What are the functions of the stomach?
- Stores food
- Disinfects food
- Breaks food down in chyme
How does the stomach break food down into chyme?
- Chemical disruption
- Physical disruption
Where do stomach secretions come from?
What are gastric pits?
Indentations in the stomach mucosa that are openings to gastric glands
What do gastric pits contain?
What do gastric glands contain?
Parietal, Chief, and G-cells, along with smooth muscle cells
Label this diagram
- A - Gastric pit (opening to gastric gland)
- B - Mucous epithelium
- C - Lymphatic vessel
- D - Lamina propria
- E - Muscularis mucosae
- F - Submucosa
- G - Oblique muscle
- H - Circular muscle
- I - Longitudinal muscle
- J - Serosa
- K - Artery and vein
- L - Myenteric plexus
- M - Gastric pit
- N - Gastric gland
- O - Mucous cells
- P - Neck
- Q - Parietal cells
- R - Chief cells
- S - Smooth muscle cells
- T - G cell
What substances are secreted by the stomach?
- Hydrochloric acid
- Proteolytic enzymes
What proteolytic enzyme is secreted by the stomach?
What is the cellular origin of hydrochloric acid in the stomach?
Parietal (oxyntic) cells
What is the purpose of HCl secreted by the stomach?
Acid keeps luminal pH < 2
What is the cellular origin of proteolytic enzymes in the stomach?
What is the function of proteolytic enzymes in the stomach?
Non-specifically breaks down proteins to peptides
What is the cellular origin of mucus in the stomach?
Neck cells (surface cells)
What are the characteristics of stomach mucus?
Why is stomach mucus sticky?
So it is not removed easily from the stomach lining
Why is stomach mucus basic?
Due to amine groups on proteins
What is the cellular origin of HCO3- in the stomach?
Neck cells (surface cells)
What is the purpose of HCO3- in the stomach?
Provides a buffer for H+ ions
Where is HCO3- secreted by neck cells into?
What is the cellular origin of gastrin?
What is the function of gastrin in the stomach?
Binds to surface receptor on parietal cell, stimulating acid and intrinsic factor
Are body fluids acid or alkaline?
Most are slightly alkaline
What must be true for a slightly alkaline body fluid to secrete H+ ions?
It must be created in large quantities
Where does the production of a large amount of body fluid with the intent of secreting H+ occur?
In the mitochondria of parietal cells
How is H+ produced in parietal cells?
By splitting water into H+ and OH- ions
What happens to OH- ions produced from the splitting of water in parietal cells?
They combine with CO2 from metabolsim to from HCO3-, which is exported to the blood
How much HCO3- enters the blood for every mole of H+ secreted into the stomach?
What allows parietal cells to produce H+ at a high rate?
They have lots of mitochondria
Can the ions produced in the mitochondria of parietal cells accumulate in the cell?
How is the problem of the ions produced by parietal cells being unable to accumulate overcome?
Parietal cells have invaginations in their cell walls called canaliculi
What do canaliculi possess that are required for their function?
What do the proton pumps in canaliculi do?
Expel H+ from parietal cells up a high concentration gradient
What is the result of the concentration gradient canaliculi are pumping against being very high?
This is a very energy intensive process
What are the proton pumps in canaliculi a key target for?
Why are the proton pumps in canaliculi a key target for drug action?
Because if inhibited, they will reduce the amount of acid in the stomach
Draw a diagram illustrating the mechanism of secretion of stomach acid
What controls gastric acid secretion?
A complex of neural and endocrine systems
What stimulates parietal cells?
How do acetylcholine, gastrin, and histamine act to control parietal cells?
They act via seperate receptors to promote acid secretion
What is Ach released from?
Postganglionic parasympathetic neurones
What stimulates the release of Ach from postganglionic parasympathetic neurones in the stomach?
Gastric distention as food arrives
What receptors does Ach act on in parietal cells?
What releases gastrin?
Endocrine cells in the stomach, G-cells
What kind of molecule is gastrin?
A 17-aa polypeptide
What does gastrin bind to?
Surface receptors in parietal cells
What stimulates gastrin secretion?
The presence of peptides and Ach from intrinsic neurones
What inhibits gastrin secretion?
Low pH in the stomach
What does the inhibition of gastrin by low pH in the stomach act as?
What releases histamine?
What happens to histamine once released?
It diffuses locally to bind to H2 receptors on parietal cells
How does histamine stimulate acid secretion?
What does histamine work as?
Why does histamine work as an amplifier?
Gastrin and Ach stimulate mast cells
What are the phases of gastric secretion?
- Cephalic phase
- Gastric phase
- Intestinal phase
What is the cephalic phase led by?
What happens in the cephalic phase?
The sight and smell of food, and the act of swallowing, activates the parasympathetic nervous system, which stimulates the release of Ach
What is the effect of the release of Ach in the cephalic phase?
It stimulates parietal cells directly and via histamine, increasing stomach acid
What happens in the gastric phase?
- Once food reaches the stomach, it causes distension, further stimulating Ach release, and subsequently parietal cells, increasing acid
- The arrival of food will also buffer the small amount of stomach acid in the stomach in between meals, causing luminal pH to rise. This disinhibits gastrin, increasing acid
- Acid and enzymes will then act on proteins to produce peptides, further stimulating gastrin release as the pH falls and the initial disinhibition is removed, increasing acid
What happens in the intestinal phase?
- Once chyme leaves the stomach in significant quantities, it stimulates the release of the hormones cholecystokinin and gastric inhibitory polypeptide from the intestines that antagonise gastrin, decreasing acid
- Coupled with this, the small amount of acid left in the stomach is no longer being buffered by food, and the low pH inhibits gastrin, decreasing acid
What is the clinical relevance of the low pH of the stomach between meals?
It can aggravate ulcers
What is the result of the low pH of the stomach between meals aggrevating ulcers?
Pain from ulcers is particuarly bad at night
What drugs may inhibit acid secretion?
- H2 receptor inhibitors
- Proton Pump Inhibitors (PPIs)
Give an example of a H2 receptor inhibitor
How does a H2 receptor inhibitor exert its effects?
Removes the amplification of gastrin / Ach signal
Give an example of a proton pump inhibitor?
How does a proton pump exert its effects?
Prevents H+ ions being pumped into parietal cell canaliculi
Why do neck cells secrete mucus?
To protect the mucosa
Why does the stomach mucosa need protection?
Because the luminal pH of the stomach is usually below 2, and without any protection, this would dissolve mucosa
What does the mucus form in the stomach?
An 'unstirred layer' that ions cannot move through easily
What happens to H+ ions in the unstirred layer?
They slowly diffuse in and react with the basic groups on mucus, and with HCO3- that is secreted by surface epithelial cells
What is the result of the unstirred layer on HCO3-?
It means it stays close to the surface cells
What is the result of HCO3- staying close to the surface cells?
The pH at the surface cells is well above 6
What stimulates mucus and HCO3- secretion?
What are prostaglandins promoted by?
Most factors that stimulate acid secretion
What agents can breach the stomachs defences?
- H. Pylori
How does alcohol breach the stomachs defences?
It dissolves the mucus, allowing the acid to attack the stomach
How does H. Pylori breach the stomachs defences?
Surface cells become infected, inhibiting mucus/HCO3- production
How do NSAIDS breach the stomach defences?
They inhibit prostaglandins, therefore reducing defences
Why are some NSAIDS not harmful to the stomachs defences?
Some are convereted to a non-ionised form by stomach acid, allowing them to pass through the mucus layer into cells before they re-ionise
Give an example of an NSAID that is converted to a non-ionised form by stomach acid?
What does a breach in the stomachs defences result in?
What does the treatment of peptic ulcers involve?
- Reducing acid secretion
- If present, eliminating H. Pylori with antibiotics
What happens in receptive relaxation?
As food travels down the oesophagus, a neural reflex carried out by the vagus nerve triggers the relaxation of the muscle in the stomach's wall
What is the purpose of receptive relaxation?
Prevents the pressure from increasing, so pressure in the stomach doesn't increase as it fills
Why is it important that the pressure in the stomach doesn't increase as it fills?
- Limits reflex
- Allows us to consume large meals
When can receptive relaxation not occur?
If there is damage to the vagus nerve
What kind of muscle does the stomach have?
Longitudinal and circular
What drives the muscle in the stomach?
Where is the pacemaker that drives the stomach located?
In the cardiac region
How often does the stomach pacemaker fire?
~3 times a minute
What does the firing of the stomachs pacemaker cause?
Regular, accelerating peristalic contractions from the cardia to the pylorus
What is the action of the stomachs pacemaker combined with to exert its effects?
The stomach's funnel shape
What is the result of the stomachs funnel shape and the firing of its pacemaker?
It mixes the contents of the stomach and moves liquid chyme into the pyloric region
When does the movement of liquid chyme into the pyloric region occur?
As the accelerating peristaltic wave overtakes larger lumps
What happens to larger lumps when the accelerating peristaltic wave overtakes them?
They are driven back into the fundus
What happens to chyme as the peristaltic wave overtakes large lumps?
It is decanted into the pyloric region
What is the oveall effect of the accelerating, rhymtic, peristaltic contraction of the stomach?
It moves solid lumps backwards into the fundus of the stomach, whilst letting liquid chyme move forwards
What happens as chyme enters the pyloric region?
A small squirt is ejected before the peristaltic wave reaches the pylorus and shuts it, so the rest of the chyme returns to the stomach
How many squirts of chyme are ejected a minute?
3, the same as the number of peristaltic waves
What is the volume of chyme squirted out affected by?
- The rate of acceleration of peristaltic wave
- Hormones from the intestine
What slows gastric emptying?