E. histolytica, or Strongyloides. Stool antigen tests also are available for Giardia. In individuals with recent antibiotic use, stools should be sent for C. difficile toxin determination.
Inflammatory etiologies are characterized by red and white blood cells in the stool. Noninflammatory diarrhea may be further evaluated by stool electrolytes, specifically sodium and potassium. Direct measurement of stool osmolality may be altered by bacterial degradation of carbohydrate so it is not routinely obtained; instead, normal plasma osmolality is assumed (290 mOsm/kg H2O). A difference of >125 mOsm/kg between stool osmolality and twice the sum of stool sodium plus potassium concentrations suggests an osmotic cause, whereas a gap of <50 mOsm/kg is consistent with secretory diarrhea. Stool Osm gaps between 50–125 mOsm/kg are difficult to categorize with certainty. Osmotic diarrhea suggests ingestion of nonabsorbed solutes such as magnesium, phosphate or sulfate. Stool or urine samples can be analyzed for sulfate, magnesium, phosphate, bisacodyl, castor oil, or anthracene derivatives.
Malabsorption is diagnosed by fecal fat detection, generally screened using qualitative tests and verified with quantified fat on a 72-h collection while the patient is ingesting >100g fat/day. Fecal fat exceeding 7 g/24 h is abnormal; however, severe diarrhea (>800 g stool/24 h) can wash fat from the bowel lumen and result in fat excretion as high as 14 g/24 h.
Lower endoscopy is indicated if there are signs of mucosal injury and even if the endoscopic appearance of the colon is normal, random biopsies should be performed to evaluate for collagenous and lymphocytic colitis. If a small intestinal etiology of malabsorption is suspected, upper endoscopy may be performed to evaluate for inflammation or malabsorption disorders such as celiac disease.
Breath testing also is used to detect bacterial overgrowth as well as lactase deficiency. Arteriography or mesenteric resonance imaging may be necessary to confirm the diagnosis of mesenteric ischemia. In selected instances, 14C-triolein breath tests can provide evidence of fat malabsorption, whereas D-xylose testing can screen for small intestinal mucosal disease. Schilling tests help distinguish small bowel disease, bacterial overgrowth, and pancreatic disease as causes of malabsorption. Pancreatic etiologies, including chronic pancreatitis and pancreatic neoplasms, can be evaluated by abdominal radiography, endoscopic retrograde pancreatography, endoscopic ultrasound, or exocrine pancreatic function tests in selected referral centers.
Secretory diarrhea should be evaluated by serum gastrin, vasoactive intestinal peptide (VIP), serotonin, calcitonin, histamine, and prostaglandins and urine 5-hydroxyindoleacetic acid to detect endocrine neoplasia. Further evaluation with abdominal computed tomography (CT), endoscopic ultrasound, and somatostatin receptor scintigraphy is performed to localize the tumor(s) and direct therapy. Octapeptide (111In-OTPA) cholecystokinin analog scanning has been used for medullary thyroid carcinoma. Rare patients will benefit from 111In-labeled leukocyte tests for inflammatory disease or 51Cr-albumin or α1–antitrypsin tests that demonstrate protein-losing enteropathy.
Differential diagnosis
High-output diarrhea of more than 200 g daily arises from two pathophysiological mechanisms: increased anion secretion and decreased absorption of electrolytes. Increased anion secretion may result from enterotoxins, endogenous hormones or neuropeptides, inflammatory mediators, bile salts, laxatives, and medications. Decreased water and electrolyte absorption develop from enterotoxins, decreased mucosal absorptive surface area, acceleration of transit with inadequate time for absorption, impaired mucosal barrier function, and ingestion of poorly absorbed osmotically active solutes. Conditions that produce high-output diarrhea are divided into osmotic, secretory, and mucosal injury categories (Table 10.1) although some diseases produce diarrhea by more than one mechanism. Patients with normal stool output of less than 200 g daily may also complain of diarrhea. Normal-output diarrhea most often results from anorectal disease, hormonally induced hyperdefecation, or functional bowel disorders in which gut sensorimotor defects alter perception and transit of lumenal contents.
Osmotic diarrhea
Under normal conditions, most ingested food is absorbed before it reaches the colon. In many diarrheal disorders, undigested nutrients are not absorbed and act as osmotic agents to draw free water into the intestinal lumen. The most common cause of osmotic diarrhea is lactase deficiency. Other causes of osmotic diarrhea include nonabsorbable laxatives, magnesium-containing antacids, medications, and candies or soft drinks that contain the poorly absorbed sugars fructose and sorbitol. Congenital defects of carbohydrate absorption include sucrase-isomaltase deficiency, trehalase deficiency, and glucose-galactose malabsorption.
Some small intestinal diseases produce osmotic diarrhea from maldigestion or malabsorption. Celiac disease is caused by hypersensitivity to dietary gluten. Patients with this disease may be asymptomatic, exhibit iron deficiency anemia, or develop diarrhea and malabsorptive symptoms. Tropical sprue is an infectious disease of unknown origin that is observed on the Indian subcontinent, Asia, the West Indies, northern South America, central and southern Africa, and Central America. It produces diarrhea and malabsorption due to villous atrophy in persons who have resided in these regions for as little as 1–3 months. Crohn’s disease involving the small intestine may lead to malabsorption and diarrhea. Whipple disease, caused by infection with Tropheryma whippelii, is diagnosed by demonstration of characteristic periodic acid–Schiff (PAS)-positive macrophages on examination of small intestinal mucosal biopsies. Congenital or acquired (secondary to trauma, lymphoma, or carcinoma) intestinal lymphangiectasia causes protein-losing enteropathy with steatorrhea as a result of obstructed lymphatic channels. Bacterial overgrowth produces steatorrhea from bile salt deconjugation, brush border injury, and mucosal inflammation. Intestinal infection with Giardia, Cryptosporidium, Isospora, or Mycobacterium avium complex produces brush border and intramucosal damage. Systemic mastocytosis and eosinophilic gastroenteritis grossly distort the intestinal mucosa and promote nutrient malabsorption. Short bowel syndrome and fistulae reduce the villous surface area available for nutrient uptake. Other conditions (e.g. postvagotomy diarrhea and thyrotoxicosis) accelerate intestinal transit, leaving inadequate time for nutrient assimilation. Adrenal insufficiency causes generalized disturbances in mucosal absorption.
Table 10.1 Causes of diarrhea
| Osmotic diarrhea | |
| Nonabsorbed solutes | Magnesium, sulfate and phosphate laxatives |
| Sorbitol, fructose, lactulose | |
| Disaccharidase deficiency | Lactase deficiency |
| Isomaltase-sucrase deficiency | |
| Trehalase deficiency | |
| Small intestinal mucosal disease | Celiac disease |
| Tropical sprue | |
| Viral gastroenteritis | |
| Whipple disease | |
| Amyloidosis | |
| Intestinal ischemia | |
| Lymphoma | |
| Giardiasis | |
| Intestinal radiation | |
| Mastocytosis | |
| Eosinophilic gastroenteritis | |
| Abetalipoproteinemia | |
| Lymphangiectasia | |
| Pancreatic insufficiency | Chronic pancreatitis |
| Pancreatic carcinoma | |
| Cystic fibrosis | |
| Reduced intestinal surface area | Small intestinal resection |
| Enteric fistulae | |
| Jejunoileal bypass | |
| Bile salt malabsorption | Bacterial overgrowth |
| Ileal resection | |
| Crohn’s disease | |
| Other medications | Olestra and orlistat |
| Secretory diarrhea | |
| Laxatives | Bisacodyl |
| Ricinoleic acid | |
| Dioctyl sodium sulfosuccinate | |
| Senna and aloe | |
| Oxyphenisatin | |
| Medications | Diuretics |
