Chapter 63 – Stomach and Vomiting

Abstract

Temporary storage of large meals – releasing ingested food slowly into the small intestine.

Chapter 63 Stomach and Vomiting

What are the functions of the stomach?

The stomach has a range of functions:

Temporary storage of large meals – releasing ingested food slowly into the small intestine.
Secretion of digestive enzymes – for example, gastrin.
Mixing – vigorous contraction of gastric smooth muscle helps mix and liquefy ingested food.
Secretion of gastric acid – in part to defend against ingested microorganisms.
Secretion of intrinsic factor (IF) – which aids the absorption of vitamin B₁₂.
Endocrine – secreting hormones to control gastric emptying.

Which substances are secreted by the stomach?

A total of 2 L of gastric fluid is produced by the stomach per day. There are five important substances secreted by the stomach:

Hydrochloric acid (HCl). The parietal cells secrete HCl to concentrations of up to 150 mmol/L (equivalent of a pH of 0.8). HCl secretion is increased by three stimuli:
1. – Histamine, which stimulates H₂ receptors – the most important stimulus for gastric acid secretion.
2. – Parasympathetic stimulation through the vagus nerve. Acetylcholine (ACh) acts as the neurotransmitter at muscarinic M₃ receptors.
3. – Gastrin, the least important direct stimulus of the parietal cells. However, gastrin has an important indirect effect, as it triggers histamine release from neighbouring enterochromaffin-like (ECL) cells.
Pepsinogen, a proenzyme secreted by the chief cells, is converted into pepsin by the acidic environment of the stomach. Pepsin is an important peptidase that starts the process of protein breakdown. Pepsinogen secretion is triggered by:
1. – Gastrin;
2. – Parasympathetic nervous activity through the vagus nerve.
Gastrin, a peptide hormone secreted by G cells in the stomach in response to:
1. – Parasympathetic nervous activity through the vagus nerve;
2. – Distension of the stomach;
3. – The presence of partially digested proteins in the stomach.
Gastrin has three main roles:
1. – Stimulation of parietal cells to secrete HCl, both directly and through stimulation of histamine release by the ECL cells;
2. – Stimulation of chief cells to secrete pepsinogen;
3. – Stimulation of gastric motility.
Gastrin secretion is controlled by negative feedback: high acid concentration releases somatostatin from δ cells, which inhibits further release of gastrin from G cells.
IF, a glycopeptide secreted by parietal cells. IF has an important role in vitamin B₁₂ absorption:
1. – Vitamin B₁₂ is released from ingested animal proteins as they are broken down in the stomach.
2. – In the low-pH environment of the stomach, IF has a low binding affinity for vitamin B₁₂, so very little is bound. Released vitamin B₁₂ is instead bound by haptocorrin, a vitamin B₁₂ binding protein. This protects the acid-sensitive structure of vitamin B₁₂.
3. – In the duodenum, vitamin B₁₂ is re-released as haptocorrin is digested by trypsin. In contrast, IF is resistant to trypsin.
4. – In the higher-pH environment of the duodenum, IF avidly binds vitamin B₁₂.
5. – In the terminal ileum, IF receptors allow absorption of the IF–vitamin B₁₂ complex.
In pernicious anaemia, autoimmune destruction of parietal cells leads to an IF deficiency. Vitamin B₁₂ therefore cannot be absorbed, resulting in a megaloblastic anaemia.
Mucus. Mucous cells secrete an HCO₃⁻-rich mucus that covers the gastric mucosa. It has two main roles:
1. – Protection of the gastric mucosa from the highly acidic contents of the stomach lumen;
2. – Lubrication of the stomach wall, protecting it from frictional damage due to vigorous peristalsis and mixing of partially digested food.

How do the parietal cells secrete gastric acid?

The parietal cells are triangular-shaped epithelial cells of the gastric mucosa (Figure 63.1). Key features are:

Their close proximity to ECL cells;
An extensive network of secretory canaliculi;
The H⁺/K⁺-ATPase pump;
Three stimulatory receptors: histamine H₂, ACh and gastrin;
One inhibitory receptor: somatostatin;
Carbonic anhydrase (CA) within the cell cytoplasm.

The main stimulus for the secretion of gastric acid is histamine, synthesised and stored by neighbouring ECL cells that release histamine in response to gastrin or parasympathetic stimuli. Histamine acts by increasing the cyclic AMP (cAMP) concentration within the parietal cell. Gastrin and ACh also directly stimulate the parietal cell, but to a lesser extent than histamine.

The mechanism for gastric acid secretion is:

CO₂ diffuses into the parietal cell from the blood.
CO₂ reacts with water to give H₂CO₃ in a reaction catalysed by CA.
H₂CO₃ dissociates into H⁺ and HCO₃. These ions then go their separate ways:
1. – In the apical membrane: the H⁺/K⁺-ATPase actively pumps H⁺ into the secretory canaliculi in exchange for K⁺. The H⁺/K⁺-ATPase is known as the proton pump.
2. – In the basolateral membrane: HCO₃⁻ is exchanged for Cl⁻. HCO₃⁻ enters the blood, where it causes a measurable increase in blood pH whenever gastric acid secretion is stimulated; this is referred to as the alkaline tide.
Cl⁻ diffuses down its concentration gradient through a Cl⁻ channel to the secretory canaliculi.
K⁺ also diffuses down its electrochemical gradient, back into the secretory canaliculi through a K⁺ channel.

The overall effect is HCl secretion into the stomach lumen and NaHCO₃ secretion into the bloodstream.

Figure 63.1 The parietal cell and secretion of gastric acid.

Clinical relevance: neutralisation of gastric acid

Neutralisation of gastric acid is a key part of the management of gastro-oesophageal reflux disease and of gastric and duodenal ulcers. Gastric acid can also be neutralised prior to induction of general anaesthesia in patients at risk of aspiration pneumonia, such as in cases of acute abdomen and pregnancy.

The neutralisation of gastric acid can achieved by:

Antacids. These alkaline drugs react directly with HCl in the gastric fluid. Gastric acid is rapidly neutralised, resulting in prompt resolution of symptoms. Antacids include:
1. – Particulate antacids: for example, aluminium hydroxide, magnesium hydroxide and calcium carbonate. Particulate antacids are so called because the aluminium, magnesium and calcium salts produced are non-absorbable, resulting in particulate matter. The importance of this is that, despite a higher pH, pulmonary aspiration of the salts of particulate antacids still cause pulmonary damage.
2. – Non-particulate antacids: for example, sodium citrate, commonly used immediately prior to caesarean section because of its speed of action and non-particulate nature.
Gastric acid inhibitors. These drugs prevent gastric acid being secreted. They therefore take longer to act than antacids but have a much longer duration of action. They target some of the steps in the synthesis of gastric acid discussed above:
1. – Histamine H₂ receptor antagonists (e.g. ranitidine) block the action of histamine on the parietal cell, thus decreasing the production of gastric acid. Some gastric acid is still secreted due to the direct effects of gastrin and ACh on the parietal cell.
2. – Proton-pump inhibitors (PPIs; e.g. omeprazole). PPIs act by irreversibly inhibiting the H⁺/K⁺-ATPase (the proton pump), the final common pathway of gastric acid secretion. They are more effective than H₂ receptor antagonists at increasing gastric pH, but longer-term use carries a greater risk of Clostridium difficile infection, osteoporosis, vitamin B₁₂ deficiency and iron-deficiency anaemia.