2/26/2009. Diarrhea. Christina Tennyson, M.D. Assistant Professor of Medicine Division of Gastroenterology Columbia University
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1 Diarrhea Christina Tennyson, M.D. Assistant Professor of Medicine Division of Gastroenterology Columbia University 1
2 Symptom: Sign: DIARRHEA stool frequency, liquidity > g/day Acute Chronic Time < 2-4 weeks > 4 weeks Cause infection or drug many Outcome self-limited treat specific disease 2
3 Features to Increase Small Bowel Surface Area From Sleisenger and Fordtran 3
4 4
5 Normal mucosa 5
6 6
7 DRA 7
8 Guanylin CAUSES OF ACUTE DIARRHEA INFECTIOUS MEDICATIONS Watery Bloody (dysentery) laxatives Enterotoxins Invasive Bacteria caffeine (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) 8
9 CAUSES OF CHRONIC DIARRHEA WATERY Enterotoxins Bile acids Fatty Acids Hormones MALABSORPTIVE Pancreatic insufficiency Bacterial overgrowth Mucosal diseases INFLAMMATORY Inflammatory bowel disease Microscopic colitis Eosinophilic gastroenteritis Mechanisms of Diarrhea Osmotic (malabsorptive) Secretory (watery) Inflammatory Motility ***Overlap exists! Diseases can involve more than one mechanism. 9
10 Stool electrolytes 290 mosm/kg- 2(stool K +Na) <50mOsm/kg SECRETORY Diarrhea due to other ions present (not-measured) >100mOsm/kg OSMOTIC Diarrhea due to poorly absorbed substance, electrolytes account for only a small portion of osmotic activity <290 mosm/kg Contaminated by adding water to sample OSMOTIC DIARRHEA CAUSES Ingestion of poorly absorbable solute Mg ++ and PO 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) 10
11 Atrophy- celiac disease Partial atrophy 11
12 Characteristics of Osmotic Diarrhea Low volumes (< 1 liter) Resolves with fasting Excess stool osmotic gap > 100 mosm/kg Low stool ph (carbohydrate malabsorption) 12
13 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 13
14 Vibrio Cholerae 14
15 CRYPT CELL 15
16 Cholera Toxin does not Inhibit the Na/glucose cotransporter 16
17 TREATMENT OF DIARRHEA ORAL REHYDRATION SOLUTIONS Utilize Na/glucose co-transporters Requires intact villus epithelium Solution must contain Na and glucose Solution must be near isosmolar relative to plasma 17
18 Hormone-secreting Tumors (rare) Agent Source Cell mediator Mechanism VIP pancreatic tumor camp secretion ganglioneuroma 5HT carcinoid tumor calcium secretion (serotonin) (intestine, lung) motility Gastrin gastrinoma calcium li acid secretion Calcitonin medullary CA calcium secretion thyroid 18
19 Viral diarrhea Rotavirus (infants) Norwalk agent (cruise-shipship diarrhea) Invades the intestinal epithelium with select villus cell damage Mechanism of diarrhea 1) absorption due to villus damage 2) secretion due to activation of the enteric nervous system NSP4 rota-toxin Treatment with ORS effective 19
20 Invasive infections Inflammatory Diarrhea Inflammatory Bowel Disease (IBD) Cytotoxins C. Difficile Toxin Ulcerative colitis Colectomy specimen following fulminant Clostridium difficile 20
21 Intestinal Inflammation Acute inflammation Prostaglandins, leukotrienes, free radicals, PAF, histamine and others stimulate active secretion Chronic inflammation Cytokines (e.g. IFN-γ, TNF-α) suppress both absorption and secretion Characteristics of inflammatory diarrhea: Damage of intestinal epithelium Exudation of protein, blood and pus into intestinal lumen Urgency, frequency, tenesmus with recto-sigmoid sg oddsease disease Bloody or watery stools Low serum protein and albumin levels 21
22 Treatment Oral rehydration Clinical evaluation Stool tests as needed Antimicrobial therapy if indicated Anti-diarrheal medication if indicated Treat underlying disease 22
Christina Tennyson, M.D. Division of Gastroenterology
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DR. PHILIP K. BLUSTEIN M.D. F.R.C.P.(C) 415 14 TH ST. NW. CALGARY AB T2N2A1 PHONE (403) 270-9555 FAX (403) 270-7479 CHRONIC DIARRHEA DEFINITION: *LOOSE, WATERY STOOLS *MORE THAN 3 TIMES A DAY *FOR MORE