GI physiology- gastric acid secretion Flashcards
What are the functions of the stomach
Stores food for 2-4 hours.
Secretes gastric juice
Allows controlled emptying of stomach contents into the small intestine.
What are the major anatomical regions of the stomach
Fundus: part of the stomach that extends above the cardiac orifice. Stores food and can expand. Linked to the oesophagus. Muscle layer in this region is thin,
and provides weak contraction.
Body: mid-portion of the stomach. Stores food and can expand. It is the major
site of exocrine secretion.
o Rugae: internal folds that allow expansion of the stomach from 50 ml
to 2 litres.
Pyloric antrum: opening to the body of the stomach. Mixes and churns food
due to strong muscular contractions. The pyloric sphincter can contract and
relax to control flow to the duodenum. Mostly endocrine secretions.
Describe the histology of gastric glands
The surface epithelium of the gastric mucosa is simple columnar, composed almost entirely of
mucous cells, which produce a protective alkaline fluid containing mucus.
There are 100 gastric pits per mm2 of the mucosa, occupying 50% of the total surface.
Describe the structure of the gastric exocrine glands
Found in the body of the stomach.
Has a different population of cells to those found in the pyloric antrum.
Surface mucous cell: located at the surface of the epithelium and secretes mucous and a
bicarbonate-rich secretion which protects against HCl.
Parietal cell: predominant cell type which is responsible for secreting HCl and intrinsic factor.
Enterochromaffin-like cell: secrete histamine which acts as a paracrine hormone to regulate
acid secretion by the parietal cells.
Chief cell: found deep within the gastric gland and secretes pepsinogen (inactive form of
pepsin).
Describe the structure of the pyloric gland (endocrine gland)
Surface mucous cell: located at the surface of the epithelium and secretes mucous and a
bicarbonate-rich secretion which protects against HCl.
Mucous neck cell: more abundant in the pyloric gland. Secrete mucous that is distinctly
different to that produced elsewhere and its function is not known.
G cell: glands responsible for endocrine secretion. Enteroendocrine cell secretes gastrin
which can act as an endocrine or paracrine hormone, increasing the production of HCl from
parietal cells.
D cell: secrete somatostatin which inhibits HCl secretion by parietal cells.
Describe the composition of gastric secretions
2-3 litre of gastric secretion per day.
Isotonic with a pH of 2-3
𝐇𝐂𝐥: kills bacteria, denatures dietary protein, activates pepsinogen, cofactor for
pepsin action.
Pepsin: initiates protein digestion.
Intrinsic factor: essential for vitamin B12 uptake in the lower ileum.
Explain how HCl is released in the parietal cell
During the fasting state, acid secretion is low and pH remains low (2-3).
After feeding, the physical presence of a meal dilutes part of the HCl to pH 4
This increases the rate of HCl secretion.
The pH within the gastric lumen decreases and plateaus within 3 hours.
Feedback mechanisms reduce the rate of acid secretion as the pH falls again
Low [H+] in the plasma (basal pole).
High [H+] in the lumen of the stomach (apical pole).
CO2 diffuses across the basal pole of the parietal cell,
and undergoes a reaction with water that is catalysed
by carbonic anhydrase. CO2 + H2O → H2CO3 → H+ +
HCO3−
H
+ pumped across the canaliculi membrane by the
H+/K+ ATPase pump, and K+ brought into the cell.
K+ is recycled by a K+ channel.
The HCO3− generated by carbonic anhydrase is pumped out of the basal pole in exchange for Cl− by the anionic exchanger
(AE2).
An alkaline tide is generated to exchange bicarbonate and prevent alkalisation of the basal cell.
Cl− exits through a Cl− channel into the lumen.
The proton pump can be inhibited by omeprazole to prevent hypersecretion of HCl.
What subcellular changes can occur in the parietal cell during acid secretion
The cytoplasm of unstimulated cells is filled with an elaborate branching system of tubular structures derived from the endoplasmic
reticulum. These are lined by microvilli, which possess the apparatus
required for H+ secretion.
When the parietal cells are stimulated to secrete by food entering the
stomach, the tubular structures fuse to form deep invaginations of the
apical membrane. These invaginations are known as secretory
canaliculi.
The formation of canaliculi results in a large (more than 10-fold)
increase in the surface area of the parietal cell membrane and brigs large numbers of [H
+] pumping sites into close
proximity with the luminal fluid.
How is pepsinogen released and activated
Activation of chief cells causes the release of pepsinogen which is held within
zymogen granules to protect the cell from the action of proteolytic enzymes.
40 amino acid pro-peptide on the catalytic site of pepsinogen needs to be
cleaved off at a low pH.
Activation of parietal cell causes the release of HCl which activates pepsinogen
at pH < 3.
What is the function of pepsin
Endopeptidase that initiates protein digestion.
Responsible for 15% of protein digestion.
pH < 2 is required for optimum proteolytic activity.
What is the role of intrinsic factor
Glycoprotein secreted by parietal cells.
It forms a complex with vitamin B12 (cobalamin) in the upper small intestine, which protects it from enzymatic digestion.
Only gastric secretion essential for life.
Absence of intrinsic factor causes pernicious anaemia.
How is Vitamin B12 absorbed
Ingestion of protein is broken down and vitamin B12 is released.
Intrinsic factor released by parietal cells within the stomach.
Intrinsic factor binds to vitamin B12 to prevent enzymatic degradation.
The complex moves through the small intestine to the terminal ileum.
Receptors on enterocytes mediate endocytosis (receptor mediated endocytosis) of the
complex.
Once inside the cell, intrinsic factor is broken down (and then excreted in faeces) and only
vitamin B12 is transported across the basal cell which binds to B12 binding protein in the
blood.
Complex is delivered to the liver by the blood where vitamin B12 can be stored for 3 years
Describe the nervous control behind gastric secretion (autonomic, endocrine and paracrine)
- Autonomic control
Sympathetic: innervates blood vessels ad gastric glands but no major control over secretion.
Parasympathetic: vagal stimulation increases secretion via direct and indirect mechanisms (HCl production, pepsinogen
release, gastrin release, mucous release, gastric smooth muscle contraction).
Enteric: submucosal and myenteric plexus increases secretion. - Endocrine control
Gastrin is the main endocrine hormone that promotes gastric secretion.
It increases: HCl production, pepsinogen release and mucous release.
Other functions of gastrin:
o Maintenance of gastric mucosal structure: promotes maturation of parietal cells and increases generation of new
epithelium within the gastric lining.
o Increases motility of GI smooth muscle (same effect as parasympathetic): activation of the pyloric sphincter. - Paracrine
Activation of the enteric neurons release ACh which increases the secretion of
HCl.
Gastrin released from G-cells:
o Endocrine effect: directly increase HCl secretion from parietal cells.
o Paracrine effect: causes the release of histamine from
enterochromaffin like cells (ECL). Histamine has a paracrine effect
which increases parietal cell HCl secretion.
If HCl secretion is too high, this then feeds back and causes the release of
somatostatin from somatostatin releasing cells (SRC). This leads to a paracrine
or endocrine effect which inhibits HCl secretion.
Describe the 3 phases of gastric secretion- cephalic, gastric and intestinal
- Cephalic phase (35% of total secretion)
Takes place before food enters the stomach and is triggered by the anticipation of food, its sight, smell and taste.
The relative contribution of the cephalic phase to overall gastric secretion is highly variable.
Signals originating in the cerebral cortex (or in the appetite centres of the amygdala and hypothalamus) are relayed to the
stomach via efferent fibres whose cell bodies lie within the dorsal motor nuclei of the vagus nerve.
Short duration
Function: Prepares stomach for receiving food.
Stimuli Anticipation of food, sight, smell and taste of food.
Components :Direct: vagal stimulation and activation of submucosal plexus.
Indirect: release of gastrin from G cells.
Gastric phase:
Occurs when food enters the stomach.
Initiates pepsinogen and mucus production.
Activated by distension of the stomach wall and the chemical content of the food. Distension activates mechanoreceptors
and initiates both local (short-loop) myenteric reflexes and long-loop vago-vagal reflexes. Both reflexes lead to the secretion
of ACh which stimulates output of gastric juice by the secretory cells of the stomach.
Long duration
Function: Homogenise and acidify chyme.
Initiate digestion of proteins by pepsin.
Stimuli: Distension of the stomach wall.
Elevated pH, peptides and amino acids from food.
Components: Distension initiates vago-vagal and enteric reflexes causing direct and indirect effects on parietal cells.
Peptides cause secretion of gastrin.
Intestinal phase (5% of total digestion)
Occurs when chyme enters the duodenum. This is believed to be due to the secretion of gastrin from G cells in the duodenal
mucosa, which encourages the gastric glands to continue secreting.
Long duration
Largely hormonal: secretin, cholecystokinin, gastric inhibitory peptide.
Function: Controls the rate of chyme entry into the duodenum.
Stimuli: Duodenal stretch
Presence of lipids and CHO and decreased pH.
Components: Initial, short lived, stimulation of gastric secretion caused by gastrin release in response to peptides in chyme.
Release of CCK and secretin have an inhibitory effect on acid secretion and gastric emptying.
Explain why the stomach doesn’t digest itself
The gastric mucosal barrier protects the stomach from the corrosively acidic gastric juice and proteases.
o Tight junctions between the cells of the mucosal epithelium prevents gastric juice from leaking to underlying
tissue.
o Mucus (secreted by surface epithelial cells and neck cells of the gastric glands) adheres to the gastric mucosa and
forms a protective layer (5 −200 μm thick). This is alkaline because the surface epithelial cells secrete a watery
fluid rich in bicarbonate and potassium ions. Unstirred water layer.
o Prostaglandins (particularly those of the E series) increase the thickness of the mucus gel layer, stimulate the production of bicarbonate and cause vasodilation of the microvasculature of the mucosa. This improves nutrient supply to damaged areas of mucosa while the increased bicarbonate content of the fluid neutralises the gastric
acid.
Effectiveness of the mucosal barrier is reduced by:
o Aspirin
o Helicobacter pylori leads to gastritis and ulceration.
Effectiveness of the mucosal barrier is increased by:
o Local factors that promote prostaglandin release.
