Case 2 - Stomach ulcer Flashcards
Where is most of the gastric juice secreted from?
Gastric glands, which open up from the gastric pits (in rugae)
What cell types are present in gastric glands and what do they produce?
Chief cells: pepsinogen and lipase
Parietal cells: HCl and intrinsic factor
Endocrine cells: gastrin and ghrelin
Mucous neck cells: mucin in acidic fluid
Surface mucous cells: mucin in alkaline fluid
D cells: somatostatin
What are some modifications the stomach has for its functions?
- Rugae = mucosal longitudinal folds so when it gets full the walls can expand out, and when its empty it gets smaller
- 3 muscle layers = extra layer of SM to help churn food; inner oblique, middle circular and outer longitudinal
What are the roles of each phase of gastric secretion?
Phase 1 - cephalic: secretes 1/3 of secretion before food enters the stomach
Phase 2 - gastric: secretes 2/3 of secretion when food reaches the stomach (due to distention and peptones)
Phase 3 - intestinal: mechanical and chemical digestion of food
How is phase 1 / cephalic secretion stimulated?
1: the sight, smell, thought and taste of food signals to the dorsal nucleus of vagus in the medulla
2: stimulates parietal and chief cells to increase HCL and pepsinogen secretion
What inhibits phase 1/ cephalic secretions?
Sympathetic nervous system, i.e. stress or emotional upset = via greater splanchnic nerve (opposes actions of vagal so decreases HCl and pepsinogen)
How is phase 2/ gastric secretion stimulated by stretch receptors?
Stretch receptors in the submucosa and muscularis externa, when stimulated:
- Stimulate vagus nerve to increase HCl and pepsin (vago-vagal reflex) = long-arc
- Stimulate submucosal plexus = short reflex arc (enteric NS)
How does the vagus nerve lead to increased HCl and pepsin?
Vagus nerve releases acetylcholine, which:
- inhibits D cells via CCK-2 receptor, to decrease somatostatin (which is inhibitory)
- stimulates G cells via M3 receptor, to increase H+ and pepsin via gastrin
How is phase 2/ gastric secretion stimulated by peptones?
Peptones (partially digested proteins) stimulate enteroendocrine G cells in antrum of stomach to release gastrin, which binds to:
- CCK2 receptors on parietal cells to increase HCl
- CCK1 receptors on chief cells to increase pepsinogen
When can pepsinogen be converted to pepsin?
When pH is 1.8-3.5, thus relies on HCl concentration
What is the negative feedback mechanism of peptones?
They act as buffers to mop up H+, when pH rises this stimulates gastric secretion and subsequent HCl release to digest proteins
What inhibits phase 2/ gastric secretion?
Sympathetic nervous system, and somatostatin:
- Antral D cells (chemoreceptors) detect low pH = release somatostatin
- Somatostatin inhibits G cells from releasing gastrin, to decrease pepsin and HCL
How does phase 3 begin?
Stomach contracts, and the peristaltic wave starts at the cardia, moves down the fundus, body and antrum and ends at the pylorus (most powerful here). Contraction of muscularis externa leads to retropulsion of chyme, i.e. around 27ml is pushed back towards the body, then around 3ml enters the duodenum (start of phase 3).
What 2 factors stimulate intestinal (phase 3) secretion?
- Intestinal gastrin: released when duodenal G cells detect high peptones in the chyme, which stimulates parietal and chief cells to release HCl and pepsinogen
- Entero-oxynctin: released when endocrine cells detect high peptones, it stimulates parietal cells for HCl production
List the inhibitors of intestinal secretion (phase 3)
Secretin
Cholecystokinin (CCK)
Gastrin inhibitory peptide (GIP)
Neurotensin and peptide YY
When is secretin released and what is its role in intestinal (phase 3) secretion?
Released by S-cells in duodenum in response to high H+ and fatty acids in the chyme:
- Inhibits antral G-cells to inhibit gastrin release, thereby decreasing HCl production
- Binds to receptors on the liver to stimualte hepatocytes to convert cholesterol to bile acids (increased bile synthesis - released into duodenum) to help emulsify FA
- Binds to receptors on pancreatic ducts to increase bicarbonate to neutralise protons
When is CCK released and what is its role in intestinal (Phase 3) secretion?
Released by enteroendocrine I cells in the duodenum in response to high H+ and peptones, and to a hyperosmolar chyme:
- Inhibits parietal cells to decrease HCl
- Potentiates secretin to increase bile synthesis
- stimulates gall bladder to contract and sphincter of Oddi to relax = release of bile
- binds to pancreatic acinar cells for exocytosis of pancreatic precursors, e.g. proteases, lipases, amylases
What is the role of peptide YY and neurotensin?
Act on parietal cells to decrease HCl production, to inhibit excessive release of acidic chyme into duodenum
When is gastric inhibitory peptide released and what is its role in intestinal secretion (phase 3)?
Released by K-cells in response to high oligosaccharides and FA:
- Binds to parietal cells to reduce HCL
- Binds to B-cells to increase insulin production, to stimulate glucose and FA uptake
What control mechanisms are in place if the chyme is very acidic?
Chemoreceptors detect high H+ and inhibit the vagal nerve to decrease stimulation of parietal cells (lowers HCl). Simultaneously, the SNS (via thoracic splanchnic nerve) acts on a1-adrenoceptors to contract the pyloric sphincter = prevents chyme entering duodenum
How is acid formed in the stomach?
- In the parietal cell, H2O and CO2 combine to form H2CO3, then dissociated into H+ and HCO3-
- H+ is pumped into stomach lumen via H+-K+ ATPase, using ATP
- HCO3- is pumped into blood via anion exchanger with Cl-
- Cl- then flows from parietal cell into the stomach lumen by chloride channels
- H+ and Cl- in the stomach lumen combines to form HCl
Where are H+/K+ ATPases found at rest?
At rest, minimal numbers are found on the cell membrane of parietal cells, and the remaining are in tubulovesicles
What can increase acid production in the stomach and how?
- Acetylcholine from vagus nerve during cephalic phase (i.e. sight of food) or gastric phase (stomach distention)
- Gastrin from G-cells, release stimulated by vagus nerve or peptones. Binds to CCK-2 on parietal cells to increase calcium = vesicular fusion
- Histamine: enterochromaffin-like cells secrete H in response to ACh and gastrin, which binds to H2 receptors on parietal cells to increase fusion of vesicles by cAMP
How do protein meals affect stomach pH?
They act as buffers (mop up H+) = raises pH after ingestion. Later, acid secretion increases for digestion (lowering pH)
What food types can increase acid reflux and how?
- Chocolate: relaxes LES so food refluxes up
- Coffee: thought to induce gastrin release which increases acid production, may also relax LES
- Citrus fruit and juices: acidic food contributing to an already acidic environment
What are the 3 main mechanisms behind gastric emptying?
- Peristaltic waves: from cardia, fundus, antrum to pylorus
- Systolic contractions of the antrum
- Reduction in the size of the stomach
Compare receptive and adaptive relaxation
Receptive relaxation: during cephalic phase, NO is released to relax SM of the stomach
Adaptive relaxation: when food enters the stomach, distention triggers local reflex of NO to relax the stomach to increase intragastric volume. This can be augmented if the bolus is high in peptones = gastrin release = more SM relaxation
Other than receptive and adaptive relaxation processes, what else contributes to relaxation of the stomach?
Chyme entering the duodenum leads to CCK, secretin and GIP release. these relax the stomach so food is held there more
What is the enterogastric reflex?
Distention of the duodenum activates the sympathetic NS, which sitmulates the pyloric sphincter. this prevents more release of substances into the duodenum from the stomach
What happens to stomach motility during fasting/ interdigestive states?
Motilin is released, which stimulates the migrating motor complex (MMC). This is a peristaltic wave that moves down the stomach to empty contents into the duodenum, and can empty those >2mm
What is a gastric ulcer?
Break in the muscosa of the stomach >5mm in diameter and penetrating to the muscularis mucosa
How might a gastric ulcer appear histologically?
Can see an ulcer base with clear margins deep into muscularis mucosa layer. The submucosa also willl have fibrosis and thickened blood vessels
Where are gastric and duodenal ulcers most common?
Gastric = lesser curvature
Duodenal = first part, just after pyloric sphincter (most common GI ulcer)