Session 4 Flashcards
Describe the functions of the stomach
[*] Food is ingested faster than it can be digested
[*] The stomach stores food whilst subjecting it to preliminary physical (via motility) and chemical disruption (via acid and enzymes) to form chyme (a semi liquid suspension of food), which is then delivered at a controlled rate to the intestines
[*] This is achieved by a complex of secretion and specialized motility. The stomach secretes acid and enzymes (mostly proteolytic), generating a luminal environment very hostile to biological material so the stomach mucosa must be protected by further secretion of mucus and alkali.
Describe the components of gastric secretion and their cellular origins
[*] Stomach secretions come from Gastric Pits, indentations in the stomach mucosa that are the openings to gastric glands.
[*] Gastric pits contain Neck cells, and gastric glands containing Parietal, Chief and G-cells along with smooth muscle cells
[*] The luminal pH is normally below 2.0, with a concentration of up to 100mmol/L of Hydrochloric acid; this is secreted by the parietal (oxyntic) cells located in the gastric pits. Parietal cells are triangular truncated.
[*] At the same time the chief cells in the gastric pits secrete enzymes, in particular pepsin, in the form of an inactive precursor pepsinogen, which is cleaved by acid in the stomach into its active form. Pepsin non-specifically breaks down proteins => peptides.
[*] Neck Cell secrete mucus which is sticky and so is not easily removed from the stomach lining and basic, due to amine groups on proteins. Neck cells also secrete HCO3- into the mucus, providing a buffer for H+ ions.
[*] G-cells (endocrine cells) secrete Gastrin which binds to surface receptors on parietal cells, stimulating acid and intrinsic factor.
Explain the mechanism of secretion of stomach acid
[*] Most body fluids are slightly alkaline so if H+ ions are to be secreted, they must be first created in quantity. This happens at numerous mitochondria in parietal cells by, in effect, splitting water, which also generates OH- which then combines with CO2 from metabolism to form HCO3-, which is exported to the blood.
[*] Every mole of H+ secreted into the stomach results in 1 mol of HCO3- entering the blood ‘the alkaline tide’. This is subsequently re-secreted into the GI tract by the pancreas and liver to neutralize the acid as it leaves the stomach.
[*] Parietal cells have lots of mitochondria, allowing them to produce H+ at a high rate. However these cannot accumulate in cells so to overcome this problem, the H+ ions are concentrated by proton pumps in the walls of canaliculi which invaginate the luminal surface of parietal cells and carry the concentrated acid into the stomach contents through the gastric pits.
- The proton pumps in the canaliculi expel H+ from parietal cells up a high concentration gradient. As the concentration gradient is high, this is a very energy intensive process
- The proton pumps in canaliculi are a key target for drug action, as if inhibited they will reduce the amount of acid in the stomach.
Outline the control of gastric acid secretion
Acid and enzyme secretion is controlled by a complex of neural and endocrine systems. Parietal cells are stimulated by ACh (Acetylcholine), Gastrin and Histamine which act through separate receptors to promote acid secretion.
Explain about Acetyline control over gastric acid secretion
Acetylcholine is released from post ganglionic, parasympathetic nerves, stimulated by gastric distension as food arrives and acts upon the muscarinic receptors on parietal cells and stimulates acid secretion by second messenger pathway.
Explain about Gastrin secretion
Gastrin is released from endocrine cells, G-cells, in the stomach. It is a (17aa) polypeptide from the Gastrin/CCK family. Gastrin binds to surface receptors on parietal cells. These G-cells are stimulated by amino acids and peptides in the stomach content, but inhibited by low pH (‘feedback’ control). Gastrin secretion is also stimulated by ACh from intrinsic neurones. Gastrin stimulates acid and intrinsic factor (important in the absorption of Vitamin B12 => could lead to anaemia if absent) secretion via second messenger pathway.
Factors affecting Gastrin Secretion:
- Stimulated by: peptides, acetyl choline from intrinsic neurones which are stimulated by physical stretch of the stomach and ACh also acts directly on parietal cells)
- Inhibited by: low pH in stomach – negative‘feedback’ control.
Explain about Histamine secretion
Histamine is released from mast cells which surround parietal cells, and diffuses locally to parietal cells, where it acts via H2 surface receptors (which are almost exclusive to the stomach). Acid secretion is then stimulated by cAMP. Histamine release is stimulated by both Gastrin and Acetylcholine so it AMPLIFIES their action. H2 receptors are uncommon, so antagonists are good at reducing acid secretion.
What are the 3 phases of gastric secretion?
- The sight and smell of food and the act of swallowing, activates the parasympathetic system, which stimulates the release of Acetylcholine. ACh stimulates parietal cells directly and via histamine (increases acid secretion). This is known as the Cephalic Phase. By the time food reaches the stomach, the acid is already there to begin digestion.
- Once the food reaches the stomach, its initial effect is to distend the stomach, further stimulating ACh release (and subsequently parietal cells, increasing acid secretion) and to raise the luminal pH of the stomach contents by buffering the relatively small amount of acid present between meals. The rise in pH DISINHIBITS gastrin secretion (increases acid secretion). Initial digestion occurs - acid and enzymes then act to produce peptides which further stimulate gastrin release as the pH falls and the initial disinhibition is removed (increases acid secretion). Histamine release is stimulated by Gastrin and AChThis is the gastric phase.
- Once chyme leaves the stomach in significant quantities it stimulates the release of chemical hormones from the intestines (Cholecystokinin and Gastric Inhibitory Polypeptide) which reduce acid secretion by antagonising Gastrin. Coupled with this, the accumulation of acid in empty stomach (no longer being buffered by food) creates the low pH which inhibits Gastrin (decreases acid secretion). This is the Intestinal Phase.
[*] The low pH of the stomach between meals can aggravate ulcers. Because of this, pain from ulcers is particularly bad at night.
Outline the ways in which gastric acid secretion may be reduced by drugs
[*] If the defences of the stomach are damaged or overwhelmed, the acids attack cells and produce gastritis then ulceration.
[*] Defences are damaged by infection with H Pylori by excess alcohol ingestion, and by non-steroidal anti-inflammatory drugs which inhibit prostaglandin production.
[*] Acid secretion may be reduced by drugs antagonising the action of histamine at H2 receptors (e.g. cimetidine) and therefore removing the amplification of Gastrin/ACh signal, or by drugs which inhibit proton pumps e.g. Omeprazole, which prevents H+ ions being pumped into parietal cell canaliculi.
[*] Also treat ulcers by eliminating H. Pylori with antibiotics.
Describe the function of the stomach defences
[*] The neck cells of the stomach mucosa secrete a thick layer of alkaline mucus, which offers some mechanical protection and traps H+ ions diffusing into it from the stomach lumen, by reacting with HCO3- ions also produced from surface epithelial cells. This prevents the pH of the surface of the mucosa cells from falling too low.
[*] The production of defences is stimulated by prostaglandins, which are promoted by most factors that stimulate acid secretion. ‘Defences match the attack’
Explain mucus as part of the stomach’s defences
[*] Mucus is sticky, so is not easily removed from the stomach lining. It is also basic, due to amine groups on the proteins.
- The mucus forms a ‘unstirred layer’ that ions cannot move through easily. H+ ions slowly diffuse in and react with the basic groups on mucus and with HCO3- that is secreted by surface epithelial cells, underneath the mucus. hCO3- diffuses the opposite way to the H+ ions and neutralizes them to produce CO2.
- Because of the unstirred layer, HCO3- stays close to the surface cells.
- This means the pH at surface cells is well above 6. The H+ ions aren’t able to reach the cells beneath the mucus.
What breaches the stomach’s defences?
- Alcohol: dissolves the mucus, allowing the acid to attack the stomach
- H. Pylori: surface cells become infected, inhibiting mucus / HCO3- production. H. Pylori is the most common cause of ulceration in the stomach.
- NSAIDS: inhibit prostaglandins, therefore reducing defences.
- Some drugs like aspirin are converted to a non-ionised form by stomach acid, allowing them to pass through the mucus layer into cells before they re-ionise.
- If the stomach’s defences are breached, it results in gastritis and peptic ulcers.
Treatment involves reducing acid secretion and if present, eliminating H. Pylori with antibiotics
Describe the patterns of motility of the stomach, including receptive relaxation and peristalsis
[*] When food is swallowed a vagal reflex (a neural reflex carried out by the vagus nerve – via an efferent pathway) produces receptive relaxation, which causes the resting tension in the walls of the stomach to reduce (triggers relaxation of the muscle in the stomach’s wall). Food is therefore accommodated without a rise in intragastric pressure, reducing the risk of reflux of acid into the oesophagus – we can consume large meals (but not if there is damage of the vagus nerve)
[*] The full stomach begins regular peristaltic contractions, triggered by a pacemaker in the cardiac region, which drives the stomach’s longitudinal and circular muscle, about 3x a minute to break down large particles and mix with acid and enzymes.
[*] These contractions sweep over the stomach from cardia to pylorus, accelerating as they move. This combined with the funnel shape of the stomach both mixes the contents and decants liquid chyme into the pyloric region. A small squirt of chyme leaves the pylorus with each peristaltic wave before the pylorus shuts.
Describe the process of gastric emptying
[*] The wave of peristalsis initially drives all stomach content ahead of it however the wave accelerates and overtakes larger lumps as it accelerates.
[*] The accelerating, rhythmic, peristaltic contraction moves solid lumps backwards into the fundus of the stomach while letting liquid chyme move forwards. As the 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.
Describe the control of gastric emptying
[*] Gastric emptying rate is controlled by feedback from the duodenum via chemical signals so that the rate of emptying of the stomach is appropriate for further digestion and absorption – squirt volume is affected by the rate of acceleration of peristaltic wave and hormones from the intestine.
- Fats greatly slow gastric emptying as they take more time to digest and absorb.
- Low pH in the duodenum also slows gastric emptying
- Hypertonicity in the duodenum also slows gastric emptying
- Rate of stomach emptying is matched to rate of digestion
Describe the parts and curvatures of the stomach
[*] The adult stomach can hold 2 to 3 litres of food. The size and position of the stomach varies, depending upon body shape, degree of distension and posture. The stomach has 5 recognisable parts and two curvatures:
Parts:
- The cardia (around the oesophageal opening)
- The fundus (above the level of the oesophageal opening)
- The body (central portion)
- The antrum – also referred to as the pyloric antrum – lower part
- The pylorus (the most distal part)
Curvatures:
- The less curvature (forming the upper concave border)
- The greater curvature (forming the lower and longer convex border)
