Harrisons Manual of Medicine, 18th Ed.

CHAPTER 46. Diarrhea, Constipation, and Malabsorption

NORMAL GASTROINTESTINAL FUNCTION

ABSORPTION OF FLUID AND ELECTROLYTES

Fluid delivery to the GI tract is 8–10 L/d, including 2 L/d ingested; most is absorbed in small bowel. Colonic absorption is normally 0.05–2 L/d, with capacity for 6 L/d if required. Intestinal water absorption passively follows active transport of Na+, Cl, glucose, and bile salts. Additional transport mechanisms include image exchange, Na+/H+ exchange, H+, K+, Cl, and HCO3  secretion, Na+-glucose cotransport, and active Na+ transport across the basolateral membrane by Na+,K+-ATPase.

NUTRIENT ABSORPTION

1. Proximal small intestine: iron, calcium, folate, fats (after hydrolysis of triglycerides to fatty acids by pancreatic lipase and colipase), proteins (after hydrolysis by pancreatic and intestinal peptidases), carbohydrates (after hydrolysis by amylases and disaccharidases); triglycerides absorbed as micelles after solubilization by bile salts; amino acids and dipeptides absorbed via specific carriers; sugars absorbed by active transport.

2. Distal small intestine: vitamin B12, bile salts, water.

3. Colon: water, electrolytes.

INTESTINAL MOTILITY

Allows propulsion of intestinal contents from stomach to anus and separation of components to facilitate nutrient absorption. Propulsion is controlled by neural, myogenic, and hormonal mechanisms; mediated by migrating motor complex, an organized wave of neuromuscular activity that originates in the distal stomach during fasting and migrates slowly down the small intestine. Colonic motility is mediated by local peristalsis to propel feces. Defecation is effected by relaxation of internal anal sphincter in response to rectal distention, with voluntary control by contraction of external anal sphincter.

DIARRHEA

PHYSIOLOGY

Formally defined as fecal output >200 g/d on low-fiber (western) diet; also frequently used to connote loose or watery stools. Mediated by one or more of the following mechanisms:

OSMOTIC DIARRHEA

Nonabsorbed solutes increase intraluminal oncotic pressure, causing out-pouring 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 coliStaphylococcus aureus), protozoa (e.g., GiardiaIsosporaCryptosporidium), 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., CampylobacterSalmonellaShigellaYersinia, invasive or enterotoxigenic E. coliVibrio parahaemolyticusClostridium 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, diver-ticular 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 (Table 46-1).

TABLE 46-1 INFECTIOUS CAUSES OF DIARRHEA IN PATIENTS WITH AIDS

image

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 46-2.

TABLE 46-2 PHYSICAL EXAMINATION IN PATIENTS WITH CHRONIC DIARRHEA

image

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 StaphylococcusCampylobacter, 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 image.

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), [14C]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.

TREATMENT Diarrhea

An approach to the management of acute diarrheal illnesses is shown in Fig. 46-1. Symptomatic therapy includes vigorous rehydration (IV or with oral glucose-electrolyte solutions), electrolyte replacement, binders of osmotically active substances (e.g., kaolin-pectin), and opiates to decrease bowel motility (e.g., loperamide, diphenoxylate); opiates may be contraindicated in infectious or inflammatory causes of diarrhea. An approach to the management of chronic diarrhea is shown in Fig. 46-2.

Image

FIGURE 46-1 Algorithm for the management of acute diarrhea. Before evaluation, consider empiric RX with (*) metronidazole and with (†) quinolone.

image

image

FIGURE 46-2 Algorithm for the management of chronic diarrhea based on accompanying symptoms or features (A) or based on a limited screening for organic disease (B). pr, per rectum; bm, bowel movement; IBS, irritable bowel syndrome; Hb, hemoglobin; Alb, albumin; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; OSM, osmolality. (Reprinted from M Camilleri: Clin Gastrol Hepatol. 2:198, 2004.)

MALABSORPTION SYNDROMES

Intestinal malabsorption of ingested nutrients may produce osmotic diarrhea, steatorrhea, or specific deficiencies (e.g., iron; folate; B12; vitamins A, D, E, and K). Table 46-3 lists common causes of intestinal malabsorption. Protein-losing enteropathy may result from several causes of malabsorption; it is associated with hypoalbuminemia and can be detected by measuring stool α1-antitrypsin or radiolabeled albumin levels. Therapy is directed at the underlying disease.

TABLE 46-3 COMMON CAUSES OF MALABSORPTION

image

CONSTIPATION

Defined as decrease in frequency of stools to <1 per week or difficulty in defecation; may result in abdominal pain, distention, and fecal impaction, with consequent obstruction or, rarely, perforation. Constipation is a frequent and often subjective complaint. Contributory factors may include inactivity, low-fiber diet, and inadequate allotment of time for defecation.

SPECIFIC CAUSES

Altered colonic motility due to neurologic dysfunction (diabetes mellitus, spinal cord injury, multiple sclerosis, Chagas’ disease, Hirschsprung’s disease, chronic idiopathic intestinal pseudoobstruction, idiopathic megacolon), scleroderma, drugs (esp. anticholinergic agents, opiates, aluminum- or calcium-based antacids, calcium channel blockers, iron supplements, sucral-fate), hypothyroidism, Cushing’s syndrome, hypokalemia, hypercalcemia, dehydration, mechanical causes (colorectal tumors, diverticulitis, volvulus, hernias, intussusception), and anorectal pain (from fissures, hemorrhoids, abscesses, or proctitis) leading to retention, constipation, and fecal impaction.

TREATMENT Constipation

A management approach is shown in Fig. 46-3. In absence of identifiable cause, constipation may improve with reassurance, exercise, increased dietary fiber, bulking agents (e.g., psyllium), and increased fluid intake. Specific therapies include removal of bowel obstruction (fecalith, tumor), discontinuance of nonessential hypomotility agents (esp. aluminum-or calcium-containing antacids, opiates), or substitution of magnesium-based antacids for aluminum-based antacids. For symptomatic relief, magnesium-containing agents or other cathartics are occasionally needed. With severe hypo- or dysmotility or in presence of opiates, osmotically active agents (e.g., oral lactulose, intestinal polyethylene glycol–containing lavage solutions) and oral or rectal emollient laxatives (e.g., docusate salts) and mineral oil are most effective.

Image

FIGURE 46-3 Algorithm for the management of chronic constipation.

image

For a more detailed discussion, see Camilleri M, Murray JA: Diarrhea and Constipation, Chap. 40, p. 308; and Binder HJ: Disorders of Absorption, Chap. 294, p. 2460, in HPIM-18.