Chronic Diarrhea: Approach to the Patient diagnostic evaluation must be rationally directed by a careful history and physical examination history, physical examination, and routine blood studies characterize the mechanism of diarrhea identify diagnostically helpful associations assess the patient's fluid/electrolyte and nutritional status onset, duration, pattern, aggravating (especially diet) and relieving factors, and stool characteristics of the diarrhea note presence or absence of fecal incontinence, fever, weight loss, pain, certain exposures (travel, medications, contacts with diarrhea), and common extraintestinal manifestations (skin changes, arthralgias, oral aphthous ulcers) The laboratory tools available to evaluate the very common problem of chronic diarrhea are extensive, and many are costly and invasive. As such, the diagnostic evaluation must be rationally directed by a careful history and physical examination (Fig. 40-3A). When this strategy is unrevealing, simple triage tests are often warranted to direct the choice of more complex investigations (Fig. 40-3B). The history, physical examination (Table 40-4), and routine blood studies should attempt to characterize the mechanism of diarrhea, identify diagnostically helpful associations, and assess the patient's fluid/electrolyte and nutritional status. Patients should be questioned about the onset, duration, pattern, aggravating (especially diet) and relieving factors, and stool characteristics of their diarrhea. The presence or absence of fecal incontinence, fever, weight loss, pain, certain exposures (travel, medications, contacts with diarrhea), and common extraintestinal manifestations (skin changes, arthralgias, oral aphthous ulcers) should be noted.

Chronic Diarrhea: Approach to the Patient family history of IBD or sprue physical findings may offer clues such as a thyroid mass, wheezing, heart murmurs, edema, hepatomegaly, abdominal masses, lymphadenopathy, mucocutaneous abnormalities, perianal fistulae, or anal sphincter laxity peripheral blood leukocytosis, elevated sedimentation rate, or C-reactive protein suggests inflammation anemia reflects blood loss or nutritional deficiencies eosinophilia may occur with parasitoses, neoplasia, collagen-vascular disease, allergy, or eosinophilic gastroenteritis blood chemistries may demonstrate electrolyte, hepatic, or other metabolic disturbances measuring tissue transglutaminase antibodies may help detect celiac disease A family history of IBD or sprue may indicate those possibilities. Physical findings may offer clues such as a thyroid mass, wheezing, heart murmurs, edema, hepatomegaly, abdominal masses, lymphadenopathy, mucocutaneous abnormalities, perianal fistulae, or anal sphincter laxity. Peripheral blood leukocytosis, elevated sedimentation rate, or C-reactive protein suggests inflammation; anemia reflects blood loss or nutritional deficiencies; or eosinophilia may occur with parasitoses, neoplasia, collagen-vascular disease, allergy, or eosinophilic gastroenteritis. Blood chemistries may demonstrate electrolyte, hepatic, or other metabolic disturbances. Measuring tissue transglutaminase antibodies may help detect celiac disease.

INITIAL MANAGEMENT BASED ON ACCOMPANYING SYMPTOMS OR FEATURES Chronic Diarrhea Exclude iatrogenic problem: medication, surgery Blood p.r. Colonoscopy + biopsy Features e.g., stool, suggest malabsorption Small bowel: imaging, biopsy, aspirate Pain aggravated before bm, relieved with bm, sense incomplete evacuation Suspect IBS Limited screen for organic disease No blood, features of malabsorption Consider functional diarrhea Dietary exclusion, e.g., lactose, sorbitol

EVALUATION BASED ON FINDINGS FROM A LIMITED AGE APPROPRIATE SCREEN FOR ORGANIC DISEASE Chronic Diarrhea Limited screen for organic disease Low Hb, Alb Abnormal MCV, MCH Excess fat in stool Colonoscopy + biopsy Small bowel: imaging, biopsy, aspirate Stool fat >20g/day Pancreatic function Normal and stool fat <14g/day Full gut transit Titrate Rx to speed of transit Low K+ Stool volume, OSM, pH Laxative screen Hormonal screen Screening tests all normal Opioid Rx + follow-up Persistent chronic diarrhea

Chronic Diarrhea

Chronic Diarrhea Diarrhea lasting > 4 weeks

Major Causes of Diarrhea According to Predominant Physiologic Mechanism Chronic Diarrhea Secretory Inflammatory Dysmotility Osmotic Steatorrheal Factitial

Secretory Causes of Diarrhea Due to derangements in fluid and electrolyte transport across the enterocolonic mucosa. Characterized by a watery, large volume fecal outputs that are typically painless and persist with fasting. No fecal osmotic gap.

Secretory Causes of Diarrhea Hormones Medications Metastatic GI carcinoid tumors Primary bronchial carcinoids Gastrinoma Pancreatic cholera VIPoma Medullary carcinoma of the thyroid Systemic mastocytosis Colorectal villous adenoma Stimulant laxatives Chronic ethanol consumption Environmental toxins

Secretory Causes of Diarrhea Bowel Resection, Mucosal Disease, Enterocolic Fistula Congenital Defects in Ion Absorption Congenital chloridorrhea Addison’s Disease

Osmotic Causes of Diarrhea When ingested, poorly absorbable, osmotically active solutes draw enough fluid into the lumen to exceed the resorptive capacity of the colon fecal water output increases in proportion to such solute load Ceases with fasting or with discontinuation of the causative agent

Osmotic Causes of Diarrhea Osmotic laxatives Carbohydrate Malabsorption Magnesium containing antacids Health supplements laxatives Acquired or congenital defects in brush border disaccharidases and other enzymes Lactase deficiency

Steatorrheal Causes of Diarrhea Increased in fecal output is caused by the osmotic effects of fatty acids, especially after bacterial hydroxylation and to a lesser extent by a neutral fat Quantitatively: stool fat>7g/d Rapid transit diarrhea may result in fecal fat up to 14g/d Daily fecal fat averages 15-25g with SI diseases >32 g with pancreatic exocrine insufficiency

Steatorrheal Causes of Diarrhea Intraluminal Maldigestion Mucosal Maldigestion Chronic pancreatitis Cystic fibrosis Pancreatic duct obstruction somatostatinoma Celiac disease Tropical sprue Whipple’s disease Mycobacterium avium intracellulare infection in AIDS patient Abetalipoprotenemia Giardia infection Colchicine, cholestyramine, neomycin Chronic schemia

Steatorrheal Causes of Diarrhea Postmucosal Lymphatic Obstruction Congenital intestinal lymphangiectasia Acquired lymphatic obstruction secondary to trauma, tumor, or infection

Inflammatory Causes of Diarrhea Accompanied by pain, fever, bleeding and other manifestation of inflammation Mechanism of diarrhea may be due to exudation, fat malabsorption, disrupted fluid/electrolyte absorption, hypersecretion or hypermotility from release of inflammatory mediators Stool analysis: leukocytes or leukocyte derived protein (calprotectin)

Inflammatory Causes of Diarrhea with severe inflammation, exudative protein loss can lead to anasarca middle aged or older person with chronic inflammatory type diarrhea, especially with blood, should be carefully evaluated to exclude colorectal tumor

Inflammatory Causes of Diarrhea Idiopathic Inflammatory Bowel Disease Primary or Secondary Forms of Immunodefeciency Crohn’s disease Chronic ulcerative colitis Microscopic colitis hypogammaglobulinemia

Inflammatory Causes of Diarrhea Eosinophilic Gastroenteritis Other causes Hypersensitivity to certain food Radiation enterocolitis Chronic graft vs host disease Behcet’s syndrome Cronkite-Canada Syndrome

Dysmotility Causes of Diarrhea Rapid transit time may accompany many diarrheas as a secondary or contributing phenomenon, but primary dysmotility is an unusual etiology Stool features often suggest a secretory diarrhea, but mild steatorrhea of up to 14 g/d can be produced by maldigestion from rapid transit alone

Factitial Causes Accounts for up to 15% unexplained diarrheas Munchausen syndrome( deception or self injury) or eating disorders (self administer laxatives alone or in combination with other medication(diuretics) Women with histories of psychiatric illness and disproportionately from careers in health care Hypotension and hypokalemia

Dysmotility Causes of Diarrhea Hyperthyroidism, carcinoid syndrome, certain drugs( PG and prokinetic drugs) may produce hypermotility with diarrhea Primary visceral neuropathies or idiopathic acquired intestinal obstruction Diabetic diarrhea Irritable bowel syndrome