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DIARRHEA

DIARRHEA. A pathophysiological Approach to Diagnosis and Treatment Prof. J. Zimmerman Gastroenterology Hadassah-Hebrew University Medical Center. Diarrhea = Increased loss of water from the GI tract. Diarrhea is a common complaint.

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DIARRHEA

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  1. DIARRHEA A pathophysiological Approach to Diagnosis and Treatment Prof. J. Zimmerman Gastroenterology Hadassah-Hebrew University Medical Center

  2. Diarrhea = Increased loss of water from the GI tract

  3. Diarrhea is a common complaint. • In the USA, >3.5 million outpatient visits for diarrhea occur each year.

  4. About 10 liters of fluid pass daily through the GI Tract Volume, ml/day

  5. 6 L absorbed 2.5 L absorbed 10 L 1.4 L absorbed 4 L 1.5 L JEJUNUM ILEUM COLON 0.1 L

  6. Water Absorption in the GI Tract • Water movement in the GI tract is passive and follows osmotic gradients. • The efficiency of water absorption is highest in the colon. • The normal colon can absorb as much as 4-5 L of water daily.

  7. Motility of the Intestine and Colon • Normal motor functions are essential for absorption. • Regulated gastric and ileal emptying facilitate reabsorption of electrolytes and fluid. • Normally, the transit time through the small bowel is about 3 hours.

  8. DEFINITIONS OF DIARRHEA • As a symptom: Abnormal frequency: > 3 bowel movements/day; Abnormal consistency: increased stool fluidity; • As a sign: Stool weight >200 g/day;

  9. “Diarrhea” must be distinguished from: • Hyper defecation: Passage of stool of a normal consistency ≥3 times/day; AND FROM • Incontinence

  10. CLINICAL CLASSIFICATION OF DIARRHEA • BY TIME COURSE (ACUTE vs. CHRONIC); • BY VOLUME (LARGE vs. SMALL); • BY PATHOPHYSIOLOGY (OSMOTIC vs. SECRETORY); • BY STOOL CHARACTERISTICS (WATERY, FATTY or INFLAMMATORY); • BY EPIDEMIOLOGY AND CLINICAL BACKGROUND (TRAVEL, ANTIBIOTICS, etc.);

  11. ACUTE DIARRHEA (< 4 week duration): Most Likely Causes • Infection; • Food poisoning; • Medications; • Initial presentation of chronic diarrhea;

  12. INFECTIONS THAT CAUSE DIARRHEA • Bacteria • Shigella, salmonella, campylobacter jejuni, C. difficile; E. coli, vibrio, aeromonas, yersinia • Viruses • Rotavirus, adenovirus, norovirus • Parasites/protozoa • Giardia, E. histolytica, cryptosporidium, microsporidia, cyclospora.

  13. MEDICATIONS THAT CAUSE DIARRHEA (1) • Acid reducing agents (PPI, H2 blockers) • Antacids • Antiarrhythmic (quinidine) • Antibiotics • Anti-inflammatory (NSAIDs) • Antihypertensives ( -blockers)

  14. MEDICATIONS THAT CAUSE DIARRHEA (2) • Antineoplastic agents • Antiretroviral agents • Colchicine • Heavy metals • Prostaglanding analogs (misoprostol)

  15. Workup of Diarrhea:Obey Sutton’s Law Willie Sutton 1901-1980

  16. Stool Examination in Diarrhea • Microscopy (WBC, RBC, parasites); • Cultures; • C. difficile toxin (when appropriate); • Giardia antigen (if appropriate); • IN CHRONIC DIARRHEA: • Occult blood; • Fecal fat; • Stool [Na+] and [K+]; • pH (if < 6 indicates CHO malabsorption) ; • Laxative screen;

  17. Diagnostic Importance of Fecal WBC Abundant WBCNo or few WBC Infections: dysentery viral C. difficile, ameba food poisoning IBD medications Ischemia laxative abuse Irradiation steatorrhea

  18. CHRONIC DIARRHEA WATERY FATTY INFLAMMATORY

  19. CHRONIC WATERY DIARRHEA • Osmotic • Secretory

  20. Water Transport in the GI Tract • The intestinal epithelium cannot maintain an osmotic gradient. • The luminal content from the duodenum to the rectum is iso-osmotic (about 290 mOsmol/kg) .

  21. OSMOTIC DIARRHEA Caused by the presence of unusual amount of poorly absorbable, osmotically active solute in the lumen

  22. Causes of Osmotic Diarrhea • Disaccharidase deficiency; • Monosaccharide malabsorption (fructose-corn syrup in soft drinks); • Ingestion of nonabsorbable materials CHO: sorbitol, lactulose, mannitol Minerals: MgSO4, Na2SO4, Na citrate, antacids • Generalized malabsorption

  23. SECRETORY DIARRHEA Intestinal ion secretion or inhibition of normal active ion absorption

  24. Causes of Secretory Diarrhea • Enterotoxins (cholera, E. coli); • Secretagogues elaborated by tumors (VIP, calcitonin); • Laxatives (ricinoleic acid, phenol-phthalein, oxyphenisatin, aloe, senna); • Bile acids/ FFA (in the colon); • Congenital defects;

  25. Differentiation between Osmotic and Secretory Diarrhea • Effect of fasting; • Volume; • Stool electrolytes and osmotic gap;

  26. CHARACTERISTICS OF OSMOTIC AND SECRETORY DIARRHEA OSMOTICSECRETORY • Volume, L/day: <1 >1 • Fasting (48 hrs): stops continues

  27. Calculation of Stool Osmotic Gap • The osmolarity of fecal fluid as it exits the rectum is close to that of plasma, i.e. 290 mOsmol/Kg. • The osmolarity of fecal fluid can be estimated from the ion concentrations: ([Na+] + [K+]) x 2 • An osmotic gap is the difference between this value and 290. A gap of up to 50 is normal.

  28. OSMOTIC AND SECRETORY DIARRHEA:FECAL FLUID ANALYSIS OSMOTICSECRETORY • [Na+], meq/L 30 100 • [K+], meq/L 30 40 • [Na+]+[K+] 60 140 • 2x([Na+]+[K+]) 120 280 • Solute gap 170 10

  29. 300 250 200 OSMOLALITY, mOsmol/Kg X Anions 150 K Na 100 50 0 Secretory Osmotic

  30. Osmotic and Secretory Diarrhea • In secretory diarrhea, calculated stool osmolarity is close to 290. The osmotic gap is <50. • In osmotic diarrhea, the stool osmolarity, as estimated from the fecal ion concentrations, is lower by more than 50 from a value of 290.

  31. ABNORMAL MOTILITY AND DIARRHEA • BOTH A RAPID AND A SLOW TRANSIT TIME MAY CAUSE DIARRHEA. • A RAPID TRANSIT TIME PREVENTS ADEQUATE TIME FOR ABSORPTION (INTESTINAL HURRY). • THE MECHANISM INVOLVES DYSFUNCTION OF THE ENTERIC NERVOUS SYSTEM. • EXAMPLES: DIABETES, POST- VAGOTOMY, AMYLOIDOSIS, IBS.

  32. ABNORMAL MOTILITY AND DIARRHEA (2) • SLOW TRANSIT TIME PROMOTES BACTERIAL OVERGROWTH AND MAY CAUSE MALABSORPTION AND DIARRHEA.

  33. COMPLEX DIARRHEA • Many of the clinically significant diarrheas are complex and have both osmotic and secretory components.

  34. Chronic Diarrhea ( >4 weeks’ duration): Most Likely Causes • Lactase deficiency; • IBS; • IBD; • Infections, mainly parasitic; • Medications and food supplements; • Previous surgery; • Endocrine: DM, hyperthyroidism, Addison’s disease;

  35. Diarrhea Evaluation (1) • Dietary history: Intake of lactose, sorbitol, fructose, caffeine; • Medications: antacids, antibiotics, quinidine, colchicine, Fe, etc. • Abdominal pain; • Tenesmus, rectal bleeding, mucus; • Intermittent diarrhea and constipation; • Nocturnal diarrhea; • Exposure to infectious agents (travel, sexual preferences);

  36. Diarrhea Evaluation (2) • Past surgical procedures (vagotomy, gastrectomy, cholecystectomy, others); • Desire to reduce weight; • Family history (cancer, IBD, celiac);

  37. Clues to diagnosis-Additional Symptoms SxDx • Fever infection, IBD, TB, Ly • Weight loss malabsorption, cancer, thyrotoxicosis • Flushing Carcinoid

  38. Clues to diagnosis-Associated Diseases DISEASEDx • Liver disease IBD, cancer • Chr. Lung disease CF • Peptic ulcer ZE syndrome • Frequent infections Ig deficiency

  39. Clues to diagnosis-Physical Findings FindingSuggested Dx • Arthritis IBD, infection, Whipple’s disease • Lymphadenopathy Ly, AIDS, Whipple • Neuropathy DM, amyloid • Postural hypotension DM, Addison

  40. Diarrhea EvaluationPhysical Examination SEVERITY CAUSE HYPOVOLEMIA? FEVER? ABDOMINAL FINDINGS?

  41. Diarrhea EvaluationPhysical Examination SEVERITY CAUSE • Clubbing; • Abdominal mass or • tenderness; • Perianal disease; • Rectal examination

  42. Chronic Diarrhea Exclude medications and surgery Blood Features Pain No blood; p.r. Suggest relieved features of malabsorption with BM malabsorption Colonoscopy small bowel Bx ?IBS ?CHO malabsor + Bx etc. Screen lactose BT

  43. REFERENCE • Sleisenger and Fordtran’s Gastrointestinal and liver disease. Chapter on diarrhea contains many useful tables of DD’s of diarrhea in different clinical settings.

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