126.96.36.199 General description
After swallowing, the chewed food is propelled rapidly, in a matter of seconds, through the oesophagus to enter the stomach. The stomach is a distensible muscular sac, about 25 cm long, with a volume of around 50 ml when empty, but which can expand to hold up to 1.5 litres or more. Its muscular walls are made of three layers of smooth muscle running in different directions, giving the stomach the ability to churn food around and physically break it up further and mix it with the stomach's own digestive juices.
The cells of the epithelium (inner lining) of the stomach produce both mucus and an alkaline, bicarbonate-containing fluid, which protect them from attack by the stomach's own acidic digestive juices. Interspersed with these cells are many millions of small holes, visible microscopically; these are the openings of the gastric pits or gastric glands. The gastric pits are lined with further epithelial, mucus-secreting cells but also contain specialised cells secreting different substances: the parietal or oxyntic cells secreting HCl (hydrochloric acid), and the chief cells, also known as zymogenic or peptic cells, which secrete proteins, particularly the pro-enzyme pepsinogen. The oxyntic cells also secrete the glycoprotein known as intrinsic factor, which is necessary for absorption of vitamin B12.
188.8.131.52 Regulation of digestive processes in the stomach
The theme of this book is the coordination of processes within the body, and it will not be surprising that the secretion of these various substances is not continuous in time; it is coordinated with the ingestion of food and its arrival in the stomach.
The control of acid secretion is summarised in Fig. 3.2. Secretion of HCl is stimulated by three factors acting at specific receptors on the oxyntic
cells: acetylcholine, the parasympathetic neurotransmitter (discussed in Section 184.108.40.206); histamine; and the peptide hormone gastrin. Maximal acid production is only achieved when all three signals are present; any one of the three will only give weak stimulation of acid production.
Histamine is released from cells in the stomach wall in response to food in the stomach. It acts locally, on nearby cells; it is thus not a true hormone, but acts in a paracrine manner. It acts at specific receptors, known as H2-receptors, on the oxyntic cells; drugs which block binding at these receptors, the ^-antagonists (e.g. cimetidine, ranitidine), have found widespread use as anti-ulcer agents, since they reduce acid secretion. The parasympathetic nervous system is activated during digestion, as noted earlier, by the taste, smell and sight of food; when food enters the stomach, distension of its walls activates stretch receptors which send signals to the brain, which in turn causes further activation of the parasympathetic nervous system (the vagus nerve), and enhances acid secretion. A traditional surgical treatment for gastric ulcers (now out of fashion) was to sever the vagus nerve, thus removing one stimulus for acid secretion. When we consider later other effects of the vagus nerve (e.g. the modulation of insulin secretion) we shall see that this could have widespread, unwanted effects. In more recent years, highly selective vagotomy was introduced, in which only those branches innervating the stomach were cut, but even this treatment has now been superseded by the use of H2-antagonists. Nowadays there is an even more direct treatment: drugs that bind to and inhibit the pump that extrudes H+ ions from the oxyntic cells (proton pump inhibitors).
Gastrin, the third regulator of acid secretion, is a 17-amino acid peptide produced by enteroendocrine cells, which are found in gastric pits in the region of the pylorus - the exit from the stomach, leading to the first part of the small intestine (the duodenum). Gastrin is a true hormone; it is released from these cells into the bloodstream and circulates in the bloodstream. There is no apparent short cut for it, although the cells it affects are near to the cells secreting it. The release of gastrin is stimulated by a number of factors arising from the food in the stomach: some amino acids and peptides released from partially digested protein in the stomach, caffeine, calcium and alcohol. In addition, stimulation of gastrin secretion is reinforced by the parasympathetic nervous system, activated during the digestive process. Gastrin acts directly on the oxyntic cells to stimulate acid secretion. It also has other actions in the small intestine, which will be considered below.
The secretion of gastrin is inhibited by too high an acidity in the stomach; when the pH falls below about 2 (the optimum for the action of pepsin) gastrin secretion declines. This seems to be brought about by release from adjacent cells of the 14-amino acid peptide somatostatin. Somatostatin is a widespread inhibitor of peptide hormone secretion: it is found throughout the intestine, in the brain and in the pancreas, and, when given intravenously, will inhibit the secretion of many peptide hormones including growth hormone, gastrin, insulin and glucagon. (Its name comes from the inhibition of growth hormone, or somatotropin, secretion.) Clearly, it could have very non-specific effects if released in sufficient quantities into the circulation, and somatostatin appears, like histamine, to act locally on adjacent or nearby cells; it is a paracrine regulator of hormone secretion. Excess acidity appears to act directly to stimulate somatostatin secretion and thus inhibit gastrin release.
The inhibition of gastrin release by excess acidity is a good example of feedback inhibition brought about by a hormonal regulator. Large amounts of protein in the stomach act as a buffer, 'soaking up' excess acid, so the pH
will rise and more gastrin will be released; as the pH falls below the optimum for pepsin action, gastrin release, and thus acid production, is diminished. The system maintains a relatively constant, and optimum, hydrogen ion concentration for digestion.
It is quite possible to live without a stomach (except for the need for injections of vitamin B12, which cannot be absorbed because of the lack of intrinsic factor), and yet the stomach normally plays an important role in digestion of food.
The mechanical activity of the stomach results in disruption and liquefaction of food particles. The acidity of the stomach also has an antibacterial action. But specific digestive activity also takes place here.
The acidic environment in the stomach stops the action of the salivary amy-lase. Nevertheless, the contractile activity of the stomach is greatest near the pylorus, and after a large meal, boluses of food which arrive from the oesophagus may remain relatively undisturbed, and salivary amylase continue to act, for up to an hour in the upper part of the stomach. It has been estimated that up to 50% of dietary starch (but usually less) may be digested by the time food leaves the stomach.
A triacylglycerol lipase is secreted from glands in the stomach (gastric lipase). This is an acid lipase, with a pH optimum of around 4 - 6, although it is still active even at a pH of 1. In other mammals a homologous lipase may be secreted higher up the gastrointestinal tract, e.g. from the serous glands of the tongue in rodents (lingual lipase). (The realisation that humans secrete a gastric lipase is relatively recent, and there are still references to human lingual lipase in the literature.) Gastric lipase may be responsible for 25% of the partial triacylg-lycerol hydrolysis necessary for fat absorption. In addition, its action seems to 'prepare' fat droplets for the action of pancreatic lipase in the small intestine.
Most proteins are denatured (that is, their quaternary, tertiary and secondary structures are lost) in an acidic environment. (Adding lemon juice to milk or egg white will 'curdle' it.) This makes the peptide chains more accessible to proteolytic enzymes, which break the peptide bonds linking the amino acids. The proteolytic enzyme produced by the chief or zymogenic cells is pepsin. This is released, as with all extracellular proteolytic enzymes, as an inactive precursor, pepsinogen. It is activated by hydrolysis, catalysed by hydrogen ions, of a single peptide bond, releasing a 42-amino acid peptide and the active enzyme. Pepsin has a very acidic pH optimum, around 2. It acts preferentially on peptide bonds in the middle of peptide chains (i.e. it is an endopeptidase), to the C-terminal side of aromatic amino acids. Thus, proteins are broken down into shorter chains.
Little absorption into the bloodstream occurs from the stomach: ethanol and some lipid-soluble drugs are absorbed, but not the normal dietary constituents. The stomach is primarily an organ of mechanical digestion, comparable to a food liquidiser. By the rhythmic contractions of the lower part of the stomach, the food is pounded into a creamy mixture known as chyme. Entry to the duodenum is regulated by a circular muscle, the pyloric sphincter. It opens at regular intervals (about twice each minute) and about 3 ml of chyme is squirted into the duodenum. The pyloric sphincter only opens partially, so that large particles are retained for further pummelling. Thus, a creamy acidic mixture of lightly digested starch, partially digested protein and coarsely emulsified fat enters the duodenum.
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