Evaluation of Acute and Chronic Diarrhea July 23, 2009 Phillip D. Smith, M.D. Division of Gastroenterology
Diarrhea ___ • Definition and Impact • Classification • Clinical Clues to the Etiology • Evaluation of Acute and Chronic Diarrhea • Cases
Definition ___ • Symptomatic definition: Increased frequency, fluidity or volume, or a combination of these • Physiologic definition: Increased absorption or decreased secretion, or usually both, causing > 200 mL liquid excretion per day
Input Absorption Diet/Saliva : 3 L/d Stomach : 2 L Jejunum : 5 L/d Bile : 1 L Pancreas : 2 L Ileum : 2-3 L Bowel : 1 L Colon : 1-2 L Total 9 L Total 8.8 L Fecal Water 100-200 mL/d Thus, diarrhea is defined as >200 mL liquid excretion per day. In extremus, the gastrointestinal tract can both absorb and secrete 20 L of water per day.
Causes of Death Worldwide Pneumonia 8.5% Diarrhea 5.8% TB 3.9% Measles 2.1% Malaria • Infections – 24.4% 1.7% Tetanus 1.1% • Ischemic Heart Disease – 12.5% Pertussis 0.7% HIV 0.6% 0 2 4 6 8 Percent Lancet 1997;349:1269
Acute Infectious Diarrhea ___ • 2 million deaths/yr worldwide • 6,000 deaths/yr in U.S. • 900,000 hospitalizations
Chronic Diarrhea ___ • 1% of U.S. population • $524 million in evaluation costs and $136 million in indirect costs
Classification ___ 1) Acute vs Chronic 2) Infectious vs Non-infectious 3) Osmotic vs Secretory 4) Inflammatory vs Non-inflammatory 5) Large intestine vs Small intestine 6) Drugs
Clinical Clues: 2) Infectious vs Non-infectious ___ • Infectious – Fever, blood, pus, epidemic, travel (bacterial in visited country and parasitic after return) • Less likely infectious – Afebrile, non-bloody, non-mucoid, sporadic, no travel
Isolation Rate (%) of Infectious Pathogens During US Military Deployments ___ Etiology Egypt Thailand South America ___ ETEC 57% 6% 42% Shigella 4 4 5 Campylobacter 0 39 13 Salmonella 2 18 9 ___National Foundation for Infectious Diseases, Special Rept., 2003
Clinical Clues: 3) Osmotic vs Secretory ___ • Osmotic – Diarrhea ceases with fasting Secretory – Diarrhea continues with fasting • Mechanism – Lumenal contents are in osmotic equilibrium at 290 mOsm/kg with other body fluids. Thus, the osmotic gap 290-2([Na] + [K]) is the amount of solutes other than Na and K in stool water.
• Osmotic – Osmotic gap > 50 mOsm/kg Secretory – Osmotic gap < 50 mOsm/kg • Osmotic – Only CHO malabsorption will cause pH <5.6. For other osmotic (and secretory) diarrheas pH >5.6.
Clinical Clues: 4) Inflammatory vs Non-inflammatory ___ • Inflammatory – Frequent, blood, pus, fever, abdominal pain, tenesmus, fecal leukocytes • Non-inflammatory – Watery stool, without blood/pus/fever/fecal leukocytes
Fecal WBCs No Fecal WBCs C. difficile colitis Giardiasis Crohn’s, Ulcerative colitis Amebiasis Shigellosis Viral enteritis Salmonellosis Toxigenic E. coli Typhoid fever (S. typhi) Salmonella carrier Invasive E. coli V. parahemolyticus Y. enterocolitica Microscopic colitis V. parahemolyticus Drug-induced diarrhea
Sensitivity of Fecal Leukocytes for Invasive Enteric Infection Patients with Patients withOrganism Positive Culture Fecal Leukocytes Campylobacter jejuni 1456 49.1%Salmonella 9540 42.1%Escherichia coli (0157:H7) 8153 65.4%Shigella 3626 72.2%Yersinia enterocolitica 2713 48.1%
Clinical Clues: 5) Large Intestine vs Small Intestine ___ • Large intestine – Frequent urges, mushy/ dark colored/rarely foul, left lower quadrant pain, tenesmus, small volume • Small intestine – Watery/light colored/foul, periumbilical/RLQ pain, large volume
Small Volume (< 400 ml) Rectal and sigmoid disease – UC, ulcerative proctitis Large Volume (> 400 ml) Osmotic – Lactase deficiency, laxatives, sprueSecretory – Cholera, ETEC, laxatives, BA malabsorp.*Dysmotility – Post-gastrectomy syndrome, carcinoid, laxatives Altered permeability – Sprue *Ileal resection, Crohn’s dis., J-I bypass, radiation
Clinical Clues: 6) Drug-Induced Diarrhea ___ • Any drug – Temporal relation to the diarrhea • Especially antibiotics
Other Clinical Clues I ___ • Nocturnal diarrhea – Organic, not irritable bowel syn. • Previous surgery – Small intestinal disruption – Bacterial overgrowth Removal >100 cm terminal ileum – Cholorretic diarrheaCholecystectomy – Cholorretic diarrhea Gastrectomy – Dumping syndrome • Debilitated patient – C. albicans (yeast, not hyphae) • Day care – Giardia, Cryptosporidium, Shigella
Small Intestinal Disruption Induces Diarrhea by Several Mechanisms ___ • Bacterial overgrowth → deconjuged bile salts → steatorrhea → osmotic diarrhea • Spill BA and hydroxylated FFA into colon → stimulation of adenyl cyclase → colonic secretion • Reduced absorptive area • Reduced transit time
Other Clinical Clues II ___ • Traveler’s diarrhea – Enterotoxigenic E. coli, Salmonella, Shigella and Campylobacter • Reactive arthritis – Salmonella, Shigella, Campylobacter,Yersinia and C. difficile • V/N ±D <7 h eating – Preformed toxin: S. aureus, B. cereus and Anisakis (emetic syndrome) • D 8-14 h > eating – Toxins formed in GI tract: C. perfrin-gens, B. cereus (diarrhea syndrome)
Other Clinical Clues III ___ • Hypogammaglobulinemia – Giardia (not IgA def.) • Hemolytic uremic syn. – E. coli 0157:H7, S. typhi, C. jejuni and S. dysenteriae • Eosinophilia – Parasites (except protozoa), eosinophilic gastroenteritis, collagen-vascular diseaseand neoplasia • Hypokalemia – Villus adenoma and VIPoma (WDHA)
Other Clinical Clues IV ___ • LLQ pain – Ulcerative colitis and irritable bowel syndrome • RLQ pain – Crohn’s disease and Yersinia • Peritoneal signs – C. difficile and E. coli 0157:H7 • Leukopenia – No pseudomembranes in C. difficile colitis
Evaluation: Acute Diarrhea ___ Acute Non-Bloody Diarrhea – Most resolve– Most are viral– Most have no complications– Most do not need evaluation Acute Bloody Diarrhea – Stool culture – Flexible sigmoidoscopy
Acute Non-bloody Acute Bloody • Low fever, mild pain • High fever, severe pain • ETEC, Giardia, Crypto, • Salmonella, Shigella, Campylobacter, E. coli C. difficile, V. cholera, 0157:H7, Yersinia norovirus, rotavirus • • IBD, vascular, ischemic Contaminated food, water or person • Nearly any drug
Evaluation: Who to Workup ___ • Acute diarrhea: Since most acute diarrheas resolve within 24 hr, evaluate patient when dehydrated, febrile or blood or pus in stool • Chronic diarrhea: Evaluate when > 2 weeks
Evaluation: Chronic Diarrhea ___ _ Step 1 History: Prior surgery, travel, city vs well water Stool: WBCs, IF for Giardia/Crypto, Sudan stain for fat, C. difficile toxin if risk factor; Stool cultures NOT indicated Blood: Eosinophil count, K+, carotene, TSH and T4, anti-endomysial and -transglutaminase Abs Endoscopy: Flexible sigmoid. for microscopic colitis
Evaluation: Chronic Diarrhea ___ Step 2 Blood: Gastrin, VIP, calcitonin (ZE, VIPoma, MCT) Stool: Microscopic examination for other parasites, if indicated Colonoscopy: IBD, lymphoma SBFT: Crohn’s disease Other: 24 hr fast
Evaluation: Chronic Diarrhea ___ Step 3 Hydrogen Breath Test: Bacterial overgrowth UGI Endoscopy: Biopsy for sprue Urine: 5-HIAA (carcinoid) and cats/VMA (pheo) Stool: pH and electrolytes Serum: Immunoglobulins Hospitalization: Fasting, 72 hr stool fat
• When Diarrhea 200-800 g/d → 20% may have > 6.4 g fat/d • When Diarrhea > 800 g/d → 60% may have 8-14 g fat/d Thus, diarrhea itself can induce fat malabsorption
• College student goes to Mexico for summer vacation. Develops acute, watery, non-inflammatory (no WBCs, blood, fever) diarrhea.
• Embassy official in Peru enjoys ceviche at a state dinner, but he does not enjoy the acute abd. pain, profuse watery diarrhea (20/day), which develops 2 days later. No fever or blood. Several others ill.
• A 44 yr old woman who runs her own bakery presents with 4 yr hx 5-8 watery move-ments/day (and night). Only medical problem is tennis elbow. Flexible sigmoidoscopy shows normal mucosa.
Match the Clinical Condition with the Stool Analysis ___ A B C D E 1. MgOH ingestion Osm 290 360 100 300 310 (mosm/kg) 2. Secretory diarrhea [Na] 100 50 10 10 20 3. CHO malabsorption (mmol/L) 4. Ingestion of polyethy- [K] 40 20 5 10 10 lene glycol solution (mmol/L) 5. Contamination of stool pH 7.1 5.0 6.5 7.0 8.0 by water or urine
• An American trekker in Nepal develops acute abd. pain, bloating, gas, foul-smelling diarrhea. No blood, fever. He does not respond to quin-olones and loses 10 lbs.
• Companion of the trekker in Nepal develops acute abd cramps, non-inflammatory diarrhea without gas or bloating. He does not respond to quinolones or to metronidazole.
• A 27 yr old med/ped resident on the GI Consult service is admitted to the hospital 3 hr after rounds with vomiting (50xs) followed by abd pain and diarrhea, resulting in dehydration. Her roommate was well, but a baby she had held at church had had a diarrheal illness a week earlier. The resident’s stool was culture negative for pathogenic enteric bacteria.
• A 45 yr old bus driver presented with 10 weeks of watery diarrhea (8-12 movements/day) but infrequently at night. He also had abdominal pain and had lost 40 lbs.
• Traveler to rural Mexico for 2 wks develops acute abd. pain, fever, grossly bloody diarrhea.
• Physician traveler, anxious about travelers’ diarrhea, takes amoxacillin while on CME boondoggle in Tahiti. Develops acute watery diarrhea, mild fever, heme positive.
• A 50 yr old woman shot in R lower abdomen 5 yrs earlier knows location of every public rest-room in the city due to the watery diarrhea she developed after bullet removed. Cured with cholestyramine.
• HIV-1-infected patient (CD4 = 210) develops acute watery diarrhea two days after returning from Mexico, where he ate large amounts of raspberries. Stool cultures negative, no fecal WBCs. Diarrhea persists despite empiric quinolones, HIV then metronidazole.
• Embassy official returning to U.S. arrives in Seattle, kisses ground, and, craving real American food, takes family to Jack-in-the-Box. Four days later, he develops abd. pain and grossly bloody diarrhea without fever.
• A woman runner with prolonged watery diarrhea presents to the ER with her second episode of hypotension and hypokalemia. Stool microbiologic analysis is negative. Flex. sig. shows a normal left colon.
Summary ___ • Explanation for the diarrhea in most patients • Logical approach will usually yield diagnosis • Failure to identify etiology – Faulty logic– Limitation (sensitivity) of diagnostic test– Yet to be identified pathogen
Summary II ___ Although the gastrointestinal tract is a complex organ and the largest reservoir of macrophages and lymphocytes in the body, its immuno-biology can be understood.