Ulcerative Colitis

1. Definition

Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease (IBD) characterised by diffuse, continuous mucosal inflammation limited to the colon ^[1][2]. The name itself tells you the disease:

• "Ulcerative" → ulcer-forming (Latin ulcus = sore/wound)
• "Colitis" → inflammation of the colon (Greek kolon = large intestine + -itis = inflammation)

Key defining features that separate UC from Crohn's disease (CD):

^[1][3]

The inflammation most commonly begins in the rectum and extends proximally in a continuous fashion — there are no "skip lesions" ^[2]. Occasionally, patients with pancolitis may develop backwash ileitis (mild ileal inflammation from reflux of colonic contents through an incompetent ileocaecal valve), but this should not be confused with true small bowel Crohn's disease.

Indeterminate colitis accounts for 10-15% of patients with IBD who fail to be classified between UC and CD ^[1][2]. This can be due to inadequate tissue biopsy or a truly indeterminate form of disease. Surgical treatment for these patients is similar to UC ^[2].

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2. Epidemiology

2.1 Global Epidemiology

• Peak age of onset: between the third and seventh decade ^[1]
  • This is a broad bimodal peak — classically, the first peak is in the 30s and a second smaller peak around the 50s–70s ^[2]
  • Compare with CD which peaks in the third decade
• Gender: F = M (no gender predominance) ^[1][2]
  • In contrast, CD has F > M globally, but M > F in East Asia ^[1]

2.2 East vs West Differences (High Yield for HKU)

Key differences in Asian/Eastern IBD populations compared to Western populations ^[1]:

• More male prevalence with CD, ileocolonic CD
• Less family clustering (genetic factors play a smaller role relative to environmental factors in Asia)
• Lower rates of surgery (5–8%)
• Fewer extraintestinal manifestations
• Less primary sclerosing cholangitis with UC
• Higher rates of penetrating and perianal disease in CD

2.3 Hong Kong–Specific Data

The distribution of UC extent in Hong Kong is roughly equal thirds ^[2]:

• Proctosigmoiditis: 34.5%
• Distal UC (left-sided): 32%
• Pancolitis (extensive): 33.5%

Prevalence of IBD in Hong Kong has been steadily rising — thought to be related to Westernisation of diet, improved hygiene (the "hygiene hypothesis"), urbanisation, and changes in the gut microbiome.

CD: urban > rural areas, higher socioeconomic classes ^[1] — this pattern is shared to some extent with UC and supports the hygiene hypothesis (less childhood microbial exposure → aberrant immune development).

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3. Risk Factors and Protective Factors

3.1 Risk Factors

3.2 Protective Factors

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4. Anatomy and Function (Relevant to UC)

4.1 The Colon

The colon extends from the caecum (ileocaecal valve) to the rectum, approximately 1.5 m in length. Anatomically divided into:

• Caecum and appendix → ascending colon → hepatic flexure → transverse colon → splenic flexure → descending colon → sigmoid colon → rectum

Key functions:

• Water and electrolyte absorption (Na⁺, Cl⁻, short-chain fatty acids)
• Storage of faecal material (the reservoir function)
• Fermentation by commensal bacteria (microbiome)

4.2 Colonic Wall Layers (Why Depth of Inflammation Matters)

From inside out:

1. Mucosa (epithelium + lamina propria + muscularis mucosae) — UC is confined here + submucosa
2. Submucosa (Meissner's plexus; blood vessels, lymphatics)
3. Muscularis propria (inner circular, outer longitudinal; Auerbach's/myenteric plexus between)
4. Serosa/adventitia

Because UC is limited to the mucosa and submucosa, it:

• Does NOT produce fistulae (fistulae require transmural inflammation to create a tract through the full wall)
• Does NOT produce deep strictures (rare — strictures in UC should raise concern for malignancy)
• Does NOT produce deep ulcers — ulcers are shallow (compare with CD: deep, "knife-cut" or "cobblestone" ulcers)
• DOES produce pseudopolyps — regenerating islands of mucosa surrounded by denuded/ulcerated mucosa give the appearance of polyps

4.3 The Rectum

The rectum is essentially always involved in UC (the "starting point" of the disease). This explains why:

• PR bleeding (haematochezia) is the hallmark symptom — the inflamed rectal mucosa is friable and bleeds easily, and blood is seen on the surface of stool
• Tenesmus (a painful, urgent desire to defecate with a sense of incomplete evacuation) — from rectal inflammation irritating stretch receptors
• Urgency and incontinence — inflamed rectum loses compliance (it becomes stiff and cannot stretch), so even small volumes of stool trigger the defecation reflex

4.4 Splenic Flexure (Clinical Relevance)

The splenic flexure is the key anatomical landmark for classifying UC extent (Montreal classification). It represents a "watershed" area of blood supply (between the SMA and IMA territories), making it vulnerable to ischaemia and a natural boundary for disease classification.

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5. Etiology and Pathophysiology

UC is an immune-mediated disease arising from a complex interplay of:

1. Genetic susceptibility
2. Environmental triggers
3. Gut microbiome dysbiosis
4. Dysregulated mucosal immune response

5.1 Genetic Susceptibility

• Over 200 IBD susceptibility loci identified via GWAS
• HLA-DR2 is associated with UC (vs. HLA-DR1/DQ5 in CD)
• Key genes include those involved in epithelial barrier function (e.g., HNF4A, CDH1) and immune regulation
• However, family clustering is less prominent in East Asia ^[1], suggesting environmental factors play a proportionally larger role in Hong Kong
• Concordance rate in monozygotic twins: ~16% for UC (vs. ~50% for CD) — confirming that environment matters more in UC

5.2 Environmental Triggers

5.3 Gut Microbiome Dysbiosis

• UC patients have reduced microbial diversity — especially a loss of Firmicutes (which produce butyrate, the main energy source for colonocytes)
• Increase in potentially pathogenic bacteria (e.g., E. coli, Fusobacterium)
• The loss of butyrate-producing bacteria means colonocytes are "starved" → epithelial barrier breakdown → increased permeability → bacterial translocation → inflammation

5.4 Dysregulated Mucosal Immune Response

Here is the core pathophysiology, step by step:

Key immunological points:

• UC is characterised by an atypical Th2 response (unlike CD which is Th1/Th17-driven)
• IL-13 is a key cytokine in UC → directly damages epithelial cells and impairs barrier function
• NKT (Natural Killer T) cells are prominent in UC colonic mucosa
• The inflammatory infiltrate (neutrophils, lymphocytes, plasma cells) is concentrated in the mucosa and submucosa — this is why inflammation doesn't extend transmurally
• Neutrophil infiltration into crypts → cryptitis and crypt abscesses (a hallmark histological feature shared with CD) ^[2]
• Chronic inflammation → crypt architectural distortion (branching, shortening, irregularity of crypts) — this is a hallmark of chronicity
• Goblet cell depletion — mucin-producing goblet cells are destroyed by the inflammatory process → loss of the protective mucus layer → further barrier compromise. (Note: In CD, goblet cells are preserved) ^[2]

5.5 Why UC Starts in the Rectum and Spreads Proximally

The rectum has the highest bacterial concentration in the colon and the thinnest mucus layer. In a genetically susceptible individual, this makes it the most vulnerable site for the initial breach of immune tolerance. The disease then spreads in a retrograde, continuous fashion because the immune response propagates along the contiguous mucosal surface.

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6. Classification

6.1 Montreal Classification of UC Extent

The Montreal classification is the standard phenotypic classification for UC ^[2]:

^[2]

From Felix's notes, the HK distribution uses a slightly different subdivision ^[2]:

• Proctitis = rectum only
• Proctosigmoiditis (34.5%) = rectum + sigmoid
• Distal UC (32%) = rectum + sigmoid + colon up to splenic flexure (= Montreal E2)
• Pancolitis (33.5%) = beyond splenic flexure (= Montreal E3)
• Backwash ileitis = ileal involvement (in the setting of pancolitis)

6.2 Disease Severity — Modified Truelove and Witts' Criteria

This is the classic bedside severity assessment for UC — used in clinical practice to determine need for admission and treatment intensity ^[2]:

Interpretation: Immediate admission is warranted in severe disease ^[2].

6.3 Comparison Between Crohn's Disease and Ulcerative Colitis

This is an extremely high-yield comparison table for exams:

Clinical Features

Biochemical Features

Histological Features

^[2]

Endoscopic Features

^[2]

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7. Clinical Features

7.1 Symptoms (with Pathophysiological Basis)

Clinical features are related to inflammatory damage in the GIT ^[1]:

A. Gastrointestinal Symptoms

B. Constitutional Symptoms

C. Anaemic Symptoms

7.2 Signs (with Pathophysiological Basis)

A. General Examination

B. Abdominal Examination

C. Digital Rectal Examination

7.3 Extraintestinal Manifestations (EIMs)

Extraintestinal manifestations are present in up to 25–40% of IBD patients globally, though fewer EIMs are seen in East Asian populations ^[1]. They can be divided into those that correlate with disease activity and those that are independent.

Key EIMs from lecture slides ^[1]:

• Musculoskeletal: peripheral or axial arthropathy
• Cutaneous: erythema nodosum, pyoderma gangrenosum
• Ocular: scleritis, uveitis
• Primary sclerosing cholangitis (PSC)

A. EIMs that Correlate with Disease Activity

These flare when the colitis flares and improve when the colitis is treated:

B. EIMs that are Independent of Disease Activity

These may occur even when colitis is in remission:

7.4 Distinguishing UC Presentation from CD at the Bedside

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8. Summary of Key Pathophysiological Connections

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Active Recall - Ulcerative Colitis (Definition, Epidemiology, Etiology, Classification, Clinical Features)

1. A 28-year-old male with UC limited to the rectum (E1 proctitis) presents complaining of constipation rather than diarrhoea. Explain why this occurs.

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In proctitis, only the rectum is inflamed. The proximal colon compensates by increasing water absorption, producing hard formed stools. The inflamed rectum produces blood and mucus but the lack of extensive colonic involvement means the secretory diarrhoea mechanism is not dominant. The impaired rectal compliance may also disrupt normal defecation coordination.

2. List 4 features that distinguish UC from CD on endoscopy and explain the pathophysiological basis for each.

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1) Continuous inflammation (vs skip lesions in CD) — UC spreads contiguously from rectum due to mucosal-limited process. 2) Shallow ulcers (vs deep in CD) — inflammation confined to mucosa/submucosa. 3) Pseudopolyps present (regenerating mucosal islands between areas of shallow ulceration). 4) No fistulae (inflammation does not reach serosa since it is not transmural). Also accept: no granulomas (Th2 response vs Th1 granulomatous in CD), goblet cell depletion (inflammatory destruction of mucin-producing cells).

3. State the Modified Truelove and Witts criteria for SEVERE ulcerative colitis (all 6 parameters).

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Severe UC: 1) >= 6 bloody stools per day, 2) Pulse > 90 bpm, 3) Temperature > 37.8C, 4) Haemoglobin < 10.5 g/dL, 5) ESR > 30 mm/h, 6) CRP > 30 mg/L. Immediate admission warranted.

4. Explain why smoking is protective in UC but harmful in CD.

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Nicotine increases colonic mucus production (protects the mucosal barrier which is key in UC), decreases pro-inflammatory cytokines (IL-1, IL-8), and improves mucosal blood flow. In CD, smoking worsens disease because it impairs the innate immune response needed to clear transmural infection/inflammation, promotes granuloma formation, and increases intestinal permeability. The opposite effects on mucosal vs transmural disease explain the divergent impact.

5. Name 4 extraintestinal manifestations of UC and classify each as correlating with disease activity or independent of it.

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Correlate with activity: 1) Peripheral arthropathy (type 1, large joint), 2) Erythema nodosum, 3) Episcleritis. Independent of activity: 4) Primary sclerosing cholangitis, 5) Pyoderma gangrenosum, 6) Ankylosing spondylitis, 7) Uveitis. (Any 4 with correct classification gets full marks.)

6. List 5 risk factors for IBD-associated colorectal neoplasia as per the lecture slides, covering patient-specific, disease-specific, and endoscopic categories.

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Patient-specific: PSC, history of colorectal neoplasia, family history of CRC in first-degree relative, early age of onset, male sex. Disease-specific: disease duration, disease extent, cumulative inflammatory burden, active inflammation. Endoscopic: stricture, shortened tubular colon, pseudopolyps. (Any 5 from these categories.)

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References

^[1] Lecture slides: Inflammatory bowel disease.pdf (pp. 2, 4, 5, 6, 9, 52) ^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Ulcerative colitis sections) ^[3] Lecture slides: GC 186. Lower and diffuse abdominal painfresh blood in stool.pdf ^[4] Senior notes: felixlai.md (Primary sclerosing cholangitis section)

Differential Diagnosis of Ulcerative Colitis

9.1 The Clinical Problem — Why Differential Diagnosis Matters

A patient presenting with bloody diarrhoea, abdominal pain, and rectal bleeding does NOT automatically have UC. The differential is broad because the colon has a limited repertoire of responses to injury — it becomes inflamed, it ulcerates, it bleeds. The key clinical challenge is distinguishing UC from conditions that mimic it, because management differs dramatically (e.g., treating infectious colitis with immunosuppression would be catastrophic; missing colorectal cancer is lethal).

The approach to differential diagnosis follows a logical framework:

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9.2 Key Differentials — Detailed Breakdown

A. Crohn's Disease (CD) — The Most Important Differential

This is the single most important differential because both are IBD, share overlapping features, and roughly 10% of cases fail to be classified between UC and CD (indeterminate colitis) ^[1][2].

Why it can mimic UC: Both can present with bloody diarrhoea, abdominal pain, weight loss, and extraintestinal manifestations. When CD is limited to the colon (colonic CD, ~32% of CD cases ^[2]), the clinical picture can be virtually indistinguishable from UC.

How to distinguish from UC:

^[1][2][3]

B. Irritable Bowel Syndrome (IBS)

Why it can mimic UC: IBS presents with chronic abdominal pain and altered bowel habits ^[2], which overlaps with mild UC.

Why it is NOT UC — first principles reasoning:

• IBS is a functional disorder — there is no organic pathology, no mucosal inflammation, no ulceration
• IBS does NOT cause:
  • Bloody stools (if a patient has blood in the stool, it is NOT IBS until proven otherwise)
  • Raised inflammatory markers (CRP, ESR, faecal calprotectin are all normal)
  • Weight loss, anaemia, fever, or nocturnal symptoms
  • Abnormal endoscopy or histology

Key distinguishing features:

Clinical pearl: Faecal calprotectin is the best non-invasive test to distinguish IBD from IBS. It is a neutrophil-derived protein (60% of neutrophil cytosol) and is the most sensitive marker of intestinal inflammation in IBD ^[5]. A normal faecal calprotectin essentially excludes active IBD and points toward IBS.

C. Infectious Colitis

Infection including E. coli, Salmonella, Shigella, Campylobacter, Yersinia, and amoebiasis should be excluded with stool studies ^[2]. C. difficile infection should be considered particularly in patients treated with antibiotics ^[2].

Why infectious colitis can mimic UC: Acute infectious colitis can produce identical symptoms — bloody diarrhoea, abdominal cramps, tenesmus, fever. On endoscopy, some infections (e.g., Shigella, E. histolytica) can cause diffuse colonic inflammation with shallow ulceration that looks exactly like UC.

Why the distinction is critical: Treating infectious colitis with immunosuppression (steroids, azathioprine) would worsen the infection catastrophically. Conversely, treating UC with antibiotics alone would not control the underlying immune-mediated process.

How to distinguish:

Specific pathogens to consider:

^[2][5][6]

D. Ischaemic Colitis

Why it can mimic UC: Ischaemic colitis presents with rapid onset of abdominal pain, haematochezia or bloody diarrhoea ^[4]. On endoscopy, the mucosa may appear oedematous, friable, and ulcerated — resembling UC.

Why it is NOT UC — first principles reasoning:

• Ischaemic colitis results from inadequate blood supply to the colon (usually from low-flow states or atherosclerotic disease), NOT from immune-mediated mucosal inflammation
• It characteristically affects watershed areas (splenic flexure and rectosigmoid junction) — these are the boundaries between the SMA and IMA territories, and between the IMA and internal iliac arteries
• The pattern is segmental (not continuous from rectum) and spares the rectum (dual blood supply from IMA and internal iliac artery protects it) — this is the opposite of UC which STARTS at the rectum

Key distinguishing features:

E. Radiation Colitis / Proctitis

Radiation colitis occurs weeks to years after abdominal or pelvic irradiation ^[2].

Why it can mimic UC: Presents with chronic bloody diarrhoea, tenesmus, and rectal bleeding — identical symptoms to UC. The rectum is often involved (because pelvic radiation for cervical/prostate/rectal cancer directly damages it).

How to distinguish:

• History of prior radiation therapy is the key clue — always ask about cancer treatment history
• Acute radiation injury often occurs within 6 weeks of therapy ^[4]; chronic radiation proctitis can develop months to years later
• Endoscopy shows telangiectasias (dilated blood vessels) in the radiated segment, which are characteristic and not seen in UC
• The inflammation is limited to the radiation field, not continuous from the rectum

F. Medication-Associated Colitis

NSAIDs can cause chronic diarrhoea and bleeding ^[2].

Why it can mimic UC: NSAIDs inhibit COX → reduced prostaglandin-mediated mucosal protection → mucosal ulceration and bleeding. The resulting colitis can look like mild-to-moderate UC on endoscopy.

How to distinguish:

• Temporal relationship with NSAID use (symptoms improve on stopping the drug)
• NSAIDs can also trigger or worsen existing UC — so this can be both a differential AND a precipitant
• Other drug causes of colitis to consider: mycophenolate mofetil, ipilimumab (immune checkpoint inhibitor colitis — increasingly common), oral contraceptives

G. Solitary Rectal Ulcer Syndrome (SRUS)

Presents with abdominal pain, altered bowel habits, and bleeding. Has a characteristic appearance on histology with a thickened mucosal layer and distortion of crypt architecture ^[2].

Why it can mimic UC: Rectal bleeding + altered bowel habits + rectal ulceration on endoscopy.

How to distinguish:

• Despite the name, there may be multiple ulcers (or even just mucosal erythema without a discrete ulcer)
• Caused by chronic straining and rectal prolapse — the mechanical trauma of repeated straining and mucosal prolapse causes ischaemic injury to the rectal mucosa
• Histology is distinctive: fibromuscular obliteration of the lamina propria with thickened muscularis mucosae — this is NOT seen in UC
• The surrounding rectal mucosa is normal (no diffuse inflammation), unlike UC where the entire rectal mucosa is inflamed

H. Colorectal Cancer (CRC)

Why it must always be considered: CRC can present with PR bleeding, change in bowel habits, tenesmus, and weight loss ^[7] — all of which overlap with UC. Furthermore, UC itself is a risk factor for CRC, so the two conditions may coexist.

How to distinguish:

• CRC typically presents in older patients ( > 50) with progressive symptoms
• Constitutional symptoms, change in stool calibre, alternating diarrhoea and constipation, IO symptoms, metastatic symptoms (jaundice, SOB, bone pain) ^[7] suggest CRC
• Endoscopy reveals a mass/lesion rather than diffuse mucosal inflammation
• In UC, strictures should be considered malignant until proven otherwise by endoscopy with biopsy ^[2] — a stricture in UC is CRC until proven otherwise

I. Diverticular Disease

Diverticular bleeding presents as painless massive PR bleeding (rupture of vasa recta) ^[8] — this is a different pattern from UC (which causes chronic bloody diarrhoea, not acute massive haemorrhage). However, diverticulitis can cause lower abdominal pain with altered bowel habits and low-grade PR bleeding, which may overlap with UC.

How to distinguish:

• Diverticular disease is primarily a disease of older patients (rare before age 30) ^[8]
• Right-sided diverticula are common in Asians ^[8] — this is important for Hong Kong
• Clinical triad of diverticulitis: lower abdominal pain + fever + leucocytosis ^[8] — UC has more prominent diarrhoea and bleeding rather than localised pain with fever
• CT scan shows pericolonic inflammation with diverticula in diverticulitis vs. mucosal thickening without diverticula in UC
• Diarrhoea rather than abdominal pain is the predominant symptom in IBD ^[4], whereas abdominal pain predominates in diverticulitis

J. Causes of Ileitis (Relevant When Backwash Ileitis Raises Concern)

Causes of ileitis include ^[6]:

• Crohn's disease
• Tuberculosis
• Radiation enteritis
• Bacterial infection (e.g., Campylobacter, Yersinia, Salmonella)

These are sometimes misdiagnosed as acute appendicitis ^[6]. If a patient being worked up for "UC" has prominent ileal disease beyond mild backwash ileitis, these differentials must be considered — particularly CD and TB in the Hong Kong context.

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9.3 Causes of PR Bleeding — Comprehensive Differential

From the lecture slides, the causes of PR bleeding should be systematically categorised ^[9]:

^[9]

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9.4 Summary — Approach to Differential Diagnosis of Suspected UC

The systematic approach involves asking four key questions:

The essential investigations to request during the differential diagnosis workup include ^[2][5]:

• Stool examination: culture, C. difficile toxin, calprotectin
• Blood tests: CBP, CRP, ESR, albumin, ferritin
• Serological markers: pANCA (UC), ASCA (CD)
• Hepatitis serology, HIV, TB testing
• Colonoscopy with biopsies (gold standard)

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Active Recall - Differential Diagnosis of Ulcerative Colitis

1. A 35-year-old woman presents with 6 weeks of bloody diarrhoea and abdominal cramps. Before starting corticosteroids, what 3 categories of infections must you exclude and how?

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1) Bacterial: Stool culture for Salmonella, Shigella, Campylobacter, E. coli O157:H7, Yersinia. 2) C. difficile: Stool PCR for toxin A and B (especially if recent antibiotic use). 3) Parasitic: Stool microscopy for ova and parasites, antigen detection for Entamoeba histolytica, Cryptosporidium, Giardia. Also: TB testing (AFB smear, culture, and/or IGRA) is mandatory in Hong Kong. Hepatitis serology and HIV testing should also be done before immunosuppression.

2. Name 4 clinical features that would favour Crohn's disease over ulcerative colitis in a patient presenting with chronic colitis.

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Any 4 of: 1) Skip lesions on endoscopy (vs continuous in UC). 2) Perianal disease (fissures, fistulae, abscesses) - up to 40% in CD, rare in UC. 3) Rectal sparing. 4) Fistula formation (enteroenteric, enterovesical, enterocutaneous). 5) Deep ulcers or cobblestone appearance. 6) Small bowel involvement. 7) Non-caseating granulomas on biopsy. 8) Abdominal mass. 9) ASCA positive (vs pANCA positive in UC).

3. How does faecal calprotectin help distinguish IBS from IBD, and why is it the best non-invasive marker?

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Faecal calprotectin is a neutrophil-derived protein constituting 60% of neutrophil cytosol. It is released when neutrophils infiltrate the intestinal wall during inflammation. It is the most sensitive marker of intestinal inflammation in IBD and correlates well with endoscopic disease activity. In IBS (functional disorder with no mucosal inflammation), calprotectin is normal (below 50 mcg/g). An elevated calprotectin strongly suggests organic inflammatory pathology (IBD, infection) and warrants colonoscopy. A normal calprotectin essentially rules out active IBD.

4. Explain why ischaemic colitis typically spares the rectum, and how this helps distinguish it from UC.

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The rectum has a dual blood supply from the IMA (superior rectal artery) and the internal iliac arteries (middle and inferior rectal arteries). This redundant supply protects it from ischaemia. Ischaemic colitis affects watershed areas (splenic flexure between SMA and IMA territories; rectosigmoid junction between IMA and internal iliac). In contrast, UC almost always starts at the rectum and extends proximally in a continuous fashion. Rectal sparing in a colitis case strongly argues against UC and favours ischaemic colitis or Crohn's disease.

5. A patient with known UC develops a colonic stricture. What is the most important concern and what should be done?

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A stricture in UC should be considered malignant until proven otherwise. UC causes mucosal/submucosal inflammation, which rarely leads to benign strictures (unlike CD where transmural fibrosis commonly causes strictures). Therefore, any stricture in UC raises high suspicion for colorectal cancer arising from the chronic inflammation-dysplasia-carcinoma sequence. The patient must undergo colonoscopy with multiple biopsies of the stricture to exclude malignancy.

References

^[1] Lecture slides: Inflammatory bowel disease.pdf (pp. 2, 6, 9, 11) ^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Ulcerative colitis sections: overview, etiology, clinical manifestation, differential diagnosis, diagnosis) ^[3] Senior notes: felixlai.md (Inflammatory bowel disease — Crohn's disease sections: comparison table, histological features) ^[4] Senior notes: felixlai.md (Diverticular disease section: differential diagnosis including ischaemic colitis) ^[5] Lecture slides: Inflammatory bowel disease.pdf (p. 11 — Diagnosis: laboratory tests, faecal calprotectin) ^[6] Lecture slides: GC 195. Lower and diffuse abdominal pain RLQ problems; pelvic inflammatory disease; peritonitis and abdominal emergencies.pdf (p. 20 — Ileitis causes) ^[7] Senior notes: maxim.md (LGIB DDx table — colorectal carcinoma features) ^[8] Senior notes: maxim.md (Diverticular disease section) ^[9] Lecture slides: GC 186. Lower and diffuse abdominal painfresh blood in stool.pdf (p. 8 — Causes of PR bleeding)

Diagnostic Criteria, Diagnostic Algorithm & Investigations for Ulcerative Colitis

10.1 Diagnostic Criteria — First Principles

There is no single gold-standard diagnostic test for UC. Unlike, say, diabetes (where a fasting glucose or HbA1c gives you a definitive cut-off), UC is diagnosed by the convergence of clinical, laboratory, endoscopic, and histological findings combined with the exclusion of other causes of colitis (especially infection and CD). Think of it as a jigsaw puzzle — no single piece is diagnostic, but when you put together the clinical picture + endoscopy + histology + negative stool studies, the diagnosis becomes clear.

The key diagnostic pillars are:

1. Compatible clinical presentation — chronic/relapsing bloody diarrhoea, tenesmus, urgency, +/- extraintestinal manifestations
2. Endoscopic findings — continuous mucosal inflammation starting from the rectum, with characteristic features (see below)
3. Histological confirmation — mucosal/submucosal inflammation with crypt architectural distortion, cryptitis/crypt abscesses, goblet cell depletion
4. Exclusion of infections and other mimics — negative stool studies, negative TB testing
5. Serological and biochemical support — pANCA positivity, raised inflammatory markers, raised faecal calprotectin

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10.2 Diagnostic Algorithm

The algorithm below reflects the systematic approach from clinical suspicion through to definitive diagnosis and disease classification:

^[1][2][5]

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10.3 History Taking — Targeted Questions

Patient history should cover ^[5]:

10.4 Physical Examination

Physical examination should include ^[5]:

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10.5 Investigation Modalities — Detailed Breakdown

A. Laboratory Tests (Blood)

Blood tests: CBP, CRP, ESR, albumin, ferritin ^[5]

B. Serological Markers

Serological markers from lecture slides and notes ^[2][5]:

C. Stool Tests

Stool examination: culture, Cl. difficile toxin, calprotectin ^[5]

Why is faecal calprotectin so useful? From first principles: when neutrophils infiltrate the inflamed intestinal wall (as happens in UC with cryptitis and crypt abscesses), they release their cytoplasmic contents into the lumen. Calprotectin constitutes 60% of the neutrophil cytoplasm. It is resistant to degradation by intestinal proteases, so it survives transit through the GI tract and can be measured in stool. The more mucosal inflammation there is, the more neutrophils infiltrate, and the higher the faecal calprotectin. This is why it correlates so well with endoscopic disease activity.

D. Infection Screening (Pre-Treatment)

Hepatitis serology, HIV, TB testing ^[5]

E. Radiological Investigations

F. Endoscopy — The Gold Standard

Imaging and endoscopy ^[5]:

Why colonoscopy and not just sigmoidoscopy?

• Colonoscopy allows you to see the full extent of disease (needed for Montreal classification E1/E2/E3, which determines treatment and surveillance strategy)
• Allows ileal intubation to assess for backwash ileitis or ileal disease that might suggest CD
• Biopsy should be taken from the left and right colon and rectum even if normal in appearance to assess for microscopic inflammation ^[2] — this is critical because treated UC may have patchy healing, and microscopic disease may exist without macroscopic changes

Contraindications to colonoscopy in UC context ^[10]:

• Known or suspected perforation
• Acute diverticulitis
• Fulminant colitis (use sigmoidoscopy instead)

Endoscopic Findings in UC

Endoscopic Severity Scoring — Mayo Endoscopic Subscore

The Mayo endoscopic subscore is widely used to grade endoscopic severity:

This score is important because it correlates with treatment decisions and is used as an endpoint in clinical trials for UC therapeutics.

G. Histological Findings — Biopsy Interpretation

Histological findings in UC ^[2]:

H. Additional Endoscopic Modalities

From lecture slides ^[5]:

^[5]

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10.6 Disease Extent Classification — Montreal System (Endoscopic)

Montreal phenotypic classification — according to extent of inflammation observed at colonoscopy ^[2]. This influences treatment modality and timing of starting surveillance and its frequency ^[2].

^[2]

UC distribution from lecture slides ^[5]: Pancolitis: Entire colon 18%; Left colitis: Up to the left flexure 28%; Proctitis: Rectosigmoid 54%

Why does extent matter?

1. Treatment: Proctitis (E1) can often be managed with topical (rectal) 5-ASA alone; left-sided (E2) may need combined oral + rectal; pancolitis (E3) always needs systemic therapy
2. CRC surveillance timing: More extensive disease = earlier and more frequent surveillance colonoscopies
3. Prognosis: Pancolitis has higher rates of hospitalisation, colectomy, and CRC risk

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10.7 Severity Assessment — Modified Truelove and Witts' Criteria

This is not a diagnostic criterion per se, but is integral to the initial workup because it determines immediate management (outpatient vs. admission, oral vs. IV therapy):

Interpretation: Immediate admission warranted in severe disease ^[2].

Why these particular parameters?

• Bloody stools/day → directly reflects the extent and severity of mucosal ulceration and bleeding
• Pulse and temperature → systemic inflammatory response; tachycardia also reflects hypovolaemia from blood/fluid loss
• Haemoglobin → chronic blood loss severity
• ESR/CRP → magnitude of the systemic inflammatory response

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10.8 Putting It All Together — The Diagnostic Synthesis

To make a diagnosis of UC, you need:

When to reconsider the diagnosis: If the patient develops features atypical for UC (perianal disease, small bowel strictures, non-caseating granulomas on biopsy, poor response to standard UC therapy), reclassify as CD or indeterminate colitis. Up to 10% of patients are reclassified over time.

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Active Recall - Diagnosis of Ulcerative Colitis

1. A patient presents with acute severe UC (8 bloody stools/day, pulse 100 bpm, temp 38.2C, Hb 9.8 g/dL). Why should you perform flexible sigmoidoscopy rather than full colonoscopy?

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In acute severe UC or fulminant colitis, full colonoscopy carries a high risk of perforation because the colonic wall is severely inflamed, thinned, and may be dilated. Full bowel preparation is also poorly tolerated and may precipitate toxic megacolon. Flexible sigmoidoscopy is safer — it does not require full bowel prep, is shorter, and is sufficient to confirm diagnosis and obtain biopsies since UC always involves the rectum. Full colonoscopy can be deferred until the acute episode has been treated.

2. List 4 stool tests you would order in a patient with suspected UC and explain the rationale for each.

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1) Stool culture (Salmonella, Shigella, Campylobacter, E. coli O157:H7, Yersinia) — exclude bacterial infectious colitis. 2) C. difficile toxin PCR (toxin A and B) — exclude antibiotic-associated pseudomembranous colitis and C. diff superinfection. 3) Stool microscopy/antigen detection for ova, parasites, Entamoeba, Giardia, Cryptosporidium — exclude parasitic causes especially amoebiasis. 4) Faecal calprotectin — neutrophil-derived marker correlating with endoscopic disease activity; most sensitive non-invasive marker; helps distinguish IBD from IBS; predicts relapse.

3. Explain why biopsies should be taken from the left colon, right colon, and rectum even when these areas appear macroscopically normal on colonoscopy.

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Three reasons: 1) Microscopic inflammation may exist even without macroscopic changes — especially in treated UC where patchy healing can occur. 2) Segmental biopsies are needed to determine the true extent of disease (Montreal classification E1/E2/E3), which affects treatment and surveillance planning. 3) Biopsies may reveal features that change the diagnosis — e.g., granulomas suggesting CD, or features of microscopic colitis. Also, AFB staining and culture of biopsies is needed to exclude enteric TB.

4. Describe 3 endoscopic features that distinguish UC from CD and explain the pathophysiological basis for each.

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1) Continuous inflammation vs skip lesions — UC spreads contiguously from rectum due to mucosal-limited retrograde immune activation; CD has patchy transmural disease. 2) Shallow ulceration vs deep ulcers/cobblestoning — UC inflammation limited to mucosa/submucosa so ulcers stay superficial; CD transmural inflammation causes deep ulcers. 3) Pseudopolyps present in UC vs absent in CD — widespread shallow ulceration in UC creates islands of regenerating mucosa; in CD focal deep ulcers do not produce this pattern. Also accept: no fistulae in UC (not transmural), friability/granularity (diffuse superficial inflammation).

5. A patient with UC has a faecal calprotectin of 400 mcg/g but a normal CRP. Is active disease likely? Explain why CRP can be normal in active UC.

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Active disease is very likely. Faecal calprotectin is the most sensitive marker of intestinal inflammation and correlates directly with endoscopic activity. CRP can be normal in active UC because UC is a mucosal/submucosal disease — the inflammation may not be extensive or deep enough to generate a significant systemic acute-phase response. CRP is produced by the liver in response to IL-6, and the IL-6 levels in UC are often lower than in CD (where transmural inflammation produces a greater systemic inflammatory signal). Up to 50% of patients with active UC can have a normal CRP. Always trust faecal calprotectin over CRP for assessing UC activity.

6. What infection screening tests must be done before starting immunosuppressive therapy in UC, and why is each important?

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1) Hepatitis B serology (HBsAg, anti-HBc) — immunosuppression/biologics can reactivate HBV causing fulminant hepatitis; need antiviral prophylaxis if positive. 2) Hepatitis C antibody — baseline screening; hepatotoxicity risk with immunosuppressants. 3) HIV testing — undiagnosed HIV with immunosuppression is dangerous. 4) TB testing (IGRA/Mantoux + CXR, AFB smear and culture of biopsies) — anti-TNF agents reactivate latent TB causing disseminated disease; mandatory in Hong Kong (intermediate TB burden). 5) Varicella status — need to know before live vaccine contraindications with biologics.

References

^[1] Lecture slides: Inflammatory bowel disease.pdf (p. 52 — IBD-associated CRC risk factors) ^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Ulcerative colitis sections: overview, diagnosis, biochemical tests, radiological tests, endoscopic findings, histological findings) ^[5] Lecture slides: Inflammatory bowel disease.pdf (pp. 7, 10, 11, 12 — Diagnosis: patient history, physical examination, laboratory tests, faecal calprotectin, imaging and endoscopy, UC distribution) ^[10] Senior notes: felixlai.md (Colonoscopy section — indications and contraindications)

Management of Ulcerative Colitis

11.1 Principles of Management

The management of UC follows a logical, step-wise framework built on two core goals ^[2]:

1. Induction of remission — control the acute flare
2. Maintenance of remission — prevent relapse long-term

Principles of management: to induce and maintain remission taking into account disease activity, disease site, disease behaviour, and patient preference ^[2].

The treatment strategy is determined by two axes:

• Disease extent (Montreal E1 / E2 / E3) — determines route of drug delivery (topical vs. oral vs. systemic)
• Disease severity (Truelove & Witts: mild / moderate / severe) — determines intensity of therapy (5-ASA → steroids → rescue → surgery)

Key treatment principles from notes ^[2]:

• Start with topical treatment if mild left-sided disease
• Start with oral treatment if extensive disease
• Combination therapy (topical + oral) is more effective in inducing remission
• Consider rescue therapy in steroid-refractory disease (Day 3)
• Consider surgical treatment if no improvement within Day 4–7 of rescue therapy

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11.2 Management Algorithm — Overview

^[2][11]

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11.3 Medical Treatment — Drug-by-Drug Breakdown

A. 5-Aminosalicylates (5-ASA)

The cornerstone of UC therapy — the first drug you reach for in mild-to-moderate disease ^[2].

Name breakdown: "5-amino" = the active amine group; "salicylate" = derived from salicylic acid (related to aspirin). These are anti-inflammatory agents that act locally on the colonic mucosa.

Initial therapy in patients with mild to moderate UC who do not have systemic symptoms based on its relative safety to other drugs ^[2].

Topical 5-ASA is the first-line treatment in mild to moderate UC in those who are willing to use rectal therapy including suppositories or enemas ^[2].

Choosing the route by disease extent:

Key formulations and differences:

B. Glucocorticoids

The second-line agents for induction — used when 5-ASA fails or for moderate-severe disease ^[2].

Critical concept: Steroids are for induction ONLY — they are NOT maintenance agents.

Calcium and vitamin D supplements required for osteoprotective effect if prescribed for more than 12 weeks ^[2].

Clinical role = Induction agent (Induction of remission). Ineffective in maintenance of remission and NOT used for long-term ^[2].

Steroid-dependent vs. steroid-refractory:

C. Immunomodulators (Thiopurines)

These are the steroid-sparing maintenance agents — the drugs that keep patients in remission and allow steroids to be withdrawn ^[2].

Methotrexate is NOT effective in UC unlike in Crohn's disease ^[2] — this is an important exam point.

D. Calcineurin Inhibitors (Rescue Therapy)

Rescue therapy agents: Cyclosporin and Tacrolimus ^[2].

E. Biologic Therapies — Anti-TNFα

The big guns — used for moderate-severe UC refractory to conventional therapy ^[2].

Name breakdown: "Anti-TNF" = antibodies against Tumour Necrosis Factor-alpha, a key pro-inflammatory cytokine. "Infliximab" = inf(usion) + -ximab (chimeric monoclonal antibody); "Adalimumab" = ada(ptive) + -mumab (fully human monoclonal antibody).

Indicated in patients with refractory disease to 5-ASA, immunomodulators, and steroids ^[2].

MUST screen for TB with CXR / QuantiFERON-TB Gold + HBV infection with HBsAg ^[2]:

• Requires TB prophylaxis with isoniazid or rifampicin ^[2]
• Requires HBV prophylaxis with entecavir ^[2]

Do not stop anti-TNFα easily unless there is deep remission of at least 18 months with normal blood and endoscopic parameters ^[2].

Contraindications ^[2]:

• Latent untreated or active TB
• Lymphoma
• Heart failure of NYHA Class III–IV (TNF-α has compensatory effects in heart failure; blocking it worsens cardiac function)
• Demyelinating disease (Multiple sclerosis) (anti-TNF can worsen or trigger CNS demyelination)
• Optic neuritis

Adverse effects ^[2]:

• Reactivation of infection (e.g., TB/HBV) — TNF-α is critical for granuloma formation and containment of intracellular pathogens; blocking it allows dormant mycobacteria to reactivate
• Lymphoma — small absolute increase in risk (especially hepatosplenic T-cell lymphoma when combined with thiopurines in young males)
• Non-melanoma skin cancer
• Infusion reactions (infliximab — chimeric antibody → can trigger anti-drug antibodies)
• Paradoxical psoriasis

F. Newer Biologics and Small Molecules (Post-2020 Updates)

These are increasingly used in UC and are high-yield for 2025/2026 exams:

G. Antibiotics

Antibiotics have MINIMAL role in treatment of active disease in UC ^[2].

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11.4 Treatment by Severity — Summary Table

^[2][11]

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11.5 Acute Severe UC — The Critical Pathway

Emergency surgery is needed in 20% of UC patients and 5–10% of Crohn's colitis patients ^[11].

Criteria (ECCO/ACG guidelines): ≥ 6 bloody stools/day + at least one of: Fever (37.8°C), tachycardia, anaemia ( < 10.5 g/dL), raised CRP ^[11].

Day-by-day management:

Predictors of colectomy ^[2]:

• BO > 12/day on Day 2 of IV steroid → Colectomy = 55%
• BO > 8/day or BO 3–8/day + CRP > 45 on Day 3 of IV steroid → Colectomy = 85%
• (Stool frequency × 0.14 × CRP) on Day 3 of IV steroid ≥ 8 → Colectomy = 75%
• Colonic dilatation > 5.5 cm → Colectomy = 75%
• Ileus with ≥ 3 small bowel loops of gas → Colectomy = 73%
• High CRP, low albumin and pH, ESR > 75, temp > 38°C on admission → 5–9× risk ^[2]

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11.6 Surgical Treatment

Surgery is usually not indicated in UC but is potentially curative ^[2]. This is a crucial distinction from CD (where surgery is NOT curative and should be avoided as long as possible).

Indications for Surgery

Emergency indications ^[2][11]:

• Fulminant colitis (acute severe colitis failing medical treatment)
• Toxic megacolon > 6 cm ^[11]
• Perforation ^[11]
• Severe bleeding (unremitting bloody diarrhoea) ^[11]
• Failure of toxic dilatation to respond to 48 hours therapy ^[11]
• Deterioration despite optimal treatment ^[11]
• Patient choice ^[11]

Elective indications ^[2][11]:

• Chronic colitis with severe symptoms ^[11]
• Steroid-dependent ^[11]
• Recurrent attacks ^[11]
• Dysplasia or cancer ^[11]
• Malignancy: treatment (biopsy-proven adenocarcinoma) or prophylaxis (dysplasia on surveillance biopsy) ^[8]
• Refractory to medical treatment ^[2]
• Debilitating extra-intestinal manifestation (thromboembolic complications) ^[2]
• Extra-intestinal manifestation (except EIMs independent of colitis activity — sacroiliitis, hepatobiliary complications) ^[8]

Surgical Options

Why is IPAA the standard of care?

• The "J-pouch" (ileo-pouch-anal anastomosis) creates a neorectum from the terminal ileum, folded into a J-shape and anastomosed to the anal canal
• Allows the patient to defecate per anum without a permanent stoma
• Mean stool frequency: ~6/day (acceptable for most patients)
• Maintains continence in most patients with intact sphincters

Complications of IPAA ^[2][8]:

• Pouchitis — most common complication (~50% lifetime risk); presents with increased stool frequency, urgency, bloody stool, fever. Treated with metronidazole and ciprofloxacin ^[2]
• Pouch-vaginal / perineal fistula ^[2]
• Anastomotic stricture ^[2]
• Anastomotic dehiscence with sepsis ^[2]
• Sexual dysfunction / infertility ^[2] (pelvic dissection can damage autonomic nerves — hypogastric and pelvic splanchnic nerves)
• Pelvic nerve damage: impotence ^[8]
• Pouch dysfunction: increased faecal frequency, urgency, incontinence ^[8]

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11.7 CRC Surveillance in UC

Long-standing UC carries an increased risk of colorectal cancer through the inflammation → dysplasia → carcinoma sequence ^[1][2].

AGA Guidelines (2010) ^[12]:

• Surveillance colonoscopy started at a maximum 8 years after UC or Crohn's colitis ^[12]
• Optimal surveillance interval not clearly defined:
  • Left-sided or extensive colitis: within 1–2 years after initial screening colonoscopy ^[12]
  • After two negative examinations, every 1–3 years ^[12]
  • Individualised (presence of other risk factors) ^[12]
• Primary sclerosing cholangitis: yearly ^[12] (PSC dramatically increases CRC risk)
• Ulcerative proctitis: NOT considered at increased risk ^[12]
• Ideally, surveillance colonoscopy should be performed when disease is in remission ^[12]

BSG Guidelines (2010) ^[13] — risk-stratified surveillance:

Surveillance methods ^[2]:

• Chromoendoscopy — highest yield for dysplasia detection; involves topical application of methylene blue or indigo carmine to enhance mucosal irregularities and facilitate targeted biopsies ^[2]
• High-definition white light colonoscopy — alternative with high diagnostic yield; preferred when chromoendoscopy yield is decreased or mucosa poorly visualised (inadequate prep, active inflammation, pseudopolyps, strictures) ^[2]
• Narrow band imaging (NBI) — does NOT enhance dysplasia detection ^[2]

Management of dysplasia ^[14]:

• Endoscopically visible dysplasia:
  • Polypoid → polypectomy ^[14]
  • Non-polypoid → endoscopic resection if complete resection is possible ^[14]
  • Surgery should be considered if not endoscopically feasible ^[14]
• Endoscopically invisible dysplasia:
  • Associated with high rate of CRC ^[14]
  • Referred to an experienced endoscopist ^[14]
  • If LGD or no dysplasia → 5% LGD changed to HGD or CRC → surveillance or surgery? ^[14]
  • If invisible HGD or multifocal LGD, surgery should be offered ^[14]

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11.8 Summary — Treatment Ladder

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Active Recall - Management of Ulcerative Colitis

1. A patient with acute severe UC has been on IV hydrocortisone for 3 days. Stool frequency is 10/day and CRP is 52 mg/L. What is the colectomy risk and what should you do next?

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Stool frequency 3-8 + CRP > 45 on Day 3 gives colectomy risk of 85% (even higher with stool freq > 8). Alternatively, Travis index = stool frequency x 0.14 x CRP = 10 x 0.14 x 52 = 72.8, far exceeding threshold of 8. Must initiate rescue therapy immediately: IV infliximab 5 mg/kg (preferred) or IV cyclosporin. Urgent surgical consultation. If no response to rescue by Day 4-7, proceed to emergency total abdominal colectomy with end ileostomy.

2. Explain why corticosteroids are used for induction but NOT maintenance in UC, giving at least 3 reasons.

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1) Studies show steroids do NOT prevent relapse — they do not alter the natural history of the disease once stopped. 2) Chronic steroid use causes unacceptable side effects: osteoporosis, adrenal suppression, diabetes, cataracts, Cushingoid features, avascular necrosis, increased infection risk. 3) Steroids cause steroid dependency in some patients (relapse on taper), which itself becomes a problem requiring escalation to thiopurines or biologics. Calcium and vitamin D supplementation required if used for > 12 weeks.

3. List 5 things you must screen for before starting anti-TNF therapy in UC and explain the rationale for each.

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1) TB (CXR + IGRA/QuantiFERON) — anti-TNF blocks granuloma formation needed to contain TB; reactivation causes disseminated TB. Prophylaxis with isoniazid if latent TB found. 2) HBV (HBsAg, anti-HBc) — immunosuppression causes HBV reactivation; prophylaxis with entecavir. 3) HCV — baseline screening. 4) HIV — immunosuppression in undiagnosed HIV is dangerous. 5) Varicella immunity — live vaccines contraindicated once on biologics; must vaccinate before if non-immune. Also assess for heart failure (NYHA III-IV is contraindication) and demyelinating disease (MS, optic neuritis).

4. Describe the 3-stage emergency surgical procedure for acute severe UC and explain why the rectum is left in situ at the first operation.

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Stage 1: Total abdominal colectomy with end ileostomy — removes the diseased colon. Rectum left in situ because: (a) rectum is extraperitoneal so dissection is technically demanding and time-consuming in a critically ill patient, (b) patient is often on high-dose steroids which impair healing — anastomosis would be at high risk of dehiscence. Foley catheter used to decompress rectal stump for 3-4 days. Stage 2: Completion proctectomy with IPAA (J-pouch) and diverting loop ileostomy — done when patient recovers and steroids are withdrawn. Stage 3: Reversal of diverting loop ileostomy — restores intestinal continuity.

5. A patient with E1 proctitis and another with E3 pancolitis both have mild UC. How does the route of 5-ASA administration differ and why?

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E1 proctitis: topical 5-ASA suppository (e.g., mesalamine 1g OD-BD). The suppository delivers drug directly to the rectal mucosa. Oral 5-ASA is released too proximally and does not achieve adequate rectal concentration. E3 pancolitis: oral 5-ASA (e.g., mesalamine 2-4.8g/day) PLUS topical 5-ASA (enema or suppository). Oral formulations release 5-ASA throughout the colon. Adding topical therapy boosts drug levels in the distal colon/rectum. Combination therapy (oral + topical) is more effective than either alone for inducing remission.

6. When should CRC surveillance colonoscopy begin in a patient with UC pancolitis, and what is the recommended surveillance method with the highest yield for dysplasia?

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Surveillance should begin at a maximum of 8 years after diagnosis of pancolitis (extensive colitis). The method with the highest yield for dysplasia detection is chromoendoscopy, which involves topical application of methylene blue or indigo carmine to enhance mucosal irregularities and facilitate targeted biopsies. High-definition white light colonoscopy is an alternative. NBI does NOT enhance dysplasia detection. Surveillance should ideally be performed when disease is in remission. Patients with concurrent PSC should have yearly surveillance. Proctitis alone is not considered at increased CRC risk.

References

^[1] Lecture slides: Inflammatory bowel disease.pdf (p. 52 — IBD-associated CRC risk factors) ^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Ulcerative colitis sections: treatment, surgical treatment, complications, prevention) ^[8] Senior notes: maxim.md (Inflammatory bowel disease: surgical indications; Surgical procedures for UC; Surgical procedures for CD) ^[11] Lecture slides: Inflammatory bowel disease.pdf (pp. 18, 19, 20 — Surgical indications, emergency surgery, colectomy) ^[12] Lecture slides: Inflammatory bowel disease.pdf (p. 56 — AGA guideline 2010 for CRC surveillance) ^[13] Lecture slides: Inflammatory bowel disease.pdf (p. 57 — BSG guideline 2010 for risk-stratified surveillance) ^[14] Lecture slides: Inflammatory bowel disease.pdf (p. 55 — Management of dysplasia)

Complications of Ulcerative Colitis

The complications of UC can be organised into three categories:

1. Local / intestinal complications — arising directly from the colonic disease
2. Extraintestinal manifestations (covered in the Clinical Features section; cross-referenced here)
3. Treatment-related complications — arising from medical or surgical therapy

This section focuses primarily on the local/intestinal complications and surgical complications, as they are the most clinically actionable and highest-yield for examinations.

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12.1 Local / Intestinal Complications

A. Stricture

What it is: A segment of colonic narrowing causing partial or complete luminal obstruction.

Pathophysiology: Repeated episodes of inflammation cause submucosal fibrosis and smooth muscle hypertrophy in the colonic wall. Even though UC is "only" mucosal/submucosal, chronic relapsing inflammation leads to fibrotic remodelling of the submucosa that can narrow the lumen sufficiently to cause obstructive symptoms ^[2].

Clinical features:

• Symptoms of intestinal obstruction — colicky abdominal pain, distension, vomiting, constipation
• May be insidious (progressive narrowing of stool calibre) or acute (complete obstruction)

The critical point — malignancy:

Strictures in UC should be considered malignant until proven otherwise by endoscopy with biopsy ^[2].

Why? In Crohn's disease, strictures are extremely common and are usually benign (transmural fibrosis). But in UC, strictures are rare because the inflammation is superficial — it doesn't normally cause the deep mural fibrosis seen in CD. So when a stricture does appear in UC, the most likely explanation is that dysplastic or malignant tissue is causing the narrowing. This is the inflammation → dysplasia → carcinoma sequence manifesting as a mass/stricture. Every UC stricture must be biopsied extensively, and if biopsies are inadequate or show any degree of dysplasia, surgery should be strongly considered.

Endoscopic features that raise concern: stricture (ulcerative colitis, longer disease duration, proximal location, symptoms) ^[1].

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B. Fulminant Colitis

What it is: The most severe form of acute UC — a life-threatening medical emergency.

Clinical features ^[2]:

• Patients present with > 10 stools per day, continuous bleeding, abdominal pain, distension, and acute severe toxic symptoms including fever and anorexia

Pathophysiology:

• Fulminant colitis represents a state where the inflammatory process has become so intense that it overwhelms the body's compensatory mechanisms
• High risk of developing toxic megacolon as the inflammatory process extends beyond the mucosa to involve the muscle layers of the colon ^[2]
  • This is the key pathophysiological concept: normally UC is limited to mucosa/submucosa, but in fulminant colitis, the inflammation breaches this boundary and damages the muscularis propria → loss of smooth muscle tone → colonic atony and dilatation
  • Inflammation of the myenteric (Auerbach's) plexus → paralysis of colonic smooth muscle → the colon "stops moving"
  • Simultaneously, inflammatory mediators (NO, prostaglandins) cause vasodilation and increased vascular permeability → massive fluid shifts into the bowel wall and lumen → further distension

Management principles:

• Immediate admission to hospital (meets Truelove & Witts severe criteria)
• IV hydrocortisone + IV fluids + VTE prophylaxis
• Aggressive monitoring (stool charts, vitals, daily bloods, serial AXR)
• Early surgical consultation — these patients can deteriorate rapidly to toxic megacolon → perforation → death
• 6–10% with ulcerative colitis have acute lower GI bleed needing emergency surgery (total colectomy) ^[15]

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C. Toxic Megacolon

What it is: The most feared acute complication of UC — a true surgical emergency.

Definition ^[2]:

• Total or segmental non-obstructive dilatation of the colon ≥ 6 cm or caecum > 9 cm AND the presence of systemic toxicity

Name breakdown: "Toxic" = systemic toxicity (sepsis-like state); "mega" = large (Greek megas); "colon" = the large bowel. So the name literally tells you: a dangerously dilated, toxic colon.

Pathophysiology (from first principles):

Clinical presentation ^[2]:

• Fever, tachycardia, hypotension, dehydration
• Electrolyte disturbances (hypokalaemia worsens colonic atony — a vicious cycle)
• Anaemia, hypoalbuminaemia
• Mental changes (encephalopathy from sepsis/metabolic derangement)
• Physical examination: abdominal distension, reduced/absent bowel sounds, diffuse tenderness, ± peritonism (if perforation has occurred)

Diagnosis ^[2]:

• Diagnosis is made by plain AXR
  • Dilated colon ≥ 6 cm (transverse colon measured) or caecum > 9 cm
  • Loss of haustral markings
  • "Thumb-printing" sign (submucosal oedema/haemorrhage causing scalloped indentations along the colonic wall)
  • Impending perforation: thumb-printing sign ^[8]

Management ^[2]:

• Bowel rest and total parenteral nutrition (TPN)
• Fluid and electrolyte replacement — aggressively correct hypokalaemia (K⁺ depletion worsens colonic atony)
• Corticosteroids (IV hydrocortisone)
• Stop all medications that reduce colonic motility — opioids, anticholinergics, loperamide, and codeine must be immediately discontinued as they worsen dilatation
• Nasogastric tube decompression + frequent position changes (rolling the patient) to help redistribute intraluminal gas
• Serial AXR (every 12–24 hours) to monitor colonic calibre
• Surgical intervention (emergency total abdominal colectomy + end ileostomy) if:
  • Failure of toxic dilatation to respond to 48 hours of therapy ^[11]
  • Deterioration despite optimal treatment ^[11]
  • Signs of perforation or peritonitis
  • Progressive dilatation on serial AXR

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D. Perforation

What it is: A full-thickness breach in the colonic wall allowing luminal contents to enter the peritoneal cavity.

Pathophysiology ^[2]:

• Most commonly occurs as a consequence of toxic megacolon
• The massively dilated, paper-thin colonic wall (especially in the transverse colon where the diameter is greatest — Laplace's law: wall tension = pressure × radius) simply bursts
• Laplace's law explains why the largest-diameter segment perforates first: T = P × r / 2w (where T = wall tension, P = intraluminal pressure, r = radius, w = wall thickness). In toxic megacolon, r increases enormously while w decreases (thinned wall) → wall tension skyrockets → perforation
• Can also occur iatrogenically during colonoscopy in severe colitis (this is why full colonoscopy is contraindicated in fulminant colitis — use flexible sigmoidoscopy instead)

Clinical features:

• Sudden severe generalised abdominal pain
• Rigidity (board-like abdomen), rebound tenderness, guarding — signs of diffuse peritonitis
• Absence of bowel sounds (paralytic ileus from peritoneal contamination)
• Haemodynamic instability → septic shock
• CXR or erect AXR: free gas under the diaphragm (pneumoperitoneum)

Prognosis ^[2]:

• Perforation with peritonitis is associated with high mortality — reported mortality rates of 27–57% in toxic megacolon with perforation
• This underscores the importance of early surgical intervention when toxic megacolon is not responding to medical therapy

Management:

• This is a surgical emergency — emergency total abdominal colectomy with end ileostomy
• Aggressive resuscitation: IV fluids, broad-spectrum IV antibiotics (cover gram-negatives and anaerobes), vasopressors if needed
• ICU admission

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E. Severe Haemorrhage

What it is: Massive, uncontrollable lower GI bleeding from the diffusely ulcerated colonic mucosa.

Pathophysiology:

• The friable, ulcerated mucosa in severe UC contains exposed submucosal vessels
• In most UC cases, bleeding is chronic and low-grade (mixed with stool as bloody diarrhoea). However, in severe colitis, diffuse erosion into submucosal arterioles can cause massive acute haemorrhage
• 6–10% with ulcerative colitis have acute lower GI bleed needing emergency surgery (total colectomy) ^[15]

Management:

• Resuscitation: IV fluids, blood transfusion, correct coagulopathy
• If haemorrhage is uncontrollable despite medical therapy → emergency total abdominal colectomy + end ileostomy ^[2][11]
• Severe bleeding (unremitting bloody diarrhoea) is an indication for emergency surgery ^[2]

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F. Colorectal Cancer (CRC)

This is the most important long-term complication of UC.

CRC in IBD patients is preceded by dysplasia ^[16]. Incidence of CRC in IBD: 18% after 30 years of colitis ^[16].

Pathophysiology — the Inflammation-Dysplasia-Carcinoma Sequence:

This is distinct from the sporadic adenoma → carcinoma sequence in non-IBD CRC. In IBD-CRC:

• The "field effect" of chronic diffuse inflammation means dysplasia can arise anywhere in the colon (not just in a single polyp)
• Dysplasia may be flat (invisible endoscopically) rather than polypoid — making detection much harder
• The risk is cumulative — longer disease duration = greater cumulative inflammatory burden = more DNA damage

Risk factors for IBD-associated colorectal neoplasia ^[1]:

^[1]

Why PSC is the strongest risk factor: PSC is associated with a 4-fold increase in CRC risk in UC patients, independent of disease duration or extent. The mechanism is thought to involve altered bile acid metabolism — PSC causes cholestasis and changes the bile acid pool, with secondary bile acids (e.g., deoxycholic acid) being directly genotoxic to colonic epithelium.

CRC Surveillance (covered in detail in the Management section; key points summarised here):

AGA Guidelines ^[12]:

• Started at a maximum 8 years after UC or Crohn's colitis
• Left-sided or extensive colitis: within 1–2 years after initial screening colonoscopy
• After two negative examinations, every 1–3 years
• PSC: yearly
• Ulcerative proctitis: NOT considered at increased risk
• Ideally performed when disease is in remission

BSG Guidelines — risk-stratified ^[13]:

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12.2 Complications Related to Surgical Treatment (Post-IPAA)

Surgery (proctocolectomy + IPAA) is curative for UC but carries its own set of complications ^[2][8]:

A. Pouchitis

The most common complication of IPAA — lifetime incidence ~50%.

What it is: Inflammation of the ileal pouch (the J-pouch that was surgically created to act as a neo-rectum).

Pathophysiology:

• The ileal mucosa of the pouch undergoes colonic metaplasia over time (the ileum starts to resemble colon histologically — because it is now a reservoir exposed to faecal stasis and bacterial colonisation)
• This metaplastic mucosa is susceptible to the same dysregulated immune response that caused UC in the first place
• Bacterial overgrowth in the pouch (due to stasis) contributes to inflammation
• Pouchitis is more common in patients who had UC (vs. FAP) — supporting the idea that the underlying immune dysregulation "follows" the patient even after the colon is removed

Clinical features:

• Pouch dysfunction + systemic illness ^[8]
• Increased stool frequency (beyond baseline of ~6/day), urgency, watery/bloody stool, abdominal cramps, fever, malaise
• Diagnosis confirmed by pouchoscopy + biopsy (endoscopic evaluation of the pouch showing erythema, ulceration, and histological acute inflammation)

Management ^[2][8]:

• Treated with metronidazole and ciprofloxacin — antibiotics work here because bacterial overgrowth is a major driver. Typically a 2-week course
• For chronic/recurrent pouchitis: oral budesonide, probiotics (VSL#3), immunomodulators, or biologics
• Rarely, pouch excision with permanent ileostomy if refractory

B. Pouch Dysfunction (Without Pouchitis)

• Increased faecal frequency (mean = 6/day), urgency, incontinence ^[8]
• This is the "new normal" after IPAA — the ileal pouch cannot replicate the storage capacity of the rectum perfectly
• Most patients adapt over 6–12 months
• Management: dietary modification (low-residue diet), loperamide for frequency, pelvic floor physiotherapy for incontinence

C. Pelvic Nerve Damage

• Impotence ^[8] — pelvic dissection during proctectomy risks injury to the autonomic nerves (hypogastric nerve = sympathetic, pelvic splanchnic nerves S2–S4 = parasympathetic)
• Sympathetic damage → retrograde ejaculation or ejaculatory failure (in males)
• Parasympathetic damage → erectile dysfunction (in males), sexual dysfunction (in females)
• Sexual dysfunction / infertility ^[2]

D. Pouch-Related Structural Complications

E. Infertility (Females)

• Infertility ^[2] — IPAA involves extensive pelvic dissection that causes adhesions around the fallopian tubes and ovaries
• Studies show ~3-fold increase in infertility after IPAA compared to medical therapy alone
• Female who wants to maintain fertility: total colectomy + ileorectal anastomosis (IRA) — this avoids pelvic dissection ^[8]
  • Trade-off: the rectum is left in situ → ongoing risk of rectal inflammation and CRC → needs continued surveillance

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12.3 Extraintestinal Complications (Cross-Reference)

These were covered in detail in the Clinical Features section. A brief high-yield summary of the key EIM-complications:

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12.4 Prognostic Indicators

Patient diagnosed before age 16 has a more aggressive initial course ^[2] — younger onset is associated with more extensive disease, higher relapse rates, and greater cumulative inflammatory burden over a lifetime.

Patient diagnosed at older age is associated with a lower risk of colectomy ^[2] — older patients tend to have less extensive disease (more likely proctitis or left-sided) and may respond better to medical therapy, or may be less suitable surgical candidates.

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12.5 Complications Summary — The Cascade

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Active Recall - Complications of Ulcerative Colitis

1. A patient with long-standing UC is found to have a colonic stricture on surveillance colonoscopy. What is your immediate concern and what investigation must be performed?

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Strictures in UC should be considered malignant until proven otherwise. Unlike CD (where transmural fibrosis commonly causes benign strictures), UC causes only mucosal/submucosal inflammation which rarely leads to benign strictures. Must perform colonoscopy with multiple biopsies of and around the stricture to exclude adenocarcinoma. If biopsies are inadequate or show any dysplasia, surgery (colectomy) should be strongly considered.

2. Define toxic megacolon, describe its pathophysiology from first principles, and name 3 medications that must be immediately discontinued.

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Definition: Total or segmental non-obstructive dilatation of colon >= 6 cm or caecum > 9 cm with systemic toxicity. Pathophysiology: Severe inflammation extends beyond mucosa to involve muscularis propria and myenteric plexus (Auerbach's) in fulminant colitis. Destruction of smooth muscle and myenteric plexus + excessive nitric oxide release causes colonic atony and dilatation. Bacterial translocation through denuded mucosa causes systemic toxicity (sepsis). Wall becomes paper-thin with high risk of perforation per Laplace's law (tension = pressure x radius). Medications to stop: 1) Opioids (reduce peristalsis via mu-receptors), 2) Anticholinergics (block muscarinic receptors needed for contraction), 3) Loperamide/codeine (anti-motility). These agents worsen colonic atony and can precipitate perforation.

3. Describe the inflammation-dysplasia-carcinoma sequence in UC and name 4 risk factors for IBD-associated CRC.

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Sequence: Chronic mucosal inflammation generates reactive oxygen species (ROS) causing cumulative oxidative DNA damage. Mutations accumulate in tumour suppressor genes (p53, APC) and oncogenes (K-ras), leading first to low-grade dysplasia (LGD), then high-grade dysplasia (HGD), then invasive adenocarcinoma. Unlike sporadic CRC (adenoma-carcinoma sequence), IBD-CRC arises from flat dysplasia in a 'field effect' of diffuse inflammation. Risk factors (any 4): PSC, disease duration, disease extent, cumulative inflammatory burden, active inflammation, pseudopolyps, stricture, FHx of CRC in first-degree relative, early age of onset, male sex, shortened tubular colon.

4. A patient develops pouchitis 1 year after IPAA for UC. Explain the pathophysiology and first-line treatment.

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Pathophysiology: The ileal J-pouch undergoes colonic metaplasia over time (exposed to faecal stasis and bacterial colonisation). This metaplastic mucosa becomes susceptible to the same dysregulated immune response that drove the original UC. Bacterial overgrowth in the stagnant pouch contributes to inflammation. Pouchitis is more common after UC (vs FAP), supporting the immune dysregulation hypothesis. First-line treatment: oral metronidazole and/or ciprofloxacin (antibiotics address the bacterial overgrowth component). Typically a 2-week course. For chronic/recurrent pouchitis, consider oral budesonide, probiotics (VSL#3), or biologics.

5. Why is perforation in toxic megacolon associated with such high mortality, and what does Laplace's law have to do with it?

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Laplace's law states that wall tension (T) is proportional to intraluminal pressure (P) multiplied by radius (r) and inversely proportional to wall thickness (w): T = Pr/2w. In toxic megacolon, the radius increases massively (dilatation) while the wall becomes paper-thin (inflammation destroys muscularis propria). This causes wall tension to skyrocket beyond the structural limit, leading to perforation. Perforation releases faecal contents into the peritoneal cavity causing diffuse faecal peritonitis. The patient is already systemically toxic (sepsis from bacterial translocation), and the addition of faecal contamination triggers overwhelming septic shock. Mortality is 27-57% because of the combination of pre-existing systemic toxicity, faecal peritonitis, and the patient's debilitated state (malnourished, anaemic, often immunosuppressed from steroids).

References

^[1] Lecture slides: Inflammatory bowel disease.pdf (p. 52 — IBD-associated CRC risk factors) ^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Ulcerative colitis: complications, surgical treatment, prevention/CRC screening) ^[4] Senior notes: felixlai.md (Primary sclerosing cholangitis section) ^[8] Senior notes: maxim.md (Inflammatory bowel disease: surgical indications; Surgical procedures for UC) ^[11] Lecture slides: Inflammatory bowel disease.pdf (pp. 18, 19, 20, 21 — Surgical indications, emergency surgery, colectomy, surgical options) ^[12] Lecture slides: Inflammatory bowel disease.pdf (p. 56 — AGA guideline 2010 for CRC surveillance) ^[13] Lecture slides: Inflammatory bowel disease.pdf (p. 57 — BSG guideline 2010 for risk-stratified surveillance) ^[15] Lecture slides: GC 186. Lower and diffuse abdominal painfresh blood in stool.pdf (p. 11 — IBD and PR bleeding) ^[16] Lecture slides: Inflammatory bowel disease.pdf (p. 51 — IBD-associated CRC, colitis-dysplasia-carcinoma sequence, 18% incidence after 30 years)