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Figure 5.13 MRI cross section through the body. The large organ at the top is the stomach, which clearly shows the liquid layer (white) floating on the solid (grey) matter duodenal bulb rises above than that in the antrum, and the pylorus prevents reflux by closing. The vagus nerve has an important role in the control of emptying, but studies on paraplegia caused by injury to the spinal cord indicate that the sympathetic division of the autonomic nervous system is also involved.

Effect of meal size and composition on gastric emptying

The empty stomach has a volume of approximately 50 ml which increases to over 1 litre when full. The stomach empties the three different components of the meal, liquid, digestible solid and indigestible solid, at different rates. For example, in a study of the emtying of a mixed meal consisting of soft drink, scrambled egg and radioopaque markers, the separate components had T50's (the time or half the component to be emptied) of 30±7 minutes, 154±11 minutes and 3 to 4 hours respectively19.

In general, the larger the amount of food ingested, the longer the period of fed activity; large meals tend to empty more slowly in the first hour and then more quickly compared to a small meal. Gastric emptying rates correlate with the nutritive density of the meal; foodstuffs slow gastric emptying equally when their concentration is expressed as kilocalories per milliliter. It is now believed that two types of receptors exist which control the rate at which the energy density is delivered to the duodenum. Two sets of duodenal receptors are involved, one stimulated by the osmotic properties of the digestion products of carbohydrate and protein, and one by the digestion products of fat. Energy is not actually sensed, but the two sets of receptors behave in tandem to control the delivery of the chyme to the duodenum by energy density.

The emptying of amino acids appears to be solely dependent upon their osmolarity, except for L-tryptophan which delays gastric emptying in concentrations which can be obtained from normal protein digestion20. Fatty acids, monoglycerides and diglycerides all delay gastric emptying, but the greatest delay is produced by fatty acids of chain lengths of 10-14 carbon atoms21. The slowing of gastric emptying produced by triglycerides depends upon their rate of hydrolysis to long-chain fatty acids.

Manometric and scintigraphic studies indicate that bland liquids such as water and saline empty from the stomach in gushes associated with co-ordinated contractions of the antrum and duodenum22. For example, during the emptying of 600 ml of a bland liquid, 13% passed into the duodenum very quickly, followed by a lag phase of 4-6 minutes, with the overall emptying having a T50 of only 15 minutes23.

Food was believed to form layers in the body of the stomach in the order in which it was swallowed, since for the first hour after ingestion of a meal peristalsis is weak, allowing the food to remain relatively undisturbed24, with the food ingested first being closest to the stomach wall. This data was generated from a study in which rats were fed successive portions of bread, each coloured with a different dye. The animals were killed, the stomachs removed, frozen and sectioned. The portions were found to be separate25. This is a simplified case which bears little resemblance to a typical human meal, which consists of a mixture of components of varying density. The human stomach is of course much larger than the rat stomach, so that the effects of sedimentation and stratification are likely to be very different. Pellets with a density of 1.2 g cm3 sink through food to the base of the greater curvature and are emptied after the majority of food (Figure 5.14). Increasing the viscosity of the gastric contents increases the rate at which dense spheres will empty from the stomach26. This suggests that the high viscosity of the medium prevents the spheres from settling into the base of the greater curvature, away from the mixing, grinding and emptying function of the antrum. Materials which have been demonstrated to float in vivo can be refloated from the antrum of the stomach to the fundus by the subsequent intake of food27 thus casting doubt on the theory of stratification.

The effects of fats and oils on gastric emptying

Although it is widely recognised that the fat content of food is the most important factor controlling gastric emptying, the majority of studies over the past 15 years have been carried out in animals such as rats, mice and dogs. The fundamental difference between these

Figure 5.14 The effect of density on gastric distribution

Heavy objects fall to base of greater curvature

Figure 5.14 The effect of density on gastric distribution species and man is posture, and since certain types of fat will layer in the stomach, their presentation to the pylorus and duodenum naturally will be different in relation to other components of the meal. This is due to the effect of gravity. This effect can be demonstrated in man since olive oil empties more slowly than an aqueous component of a meal when subjects are seated whereas, in the decubitus position (lying), it empties faster28 29.

The delayed emptying of fat is not just due to the fact that it floats on the meal, and hence emptyies last when subjects are upright, but the presence of fat in the intestine causes the fundus to relax. This lowers the intragastric pressure, increasing the reservoir function of the stomach. It also inhibits antral contractile activity, increases pyloric contraction and narrows the pyloric lumen15. This has the effect of significantly increasing the lag phase of the meal after an initial amount has entered the small intestine23. The movement of food from the proximal to the distal stomach still occurs; however, it is followed by a retrograde movement of food back to the proximal stomach, and this may also contribute to the increased lag phase. This redistribution of food in the stomach is also seen after intraduodenal infusion of lipid30. Interestingly, the emptying of the oil follows a linear pattern rather than the expected monoexponential emptying typical of liquids.

Dietary fat is ingested in three forms: 1) in solid food, 2) as aqueous emulsions, and 3) as unemulsified, liquid oil. To complicate matters, the gastric residence of a meal with identical composition will be prolonged if the fat content is used to fry the food rather than ingested as the cold oil31. Ingestion of a high fat meal increases satiety and a feeling of epigastric fullness for a longer period than an energy-matched low fat meal. It will influence the amount of food taken at the next meal even though the amount of food remaining in the stomach from the first meal is approximately the same32. The addition of fat to a meal will also prolong the time for which the meal elevates gastric pH33.

The behaviour of oils within the stomach is also affected by the other constituents of the meal. When 60 ml of 99mTc labelled oil was given to subjects with 290 ml of 113mIn-labelled soup, gastric emptying of the oil was significantly slower than the soup (time to 50% emptying 139 versus 48 min)34. Oil was retained in the proximal stomach and retrograde movement of oil from distal into proximal stomach was noted. The second arm of this study investigated the relative gastric residence time of 113mIn-labelled minced beef, 99mTc-labelled oil and non-labelled soup. In this case, there was no difference in emptying of oil and beef from the stomach, but again more oil was retained in the proximal stomach whereas more beef was retained in the distal stomach. In another study35 the effect of adding 60 g of margarine into either the soup or mashed potato component of a meal was investigated. The addition of margarine to either component significantly delayed the gastric emptying of the mashed potato, but the pattern of emptying of the potato varied depending which component was fat-enriched. Incorporation of fat into the soup increased the lag phase but did not influence the slope of emptying of the mashed potato, while incorporation of fat into the mashed potato reduced the slope of emptying of the mashed potato but did not influence its lag phase.

When ingested as part of a mixed meal, water invariably leaves the stomach faster than fat36. Solid fat, extracellular fat, and intracellular fat phases of a meal empty together, in parallel, after an initial lag26. The way in which fat is emptied from the stomach is species dependent. In humans, significantly less extracellular fat than intracellular fat empties from the stomach on or in solid food particles (22% versus 51%). In dogs, 81% of the extracellular fat empties as an oil, 13% empties on the solid particles, and only 6% empties as a stable, aqueous emulsion. Sixty-six percent of the intracellular fat emptied in the solid food particles, 20% as a stable, aqueous emulsion, and 14% as an oil. The conclusion from this study was that the majority of the intracellular fat empties within the solid food phase, whereas most of the extracellular fat empties as an oil phase26.

Dietary fats leave the stomach faster, but are absorbed less efficiently, after homogenised meals, compared to being given as a mixed phase meal37. Co-ingestion of fat with carbohydrate results in a significant flattening of the postprandial glucose curves, the effect being more pronounced for carbohydrates such as mashed potatoes which are more rapidly absorbed than carbohydrates such as lentils38.

In humans, duodenogastric reflux occurs both after meals and under fasting conditions. The reflux rate is on the average 13 times smaller than the emptying rate, but is higher with a lipid than with a protein meal, and is independent of the rate of gastric emptying. The concentration and total amount of duodenal contents refluxed back to the stomach were higher after lipid than after protein meals. The increased gastric concentration and accumulation of duodenal contents after lipid meals is due to slowed gastric clearing and increased reflux of duodenal contents. Under fasting conditions, the reflux rate was lower and the gastric concentration of duodenal contents was higher than after either type of meal39.

The distribution of the fat within the stomach can be changed with disease. Patients with non-ulcer dyspepsia demonstrate an abnormal intragastric distribution of dietary fat. In control subjects, approximately three-quarters of the fatty test meal was located in the proximal stomach during the lag period and during emptying. In the group of patients with non-ulcer dyspepsia, significantly less of the fatty test meal was found in the proximal stomach during emptying, and the time taken for half the meal to empty was significantly delayed40.

It is often believed that a high fat meal produces nausea in conjunction with motion. However, the nausea produced does not appear to be related to the fat being present in the stomach, but rather the small intestine41. Nausea is at its greatest when motion of the body occurs when half of a fatty meal has emptied into the small intestine, but is interesting that gastric residence of the fat is not correlated with the symptoms.

There is a positive correlation between lipid intake and reflux in morbidly obese people42. This is likely to be due to a combination of an increase in gastric residence of the meal due to the high calorific density of the fat, and a decrease in lower oesophageal sphincter pressure produced by fatty meals. Interestingly, intravenous lipid emulsions do not affect lower oesophageal sphincter pressure or increase pathological reflux episodes43.

Physiological factors which influence gastric emptying

Gastric emptying follows a circadian rhythm, with slower emptying occurring in the afternoon compared to the morning (Figure 5.15)44. This effect can be very marked; in the study illustrated there was over a 50% decrease in emptying rate in the solid phase of the meal when it was eaten in the evening compared to the morning.

In women, pregnancy and the menstrual cycle can drastically alter the transit of materials in various regions of the gastrointestinal tract. Often pregnant women suffer from heartburn and constipation which is attributed to decreased oesophageal pressure and impaired colonic motility. During the normal menstrual cycle mouth to caecum transit is significantly longer in the luteal phase than in the follicular phase45.

There are conflicting reports as to the effect of obesity on gastrointestinal transit. Some studies show no effect, whilst others report delayed emptying of solids particularly in men, a phenomenon which is not reversed after significant weight loss46 47. Other studies show an inverse association between body mass index and mean gastric emptying time of test meals such as radiolabelled cellulose fibre. Body mass index had no influence on other transit variables48.

Heavy exercise was found to increase the gastric emptying rate of digestible solids in healthy men49.

Remaining in Stomach (%)

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