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.

Rapid intestinal transit as a primary cause of severe chronic diarrhea in patients with amyloidosis.

OBJECTIVE: The cause of severe diarrhea in patients with systemic amyloidosis is obscure. We therefore performed pathophysiological studies in three such patients in an effort to determine the mechanism of amyloid diarrhea. METHODS: Epithelial cell absorption rate of electrolytes was measured during steady state GI perfusion of a saline-mannitol solution. GI transit time of PEG and absorption of radiolabeled bile acid were measured simultaneously while subjects ingested three meals per day. To obtain a diarrhea control group for transit time and bile acid absorption, normal subjects were studied when they had diarrhea caused by ingestion of Milk of Magnesia (MOM). RESULTS: Diarrhea could not be explained by malabsorption of ingested nutrients, bacterial overgrowth, bile acid malabsorption, or epithelial cell malabsorption of electrolytes. However, 25% of polyethylene glycol (PEG) ingested with a standard meal was recovered in stool in 45 min, which is 10 times faster than in normal subjects with equally severe diarrhea caused by ingestion of MOM. All of the patients had autonomic neuropathy that remained unrecognized for 15-36 months after onset of chronic diarrhea; it seems likely that this was the cause of rapid transit. CONCLUSIONS: Severe chronic diarrhea in three patients with systemic amyloidosis was mediated by extremely rapid transit of chyme and digestive secretions through the intestine.

Abnormal passive chloride absorption in cystic fibrosis jejunum functionally opposes the classic chloride secretory defect.

Due to genetic defects in apical membrane chloride channels, the cystic fibrosis (CF) intestine does not secrete chloride normally. Depressed chloride secretion leaves CF intestinal absorptive processes unopposed, which results in net fluid hyperabsorption, dehydration of intestinal contents, and a propensity to inspissated intestinal obstruction. This theory is based primarily on in vitro studies of jejunal mucosa. To determine if CF patients actually hyperabsorb fluid in vivo, we measured electrolyte and water absorption during steady-state perfusion of the jejunum. As expected, chloride secretion was abnormally low in CF, but surprisingly, there was no net hyperabsorption of sodium or water during perfusion of a balanced electrolyte solution. This suggested that fluid absorption processes are reduced in CF jejunum, and further studies revealed that this was due to a marked depression of passive chloride absorption. Although Na+-glucose cotransport was normal in the CF jejunum, absence of passive chloride absorption completely blocked glucose-stimulated net sodium absorption and reduced glucose-stimulated water absorption 66%. This chloride absorptive abnormality acts in physiological opposition to the classic chloride secretory defect in the CF intestine. By increasing the fluidity of intraluminal contents, absence of passive chloride absorption may reduce the incidence and severity of intestinal disease in patients with CF.

Accurate enzymatic measurement of fecal bile acids in patients with malabsorption.

Quantitation of fecal bile acid excretion can help elucidate the cause of diarrhea or steatorrhea. Fecal bile acids can be measured with gas chromatography-mass spectrometry, but this is time-consuming, expensive, and not available for clinical use. Relatively simple enzymatic methods have been described for the measurement of fecal 3alpha-hydroxy bile acids, but these have not been validated in patients with gastrointestinal disease. We found that an enzymatic method yielded falsely low results in patients with malabsorption syndromes for two reasons: First, the preliminary hydrolysis step did not completely deconjugate bile acids, precluding their extraction into diethyl ether for enzymatic assay. Second, long-chain fatty acids inhibited 3alpha-hydroxysteroid dehydrogenase activity. By increasing the duration of hydrolysis and the concentration of enzyme, we developed a simple, accurate, and reproducible method for measuring fecal 3alpha-hydroxy bile acids that agreed well with values obtained with the use of gas chromatography-mass spectrometry (R =.95), both in normal subjects and in patients with malabsorption syndromes.

Conjugated bile acid replacement therapy reduces urinary oxalate excretion in short bowel syndrome.

BACKGROUND: Patients with short bowel syndrome (SBS) have steatorrhea, in part because of bile acid malabsorption that causes decreased bile acid secretion into the duodenum and consequent fat maldigestion. In SBS patients with colon in continuity, luminal calcium forms calcium fatty acid soaps rather than precipitating as insoluble calcium oxalate. Soluble oxalate is hyperabsorbed by the colon leading to hyperoxaluria and an increased risk for renal calcium oxalate stones and deposits. The authors hypothesized that oral ingestion of conjugated bile acids would increase fat absorption and thereby decrease calcium fatty acid soap formation and oxalate hyperabsorption. METHODS: The effect of conjugated bile acid replacement therapy (9 g/d) on fecal fat excretion and urine oxalate excretion was measured in an appropriate patient, utilizing the metabolic balance technique. The effects of chronic bile acid replacement therapy on oxalate excretion and nutritional status also were measured in a 3-month outpatient study. RESULTS: Natural conjugated bile acid replacement therapy reduced fecal fat excretion from 119 to 79 g/d (Delta40 g/d), and urinary oxalate excretion from 87 to 64 mg/d (966 to 710 micromol/d; Delta23 mg/d). Cholylsarcosine, a synthetic conjugated bile acid, had similar but less powerful effects. During a 3-month outpatient trial of natural conjugated bile acids (9 g/d), urine oxalate decreased to normal levels (27 mg/d) in association with weight gain, decreased hunger, and decreased hyperphagia. CONCLUSION: Conjugated bile acid replacement therapy reduced fecal fat excretion, reduced urinary oxalate excretion, and improved nutritional status in a patient with SBS with colon in continuity, hyperoxaluria, and oxalate nephrolithiasis.