Physiology of the stomach and duodenum

Introduction

The stomach mechanically breaks up ingested food and, together with the actions of acid and pepsin, forms chyme that passes into the duodenum. In contrast to the acidic environment of the stomach, that of the duodenum is alka­line, as a result of the secretion of bicarbonate ions from both the pancreas and the duodenum. This neutralises the acid chyme and adjusts the osmolarity to approximately that of plasma. Endocrine cells in the duodenum produce cholecystokinin that stimulates the pancreas to produce trypsin and the gall bladder to contract. Secretin is also produced by the endocrine cells of the duodenum. This hormone inhibits gastric acid secretion and promotes production of bicarbonate by the pancreas.

Gastric acid secretion

The secretion of gastric acid and pepsin tends to run in parallel, although the understanding of the mechanisms of gastric acid secretion is considerably greater than that of pepsin. Numerous factors are involved to some degree in the production of the gastric acid. These include neurotransmitters, neuropeptides and peptide hormones, and several other factors. This complexity need not detract from the fact that there are basic principles that are relatively easily understood (Fig. 51.4). As mentioned above, hydrogen ions are produced by the parietal cell by the proton pump. Although there is a multiplicity of factors that can act on the parietal cell, it is now widely accepted that the most important of these transmitters is histamine, which acts via the H2 receptor. Histamine in turn is produced by the ECL cells of the stomach and acts in a paracrine (local) fashion on the parietal cells. These relationships explain why proton pump inhibitors can abolish gastric acid secretion, as they act on the final common pathway secretion, and why H2-receptor antagonists have such profound effects on gastric acid secretion, even though this is not insurmountable (Fig. 51.4). The ECL cell produces histamine in response to a number of stimuli that include the vagus and gastrin. Gastrin is released by the G cells in response to the presence of the food in the sto­mach. The production of gastrin is inhibited by acid, hence creating a negative-feedback loop. Various other peptides, including secretin, inhibit gastric acid secretion.

Classically, three phases of gastric secretion are described. The cephalic phase is mediated by vagal activity secondary to sensory arousal as first demonstrated by Pavlov. The gastric phase is a response to food within the stomach that is medi­ated principally, but not exclusively, by gastrin. In the intesti­nal phase, the presence of chyme in the duodenum and small bowel inhibits gastric emptying and, as mentioned above, the acidification of the duodenum leads to the production of secretin that also inhibits gastric acid secretion, along with numerous other peptides originating from the gut. The stomach also possesses somatostatin containing D cells. Somatostatin is released in response to a number of factors including acidification. This peptide acts probably on the G cell, the ECL cell and the parietal cell itself to inhibit the production of acid both directly and via intermediate pathways.

Gastric mucus and the gastric mucosal barrier

The gastric mucous layer is essential to the integrity of the gastric mucosa. It is a viscid layer of mucopolysaccharides produced by the mucus-producing cells of the stomach and the pyloric glands. Gastric mucus is an important physio­logical barrier to protect the gastric mucosa from mechanical damage, and also the effects of acid and pepsin. Its consider­able buffering capacity is enhanced by the presence of bicar­bonate ions within the mucous. Many factors can lead to the break down of this gastric mucous barrier. These include bile, nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, trauma and shock. Tonometry studies have shown that of all the gastrointestinal tract the stomach is the most sensitive to ischaemia following a hypovolaemic insult and also the slowest to recover. This may explain the high incidence of stress ulceration in the stomach.

Peptides and neuropeptides in the stomach and duodenum

As with most of the gastrointestinal tract, the stomach is richly endowed with sources of peptide hormones and neuro­transmitters. Previously nerves and endocrine cells were considered distinct in terms of their products. However, it is increasingly realised that there is enormous overlap within these systems. Many peptides recognised as hormones may also be produced by neurons, hence the term neuropeptides. The term ‘messenger’ can be used to describe all such products. There are three conventional modes of action which overlap.

  Endocrine the messenger is secreted into the circulation where it affects tissues which may be remote from the site of origin (Bayliss and Starling).

  Paracrine messengers are produced locally and have local effects on tissues. Neurons and endocrine cells both act in this way.

 Neurocrine (classical neurotransmitter) — messengers are produced by the neuron via the synaptic knob and pass across the synaptic cleft to the target.

The autocrine mode of action should be mentioned for com­pleteness. Here messengers are released from cell to act on receptors on the same cell’s surface membrane. Many growth factors such as epidermal growth factor and transforming growth factors alpha and beta work in this way.

Many peptide hormones act on the intrinsic nerve plexus of the gut (see later) and influence motility. Similarly, neuropeptides may influence the structure and function of the mucosa. Some of these peptides, neuropeptides and neuro­transmitters are shown in Table 51.1.

Gastroduodenal motor activity

The motility of the entire gastrointestinal tract is modulated to a large degree by its intrinsic nervous system. Critical in this discussion is the migrating motor complex (MMC). In the fasted state and after food has cleared the small bowel there is a period of quiescence lasting in the region of 40 minutes (phase I). There follows a series of waves, also lasting for about 40 minutes, of electrical and motor activity propagated from the fundus of the stomach in a caudal direction at a rate of about three per minute (phase II). These pass as far the pylorus but not beyond. Duodenal slow waves are generated in the duodenum at a rate of about 10 per minute that carry down the small bowel. The amplitude of these contractions increases to a maximum in phase III that lasts for about 10 minutes. This 90-minute cycle of activity is then repeated. From the duodenum the MMC moves distally at 5—10 cm/minute reaching the terminal ileum after 1.5 hours.

     Following a meal the stomach exhibits receptive relaxation which lasts for a few seconds. Following this adaptive relaxa­tion occurs which allows the proximal stomach to act as a reservoir. Most of the peristaltic activity is found in the distal stomach (the antral mill) and the proximal stomach demon­strates only tonic activity. The pylorus, which is most com­monly open, contracts with the peristaltic wave and allows only a few millilitres through at a time. The antral contraction against the closed sphincter is important in the milling activity of the stomach. Although the duodenum is capable of generating 10 waves per minute, after a meal it only contacts after an antral wave reaches the pylorus. The coordination of the motility of the antrum, pylorus and duodenum means that only small quantities of food reach the small bowel at a time. Motility is influenced by numerous factors including mech­anical stimulation and neuronal and endocrine influences.