GASTROINTESTINAL

SECRETIONS
Dr Nyongesa
MBCHB II yr 2024
Topic outline
Salivary secretions
Gastric secretions
Pancreatic secretions
Bile
Salivary secretion
• Produced by the 3 major salivary glands
• Total daily production: 1000-1500mls
• Production: a 2 step process
• Primary secretion by acini
• Modification of primary secretion by
ducts: Na and Cl are extracted, K and
HCO- are added
• Triggers: site/smell/thought of food
• Regulation
• PNS plays a prominent role
• SNS: increases proteinacous content
• mmm
Functions of saliva
• Initiate digestion
• Protection of oral cavity
• Lubricate food bolus
• Solvent for tastants
• Neutralise refluxed gastric secretions
• Keep mouth and teeth clean
Gastric secretions
• Total secretions per day: 2000-5000mls
• Phases:
• Cephalic: control by brain, vagal input from dorasal vagal complex, NTs: Ach and GRP
• Gastric : mechanical and chemical stimuli, most significant: gastrin release
• Intestinal: inhibitor pathways are restores, increased SST activity
• Components of gastric secretion
• Pepsinogens: synthesized by chief cells
• Pepsin digest dietary proteins
• Can be Group I or group II
• Serum levels correlate with acid output
Mechanism of HCL secretion
• Cl- loaded into cell via basolateral
Cl-/HCO3 anion exchanger, NKCCL
and SCL26A7 Cl- channel
• CL- channel at apex: CLIC-6, CFTR
Regulation of gastric secretion
• Receptors are located on basolateral membrane
• Gastrin from antral G cells: binds on CCK2, increases cytoplasmic calcium
• Histamine from oxyntic ECL cells binds on H2R, increases cAMP, which activates
PKA
• Ach from vagal cholinergic binds on M3: Direct and indirect activation of parietal
cells
• Above actions lead to activation of proton pumps and activation of luminal Cl- and
K+ conductance
• Actions are synergistic
• Inhibition of gastrin: SST and IL-1beta
Gastric defense
• Premucosal: bicarbonate and mucin barrier
• Mucosal: Phospholipid cap and tight epithelial junctions
• Trefoil peptides
• Growth factors: HIF, VEGF, bFGF
• Submucosal: microcirculation
• Alkaline tide
• NTs: CGRP, NO, H2S
Pancreatic secretions
• Clear alkaline isosmotic to plasma
• About 1500mls per day
• Contents:
• Enzymes: 3 major forms: proteases, lipases, amylase
• Others phospholipase and colipase
• Proteases are secreted in inactive state
• Cations: sodium and potassium
• Anions: Cl- and HCO3
Chloride and bicarbonate have flow
mediated reciprocal relationship
HCO#
• Secreted by pancreatic centroacinar and duct cells against concentration gradient
• Derived from hydration of CO2 by CA and also from direct HCO3 uptake by
Na/HCO3 cotransporter
Cl-
• Secreted into duct lumen by CFTR and calcium dependent channel
• High concentration of CL- in duct lumen results to exchange of cl with HCO3
through CL-/HCO3 antiporter.
States of pancreatic secretion
Basal state
• During fasting or interdigestive period
• Low volume production: Enzyme is
10% of maximal capacity, HCO3 is 2%
• Relatively increased production at
intervals of 60-120 minutes
• Corresponds to phase III of MMC
• Cholinergic input stimulates
• Alpha adrenergic input inhibits
Postprandial phase
• Occurs during/after meal intake
• Enzyme and HCO3 production is 60-75% of
maximal capacity
• Has 3 phases:
• Cephalic: 25%, vagal cholinergic
• Gastric: 10%, vagovagal reflex
• Intestinal : predominant phase. Secretin and
cholinergic input
• Digestive enzymes secretion:
• Stimulants: fatty acids, AA, oligopptds and Ca
• Hormone: CCK
Protective mechanisms against
pancreatic autodigestion
• Digestive enzymes are secreted in inactive form
• The enzymes are enclosed in membrane bound secretory granules
• Enterokinase is located on brush border of intestinal lumen
• Pancreatic secretes trypsin inhibitor
• Pancreatic duct cells secrete a lot of fluid to flush enzymes away
Regulation of secretion
• Secretin: copius secretion of alkaline pancreatic juice, poor in enzymes. Uses
cAMP pathway
• CCK: release of zymogen granules. Juice is small amount but rich in enzymes. Uses
PLPC pathway
• Ach: Vagal stimulation; release of zymogen granules, small amounts. Uses PLPC
pathway
Bile secretion
• Bile is produced in the liver and stored in gall bladder
• About 500mls produced daily
• Constituents of bile:
• Water : 80%
• 20%: lipids, bile salts, metabolites, electrolytes
• Function of bile:
• Digestion and absorption of fats
• Excretion of lipid soluble metabolites and xenobiotics
• Disposal of cholesterol
Bile salts
• Hepatocytes synthesize bile salts from cholesterol
• Primary bile salts: cholic and chenodeoxycholic acids
• Bile salts conjugate to glycine and taurine for hydrophilicity
• The complexes are pumped across canaliculus into biliary tree by bile salt export
pump (BSEP)
• Water passively follows these constituents to create bile flow
• Hence components of bile formation are 3:
• Bile acid dependent
• Bile acid independent
• Ductular
Bile salts at intestinal level
• From micelles once critical micellar concentration is reached.
• Facilitate fat absorption
• 90-95% are absorbed in the terminal ileum:
• At brush border: sodium bile salt cotransport system
• Intracellular to portal system: organic solute transporter
• Small amounts are passively absorbed in proximal small intestine
• Absorbed bile acids are transported to liver by portal system
• Uptake by hepatocytes is through Na dependent (75%) and independent pathways
Secondary bile acids
• 5-10% of bile salts are delivered to colon.
• Colonic bacteria metabolise them to form secondary bile acids
• Deoxycholic acid from cholic acid
• Lithocholic acid from chenodeoxycholic acid: least soluble
• Taurocholic acid
• Ursodeoxycholic acid