Diarrhoea due to disorders of gut mucosal structure and function

Mechanisms

1. Reduced absorptive surface area
   • Villous atrophy, mucosal ulceration, inflammation or surgical loss of bowel reduces the area available for absorption.
   • Poor absorption of water and sodium directly increases stool volume.
   • Malabsorption of carbohydrate, fat and protein leaves osmotically active material in the lumen.
2. Enterocyte dysfunction
   • Injured enterocytes cannot adequately transport glucose, amino acids, electrolytes, fatty acids and micronutrients.
   • Inflammation also impairs sodium and water absorption and may stimulate secretion of fluid into the gut.
3. Loss of brush-border enzymes
   • Deficiency of disaccharidases, especially lactase, causes carbohydrate malabsorption.
   • Undigested sugars increase luminal osmolality and are fermented by colonic bacteria, causing watery acidic diarrhoea, abdominal distension and flatulence.
4. Fat malabsorption
   • Failure of mucosal uptake or intracellular processing of fatty acids causes steatorrhoea: bulky, pale, greasy, foul-smelling stools.
   • Unabsorbed fatty acids promote colonic water secretion and bind calcium and magnesium, contributing to mineral loss.
5. Bile salt malabsorption
   • Diseased or resected terminal ileum fails to reabsorb bile salts.
   • Excess bile acids entering the colon stimulate colonic salt and water secretion, causing watery diarrhoea.
   • Reduced bile salt pool also impairs micelle formation, worsening fat malabsorption.
6. Defective lymphatic transport
   • Chylomicrons cannot be transported from enterocytes through intestinal lymphatics.
   • This causes fat malabsorption and usually mild to moderate steatorrhoea; it may coexist with protein-losing enteropathy.

Causes

Important examples

• Coeliac disease: immune-mediated response to gluten causes villous atrophy, crypt hyperplasia and mucosal inflammation. Loss of villous surface area and brush-border enzymes produces malabsorption, diarrhoea, weight loss and iron deficiency. Bailey and Love's Short Practice of Surgery, p. 1336.
• Crohn disease affecting small bowel or ileum: inflammation decreases absorptive surface. Terminal ileal involvement leads to vitamin B12 deficiency and bile acid malabsorption. Bile acids then enter the colon and stimulate secretory diarrhoea.
• Postinfectious enteropathy: infection can temporarily damage villi and reduce disaccharidase activity, especially lactase, producing secondary lactose intolerance and osmotic diarrhoea.
• Short-bowel syndrome: extensive resection reduces mucosal surface, so water, electrolyte and nutrient absorption become inadequate. If terminal ileum is removed, bile salt malabsorption further contributes to diarrhoea.
• Intestinal lymphangiectasia: impaired lymphatic transport prevents normal chylomicron transfer. Fat is lost in stool and protein may be lost into the intestinal lumen. Sleisenger and Fordtran's Gastrointestinal and Liver Disease, p. 2053.

Clinical stool pattern

• Osmotic diarrhoea: improves with fasting; due to unabsorbed carbohydrate or other solutes.
• Fatty diarrhoea/steatorrhoea: bulky, greasy stool with weight loss and deficiencies of vitamins A, D, E and K.
• Inflammatory diarrhoea: may contain blood or mucus and is associated with pain, fever and raised inflammatory markers.
• Bile acid diarrhoea: watery diarrhoea, often after terminal ileal disease or resection.

Conclusion