Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1989 Oct;84(4):1056–1062. doi: 10.1172/JCI114267

Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose.

H F Hammer 1, C A Santa Ana 1, L R Schiller 1, J S Fordtran 1
PMCID: PMC329760  PMID: 2794043

Abstract

The purpose of these studies was to gain insight into the pathophysiology of pure osmotic diarrhea and the osmotic diarrhea caused by carbohydrate malabsorption. Diarrhea was induced in normal volunteers by ingestion of polyethylene glycol (PEG), which is nonabsorbable, not metabolized by colonic bacteria, and carries no electrical charge. In PEG-induced diarrhea, (a) stool weight was directly correlated with the total mass of PEG ingested; (b) PEG contributed 40-60% of the osmolality of the fecal fluid, the remainder being contributed by other solutes either of dietary, endogenous, or bacterial origin; and (c) fecal sodium, potassium, and chloride were avidly conserved by the intestine, in spite of stool water losses exceeding 1,200 g/d. Diarrhea was also induced in normal subjects by ingestion of lactulose, a disaccharide that is not absorbed by the small intestine but is metabolized by colonic bacteria. In lactulose-induced diarrhea, (a) a maximum of approximate 80 g/d of lactulose was metabolized by colonic bacteria to noncarbohydrate moieties such as organic acids; (b) the organic acids were partially absorbed in the colon; (c) unabsorbed organic acids obligated the accumulation of inorganic cations (Na greater than Ca greater than K greater than Mg) in the diarrheal fluid; (d) diarrhea associated with low doses of lactulose was mainly due to unabsorbed organic acids and associated cations, whereas with larger doses of lactulose unmetabolized carbohydrates also played a major role; and (e) the net effect of bacterial metabolism of lactulose and partial absorption of organic acids on stool water output was done dependent. With low or moderate doses of lactulose, stool water losses were reduced by as much as 600 g/d (compared with equimolar osmotic loads of PEG); with large dose, the increment in osmotically active solutes within the lumen exceeded the increment of the ingested osmotic load, and the severity of diarrhea was augmented.

Full text

PDF
1056

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ameen V. Z., Powell G. K. A simple spectrophotometric method for quantitative fecal carbohydrate measurement. Clin Chim Acta. 1985 Oct 31;152(1-2):3–9. doi: 10.1016/0009-8981(85)90169-x. [DOI] [PubMed] [Google Scholar]
  2. Andersson D. E., Nygren A. Four cases of long-standing diarrhoea and colic pains cured by fructose-free diet--a pathogenetic discussion. Acta Med Scand. 1978;203(1-2):87–92. doi: 10.1111/j.0954-6820.1978.tb14836.x. [DOI] [PubMed] [Google Scholar]
  3. Bo-Linn G. W., Santa Ana C. A., Morawski S. G., Fordtran J. S. Starch blockers--their effect on calorie absorption from a high-starch meal. N Engl J Med. 1982 Dec 2;307(23):1413–1416. doi: 10.1056/NEJM198212023072301. [DOI] [PubMed] [Google Scholar]
  4. Brady C. E., 3rd, DiPalma J. A., Morawski S. G., Santa Ana C. A., Fordtran J. S. Urinary excretion of polyethylene glycol 3350 and sulfate after gut lavage with a polyethylene glycol electrolyte lavage solution. Gastroenterology. 1986 Jun;90(6):1914–1918. doi: 10.1016/0016-5085(86)90261-1. [DOI] [PubMed] [Google Scholar]
  5. CHANEY A. L., MARBACH E. P. Modified reagents for determination of urea and ammonia. Clin Chem. 1962 Apr;8:130–132. [PubMed] [Google Scholar]
  6. Charney E. B., Bodurtha J. N. Brief clinical and laboratory observations. J Pediatr. 1981 Jan;98(1):157–158. doi: 10.1016/s0022-3476(81)80563-x. [DOI] [PubMed] [Google Scholar]
  7. Collin D. P., McCormick P. G. Determination of short-chain fatty acids in stool ultrafiltrate and urine. Clin Chem. 1974 Sep;20(9):1173–1180. [PubMed] [Google Scholar]
  8. Conn H. O., Leevy C. M., Vlahcevic Z. R., Rodgers J. B., Maddrey W. C., Seeff L., Levy L. L. Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology. 1977 Apr;72(4 Pt 1):573–583. [PubMed] [Google Scholar]
  9. Davis G. R., Santa Ana C. A., Morawski S. G., Fordtran J. S. Development of a lavage solution associated with minimal water and electrolyte absorption or secretion. Gastroenterology. 1980 May;78(5 Pt 1):991–995. [PubMed] [Google Scholar]
  10. FLINN R. B., MERRILL J. P., WELZANT W. R. Treatment of the oliguric patient with a new sodium-exchange resin and sorbitol; a preliminary report. N Engl J Med. 1961 Jan 19;264:111–115. doi: 10.1056/NEJM196101192640302. [DOI] [PubMed] [Google Scholar]
  11. Florent C., Flourie B., Leblond A., Rautureau M., Bernier J. J., Rambaud J. C. Influence of chronic lactulose ingestion on the colonic metabolism of lactulose in man (an in vivo study). J Clin Invest. 1985 Feb;75(2):608–613. doi: 10.1172/JCI111738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Flourie B., Florent C., Jouany J. P., Thivend P., Etanchaud F., Rambaud J. C. Colonic metabolism of wheat starch in healthy humans. Effects on fecal outputs and clinical symptoms. Gastroenterology. 1986 Jan;90(1):111–119. doi: 10.1016/0016-5085(86)90082-x. [DOI] [PubMed] [Google Scholar]
  13. Giller J., Phillips S. F. Electrolyte absorption and secretion in the human colon. Am J Dig Dis. 1972 Nov;17(11):1003–1011. doi: 10.1007/BF02239140. [DOI] [PubMed] [Google Scholar]
  14. Goldberg L. D., Ditchek N. T. Chewing gum diarrhea. Am J Dig Dis. 1978 Jun;23(6):568–568. doi: 10.1007/BF01072704. [DOI] [PubMed] [Google Scholar]
  15. Goy J. A., Eastwood M. A., Mitchell W. D., Pritchard J. L., Smith A. N. Fecal characteristics contrasted in the irritable bowel syndrome and diverticular disease. Am J Clin Nutr. 1976 Dec;29(12):1480–1484. doi: 10.1093/ajcn/29.12.1480. [DOI] [PubMed] [Google Scholar]
  16. Gryboski J. D. Diarrhea from dietetic candies. N Engl J Med. 1966 Sep 29;275(13):718–718. doi: 10.1056/NEJM196609292751309. [DOI] [PubMed] [Google Scholar]
  17. Hickey C. A., Calloway D. H., Murphy E. L. Intestinal gas production following ingestion of fruits and fruit juices. Am J Dig Dis. 1972 May;17(5):383–389. doi: 10.1007/BF02231287. [DOI] [PubMed] [Google Scholar]
  18. Krejs G. J., Walsh J. H., Morawski S. G., Fordtran J. S. Intractable diarrhea. Intestinal perfusion studies and plasma VIP concentrations in patients with pancreatic cholera syndrome and surreptitious ingestion of laxatives and diuretics. Am J Dig Dis. 1977 Apr;22(4):280–292. doi: 10.1007/BF01072184. [DOI] [PubMed] [Google Scholar]
  19. Livesey G., Elia M. Estimation of energy expenditure, net carbohydrate utilization, and net fat oxidation and synthesis by indirect calorimetry: evaluation of errors with special reference to the detailed composition of fuels. Am J Clin Nutr. 1988 Apr;47(4):608–628. doi: 10.1093/ajcn/47.4.608. [DOI] [PubMed] [Google Scholar]
  20. Menzies I. S., Laker M. F., Pounder R., Bull J., Heyer S., Wheeler P. G., Creamer B. Abnormal intestinal permeability to sugars in villous atrophy. Lancet. 1979 Nov 24;2(8152):1107–1109. doi: 10.1016/s0140-6736(79)92507-8. [DOI] [PubMed] [Google Scholar]
  21. Miller T. L., Wolin M. J. Fermentations by saccharolytic intestinal bacteria. Am J Clin Nutr. 1979 Jan;32(1):164–172. doi: 10.1093/ajcn/32.1.164. [DOI] [PubMed] [Google Scholar]
  22. Ruppin H., Bar-Meir S., Soergel K. H., Wood C. M., Schmitt M. G., Jr Absorption of short-chain fatty acids by the colon. Gastroenterology. 1980 Jun;78(6):1500–1507. [PubMed] [Google Scholar]
  23. Saunders D. R., Wiggins H. S. Conservation of mannitol, lactulose, and raffinose by the human colon. Am J Physiol. 1981 Nov;241(5):G397–G402. doi: 10.1152/ajpgi.1981.241.5.G397. [DOI] [PubMed] [Google Scholar]
  24. Schiller L. R., Emmett M., Santa Ana C. A., Fordtran J. S. Osmotic effects of polyethylene glycol. Gastroenterology. 1988 Apr;94(4):933–941. doi: 10.1016/0016-5085(88)90550-1. [DOI] [PubMed] [Google Scholar]
  25. Schmulen A. C., Lerman M., Pak C. Y., Zerwekh J., Morawski S., Fordtran J. S., Vergne-Marini P. Effect of 1,25-(OH)2D3 on jejunal absorption of magnesium in patients with chronic renal disease. Am J Physiol. 1980 Apr;238(4):G349–G352. doi: 10.1152/ajpgi.1980.238.4.G349. [DOI] [PubMed] [Google Scholar]
  26. Sheikh M. S., Maguire J. A., Emmett M., Santa Ana C. A., Nicar M. J., Schiller L. R., Fordtran J. S. Reduction of dietary phosphorus absorption by phosphorus binders. A theoretical, in vitro, and in vivo study. J Clin Invest. 1989 Jan;83(1):66–73. doi: 10.1172/JCI113886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Vince A., Killingley M., Wrong O. M. Effect of lactulose on ammonia production in a fecal incubation system. Gastroenterology. 1978 Mar;74(3):544–549. [PubMed] [Google Scholar]
  28. WEIJERS H. A., VAN DE KAMER J. H. Aetiology and diagnosis of fermentative diarrhoeas. Acta Paediatr. 1963 Jul;52:329–337. doi: 10.1111/j.1651-2227.1963.tb03788.x. [DOI] [PubMed] [Google Scholar]
  29. Yajima T. Contractile effect of short-chain fatty acids on the isolated colon of the rat. J Physiol. 1985 Nov;368:667–678. doi: 10.1113/jphysiol.1985.sp015882. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES