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Biomedical subjects

J S Fordtran

Publications and source records attributed to J S Fordtran.

At least 145 records · Page 8Linked to original sources

Gastric acid secretion rate and buffer content of the stomach after eating. Results in normal subjects and in patients with duodenal ulcer.

New methods are described by which the buffer content and the rate and pattern of net gastric acid secretion in human subjects fed normal meals can be measured by use of sodium bicarbonate infusion to control intragastric pH. With these techniques, it was shown that the rate of acid secretion in response to a steak meal in seven duodenal ulcer patients was twice the rate achieved in six control subjects and that the amount of acid secreted after eating exceeded the peak histamine response in the ulcer patients but not in the controls. Meal-stimulated acid secretion, expressed as a function of the peak histamine response, was roughly correlated with the serum gastrin concentration (r = 0.45), but it was concluded that other factors must also contribute to the higher than normal secretory responses to a meal found in duodenal ulcer patients. Measurement of buffer content of the stomach revealed that the duodenal ulcer patients emptied the meal buffer at a much more rapid rate than the normal subjects. By 2 h after eating, the ulcer subjects had less than half as much buffer in their stomachs as the controls. The combination of acid hypersecretion and rapid buffer emptying leads to abnormally high gastric acidity after a meal in duodenal ulcer patients. These results suggest that, in addition to a large parietal cell mass, parietal cell responsiveness to a meal and the rate of buffer emptying may be important in the pathogenesis of duodenal ulcer.

Adult↗

Effect of dietary calcium and age on jejunal calcium absorption in humans studied by intestinal perfusion.

Jejunal calcium absorption was measured from test solutions containing 1.0, 2.5, 5, and 10 mM calcium (as calcium gluconate). Absorption rates increased progressively as luminal calcium concentration was increased, although there was a tendency toward saturation of the absorptive process at the higher concentrations. Calcium absorption was higher in normal young adults than in normal subjects over age 60. In both groups a 300 mg calcium diet for 4-8 wk enhanced calcium absorption relative to absorption rates after 4-8 wk on a 2,000 mg calcium diet. This adaptation was more definite and dramatic in the young than in the old subjects. Indirect estimates suggest that adaptation to a low calcium diet and the higher absorption in young than old normal subjects are mediated by an increased V(max) rather than a decreased K(m).

Adult↗

Thyrocalcitonin and the jejunal absorption of calcium, water, and electrolytes in normal subjects.

Jejunal absorption of calcium, water, and electrolytes was measured in 10 normal subjects by the triple-lumen perfusion method. During the control period, water and electrolyte movements were minimal when a bicarbonate-free test solution was infused. By contrast, bicarbonate-containing solutions were readily absorbed in the control period. Intravenous infusion of synthetic salmon calcitonin (SCT) (1 Medical Research Council U/kg wt/h) over 110-120 min resulted in a marked jejunal secretion of water, sodium, potassium, and chloride in 8 of the 10 subjects. This jejunal secretion occurred with both the bicarbonate-free and the bicarbonate-containing test solutions. Calcium absorption was not affected by SCT, and the serum calcium concentration did not fall during SCT infusion. These results suggest that diarrhea in patients with medullary carcinoma of the thyroid may be due to intestinal secretion secondary to high blood concentrations of thyrocalcitonin.

Adult↗

The role of intraluminal sodium in glucose absorption in vivo.

Active glucose absorption is thought to depend on a gradient of sodium ion concentration across the brush border membrane of intestinal epithelial cells. This concept is generally accepted, although its validity has never been adequately evaluated in the human small intestine in vivo. According to this hypothesis, the rate of glucose absorption should decrease markedly if the luminal sodium concentration is markedly reduced, and glucose absorption against a concentration gradient should cease entirely if luminal sodium is lower than intracellular sodium concentration. In the present series of experiments we were not able to show an important role of intraluminal sodium concentration in the active absorption of glucose from the human, rat, and dog ileum in vivo. Specifically, glucose absorption was minimally reduced or not reduced at all when intraluminal sodium concentration was reduced from 140 to as low as 2.5 mEq/liter. The discrepancy between our results and those of previous workers whose data suggest that removal of intraluminal sodium should markedly inhibit active glucose absorption is not entirely clear, but there are a number of differences in experimental design between most previous studies and our own. Although our data show that active glucose absorption proceeds at a near normal rate even when lumen sodium concentration is reduced below 3 mEq/liter, our results do not disprove the sodium gradient theory because of the theoretic possibility that the microclimate adjacent to the brush border has a high concentration of sodium even when luminal sodium concentration is markedly reduced. The validity of the sodium gradient hypothesis would appear to be critically dependent on such a microclimate.

Adult↗

Pathogenesis of congenital alkalosis with diarrhea. Implications for the physiology of normal ileal electrolyte absorption and secretion.

Using a triple-lumen constant perfusion system, we have studied ileal electrolyte transport in a patient with congenital alkalosis with diarrhea and made the following observations. First, chloride cannot be transported against electrochemical gradients, but can be readily absorbed or secreted down electrochemical gradients. Second, chloride secretion down an electrochemical gradient can be increased by raising lumen bicarbonate concentration. Third, sodium absorption does occur against electrochemical gradients and is associated with hydrogen ion secretion. Fourth, electrical potential difference (PD) between lumen and blood is near zero when lumen sodium concentration is 140 mEq/liter. Fifth, a normal sodium diffusion potential is present. Sixth, potassium is transported passively in response to electrochemical gradients. The ileal electrolyte transport disorder of congenital alkalosis with diarrhea can be simulated exactly in normal subjects perfused with a solution in which chloride is replaced with poorly absorbable sulfate and phosphate. These results can be explained by postulating a single defect in the double ion exchange model (sodium-hydrogen, chloride-bicarbonate) previously proposed for normal ileal transport: i.e., normal sodium-hydrogen exchange, but a chloride-bicarbonate exchange that is incapable of transporting chloride against an electrochemical gradient, yet continues to transport anions passively. In contrast, the results appear incompatible with the concept of ileal electrogenic sodium transport.

Adult↗

Ion transport during cholera-induced ileal secretion in the dog.

To assess the ion transport mechanism by which cholera causes the small bowel to secrete, ion transport rates and electrical potential difference (PD) were determined simultaneously in the normal and choleragen-treated dog ileum in vivo. The results indicate that, during cholera, HCO(3) is actively secreted (i.e., against both an electrical and a concentration gradient); Cl is also actively secreted, against a modest electrochemical gradient. Electrogenic pumping of one or both of these anions is probably responsible for an observed PD change of approximately 13 mv (lumen negative). Na secretion can be accounted for entirely by passive ion movement. K secretion can be partly explained by passive diffusion secondary to the negative intraluminal PD; however, its concentration in the secreted fluid is two to three times higher than expected on the basis of passive forces, suggesting a component of active K secretion. The PD response of the choleragen-treated ileum is normal in response to glucose, but there was no PD response to saline-free mannitol perfusion. This suggests that the normal differential permeability of the ileum to anions and cations may be altered by choleragen, although other explanations of this finding are also possible.

Animals↗

Mechanism of bicarbonate absorption and its relationship to sodium transport in the human jejunum.

Using a constant perfusion technique, sodium and bicarbonate absorption was studied in human subjects. The following observations were made on sodium absorption from saline solution: (a) the rate of sodium absorption is markedly influenced by bulk water flow, (b) when net water flow is zero, sodium absorption is zero if there are no concentration gradients between plasma and lumen that favor net NaCl diffusion; and (c) the PD between abraded skin and jejunal lumen is near zero when saline is perfused and does not change with partial substitution of sulfate or bicarbonate for chloride. Based on these observations, we conclude that sodium absorption from saline is entirely passive in the human jejunum. On the other hand, in the presence of bicarbonate sodium is absorbed actively against electrochemical gradients. The mechanism of the link between bicarbonate and sodium absorption was studied in normal subjects and in 11 patients with pernicious anemia; the latter were chosen because they do not secrete gastric acid which can react with bicarbonate in the jejunal lumen. We observed that bicarbonate absorption (a) occurs against steep electrochemical gradients, (b) does not generate a potential difference between abraded skin and jejunal lumen, (c) is inhibited by acetazolamide, and (d) generates a high CO2 tension in jejunal fluid. These observations suggest that bicarbonate absorption is mediated by active hydrogen secretion, rather than by bicarbonate ion transport per se, and that the link between sodium and bicarbonate transport is best explained by a sodium-hydrogen exchange process.

Acetazolamide↗

Interrelationships of chloride, bicarbonate, sodium, and hydrogen transport in the human ileum.

Using a triple-lumen constant perfusion system, the following observations were made in normal subjects. First, chloride, bicarbonate, and sodium were found to exhibit net movement across ileal mucosa against electrochemical gradients. Second, during perfusion with a balanced electrolyte solution simulating plasma, the ileum generally absorbed, but sometimes secreted fluid. A reciprocal net movement of chloride and bicarbonate was noted when sodium movement was zero. Increasing rates of sodium absorption were associated with decreasing bicarbonate secretion rates and finally bicarbonate absorption. Even when bicarbonate was absorbed ileal contents were alkalinized (by contraction of luminal volume). Third, net chloride movement was found to be sensitive to bicarbonate concentration in ileal fluid. For instance, chloride was absorbed from solutions containing 14 or 44 mEq/liter of bicarbonate, but was secreted when ileal fluid contained 87 mEq/liter of bicarbonate. Fourth, when chloridefree (sulfate) solutions were infused, the ileum absorbed sodium bicarbonate and the ileal contents were acidified. Fifth, when plasma-like solutions were infused, the potential difference (PD) between skin and ileal lumen was near zero and did not change when chloride was replaced by sulfate in the perfusion solution. These results suggest that ileal electrolyte transport occurs via a simultaneous double exchange, Cl/HCO2 and Na/H. In this model neither the anion nor the cation exchange causes net ion movement; net movement results from the chemical reaction between hydrogen and bicarbonate. No other unitary model explains all of the following observations: (a) human ileal transport in vivo is essentially nonelectrogenic even though Na, Cl, and HCO3 are transported against electrochemical gradients, (b) the ileum can secrete as well as absorb, (c) ileal contents are alkalinized during absorption of or during secretion into a plasma-like solution, and (d) the ileum acidifies its contents when sulfate replaces chloride. Data obtained with a carbonic anhydrase inhibitor support the proposed model.

Acetazolamide↗