Physiological Pharmaceutics

84 Physiological Pharmaceuticscauses rapid acid production, but mixing in this region is poor, so that the extendedbuffering effect of the food is observed. As the food moves into the antrum, the vigorousmixing not only reduces particle size of the food, but mixes it with the gastric acid whichwas produced higher in the stomach. The pH in the antrum remains low, despite the factthat there are no parietal cells in this region, since much of the food has been neutralizedwhile stored in the body of the stomach (note: the small peak seen after 30 minutes was dueto the administration of 50 ml of water for a separate phase of the experiment, and shouldbe ignored).Acid secretion is increased after hot or cold meals even though temperature of themeal per se does not alter gastric emptying. It takes significantly longer for cold meals tobe brought to body temperature than hot meals 2 . Content of the meal also affects gastricpH; for example, a pure carbohydrate meal given as a pancake has no detectable effect onacidity 3 , while a protein meal of similar calorific value has a significant buffering effect 4 . Aliquid meal, rather than a mixed phase meal, with a balance of carbohydrate and proteinhas a strong buffering effect but the pH rapidly returns to basal levels as the liquid isemptied. The situation is complicated by feedback effects; for example pepsin normallyhydrolyses proteins to peptides and amino acids, which are potent secretagogues, andincrease the acidification of gastric contents. However pepsin is inactivated above pH 5, soa large meal which raises the pH above this value will prevent the production of thesesubstances, and peak gastric acid secretion will be reduced.Circadian rhythm of acidityA circadian rhythm of basal gastric acidity is known to occur with acid output being highestin the evening and lowest in the morning (Figure 5.9) 5 . The daytime patterns of gastric pHvary greatly between individuals, in part due to the differences in the composition of mealsand the variable responses of acid secretion and gastric emptying. However, nocturnalpatterns of gastric acidity are very similar with very low pHs between midnight and earlymorning 3 . The later in the day the evening meal is taken, the later the nocturnal peak ofacidity occurs 6 ; it is therefore important to standardise the time for the evening meal whencomparing the nocturnal effects of anti-secretory drugs.Figure 5.9 Circadian variation in gastric acidity