Proximal jejunum

Lindahl, A., Ungell, A. L Knutson, L Lennemas, H. Characterization of fluids from the stomach and proximal jejunum in men and women. Pharm. Res. 1997, 14,497-502. 

When food is ingested, the pH in the stomach can rise briefly to 7, but after 0.1 h drops to pH 5, after 1 h to pH 3, and after 3 h to the fasted value. The movement of food down the small intestine causes the pH in the proximal jejunum to drop to as low as 4.5 in 1-2 h after food intake, but the distal portions of the small intestine and the colon are not dramatically changed in pH due to the transit of food. The... 

The surface area in the luminal side of the small intestine per unit length of the serosal (blood) side is enormous in the proximal jejunum, and steadily decreases (to about 20% of the starting value [62]) in the distal portions of the small intestine. The surface area is increased threefold [69] by ridges oriented circumferentially around the lumen. Similar folds are found in all segments of the GIT, except the mouth and esophagus [66]. Further 4—10-fold expansion [62,69] of the surface is produced by the villi structures, shown schematically in Fig. 2.4. The layer of epithelial cells lining the villi structures separate the lumen from the circulatory system. Epithelial cells are made in the crypt folds of the villi, and take about... 

McEwan, G. and M. Lucas. The effect of E. coli STa enterotoxin on the absorption of weakly dissociable drugs from rat proximal jejunum in vivo, Br.J. Pharmacol. 1990, 101, 937-943... 

Location and extent Gastric stomach Similar flora present in duodenum and proximal jejunum Small intestine, segmental or global Backwards colonization of the stomach in severe forms... 

Fig. 4. The normal nocturnal migrating motor complex (MMC) recorded in the duodenum (upper tracing) and proximal jejunum (lower tracing) of a 91-year-old healthy woman. A short period is shown in high resolution in the lower panel. Phase III is preceded by phase II with some contractile activity, usually limited during sleep, and succeeded by contractile quiescence, phase I. The sequence of phase III-I-II-III constitutes one MMC cycle, and recurs during fasting (modified with permission from Husebye and Engedal [79]).

Due to the paucity of data for humans, it might be helpful to look at the canine model. In general, mean intestinal transit and flow rates of the dog correspond well to analogous data from humans. Flow rates in the canine jejunum after administration of 200-600 mL of various liquid meals ranged between 1 and 4mL/min and sometimes up to 7 mL/min (72-76). Further, intestinal flow rates are highest in phase II/III of the MMC, followed by post-prandial flow rates. Flow rates in the canine duodenum and the proximal jejunum after administration of various liquids range between 2 and 13 mL/ min (30,43,77). For instance, median duodeno-jejunal flow... 

Lucas M (1983) Determination of acid surface pH in vivo in rat proximal jejunum. Gut 24 734-739. 

About 10-25%, i.e. 50-200 pg, of the daily dietary intake of folic acid in yeasts, liver, and green vegetables is absorbed via active and passive transport in the proximal jejunum. As humans do not have dihydropteroate synthetase, which synthesizes folic acid in bacteria, we require folic acid in the diet. Only small amounts of folate can be stored in the body and dietary deficiency for only a few days can result in symptomatic folate deficiency. 

The average diet in the USA contains 10-15 mg of elemental iron daily. A normal individual absorbs 5-10% of this iron, or about 0.5-1 mg daily. Iron is absorbed in the duodenum and proximal jejunum, although the more distal small intestine can absorb iron if necessary. Iron absorption increases in response to low iron stores or increased iron requirements. Total iron absorption increases to 1-2 mg/d in menstruating women and may be as high as 3-4 mg/d in pregnant women. 

Unaltered folic acid is readily and completely absorbed in the proximal jejunum. Dietary folates, however, consist primarily... 

Unaltered folic acid is readily and completely absorbed in the proximal jejunum. Dietary folates, however, consist primarily of polyglutamate forms of N 5-methyltetrahydrofolate. Before absorption, all but one of the glutamyl residues of the polyglutamates must be hydrolyzed by the enzyme -1-glutamyl transferase ("conjugase") within the brush border of the intestinal mucosa. 

Because P-gp expression was reported to increase from the proximal to the distal regions of the small intestine (Yumoto et al. 1999), Lacombe et al. suggested gastroretentive or immediate release dosage forms for the delivery of P-gp substrates (Lacombe et al. 2004). It has been shown, for example, in everted gut sacs of rats that the transport of digoxin is about 2.5-fold higher in the proximal jejunum in comparison to the terminal ileum. 

Calcium is absorbed in the intestine by two distinct mechanisms, an active process that is vitamin D dependent and another that is vitamin D independent. When the dietary intake of calcium is low, the intestinal uptake of calcium occurs by an active transport process that is vitamin D dependent. Active transport is most efficient in the duodenum and proximal jejunum, areas of the intestine that have a pH close to 6.0 and where calbindin, a calcium transport protein, is present. However, the amount of calcium absorbed in the ileum may be greater than that absorbed in the duodenum and jejunum... 

When Thomson et al. (45) used an occulsive balloon to perfuse 54Mn into the duodenum and proximal jejunum of eight subjects, the rate of absorption averaged 27% over a 1 hour period. Mena et al. (46) had previously found a lower rate of absorption, 3%, for orally administered 54Mn by whole body counting for two weeks. However these authors felt that the measurements may have underestimated the amount actually absorbed since they could not account for the amount that had been absorbed and re-excreted. 

Q4 The water-soluble vitamins (B and C) and essential minerals, such as iron, are absorbed in the small intestine. The reabsorption of iron in the duodenum and proximal jejunum involves a complex active transport process. When there is a large reduction in the surface area of this part of the gut, there is a marked reduction in reabsorption of iron (and B vitamins). Haemoglobin synthesis is decreased, leading to development of anaemia, which is a common symptom in celiac disease. 

Dietary thiamin phosphates are hydrolyzed by intestinal phosphatases, and the resultant free thiamin is absorbed by active transport in the duodenum and proximal jejunum, with little absorption in the rest of the small intestine. 

Lennemas et al. have developed a method for measuring human effective permeability (H-Peff) using a regional intestinal perfusion technique. In this method, a perfusion apparatus consisting of a multichannel tube with two inflatable balloons (10 cm apart) is swallowed by the patient and eventually located in the proximal jejunum. Dilute solutions of the test drag are introduced at the inlet located at the center of the 10 cm section, and the loss of drag is determined from the concentration in the outlet intestinal perfusate. In such a fashion, the H-Peff for 22 carefully selected drug molecules has been determined and a theoretical model of H-Peff has been developed. " The small size of the published H-Peff database is most likely due to the expense of the human measurement. 

Glucose-dependent insulinotropic polypeptide is originally known as gastric inhibitory polypeptide (GIP), which is a 42-residue peptide first isolated by Brown and Dryburgh (14). It is secreted from the duodenum and proximal jejunum in response to food. Two major physiological effects of GIP are inhibition of gastric acid secretion and stimulation of insulin release. 

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