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Diarrhea

Donald P. Kotler, MDChief, GI Division

St. Luke’s-Roosevelt Hospital Center

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Intestinal mucosa• Large surface area• Stable ionic microenvironment• Epithelial cell turnover• Epithelial cell maturation• Structural and functional adaptations• Epithelial cell polarity

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Pathophysiology of diarrhea• Osmotic

– decreased surface area– unabsorbable solute

• Secretory– nutrient– toxin– other mediator

• Mixed mechanisms

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Pathogenic mechanisms

• Decreased mucosal surface area• Ileal dysfunction• Exudative enteropathy• Inflammatory or tumor-associated

secretagogues• Altered motility

– Slow transit/bacterial overgrowth– Rapid transit

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Consequences of intestinal resection

RapidNormalTransit

DecreasedNormalAdaptation

DecreasedNormalB12, bile saltabsorption

NormalNormal (if <75%)Total nutrientabsorption

IIeal resectionJejunal resection

Normal mucosa

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Partial villus atrophy

Cryptosporidiosis

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Cryptosporidiosis

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Celiac disease

Viruses associated with gastroenteritis

• Rotaviruses• Adenoviruses• Caliciviruses• Norwalk like viruses or SRSV (Small Round

Structured Viruses)• Astroviruses• SRV (Small Round Viruses)• Coronaviruses• Toroviruses

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Crohn’s ileitis

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Diarrhea and ileal resection

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Mycobacterium avium

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Mycobacterium avium

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Cytomegalovirus colitisUlcerative colitis

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Serum creatinine concentration

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9-O

ct

10-O

ct

11-O

ct

12-O

ct

13-O

ct

16-O

ct

17-O

ct

19-O

ct

20-O

ct

24-O

ct

26-O

ct

29-O

ct

30-O

ct

1-N

ov

3-N

ov

190 lb 202 lbWeight

60 liters of IV fluid

220 lb

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Practice guidelines for themanagement of infectious diarrhea

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Guidelines - why?

• Response to need for cost effectiveapproach to diagnosis and management

• Evidence-based approach– Identify uncertainties– Grades the quality of the evidence as much as

the evidence itself• Work in progress: needs periodic revision

Guidelines

• A - Good evidence torecommend

• B - Fair evidence torecommend

• C - Poor evidence torecommend for or against

• D - Fair evidence torecommend against

• E - Good evidence torecommend against

• I - At least 1 RCT• II - At least 1 well-

designed trial– not RCT– cohort, case control,

dramatic uncontrolledstudies

• III - Expert opinion

Strength Quality

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Diarrhea: magnitude of the problem• Second leading cause of morbidity and mortality

worldwide• >200 million cases of diarrhea per year in the US• 73 million physician consultations, 1.8 million

hospitalizations, 3,100 deaths (mostly in the elderly)• Other morbidities: HUS, Guillain-Barre, malnutrition• Etiology hardly ever determined• Etiologic diagnosis usually is too late to be of clinical

use in outpatients• Often untreated, even if diagnosis is made• The large majority of cases are self-limited in

otherwise healthy children and adults

The conflict

Cost containment

Widening array of enteric pathogens:enterohemorrhagic E coli, Salmonella,Shigella, Cyclospora, Cryptosporidium,Giardia, Campylobacter jejuni,Clostridium difficile, microsporidia,caliciviruses, other enteric viruses

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Etiologic diagnosis: who cares?

• Public health: passive surveillance forcommon source outbreaks or seriouspathogens

• Bioterrorism• Vulnerable populations

– Extremes of life– Malnourished– Immune deficient

Other considerations• Regional and seasonal variation in the US• Globalization• Infections promoted by crowding and

uncertain hygeine– Child care– Schools– Cruise ships

• Decreased recovery with immune deficiency:HIV, immune suppressed, post-transplant,aging

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Guidelines• Oral rehydration• Clinical and epidemiological evaluation• Stool tests• Antimicrobial therapy• Antidiarrheals• Available immunizations

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Clinical recommendations• Initial rehydration: ORS A-I

– available commercially– 3.5 gm NaCl, 2.5 gm NaHCO3, 1.5 gm KCl , and

20 gm glucose or glucose polymer per liter ofwater

– glucose can be supplied as sucrose or cookedcereal flour

– Na 90 mM, K 20 mM, Cl 80 mM, HCO3 30 mM,glucose 111 mM

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Composition of oral solutions

730 690 3Apple juice

540 500 3Ginger ale

145 111 20Sports drink

450 0 250Chicken soup

310 111 90WHO-ORSosmolalityGlucose Na

Na and glucose as mM, osmolality in mosm