Diarrhea

• Passage of loose or watery stools with increased frequency (>3 times/day)
• Results from impaired water absorption or excessive secretion in the intestines
• Associated with passage of mushy or liquid stools (Bristol stool types 6 and 7) ( figure 1)
• Should be differentiated from:
  • Simple passage of loose stools without increased frequency
  • Fecal incontinence without change in stool character
  • Paradoxical diarrhea (loose stool around hard stool impaction)

By Duration

• Acute diarrhea (<14 days)
  • Most commonly infectious (viral > bacterial > parasitic)
  • Usually self-limited
• Persistent diarrhea (14-30 days)
  • Infections remain common
  • Noninfectious causes become increasingly likely
• Chronic diarrhea (>30 days)
  • More commonly noninfectious
  • Requires systematic diagnostic evaluation

By Mechanism

• Osmotic diarrhea
  • Caused by nonabsorbable solutes drawing water into gut
  • Improves with fasting
  • Examples: lactose intolerance, sorbitol ingestion
• Secretory diarrhea
  • Excessive secretion of water and electrolytes
  • Persists despite fasting
  • High-volume, watery stools
  • Examples: cholera, VIPoma, ETEC
• Inflammatory diarrhea
  • Mucosal damage with fluid, blood, and mucus leakage
  • Frequent, small-volume stools with tenesmus
  • Positive fecal leukocytes/lactoferrin
  • Examples: Shigella, Campylobacter, IBD
• Motility-related diarrhea
  • Accelerated intestinal transit
  • Reduced absorption time
  • Examples: hyperthyroidism, diabetic neuropathy

Etiology

• Most cases of acute diarrhea are infectious. table 1 categorizes the major pathogens:
• Viral Causes (Most Common)
  • Norovirus: Most common cause in adults, outbreaks in closed settings
  • Rotavirus: Previously most common in children, now reduced by vaccination
  • Adenovirus, Astrovirus: Less common causes
  • Typically present with watery diarrhea, nausea, vomiting
  • Self-limited course (24-72 hours)
• Bacterial Causes
  • Noninflammatory (Watery) Diarrhea:
    • Enterotoxigenic E. coli (ETEC): Most common cause of traveler's diarrhea
    • Vibrio cholerae: "Rice-water" stools, severe dehydration
    • Staphylococcus aureus: Preformed toxin, rapid onset (2-6 hours)
    • Bacillus cereus: Associated with reheated rice
    • Clostridium perfringens: Associated with meat dishes
  • Inflammatory (Bloody) Diarrhea: table 2
    • Shigella: Bacillary dysentery, can cause seizures in children
    • Campylobacter: Most common bacterial cause, associated with poultry
    • Salmonella: Can be typhoidal or nontyphoidal table 3
    • Enterohemorrhagic E. coli (EHEC/STEC): O157:H7, risk of HUS
    • Yersinia enterocolitica: Can mimic appendicitis
  • Parasitic Causes
    • Giardia lamblia: Prolonged watery diarrhea, malabsorption table 4 and figure 2
    • Cryptosporidium: Self-limited in immunocompetent, chronic in immunocompromised
    • Entamoeba histolytica: Bloody diarrhea, liver abscess table 5
  • Special Situations
    • Clostridioides difficile
      • Recent antibiotic use (especially clindamycin, fluoroquinolones, cephalosporins)
      • Hospital or nursing home exposure
      • Can range from mild diarrhea to toxic megacolon
• Risk Factors
  • Travel to endemic areas: ETEC, Salmonella, Shigella, Entamoeba
  • Day care/institutional settings: Viral gastroenteritis, Shigella
  • Contaminated food/water: Various pathogens
  • Recent antibiotic use: C. difficile
  • Immunocompromised states: Increased risk for protozoal infections

Clinical Features

• General symptoms: Abdominal cramps, nausea, vomiting, fever
• Noninflammatory diarrhea: Large-volume, watery stools without blood
• Inflammatory diarrhea: Small-volume, frequent stools with blood/mucus, tenesmus
• Dehydration signs: Dry mucous membranes, decreased skin turgor, tachycardia

Diagnosis

A systematic approach is recommended for evaluation: figure 3

Indications for Testing

• Bloody diarrhea
• Severe symptoms (high fever, severe abdominal pain, dehydration)
• Duration >7 days
• Immunocompromised patients
• Elderly patients (>70 years)
• Recent travel or antibiotic use

Diagnostic Tests

• Stool studies
  • Fecal leukocytes/lactoferrin: Suggests inflammatory diarrhea
  • Stool culture: For bacterial pathogens
  • Multiplex PCR: Higher sensitivity, rapid results
  • C. difficile toxin assay: If recent antibiotic use
  • Ova and parasites: If persistent symptoms or travel history
• Blood tests
  • CBC: Leukocytosis, anemia
  • Electrolytes: Assess dehydration, electrolyte imbalances
  • Blood cultures: If systemic symptoms

Management

Supportive Care (Primary Treatment)

• Oral rehydration
  • First-line for mild to moderate dehydration
  • ORS contains glucose and sodium for optimal absorption
• IV fluids
  • Severe dehydration or inability to tolerate oral fluids
  • Normal saline or lactated Ringer's solution
• Diet
  • Continue regular diet as tolerated
  • Avoid lactose temporarily if concern for secondary lactase deficiency

Antimotility Agents

• Loperamide: μ-opioid agonist, reduces intestinal motility
• Diphenoxylate-atropine: Opioid with anticholinergic
• Contraindications:
  • Bloody diarrhea
  • Suspected C. difficile
  • High fever

Antibiotics

Generally NOT recommended for most acute diarrhea. Consider in:

• Severe disease (hospitalization required)
• Immunocompromised patients
• Specific pathogens:
  • Shigella: Azithromycin or ciprofloxacin
  • C. difficile: Oral vancomycin or fidaxomicin
  • Giardia: Tinidazole or nitazoxanide
• Avoid antibiotics in STEC/EHEC due to increased HUS risk

Etiology

• Functional Disorders (Most Common)
  • Irritable bowel syndrome (IBS)
    • Altered bowel habits with abdominal pain
    • Symptoms worse with stress, better at night
    • Rome criteria for diagnosis
  • Functional diarrhea: Similar to IBS but without pain
• Inflammatory Bowel Disease
  • Crohn's disease
    • Transmural inflammation, skip lesions
    • Can affect entire GI tract
    • Complications: fistulas, strictures
  • Ulcerative colitis
    • Mucosal inflammation, continuous from rectum
    • Bloody diarrhea with urgency
  • Microscopic colitis
    • Normal colonoscopy, abnormal histology
    • Associated with NSAIDs, smoking
• Malabsorptive Disorders
  • Celiac disease
    • Gluten-sensitive enteropathy
    • Villous atrophy, malabsorption
    • Iron deficiency anemia common
  • Lactose intolerance
    • Lactase deficiency
    • Symptoms with dairy consumption
  • Small intestinal bacterial overgrowth (SIBO)
  • Pancreatic insufficiency: Steatorrhea, weight loss
  • Bile acid diarrhea: Common post-cholecystectomy
• Endocrine Causes
  • Hyperthyroidism: Increased motility, malabsorption
  • Diabetes mellitus: Autonomic neuropathy
  • VIPoma: Secretory diarrhea, hypokalemia
  • Carcinoid syndrome: Flushing, wheezing, diarrhea
  • Zollinger-Ellison syndrome: Gastrinoma, peptic ulcers

Diagnostic Approach

• History: Duration, pattern, associated symptoms, medications
• Blood tests
  • CBC: Anemia (iron, B12 deficiency)
  • Electrolytes, albumin
  • Thyroid function tests
  • Celiac serologies (anti-tTG IgA)
  • Inflammatory markers (CRP, ESR)
• Stool tests
  • Fecal calprotectin/lactoferrin: Inflammatory vs non-inflammatory
  • Fecal fat: Malabsorption
  • Stool osmotic gap: Osmotic vs secretory
• Endoscopy
  • Colonoscopy with biopsy: IBD, microscopic colitis
  • EGD with duodenal biopsy: Celiac disease

Management

Treatment is disease-specific:

• IBS: Dietary modification (low FODMAP), antispasmodics, psychotherapy
• IBD: 5-ASA compounds, corticosteroids, immunomodulators, biologics
• Celiac disease: Strict gluten-free diet
• Lactose intolerance: Lactase supplements, dairy restriction
• Microscopic colitis: Budesonide
• Bile acid diarrhea: Cholestyramine

• Most common cause: Enterotoxigenic E. coli (ETEC)
• Other causes: Campylobacter, Salmonella, Shigella, viruses, parasites
• Prevention:
  • Avoid tap water, ice, raw vegetables, street food
  • Prophylactic antibiotics NOT routinely recommended
• Treatment:
  • Most cases self-limited
  • Antibiotics (azithromycin, ciprofloxacin) can shorten duration
  • Consider treatment if severe symptoms or >14 days duration

General Complications

• Dehydration: Most common, especially in children and elderly
• Electrolyte imbalances: Hyponatremia, hypokalemia
• Metabolic acidosis: Non-anion gap from bicarbonate loss

Disease-Specific Complications

• Hemolytic uremic syndrome (HUS)
  • Associated with STEC (E. coli O157:H7), Shigella
  • Triad: microangiopathic hemolytic anemia, thrombocytopenia, AKI
  • Schistocytes on blood smear figure 4
• Toxic megacolon
  • Life-threatening colonic dilation
  • Associated with UC, C. difficile
• Reactive arthritis
  • Post-infectious inflammatory arthritis
  • Associated with Salmonella, Shigella, Yersinia, Campylobacter
• Guillain-Barré syndrome
  • Associated with Campylobacter infection
  • Ascending paralysis