Gastrointestinal Secretions
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- Created by: amazingemilyjones
- Created on: 23-04-19 12:29
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
- Parasympathetic - increase
- 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)
- Cephalic phase
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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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