What causes diarrhea?

What Causes Loose Stool (Diarrhea)

Loose stools result from disturbances in intestinal water and electrolyte balance, with causes broadly categorized into colonic/inflammatory, small bowel malabsorptive, pancreatic, endocrine, and drug-induced etiologies. 1

Primary Pathophysiologic Mechanisms

Diarrhea occurs when the intestine fails to complete absorption of electrolytes and water from luminal contents. 2 The two main mechanisms are:

• Secretory diarrhea: Results from impaired electrolyte absorption, bacterial toxins, bile acids, circulating hormones, or drugs—characterized by liquid loose stools that persist with fasting 1, 3
• Osmotic diarrhea: Caused by nonabsorbable substances in the gut lumen (carbohydrate malabsorption, laxatives, sorbitol)—typically resolves with fasting 2, 4
• Malabsorptive diarrhea: Presents with bulky, malodorous, pale stools (steatorrhea) from fat malabsorption 1
• Inflammatory diarrhea: Characterized by liquid stools with blood or mucus discharge 1

Major Categories of Causes

Colonic/Inflammatory Causes

• Inflammatory bowel disease (ulcerative colitis, Crohn's disease) 1, 5
• Microscopic colitis 1, 5
• Colonic neoplasia 1, 5
• Infectious colitis (bacterial, viral, parasitic—especially Giardia and C. difficile) 1, 6

Small Bowel Causes

• Celiac disease: Leading small bowel cause of malabsorption 1, 5
• Bile acid malabsorption: Particularly after terminal ileum resection or cholecystectomy (up to 10% post-cholecystectomy patients) 1, 7, 5
• Small bowel bacterial overgrowth: Common after gastric surgery or with autonomic dysfunction 1
• Disaccharidase deficiency (lactose intolerance) 1, 5
• Other enteropathies: Whipple's disease, tropical sprue, amyloid, lymphoma 1

Pancreatic Causes

• Chronic pancreatitis 1, 5
• Pancreatic carcinoma 1, 5
• Cystic fibrosis 1, 5

Endocrine Causes

• Hyperthyroidism: Accelerates intestinal transit time through direct endocrine effects 1, 5, 8
• Diabetes mellitus: Multiple mechanisms including autonomic neuropathy, bacterial overgrowth, bile acid malabsorption, and metformin effects 1, 5, 8
• Addison's disease and hypoparathyroidism: Cause diarrhea through endocrine effects and autonomic dysfunction 1, 8
• Hormone-secreting tumors: VIPoma, gastrinoma, carcinoid 1, 5

Drug-Induced Causes

Up to 4% of chronic diarrhea cases are medication-related. 1, 5 Common culprits include:

• Antibiotics: Account for 25% of drug-induced diarrhea 9
• Magnesium-containing antacids and laxatives 1, 9
• NSAIDs, prostaglandins, colchicine 1, 9
• Antiarrhythmic drugs and antineoplastic agents 1, 9
• Sugar-free products containing sorbitol or fructose 5, 9
• Metformin in diabetic patients 5, 8

Surgical/Anatomic Causes

• Extensive ileal/right colon resections: Lead to fat and carbohydrate malabsorption, decreased transit time, bile acid malabsorption 1
• Post-gastric/bariatric surgery: Can cause dumping syndrome or bacterial overgrowth 1, 7
• Post-cholecystectomy: Increased gut transit and bile acid malabsorption 1, 7

Other Causes

• Alcohol abuse: Causes rapid gut transit, decreased disaccharidase activity, pancreatic dysfunction 1, 5
• Autonomic neuropathy: Particularly in diabetes and systemic sclerosis 1, 5
• Factitious diarrhea: Laxative abuse 1, 5

Critical Clinical Distinctions

Red Flags Suggesting Organic Disease

Nocturnal or continuous diarrhea, duration <3 months, and significant weight loss strongly suggest organic rather than functional causes. 1, 8

• Blood or mucus in stool: Indicates inflammatory/colonic pathology 1
• Nocturnal diarrhea: Essentially rules out functional disorders 8
• Significant weight loss: Suggests malabsorption or malignancy 1

Functional vs. Organic

The absence of red flags with positive Manning or Rome criteria suggests functional bowel disturbance (irritable bowel syndrome), but specificity is only 52-74%. 1, 4

Common Pitfalls

• Don't attribute diabetic diarrhea solely to autonomic neuropathy—consider bacterial overgrowth, bile acid malabsorption, and metformin effects 7, 8
• Don't overlook medication review—including over-the-counter supplements and sugar-free products 7, 5
• Don't miss bile acid malabsorption—particularly in diabetic patients and those with prior ileal resection or cholecystectomy 7, 5
• Acute infectious diarrhea is usually viral and self-limiting, requiring diagnostic workup only with severe dehydration, bloody stools, persistent fever, or immunocompromise 6