2/26/2009 Diarrhea Christina Tennyson, M.D. Assistant Professor of Medicine Division of Gastroenterology Columbia University Features to Increase Small DIARRHEA Bowel Surface Area Symptom: stool frequency, liquidity Sign: > 200-250 g/day AtAcute Chron ic Time < 2-4 weeks > 4 weeks Cause infection or drug many Outcome self-limited treat specific disease From Sleisenger and Fordtran 1 2/26/2009 Normal mucosa 2 2/26/2009 CAUSES OF ACUTE DIARRHEA INFECTIOUS MEDICATIONS Watery Bloody (dysentery) laxatives Enterotoxins Invasive Bacteria caffeine DRA (cholera, E coli) (Salmonella, Shigella, metformin Viral E. Coli 0157, Campy) cholinergics (rotavirus, Norwalk) Cytotoxins prostaglandins Parasitic (Shiga, E. Coli, protease inhibitor (giardia, crypto) C. Diff, Anthrax) Antibiotics **Not complete list! Parasitic (E. Histolytica) CAUSES OF CHRONIC DIARRHEA WATERY MALABSORPTIVE INFLAMMATORY •Enterotoxins •Pancreatic •Inflammatory insufficiency bowel disease •Bile acids •Bacterial •Microscopic colitis •Fatty Acids overgrowth •Eosinophilic • Hormones •Mucosal diseases gastroenteritis Mechanisms of Diarrhea • Osmotic (malabsorptive) • Secretory (watery) • Inflammatory • Motility Guanylin ***Overlap exists! Diseases can involve more than one mechanism. 3 2/26/2009 Stool electrolytes Partial atrophy • 290 mOsm/kg- 2(stool K +Na) • <50mOsm/kgÆ SECRETORY – Diarrhea due to other ions present (not-measured) • >100mOsm/kgÆOSMOTIC – Diarrhea due to poorly absorbed substance, electrolytes account for only a small portion of osmotic activity • <290 mOsm/kg Æ Contaminated by adding water to sample OSMOTIC DIARRHEA CAUSES • Ingestion of poorly absorbable solute ++ --- Mg and PO4 containing laxatives, antacids Sorbitol in sugar free candies, gum Fructose containing fruits, soda Lactulose • Acquired lactase deficiency • Malabsorptive diseases mucosal (e.g. celiac disease, tropical sprue) maldigestion (e.g. bacterial overgrowth) Atrophy- celiac disease Characteristics of Osmotic Diarrhea • Low volumes (< 1 liter) • Resolves with fasting • Excess stool osmotic gap > 100 mOsm/kg • Low stool pH (carbohydrate malabsorption) 4 2/26/2009 Vibrio Cholerae Causes of Secretory Diarrhea • Bacterial Enterotoxins (cholera, E. Coli LT,ST) • Hormones and Neurotransmitters ((,VIP, 5-HT,,,, Substance P, calcitonin, acetylcholine) • Inflammation (prostaglandins, leukotrienes, cytokines, histamine) • Bile acids and hydroxylated fatty acids Characteristics of Secretory Diarrhea • Large stool volumes (> 1 Liter/day) • Persists with fasting (also nocturnal) • No WBCs or RBCs in the stool • Absence of fever • No stool osmotic gap CRYPT CELL 5 2/26/2009 Cholera Toxin does not Inhibit the Na/glucose cotransporter TREATMENT OF DIARRHEA ORAL REHYDRATION SOLUTIONS Hormone-secreting Tumors (rare) • Utilize Na/glucose co-transporters Agent Source Cell mediator Mechanism • Requires intact villus epithelium VIP pancreatic tumor cAMP secretion ganglioneuroma • Solution must contain Na and glucose 5HT carcinoid tumor calcium secretion • Solution must be near isosmolar relative (serotonin) (intestine, lung) motility to plasma Gastrin gastrinoma calcium acid secretion Calcitonin medullary CA calcium secretion thyroid 6 2/26/2009 Colectomy specimen following fulminant Clostridium difficile Viral diarrhea Intestinal Inflammation • Rotavirus (infants) Norwalk agent (cruise-ship diarrhea) • Acute inflammation • Invades the intestinal epithelium with select Prostaglandins, leukotrienes, free villus cell damage radicals,,, PAF, histamine and others • MhiMechanism o fdihf diarrhea 1) absorption due to villus damage stimulate active secretion 2) secretion due to • Chronic inflammation activation of the enteric nervous system Cytokines (e.g. IFN-γ, TNF-α) suppress NSP4 rota-toxin both absorption and secretion • Treatment with ORS effective Inflammatory Diarrhea Characteristics of inflammatory • Invasive infections diarrhea: • Damage of intestinal epithelium • Inflammatory Bowel Disease (IBD) • Exudation of protein, blood and pus into intestinal lumen • Cytotoxins • Urgency, frequency, tenesmus with – C. Difficile Toxin recto-sigmoid disease • Bloody or watery stools Ulcerative colitis • Low serum protein and albumin levels 7 2/26/2009 Treatment • Oral rehydration • Clinical evaluation • Stool tests as needed • Antimicrobial therapy if indicated • Anti-diarrheal medication if indicated • Treat underlying disease 8.