GTT3. GIT secretions

• Saliva: primary secretion is made by acinar cells, it is driven by the Na+/K+ ATPase pump on the basolateral membrane to generate a low Na+ concentration inside the cell. K+ and Cl- also enter cell. On the luminal/apical membrane there are Cl- channels and aquaporins for these to enter the lumen. Na+ also moves out through leaky paracellular junctions. This secretion is isotonic with plasma

  This is modified, Na+ and Cl- reabsorbed, and K+ and HCO3- added (HCO3-/Cl- antiporter) resulting in a HCO3- rich hypotonic solution, with composition depending on flow rate - faster flow less reabsorption
• Functions of saliva include lubrication, starch digestion, antimicrobial activity and pH and ion concentration to prevent demineralisation.

  Other saliva components:

  • ions e.g. calcium and phosphate
  • mucins (glycoproteins) lysozyme and amylase, exocytosis from acinar cells
  • immunoglobin A from B lymphocytes binds to basolateral receptors of acinar cells and transported into lumen of gland
• Salivary glands include:

  • parotid : amylase > mucus, serous
  • submandibular : amylase < mucus
  • sublingual & minor mucous : mucus

  basal condition has most flow from the submandibular gland, and stimulated flow from parotid

  PNS stimulation increases formation of fluid and electrolyte components of saliva, SNS stimulation increases release of macromolecular components

  oesophageal secretions are from widespread minor glands, producing only mucus. they are neurally controlled
• Phases of digestion:

  • cephalic phase : pre-digestion, salivary and gastric secretions stimulated, starch digestion starts. ANS neurally controlled
  • gastric phase : stomach secretes in response to presence of food, mechanical breakdown by increased gastric motility, protein digestion starts. Controlled neurally (externally & enteric) and hormonally
  • intestinal phase : food in the small intestine causes release of hormones to inhibit gastric secretion and motility, and release biliary and pancreatic secretions in duodenum. Most digestion and absorption. Neural and hormonal control
• The gastric mucosa contains chief / peptic cells that release pepsinogen, and parietal / oxyntic cells that produce HCl and intrinsic factor. Other secretions include mucus from surface enterocytes, gastric lipase, water.

  Acid secretion occurs from reaction between CO2 and H2O by carbonic anhydrase forming HCO3- and H+. HCO3-/Cl- antiporter removes HCO3- to capillary and obtains Cl-, H+ secreted into lumen using ATP by H+/K+ , Cl- also transported to lumen. Net ion movement is into lumen accompanied by water due to osmosis.
• In the resting condition H+ pumps are confined in intracellular tubulovesicles. When stimulated, they rearrange and fuse with canaliculi continuous with luminal membrane so increase SA for HCl secretion.

  Regulation by parietal cells can be:

  • neural : ACh on muscarinic receptors, H+ secretion
  • endocrine : gastrin in blood binds G receptor, H+ secretion
  • paracrine : ACh binding to ECL M receptors causes histamine release which binds to parietal H2 receptors.
  • inhibition occurs by negative feedback when ACh binds M receptors, so SST inhibits ECL activity and also parietal and G cell secretion.
• Endocrine factors affecting stomach:

  • gastrin from pyloric antrum increases gastric secretions and motility. Stimulated by proteins, coffee and alcohol, and inhibited by low gastric pH as no food stimulation
  • CCK (cholecystokinin) from duodenal wall depresses gastric motility and secretion, stimulated by fats
  • secretin from duodenal wall inhibits gastric secretion, it is stimulated by acid
  • GIP (from SI) and GLP-1 from ileum / colon inhibit gastric motility and secretion, and is stimulated by fat and chyme in the lumen. Metabolic effect on pancreas for insulin secretion
• Small intestine secretes mucus from goblet cells, isotonic saline from crypt cells, and alkaline mucus from Brunner’s glands. They secrete H2O into lumen following Na+ from pump. Surface enterocytes on villi also make digestive enzymes embedded in glycocalyx of brush border and HCO3- rich fluid.

  Aside from CCK and secretin, small intestine secretions are also affected by GIP and GLP-1 stimulated by presence of fats, which inhibit gastric activity. Distension also produces vagal afferents and efferents to increase motility via ENS, and increase pancreatic juice
• Pancreatic secretions are discharged alongside biliary secretions from intra-hepatic bile ducts when the sphincter of Oddi relaxes, allowing passage to duodenum.

  Main components of pancreas exocrine secretions are:

  • alkaline fluid rich in HCO3- from pancreatic duct cells, neutralise acidic chyme
  • digestive enzymes from acinar cells stored intracellularly as inactive precursors in zymogen granules. Released by exocytosis

  pancreatic secretion affected by CCK which induces enzyme-rich secretion from acinar cells, and secretin (stimulated by acidic chyme) which induces bicarbonate-rich secretions
• In pancreatic duct cells, alkaline fluid is produced as H2CO3 is formed by carbonic anhydrase. Energy is provided by Na+ pump on basal side of cell, and HCO3- efflux occurs on luminal side via an anion exchanger.

  Defect in Cl- channel (CFTR) causes cystic fibrosis so secretion not produced, therefore no delivery of enzymes.

  Matched to acid load arriving from stomach using negative feedback: acidic chyme increases secretin so bicarbonate, which neutralises acid in SI meaning less secretin released from duodenal wall
• Bile: the primary secretion is made in the liver, solutes extracted from blood by hepatocytes and discharged into bile canaliculi containing extracellular fluid. Contains salt/acid component important for emulsification of fats, bile pigments including bilirubin from Hb porphyrin ring for excretion, cholesterol and lecithin

  Secondary modification occurs along bile ducts where H2O and HCO3- added, stimulated by secretin.

  Release is from gallbladder when stimulated by CCK to contract, and sphincter of Oddi to relax
• Gut hormones also contribute to regulation of metabolism.

  Release stimulated by food:

  • GIP from SI stimulates insulin release (feedforward function) for glucose, aa absorption
  • GLP-1 from ileum / colon also stimulates insulin release and inhibits glucagon release, promotes satiety
  • CCK from SI promotes satiety

  Release inhibited by food:

  • ghrelin from stomach and other GIT promotes appetite and feeding behaviour, ‘hunger hormone‘
• Colon secretions include mucus for lubrication, HCO3- in exchange for Cl-, and some secretion of K+. The luminal Na+ channel means it is absorbed into the cell more than Cl- so there is a net negative potential in the lumen of -30mV. This drives K+ movement into the lumen via a paracellular pathway.
• GI secretion dysfunctions:

  • saliva : dry mouth so difficulty swallowing, enamel damage, less microbiological protection
  • gastric atrophy: lack of intrinsic factor causes pernicious anaemia. gastritis due to H. pylori infection leads to failure of mucosal barrier so gastric and duodenal ulcers. excess acid production causes ulcers, SI malabsorption, diarrhoea
  • pancreatitis : malabsorption as not enough enzymes. cystic fibrosis means reduced Cl- conductance reduces pancreatic juice formation so less enzyme delivery to duodenum
  • bililary : malabsorption due to inadequate fat digestion