Carol A. Santa Ana

A Clinical Study of Patients With Fecal Incontinence and Diarrhea

Clinical and pathophysiologic studies were carried out in 29 patients with chronic diarrhea and incontinence. Most of these patients had been extensively investigated for diarrhea, whereas closer questioning revealed that the major (but previously unmentioned) problem was incontinence for liquid stools. Incontinent patients were, as a group, abnormal with regard to anal sphincter pressure, the ability to retain a solid sphere in the rectum as weights were applied, and the ability to retain saline that had been infused into the rectum. They were, however, no different from control subjects with regard to sphincter length and squeeze duration and with regard to the ability to detect the presence of fluid infused into the rectum. Estimation of sphincter tone by digital examination did not correlate with any objective measure of anal sphincter function or with continence to rectally infused saline. Analysis of the individual data from incontinent diarrhea patients showed that most of these patients had low stool volumes, low sphincter pressures, and an impaired ability to retain saline infused into the rectum. These results would be compatible with a defect in the function of the sphincter muscles. However, some patients had sphincter pressures well within the normal range, low stool volumes, and impaired saline continence. It seems likely that these patients have an abnormality in the continence mechanism other than a muscular weakness of the anal sphincter. Finally, 2 patients had sphincter pressures well within the normal range and good continence to saline, but passed very large amounts of -stool. Such patients probably represent a situation where large volume diarrhea overwhelms a fairly normal mechanism for preserving continence. Our results suggest that measurement of stool volume, sphincter pressure, and ability to retain rectally infused saline may aid in the diagnostic and therapeutic evaluation of patients with chronic diarrhea and fecal incontinence.

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.

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.

The contribution of malabsorption to the reduction in net energy absorption after long-limb Roux-en-Y gastric bypass

BACKGROUND Roux-en-Y gastric bypass (RYGB) restricts food intake, and when the Roux limb is elongated to 150 cm, the procedure is believed to induce malabsorption. OBJECTIVE Our objective was to measure total reduction in intestinal absorption of combustible energy after RYGB and the extent to which this was due to restriction of food intake or malabsorption of ingested macronutrients. DESIGN Long-limb RYGB was performed in 9 severely obese patients. Dietary intake and intestinal absorption of fat, protein, carbohydrate, and combustible energy were measured before and at 2 intervals after bypass. By using coefficients of absorption to measure absorptive function, equations were developed to calculate the daily gram and kilocalorie quantities of ingested macronutrients that were not absorbed because of malabsorption or restricted food intake. RESULTS Coefficients of fat absorption were 92 ± 1.3% before bypass, 72 ± 5.5% 5 mo after bypass, and 68 ± 8.7% 14 mo after bypass. There were no statistically significant effects of RYGB on protein or carbohydrate absorption coefficients, although protein coefficients decreased substantially in some patients. Five months after bypass, malabsorption reduced absorption of combustible energy by 124 ± 57 kcal/d, whereas restriction of food intake reduced energy absorption by 2062 ± 271 kcal/d. Fourteen months after bypass, malabsorption reduced energy absorption by 172 ± 60 kcal/d compared with 1418 ± 171 kcal/d caused by restricted food intake. CONCLUSION On average, malabsorption accounted for ≈6% and 11% of the total reduction in combustible energy absorption at 5 and 14 mo, respectively, after this gastric bypass procedure.

Effect of the Time of Administration of Calcium Acetate on Phosphorus Binding

Phosphorus binders are given to patients with renal failure to increase gastrointestinal excretion of phosphorus. To determine the relative importance of the binding of dietary as compared with endogenous phosphorus and to determine the optimal dose schedule, we gave either 4.4 g of calcium acetate (25 mmol of calcium) or a placebo to six normal subjects on each of seven different schedules in a randomized sequence. The net gastrointestinal balance of phosphorus and calcium was determined by a one-day lavage technique. After a meal containing approximately 12 mmol of phosphorus, the mean phosphorus absorption (+/- SE) measured 9.17 +/- 0.36 mmol (78 percent) with placebo but decreased to 3.81 +/- 0.58 mmol (31 percent) when calcium acetate was given immediately before the meal (representing binding of 5.36 +/- 0.77 mmol of phosphorus). Similar binding was observed when calcium acetate was given immediately after the meal and when half the dose was given before and half after the meal. In contrast, when calcium acetate was given two hours after the meal or while the subject was fasting, phosphorus binding was reduced to 2.00 +/- 0.52 mmol and 1.81 +/- 0.84 mmol, respectively. Calcium absorption from calcium acetate averaged 21 +/- 1 percent when the binder was given with a meal; absorption from calcium acetate averaged 40 +/- 4 percent when the binder was given while the subject was fasting. We conclude that calcium acetate increases fecal excretion of phosphorus by binding both dietary and endogenous phosphorus, but the binding of dietary phosphorus is quantitatively much more important. For the most efficient phosphorus binding, calcium (and presumably other phosphorus-binding cations) should be given with meals.

A low-sodium solution for gastrointestinal lavage

Golytely is a sodium sulfate-based solution used for lavage cleansing of the colon. Although most patients and physicians prefer Golytely lavage over other methods of bowel cleansing, its highly salty taste is a drawback. This report describes the development of a modified lavage solution that has a barely perceptible salty taste. This solution was developed by removing sodium sulfate, increasing the concentration of polyethylene glycol, and making minor adjustments in the concentration of other salts. Golytely, reduced sodium sulfate Golytely (Golytely-RSS), and a balanced electrolyte solution were infused into the stomachs of normal subjects. After steady-state lavage conditions were established, the rates of fluid and electrolyte absorption were measured. Average fluid absorption rate was 791 ml/h with the balanced electrolyte solution, compared with only 63 and 45 ml/h with Golytely and Golytely-RSS, respectively. Golytely-RSS was studied at 3 infusion rates, from 0.9-1.8 L/h, and the time and volume of solution required for colon cleansing was determined; the lower infusion rate (0.9 L/h) took longer but required less solution to cleanse the colon. In conclusion, Golytely-RSS has the essential feature of Golytely; i.e., lavage is associated with negligible salt and water absorption. The less-salty taste of Golytely-RSS may make it less difficult to drink and thereby enhance patient compliance; the total volume of solution required for cleansing is less when the solution is ingested at 0.9 L/h than when the ingestion rate is 1.8 L/h.

Osmotic effects of polyethylene glycol

Polyethylene glycol (PEG) has been used to increase the osmotic pressure of fluids used to cleanse the gastrointestinal tract. However, little is known about its osmotic activity. To investigate this activity systematically, solutions of PEG of differing molecular weights were made and subjected to measurement of osmolality by both freezing point depression and vapor pressure osmometry. Measured osmolality was increasingly greater than predicted from average molecular weight as PEG concentration increased. Measurement of sodium activity in NaCl/PEG solutions by means of an ion-selective electrode suggested that the higher than expected osmolality could be due in part to interactions that, in effect, sequestered water from the solution. Osmolality was consistently greater by freezing point osmometry than by vapor pressure osmometry. To determine which osmometry method reflected biologically relevant osmolality, normal subjects underwent steady-state total gut perfusion with an electrolyte solution containing 105 g/L of PEG 3350. This produced rectal effluent that was hypertonic by freezing point osmometry but isotonic by vapor pressure osmometry. Assuming that luminal fluid reaches osmotic equilibrium with plasma during total gut perfusion, this result suggests that the vapor pressure osmometer accurately reflects the biologically relevant osmolality of intestinal contents. We conclude that PEG exerts more of an osmotic effect than would be predicted from its molecular weight. This phenomenon may reflect interactions between PEG and water molecules that alter the physical chemistry of the solution and sequester water from the solution.

Effect of D-glucose on intestinal permeability and its passive absorption in human small intestine in vivo

BACKGROUND Based on studies in animals, it has been proposed that carrier-mediated D-glucose absorption markedly enhances passive permeability of the jejunal mucosa, allowing the majority of D-glucose absorption to proceed passively. In this study, we evaluated this hypothesis in the human jejunum in vivo. METHODS Using the constant perfusion, nonabsorbable marker technique, permeability of jejunal mucosa was assessed by measuring the ratio of diffusion rates of urea/L-xylose and mannitol/L-xylose. Passive D-glucose absorption was quantitated using L-glucose and mannitol as probes for D-glucose. RESULTS Addition of D-glucose to perfused solutions did not change the diffusion ratios, indicating that D-glucose has no effect on the size of channels for passive diffusion across the jejunal mucosa. The fraction of total D-glucose absorption that could be attributed to a passive mechanism averaged 5%. In the human ileum in vivo, we detected no evidence of passive D-glucose absorption. CONCLUSIONS Carrier-mediated D-glucose absorption does not increase passive permeability of human jejunal mucosa to solutes with molecular radii between 2.6 and 4.0 A. The amount of D-glucose absorbed passively from the human jejunum is trivial compared with the overwhelmingly dominant mechanism, carrier-mediated transport. Our results do not support the concept that sodium-dependent nutrient transport increases tight junction permeability.

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.

Urinary excretion of polyethylene glycol 3350 and sulfate after gut lavage with a polyethylene glycol electrolyte lavage solution

Ingestion of an electrolyte lavage solution containing polyethylene glycol 3350 and sulfate is an effective method of cleansing the colon for diagnostic studies. Polyethylene glycol and sulfate are considered poorly absorbed from the gastrointestinal tract. Because of the quantities administered, concern exists about potential toxicity of absorption of even a small percentage, particularly for polyethylene glycol. We measured the urinary excretion of both polyethylene glycol and sulfate in normal subjects and inflammatory bowel patients. Absorption of polyethylene glycol can be assessed by measuring recovery in urine, as 85%-96% of an intravenous load is excreted in urine. Similarly, appreciable sulfate absorption would exceed renal tubular reabsorption and result in increased urinary excretion. Mean percent polyethylene glycol load recovered in urine was minimal and similar for normal (0.06%) and inflammatory bowel (0.09%) subjects. Urinary sulfate excretion after lavage was also similar for both groups and was not different from baseline. These results do not suggest the likelihood of toxicity due to polyethylene glycol 3350 or sulfate absorption during gut lavage with this solution.