At any one time, the shape of the stomach and duodenum is influenced by its contents and by surrounding organs. Particularly, the liver flattens the stomach. The proximal stomach assumes an almost vertical position in upright man, and its distal part ascends to the outlet.8 The inner (medial) curve of the J is known as the lesser gastric curvature for it is shorter than its opposite at the outside (lateral) the greater curvature. The lesser curvature is bent at the incisura angularis, the fulcrum between proximal and distal stomach (Fig. 1). The stomach is widest (roughly 10 cm in man) and most compliant at and above its inlet, and becomes stiff and narrow towards its outlet (the diameter of the human pylorus is 1 cm and less). The proximal fundus/corpus segment is a spacious reservoir;8,24 the distal antrum/pylorus segment is a thick walled muscular conduit, pump and sphincter.8,10–14,17 The fundus, upstream and lateral from the inlet, resembles a hemisphere when distended by an air bubble of 2–4 cm height.1,24 The gastric corpus (body) extends from below the gastric inlet (cardia) to the incisura angularis. Its lumen is collapsed in the empty stomach.24 Food boluses entering the stomach collect below the fundic air bubble, wedge into the corpus, and slide into the distal stomach (Fig. 2) along the lesser curvature (Magenstrasse). Additional contents expand the gastric corpus to a cylindrical lumen whose mucosal folds are flattened.1,24 The antrum is shaped like a cone when distended and like a tube when contracted.1,63 The sinus is the wedge shaped8,24,63 dependent segment of the stomach which bulges opposite the incisura (Figs 1–3). The distance between the uppermost pole of the fundus and the lowermost pole of the sinus averages 20 cm in men and 22 cm in women. The distance from the pole of the sinus to the gastric outlet averages 8 cm.24 These distances increase with gastric filling (Fig. 2) and decrease as digestion and emptying proceed.
Figure 2. Unfolding and pelvic descent of the human stomach. The ‘Magenstrasse’. (A–D) The fasting stomach is collapsed except for the fundus which is distended by an air bubble of 200–300 mL. Food passing the cardia collects under the bubble (A), gradually wedges into the corpus (B), and slides into the sinus. The high baseline tone of the corpus narrows the passage from the proximal to the distal stomach (C). Sequential food boluses distend the passage from below (as they accumulate as bolus II in the sinus and as bolus I below the air bubble (D). The narrow passage shown in (c) is what radiologists refer to as ‘Magenstrasse’, a term introduced by anatomists to define the smooth groove the gastric mucosa forms along the lesser curvature in contrast to the prominent mucosal folds (called gastric rugae) the inner gastric surface forms in the remainder of the proximal stomach. (E) Pelvic descent of dependent part (caudal pole) of stomach in response to eating. The lines represent the outline of the dependent part of the stomach after 4, 12, 16 and 20 bites. The stomach has expanded several centimetres towards the pelvis. As the greater curvature moves caudad and to the left from the pyloric orifice, the sinus forms between antrum and corpus. Redrawn from Groedel.
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These anatomical features have likely implications2,8,63–68 for the distribution of luminal contents and their motions in response to contractions (Fig. 4). The stomach resembles a bakers decorating bag whose contents are pressed into an ever narrower and stiffer conduit. Food layers in the stomach (Fig. 3), and layer by layer, the gastric contents become pasty then liquid as they approach the pylorus.24 Sediment and debris heavier than water collect in the sinus,66,68 whereas fat floats on top of the gastric contents,2,69,69A and is held back by the incisura (Fig. 4A). Liquids are made increasingly viscous as they move distally because secretions are combined with the tiny particles resulting from the break down of solids.67 At the same time, the vertical position of the stomach promotes layering of contents according to density. Recent boluses are stacked vertically along the lesser curvature, whereas earlier ones spread horizontally along the greater curvature (Fig. 3). The leading edge of a bolus pushes into earlier boluses and spreads them into thin layers.24 Boluses nesting inside earlier boluses escape the low pH required for peptic digestion and this allows salivary digestion to continue in an alkaline milieu.24 The very gradual penetration of the food bolus by gastric secretions has been visualized by echoplanar imaging.67
Figure 4. Hypothetical implications of the configuration of the stomach at rest and during digestive activity on the disposition of its luminal contents. (A) Layering and phase discrimination. Contents layer in the vertical stomach according to their density. Particles (gravity of 1.2) settle in the sinus, fat (gravity of 0.9) floats on top, with watery contents in between. Watery contents fill the distal antrum and escape into the descending duodenum ahead of solid particles and fat. Small particles moving with the aqueous phase advance over the pyloric ridge into the duodenum (decanting), while fat is retained by the incisura (skimming). (B) Deflection of particles and fat droplets by the antral boundaries. The conical shape of the antrum with the pylorus at its upper end would acts like an inverted funnel. During flow pulses, watery contents and tiny particles of water density make up the rapid core stream. Large particles and fat droplets move along the boundaries and are likely to be retained by the walls of the antrum. Sequential flow pulses would deposit gastric contents in the distal stomach according to their density gradients. (C) Shuttling of particles by antral contractions. As contractions indent the sinus and the antrum, they propel portions of sediment from the sinus towards the pylorus. As contraction depth and velocity increases towards the pylorus, particles roll back in a tumbling motion. (D) Actions of the incisura. As the peristaltic contraction invades the sinus, it lifts sediment up to the incisura. The incisura would partition, compress and scrape across the sediment similar to the actions of a pestle inside a mortar.
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The duodenal bulb is a receptacle for gastric effluent.22,25 Pancreatico-biliary secretions and duodenal contents are also likely to collect in the bulb: all duodenal contractions return aliquots towards the pylorus.28,58,59 Nutrients streaming out of the pylorus would stir the contents of the bulb by a nozzle effect. The sharp bend between the first and second duodenal segment probably further deflects and partitions gastric effluent.
Phase discrimination by the stomach
The segment that includes the pylorus and the distal antrum are critical to gastric sieving. Sieving refers to phase discrimination whereby the stomach empties aqueous solutions, while retaining particles >1 mm in size, and those of greater or lesser density than water. Sieving is often simplistically equated with straining in which soup is passed through a mesh to remove bulky material. Straining is likely to operate primarily towards the end of gastric flow pulses when the pylorus closes ahead of dense and particulate contents. Since most gastric outflow occurs while the lumina of stomach and duodenum form a common-cavity30 additional flow phenomena must contribute to sieving.
The gastric outlet is located well above the most dependent part of the stomach, and it is proposed that this contributes to sieving. Accordingly, pulses of flow carry liquids and tiny isodense particles through the pylorus into the descending duodenum, but stop before bulkier particles reach the rim formed by the gastroduodenal junction (Fig. 4B). Sieving would be achieved through a process akin to decanting63 and the antrum and pylorus would sort contents by density gradients. Tiny isodense particles would be carried by the core stream towards the pylorus. Large and comparatively heavy particles and buoyant fat globules would move at the fluid boundaries and be deflected by the walls of the antrum (Fig. 4A,B).
Contractions (Fig. 5) accelerate towards the pylorus4,31 and might outpace particles (Fig. 4C). As contractions approach the pylorus, flow back into the stomach increases at the expense of flow forward into the duodenum.1,10,20,22,25,27,30 Retrograde flow (or ‘bolus escape’) is favoured by the wide open lumen upstream and the narrow lumen towards the pylorus.20,23,26,63,65 The above concepts remain to be tested by rigorous numerical analysis.
Figure 5. Changes in configuration of human stomach. As the contraction advances from 1 to 6, it indents the caudal pole of the stomach (the sinus) and lifts its up and towards the pylorus. At the same time, the incisura deepens and forms a more acute angle between proximal and distal stomach. Note how the terminal antrum has narrowed at stage 6 as compared with stage 1. Contractions in response to a mixed solid–liquid meal to which a small amount of barium was added. After Groedel.
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Computing flow based on boundary movements
The first computations of flow and mixing in the human stomach was published in December 2004 by the group of James Brasseur.61 Based on realistic data of the geometry, luminal pressures and boundary movements from simultaneous MRI and high resolution manometry in the human stomach, the model demonstrated the strongest fluid motions around the lumen occlusion generated by contractions in the antrum. Fluid motions were of two distinct patterns. The first pattern corresponded to the well known retropulsive jet1,5,20,22,25,30,63 during the terminal antral contraction. Jet velocity increased up to 7.5 mm s−1 in proportion to lumen occlusion, but was not affected by pyloric closure or other physiologic parameters tested. The fluid jet spread particles along the long axis of the stomach, more so distally than proximally. The second fluid motion identified were flow vortices (or eddies) that circulated particles between successive contraction waves. Flow eddies have escaped detection by imaging, but are critical to digestion by producing radial mixing.21,61,62 Eddies might carry gastric secretions from the mucosal surface towards the core of the gastric lumen, help to hydrate food boluses, and to carry off surface particles (elution).
Gastric contractions and dynamic changes in gastric configuration
Flow in and out of the stomach is mediated by the complex movements of the gastric boundaries during contractions. Contractions start as increases in gastric tone that flatten and narrow the fundus,1,65 shorten the greater curvature, affect the position of the incisura, and redraw the borders between the proximal and distal stomach. Peristaltic contractions are born of tone contractions as shallow indentations on the proximal greater curvature, about 15 cm above the pylorus in the human stomach.1–5,61 Indentations deepen as they propagate distally and often virtually occlude the antral lumen (Fig. 4). The frequency and propagation of phasic contractions are controlled by the gastric pacesetter, an oscillating membrane potential whose frequency approximates 3 cycles min−1 in man. Propagation velocity averages 2.5 mm s−1, and increases from the proximal to the distal stomach.1–5,31 At any one time, two to three peristaltic contractions involve sequential sections of the stomach, each taking approximately 60 s to advance from the fundus to the pylorus. Peristaltic contractions indent the gastric wall over the short band width of 1–2 cm.26,61,65 The contraction width increases as the contraction approaches the proximal pyloric loop (Fig. 4) and closes in rapid sequence, a 3 cm or longer segment of the lumen.22,63 This so-called ‘terminal antral contraction’ or ‘antral systole’ produces dramatic flow (see below). Flow in the proximal stomach is slow by comparison, and occurs over shorter distances.61
Meals, by their volume, chemical and physical properties, affect the amplitude of contractions, the length of their propagation (between the sites at which they originate and where they terminate), and the duration of time the stomach generates peristalsis.1–5 Large meals stimulate powerful phasic contractions through the corporo-antral reflex1,33,37,48 and contractions originate higher up in the stomach. Contractions are deep with aqueous contents, and shallow when contents are highly viscous.20,23 With liquid meals containing few calories, the stomach may be empty after a few contractions. With substantial meals of meat and vegetables, contractions may go on for hours.
Contractions indent the greater curvature more than the lesser curvature.1–5,20,23,65 This is because13,14 contractions originate on the proximal greater curvature, and move the compliant greater curvature towards the stiff lesser curvature (rather than moving both equally towards a midline). Contractions presumably move more slowly along the shorter lesser than along the greater curvature, and lead to complex movements of the incisura while sequentially indenting and lifting the greater curvature from the gastric body to the antrum.24,79
The terminal antral contraction and the retrograde jet
Ehrlein and Schemann distinguished three phases of antral flow in the dog:25 in the first phase of propulsion, the contraction reaches the proximal antrum, and drives chyme into the middle and terminal antrum. In the second phase, evacuation and retropulsion, some chyme escapes through the relaxed pylorus and some is returned towards the gastric body. In the third phase, retropulsion and grinding, the contraction advances at increasing speed and virtually occludes the terminal antrum and pylorus lead to forceful grinding and retropulsion.
Dynamic contrast studies,20,22,25 ultrasound observations,68 and fluid mechanical models61 show the striking impact of terminal antral contractions on particle dispersion. C Code commented:1‘Terminal antral contractions mix, reduce the particle size of and emulsify the gastric contents. Simple mixing of contents accompanies all peristaltic activity. The mixing activity of the terminal antral contraction is unique. When the pyloric canal closes…contents are forcefully retropelled towards the corpus through the narrow orifice of the advancing contraction. This squirting has a nozzle effect which mixes and emulsifies contents. Besides mixing and emulsifying, terminal contractions rub and grind the contents. No measurements have been made of the effectiveness of this process’.
In preliminary studies, retrograde jets occurred 5.6 + 2.2 s before pyloric closure and lasted 7.2 + 3.1 s. The leading edge of the jet moved some 15 mm upstream. The trajectory of individual particles was much longer, their velocity declined from around 13 mm s−1 at the peak to around 8 mm s−1 towards the end. As the jet pointed sequentially towards the gastric cardia and the dependent part of the curvature, it stirred up sediment and swirled particles in the gastric body.65,80
The terminal antral contraction produces impressive flow patterns.1,20,25,34,65 However, jets are no more than the dramatic finale to digestive processes already well under way. Normally, only liquid chyme and small particles79 reach the distal antrum, and even after the antrum and pylorus are resected, two-thirds of food particles are adequately digested.2
Forces controlling gastric emptying
Changes in gastric tone (size), and the propagating indentation of gastric peristalsis provide the momentum to gastric emptying. The emptying rate is determined by the balance between driving and resistive forces.25 With aqueous and isotonic meals, the proximal stomach shrinks promptly, and the distal stomach and gastroduodenal junction widen. Rapid gastric outflow is accompanied by net gastric emptying (reduction in gastric volume). In contrast, high caloric and poorly digestible meals lead to profound and prolonged relaxation of the proximal stomach and tonic closure of antrum, pylorus and duodenum.22,25,29 Contents may take hours to advance from the proximal to the distal stomach.1–3,25 Gastric outflow is pulsatile, with individual flow pulses out of the pylorus in the range of 2–3 mL after regular meals in dogs.81
Gastric emptying occurs largely as an isotonic process, through a patent pylorus and without a sizeable antro-duodenal pressure gradient.22,25,30,57,58,65,73 Pressure pulses generated by peristaltic contractions may modulate outflow, and generate forces that promote mixing and digestion.65 A recent numerical analysis sheds additional light on these issues: the pressure differences necessary to produce pyloric flow are too small to be measurable by manometry. It was proposed that ‘the slight pressurization of the terminal antrum by an antral contraction wave still several centimetres from an open pylorus may be sufficient to significantly augment transpyloric flow generated by global common cavity pressure difference between the stomach and duodenum maintained by fundic muscle tone’.61
Liquids clear the stomach at a rate proportional to their intragastric volume or by first-order-kinetics. The rate at which the stomach empties increases before it declines,2,23,25 an emptying pattern best represented by a power exponential curve.2,5 The forces behind this are presumably the high gastric wall tension generated by large volumes and the large volumes displaced by any contraction in that setting.
Solid particles empty from the stomach by fundamentally different zero-order kinetics, that is independent of gastric volume.2 The stomach retains for digestion particles whose diameter exceeds 1 mm and those whose density differs from water. If particles are ingested at 10 mm size, they are reduced to a median of 0.05 mm upon arrival in the duodenum.2,55 The duration of the digestive phase depends on the physical properties of the food: soft noodles and eggs are processed faster than comparatively compact cooked liver.2,55 If liver is fed as both large and small particles, both leave the stomach eventually at the same size and rate, but there is a longer time delay before the large ones appear. There is, therefore, a delay up to several hours between the ingestion and the efflux of solids (or of the chyme that derives from their dispersion). As the viscosity of gastric contents increases, even large and dense particles may be dragged along.2,3 The time delay also reflects the rate at which the proximal stomach delivers nutrients to the antrum. For this, the stomach needs to recover its tone and phasic contractions after the meal and to secrete acid and enzymes that soften and suspend solids. Solid meals induce more profound inhibition of gastric contractions than liquids, and also induce larger secretory responses.67,68 The gastric emptying of solids is delayed when acid secretion is suppressed, particularly by proton pump inhibitors.82
The digestion and emptying of solids proceed in parallel. Not all gastric contents are digested by the time solids or their derivates start emptying from the stomach. Hundreds of contraction waves may be required to digest and empty a solid meal of meat and vegetables.2,78 The flow generated by each contraction has to be controlled so that large and compact particles are retained for digestion while fluid and isodense tiny particles suspended in the fluid are allowed into the duodenum. More energy is required to digest meals of fat and protein than of carbohydrates.2,6,7,52–54 The steady rate at which the stomach clears solid derivates has been linked to the intrinsic frequency of the gastric pacesetter controlling antral contractions. Meyer proposed that the zero-order kinetics for solid emptying relates to this finite process.2
Where and how quickly medicinal preparations release the active drug affects pharmacodynamics, and imaging and modelling is about to revolutionize the design of drug preparations. Preparations of various size, composition and fracture strength have been tracked by echoplanar imaging.66,83–85 The residence time of particles in the stomach increases with their fracture strength, just as soft pasta empties faster than more solid liver.2,54,66
Bidirectional flow across the pylorus and the nozzle effect. Role of the duodenal bulb (cap)
Flow out of the stomach occurs largely as individual gushes (pulsatile flow). In dogs, chyme squirts out of the pylorus about every 12 s, at flow rates at 3 mL s−1 and higher. Flow turns more steady beyond the duodenal bulb as more frequent flow pulses move smaller volumes.81 Pyloric flow resistance of 2.2 mL mmHg s−1 is much higher than duodenal flow resistance (0.7 mL mmHg s−1), which still dampens gastric outflow.29 Chyme squirts out of the narrow pyloric orifice into the wide duodenal bulb to form a vortex. This nozzle effect is likely to mix gastric effluent with duodenal contents and pancreaticobiliary secretions.
In up to 60% of gastric contraction cycles, the duodenal bulb contracts before the terminal antrum. This leads to retrograde flow across the pylorus.25,86 Pancreaticobiliary secretions might thus be injected and forcefully mixed into nutrients just about to leave the stomach.
Duodenal contractions and flow
Duodenal contractions ensure that pancreaticobiliary secretions work on gastric chyme. Most contractions occlude the lumen maximally around the middle section of the descending duodenum, at or below the papilla of Vater.28,29 From there, the contraction expands proximally and distally, separating contents and moving some towards the stomach and some towards the distal duodenum. As the duodenum relaxes, these contents would flow back. This to-and-fro movement produced by segmental contractions is likely to have a powerful mixing effect.
The activity of the duodenum28 is highly susceptible to the chemical composition of luminal contents. In response to isotonic saline, the human duodenum generates propagating contractions that swiftly sweep the bolus caudad. Hypertonic saline or acid elicit a tonic contraction which virtually occludes the duodenal lumen. Frequent rhythmic contractions lead to high luminal pressures. Fat makes the duodenum a flaccid bag whose shallow contractions act on contents seemingly at random.29
In their classical computations, Macagno and Christensen relied on geometric simplifications to describe wall movements gleaned from still photos and defined flow patterns without the benefit of current computing power. Nevertheless, many of their conclusions remain valid to date. Thus, they showed that a series of longitudinal contractions draws a compact fluid bolus out into thin convoluted layers, which would promote diffusion and convective mixing.21 They also demonstrated that retrograde and radial flow60 are intrinsic features of peristaltic movements in addition to the laminar antegrade flow they are often naively identified with.65,87–90
Gastrointestinal secretions, and the hydration, dilution and elution of food
To the food and drink ingested, the stomach and duodenum add their secretions. Malagelada has estimated that the cumulative volume cleared by the stomach is double or triple the volume of the original meal.3,53 Ehrlein found that the stomach of dogs fed mashed potatoes and olive oil enlarged over the first hour before outflow outweighed secretory input.23,25
Secretions render meals less compact and less concentrated. Nutrients are hydrated and diluted to decrease their physical consistency, caloric density and osmolality.2,4 Swelling, softening, and disintegration of particles serve to suspend them and carry them in liquid medium. In currents and counter currents particles are further ground down by shear stresses and are effectively mixed with digestive secretions.
Contemporary imaging can directly visualize how the physical state of food is altered by digestion.1,2,78 When the gastric dilution of a highly viscous polysaccharide meal was monitored by echoplanar imaging,67 secretions diluted initially only the contents close to the gastric walls. In the second hour, secretions penetrated the core of the food bolus. Contractions moved solid gastric contents in a process of elution as they rushed fluid over the surface of the softened food bolus. This is similar to how discrete beans were transformed over hours of contractions into a paste, bits of which were dragged out of the pylorus by fluid streams.63,65
The suppression of gastric acid secretion slows gastric emptying, even of liquids.82 This is related to the increased intragastric pH and the release of gastrin which relaxes the proximal stomach and thereby delays the delivery of gastric contents. How the lack of secretions interferes with digestive processes has not been studied in detail.
In the duodenum, the gastric effluent is exposed to bile and to pancreatic secretions. Gallbladder contractions and pancreaticobiliary flow alternate with the gastric emptying of fats, presumably to allow for effective mixing of fats, bile salts and enzymes.91–95 Bicarbonate neutralizes gastric acid, and allows pancreatic enzymes to reduce proteins to amino acids, and carbohydrates to hexoses. Bile salts clear fats by micellar solubilization; this allows water soluble pancreatic lipases to split fats. Knowledge of these processes derives primarily from in vitro experiments or from examination by freeze fracture of luminal samples.78,86,95,96 The in vivo topography of these physico-chemical changes remains to be clarified.
Chyme and its constituents
Chyme is food altered by the mechanical and secretory activity of the stomach and intestines. It is a multi-phase slurry of nutrients in various physical states (liquid, globular, pasty or particulate) suspended in secretions. The suspension serves luminal transit, enzymatic digestion and absorption. Chyme composition has not been mapped in detail over the course of digestion or at precise points in the stomach and duodenum. It is likely that within any bolus of chyme zones of specific pH, of stages of micellar solubilization and of nutrient hydrolysis rapidly form and disappear under the influence of contractions and secretions of acid, bicarbonate, bile and enzymes.
Late in digestion, the stomach empties an increasingly pasty chyme. This has been ascribed to lesser amounts of fluid and secretions available to carry particles.2,3 However, digestion renders gastric contents increasingly viscous by releasing small particles into the fluid medium. Viscous solutions would be expected to carry larger particles in the fluid stream than aqueous secretions.2,54 Moreover, as the stomach shrinks in size, its greater curvature shortens and moves towards the lesser curvature. This lifts sediment and debris from its dependent parts towards the pylorus.2,54
The size of food particles and fat droplets
Liver ingested as 10 mm cubes is recovered in duodenal samples as particles well below 1 mm: 95% of particles are <0.5 mm in size, and their median distribution corresponds to a tiny 50 μm.2,7,54 Breaking up a few large particles into many tiny particles enlarges the surface at which enzymes attack substrate. Dogs normally absorb up to 85% of fat from liver. Once the dogs undergo a truncal vagotomy with antrectomy, they absorb less than half the liver fat. Less complete break down in the stomach means half the liver particles are still 0.5 mm or larger in the mid-intestine, and do not release intracellular fat for digestion and absorption.2,54
Fat may be liquid or solid at ingestion2,54 and is less dense (specific gravity of 0.9) than water and most solid foods (specific gravity of 1.2). Fat is easily dispersed into tiny spherules, but these may coalesce into larger globules unless they are stabilized or attach to the hydrophobic surfaces of food particles.6,52,86,95,96
Armand and coworkers have studied the emulsification of fat by the stomach and duodenum.97–103 The stomach reduced the median diameter of fat droplets from around 57 to 17 μg. This increased the emulsion surface area from 0.7 m2 g−1 lipid to 2.1 m2 g−1 in the stomach and to 1.6 m2 g−1 in the duodenum. At 1 h, the mean concentration of emulsion surface was 270 m2 L−1 in the stomach and 78 m2 L−1 in the duodenum.