Pancreaticobiliary Secretions Research Articles

Postgastrectomy Syndromes

Anatomic and physiological changes introduced by gastric surgery result in postgastrectomy syndromes in approximately 20% of patients. Most of these disorders are caused by operation-induced abnormalities in the motor functions of the stomach, including disturbances in the gastric reservoir function, the mechanical-digestive function, and the transporting function. Division of the vagal innervation to the stomach and ablation or bypass of the pylorus are the most significant factors contributing to postgastrectomy syndromes. Either rapid or slow emptying may result, depending on the relative importance of lack of a compliant gastric reservoir, loss of an effective contractile force, and loss of controlling factors that slow or speed gastric emptying and result in duodenal-gastric reflux. Clearly defining which syndrome is present in a given patient is critical to developing a rational treatment plan. In syndromes with slow gastric emptying, bilious vomiting, or alkaline reflux gastritis, the use of endoscopy is essential to rule out mechanical causes of the syndrome. Contrast radiography and scintigraphic gastric emptying studies are useful to document rapid or delayed gastric emptying. Postgastrectomy syndromes often abate with time. Conservative measures, including medical, dietary, and behavioral therapy, should be given at least a 1-year trial. If these nonoperative measures fail, surgical therapy is recommended. The Roux-en-Y gastrojejunostomy is useful for patients with dumping, because it slows gastric emptying and the transit of chyme through the Roux limb. The same operation helps patients with alkaline reflux gastritis, because it diverts pancreaticobiliary secretions away from the gastric remnant. Near-total gastrectomy, which reduces the size of a flaccid gastric reservoir, can be used to treat delayed gastric emptying. This operation should be combined with the Roux procedure to prevent postoperative reflux gastritis and esophagitis. Newer techniques, such as gastrointestinal pacing and the uncut Roux operation, may improve the treatment of the postgastrectomy syndromes in the future.

Cellular and molecular basis of intestinal and pancreatic adaptation.

This article reviews the structural and functional changes which develop in the intestine and pancreas in response to a variety of stimuli and which characterise adaptive hyper- or hypo-plasia. It then discusses the principal physiological mechanisms controlling this adaptive growth. In the gut, these include luminal nutrition, endocrine, autocrine and paracrine hormonal influences, growth factors, enterotrophic components of pancreatico-biliary secretions, neural factors, changes in blood flow and mesenchyme-epithelial interactions. The cell biology of adaptive growth involves cell membrane receptors (first messengers) and a cascade of intracellular second messengers, the best studied of which is changes in polyamine metabolism and in related enzymes. The effects of ornithine decarboxylase (ODC) blockade with difluoromethyl ornithine (DFMO) and of diamine oxidase (DAO) blockade with aminoguanidine, are described. In general, DFMO inhibits or prevents adaptive hyperplasia while in the small bowel, aminoguanidine treatment induces 'supranormal' adaptation. However, both the gut and the pancreas transport 'exogenous' (ingested in food and circulating in the blood stream) polyamines across their apical and basolateral membranes. The influence of this exogenous polyamine transport on 'endogenous' (enzyme-regulated) intracellular polyamine concentrations, is largely unknown. Finally, the molecular biology of adaptive growth is described briefly--as illustrated by the use of a growth hormone transgenic model in which mice develop marked intestinal mucosal hyperplasia and increases in the relative abundance of insulin-like growth factor-I (IGF-I) mRNA in the intestine.

Effect of duodenal switch procedure on gastric acid production, intragastric pH, gastric emptying, and gastrointestinal hormones

The duodenal switch operation preserves the pylorus and the proximal 3 to 7 cm of duodenum in continuity with the stomach while diverting pancreaticobiliary secretions. We compared it with the Roux-en-Y without vagotomy or antrectomy in 12 dogs with innervated gastric pouches. Acid secretion was inhibited between tests using ranitidine in the Roux-en-Y group only, but two of the six dogs still developed stomal ulcers and the remainder showed stomal hyperemia. This may be due to a significant increase in gastric acid output after Roux-en-Y, but gastric emptying and plasma gastrin, cholecystokinin, secretin, gastric inhibitory polypeptide, peptide YY, and neurotensin were similar after both procedures. In 12 patients and a further 6 dogs, the duodenal switch caused no significant change in the intragastric pH environment as assessed by intragastric pH monitoring. The duodenal switch is a suitable procedure for pancreaticobiliary diversion.

Cancer associated antigen CA19-9 in colonic effluent of patients with neoplasia of the colon and inflammatory bowel disease

We measured colonic effluent samples from 10 patients with colorectal cancer, 13 with adenomatous polyps, 14 with normal colons and compared them to 10 patients with inflammatory bowel disease by measuring this CA19-9 content. Results showed considerable overlap between the different pathologic categories, making differentiation impossible. A lower level of CA19-9 in the effluent samples from patients with adenomas was noted. These differences were reproducible for assays performed several months apart. CA19-9 may originate from the upper gastrointestinal tract since large amounts are present in pancreatico-biliary secretions. This antigen is therefore not useful in the diagnosis of neoplasia or inflammatory bowel disease using colonic effluent samples as the test material.

DNA adducts, detected by 32P-postlabelling, in the foregut of patients with familial adenomatous polyposis and in unaffected controls.

Duodenal neoplasms in patients with familial adenomatous polyposis (FAP) cluster around the ampulla; duodenal neoplasia is common but gastric neoplasia is rare. These observations suggest that bile enhances neoplasia by carrying carcinogens to target cells. A critical step in carcinogenesis is the reaction of carcinogens with DNA to form chemical adducts. Using 32P-postlabelling to measure DNA adducts we asked: (i) are there more adducts in the duodenum of patients with FAP than in the duodenum of normal patients? (ii) Are there more adducts in the duodenum than in the stomach? We measured adducts in duodenal biopsies from 51 patients with FAP and 30 age-matched controls; and paired gastric and duodenal biopsies from 31 FAP patients and six controls. The foregut of 90% of all patients studied contained DNA modifications with characteristics of aromatic non-polar DNA adducts. In duodenal biopsies, adduct labelling per 10(9) DNA nucleotides was significantly higher in FAP patients (median 15.0, range 0-162) than in normal patients (median, 7.5, range 0-40; P = 0.0002). In paired duodenal and gastric biopsies from 31 FAP patients, adduct labelling was significantly higher in duodenal DNA (median 15, range 0-109) than in stomach DNA (median 8.0, range 0-40; P = 0.0004). Age, gender or smoking did not account for these differences. Gastric adducts (median 3.5, range 0-10) were lower than duodenal adducts (median 8.5, range 0-29) in paired biopsies from six control patients, P = 0.031). These results support the hypothesis that pancreaticobiliary secretions may be involved in the pathogenesis of foregut neoplasia in FAP.

Human duodenal mucosal bicarbonate secretion—physiological and clinical aspects

Over the past few years, we have addressed some of the components that regulate human duodenal bicarbonate secretion (DBS) using a technique for the isolation of a 4-cm duodenal segment from gastric, pancreaticobiliary and distal intestinal secretions. Our observations are summarized as follows. Resting DBS is, to a large extent, maintained by vagal innervation; atropine decreases basal bicarbonate secretion by approximately 80%. Luminal acidification with HCI (H+) is a major physiological stimulus of DBS, resulting in a prompt and significant increase of 3- to 4-fold. H(+)-stimulated DBS is likely to be mediated, at least in part, by prostaglandins of the E class, and by VIP. Each of the latter stimulates DBS independently in a dose-related manner. Since atropine is without effect on the response induced by luminal H+ and sham feeding, in both cases DBS is probably stimulated via a non-cholinergic pathway(s). Moreover, since basal, H(+)- and PGE2-stimulated proximal DBS are unaltered when the plasma-to-lumen bicarbonate concentration gradient is abolished, it may be concluded that DBS in humans involves active transport processes. It is significant that compared to normal subjects, patients with duodenal ulcers show markedly diminished basal and H(+)-stimulated proximal DBS. Furthermore, there is surprisingly little overlap between duodenal ulcer (DU) patients and normal subjects. These findings suggest that an intrinsic cellular or subcellular defect in proximal duodenal mucosal bicarbonate secretion is present in patients with duodenal ulcer disease.

Gastrointestinal luminal polyamines: cellular accumulation and enterohepatic circulation

The concentration of polyamines contained in the lumen of the gut was quantified. The duodenum and jejunum of the rat contained 2-3 mM putrescine and 1-2 mM cadaverine, whereas in the ileum and colon the concentration of these polyamines was significantly less. In addition, the concentrations of spermine and spermidine in the intestinal lumen were low to undetectable. Putrescine in the lumen of the gut was over 90% free with only 10% or less bound to protein. The activity of the enzymes responsible for the synthesis of polyamines was also measured. In contrast to concentration, enzyme activity was found to be high in the ileum, cecum, and colon and nonexistent in the duodenal and jejunal lumen. This suggested the potential for enterohepatic circulation of polyamines that were synthesized by the colonic microflora and transported to the proximal gut via the portal circulation and biliary tree. Indeed, when [14C]putrescine was instilled into the lumen of the gut, it was secreted in pancreaticobiliary secretions. Upper and lower jejunum and colon all supported enterohepatic circulation of polyamines, whereas it was absent in the ileum. Polyamine accumulation in IEC-6 cells grown under in vitro conditions was also measured. Putrescine was transported under time- and temperature-dependent but sodium-independent conditions. The transporter displayed little selectivity for the various polyamines and compounds with related structures but did not recognize amino acids. The Michaelis constant for putrescine accumulation was 1.26 x 10(-6) M with a maximal velocity of the enzyme reaction of 5,184 pmol putrescine.mg protein-1.h-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Digestive tract motor correlates of vomiting and nausea

The digestive tract from the upper esophageal sphincter to the ileum participates in the vomiting process, but the role of the digestive tract in nausea is unclear. In preparation for vomiting, the proximal stomach relaxes and the small intestine is evacuated orad in a single mass movement by a retrograde giant contraction and caudad in a stripping fashion by a series of phasic contractions. Orad evacuation of the small intestine may not only remove offending substances but may also dilute. or buffer gastric contents with intestinal and pancreaticobiliary secretions. In association with retching and vomiting, the striated muscle of the esophagus contracts longitudinally, pulling the relaxed proximal stomach into the thoracic cavity forming a funnel from stomach to esophagus. However, gastric evacuation does not occur until the hiatal fibers of the diaphragm relax during vomitus expulsion. Nausea is a subjective feeling in humans that is difficult to identify in animals. Various changes in digestive tract activity have been associated with nausea, but no evidence suggests that these events cause nausea. The prodromal signs of vomiting (e.g., increased heart rate and respiration) that occur concomitantly with the gastrointestinal motor correlates of vomiting have been considered autonomic indices of nausea in animals, but this has not been proven. Regardless, the gastrointestinal motor correlates of vomiting do not cause the prodromata. The emetic central pattern generator may be organized in parallel with respect to its individual autonomic correlates, but as groups of responses, the autonomic and somatomotor correlates may be organized in series.

Selective Precipitation of 14 kDa Stone/Thread Proteins by Concentration of Pancreaticobiliary Secretions

SUMMARYConcentrated proteins in pancreatic juice could precipitate and plug pancreatic ducts, initiating pancreatic disease. In cystic fibrosis (CF), pancreatic fluid secretion is impaired due to defective anion transport and proteins are hyperconcentrated. To determine whether proteins in pancreatic secretions precipitate selectively or nonspecifically, duodenal secretions were obtained from subjects with and without cystic fibrosis, during pancreatic stimulation with cholecystokinin (CCK) and secretin, dialyzed against phosphate‐buffered saline (PBS), and concentrated in stages by ultrafiltration. Precipitates obtained by centrifugation at 15,600 g for 10 min at 4°C were analyzed by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. The only protein band regularly enriched in precipitates from 10 CF and 9 non‐CF samples had an Mr of approximately 14,000. Monoclonal antibodies, raised independently in two laboratories against either pancreatic stone protein (PSP) or pancreatic thread protein (PTP), reacted with the Mr 14,000 protein(s). Differential extraction of PTP and PSP by 0.1N HC1 and 10% sodium citrate produced Mr 14,000 products that reacted equally with each monoclonal antibody (MAB). Two‐dimensional gel electrophoresis demonstrated two Mr 14,000 spots in each extract with pI's of 5.8 and 6.0. Each spot reacted equivalently with the MABs for PSP and PTP. PSP/PTP type proteins are sparingly soluble in pancreatic secretions and could contribute to protein plugging in pancreatic disease.

Selective precipitation of 14 kDa stone/thread proteins by concentration of pancreaticobiliary secretions: relevance to pancreatic ductal obstruction, pancreatic failure, and CF.

Concentrated proteins in pancreatic juice could precipitate and plug pancreatic ducts, initiating pancreatic disease. In cystic fibrosis (CF), pancreatic fluid secretion is impaired due to defective anion transport and proteins are hyperconcentrated. To determine whether proteins in pancreatic secretions precipitate selectively or nonspecifically, duodenal secretions were obtained from subjects with and without cystic fibrosis, during pancreatic stimulation with cholecystokinin (CCK) and secretin, dialyzed against phosphate-buffered saline (PBS), and concentrated in stages by ultrafiltration. Precipitates obtained by centrifugation at 15,600 g for 10 min at 4 degrees C were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The only protein band regularly enriched in precipitates from 10 CF and 9 non-CF samples had an Mr of approximately 14,000. Monoclonal antibodies, raised independently in two laboratories against either pancreatic stone protein (PSP) or pancreatic thread protein (PTP), reacted with the Mr 14,000 protein(s). Differential extraction of PTP and PSP by 0.1N HCl and 10% sodium citrate produced Mr 14,000 products that reacted equally with each monoclonal antibody (MAB). Two-dimensional gel electrophoresis demonstrated two Mr 14,000 spots in each extract with pI's of 5.8 and 6.0. Each spot reacted equivalently with the MABs for PSP and PTP. PSP/PTP type proteins are sparingly soluble in pancreatic secretions and could contribute to protein plugging in pancreatic disease.

Further characterisation of the 'ileal brake' reflex in man--effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.

Previous studies have shown that ileal infusion of partially digested triglyceride inhibits jejunal motility. The partial digest used in those studies contained a mixture of glycerol, free fatty acid, mono-, di-, and triglycerides. In Part I of the present study we have separately infused emulsions containing either glycerol 3.1 g (n = 6), oleic acid 9.6 g (n = 6), triolein 10 g (n = 12), or medium chain triglycerides 10 g (n = 6) into the ileum and have recorded the effect this has on jejunal motility. Five further subjects received infusions of partial hydrolysates of corn starch 10 g and lactalbumin 7 g. Marked inhibition of jejunal pressure wave activity was seen after all three lipid infusions, per cent activity falling from a control of 37.7 (7.7) to 6.2 (2.1) and 22.4 (8.2)% 30 min after completing the oleic acid and triolein infusions respectively, and from a control value of 39.5 (4.1) to 17.7 (4.7) after MCTs (all p less than 0.05). No significant fall occurred after infusion of glycerol, protein or carbohydrate. All three lipid infusions raised plasma concentrations of neurotensin, enteroglucagon and peptide YY equally effectively, although only the rise in peptide YY correlated significantly with the inhibition of jejunal pressure wave activity (r = 0.80, n = 6, p less than 0.05). In Part II of this study six subjects received a 3 ml/min jejunal infusion of an isotonic carbohydrate saline solution followed after three hours by a similar infusion of a partial digest of lipid. During each infusion flow and transit time was measured by marker and dye dilution. Jejunal infusion of the carbohydrate-saline solution was associated with low jejunal flow, 4.7 (1.0) ml/min and a mean transit time through the 50 cm study segment of 36.5 (7.1) min. By contrast jejunal infusion of partially digested triglyceride was associated with a markedly increased flow, 9.0 (1.2) ml/min, a fall in mean transit time to 20.3 (2.6) min and significant rises in pancreaticobiliary secretions. Jejunal triglyceride also increased the incidence of prolonged high amplitude jejunal pressure waves in four of six subjects. These studies suggest that there are important differences in the jejunal response to ileal versus jejunal lipid. While long and median chain free fatty acids infused into the ileum exert an inhibitory effect on jejunal motility, when infused directly into the jejunum partially digested triglyceride accelerates transit, increases jejunal flow and subtly alters the pattern of jejunal contractions.

Specific receptors for epidermal growth factor in rat intestinal microvillus membranes.

Epidermal growth factor (EGF) is present in high concentrations in milk, salivary, and pancreaticobiliary secretions. EGF, delivered to the intestinal lumen by these fluids, appears to influence intestinal proliferation. Because EGF exerts its mitogenic effect through binding to specific membrane-bound receptors, binding studies of 125I-labeled EGF to purified microvillus membrane (MVM) preparations from fetal, newborn, and adult rat small intestine were performed. Using the membrane filter technique, binding of 125I-EGF to adult MVM was specific, saturable, and reversible. Adult and fetal MVM binding was rapid and reached a plateau after 30 min at both 20 and 37 degrees C. No binding was detected at 4 degrees C. Specific binding increased linearly from 0 to 75 micrograms MVM protein. Scatchard analysis revealed a single class of receptors in fetal and adult MVM with an association constant of 1.0 +/- 0.35 X 10(9) and 2.3 +/- 1.6 X 10(9) M-1, respectively. Binding capacity was 435.0 +/- 89 and 97.7 +/- 41.3 fmol 125I-EGF bound/mg MVM protein for fetal and adult MVM, respectively. Newborn MVM binding was negligible. After binding, cross-linking utilizing disuccinimidyl suberate, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, autoradiography revealed a 170-kDa receptor. These data demonstrate specific receptors for EGF on MVM of rat small intestine and, thus, suggest a mechanism for the intraluminal regulation of enterocyte proliferation by EGF.

Composition of the refluxed material determines the degree of reflux esophagitis in the dog

To evaluate the influence of the composition of refluxed material in the pathogenesis of esophagitis, a dog model was used to allow esophageal reflux of gastric secretions, duodenal pancreaticobiliary secretions, and a combination of both. Control dogs had only an esophageal incision. Incompetence of the cardia was established in five other groups by transecting the distal sphincter and creating a hiatal hernia. Two groups received moderate or maximal histamine stimulation of gastric secretion. A gastroje-junostomy, pyloromyotomy, and duodenal closure distal to the papilla were added in the other three groups, creating duodenogastric reflux; two were stimulated with histamine and one had a truncal vagotomy and no histamine. Radiologic, manometric, and pH studies showed that incompetence of the cardia was obtained. The dogs were killed 4 wk postoperatively and evaluated for gross and microscopic evidence of esophagitis. Erosive esophagitis was found only in dogs with reflux of gastric juice following maximal acid stimulation. Microscopic reflux changes in esophageal mucosa were seen in all groups; again, changes were most pronounced in dogs with maximal gastric stimulation. The combination of duodenogastric reflux and moderate gastric stimulation produced more significant alterations in microscopic reflux criteria than did moderate gastric stimulation alone. Our conclusions are as follows: In a dog model of gastroesophageal reflux of various combinations of gastric and duodenal secretory components, erosive esophagitis occurred only with maximal gastric stimulation in the absence of duodenogastric reflux. All reflux combinations, however, produced some degree of microscopic changes, suggesting they could eventually cause gross changes with a lengthened experimental time span.

Administration of caerulein to rats promotes antral epithelial cell renewal.

The growth-promoting effect of caerulein on antral gastric mucosa was explored using Wistar rats. Implanted osmotic minipumps were used to administer submaximal doses of either caerulein or saline to normal rats for up to 4 days. In one group, reflux of bile and pancreatic juice into the stomach was avoided by previous surgical diversion of the distal common bile duct to the jejunum. DNA synthetic and mitotic activity in the antrum epithelium were estimated by 3H-thymidine pulse labelling and autoradiography during the administration of the peptide. The rate of cell migration was determined in animals killed 1, 2 and 3 days after the 3H-thymidine pulse. Administration of caerulein to normal rats provoked significant increases in both labelling and mitotic indices, and a significant acceleration of the upward cell migration in the glandular tubes. In the animals with distal diversion of bile and pancreatic secretions both labelling and mitotic indices were also increased over control values under the effect of the peptide. These data indicate that administration of caerulein stimulates cell proliferation in the antral gastric mucosa. This effect cannot be explained through increased reflux of pancreaticobiliary secretions in the stomach.

Effect of removal of pancreaticobiliary secretions on adaptation to short bowel in orally nourished rats

To evaluate the need for intraluminal pancreaticobiliary secretions for mucosal adaptation in animals with short bowel, groups of paired rats were prepared with: 1) normal bowel length, 2) 60% proximal small bowel bypass, and 3) similar bypass of distal bowel. One animal in each pair underwent operative diversion of pancreaticobiliary secretions to distal (group 1) or bypassed intestine (groups 2 and 3). Rats were fed an elemental diet and killed 1 month later. Mucosal wet weight, protein content, and DNA content were measured in comparable segments of proximal jejunum and mid-small bowel. Within each group the patterns of response of the three measures of mucosal mass were similar. Group 1: removal of secretions was associated with a 20 to 30% increase in mass in both segments. Group 2: after proximal bypass, mass doubled in mid-small bowel (in continuity) whether or not pancreaticobiliary secretions were removed. Group 3: after distal bypass, no change in mass was apparent in the jejunum even with removal of secretions. We conclude that intraluminal pancreaticobiliary secretions are not required for maintenance of mucosal mass or adaptation to short bowel in animals fed an elemental diet.

Adaptive regulation of sugar and amino acid transport by vertebrate intestine.

The adaptive regulation of sugar and amino acid transport by vertebrate intestine constitutes a neglected area. We review the patterns, signals, and mechanisms involved in adaptation. Mechanisms include changes in mucosal mass, specific transport systems, and the sodium gradient. Signals include the transported solutes themselves, hormones, and pancreaticobiliary secretions. The pattern of adaptation is examined for effects of dietary solutes, starvation, hyperphagia, dietary bulk, diabetes, intestinal position, intestinal resection, time of day, season of the year, hibernation, gestation, lactation, and aging and for differences among species. These observed patterns are compared with the patterns predicted by a simple teleologically deduced hypothesis: increased metabolic requirements should be met by increased absorption achieved through increased mucosal mass, while nutritionally essential solutes and nonessential solutes used as calorie sources should, respectively, repress and induce their own transport. We conclude with a summary of major unsolved questions in this area.

Evidence for a humoral mechanism after small intestinal resection: Exclusion of gastrin but not enteroglucagon

It is generally agreed that the adaptive response in the residual bowel after major intestinal resection is dependent on luminal nutrition and pancreaticobiliary secretions. Recent evidence, however, suggests that humoral mechanisms, e.g., gastrin or enteroglucagon, may also play a part in this process. A 75% proximal small bowel exclusion was performed in 16 male Wistar rats and the excluded bowel was fashioned into a Thiry-Vella fistula. Half of the animals were allowed food ad libitum, while the rest were fed intravenously. The animals were killed at 12 days, and plasma, gastrin, and enteroglucagon were measured, while cell proliferation was determined by measuring the crypt cell production rate employing a stathmokinetic method using vincristine and crypt microdissection. In addition to these animals, 16 rats had a jejunal transection only, with half of these animals nourished intravenously, while the remainder were allowed food ad libitum. In the Thiry-Vella rats, plasma enteroglucagon was greater with oral feeding (566 ± 59 pmol/L) than with intravenous feeding (120 ± 42 pmol/L) (p < 0.01), but gastrin levels did not differ in the two groups. In the ileum in continuity, crypt cell production rate per hour was greater in the orally fed animals (52 ± 8) compared with the intravenously fed group (18 ± 5) (p < 0.001). In the excluded fistula, crypt cell production rate per hour was reduced by 23.8 ± 2 in orally fed rats, but this was greater than in the intravenously fed group (16 ±1.5) (p < 0.01). Both orally and intravenously fed transected rats had significantly lower plasma hormone levels, and reduced crypt cell production rate compared with the respective Thiry-Vella groups. This study suggests a distinct role for a humoral agent responsible for the proliferative changes seen after small bowel resection, and in this respect enteroglucagon appears more relevant than gastrin.

8 - Nutritional Aspects of Malabsorption: Short Gut Adaptation

Adaptation of remaining small bowel after extensive intestinal resection plays an important part in maintaining adequate nutrition. The metabolic consequences of short bowel depend upon the anatomic extent of bowel removed, the functional condition of remaining digestive organs and the degree to which adaptive changes occur. The pathophysiology of short bowel results primarily from the abnormal absorption of nutrients and selective metabolites leading to malnutrition and other organ complications. Nutrients in the lumen of the small intestine are required to stimulate the process of intestinal adaptation (mucosal hyperplasia). This stimulation may be mediated via direct mucosal absorption or metabolism of nutrients, the presence of pancreaticobiliary secretions in the intestine, trophic effects of circulating enteric hormones, or neurovascular influences. Understanding the mechanisms by which mucosal growth may be stimulated could lead to important clinical applications.

Meal-stimulated secretin release in man: effect of acid and bile.

Nine normal subjects were studied before and after intragastric instillation of a liquid meal. Gastric emptying rates of acid and pancreaticobiliary secretions were quantitated by means of a dilution indicator technique. A significant, positive correlation was found between load of acid to the duodenum and the concentration of secretin in plasma. No correlation was found between load of the bile acids and plasma secretin. The buffering capacity of gastric contents should be taken into account when fasting and postprandial periods are compared. Plasma secretin concentration remained low during the first postprandial hour. Maximum secretin concentrations and duodenal disappearance rate of acid was observed 1 1/2-2 h after instillation of the meal. In contrast, trypsin output was maximum within 10 min. The data support the concept that in man release of secretin is governed principally by the amount of hydrogen ions emptied into duodenum and indicate the importance of secretin in the late postprandial period, when the acidity of the gastric contents is high.

Predominant role of bile in modulation of early postresectional enteric hyperplasia.

Pancreaticobiliary secretions modulate compensatory hyperplasia after proximal small-bowel resection. To investigate the individual contributions of bile and pancreatic juice, levels of nucleic acids in ileal mucosa of the rat were examined 48 hours after performance of jejunectomy with selective exclusion of bile or pancreatic juice. Exclusion of bile alone inhibited the postresectional increase in levels of RNA and DNA. Exclusion of pancreatic juice (but provision of bile) did not inhibit a rise in ileal RNA or DNA levels after jejunectomy. Presence of bile seems to be one of the major elements in the early stages of adaptive hyperplasia of the ileum.