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,
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
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.