DiarrheaDiarrhea

Christina Tennyson, M.D.Assistant Professor of MedicineAssistant Professor of Medicine

Division of GastroenterologyColumbia UniversityColumbia University

DIARRHEADIARRHEASymptom: stool frequency, liquidity y p q y, q y

Sign: > 200-250 g/day

Acute Chronic

Time < 2-4 weeks > 4 weeks

Cause infection or drug manyCause infection or drug many

Outcome self-limited treat specific disease

Features to Increase Small Bowel Surface Area

From Sleisenger and Fordtran

Normal mucosaNormal mucosa

DRA

GuanylinGuanylin

CAUSES OF ACUTE DIARRHEA

INFECTIOUS MEDICATIONS

Watery Bloody (dysentery) laxatives y y ( y y)Enterotoxins Invasive Bacteria caffeine(cholera, E coli) (Salmonella, Shigella, metforminViral E Coli 0157 Campy) cholinergicsViral E. Coli 0157, Campy) cholinergics (rotavirus, Norwalk) Cytotoxins prostaglandinsParasitic (Shiga, E. Coli, protease inhibitor

A ibi i(giardia, crypto) C. Diff, Anthrax) Antibiotics**Not complete list!

ParasiticParasitic(E. Histolytica)

CAUSES OF CHRONIC DIARRHEA

WATERY

•Enterotoxins

INFLAMMATORY

•Inflammatory

MALABSORPTIVE

•Pancreatic•Enterotoxins

•Bile acids

F A id

•Inflammatory bowel disease

•Microscopic colitis

•Pancreatic insufficiency

•Bacterial•Fatty Acids

• Hormones

Microscopic colitis

•Eosinophilic gastroenteritis

Bacterial overgrowth

•Mucosal diseases g

Mechanisms of DiarrheaMechanisms of Diarrhea

• Osmotic (malabsorptive)Osmotic (malabsorptive)

S t ( t )• Secretory (watery)

• Inflammatory

• Motility

***Overlap exists! Diseases can involve more than one mechanism.

Stool electrolytesStool electrolytes

• 290 mOsm/kg- 2(stool K +Na)290 mOsm/kg- 2(stool K +Na)

• <50mOsm/kg SECRETORY50mOsm/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 activityy p y

• <290 mOsm/kg Contaminated by adding water to sample

OSMOTIC DIARRHEAOS O C

CAUSESI ti f l b b bl l t• Ingestion of poorly absorbable solute

Mg++ and PO4--- containing laxatives, antacids

Sorbitol in sugar free candies, gumg , gFructose containing fruits, sodaLactulose

• Acquired lactase deficiency• Acquired lactase deficiency

• Malabsorptive diseasesMalabsorptive diseasesmucosal (e.g. celiac disease, tropical sprue)maldigestion (e.g. bacterial overgrowth)

Atrophy- celiac disease

Partial atrophyPartial atrophy

Characteristics of OsmoticCharacteristics of Osmotic Diarrhea

• Low volumes (< 1 liter)• Resolves with fastingResolves with fasting• Excess stool osmotic gap > 100 mOsm/kg

L t l H ( b h d t l b ti )• Low stool pH (carbohydrate malabsorption)

Causes of Secretory DiarrheaCauses of Secretory Diarrhea

• Bacterial EnterotoxinsBacterial Enterotoxins(cholera, E. Coli LT,ST)

• Hormones and NeurotransmittersHormones and Neurotransmitters(VIP, 5-HT, Substance P, calcitonin, acetylcholine)y )

• Inflammation(prostaglandins, leukotrienes, (p gcytokines, histamine)

• Bile acids and hydroxylated fatty acidsy y y

Characteristics of SecretoryCharacteristics of Secretory Diarrhea

• Large stool volumes (> 1 Liter/day)• Persists with fasting (also nocturnal)Persists with fasting (also nocturnal)• No WBCs or RBCs in the stool

Ab f f• Absence of fever• No stool osmotic gap

Vibrio Cholerae

CRYPT CELL

Cholera Toxin does not Inhibit the Na/glucose cotransporter

TREATMENT OF DIARRHEATREATMENT OF DIARRHEAORAL REHYDRATION SOLUTIONS

• Utilize Na/glucose co-transporters• Requires intact villus epitheliumRequires intact villus epithelium• Solution must contain Na and glucose

S l ti t b i l l ti• Solution must be near isosmolar relative to plasma

Hormone-secreting Tumors (rare)

Agent Source Cell mediator Mechanism

VIP pancreatic tumor cAMP secretionVIP pancreatic tumor cAMP secretionganglioneuroma

5HT carcinoid tumor calcium secretion (serotonin) (intestine, lung) motility

Gastrin gastrinoma calcium acid secretion

Calcitonin medullary CA calcium secretion thyroid

Viral diarrhea• Rotavirus (infants)( )

Norwalk agent (cruise-ship diarrhea)• Invades the intestinal epithelium with select

ill ll dvillus cell damage• Mechanism of diarrhea

1) absorption due to villus damage1) absorption due to villus damage2) secretion due to

activation of the enteric nervous systemNSP4 rota-toxin

• Treatment with ORS effective

Inflammatory Diarrheay• Invasive infections

• Inflammatory Bowel Di (IBD)Disease (IBD)

C i• Cytotoxins – C. Difficile Toxin

Ulcerative colitis

Colectomy specimen following fulminant Clostridium difficile

Intestinal Inflammation

• Acute inflammationProstaglandins, leukotrienes, free g , ,radicals, PAF, histamine and others stimulate active secretion

• Chronic inflammationCytokines (e g IFN-γ TNF-α) suppressCytokines (e.g. IFN γ, TNF α) suppress both absorption and secretion

Characteristics of inflammatoryCharacteristics of inflammatory diarrhea:

• Damage of intestinal epithelium• Exudation of protein blood and pus intoExudation of protein, blood and pus into

intestinal lumen• Urgency frequency tenesmus with• Urgency, frequency, tenesmus with

recto-sigmoid disease Bl d t t l• Bloody or watery stools

• Low serum protein and albumin levels

TreatmentTreatment• Oral rehydration• Oral rehydration• Clinical evaluation• Stool tests as needed• Antimicrobial therapy if indicatedpy• Anti-diarrheal medication if indicated• Treat underlying disease• Treat underlying disease