E xplain diarrhoea

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Diarrhoea

Definition

Diarrhoea is a symptom, not a disease, defined as the passage of abnormally loose or watery stools, typically three or more times per day. Objectively, stool output exceeding 200 g/day is generally accepted as the upper limit of normal in Western countries. It is classified as:

Acute - lasting < 4 weeks (most cases resolve within days)
Chronic - lasting ≥ 4 weeks, which warrants investigation to exclude serious pathology

- Sleisenger and Fordtran's Gastrointestinal and Liver Disease, p. 204

Epidemiology

7.5% of Americans have acute gastroenteritis symptoms in any given month
Over 3.5 million outpatient visits for diarrhoea occur annually in the USA, with >180,000 hospital admissions and ~3,000 deaths per year
Chronic diarrhoea affects ~6.6% of the general population per year
In developing countries, acute infectious diarrhoea remains a leading cause of death, especially in children

- Sleisenger and Fordtran's, p. 204

Pathophysiology

Normally, the small intestine and colon absorb 99% of the ~9-10 litres of fluid that passes the ligament of Treitz daily (from oral intake plus secretions from salivary glands, stomach, liver, and pancreas). A reduction in net water absorption of as little as 1% is sufficient to cause diarrhoea.

Three fundamental mechanisms disrupt this:

Altered rate of mucosal water/electrolyte transport in the small intestine or colon
Rapid transit - less time available for water absorption, especially in the colon
Altered stool solids composition - changing stool consistency independent of water content

- Sleisenger and Fordtran's, p. 205

Classification of Diarrhoea by Mechanism

The four general pathophysiological mechanisms are:

Frameworks for Internal Medicine

1. Osmotic Diarrhoea

Caused by non-absorbable solutes in the intestinal lumen that retain water osmotically.

Classic example: lactase deficiency - undigested lactose stays in the lumen, retains water, and colonic bacteria degrade it into more osmotically active particles
Other causes: osmotic laxatives (Mg²⁺, phosphate, sulphate), fructose/sorbitol ingestion, FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), polyethylene glycol
Key feature: resolves with fasting - stops when the offending substance is removed
Stool electrolytes are low; there is a measurable fecal osmotic gap

2. Secretory Diarrhoea

Caused by net secretion of anions (Cl⁻ or HCO₃⁻), net secretion of K⁺, or net inhibition of Na⁺ absorption by the enterocolonic mucosa.

The diagram below shows the mechanism at crypt epithelial cells - cholera toxin activates adenylyl cyclase (AC) via a G-protein (Gs), raising intracellular cAMP, which opens CFTR Cl⁻ channels in the apical membrane. Na⁺ and water follow passively into the lumen:

Costanzo Physiology, Fig. 8.36

Key features of secretory diarrhoea:

Large volume, watery stools that are typically painless
Persists with fasting (unlike osmotic)
No fecal osmotic gap
Caused by: bacterial enterotoxins (E. coli, V. cholerae), VIP-secreting tumours (VIPoma), carcinoid, gastrinoma, medullary thyroid cancer, bile acid malabsorption, drugs/laxatives, congenital transport defects

The most common cause is infection. E. coli heat-stable enterotoxin acts on guanylate cyclase C receptors, raising cGMP and stimulating Cl⁻ secretion via CFTR. Many enterotoxins also block Na⁺-H⁺ exchange, reducing absorption.

- Sleisenger and Fordtran's, p. 206

3. Inflammatory (Exudative) Diarrhoea

Mucosal disruption results in exudation of serum, blood, and mucus into the intestinal lumen; destruction of absorptive epithelium also causes malabsorption.

Associated with: abdominal pain, fever, tenesmus, bloody/mucoid stools
Stool shows polymorphonuclear leukocytes or inflammatory proteins (calprotectin, lactoferrin)
Causes: invasive bacterial infections (Salmonella, Shigella, Campylobacter, C. difficile), IBD (Crohn's disease, ulcerative colitis), radiation injury, GI malignancies, ischaemic colitis
Life-threatening complication: toxic megacolon (fever, tachycardia, abdominal distension, delirium)

4. Dysmotility Diarrhoea

Altered intestinal motility reduces contact time between luminal contents and the absorptive mucosa.

Causes: irritable bowel syndrome (IBS), hyperthyroidism, prokinetic drugs, postvagotomy, visceral neuropathies

Electrolyte Consequences

Diarrhoeal fluid is rich in:

HCO₃⁻ (from salivary, pancreatic, and intestinal secretions) → loss causes hyperchloremic normal anion-gap metabolic acidosis
K⁺ (via flow-rate-dependent colonic K⁺ secretion) → loss causes hypokalaemia
Water/Na⁺ → hypovolaemia, reduced intravascular volume, and circulatory collapse in severe cases

Baroreceptor and renin-angiotensin-aldosterone mechanisms attempt to restore blood pressure but are overwhelmed if losses are large or rapid.

- Costanzo Physiology, p. 392

Major Causes by Duration

Acute Diarrhoea (< 4 weeks)

Category	Examples
Viral	Norovirus, rotavirus, adenovirus
Bacterial (non-invasive/toxin)	E. coli (ETEC), V. cholerae, S. aureus, Bacillus cereus
Bacterial (invasive)	Salmonella, Shigella, Campylobacter, C. difficile
Protozoal	Giardia, Cryptosporidium, Entamoeba histolytica
Drugs	Antibiotics, NSAIDs, antacids, laxatives
Dietetic	Excessive FODMAPs, alcohol

Chronic Diarrhoea (≥ 4 weeks) by Mechanism

Secretory causes: stimulant laxatives, chronic ethanol, bile acid malabsorption (BAD - accounts for ~40% of unexplained chronic diarrhoea), hormone-producing tumours (VIPoma, carcinoid, gastrinoma), Addison's disease, congenital electrolyte transport defects

Osmotic causes: lactase/disaccharide deficiency, non-absorbable carbohydrates, FODMAPs, osmotic laxatives

Steatorrheal/malabsorptive: pancreatic exocrine insufficiency, celiac disease, Whipple's disease, bacterial overgrowth, short bowel syndrome

Inflammatory: IBD (Crohn's, ulcerative colitis), microscopic colitis, lymphocytic/collagenous colitis, eosinophilic gastroenteritis, radiation enteritis

Dysmotility: IBS, hyperthyroidism, postvagotomy, prokinetics

Iatrogenic: post-cholecystectomy, ileal resection, bariatric surgery

- Harrison's Principles of Internal Medicine 22E, Table 49-3

Clinical Evaluation

History

Duration, frequency, volume, consistency, presence of blood/mucus
Associated symptoms: fever, weight loss, abdominal pain, tenesmus
Dietary history, travel history, medications, family history
Epidemiologic context (immunosuppression, HIV, hospitalisation)

Physical Examination

Signs of dehydration: tachycardia, hypotension, reduced skin turgor, dry mucous membranes
Abdominal examination: distension, tenderness, bowel sounds
Perianal inspection

Investigations

For acute diarrhoea:

Most resolve without investigation
Stool cultures + microscopy if: fever, bloody stool, immunosuppression, symptoms > 3-4 days
Stool for C. difficile toxin in hospital-acquired or post-antibiotic diarrhoea

For chronic diarroea:

Stool characterisation: watery vs. fatty vs. inflammatory
Basic bloods: FBC, CRP, ESR, LFTs, TFTs, coeliac antibodies (anti-tTG)
Stool osmotic gap = 290 - 2×(stool Na + stool K): gap >50 mOsm/kg = osmotic; gap <50 = secretory
Faecal calprotectin (screens for organic vs. functional cause)
Colonoscopy + biopsy for inflammatory or neoplastic causes
CT/MRI enterography for small bowel disease
SeHCAT scan or serum FGF-19 for bile acid malabsorption

Treatment

Acute Diarrhoea

Oral rehydration therapy (ORT) is the cornerstone - glucose-coupled Na⁺ transport is preserved even in secretory diarrhoea
Antimotility agents: loperamide (reduces stool frequency, does not use in bloody/febrile diarrhoea)
Antibiotics only for specific organisms (Shigella, Campylobacter, C. difficile, cholera), traveller's diarrhoea, or immunocompromised patients
Bismuth subsalicylate has antisecretory and antimicrobial effects

Chronic Diarrhoea

Treatment directed at the underlying cause wherever possible
Bile acid sequestrants (cholestyramine, colesevelam) for BAD
Pancreatic enzyme replacement for exocrine insufficiency
Gluten-free diet for coeliac disease
5-aminosalicylates, steroids, biologics for IBD
Budesonide for microscopic colitis
Somatostatin analogues (octreotide) for VIPoma/carcinoid diarrhoea
Low-FODMAP diet for IBS-diarrhoea

Complications

Complication	Mechanism
Dehydration	Volume loss (up to 9+ L/day in severe cases)
Metabolic acidosis	HCO₃⁻ loss in stool
Hypokalaemia	K⁺ loss in diarrhoeal fluid
Hypovolaemic shock	Circulatory collapse if losses are massive/rapid
Malnutrition	Chronic malabsorptive diarrhoea
Toxic megacolon	Inflammatory diarrhoea complication

Special Populations

HIV/AIDS: Diarrhoea occurred in up to 90% of patients pre-HAART. Common organisms: Cryptosporidium (most frequent protozoa), CMV, MAC, Microsporidium. Now more often HAART-induced or from unrelated disorders.
Hospitalized patients: C. difficile toxin-mediated colitis, overflow diarrhoea from faecal impaction, ischaemic colitis, tube feeding
Diabetics: Autonomic neuropathy (altered motility), associated coeliac disease, pancreatic exocrine insufficiency, metformin/acarbose side effects
Children: Rotavirus is the leading cause worldwide; oral rehydration is the mainstay of management

Sources: Sleisenger and Fordtran's Gastrointestinal and Liver Disease; Harrison's Principles of Internal Medicine 22E; Costanzo Physiology 7th Ed.; Frameworks for Internal Medicine

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