The Pyloric Sphincteric Cylinder in Health and Disease

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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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