Gastric secretion

Oesophagus connects to fundus and body where food is

stored and acid is released
Bottom half controls and mixes food
Gastric juice produced by gastric glands in stomach body:
 Mainly HCl – not for digestion/absorption but kill
bacteria/viruses contained in food and reduces risk of
infection
 Pepsinogen activated via HCl into pepsin (a protolytic enzyme) significant digestion occurs within lumen of stomach
via pepsin activity. Cells are made of protein. So inactivated form of pepsin
is formed first otherwise pepsin would have attacked cells making the
pepsinogen hence requires activation once produced
 Intrinsic factor binds to VitB12 and undergoes endocytosis in duodenum
 Mucus is a thick/viscous coat on stomach surface which protects mucosa of
stomach from damage from pepsin and acid secretion. Also provides
further lubrication for movement of food
Gastric glands are invaginations of the lumen of stomach and are present in
fundus and body
Mucous cells are produced at top of the gland, parietal cells in the mid-range
(which produce HCl and intrinsic factor) and chief cells produce pepsinogen.
Cell division also occurs in these glands similar to crypts seen earlier.
HCl Secretion
Inside a cell, pH is 7 hence H+ ion conc. is 10 -7M, in lumen its higher which
can be 100,000x greater – huge gradient – from inside of parietal cell to lumen.
At lumen is apical membrane; here very tight junctional complexes allow very few ions - prevent H+ ion movement.
Acid is made from 2 precursor molecules – H2O and CO2 which combine via carbonic anhydrase which catalyses
production of protons and carbonate ions – A Mechanism which moves protons out causes this reaction to continue
Apical membrane are proton pumps – similar to Na/K ATPase – transport K+ in exchange of protons – requires ATP
 ADP – each ATP move 2K+ in and 2H+ out
Alongside are Cl- channels to form HCl outside the cell.
Blockage of Cl- channels blocks Cl- ions inside which in turn
causes accumulation of H+ outside as it is not forming HCl
to get rid of the protons.
K+ ions exit again via K+ channel and this process continues
Basolateral membrane has a range of transporters
Excess of bicarbonate in blood causes elevation in pH of
blood
This mechanism is controlled by 3 different transport
molecules: ACh, Gastrin and Histamine
ACh from enteric nerves, gastrin (peptide) acts on parietal cells
and histamine which is a paracrine transmitter (its activity is
central to treating ulcers in stomach/intestine walls)
Receptor activation by these mediators activates membrane
channels of parietal cells and also causes changes in their cell
structures
When stimulated, vesicles fuse into apical membrane and
massively increase surface area of apical membrane and
increase number of active channels.
6-10x fold increase in number of proton pumps available for secretion
Control of gastric secretion in organ level
Produced 3L per day – basal secretion is 10% of max rate. Increases 10x fold when food is in stomach
3 Phases in Control; though are active together
Cephalic phase: neuronal phase of secretion. Entirely stimulatory phase.
Mainly associated with smell, taste in mouth, sound or food.
Nerves from mouth go to medulla oblongata which control vagus nerve which innervates stomach and releases ACh
directly onto parietal cell area to increase acid secretion and also increases stimulation of G cells – produce gastrin
which travels via blood into body of stomach which stimulates parietal cell activity also.
Peptides are produced by parasympathetic nerves and also produce GRP as well as ACh which acts as a
neurotransmitter

Gastric phase: Mainly stimulatory but also inhibitory

Food in stomach, distension and chemicals causes cell activation
Local nerves and vagovagal reflexes cause parasympathetic nerve stimulation and cause acid secretion which also
stimulate gastrin and also secretogogues - peptides, caffeine  All produce acid in the end
Inhibition: Local reflexes where gastrin is produced causes acid secretion but if environment of stomach is too
acidic than pH 2, then this inhibits gastrin secretion
Intestinal phase: mainly inhibitory
Food reaches upper part of SI and food here has low pH as it has come from stomach and also contains fats and
peptides. pH and content stimulate enteroendocrine cells and cause negative feedback on acid secretion in stomach
Due to nerve reflexes – enterogastric reflex – links to stomach
But when nerves were cut, inhibition still occurs due to hormones also involved. As food reaches small intestine,
Secretin, CCK and other peptide hormones such as GIP
are produced which all inhibit gastrin secretion
Cellular level of control:
Parietal cell has proton pumps on luminal membrane and
receptors for gastrin and Ach
This is an additional phase… in wall of stomach, there are
endocrine cells called ECL cells which carry receptors of
gastrin and Ach receptors as well
ECL produces histamine – paracrine transmitter which
diffuses to parietal cells and stimulates acid secretion
Endocrine cells produce somatostatin which has negative effects on ECL cells and inhibits histamine and gastrin
production – healthy people have this but problems can cause ulcers

Mucosal protection
Too much acid destroys cells so mucus protects stomach and duodenum. It contains:
 Mucus is thick and made of glycoproteins connected to sugar molecules and accumulate H 2O inside
 Bicarbonate ions neutralise acids
Stimulated by irritation from nerve and vagal reflexes, secretin hormones and also prostaglandin – important in
immune response when protecting the body
Their synthesis is inhibited by hormones such as gastrin and ibuprofen – these drugs impair the mucosal protection
and so stomach cannot protect against acid or infection resulting in ulcers.
Ulcer treatment
Ulcers can damage right through GI walls and into blood vessels
Ulcer = acid/enzyme damage to stomach or intestinal wall (10% affected). Treatment discoveries:
 Vagotomy (surgery) decreases vagal stimulation
 Histamine receptor antagonists which target histamine receptors on parietal cells type (H 2) inhibit secretion
 H-+K+ ATPase inhibitors
 Antibiotics which kills bacteria Helicobacter pylori:
 Bacteria living in low pH of stomach
 Observed in majority of ulcer patients
 Metabolise/breakdown urea (contains ammonium) which is alkaline  local increase in pH with NH3 release
 Inflammation of antrum which inhibits somatostatin release = increases acid secretion
 Anti-biotics “cure” ulcer disease
 Both of these drugs required constant delivery or ulcers grow back again