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)
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.
Bristol Stool Form Scale (from lecture slide) [1]:
| Type | Description |
|---|---|
| 1 | Separate hard lumps, like nuts (hard to pass) |
| 2 | Sausage-shaped but lumpy |
| 3 | Like a sausage but with cracks on the surface |
| 4 | Like a sausage or snake, smooth and soft |
| 5 | Soft blobs with clear-cut edges |
| 6 | Fluffy pieces with ragged edges, a mushy stool |
| 7 | Watery, no solid pieces, entirely liquid |
Types 1–2 correspond to constipation; Types 6–7 correspond to diarrhea. These map directly to IBS subtyping: IBS-C patients report predominantly Bristol types 1–2, while IBS-D patients report predominantly Bristol types 6–7. [1]
| Feature | Acute Diarrhea | Chronic Diarrhea |
|---|---|---|
| Duration | < 4 weeks | ≥ 4 weeks [1] |
| Common cause | Infection (viral, bacterial) | IBS, IBD, malabsorption, drugs |
| Approach | Supportive ± empiric abx | Systematic workup by mechanism |
Acute diarrhea can be further sub-classified as inflammatory (dysentery-type: bloody, mucoid, febrile) or non-inflammatory (watery, non-bloody). This distinction guides initial empiric management. [1]
Chronic diarrhea = loose stools that last > 4 weeks, usually means ≥ 3 loose stools/day. [1]
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 calculation conventionally assumes stool osmolality is 290 mOsm/kg. Do not substitute a measured stool osmolality into the gap: collection dilution and bacterial metabolism after passage can make the measured value misleading. The lecture's stool Na < 60 mmol/L → osmotic; stool Na > 90 mmol/L → secretory rule is a shortcut, not a stand-alone diagnosis. Mixed mechanisms are common.
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 |
| Coeliac serology | tTG-IgA plus total IgA (with an IgG-based test if IgA deficient) | Recommended initial screen in chronic diarrhea |
| HIV | Test when exposure history or the pattern of opportunistic infection warrants it | Risk-based |
The slide lists ANF, p-ANCA and serum immunoglobulins broadly. In contemporary practice, they are targeted tests, not a routine chronic-diarrhea panel. In particular, p-ANCA/ASCA do not establish an IBD diagnosis. Initial non-invasive assessment should include coeliac serology and, where appropriate, fecal calprotectin before specialist referral [15].
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 a useful non-invasive marker of intestinal neutrophilic inflammation. A low result supports a positive diagnosis of IBS in a younger, otherwise low-risk patient with typical symptoms and normal screening tests; a high result supports further assessment for inflammation. It is not an IBS/IBD binary switch: infection, colorectal neoplasia, NSAIDs and other inflammatory disorders can elevate it, while mild or isolated small-bowel Crohn's disease may occasionally produce a low result. Thresholds are assay- and pathway-specific; the BSG IBS pathway gives examples of < 100 μg/g low, 100–249 indeterminate and ≥250 high, with medication review/repeat testing for an indeterminate result [16].
Fecal Calprotectin – High Yield
Low fecal calprotectin → active colonic inflammation less likely in the right clinical setting. High fecal calprotectin → investigate an inflammatory cause; it does not by itself diagnose IBD. Alarm features, older age/cancer risk or persistent unexplained symptoms still warrant the appropriate endoscopic or imaging pathway. Antibodies (ASCA, p-ANCA) are not diagnostic. [15][16]
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.
The slide labels an additional test as "serum alpha-1-AT clearance". The clinically meaningful test is stool A1AT clearance, calculated from a timed stool collection and a paired serum A1AT concentration; a serum value alone does not measure enteric clearance.
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.
How to Read the Imaging Slides
- SBFT (slides 16–17): look for a long narrowed small-bowel segment, irregular mucosa and upstream dilatation. The contrast study outlines the lumen but says little about disease outside the bowel wall.
- CT/MR enterography (slides 17 and 19): cross-sectional imaging adds mural thickening and enhancement, mesenteric inflammation, strictures and penetrating complications such as fistulae or abscesses. MRE avoids ionising radiation; CT is fast and valuable in an acute complication.
- Chronic pancreatitis (slide 18): the AXR shows coarse calcification projected over the pancreas; CT localises parenchymal/intraductal calcification and ductal stones. These findings support pancreatic exocrine insufficiency as a cause of maldigestion.
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)
Ileocolonoscopy with segmental biopsy is central to diagnosis and assessment, but IBD has no single gold-standard test: the diagnosis integrates the clinical pattern, exclusion of infection, endoscopy/histology and small-bowel imaging where indicated. In chronic watery diarrhea, right- and left-colon biopsies can diagnose microscopic colitis even when the mucosa looks normal [15].
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]
Endoscopy: Translate the Pictures into Words
- UC pattern: diffuse erythema, loss of the normal vascular pattern, granularity/friability and superficial ulceration in a continuous segment; chronic disease may leave post-inflammatory pseudopolyps.
- Crohn pattern: patchy aphthae that may coalesce into deep linear or serpiginous ulcers, with intervening edematous mucosa producing cobblestoning. Ileal disease and rectal sparing support but do not prove Crohn's disease.
- Capsule slide: small white-based aphthous/linear ulcers are visible beyond conventional endoscopic reach, but these are not specific; exclude a relevant stricture first because retention can occur.
- Balloon-enteroscopy diagram: sequential balloon inflation anchors the overtube and pleats the small bowel onto it, enabling deep insertion, biopsy and therapy rather than imaging alone.
Management: specific treatment directed to the cause of the disease + supportive treatment. [1]
Supportive options listed:
- Antibiotics only when a treatable infectious cause or a specific empiric indication is present
- Anti-diarrheal drugs (loperamide, diphenoxylate) for selected non-inflammatory diarrhea after hydration
- Octreotide (for neuroendocrine/secretory diarrhea)
- Intraluminal absorbents (charcoal was lecture-listed but is not routine evidence-based therapy)
- Bile acid binding resin (cholestyramine)
- Bismuth compounds
Avoid antimotility drugs when there is bloody/inflammatory diarrhea, fever, suspected C. difficile, severe active colitis or toxic megacolon risk. They are symptom control, never a substitute for fluid/electrolyte replacement [17].
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"). Routine tests do not identify an explanatory structural disease, but that does not mean "nothing is abnormal": altered visceral sensation, motility, brain–gut processing and sometimes low-grade mucosal/microbiome changes contribute. Rome IV deliberately says pain is related to defecation; it need not be relieved by it.
Lecture-era estimate: population prevalence 9–25% globally [1]
IBS is the commonest cause of chronic diarrhea overall. It is more common in younger patients and females.
The world map is useful for showing that reported prevalence varies, but its regional percentages should not be memorised as current population facts. Estimates change substantially with the diagnostic criteria, survey method and era; Rome IV generally yields lower prevalence than older definitions.
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% (Bristol 6–7) |
| IBS-C (constipation) | Hard stool ≥25% AND loose/watery stool < 25% (Bristol 1–2) |
| IBS-M (mixed) | Hard stool ≥25% AND loose/watery stool ≥25% (Bristol 1–2 AND 6–7) |
| IBS-U (unsubtyped) | Insufficient abnormality to meet criteria for C, D, or M |
The 25% cut-offs refer to bowel movements with abnormal stool form, not all bowel movements. Plot hard/lumpy stools (Bristol 1–2) against loose/watery stools (Bristol 6–7), as in the quadrant diagram on slide 33.
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 | Possible strain-specific benefit; evidence is heterogeneous, so avoid presenting the class as uniformly effective |
| Rifaximin (antibiotic) | Non-systemic; targets gut bacteria |
For Constipation (IBS-C):
| Agent | Mechanism |
|---|---|
| Psyllium | Bulk-forming fiber |
| PEG (polyethylene glycol) | Improves constipation; benefit for global IBS pain is less certain |
| Prucalopride (5-HT4 agonist) | Lecture-listed; primarily a chronic idiopathic constipation drug rather than an established IBS-specific therapy |
| 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) | Evidence is inconsistent; not a default analgesic, though it may be selected for comorbid mood symptoms |
| Lubiprostone / linaclotide | IBS-C secretagogues that improve global symptoms; linaclotide also has evidence for abdominal pain |
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]. Read the graph critically: after a 14-day course, adequate relief was only about 8 percentage points higher than placebo, and relief declined in both arms during follow-up. Current AGA guidance supports rifaximin for IBS-D and retreatment after an initial response if symptoms recur; TCAs and antispasmodics are other symptom-directed options [18]. Low-FODMAP therapy should be time-limited, followed by reintroduction and personalisation, ideally with dietetic support [19].
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 | Usually begins in the rectum; apparent rectal sparing can occur after treatment and in some atypical/pediatric cases | Rectal involvement is variable |
| Small bowel | Disease is colonic; mild backwash ileitis can accompany extensive colitis | Frequently involves terminal ileum/small bowel but may be isolated to the colon or upper GI tract |
| Depth | Predominantly mucosal; severe ulceration can extend deeper | Transmural (mucosa to serosa) |
| Gross features | Ulcerations, crypt distortion, pseudopolyps | Cobblestone appearance, linear ulcerations, fissures, narrowed lumen, thickened wall, abscess |
| Stricture/fistula | Not typical; a UC stricture is a cancer warning until assessed | Characteristic penetrating/stricturing complications |
| RADIOLOGICAL | ||
| Pattern | Diffuse, continuous | Patchy |
| Stricture/fistula | Not typical | May occur |
| ENDOSCOPIC | ||
| Mucosa | Hyperemic, diffusely granular | Aphthous lesions, cobblestone |
| Ulcers | Shallow ulcers | Solitary and deep ulcers |
| HISTOLOGICAL | ||
| Inflammation | Superficial, continuous | Transmural, patchy |
| Granulomas | Crypt-injury-associated granulomas can occur, but true epithelioid granulomas away from ruptured crypts argue against UC | Non-caseating granulomas are supportive and specific after infection is excluded, but are found in only a minority of mucosal biopsies |
| Goblet cells | Mucin/goblet-cell depletion may occur in active disease | May be preserved; not a reliable stand-alone discriminator |
High Yield: Granulomas in IBD
A well-formed non-caseating granuloma away from crypt injury supports Crohn's disease, but most Crohn's mucosal biopsies do not contain one. Caseation strongly favours infection such as intestinal tuberculosis rather than Crohn's. This was the discriminator in the 2020 MCQ: ileal ulcers with a caseating granuloma → intestinal TB [5].
The lecture's historical datasets show increasing worldwide IBD incidence and a marked rise in Hong Kong through 2011–2014. [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.
How to read the epidemiology figures: the world maps compare studies published in different eras and demonstrate emergence and geographic spread, not a head-to-head contemporary league table. The Hong Kong line graph is a specific historical cohort: total age-adjusted incidence rose from ~0.1/100,000 (1981–1985) to ~3.1/100,000 (2011–2014), with CD catching UC at ~1.5/100,000 each in the final interval (Ng SC, Leung WK et al., IBD 2016) [1]. Keep the dates attached to these numbers.
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 | Lower observed incidence (not a preventive treatment) | Higher risk and worse course |
| 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.
These are epidemiological associations, not treatments: do not advise smoking or appendicectomy to prevent UC. In established Crohn's disease, smoking cessation is an important modifiable intervention.
CD Location (Vienna/Montreal) [1]:
- L1: Ileal
- L2: Colonic
- L3: Ileocolonic
- L4: Isolated upper GI disease
CD location frequencies (from lecture slide) [1]:
- Small intestine and colon: 40–55%
- Small intestine only: 25–30%
- Colon only: 20–25%
- Upper GI (esophagus/stomach/duodenum): 3–5%
- Anorectal disease (fistulae, fissures, abscesses): 30–40%
- Rectal involvement: 11–26%
CD Behavior (Vienna/Montreal) [1]:
- B1: Non-stricturing, non-penetrating
- B2: Stricturing
- B3: Penetrating
- p: Perianal disease modifier (Montreal addition)
The location diagram also makes two visual points easy to miss: Crohn's can involve discontinuous sites from mouth to anus, and perianal fistula/abscess is recorded separately because it modifies prognosis and management. The percentages on slide 51 describe an older cohort and should be treated as approximate, not diagnostic probabilities.
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.
Visual Recognition: Skin and Eye Slides
- Erythema nodosum: tender, erythematous subcutaneous nodules, classically on the shins; they do not ulcerate.
- Pyoderma gangrenosum: the serial photographs show a rapidly ulcerating lesion with a tender violaceous/undermined border, followed by healing with residual discoloration/scarring. It is a clinical diagnosis of exclusion; trauma/debridement can worsen it through pathergy.
- Episcleritis: sectoral superficial redness, often tracking bowel activity and usually without the marked pain/photophobia of uveitis.
- Anterior uveitis: a painful photophobic red eye with ciliary/perilimbal injection; this needs urgent ophthalmic assessment because vision is at risk.
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
Acute severe UC (ASUC) and toxic megacolon are related but not synonymous. ASUC is a clinical emergency (classically ≥6 bloody stools/day plus systemic toxicity). Toxic megacolon adds non-obstructive colonic dilatation, usually > 6 cm, plus systemic toxicity and can complicate IBD or infectious colitis.
Contemporary ASUC priorities [20]:
- Admit under gastroenterology with early colorectal-surgical and stoma-team involvement; monitor stool frequency, examination, CRP, blood count, albumin and electrolytes.
- Send stool culture and C. difficile testing; perform non-invasive imaging and an early, limited flexible sigmoidoscopy with biopsies when safe. Assess for CMV in the appropriate steroid-refractory context.
- Give IV corticosteroids promptly, fluid/electrolyte replacement, nutritional assessment/support and pharmacological VTE prophylaxis unless contraindicated. Routine bowel rest or TPN is not a treatment for colitis; use enteral feeding when tolerated and reserve parenteral nutrition for a genuine inability to feed enterally [26].
- Reassess objectively by day 3. Steroid non-response should trigger rescue infliximab or ciclosporin (when appropriate) and a parallel surgical plan.
- Do not delay colectomy for perforation, uncontrolled haemorrhage, worsening toxic megacolon or clinical deterioration. Failure to respond to rescue treatment within about 7 days also favours surgery; delay increases complications.
Lecture-era summary: cancer risk rises with duration and inflammatory burden; extensive colitis and concurrent PSC increase risk. [1]
Current surveillance is risk-stratified, not automatically every 1–2 years for everyone. BSG 2025 advises a risk-assessment colonoscopy 8 years after symptom onset, or from IBD diagnosis in PSC-associated colitis. Subsequent intervals depend on inflammation, disease extent, PSC, stricture, dysplasia, family history and prior examinations: examples include annual surveillance for PSC/moderate active inflammation/stricture/dysplasia, every 3 years for mild active inflammation or extensive disease, and population screening with 10-year reassessment for people close to population risk [21]. Local guidance may differ.
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
On slide 60, the repeated rounded soft-tissue impressions are thickened edematous haustral folds ("thumbprints"). On slide 61, the important finding is a markedly dilated, relatively ahaustral colonic segment. Diameter alone does not diagnose toxic megacolon; add the patient's systemic toxicity and exclude mechanical obstruction.
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 |
ASCA and pANCA are neither sensitive nor specific enough to establish or exclude IBD. They are occasionally adjunctive in unresolved IBD-unclassified cases, but are not routine first-line diagnostic tests.
TB vs Crohn's — This is critical in Hong Kong. Caseation, confluent/large granulomas, transverse/circumferential ulcers, necrotic lymph nodes or microbiological evidence favour intestinal TB; longitudinal ulcers, cobblestoning and perianal disease favour Crohn's. No single feature is absolute. Seek tissue for mycobacterial testing and specialist input rather than treating a response to an empirical anti-TB trial as a diagnostic test; immunosuppression in unrecognised TB can be catastrophic.
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 pyramid is explicitly a traditional, lecture-era model, not a universal sequence. Treatment is now selected by diagnosis, severity, disease location/behaviour, prognostic risk, comorbidity, prior drug exposure and patient preference. For moderate-to-severe UC and CD, current AGA guidance supports early advanced therapy rather than mandatory failure of corticosteroids/thiopurine step-up [22][23]. Steroids induce remission but do not maintain it; surgery is not merely the final failed rung and may be the best timely treatment for a complication or selected localised disease.
1. 5-Aminosalicylates (5-ASA)
Lecture-era indications: mild to moderately severe UC and colonic CD; maintenance of remission. [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.
Current correction: 5-ASA remains a key induction and maintenance therapy for mild-to-moderate UC, with oral and/or rectal delivery chosen by extent. ECCO 2024 recommends against 5-ASA for induction or maintenance of Crohn's disease, regardless of location, because clinically meaningful efficacy is lacking [24]. Do not generalise the old "colonic CD" line to modern Crohn's care.
2. Corticosteroids
Used for short-term induction in selected active disease, never maintenance. Includes oral prednisolone, IV hydrocortisone/methylprednisolone for ASUC, and oral controlled-release budesonide for mild-to-moderate Crohn's limited to the ileum and/or ascending colon. Budesonide is not simply a "topical" treatment and is formulation/location dependent. Minimise cumulative steroid exposure and establish an effective steroid-sparing maintenance plan.
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. Its delayed action means thiopurine monotherapy is not an induction treatment for active UC or CD. Before treatment, assess TPMT and consider NUDT15 genotype, whose loss-of-function variants are especially relevant in Asian populations; neither replaces serial CBC and liver-test monitoring. Discuss pancreatitis, infection, non-melanoma skin cancer and lymphoma risk, and account for age, EBV status and combination therapy [24][25].
4. Biologics
Biologics for IBD [1]:
| Mechanistic class | Current examples (indications/approval vary by UC vs CD and jurisdiction) | What the pathway diagram means |
|---|---|---|
| Anti-TNF | Infliximab, adalimumab; golimumab (UC), certolizumab pegol (CD in some jurisdictions) | Neutralise an extracellular inflammatory cytokine |
| Anti-integrin | Vedolizumab | Blocks α4β7–MAdCAM-1 lymphocyte homing to the gut |
| Anti-IL-12/23 p40 | Ustekinumab | Blocks the shared p40 subunit; it is not a selective anti-IL-23 drug |
| Selective anti-IL-23 p19 | Risankizumab, mirikizumab, guselkumab | Blocks IL-23 signalling while sparing IL-12 |
| JAK inhibitor (oral small molecule) | Tofacitinib (UC), upadacitinib (UC/CD) | Blocks intracellular cytokine signalling rather than a single extracellular ligand |
| S1P receptor modulator (oral small molecule) | Ozanimod, etrasimod (UC) | Retains lymphocytes in lymphoid tissue and reduces trafficking to bowel |
Slide 70 groups targets into four visual levels: extracellular cytokine blockade, intracellular JAK signalling, direct cytokine targeting and lymphocyte trafficking. Slide 71's TYK inhibitors and oral integrin inhibitors were a pipeline overview, not a statement that every class was approved. Likewise, brazikumab, etrolizumab and ontamalimab on the older figure should not be presented as routine current therapies. Current AGA living guidance includes several agents that were investigational when the figure was published [22][23].
Lecture-listed indications [1]: standard treatment not working, corticosteroid-refractory ASUC, fistulising disease and selected extra-intestinal manifestations.
The modern decision is broader: early advanced therapy may be appropriate at diagnosis in moderate-to-severe or prognostically high-risk disease. In ASUC, only selected rescue regimens (classically infliximab or ciclosporin) belong in the urgent day-3 pathway; do not substitute any drug from the general advanced-therapy list.
Lecture-listed risks [1]: serious/opportunistic infection, TB or HBV reactivation with anti-TNF therapy, herpes zoster with JAK inhibition, and malignancy concerns.
Critical Safety Point: Screen Before Biologics
Before anti-TNF and other relevant immunosuppressive/advanced therapy, perform a therapy- and risk-tailored infection screen and update vaccination where possible. For anti-TNF this includes latent-TB assessment (exposure/risk history, chest imaging and IGRA and/or TST according to local pathway) and HBV serology (HBsAg, anti-HBc, anti-HBs), with specialist prophylaxis/treatment when indicated. Check for active infection before escalating immunosuppression [27].
Do not reduce malignancy counselling to "anti-TNF causes lymphoma." ECCO finds the clearest signal with thiopurines, and lymphoma risk is higher with combined thiopurine–anti-TNF therapy than with either monotherapy; absolute risk remains low and varies with age, sex and EBV status [25]. JAK inhibitors require separate cardiovascular, thrombotic, malignancy and infection risk assessment according to product/local guidance.
5. Surgery
Lecture-era statement: > 50% of CD patients require surgery during their lifetime. Surgery is not curative for CD and postoperative recurrence often begins near 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]
Modern surgery rates vary by cohort, era, phenotype and therapy; quote the slide's > 50% only with that context. For UC, total proctocolectomy removes the colon/rectum and therefore eliminates colonic UC and colitis-associated CRC risk, but "curative" should not imply that every disease consequence disappears: pouchitis, surgical morbidity, PSC and some extraintestinal manifestations may persist. A common reconstruction is ileal pouch–anal anastomosis (IPAA, "J-pouch").
Historical Hong Kong data in the lecture showed a lower cumulative colectomy rate than the compared Western cohort [1]:
- Copenhagen (n=1161): ~9% at 1 year, ~24% at 10 years, ~30% at 15 years
- Hong Kong (n=172): ~2% at 1 year, ~7% at 10 years
- Japan: ~4.1%; Korea: ~2.0% (reported values)
HK CD surgery-free survival: the older Kaplan–Meier curve falls steeply early, then more gradually, to ~55% at 10 years (Chow et al., 2008). Tick marks represent censored observations, not surgery events. These graphs describe those cohorts and treatment eras; they do not predict an individual patient's present-day outcome.
7. Integration with Related Material
- Indeterminate colitis accounts for ~10% of IBD cases
- Surgical indications overlap with medical lecture content
- Proctocolectomy removes colonic UC and colitis-associated cancer risk; pouch/surgical complications and some extraintestinal disease can remain. Intestinal resection is not curative for 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
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.
- A low fecal calprotectin supports IBS in an appropriate low-risk setting; a high result indicates inflammation but is not specific for IBD.
-
IBD
- UC = usually continuous from the rectum and predominantly mucosal; treatment can create patchiness/rectal sparing, and backwash ileitis can occur.
- CD = skip lesions, transmural disease, deep/serpiginous ulcers, strictures and fistulae; granulomas are supportive but present in a minority of biopsies.
- Smoking is epidemiologically associated with lower UC incidence but worsens CD; it is never advised as UC treatment/prevention.
- NOD2 mutations → CD risk.
- ASCA → CD, pANCA → UC (but not diagnostic alone).
-
IBD Treatment
- The slide's step-up pyramid is historical. Mild-moderate UC uses 5-ASA; routine 5-ASA is not recommended for CD. Moderate-severe/high-risk disease may merit early advanced therapy.
- Steroids induce but do not maintain remission; thiopurines are slow and require TPMT/NUDT15 consideration plus ongoing CBC/LFT monitoring.
- Screen for TB and HBV before anti-TNF therapy according to local pathways, and tailor infection/vaccine assessment to the chosen drug.
- Proctocolectomy removes colonic UC but can be followed by pouch complications/EIMs; surgery is not curative for CD and recurrence is common.
-
Toxic megacolon
- Colonic dilatation plus systemic toxicity. ASUC needs hospitalisation, IV steroids, stool infection testing, VTE prophylaxis and early surgical input; assess response by day 3 for rescue therapy or surgery.
-
CRC risk in UC
- Baseline risk assessment at about 8 years after symptom onset (immediately for PSC-associated colitis), then a risk-stratified interval rather than automatic 1–2-yearly colonoscopy for everyone.
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) [15] British Society of Gastroenterology guideline: investigation of chronic diarrhoea in adults, 3rd edition [16] British Society of Gastroenterology guideline: management of irritable bowel syndrome [17] Infectious Diseases Society of America guideline: diagnosis and management of infectious diarrhoea [18] American Gastroenterological Association guideline: pharmacological management of IBS-D [19] American Gastroenterological Association clinical practice update: diet in IBS [20] British Society of Gastroenterology guideline: inflammatory bowel disease in adults, 2025 [21] British Society of Gastroenterology guideline: colorectal surveillance in IBD, 2025 [22] American Gastroenterological Association living guideline: moderate-to-severe ulcerative colitis [23] American Gastroenterological Association guideline: moderate-to-severe Crohn's disease [24] ECCO guideline: therapeutics in Crohn's disease—medical treatment, 2024 [25] ECCO guideline: inflammatory bowel disease and malignancies [26] ECCO consensus: dietary management of inflammatory bowel disease [27] ECCO guideline: prevention, diagnosis and management of infections in IBD, 2026
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.