Lecture 28 - Gastric Acid Secretion Flashcards
What are the components of gastric secretions?
Acid
Pepsin
Intrinsic factor
Mucus
What is the function of acid in gastric secretions?
Protective role
Denature proteins
Optimum pH for many digestive enzymes
Render fluid isosmotic
- (150 mM HCl - (HCO3-) - neutralised part)
What is the function of pepsin?
Protein digestion
What is the role of intrinsic factor in gastric secretions?
Vitamin B12 absorption (DNA, red blood cells, pernicious anaemia)
What is the role of mucus in gastric secretions?
Protects against acid and mechanical forces
What luminal secretion occurs at the LES and cardia?
Mucus
HCO3-
What luminal secretion occurs at the fundus and body?
H+
Intrinsic factor
Mucus
HCO3-
Pepsinogens
Lipase
What luminal secretion occurs at the antrum and pylorus?
Mucus
HCO3-
What is the apical HCO3-/Cl- exchanger in salivary duct cells driven by?
Cl- via CFTR
Where does the HCO3- come from in salivary duct cells?
Either carboanhydrase reaction or from basolateral side
What cells make up the gastric glands in body of stomach?
Surface cells
Mucus secreting cells
Oxyntic (parietal) cells
Chief cells
Enterochromaffin like (ECL) cells
What do the surface cells in gastric glands secrete?
HCO3-
What do the parietal cells in gastric glands secrete?
Acid
Intrinsic factor
What do the chief cells in gastric glands secrete?
Pepsinogen
What do ECL cells in gastric glands secrete?
Histamine
How much is secreted by the gastric glands per day?
2-3 L per day
When do gastric secretion composition change?
Eating or fasting phase
What do ECL cells sit in close proximity to?
Oxyntic (parietal) cells
What is the rate of gastric secretion between meals?
15-30ml/h
What is gastric secretion between meals secreted by?
Surface cells
What is the gastric secretion composition between meals?
Isosmotic solution with similar [Na+] as plasma but higher [HCO3-]
Also mucus
What is the rate of gastric secretion while eating?
150ml/hr (5-10x higher)
What is the composition of gastric secretion while eating?
Isosmotic (150 mM) solution of HCl produced by parietal cells
Pepsinogen
Intrinsic factor
More mucus
What is the final gastric secretion osmolality and why?
Remember surface cells secrete HCO3-
H+ + HCO3 <=> H2CO3 <=> H2O + CO2
Therefore final gastric secretion has an osmolality of ≈ 200 mOsmol/L
What does final composition of gastric secretion depend on?
Rate of secretion
Gastric secretions
A. consist of bile acids.
B. between meals have a rate of 3 mL/min.
C. of surface epithelium are mucus and bicarbonate.
D. of chief cells contain intrinsic factor.
C. of surface epithelium are mucus and bicarbonate.
A - Does not
B - 15-30ml/hr
D - Chief cells have pepsinogen, Parietal cells have intrinsic factor
What is associated with the stimulation of acid secretion in gastric glands?
A number of structural changes in parietal cell
What is the structure of non secreting parietal cell?
Small intracellular canaliculi
Short stubby microvilli at apical pole
Extensive tubulovesicular system
What does the tubulovesicular system hold in non-secreting parietal cells?
Holds the components for acid secretion, but they are quiescent
What is the structure of secreting parietal cell?
Extensive canaliculi
Large apical microvilli
Mitochondria located around basolateral membrane
What are the changes in parietal cells from nonsecreting to secreting?
Disappearance of
tubulovesicular system
Development of extensive intracellular canaliculi
Appearance of large apical microvilli
Increase surface area of apical membrane 50-100-fold
What is the function of structural changes in parietal cells?
To insert H/K-ATPase into apical membrane
- 80% of the protein in the tubulovesicular membrane is the H+,K+ -ATPase
H+,K+ -ATPase is responsible for acid secretion
- primary active transporter (potassium driven opposed to sodium driven)
What are the events at the apical membrane of secreting parietal cell?
K+ and Cl- diffuse down their electrochemical gradients into the lumen via channels
K+ is recycled back across the apical membrane via H+,K+ -ATPase
Secretion of HCl
Water follows passively
The secretion of hydrochloric acid (HCl)
A. is dependent on an apical (luminal) K+ gradient.
B. requires an apical bicarbonate gradient.
C. requires an apical Na+ gradient.
D. requires the change of the parietal cells from large intracellular canaliculi to an extensive tubulovesicular system
A. is dependent on an apical (luminal) K+ gradient.
B & C - K+ gradient
D - Opposite
What is the source of H+ ions that are secreted in parietal cells?
Carboanhydrase reaction
What is the function of Na/K+ ATPase in unstimulated parietal cells?
Maintains K+ in cell above equilibrium
What is the function of basolateral K+ channels in unstimulated parietal cells?
Recycles K+ and generates membrane potential
What is the role of basolateral NHE and Cl/HCO3 exchanger in unstimulated parietal cells?
pH homeostasis and maintenance of Cl- above equilibrium
What is omeprazole?
Drug that is used to treat gastric ulcers or reflux.
Targets Hydrogen/Potasium ATPase which is found only in stomach (one type in kidney but not important).
- Drug is very specific
What is the function of the basolateral Cl/HCO3 exchanger in stimulated parietal cells?
For each mole of H+ ion secreted an equivalent amount of base is produced
This is extruded across the basolateral membrane by the Cl-/HCO3- exchanger (alkaline tide after a meal)
This provides the Cl- ion that is secreted with H+
Where is mucus secreted from in gastric glands?
Mucus secreted by mucus neck cells in glands and surface cells
What do the surface cells in mucus glands secrete?
Mucus and HCO3 rich solution
Why do we have mucus and HCO3 in gastric secretions?
To provide a layer of alkaline mucus that protects stomach from abrasion and acidic pH
