Case: Diarrhoea and Malabsorption
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Lesson 8 of 16
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Case: Diarrhoea and Malabsorption
Types of Diarrhoea
- Osmotic diarrhoea: non-absorbed solute retains water in lumen (e.g., lactase deficiency, lactulose, osmotic laxatives). Stops with fasting.
- Secretory diarrhoea: active secretion of Cl⁻ (and water) into lumen exceeds absorptive capacity (e.g., cholera, VIPoma, carcinoid). Continues with fasting; large volume, watery.
- Inflammatory diarrhoea: mucosal damage → loss of absorptive surface + exudation of mucus, blood, protein (e.g., Crohn's, UC, infectious colitis). May contain blood/mucus.
- Dysmotility diarrhoea: rapid transit reduces contact time for absorption (e.g., post-vagotomy, IBS-D, hyperthyroidism).
Cholera — Secretory Diarrhoea
Vibrio cholerae produces cholera toxin (CT-B binds GM1 ganglioside on enterocyte surface; CT-A enters cell → permanently activates adenylyl cyclase → ↑↑ cAMP → activates PKA → phosphorylates CFTR → massive Cl⁻ secretion into lumen → Na⁺ and water follow → watery diarrhoea up to 20 L/day → isosmotic fluid loss.
Systemic consequences: isosmotic loss → haematocrit increases (cells concentrate) but plasma [Na⁺] and [Cl⁻] unchanged. K⁺ secreted in stool → hypokalaemia. HCO₃⁻ secreted → metabolic acidosis → respiratory compensation (Kussmaul breathing). Hypovolaemia → tachycardia, vasoconstriction (pale/cold skin), oliguria (pre-renal), raised urea, RAAS activation, ADH release, elevated cortisol and adrenaline. Severe: reduced LOC, shock.
Oral rehydration therapy (ORT): Na⁺-glucose co-transporter (SGLT1) is not inactivated by cholera toxin (cAMP acts on CFTR, not SGLT1) → oral glucose + Na⁺ solution restores absorptive transport → drives Na⁺ and water absorption. Simple, cheap, life-saving.
Malabsorption
Causes: small bowel mucosal disease (coeliac disease: gluten-triggered villous atrophy), pancreatic exocrine insufficiency (chronic pancreatitis, CF), bile salt deficiency (cholestasis, ileal resection), bacterial overgrowth (deconjugation of bile salts), surgical resection (short bowel syndrome). Features: steatorrhoea (fatty stools, fat-soluble vitamin deficiency), weight loss, diarrhoea, nutritional deficiencies.