Diarrhoea
Diarrhoea is the passage of three or more loose or watery stools per day, or more frequently than is normal for the individual, resulting from increased intestinal secretion, decreased absorption, or altered motility.
Diarrhoea
1. Definition
Diarrhoea literally comes from the Greek "diarrhoia" — "dia" = through, "rhein" = to flow. It means flowing through — an apt description of the clinical problem.
Diarrhoea is defined as the passage of abnormally liquid or unformed stools at an increased frequency (typically ≥ 3 times per day), OR a stool weight/volume exceeding 200 g/day. [1]
In clinical practice, what matters most is the change from baseline for that patient. Someone who normally opens their bowels once daily and now goes 4–5 times with loose stools — that is diarrhoea, even if total weight is under 200 g.
| Category | Duration | Typical Implication |
|---|---|---|
| Acute diarrhoea | < 2 weeks | Usually infectious |
| Persistent diarrhoea | 2–4 weeks | May be infectious or early non-infectious cause |
| Chronic diarrhoea | > 4 weeks | Usually non-infectious (IBD, IBS, malabsorption, neoplasia, endocrine) |
Common Student Pitfall
Establish what the patient means by diarrhoea. [1] Patients often use "diarrhoea" to describe urgency, frequency, or even faecal incontinence — none of which necessarily mean loose stool. Always clarify stool consistency (Bristol Stool Chart types 5–7 = diarrhoea) and frequency.
- Spurious (overflow) diarrhoea: Remember spurious diarrhoea and the rectal examination in the elderly. [1] Liquid stool leaking around impacted faeces in the rectum — especially in elderly or immobile patients. The rectal exam is diagnostic.
- Functional diarrhoea: Yes, diarrhoea may be a manifestation of anxiety state or irritable bowel syndrome. [1] IBS rarely causes nocturnal diarrhoea but causes recurrent pain in the right hypochondrium. [1]
2. Epidemiology
- Diarrhoeal diseases remain the second leading cause of death in children under 5 worldwide (~525,000 deaths/year, WHO 2024), predominantly in low-income countries.
- In adults, acute infectious diarrhoea is overwhelmingly self-limiting, but certain populations (elderly, immunocompromised, travellers) carry higher morbidity and mortality.
- Infectious gastroenteritis is a notifiable disease in HK. Norovirus is the leading cause of viral gastroenteritis outbreaks, particularly in residential care homes and schools.
- Bacterial causes: Vibrio parahaemolyticus (from raw/undercooked seafood — very common in HK), Salmonella, Campylobacter, and increasingly antibiotic-resistant organisms.
- Parasitic: Giardia lamblia, Entamoeba histolytica (especially in travellers returning from Southeast Asia / mainland China).
- C. difficile infection (CDI): increasingly recognised in HK hospitals; associated with prior antibiotic use and PPI exposure.
- Inflammatory bowel disease (IBD): incidence is rising in Hong Kong and East Asia. IBD occurs between 30–70s with NO gender predominance (for UC), while Crohn's disease has a female predominance. [3]
- IBS: prevalence 3.7% in HK (Rome II criteria), up to 25% in East Asia [5] — an important cause of chronic diarrhoea.
- Colorectal cancer: HK has one of the highest rates globally; can present with diarrhoea (especially alternating bowel habits).
| Category | Risk Factors |
|---|---|
| Host factors | Extremes of age (< 5y, > 70y), immunocompromise (HIV, transplant, chemotherapy), achlorhydria (PPI use), prior GI surgery (gastrectomy, ileal resection) |
| Infectious exposure | Travel (travellers' diarrhoea), contaminated water/food, raw shellfish (HK!), institutional outbreaks, sexual practices (MSM — Shigella, Entamoeba) |
| Medications | Alcohol, antibiotics, digoxin, colchicine, cytotoxic agents, H₂-receptor antagonists, iron compounds, laxatives, metformin, sildenafil, statins, thyroxine [1] |
| Medical Hx | Infectious gastroenteritis in prior 1 year is a risk factor [3]; prior IBD; diabetes (autonomic neuropathy) |
| Surgical Hx | Cholecystectomy (bile acid diarrhoea), ileal resection, gastric surgery (dumping), prior appendicectomy is a risk factor for Crohn's disease [3] but protective for ulcerative colitis [3] |
| Family Hx | IBD, coeliac disease, colorectal cancer [3] |
| Social Hx | Smoking is a risk factor for Crohn's disease (ONLY Crohn's, NOT UC) — conversely, smoking is protective for ulcerative colitis [3] |
High Yield — Smoking and IBD
Smoking and IBD is a classic exam question. Remember: Smoking is BAD for Crohn's (worsens disease, increases relapse) but paradoxically PROTECTIVE for UC. The mechanism is not fully understood but may relate to effects of nicotine on colonic mucus production, cytokine profiles, and mucosal blood flow.
3. Anatomy and Physiology Relevant to Diarrhoea
Understanding diarrhoea requires understanding normal intestinal fluid handling. Think of the gut as a massive fluid-processing factory.
Every day, approximately 9 litres of fluid enters the GI tract:
- ~2 L oral intake
- ~1 L saliva
- ~2 L gastric secretion
- ~1 L bile
- ~2 L pancreatic juice
- ~1 L small intestinal secretion
Of this 9 L, the small intestine absorbs ~7–8 L, and the colon absorbs ~1–1.5 L. Only 100–200 mL appears in stool.
The colon has a maximum absorptive capacity of ~4–5 L/day. Any process that delivers > 5 L of fluid to the colon, or impairs colonic absorption, will overwhelm the system and produce diarrhoea.
| Segment | Key Absorptive Mechanisms | Key Secretory Mechanisms |
|---|---|---|
| Duodenum/Jejunum | Na⁺-glucose co-transport (SGLT1), Na⁺-amino acid co-transport, osmotic water absorption | Cl⁻ secretion via CFTR channels, HCO₃⁻ secretion |
| Ileum | Na⁺/H⁺ exchange, Cl⁻/HCO₃⁻ exchange (coupled electroneutral NaCl absorption), bile acid reabsorption (terminal ileum via ASBT transporter) | Cl⁻ secretion (CFTR) |
| Colon | Electroneutral NaCl absorption (ENaC channels in distal colon regulated by aldosterone), short-chain fatty acid (SCFA) absorption | Cl⁻ and K⁺ secretion, mucus secretion |
Why is the Na⁺-glucose co-transporter (SGLT1) clinically important? Because it is the basis for oral rehydration solution (ORS): glucose in ORS drives sodium absorption, which in turn drives water absorption. This single mechanism saves millions of lives.
- The small bowel has segmenting contractions (mix chyme) and peristaltic contractions (propel contents aborally). Transit time is ~3–5 hours.
- The colon has haustra segmentation (slows transit, promotes absorption) and mass movements (propels faecal material distally). Transit time is ~12–36 hours.
- The migrating motor complex (MMC) is a cyclical "housekeeper" pattern during fasting that sweeps residual material through the small bowel.
Any process that accelerates transit (e.g., hyperthyroidism, IBS-D) reduces contact time for absorption → diarrhoea. Conversely, processes that slow transit (e.g., opioids, diabetic autonomic neuropathy with small bowel stasis) can allow bacterial overgrowth → diarrhoea.
The colon contains ~10¹³–10¹⁴ bacteria. Normal flora:
- Ferment undigested carbohydrates → short-chain fatty acids (butyrate, propionate, acetate) → colonic energy source + promotes water/Na⁺ absorption
- Resist colonisation by pathogens (colonisation resistance)
- Disruption by antibiotics → C. difficile overgrowth, osmotic diarrhoea from unfermented carbohydrates
From senior notes [5]:
- Watershed areas between SMA and IMA territories are vulnerable to ischaemia:
- Griffiths' point (splenic flexure) — between ascending left colic artery and marginal artery of Drummond
- Sudeck's point (rectosigmoid junction) — between left colic artery and superior rectal artery
- Ischaemic colitis can present with bloody diarrhoea and cramping abdominal pain, particularly in elderly patients with cardiovascular risk factors.
4. Aetiology and Pathophysiology
This is the core of understanding diarrhoea. Every cause of diarrhoea operates through one (or more) of four fundamental pathophysiological mechanisms:
4.1 The Four Mechanisms of Diarrhoea
Mechanism: Poorly absorbed, osmotically active solutes remain in the gut lumen, drawing water into the lumen by osmosis.
Key feature: Diarrhoea stops with fasting (because the offending solute is no longer being ingested).
Stool osmotic gap = 290 − 2 × (stool Na⁺ + stool K⁺). An osmotic gap > 125 mOsm/kg suggests osmotic diarrhoea (unmeasured solutes in the lumen).
| Cause | Mechanism |
|---|---|
| Lactase deficiency | Undigested lactose remains in the lumen → osmotic water retention + bacterial fermentation → gas, bloating, watery diarrhoea. Very common in East Asians (~90% lactase non-persistence). |
| Osmotic laxatives (lactulose, MgSO₄, polyethylene glycol) | Non-absorbable solutes in lumen. |
| Sorbitol/mannitol (dietetic foods, gums, mints) [2] | Sugar alcohols are poorly absorbed → osmotic diarrhoea. |
| Malabsorption syndromes (see below) | Unabsorbed nutrients remain in lumen. |
Mechanism: Active secretion of ions (predominantly Cl⁻ via CFTR) exceeds absorption. Water follows ions into the lumen.
Key feature: Diarrhoea persists despite fasting. Usually large volume and watery. Stool osmotic gap is < 50 mOsm/kg (because the osmolality is accounted for by electrolytes).
| Cause | Mechanism |
|---|---|
| Cholera toxin (V. cholerae) | Toxin permanently activates Gs → ↑cAMP in enterocytes → opens CFTR Cl⁻ channels → massive Cl⁻ and water secretion (up to 20 L/day — "rice-water stools") |
| Enterotoxigenic E. coli (ETEC — travellers' diarrhoea) | Heat-labile toxin (LT) → ↑cAMP; heat-stable toxin (ST) → ↑cGMP → Cl⁻ secretion |
| Bile acid malabsorption [2] | Bile acid malabsorption occurs when terminal ileum fails to reabsorb bile acids. It may cause osmotic diarrhoea and induce secretory diarrhoea (at higher level). Unabsorbed bile acids stimulate colonic Cl⁻ secretion. Occurs after ileal resection, Crohn's disease, or idiopathic (primary bile acid diarrhoea). Post-cholecystectomy diarrhoea often has a bile acid component. |
| Endocrine tumours: VIPoma, carcinoid syndrome, Zollinger-Ellison syndrome [2] | VIPoma: VIP activates adenylate cyclase → ↑cAMP → secretory diarrhoea (WDHA syndrome: Watery Diarrhoea, Hypokalaemia, Achlorhydria). Carcinoid: 5-HT stimulates intestinal secretion/motility and inhibits intestinal absorption → watery, non-bloody diarrhoea [6]. Gastrinoma: excess gastric acid overwhelms duodenal buffering capacity → low pH inactivates pancreatic lipase → steatorrhoea + direct mucosal damage. |
| Microscopic colitis (collagenous/lymphocytic) | Chronic watery diarrhoea in elderly women, often drug-induced (PPIs, NSAIDs, SSRIs). Colonic mucosa looks grossly normal on colonoscopy — must biopsy. |
| Laxative abuse [2] | Stimulant laxatives (senna, bisacodyl) stimulate Cl⁻ secretion and inhibit absorption. |
| Villous adenoma of colon | Rarely, large villous adenomas secrete mucus rich in K⁺ and Cl⁻, causing secretory diarrhoea with hypokalaemia and alkalosis [4]. |
Mechanism: Damage to the intestinal mucosa → exudation of blood, mucus, protein, and inflammatory cells into the lumen. This disrupts both absorption and barrier function.
Key features: Mucoid, bloody stools with PMN in stools. [2] Frequently associated with fever, abdominal pain, and systemic inflammatory response.
| Cause | Mechanism |
|---|---|
| Inflammatory bowel disease (IBD) | Ulcerative colitis: Immune-mediated diffuse continuous mucosal and submucosal inflammation [3], starting from the rectum and extending proximally. Crypt abscesses, goblet cell depletion, pseudopolyps. Bloody diarrhoea with mucus. Crohn's disease: Immune-mediated focal patchy transmural inflammation [3] anywhere mouth-to-anus (commonest: terminal ileum and colon). Granulomas (must exclude TB), skip lesions, deep ulcers, fistulae, abscesses. Diarrhoea may be bloody or non-bloody depending on location. |
| Invasive bacterial infection | Shigella, Salmonella, Campylobacter, C. difficile, invasive E. coli (EIEC, EHEC) — organisms invade mucosa or produce cytotoxins → mucosal necrosis, inflammation, bloody diarrhoea (dysentery). |
| C. difficile | Commonly associated with Clostridium difficile and patients usually has a history of antibiotic use. [3] Toxin A (enterotoxin) and toxin B (cytotoxin) → mucosal inflammation, pseudomembrane formation, watery-to-bloody diarrhoea. |
| Intestinal tuberculosis | Important DDx in HK. Usually ileocaecal involvement. Granulomatous inflammation (must distinguish from Crohn's). Diarrhoea, abdominal pain, weight loss, night sweats. |
| Ischaemic colitis | Hypoperfusion → mucosal ischaemia → sudden onset cramping abdominal pain with mild-to-moderate rectal bleeding developing ≤ 24h [5]. Usually affects watershed areas. |
| Radiation colitis | Hx of abdominal irradiation [2]. Acute or chronic mucosal damage → bloody diarrhoea. |
| Colorectal carcinoma | Worrying signs: alternating diarrhoea and constipation, passage of mucus, tenesmus, pencil-thin stools [2]. |
Mechanism: Altered intestinal transit time → if too fast, there is insufficient contact time for absorption; if too slow, bacterial overgrowth may occur.
| Cause | Mechanism |
|---|---|
| IBS-D | Altered motility: ↑frequency, irregularity of luminal contractions [5]; visceral hypersensitivity [5]; serotoninergic imbalance: ↑5-HT release in IBS-D [5] |
| Hyperthyroidism | Excess thyroid hormone increases GI motility → reduced transit time → diarrhoea |
| Diabetic autonomic neuropathy | Paradoxically, can cause both diarrhoea (↑motility, SIBO) and constipation |
| Post-vagotomy | Disrupted vagal control of gastric emptying → rapid gastric emptying → dumping syndrome with diarrhoea |
| Carcinoid syndrome | 5-HT stimulates intestinal secretion/motility [6] |
4.2 Aetiology by Clinical Setting
| Category | Organisms / Causes | Key Features |
|---|---|---|
| Viral | Norovirus (commonest cause of outbreaks in HK), Rotavirus (children), Adenovirus, Astrovirus | Watery, self-limiting 1–3 days, N&V prominent, low-grade fever. Norovirus: projectile vomiting, highly contagious, winter peaks. |
| Bacterial — toxin-mediated (food poisoning) | Staphylococcus aureus (preformed toxin), Bacillus cereus (emetic type) | Very short incubation (1–6 hours), prominent vomiting, self-limiting < 24h. No fever. |
| Bacterial — enterotoxigenic | ETEC, V. cholerae, C. perfringens | Watery, secretory. ETEC = commonest travellers' diarrhoea. |
| Bacterial — invasive/inflammatory | Salmonella, Shigella, Campylobacter jejuni, EHEC (O157:H7), Yersinia | Fever, bloody diarrhoea (dysentery), abdominal pain. Campylobacter is commonest bacterial cause in many countries. |
| Parasitic | Giardia lamblia, Entamoeba histolytica, Cryptosporidium | Giardiasis (profuse bubbly diarrhoea) is more common than realised. [1] Amoebic dysentery: bloody "anchovy sauce" stools. |
| C. difficile infection | Post-antibiotic exposure | History of antibiotic use [3]. Watery to bloody diarrhoea, cramping, fever, ↑WCC. Can cause toxic megacolon [3]. |
| Drug-induced | Alcohol, antibiotics, digoxin, colchicine, cytotoxic agents, H₂-receptor antagonists, iron compounds, laxatives, metformin, sildenafil, statins, thyroxine [1]; also Acid-suppressing agents: antacids (esp Mg-containing), H₂RA, PPI; β-blocker, NSAID/5-ASA, misoprostol, theophylline, vitamin and mineral supplements, herbal products [2] | Mechanism varies: osmotic (Mg antacids, metformin), secretory (misoprostol, colchicine), altered flora (antibiotics), motility changes (erythromycin acts as motilin agonist). |
| Food allergy/intolerance | Lactose intolerance, fructose malabsorption | Osmotic mechanism. Extremely common in Hong Kong (East Asian lactase non-persistence ~80–90%). |
Chronic diarrhoea is categorised into inflammatory, watery (secretory/osmotic/motility), and fatty (malabsorptive): [2]
| Inflammatory | Watery | Fatty (Malabsorptive) | |
|---|---|---|---|
| Causes | IBD (Crohn's, UC); Chronic infections (C. difficile, M. tuberculosis); CA colon; Chronic ischaemia | Secretory: endocrine tumours (VIPoma, carcinoid, ZES), bile salt malabsorption, laxative abuse. Osmotic: lactase deficiency, osmotic laxatives, (malabsorption). Motility: IBS, hyperthyroidism | Enteropathy: coeliac disease, short gut syndrome, Crohn's disease. Pancreatic insufficiency: chronic pancreatitis, CA pancreas, CF |
| Clinical features | Mucoid, bloody stools; PMN in stools | Watery diarrhoea; Changes with fasting (↓ in osmotic, motility; persists in secretory — usually large volume) | Watery diarrhoea + steatorrhoea + weight loss + nutritional deficiency |
| Ix | CBC, L/RFT, APR; Stool microbiology; Appropriate imaging; Ileocolonoscopy ± Bx | CBC, L/RFT, APR; Spot stool for Na/K; Appropriate imaging; Endoscopy as indicated | CBC, L/RFT, APR; Spot ± timed stool; Appropriate imaging; Endoscopy as indicated |
Drug-Induced Diarrhoea — Don't Forget!
Drug-induced diarrhoea [2] is one of the most commonly overlooked causes. Always take a thorough drug history. Key offenders:
- Metformin: osmotic mechanism (accumulation of unabsorbed substrates)
- PPIs: altered gut microbiome → ↑risk of CDI, SIBO
- Antibiotics: direct mucosal irritation + altered flora
- Colchicine: inhibits microtubule function in rapidly dividing enterocytes
- Magnesium-containing antacids: osmotic
- SSRIs: ↑serotonin in gut → ↑secretion and motility
5. Classification Systems
- Acute (< 2 weeks), Persistent (2–4 weeks), Chronic (> 4 weeks)
- Osmotic, Secretory, Inflammatory, Motility-related (as detailed above)
- Watery: osmotic or secretory
- Bloody/mucoid (dysentery): inflammatory
- Fatty (steatorrhoea): malabsorptive — pale, bulky, foul-smelling, floating stools that are difficult to flush
- Small bowel diarrhoea: large-volume, watery, rarely bloody, may have steatorrhoea, periumbilical/RIF pain
- Large bowel (colonic) diarrhoea: small-volume, frequent, may be bloody/mucoid, urgency, tenesmus, lower abdominal/suprapubic pain
| Osmotic | Secretory | |
|---|---|---|
| Fasting | Diarrhoea stops | Diarrhoea persists |
| Stool volume | Usually < 1 L/day | Often > 1 L/day |
| Stool osmotic gap | > 125 mOsm/kg | < 50 mOsm/kg |
6. Clinical Features
6.1 Symptoms (with Pathophysiological Basis)
Key history: Establish what the patient means by diarrhoea. Analyse the nature of the stools, frequency, associated symptoms (e.g. abdominal pain) and constitutional symptoms such as fever and weight loss. Drug history, travel history and family history. [1]
| Symptom | Pathophysiological Basis |
|---|---|
| Watery stools | Secretory or osmotic mechanism — unabsorbed solutes or active ion secretion draw water into the lumen |
| Bloody stools | Mucosal inflammation/ulceration → damage to blood vessels in the lamina propria or submucosa (invasive infection, IBD, ischaemia, colorectal cancer) |
| Mucus in stools | Exudation from inflamed goblet cells and colonic mucosa; also seen in IBS (but without blood) and villous adenoma |
| Steatorrhoea (pale, bulky, oily, foul-smelling, floating, difficult to flush) | Fat malabsorption → undigested fat in stool. Causes: pancreatic insufficiency (no lipase), bile salt deficiency (no emulsification), small bowel mucosal disease (no absorptive surface). Floats because of gas from bacterial fermentation of undigested fat. |
| Profuse bubbly diarrhoea [1] | Characteristic of Giardia — the trophozoites coat the duodenal/jejunal mucosa, impairing fat and carbohydrate absorption. Fermentation of unabsorbed carbohydrates produces gas → bubbly/frothy stools. |
| Rice-water stools | V. cholerae — massive secretory diarrhoea. Stools contain mucus flecks in clear fluid. |
| Symptom | Pathophysiological Basis |
|---|---|
| Abdominal pain — cramping/colicky | Increased peristalsis or bowel distension from luminal fluid/gas. IBS-D pain is characteristically associated with defecation [5] — relieved or worsened by defecation. |
| Abdominal pain — constant, localised | Transmural inflammation (Crohn's), ischaemia, perforation, abscess |
| Tenesmus (sensation of incomplete evacuation + constant urge) | Rectal/distal colonic inflammation — inflamed rectum sends persistent afferent signals to defecation centres even when empty. Classic in UC proctitis, rectal cancer. |
| Urgency | Rectal irritability from inflammation or rapid colonic transit |
| Nausea and vomiting | Common in viral gastroenteritis (vagal stimulation from upper GI inflammation); also in food poisoning (preformed toxins stimulate vagal afferents). In bowel obstruction: retrograde propulsion. |
| Borborygmi (audible bowel sounds) | Hyperperistalsis — increased contractions moving fluid and gas through narrowed or irritated bowel |
| Bloating and flatulence | Bacterial fermentation of unabsorbed carbohydrates (lactose intolerance, SIBO, IBS). Gas production (H₂, CO₂, CH₄). |
| Alternating diarrhoea and constipation [2] | Worrying sign of colorectal cancer — tumour intermittently obstructs then allows passage. Also seen in IBS-M. |
| Pencil-thin stools [2] | Suggest distal colonic or rectal narrowing (cancer, stricture). |
| Symptom | Pathophysiological Basis |
|---|---|
| Fever | Inflammatory response to invasive infection, or systemic inflammation in IBD/ischaemia. High fever ≥ 38.5°C suggests inflammatory diarrhoea requiring investigation [2]. |
| Weight loss | Malabsorption (coeliac, chronic pancreatitis), increased catabolism (malignancy, IBD flare), reduced intake (anorexia from illness). Constitutional symptoms: loss of appetite, loss of weight, malaise [2] — think malignancy. |
| Dehydration — thirst, dry mucous membranes, reduced skin turgor, tachycardia, hypotension, oliguria | Fluid and electrolyte loss exceeding intake. Dehydration and electrolyte imbalance from reduced oral intake, vomiting, defective intestinal absorption, transudation of fluid into peritoneal cavity [4]. |
| Fatigue/weakness | Hypokalaemia (from K⁺ loss in stool — especially secretory diarrhoea), anaemia (iron/B12/folate deficiency in malabsorption; chronic disease in IBD), dehydration. |
| Night sweats | TB, lymphoma, severe IBD, malignancy |
| Feature | Associated Condition | Mechanism |
|---|---|---|
| Episcleritis / uveitis, oral ulcers, arthritis, skin rashes [2] | IBD | Immune-mediated extra-intestinal manifestations — circulating immune complexes, molecular mimicry, shared epitopes |
| Flushing (red/violaceous, face/neck/upper chest) [6] | Carcinoid syndrome | Overproduction of histamine, kallikrein → accounts for flushing [6] |
| Dermatitis herpetiformis (intensely pruritic papules/vesicles) | Coeliac disease | IgA deposition at dermal papillae → granular IgA on immunofluorescence |
| Necrolytic migratory erythema [6] | Glucagonoma | Hypoaminoacidaemia from glucagon excess → epidermal necrosis |
| Erythema nodosum / Pyoderma gangrenosum | IBD (esp. Crohn's) | Immune-mediated cutaneous manifestation |
| Aphthous ulcers | Crohn's disease, coeliac disease, Behçet's | Immune-mediated mucosal inflammation |
| Hyperpigmentation, vitiligo | Addison's disease (adrenal insufficiency) | ↑ACTH stimulates melanocytes (diarrhoea from cortisol deficiency → altered Na⁺/water handling) |
| Goitre, tremor, exophthalmos | Hyperthyroidism | Thyroid hormone excess → ↑GI motility |
| Wheezing and dyspnoea [6] | Carcinoid syndrome | Bronchospasm (10–20%): often during flushing episodes [6] — from histamine and serotonin |
6.2 Signs (with Pathophysiological Basis)
Key examination: Focus on the general state (especially of severe gastroenteritis), the abdomen, rectum and skin. Ideally the stool should be examined (note the presence of blood, mucus or steatorrhoea). [1]
| Sign | Significance | Pathophysiological Basis |
|---|---|---|
| Dehydration signs: dry mucous membranes, reduced skin turgor, sunken eyes, tachycardia, hypotension, CRT > 2s | Severity assessment | Fluid loss from GI tract > intake. Intravascular volume depletion → sympathetic compensation (↑HR) → if severe, hypotension. |
| Cachexia / muscle wasting | Chronic diarrhoea with malabsorption, malignancy | Protein-energy malnutrition. ↑GI loss (e.g. intestinal fistula, diarrhoea) is a predisposing factor for malnutrition; muscle wasting causes respiratory muscle weakness → respiratory failure [8]. |
| Pallor | Anaemia | Iron deficiency (chronic blood loss in IBD/CRC; malabsorption in coeliac), B12/folate deficiency (terminal ileum disease/resection), anaemia of chronic disease |
| Lymphadenopathy | Infection, lymphoma, metastatic CRC | Reactive or neoplastic |
| Peripheral oedema | Hypoalbuminaemia | Protein-losing enteropathy (IBD, lymphangiectasia) or malabsorption → ↓albumin → ↓oncotic pressure → oedema |
| Thyrotoxic signs (goitre, tremor, lid lag, lid retraction, exophthalmos) [2] | Hyperthyroidism | Excess T₃/T₄ → ↑GI motility → diarrhoea |
| Sign | Significance | Pathophysiological Basis |
|---|---|---|
| Distension | Bowel obstruction, toxic megacolon, ascites | Gas/fluid accumulation proximal to obstruction; paralytic ileus; peritoneal fluid |
| Tenderness — localised | Appendicitis, diverticulitis, Crohn's abscess, ischaemic colitis | Localised peritoneal inflammation → somatic pain |
| Tenderness — diffuse with guarding/rigidity | Perforation, generalised peritonitis | Transmural inflammation → parietal peritoneal irritation → reflex muscle contraction |
| Peritoneal signs suggestive of acute inflammation [2] | Surgical emergency | As above |
| Palpable mass — RIF | Crohn's (inflammatory mass/abscess), caecal tumour, appendiceal abscess, ileocaecal TB | Transmural inflammation with phlegmon/abscess formation in Crohn's; neoplastic mass in CRC |
| Palpable mass — LIF | Sigmoid cancer, diverticular abscess | Tumour or pericolic inflammatory mass |
| Hepatomegaly | Metastatic disease (CRC liver mets), carcinoid liver metastases, amoebic liver abscess | CRC commonly metastasises to liver via portal venous drainage. Carcinoid syndrome largely signifies liver mets as normal liver inactivates bioactive hormonal products [6]. |
| Hyperactive bowel sounds | Infectious diarrhoea, early obstruction, IBS | Increased peristaltic activity |
| Absent bowel sounds | Paralytic ileus, late obstruction, peritonitis | Loss of peristaltic activity from neuromuscular dysfunction or peritoneal irritation |
The rectal examination is essential [1] — don't skip it!
| Finding | Significance |
|---|---|
| Empty rectum with loose stool on glove | Active diarrhoea |
| Loaded rectum with liquid stool | Spurious (overflow) diarrhoea — faecal impaction with overflow |
| Rectal mass | Rectal carcinoma |
| Blood/mucus on glove | Inflammatory/neoplastic colonic disease |
| Tender, boggy prostate | Prostatic abscess (can present with diarrhoea as a red herring in elderly) |
| Anal involvement (fissures, fistulae, skin tags, perianal abscess) [2] | Crohn's disease — anorectal exam: note anal involvement in Crohn's disease [2] |
| Finding | Significance |
|---|---|
| Erythema nodosum (tender, red nodules on shins) | IBD, infections, sarcoidosis |
| Pyoderma gangrenosum (painful, rapidly enlarging ulcers with undermined violaceous borders) | IBD (especially UC) |
| Dermatitis herpetiformis (intensely pruritic grouped vesicles on extensor surfaces) | Coeliac disease |
| Necrolytic migratory erythema | Glucagonoma |
| Venous telangiectasiae (nose, upper lip, malar area) [6] | Carcinoid syndrome — appears late due to prolonged vasodilation [6] |
| Angular cheilitis, glossitis | Nutritional deficiency (iron, B12, folate) from malabsorption |
7. Metabolic and Electrolyte Consequences of Diarrhoea
This is extremely high-yield for chemical pathology questions.
Stool is rich in K⁺ (typically 30–80 mmol/L). Diarrhoea → K⁺ loss → hypokalaemia.
Approach to hypokalaemia with diarrhoea [4]:
- Check plasma HCO₃⁻ to determine acid-base status
- Check paired spot urine K⁺ to determine renal vs. extrarenal loss
| Scenario | Plasma HCO₃⁻ | Urine K⁺ | Interpretation |
|---|---|---|---|
| Acute diarrhoea | ↓ (metabolic acidosis) | < 20 mmol/L | Extrarenal K⁺ loss with metabolic acidosis from HCO₃⁻ loss in stool (lower GI secretions are rich in HCO₃⁻) |
| Chronic diarrhoea / laxative abuse | ↑ (metabolic alkalosis) | < 20 mmol/L | Extrarenal K⁺ loss; alkalosis develops from volume contraction → ↑aldosterone → HCO₃⁻ reabsorption |
Why does acute diarrhoea cause metabolic acidosis? Lower GI secretions (ileal and colonic) are rich in HCO₃⁻. Loss of this HCO₃⁻ → non-anion-gap metabolic acidosis (NAGMA, also called hyperchloraemic metabolic acidosis — the kidneys retain Cl⁻ to maintain electroneutrality).
Why does chronic diarrhoea sometimes cause metabolic alkalosis? Chronic volume depletion → secondary hyperaldosteronism → ↑H⁺ secretion in distal nephron + ↑HCO₃⁻ reabsorption → contraction alkalosis. Laxative abuse often presents this way.
- Acute watery diarrhoea: Hypotonic fluid depletion → water loss → ↑Na concentration AND Na loss → ↓ECF volume [4]. The net effect on [Na⁺] depends on the relative loss of water vs. sodium:
- If the patient drinks plain water to compensate → dilutional hyponatraemia
- If the patient is unable to drink (e.g., severe vomiting, altered consciousness) → hypernatraemia
- GI causes of hypotonic fluid depletion include vomiting and diarrhoea [4]
- Loss of HCO₃⁻-rich intestinal secretions → NAGMA
- The mnemonic for NAGMA causes: HARDUPS — Hyperalimentation, Acetazolamide/Addison's, Renal tubular acidosis, Diarrhoea, Uretero-sigmoidostomy, Pancreatic fistula, Saline (excessive NS infusion)
| Disturbance | Mechanism |
|---|---|
| Hypomagnesaemia | Mg²⁺ lost in stool; coeliac/Crohn's impairs Mg absorption |
| Hypocalcaemia | ↓vitamin D absorption in fat malabsorption → ↓Ca²⁺; also hypoMg impairs PTH secretion |
| Hypophosphataemia | Malabsorption; refeeding syndrome risk in malnourished chronic diarrhoea patients |
| Zinc deficiency | Chronic diarrhoea depletes zinc → further impairs mucosal healing (vicious cycle). WHO recommends zinc supplementation for children with acute diarrhoea. |
8. Special Populations
Opportunistic infections become important:
- CMV colitis — especially in HIV with CD4 < 50; also post-transplant
- Cryptosporidium — chronic watery diarrhoea, no effective treatment (immune reconstitution is key)
- Microsporidium — chronic diarrhoea in AIDS
- Mycobacterium avium complex (MAC) — disseminated disease with diarrhoea, CD4 < 50
- Isospora belli — treatable with cotrimoxazole
- Drug side effects (antiretrovirals, immunosuppressants)
- Remember spurious diarrhoea and the rectal examination in the elderly [1]
- UTI in elderly: clinical presentation is notoriously non-specific — may present with poor appetite, nausea and vomiting, diarrhoea, fever without localising signs [9]
- Ischaemic colitis: elderly with CVS risk factors
- Medications: polypharmacy → drug-induced diarrhoea
- C. difficile: higher risk due to frequent antibiotic exposure and hospitalisation
- Colorectal cancer: age is the strongest risk factor
- Most commonly ETEC (enterotoxigenic E. coli)
- Self-limiting in majority; empirical azithromycin or fluoroquinolone for severe/inflammatory cases
- Prevention: food and water hygiene; bismuth subsalicylate or rifaximin for prophylaxis in high-risk travellers
| Surgery | Mechanism of Diarrhoea |
|---|---|
| Cholecystectomy | Loss of gallbladder reservoir → continuous bile acid delivery to gut → bile acid diarrhoea |
| Ileal resection | Loss of bile acid reabsorption site → bile acids in colon stimulate Cl⁻ secretion (secretory diarrhoea); if > 100 cm resected → also fat malabsorption (insufficient bile acids) |
| Gastrectomy / vagotomy | Dumping syndrome: rapid gastric emptying → osmotic diarrhoea in the small bowel |
| Short bowel syndrome | Insufficient absorptive surface → malabsorptive diarrhoea |
| Whipple procedure | Pancreatic insufficiency → fat malabsorption → steatorrhoea |
High Yield Summary
Definition: ≥ 3 loose/liquid stools per day or stool weight > 200 g/day. Classify by duration: acute (< 2 wk), persistent (2–4 wk), chronic (> 4 wk).
Four pathophysiological mechanisms: Osmotic (stops with fasting, gap > 125), Secretory (persists with fasting, large volume, gap < 50), Inflammatory (bloody, mucoid, PMN+), Motility disorder (altered transit).
Hong Kong relevance: Norovirus outbreaks, V. parahaemolyticus (raw seafood), rising IBD incidence, high CRC rates, lactose intolerance (~80–90% East Asians), intestinal TB as Crohn's mimic.
Critical history points: What does the patient mean by diarrhoea? Stool consistency (Bristol chart), frequency, blood/mucus, associated pain, timing (nocturnal = organic), drug history, travel history, family history.
Smoking & IBD: Smoking is a risk factor for Crohn's but protective for UC.
Appendicectomy & IBD: Prior appendicectomy is a risk factor for Crohn's but protective for UC.
Metabolic consequences: Hypokalaemia (K⁺ loss in stool), NAGMA (HCO₃⁻ loss in stool in acute diarrhoea), dehydration → pre-renal AKI.
Drug-induced: Alcohol, antibiotics, metformin, colchicine, Mg-antacids, PPIs, SSRIs, laxatives, statins, iron — always check drug history.
Don't forget: Spurious diarrhoea in elderly (DRE!), overflow around impacted stool.
IBS: Very common, does NOT cause nocturnal diarrhoea, pain is associated with defecation.
Active Recall - Diarrhoea (Definition, Epidemiology, Etiology, Clinical Features)
[1] Lecture slides: murtagh merge.pdf (Diarrhoea section) [2] Senior notes: Ryan Ho Fundamentals.pdf (Section 3.3.8 Chronic Diarrhoea, p289–290; Section on Lower GI Bleeding / Colorectal evaluation, p264, p283) [3] Senior notes: felixlai.md (IBD section: Etiology, Epidemiology, Clinical Manifestation, Pathological/Endoscopic features; Volvulus/Toxic megacolon section) [4] Senior notes: Ryan Ho Chemical Path.pdf (Hyponatraemia p13; Hypokalaemia p18) [5] Senior notes: Ryan Ho GI.pdf (IBS section p118; Ischaemic Colitis p146; Malabsorption/Coeliac p126) [6] Senior notes: Ryan Ho Endocrine.pdf (Carcinoid Syndrome p103; Glucagonoma p102) [7] Senior notes: Ryan Ho Critical Care.pdf (AKI and Renal Support p25) [8] Senior notes: Ryan Ho Fluids and Nutrition.pdf (Malnutrition predisposing factors p7) [9] Senior notes: Ryan Ho Urogenital.pdf (UTI in elderly p128)
Differential Diagnosis of Diarrhoea
The differential diagnosis of diarrhoea is one of the broadest in medicine. The key to navigating it efficiently is a structured framework that triages by acuity (acute vs. chronic), mechanism (osmotic / secretory / inflammatory / motility / fatty), and clinical context (age, travel, drugs, immunocompromise). Let's build this from first principles.
Murtagh's approach is a powerful clinical reasoning tool: start with the probability diagnosis (the common things), then systematically exclude the serious disorders not to be missed, check for pitfalls (often missed), run through the masquerades checklist, and finally ask — "is the patient trying to tell me something?" [1]
2. Probability Diagnoses (Common Things Are Common)
These are what you will see day in, day out on the wards and in clinic.
| Diagnosis | Why It's Common | Key Differentiating Feature |
|---|---|---|
| Gastroenteritis / infective enteritis [1] | By far the commonest cause worldwide. Viral (norovirus, rotavirus) > bacterial > parasitic. | Self-limiting (< 7 days), often preceded by N&V, contact/food history, no alarm features. |
| Dietary indiscretion [1] | Overeating, spicy foods, excessive alcohol, caffeine — these directly stimulate gut motility or secretion. | Temporal relationship to dietary intake; no systemic upset. |
| Antibiotic reaction [1] | Antibiotics disrupt normal colonic flora → osmotic diarrhoea from unfermented carbohydrates + loss of colonisation resistance. | Onset during or shortly after antibiotic course. Must always consider C. difficile as a more serious cause. |
| Diagnosis | Why It's Common | Key Differentiating Feature |
|---|---|---|
| Irritable bowel syndrome (IBS) [1] | Prevalence up to 25% in East Asia, 3.7% in HK [5]. The single most common cause of chronic diarrhoea referred to gastroenterology. | IBS rarely causes nocturnal diarrhoea but causes recurrent pain in the right hypochondrium. [1] Pain related to defecation. No alarm features, no weight loss. Diagnosis of exclusion (Rome IV). |
| Drug reactions (e.g. laxatives) [1] | Polypharmacy is rampant. Drugs that can cause diarrhoea: alcohol, antibiotics, digoxin, colchicine, cytotoxic agents, H₂-receptor antagonists, iron compounds, laxatives, metformin, sildenafil, statins, thyroxine. [1] Also acid-suppressing agents (esp Mg-containing antacids), H₂RA, PPI, caffeine, β-blocker, NSAID/5-ASA, misoprostol, theophylline, vitamin and mineral supplements, herbal products [2][5] | Temporal relationship to drug initiation. Resolves on withdrawal (or dose reduction). |
| Chronic infections [1] | Particularly important in Hong Kong: parasites (Giardia, Entamoeba), C. difficile, TB. In immunocompromised: CMV, Cryptosporidium, MAC. | Persistent/relapsing course; travel history; antibiotic exposure for CDI; immunosuppression for opportunistic infections. |
IBS vs. Organic Disease — The Night-Time Rule
IBS rarely causes nocturnal diarrhoea. [1] If a patient is woken from sleep by diarrhoea, think organic: IBD, microscopic colitis, secretory tumours, diabetic autonomic neuropathy. This single question — "Does the diarrhoea wake you at night?" — has tremendous discriminating power.
3. Serious Disorders Not to Be Missed
These are the diagnoses that will harm or kill the patient if you miss them. You must actively exclude these in every case.
| Diagnosis | Why You Must Not Miss It | Key Differentiating Features |
|---|---|---|
| Colorectal cancer (CRC) [1] | HK has one of the highest CRC rates globally. Curable if caught early; lethal if missed. | Alternating diarrhoea and constipation, passage of mucus, tenesmus, pencil-thin stools [2]. Age > 50, male, FHx, Hx of IBD/polyps. Iron-deficiency anaemia (R-sided), fresh blood PR (L-sided). CRC can only be excluded with colonoscopy. [3] |
| Ovarian cancer [1] | Peritoneal carcinomatosis can cause diarrhoea through serosal inflammation of bowel loops, obstruction, or malabsorption. | Vague abdominal bloating, early satiety, pelvic pain. Insidious onset in postmenopausal women. CA-125, CT, pelvic exam. |
| Peritoneal cancer [1] | Primary peritoneal carcinoma or peritoneal carcinomatosis from any GI/gynae primary. | Ascites, abdominal distension, weight loss, altered bowel habit. |
| Diagnosis | Why Serious | Key Features |
|---|---|---|
| Cholera [1] | Massive secretory diarrhoea → fatal dehydration within hours if untreated. | Rice-water stools, profound dehydration, endemic/epidemic setting. |
| Typhoid / paratyphoid [1] | Bacteraemia → systemic sepsis, intestinal perforation, haemorrhage. | Stepladder fever, relative bradycardia, rose spots, hepatosplenomegaly. Diarrhoea is actually a later feature; early disease may have constipation. |
| Amoebiasis [1] | Entamoeba histolytica → amoebic dysentery, liver abscess. | Bloody "anchovy sauce" stools, RUQ pain (liver abscess), travel to endemic areas. |
| Enterohaemorrhagic E. coli (EHEC) [1] | O157:H7 → HUS (haemolytic uraemic syndrome), especially in children. | Bloody diarrhoea WITHOUT fever (toxin-mediated, not invasive), ↑LDH, ↓platelets, fragmented RBCs, AKI. Do NOT give antibiotics — may increase toxin release and HUS risk. |
| Malaria [1] | Can present with diarrhoea especially in children; severe P. falciparum has high mortality. | Travel to endemic area, cyclical fevers/rigors, splenomegaly, pancytopenia. |
| HIV infection (AIDS) [1] | Chronic diarrhoea is extremely common in advanced HIV — multiple aetiologies including opportunistic infections, HIV enteropathy, medication side effects. | Risk factors for HIV, weight loss, oral candida, generalised lymphadenopathy, CD4 count guides differential. |
| Crohn's Disease | Ulcerative Colitis | |
|---|---|---|
| Inflammation | Focal patchy, transmural [3] | Diffuse continuous, mucosal and submucosal [3] |
| Distribution | Mouth to anus; skip lesions | Starts at rectum, extends proximally; no skipping |
| Key histology | Granuloma (MUST exclude TB) [3] | Crypt abscesses, goblet cell depletion, pseudopolyps [3] |
| Key DDx challenge | vs. intestinal TB (both granulomatous, both ileocaecal) | vs. infectious colitis, radiation colitis, ischaemic colitis |
| Unique complications | Fistulae, abscesses, strictures [3] | Toxic megacolon (colon ≥ 6 cm + systemic toxicity) [3] |
Both IBD conditions must be differentiated from: infectious colitis (E. coli, Salmonella, Shigella, Campylobacter, Yersinia, amebiasis — excluded with stool studies), C. difficile (particularly in patients treated with antibiotics), and irritable bowel syndrome (chronic abdominal pain and altered bowel habits in the absence of organic cause). [3]
Most common cause of intestinal obstruction in infants between 6–36 months of age. [7] In adults, intussusception is uncommon and usually driven by a pathological lead point (polyp, lymphoma, Meckel's diverticulum). [7] Presents with colicky pain, "redcurrant jelly" stools (bloody mucus), and a sausage-shaped mass.
A pelvic appendix (21% of cases [4]) can irritate the rectum/sigmoid → diarrhoea rather than the "classic" RIF pain. This is a classic pitfall — the diarrhoea misleads you away from the surgical diagnosis. Think of it when a patient has diarrhoea + low-grade fever + pelvic/suprapubic discomfort + DRE tenderness.
These are the ones that get missed on rounds. Examiners love them.
| Diagnosis | Why It's Missed | Key Clue |
|---|---|---|
| Coeliac disease [1] | Up to 50% asymptomatic; many present with mild IBS-like symptoms rather than classic steatorrhoea. Rare in Asians but increasingly recognised. | IgA anti-tTG antibody. Steatorrhoea, dermatitis herpetiformis, iron/B12/folate deficiency, osteoporosis. |
| Faecal impaction with spurious diarrhoea [1] | Remember spurious diarrhoea and the rectal examination in the elderly. [1] Carers/nurses report "diarrhoea" — it's actually overflow liquid stool around an impacted mass. | Elderly, immobile, on opioids/anticholinergics. DRE reveals loaded rectum. |
| Lactase deficiency [1] | Prevalence up to 90% in adult Asians [5] — so common it's often not considered as a "diagnosis." | Symptoms after dairy intake (bloating, cramps, watery diarrhoea). Hydrogen breath test or empirical lactose-free trial. [3] |
| Giardia lamblia infection [1] | Giardiasis (profuse bubbly diarrhoea) is more common than realised. [1] Stool O&P has poor sensitivity (single sample ~50%); need 3 samples or stool antigen test. | Profuse bubbly/frothy diarrhoea, bloating, foul-smelling stool. Travel history or contaminated water. |
| Cryptosporidium infection [1] | Especially in immunocompromised (HIV CD4 < 100). Modified acid-fast stain on stool or PCR needed. | Profuse watery diarrhoea, often chronic in immunocompromised. |
| Malabsorption states [1] | Chronic pancreatitis, short gut, Crohn's → steatorrhoea may be subtle. Patients may present with nutritional deficiency (anaemia, osteoporosis) rather than frank diarrhoea. | Weight loss, nutritional deficiencies out of proportion to apparent disease. |
| Vitamin C and other oral drugs [1] | High-dose vitamin C is osmotically active → osmotic diarrhoea. Often self-prescribed, not volunteered in drug history. | Ask specifically about supplements and "natural" remedies. |
| Nematode infections: strongyloides (threadworm), whipworm, hookworm [1] | Chronic low-grade infections may persist for decades (strongyloides autoinfection cycle). Can reactivate catastrophically with immunosuppression (hyperinfection syndrome). | Eosinophilia, travel/endemic area, perianal itch (threadworm), iron-deficiency anaemia (hookworm). |
| Radiotherapy [1] | Radiation colitis: occurs in weeks to years after abdominal or pelvic irradiation. [3] Late radiation enteritis may present years after treatment. | History of RT for cervical/prostate/rectal/bladder cancer. Telangiectasiae on endoscopy. |
| Diverticulitis [1] | Diarrhea rather than abdominal pain may be the predominant symptom in some cases [3], particularly with colonic irritation or microperforation. | LIF pain (sigmoid) or RIF pain (Asian: right-sided diverticulosis more common [4]), fever, ↑WCC. CT is diagnostic. |
| Post-GIT surgery [1] | Cholecystectomy (bile acid diarrhoea), ileal resection, gastrectomy/vagotomy (dumping), Whipple (pancreatic insufficiency). | Surgical history! Mechanism varies — bile acid, rapid transit, malabsorption. |
| Ischaemic colitis (elderly) [1] | Watershed ischaemia presenting with crampy pain + bloody diarrhoea. Can be transient and self-resolving, so often missed if not scoped. | Elderly, CVS risk factors, sudden onset LIF pain, mild rectal bleeding within 24h. |
Rarities (but examinable) [1]
| Diagnosis | Key Features |
|---|---|
| Addison disease [1] | Cortisol deficiency → impaired Na⁺/water absorption, ↑GI motility. Hyperpigmentation, hypotension, hyperkalaemia, hyponatraemia. |
| Carcinoid tumours [1] | Episodic flushing (85%), diarrhoea (80%), bronchospasm (10–20%), carcinoid heart disease [6]. Signifies liver metastases. |
| Short bowel syndrome [1] | After massive small bowel resection (< 200 cm remaining). Malabsorptive diarrhoea, nutritional deficiency. |
| Amyloidosis [1] | Amyloid deposition in GI wall → dysmotility, malabsorption, autonomic neuropathy → diarrhoea. |
| Toxic shock [1] | S. aureus or Strep toxin-mediated multiorgan failure. Profuse watery diarrhoea, fever, rash, shock. |
| Zollinger–Ellison syndrome [1] | Gastrinoma → massive acid hypersecretion → inactivates pancreatic lipase → steatorrhoea; also direct mucosal damage → secretory diarrhoea. |
These are systemic diseases that "masquerade" as GI disease. Think of them when the diarrhoea doesn't fit a typical GI pattern.
| Masquerade | Mechanism | Key Clue |
|---|---|---|
| Diabetes [1] | Autonomic neuropathy → disordered motility (alternating diarrhoea/constipation), SIBO. Also osmotic diarrhoea from metformin or sorbitol in "sugar-free" diabetic foods. | Long-standing poorly controlled DM, postural hypotension, gastroparesis, peripheral neuropathy. |
| Drugs [1] | Multiple mechanisms (see drug list above). | Always take a thorough drug history, including OTC and supplements. [1] |
| Hyperthyroidism [1] | Excess thyroid hormone → ↑intestinal motility → ↓transit time → diarrhoea. | Weight loss despite good appetite, heat intolerance, tremor, tachycardia/AF, goitre, thyroid eye disease. |
Is the Patient Trying to Tell Me Something?
Yes, diarrhoea may be a manifestation of anxiety state or irritable bowel syndrome. [1] Functional GI disorders are driven by the brain-gut axis. Anxiety activates the autonomic nervous system → ↑colonic motility and secretion via vagal and sympathetic pathways. Serotonin (5-HT) is the key neurotransmitter — 95% of the body's serotonin is in the gut. This is why SSRIs (which increase serotonin) can worsen diarrhoea, and why 5-HT₃ antagonists (ondansetron, alosetron) help IBS-D.
6. Differential Diagnosis by Clinical Context
| Feature | Non-Inflammatory (Watery) | Inflammatory (Dysentery) |
|---|---|---|
| Organisms | Norovirus, Rotavirus, ETEC, V. cholerae, C. perfringens, S. aureus (preformed toxin), B. cereus | Shigella, Salmonella, Campylobacter, EHEC, C. difficile, E. histolytica, Yersinia |
| Site of action | Proximal small bowel (toxin-mediated) | Colon / distal ileum (mucosal invasion or cytotoxin) |
| Stool | Watery, large volume, no blood | Bloody, mucoid, small volume, frequent |
| Fever | Low-grade or absent | High-grade (≥ 38.5°C) [2] |
| Pain | Periumbilical, crampy, mild | Lower abdominal, severe, with tenesmus |
| WCC | Normal | Elevated (leukocytosis with left shift) |
| Stool WBC | Absent | Present (PMN) |
This table ties together aetiology, mechanism, and the distinguishing features:
| Mechanism | Conditions | Stool Character | Fasting Test | Stool Osmotic Gap |
|---|---|---|---|---|
| Osmotic | Lactase deficiency, osmotic laxatives, Mg antacids, sorbitol/mannitol, vitamin C [1][2] | Watery, improves with fasting | Stops | > 125 mOsm/kg |
| Secretory | VIPoma, carcinoid, ZES, bile acid malabsorption, laxative abuse (stimulant), microscopic colitis [2][5] | Watery, large volume, persists with fasting | Persists | < 50 mOsm/kg |
| Inflammatory | IBD (Crohn's/UC), C. difficile, M. tuberculosis, CRC, ischaemic colitis, radiation colitis [2][5] | Bloody, mucoid, PMN+ | Variable | Variable |
| Malabsorptive | Coeliac disease, chronic pancreatitis, CA pancreas, CF, short gut syndrome, Crohn's (ileal) [2][5] | Steatorrhoea (pale, bulky, oily, foul) | Variable | Variable |
| Motility | IBS, hyperthyroidism, diabetic autonomic neuropathy [2][5] | Watery, often alternating with constipation | Stops or improves | Variable |
| Condition | Why Particularly Relevant in HK |
|---|---|
| Intestinal TB | High prevalence of TB in HK. Ileocaecal involvement mimics Crohn's disease (both granulomatous). Granuloma in Crohn's — MUST exclude TB. [3] AFB smear/culture on biopsy specimens is mandatory. |
| Right-sided diverticulitis | Right-sided diverticulitis is more common in Asian population. [3] May mimic appendicitis (RIF pain + fever + ↑WCC). CT is diagnostic. |
| Lactose intolerance | Up to 90% of adult Asians are lactase-deficient [5]. Consider in any chronic watery diarrhoea with dairy exposure. |
| Vibrio parahaemolyticus | Raw/undercooked seafood (very common in HK cuisine). Explosive watery diarrhoea 12–24h after ingestion. |
| CRC | HK has one of the highest global incidence rates. Screening colonoscopy recommended from age 45–50. |
These are the features that should trigger urgent investigation rather than expectant management:
- Weight loss, constitutional symptoms
- PR bleeding
- Old age onset (> 50y)
- FHx of CA colon or IBD
- Nocturnal diarrhoea (organic until proven otherwise)
- Anaemia, leukocytosis, ↑ESR/CRP
- +ve FOBT
- Abnormal biochemistry
- High fever ≥ 38.5°C
- Severe dehydration requiring hospitalisation
High Yield — When NOT to Investigate
In some instances such as acute self-limiting diarrhoea, nil investigation is required. [1] Most acute viral gastroenteritis resolves in 1–3 days. The indications for investigation of acute diarrhoea are: severe illness requiring hospitalisation, inflammatory features (bloody/mucoid, high fever), high-risk hosts (elderly, immunocompromised, pregnant, prior IBD), and persistent diarrhoea > 1 week. [2]
| Acute | Chronic | |
|---|---|---|
| Probability | Gastroenteritis, dietary indiscretion, antibiotic reaction [1] | IBS, drug reactions, chronic infections [1] |
| Serious | Cholera, typhoid, EHEC, amoebiasis, malaria, C. difficile, intussusception, pelvic appendicitis [1] | CRC, ovarian CA, IBD, HIV, pseudomembranous colitis [1] |
| Pitfalls | Giardia, Cryptosporidium, spurious diarrhoea [1] | Coeliac disease, lactose intolerance, radiation colitis, ischaemic colitis, post-GIT surgery, nematodes, drug/supplement-induced, diverticulitis [1] |
| Masquerades | Drugs, anaphylaxis (GI symptoms) [10] | Diabetes, drugs, hyperthyroidism [1] |
| Rarities | Toxic shock [1] | Addison's, carcinoid, ZES, amyloidosis, short bowel syndrome [1] |
| Functional | — | Anxiety state, IBS [1] |
High Yield Summary — DDx of Diarrhoea
-
Always clarify what the patient means by "diarrhoea" — consistency matters more than frequency.
-
Murtagh framework: Probability → Serious not to miss → Pitfalls → Masquerades → Psychosocial.
-
Acute: Most common = viral gastroenteritis. Investigate only if severe, inflammatory, high-risk host, or persistent > 1 week.
-
Chronic: Categorise by stool type — inflammatory (bloody/mucoid), watery (osmotic vs secretory vs motility), fatty (malabsorptive).
-
Nocturnal diarrhoea = organic until proven otherwise (rules against IBS).
-
Spurious diarrhoea in the elderly = overflow around faecal impaction. DRE is diagnostic.
-
Hong Kong-specific DDx: Intestinal TB (vs Crohn's — must do AFB), right-sided diverticulitis, V. parahaemolyticus, lactose intolerance (90% Asians), CRC (very high incidence).
-
Always check drug history — drugs are one of the commonest treatable causes across all age groups.
-
Masquerades: Diabetes (autonomic neuropathy + metformin), hyperthyroidism, Addison's disease.
-
Alarm features mandate investigation: weight loss, PR bleeding, old onset, FHx CRC/IBD, nocturnal symptoms, anaemia, raised inflammatory markers.
Active Recall - Differential Diagnosis of Diarrhoea
References
[1] Lecture slides: murtagh merge.pdf (Diarrhoea section, p32–34) [2] Senior notes: Ryan Ho Fundamentals.pdf (Section 3.3.8 Chronic Diarrhoea p290; Acute Diarrhoea p289; Lower GI Bleeding evaluation p283) [3] Senior notes: felixlai.md (IBD section: Crohn's DDx, UC DDx, Endoscopic/histological features, Diverticulitis DDx, Appendicitis DDx) [4] Senior notes: maxim.md (Acute appendicitis anatomy, Diverticular disease) [5] Senior notes: Ryan Ho GI.pdf (IBS p118–119; Chronic Diarrhoea p115; Lactose intolerance p130; Ischaemic colitis p146) [6] Senior notes: Ryan Ho Endocrine.pdf (Carcinoid Syndrome p103) [7] Senior notes: felixlai.md (Intussusception section) [10] Senior notes: Ryan Ho Critical Care.pdf (Anaphylactic shock — GI symptoms p24)
Diagnostic Criteria, Algorithm and Investigations for Diarrhoea
There is no single universally mandated "diagnostic criterion" for diarrhoea in the way there is for, say, rheumatoid arthritis. Instead, the diagnosis is clinical and operational:
| Parameter | Threshold | Explanation |
|---|---|---|
| Stool frequency | ≥ 3 times/day [2] | Increased frequency compared to baseline |
| Stool weight | > 250 g/24h [2] | Objective quantification; rarely measured outside research |
| Stool fluidity | Increased (Bristol Stool Chart types 5–7) [2] | Patient-reported; always clarify what they mean by "diarrhoea" |
The real diagnostic challenge is not "does this patient have diarrhoea?" — that is usually obvious — but rather "what is causing it?" and "does it need investigation at all?"
In some instances such as acute self-limiting diarrhoea nil is required. [1] Most acute diarrhoea is viral gastroenteritis and resolves within 1–3 days with supportive care alone. Investigation is indicated when the clinical picture suggests something more serious:
Indications for laboratory evaluation in acute diarrhoea [2]:
- Severe illness (e.g., necessitating hospitalisation)
- Inflammatory diarrhoea (bloody, mucoid, high fever ≥ 38.5°C)
- High-risk hosts (age ≥ 70y, comorbidities, immunocompromised, prior IBD, pregnant)
- Persistent diarrhoea for > 1 week
1.2 Diagnostic Criteria for Key Specific Causes
Some underlying causes of diarrhoea have their own formal diagnostic criteria. The important ones to know:
IBS is a diagnosis of exclusion made when the Rome IV criteria are met AND alarm features are absent:
Recurrent abdominal pain on average ≥ 1 day/week, associated with ≥ 2 of: [5]
- Related to defecation
- Associated with change in frequency of stools
- Associated with change in form (appearance) of stools
For the past 3 months, with symptom onset ≥ 6 months before diagnosis. [5]
Why "related to defecation" rather than "relieved by defecation"? Because Rome IV recognises that pain may worsen with defecation in some IBS patients (not just improve). The previous Rome III criterion of "relief" was too restrictive.
Alarm features alerting to alternative diagnosis [5]:
- Hx: weight loss, constitutional symptoms, PR bleeding, old age onset, FHx of CA colon or IBD
- Ix: +ve FOBT, anaemia, leukocytosis, ↑ESR, abnormal biochemistry
IBD is diagnosed by the combination of clinical features, endoscopic findings, histology, and exclusion of infective/other causes. There is no single blood test or criterion. Key diagnostic elements:
- Crohn's disease: Focal patchy transmural inflammation + non-caseating granulomas on biopsy (MUST exclude TB [3]); skip lesions on endoscopy; deep ulcers; fistulae
- Ulcerative colitis: Diffuse continuous mucosal and submucosal inflammation starting from the rectum [3]; crypt abscesses, goblet cell depletion, pseudopolyps; classified by Montreal phenotypic classification [3]:
| Classification | Description |
|---|---|
| E1 | Proctitis — involvement limited to rectum |
| E2 | Left-sided (distal UC) — involvement extending up to splenic flexure |
| E3 | Extensive (pancolitis) — involvement extending proximal to splenic flexure |
Diagnosed by the combination of:
- Clinical: diarrhoea (≥ 3 unformed stools in 24h) + history of antibiotic exposure
- Laboratory: C. difficile toxin A (enterotoxin) and B (cytotoxin) by PCR [3] or toxin EIA + GDH screening algorithm
- Serology: IgA anti-tissue transglutaminase (anti-tTG) antibody positive (if IgA deficient → use IgG anti-tTG or anti-deamidated gliadin peptide)
- Small bowel biopsy (duodenal D2/D3): villous atrophy, crypt hyperplasia, inflammatory infiltrates in lamina propria
- Clinical response to gluten-free diet confirms the diagnosis
Toxic megacolon is defined as total or segmental non-obstructive dilatation of colon ≥ 6 cm or caecum > 9 cm AND the presence of systemic toxicity. [3]
The algorithm is fundamentally about answering a series of questions in order: Is this acute or chronic? → Is investigation needed? → What type of diarrhoea is it? → What specific tests are needed?
Key Principle
No firm rule — investigation is directed by Hx and P/E. [2][5] The algorithm above is a guide, not a rigid protocol. A young patient with watery diarrhoea after starting metformin needs only a drug history, not a colonoscopy. An elderly man with iron-deficiency anaemia and altered bowel habits needs an urgent colonoscopy regardless of stool character.
3. Investigation Modalities — Detailed Breakdown
Minimum investigations include blood tests and stool examination, imaging, and endoscopy ± biopsy. [2][5]
| Test | What It Tells You | Key Findings and Interpretation |
|---|---|---|
| CBC [2][5] | Anaemia, leukocytosis, eosinophilia, thrombocytosis [2] | Microcytic anaemia (iron deficiency) → chronic blood loss (CRC, IBD), malabsorption (coeliac). Macrocytic anaemia → B12 deficiency (terminal ileum disease/resection), folate deficiency (proximal SB disease). Leukocytosis → infection, IBD flare. Eosinophilia → parasite infestation, allergy, collagen vascular diseases, eosinophilic gastroenteritis, neoplasm [5]. Thrombocytosis → reactive in IBD/infection (acute phase reactant). |
| APR: ESR, CRP [1][2][5] | Systemic inflammation | Elevated in IBD, infection, malignancy. CRP in Crohn's disease is typically higher than in UC; CRP monitoring under therapy is useful to document efficacy of anti-inflammatory treatment. [3] Normal ESR/CRP argues against active inflammatory or infectious cause (but does NOT exclude microscopic colitis, IBS, or osmotic causes). |
| LFT [2][5] | Albumin, liver function | Hypoalbuminaemia [3] → malabsorption and protein-losing enteropathy. Also think chronic liver disease, nephrotic syndrome. Low albumin is a marker of malnutrition severity. Deranged LFTs → think metastatic disease (CRC liver mets), PSC (associated with UC), amoebic liver abscess. |
| RFT and electrolytes (U&E) [1][2][5] | Hydration, renal function, electrolytes | ↑Creatinine/urea → pre-renal AKI from dehydration. Hypokalaemia → stool K⁺ loss (see chemical path approach below). Metabolic acidosis (↓HCO₃⁻) → acute diarrhoea (HCO₃⁻-rich stool loss). Metabolic alkalosis (↑HCO₃⁻) → chronic diarrhoea, laxative abuse. Hyponatraemia or hypernatraemia → depends on relative water vs. Na loss and oral intake. |
| TFT [2][5] | Thyroid function | Hyperthyroidism → ↑GI motility → diarrhoea. Order in any chronic watery diarrhoea without obvious cause. |
| Serology [2][5] | Specific aetiologies | AutoAb for IBD: p-ANCA (UC), ASCA (Crohn's) [5] — supportive, not diagnostic alone. IgA anti-tTG → coeliac disease. Serum Ig levels → hypogammaglobulinaemia → recurrent GE [5]. ± HIV Ab if noted lymphopenia [5]. |
| Glucose / HbA1c | Diabetes | Diabetic autonomic neuropathy causing diarrhoea; also DKA can present with diarrhoea. |
| Serum iron and vitamin B12 level [3] | Nutritional deficiency | Vitamin B12 deficiency [3] → terminal ileum disease (Crohn's, resection). Iron deficiency → chronic GI blood loss or malabsorption. |
This is a high-yield exam topic — the systematic approach to determining the cause of hypokalaemia [4][11]:
Step 1: Check plasma HCO₃⁻ — is there metabolic acidosis or alkalosis? Step 2: Check paired spot urine K⁺ — is K loss renal ( > 20 mmol/L) or extrarenal ( < 20 mmol/L)?
| Plasma HCO₃⁻ | Urine K⁺ | Interpretation |
|---|---|---|
| ↓ (acidosis) | < 20 mmol/L | Acute diarrhoea [4] — extrarenal K loss with HCO₃⁻ loss in stool |
| ↑ (alkalosis) | < 20 mmol/L | Chronic diarrhoea, laxative abuse, previous diuretics, villous adenoma of colon [4] |
| ↓ (acidosis) | > 20 mmol/L | Type 1 or 2 renal tubular acidosis [4] |
| ↑ (alkalosis) | > 20 mmol/L | Vomiting, mineralocorticoid excess, current diuretics, gentamicin, Mg depletion [4] |
Why does acute diarrhoea cause acidosis + low urine K? Lower GI secretions are HCO₃⁻-rich → loss of alkali → metabolic acidosis. K⁺ is lost in the stool (extrarenal), so the kidney appropriately conserves K⁺ → low urine K⁺.
Why does chronic diarrhoea sometimes cause alkalosis? Chronic volume depletion → secondary hyperaldosteronism → increased H⁺ secretion in distal nephron + HCO₃⁻ reabsorption → contraction alkalosis.
A useful further tool in the chemical pathology workup of metabolic acidosis from diarrhoea is distinguishing it from RTA using the urine anion gap and urine osmolal gap [11]:
| Diarrhoea | Distal RTA | |
|---|---|---|
| Urine pH | Usually < 5.3 | Always > 5.5 |
| Urine AG | Negative (decreased) — kidneys are appropriately excreting NH₄⁺ | Positive (increased) — kidneys cannot acidify urine |
| Urine OG | Increased — unmeasured NH₄⁺ contributes to osmolality | Decreased |
3.3 Stool Analysis
Stool analysis is the single most informative investigation class in diarrhoea. Think of it as "blood tests for the gut."
Ideally the stool should be examined (note the presence of blood, mucus or steatorrhoea). [1]
| Observation | Interpretation |
|---|---|
| Watery, no blood | Osmotic, secretory, or motility-related |
| Bloody / mucoid | Inflammatory (invasive infection, IBD, ischaemia, CRC) |
| Pale, bulky, oily, foul-smelling, floating | Steatorrhoea → fat malabsorption |
| Rice-water | V. cholerae |
| "Redcurrant jelly" | Intussusception (blood + mucus) |
| Test | Principle | Key Findings |
|---|---|---|
| Stool for occult blood | Detects haemoglobin/haem in stool. Routinely ordered unless gross blood. [5] | Positive → occult GI bleeding (CRC, IBD, angiodysplasia). False positives with red meat, iron supplements, NSAIDs. |
| Stool for Na⁺, K⁺ → Stool osmolal gap | Stool osmolal gap = stool osmolarity − 2 × [stool Na⁺ + stool K⁺] [5]. Stool osmolarity is assumed to be ~290 mOsm/kg (isotonic with plasma). | ↑ gap ( > 125 mOsm/kg) = osmotic diarrhoea (unmeasured solutes like lactose, Mg²⁺ in lumen). ↓ gap ( < 50 mOsm/kg) = secretory diarrhoea (electrolytes account for nearly all osmolality). [5] |
| Stool pH | Reflects colonic fermentation products. | pH < 5.6 → carbohydrate malabsorption [5] (e.g., lactose intolerance — unabsorbed lactose fermented by bacteria → lactic acid → acidifies stool). |
| Stool for leukocytes (WBC) | Presence of PMNs indicates mucosal inflammation. | Positive → inflammatory cause [5] (invasive infection, IBD). Absent in osmotic, secretory, motility causes. |
| Faecal calprotectin | 24 kDa dimer of Ca-binding proteins [5] released by neutrophils. A surrogate marker for intestinal inflammation. Stable at room temperature [5] — practical advantage. | ↑ in: (1) infectious diarrhoea; (2) Crohn's or UC; (3) cancer [5]. Usually used for triage → negative result makes serious inflammatory pathology unlikely. [5] Excellent for distinguishing IBS (calprotectin normal) from IBD (calprotectin elevated). Cut-off typically 50 μg/g (some centres use 100 or 150 μg/g). |
Faecal Calprotectin — The IBD vs IBS Gatekeeper
Faecal calprotectin is one of the most useful non-invasive tests in chronic diarrhoea workup. It has > 90% sensitivity and ~80% specificity for distinguishing IBD from IBS. A normal calprotectin essentially rules out active IBD and avoids the need for colonoscopy in low-risk patients. Think of it as the "troponin of the gut" — it tells you there is inflammation, but not the specific cause.
| Test | What It Detects | When to Order |
|---|---|---|
| Stool culture [1] | Bacterial pathogens: Salmonella, Shigella, Campylobacter, Yersinia, E. coli O157:H7, Aeromonas, Plesiomonas [5] | Inflammatory diarrhoea, severe watery diarrhoea, persistent > 1 week, high-risk host |
| Stool microscopy for ova and cysts [1] | Protozoa: Entamoeba, Giardia, Cryptosporidium [3]; helminths | Travel history, chronic diarrhoea, eosinophilia. Need 3 samples to improve sensitivity (single sample sensitivity ~50% for Giardia). |
| Stool antigen detection [3] | E. coli O157:H7, Entamoeba, Cryptosporidium, Giardia [3] | More sensitive than microscopy for specific organisms. Giardia stool antigen is now first-line. |
| C. difficile toxin PCR [1][3] | C. difficile toxin A (enterotoxin) and B (cytotoxin) [3] | History of antibiotic use [3]; hospitalised patients; healthcare-associated diarrhoea. Many centres use a two-step algorithm: GDH screen (high sensitivity) → if positive, confirm with toxin EIA or PCR (high specificity). |
| Shiga toxin test [3] | Shiga toxin (EHEC) | Bloody diarrhoea without fever (especially children) → HUS risk |
| Multipathogen PCR panel | Simultaneous detection of bacterial, viral, and parasitic pathogens | Inflammatory diarrhoea or diagnostic uncertainty. Rapid turnaround but more expensive. |
| Test | Principle | Key Findings |
|---|---|---|
| 24-hour stool fat excretion [5] | Quantitative fat measurement on a standardised 100 g fat/day diet for 72 hours. NOT commonly performed [5] but gold standard for documenting steatorrhoea. | Normal: < 9% of intake. Malabsorption/maldigestion: > 18 g/day. Malabsorptive ( < 8 g/100 g stool) vs maldigestive ( > 8 g/100 g stool) — the latter suggests pancreatic insufficiency or biliary steatorrhoea [5]. |
| Faecal elastase-1 | Pancreatic elastase is resistant to intestinal degradation. Measures pancreatic exocrine function. | < 200 μg/g = pancreatic exocrine insufficiency; < 100 μg/g = severe insufficiency. False low in watery stool (dilution). |
| Stool laxative screen | Detects stimulant laxatives (phenolphthalein, bisacodyl, senna) or osmotic laxatives (Mg²⁺, PEG) | Important when factitious/laxative-abuse diarrhoea is suspected (often young women, healthcare workers). Check stool Mg²⁺ (normal < 45 mmol/L; elevated in Mg-containing laxative abuse). |
| Modality | Indications | Key Findings |
|---|---|---|
| CXR [3] | Indicated in patients presenting with fever or if perforation is suspected [3] | Free subdiaphragmatic air → perforation (e.g., toxic megacolon, perforated diverticulitis). Pulmonary TB (miliary pattern, upper lobe consolidation) → consider intestinal TB. |
| AXR (supine) [3] | Indicated to evaluate for colonic calibre [3]. Also: bowel gas pattern, calcifications. | Toxic megacolon: colon ≥ 6 cm or caecum > 9 cm [3]. Thumbprinting → mucosal oedema (ischaemic colitis, IBD). Pancreatic calcifications → chronic pancreatitis. Dilated SB loops → small bowel obstruction. |
| CT abdomen/pelvis with IV contrast [12] | Suspected complicated pathology: diverticulitis, abscess, perforation, obstruction, mesenteric ischaemia, staging of CRC | Bowel wall thickening (IBD, infection, ischaemia), pericolonic fat stranding (diverticulitis), abscess, free fluid, mesenteric vessel occlusion, lymphadenopathy, liver metastases. |
| CT/MR enterography [5] | For IBD and its complications [5]. Gold standard for small bowel Crohn's assessment. | Mural hyperenhancement, wall thickening, "comb sign" (engorged vasa recta), strictures, fistulae, abscesses. MR enterography preferred (no radiation) for young IBD patients needing serial imaging. |
| USG abdomen [5] | Pancreatic disease [5], gallstones, liver metastases, ascites | Pancreatic calcification/duct dilatation (chronic pancreatitis), gallstones (post-cholecystectomy bile acid diarrhoea), hepatomegaly/liver lesions. |
| Barium follow-through / SB enema [1][5] | Mucosal abnormalities [5] of small bowel. Largely replaced by CT/MR enterography but may still be used. | "String sign" (narrowed terminal ileum in Crohn's), cobblestoning, fistulae, diverticulae, strictures. Selective radiology (e.g. small bowel enema) [1]. |
| SeHCAT scan | ⁷⁵Se-homotaurocholic acid retention test. Gold standard for bile acid malabsorption. | 7-day retention < 15% → bile acid malabsorption (< 10% moderate, < 5% severe). Not widely available in HK; empirical trial of cholestyramine is often used instead. |
AVOID Endoscopy for Acute Abdomen
AVOID endoscopy for acute abdomen: sealed-off perforation may open by gas insufflation during endoscopy. [12] If you suspect perforation (free air on CXR/AXR, peritoneal signs on examination), endoscopy is contraindicated. Get a CT scan instead.
3.5 Endoscopy
Endoscopy is the definitive investigation for many causes of chronic diarrhoea and is essential whenever inflammatory or neoplastic pathology is suspected.
Colonoscopy + Biopsy is indicated for inflammatory diarrhoea workup. [3]
| Aspect | Details |
|---|---|
| Indications | Chronic diarrhoea (especially inflammatory), suspected IBD, suspected CRC, persistent infectious diarrhoea, evaluation after positive calprotectin or occult blood |
| Key principle | Biopsy should be taken from the left and right colon AND rectum even if normal in appearance [3] — this is critical because microscopic colitis (collagenous or lymphocytic colitis) has a grossly normal mucosa but diagnostic histological changes. Similarly, early or mild IBD may look subtle macroscopically. |
| IBD-specific | MUST do AFB smear and culture with sensitivity testing to rule out enteric TB [3] — absolutely mandatory in Hong Kong and Asia, where intestinal TB and Crohn's disease overlap significantly. |
Endoscopic findings and their interpretation:
| Finding | Condition | Why |
|---|---|---|
| Diffuse continuous inflammation starting from rectum | Ulcerative colitis | Immune-mediated mucosal inflammation that always involves rectum and extends proximally without gaps |
| Skip lesions, deep longitudinal ulcers, cobblestoning | Crohn's disease | Transmural inflammation in discontinuous patches; deep ulcers from full-thickness involvement |
| Pseudomembranes (yellowish adherent plaques) | C. difficile colitis | Fibrin + inflammatory debris + necrotic epithelium overlying inflamed mucosa |
| Pseudopolyps | Ulcerative colitis (chronic) | Islands of regenerating mucosa surrounded by denuded ulcerated mucosa create a polypoid appearance |
| Thumbprinting, segmental colitis at watershed areas | Ischaemic colitis | Submucosal oedema/haemorrhage in watershed zones (splenic flexure, rectosigmoid) |
| Grossly normal mucosa | Microscopic colitis | Inflammation is only at the histological level — must biopsy even if normal |
| Mass, stricture, ulcerated mass | Colorectal cancer | Neoplastic growth; always biopsy |
| Telangiectasiae, pallor, friability | Radiation proctitis/colitis | Vascular sclerosis and new vessel formation after radiation damage |
| Ileocaecal ulceration with surrounding inflammation | Crohn's disease OR intestinal TB | Both cause ileocaecal disease — TB has transverse ulcers, patulous ileocaecal valve, caseating granulomas on Bx; Crohn's has longitudinal ulcers, cobblestoning, non-caseating granulomas |
Histological findings to know:
| Histology | Condition |
|---|---|
| Non-caseating granulomas (must exclude TB) [3] | Crohn's disease |
| Caseating granulomas + AFB positive | Intestinal TB |
| Crypt abscesses, crypt distortion, goblet cell depletion | Ulcerative colitis |
| Villous atrophy + crypt hyperplasia + intraepithelial lymphocytes | Coeliac disease (duodenal biopsy) |
| Thickened subepithelial collagen band ( > 10 μm) | Collagenous colitis |
| Intraepithelial lymphocytosis ( > 20 per 100 epithelial cells) | Lymphocytic colitis |
| Indication | Key Finding |
|---|---|
| Suspected coeliac disease | Duodenal biopsy (D2/D3): villous atrophy, crypt hyperplasia, inflammatory infiltrate |
| Suspected Whipple's disease | PAS-positive macrophages in lamina propria |
| Suspected Giardia (stool negative) | Duodenal aspirate for trophozoites; mucosal biopsy |
| Suspected tropical sprue | Non-specific villous atrophy, crypt hyperplasia |
| Zollinger-Ellison syndrome | Multiple duodenal/jejunal ulcers; thick rugal folds in stomach |
- Video capsule endoscopy (VCE): Non-invasive visualisation of entire small bowel. Used when CT/MR enterography is inconclusive and small bowel Crohn's, obscure GI bleeding, or small bowel tumours are suspected.
- Double-balloon enteroscopy (DBE): Allows biopsy and therapy (e.g., dilatation of Crohn's strictures) in the small bowel.
| Test | What It Tests | Interpretation |
|---|---|---|
| Lactose hydrogen breath test | Lactase activity. Patient ingests 50 g lactose; breath H₂ measured at intervals. Undigested lactose fermented by colonic bacteria → H₂ absorbed → exhaled. | Rise in breath H₂ > 20 ppm above baseline confirms lactose malabsorption. Reproduction of symptoms during test confirms clinical intolerance. |
| Glucose hydrogen breath test | Small intestinal bacterial overgrowth (SIBO). Glucose is normally absorbed in proximal SB; if bacteria are present, they ferment it → early H₂ peak. | Early rise in breath H₂ ( < 90 min) suggests SIBO. |
| D-xylose absorption test | Small bowel mucosal absorptive function. D-xylose is absorbed in proximal SB without need for pancreatic enzymes. | Low urinary excretion / low serum level → mucosal malabsorption (coeliac, tropical sprue). Normal → pancreatic or biliary cause of malabsorption. |
| Schilling test | B12 absorption (now rarely performed, largely replaced by serum B12 + anti-IF antibody + MMA levels). | Helps localise cause of B12 deficiency (pernicious anaemia vs. terminal ileum disease vs. SIBO vs. pancreatic insufficiency). |
| SeHCAT scan | Bile acid retention (see imaging section above) | < 15% 7-day retention → bile acid malabsorption |
| Fasting gut hormone panel | Secretory causes: VIP, gastrin, serotonin (5-HIAA in 24h urine), chromogranin A, calcitonin | Elevated VIP → VIPoma. Elevated gastrin → Zollinger-Ellison. Elevated 5-HIAA → carcinoid. |
| Type | First-Line Investigations | Second-Line / Targeted |
|---|---|---|
| Acute — mild, self-limiting | Nil required [1] | Only if persistent > 1 week or worsening |
| Acute — severe / inflammatory / high-risk | CBC, L/RFT, U&E; stool culture, microscopy for O+C, C. diff toxin PCR; ± blood cultures [1][2] | Endoscopy if persistent; CT if perforation/abscess suspected |
| Chronic — Inflammatory | CBC, APR, L/RFT; faecal calprotectin; stool microbiology; ileocolonoscopy + Bx (with AFB) [2][3][5] | CT/MR enterography for SB Crohn's; serology (ASCA, p-ANCA) |
| Chronic — Watery (Osmotic) | Stool Na/K → osmolal gap; stool pH; dietary review; lactose H₂ breath test [5] | Trial of lactose-free diet; stool laxative screen if suspected factitious |
| Chronic — Watery (Secretory) | Stool Na/K → osmolal gap; fasting gut hormone panel; CT abdomen; colonoscopy + random Bx [2][5] | SeHCAT for bile acid malabsorption; 24h urine 5-HIAA for carcinoid; octreotide scan for NET localisation |
| Chronic — Watery (Motility) | Rome IV criteria; TFT; HbA1c; exclude organic causes first [5] | Anorectal manometry, colonic transit study (rarely needed) |
| Chronic — Fatty (Malabsorptive) | Faecal elastase-1; coeliac serology (IgA anti-tTG); duodenal Bx; CT/MR pancreas [2][5] | 24h stool fat; SB biopsy/imaging; ERCP/MRCP for pancreatic duct disease |
High Yield Summary — Diagnosis of Diarrhoea
-
Most acute diarrhoea needs NO investigation — only investigate if severe, inflammatory, high-risk host, or persistent > 1 week.
-
Key investigations to remember (Murtagh): microscopy and culture of stool, FBE, ESR/CRP, C. difficile tissue culture assay, U&E, specific tests for organisms, endoscopy, selective radiology. [1]
-
Faecal calprotectin is the gatekeeper between IBS and IBD — stable at room temperature, ↑ in infection, IBD, and cancer, negative result makes serious pathology unlikely.
-
Stool osmolal gap = 290 − 2(Na + K): > 125 = osmotic; < 50 = secretory. This single test distinguishes two fundamentally different mechanisms.
-
Stool pH < 5.6 → carbohydrate malabsorption (fermentation produces acid).
-
Colonoscopy with biopsy — always biopsy even if mucosa looks normal (microscopic colitis!); always send for AFB in Hong Kong (TB vs Crohn's).
-
Hypokalaemia workup: Plasma HCO₃⁻ + paired spot urine K⁺ → acute diarrhoea = acidosis + low urine K; chronic/laxative = alkalosis + low urine K.
-
Faecal elastase-1 < 200 μg/g → pancreatic exocrine insufficiency (cause of fatty diarrhoea).
-
Toxic megacolon = colon ≥ 6 cm or caecum > 9 cm + systemic toxicity on AXR — a surgical emergency.
-
IBS = Rome IV (pain ≥ 1 day/wk for 3 months, related to defecation + change in frequency/form, onset ≥ 6 months ago) + NO alarm features.
Active Recall - Diagnosis and Investigations of Diarrhoea
References
[1] Lecture slides: murtagh merge.pdf (Diarrhoea section, p32–34) [2] Senior notes: Ryan Ho Fundamentals.pdf (Section 3.3.7 Acute Diarrhoea p286–287; Section 3.3.8 Chronic Diarrhoea p290–291) [3] Senior notes: felixlai.md (IBD diagnosis: Crohn's section p960; UC section p978; Montreal classification; AFB requirement; toxic megacolon definition) [4] Senior notes: Ryan Ho Chemical Path.pdf (Hypokalaemia approach p18) [5] Senior notes: Ryan Ho GI.pdf (Chronic Diarrhoea workup p115–116; IBS Rome IV p119; Lactose intolerance p130) [11] Senior notes: Ryan Ho Urogenital.pdf (RTA vs diarrhoea differentiation table p44; Hypokalaemia diagnostic evaluation p25) [12] Senior notes: maxim.md (Acute abdomen investigations, imaging of choice, avoid endoscopy in acute abdomen p87)
Management of Diarrhoea
The management of diarrhoea is never a one-size-fits-all algorithm. The treatment depends entirely on (1) acuity (acute vs. chronic), (2) severity (mild self-limiting vs. life-threatening dehydration), (3) mechanism (osmotic / secretory / inflammatory / motility / malabsorptive), and (4) the specific underlying cause. Let's build this from first principles.
Think of diarrhoea management as three parallel tracks running simultaneously:
- Resuscitation and supportive care — keep the patient alive and haemodynamically stable (fluids, electrolytes)
- Symptomatic treatment — reduce stool frequency and discomfort (anti-diarrhoeals, dietary changes)
- Specific treatment — treat the underlying cause (antibiotics for infection, biologics for IBD, surgery for CRC, etc.)
The balance between these tracks shifts depending on context. In a 25-year-old with 2 days of watery diarrhoea after a dodgy takeaway, track 1 (ORS) and waiting is sufficient. In a 70-year-old with bloody diarrhoea, fever, and hypotension, all three tracks fire simultaneously.
3. Track 1 — Resuscitation and Fluid/Electrolyte Management
This is the single most important intervention in acute diarrhoea. More lives are saved by ORS than by any antibiotic.
ORS: replace established deficits in 4 hours + ongoing loss + normal daily requirement. [2]
Why does ORS work? The Na⁺-glucose co-transporter (SGLT1) on the enterocyte brush border remains functional even during secretory diarrhoea (cholera toxin targets Cl⁻ secretion, not glucose-coupled Na⁺ absorption). Glucose in ORS drives Na⁺ absorption, and water follows osmotically. This is why ORS contains both glucose AND sodium — neither alone works as well.
| Component | WHO-ORS (2006 reduced osmolarity) | Rationale |
|---|---|---|
| Na⁺ | 75 mmol/L | Replaces Na⁺ lost in stool |
| K⁺ | 20 mmol/L | Replaces K⁺ lost in stool |
| Glucose | 75 mmol/L | Drives SGLT1-mediated Na⁺/water absorption |
| Citrate | 10 mmol/L | Buffer to counteract metabolic acidosis |
| Osmolarity | 245 mOsm/L | Hypotonic → better water absorption than old formula |
Practical point: In mild cases, commercially available sports drinks or dilute fruit juice with added salt can serve as makeshift ORS, but the WHO formulation is preferred for moderate-to-severe dehydration.
IV fluid if shock, unconscious, paralytic ileus, or fail oral rehydration. [2]
| Indication | Fluid Choice | Rationale |
|---|---|---|
| Hypovolaemic shock | Rapid fluid challenge: 500–1000 mL NS or Ringer's lactate over 5–10 min [13] | Isotonic crystalloid expands intravascular volume. Ringer's lactate is preferred because it contains lactate (metabolised to HCO₃⁻, helps correct acidosis) and has a more physiological electrolyte composition than NS (which can worsen hyperchloraemic acidosis). |
| Ongoing losses | Guided by losses: replace volume-for-volume with appropriate fluid | GI losses (NG aspirates, vomiting, fistula, stoma, diarrhoea, intraluminal) [8] should be replaced. Diarrhoeal stool is roughly isotonic — NS or Ringer's with KCl supplementation is appropriate. |
| Maintenance | 30–40 mL/kg/day [8] water + 1–1.17 mmol/kg/day Na⁺ + 0.9–1.3 mmol/kg/day K⁺ | Once deficits are replaced and the patient is stable, maintenance fluids cover insensible losses and baseline requirements. |
Aim: restore tissue perfusion as evident by urine output > 0.5 mL/kg/h. [8]
| Abnormality | Correction | Caution |
|---|---|---|
| Hypokalaemia | Oral KCl if mild (K⁺ 3.0–3.5); IV KCl if severe (K⁺ < 3.0 or symptomatic). Max rate: 10–20 mmol/h peripherally, 40 mmol/h centrally with cardiac monitoring. | Never give K⁺ bolus — risk of fatal arrhythmia. Always check Mg²⁺ — hypoMg impairs K⁺ repletion [4]. |
| Metabolic acidosis | Usually self-corrects with volume resuscitation + K⁺ replacement. NaHCO₃ only if pH < 7.1. [11] | Risks of NaHCO₃: hypokalaemia by transcellular shift, ↓ionic calcium, volume expansion, paradoxical cerebral acidosis [11]. |
| Hypomagnesaemia | IV MgSO₄ 2–4 g over 2–4 hours if severe; oral Mg supplement if mild. | GI causes of hypoMg: ↓intake, malabsorption, chronic diarrhoea, intestinal resection [4]. |
| Hyponatraemia / Hypernatraemia | Correct slowly (max 8–10 mmol/L per 24 hours for hypoNa). | Rapid correction of hypoNa → central pontine myelinolysis. Rapid correction of hyperNa → cerebral oedema. |
The AKI Trap
Severe diarrhoea → pre-renal AKI is extremely common. Treat hypotension by aggressive fluid resuscitation. Do NOT give diuretics. [14] Stop nephrotoxic drugs (NSAIDs, ACEI/ARB) [14][15]. Monitor urine output. If oliguric despite adequate resuscitation, consider intrinsic renal disease (ATN) and involvement of renal team.
4. Track 2 — Symptomatic / Supportive Treatment
Dietary changes: avoid dairy products [2] — dairy products may be difficult to digest in presence of diarrhoea due to secondary lactose malabsorption [2]. This occurs because inflammation or villous damage from any cause temporarily depletes brush-border lactase, even in patients who are normally lactose-tolerant.
| Recommendation | Rationale |
|---|---|
| Small frequent meals, bland diet (BRAT: bananas, rice, applesauce, toast) | Easy to digest, low fibre reduces mechanical stimulation of inflamed gut |
| Avoid dairy | Secondary lactose malabsorption |
| Avoid caffeine, alcohol | Both stimulate intestinal motility and secretion |
| Avoid high-osmolality foods (sorbitol/mannitol in "sugar-free" products) | Osmotic diarrhoea |
| Low FODMAP diet (for IBS) [5] | FODMAPs ("fermentable oligo-, di-, mono-saccharides and polyols") are poorly absorbed, osmotically active, and fermented by bacteria → gas, bloating, diarrhoea |
| Agent | Mechanism | Indications | Contraindications / Cautions |
|---|---|---|---|
| Loperamide (Imodium) [2][5] | μ-opioid receptor agonist in the myenteric plexus → ↓peristalsis, ↑transit time, ↑water and electrolyte absorption, ↑anal sphincter tone. Does NOT cross BBB → no central opioid effects. "Loper" = Latin loper relates to running — it stops the "running." | Non-inflammatory acute diarrhoea in adults; chronic diarrhoea (IBS-D, short bowel syndrome, high stool output). Useful in managing chronic diarrhoea in patients with high stool output. [3] | To be used with caution in afebrile inflammatory diarrhoea. Antimotility agents may prolong/exacerbate illness in inflammatory diarrhoea [2] — by slowing transit, you keep invasive organisms and toxins in contact with mucosa longer → risk of toxic megacolon (especially in EHEC, C. difficile, Shigella). Absolute CI: bloody/febrile diarrhoea, suspected C. difficile, children < 2 years. |
| Diphenoxylate-atropine (Lomotil) [5] | μ-opioid agonist (diphenoxylate) + anticholinergic (atropine added to discourage abuse). Similar mechanism to loperamide. | Alternative to loperamide for symptomatic relief. | Same cautions as loperamide. Atropine component → anticholinergic side effects (dry mouth, urinary retention, tachycardia). |
| Bismuth subsalicylate [2] | Multiple mechanisms: antisecretory (blocks prostaglandin-mediated Cl⁻ secretion), antimicrobial (direct bactericidal), anti-inflammatory. Bismuth salicylate as alternative to antimotility agents [2]. | Travellers' diarrhoea (prophylaxis and treatment), mild acute diarrhoea. | Salicylate component → avoid in aspirin allergy, children (Reye's syndrome), patients on anticoagulants. Black stools (harmless but may mimic melaena). |
| Octreotide [5] | Somatostatin analogue → ↓motility, ↓intestinal secretion, ↓splanchnic blood flow. | Useful in neuroendocrine tumour [5] (carcinoid syndrome, VIPoma), high-output enterocutaneous fistula, dumping syndrome, refractory secretory diarrhoea. | Expensive, requires SC injection; can cause gallstones (↓gallbladder motility), hyperglycaemia. |
| Cholestyramine (bile acid sequestrant) [5] | Bile acid-binding resin → binds unabsorbed bile acids in the colonic lumen → prevents bile-acid-stimulated Cl⁻ secretion. "Cholestyramine" = cholesterol + styrene resin + amine. | Bile acid malabsorption [5] (post-ileal resection, Crohn's, post-cholecystectomy diarrhoea, IBS-D). Used with caution since it will impair fat-soluble vitamin absorption. [3] | Impairs absorption of fat-soluble vitamins (A, D, E, K) and many oral medications (take other drugs 1 hour before or 4 hours after). GI side effects (bloating, constipation). No effects on diarrhoea caused by carbohydrate malabsorption. [3] |
| Intraluminal adsorbents (charcoal) [5] | Adsorbs toxins, gases, and drugs in the GI lumen. | Limited evidence; sometimes used for toxin-related diarrhoea or excessive gas. | May adsorb medications → reduce efficacy. |
| Racecadotril (acetorphan) | Enkephalinase inhibitor → prevents breakdown of endogenous enkephalins → ↓intestinal Cl⁻/water secretion WITHOUT affecting motility. | Acute watery diarrhoea (especially in children); used in some European/Asian centres. | Advantage over loperamide: antisecretory without antimotility effect → theoretically safer in inflammatory diarrhoea. |
Golden Rule: Antimotility Agents in Inflammatory Diarrhoea
Antimotility agents (loperamide, diphenoxylate) may prolong or exacerbate illness in inflammatory diarrhoea. [2] In bloody/febrile diarrhoea, or suspected EHEC / C. difficile / Shigella, these agents can precipitate toxic megacolon or HUS. Use bismuth subsalicylate or racecadotril as alternatives if symptomatic relief is needed.
5. Track 3 — Specific Treatment by Clinical Setting
5.1 Acute Infectious Diarrhoea
Antibiotics are NOT indicated unless inflammatory, severe watery diarrhoea, or high-risk patients. [2]
Why not give antibiotics to everyone? Most acute diarrhoea is viral (antibiotics useless), self-limiting (antibiotics unnecessary), and inappropriate antibiotic use drives resistance and increases C. difficile risk. For EHEC, antibiotics may paradoxically increase Shiga toxin release and HUS risk.
| Indication for Empirical Antibiotics | Rationale |
|---|---|
| Inflammatory diarrhoea (bloody, mucoid, high fever ≥ 38.5°C) | Likely invasive bacterial pathogen requiring treatment |
| Severe watery diarrhoea (e.g., cholera-like, profuse) | Risk of fatal dehydration; antibiotics shorten illness duration |
| High-risk hosts (elderly ≥ 70, immunocompromised, pregnant, prior IBD) | Higher morbidity/mortality from untreated infection |
| Travellers' diarrhoea (moderate-to-severe) | Shortens illness by 1–2 days |
Empirical Tx: azithromycin (if inflammatory) or fluoroquinolones. [2]
| Agent | Dose | Indication | Notes |
|---|---|---|---|
| Azithromycin | 500 mg daily × 3 days (or single 1 g dose) | First-line empirical for inflammatory diarrhoea [2]. Travellers' diarrhoea. | Preferred over fluoroquinolones due to rising quinolone resistance in Campylobacter (especially in Asia). Effective against Shigella, Salmonella, Campylobacter. |
| Fluoroquinolone (ciprofloxacin, levofloxacin) | Ciprofloxacin 500 mg BD × 3–5 days | Alternative empirical therapy | Excellent GI penetration. Increasing resistance in Asia (especially Campylobacter). Avoid in children and pregnancy (cartilage damage). Risk of tendinopathy, QT prolongation, C. difficile. |
| Rifaximin | 200 mg TDS × 3 days | Non-invasive travellers' diarrhoea | Non-absorbable → acts locally in the gut with minimal systemic side effects. NOT for invasive/febrile diarrhoea. |
| Organism | Specific Treatment | Key Points |
|---|---|---|
| C. difficile | Metronidazole (mild–moderate first episode: 500 mg TDS × 10–14 days) [2]. Oral vancomycin 125 mg QDS × 10 days (preferred first-line per 2021 IDSA/SHEA guidelines for all CDI). Fidaxomicin 200 mg BD × 10 days (lower recurrence rate). | Stop offending antibiotic if possible. For severe/fulminant CDI: oral vancomycin ± IV metronidazole. For recurrent CDI: fidaxomicin, vancomycin taper/pulse, or faecal microbiota transplant (FMT). |
| Salmonella (non-typhoidal) | Usually self-limiting — antibiotics only if severe, bacteraemic, immunocompromised, or extremes of age. If needed: ciprofloxacin or azithromycin. | Antibiotics may prolong carrier state in uncomplicated gastroenteritis. |
| Shigella | Azithromycin or ciprofloxacin × 3 days. | Always treat (highly contagious, can cause dysentery). |
| Campylobacter | Azithromycin 500 mg daily × 3 days (if within 3 days of onset; later treatment less effective). | Most common bacterial cause. High fluoroquinolone resistance in Asia → use azithromycin first-line. |
| Cholera | Doxycycline 300 mg single dose (adults) or azithromycin 1 g single dose. | Antibiotics shorten duration and stool volume by 50%. |
| EHEC (O157:H7) | NO antibiotics — supportive care only. | Antibiotics may ↑Shiga toxin release → ↑HUS risk. Avoid antimotility agents. Monitor for HUS (↓platelets, ↑LDH, ↓Hb, AKI). |
| Giardia | Metronidazole 250 mg TDS × 5–7 days or tinidazole 2 g single dose. | Giardiasis is more common than realised. [1] |
| Entamoeba histolytica | Metronidazole 750 mg TDS × 7–10 days → followed by luminal agent (diloxanide furoate or paromomycin) to eliminate cysts. | Two-phase treatment essential: metronidazole kills trophozoites but NOT cysts in gut lumen. |
| Listeria | Amoxicillin or cotrimoxazole [2] | Important in pregnancy, neonates, elderly, immunocompromised. |
| Intestinal TB | Standard anti-TB regimen: RIPE (rifampicin, isoniazid, pyrazinamide, ethambutol) × 2 months → RI × 4 months. | Critical DDx in HK. Must confirm diagnosis before starting — empirical anti-TB trial if highly suspicious and Crohn's excluded. |
C. difficile — Current Guidelines (2021 IDSA/SHEA Update)
The management of CDI has evolved. Oral vancomycin or fidaxomicin is now preferred over metronidazole as first-line for ALL CDI episodes (including initial non-severe). Metronidazole is relegated to second-line when vancomycin/fidaxomicin are unavailable. For recurrent CDI, faecal microbiota transplant (FMT) is highly effective (85–90% cure rate after ≥ 2 recurrences) and now available as standardised preparations.
5.2 Chronic Diarrhoea — Treatment by Mechanism and Cause
IBD management is complex and centres on inducing and maintaining remission, taking into account disease activity, disease site, disease behaviour, and patient preference. [3]
Crohn's Disease — Step-Up (or Accelerated Step-Up) Approach:
| Drug Class | Examples | Mechanism | Indications | Key Points |
|---|---|---|---|---|
| 5-Aminosalicylates (5-ASA) [3] | Mesalazine (Pentasa, Asacol), sulfasalazine | Topical anti-inflammatory — inhibits NF-κB, scavenges free radicals, inhibits prostaglandin/leukotriene synthesis in gut mucosa. "5-ASA" = 5-aminosalicylic acid (the active moiety of sulfasalazine). | Mild-to-moderate UC (first-line for induction and maintenance); mild Crohn's colitis (less effective). | Sulfasalazine = 5-ASA linked to sulfapyridine (carrier); sulfa component causes most side effects (rash, headache, oligospermia). Mesalazine avoids sulfa side effects. |
| Antibiotics [3] | Ciprofloxacin, metronidazole | Efficacy may be due to treatment of undetected pathogen, bacterial overgrowth, or unsuspected microperforation. [3] | Active luminal disease (colonic Crohn's but NOT isolated small intestine disease); perianal diseases (fistula); septic complications (abscess, wound infections). [3] | Metronidazole long-term → peripheral neuropathy. |
| Corticosteroids | Prednisolone (systemic), budesonide (topical/oral controlled-release) | Suppress multiple inflammatory pathways (NF-κB, cytokines, arachidonic acid cascade). Budesonide has high first-pass hepatic metabolism → fewer systemic side effects. | Moderate-to-severe flares (induction only — NOT for maintenance). Budesonide for ileal/right-sided Crohn's. | Side effects: Cushingoid, osteoporosis, DM, infection, adrenal suppression. Always plan steroid taper. |
| Immunomodulators [3] | Azathioprine (AZA), 6-Mercaptopurine (6-MP), Methotrexate (MTX) | AZA/6-MP: purine analogues → inhibit DNA synthesis in rapidly dividing lymphocytes. MTX: folate antagonist → anti-inflammatory and immunosuppressive. | Steroid-dependent or steroid-refractory disease; maintenance of remission. MTX is indicated in active or relapsing disease refractory to or intolerant of AZA or 6-MP. [3] MTX is NOT effective in UC unlike in Crohn's. [3] | Check TPMT/NUDT15 before starting AZA/6-MP (risk of myelosuppression in deficient patients — especially important in East Asians who have higher NUDT15 variant prevalence). Monitor FBC regularly. |
| Biologic therapies (Anti-TNFα) [3] | Infliximab (Remicade), Adalimumab (Humira) | Monoclonal antibodies that bind TNFα → neutralise this key pro-inflammatory cytokine → ↓mucosal inflammation, ↓fistula formation. | Refractory disease or patients with extra-intestinal manifestations and fistulas. [3] Also: adverse prognostic factors (young age < 40, extensive SB disease, perianal involvement, strictures, deep ulcers, steroids required initially) → early introduction (top-down approach). [3] | MUST screen for TB (CXR + QuantiFERON-TB Gold) and HBV (HBsAg) [3]. TB prophylaxis with isoniazid or rifampicin; HBV prophylaxis with entecavir. [3] Contraindications: latent untreated/active TB, lymphoma, heart failure NYHA III–IV, demyelinating disease (MS), optic neuritis. [3] Adverse effects: reactivation of TB/HBV, lymphoma, non-melanoma skin cancer. [3] Dosing: Infliximab: induction IV 5 mg/kg at 0, 2, 6 weeks; maintenance IV 5 mg/kg Q8 weeks. Adalimumab: induction SC 160 mg at 0 week, 80 mg at 2 weeks; maintenance SC 40 mg Q2 weeks. [3] Do not stop anti-TNFα easily unless deep remission of at least 18 months with normal blood and endoscopic parameters. [3] |
| Newer biologics | Vedolizumab (anti-α4β7 integrin), ustekinumab (anti-IL-12/23) | Vedolizumab: gut-selective — blocks lymphocyte trafficking to GI mucosa. Ustekinumab: blocks IL-12 and IL-23 → ↓Th1/Th17 inflammation. | Anti-TNF failures or contraindications. UC and Crohn's. | Vedolizumab is gut-selective → lower systemic immunosuppression → lower infection risk. |
| JAK inhibitors | Tofacitinib, upadacitinib | Inhibit Janus kinases → block intracellular signalling of multiple cytokines. | Moderate-to-severe UC (tofacitinib); Crohn's (upadacitinib). | Oral administration (advantage over IV/SC biologics). Risks: VTE, herpes zoster, hyperlipidaemia. |
Crohn's Disease — Surgical Treatment [3]:
Surgical treatment is NOT curative in Crohn's disease and is mainly used to treat complications only. [3] Bowel-preserving surgery should be performed — conservative and minimal resection as possible. [3] Extended resection does not decrease recurrence. [3]
| Indication | Procedure |
|---|---|
| Persistent symptoms refractory to medical treatment [3] | Resection of affected segment |
| Severe bleeding [3] | Segmental resection |
| Strictures (intestinal obstruction) [3] | Short ( < 10 cm): Heineke-Mikulicz strictureplasty. Long (10–20 cm): Finney strictureplasty. Distal ileal: balloon dilatation. Bypass is NOT recommended (7% malignancy risk in bypassed segment). [3] No role for strictureplasty in Crohn's colitis. [3] |
| Abscess [3] | Percutaneous CT-guided drainage → delayed resection |
| Fistula [3] | SNAP principle: Sepsis control (Abx + drainage), Nutrition (TPN aids fistula closure), Anatomical localisation (imaging), Procedure (infliximab or en-bloc resection with primary anastomosis + diverting stoma). [3] |
| Perforation/sepsis [3] | Emergency surgery |
| Perianal disease [3] | EUA + seton drainage; medical therapy (infliximab + AZA) |
| Large bowel | Right hemicolectomy (most commonly performed). Total colectomy + IRA if rectum spared. Total proctocolectomy + IPAA if limited perianal disease. Total proctocolectomy + end ileostomy if rectum affected. [3] |
Ulcerative Colitis — Similar Step-Up Approach but Key Differences:
- 5-ASA is first-line for both induction and maintenance (much more effective in UC than Crohn's)
- Topical therapy (rectal 5-ASA suppositories/enemas) is critical for proctitis (E1) and left-sided disease (E2)
- Methotrexate is NOT effective in UC [3]
- Cyclosporine (IV) can be used as rescue therapy in acute severe UC refractory to IV steroids
- Surgery is curative in UC: total proctocolectomy + IPAA ("J-pouch") is the definitive operation
- Indications for surgery in UC: failure of medical therapy, toxic megacolon, perforation, uncontrollable haemorrhage, dysplasia/cancer
IBS management is a multifaceted approach: [5]
| Domain | IBS-D Specific | IBS-C Specific | All Subtypes |
|---|---|---|---|
| Education | Reassurance and education may already be sufficient [5] | Same | Same |
| Diet | Low FODMAP diet [5] | High dietary fibre diet [5] | Identify individual triggers |
| Pharmacotherapy | Opioid agonist (loperamide); Bile salt sequestrants (cholestyramine); Probiotics; Rifaximin [5] | Dietary fibre (psyllium); Laxative (PEG); Chloride channel activator (lubiprostone); Guanylate cyclase C agonist (linaclotide)** [5] *(Cause diarrhoea — only for IBS-C) [5] | Peppermint oil; Antispasmodics (otilonium, mebeverine); TCA (amitriptyline, desipramine); SSRI (citalopram, paroxetine, sertraline) [5] |
| Psychotherapy | Psychological treatment if refractory to medications [5] | Same | CBT, hypnotherapy |
Why TCAs for IBS pain? Tricyclic antidepressants have visceral analgesic properties independent of their antidepressant effect — they modulate pain signalling in the brain-gut axis via noradrenergic and serotonergic pathways. Start at low dose (amitriptyline 10–25 mg nocte). Bonus: TCAs have anticholinergic effects that slow transit → helpful in IBS-D but may worsen IBS-C.
Management of malabsorption: [5]
| Cause | Specific Treatment |
|---|---|
| Coeliac disease | Strict lifelong gluten-free diet (GFD). Dietary supplements: Ca, Mg, Fe, folate, vitamin A, B12, D, K. [5] |
| Pancreatic exocrine insufficiency | Pancreatic enzyme supplement (pancreatin/CREON) [5] — take with meals. Dose adjusted to stool output. Low-fat diet if steatorrhoea persists despite enzymes. PPI may improve enzyme efficacy (prevents acid degradation of enzymes). |
| Bile acid malabsorption | Cholestyramine [5] (bile acid-binding resin). If intolerant → colesevelam (better tolerated). |
| Short bowel syndrome [3] | High fat + low carbohydrate + low oxalate diet. Antisecretory agents (PPIs/H₂ blockers). Antimotility agents (loperamide). Adaptive agents: Glucagon-like peptide 2 (GLP-2) analogue — teduglutide — promotes intestinal adaptation in PN-dependent adults. [3] Enteral nutrition should be initiated promptly to support intestinal adaptation. [3] |
| SIBO | Rifaximin (non-absorbable antibiotic). Treat underlying motility disorder. |
| Lactose intolerance | Lactose-free diet or lactase enzyme supplements with dairy meals. |
Enteral and parenteral supplementation [5] may be needed for severe malabsorption:
- Enteral feeding is ALWAYS FIRST CHOICE if GI tract can be used safely [8] — luminal nutrients → ↓gut mucosal atrophy → ↓bacterial translocation into blood [8]
- C/I to enteral feeding: complete SB IO or ileus, inadequately treated shock, severe diarrhoea, proximal SB fistula, severe pancreatitis [8]
- Parenteral nutrition (TPN) reserved for when enteral route is not possible
- Octreotide: ↓motility, useful in neuroendocrine tumour [5] — controls symptoms (flushing, diarrhoea) in carcinoid syndrome and VIPoma
- Definitive treatment: surgical resection if localised; peptide receptor radionuclide therapy (¹⁷⁷Lu-DOTATATE) for metastatic disease
- Somatostatin analogue for symptomatic control [5]
The simplest and most effective management: identify and stop (or substitute) the offending drug [1]. Common culprits and alternatives:
| Offending Drug | Mechanism | Alternative |
|---|---|---|
| Metformin [1] | Osmotic (gut accumulation) + altered microbiome | Extended-release formulation (less GI upset), SGLT2 inhibitor, DPP-4 inhibitor |
| PPIs [1] | Altered gut microbiome, ↑CDI risk, microscopic colitis | Step down to H₂RA, or lowest effective PPI dose |
| Antibiotics [1] | Disrupted flora | Probiotics may help; if CDI → specific CDI treatment |
| NSAIDs [1] | Direct mucosal injury + altered prostaglandin-mediated absorption | Paracetamol, COX-2 selective (lower GI risk), topical NSAID |
| Colchicine [1] | Disrupts microtubule function in enterocytes → impaired absorption | Reduce dose; alternative gout prophylaxis (allopurinol, febuxostat) |
Remember spurious diarrhoea and the rectal examination in the elderly. [1]
Management: disimpaction (manual if necessary, then osmotic laxatives such as polyethylene glycol/macrogol to clear residual stool), followed by a bowel regimen to prevent re-impaction (regular fibre + adequate hydration + stool softeners). Do NOT give anti-diarrhoeals — this will make the impaction worse!
6. Special Situations
This is a medical/surgical emergency. Defined as total or segmental non-obstructive dilatation of colon ≥ 6 cm or caecum > 9 cm with systemic toxicity. [3]
| Step | Management |
|---|---|
| Resuscitation | IV fluids, electrolyte correction, blood transfusion if needed |
| Medical therapy | IV corticosteroids (hydrocortisone 100 mg QDS) for IBD-related; IV vancomycin + IV metronidazole for CDI-related; broad-spectrum antibiotics |
| Decompress | NGT suction; avoid opioids and anticholinergics (↓motility) |
| Serial monitoring | Daily AXR, frequent vitals, surgical consultation |
| Surgery | Indications: failure to improve in 48–72h, perforation, uncontrolled haemorrhage, progressive dilatation. Subtotal colectomy with end ileostomy. |
- Identify specific opportunistic pathogen (CMV → ganciclovir; Cryptosporidium → optimise ART for immune reconstitution; MAC → clarithromycin + ethambutol; Isospora → cotrimoxazole)
- Exclude drug-induced (antiretrovirals, immunosuppressants)
- Nutritional support is critical
Hospitalise. IV hydrocortisone 100 mg QDS. If no response in 72 hours → rescue therapy (IV ciclosporin or infliximab) or emergency colectomy.
High Yield Summary — Management of Diarrhoea
-
Resuscitation first: ORS for mild-moderate; IV NS/Ringer's for severe/shock. Correct K⁺, HCO₃⁻, Mg²⁺.
-
Most acute diarrhoea needs NO antibiotics — only for inflammatory, severe, or high-risk patients. Empirical: azithromycin (first choice) or fluoroquinolone.
-
C. difficile: Oral vancomycin or fidaxomicin (first-line per 2021 guidelines). Metronidazole is second-line. FMT for recurrent CDI.
-
EHEC: NO antibiotics, NO antimotility agents — supportive care only. Monitor for HUS.
-
Loperamide: Excellent for non-inflammatory diarrhoea and IBS-D. CONTRAINDICATED in febrile/bloody diarrhoea (risk of toxic megacolon).
-
IBD: Step-up approach (5-ASA → steroids → immunomodulators → biologics). Anti-TNFα requires screening for TB + HBV before starting. Crohn's surgery is NOT curative; UC surgery (proctocolectomy) IS curative.
-
Malabsorption: Treat the cause (GFD for coeliac, CREON for pancreatic insufficiency, cholestyramine for bile acid malabsorption) + nutritional supplementation.
-
IBS: Reassurance, low FODMAP diet, loperamide for IBS-D, TCA for pain, psychological therapy if refractory.
-
Drug-induced diarrhoea: Stop or substitute the offending drug.
-
Spurious diarrhoea: Disimpaction, NOT anti-diarrhoeals.
Active Recall - Management of Diarrhoea
References
[1] Lecture slides: murtagh merge.pdf (Diarrhoea section, p32–34) [2] Senior notes: Ryan Ho Fundamentals.pdf (Section 3.3.7 Acute Diarrhoea Mx p289; Section 3.3.8 Chronic Diarrhoea Mx p292) [3] Senior notes: felixlai.md (Crohn's treatment p964–968; UC treatment p985; Diverticulitis treatment p948; Short bowel syndrome treatment p1588; Intussusception treatment p1552; Crohn's surgical treatment p968) [4] Senior notes: Ryan Ho Chemical Path.pdf (Hypokalaemia p18; Hypomagnesaemia p28) [5] Senior notes: Ryan Ho GI.pdf (IBS management p119; Chronic Diarrhoea management p117; Malabsorption management p117) [8] Senior notes: Ryan Ho Fluids and Nutrition.pdf (Fluid therapy p5; Enteral feeding p9; Daily requirements p7) [11] Senior notes: Ryan Ho Urogenital.pdf (Metabolic acidosis management p39; AKI management p98) [13] Senior notes: Ryan Ho Critical Care.pdf (Hypovolaemic shock management p21) [14] Senior notes: Ryan Ho Critical Care.pdf (AKI approach p26) [15] Senior notes: Ryan Ho Urogenital.pdf (AKI management principles p98)
Complications of Diarrhoea
Complications of diarrhoea span a wide spectrum — from the immediate, life-threatening metabolic derangements of acute severe diarrhoea, through to the chronic nutritional and end-organ consequences of prolonged malabsorptive states. The key is to understand that complications arise not just from the diarrhoea itself (fluid/electrolyte/nutrient loss) but also from the underlying cause (e.g., toxic megacolon in IBD, HUS in EHEC) and from treatment (e.g., pouchitis after surgery, refeeding syndrome during nutritional rehabilitation). Let's work through each systematically.
1. Acute Complications of Diarrhoea
These are the complications that will kill a patient within hours to days if not recognised and treated.
Mechanism: Diarrhoeal stool is approximately isotonic with plasma. Large-volume losses (especially in cholera, ETEC, VIPoma) deplete the extracellular fluid compartment → ↓intravascular volume → ↓cardiac preload → ↓cardiac output → tissue hypoperfusion → shock.
Why children and elderly are most vulnerable: Children have a higher body-surface-area-to-volume ratio → faster insensible losses; elderly have reduced renal concentrating ability, blunted thirst response, and often have pre-existing cardiovascular disease limiting compensatory reserve.
| Severity | Signs | Estimated Fluid Deficit |
|---|---|---|
| Mild ( < 4%) | Thirst only, no clinical signs [8] | < 40 mL/kg |
| Moderate (4–6%) | ↑Capillary refill > 2s, tachypnoea, mildly ↓tissue turgor [8] | 40–60 mL/kg |
| Severe (≥ 7%) | Very delayed capillary refill, shock, deep/acidotic breathing, ↓↓tissue turgor [8] | ≥ 70 mL/kg |
Clinical features of hypovolaemic shock: vasoconstriction leading to pallor, peripheral cyanosis, cold extremities, delayed capillary refill; empty peripheral veins; tachycardia; sweating. [13]
Complications of shock include: multi-organ failure, disseminated intravascular coagulation (DIC), acute kidney injury (see below), and death if untreated.
1.2 Electrolyte Disturbances
These are extremely high-yield for both clinical practice and exams.
Mechanism: Stool K⁺ concentration is 30–80 mmol/L. Large-volume diarrhoea → massive extrarenal K⁺ loss. In chronic diarrhoea, secondary hyperaldosteronism (from volume depletion) further augments renal K⁺ wasting.
Extrarenal K⁺ loss with diarrhoea: paired spot urine K⁺ < 20 mmol/L. [4]
- Acute diarrhoea: associated with acidosis (↓HCO₃⁻) and urine K < 20 mmol/L [4]
- Chronic diarrhoea / laxative abuse: associated with alkalosis (↑HCO₃⁻) and urine K < 20 mmol/L [4]
Clinical consequences of hypokalaemia (especially when K⁺ < 2.5 mmol/L):
- Muscular dysfunction: LL > UL proximal muscle weakness, myalgia, cramps, paralysis [11]
- GI dysfunction: ileus, abdominal distension, anorexia, vomiting, constipation [11] — paradoxically, hypokalaemia from diarrhoea can then cause ileus, creating a vicious cycle
- Rhabdomyolysis: intense myalgia, myoglobinuria, renal failure [11] — in normal muscle, K⁺ released during contraction mediates local vasodilation; with systemic hypoK, this vasodilatory response fails → muscle ischaemia → rhabdomyolysis
- Cardiac arrhythmia (esp when K⁺ < 2.0): ↓T wave flattening and ↑U wave amplitude, prolonged QT interval, variety of arrhythmias [11]
- Nephrogenic DI: usually late, only seen in chronic hypoK ( > 2–3 weeks) [11] — chronic hypokalaemia impairs aquaporin-2 insertion in collecting duct → inability to concentrate urine → polyuria, worsening dehydration
Mechanism: Lower GI secretions (ileal, colonic) are rich in HCO₃⁻. Diarrhoeal loss of HCO₃⁻ → fall in plasma HCO₃⁻ → metabolic acidosis. The kidneys retain Cl⁻ to maintain electroneutrality → hyperchloraemia. This is a normal anion gap metabolic acidosis (NAGMA).
Distinguishing diarrhoea from RTA (both cause NAGMA with hypoK) [11]:
| Parameter | Diarrhoea | Distal RTA |
|---|---|---|
| Urine pH | Usually < 5.3 | Always > 5.5 |
| Urine AG | Negative (decreased) | Positive (increased) |
| Urine OG | Increased | Decreased |
Why is the urine anion gap negative in diarrhoea? In response to acidosis, the kidney appropriately increases ammonium (NH₄⁺) excretion. NH₄⁺ is excreted with Cl⁻ → unmeasured cation in urine → makes the urine anion gap negative. In distal RTA, the kidney cannot acidify urine or excrete NH₄⁺, so the urine AG remains positive.
Consequences of severe metabolic acidosis (pH < 7.1):
- Heart: ↓contractility, arrhythmias, ↓response to catecholamines [11]
- Vascular: arterial dilatation, ↓response to catecholamines [11]
- Respiratory: compensatory hyperventilation (Kussmaul breathing) [11]
- Metabolic: insulin resistance, hyperK (transcellular H⁺/K⁺ shift), ↓ATP synthesis [11]
- Cerebral: altered mental status, coma [11]
Mechanism: Chronic diarrhoea → volume depletion → secondary hyperaldosteronism → ↑H⁺ secretion in distal nephron + ↑HCO₃⁻ reabsorption in proximal tubule → metabolic alkalosis. Laxative abuse follows the same mechanism.
Mechanism: Diarrhoeal fluid is roughly isotonic. The resulting serum Na⁺ depends on what the patient drinks to replace losses:
- If they drink hypotonic fluids (plain water, dilute juice) → hyponatraemia (dilutional)
- If they cannot drink (altered consciousness, severe vomiting) → hypernatraemia (water deficit exceeds Na deficit)
GI causes of hypoMg: ↓intake, ↓absorption, malabsorption, chronic diarrhoea, intestinal resection. [4]
Why hypoMg matters: Mg²⁺ is a cofactor for Na⁺/K⁺-ATPase. HypoMg → impaired K⁺ repletion (refractory hypokalaemia) and impaired PTH secretion → secondary hypocalcaemia. You cannot fix the K⁺ until you fix the Mg²⁺.
In malabsorptive diarrhoea: fat malabsorption → ↓vitamin D absorption → ↓intestinal Ca²⁺ absorption → hypocalcaemia. Additionally, unabsorbed fatty acids bind Ca²⁺ in the lumen (saponification) → further Ca²⁺ loss. HypoMg compounds this by impairing PTH secretion and PTH end-organ responsiveness.
Clinical features: Perioral and acral paraesthesiae, carpopedal spasm, Trousseau's sign, Chvostek's sign, prolonged QT, seizures.
Mechanism: Hypovolaemia from diarrhoea → ↓renal perfusion → pre-renal AKI. If prolonged → ischaemic damage to tubular epithelium → acute tubular necrosis (ATN), i.e., intrinsic renal disease.
Key point: Prolonged pre-renal disease will progress to become ATN [14]. Early, aggressive fluid resuscitation is the single most important intervention. Stop nephrotoxic drugs (NSAIDs, ACEI/ARB). [14]
Mechanism: Complication specifically of enterohaemorrhagic E. coli (EHEC, O157:H7) and occasionally Shigella. Shiga toxin → endothelial damage in glomerular capillaries → platelet activation and fibrin deposition → microangiopathic haemolytic anaemia (MAHA) + thrombocytopenia + AKI.
Triad: (1) Microangiopathic haemolytic anaemia (schistocytes on blood film, ↑LDH, ↑bilirubin, ↓haptoglobin), (2) Thrombocytopenia, (3) AKI.
Why antibiotics are contraindicated in EHEC: Antibiotics may lyse bacteria → release more Shiga toxin → worsen HUS. Antimotility agents also prolong toxin contact with mucosa → increased risk.
HUS — A Preventable Complication
HUS develops in approximately 5–10% of children with EHEC O157:H7 infection. The risk is INCREASED by antibiotic use and antimotility agents. Management is supportive: IV fluids, RBC/platelet transfusion as needed, dialysis for AKI. Plasma exchange is indicated for atypical HUS (complement-mediated) but NOT for typical Shiga-toxin HUS.
2. Complications of Specific Underlying Causes
2.1 Inflammatory Bowel Disease (IBD)
Total or segmental non-obstructive dilatation of colon ≥ 6 cm or caecum > 9 cm and the presence of systemic toxicity. [3]
- Much more common in UC [5] but can occur in Crohn's colitis, and in C. difficile and CMV colitis [5]
- Presents with fever, tachycardia, hypotension, dehydration, electrolyte disturbances, anaemia, hypoalbuminaemia and mental changes [3]
- High risk of developing toxic megacolon as inflammatory process extends beyond mucosa to involve muscle layers of the colon [3] → muscle paralysis → massive dilatation
Pathophysiology from first principles: Severe transmural inflammation → destruction of myenteric (Auerbach's) plexus → loss of coordinated smooth muscle contraction → colonic atony and dilatation. Simultaneously, damaged mucosa loses its barrier function → bacterial toxins translocate freely into the bloodstream → systemic toxicity.
Management [5]:
- Close monitoring, resuscitation, complete bowel rest (NPO ± TPN), NGT decompression
- IV steroids (not 5-ASA), broad-spectrum antibiotics
- Avoid colonoscopy (risk of perforation) and anti-diarrhoea / antispasmodic drugs
- Outcome: 50% responds to medical Rx, 50% require urgent colectomy (if not responding in 3–7 days) [5]
Occurs due to repeated episodes of inflammation or muscle hypertrophy. [3] Should be considered malignant until proven otherwise by endoscopy with biopsy. [3]
In Crohn's disease specifically [5]:
- Cause: chronic inflammation → mucosal thickening, scarring, adhesions → intestinal obstruction
- S/S: partial (colicky abdominal pain) or frank IO
Causes: transmural inflammation → sinus tracts [5]:
- Anal fissures (20%): intense pain with defecation, can occur at atypical location (not midline) — in contrast to typical anal fissures which are almost always at the posterior midline
- Perianal fistula (20–30%): persistent anal pain, painful defecation, purulent discharge
- Anorectal abscesses (~50%): severe, constant anal pain worsened by sitting/defecation
Patients present with > 10 stools per day, continuous bleeding, abdominal pain, distension and acute severe toxic symptoms including fever and anorexia. [3] This is the step before toxic megacolon — early recognition and aggressive IV steroid therapy is crucial.
Chronic inflammation of colon → ↑risk of CA colon. [5] Can occur in both UC and Crohn's colitis. [5]
- Risk factors: ↑extent and ↑duration of colitis [5]
- Time frame: ~8–10 years after onset in extensive disease, ~10–15 years after onset in limited or left-sided disease [5]
- Surveillance colonoscopy is recommended starting 8 years after disease onset, with biopsies at regular intervals to detect dysplasia
| Complication | Mechanism |
|---|---|
| Pouchitis | Inflammation of the ileal pouch (J-pouch). Most common complication of IPAA. Treated with metronidazole and ciprofloxacin. [3] |
| Pouch-vaginal / perineal fistula [3] | Breakdown of staple/suture line |
| Anastomotic stricture [3] | Fibrosis at the anastomotic site |
| Anastomotic dehiscence with sepsis [3] | Technical failure → faecal peritonitis |
| Sexual dysfunction / Infertility [3] | Damage to pelvic nerves during proctectomy; adhesions around fallopian tubes |
| Complication | Mechanism | Key Features |
|---|---|---|
| Abscess (17%) [3] | Microperforation contained by pericolonic fat and mesentery → localised collection of pus | Persistent fever and abdominal pain despite 3 days of antibiotics; may develop pyogenic liver abscess via portal circulation [3]. Management: percutaneous CT-guided drainage if ≥ 5 cm [12] |
| Fistula [3] | Inflammation erodes into adjacent organs | MC colovesical fistula → recurrent dysuria, pneumaturia, faecaluria [12]. Also colovaginal (vaginal faeces/flatus in post-hysterectomy patients), coloenteric, colocutaneous. |
| Obstruction [3] | Acute: pericolonic inflammation compresses lumen. Chronic: recurrent attacks → progressive fibrosis and scarring → intestinal strictures [3] | Partial → colicky pain; complete → acute LBO |
| Perforation [3] | Rupture of diverticular abscess or inflamed diverticulum into peritoneal cavity [3] → generalised purulent or faecal peritonitis | Classified by Hinchey classification [12]: Stage I (pericolic abscess, 0% mortality) → Stage IV (faecal peritonitis, 50% mortality) |
| Massive haemorrhage | Rupture of vasa recta across the dome of a diverticulum [12] | Painless massive PR bleeding [12]; most common cause of massive lower GI bleeding (30–50%) |
| Complication | Associated Organism | Mechanism |
|---|---|---|
| HUS | EHEC (O157:H7), Shigella | Shiga toxin → endothelial damage → MAHA + thrombocytopenia + AKI (see above) |
| Guillain-Barré syndrome | Campylobacter jejuni | Molecular mimicry: anti-ganglioside antibodies against Campylobacter lipopolysaccharides cross-react with peripheral nerve gangliosides → acute inflammatory demyelinating polyneuropathy |
| Reactive arthritis | Salmonella, Shigella, Campylobacter, Yersinia | HLA-B27-associated immune reaction: bacterial antigens presented to T-cells → inflammatory arthritis (typically large joints of lower limbs), conjunctivitis, urethritis (Reiter's syndrome) |
| Erythema nodosum | Yersinia, Campylobacter, Salmonella | Immune-complex mediated panniculitis → tender red nodules on shins |
| Intestinal perforation | Salmonella typhi (typhoid), severe C. difficile | Typhoid: necrosis of Peyer's patches in terminal ileum → perforation (classically week 3). CDI: transmural necrosis in severe/fulminant disease. |
| Chronic carriage | Salmonella typhi | Bacteria persist in gallbladder (favoured by gallstones) → intermittent faecal shedding. Important for public health (e.g., "Typhoid Mary"). |
| Amoebic liver abscess | Entamoeba histolytica | Trophozoites invade colonic mucosa → enter portal venous system → seed in liver → abscess formation. Typically single, right lobe. "Anchovy sauce" pus on aspiration. |
SBS (from extensive bowel resection or disease) is a cause of chronic diarrhoea, but it also leads to a cascade of complications that are highly examinable [3][5][16]:
| Complication | Mechanism |
|---|---|
| Watery diarrhoea [16] | Reduction of absorptive surface area, decrease in intestinal transit time, SIBO, or malabsorbed bile salts in colon leading to bile acid diarrhoea (secretory) [16] |
| D-lactic acidosis [16] | Bacterial fermentation of unabsorbed carbohydrates in intact colon → D-lactate production (not L-lactate) → neurological syndrome: altered mental status, confusion to coma, slurred speech, seizures, ataxia [16]. Standard lactate assays measure L-lactate only → may miss D-lactic acidosis. |
| Fat-soluble vitamin deficiency (A, D, E, K) [16] | Fat malabsorption → impaired absorption of vitamins dissolved in fat. Vitamin A = night blindness. Vitamin D = metabolic bone disease/rickets. Vitamin E = neuromuscular disorders, haemolysis. Vitamin K = bleeding tendency. [16] |
| Vitamin B12 deficiency [16] | Distal ileum is the primary site for B12-IF complex absorption [16]. Ileal resection → B12 malabsorption → macrocytic anaemia, neuropsychiatric dysfunction, subacute combined degeneration of the spinal cord. |
| Electrolyte deficiency (Ca, Mg) [16] | HypoMg: Mg binds to unabsorbed fatty acids → lost in stool. HypoCa: secondary to vitamin D deficiency AND hypoMg (impairs PTH secretion). [16] Perioral paraesthesiae, carpopedal spasm, Trousseau/Chvostek signs. |
| Trace element deficiency (Zn, Cu, Se) [16] | Zinc = impaired intestinal absorption and growth. Copper = metabolic bone disease. Selenium = cardiomyopathy. [16] |
| Iron deficiency [16] | Inadequate absorption or GI bleeding from anastomotic ulcers [16] |
| Essential fatty acid deficiency [16] | Hair loss, fatty infiltration of liver, poor growth, poor wound healing [16] |
| Metabolic bone disease [16] | Primary due to malabsorption of calcium and vitamin D → osteomalacia, osteopenia, osteoporosis, secondary hyperparathyroidism [16] |
| Oesophagitis / PUD [16] | Gastrin hypersecretion due to loss of inhibitory hormones (GIP, VIP) produced in proximal gut [16]. Managed with PPIs. |
| Gallstones [16] | Ileal resection interrupts enterohepatic circulation of bile acids → bile supersaturated with cholesterol. Bile stasis from absence of meals (on TPN) → ↓CCK-mediated gallbladder contraction → biliary sludge and pigmented gallstones. [16] |
| Calcium oxalate kidney stones [16] | Normally, dietary Ca binds oxalate in the gut lumen. In fat malabsorption, Ca binds preferentially to unabsorbed fatty acids → free oxalate is absorbed by the colon → filtered by kidneys → calcium oxalate stones. [16] Prevention: increased fluid intake, low oxalate diet, correction of metabolic acidosis with potassium citrate [16]. |
| TPN-associated complications [16] | Catheter-associated infection, mechanical failure (thrombosis/occlusion), hepatic steatosis and cholestasis [16] |
| SIBO [5] | Loss of IC valve → ↓transit time + loss of barrier to colonic bacteria refluxing into SB → bacterial overgrowth → deconjugation of bile acids (worsens fat malabsorption) + B12 consumption + gas production (bloating, flatulence) [16] |
Gallstones AND Kidney Stones in SBS — Understand the Logic
Both gallstones and kidney stones are classic complications of ileal resection, but the mechanisms are completely different. Gallstones: disrupted enterohepatic circulation → cholesterol-supersaturated bile. Kidney stones: unabsorbed fatty acids bind calcium → free oxalate absorbed by colon → hyperoxaluria → calcium oxalate stones. Note that if the colon is also resected, oxalate stones do NOT form (no colon to absorb oxalate) but gallstones still occur.
These develop insidiously in patients with chronic malabsorptive or inflammatory diarrhoea.
| Complication | Mechanism | Clinical Features |
|---|---|---|
| Protein-energy malnutrition | Malabsorption + increased catabolism + reduced intake → negative nitrogen balance | Weight loss, ↓muscle bulk, fatigue, malaise [5]. Hypoproteinaemia → bowel oedema inhibits GI function, wound oedema inhibits healing, prevents normal cardiovascular response to shock. Muscle wasting → respiratory muscle weakness → respiratory failure and chest infections. [8] |
| Iron-deficiency anaemia | Chronic GI blood loss (IBD, CRC) + malabsorption of iron (coeliac, Crohn's — duodenum/jejunum is the site of iron absorption) | Microcytic hypochromic anaemia, angular stomatitis, glossitis, koilonychia |
| Megaloblastic anaemia | B12 deficiency (terminal ileum disease/resection) or folate deficiency (jejunal disease, e.g., coeliac) | Macrocytic anaemia, hypersegmented neutrophils, glossitis, neuropathy (B12) |
| Osteoporosis / Osteomalacia | Vitamin D + Ca²⁺ malabsorption → ↓bone mineralisation. Steroid use in IBD further accelerates bone loss. | Low-trauma fractures, bone pain, proximal myopathy (osteomalacia) |
| Peripheral neuropathy / Subacute combined degeneration | B12 deficiency → impaired myelin synthesis in dorsal columns and corticospinal tracts | Loss of vibration/proprioception (dorsal columns), spastic paraparesis (corticospinal tracts), peripheral neuropathy |
| Coagulopathy | Vitamin K malabsorption → deficiency of clotting factors II, VII, IX, X (all synthesised in the liver and require vitamin K as cofactor for gamma-carboxylation) | Easy bruising, prolonged PT/INR, mucosal bleeding |
Refeeding Syndrome
When a malnourished patient with chronic diarrhoea is refed (enterally or parenterally), there is a risk of refeeding syndrome [17]:
Pathogenesis [17]:
- Starvation → ↓body stores of PO₄, K, Mg, vitamins
- Refeeding → ↑blood glucose → ↑insulin → ↑cellular uptake of PO₄, K, Mg
- Precipitate acute hypophosphataemia, hypokalaemia, hypomagnesaemia
Consequences [17]:
- Muscle weakness: ↓contractility, myalgia, tetany, rhabdomyolysis, respiratory failure
- CVS: ↓contractility, heart failure, arrhythmia
- GI: diarrhoea (due to atrophy of intestinal mucosa), liver derangement
- Neurological: tremors, paraesthesia, delirium, seizures, Wernicke-Korsakoff syndrome (B₁ deficiency)
Management: reduce nutritional support and correct hypoPO₄, hypoK, hypoMg. [17] Always give thiamine (B₁) before or concurrent with refeeding to prevent Wernicke's encephalopathy.
| Treatment | Complication | Mechanism |
|---|---|---|
| Loperamide in inflammatory diarrhoea | Toxic megacolon, prolonged infection | Slows transit → toxins/organisms in contact with mucosa longer → transmural damage |
| Antibiotics | C. difficile infection | Disrupts normal colonic flora → loss of colonisation resistance → CDI overgrowth |
| Chronic PPI use | CDI, SIBO, microscopic colitis, hypoMg | Acid suppression → altered gut microbiome; impaired Mg absorption |
| Total proctocolectomy + IPAA | Pouchitis (most common), pouch-vaginal fistula, anastomotic stricture, sexual dysfunction, infertility [3] | Pouchitis: bacterial stasis in neorectum → inflammation. Others: surgical complications. |
| Chronic TPN | Catheter-associated infection, hepatic steatosis and cholestasis, mechanical failure [16] | Central line infection; hepatotoxicity from lipid emulsions and absence of enteral stimulation of bile flow |
| Enteral feeding [8] | GI: distension, cramping, N/V, diarrhoea/constipation, intestinal ischaemia. Metabolic: dehydration, electrolyte disturbance (esp hyperNa), hyperglycaemia. Mechanical: malpositioning, tube blockage. Infectious: aspiration pneumonia, bacterial contamination, PEG site infection, peritonitis. [8] | Hyperosmolar feeds draw water into lumen → osmotic diarrhoea; rapid infusion overwhelms absorptive capacity; aspiration from reflux |
| Anti-TNFα therapy (IBD) | Reactivation of TB/HBV, lymphoma, non-melanoma skin cancer [3] | Immunosuppression → inability to contain latent infections or surveil for malignant cells |
| Corticosteroids (IBD) | Osteoporosis, DM, Cushing's, adrenal suppression, infection, avascular necrosis | Multi-system effects of chronic glucocorticoid excess |
| AZA/6-MP | Myelosuppression, pancreatitis, hepatotoxicity, lymphoma | Purine analogue toxicity; check TPMT/NUDT15 before starting |
| Timeframe | Complications |
|---|---|
| Immediate (hours–days) | Dehydration, hypovolaemic shock, hypokalaemia (arrhythmia, ileus, rhabdomyolysis), metabolic acidosis, AKI (pre-renal), HUS (EHEC) |
| Short-term (days–weeks) | Toxic megacolon, perforation, intestinal ischaemia, sepsis/bacteraemia, Guillain-Barré syndrome (post-Campylobacter), reactive arthritis, refeeding syndrome (during recovery) |
| Long-term (weeks–months–years) | Malnutrition (protein-energy, micronutrients), anaemia (Fe, B12, folate), osteoporosis/osteomalacia, nephrolithiasis (calcium oxalate), cholelithiasis, neuropathy (B12), coagulopathy (vitamin K), colorectal cancer (IBD), strictures, fistulae, short bowel complications |
High Yield Summary — Complications of Diarrhoea
-
Dehydration → shock → AKI: the immediate life threat. Resuscitate aggressively. Pre-renal AKI progresses to ATN if prolonged.
-
Hypokalaemia: stool K⁺ loss. Consequences = arrhythmia (ECG: flat T, tall U, prolonged QT), muscle weakness, ileus, rhabdomyolysis, nephrogenic DI. Cannot correct K⁺ without correcting Mg²⁺ first.
-
NAGMA: HCO₃⁻ loss in stool. Distinguish from RTA by urine pH ( < 5.3 in diarrhoea vs > 5.5 in distal RTA) and urine AG (negative in diarrhoea, positive in RTA).
-
HUS: EHEC complication. Triad: MAHA + thrombocytopenia + AKI. Antibiotics and antimotility agents are CONTRAINDICATED.
-
Toxic megacolon: colon ≥ 6 cm + systemic toxicity. Avoid colonoscopy, antimotility agents, anticholinergics. IV steroids + antibiotics. 50% need colectomy.
-
Crohn's complications: strictures → obstruction; transmural inflammation → fistulae (enteroenteric, enterovesical, enterovaginal) + abscesses; perianal disease.
-
Short bowel syndrome complications: D-lactic acidosis, gallstones (disrupted enterohepatic circulation), calcium oxalate kidney stones (free oxalate absorbed by colon), fat-soluble vitamin deficiency, B12 deficiency, metabolic bone disease.
-
Refeeding syndrome: in malnourished chronic diarrhoea patients — refeeding triggers insulin surge → cellular K/PO₄/Mg uptake → acute hypoPO₄/hypoK/hypoMg. Give thiamine first.
-
CRC risk in IBD: increases with extent and duration of colitis. Surveillance colonoscopy from 8 years.
Active Recall - Complications of Diarrhoea
References
[3] Senior notes: felixlai.md (UC complications/prognosis p987; Diverticulitis complications p951; IPAA complications p986–987; SBS complications p1586–1587; SBS pathogenesis p1585) [4] Senior notes: Ryan Ho Chemical Path.pdf (Hypokalaemia approach p18; Hypomagnesaemia p28) [5] Senior notes: Ryan Ho GI.pdf (Crohn's complications p122; SBS clinical features p127; Toxic megacolon management p122) [8] Senior notes: Ryan Ho Fluids and Nutrition.pdf (Malnutrition consequences p7; Enteral feeding complications p10) [11] Senior notes: Ryan Ho Urogenital.pdf (Metabolic acidosis consequences p39; Hypokalaemia clinical features and evaluation p25; RTA vs diarrhoea table p44) [12] Senior notes: maxim.md (Diverticular disease complications and Hinchey classification p194) [13] Senior notes: Ryan Ho Critical Care.pdf (Hypovolaemic shock clinical features p21) [14] Senior notes: Ryan Ho Critical Care.pdf (AKI approach p26) [16] Senior notes: felixlai.md (SBS complications p1586–1587; SBS pathogenesis p1585) [17] Senior notes: Ryan Ho Psychiatry.pdf (Refeeding syndrome p215)
High Yield Summary
Definition: ≥ 3 loose/liquid stools per day or stool weight > 200 g/day. Classify by duration: acute (< 2 wk), persistent (2–4 wk), chronic (> 4 wk).
Four pathophysiological mechanisms: Osmotic (stops with fasting, gap > 125), Secretory (persists with fasting, large volume, gap < 50), Inflammatory (bloody, mucoid, PMN+), Motility disorder (altered transit).
Hong Kong relevance: Norovirus outbreaks, V. parahaemolyticus (raw seafood), rising IBD incidence, high CRC rates, lactose intolerance (~80–90% East Asians), intestinal TB as Crohn's mimic.
Critical history points: What does the patient mean by diarrhoea? Stool consistency (Bristol chart), frequency, blood/mucus, associated pain, timing (nocturnal = organic), drug history, travel history, family history.
Smoking & IBD: Smoking is a risk factor for Crohn's but protective for UC.
Appendicectomy & IBD: Prior appendicectomy is a risk factor for Crohn's but protective for UC.
Metabolic consequences: Hypokalaemia (K⁺ loss in stool), NAGMA (HCO₃⁻ loss in stool in acute diarrhoea), dehydration → pre-renal AKI.
Drug-induced: Alcohol, antibiotics, metformin, colchicine, Mg-antacids, PPIs, SSRIs, laxatives, statins, iron — always check drug history.
Don't forget: Spurious diarrhoea in elderly (DRE!), overflow around impacted stool.
IBS: Very common, does NOT cause nocturnal diarrhoea, pain is associated with defecation.
High Yield Summary — DDx of Diarrhoea
-
Always clarify what the patient means by "diarrhoea" — consistency matters more than frequency.
-
Murtagh framework: Probability → Serious not to miss → Pitfalls → Masquerades → Psychosocial.
-
Acute: Most common = viral gastroenteritis. Investigate only if severe, inflammatory, high-risk host, or persistent > 1 week.
-
Chronic: Categorise by stool type — inflammatory (bloody/mucoid), watery (osmotic vs secretory vs motility), fatty (malabsorptive).
-
Nocturnal diarrhoea = organic until proven otherwise (rules against IBS).
-
Spurious diarrhoea in the elderly = overflow around faecal impaction. DRE is diagnostic.
-
Hong Kong-specific DDx: Intestinal TB (vs Crohn's — must do AFB), right-sided diverticulitis, V. parahaemolyticus, lactose intolerance (90% Asians), CRC (very high incidence).
-
Always check drug history — drugs are one of the commonest treatable causes across all age groups.
-
Masquerades: Diabetes (autonomic neuropathy + metformin), hyperthyroidism, Addison's disease.
-
Alarm features mandate investigation: weight loss, PR bleeding, old onset, FHx CRC/IBD, nocturnal symptoms, anaemia, raised inflammatory markers.
High Yield Summary — Diagnosis of Diarrhoea
-
Most acute diarrhoea needs NO investigation — only investigate if severe, inflammatory, high-risk host, or persistent > 1 week.
-
Key investigations to remember (Murtagh): microscopy and culture of stool, FBE, ESR/CRP, C. difficile tissue culture assay, U&E, specific tests for organisms, endoscopy, selective radiology. [1]
-
Faecal calprotectin is the gatekeeper between IBS and IBD — stable at room temperature, ↑ in infection, IBD, and cancer, negative result makes serious pathology unlikely.
-
Stool osmolal gap = 290 − 2(Na + K): > 125 = osmotic; < 50 = secretory. This single test distinguishes two fundamentally different mechanisms.
-
Stool pH < 5.6 → carbohydrate malabsorption (fermentation produces acid).
-
Colonoscopy with biopsy — always biopsy even if mucosa looks normal (microscopic colitis!); always send for AFB in Hong Kong (TB vs Crohn's).
-
Hypokalaemia workup: Plasma HCO₃⁻ + paired spot urine K⁺ → acute diarrhoea = acidosis + low urine K; chronic/laxative = alkalosis + low urine K.
-
Faecal elastase-1 < 200 μg/g → pancreatic exocrine insufficiency (cause of fatty diarrhoea).
-
Toxic megacolon = colon ≥ 6 cm or caecum > 9 cm + systemic toxicity on AXR — a surgical emergency.
-
IBS = Rome IV (pain ≥ 1 day/wk for 3 months, related to defecation + change in frequency/form, onset ≥ 6 months ago) + NO alarm features.
High Yield Summary — Management of Diarrhoea
-
Resuscitation first: ORS for mild-moderate; IV NS/Ringer's for severe/shock. Correct K⁺, HCO₃⁻, Mg²⁺.
-
Most acute diarrhoea needs NO antibiotics — only for inflammatory, severe, or high-risk patients. Empirical: azithromycin (first choice) or fluoroquinolone.
-
C. difficile: Oral vancomycin or fidaxomicin (first-line per 2021 guidelines). Metronidazole is second-line. FMT for recurrent CDI.
-
EHEC: NO antibiotics, NO antimotility agents — supportive care only. Monitor for HUS.
-
Loperamide: Excellent for non-inflammatory diarrhoea and IBS-D. CONTRAINDICATED in febrile/bloody diarrhoea (risk of toxic megacolon).
-
IBD: Step-up approach (5-ASA → steroids → immunomodulators → biologics). Anti-TNFα requires screening for TB + HBV before starting. Crohn's surgery is NOT curative; UC surgery (proctocolectomy) IS curative.
-
Malabsorption: Treat the cause (GFD for coeliac, CREON for pancreatic insufficiency, cholestyramine for bile acid malabsorption) + nutritional supplementation.
-
IBS: Reassurance, low FODMAP diet, loperamide for IBS-D, TCA for pain, psychological therapy if refractory.
-
Drug-induced diarrhoea: Stop or substitute the offending drug.
-
Spurious diarrhoea: Disimpaction, NOT anti-diarrhoeals.
High Yield Summary — Complications of Diarrhoea
-
Dehydration → shock → AKI: the immediate life threat. Resuscitate aggressively. Pre-renal AKI progresses to ATN if prolonged.
-
Hypokalaemia: stool K⁺ loss. Consequences = arrhythmia (ECG: flat T, tall U, prolonged QT), muscle weakness, ileus, rhabdomyolysis, nephrogenic DI. Cannot correct K⁺ without correcting Mg²⁺ first.
-
NAGMA: HCO₃⁻ loss in stool. Distinguish from RTA by urine pH ( < 5.3 in diarrhoea vs > 5.5 in distal RTA) and urine AG (negative in diarrhoea, positive in RTA).
-
HUS: EHEC complication. Triad: MAHA + thrombocytopenia + AKI. Antibiotics and antimotility agents are CONTRAINDICATED.
-
Toxic megacolon: colon ≥ 6 cm + systemic toxicity. Avoid colonoscopy, antimotility agents, anticholinergics. IV steroids + antibiotics. 50% need colectomy.
-
Crohn's complications: strictures → obstruction; transmural inflammation → fistulae (enteroenteric, enterovesical, enterovaginal) + abscesses; perianal disease.
-
Short bowel syndrome complications: D-lactic acidosis, gallstones (disrupted enterohepatic circulation), calcium oxalate kidney stones (free oxalate absorbed by colon), fat-soluble vitamin deficiency, B12 deficiency, metabolic bone disease.
-
Refeeding syndrome: in malnourished chronic diarrhoea patients — refeeding triggers insulin surge → cellular K/PO₄/Mg uptake → acute hypoPO₄/hypoK/hypoMg. Give thiamine first.
-
CRC risk in IBD: increases with extent and duration of colitis. Surveillance colonoscopy from 8 years.
Cough
Cough is a protective reflex involving forceful expulsion of air from the lungs to clear the airways of irritants, secretions, or foreign particles.
Dizziness
Dizziness is a nonspecific symptom encompassing sensations of lightheadedness, unsteadiness, presyncope, or vertigo, arising from cardiovascular, neurological, vestibular, or systemic causes.