Secretions of the Stomach Flashcards
What are the 4 main functions of the stomach?
Stores food
Mixes food with secretions
Regulates release of food into duodenum
Secretes gastric juices
Describe the anatomy of the stomach
Oesophagus Cardia Fundus Corpus Antrum Pylorus Duodenum
What are the 6 cell types in the stomach? What do they secrete?
Mucous Neck cells - mucous, bicarbonate Parietal cell - IF and acid ECL cell - histamine G cell - gastrin D cell - somatostatin Chief cell - pepsinogen and lipase
Describe the difference in terms of cells present between the corpus and antrum of the stomach.
Corpus - parietal cells and chief cells (ECL and D cells)
Antrum - D cells, G cells
What is the H-K made up of and what are their separate functions?
Requires both for full activity
alpha subunit - catalytic function
beta subunit - apaical membrane targeting
Which enzyme is involved in generation of H+ ions. What is the equation?
carbonic anhydrase
H2CO3 –> H2O + CO2
How does the HCO3 leave the parietal cell? What phenomenon does this lead to?
exits across the basolateral membrane via the Cl-HCO3 exchanger, Alkaline tide!
What is involved in the direct and indirect stimulation of acid secretion?
Direct - ACh, gastrin, histamine
Indirect - ACh, gastrin –> histamine
By what receptor and following pathway do each of the following affect the H-K pump:
- acetylcholine
- gastrin
- histamine
- M3 receptor, Gq protein –> PKC –> Ca2+
- CCKb receptor, Gq protein –> PKC –> Ca2+
- H2 receptor, Gs protein –> adenylyl cyclase –> cAMP –> PKA
What kind of hormone is somatostatin?
Which cells is it released from? Where are these? What triggers release from these areas?
What is its affect on parietal cells?
- protein hormone
- D cells in corpus (neural and hormonal mechanisms)
- D cells in antrum (low intra-luminal pH)
- inhibits adenylyl cyclase so antagonising the stimulatory effect of histamine
Describe indirect regulation of histamine by somatostatin in the corpus and antrum
Corpus - somatostatin inhibits the release of histamine from ECL cells
Antrum - somatostatin inhibits release of gastrin from G cells
What triggers acid secretion in the corpus?
Distention of the stomach causes ACh release by the vagus nerve
- direct effect on parietal cells
- direct effect on ECL cells –> histamine
- stimulation of D cells -/-> inhibits somatostatin release
What triggers acid secretion in the antrum?
G and D cells are subject to vagal stimulation
- G cells, gastrin release
- D cells, inhibits release of somatostatin
What are the 2 consequences of the antral luminal environment?
high luminal H+ stimulates the D cells to release somatostatin (-ve regulatory loop)
Products of protein digestion stimulates the G cells to release gastrin, stimulating acid secretion (+ve loop)
Name 8 things that inhibit acid secretion: s C V G n p p s
somatostatin CCK VIP GIP neurotensin peptide YY prostaglandins secretin
What is the main pharmacological inhibitors of acid secretion?
What is a common drug used?
Proton pump inhibitors –> Omeprazole
What drugs used to be used to reduce acid secretion?
Why are they less effective?
What were side effects?
H2 receptor antagonists
Inferior to PPI as only target one trigger of secretion
Peristalsis and Gastric emptying (may require pyloroplasty)
What are the 4 phases of gastric acid secretion?
Describe each
- Basal - circadian rhythm (high at night)
- Cephalic - smell, sight, taste –> vagus nerve, ACh only
- Gastric - stomach distention, Ach release, also presence of protein in stomach leads to gastrin release
- Intestinal – inhibitory phase, HCl in duodenum leads to secretin, somatostatin and CCK release. Somatostatin inhibits effect of histamine,
- What are pepsinogens?
- What is the major trigger for pepsinogen release?
- What is it converted to and what triggers this?
- Proteolytic proenzymes secreted by chief cells
- Acetylcholine
- low pH converts pepsin
How do prostaglandins protect the gastric mucosa?
stimulate HCO3- release to maintain pH of 7
inhibit acid secretion
stimulate mucous secretion
Describe the mechanism of action of NSAID’s and their subsequent side effects?
COX 1 - platelet aggregation, gastric mucosa, kidney
COX 2 - inflammation
non selective so inhibit both pathways –> gastritis, peptic ulcers, dyspepsia
COX 2 seletive inhibitors removed from the market due to increased risk of heart attack
What is H. pylori?
What does it cause?
What is it classed as?
Helicobacter pylori - gram-negative microaerophilic bacterium
colonises the stomach of 40% of humans
Causes acid production and barrier damage –>
- gastritis
- gastric and duodenal ulcers
- gastric cancer
Class 1 carcinogen
What is the mechanism of action for damage caused by H.pylori?
Urease produced by HP converts urea into ammonium ions which is toxic to the mucosa.
What effects does H.pylori have in the antrum and corpus?
Corpus
- reduced acid secretion and hypochlorhydria –> gastric ulcers
Antrum
- hypergastrinaemia and decreased somatostatin release –> increase acid procuction –> duodenal ulcers
What is the treatment for H.pylori?
Triple therapy
- amoxicillin
- clarithromycin
- proton pump inhibitor e.g. omeprazole
Explain the relationship between intrinsic factor and pernicious anaemia.
IF produced by parietal cells
Necessaru for absorption of vitamin B12 in the terminal ileum
Loss of this axis results in pernicious anaemia –> megaloblastic anaemia
Pernicious anaemia is an autoimmune atrophic gastritis, in which auto-antibodies are directed against parietal cells and results in their destruction
