книги студ / color atlas of physiology 5th ed[1]. (a. despopoulos et al, thieme 2003)

Stomach Structure and Motility

Structure. The cardia connects the esophagus to the upper stomach (fundus), which merges with the body (corpus) followed by the antrum of the stomach. The lower outlet of the stomach (pylorus) merges with the duodenum (!A). Stomach size is dependent on the degree of gastric filling, but this distension is mainly limited to the proximal stomach (!A, B). The stomach wall has an outer layer of longitudinal muscle fibers (only at curvatures; regulates stomach length), a layer of powerful circular muscle fibers, and an inner layer of oblique muscle fibers. The mucosa of the tubular glands of the fundus and corpus contain chief cells (CC) and parietal cells (PC) (!A) that produce the constituents of gastric juice (!p. 242). The gastric mucosa also contains endocrine cells (that produce gastrin in the antrum, etc.) and mucous neck cells (MNC).

Functional anatomy. The stomach can be divided into a proximal and a distal segment (!A). A vagovagal reflex triggered by swallowing a bolus of food causes the lower esophageal sphincter to open (!p. 238) and the proximal stomach to dilate for a short period (receptive relaxation). This continues when the food has entered the stomach (vagovagal accommodation reflex). As a result, the internal pressure hardly rises in spite of the increased filling. Tonic contraction of the proximal stomach, which mainly serves as a reservoir, slowly propel the gastric contents to the distal stomach. Near its upper border (middle third of the corpus) is a pacemaker zone (see below) from which peristaltic waves of contraction arise due mainly to local stimulation of the stomach wall (in response to reflex stimulation and gastrin; !D1). The peristaltic waves are strongest in the antrum and spread to the pylorus. The chyme is thereby driven towards the pylorus (!C5, 6, 1), then compressed (!C2, 3) and propelled back again after the pylorus closes (!C3, 4). Thereby, the food is processed, i.e., ground, mixed with gastric juices and digested, and fat is emulsified.

The distal stomach contains pacemaker cells (interstitial Cajal cells), the membrane potential of which oscillates roughly every 20 s, producing characteristic slow waves (!p. 244). The velocity (0.5–4 cm/s) and amplitude

(0.5–4 mV) of the waves increases as they spread to the pylorus. Whether and how often contraction follows such an excitatory wave depends on the sum of all neuronal and hormonal influences. Gastrin increases the response frequency and the pacemaker rate. Other hormones like GIP inhibit this motility directly, whereas somatostatin (SIH) does so indirectly by inhibiting the release of GRP (!D1 and p. 234).

Gastric emptying. Solid food remains in the stomach until it has been broken down into small particles (diameter of !1 mm) and suspended in chyme. The chyme then passes to the duodenum. The time required for 50% of the ingested volume to leave the stomach varies, e.g., 10—20 min for water and 1–4 hours for solids (carbohydrates ! proteins ! fats). Emptying is mainly dependent on the tone of the proximal stomach and pylorus. Motilin stimulates emptying of the stomach (tone of proximal stomach rises, pylorus dilates), whereas decreases in the pH or osmolality of chyme or increases in the amount of long-chain free fatty acids or (aromatic) amino acids inhibit gastric emptying. Chemosensitive enterocytes and brush cells of the small intestinal mucosa, enterogastric reflexes and certain hormones (CCK, GIP, secretin and gastrin; !p. 234) mediate these regulatory activities (!D2). The pylorus is usually slightly open during the process (free flow of “finished” chyme). It contracts only 1) at the end of “antral systole” (see above) in order to retain solid food and 2) when the duodenum contracts in order to prevent the reflux of harmful bile salts. If such reflex does occur, refluxed free amino acids not normally present in the stomach elicit reflex closure of the pylorus (!D2).

Indigestible substances (bone, fiber, foreign bodies) do not leave the stomach during the digestive phase. Special contraction waves called migrating motor complexes (MMC) pass through the stomach and small intestine roughly every 1.5 hours during the ensuing interdigestive phase, as determined by an intrinsic “biological clock.” These peristaltic waves transport indigestible substances from the stomach and bacteria from the small intestine to the large intestine. This “clearing phase” is controlled by motilin.

Pylorus

Osmolality

Tryptophan

Gastrin

SIH

Motilin

CCK, GIP

Secretin

2 Proximal stomach and pylorus (emptying)

Gastric Juice

The tubular glands of the gastric fundus and corpus secrete 3–4 L of gastric juice each day. Pepsinogens and lipases are released by chief cells and HCl and intrinsic factor ( !p. 260) by parietal cells. Mucins and HCO3– are released by mucous neck cells and other mucous cells on the surface of the gastric mucosa.

Pepsins function as endopeptidases in protein digestion. They are split from pepsinogens exocytosed from chief cells in the glandular and gastric lumen at a pH of !6. Acetylcholine (ACh), released locally in response to H+ (and thus indirectly also to gastrin) is the chief activator of this reaction.

Gastric acid. The pH of the gastric juice drops to ca. 0.8 during peak HCl secretion. Swallowed food buffers it to a pH of 1.8–4, which is optimal for most pepsins and gastric lipases. The low pH contributes to the denaturation of dietary proteins and has a bactericidal effect.

HCl secretion (!A). The H+/K+-ATPase in the luminal membrane of parietal cells drives H+ ions into the glandular lumen in exchange for K+ (primary active transport, !A1 and p. 26), thereby raising the H+ conc. in the lumen by a factor of ca. 107. K+ taken up in the process circulates back to the lumen via luminal K+ channels. For every H+ ion secreted, one HCO3– ion leaves the blood side of the cell and is exchanged for a Cl– ion via an anion antiporter (!A2). (The HCO3– ions are obtained from CO2 + OH–, a reaction catalyzed by carbonic anhydrase, CA). This results in the intracellular accumulation of Cl– ions, which diffuse out of the cell to the lumen via Cl– channels (!A3). Thus, one Cl– ion reaches the lumen for each H+ ion secreted.

The activation of parietal cells (see below) leads to the opening of canaliculi, which extend deep into the cell from the lumen of the gland (!B). The canaliculi are equipped with a brush border that greatly increases the luminal surface area which is densely packed with membrane-bound H+/K+ ATPase molecules. This permits to increase the secretion of H+ ions from 2 mmol/hour at rest to over 20 mmol/hour during digestion.

Gastric acid secretion is stimulated in phases by neural, local gastric and intestinal factors (!B). Food intake leads to reflex secretion of gastric juices, but deficient levels of glucose in the brain can also trigger the reflex. The optic, gustatory and olfactory nerves are the afferents for this partly conditioned reflex (!p. 236), and efferent impulses flow via the vagus nerve. ACh directly activates parietal cells in the fundus (M3 cholinoceptors !B2). GRP (gastrin-releasing peptide) released by neurons stimulates gastrin secretion from G cells in the antrum (!B3). Gastrin released in to the systemic circulation in turn activates the parietal cells via CCKB receptors (= gastrin receptors). The glands in the fundus contain H (histamine) cells or ECL cells (enterochromaf- fin–like cells), which are activated by gastrin (CCKB receptors) as well as by ACh and !3 adrenergic substances (!B2). The cells release histamine, which has a paracrine effect on neighboring parietal cells (H2 receptor). Local gastric and intestinal factors also influence gastric acid secretion because chyme in the antrum and duodenum stimulates the secretion of gastrin (!B1 and p. 235, A).

Factors that inhibit gastric juice secretion:

(a) A pH of !3.0 in the antral lumen inhibits G cells (negative feedback, !B1, 3) and activates antral D cells, which secrete SIH (!p. 234), which in turn has a paracrine effect. SIH inhibits H cells in the fundus as well as G cells in the antrum (!B2, 3). CGRP released by neurons (!p. 234) activates D cells in the antrum and fundus, (!B2, 3). (c) Secretin and GIP released from the small intestine have a retrograde effect on gastric juice secretion (!B1). This adjusts the composition of chyme from the stomach to the needs of the small intestine.

Protection of the gastric mucosa from destructive gastric juices is chiefly provided by

(a) a layer of mucus and (b) HCO3– secretion by the underlying mucous cells of the gastric mucosa. HCO3– diffuses through the layer of mucus and buffers the acid that diffuses into it from the lumen. Prostaglandins PGE2 and PGI2 promote the secretion of HCO3–. Anti-inflam- matory drugs that inhibit cyclooxygenase 1 and thus prostaglandin production (!p. 269) impair this mucosal protection and can result in ulcer development.

Small Intestinal Function

The main function of the small intestine (SI) is to finish digesting the food and to absorb the accumulated breakdown products as well as water, electrolytes and vitamins.

Structure. The SI of live human subjects is about 2 m in length. It arises from the pylorus as the duodenum and continues as the jejunum, and ends as the ileum, which merges into the large intestine. From outside inward, the SI consists of an outer serous coat (tunica serosa, !A1), a layer of longitudinal muscle fibers

(!A2), the myenteric plexus (Auerbach’s plexus, !A3), a layer of circular muscle fibers (!A4), the submucous plexus (Meissner’s plexus, !A5) and a mucous layer (tunica mucosa, !A6), which is covered by epithelial cells (!A13–15). The SI is supplied with blood vessels (!A8), lymph vessels (!A 9), and nerves (!A10) via the mesentery (!A7). The surface area of the epithelial-luminal interface is roughly 300–1600 times larger (!100 m2) than that of a smooth cylindrical pipe because of the Kerckring’s folds (!A11), the intestinal villi (!A12), and the enterocytic microvilli, or the brush border (!A13).

Ultrastructure and function. Goblet cells

(!A15) are interspersed between the resorbing enterocytes (!A14). The mucus secreted by goblet cells acts as a protective coat and lubricant. Intestinal glands (crypts of Lieberkühn, !A16) located at the bases of the villi contain

(a) undifferentiated and mitotic cells that differentiate into villous cells (see below), (b) mucous cells, (c) endocrine and paracrine cells that receive information about the composition of chyme from chemosensor cells, and (d) immune cells (!p. 232). The chyme composition triggers the secretion of endocrine hormones and of paracrine mediators (!p. 234). The tubuloacinar duodenal glands (Brunner’s glands), located deep in the intestinal wall (tela submucosa) secrete a HCO3–-rich fluid containing urogastrone (human epidermal growth factor), an important stimulator of epithelial cell proliferation.

Cell replacement. The tips of the villi are continually shed and replaced by new cells from the crypts of Lieberkühn. Thereby, the entire SI epithelium is renewed every 3–6 days. The dead cells disintegrate in the lumen, thereby releasing enzymes, stored iron, etc.

Intestinal motility is autonomously regulated by the enteric nervous system, but is influenced by hormones and external innervation (!p. 234). Local pendular movements (by longitudinal muscles) and segmentation (contraction/relaxation of circular muscle fibers) of the SI serve to mix the intestinal contents and bring them into contact with the mucosa. This is enhanced by movement of the intestinal villi (lamina muscularis mucosae). Reflex peristaltic waves (30–130 cm/min) propel the intestinal contents towards the rectum at a rate of ca. 1 cm/min. These waves are especially strong during the interdigestive phase (!p. 240).

Peristaltic reflex. Stretching of the intestinal wall during the passage of a bolus (!B) triggers a reflex that constricts the lumen behind the bolus and dilates that ahead of it. Controlled by interneurons, cholinergic type 2 motoneurons with prolonged excitation simultaneously activate circular muscle fibers behind the bolus and longitudinal musculature in front of it. At the same time the circular muscle fibers in front of the bolus are inhibited (accommodation) while those behind it are disinhibited (!B and p. 234).

Pacemakers. The intestine also contains pacemaker cells (interstitial Cajal cells). The membrane potential of these cells oscillates between 10 and 20 mV every 3–15 min, producing slow waves (!C1). Their amplitude can rise (less negative potential) or fall in response to neural, endocrine or paracrine stimuli. A series of action potentials (spike bursts) are fired once the membrane potential rises above a certain threshold (ca. –40 mV) (!C2). Muscle spasms occur if the trough of the wave also rises above the threshold potential (!C3).

Impulse conduction. The spike bursts are conducted to myocytes via gap junctions (!p. 70). The myocytes then contract rhythmically at the same frequency (or slower). Conduction in the direction of the anus dwindles after a certain distance (!D, pacemaker zone), so more distal cells (with a lower intrinsic rate) must assume the pacemaker function. Hence, peristaltic waves of the small intestine only move in the anal direction.