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The relationship of the sphincter of Oddi to the stomach, duodenum and gall-bladder.

Flow through the sphincter of Oddi was studied by a constant-pressure perfusion apparatus, and by using a constant rate of infusion and measuring pressure changes just proximal to the sphincter. Pressure changes from balloons placed in the gastric antrum and duodenum were recorded. Despite considerable variation in activity and behaviour, the following conclusions were reached.1. The sphincter of Oddi appears to be partially autonomous but is readily affected by changes in duodenal tone.2. Reflex inhibition of the sphincter of Oddi is seen on electrical and mechanical stimulation of the gall-bladder but not with passive pressure changes within the gall-bladder.3. This reflex is relayed through the coeliac ganglion.4. There is a definite relationship between gastric antral activity and flow through the sphincter of Oddi. This is more obvious when food is present in the stomach.5. Mechanical or electrical stimulation of the stomach, duodenum, or upper small bowel influences the tone of the sphincter of Oddi.

Ampulla of Vater↗

Mucous change in the human duodenum: a light and electron microscopic study and correlation with disease and gastric acid secretion.

The significance of mucous change in the human duodenum in a series of patients with peptic ulcer disease has been appraised. No specific correlation was demonstrated with the acid output of the stomach if the extent of the change is considered, but it was shown to be more common in the higher acid states. Electron microscopic studies confirmed the specific structure of the mucous cells of the duodenum and suggest that they arise either by transformation of Brunner's gland cells or as a distinctive population in the crypts. It is suggested that the mucous change is a protective mechanism involved in some way as yet unknown with the healing of ulcers.

Biopsy↗

Effects of proximal gastric vagotomy (PGV) followed by total vagotomy (TV) on postprandial and fasting myoelectrical activity of the canine stomach and duodenum.

Experiments were designed to study the effect of proximal gastric vagotomy (PGV) followed by total vagotomy (TV) on the myoelectrical activity of the canine stomach and duodenum after a meat meal and during fasting. Dogs were prepared with chronically implanted Ag-AgCl-electrodes on the stomach and duodenum. Recordings of electrical activity were made for one hour after the ingestion of a meat meal and records of four to six hours were taken on the fasting animals. In the postprandial records no effect on co-ordination of antral and duodenal myoelectrical activity was found after either PGV or TV. These results suggest that the co-ordinating mechanism is not dependent on vagal innervation. Impairment of gastric emptying after TV does not appear to be due to disturbance of antral-duodenal conduction. Normal patterns of fasting activity were found in control and after PGV. They were grossly disturbed after TV, probably because of delayed gastric emptying. These findings suggest that PGV does not delay gastric emptying as does TV, and that the proximal vagal supply to the stomach is unimportant in the control of fasting activity.

Action Potentials↗

Vitamin E concentrations in the human stomach and duodenum--correlation with Helicobacter pylori infection.

BACKGROUND: Vitamin E (alpha-tocopherol) is an important endogenous antioxidant and may also act as an anticarcinogen. AIM: To determine the vitamin E status of subjects with, and without, gastroduodenal inflammation and Helicobacter pylori infection. SUBJECTS: 36 patients undergoing routine gastroscopy for investigation of dyspepsia. METHODS: High performance liquid chromatography with fluorometric detection was used to determine alpha-tocopherol values. RESULTS: In H pylori negative subjects with normal gastroduodenal histology (n = 11) median alpha-tocopherol values (ng/mg tissue weight) were significantly higher in the corpus (16.4, interquartile range (IQR) 8.9-22.6) than in the antrum (3.0, IQR 2.6-6.7, p = 0.001) or duodenum (6.7, IQR 2.5-8.4, p = 0.001). H pylori infection (n = 19) was associated with a reduction in the corpus alpha-tocopherol values (median 8.3, IQR 4.9-13.7, p < 0.05) but there was no significant change in the antral concentrations although this was the main site of inflammation and neutrophil activity. Duodenal alpha-tocopherol values were not significantly changed in the presence of duodenitis or gastric H pylori infection. alpha-Tocopherol was not detected in the gastric juice of any of the subjects. Plasma alpha-tocopherol concentrations in the H pylori negative subjects (median 10.4 mg/l, IQR 7.2-11.9) were not significantly different to the values in the H pylori positive subjects (median 11.1 mg/l, IQR 7.6-12.7). CONCLUSIONS: Concentrations of alpha-tocopherol in H pylori negative subjects are higher in the corpus than in the antrum or duodenum. In the presence of predominantly antral H pylori infection and neutrophil activity the major change seen is a reduction in corpus alpha-tocopherol values while antral concentrations are maintained. These findings may reflect a mobilisation of antioxidant defences to the sites of maximal inflammation in the stomach.

Adult↗

Serrated adenoma of the duodenum.

The duodenum is the most common site for extracolonic adenomas in patients with familial adenomatous polyposis (FAP). These adenomas are usually tubular, villous, or tubulovillous. This report describes a patient with FAP who had a duodenal adenoma with a different histology--it had the microscopic attributes of a serrated adenoma--tumours that are relatively common in the colorectal mucosa and are occasionally found in the stomach. A 78 year old man with FAP and multiple adenomas was colectomised and the rectum amputated. Several years later he developed silent jaundice. The surgical specimen showed an adenomatous growth juxtaposing the papilla of Vater. The adenoma had epithelial fronds with crenated, sawtooth-like configurations caused by scalloped epithelial infolding. The nuclei covering the notched fronds were pleomorphic, stratified, either cigar shaped with irregular chromatin deposits or vesicular shaped with a large nucleolus. One area showed involvement of a duct by neoplastic epithelium with extension into periluminal glands. No invasive carcinoma was present. Serrated adenomas differ from tubular and villous adenomas in their histological organisation and their initial pattern of cell proliferation and genotypic aberration. Increased awareness of the existence of serrated neoplasms in the duodenum may result in similar cases being reported in the future.

Adenoma↗

Gastric epithelium in the duodenum: its association with Helicobacter pylori and inflammation.

Duodenal biopsy specimens from 471 adults and 47 children were examined to determine the prevalence and distribution of gastric epithelium in the duodenal bulb in relation to age, gender, gastroduodenal inflammation, smoking, alcohol and consumption of nonsteroidal anti-inflammatory drugs (NSAID). Gastric metaplasia was present in the anterior wall duodenal biopsy specimen in 31%, was significantly less common in patients under 17 than in adults, and was more common in males than females. In sixty two adults who underwent multiple radial duodenal biopsy gastric metaplasia was randomly distributed around the duodenal circumference; sixty three per cent of the patients with gastric metaplasia found on multiple biopsy were detected by just the anterior biopsy. Gastric metaplasia was not obviously associated with alcohol, cigarette, or NSAID consumption. While the presence of gastric metaplasia was associated with adulthood, male sex, and low fasting gastric juice pH, its extent was associated with active duodenitis and Helicobacter-associated gastritis. On logistic regression, gastric metaplasia in the duodenum and gastric Helicobacter pylori were independent predictors of active duodenitis, but were not significantly associated with inactive duodenal inflammation. H pylori was observed in duodenal biopsy specimens from 32 patients, all with active duodenitis; bacteria were present only on foci of gastric metaplasia, and were more likely to be seen when the metaplasia was extensive. It is proposed that inflammatory injury to the duodenal mucosa by H pylori may stimulate the development of further gastric metaplasia, and that the area of duodenum susceptible to colonisation with H pylori may therefore increase progressively until mucosal integrity is compromised and ulceration supervenes.

Adolescent↗

The use of water ingestion to distinguish the gallbladder and duodenum on cholescintigrams.

Cholescintigraphic diagnosis of acute cholecystitis requires accurate assessment of gallbladder nonvisualization. Confusion may occur when the gallbladder overlies the duodenal sweep or when labeled bile pools in the duodenum. Gallbladder activity could not be differentiated from duodenal activity in 21 patients. The oral ingestion of 225 ml of water permitted successful differentiation of the gallbladder from the duodenum. In 25 control subjects, it was demonstrated that that volume of water did not have a cholecystokinetic effect.

Acute Disease↗

Expression of enteropeptidase in differentiated enterocytes, goblet cells, and the tumor cells in human duodenum.

Enteropeptidase (EP) is a serine proteinase and activates trypsinogen to trypsin, thus playing an important role in food digestion. Nevertheless, the localization of EP is still controversial, likely due to a lack of studies using specific antibodies against EP. The aim of this study was to define cellular localization of EP in human duodenum and expression in tumor cells at the duodenal region. Immunohistochemical staining for resected tissues was performed with two antibodies against recombinant EP light and heavy chains, respectively. In situ hybridization was done with two RNA probes that include either the light or the heavy chain sequences of proEP, respectively. The two antibodies reacted with enterocytes, accentuated on the brush border, and goblet cells, with increasing intensity from the bottom of crypts to the top of villi. Paneth cells, neuroendocrine cells, Brunner's glands, lymphocytes, smooth muscle, or connective tissue did not react with the antibodies. The two RNA probes detected EP mRNA expression only in enterocytes and goblet cells. EP is produced in enterocytes and goblet cells, and the localization on the brush border of the cells is reasonable for the physiological activation of digestive enzymes. Interestingly, the antibodies reacted with tumor cells in duodenal polyps and adenocarcinoma at the duodenum but not in Brunner's gland adenoma. EP seems to be a marker of differentiated enterocytes and goblet cells, which suggests the existence of a common progenitor of these cells. Furthermore, EP may be a useful marker of tumor cells originating from these cells.

Duodenal Neoplasms↗

Processing of vegetable-borne carotenoids in the human stomach and duodenum.

Carotenoids are thought to diminish the incidence of certain degenerative diseases, but the mechanisms involved in their intestinal absorption are poorly understood. Our aim was to obtain basic data on the fate of carotenoids in the human stomach and duodenum. Ten healthy men were intragastrically fed three liquid test meals differing only in the vegetable added 3 wk apart and in a random order. They contained 40 g sunflower oil and mashed vegetables as the sole source of carotenoids. Tomato purée provided 10 mg lycopene as the main carotenoid, chopped spinach (10 mg lutein), and carrot purée (10 mg beta-carotene). Samples of stomach and duodenal contents and blood samples were collected at regular time intervals after meal intake. all-trans and cis carotenoids were assayed in stomach and duodenal contents, in the fat and aqueous phases of those contents, and in chylomicrons. The cis-trans beta-carotene and lycopene ratios did not significantly vary in the stomach during digestion. Carotenoids were recovered in the fat phase present in the stomach during digestion. The proportion of all-trans carotenoids found in the micellar phase of the duodenum was as follows (means +/- SE): lutein (5.6 +/- 0.4%), beta-carotene (4.7 +/- 0.3%), lycopene (2.0 +/- 0.2%). The proportion of 13-cis beta-carotene in the micellar phase was significantly higher (14.8 +/- 1.6%) than that of the all-trans isomer (4.7 +/- 0.3%). There was no significant variation in chylomicron lycopene after the tomato meal, whereas there was significant increase in chylomicron beta-carotene and lutein after the carrot and the spinach meals, respectively. There is no significant cis-trans isomerization of beta-carotene and lycopene in the human stomach. The stomach initiates the transfer of carotenoids from the vegetable matrix to the fat phase of the meal. Lycopene is less efficiently transferred to micelles than beta-carotene and lutein. The very small transfer of carotenoids from their vegetable matrices to micelles explains the poor bioavailability of these phytomicroconstituents.

Adult↗

Chloride conductance of CFTR facilitates basal Cl-/HCO3- exchange in the villous epithelium of intact murine duodenum.

Villi of the proximal duodenum are situated for direct exposure to gastric acid chyme. However, little is known about active bicarbonate secretion across villi that maintains the protective alkaline mucus barrier, a process that may be compromised in cystic fibrosis (CF), i.e., in the absence of a functional CF transmembrane conductance regulator (CFTR) anion channel. We investigated Cl(-)/HCO(3)(-) exchange activity across the apical membrane of epithelial cells located at the midregion of villi in intact duodenal mucosa from wild-type (WT) and CF mice using the pH-sensitive dye BCECF. Under basal conditions, the Cl(-)/HCO(3)(-) exchange rate was reduced by approximately 35% in CF compared with WT villous epithelium. Cl(-)/HCO(3)(-) exchange in WT and CF villi responded similarly to inhibitors of anion exchange, and membrane depolarization enhanced rates of Cl(-)(out)/HCO(3)(-)(in) exchange in both epithelia. In anion substitution studies, anion(in)/HCO(3)(-)(out) exchange rates were greater in WT epithelium using Cl(-) or NO(3)(-), but decreased to the level of the CF epithelium using the CFTR-impermeant anion, SO(4)(2-). Similarly, treatment of WT epithelium with the CFTR-selective blocker glybenclamide decreased the Cl(-)/HCO(3)(-) exchange rate to the level of CF epithelium. The mRNA expression of Slc26a3 (downregulated in adenoma) and Slc26a6 (putative anion exchanger-1) was similar between WT and CF duodena. From these studies of murine duodenum, we conclude 1) characteristics of Cl(-)/HCO(3)(-) exchange in the villous epithelium are most consistent with Slc26a6 activity, and 2) Cl(-) channel activity of CFTR facilitates apical membrane Cl(-)(in)/HCO(3)(-)(out) exchange by providing a Cl(-) "leak" under basal conditions.

Animals↗

Diurnal pH changes in duodenum of conscious dogs.

Continuous measurements of intraduodenal pH changes were made in five healthy conscious dogs by means of a miniature pH electrode inserted into the duodenum through a chronically implanted duodenal cannula. Gastric motor activity was also recorded simultaneously by means of a chronically implanted force transducer. When dogs were fed once a day with a measured volume of dog food, it was found that 24-h pH changes in the duodenal contents could be divided into three major periods: the weak acid period, the strong acid period, and alkaline period. The weak acid period lasted for 9.2 +/- 0.43 h after feeding with the duodenal pH ranging from 7.0 to 4.0. The weak acid period was gradually changed to the strong acid period in which the duodenal pH fluctuated widely from 8.0 to 1.0. This period lasted for 5.2 +/- 0.26 h. After the strong acid period, pH of the duodenum abruptly turned alkaline and remained between 7.0 and 8.3 until the next meal. These three periods of pH change are closely related to those of three different gastric motor patterns; the digestive, intermediate, and interdigestive patterns, respectively.

Animals↗

Alkaline secretion by amphibian duodenum. I. General characteristics.

Stripped, proximal bullfrog duodenum was mounted in an Ussing chamber between HCO3--buffered nutrient (serosal) and unbuffered secretory (luminal) solutions. This preparation showed stable electrical parameters and caused alkalinization of the secretory solution at a rate of 0.95 +/- 0.03 mueq.cm-2.h-1 (mean +/- SE; n = 100). Anoxia and 2,4-dinitrophenol each reduced alkalinization by 50-60%, but acetazolamide (5 X 10(-4)M) had no effect. Removal of nutrient HCO3- and CO2 reduced alkalinization by over 90%, whereas increasing nutrient [HCO3-] at constant partial pressure of CO2 (PCO2) or increasing nutrient PCO2 at constant [HCO3-] each caused saturable increases in alkalinization, despite opposite effects on nutrient pH. Dibutyryl adenosine 3',5'-cyclic monophosphoric acid, but not dibutyryl guanosine 3',5'-cyclic monophosphoric acid, increased luminal alkalinization to 167 +/- 21% of control. Removal of nutrient, but not secretory, Na+ reduced alkalinization by 74%. Changes in the rate of alkalinization were accompanied by corresponding changes in potential difference and short-circuit current. Removal of Cl- or nutrient K+ or addition of histamine, thiocyanate, or catecholamines had no effect on electrical or secretory characteristics. We conclude that a) the amphibian duodenum transports alkali from nutrient to secretory solutions by both active and passive processes, b) there is a small secretion of endogenous HCO3-, c) alkaline secretion is electrogenic, d) Cl- does not contribute to the short-circuit current, e) alkaline secretion is partially dependent on nutrient Na+ that acts in a facilitatory, not cotransport, role, f) there is no Cl--HCO3- exchange, and g) alkaline secretion is independent of nutrient pH.

Acid-Base Equilibrium↗

Transport of calcium by duodenum of spontaneously hypertensive rat.

The absorption of calcium by segments of duodenum obtained from spontaneously hypertensive (SH) rats and normotensive Wistar-Kyoto (WKy) rats was measured before and after the development of hypertension. The systolic blood pressure (SBP) of 5-wk-old SH rats (116 +/- 4 Torr) was significantly elevated above that of age-matched WKy rats (103 +/- 3 Torr) but was not at a level generally considered to be hypertensive. Values obtained for calcium transport [ratio of serosal-to-mucosal fluid 45Ca2+ concn (S/M ratio)] from everted duodenal sacs were similar between the two groups at this age. At 12 wk of age, SH rats exhibited a SBP (153 +/- 4 Torr) well above that of WKy controls (127 +/- 3 Torr), and calcium S/M ratios for duodenal sacs were significantly greater than the WKy control values. Similarly, the in vivo uptake of calcium in duodenal segments was significantly elevated in 12-wk-old SH rats compared with WKy controls. The administration of vitamin D3 or its metabolite, 25-hydroxycholecalciferol, had no detectable effect on duodenal transport of calcium in 12-wk-old SH or WKy rats. By comparison, 1,25-dihydroxycholecalciferol produced a significant increase in duodenal calcium transport both in vitro and in vivo in WKy but not in SH rats. The results indicate a distinct abnormality in the transport of calcium in the duodenum of SH rats, suggesting that the decrease in duodenal uptake of calcium that normally occurs with maturation is slow to develop in this rat strain.

Animals↗

Patterns of electrical activity and neural responses in canine proximal duodenum.

The patterns of electrical activity and neural inputs to the proximal duodenum between the pyloric sphincter and the sphincter of Oddi were studied in muscles of the dog. Smooth muscle cells in the most proximal region were electrically quiescent, but slow waves were recorded in all regions distal to the first few millimeters. Electrical activity was recorded from circular muscle cells near the myenteric and submucosal surfaces of the circular layer, and slow wave activity was similar in both regions. The nature of neural inputs was also characterized. With electrical field stimulation, responses in cells near the submucosal surface were predominantly excitatory junction potentials (EJPs); near the myenteric border responses were either inhibitory junction potentials (IJPs) or biphasic responses (i.e., small EJPs followed by IJPs). EJPs were blocked by atropine. IJPs were nonadrenergic and noncholinergic (NANC), and several experiments suggested that nitric oxide (NO), or a NO-releasing compound, serves as the inhibitory neurotransmitter in this region. Exogenous NO caused hyperpolarization of membrane potential. IJPs and the hyperpolarization response to NO were sensitive to apamin. These data describe the myogenic mechanisms and neurogenic apparatus that appear to regulate motility in the most proximal region of the duodenum.

Animals↗

Adherent surface mucus gel restricts diffusion of macromolecules in rat duodenum in vivo.

The aim of this study was to investigate the permeability of the adherent mucus gel layer in rat duodenum in vivo to macromolecules applied in the lumen. Rats were anesthetized with thiobarbiturate, and the duodenum was perfused with isotonic NaCl solution containing large-molecular-size secretagogues. Effects on mucosal HCO(-)(3) secretion and blood-to-lumen (51)chromium-labeled EDTA clearance were used as indexes that compounds had migrated across the mucus layer. Exposure to a low concentration of papain (10 U/100 ml) for 30 min removed the mucus layer without damage to the epithelium and induced or markedly enhanced HCO(-)(3) secretory responses to cholera toxin (molecular mass of 85 kDa) or glucagon (3.5 kDa). Water extracts from a VacA cytotoxin (89 kDa) producing Helicobacter pylori strain, but not from a toxin-negative isogenic mutant, caused a small increase in HCO(-)(3) secretion but only after the mucus layer had been removed by papain. The duodenal surface mucus gel thus significantly restricts migration of macromolecules to the duodenal surface. Release of bacterial toxins at the cell-mucus interface may enhance or be a prerequisite for their effects on the gastrointestinal mucosa.

Animals↗

Propagation of individual spikes as "patches" of activation in isolated feline duodenum.

Asynchrony of spikes has made it difficult to study the spatial and temporal behavior of spikes in the gastrointestinal system. By simultaneously recording from a large number of closely spaced electrodes, we investigated the propagation of individual spikes. Recordings were performed from the serosal surface of the isolated feline duodenum at 240 sites simultaneously. Analysis of the tracings made it possible to reconstruct the propagation of individual spikes. Spikes propagate in the longitudinal and circumferential directions in self-limiting areas or "patches." Conduction within patches may occur in the orad or aborad direction irrespective of the direction of the slow wave. Most of the patches are smaller (<40 mm(2)), although inhomogeneous activation by the preceding slow wave may increase their size. Stimulation by ACh, TTX, or tetraethylammonium does not affect the average patch size but does increase significantly their number and distribution in the duodenum [from 26% (control) to 56%, 61%, and 72%, respectively]. In conclusion, individual spikes activate limited areas or patches in the small intestine, and pharmacological stimulation increases the number and distribution of these patches. In the small intestine, this pattern of activation would induce localized contractions. Contraction could be modulated by the size, number, and distribution of spike patches.

Acetylcholine↗

Epithelial calcium transporter expression in human duodenum.

Calcium absorption in intestine and kidney involves transport through the apical membrane, cytoplasm, and basolateral membrane of the epithelial cells. Apical membrane calcium influx channels have recently been described in rabbit (epithelial calcium channel, ECaC) and rat (calcium transport protein, CaT1). We amplified from human duodenum a 446-base partial cDNA probe (ECAC2) having a predicted amino acid similarity of 97% to rat CaT1. Duodenum, but not ileum, colon, or kidney, expressed a 3-kb transcript. A larger transcript was also found in placenta and pancreas, and a different, faint transcript was found in brain. In duodenal biopsies from 20 normal volunteers, expression varied considerably but was not significantly correlated with vitamin D metabolites. This signal correlated with calbindin-D(9k) (r = 0.48, P < 0.05) and more strongly with the plasma membrane calcium ATPase PMCA1 (r = 0.83, P < 0.001). These data show that although individual variations in calcium channel transcripts are not vitamin D dependent, expression of genes governing apical entry and basolateral extrusion are tightly linked. This may account for some of the unexplained variability in calcium absorption.

Amino Acid Sequence↗

Phase lock of electrical slow waves and spike bursts in cat duodenum.

The phase relationship between slow waves and spike bursts was studied in vitro in the cat duodenum. Electrodes were arranged radially about the duodenum. Records were read for T1, the time between the slow-wave "valley" and the first spike, and T2, the time between successive valleys. The distributions of the ratio T1/T2 showed very small differences, not uniquely attributable to radial electrode position. The distribution of T1/T2 indicated that spike bursts began 58.8% of the way through a slow-wave cycle, measured from the valley. Also, electrodes were arranged longitudinally and records were read to determine deltaSW, the slow-wave delay time between adjacent electrode positions, and deltaS, the spike burst delay time between adjacent electrode positions. The correlation of deltaS and deltaSW suggested a linear relation, and a regression resulted in a good linear description. These results are consistent with an assumed phase lock of spike bursts to slow waves.

Animals↗