Physiology

Formally defined as fecal output >200 g/d on low-fiber (western) diet; also frequently used to connote loose or watery stools. Considered acute if <2 weeks duration, persistent if 2-4 weeks, and chronic if >4 weeks. Mediated by one or more of the following mechanisms:

Osmotic Diarrhea

Nonabsorbed solutes increase intraluminal oncotic pressure, causing outpouring of water; usually ceases with fasting; stool osmolal gap >40 (see below). Causes include disaccharidase (e.g., lactase) deficiencies, pancreatic insufficiency, bacterial overgrowth, lactulose or sorbitol ingestion, polyvalent laxative abuse, celiac or tropical sprue, and short bowel syndrome. Lactase deficiency can be either primary (more prevalent in blacks and Asians, usually presenting in early adulthood) or secondary (from viral, bacterial, or protozoal gastroenteritis, celiac or tropical sprue, or kwashiorkor).

Secretory Diarrhea

Active ion secretion causes obligatory water loss; diarrhea is usually watery, often profuse, unaffected by fasting; stool Na⁺ and K⁺ are elevated with osmolal gap <40. Causes include viral infections (e.g., rotavirus, Norwalk virus), bacterial infections (e.g., cholera, enterotoxigenic Escherichia coli, Staphylococcus aureus), protozoa (e.g., Giardia, Isospora, Cryptosporidium), AIDS-associated disorders (including mycobacterial and HIV-induced), medications (e.g., theophylline, colchicine, prostaglandins, diuretics), Zollinger-Ellison syndrome (excess gastrin production), vasoactive intestinal peptide (VIP)-producing tumors, carcinoid tumors (histamine and serotonin), medullary thyroid carcinoma (prostaglandins and calcitonin), systemic mastocytosis, basophilic leukemia, distal colonic villous adenomas (direct secretion of potassium-rich fluid), collagenous and microscopic colitis, and choleraic diarrhea (from ileal malabsorption of bile salts).

Exudative Diarrhea

Inflammation, necrosis, and sloughing of colonic mucosa; may include component of secretory diarrhea due to prostaglandin release by inflammatory cells; stools usually contain polymorphonuclear leukocytes as well as occult or gross blood. Causes include bacterial infections (e.g., Campylobacter, Salmonella, Shigella, Yersinia, invasive or enterotoxigenic E. coli, Vibrio parahaemolyticus, Clostridium difficile colitis [frequently antibiotic-induced]), colonic parasites (e.g., Entamoeba histolytica), Crohn's disease, ulcerative proctocolitis, idiopathic inflammatory bowel disease, radiation enterocolitis, cancer chemotherapeutic agents, and intestinal ischemia.

Altered Intestinal Motility

Alteration of coordinated control of intestinal propulsion; diarrhea often intermittent or alternating with constipation. Causes include diabetes mellitus, adrenal insufficiency, hyperthyroidism, collagen-vascular diseases, parasitic infestations, gastrin and VIP hypersecretory states, amyloidosis, laxatives (esp. magnesium-containing agents), antibiotics (esp. erythromycin), cholinergic agents, primary neurologic dysfunction (e.g., Parkinson's disease, traumatic neuropathy), fecal impaction, diverticular disease, and irritable bowel syndrome. Blood in intestinal lumen is cathartic, and major upper GI bleeding leads to diarrhea from increased motility.

Decreased Absorptive Surface

Usually arises from surgical manipulation (e.g., extensive bowel resection or rearrangement) that leaves inadequate absorptive surface for fat and carbohydrate digestion and fluid and electrolyte absorption; occurs spontaneously from enteroenteric fistulas (esp. gastrocolic).

Evaluation History

Diarrhea must be distinguished from fecal incontinence, change in stool caliber, rectal bleeding, and small, frequent, but otherwise normal stools. Careful medication history is essential. Alternating diarrhea and constipation suggests fixed colonic obstruction (e.g., from carcinoma) or irritable bowel syndrome. A sudden, acute course, often with nausea, vomiting, and fever, is typical of viral and bacterial infections, diverticulitis, ischemia, radiation enterocolitis, or drug-induced diarrhea and may be the initial presentation of inflammatory bowel disease. More than 90% of acute diarrheal illnesses are infectious in etiology. A longer (>4 weeks), more insidious course suggests malabsorption, inflammatory bowel disease, metabolic or endocrine disturbance, pancreatic insufficiency, laxative abuse, ischemia, neoplasm (hypersecretory state or partial obstruction), or irritable bowel syndrome. Parasitic and certain forms of bacterial enteritis can also produce chronic symptoms. Particularly foul-smelling or oily stool suggests fat malabsorption. Fecal impaction may cause apparent diarrhea because only liquids pass partial obstruction. Several infectious causes of diarrhea are associated with an immunocompromised state. A pathophysiologic mechanism-based list of causes is shown in Table 42-1 Major Causes of Chronic Diarrhea According to Predominant Pathophysiologic Mechanism.

Physical Examination

Signs of dehydration are often prominent in severe, acute diarrhea. Fever and abdominal tenderness suggest infection or inflammatory disease but are often absent in viral enteritis. Evidence of malnutrition suggests chronic course. Certain signs are frequently associated with specific deficiency states secondary to malabsorption (e.g., cheilosis with riboflavin or iron deficiency, glossitis with B₁₂, folate deficiency). Questions to address in pts with chronic diarrhea are shown in Table 42-2 Physical Examination in Pts with Chronic Diarrhea.

Stool Examination

Culture for bacterial pathogens, examination for leukocytes, measurement of C. difficile toxin, and examination for ova and parasites are important components of evaluation of pts with severe, protracted, or bloody diarrhea. Presence of blood (fecal occult blood test) or leukocytes (Wright's stain) suggests inflammation (e.g., ulcerative colitis, Crohn's disease, infection, or ischemia). Gram's stain of stool can be diagnostic of Staphylococcus, Campylobacter, or Candida infection. Steatorrhea (determined with Sudan III stain of stool sample or 72-h quantitative fecal fat analysis) suggests malabsorption or pancreatic insufficiency. Measurement of Na⁺ and K⁺ levels in fecal water helps to distinguish osmotic from other types of diarrhea; osmotic diarrhea is implied by stool osmolal gap > 40, where stool osmolal gap = osmol_serum [2 × (Na⁺ + K⁺ )_stool].

Laboratory Studies

Complete blood count may indicate anemia (acute or chronic blood loss or malabsorption of iron, folate, or B₁₂), leukocytosis (inflammation), eosinophilia (parasitic, neoplastic, and inflammatory bowel diseases). Serum levels of calcium, albumin, iron, cholesterol, folate, B₁₂, vitamin D, and carotene; serum iron-binding capacity; and prothrombin time can provide evidence of intestinal malabsorption or maldigestion.

Other Studies

D-Xylose absorption test is a convenient screen for small-bowel absorptive function. Small-bowel biopsy is especially useful for evaluating intestinal malabsorption. Specialized studies include Schilling test (B₁₂ malabsorption), lactose H₂ breath test (carbohydrate malabsorption), [¹⁴ C]xylose and lactulose H₂ breath tests (bacterial overgrowth), glycocholic breath test (ileal malabsorption), triolein breath test (fat malabsorption), and bentiromide and secretin tests (pancreatic insufficiency). Sigmoidoscopy or colonoscopy with biopsy is useful in the diagnosis of colitis (esp. pseudomembranous, ischemic, microscopic); it may not allow distinction between infectious and noninfectious (esp. idiopathic ulcerative) colitis. Barium contrast x-ray studies may suggest malabsorption (thickened bowel folds), inflammatory bowel disease (ileitis or colitis), tuberculosis (ileocecal inflammation), neoplasm, intestinal fistula, or motility disorders.