Gastrointestinal Secretions

Gastrointestinal Secretions

Gastrointestinal Secretions

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GI Secretions

  • In the GI tract, secretion is stimulated by chemical mediators exerting secretagogue action
    • endocrine - hormonal, e.g. gastrin
    • paracrine - non-hormonal, e.g. histamine
    • neurocrine - non-endocrine hormones, e.g. acetylcholine
  • Inhibition by endocrine and neurocrine mechanisms
  • Secretions have:
    • Digestive function - saliva, gastric juice, pancreatic juice, bile
    • No digestive function - duodenal and jejunal secretion, large intestinal secretion
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Saliva

Saliva

  • Primary roles
    • lubrication (mucopolysaccharides)
    • initiation of digestion (salivary amylase; lingual lipase)
  • Secondary roles
    • anti-infective (lysozyme; IgA-binding glycoprotein)
    • evaporative cooling, in panting animals
    • buffering
  • Parotid gland - watery solution containing amylase
  • Submandibular - compound, as parotid but with some mucous cells
  • Sublingual - compound, mostly mucous cells, least amylase
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Saliva

Saliva

Saliva

Control of Salivary Secretion

  • Autonomic Innervation
    • Parasympathetic - increase
      • general level of saliva in mouth
      • drooling - smell/thought of food
    • Sympathetic - decrease
      • dehydration
      • nerves
  • Food stimulates taste receptors
    • Superior and inferior salivatory nuclei in brain stem
    • Parasympathetic innervation via glossopharyngeal and facial nerves
    • Stimates salivation
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Gastric Secretion

Gastric Secretion

  • Secretory cells of the oxyntic region are located in mucosal structures called gastric pits (oxyntic glands)

Gastrin Secretion

  • Major controller of gastric secretions
  • Released into the blood (enteroendocrine) in response to stimuli
  • Several biologically active forms according to species. In human:
    • 'big' gastrin: 34 amino acids
    • 'little' gastrin: 17 amino acids
  • Produced in G cells in gastric antrum (open APUD cells)
  • Exerts action through stimulation of cholecystokinin (CCK) type B receptors on parietal cells and enterochromaffin-like cells (ECL)
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Gastrin Secretion

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The Proton Pump

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Gastric Acid

  • Before, during and after ingestion, secretion is regulated in three distinct phases
    • Cephalic phase
      • Vagal stimulation causes release of gastrin and histamine
    • Gastric phase
      • Chemical stimulation and distension 
    • Intestinal phase
      • Presence of chyme in duodenum inhibits acid secretion and motility via release of secretin (+ GIP and CCK)
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Cephalic Phase of Regulation (Stimulatory)

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Gastric Phase of Regulation (Stimulatory)

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Intestinal Phase of Regulation (Inhibitory)

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Acid Reflux

  • Block ACh: muscarinic antagonists, pirenzepine (M1 receptor antagonist) - ulcers
  • Block histamine: histamine H2 antagonists, cimetidine (Tagamet), ranitidine (Zantac)
  • Block K+/H+-ATPase: proton pump inhibitors (PPIs), omeprazole, lansoprazole
  • Inhibit gastrin: CCK2 receptor antagonists
  • Boost secretin action: secretin receptor agonists
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Pepsins

  • Secreted as precursor zymogens - pepsinogens
  • Primary proteolytic enzyme
  • Secretion is stimulated mainly by ACh during cephalic and gastric phases
  • H+ is necessary for the activation of pepsins

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Pancreatic Juice and Bile

  • Pancreas has both endocrine and exocrine function
    • endocrine: insulin, glucagon
    • exocrine: pancreatic juice (enzymes and HCO3-)
  • Non-digestive endocrine hormones secreted by cells in the islets of langerhans
    • alpha cells - produce glucagon
    • beta cells - produce insulin
    • delta cells - produce somatostatin
  • Digestive exocrine enzymes and HCO3- secreted by tubuloacinar glands
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The Incretin Effect

  • Two major incretin peptides (decrease blood glucose) in intestinal secretions
    • GIP - glucose-dependent insulinotropic peptide
    • GLP-1 - glucagon-like peptide 1
  • GIP has minor role to control gastric secretion and motility
    • major role is insulin release by endocrine pancreas
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Diabetes and the Incretin Effect

  • Oral glucose produces more exaggerated insulin release than IV glucose infusion
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Exploiting the Incretin Effect

  • Inhibit the breakdown of incretins
    • Gliptins inhibit GIP and GLP-1 breakdown by the enzyme dipeptidyl peptidase-IV (DPP-IV)
  • Incretin mimetics
    • Exenatide is a synthetic version of exendin-4 (from Gila monster salivs) which produces the same effects as GLP-1 (used in conjunction with metformin)
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Pancreatic Enzymes

  • Secreted from acinar cells by exocytosis in response to neural and hormonal stimuli
  • Active enzymes
    • pancreatic lipase
    • alpha-amylase
    • deoxyribonuclease
  • Zymogen precursors in pancreatic juice are activated enzymatically in the small intestine
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Pancreatic Enzymes

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Regulation of Exocrine Pancreatic Secretion

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Cystic Fibrosis Transmembrane Conductance Regulato

  • Plays a key role in regulating HCO3- secretion
  • In resting duct cells, CFTR is a cytosolic protein
  • Secretin stimulates the insertion of the CFTR protein into the apical membrane
  • Expected gastrointestinal symptoms:
    • thick, sticky mucous
    • malnutrition
    • poor fat digestion - oily stools
    • poor protein digestion - lack of weight gain
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Pancreatic Bicarbonate Secretion

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Bile

  • Secreted more or less continuously by polygonal hepatocytes of the liver
    • canaliculi --> hepatic ductal system --> bile duct
  • In the interdigestive period, hepatic bile stored in the gall bladder - concentrated by water resorption
  • Primary bile acids - cholesterol derivatives synthesised in liver
    • cholic acid, chenodeoxycholic acid
    • conjugated with amino acids to become water soluble
    • glycocholic acid, taurocholic acid
  • Secondary bile acids - dehydroxylated forms via gut bacterial enzymes
    • deoxycholic acid, lithocholic acid
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Bile

  • Conjugated bile salts are amphipathic, i.e. both hydrophilic and hydrophobic
  • Emulsification and solubilisation of fats
  • Transport and absorption of fat-soluble vitamins
  • Elimination of cholesterol

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Regulation of Bile Secretion

  • Gall-bladder contraction stimulated by cholecystokinin (CCK)
    • CCK release is stimulated by presence of fat in duodenum
  • Bile duct HCO3- secretion stimulated by secretin
    • secretin release in stimulated by presence of H+ in duodenum
  • Factors that regulate pancreatic secretion also regulate bile secretion
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Intestinal Secretions

  • Contain few or unimportant digestive enzymes, in most species
  • Ileum
    • mucos, HCO3-, water
    • Brunner's glands, predominantly under enteric nervous control - mucin to protect from acid chyme
  • Colon
    • mucus
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