3. ACID PRODUCTION
OVERVIEW
ā£ The stomach is a gastrointestinal organ that is responsible for
preliminaryĀ digestionĀ and destroying any potential pathogenic
microorganisms that may have been ingested
ā£ It is an acidic environment with a pH that can vary
betweenĀ 1.5-3.5
ā£ Learning Goal
ā£ To outline the production of stomach acid, the regulation of
this and some clinical conditions that result from this process
going wrong
4. ACID PRODUCTION
HYDROCHLORIC ACID PRODUCTION
ā£ HCl is produced by theĀ parietal cellsĀ of the stomach
ā£ To begin with, water (H2O) and carbon dioxide (CO2) combine within the
parietal cell cytoplasm to produce carbonic acid (H2CO3), which is
catalyzed byĀ carbonic anhydrase
ā£ Carbonic acid then spontaneously dissociates into a hydrogen ion (H+)
and a bicarbonate ion (HCO3ā)
ā£ The hydrogen ion that is formed is transported into the stomach lumen
via the H+ā K+Ā ATPase ion pump (aka proton pump)
ā£ This pump uses ATP as an energy source to exchange potassium ions with
H+Ā ions (H+ out of and K+ in to the parietal cells of the stomach)
5. ACID PRODUCTION
HYDROCHLORIC ACID PRODUCTION
ā£ The bicarbonate ion is transported out of the cell into the blood via a
transporter protein calledĀ anion exchangerĀ
ā£ As the bicarbonate ion is moved out of the cell it is exchanged for a
chloride ion (Clā) coming in
ā£ This chloride ion is then transported into the stomach lumen via a
chloride channel
ā£ This results in both hydrogen and chloride ions being present within the
stomach lumen
ā£ Their opposing charges lead to them associate with each other to
formĀ hydrochloric acidĀ (HCl)
7. ACID PRODUCTION
CONTROL OF ACID PRODUCTION
ā£ At rest, the number of H+ā K+Ā ATPases present within the
parietal cell membrane is minimal
ā£ The rest are sequestered withinĀ tubulovesiclesĀ in the parietal
cell
ā£ Upon stimulation the vesicles fuse with the cell membrane
which leads to the increased insertion of H+ā K+Ā ATPase into
the membrane
ā£ Allowing for the increased movement of hydrogen ions into the
stomach and so increasing acid production
8. ACID PRODUCTION
INCREASING ACID PRODUCTION
ā£ There are three ways in which acid production is increased
ā£ 1. The main regulation pathway involves the hormoneĀ gastrinĀ which is secreted from
G cells in the stomach
ā£ G cells are activated by:
ā£ the vagus nerve
ā£ gastrin related peptide
ā£ peptides in the stomach lumen produced via protein digestion
ā£ Activation of the G cells leads to the production of gastrin which is released into
the blood and travels through the blood until it reaches the parietal cells
ā£ Gastrin binds to CCK receptors on the parietal cells which also elevates
intracellular calcium levels causing increased vesicular fusion
9. ACID PRODUCTION
INCREASING ACID PRODUCTION
ā£ 2. ACh is released from theĀ vagus nerve
ā£ This is released firstly during theĀ cephalic phaseĀ of digestion, which is activated
upon seeing or chewing food, leading to direct stimulation of parietal cells via
the vagus nerve
ā£ It is also produced during the gastric phase of digestion when intrinsic nerves
detect distension of the stomach, stimulating the production of ACh by the
vagus nerve
ā£ 3. Enterochromaffin like cells in the stomach secrete histamine which binds
toĀ H2Ā receptors on the parietal cells
ā£ These cells release histamine in response to the presence of gastrin and ACh
ā£ This leads to increased fusion however it is via the secondary messenger cAMP
as opposed to calcium in the other methods
10. ACID PRODUCTION
DECREASING ACID PRODUCTION
ā£ There are a number of ways in which acid production can be decreased
ā£ The first of these is via accumulation of acid in the empty stomach between meals
ā£ This increase in acid leads to a lower pH within the stomach, which inhibits the secretion of
gastrin, via the production ofĀ somatostatinĀ fromĀ D cells
ā£ Once food has been broken down intoĀ chyme, it passes into the duodenum, triggering
theĀ enterogastric reflex
ā£ This reflex can be stimulated by distention of the small bowel, if there is excess acid in the
upper intestine, the presence of protein breakdown products as well as excess irritation to the
mucosa
ā£ Inhibitory signals are sent to the stomach via the enteric nervous system, as well as signals to
medulla ā reducing vagal stimulation of the stomach
ā£ The enterogastric reflex, is important for slowing down gastric emptying when the intestines
are already filled
11. ACID PRODUCTION
DECREASING ACID PRODUCTION
ā£ The presence of chyme within the duodenum also stimulatesĀ entero-
endocrine cellsĀ to releaseĀ cholecystokininĀ andĀ secretin
ā£ Both of which play a variety of important roles in completing
digestion, but also inhibit gastric acid secretion
ā£ Secretin is released by the S cells of the duodenum when there is
excessive acid production in the stomach
ā£ Other hormones including glucose dependent insulinotropic
peptide (GIP) and vasoactive intestinal polypeptide also work to
decrease acid production in the stomach
15. ACID PRODUCTION
REVIEW QUESTIONS
ā£ Which cells in the lining of the stomach are responsible for
the production of hydrochloric acid?
ā£ G cells
ā£ Parietal cells
ā£ Enterochromaffin cells
ā£ D cells
16. ACID PRODUCTION
REVIEW QUESTIONS
ā£ Which cells in the lining of the stomach are responsible for
the production of hydrochloric acid?
ā£ G cells
ā£ Parietal cells
ā£ Enterochromaffin cells
ā£ D cells
17. ACID PRODUCTION
REVIEW QUESTIONS
ā£ What is the main method used to increase stomach acid
production?
ā£ Direct stimulation via the vagus nerve
ā£ The hormone gastrin
ā£ Histamine release from ECL cells
ā£ None of the above are involved
18. ACID PRODUCTION
REVIEW QUESTIONS
ā£ What is the main method used to increase stomach acid
production?
ā£ Direct stimulation via the vagus nerve
ā£ The hormone gastrin
ā£ Histamine release from ECL cells
ā£ None of the above are involved
19. ACID PRODUCTION
REVIEW QUESTIONS
ā£ What do proton-pump inhibitors (PPIs) block?
ā£ Histamine receptors
ā£ Hydrogen ion uniporter
ā£ Hydrogen-Potassium ATPase
ā£ Sodium-Hydrogen antiporter
20. ACID PRODUCTION
REVIEW QUESTIONS
ā£ What do proton-pump inhibitors (PPIs) block?
ā£ Histamine receptors
ā£ Hydrogen ion uniporter
ā£ Hydrogen-Potassium ATPase
ā£ Sodium-Hydrogen antiporter
21. ACID PRODUCTION
REVIEW QUESTIONS
ā£ What organisms are patients with achlorhydria NOT at an
increased risk to?
ā£ Helicobacter pylori
ā£ Salmonella typhi
ā£ Vibrio cholerae
ā£ Pneumocystis jiroveci
22. ACID PRODUCTION
REVIEW QUESTIONS
ā£ What organisms are patients with achlorhydria NOT at an
increased risk to?
ā£ Helicobacter pylori
ā£ Salmonella typhi
ā£ Vibrio cholerae
ā£ Pneumocystis jiroveci
ā£ Pneumocystis is a fungal infection that typically develops in
immuno-compromised hosts.
23. ACID PRODUCTION
REVIEW QUESTIONS
ā£ Which of these can decrease acid production in the
stomach?
ā£ Somatostatin
ā£ CCK
ā£ Secretin
ā£ All of the above
24. ACID PRODUCTION
REVIEW QUESTIONS
ā£ Which of these can decrease acid production in the
stomach?
ā£ Somatostatin
ā£ CCK
ā£ Secretin
ā£ All of the above
26. MUCUS PRODUCTION
OVERVIEW
ā£ Learning Goals
ā£ To discuss the production of gastric mucus in the
stomach
ā£ To look at the cells that make up the mucosa of the
stomach, the process of mucus production and the
control mechanisms involved in its secretion
27. MUCUS PRODUCTION
GASTRIC MUCUS
ā£ Gastric mucus is a gel-mucous barrier secreted by epithelial cells and glandular
cells in the stomach wall
ā£ It acts as part of a barrier that protects the stomach wall from the acid and
digestive enzymes within the stomach lumen
ā£ This barrier is also made up of a bicarbonate secretion and the epithelial cells
themselves, which are tightly joined together
ā£ Together, these components prevent the stomach from effectively digesting itself
ā£ Mucus is secreted by the stomach epithelial cells, but the mucus is mainly secreted
fromĀ foveolar cells,Ā found in the necks of the gastric pits
ā£ Mucus-secreting cells are the most abundant cell type in the stomach, giving
indications of how important mucus is to the functioning stomach
29. MUCUS PRODUCTION
CELLULAR ANATOMY
ā£ The cells that make up the epithelial layer are not spread across the stomach wall equally
ā£ All across the stomach are deep gastric glands
ā£ These are pits formed byĀ indentationsĀ of stomach epithelial cells
ā£ In the extreme zones of the stomach ā theĀ pyloric regionĀ and the cardia ā these gastric
glands only secrete mucus
ā£ In the other regions however, there is greater cellular diversity in the constituents of the
gastric glands:
ā£ Parietal cellsĀ secreteĀ hydrochloric acidĀ andĀ Intrinsic factor
ā£ Chief cellsĀ secreteĀ pepsinogens
ā£ ECL cellsĀ secreteĀ histamine
31. MUCUS PRODUCTION
MUCUS PRODUCTION
ā£ The production of mucus is conducted by stomach surface epithelial cells andĀ foveolar
cells
ā£ The mucus itself is around 95 per cent water, with the remaining five per cent made up of
polymers that give the mucus its gel-like viscosity
ā£ The viscosity of mucus is dynamic and can be altered by the rate of secretion from
glandular cells or rate of breakdown by proteolytic enzymes within the stomach lumen
ā£ TheĀ bicarbonateĀ element of the mucus is important as it allows anĀ increased pHĀ local to
the epithelial cells, protecting them from the highly acidic stomach environment
ā£ These bicarbonate ions are formed in the mucus-secreting cells by reacting carbon
dioxide with water, using the enzyme carbonic anhydrase
ā£ The bicarbonate ions are then pumped into the mucus layer by exchanging them with
chloride ions
32. MUCUS PRODUCTION
CONTROL OF SECRETION
ā£ Much like the control of salivary secretions, the gastric secretions
(including mucus secretion) is largely controlled by neural influences
ā£ An increase in mucus production is signalled by a stimulation of
theĀ Vagus nerveĀ (Cranial nerve 10) and is mediated byĀ prostaglandins
ā£ The cells respond to external factors such as mechanical stress and
elements of the cephalic and gastric digestion phases by increasing
mucus productions as required
ā£ In healthy patients, there is always a thick mucus layer to protect the
stomach from auto-digestion
38. MUCUS PRODUCTION
REVIEW QUESTIONS
ā£ Which of the following does NOT predispose to peptic
ulcer disease?
ā£ NSAIDs
ā£ Helicobacter Pylori
ā£ Achlorhydria
ā£ Zollinger-Ellison Syndrome
39. MUCUS PRODUCTION
REVIEW QUESTIONS
ā£ Which of the following does not predispose to peptic
ulcer disease?
ā£ NSAIDs
ā£ Helicobacter Pylori
ā£ Achlorhydria
ā£ Zollinger-Ellison Syndrome
42. MUCUS PRODUCTION
REVIEW QUESTIONS
ā£ What is the role of the mucus production in the GI system?
ā£ Increases pH to protect the lining of the stomach
ā£ Works to decrease the pH of the stomach
ā£ Stimulates the enteric nervous system
ā£ Increases the risk of peptic ulcer formation
43. MUCUS PRODUCTION
REVIEW QUESTIONS
ā£ What is the role of the mucus production in the GI system?
ā£ Increases pH to protect the lining of the stomach
ā£ Works to decrease the pH of the stomach
ā£ Stimulates the enteric nervous system
ā£ Increases the risk of peptic ulcer formation
ā£ TheĀ bicarbonateĀ element of the mucus allows anĀ increased
pHĀ local to the epithelial cells, protecting them from the highly
acidic stomach environment.
45. APPETITE
OVERVIEW
ā£ In order to ensure that we continue to eat food to fuel our
bodies, we experience the sensation ofĀ hunger
ā£ Learning Goal
ā£ To look at the key signals involved in the control of
appetite, including those that promote hunger and
those that causeĀ satiety
46. APPETITE
APPETITE CONTROL CENTRE
ā£ Within in hypothalamus lies theĀ arcuate nucleus,Ā which plays
a key role in the control of appetite
ā£ TheĀ appetite centreĀ contains both primary and secondary
neurones
ā£ The primary neurones process external signals
ā£ neuronal, hormonal or nutritional
ā£ The secondary neurones are then responsible for co-
ordinating the inputs received via the primary neurone
47. APPETITE
APPETITE CONTROL CENTRE
ā£ These primary neurones are either excitatory or inhibitory and each release specific
neurotransmitters
ā£ Excitatory
ā£ Neuropeptide Y (NPY) and Agouti-related peptide (AgRP)
ā£ These promote hunger
ā£ Inhibitory
ā£ POMC and CART
ā£ POMC can be cleaved into other neurotransmitters such as Ī±-MSH and Ī²-
endorphin
ā£ These suppress hunger
48. APPETITE
HORMONAL SIGNALS - FROM THE GUT
ā£ GhrelinĀ
ā£ a peptide hormone produced in the pancreas and released from the stomach wall
when the stomach is empty
ā£ stimulates the excitatory primary neurones, and thereforeĀ stimulates appetite
ā£ when the stomach is full, ghrelin release is inhibited, thus the appetite stimulus is also
inhibited
ā£ PYYĀ (full name ā peptide tyrosine tyrosine)
ā£ a short peptide hormone released by cells in the ileum and colon in response to
feeding
ā£ inhibits the excitatory primary neurones of the arcuate nucleus
ā£ causesĀ appetite suppression
49. APPETITE
HORMONAL SIGNALS - FROM THE BODY
ā£ LeptinĀ
ā£ a peptide hormone released into the blood by adipocytes (fat cells)
ā£ stimulates the inhibitory neurones and inhibits the excitatory
neurones in the arcuate nucleus to causeĀ suppression of appetite
ā£ InsulinĀ
ā£ a hormone released from beta cells in the islets of Langerhans of
the pancreas
ā£ suppresses appetiteĀ in a similar way to leptin
54. APPETITE
REVIEW QUESTIONS
ā£ Which of the following is the action of PYY?
ā£ Inhibits excitatory appetite neurones
ā£ Stimulates excitatory appetite neurones
ā£ Inhibits inhibitory appetite neurones
ā£ None of the above
55. APPETITE
REVIEW QUESTIONS
ā£ Which of the following is the action of PYY?
ā£ Inhibits excitatory appetite neurones
ā£ Stimulates excitatory appetite neurones
ā£ Inhibits inhibitory appetite neurones
ā£ None of the above
60. References
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purposes only in compliance with the terms of use policy.
Specific portions referenced in this summary are as follows:
ā£ https://teachmephysiology.com/gastrointestinal-system/stomach/acid-production/
ā£ https://teachmephysiology.com/gastrointestinal-system/stomach/mucus-
production/
ā£ https://teachmephysiology.com/gastrointestinal-system/stomach/gastrointestinal-
system-stomach-appetite/
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