GC033 Chronic Diarrhea: Irritable Bowel Syndrome And Inflammatory Bowel Disease
Chronic diarrhea in the context of irritable bowel syndrome (a functional disorder with altered bowel habits and abdominal pain without structural pathology) versus inflammatory bowel disease (chronic immune-mediated intestinal inflammation, including Crohn's disease and ulcerative colitis, with mucosal damage and systemic manifestations).
This lecture, delivered by Prof. W.K. Leung (HKU Division of Gastroenterology and Hepatology), covers the clinical approach to chronic diarrhea — a symptom lasting > 4 weeks that demands systematic classification by mechanism before jumping to diagnosis. The lecture then deep-dives into two major causes that dominate exam questions: Irritable Bowel Syndrome (IBS) (a functional/motility disorder) and Inflammatory Bowel Disease (IBD) (an organic inflammatory disorder comprising Ulcerative Colitis and Crohn's Disease). The conceptual backbone is learning to differentiate organic from functional disease, correctly classify diarrhea mechanisms, and apply the right investigations and treatments.
Learning Objectives (lecture-derived) [1]:
- Define diarrhea and chronic diarrhea
- Classify chronic diarrhea by pathophysiological mechanism
- Approach the workup of chronic diarrhea (history, exam, labs, stool, imaging, endoscopy)
- Diagnose and manage IBS using Rome IV criteria
- Differentiate UC from CD (radiological, endoscopic, histological)
- Understand IBD epidemiology, etiology, complications, and treatment (including biologics and surgery)
Exam Relevance: This is one of the highest-yield GI lectures. Past papers repeatedly test UC vs CD differentiation, Rome IV criteria, fecal calprotectin, IBS alarm features, IBD complications, and biologic indications.
1. Definition and Classification of Diarrhea
"Bowel habits vary widely between individuals. Must first evaluate patient's normal bowel patterns and nature of symptoms." [1]
This matters because what one patient considers "diarrhea" may be another person's baseline. The clinical definition requires deviation from the individual's norm.
Diarrhea is defined as: increase in daily stool volume, frequency and fluidity — stool weight > 250 g/24h, > 2–3 times/day or increased liquidity. [1]
In practice, nobody measures stool weight. You rely on frequency (≥3/day) and consistency (loose/watery). The Bristol Stool Chart is a useful clinical adjunct.
This is the intellectual framework the entire lecture builds upon. Understanding the mechanism tells you which investigations to order and which treatments to use.
| Mechanism | Key Features | Fasting Test | Causes (lecture-listed) |
|---|---|---|---|
| Osmotic | Poorly absorbed solutes draw water into lumen; low stool Na ( < 60 mmol/L); high osmotic gap | Resolves with fasting | Lactase deficiency, laxative abuse, malabsorption [1] |
| Secretory | Active ion secretion by epithelium; high stool Na ( > 90 mmol/L); large-volume watery diarrhea | Persists despite fasting | Endocrine tumors (VIPoma), bile salt malabsorption, laxative abuse [1] |
| Malabsorptive | Failure to absorb nutrients → steatorrhea, weight loss, nutrient deficiency; osmotic component | Resolves with fasting | Small bowel diseases/resection, bacterial overgrowth, pancreatic diseases [1] |
| Inflammatory | Mucosal damage → mucus, blood, PMN in stool | Persists | Crohn's disease, Ulcerative colitis [1] |
| Motility | Altered transit; may overlap with osmotic | Variable | Irritable bowel syndrome [1] |
| Chronic infection | Ongoing pathogen | Persists | TB, Giardia, C. difficile |
High Yield Discriminator: Fasting Test
Why does the fasting test work? Osmotic diarrhea depends on the presence of an unabsorbed solute in the lumen. Remove oral intake → remove the solute → diarrhea stops. Secretory diarrhea involves pathologic activation of chloride channels or cAMP/cGMP pathways in enterocytes, so secretion continues even when the patient is NPO.
Stool osmotic gap = 290 − 2 × (stool Na + stool K)
- Osmotic diarrhea: gap > 125 mOsm/kg (unmeasured solutes are driving water into lumen)
- Secretory diarrhea: gap < 50 mOsm/kg (electrolytes account for most of stool osmolality)
The lecture mentions stool Na < 60 mmol/L → osmotic; stool Na > 90 mmol/L → secretory [1]. This is essentially a shortcut for the same concept.
Drug-induced diarrhea is a crucial cause to exclude early. The lecture lists [1]:
| Drug Category | Examples | Mechanism |
|---|---|---|
| Acid-suppressing | Mg-containing antacids, H2-RA, PPI | Mg is osmotic; PPI alters gut flora |
| Alcohol | — | Direct mucosal irritant, ↑motility |
| Antibiotics | — | Disrupts microbiome → C. diff risk |
| Antihypertensives | Beta-blockers | ↑GI motility |
| Anti-inflammatory | NSAIDs, 5-aminosalicylates | Mucosal damage |
| Others | Colchicine, misoprostol, theophylline | Various |
| Supplements | Vitamin/mineral supplements, herbal products | Osmotic (iron, Mg) |
| Caffeine | Coffee, tea, colas | Methylxanthine → ↑secretion/motility |
| Sugar alcohols | Sorbitol, mannitol (dietetic foods, gums, mints) | Osmotic diarrhea |
Exam Trap
Always ask about drugs, supplements, and dietary habits (including sugar-free gums/mints containing sorbitol) in a patient with chronic diarrhea. This is a frequently missed history point in OSCEs.
3. Clinical Approach to Chronic Diarrhea
Key questions (synthesized from lecture + supporting material) [1][3][4]:
- Onset and duration: When did it start? Gradual vs sudden?
- Stool character: Watery? Bloody/mucoid? Greasy/foul-smelling? Undigested food?
- Volume and frequency: Large-volume watery → secretory; small frequent bloody → inflammatory
- Relationship to fasting: Does it stop when you don't eat?
- Associated symptoms: Weight loss, fever, night sweats, joint pain, mouth ulcers, eye symptoms, skin rashes
- Dietary history: Dairy (lactose intolerance), wheat (celiac), FODMAPs, caffeine, sugar-free products
- Drug history: Full list including OTC, supplements, herbal remedies
- Travel history: Tropical infections, parasites
- Surgical history: Bowel resection, cholecystectomy (bile salt malabsorption)
- Family history: IBD, colorectal cancer, celiac disease
- Sexual history: HIV risk
- Psychological: Stress, anxiety, depression (IBS association)
Physical examination should assess [1]:
| Domain | What to Look For | Why |
|---|---|---|
| Fluid/electrolyte status | Dehydration signs, postural hypotension | Severity assessment |
| Nutritional status | BMI, muscle wasting, temporal wasting | Malabsorption/malignancy |
| Vitamin deficiency | Angular stomatitis (B2), glossitis (B12/folate), dermatitis (niacin), bruising (vit K) | Malabsorption |
| Skin | Rash, flushing (carcinoid), pyoderma gangrenosum, erythema nodosum | IBD, neuroendocrine |
| Thyroid | Masses, toxic signs | Thyrotoxicosis |
| Mouth | Ulcers | Crohn's, celiac |
| Joints | Arthritis | IBD, reactive arthritis |
| Abdomen | Hepatomegaly; tenderness; distension; masses | IBD, malignancy, liver disease |
| Anorectal | Mass, anal tone, perianal disease | Crohn's (perianal fistulae/abscess) |
| Signs of toxicity | Fever, distended/rigid/tender abdomen | Toxic megacolon, peritonitis |
High Yield Physical Exam Finding
Perianal disease (fistulae, abscess, skin tags, fissures) is a hallmark of Crohn's disease and may be the presenting complaint. This was tested in the 2020 MCQ: a 20-year-old man with recurrent perianal abscess + RLQ tenderness → answer is Crohn's disease [5].
3.3 Investigations
Laboratory tests [1]:
| Test | What It Shows | Relevance |
|---|---|---|
| CBC | Anemia (GI blood loss), leukocytosis (inflammation), eosinophilia (parasites, allergy, eosinophilic GE, neoplasms) | Screening |
| ESR, CRP | Inflammatory markers | Differentiates organic from functional |
| Electrolytes | Na, K, Ca, P, Mg | Depletion assessment |
| LFT | Albumin (protein loss, malnutrition), glucose | Nutritional status, liver disease |
| TSH | Thyrotoxicosis | Metabolic cause |
| HIV | Immunosuppression → chronic infections | Risk-based |
| ANF, p-ANCA, serum Ig | Autoimmune screen | IBD, celiac, immunodeficiency |
Stool analysis (spot) [1]:
| Test | Interpretation |
|---|---|
| Stool fat | Malabsorption or maldigestion |
| Stool Na | < 60 mmol/L → osmotic; > 90 mmol/L → secretory |
| Stool pH | *** < 5.6 → carbohydrate malabsorption; < 5.3 → osmotic diarrhea*** |
| Stool culture & microscopy | C. difficile toxin, Aeromonas, Plesiomonas, protozoan/parasitic (Giardia) |
| Stool leukocytes | Inflammatory cause |
| Stool occult blood | GI bleeding, malignancy |
| Fecal calprotectin | Indicates migration of neutrophils to intestinal mucosa |
Fecal calprotectin: 24 kDa dimer of calcium-binding proteins. Indicates migration of neutrophils to the intestinal mucosa. Elevated in infectious diarrhea, Crohn's disease, UC, and cancer. Stable at room temperature. [1]
Why it matters: Fecal calprotectin is the single most useful non-invasive test to differentiate IBS (functional, calprotectin normal) from IBD (inflammatory, calprotectin elevated). It has high negative predictive value — a normal calprotectin makes IBD very unlikely and may spare the patient a colonoscopy. [2][6]
Fecal alpha-1-antitrypsin concentration → suggestive of excessive GI protein loss. Labeled human serum scan → localization of source. [1]
Conditions: IBD, sprue, Whipple's disease, allergic gastroenteropathy, intestinal lymphangiectasia, constrictive pericarditis, congenital hypogammaglobulinemia.
Alpha-1-antitrypsin (A1AT) is resistant to proteolysis in the gut, so if it appears in stool, it must have leaked from damaged mucosa → evidence of protein-losing enteropathy.
Imaging modalities [1]:
| Modality | Use |
|---|---|
| Plain AXR | Calcification → chronic pancreatitis; toxic megacolon |
| Barium meal | Non-specific |
| Small bowel follow through (SBFT) | SB and ileal abnormalities in Crohn's disease (long stricture segments) |
| Barium enema | Colon cancer, polyps, mucosal disease (IBD, ischemia, radiation, laxative abuse) |
| Ultrasound | Biliary obstruction, pancreatic disease |
| CT/MRI enterography | IBD complications (stricture, fistula, abscess) |
| Lymphangiogram | Lymphangiectasia |
MR Enterography: assessing SB mucosal inflammation, fistula, abscess and stricture. Radiation-free. Needs oral contrast to distend SB. [1]
MRE is now preferred over SBFT for Crohn's disease assessment because it is radiation-free (important in young IBD patients who need repeated imaging) and provides superior soft-tissue contrast for detecting mural inflammation, fistulae, and abscesses.
Endoscopy [1]:
- Upper (OGD): duodenal biopsy for celiac disease, Whipple's disease, Crohn's
- Lower (sigmoidoscopy/colonoscopy): mucosal biopsy for IBD, opportunistic infections, microscopic colitis
- Mid (small bowel enteroscopy / capsule endoscopy)
Colonoscopy with ileal intubation and biopsy is the gold standard for diagnosing and assessing IBD. Even if the mucosa looks grossly normal, random biopsies can diagnose microscopic colitis (a frequently overlooked cause of chronic watery diarrhea, especially in elderly women on NSAIDs).
Capsule endoscopy in CD — useful for visualizing small bowel mucosal lesions not reachable by standard endoscopy. Must ensure non-stricturing disease to avoid capsule retention. [1][7]
Balloon enteroscopy — allows tissue sampling and therapeutic intervention in the small bowel. [1]
Management: specific treatment directed to the cause of the disease + supportive treatment. [1]
Supportive options listed:
- Antibiotics (if infectious cause identified)
- Anti-diarrheal drugs (loperamide, diphenoxylate)
- Octreotide (for neuroendocrine/secretory diarrhea)
- Intraluminal absorbents (charcoal)
- Bile acid binding resin (cholestyramine)
- Bismuth compounds
Dietary supplements: Ca, Mg, K, Fe, folate, Vit A, D, K, B12. Anti-diarrheal agents: cholestyramine (bile salt related diarrhea), lomotil, loperamide. Pancreatic enzyme supplement. Enteral and parenteral supplementation. [1]
4. Irritable Bowel Syndrome (IBS)
IBS: Abdominal pain — relieved by defecation, altered frequency, altered consistency. [1]
Rome IV criteria: Recurrent abdominal pain, on average at least 1 day/week in the last 3 months, associated with ≥ 2 of the following:
- Related to defecation
- Associated with a change in frequency of stool
- Associated with a change in form (appearance) of stool For the last 3 months with symptom onset at least 6 months before diagnosis. [1]
Breaking this down from first principles: IBS is a disorder of gut-brain interaction (formerly "functional bowel disorder"). There is no structural or biochemical abnormality detectable by routine tests. The Rome criteria formalize the clinical pattern: recurrent abdominal pain temporally linked to bowel habit changes. The 3-month/6-month rule ensures chronicity and excludes transient, self-limiting conditions.
Population prevalence: 9–25% globally (slide shows geographic variation: Hong Kong ~14%, North America ~15%, South America ~19–23%) [1]
IBS is the commonest cause of chronic diarrhea overall. It is more common in younger patients and females.
Pathophysiological features [1]:
- Brain-Gut axis — bidirectional communication between CNS and enteric nervous system
- Autonomic nervous system — dysregulation contributes to motility and visceral sensitivity changes
- Altered bowel motility [motor] — ↑frequency and irregularity of contractions
- Visceral hypersensitivity [sensory] — ↓pain thresholds for luminal distension
- Psychosocial factors — anxiety, depression, somatization strongly associated
- Neurotransmitter imbalance (serotonin) — 5-HT modulates GI motility and secretion; ↑5-HT in IBS-D, ↓5-HT in IBS-C
Additional factors from supporting sources [3][8]:
- Alteration in gut microbiota: quantitative and qualitative changes demonstrated
- Small intestinal bacterial overgrowth (SIBO): may be present in some patients
- Post-infectious IBS: following E. coli O157:H7, Campylobacter
- Dietary factors: intolerance to FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) or gluten
IBS subtypes [1]:
| Subtype | Definition |
|---|---|
| IBS-D (diarrhea) | Loose/watery stool ≥25% AND hard stool < 25% |
| IBS-C (constipation) | Hard stool ≥25% AND loose/watery stool < 25% |
| IBS-M (mixed) | Hard stool ≥25% AND loose/watery stool ≥25% |
| IBS-U (unsubtyped) | Insufficient abnormality to meet criteria for C, D, or M |
Features against IBS [1]:
| History | Investigations |
|---|---|
| Weight loss | Positive occult stool |
| Rectal bleeding | Anemia |
| Onset in older patients | ↑WBC |
| Family history of CA colon or IBD | ↑ESR |
| Abnormal biochemistry |
These are red flags that should prompt investigation for organic disease (IBD, colorectal cancer, celiac disease) rather than accepting a diagnosis of IBS.
Exam Discriminator: IBS vs IBD
The 2024 MCQ tests this directly [9]: a young man with crampy pain + diarrhea recurring every few months + unintended weight loss → the weight loss is the discriminator. Weight loss is a red flag against IBS and should prompt investigation for IBD or malignancy. The answer for that question is Inflammatory bowel disease, not IBS.
Multi-faceted approach: Education, Reassurance, Dietary modifications, Pharmacotherapy, Psychological treatments. [1]
Pharmacotherapy by Symptom
Treatment targets predominant symptoms [1]:
For Diarrhea (IBS-D):
| Agent | Mechanism |
|---|---|
| Loperamide (opioid agonist) | Slows motility, ↑transit time |
| Low FODMAP diet | Reduces fermentable substrates |
| Cholestyramine (bile salt sequestrant) | Binds bile acids causing diarrhea |
| Probiotics | Modulates gut microbiota |
| Rifaximin (antibiotic) | Non-systemic; targets gut bacteria |
For Constipation (IBS-C):
| Agent | Mechanism |
|---|---|
| Psyllium | Bulk-forming fiber |
| PEG (polyethylene glycol) | Osmotic laxative |
| Prucalopride (5-HT4 agonist) | Prokinetic → ↑colonic motility |
| Lubiprostone (chloride channel activator) | ↑Cl⁻ secretion into lumen → ↑fluid |
| Linaclotide (guanylate cyclase C agonist) | ↑cGMP → ↑Cl⁻/HCO₃⁻ secretion + ↓visceral pain |
For Pain:
| Agent | Mechanism |
|---|---|
| Smooth muscle antispasmodics (otilonium, mebeverine) | Relax smooth muscle, reduce spasm |
| Peppermint oil | Calcium channel blocker in smooth muscle |
| TCA (amitriptyline, desipramine) | Modulate central pain perception + slow motility |
| SSRI (citalopram, paroxetine, sertraline) | Modulate CNS pain processing |
| Lubiprostone | Also listed for pain (IBS-C with pain) |
| Linaclotide | Also reduces visceral pain via cGMP |
Rifaximin: an oral, non-systemic, broad-spectrum antibiotic that targets the gut and is associated with a low risk of bacterial resistance. [1]
Rifaximin has shown benefit in IBS without constipation in the TARGET trials (Pimentel et al., NEJM 2011) [1]. It likely works by modifying the gut microbiome and reducing bacterial overgrowth and endotoxin production.
5. Inflammatory Bowel Disease (IBD)
IBD comprises [1]:
- Ulcerative Colitis (UC): confined to mucosa & submucosa of colon, continuous lesion
- Crohn's Disease (CD): extends from mucosa to serosa, can involve the whole GI tract, skip lesions
- Indeterminate Colitis: cannot be classified as UC or CD (~10%)
This is the single most testable table in the lecture [1]:
| Feature | Ulcerative Colitis | Crohn's Disease |
|---|---|---|
| Location | Usually rectum and colon | Any part of GI tract |
| Distribution | Diffuse and continuous | Patchy, skip lesions |
| Rectosigmoid | Always involved | Involved in ~50% |
| Small bowel | No involvement | Usually involves SB and terminal ileum |
| Depth | Mucosa and submucosa only | Transmural (mucosa to serosa) |
| Stricture/fistula | No | Yes |
| RADIOLOGICAL | ||
| Pattern | Diffuse, continuous | Patchy |
| Stricture/fistula | No | Yes |
| ENDOSCOPIC | ||
| Mucosa | Hyperemic, diffusely granular | Aphthous lesions, cobblestone |
| Ulcers | Shallow ulcers | Solitary and deep ulcers |
| HISTOLOGICAL | ||
| Inflammation | Superficial, continuous | Transmural, patchy |
| Granulomas | Rarely seen | Common (non-caseating) |
| Goblet cells | Depleted | Present |
High Yield: Granulomas in IBD
Granulomas are common in Crohn's disease (non-caseating) but rarely seen in UC. However, if the granuloma is caseating, think of intestinal tuberculosis, NOT Crohn's. This was tested in the 2020 MCQ: ileal ulcers with caseating granuloma → intestinal TB, not Crohn's [5].
Increasing worldwide IBD incidence, especially since 1980. [1] Hong Kong IBD incidence is rising — total incidence ~3/100,000. [1]
| CD | UC | |
|---|---|---|
| Median age of onset | 30 years | 41 years |
| Male predominance | 65% | 56% |
| Family history | ~3% | ~3% |
| Median Hb | 11.6 g/dL (lower) | 12.9 g/dL |
CD patients are younger at onset and more anemic — reflecting the transmural nature and frequent SB involvement causing iron/B12 malabsorption.
Generally unknown. Family aggregation suggests genetic basis. Environmental (diet, infection), immunological, and gut microbiota factors all contribute. [1]
Environmental and Genetic Risk Factors [1]:
| Factor | UC | CD |
|---|---|---|
| Smoking | ↓ risk (protective) | ↑ risk |
| Appendicectomy | ↓ risk | ? No effect |
| NOD2 gene SNP | No effect | ↑ risk |
| MHC genes | Complicated | Complicated |
Why does smoking have opposite effects? The mechanism is not fully understood. In UC, nicotine may increase mucus production and decrease pro-inflammatory cytokine production in the colon. In CD, smoking may impair innate immunity and promote the Th1/Th17 inflammatory pathway involved in transmural inflammation.
NOD2 (CARD15) is the most well-established genetic risk factor for CD. It encodes an intracellular receptor for bacterial muramyl dipeptide. Loss-of-function mutations impair innate immune defense against gut bacteria → aberrant inflammatory response.
CD Location (Vienna/Montreal) [1]:
- L1: Ileal
- L2: Colonic
- L3: Ileocolonic
- L4: Isolated upper GI disease
CD Behavior (Vienna/Montreal) [1]:
- B1: Non-stricturing, non-penetrating
- B2: Stricturing
- B3: Penetrating
- p: Perianal disease modifier (Montreal addition)
UC Phenotype [1]:
- Proctitis (rectum only)
- Left-sided colitis (up to splenic flexure)
- Extensive colitis (beyond splenic flexure; pancolitis if entire colon)
Crohn's Disease: prolonged diarrhea (may be watery or bloody), fever, abdominal pain (often RLQ if terminal ileum involved), weight loss, perianal disease, malnutrition.
Ulcerative Colitis: bloody diarrhea with mucus, urgency, tenesmus, colicky abdominal pain. Bowel movements are frequent and small in volume due to rectal inflammation. [4]
Extraintestinal complications [1]:
| System | Manifestation |
|---|---|
| Musculoskeletal | Peripheral arthropathy, spondylitis (ankylosing spondylitis-like) |
| Hepatobiliary | Gallstones (esp CD — bile salt malabsorption), Primary Sclerosing Cholangitis (esp UC) |
| Renal | Kidney stones (oxalate — CD) |
| Skin | Pyoderma gangrenosum, erythema nodosum, aphthous ulcers |
| Eyes | Uveitis, iritis, episcleritis, scleritis |
| Vascular | Arterial/venous thromboembolism |
| Hematology | Autoimmune hemolytic anemia, anemia of chronic disease |
Which EIMs Track Disease Activity?
Track with disease activity: Erythema nodosum, peripheral (Type I) arthritis, episcleritis, aphthous ulcers → improve when IBD is controlled.
Independent of disease activity: Pyoderma gangrenosum, Primary Sclerosing Cholangitis, Ankylosing Spondylitis, uveitis → can persist even in remission.
5.8 Complications
[1]:
- Malnutrition: protein, calorie and vitamin deficiencies; poor intake, protein-losing enteropathy, malabsorption
- Abscesses and fistulae: extension of mucosal fissure/ulcer through bowel wall into extra-intestinal tissue; abscess in peritoneal cavity; fistula to adjacent viscera (bladder, vagina), abdominal wall
- Stricture/obstruction: mucosal thickening from active inflammation, scarring, adhesions, food impaction
- Perianal disease: abscess, fistula, anal fissures
Fistula types (from supporting sources) [10]:
- Enteroenteric → palpable mass
- Enterovesical → UTI symptoms, pneumaturia, fecaluria
- Enterovaginal → passage of gas/feces per vagina
- Enterocutaneous → drainage to skin surface
- Retroperitoneal → psoas abscess, hydronephrosis
[1]:
- Toxic megacolon:
- Diagnosed by plain AXR (transverse colon diameter > 6 cm)
- Clinical features: fever > 38°C, heart rate > 120/min, anemia, low albumin
- Exclude coexisting C. difficile or CMV infection
- Treatment: bowel rest and TPN, fluid/electrolyte replacement, corticosteroids, close monitoring
- Outcome: ~50% respond to medical treatment; ~50% require urgent colectomy if not responding in 3–7 days
- Colorectal cancer
Moderately increased risk of colon cancer. Extensive disease: 8–10 years after onset. Need regular endoscopic surveillance in long-standing extensive disease (every 1–2 years). Higher risk with concurrent primary sclerosing cholangitis. [1]
AXR findings [1]:
- Thumb printing: mucosal edema causing round indentations along bowel wall
- Toxic megacolon: dilated transverse colon > 6 cm with loss of haustral markings
No single test or gold standard. Diagnosed by endoscopic, radiological, pathological and/or biochemical findings. Rule out infection, especially TB. [1]
Investigations [1]:
- CBC (anemia, high WBC)
- CRP
- Stool (WBC, bacteria, parasites)
- Serology: ASCA (anti-Saccharomyces cerevisiae antibodies), pANCA
- Colonoscopy/sigmoidoscopy with biopsy:
- CD → granuloma
- UC → mucosal inflammation, glandular distortion and atrophy
- Small bowel series (CD)
- CT or MR enteroclysis/enterography (CD)
- CT scan for diagnosis and complications
| Serology | More Associated With |
|---|---|
| ASCA positive | Crohn's disease |
| pANCA positive | Ulcerative colitis |
However, as noted in the senior notes: "antibodies are useless in diagnosing IBD" — they are neither sensitive nor specific enough for diagnosis; they are adjuncts for subtyping in indeterminate colitis [2][6].
TB vs Crohn's — This is critical in Hong Kong where TB is still prevalent. Caseating granulomas → TB; non-caseating granulomas → Crohn's. [5] Also: TB tends to have circumferential ulcers, peritoneal involvement, and responds to anti-TB treatment trial.
5.10 Treatment of IBD
Induction of remission during acute flare-up. Maintenance of remission. Modification of clinical course — reduce surgery and complications, improve nutritional status, cancer prevention, improve QoL. [1]
5-ASA (in UC) → Steroids → Thiopurines → Biologics → Surgery [1]
This "step-up" approach starts with the least potent and escalates. Modern practice increasingly uses "top-down" or "treat-to-target" strategies in high-risk patients, but the GC lecture presents the traditional framework.
1. 5-Aminosalicylates (5-ASA)
Indications: mild to moderately severe UC and colonic CD. Maintenance of remission. Local anti-inflammatory action. [1]
- Sulphasalazine = sulphapyridine + 5-ASA
- Side effects: skin rash, hemolysis, neutropenia, male infertility, pancreatitis
- 5-ASA analogues: Mesalazine, Olsalazine
- Routes: oral, enema, or suppository
Why sulphasalazine causes male infertility: sulphapyridine (the carrier molecule) reduces sperm count and motility. This is reversible on stopping the drug. Mesalazine does not have this effect because it lacks the sulphapyridine component.
2. Corticosteroids
Used for induction of remission in moderate-severe flares. NOT for maintenance (due to side effects and steroid dependency). Includes oral prednisolone, IV hydrocortisone (for severe flares), and topical budesonide (for ileal/right-sided CD with fewer systemic effects).
3. Immunomodulators
Azathioprine / 6-Mercaptopurine [1]:
- Indications: frequently relapsing disease, steroid-sparing, fistulating CD
- Delayed onset: ~3 months (so not suitable for acute induction alone)
- Well tolerated, side effects in ~10%
- Side effects: bone marrow suppression, allergy, hepatotoxicity, pancreatitis
Azathioprine is a prodrug → converted to 6-mercaptopurine → then to 6-thioguanine nucleotides (active metabolites) which inhibit purine synthesis and suppress lymphocyte proliferation. The enzyme TPMT (thiopurine methyltransferase) metabolizes the drug — patients with low TPMT activity are at risk of severe myelosuppression. TPMT genotyping or phenotyping should ideally be done before starting.
4. Biologics
Biologics for IBD [1]:
| Class | Agents | Target |
|---|---|---|
| Anti-TNFα | Infliximab, Adalimumab, Certolizumab Pegol | TNF-alpha |
| Anti-adhesion molecules | Vedolizumab | α4β7 integrin (gut-selective) |
| Anti-IL-23 | Ustekinumab, Risankizumab | IL-12/23 p40 (ustekinumab) or IL-23 p19 (risankizumab) |
| JAK inhibitors | Tofacitinib, Upadacitinib | Janus kinase pathway |
Small molecules (oral): S1P modulators, JAK inhibitors, TYK inhibitors, oral integrin inhibitors. [1]
Indications for biologics [1]:
- Standard treatment not working
- Acute severe UC not responding to steroid
- Fistulising disease
- Extra-intestinal manifestations (e.g., pyoderma gangrenosum)
Risks of biologics [1]:
- Infection: reactivation of latent TB & latent viral infection e.g., HBV (anti-TNFs); Herpes zoster (JAK inhibitors)
- Malignancy: Lymphoma (anti-TNFs)
Critical Safety Point: Screen Before Biologics
Before starting anti-TNF therapy, you MUST screen for latent TB (CXR + IGRA/tuberculin test) and check HBV status (HBsAg, anti-HBc, anti-HBs). Reactivation of latent TB or HBV can be fatal. This is a high-yield exam point.
5. Surgery
> 50% of CD patients require surgery during their lifetime. Surgery is NOT curative for CD — disease recurs close to the anastomosis. [1] Indications: severe bleed, perforation, stricture, fistula, abscess, failed medical treatment, risk of cancer. [1] Procedures: resection of diseased intestine (CD), stricturoplasty, colectomy/proctocolectomy (acute severe UC and CRC). [1]
For UC, total proctocolectomy IS curative (removes all colonic mucosa). Common reconstruction: ileal pouch-anal anastomosis (IPAA / "J-pouch").
Hong Kong data: cumulative colectomy rate in UC is lower than Western data (Copenhagen ~30% at 15 years vs Hong Kong lower). [1]
7. Integration with Related Material
- Indeterminate colitis accounts for ~10% of IBD cases
- Surgical indications overlap with medical lecture content
- Proctocolectomy is curative for UC but not CD
- Chronic non-specific diarrhea ("toddler's diarrhea") is the most common cause in pediatrics
- Celiac disease uncommon in Asian populations but important differential
- Bloody stool + fever + cramps in a child → consider bacterial causes AND initial presentation of IBD
- Anterior uveitis is the commonest ocular manifestation of IBD
- Associated with HLA-B27, particularly in IBD with axial spondyloarthropathy
- Presents with ocular pain, photophobia, ciliary flush
- Type I: acute pauciarticular, tracks with intestinal disease activity
- Type II: polyarticular, independent of disease activity
- HLA-B27 positive in 50–75% of IBD-associated axial spondyloarthritis
Based on past papers and lecture content:
MCQ-Style:
- A 20-year-old man with recurrent perianal abscess, RLQ tenderness, weight loss → Most likely diagnosis? → Crohn's disease (2020 Q32) [5]
- Ileal ulcers with caseating granuloma → Intestinal TB, not Crohn's (2020 Q33) [5]
- Young man with crampy pain, diarrhea, weight loss recurring for 1 year → IBD (2024 Q24) [9]
- Elderly woman with anxious personality, crampy pain, constipation, incomplete emptying → IBS vs colorectal cancer (weight loss present → investigate) (2024 Q25) [9]
SAQ-Style:
- "List 4 mechanisms of chronic diarrhea and give one example of each."
- "State the Rome IV criteria for IBS."
- "Compare UC and CD in terms of distribution, depth of inflammation, endoscopic appearance, and histology." (classic table question)
- "List the extraintestinal manifestations of IBD."
- "Name 4 indications for biologic therapy in IBD."
- "What investigations would you order for a patient with chronic bloody diarrhea? Explain your rationale."
Mini-Case Style:
- A 25-year-old with 6 months of bloody diarrhea, weight loss, perianal fistula. CRP elevated, fecal calprotectin high. Colonoscopy shows skip lesions with deep ulcers and cobblestone mucosa. Biopsy shows non-caseating granulomas.
- Diagnosis: Crohn's disease
- Classification: Montreal L3 B3p
- Initial management: steroids for induction → azathioprine for maintenance → biologics if refractory
High Yield Summary
Chronic Diarrhea: ≥4 weeks, ≥3 loose stools/day. Classify by mechanism: osmotic (resolves with fasting), secretory (persists with fasting), malabsorptive, inflammatory, motility, infectious. Always exclude drugs.
IBS: Rome IV = recurrent abdominal pain ≥1 day/week for 3 months + ≥2 of: related to defecation, change in frequency, change in form. Onset ≥6 months before diagnosis. Alarm features (weight loss, bleeding, older onset, FHx, abnormal labs) → investigate for organic disease. Fecal calprotectin is the key discriminator (normal in IBS, elevated in IBD).
IBD: UC = continuous, mucosal, always starts at rectum, shallow ulcers, goblet cell depletion. CD = skip lesions, transmural, any part of GI tract, deep ulcers, granulomas, strictures, fistulae. Smoking protects against UC but worsens CD. NOD2 mutations → CD risk. ASCA → CD, pANCA → UC (but not diagnostic alone).
IBD Treatment: Step-up = 5-ASA → steroids → thiopurines → biologics → surgery. Biologics (anti-TNF, vedolizumab, ustekinumab, JAK inhibitors) indicated when standard therapy fails, acute severe UC steroid-refractory, fistulising disease, or refractory EIMs. Screen for latent TB and HBV before anti-TNFs. Surgery is curative for UC (proctocolectomy) but NOT for CD (recurrence at anastomosis).
Toxic megacolon: diagnosed on AXR, features = fever > 38, HR > 120, anemia, low albumin. Exclude C. diff/CMV. ~50% need colectomy if unresponsive to medical treatment in 3–7 days.
CRC risk in UC: increased after 8–10 years of extensive disease. Surveillance colonoscopy every 1–2 years. Higher risk with concurrent PSC.
Active Recall - Chronic Diarrhea, IBS and IBD
[1] Lecture slides: GC 033. Chronic diarrhea_irritable bowel syndrome and inflammatory bowel disease.pdf [2] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf [3] Senior notes: Maksim Medicine Notes.pdf (IBS and enteric infections sections) [4] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (chronic diarrhea and IBD sections) [5] Past papers: 2020 Fourth Summative Assessment MCQ paper.pdf (Q32, Q33) [6] Senior notes: Block A - Gastrointestinal Data Interpretation.pdf (Case 4 - fecal calprotectin) [7] Senior notes: Block A - Coffee ground vomitus tarry stool upper GI bleeding.pdf (capsule endoscopy indications) [8] Senior notes: Ryan Ho GI.pdf (IBS and chronic diarrhea sections) [9] Past papers: 2024 Fourth Summative MCQ.pdf (Q24, Q25) [10] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (Crohn's fistula types and EIMs) [11] Lecture slides: Inflammatory bowel disease.pdf (General Surgery) [12] Lecture slides: GC 142. A child with loose stool.pdf [13] Senior notes: Ryan Ho Opthalmology.pdf (uveitis section) [14] Senior notes: Ryan Ho Rheumatology.pdf (enteropathic arthritis)
GC032 Chest Pain On Exertion: Ischaemic Heart Disease; Angina Pectoris
Angina pectoris is episodic chest pain or discomfort caused by transient myocardial ischemia due to an imbalance between myocardial oxygen supply and demand, typically provoked by exertion or stress and relieved by rest or nitrates.
GC034 Chronic Kidney Disease And Its Complications
Chronic kidney disease is a progressive, irreversible decline in kidney function (GFR <60 mL/min/1.73 m² for ≥3 months or evidence of kidney damage) leading to complications such as anemia, mineral-bone disorder, cardiovascular disease, electrolyte imbalances, and ultimately end-stage renal failure.