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Biomedical subjects

C A Santa Ana

Publications and source records attributed to C A Santa Ana.

51 records · Page 3Linked to original sources

Gas production after reaction of sodium bicarbonate and hydrochloric acid.

Ingestion of sodium bicarbonate has been implicated as one of the proximate causes of spontaneous gastric rupture. However, the volume and rate of gas released from the reaction of ingested sodium bicarbonate and gastric acid has not been previously studied in detail. We, therefore, developed an in vitro method for measuring gas release after addition of sodium bicarbonate to a solution containing hydrochloric acid. From the results of our studies, we conclude that even though hydrochloric acid and sodium bicarbonate react instantaneously, the resulting gas production is slow, mainly because CO2 produced from the dehydration of carbonic acid dissolves in water and is only slowly released into the gas phase. The major exogenous factors that determine the rate of gas release are the volume of the solution, the quantity of reactants, the air volume over the reaction mixture, the partial pressure of CO2 of the acid solution before the addition of bicarbonate, and the stirring rate. The presence of food, alcohol, and carbonic anhydrase had relatively little if any effect. Based on our results, we believe that ingestion of the recommended dose of sodium bicarbonate (one-half teaspoon) would result in only small amounts of sudden gas release, probably not enough to be an important factor in causing spontaneous gastric rupture. On the other hand, we measured the amount of sodium bicarbonate that people actually select to take for indigestion, and all exceeded the recommended dose. Some people selected doses of bicarbonate that would result in several hundred milliliters of gas release within 3 min; it seems likely that such injudicious ingestion of sodium bicarbonate, if taken when the stomach was distended with air, food, and liquid, could be an important factor in spontaneous gastric rupture.

Bicarbonates↗

Mechanism of the antidiarrheal effect of loperamide.

To determine whether the antidiarrheal effect of loperamide is due to an effect on intestinal motor function or to an acceleration of the rate of absorption by the intestine (as has been suggested recently), we studied absorption during experimental diarrhea produced by the rapid intragastric infusion of electrolyte solution. In studies in which a 2700-ml bolus of electrolyte solution was infused into the stomach over 90 min, loperamide delayed the appearance of rectal effluent in each of 5 subjects and decreased the volume of rectal effluent from 1090 +/- 118 to 770 +/- 73 ml (p = 0.05). When intragastric infusion was continued for 5 h, producing steady-state total gut perfusion, the volume of effluent produced per unit time and the concentration of a nonabsorbable polyethylene glycol marker in rectal effluent was not different with or without loperamide, indicating that loperamide did not alter the rate of absorption by intestinal mucosal cells. Loperamide also had no effect during steady-state perfusion when absorption rates were reduced by intravenous infusion of vasoactive intestinal polypeptide. Loperamide did substantially increase the intraluminal volume of the total gut, from 985 +/- 131 to 1764 +/- 195 ml (p less than 0.02). These results suggest that loperamide exerts its antidiarrheal effect by a change in the motor function of the intestine, which results in increased capacitance of the gut and a delay in the passage of fluid through the intestine. This change in motor function, rather than a change in the rate of absorption by intestinal mucosal cells, is responsible for the antidiarrheal effect of loperamide in our experimental diarrhea model.

Adult↗

Lithium absorption in tight and leaky segments of intestine.

There is significant absorption of Li+ by human jejunum and ileum, but negligible absorption by human colon. Thus, a proximal-to-distal gradient of decreasing Li+ absorption and increasing junctional tightness exists in intestine as well as in renal tubule. For six leaky epithelia the relative permeabilities of K+, Na+, and Li+ by the junctional route are in the sequence PK greater than PNa greater than PLi and all fall within a factor of 2.5. In contrast, for tight epithelia PLi approximately PNa much greater than PK in the amiloride-sensitive channel of the apical membrane, but PK much greater than PLi approximately PNa in the basolateral membrane. The ability of several tight epithelia to sustain nonzero transepithelial Li+ absorption despite this basolateral barrier may be due to Na+/Li+ countertransport at the basolateral membrane, resulting in secondary active transport of Li+ across the epithelium.

Adult↗

Evaluation of chloride/bicarbonate. Exchange in the human colon in vivo.

During perfusion of a plasma-like solution, colonic absorption rate of chloride was much higher than the secretion rate of bicarbonate (34 vs. 3.5 meq/h, respectively). This might suggest that anion exchange (Cl/HCO3) accounts for only a small fraction of total chloride absorption. However, if the colon absorbs as well as secretes bicarbonate, this reasoning would underestimate the magnitude of the anion exchange. To see if the colon absorbs bicarbonate, we perfused a chloride-free solution (which would eliminate bicarbonate secretion via (Cl/HCO3 exchange) and found that the colon absorbed bicarbonate at a rate of 5.1 meq/h. Calculation of electrochemical gradients and measurement of luminal fluid PCO2 indicated that this bicarbonate absorption was mediated passively in response to electrical gradients, rather than via reversed Cl/HCO3 exchange or acid secretion. The combined results of the plasma-like and chloride-free perfusion experiments suggest Cl/HCO3 exchange at a rate of 8.6 meq/h (the sum of bicarbonate movements, 3.5 and 5.1 meq/h, observed in the two experiments). To obtain a second estimate under different experimental conditions, a choline chloride-choline bicarbonate (sodium-free) solution was perfused; with this solution, chloride and bicarbonate absorption dependent on active sodium transport should be eliminated or markedly reduced, and the magnitude of Cl/HCO3 exchange should be revealed. This experiment suggested a Cl/HCO3 exchange rate of 9.3 meq/h, similar to the first estimate. As chloride was absorbed at a rate of 34 meq/h during perfusion of the plasma-like solution, the Cl/HCO3 exchange provides for approximately one-fourth of total chloride absorption.

Absorption↗

Purging and calorie absorption in bulimic patients and normal women.

Self-induced purging with laxatives is common among bulimic persons, who assume that purging reduces intestinal absorption of ingested calories. However, the efficacy of purging in reducing calorie absorption has never been studied, probably because the standard calorie balance procedure is expensive and time consuming. With a recently devised method, calorie absorption during a single day was measured to determine to what extent phenolphthalein or saline purge reduced calorie absorption. In two bulimic patients who regularly used laxatives for weight control and five normal young women, even extreme purging producing 4 to 6 L of diarrhea caused calorie absorption to decrease by only about 12% of calorie intake. The theoretical basis on which laxatives are taken for weight control is unsound.

Adult↗

Pathogenesis of fecal incontinence in diabetes mellitus: evidence for internal-anal-sphincter dysfunction.

We studied 16 patients with diabetes and fecal incontinence. The onset of incontinence coincided with the onset of chronic diarrhea in most patients. Episodes of incontinence occurred when stools were frequent and loose; however, 24-hour stool weights were usually within normal limits. All patients had evidence of autonomic neuropathy, and one third had steatorrhea. Incontinent diabetics had a lower mean basal anal-sphincter pressure than 35 normal subjects (63 +/- 4 vs. 37 +/- 4 mm Hg; P less than 0.001), reflecting abnormal internal-anal-sphincter function. The increment in sphincter pressure with voluntary contraction (external-sphincter function) was not significantly different from normal. Incontinent diabetics also had impaired continence for a solid sphere and for rectally infused saline. In contrast, 14 diabetics without diarrhea or incontinence had normal sphincter pressures and normal results on tests of continence, even though 79 per cent had evidence of autonomic neuropathy and nearly half had steatorrhea. We conclude that incontinence in diabetic patients is related to abnormal internal-anal-sphincter function, and that as a group, diabetics without diarrhea do not have latent defects in continence.

Adult↗

Starch blockers--their effect on calorie absorption from a high-starch meal.

It has been known for more than 25 years that certain plant foods, such as kidney beans and wheat, contain a substance that inhibits the activity of salivary and pancreatic amylase. More recently, this antiamylase has been purified and marketed for use in weight control under the generic name "starch blockers." Although this approach to weight control is highly popular, it has never been shown whether starch-blocker tablets actually reduce the absorption of calories from starch. Using a one-day calorie-balance technique and a high-starch (100 g) meal (spaghetti, tomato sauce, and bread), we measured the excretion of fecal calories after normal subjects had taken either placebo or starch-blocker tablets. If the starch-blocker tablets had prevented the digestion of starch, fecal calorie excretion should have increased by 400 kcal. However, fecal calorie excretion was the same on the two test days (mean +/- S.E.M., 80 +/- 4 as compared with 78 +/- 2). We conclude that starch-blocker tablets do not inhibit the digestion and absorption of starch calories in human beings.

Adult↗

Studies of the mechanism of the antidiarrheal effect of codeine.

To determine whether the antidiarrheal action of opiate drugs in humans is due to enhanced intestinal absorption rates, as suggested by recent experiments in animals, or is due to altered intestinal motility, as traditionally thought, we studied the effect of therapeutic doses of codeine on experimental diarrhea and on the rate of intestinal absorption of water and electrolytes in normal human subjects. Our results show that codeine (30-60 mg i.m.) markedly reduced stool volume during experimental diarrhea induced by rapid intragastric infusion of a balanced electrolyte solution. There was, however, no evidence that codeine stimulated the rate of intestinal absorption in the gut as a whole or in any segment of the gastrointestinal tract, either in the basal state or when absorption rates were reduced by intravenous infusion of vasoactive intestinal polypeptide. We also measured segmental transit times to determine whether and where codeine delayed the passage of fluid through the intestine. Codeine caused a marked slowing of fluid movement through the jejunum, but had no effect on the movement of fluid through the ileum or colon. In other studies, we found that the opiate antagonist naloxone did not significantly affect water or electrolyte absorption rates in the jejunum or ileum. We conclude (a) that therapeutic doses of codeine increase net intestinal absorption (and thereby reduce stool volume) by increasing the contact time of luminal fluid with mucosal cells, not by increasing the rate of absorption by the mucosal cells; and (b) that endogenous opiates do not regulate intestinal absorption in humans.

Adult↗

Permeability characteristics of human jejunum, ileum, proximal colon and distal colon: results of potential difference measurements and unidirectional fluxes.

In order to assess the passive permeability characteristics of the human intestine in vivo, we measured potential difference in the jejunum, ileum, proximal colon, and distal colon during perfusion of various test solutions that were designed to establish chemical gradients for sodium or chloride, or both or neither. In addition, unidirectional fluxes of sodium and chloride were measured in 30-cm segments of the jejunum and ileum and entire colon during perfusion of balanced electrolyte solution. These studies indicate that there are marked differences in the pathways for passive ion movement in the areas of the intestine studied. In the jejunum, this pathway appears to be highly permeable to both sodium and chloride with modest cation selectivity. In the ileum this pathway is much more cation selective, predominantly because of a relative impermeability to chloride. In the colon, on the other hand, these passive pathways appear to be more anion than cation selective. The implication of these results for normal transport physiology are discussed.

Action Potentials↗

Effect of vasoactive intestinal polypeptide on active and passive transport in the human jejunum.

The effect of intravenous vasoactive intestinal polypeptide (VIP) on normal transport mechanisms in the human jejunum in vivo was examined with the triple-lumen, steady-state perfusion technique. By using special test solutions that revealed different aspects of jejunal transport, we were able to evaluate the effect of VIP on specific transport processes, such as active bicarbonate absorption, active chloride secretion, and passive absorption or secretion of sodium chloride. At an infusion rate of 200 pmol/kg per h, VIP inhibited active bicarbonate absorption by approximately 42%, stimulated active chloride secretion to a slight extent, and slightly reduced passive sodium chloride absorption. A larger dose of VIP, 400 pmol/kg per h, had essentially the same effect on active bicarbonate absorption and active chloride secretion, but it markedly depressed passive sodium chloride absorption and also inhibited passive secretion induced by mannitol. VIP reduced the lumen-to-plasma unidirectional sodium and chloride flux rates, while the plasma-to-lumen flux rates were decreased to a lesser extent or remained unchanged. The potential difference became more lumen-negative with VIP, but the sodium diffusion and glucose-stimulated potential were not affected. We conclude that the major effect of VIP in the human jejunum is to decrease the normal absorption of water and electrolytes--not only active bicarbonate-mediated absorption, but also the passive absorption in response to osmotic forces generated by active or facilitated absorptive processes. Although an increase in chloride secretion does occur, this does not appear to be of major importance.

Adult↗

Active chloride secretion in the normal human jejunum.

To determine whether the small intestine normally secretes fluid, it would be necessary to reduce or inhibit the greater absorptive processes that would otherwise mask such secretion if present. To do this, we perfused bicarbonate-free solutions in the jejunum of normal subjects, because it has been shown that active absorption from this part of the human small intestine is dependent on luminal bicarbonate. We found that the jejunum did secrete sodium chloride and water when isotonic bicarbonate-free solutions were perfused. Further studies revealed that the sodium secretion was passive, but that chloride was secreted against an electrochemical gradient and that observed chloride flux ratios did not agree with the flux ratios calculated for passive chloride movement. We conclude, therefore, that the normal jejunum actively secretes chloride, but that this is masked by greater absorptive processes when balanced electrolyte solutions are perfused. The rate of this active chloride secretion may be one of the factors that regulate the rate of fluid absorption in the normal human intestine.

Bicarbonates↗

Chronic diarrhea of unknown origin.

We studied 27 patients with severe chronic diarrhea for which extensive investigations carried out at other institutions had failed to reveal a diagnosis. They were studied by standard diagnostic methods as well as by careful fecal analysis and intestinal perfusion. If they were incontinent of feces, anal sphincter function tests were performed. Although many were suspected of having pancreatic cholera syndrome, this diagnosis could not be established in a single patient. The most common diagnosis that could be established was surreptitious ingestion of drugs (laxatives in 7 patients and diuretics in 2). Other specific diagnoses included ulcerative colitis in 2 patients, allergy to beef in 1, and bacterial overgrowth of the small intestine in 1. Thus, we were able to establish a specific diagnosis in 13 patients. Of the remaining 14 patients, 8 had findings suggestive of irritable bowel syndrome, and 2 others had anal sphincter dysfunction as the major cause of their disability. The other 4 undiagnosed patients had severe secretory (3 patients) or osmotic (1 patient) diarrhea. Follow-up interviews at 6 mo-6 yr failed to reveal evidence of a cause for diarrhea that had been overlooked during our studies. The diagnostic approach to patients with unexplained diarrhea is discussed. The importance of a search for surreptitious drug ingestion and accurate measurement of bowel movement frequency and stool weight is emphasized.

Adult↗

Acute effect of diphenoxylate with atropine (Lomotil) in patients with chronic diarrhea and fecal incontinence.

Fifteen patients with chronic diarrhea and fecal incontinence were admitted to a clinical research center and treated for 3 days with either placebo or diphenoxylate with atropine (Lomotil). The patients were then crossed over to the alternate medication. Lomotil had no effect on rectal or anal sphincter pressure or on continence for saline that had been infused into the rectum. However, Lomotil therapy reduced average stool frequency (from 4.9 to 2.6 times/day) and average stool weight (from 460 to 256 g/day). These results suggest that temporary or intermittent therapy with Lomotil and related drugs might benefit patients with chronic diarrhea and fecal incontinence. They should do this by virtue of a reduction in stool frequency and stool volume, without a deleterious effect on the defense mechanisms against incontinence.

Adult↗

Development of a lavage solution associated with minimal water and electrolyte absorption or secretion.

Ingestion of large volumes of a balanced electrolyte solution has previously been shown to be an effective method of cleaning the colon for diagnostic studies. However, in this paper we have shown that total gut perfusion with such a solution results in absorption of 2400 ml water and 375 meq of sodium over 3 hr, which is the approximate time required to clean the colon by this technique. This might be hazardous to patients who are unable to readily excrete a salt and water load. We, therefore, designed a solution containing mainly sodium sulfate that was associated with only trivial amounts of water and sodium absorption or secretion during total gut perfusion. This new solution might be useful in colon cleansing before colonoscopy, barium enema, and surgery. In addition, such a solution may have some therapeutic indications, including bowel cleaning in patients with hepatic encephalopathy or as a rapid washout technique for ingested toxins.

Diarrhea↗

Inhibition of water and electrolyte absorption by polyethylene glycol (PEG).

Polyethylene glycol (PEG) is commonly used as a nonabsorbable volume marker in intestinal perfusion and flow studies. It has been assumed that PEG does not affect water and electrolyte movement, but this has not been extensively investigated. Using triple-lumen tube perfusion technique, we examined the effect of various PEG concentrations (0, 2, 5, 10, and 20 g/liter) on water and electrolyte absorption by the jejunum and ileum in normal subjects. 14C-labeled PEG served as the nonabsorbable marker in the 0 PEG concentration solution. There was a progressive reduction in water, sodium, and chloride absorption as the concentrations of PEG was increased from 0 to 20 g/liter. Though further studies are necessary to establish the mechanism responsible for this PEG effect, the observed changes in luminal fluid osmolality and electrolyte concentrations suggest that the reduction in absorption most likely results from an osmotic effect rather than an inhibition of active absorption or stimulation of secretion.

Electrolytes↗