Diarrhea
Epidemiology
Etiology
Diarrhea is classified by mechanism (secretory, osmotic, inflammatory) or duration (acute <2 wks, persistent 2-4 wks, chronic >4 wks). Stool characteristics and patient history are key to diagnosis.
| Feature | Non-Inflammatory Diarrhea | Inflammatory Diarrhea (Dysentery) |
|---|---|---|
| Pathology | No mucosal invasion; toxin-mediated | Mucosal invasion & destruction |
| Location | Small Bowel | Colon |
| Stool Volume | Large | Small, frequent |
| Stool Content | Watery | Bloody, mucoid (pus) |
| Fever | Usually absent | Common |
| Fecal WBCs | Absent | Present |
| Key Symptom | Dehydration | Tenesmus, severe abd pain |
| Example Bugs | V. cholerae, ETEC, Norovirus, Giardia | Shigella, Campylobacter, EHEC, Salmonella |
I. Watery Diarrhea: Non-inflammatory
Characterized by large volume, watery stools without blood or pus. Fecal leukocytes are typically absent.
A. Secretory Diarrhea
- Hallmark: Persists with fasting. Stool osmotic gap <50 mOsm/kg. Caused by net secretion of electrolytes/water.
- Distinguishing Features:
- Vibrio cholerae: Profuse "rice-water" stools, severe dehydration. Toxin activates Gs → ↑cAMP.
- ETEC (Enterotoxigenic E. coli): #1 cause of traveler's diarrhea. Watery stools, cramps. Heat-labile (↑cAMP) and heat-stable (↑cGMP) toxins.
- Norovirus: #1 cause of adult gastroenteritis. Outbreaks on cruise ships, schools, hospitals. Vomiting is a prominent feature.
- Rotavirus: #1 cause of severe diarrhea in unvaccinated children. Vomiting, fever.
- VIPoma/Carcinoid Syndrome: Rare endocrine tumors causing chronic diarrhea. Associated with flushing, wheezing (carcinoid).
B. Osmotic Diarrhea
- Hallmark: Stops with fasting. Stool osmotic gap >125 mOsm/kg. Caused by non-absorbable solutes in the gut.
- Distinguishing Features:
- Lactose Intolerance: Diarrhea, bloating, flatulence after consuming dairy.
- Laxative Abuse: Often seen in patients with eating disorders.
- Celiac Disease: Can present with osmotic diarrhea and/or steatorrhea.
II. Inflammatory/Invasive Diarrhea (Dysentery)
- Hallmark: Bloody or mucoid, small-volume stools. Associated with fever, tenesmus, and severe abdominal pain. Fecal leukocytes/calprotectin are present.
- Distinguishing Features:
- Campylobacter jejuni: Most common cause of bacterial gastroenteritis in the US. Source: undercooked poultry. Antecedent for Guillain-Barré syndrome and reactive arthritis.
- Shigella: Very low infectious dose. High fever, tenesmus. Shiga toxin can cause hemolytic uremic syndrome (HUS), especially in children.
- Salmonella (non-typhoidal): Source: poultry, eggs, pet reptiles. Can cause osteomyelitis in sickle cell disease patients.
- EHEC (Enterohemorrhagic E. coli O157:H7): Source: undercooked beef. Causes bloody diarrhea without fever. Toxin causes HUS. Do NOT treat with antibiotics (increases HUS risk).
- Yersinia enterocolitica: Source: contaminated pork, milk. Causes fever, RLQ pain, mimicking appendicitis (pseudoappendicitis).
- Clostridioides difficile: History of antibiotic use (esp. clindamycin, fluoroquinolones) or hospitalization. Watery or bloody diarrhea. Dx: stool toxin A/B assay. Tx: Oral vancomycin or fidaxomicin.
III. Protozoal Diarrhea
- Distinguishing Features:
- Giardia lamblia: Hiker/camper drinking from a freshwater stream. Causes foul-smelling, fatty stools (steatorrhea), bloating, and flatulence. No blood.
- Entamoeba histolytica: Travel to developing nations. Causes dysentery (bloody diarrhea) and can lead to liver abscess ("anchovy paste" aspirate).
- Cryptosporidium: Severe, chronic, watery diarrhea in immunocompromised patients (e.g., AIDS with CD4 < 100). Oocysts on acid-fast stain.
IV. Pre-formed Toxin (Rapid Onset Food Poisoning)
- Hallmark: Symptoms appear very quickly (1-8 hours) after ingestion. Vomiting is often more prominent than diarrhea.
- Distinguishing Features:
- Staphylococcus aureus: Rapid onset vomiting, cramps, and diarrhea. Source: mayonnaise, potato salad, custards left at room temp.
- Bacillus cereus: Emetic type (rapid onset) from reheated fried rice. Diarrheal type has a longer incubation.
Watery diarrhea
Viral
| Norovirus (Norwalk) virus | Rotaviruses | Adenovirus | Astrovirus | |
|---|---|---|---|---|
| Genome/structure | Positive ss RNA, non-enveloped, Star of David | ds RNA (11 segments), non-enveloped, Wheel-like | ds DNA, non-enveloped, type 40/41, fibers (penton) | Positive ss RNA, non-enveloped |
| High risk | Group settings, e.g., cruise ships | Infants | Infants, older children, adults | Infants, elderly, immunocompromised |
| Seasonality | Occurs year round | November-April peak | Late fall and winter peak | Winter peak |
| Vaccine | No | Yes Prevalence in developed countries has decreased dramatically due to vaccination. |
No | No |
Bloody diarrhea
- Campylobacter jejuni
- Poultry, unpasteurized milk (natural gut flora in birds)
- Contact with infected persons or infected animals (e.g., pigs, dogs, cats)
Pathophysiology
Inflammatory
- EHEC
- Shiga-like toxin: bloody diarrhea
- Enhanced cytokine release (mainly renal epithelial cells) → HUS (no invasion of host cells)
- Shigella
- Spread from cell to cell → invasion of M cells (MALT)
- Shiga toxin
- Campylobacter
- Type IV secretion system (T4SS)
- Cytolethal-distending toxin
- Non-Typhi Samonella
- Flagellar motility
- Endotoxin
- Clostridioides difficile
- Toxin A (enterotoxin)
- Toxin B (cytotoxin)
- Yersinia Enterocolitica
- Amebic Dysentery
- Vibrio parahaemolyticus/vulnificus
Noninflammatory
- ETEC
- Heat-labile toxin
- Overactivates adenylate cyclase → ↑ cAMP → ↑ secretion of chloride and water efflux into the intestinal lumen → watery diarrhea
- Heat-stable toxin
- Activation of guanylate cyclase → ↑ cGMP → ↓ NaCl reabsorption → water efflux into the intestinal lumen → secretory diarrhea
- Heat-labile toxin
- V. cholerae
- Cholera toxin (enterotoxin): “rice-water” diarrhea
- Same with heat-labile toxin
- Permanently activates Gs protein → overactivation of adenylate cyclase → ↑ cAMP → ↑ secretion of chloride and water efflux into the intestinal lumen → watery diarrhea.
- Cholera toxin (enterotoxin): “rice-water” diarrhea
- Giardiasis
- Impaired function and structure of intestinal tissue, resulting in malabsorption and diarrhea
- Gastroenteritis from preformed enterotoxin (S. aureus, B. cereus)
- See Food poisoning
- S. aureus: Enterotoxin B
- Forms pores in enterocyte membranes → leakage of Na+ and water into the intestinal lumen
- C. perfringens
- Exotoxins
- Clostridium perfringens alpha toxin
- Acts as a phospholipase → degrades cell membranes and tissue.
- Enterotoxin (heat-labile)
- Responsible for food poisoning.
- Cryptosporidiosis
- Norovirus
- Rotavirus
Clinical features
Diagnostics
Treatment
Antidiarrheal agents
- Bismuth subsalicylate
- Converts to bismuth and salicylic acid in the GI tract
- Has antisecretory, antimicrobial, and antiinflammatory effects
- Can be used in bacterial diarrhea
- Loperamide
- Opioid receptor agonist that increases intestinal transit time
- Loperamide acts on intestinal μ-receptors and inhibits intestinal peristalsis and intestinal fluid secretion, and increases sphincter tone.
- Best initial treatment for chemotherapy-induced diarrhea
- Cautions
- Should not be used for > 48 hours without reevaluation of the patient
- Opioid receptor agonist that increases intestinal transit time
Warning
Loperamide should be avoided in patients with suspected invasive diarrhea with inflammatory features, as it reduces intestinal motility, which consequently increases the risk of bacterial colonization and invasion.