T1 L4: Salivary & gastric secretions

• Contents of saliva

  • water - dissolving food
  • Electrolytes (K+, HCO3-, Na+, (PO4)3-) - buffers for acidic foods
  • Enzymes - aid initial breakdown of food
  • Secretory IgA - prevents microbial attachment to epithelium
  • Mucin - forms mucus providing lubrication
  • Waste products - small amounts of urea for recycling
• Salivary enzymes

  1. Salivary amylase - starch to maltose
  2. Lingual lipase - triglycerides to fatty acids + diglycerides
  3. Lysozyme - hydrolysis of peptidoglycan in gram negative bacteria
  4. Lactoferrin - chelates iron to prevent microbial growth
  5. Kallikrein - converts plasma protein alpha-2-globin to bradykinin (potent vasodilator)
• Major salivary glands

  1. Parotid salivary gland
  2. Inferior and anterior to ears
  3. watery secretions
  4. majority of salivary amylase production
  5. Submandibular salivary gland
  6. floor of mouth, medial to mandible
  7. mixed serous and mucus secretions
  8. Sublingual salivary gland
  9. below tongue, superior to submandibular
  10. most viscous secretions, mostly for lubrication

  
• Salivary gland structure

  Salivon - functional unit of salivary glands

  Clusters of acinar cells (1) around a central cavity form the acinus (2)

  Ductal cells (3) form the connecting ducts

  Contractile myoepithelial cells (4) around salivon aid secretion

  
• Formation of hypotonic saliva

  Acinar - formation

  1. Cl- actively pumped through acinar cells into acinus
  2. Increased negative charge in acinus; Na+ diffuses through leaky tight junctions between cells
  3. H2O follows from cells and leaky tight junction - salivary solution is now isotonic

  Ductal - modification

  tight junctions in ductal cells are not leaky so water can't diffuse.

  1. Cl- and Na+ ions are actively removed from saliva
  2. K+ and HCO3- are secreted into saliva - saliva now hypotonic as it passes through the ducts

  
• Salivary flow rate & composition

  is always K+ rich, hypotonic secretion with electrolyte composition

  Na+ and Cl-< plasma

  HCO3 and K+ > plasma

  at higher rates of secretion reduced reabsorption of electrolytes produces alkaline, HCO3- rich (acid neutralising) saliva with increased tonicity closer to that of primary isotonic saliva

  
• Autonomic regulation of salivary secretions

  Thought, sight, smell and oral mechanoreceptor activation signals the salivary centre in the medulla.

  Simple reflex: mechanoreceptor activation from food in the mouth

  Conditioned reflex: Thought, sight, smell activates salivary centre in medulla oblongata
• Parasympathetic innervation of salivary secretion

  • majority of innervation
  • facial nerve passes through submandibular ganglion (1) and innervates sublingual and submandibular glands
  • glossopharyngeal nerve passes through otic ganglion (2) and innervates parotid gland
  • Promotes continuous secretion of watery saliva
  • Acetylcholine at muscarinic receptors activates myoepithelial cell contraction
  • inhibited by fatigue, sleep, fear and dehydration

  
• Sympathetic innervation of salivary secretion

  • secretion of a smaller amount of more mucus rich saliva
  • sympathetic innervation of parotid gland passes through superior cervical ganglion (1)
  • when sympathetic innervation is dominant, people often describe a dry mouth

  
• Sjogren's syndrome 


  pathophysiology: autoimmune destruction of salivary and lacrimal glands

  cause: exact cause unknown; likely viral environmental trigger

  symptoms: dry eyes and mouth (sicca symptoms)

  treatment: no cure, management through artificial replacement of saliva (sprays) and tears (eye drops)

  
• Major functions of the stomach

  Motor: storage, mixing, emptying

  Secretory: gastric juice secretion

  Humoral: regulation of endocrine secretions (gastrin, histamine, somatostatin)
• Stomach wall physiology

  Types of cells in stomach wall

  Exocrine cells:

  • (1) Surface mucosal cells: secrete mucus
  • (2) Mucous neck cells: secrete mucus
  • (3) Parietal (oxyntic) cells: secrete HCl & intrinsic factor
  • (4) Chief (peptic) cells: secrete pepsinogen & gastric lipase

  Endocrine cells:

  • (5) G cells: secrete gastrin
  • (6) D cells: secrete somatostatin
  • (7) ECL (enterochromaffin-like) cells: secrete histamine

  
• Gastric juice contents

  • water (99%) medium
  • Hydrochloric acid (pH 1-3)
  • converts pro-enzyme pepsinogen to pepsin
  • denatures proteins and kills microorganisms
  • Stimulates hormones for bile and pancreatic juice
  • Mucin
  • forms mucus providing protection to stomach lining
  • Pepsinogen
  • converted to pepsin that cleaves peptide bonds
  • Gastric lipase
  • conversion of triglycerides to fatty acids
  • Intrinsic factor IF
  • vitamin B12 absorption in the ileum, helping erythropoiesis in bone marrow
• HCl production

  Parietal cells have a canalicular structure

  1. Carbonic anhydrase forms carbonic acid from CO2 and H2O which dissociates to provide free H+
  2. Proton pumps actively pump out H+ out of the parietal cells into the chyme through the apical membrane
  3. Cl-/HCO3- antiporters pump out HCO3 through the basolateral membrane whilst bringing Cl- in, making gastric venous blood alkaline
  4. Cl- diffuses out of the apical surface into the chyme, fusing with H+ to form HCl

  
• Regulation of gastric secretion

  D cells release Somatostatin which acts as inhibitory control of:

  • G cells (inhibited gastrin production)
  • ECL cells (inhibited histamine production; also by Cimetidine)
  • ENS (inhibited Acetylcholine secretion; also by Atropine)

  Omeprazole: proton pump inhibitor
• Gastrin physiology

  Gastrin secretion normally triggered by presence of specific peptides (gastrin releasing peptide) in response to vagal nerve stimulation

  High stomach acidity causes D cells to secrete somatostatin, preventing release of gastrin

  Additionally, gastrin promotes:

  • chief cell secretion of pepsinogen
  • lower oesophageal sphincter contraction
  • stomach motility
  • relaxation of the pyloric sphincter

  
• Phases of gastric secretion

  1. Cephalic Phase
  2. vagal stimulation of parietal, chief and G cells leads to gastrin rich gastric juice
  3. Gastric phase
  4. vagal reflexes, distension and gastrin further drives gastric juice production
  5. Production of mucus is accelerated to compensate for increased acidity
  6. Intestinal phase
  7. Chyme pH > 3 triggers: peptides stimulate gastric secretion via further gastrin release and vagal stimulation
  8. Chyme pH < 2 tiggers: gastric juice secretions are inhibited via gastric inhibitory peptide, cholecystokinin and secretin
• Gastric mucosal resistance

  • Surface mucus glands secrete a viscous mucus barrier protecting the tissue from acid and enzyme damage
  • Epithelial cells secrete HCO3- neutralising the acidic gastric juices
  • Apical membrane is also impermeable to H+ preventing uptake by mucosal cells
  • Tight junctions stop HCl damaging underlying tissue in submucosa

  
• Acute gastritis

  Pathophysiology: inflammation of gastric mucosa

  Causes: helicobacter pylori infection, smoking, alcohol, (non-steroidal anti-inflammatory durgs) NSAIDs

  Symptoms: pain, indigestion, nausea

  Treatment: antibiotic therapy to eradicate H. pylori; acid inhibition to promote healing (Omeprazole)

  
• Autoimmune gastritis

  Pathophysiology:

  • Autoimmune destruction of gastric parietal cells
  • Insufficient acid secretion (hypochlorhydria)
  • Intrinsic factor deficiency and lack of B12 absorption (pernicious anaemia)

  Cause: exact cause unknown; likely viral environmental trigger

  Symptoms: nausea, weakness and fatigue; headaches, weight loss

  Treatment: no cure; artificial replacement of B12 and iron

  
• What is the function of Intrinsic Factor?

  vitamin B12 absorption
• What is the function of Somatostatin?

  inhibitory: inhibits G cells, ECL cells, ENS
• What is the function of Atropine?

  Anticholinergic
• What is the function of Cimetidine?

  antihistaminic
• What is the function of ECL cells?

  histamine secretion
• What is the function of D cells?

  somatostatin secretion
• What is the function of G cells?

  gastrin secretion
• What is the function of chief cells?

  secrete pepsinogen and lipase
• What is the function of parietal cells?

  secrete HCL, intrinsic factor