The Mucous Membrane or Mucosa #

The mucous membrane of the stomach and first part of the duodenum consists of 3 layers; an outermost muscularis mucosae, a middle lamina propria and an innermost glandular epithelial lining, bordering the lumen.

Stomach #

Muscularis Mucosae #

The muscularis mucosae, a thin layer of smooth muscle, forms the border between the mucosa and submucosa. It consists of outer longitudinal and inner circular fibres; from the inner layer strands of smooth muscle cells extend through the lamina propria toward the luminal surface between the gastric glands. It is surmized that contraction of these strands may compress the glands, thereby facilitating their emptying (Bloom and Fawcett l975).

Lamina Propria #

The lamina propria occupies the narrow region between the muscularis mucosae and the surface epithelial cells with their glands. It extends into the area between the necks of the glands and forms a basement membrane on which the epithelial cells rest. There is little lamina propria in the fornix and body, where the gastric glands are numerous and closely packed; it is more prominent in the cardiac and pyloric zones (Ito l967).

The lamina propria consists of a delicate network of collagenous and reticular fibres and a few fibroblasts or reticular cells. The meshes of the network contain plasma cells, mast cells, eosinophilic leucocytes and lymphocytes. Local accumulations of lymphocytes may occur in the cardiac and pyloric regions. Strands of smooth muscle traverse this layer, which also contains fine capillaries, lymphatic vessels and nerve fibres.

Epithelial Lining #

The entire luminal surface of the mucosa is covered by a layer of simple columnar cells, called the surface mucus cells. Numerous tubular invaginations of the surface, the gastric pits or foveolae, are lined by the same type of cell (Ito l967). In the pyloric region the pits are deeper than in the remainder of the stomach, extending at least halfway to the muscularis mucosae. They are V-shaped, tapering off into the glands that open into them (Bevelander and Ramaley l979).

The mucus-secreting columnar cells lining the luminal surface and the pits are joined near their free surfaces to each other by tight junctions (Ham l974). It is surmized that this arrangement forms one of the mechanisms by which the underlying layers are protected against luminal acid. The supranuclear portions of the cells just below their free surfaces contain dense, homogeneous, spherical or ovoid granules consisting of a type of mucigen (Bloom and Fawcett l975). Upon release into the lumen, the granules give rise to the layer of mucus that covers the luminal surface of the mucosa. In the cells of the gastric pits, the granules become progressively less abundant at deeper levels, and in the bottom of the pits they from only a thin layer immediately beneath the cell surface. Cells of this kind continue into the necks of the gastric glands. Under physiological conditions, the surface mucus cells are continuously desquamated into the lumen and are completely replaced every 3 days (Ham l974; Bloom and Fawcett l975). Newly formed cells appear in the deeper parts of the foveolae and in the necks of the glands; these are slowly displaced upward and continually replace those lost on the surface.

Three Mucosal Zones #

The entire thickness of the mucous membrane in all parts of the stomach is occupied by a multitude of glands which open into the bottom of the gastric pits. The blind ends of the glands extending into the mucosa are slightly expanded and coiled, sometimes dividing into 2 or 3 branches. On the basis of the cell population in the glands, the gastric mucosal coat is differentiated into 3 zones:

Cardiac Zone #

This zone consists of a narrow, ring-shaped area around the gastro-oesophageal junction, containing the cardiac glands. These glands have wide lumina and shallow pits and are composed overwhelmingly of mucus-secreting cells. They may contain a few neuroendocrine cells, also called APUD cells on account of their capacity to synthesize monoamines through a process of Amine Precursor Uptake and Decarboxylation (vide infra). In the transitional area, where this zone is continuous with the second or oxyntic zone, a few parietal cells may be present. The glands of the cardiac zone secrete mucus and very little, if any, enzymes.

Oxyntic Zone #

This zone comprises the greater part of the fornix and corpus, i.e. the proximal two-thirds or more of the stomach. The glands are variously known as fundic glands, proper gastric glands or principal gastric glands. As one of their most important properties is the secretion of gastric acid, Grossman (l958) suggested the term "oxyntic" (Greek: acid- forming) as an appropriate indicator of this glandular zone. The mucosa here is much deeper than in the cardiac zone and contains a greater number of glands. The pits are shallow and the glands extending from the bottoms of the pits are 2 to 3 times as long as the pits are deep.

Each principal gastric gland is composed of 4 kinds of cells (Bevelander and Ramaley l979):

1. Chief, zymogenic or peptic cells. These are situated mostly in the deeper parts of the glands. They exhibit secretory granules containing the precursors of pepsin.

2. Parietal or oxyntic cells. These are most numerous in the necks of the glands. They do not border directly on the lumen, but are crowded away from it by peptic cells. Each cell is roughly triangular in shape, with the apex projecting towards the lumen between the sides of two peptic cells that border it. These cells are intensely acidophilic, contain the gastric proton pump mechanism, and produce the antecedent of hydrochloric acid; they are also believed to elaborate intrinsic factor. The secretion of oxyntic cells must pass between adjacent peptic cells that almost cover them, to reach the lumen.

3. Neck mucous cells. These cells resemble the mucous cells of the cardiac and pyloric zones. They are relatively few in number and are lodged between the parietal cells in the necks of the glands; they are smaller than the surface mucous cells and their mucigen granules are larger and less dense than those of the surface cells (Bevelander and Ramaley l979). The secreted mucus is somewhat different from that secreted by the surface mucous cells (Leeson l976).

4. Neuroendocrine or APUD cells. These small, granulated cells occur singly in the epithelium of the gastric mucosa (Bloom and Fawcett l975). They are scattered between the peptic cells and are few in number. It is accepted that some of these cells are the site of synthesis and storage of serotonin (5-hydroxytryptamine). Cells of the APUD line are much more numerous in the pyloric mucosal zone and will be described separately (Chap. 9).

The glands of the oxyntic zone produce nearly all the enzymes and hydrochloric acid secreted in the stomach; they also produce some of the mucus.

Pyloric Zone #

This zone comprises roughly the distal third of the stomach. Normally it extends further along the lesser curvature than the greater, but its boundaries may vary (vide infra). The pits are deeper in this zone than elsewhere in the stomach, extending into the mucous membrane for half its thickness. The glands are also of a simple, branched tubular type, but they branch more extensively and the tubules are coiled.

The glands contain the following types of cells:

1. Mucous cells resembling the neck mucous cells of the oxyntic glands. These large, mucus-secreting cells constitute the overwhelming number of cells in the pyloric glands. They have a pale cytoplasm containing indistinct granules, the nucleus is often flattened against the base of a cell, and short microvilli covered by a layer of mucus, are present on the luminal surface.

2. Parietal cells. A few isolated parietal cells may be present among the mucous cells (Ito l967). Parietal cells also occur in the transitional region between the pyloric and oxyntic zones (Bevelander and Ramaley l979).

3. Neuroendocrine or APUD cells. These cells are much more numerous in the pyloric than in the cardiac and oxyntic zones; when compared with the mucous cells they are still relatively few in number. With light microscopy they have been called enterochromaffin cells. With electron microscopy their cytoplasmic granules are clearly visible after staining with chromium or silver salts. On the basis of their staining reactions, the cells have been divided into two types, viz. argentaffin cells, in which the granules reduce silver without pretreatment, and argyrophilic cells, in which a reducing substance is required before the granules will react with silver (Bloom and Fawcett l975) (Chap. 9).

The glands of the pyloric mucosal zone do not produce enzymes, but secrete mucus; this zone is also an important producer of endocrine, paracrine or neurocrine regulatory peptides by virtue of the APUD cells contained in its glands (Chap 9).

Anatomical Extent and Boundaries of the Pyloric Mucosal Zone #

The various mucosal zones of the stomach are not sharply delimited, and along the borderlines the glands of one region mingle with those of the adjoining region; intermediate glands may be present between the pyloric and body (i.e. oxyntic) mucosal zones (Bloom and Fawcett l975).

The extent of the pyloric mucosal zone, and its boundaries on the oral and aboral sides, may be determined by microscopic, macroscopic, surgical and other methods. The microscopic identification of the pyloric mucosa in morbid anatomical specimens is probably the most accurate method of determining the boundaries of this zone. For instance, it has been stated in histology that the pyloric mucosal zone usually comprises the distal 4-5cm of the stomach, and that it extends farther along the lesser curvature than the greater (Bloom and Fawcett 1975).

Border on Aboral Side

Using macroscopic techniques in 53 fresh, non-diseased post-mortem specimens, Landboe-Christensen (l944) found that the border between pyloric and duodenal mucosa might lie either on the perpendicular, duodenal side of the pyloric ring, at the top of the ring, or on the sloping gastric side of the ring. With ageing there was a tendency for the border to shift from the duodenal to the gastric side of the ring.

Using microscopic methods in 110 cases of partial gastrectomy for duodenal ulcer, Oi and Sakurai (l959) came to essentially similar conclusions. In all specimens the border was within 5.0 mm of the summit of the pyloric "sphincter muscle" (presumably the pyloric ring), either on the duodenal or on the gastric side. The pyloric mucosa was in direct contact with the duodenal mucosa, i.e. the border could be identified as a line, in contrast to the border between pyloric and oxyntic mucosa, which consisted of a transitional zone of varying width.

Border on Oral Side

Landboe-Christensen (l944) studied the extent of the pyloric mucosal zone on the oral side by macroscopic tehcniques in 47 non-diseased, fresh post-mortem specimens. In all instances this zone was longer on the lesser than on the greater curvature, covering on average 7.2 cm of the lesser, and 5.2 cm of the greater curvature. The average percentage of the lesser curvature covered was 44 percent, and the average percentage of the greater curvature covered was 12 percent. The border between pyloric and oxyntic mucosa was irregular, often dentate or tortuous, and as a rule a number of islets of oxyntic mucosa were encountered in the pyloric zone. There was a transitional area of varying width between the two zones. In practice, a line drawn from the junction of the upper three- fifths and lower two-fifths of the lesser curvature, running downwards and to the right, indicates the approximate boundary of pyloric mucosa (Fig. 5.1).

Dean and Mason (l964) studied 117 fresh gastric resection specimens microscopically (resected for either duodenal or gastric ulcer). In l8 cases of duodenal ulcer the average length of pyloric mucosa along the lesser curvature was 9.0cm, and along the greater curvature 7.4 cm. On an average the pyloric mucosa extended for l.5cm further up the lesser than the greater curvature. In the majority of all duodenal ulcer specimens the transitional zone between pyloric and oxyntic mucosa varied from 0.5 to 5.0 cm in width, the average width being 1.0cm. The upper limit of the pyloric mucosa showed wide individual variations. Patients with gastric ulcers tended to have a greater extent of pyloric mucosa than those with duodenal ulcers, and women with gastric ulcers had more pyloric mucosa than men with gastric ulcers.

Fig. 5.1. Relationship between pyloric sphincteric cylinder and pyloric mucosal zone in normal stomach. Arrows, contracted sphincteric cylinder; broken line, approximate border between pyloric and oxyntic mucosal zones.

Schrager et al. (l967) studied the "antrum" microscopically in 45 normal stomachs obtained at necropsy, in 75 resection specimens of duodenal ulcer and in 40 specimens of gastric ulcer. Normal stomachs showing clear histology were not easily obtained due to the speed with which autolysis occurs after death; in only 13 could measurements be made. Normally the average length of pyloric mucosa between the "sphincter" (i.e. the pyloric ring) and the boundary zone on the lesser curvature was 8.9 cm, with an average "sphincter" to cardia distance of 22.5 cm. Thus the pyloric zone encompassed 40 percent of the lesser curvature. On the greater curvature the average figures were 4.8 cm, 39 cm and 12 percent respectively. Comparative studies showed that in the majority of duodenal ulcer patients the pyloric zone was larger than in normal controls, and in the majority of gastric ulcer cases it was almost twice the normal size.

In surgical pH monitoring tests, Capper et al. (l962, l966) found a wide variation in size between the small pyloric zone of duodenal ulcer and the larger zone of gastric ulcer cases. With duodenal ulceration the zone was usually of normal size or smaller, extending to a line 3.0 to 4.0 cm from the pylorus. (In their only normal subject, the pyloric zone was 4.0 to 5.0 cm in length.) In gastric ulcer cases the pyloric zone was very much larger, at times encompassing the whole of the lesser curvature. Capper et al. concluded that the junction between the distal alkaline, pyloric zone and the proximal oxyntic zone was not static, but that it might migrate up and down the stomach. The alkaline zone could have been a normal "antrum", but it could also have represented oxyntic mucosa which had been altered by gastritis. Royston et al. (l978) found in patients with duodenal ulcer, that the mean area of the "antrum", as defined histologically, was double the mean antral area defined as the alkaline zone in the pH studies of Capper et al. (l962, l966).

The test of Moe et al (l965, l966) was based on the differential excretion of dyestuffs from the gastric corpus and the "antrum" in dogs. The mean area of the "antrum" was found to occupy 20 percent of the total gastric area, with a range of 10 to 30 percent. A modification of the test was used by Hedenstedt et al (l967) in humans, the results being controlled histologically. On the whole, the pyloric zone was found to be larger than that determined by Moe's test. In all cases the extent of pyloric mucosa was greater on the lesser than on the greater curvature. Amdrup et al (l972) used the congo red test for a precise determination of the "antrum" prior to antrectomy for gastric ulcers. In their experience the "antrum" in gastric ulcer cases was often larger than in duodenal ulcer cases, sometimes extending high up on the lesser curvature and occasionally as far as the cardia.

Duodenum #

The duodenal mucous membrane also consists of 3 layers, but these differ from those of the stomach in several respects.

Muscularis Mucosae #

The muscularis mucosae, consisting of outer longitudinal and inner circular fibres, forms the border between mucosa and submucosa. It is pierced by the ducts of Brunner's glands located in the submucosa; from it muscular strands extend into the cores of the villi on the luminal surface.

The villi are finger-like projections about 1.0mm in height, on the surface of the mucosa; they are covered by a layer of columnar cells which themselves have a brush border of microvilli.

Lamina Propria #

The lamina propria, consisting of a network of reticular fibres and a loose network of connective tissue, forms the cores of the villi. It contains lymphocytes, plasma cells and occasional eosinophils. The core of each villus also contains a lymphatic vessel continuous with the lymphatic plexus of the submucosa, smooth muscle fibres continuous with the muscularis mucosae, a nerve twig from Meissner's plexus in the submucosa, an arteriole and a venule.

Between the villi are the crypts of Lieberkühn (also known as the intestinal glands); these are simple tubular glands lined by low columnar epithelium. The ducts of Brunner's glands open into the base of the crypts.

Epithelial Lining #

The epithelial lining of the luminal surface of the duodenal mucosa consists of the columnar cells mentioned above, interspersed with goblet cells, Paneth cells and APUD cells (Chap. 9).

The columnar cells produce a variety of digestive enzymes and have an absorptive capacity; they are much more numerous in the remainder of the small bowel than in the duodenum. The goblet cells secrete mucus. Paneth cells are located in the base of the crypts of Lieberkühn. Each cell is pyramidal in shape with a broad base resting against the basal lamina, and a narrow apex facing the lumen; it shows features of exocrine secretion with prominent secretory granules said to contain high activities of lysozyme, a bacteriolytic enzyme that degrades bacterial cell walls (Erlandsen et al. l974). There is speculation that Paneth cells may help to regulate the microbiological flora; however, their role in the function of the small intestine is largely unknown (Trier and Madara l98l). They increase in number from duodenum to ileum and represent a relatively stable cell population, seldom being seen in mitosis; they are present in the small intestine of humans and other primates, ruminants, mice and hamsters, but do not occur in dogs, cats and pigs (Trier and Madara l98l).

Additional Features of the Mucosa #

The mucous membrane of the living stomach is grayish pink, except for paler zones at the cardia and pylorus, corresponding to the respective mucosal zones (Bloom and Fawcett l975). The macroscopic, naked-eye assessment of the extent of the pyloric mucosal zone in fresh gastric resection specimens may be quite accurate; according to Dean and Mason (1964); it is said that the pyloric mucosa is flat during life, whereas that of the fornix is rugose. However, naked-eye identification cannot always be regarded as very accurate (Capper et al. 1966). After death the colour turns to a darker grey and the whole membrane becomes softer. Postmortem changes due to autolysis of the mucosa set in rapidly.

In the normal empty, contracted and partially filled stomach, the mucosa is elevated into numerous macroscopic folds or rugae which project into the lumen. Each fold consists of a double layer of mucosa with a central core of submucous tissue. It is said that by virtue of the folds the secretory surface is increased significantly over that of a simple cylinder of similar dimensions (Hendrix 1974). The plication of the mucosa is possible because of the loose consistency of the submucosa and the contractile activity of the muscularis mucosae (Bloom and Fawcett 1975).

The mucosal folds in the pyloric region can be demonstrated readily in the intact, living human stomach by radiographic techniques. Swallowing a few mouthfulls of a suitable barium sulphate suspension on the empty stomach, and applying graduated compression on the anterior abdominal wall, shows the folds to advantage (Chap. 13). By means of image intensification and TV monitoring the movements of the mucosal folds may be studied (Chap. 13).

The size of the folds is determined by the volume of the submucosa (Forssell l923, l934) and degree of distension of the lumen; increasing luminal distension causes progressive effacement of the folds. A similar but more pronounced effect is seen when contraction of the muscularis externa is abolished by the administration of anticholinergic substances, and simultaneous distension of the lumen obtained by means of air or gas insufflation. Under these circumstances macroscopic folds may disappear altogether. This principle is utilized in the upper gastrointestinal double contrast radiographic examination.

The position or direction of the mucosal folds during life depends mainly on the degree of contraction or relaxation of the muscularis externa. In his epic studies Forssell (l923, l934, l939) demonstrated "independent but co-ordinated" contractions of the muscularis externa and mucosa (brought about by contractions of the muscularis mucosae). One of the best examples of this phenomenon is seen during contraction of the pyloric sphincteric cylinder. Normally, when the cylinder is relaxed, its mucosal folds are circular; during contraction the folds change in direction, and with maximal contraction only longitudinal folds are seen in the fully contracted cylinder (Chap. 13).

When examining the surface of the gastric mucosa with a magnifying lens in the fresh specimen, it is seen to be divided into a multitude of small, slightly elevated polygonal areas by numerous linear depressions. These raised areas, which measure from 1.0 to 6.0 mm in diameter, are called the areae gastricae. On the surface of the areae gastricae numerous small tubular invaginations, the gastric pits or foveolae, are seen. It is into the bottom of these pits that the gastric glands open. Double contrast radiographic examination demonstrates the areae gastricae (Chap. 13). They are seldom visible endoscopically (Mcintosh and Kreel l977).

The mucous membrane of the first part of the duodenum, unlike that of the stomach, usually appears smooth, but on close inspection is seen to be thrown into rudimentary folds. Grossly visible crescentic mucosal folds (plicae circulares or valves of Kerckring) commence 2.5 to 5.0 cm distal to the pylorus, extending half to two-thirds of the way around the lumen.

Discussion #

Two anatomico-functional divisions of the pyloric part of the stomach are clearly identifiable. The first, the muscular pyloric sphincteric cylinder, is a tube of thickened muscularis externa, approximately 3.0 to 5.0 cm in length when fully contracted (in adults). It is definable in morbid anatomical specimens, in which it is seen to end in an aboral thickening, the pyloric sphincteric ring (which forms the peripheral part of the pyloric ring) (Chap. 3, 11). The pyloric sphincteric cylinder is also clearly definable in radiographic motility studies during life (Chap. 13).

The second anatomico-functional entity in the distal stomach is the pyloric mucosal zone, containing mucus secreting and neuroendocrine cells. (Radiologically there are no differentiating features between the various mucosal zones). Unlike the cylinder, the mucosal zone may vary in extent in pathological conditions.

Anatomically the pyloric mucosal zone differs from the sphincteric cylinder in extent as well as in shape. In the normal stomach the mucosal zone is longer than the cylinder, especially on the lesser curvature. While the cylinder is roughly triangular in shape or fan-shaped, with the apex on the lesser and the base on the greater curvature (when contracted), the greatest length of the mucosal zone occurs on the lesser curvature (Fig. 5.1).

The entire sphincteric cylinder is lined by pyloric mucosa. Aborally both the mucosal zone and the cylinder end at the pyloric ring. At the oral end of the cylinder pyloric mucosa extends into the more proximal part of the stomach.

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