Regulation And Disorders Of Gastric Secretion Flashcards
Describe the stomach (anatomically), and what each part of it secretes.
It is made up of a fundus, body, antrum, and pylorus.
FUNDUS: has glands that secrete pepsinogen, mucus, and acid
CARDIAC-AREA: mucus-secreting
PYLORIC-AREA: mucus-secreting
BODY: contains chief cells (pepsinogen-secreting) and parietal cells (intrinsic factor-secreting)
ANTRUM: secretes mucus, pepsinogen and gastrin
[the cardiac area of the stomach is where the contents of the oesophagus enter the stomach]
How is gastric acid made in the stomach lumen?
HCO3- is exchanged for Cl- in the blood, decreasing the acidity of the venous blood from the stomach compared to the blood serving it.
The excess Cl- diffuses into the stomach through chloride channels as the H+ is pumped into the stomach lumen (K+/H+ ATPase pumps H+ out of the stomach lumen).
The net effect is the net flow of H+ and Cl- out of the parietal cells and into the stomach lumen.
List some gastric secretions and their functions.
MUCUS: alkaline, thick and sticky; increased HCO3-; forms a water-insoluble gel on epithelial surfaces, protecting against H+ secretion
RENNIN: curdles milk into casein clots (particularly in children)
LIPASE: converts triglycerides into fatty acids and glycerol
INTRINSIC FACTOR: aids in the absorption of Vit B12, preventing pernicious anaemia
HCL: kills bacteria; acid denaturation of digested food; activates pepsinogen (for protein digestion)
What are the two different ways in which we can control HCl secretion?
DIRECTLY: In the direct pathway, ACh, gastrin and histamine stimulate the parietal cell directly, triggering the secretion of H+ into the lumen.
INDIRECTLY: In the indirect pathway, ACh and gastrin also stimulate the ECL cells, resulting in the secretion of histamine. Histamine then acts on the parietal cell.
What are the three phases of digestion?
1) Cephalic
2) Gastric
3) Intestinal
Describe acid secretion regulation during the cephalic phase.
During the cephalic phase, smell, sight, taste, chewing, etc. stimulate ACh release.
The ACh stimulates histamine release from ECL cells. The ACh also acts directly on the parietal cells, stimulating HCl secretion.
Acid secretion decreases as the acidity of the lumen increase.
Explain why.
Acid can be damaging, so we need a way to regulate and curtail (decrease) HCl release. We do this by HCL-stimulating somatostatin-releasing cells (D cells).
Somatostatin inhibits ECL and G-cells to curtail the hypersecretion of acid.
Describe acid secretion regulation during the gastric phase.
During the gastric phase, increased distention of the stomach increases peptide concentration, which increases the acidity of the stomach.
The combination of H+ and proteins decreases the [H+]. By acting as a buffer, the proteins remove the inhibitory powers of HCl on gastric secretion and, hence, acid secretion.
This then increases gastrin-mediated acid secretion.
Describe acid secretion regulation during the intestinal phase.
During the intestinal phase, there is a balance of the secretory activity of the stomach and the digestive and absorptive capacities of the small intestine.
The high acidity of the duodenal contents reflexly inhibits acid secretion (since the increased acidity would inhibit the activity of digestive enzymes, bicarbonate and bile salts).
The distention of the duodenum, a hypertonic solution (indicating that the food has already been digested), amino acids, fatty acids, and monosaccharides all inhibit acid secretion.
Thus, the inhibition of acid secretion in the small intestine depends on:
-the composition of the cyme
-the volume of the chyme
How is acid secretion inhibited during the intestinal phase?
Short (within the ENS) and long (vagal) neuronal reflexes and hormones (enterogastrones) inhibit acid secretion by the parietal cells or gastrin secretion by the G cells, which is inhibited by somatostatin.
Increased sympathetic discharge is inhibitory.
Decreased parasympathetic discharge is stimulatory.
List some HCl secretion stimulants or factors that increase HCl secretion.
histamine
acetylcholine
gastrin
caffeine
alcohol
NSAIDs
nicotine
H. Pylori
Zollinger-Ellison Syndrome
hyperparathyroidism
stress
[HCl] can reach 150 mM. What does this depend on?
rate of secretion
amount of buffering provided by the resting juice
composition of the ingested food
gastric motility
rate of gastric emptying
amount of diffusion back into the mucosa
In what ways is HCl essential for life?
defence
protein digestion: activates pepsinogen to pepsin
stimulates flow of bile and pancreatic juice
A lack of HCl causes the failure of protein digestion (achlorhydria or hypochlorhydria = when the production of gastric acid in the stomach is low or absent).
What stimulates the secretion of pepsinogen?
There are parallels between acid secretion and pepsinogen secretion. The stimulators/inhibitors of acid secretion during the cephalic and intestinal phases exert the same effect on pepsinogen secretion.
Pepsin is secreted by chief cells in the form of pepsinogen (zymogen). It becomes activated if [H+] is high; the shape of the enzyme is altered by the high acidity which exposes its active site.
It is inactivated upon entry of food in the small intestine (HCO3- and peptides neutralise the H+).
What is the point of pepsin secretion?
It initiates the digestion of proteins by degrading food proteins into peptides. However, it is not required for food digestion.
There are other enzymes that can digest proteins, such as trypsin, chymotrypsin and elastases.
What are some symptoms of HCl deficiency?
presence of undigested food in the stool
flatulence and bloating
white spots on fingernails (?)
drowsiness after meals (?)
lack of intrinsic factor
increased chances of H. Pylori infection
What would be the treatment of HCl deficiency?
bitter herbs may stimulate HCl secretion
dandelions, devil’s claw, yarrow and wormwood teas may be useful
lemon juice and vinegar stimulate HCl secretion
Vit B1 stimulates HCl secretion by the stomach
How do NSAIDs (e.g. aspirin) play a role in gastric acid secretion disorders?
NSAIDs cause the topical irritation of the gut.
They impair the barrier properties of the mucosa by suppressing gastric prostaglandin synthesis. They also decrease gastric mucosal blood flow and inhibit platelet aggregation, both interfering with the repair of superficial injury.
The presence of acid in the stomach promotes NSAID-mediated gastric disorders.
It impairs the restitution (healing) process. It also inactivates FGF (fibroblast growth factor), which interferes with the haemostasis process.
Describe the mechanism of peptic (gastric or duodenal) ulcer formation.
The breakage of the mucosal barrier causes an imbalance between protective and damaging factors.
This exposes the tissues to the erosive effects of HCl and pepsin.
10% of the population is affected by ulcers. The sites where you’d be affected are the oesophagus, stomach and duodenum.
List some factors predisposing to peptic ulceration.
H. Pylori
smoking
genetic factors
stress
NSAIDs
List some factors that prevent the infection of the gastric mucosa.
HCl, pepsin
mucus production
peristalsis and fluid movement
seamless epithelium with tight junctions
fast cell turnover
IgA secretion at mucosal surfaces
Peyer’s Patches
List some protective factors that prevent the autodigestion of the stomach.
secretion of alkaline mucus and HCO3-
protein content of food
presence of tight junctions between epithelial cells lining the stomach and fibrin coat
replacement of damaged cells within the gastric pits
prostaglandins (E and I): inhibit acid secretion and enhance blood flow
Describe H. Pylori.
It is a gram-negative, spiral-shaped (can be coccoid too) aerobic bacterium.
It penetrates the gastric mucosa (it is able to survive the harsh conditions of the stomach). It is highly pathogenic, with many virulence factors.
List some virulence factors of H. Pylori.
motility: flagella, moves close to the epithelium
produces urease (which converts urea to ammonia, which buffers gastric acid and produces CO2)
cytotoxin-associated antigen (CagA): inserts pathogenicity islands and confers ulcer-forming potential; causes apoptosis of cells and affects tight junctions
vacuolating toxin A (VacA): alters the trafficking of intracellular proteins in gastric cells
