Gastrointestinal System

Stomach Physiology

Function of Stomach

Temporary storage of food input.

The stomach converts the episodic input of food from the oesophagus into a more continuous output of chyme into the duodenum.

The fundus and body (i.e. the proximal stomach) act as a reservoir. Their walls are highly distensible and there is little increase in intra-gastric pressure until the stomach volume exceeds a litre.

This adaptation is the result of a vagal reflex initiated by stretch receptors in the oesophagus (‘receptive relaxation’) and as a consequence of the presence of food in the proximal stomach (‘adaptive relaxation’). It involves the release of the inhibitory neurotransmitters vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) from the enteric nervous system.

When empty, the stomach has a volume of about 50 ml but it can expand to hold 4 litres. Its contractile characteristics when it contains food (the ‘fed’ state) are different to those when it is empty (the ‘fasted’ state).

Mechanical breakdown of food into smaller particles.
Chemical digestion with breakdown of proteins.
Secretion of intrinsic factor, vital for vitamin B12 absorption.
Regulation of output of chyme into the duodenum.

Lower Oesophageal Sphincter

Swallowed food enters the stomach after passing through the lower oesophageal sphincter (LOS). This is a physiological sphincter (so cannot be defined anatomically), formed by the tonic contraction of the circular muscle of the lowest 2–4 cm of the oesophagus. The LOS is normally closed with a pressure 15–25 mmHg above gastric pressure. This barrier pressure is maintained when intra-gastric pressure rises.

On swallowing the LOS begins to relax. This is mediated by the inhibitory neurotransmitters vasoactive intestinal polypeptide (VIP) and nitric oxide (NO). When the peristaltic wave arrives, the food bolus is able to pass into the stomach. It then regains its tone.

LOS Tone

The LOS is the most important mechanism in preventing gastric contents refluxing into the oesophagus. Its tone is affected by various factors.

Other mechanisms may contribute, including:

The acute angle at which the oesophagus joins the stomach

The passage of the oesophagus through the crura of the diaphragm

Stomach Contents

The volume and pH of stomach contents are determined by oral intake, gastric juice and gastric emptying.

Gastric juice consists of the secretions of the gastric gland cells which secrete into the gastric lumen. It includes:

Hydrochloric Acid

Hydrochloric acid is secreted into the gastric lumen from the apical surface of parietal cells.

On the basolateral membrane of these cells are receptors for gastrin, acetylcholine and histamine (H2). Binding of these substances increases acid production by activating second messengers which increase protein phosphorylation and hence activation of an H+/K+ ATPase.

Water (H2O) and carbon dioxide (CO2) from cellular metabolism form carbonic acid (H2CO3)
This then dissociates into hydrogen ions (H+) and bicarbonate (HCO3−)
Hydrogen is pumped out of the cell by the proton pump on the apical membrane in exchange for potassium (K+) (Fig 1c)
Bicarbonate is exchanged for extracellular chloride ions (Cl−) across the basolateral membrane
Chloride leaves the parietal cell with potassium ions across the apical membrane
Potassium ions are then exchanged for intracellular H+ by the H+/K+ ATPase proton pump
Thus hydrochloric acid is secreted by the parietal cells’ apical membrane in association with an alkaline tide from the basolateral membrane.

Functions of Gastric Acid:

Facilitates the breakdown of protein
Activates inactive pepsinogens to pepsins
Provides optimal conditions for pepsin activity
Improves solubility and hence absorption of calcium and iron
Kills pathogenic micro-organisms

Pepsinogens

Pepsin is a collection of proteolytic enzymes which facilitates protein digestion. It is stored as an inactive precursor (pepsinogen) in membrane-bound zymogen granules in the chief cells. After secretion it is converted to active pepsin in the acidic environment of the stomach. Pepsins hydrolyze peptide bonds within the protein molecules, producing polypeptides and amino acids. Their maximal proteolytic activity occurs at a pH less than three.

Release of pepsin is stimulated by:

Vagal stimulation
Acid pH
Gastrin
Secretin (from duodenum)
β stimulation

Mucus

Gastric mucus ensures that the stomach doesn’t digest itself. It protects the mucosa from auto-digestion by the strong acid and proteolytic enzymes and also from mechanical stresses resulting from the muscular grinding. It is secreted by the mucus neck cells at the openings of the gastric pits and by the surface epithelial cells and forms a layer up to 200 μm thick. The surface epithelial cells secrete a watery fluid, rich in bicarbonate, which creates a pH gradient − the mucosa is at a neutral pH while the stomach contents are at pH 2.

Production of mucus is stimulated by vagal stimulation, gastrin and prostaglandins E2 and I2. These prostaglandins are synthesised by the gastric mucosa. They also stimulate the secretion of bicarbonate and increase mucosal blood flow, and so have a cytoprotective effect.

The alkaline mucus and the tight junctions between the epithelial cells form the mucosal barrier. This prevents gastric juice from leaking into the walls of the stomach. If this occurs, the underlying tissues become inflamed and the patient develops gastritis

Peptic ulceration occurs when either the mucosal resistance is reduced and/or gastric acid secretion is increased. Most ulcers are associated with the presence of Helicobacter pylori, a gram-negative rod bacterium found deep in the mucus layer where the neutral pH is optimal for its growth. It is associated with a sustained increase in gastrin release (and consequently hypersecretion of acid) and production of ammonia, which causes cell damage.

Intrinsic Factor

Intrinsic factor is a glycoprotein secreted by the parietal cells into the stomach lumen in response to the same stimuli that promote acid secretion. It is essential for the absorption of ingested vitamin B12 (cobalamin). It binds the vitamin in the stomach and protects it from enzymatic destruction during its passage through the gut. The complex of intrinsic factor and vitamin B12 is then absorbed in the terminal ileum.

Vitamin B12 deficiency causes a megaloblastic anaemia

Following a total gastrectomy, anaemia is more likely to be due to iron deficiency (as a consequence of reduced absorption of iron because of the loss of the acidic environment) than to vitamin B12 deficiency (due to the absence of intrinsic factor).

Gastrin

Gastrin is produced by G cells, which are found in the gastric glands in the antrum of the stomach and in the duodenum. Unlike the other gastric secretions, it is not a constituent of gastric juice: rather, it is a hormone and is released into the bloodstream in response to vagal stimulation, distension of the antrum or duodenum, and the presence of amino acids and peptides.

It is a powerful stimulus for the release of gastric acid and also causes the release of enzymes and mucus from the gastric glands. It increases gastric and gut motility and regulates mucosal growth.

Gastrin release is inhibited by gastric acidity and secretin (release of which is stimulated by duodenal acidity).

Water

Electrolytes, particularly K+, Cl−

It has a pH of 1–1.5 and the stomach produces about 2 litres a day. There are other secreting cells in the gastric glands, the entero-endocrine cells. These produce hormones that reach their effector sites via the bloodstream (e.g. gastrin from G cells, somatostatin from D cells).

Phases of Secretion

During fasting there is little or no secretion of gastric juice and the stomach contains only about 30 ml of fluid.

With the ingestion of food the rate of secretion of the glands increases and the composition of gastric juice varies. This is considered to occur in three phases (cephalic, gastric and intestinal) although the timing and mechanisms of these phases overlaps.

The cephalic phase
The gastric phase
The intestinal phase

Gastric Emptying

Stomach emptying occurs when the pressure generated by the antral pump exceeds the resistance of the pyloric sphincter. Antral pump activity is increased by gastric distension (mediated by vagal reflexes). In general, gastric emptying occurs at a rate proportional to the volume of the stomach – the fuller the stomach, the more rapidly it empties. The speed of emptying for liquids or contents consisting of smaller particles is faster than for solids.

Thus, in the normal stomach, 95% of an ingested clear liquid reaches the duodenum within an hour and 50% of a meal will pass the pylorus in two hours.