Common Causes of Heart Disease: Epidemiology, Genetics, Pathogenesis, and Clinical Course

1. Rheumatic / Valvular Heart Disease

Epidemiology

Genetic Basis

• The immunoglobulin heavy chain locus (specifically the IGHV4-61*02 allele)
• Complement factor H genes
• HLA class II alleles (HLA-DQ A and B subtypes) - both susceptibility and protective variants exist
• Polymorphisms in TNF and mannose-binding lectin genes

Pathogenesis

1. Antigen-presenting cells process GAS antigens and present them to T cells
2. Cross-reactive antibodies bind endothelial cells on heart valves, activating VCAM-1
3. Activated lymphocytes are recruited; complement-mediated lysis of endothelial cells releases host peptides (laminin, keratin, tropomyosin)
4. Cross-reactive T cells invade the heart, amplifying damage via epitope spreading
5. Aschoff bodies (pathognomonic granulomatous lesions with Anitschkow cells) form in the myocardium and valves

• Harrison's Principles of Internal Medicine 22E, pp. 2897-2900

Clinical Evolution and Course

• Latent period: ~3 weeks (range 1-5 weeks) between GAS infection and ARF onset; chorea and indolent carditis may follow latencies up to 6 months
• Acute ARF: polyarthritis (60-75%), carditis (50-75%), Sydenham's chorea (up to 30% in some populations), erythema marginatum, subcutaneous nodules
• Carditis: up to 75% of ARF cases develop RHD. Early lesion = mitral regurgitation ± aortic regurgitation. Later (years to decades of recurrent episodes): leaflet thickening, scarring, calcification → mitral stenosis (hallmark of chronic RHD), also aortic stenosis/regurgitation
• Chronic RHD: patients are often asymptomatic for many years. When significant obstruction or regurgitation develops, symptoms include dyspnoea, fatigue, palpitations (atrial fibrillation is common), and eventually heart failure
• Complications: atrial fibrillation (from left atrial dilatation in mitral stenosis), systemic embolism, infective endocarditis, pulmonary hypertension, and right heart failure
• Prevention: secondary prophylaxis with long-term penicillin (benzathine penicillin G, every 3-4 weeks) is the cornerstone of management to prevent recurrences and halt valvular progression

2. Ischemic Heart Disease (IHD)

Epidemiology

• Chronic stable angina (chronic coronary syndrome)
• Acute coronary syndromes (ACS): unstable angina, NSTEMI, and STEMI
• Ischaemic cardiomyopathy / heart failure with reduced ejection fraction (HFrEF)
• Sudden cardiac death

Genetic Basis

• 9p21.3 locus (near CDKN2A/B): the strongest individual locus, associated with ~30% increased relative risk per allele; mechanism involves regulation of cell proliferation in the vessel wall
• LPA gene variants: elevated lipoprotein(a) levels confer substantial additional risk
• PCSK9 variants: loss-of-function variants markedly lower LDL and reduce CAD risk
• LDLR, APOB, APOE: variants in lipoprotein handling genes; familial hypercholesterolaemia (FH) - caused by LDLR mutations (most common), APOB mutations, or PCSK9 gain-of-function variants - produces very high LDL and premature IHD
• Heritability of CAD is approximately 40-60%; polygenic risk scores incorporating thousands of SNPs are increasingly used to identify high-risk individuals

Pathogenesis

1. Endothelial injury (from hypertension, oxidised LDL, smoking, haemodynamic shear stress): increases endothelial permeability, upregulates adhesion molecules (VCAM-1, ICAM-1)
2. Lipid accumulation: LDL enters the subintimal space, undergoes oxidative modification; oxidised LDL is pro-inflammatory
3. Monocyte recruitment: monocytes adhere to activated endothelium, transmigrate, and differentiate into macrophages, which take up modified LDL via scavenger receptors to become foam cells (early fatty streak)
4. Smooth muscle cell (SMC) migration: SMCs migrate from media to intima, proliferate, secrete extracellular matrix, forming the fibrous cap
5. Plaque progression: the plaque develops a necrotic lipid core (dead foam cells) covered by fibrous cap; the fibrous cap is thin in "vulnerable plaques"
6. Plaque rupture or erosion: triggers thrombus formation on the exposed lipid core or denuded endothelium; this is the precipitating event in most ACS

Clinical Evolution and Course

• Asymptomatic subclinical atherosclerosis: fatty streaks can appear in the aorta in childhood; significant plaques develop over decades
• Stable angina: effort-induced chest pain (substernal, pressurelike, radiating to arm/jaw), relieved by rest or nitroglycerin; represents fixed stenosis with preserved resting flow
• ACS spectrum: sudden onset or rapidly worsening angina at rest; STEMI presents with ST elevation on ECG and requires urgent reperfusion (PCI or thrombolysis); NSTEMI has troponin elevation without ST elevation
• Post-MI remodelling: surviving myocardium undergoes compensatory hypertrophy; infarcted zone undergoes fibrotic scarring; progressive left ventricular dilation may lead to ischaemic cardiomyopathy (HFrEF) over months to years
• Long-term course: determined by extent of left ventricular dysfunction, presence of residual ischaemia, arrhythmia risk, and comorbidities. Ejection fraction <35-40% carries substantial mortality risk and may warrant ICD implantation
• Complications: arrhythmias (VF causing sudden cardiac death - especially in first 24-48 hours post-MI), papillary muscle rupture (acute mitral regurgitation), ventricular septal rupture, free wall rupture, Dressler syndrome (post-infarction pericarditis), mural thrombus and embolism

3. Hypertrophic Cardiomyopathy (HCM)

Epidemiology

Genetic Basis

• Robbins & Kumar Basic Pathology, p. 373-374

Pathogenesis

1. Diastolic dysfunction: the stiffened, hypercontractile myocardium fails to fully relax during diastole → impaired ventricular filling → raised end-diastolic pressure → pulmonary venous hypertension
2. Asymmetric septal hypertrophy (ASH): present in 90% of cases - disproportionate thickening of the ventricular septum relative to the free wall compresses the left ventricular cavity into a "banana-like" shape on cross-section
3. Left ventricular outflow tract (LVOT) obstruction: systolic anterior motion (SAM) of the anterior mitral leaflet contacts the hypertrophied septum during systole in approximately one-third of patients, causing dynamic obstruction; this is the substrate for the characteristic harsh systolic ejection murmur (which increases with Valsalva and decreases with squatting)
4. Myocardial ischaemia: massive hypertrophy + high LV pressures + reduced coronary reserve (insufficient capillary density for the hypertrophied mass) → angina even without epicardial CAD
5. Histology: the cardinal histologic triad is marked myocyte hypertrophy, haphazard myocyte and myofiber disarray, and interstitial fibrosis - disarray being pathognomonic and likely the substrate for arrhythmias and SCD

Clinical Evolution and Course

• Presentation: commonly manifests during postpubertal growth spurt; can present at any age; many patients remain asymptomatic for decades and are diagnosed incidentally on echocardiography or during family screening
• Symptoms: exertional dyspnoea (most common), angina (from myocardial ischaemia), presyncope/syncope (from obstruction or arrhythmia), and palpitations (from AF or ventricular arrhythmias)
• SCD risk: the most feared complication; risk factors include: prior cardiac arrest, sustained VT, family history of SCD, massive hypertrophy (septal thickness ≥30 mm), unexplained syncope, abnormal blood pressure response to exercise, and non-sustained VT on Holter. ICD implantation is recommended in those with high SCD risk
• Atrial fibrillation: occurs in up to 25% of patients with HCM; causes significant haemodynamic deterioration and embolic risk; anticoagulation is warranted
• End-stage HCM: ~5-10% of patients develop a "burnt-out" or dilated phase with ventricular dilation, systolic dysfunction, and progressive heart failure, often requiring advanced therapies (transplantation or LVAD)
• Medical management: negative inotropes/dromotropes (beta-blockers, verapamil, diltiazem) to promote ventricular relaxation and reduce outflow obstruction; disopyramide added for obstruction-related symptoms; mavacamten (cardiac myosin inhibitor) is a newer targeted therapy
• Septal reduction therapy: surgical myectomy (Morrow procedure) or alcohol septal ablation for drug-refractory symptomatic obstruction

4. Inflammatory Heart Disease (Myocarditis and Pericarditis)

Epidemiology

Genetic Basis

• HLA alleles influence immune response to viral antigens and autoantigen presentation
• In immune checkpoint inhibitor (ICI)-associated myocarditis, immune checkpoint gene variants (PD-1, CTLA-4 pathway) modulate risk
• In Chagas disease (T. cruzi), HLA and cytokine gene polymorphisms influence who develops chronic cardiomyopathy vs. remains in the indeterminate phase
• Genetic cardiomyopathies (e.g., DCM-associated mutations) can lower the threshold for clinically apparent myocarditis following viral infection

Pathogenesis of Myocarditis

• Most common: Parvovirus B19 (infects cardiac endothelial cells, not myocytes), human herpesvirus 6 (HHV-6)
• Classic: Coxsackievirus B and other enteroviruses (infect cardiac myocytes via the CAR receptor - coxsackievirus-adenovirus receptor; also uses DAF/CD55 as co-receptor)
• Others: CMV, HIV, influenza, adenovirus, SARS-CoV-2

• Innate immunity: pattern recognition receptors (TLRs) detect viral PAMPs; interferons are produced; NK cells are recruited
• Adaptive immunity: T cell (especially cytotoxic CD8+) infiltrates develop; in most cases this is protective and clears the virus; B cells produce neutralising antibodies
• Immunopathology: when the immune response is excessive or misdirected, T cells and antibodies target self-antigens (e.g., cardiac myosin heavy chain) - autoimmune myocarditis ensues even after viral clearance
• Dallas criteria (histologic diagnosis): active myocarditis = inflammatory infiltrate with myocyte necrosis or damage not consistent with ischaemia

• Trypanosoma cruzi (Chagas disease): endemic in Latin America; ~300,000 infected individuals live in the US; ~10% die during acute attack; others enter a silent indeterminate phase; 10-20 years later, chronic immune-mediated cardiomyopathy with heart failure and arrhythmia develops in ~30%
• Borrelia burgdorferi (Lyme disease): myocarditis in ~5% of Lyme disease cases; manifests mainly as self-limited conduction system disease (AV block), often requiring temporary pacing
• Toxoplasma gondii: particularly in immunocompromised hosts
• mRNA COVID-19 vaccination: rare post-vaccination myocarditis, especially in male adolescents/young adults after the 2nd dose; most cases recover uneventfully
• Immune checkpoint inhibitors (ICIs): incidence 0.3-1%; can cause fulminant myocarditis; treated with high-dose corticosteroids ± T-cell inhibitors (alemtuzumab, abatacept)
• Drug hypersensitivity myocarditis: eosinophilic infiltrate; typically mild; rarely fatal
• Autoimmune diseases: SLE, polymyositis, sarcoidosis (granulomatous myocarditis)
• Braunwald's Heart Disease, pp. 699-735; Robbins & Kumar Basic Pathology, p. 375

Clinical Evolution and Course

• Acute presentation: highly variable - ranges from subclinical (incidental troponin elevation) to fulminant heart failure, cardiogenic shock, or life-threatening arrhythmia
• Classic presentation: young patient with flu-like prodrome followed days to weeks later by chest pain (pericarditic or pleuritic), dyspnoea, palpitations, and signs of heart failure
• ECG: may show ST changes (diffuse or focal), T-wave inversions, arrhythmias, or conduction block
• Cardiac MRI: most sensitive non-invasive test; shows myocardial oedema (T2-weighted hyperintensity) and late gadolinium enhancement (LGE) reflecting fibrosis/inflammation
• Endomyocardial biopsy (EMB): remains the histologic gold standard but has sampling error; recommended in haemodynamically unstable patients with suspected fulminant myocarditis
• Most common outcome: self-limited with full recovery in 4-6 weeks when supportive care is provided
• Poor outcome predictors: fulminant presentation, ventricular dysfunction, giant cell myocarditis (requires aggressive immunosuppression), eosinophilic myocarditis
• Chronic outcome: 10-30% develop persistent ventricular dysfunction leading to DCM; these patients require standard heart failure therapy (ACE inhibitors, beta-blockers, diuretics, aldosterone antagonists); advanced heart failure may require LVAD or transplantation
• Giant cell myocarditis: rare, rapidly progressive, fatal without immunosuppression or transplantation; associated with autoimmune conditions and thymoma

• Most commonly viral/idiopathic; also seen in ARF, post-MI (Dressler syndrome), uraemia, autoimmune disease, malignancy, post-cardiac surgery
• Presents with sharp pleuritic chest pain (worse supine, relieved sitting forward), pericardial friction rub, diffuse saddle-shaped ST elevation on ECG
• Treatment: NSAIDs + colchicine (reduces recurrence); corticosteroids reserved for non-responders or specific causes (autoimmune, uraemic)
• Complications: pericardial effusion, cardiac tamponade, constrictive pericarditis (fibrotic restriction of diastolic filling, usually after recurrent/prolonged inflammation)

Summary Comparison Table

• Harrison's Principles of Internal Medicine 22E (2025), Chapter 371 (Rheumatic Fever and RHD), pp. 2897-2902
• Braunwald's Heart Disease, 2-Vol Set (Chapter 55, Myocarditis), pp. 699-735
• Robbins & Kumar Basic Pathology (Cardiomyopathy/Myocarditis chapter), pp. 370-376
• Goldman-Cecil Medicine (Rheumatic Valvular Heart Disease; Aortic Stenosis chapters), pp. 608-640

Heart Disease: Exam-Focused Guide

1. RHEUMATIC / VALVULAR HEART DISEASE

The Core Concept

Throat infection → immune system attacks the heart valves by mistake

Pathogenesis (How it happens)

Exam tip: Always say "mitral valve is almost always involved." The progression is: Regurgitation (acute) → Stenosis (chronic)

Clinical Manifestations

• Mitral stenosis → rumbling mid-diastolic murmur at apex, opening snap
• Mitral regurgitation → pansystolic murmur radiating to axilla
• Atrial fibrillation (from dilated left atrium)
• Dyspnoea, fatigue, haemoptysis (in mitral stenosis)
• Signs of right heart failure when pulmonary hypertension develops

Course

GAS throat infection
        ↓
Acute Rheumatic Fever (3 weeks later)
        ↓
Carditis → valve damage (regurgitation initially)
        ↓
Recurrent episodes over years → scarring and fibrosis
        ↓
Mitral/Aortic STENOSIS (chronic RHD)
        ↓
Atrial fibrillation → systemic embolism
        ↓
Left heart failure → pulmonary hypertension → right heart failure

• Asymptomatic for many years after initial valve damage
• Symptoms appear in 3rd-5th decade in high-burden countries
• Secondary prophylaxis (benzathine penicillin every 3-4 weeks) prevents progression

2. ISCHEMIC HEART DISEASE (IHD/CAD)

The Core Concept

Narrowed coronary arteries → not enough blood to heart muscle → muscle dies

Pathogenesis (How it happens)

Exam tip: Stable angina = supply-demand mismatch. ACS = acute thrombosis. Complete occlusion = STEMI. Partial = NSTEMI/Unstable angina.

Clinical Manifestations

• Chest pain/tightness: substernal, radiates to left arm/jaw
• Triggered by exertion, cold, stress
• Relieved by rest or GTN spray within 5 minutes
• Normal ECG at rest; ST depression on exercise test

• Severe, crushing central chest pain at rest
• Radiation to left arm, jaw, back
• Sweating, nausea, vomiting
• Breathlessness
• "Silent MI" in diabetics and elderly (no chest pain!)
• ECG: ST elevation (STEMI) or ST depression/T-wave changes (NSTEMI)
• Troponin elevated (rises 3-6 hours post-infarct, peaks 24h)

• Dyspnoea, orthopnoea, ankle swelling
• Reduced ejection fraction

Course

Risk factors (years/decades of atherosclerosis)
        ↓
Asymptomatic subclinical disease
        ↓
Stable angina (fixed stenosis, intact cap)
        ↓
Plaque rupture → ACS
   ├─ NSTEMI (partial occlusion, no full thickness infarct)
   └─ STEMI (complete occlusion, full thickness infarct)
        ↓
Post-MI complications:
   - Arrhythmias (VF/VT) → Sudden cardiac death
   - Pump failure → Cardiogenic shock
   - Papillary muscle rupture → Acute MR
   - Ventricular septal rupture
   - LV aneurysm / mural thrombus
        ↓
Ischaemic cardiomyopathy (HFrEF)

3. HYPERTROPHIC CARDIOMYOPATHY (HCM)

The Core Concept

Genetic mutation → heart muscle proteins are overactive → heart muscle grows too thick → can't relax properly → outflow blocked + risk of sudden death

Pathogenesis (How it happens)

• MYH7 (beta-myosin heavy chain) - 35-40%
• MYBPC3 (myosin-binding protein C) - 25-30%
• TNNT2 (Troponin T) - 5%

• Myocyte hypertrophy
• Myofiber disarray (fibres running in random directions) ← unique to HCM
• Interstitial fibrosis

Exam tip: In HCM, the problem is DIASTOLE (filling), not systole. EF is normal or increased. The murmur INCREASES with Valsalva/standing (less preload → more obstruction) and DECREASES with squatting.

Clinical Manifestations

• Jerky/bifid pulse (spike and dome)
• Double apical impulse
• Harsh ejection systolic murmur at left sternal edge
• Murmur louder with: standing, Valsalva, dehydration
• Murmur softer with: squatting, lying down, passive leg raise

Course

Inherited sarcomeric mutation (present at birth)
        ↓
Phenotype usually develops in adolescence/young adulthood
(postpubertal growth spurt)
        ↓
Many remain asymptomatic (diagnosed on screening)
        ↓
Symptomatic: dyspnoea, angina, syncope, palpitations
        ↓
Risk of sudden cardiac death (especially in athletes)
        ↓
~5-10% develop "burnt-out" dilated phase
(ventricle dilates, EF drops → end-stage HF)

• Prior cardiac arrest or sustained VT
• Family history of SCD
• Massive hypertrophy (septum ≥ 30mm)
• Unexplained syncope
• Abnormal BP response to exercise
• Non-sustained VT on Holter monitor

4. INFLAMMATORY HEART DISEASE (Myocarditis & Pericarditis)

The Core Concept

Infection (usually viral) or autoimmune process → inflammation of the heart muscle or its lining → can destroy muscle → heart failure or sudden death

MYOCARDITIS

Pathogenesis (3 phases - easy to remember)

• Most common: Coxsackievirus B, Parvovirus B19, HHV-6, enteroviruses
• Virus enters via respiratory/GI tract → travels to heart via bloodstream
• Coxsackievirus binds the CAR receptor (Coxsackievirus-Adenovirus Receptor) at the intercalated disc
• Directly lyses myocytes and disrupts dystrophin (cytoskeletal protein)

• Innate immunity (NK cells, interferons) tries to clear virus
• CD8+ cytotoxic T cells kill infected myocytes
• Antibodies may cross-react with cardiac myosin → autoimmune myocarditis (persists even after virus cleared)
• If immune response is appropriate → virus cleared, recovery
• If excessive or misdirected → continued myocyte destruction

• Chronic inflammation → fibrosis → ventricular dilation → dilated cardiomyopathy (DCM)
• Some patients have persistent viral genome in myocardium without active inflammation

Exam tip: Myocarditis is the link between viral infection and dilated cardiomyopathy.

Key Causes to Know

Clinical Manifestations of Myocarditis

• Flu-like prodrome (fever, myalgia) 1-2 weeks before cardiac symptoms
• Chest pain (often pleuritic/pericarditic)
• Dyspnoea, fatigue
• Palpitations, syncope
• Signs of heart failure (raised JVP, S3 gallop, basal crackles, oedema)
• ECG: ST changes, T-wave inversions, arrhythmias, heart block
• Raised troponin (myocyte necrosis)
• Cardiac MRI: shows oedema and late gadolinium enhancement (LGE) = gold standard non-invasive test
• Endomyocardial biopsy (EMB): gold standard histologic diagnosis (Dallas criteria)

PERICARDITIS (quick summary)

• Inflammation of pericardial sac
• Causes: viral (most common), post-MI (Dressler's syndrome), TB, uraemia, autoimmune, malignancy
• Sharp pleuritic chest pain - worse lying flat, better sitting forward
• Pericardial friction rub on auscultation
• ECG: saddle-shaped ST elevation in all leads + PR depression
• Treatment: NSAIDs + Colchicine (prevents recurrence)
• Complication: Cardiac tamponade (Beck's triad: hypotension + muffled heart sounds + raised JVP) → emergency pericardiocentesis

Course of Myocarditis

Viral infection (prodrome)
        ↓
Acute myocarditis (chest pain, dyspnoea, arrhythmias)
        ↓
Most common outcome (majority): FULL RECOVERY in 4-6 weeks
        ↓ (minority)
Persistent ventricular dysfunction
        ↓
Dilated cardiomyopathy (HFrEF) → Heart failure
        ↓
Advanced heart failure → Transplant / LVAD

QUICK EXAM COMPARISON TABLE

Final Exam Tip: For any question on heart disease, structure your answer as: (1) Cause/trigger → (2) What happens to the heart structure (pathology) → (3) What symptoms result → (4) What complications/outcome follows. This framework works for all four types.

Upper and Lower GI Bleeding: Aetiology - Exam-Focused Guide

FIRST: Key Definitions You Must Know

Exam tip: Melaena = blood has been digested = source is proximal (UGIB or proximal small bowel). Haematochezia = bright red = source is distal (colon/rectum) - but 15% of massive haematochezia is actually from a brisk UGIB source.

THE ANATOMICAL DIVIDING LINE

• UGIB = Oesophagus, Stomach, Duodenum (proximal to ligament of Treitz)
• LGIB = Jejunum, Ileum, Colon, Rectum, Anus (distal to ligament of Treitz)

PART 1: UPPER GI BLEEDING (UGIB)

Epidemiology Quick Facts

• Incidence: 40-150 per 100,000 persons/year
• Mortality: 6-10% (death usually from comorbidities, not exsanguination)
• Bleeding is self-limited in 80% without specific therapy
• Of those who re-bleed, mortality rises to 30-40%

CAUSES OF UGIB (Frequency Order - Memorise This!)

DETAILED AETIOLOGY OF UGIB

1. PEPTIC ULCER DISEASE (PUD) - Most Common ~50%

Normal: Protective mucus/bicarbonate layer balances acid attack
         ↓
Disruption of this balance → mucosal injury → ulceration

• Gram-negative spiral bacterium living in the gastric mucosa
• Produces urease → splits urea into ammonia → neutralises local acid, allowing survival
• Causes chronic inflammation (gastritis) → breaks down the mucosal protective barrier
• Upregulates gastrin → increases acid secretion → worsens mucosal injury
• Present in ~70-90% of duodenal ulcers and ~60-70% of gastric ulcers globally

• COX-1 inhibition → reduced prostaglandin (PGE2, PGI2) synthesis
• Prostaglandins normally: stimulate mucus, stimulate bicarbonate, maintain mucosal blood flow
• Without prostaglandins → mucosal defences collapse → ulceration
• NSAIDs also have direct toxic effect on mucosa ("topical injury")
• Risk is dose-dependent; aspirin increases risk even at low doses

• Zollinger-Ellison Syndrome (ZES): gastrin-secreting tumour (gastrinoma) in pancreas/duodenum → massive acid secretion → multiple, refractory ulcers
• Less commonly: stress ulcers in critically ill patients (ICU, burns = Curling's ulcer, head injury = Cushing's ulcer)

• Epigastric pain: DU - "hunger pain" relieved by food; GU - worsened by food
• Haematemesis (fresh blood or coffee grounds)
• Melaena
• Rarely: haematochezia (if massive)
• Signs of haemorrhagic shock in severe bleeds

Exam tip: Duodenal ulcers are 4x more common than gastric. All gastric ulcers must be biopsied (to exclude malignancy). H. pylori eradication reduces rebleeding rates from ~50% to <5%.

2. OESOPHAGEAL AND GASTRIC VARICES - ~20%

Liver cirrhosis (most common cause) → hepatic fibrosis + nodular regeneration
        ↓
Increased resistance to portal blood flow
        ↓
Portal hypertension (portal pressure >10-12 mmHg)
        ↓
Blood diverted through collateral channels
        ↓
Left gastric vein → oesophageal submucosal veins → VARICES
        ↓
Varix wall tension ↑ (LaPlace's law: T = P × r) → rupture → massive haemorrhage

• Prehepatic: portal vein thrombosis, splenic vein thrombosis
• Intrahepatic (most common): cirrhosis (alcohol, viral hepatitis, NAFLD, autoimmune), schistosomiasis (in endemic areas)
• Posthepatic: Budd-Chiari syndrome, constrictive pericarditis, right heart failure

• Massive haematemesis (bright red blood) - "vomiting blood like a tap"
• Signs of chronic liver disease: jaundice, ascites, spider naevi, palmar erythema, caput medusae, splenomegaly
• High mortality per variceal bleed episode: ~20-30%
• Encephalopathy can be precipitated by the bleed (blood = large protein load in gut)

Exam tip: Varices bleed because pressure is high, NOT because the vessel wall is fragile. Key risk factor for rupture = variceal size + red wale signs on endoscopy.

3. EROSIVE GASTRITIS / OESOPHAGITIS - ~5-10%

• NSAIDs and aspirin
• Alcohol (direct mucosal toxicity)
• Stress (critically ill patients, burns, major surgery, head injury)
• H. pylori infection
• Erosive oesophagitis: severe GERD → acid damages lower oesophageal mucosa → erosions/ulcers

• Loss of protective mucous layer → acid comes in direct contact with mucosa → inflammation and erosion → capillary bleeding

• Usually less severe bleeding than peptic ulcer (capillary ooze vs. arterial)
• Epigastric discomfort, heartburn (oesophagitis)
• Coffee-ground vomiting, melaena

4. MALLORY-WEISS TEAR - ~4%

• Forceful, repeated vomiting → sudden rise in intra-abdominal pressure against a closed glottis → shearing force on the GEJ mucosa → longitudinal tear → arterial bleeding from submucosal vessels

• History of retching/vomiting before blood appears
• Haematemesis (usually self-limited)
• Usually stops spontaneously; endoscopic therapy if persistent

5. DIEULAFOY LESION - ~3%

• Recurrent massive haematemesis with no obvious ulcer on endoscopy
• Easy to miss - looks like a tiny red spot between bleeds
• Classically in elderly men
• Can be life-threatening; requires endoscopic therapy (clips, band ligation) or angiographic embolisation

6. AORTOENTERIC FISTULA - Rare but must know

Exam tip: Always ask about prior aortic surgery in a patient with unexplained UGIB.

7. HAEMOBILIA - Rare

8. BOERHAAVE SYNDROME - Rare but serious

PART 2: LOWER GI BLEEDING (LGIB)

Epidemiology Quick Facts

• Incidence: ~20 per 100,000/year
• Most patients are >70 years old
• Typically presents as painless haematochezia (bright red blood PR)
• Stops spontaneously in ~80% of cases
• Most common cause requiring hospitalisation = diverticular disease

CAUSES OF LGIB (Frequency Order - Memorise This!)

DETAILED AETIOLOGY OF LGIB

1. DIVERTICULAR DISEASE - Most Common Acute LGIB

Low-fibre diet → increased intraluminal pressure → colonic wall weakness
        ↓
Mucosa herniates through muscle at vascular penetration points
        ↓
Artery (vasa recta) becomes draped over neck of diverticulum
        ↓
Vessel wall injured by faecal trauma or increased pressure → ruptures
        ↓
Massive arterial haemorrhage into the colonic lumen

• Elderly patient (most common in >60 years)
• Sudden onset of painless haematochezia (large volume bright red or maroon blood)
• No preceding symptoms (unlike IBD)
• Stops spontaneously in ~80% of cases
• Rebleeds in ~25% within next year

Exam tip: Diverticula are most common in sigmoid, but bleed from the right colon. Painless is the key word.

2. ANGIODYSPLASIA (Arteriovenous Malformations) - ~2-30%

• Chronic intermittent obstruction of submucosal veins during colonic contraction → over decades → venous dilatation → capillary dilatation → arteriovenous communication forms
• Associated conditions: aortic stenosis (Heyde syndrome), chronic renal failure, von Willebrand disease

• Elderly patients
• Painless haematochezia or melaena (can be occult)
• Recurrent episodes
• Iron-deficiency anaemia from slow, chronic blood loss
• Diagnosed by colonoscopy or capsule endoscopy

Exam tip: Angiodysplasia is the most common cause of small bowel bleeding (70-80% of small intestinal LGIB) and a major cause of obscure GI bleeding.

3. COLORECTAL CANCER AND POLYPS - ~11-20%

• Tumour outgrows its blood supply → central necrosis + surface ulceration → bleeding
• Mucosal friability from tumour surface → bleeding on defaecation
• Large sessile polyps: similar surface ulceration

• Change in bowel habit (alternating diarrhoea/constipation)
• Haematochezia (blood mixed with stool, not just on surface)
• Iron-deficiency anaemia (often the first presentation, especially right-sided tumours)
• Weight loss, anorexia
• Palpable mass (if large)
• Left-sided tumours: bright red blood, change in stool calibre
• Right-sided tumours: occult bleeding → anaemia (blood mixed into liquid faeces)

Exam tip: Any patient >50 with iron-deficiency anaemia and haematochezia needs colonoscopy to exclude CRC until proven otherwise.

4. COLITIS - ~9-21%

• Causes: Salmonella, Shigella, Campylobacter, E. coli O157:H7, C. difficile (pseudomembranous colitis)
• Mechanism: Bacterial toxins and direct invasion → mucosal inflammation and ulceration → bloody diarrhoea
• Key features: Fever, diarrhoea, abdominal cramps + blood

• Most common type of intestinal ischaemia
• Most commonly affects the watershed areas: splenic flexure and rectosigmoid junction (least collateral blood supply)
• Causes: Low flow states (shock, heart failure), atherosclerosis, post-aortic surgery
• Mechanism: Ischaemia → mucosal necrosis → bloody diarrhoea + abdominal pain
• Clinical: Elderly patient; sudden onset bloody diarrhoea + left-sided abdominal pain after meals or post-surgery

• Follows pelvic radiotherapy (for prostate, cervical, rectal cancers)
• Mechanism: Radiation → endarteritis of submucosal vessels → ischaemia → mucosal atrophy → telangiectasia formation → chronic low-grade or acute bleeding
• Presents months to years after radiation

5. ANORECTAL CAUSES - ~4-10%

• Dilated submucosal vascular cushions of the anal canal
• Internal haemorrhoids (above dentate line): painless bright red blood on toilet paper or dripping after defaecation
• External haemorrhoids (below dentate line): painful when thrombosed; may bleed
• Causes: constipation, straining, pregnancy, portal hypertension
• Most common cause of rectal bleeding overall (though usually minor)

Exam trap: Haemorrhoids are common but must never be assumed to be the cause in older patients without excluding CRC.

• A tear/split in the mucosa of the anal canal
• Located most commonly at the posterior midline (anterior midline in women)
• Mechanism: Hard stool → tearing of anal mucosa → spasm of internal anal sphincter → ischaemia → failure to heal
• Classical features: Severe pain on defaecation (patient afraid to open bowels) + small amount of bright red blood on toilet paper/surface of stool (blood NOT mixed into stool)
• If off-midline fissure: suspect Crohn's disease, anal cancer, syphilis, HIV

• Prolapse of rectal mucosa → mucosal ischaemia → ulceration → bleeding
• Solitary rectal ulcer syndrome: recurrent straining → ischaemia → ulcer on anterior rectal wall

6. MECKEL'S DIVERTICULUM - Rare but classic exam question

• Children and young adults
• Painless rectal bleeding (often substantial volume)
• Melaena or haematochezia (brick-red stool)
• Diagnosed by Meckel's scan (Tc-99m pertechnetate) - taken up by ectopic gastric mucosa

QUICK COMPARISON TABLE: UGIB vs. LGIB

MEMORY AID: CAUSES OF UGIB - "PEV-MADA"

• P - Peptic ulcer (most common)
• E - Erosive gastritis/oesophagitis
• V - Varices (oesophageal/gastric)
• M - Mallory-Weiss tear
• A - Angiodysplasia/AVM
• D - Dieulafoy lesion
• A - Aortoenteric fistula / Aorta (+ cancer)

MEMORY AID: CAUSES OF LGIB - "DACA-MAR"

• D - Diverticular disease (most common acute)
• A - Angiodysplasia
• C - Colitis (IBD, infective, ischaemic, radiation)
• A - Anorectal (haemorrhoids, fissures)
• M - Malignancy / polyps (CRC)
• A - Angiodysplasia (small bowel)
• R - Rare: Meckel's, radiation proctitis, rectal ulcer

FINAL EXAM FRAMEWORK FOR ANY GI BLEEDING QUESTION

1. Define UGIB vs. LGIB by anatomical landmark
2. List causes in frequency order
3. For each cause, state:
   • What it is (definition)
   • Why/how it bleeds (mechanism)
   • Classic clinical scenario (age, history, associated features)
   • Key distinguishing feature

Acute and Chronic Diarrhoea: Aetiology - Exam-Focused Guide

FIRST: KEY DEFINITIONS (Always state these!)

Exam tip: Duration is the single most important initial classifier. Always state it.

THE 4 MECHANISMS OF DIARRHOEA (Must Know!)

NORMAL: Water absorbed > water secreted → formed stool
DIARRHOEA: Water absorbed < water secreted (or lost) → loose stool

Exam trick: "Does diarrhoea stop with fasting?" = key question to distinguish secretory (No) from osmotic (Yes)

PART 1: ACUTE DIARRHOEA (<2 WEEKS)

80% is Infectious - Think Food and Water

Classification of Infectious Diarrhoea

Exam tip: Watery diarrhoea = small bowel origin = large volume, no blood. Bloody diarrhoea (dysentery) = large bowel origin = small volume, blood/mucus, pain, tenesmus.

A. VIRAL CAUSES (Most common overall in developed world)

1. Norovirus (Most Common Viral Cause in Adults)

• Aka: Winter vomiting disease
• Spread: Faeco-oral; very low infectious dose; highly contagious; cruise ships, hospitals, restaurants
• Mechanism: Invades small intestinal villous epithelial cells → loss of mature absorptive cells → osmotic diarrhoea (carbohydrate malabsorption) + some secretory component
• Clinical features:
  • Sudden onset nausea + vomiting (prominent) + watery diarrhoea
  • Low-grade fever, myalgia, headache
  • Duration: 24-72 hours (self-limiting)
  • No blood in stool

2. Rotavirus (Most Common Viral Cause in Children Worldwide)

• Spread: Faeco-oral; leading cause of childhood diarrhoea deaths globally (replaced by Norovirus in vaccinated populations)
• Mechanism: Destroys mature absorptive villous tip cells → replaced by immature secretory crypt cells → secretory + osmotic diarrhoea (carbohydrate malabsorption, especially lactose)
• Clinical features:
  • Children 6 months - 2 years
  • Watery diarrhoea + vomiting + fever for 3-8 days
  • Can cause severe dehydration rapidly in infants
  • Vaccine available (RotaTeq, Rotarix)

3. Other Viruses

• Adenovirus types 40/41: Second most common viral cause in children; longer duration (up to 10 days); less vomiting
• Astrovirus, Sapovirus: Similar to norovirus but less common
• CMV: Important in immunocompromised (AIDS, transplant patients) → haemorrhagic colitis

B. BACTERIAL CAUSES

Mechanism Reminder:

• Enterotoxin producers → stimulate cAMP/cGMP → active Cl⁻ secretion → watery diarrhoea (no mucosal damage)
• Invasive organisms → penetrate mucosa → inflammatory response → dysentery (blood, pus, fever)
• Cytotoxin producers → kill mucosal cells → inflammatory diarrhoea

1. Vibrio cholerae (Prototype Secretory Diarrhoea)

• Endemic: South Asia, sub-Saharan Africa; epidemics after natural disasters
• Spread: Contaminated water (large inoculum needed: 10⁵-10⁸ organisms)
• Mechanism:

  V. cholerae adheres to small bowel brush border via toxin-coregulated pilus
          ↓
  Secretes cholera toxin (A+B subunits)
          ↓
  B subunit binds GM1 ganglioside receptor on enterocyte
          ↓
  A subunit translocates inside cell → ADP-ribosylates Gs protein → 
  persistent activation of adenylate cyclase
          ↓
  ↑↑ cAMP → Cl⁻ pumped into gut lumen, Na+ and water follow
          ↓
  No mucosal damage - pure secretory diarrhoea
  

• Clinical features:
  • "Rice-water stools" - watery, no odour, no blood
  • Extremely high volume (up to 10-20 L/day!)
  • Rapid, severe dehydration → hypovolaemic shock, muscle cramps
  • NO fever (no mucosal invasion)
  • Vomiting common
  • Mortality >50% untreated; <1% with ORS

Exam tip: Cholera = NO fever, NO blood, NO WBCs in stool, MASSIVE volume = pure secretory. Treatment = ORS ± doxycycline.

2. Enterotoxigenic E. coli (ETEC) - Most Common Cause of Traveller's Diarrhoea

• Who gets it: Travellers to developing countries (10-45% of traveller's diarrhoea)
• Mechanism:
  • Produces Heat-Labile toxin (LT): Same mechanism as cholera toxin → ↑cAMP → secretory diarrhoea
  • Produces Heat-Stable toxin (ST): Activates guanylate cyclase → ↑cGMP → secretory diarrhoea
  • First adheres via Colonization Factor Antigen (CFA) then releases toxin
• Clinical features:
  • Watery diarrhoea with nausea and cramps
  • No fever, no blood
  • Self-limiting in 3-5 days

3. Shigella (Prototype Inflammatory Diarrhoea / Dysentery)

• Spread: Very low infectious dose (10-100 organisms); person-to-person; faeco-oral; contaminated food/water
• Mechanism:

  Shigella ingested → reaches colon
          ↓
  Invades colonic epithelial cells (especially M cells over Peyer's patches)
          ↓
  Escapes vacuole into cytoplasm → intracellular multiplication
          ↓
  Cell-to-cell spread → ulceration of colonic mucosa
          ↓
  S. dysenteriae type 1 also produces Shiga toxin (cytotoxin) → inhibits 
  protein synthesis → cell death + haemorrhagic colitis
  

• Clinical features:
  • Initially watery diarrhoea → rapidly becomes bloody (dysentery)
  • Severe abdominal cramps, tenesmus (constant urge to defaecate)
  • High fever, toxaemia
  • WBCs + RBCs in stool
  • Complications: HUS (Haemolytic Uraemic Syndrome) with Shiga toxin strains, reactive arthritis (Reiter's syndrome)

4. Salmonella

• Source: Poultry, eggs, reptiles
• Incubation: 6-48 hours
• Mechanism: Invades small bowel and colonic mucosa → inflammatory diarrhoea; also stimulates prostaglandins → secretory component
• Clinical: Watery or bloody diarrhoea + fever + vomiting; self-limiting in 3-7 days; bacteraemia in immunocompromised

• Mechanism: Penetrates intestinal epithelium → enters lymphatics/bloodstream (bacteraemia) → RES (liver, spleen, bone marrow) → sepsis
• Clinical: Stepwise rising fever, relative bradycardia, rose spots (salmon-coloured spots on trunk), hepatosplenomegaly, constipation in early stages then diarrhoea ("pea-soup" stools), splenomegaly
• Complications: Intestinal perforation, intestinal haemorrhage (most feared)
• Stool WBCs: Mononuclear cells (lymphocytes, not PMNs) - unique to enteric fever

5. Campylobacter jejuni

• Most common bacterial cause of diarrhoea in developed countries
• Source: Undercooked poultry; unpasteurised milk; puppies/kittens
• Mechanism: Invades small and large intestinal mucosa → inflammatory diarrhoea; also produces enterotoxin (minor secretory component)
• Clinical features:
  • Prodrome of fever, headache, myalgia (flu-like)
  • Bloody diarrhoea + severe abdominal cramps
  • Often mistaken for appendicitis (right iliac fossa pain)
  • Self-limiting in 3-7 days
  • Complications: Guillain-Barré syndrome (molecular mimicry between bacterial lipopolysaccharide and gangliosides in myelin), reactive arthritis

6. Enterohemorrhagic E. coli (EHEC) - E. coli O157:H7

• Source: Undercooked beef burgers; unpasteurised milk; contaminated produce
• Mechanism:
  • Attaches to colonic epithelium (attaching-effacing lesion) and produces Shiga-like toxin (verotoxin)
  • Toxin inhibits protein synthesis → colonic cell death → haemorrhagic colitis
• Clinical features:
  • Watery diarrhoea initially → frank haemorrhagic colitis (bloody diarrhoea)
  • NO or low-grade fever (distinguishes from Shigella)
  • Severe abdominal cramps
  • Complication: HUS = Microangiopathic haemolytic anaemia + thrombocytopenia + acute kidney failure (especially in children) - Do NOT give antibiotics (increases Shiga toxin release → worsens HUS)

7. Clostridioides (Clostridium) difficile (C. diff)

• Context: Hospital-acquired (nosocomial); follows antibiotic use → disrupts gut microbiome → C. diff spores germinate and overgrow
• Risk factors: Recent antibiotics (especially clindamycin, fluoroquinolones, broad-spectrum), age >65, hospitalisation, PPI use
• Mechanism:

  Spores ingested → survive gastric acid → germinate in colon
          ↓
  Antibiotic-disrupted microbiome allows colonisation
          ↓
  Produces Toxin A (enterotoxin) + Toxin B (cytotoxin)
          ↓
  Toxins glucosylate Rho-GTPases → disrupt actin cytoskeleton → 
  loss of tight junctions → fluid leakage + inflammation
          ↓
  Pseudomembrane formation (1-2mm whitish-yellow plaques on colon)
  

• Clinical features:
  • Watery diarrhoea (up to 10-15 stools/day) + abdominal cramps + fever
  • Foul-smelling stools
  • Leukocytosis (WBC >15,000) is a key feature
  • Colonoscopy/CT: pseudomembranes (pathognomonic)
  • Fulminant CDI: Toxic megacolon, perforation, septic shock - surgical emergency

Exam tip: C. diff = suspect in ANY patient with diarrhoea after antibiotics. Treatment = stop causative antibiotic + give oral vancomycin or fidaxomicin (not metronidazole for severe disease). Recurrence = faecal microbiota transplant (FMT).

8. Staphylococcus aureus (Food Poisoning)

• Mechanism: Pre-formed toxin (not the bacteria) - ingested in contaminated food (cream, custard, meat)
• Incubation: 1-6 hours (shortest of all food poisoning = toxin already present)
• Clinical: Sudden onset vomiting + watery diarrhoea. Self-limiting in 24 hours. NO fever typically.
• Source: Food handlers with skin infections (S. aureus from hands contaminates food)

9. Bacillus cereus (Two Syndromes)

• Emetic syndrome (fried rice, incubation 1-6h): Pre-formed toxin → nausea/vomiting dominant
• Diarrhoeal syndrome (meat, vegetables, incubation 8-16h): Enterotoxin produced in gut → watery diarrhoea

10. Clostridium perfringens

• Source: Reheated meat, poultry, gravy
• Incubation: 8-16 hours
• Produces enterotoxin in gut → watery diarrhoea; NO vomiting typically
• Self-limiting in 24 hours

C. PARASITIC CAUSES

1. Giardia lamblia (Most Common Parasitic Cause Worldwide)

• Spread: Faeco-oral; contaminated freshwater (hikers/campers); day-care centres; resistant to chlorination
• Mechanism:
  • Cysts ingested → excyst in duodenum → trophozoites attach to small bowel brush border via ventral adhesive disc
  • Mechanical disruption of absorptive surface + brush border enzyme damage → malabsorption → osmotic + some secretory diarrhoea
  • Does NOT invade mucosa (no blood, no fever)
• Clinical features:
  • Gradual onset (1-3 weeks incubation)
  • Watery, foul-smelling, greasy/fatty diarrhoea (steatorrhoea)
  • Bloating, flatulence, belching (sulphurous burps)
  • Abdominal cramps, nausea
  • NO blood, NO fever
  • May become chronic (weeks to months)
  • Weight loss and malabsorption in prolonged cases

Exam tip: Giardia = watery + fatty + bloating + NO blood. Think: hiker who drank stream water, day-care worker, traveller.

2. Entamoeba histolytica (Amoebiasis)

• Spread: Faeco-oral; contaminated food/water; tropical countries
• Mechanism:
  • Cysts ingested → trophozoites invade colonic mucosa via proteases and galactose/N-acetylgalactosamine lectins
  • Create flask-shaped ulcers (undermined edges) in colon → inflammatory dysentery
  • Can penetrate portal vessels → liver → amoebic liver abscess (right lobe)
• Clinical features:
  • Gradual onset bloody mucoid diarrhoea (amoebic dysentery)
  • Less severe systemic toxaemia than Shigella
  • Right upper quadrant pain if liver abscess develops
  • "Anchovy sauce" pus in liver abscess

3. Cryptosporidium

• Resistant to chlorine; important in immunocompromised (AIDS with CD4 <100 → profuse, chronic, life-threatening diarrhoea)
• In immunocompetent: self-limiting watery diarrhoea 1-3 weeks
• Spread: contaminated water, calves

PART 2: CHRONIC DIARRHOEA (>4 WEEKS)

Mainly Non-Infectious - Classify by Mechanism

A. INFLAMMATORY CAUSES

1. Inflammatory Bowel Disease (IBD) - Crohn's & Ulcerative Colitis

2. Microscopic Colitis (Collagenous / Lymphocytic)

• Who: Middle-aged to elderly women; often on NSAIDs or SSRIs
• Normal colonoscopy appearance (hence "microscopic" - diagnosed on biopsy)
• Mechanism: Subepithelial collagen deposition (collagenous) or lymphocytic infiltration → impaired water absorption → watery diarrhoea
• Clinical: Chronic, watery, non-bloody diarrhoea (5-10 stools/day), often nocturnal; no weight loss initially

B. MALABSORPTIVE CAUSES

1. Coeliac Disease (Gluten-Sensitive Enteropathy)

• Mechanism:

  Dietary gluten (gliadin fraction) in genetically susceptible individuals
          ↓
  Gliadin deamidated by tissue transglutaminase (tTG) → binds HLA-DQ2/DQ8
          ↓
  CD4+ T-cell activation → mucosal inflammation
          ↓
  Villous atrophy + crypt hyperplasia → reduced absorptive surface
          ↓
  Malabsorption (fat, carbohydrate, protein, fat-soluble vitamins)
  

• Clinical features:
  • Steatorrhoea (fatty, pale, floating, offensive stools), chronic diarrhoea
  • Weight loss, abdominal bloating, fatigue
  • Iron-deficiency anaemia (duodenal malabsorption of iron and folate)
  • Dermatitis herpetiformis (itchy blistering rash on elbows/knees/buttocks)
  • Osteoporosis (calcium malabsorption)
  • Associated with HLA-DQ2 (90%) and HLA-DQ8
  • Diagnosis: Anti-tTG IgA antibodies + duodenal biopsy (Marsh criteria)

2. Chronic Pancreatitis / Exocrine Pancreatic Insufficiency

• Causes: Chronic alcohol use (most common), cystic fibrosis, autoimmune, hereditary
• Mechanism: Progressive destruction of pancreatic acini → loss of lipase, protease, amylase → fat malabsorption (steatorrhoea) when >90% of exocrine function lost
• Clinical:
  • Severe steatorrhoea (oily, greasy stools)
  • Weight loss, malnutrition
  • Diabetes mellitus (if islets also damaged)
  • Chronic abdominal pain
  • Diagnosis: Faecal elastase-1 (low), CT pancreas

3. Small Intestinal Bacterial Overgrowth (SIBO)

• Definition: Abnormal colonisation of the small bowel with colonic-type bacteria (>10³ CFU/mL in jejunum)
• Causes: Impaired motility (diabetes, scleroderma, post-surgical), anatomical abnormalities (blind loops, strictures), achlorhydria
• Mechanism: Bacteria deconjugate bile salts → impaired fat micelle formation → steatorrhoea; bacteria consume B12 → deficiency; produce gas → bloating
• Clinical: Diarrhoea, steatorrhoea, bloating, B12 deficiency (megaloblastic anaemia)

C. SECRETORY CAUSES (Chronic Non-Infectious)

Key feature: Large volume watery diarrhoea that does NOT stop with fasting

1. VIPoma (Verner-Morrison Syndrome / Pancreatic Cholera)

• Vasoactive Intestinal Peptide-secreting tumour (usually pancreatic)
• VIP → activates adenylate cyclase → ↑cAMP → massive Cl⁻ and water secretion (exactly like cholera)
• Clinical triad: WDHA = Watery Diarrhoea, Hypokalaemia, Achlorhydria
• Up to 5-10L/day watery diarrhoea

2. Carcinoid Syndrome

• Serotonin-secreting tumour (usually small bowel or appendix)
• Clinical: Episodic watery diarrhoea + flushing + wheezing + right-sided valvular heart disease
• Diarrhoea from serotonin-mediated increased gut motility + secretion

3. Zollinger-Ellison Syndrome (Gastrinoma)

• Gastrin-secreting tumour → massive acid secretion
• Acid floods the duodenum → inactivates pancreatic enzymes, damages mucosa → diarrhoea + steatorrhoea + multiple peptic ulcers
• Suspect: Multiple/refractory peptic ulcers + diarrhoea

4. Bile Acid Diarrhoea (Bile Salt Malabsorption)

• Normal: Bile acids absorbed in terminal ileum (enterohepatic circulation)
• When terminal ileum is diseased (Crohn's) or resected → bile acids spill into colon → irritate colonocytes → secretory diarrhoea
• Also after cholecystectomy (post-cholecystectomy diarrhoea)

D. OSMOTIC CAUSES

Key feature: Diarrhoea STOPS with fasting; osmotic gap in stool elevated

1. Lactose Intolerance

• Mechanism: Deficiency of brush-border lactase enzyme → undigested lactose in colon → fermented by bacteria → gas (H₂, CO₂) + short-chain fatty acids → osmotic pull → watery diarrhoea
• Clinical: Diarrhoea + bloating + flatulence + abdominal cramps after dairy intake
• Diagnosis: Hydrogen breath test; improvement on lactose-free diet

2. Laxative Abuse / Osmotic Laxatives

• Magnesium salts, lactulose, polyethylene glycol - attract water by osmosis
• Can cause diarrhoea (intended or via abuse)

3. Sugar Alcohols / Artificial Sweeteners

• Sorbitol, mannitol, xylitol (in chewing gum, diet foods) - not absorbed → osmotic diarrhoea

E. FUNCTIONAL CAUSES

Irritable Bowel Syndrome (IBS)

• Most common GI diagnosis worldwide (10-15% of population)
• Definition: Chronic abdominal pain + altered bowel habit (diarrhoea, constipation, or mixed) without structural or biochemical abnormality
• Mechanism: Multi-factorial:
  • Gut hypersensitivity (visceral hyperalgesia)
  • Altered gut motility
  • Abnormal brain-gut axis signalling
  • Microbiome dysbiosis
  • Post-infectious IBS (~10% of cases follow acute gastroenteritis - especially Campylobacter)
• Clinical features:
  • Rome IV Criteria: Recurrent abdominal pain ≥1 day/week in last 3 months + ≥2 of: related to defaecation; change in frequency; change in form (appearance) of stool
  • Bloating, excessive flatulence
  • Urgency, tenesmus, sensation of incomplete evacuation
  • Symptoms worse with stress, menstruation
  • No alarm features (no blood, no weight loss, no nocturnal symptoms, no fever, no anaemia)

Alarm features that EXCLUDE IBS and require urgent investigation: rectal bleeding, weight loss, nocturnal diarrhoea, age >50 at first presentation, family history of CRC or IBD, anaemia, raised inflammatory markers (CRP, ESR, faecal calprotectin)

F. DRUG-INDUCED DIARRHOEA

QUICK MASTER TABLE: ACUTE INFECTIOUS DIARRHOEA

MEMORY AIDS

Acute Diarrhoea Causes - "Can't Stop Vomiting Every Second" (CSVES)

• C - Campylobacter, Cryptosporidium, C. diff
• S - Shigella, Salmonella, S. aureus
• V - Vibrio cholerae, Viruses (Norovirus, Rotavirus)
• E - E. coli (ETEC, EHEC, EPEC)
• S - Stools from parasites (Giardia, Entamoeba)

Chronic Diarrhoea Causes - "SIIMFD"

• S - Secretory (VIPoma, carcinoid, bile acid)
• I - Inflammatory (IBD, microscopic colitis)
• I - IBS (functional)
• M - Malabsorption (coeliac, pancreatic insufficiency, SIBO)
• F - Food-related (lactose intolerance, osmotic)
• D - Drugs (antibiotics, metformin, laxatives)

EXAM FRAMEWORK FOR ANY DIARRHOEA QUESTION

1. Define - acute (<2 weeks) vs. chronic (>4 weeks)
2. Classify by mechanism - secretory / osmotic / inflammatory / motility
3. List causes - infectious vs. non-infectious
4. For each cause state - organism/disease, mechanism, clinical features, key distinguishing clue
5. Differentiate watery (small bowel) from bloody (large bowel) diarrhoea