites and etiologies of peptic ulcers 2 References Assigned reading from your text: Hall Chapter 65 3 I. General Principles of Alimentary Tract Secretions 4 General Principles Of Alimentary Tract Secretion q Two main secretions in the alimentary tract: – Digestive enzymes (mouth to small intestine) vary depending on food type – Mucus (mucous glands located from mouth to anus) lubricates and protects q Types of glands: Most GI epithelium covered with billions of single-cell mucous glands (goblet cells) that respond to irritation of the epithelium; extrude mucus onto the epithelial surface The stomach and upper duodenum have large numbers of deep tubular glands that secrete acid and pepsinogen Many GI surfaces have pits, invaginations into the submucosa, containing specialized secretory cells- small intestine has crypts of Lieberkühn Other complex glands provide secretions for digestion: -Salivary glands -Pancreas -Liver 5 Stimulation of Secretion q Activation of the ENS stimulates secretion: Food physically contacting the epithelium/glands stimulates mucus secretion Local epithelium stimulation activates the ENS Tactile stimulation Chemical irritation Distention of the gut wall q Autonomic stimulation of secretion: Parasympathetic stimulation greatly increases glandular secretions Sympathetic stimulation has a dual effect: Alone slightly stimulates secretion from glands It also stimulates vasoconstriction which reduces secretion q GI hormones regulate the volume and composition of secretions These hormones are polypeptides secreted by GI mucosa, absorbed into blood, and carried to the glands where they regulate secretion 6 GI Hormones- aka Gut-Brain Peptides q Gastrointestinal hormones are peptides Most are NTs in the ENS and CNS Release of hormones influenced by chemical environment in GI lumen Enteroendocrine cells have microvilli-bearing receptors that “taste” gut lumen GI hormones are either: secreted into capillary blood (endocrine) or they diffuse locally to target cell (paracrine) Examples include serotonin, somatostatin, and histamine 7 8 Mechanism of Secretion by Glandular Cells q Organic substances secreted by glandular cells are formed by: Transport of nutrients by the blood to the base of the glandular cell Mitochondria form ATP for the synthesis of the substance in the endoplasmic reticulum and Golgi complex; ribosomes form the proteins to be secreted The Golgi packages secretory vesicles for storage in the apical ends of the secretory cells Signals for secretion increase the cell membrane permeability to calcium ions Calcium entry into the cell provokes exocytosis of contents to the exterior Water and electrolytes pass through the cells aiding secretion 9 Mucus Secretion q Mucous glands secrete mucus directly onto the surface of epithelium in response to the presence of food Structures of the small intestine. The inner wall of the small intestine is covered by numerous folds of mucous membrane called plicae circulares. The surface of these folds contains tiny projections called villi and microvilli, which further increase the total area for absorption. Absorbed nutrients are moved 10 into circulation by blood capillaries and lacteals, or lymph channels.Encyclopædia Britannica, Inc. Mucus Lubricates and Protects the GI Tract q Mucous glands secrete mucus directly onto the surface of epithelium in response to the presence of food q Mucus is a thick secretion composed of water, electrolytes, and glycoproteins composed of large polysaccharides and small quantities of protein q It is a lubricant and a protectant for the gut wall: Adheres tightly to surfaces as a thin film Has sufficient body to prevent food from actually contacting the gut wall Has low resistance to promote slippage of particles Adheres fecal particles together Resists digestion by GI enzymes Glycoproteins buffer pH 11 II. Secretion of Saliva 12 Secretion Of Saliva q Saliva contains a serous secretion and a mucus secretion Stage 1 – Acini Primary secretion- contains two main proteins – Serous secretion Ptyalin (an ⍺-amylase) digests starches pH range 6.0-7.0 ideal for ptyalin action – Mucus secretion Mucin (in mucus) protects and lubricates – K+ actively secreted in exchange for Na+ Stage 2 - Salivary ducts – Secondary secretion of bicarbonate ions protect mucosa – Caused by passive exchange of HCO3- for Cl- 13 Functions Of Saliva q Functions of Saliva Lubrication – Reduces bacteria and bacterial growth – – – – 0.5 ml/min saliva produced Washes away pathogenic bacteria and food particles Proteolytic enzymes, mainly lysozyme, attacks bacterial cell walls Lactoferrin chelates iron-interrupts replication Contains significant amounts of antibodies (IgA) Aids digestion – – a-amylase hydrolyzes 75% starch before denaturing by HCl Lingual lipase hydrolyzes triglycerides q Antisialogogues (glycopyrrolate, atropine, scopolamine) inhibit saliva secretion Desirable for laryngoscopy Makes swallowing food difficult (illustrates the lubricating quality of saliva/mucus) 14 Salivary Glands q Glands: All are Bilateral- produce 800-1500 ml/day mildly alkaline fluid daily 3 Primary glands + buccal glands Parotid Gland (Largest): 25% saliva- only serous secretion Submandibular (Submaxillary) Gland: 70% serous/mucus Sublingual Gland: Secretes 5% serous/mucus Buccal glands are smaller- secrete only mucus 15 Control Of Secretion q Parasympathetic stimulation promotes secretion CN VII (facial nerve) to Submandibular gland Sublingual glands CN IX (glossopharyngeal nerve) to Parotid gland q Sympathetic stimulation inhibits secretion Via sympathetic chain ganglia to all glands Sleep, dehydration, fatigue, fear inhibit salivation 16 Esophageal Secretions q Esophagus secretes only mucus to maintain lubrication for swallowing Main body is lined with simple mucous glands: – Lubricates food in transit The gastric end is lined with compound mucous glands: – Secrete alkaline mucus – Protects against gastric acid that may reflux 17 III. Gastric Secretion 18 Gastric Secretions q Two important types of tubular glands Oxyntic glands (gastric glands) and pyloric glands – Produce 1-2 liters secretions/ day from many cell types Oxyntic (acid-forming) glands – Located inside body and fundus- proximal 80% stomach – Secrete acidic solution with pH 0.8 when stimulated No mucus layer inside gland- have thick plasma membranes Tight junctions resist H+ diffusion into submucosa – Three cell types: Parietal (oxyntic) cells – Hydrochloric acid and intrinsic factor (B12 absorption in ileum) Peptic or chief cells- secrete pepsinogen Mucous neck cells- mucus Enterochromaffin-like cells secrete histamine Pyloric glands – – Located in antrum- distal 20% stomach Secrete mucus and gastrin 19 Oxyntic Secretions q Oxyntic glands are found in the body and fundus of stomach Hydrochloric acid is formed at the villus-like projections inside these canaliculi and conducted through the canaliculi to secrete acid The main driving force for HCl acid secretion by parietal cells is a H+-K+ ATPase pump 20 Oxyntic (Acidic) Secretions q Oxyntic glands are found in the body and fundus of stomach Hydrochloric acid is formed at the villus-like projections inside these canaliculi and conducted through the canaliculi to secrete acid In the interdigestive period, secretion is mostly mucus- with little pepsin, and no acid 21 Nonoxyntic Secretions q Nonoxyntic secretions resemble ISF, lower production Superficial or surface mucous cells at surface of the lumen Stem cell near neck of gastric glands repair damage of gastritis from H. Pylori, smoking, ETOH, NSAIDS, and chronic stress q Mucus-bicarbonate barrier Prostaglandins stimulate secretion of mucus and HCO3-1 Mucus forms a protective layer rich in HCO3-1 to buffer H+ NSAIDS inhibit PG synthesis leaving mucus susceptible to low pH Lange-Big Picture Medical Physiology. Figure 7-13: The mucus-bicarbonate barrier for gastric mucosal protection. Surface epithelial cells secrete HCO3-, which become trapped in a layer of mucus at the mucosal surface. H+ is neutralized by HCO3- as it diffuses through the surface mucus. 22 Hydrochloric Acid (HCL) Production q Acetylcholine, gastrin, and histamine stimulate hydrochloric acid production Ach released by parasympathetic stimulation causes: – – – Pepsinogen by peptic cells HCL by parietal cells Mucus by mucous cells Gastrin and histamine strongly stimulate acid secretion by parietal cells (not other cells) q Pepsinogen inactive when secreted – – Activated by Ach and HCL Pepsin is a proteolytic enzyme in an acidic medium q Intrinsic factor is essential for B12 absorption – – In chronic gastritis, achlorhydria results & intrinsic factor production is diminished which is required for B12 absorption Pernicious anemia develops due to RBCs inability to mature with an absence of Vit B12 absorption 23 Inhibition of HCL q Inhibition of Gastric Acid Secretion in the stomach Gastric acid secretion maximal at 1-2 hours postprandially Decreased pH inhibits gastrin secretion Direct inhibition of Antral G-cells (endocrine) stimulates indirect Somatostatin secretion by antral D-cells In the duodenum, feedback inhibition of H+ secretion occurs in response to H+, fatty acids, and hypertonicity Secretin is the primary hormone released in response to low pH in the duodenum 24 Phases of Secretion q Gastric secretions occur according to phase of digestion 30% secretions in the Cephalic Phase -From sight, smell, thought, or taste of food 60% secretions in the Gastric Phase- Results from food in stomach 10% secretions in the Intestinal Phase- From the presence of food in the duodenum 25 IV. Pancreatic Secretion 26 Exocrine Pancreas q Consists of compound alveolar (acinar) glands that secrete into a system of ducts Secretory portion of endocrine pancreas – an acinus- is made of pyramidal shaped cuboidal epithelial cells around a central lumen – similar to salivary gland Ultimately will empty into the duodenum at the hepatopancreatic ampulla Pancreatic Digestive Enzymes q Acinar cells secrete digestive enzymes for: Proteins Proteolytic enzymes in active form Trypsinogen- most abundant- trypsin Chymotrypsinogen- chymotrypsin Procarboxypeptidase- carboxypolypeptidase Same cells produce trypsin inhibitor- prevents activation Starch Pancreatic Amylase (a-Amylase) hydrolyzes starches Fat digestion Pancreatic Lipase- hydrolyzes fat Cholesterol esterase- hydrolyzes cholesterol esters Phospholipase- splits fatty acids from phospholipids Exocrine Pancreas - Zymogens q Proteases stored as inert zymogens in acinar cells Zymogens (proenzymes that end in –ogen) require activation after secretion To avoid damage of that organ Typically found in salivary and pancreatic acinar cells Remain inactive when released into alkaline pancreatic secretions by action of trypsin inhibitor Trypsin activates all other pancreatic zymogens- trypsin inhibitor prevents activation Activated only when they reach the duodenum where brush border enzyme enterokinase (aka enteropeptidase) cleaves trypsinogen to trypsin- then cleaves other proenzymes In pancreatitis or obstruction, pooled pancreatic secretions become activated and the organ autodigests 29 Bicarbonate Production q HCO3- and H2O produced by the ductules and ducts leading from the acini Bicarbonate ions and water are secreted by the epithelial cells of the ductules and ducts Small radicle ducts coalesce to form the main pancreatic duct When stimulated, the bicarbonate ion concentration can rise to as high as 145 mEq/L- 5 x plasma concentration “Alkaline tide”- neutralizes the hydrochloric acid emptied into the duodenum from the stomach Overall movement of sodium and bicarbonate ions from blood into duct creates an osmotic pressure gradient that causes osmosis of water into the pancreatic duct 30 Regulation of Pancreatic Secretion q 80% of pancreatic secretion is via hormones Pancreatic enzymes function optimally an alkaline environment (pH 7.0-8.0) Cholecystokinin (CCK) contributes pancreatic enzymes: Produced in I-Cells of Duodenum and Proximal Jejunum controls secretion when food enters small intestine Secretin stimulates copious secretion of bicarbonate ions which neutralizes gastric chyme- Stimulated by acidic chyme entering small intestine Acetylcholine is released from parasympathetic vagus nerve endings and other ENS nerves 31 Biliary Tree q The biliary tree is the network of ducts (vessels) that coordinates the secretions of the liver, pancreas, and gallbladder into the duodenum Main pancreatic duct of Wirsung Releases inactive enzymes from the gland and NaHCO3 from the internal ducts It fuses with the common bile duct Combined ducts enter the duodenum at the hepatopancreatic ampula where the hepatopancreatic sphincter (of Oddi) surrounds the duct regulates entry of bile and pancreatic secretions Accessory pancreatic duct branches off the main and delivers secretions to the duodenum Hepatopancreatic Sphincter of Oddi Main Pancreatic Duct (Wirsung) Hepatopancreatic sphincter (Oddi) Controls the flow of bile and pancreatic juice into the second part of the duodenum Hepatopancreatic ampulla (Vater) Accessory pancreatic duct (Santorini) Accessory pancreatic duct V. Bile Secretion by the Liver 35 Bile Is Produced By Hepatocytes q Live produces 500-1000 ml bile/day q Bile – Is made of bile acids, bile pigments, and other substances dissolved in alkaline solution similar to pancreatic juice q Bile acids- not enzymes- serve 2 functions: – – Emulsify large fat particles into smaller particles for pancreatic lipase enzymes Aid in absorption of digest fat end products through intestinal mucosal membrane q Bile acids are most important component in bile – – Synthesized from cholesterol and secreted into the bile conjugated to glycine or taurine Primary bile acids formed in liver are cholic acid and chenodeoxycholic acid q Enterohepatic circulation– – – – Some components of bile are reabsorbed in the intestine and excreted again by the liver Bile salts form micelles - amphipathic 95% of bile salts are absorbed from the small intestine- the terminal ileum Absorbed bile acids are transported back to the liver in the portal vein and reexcreted in the bile 36 q Bile serves as a means of excretion of bilirubin and excess cholesterol & is secreted in two stages: 1) Initially, hepatocytes secrete large amounts bile acids, cholesterol, and other constituents 2) Canaliculi empty into terminal bile ducts then Hepatic ducts before finally Reaching the (common) bile duct From ducts bile empties into duodenum or to gallbladder 37 Bile and Cholecystokinin (CCK) q CCK stimulates gallbladder contraction and emptying– esp with fatty foods Secretin stimulates a watery sodium bicarbonate solution from the liver as bile travels through the ducts; can double bile secretion When food doesn’t contain fat, gallbladder empties poorly When significant amount of fat is present, gallbladder empties completely in about 1 hour q CCK stimulates relaxation of the Sphincter of Oddi Allows bile and pancreatic juice to flow into the intestinal lumen 38 Bile Salts Are Formed In Hepatocytes From Cholesterol Cholesterol combines with bile salts and lecithin to form ultramicroscopic micelles in a colloidal solution When the bile is concentrated in gallbladder, bile salts and lecithin become concentrated along with cholesterol 39 Gallstones q Under abnormal conditions, cholesterol precipitates and forms gallstones High fat diet Inflammation of the gallbladder epithelium changes absorption of water and bile salts – Leaves behind cholesterol – Small crystals form on the surface of the mucosa and progress to gallstones 40 VI. Intestinal Secretions 41 Secretions of the Intestines q Small intestine’s primary function is to absorb nutrients and digestive products into blood Secretions of the small intestine are regulated by local enteric reflexes Brunner’s glands are compound mucous glands of the early duodenum that secrete protective mucus in response to: – tactile stimulation – vagal stimulation – and the GI hormone secretin – Inhibited by sympathetic stimulation- anxiety may be a source of peptic ulcers (~50%) q Crypts of Lieberkuhn are pits covering the small intestine Lie between intestinal villi Contain Paneth cells full of defensins (many gut bacteria) Both the villi and crypts composed of two types of cells: – Goblet cells secrete mucus – Enterocytes secrete water, electrolytes, and contain digestive enzymes 42 Secretions of the Intestines q Enterocytes covering villi contain digestive enzymes that digest substances as they are being absorbed through the epithelium – Peptidases split proteins into AA – Sucrase, maltase, isomaltase, and lactase split disaccharides- monosaccharides – Intestinal lipase splits neutral fats into glycerol and fatty acids q Secretions of the Large Intestine Parasympathetic stimulation increases mucus production No villi- no digestive enzymes secreted 43 Pathophysiology- Peptic Ulcers q Peptic ulcers: can occur in stomach or duodenum Duodenal (80%); gastric (20%) Gastric ulcers have a high rate of incidence in antrum & pylorus Infection with helicobacter pylori bacterium- accommodates to acid in stomach; colonizes and destroys antral mucosal barrier, exposes epithelium to acidà ulceration q NSAIDS inhibit PGH2 synthesis and subsequently PGE2 synthesis q Stress ulcers (low overall incidence)- due to major physiologic stress Occurrence mostly in fundus Causes: Stomach ischemia; Major physical stress (eg burns) Major surgical procedures Major physiologic stress 44 1. A patient suffering from anemia comes to his physician complaining of frequent bouts of gastroenteritis. A blood test reveals antibodies directed against gastric parietal cells. The anemia in this patient is attributable to hyposecretion of which gastric product? A. B. C. D. E. Histamine Gastrin Pepsinogen Intrinsic factor Hydrochloric acid 2. A patient has a 6-month history of heartburn, weight loss, and has been diagnosed with increased output of gastric acid in the fasting state. The patient most likely has a tumor secreting which of the following hormones? A. B. C. D. E. Secretin Somatostatin Motilin Gastrin Cholecystokinin 3. Which of the following has the highest pH? A. B. C. D. E. Gastric juice Colonic luminal contents Pancreatic juice Saliva Contents of the intestinal crypts 4. Digestion of which of the following is impaired to the greatest extent in patients with achlorhydria? A. Carbohydrate B. Fat C. Protein 5. After a patient undergoes a resection of the entire ileum and a portion of the jejunum, what condition is likely to occur? A. Atrophic gastritis B. Constipation C. Gastric ulcer 45