Steatorrhea and Hyperoxaluria in Severely Obese Patients Before and After Roux-en-Y Gastric Bypass.

BACKGROUND AND AIMS: Hyperoxaluria after Roux-en-Y gastric bypass (RYGB) is generally attributed to fat malabsorption. If hyperoxaluria is indeed caused by fat malabsorption, magnitudes of hyperoxaluria and steatorrhea should correlate. Severely obese patients, prior to bypass, ingest excess dietary fat that can produce hyperphagic steatorrhea. The primary objective of the study was to determine whether urine oxalate excretion correlates with elements of fat balance in severely obese patients before and after RYGB. METHODS: Fat balance and urine oxalate excretion were measured simultaneously in 26 severely obese patients before and 1 year after RYGB, while patients consumed their usual diet. At these time points, stool and urine samples were collected. Steatorrhea and hyperoxaluria were defined as fecal fat >7 g/day and urine oxalate >40 mg/day. Differences were evaluated using paired 2-tailed t tests. RESULTS: Prior to RYGB, 12 of 26 patients had mild to moderate steatorrhea. Average urine oxalate excretion was 61 mg/day; there was no correlation between fecal fat and urine oxalate excretion. After RYGB, 24 of 26 patients had steatorrhea and urine oxalate excretion averaged 69 mg/day, with a positive correlation between fecal fat and urine oxalate excretions (r = 0.71, P < .001). For each 10 g/day increase in fecal fat output, fecal water excretion increased only 46 mL/day. CONCLUSIONS: Steatorrhea and hyperoxaluria were common in obese patients before bypass, but hyperoxaluria was not caused by excess unabsorbed fatty acids. Hyperphagia, obesity, or metabolic syndrome could have produced this previously unrecognized hyperoxaluric state by stimulating absorption or endogenous synthesis of oxalate. Hyperoxaluria after RYGB correlated with steatorrhea and was presumably caused by excess fatty acids in the intestinal lumen. Because post-bypass steatorrhea caused little increase in fecal water excretion, most patients with steatorrhea did not consider themselves to have diarrhea. Before and after RYGB, high oxalate intake contributed to the severity of hyperoxaluria.

Is achlorhydria a cause of iron deficiency anemia?

We re-evaluated the old hypothesis that gastritis-induced achlorhydria is a cause of iron deficiency anemia (IDA) in humans. First, we analyzed the currently available research on the association between achlorhydria and IDA. When gastric acid secretion was measured after maximal stimulation, the frequency of achlorhydria (or severe hypochlorhydria) was 44% in patients with idiopathic IDA and 1.8% in healthy controls. In some patients with pernicious anemia, presumed achlorhydria preceded the development of IDA in time. However, we found no credible evidence that IDA caused gastritis or that IDA preceded the development of achlorhydria. Thus, correlational results favor achlorhydria as the causal factor in the association between achlorhydria and IDA. Second, we sought to determine whether gastritis and achlorhydria cause negative iron balance. When biosynthetic methods were used to isotopically label iron in food, achlorhydric patients were found to have severe malabsorption of nonheme iron, which persisted after the development of IDA. In 1 study, achlorhydria reduced the normal increase in heme-iron absorption from hemoglobin in response to iron deficiency. After an injection of isotopic iron into normal men, the physiologic loss of iron from the body was found to be 1 mg/d. Patients with chronic gastritis had excess fecal loss of isotopically tagged plasma iron. Calculations based on these results indicate that the absorption of iron from a typical Western diet by achlorhydric patients would be less than physiologic iron losses, creating a negative iron balance that could not be overcome by the adaptive increase in duodenal iron absorptive capacity that occurs in response to iron deficiency. The combination of results from these correlational and pathophysiologic studies supports the hypothesis that gastritis-induced achlorhydria can be an independent cause of IDA.

Intestinal and renal effects of low-volume phosphate and sulfate cathartic solutions designed for cleansing the colon: pathophysiological studies in five normal subjects.

OBJECTIVES: Ingestion of a concentrated low-volume phosphate solution produces copious diarrhea, which cleanses the colon, but it occasionally causes renal failure due to calcium phosphate precipitation in renal tubules. We hypothesized that a concentrated low-volume sulfate solution would be an equally effective cathartic, and that urine produced after sulfate would have less tendency to precipitate calcium salts than urine produced after phosphate. METHODS: Hydrated subjects ingested 75 ml of phosphosoda or an equimolar dose of sulfate salts in a small volume of solution. Four liters of PEG (polyethylene glycol) lavage solution was the control. All solutions were administered in split doses, 10 h apart. Propensity of urine to precipitate at pH 6.4 (the pH of renal tubular fluid) was assessed by determining the minimal calcium concentration that caused precipitation. RESULTS: Average diarrheal stool weight was 2,004 g after phosphate, 2,854 g after sulfate, and 3,021 g after PEG (P<0.001). Average calcium concentration (in mg/dl) required to induce urine precipitation at pH 6.4 was 43 after PEG, 10 after PO(4), and 187 after SO(4) (P=0.009). CONCLUSIONS: (i) In equimolar doses, sulfate produced 42% more diarrheal stool weight than phosphate. (ii) Phosphate increased the propensity for calcium salt precipitation in urine at pH 6.4, whereas sulfate did not. (iii) These results suggest that a hypertonic low-volume sulfate solution would be an effective cathartic for colon cleansing and that sulfate-induced catharsis would be less likely than phosphate catharsis to produce calcium salt deposition in renal tubules.

Stimulated active potassium secretion in a patient with colonic pseudo-obstruction: a new mechanism of secretory diarrhea.

BACKGROUND & AIMS: Secretory diarrhea is caused by inhibition of intestinal active sodium absorption and stimulation of active chloride secretion. The resulting increase in fecal sodium salts causes an isotonic increase in fecal water output. Abnormalities in potassium transport are not known to be a cause of secretory diarrhea. The aim of our report is to describe a patient with secretory diarrhea that was mediated by excess intestinal secretion of potassium. METHODS: A 78-year-old woman developed colonic pseudo-obstruction, complicated by severe diarrhea and hypokalemia. Her stools were collected quantitatively on 11 occasions and analyzed for electrolyte concentrations. Rectosigmoid potential difference was measured. RESULTS: The diarrheal fluid had a very high potassium concentration (130-170 mEq/L) and a very low sodium concentration (4-15 mEq/L). Stool potassium losses were as high as 256 mEq/day (normal, 9 mEq/day), and fecal sodium losses were never higher than 13 mEq/day. Potential difference between colonic lumen and a peripheral reference electrode was -14 mV (lumen side negative). CONCLUSIONS: Fecal potassium salts were the exclusive driving force for severe secretory diarrhea in a patient with colonic pseudo-obstruction. The high fecal output of potassium was due to stimulation of active colonic potassium secretion, possibly because of changes in autonomic nervous system activity and distention of the colon in association with colonic pseudo-obstruction. The extremely low fecal excretion of sodium indicates that active sodium absorption was not inhibited. This case study reveals an ion transport mechanism of secretory diarrhea that has not been previously appreciated.

Inhibition of neutral sodium absorption by a prostaglandin analogue in patients with cystic fibrosis.

BACKGROUND & AIMS: In normal intestine, cyclic nucleotides (adenosine 3',5'-cyclic monophosphate [cAMP], guanosine 3',5'-cyclic monophosphate) and Ca(2+) inhibit neutral sodium absorption. In contrast, in the jejunum of a knockout mouse model of cystic fibrosis (CF), agents that elevate intracellular cAMP levels did not inhibit neutral sodium absorption, suggesting that the antiabsorptive effect of cAMP is dependent on the cystic fibrosis transmembrane conductance regulator (CFTR). The aim of the present study was to determine if a prostaglandin E(1) analogue, which causes elevation of intracellular cAMP and Ca(2+) levels, inhibits neutral sodium absorption in patients with CF in vivo. METHODS: Electrolyte and water absorption/secretion was measured during steady state perfusion of the jejunum with a balanced electrolyte solution. Patients with CF and healthy subjects were studied under basal conditions and during intraluminal infusion of a prostaglandin E(1) analogue (misoprostol). RESULTS: The rate of neutral sodium absorption in the basal state was similar in healthy subjects and patients with CF. Prostaglandin infusion markedly reduced neutral sodium absorption in both healthy subjects and patients with CF. Prostaglandin caused high rates of electrolyte and water secretion in healthy subjects but only trivial rates of secretion in patients with CF. CONCLUSIONS: CFTR mutations causing CF in humans do not prevent prostaglandin E(1) inhibition of neutral sodium absorption, even though these mutations produce a severe defect in prostaglandin-stimulated electrolyte secretion. These findings suggest that an intact antiabsorptive response to either cAMP or Ca(2+) may contribute to the relatively low level of intestinal disease in patients with CF.

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.