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Chapter 4 (page 18)
The border might be sharp but in some cases there was a narrow transitional zone, usually
on the duodenal side of the ring. Occasionally scattered or solitary islets of Brunner's
glands were seen in the pyloric mucosa. In the age group of 25 years and under, the
border was on the duodenal side of the ring in half the cases; as age advanced, the border
tended to spread on to the pyloric ring and in subjects over 50 years of age the pyloric
ring was crossed by Brunner islets in up to four-fifths of the cases. The border also
tended to become less sharp with advancing age.
Brunner's glands produce a mucous secretion which forms a protective lining on the
duodenal mucosa, preventing epithelial damage by chemical or mechanical trauma
(Florey and Harding l934; Griffith and Harkins l956). The mucin secreted has a high
bicarbonate content, rendering it alkaline and affording further protection against acid
gastric chyme (Griffith and Harkins l956). However, it is possible that the alkaline
secretion in the duodenum originates from the surface epithelium and not from Brunner's
glands (Flemström and Garner l984). In man Brunner's glands have been shown to
contain and secrete epidermal growth factor (EGF) (Elder et al. l978; Heitz et al. l978), a
peptide comprising 53 amino acids (Gregory l975). EGF is also produced in the
submandibular salivary glands (Hollenberg l979). Mouse EGF is chemically similar to
human urogastrone, a polypeptide prepared from urine (Elder et al. l978). Mouse EGF
and human urogastrone are closely related structures and seem to be identical in biologic
activity; physical data on human EGF suggest that the material is urogastrone (Elder et
al. l978).
Both polypeptides have a number of biologic effects in common, including inhibition of
gastric acid secretion and a cytoprotective effect on the gastroduodenal mucosa.
Intraduodenal as well as intragastric instillation of EGF prevents the development of
experimental duodenal and gastric ulcers in the rat (Kirkegaard et al l983). Both
substances are powerful mitogens, causing epithelial proliferation and keratinization of
squamous epithelial cells in tissue cultures (Elder et al. l978). Experimental intragastric
installation of EGF increases the synthesis and contents of DNA and RNA in the
gastroduodenal mucosa (Dembinski et al. l982). It was suggested that EGF and
urogastrone might have a role in the control of gastric secretion as well as in mucosal
growth and the known rapid turnover of cells lining the gut (Elder et al. l978).
By means of immunohistochemical studies in the rat Kirkegaard et al (l98l) demonstrated
a dense network of vasoactive intestinal polypeptide (VIP) immunoreactive nerve fibres
around the acini of Brunner's glands as well as small ganglia with VIP immunoreactive
nerve-cell bodies close to the glands. Intravenous infusions of VIP increased
bicarbonate, protein and mucin output from the Brunner's glands, and it was suggested
that physiological secretion from these glands might be stimulated by the VIP nerves.
Ferri et al. (l984) studied the innervation of Brunner's glands in humans in specimens
obtained during gastrectomy for gastric or extragastric carcinoma. In the duodenal
submucosa numerous VIP and substance P nerve fibres were noted in the ganglia of
Meissner's plexus and in the internodal strands. VIP immunostaining also revealed a rich
supply of fibres at the periphery of Brunner's glands, but only a few of these were seen to
enter the glands and reach the acinar cells. Nerve bundles immunostained for met-
enkephalin ran in the internodal strands of the duodenal submucosa and formed dense
networks in occasional ganglia. The study showed that in cases of gastric carcinoma in
man, the Brunner's glands did not have the rich supply of VIP containing nerves as was
the case in rats.
Immunohistochemical studies in the rat showed that as in man, EGF was almost
exclusively present in the secretory cells of Brunner's glands (Kirkegaard et al. l984). It
was shown that VIP stimulated secretion of EGF and bicarbonate from Brunner's glands,
an effect which was inhibited by somatostatin. According to Kirkegaard et al. (l984) the
mechanism controlling Brunner's gland secretion was complex and not fully elucidated.
The autonomic nervous system, local factors and a hormonal mechanism were probably
all involved.
According to Skov Olsen et al. (l985) evidence has accumulated to show that cholinergic,
adrenergic and VIP-containing nerves innervate and thereby influence the secretion from
Brunner's glands. They confirmed the presence of VIP containing nerves in these glands
in the rat. The influence of the sympathetic nervous system and adrenergic agonists on
basal and VIP stimulated flow rate and secretion of EGF from Brunner's glands was
studied. It was confirmed that the sympathetic nervous system had an inhibitory effect
on Brunner's gland secretion. Chemical sympathectomy increased the flow rate and
output of EGF (but depleted the glands of EGF) whereas the alpha-adrenergic agonist
noradrenaline inhibited the secretion. VIP was found to increase Brunner's gland
secretion and total output of EGF; VIP probably also increased the synthesis of EGF.
Fuse et al. (l990) determined the thickness of Brunner's glands in surgically resected
duodenal ulcer specimens and normal controls. The maximum mean thickness in
controls was l.54 ± 0.38 mm; in duodenal ulceration it varied widely from 0.5 to 5.0 mm.
In most duodenal ulcer cases the glands were thickest within 1.0 cm of the centre of the
ulcer; in a small minority of cases of duodenal ulceration the layer of Brunner's glands
remained diffusely thin. It was concluded that Brunner's glands became hyperplastic in
duodenal ulceration, especially near the ulcer; this was probably a defense mechanism
against acid and peptic digestion. In cases of healed duodenal ulceration Brunner's
glands were thin at the centre of the scar; this histological finding corresponded to the
depressed, scarred area observed endoscopically, and suggested decreased mucosal
resistance.
The fact that the submucosa of the first part of the duodenum is much narrower than that
of the stomach, and that it contains multiple Brunner's glands which pierce the muscularis
mucosae (thus virtually attaching the mucosa to the muscular layer), means that its
inherent ability to move is much less than that of the submucosa of the pyloric sphincteric cylinder.
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