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Author: Laurence Scott Bailen, M.D.
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1. Objectives: Pathophysiology of Diarrhea

  1. To be able to describe five major categories of causes of diarrhea

  2. To understand that there is considerable overlap in the pathophysiology of diarrhea in clinical conditions

  3. Understand the fecal osmotic gap in evaluating patients with chronic diarrhea

  4. Understand how small intestinal bacterial overgrowth syndrome results in malabsorption

  5. Understand the epidemiology, clinical presentation, and diagnosis of celiac disease

  6. Understand the current hypothesis for the pathogenesis of celiac disease

  7. Understand the mechanism of diarrhea in the two more common causes of secretory diarrhea due to excess secretion of a hormone: Zollinger-Ellison syndrome (gastrinoma) and carcinoid syndrome (serotonin, bradykinin and others)

  8. Understand the diagnostic tests used to evaluate patients with chronic diarrhea with attention to the tests for malabsorption such as the d-xylose test

2. Pathophysiology of Diarrhea and Malabsorption

2.1. Introduction

Diarrhea may best be defined as doctors Roux and Ryle did in 1924: “Diarrhea is the too rapid evacuation of too fluid stools." Normal stooling varies from three bowel movements per week to three bowel movements per day. Patients may report diarrhea when their own normal pattern of bowel movements is altered. Loosening of the stool occurs when daily fecal water output increases by only 50-60mL. An increase of fecal water excretion of 100mL is sufficient to increase daily stool weight by 200grams/24 hours, the upper limit of normal.

The major causes of diarrhea, outlined in Table 1 , may be classified into five broad categories related to their pathophysiology:

  1. Osmotic diarrhea,

  2. Malabsorption /maldigestion/fatty diarrhea (steatorrhea),

  3. Inflammatory diarrhea,

  4. Secretory diarrhea, or

  5. Altered motility.


This section will review the pathophysiology of some of the more common and important causes of diarrhea in these categories. It should be remembered, though, that these categories are not absolute and that in any one individual disease or syndrome one or more pathophysiologic processes may be the mechanism behind the development of diarrhea. For example, Crohn’s disease may cause diarrhea based on an inflammatory, malabsorptive, and secretory pathophysiology. In addition, some causes of malabsorption or maldigestion may not necessarily be associated with diarrhea.

Diarrhea may also be divided into acute diarrhea and chronic diarrhea . Acute diarrheal states (diarrhea lasting less than 4 weeks) are most commonly due to infectious causes. However, many different medications or ischemia to the intestines can cause acute diarrhea. Chronic diarrhea is diarrhea which lasts for longer than 4 weeks.

This section will not only discuss the pathophysiology of diarrhea, but also the evaluation and treatment of patients with diarrhea. This section will NOT focus on inflammatory bowel disease or infectious diarrhea, as these entities are covered elsewhere.

Table 1. Major Causes of Diarrhea

Osmotic diarrhea :

  • Osmotic laxative abuse

    • Mg(OH)2), MgSO4, Na2SO4, Lactulose, Polyethylene glycol

  • Carbohydrate malabsorption

    • Lactose intolerance

Malabsorption/Maldigestion/Fatty Diarrhea

  • Malabsorption syndromes

    • Mucosal diseases of small intestine (e.g. Celiac sprue)

    • Short bowel syndrome (after multiple surgical resections)

    • Small bowel bacterial overgrowth

      • Mesenteric ischemia

  • Maldigestion

    • Pancreatic insufficiency (chronic pancreatitis, cystic fibrosis)

    • Reduced luminal bile acid

Inflammatory diarrhea

  • Inflammatory bowel disease

    • Ulcerative colitis

    • Crohn’s disease

    • Lymphocytic or collagenous colitis

    • Ulcerative jejunoileitis (rare complication of celiac sprue)

  • Infections

    • Invasive bacterial infection (Clostridium difficile, E.Coli 0157:H7 and others)

    • Phenolphthalein, anthraquinones, bisacodyl, senna, aloe, ricinoleic acid (castor oil), dioctyl sodium sulfosuccinate

  • Ischemic Colitis

  • Radiation enterocolitis

  • Neoplasia: colon carcinoma, lymphoma

Secretory diarrhea

  • Non-osmotic laxative use

    • Phenolphthalein, anthraquinones, bisacodyl, senna, aloe, ricinoleic acid (castor oil), dioctyl sodium sulfosuccinate

  • Congential chloridorrhea

  • Infectious diarrhea: liberation of bacterial toxins

  • Ileal bile acid malabsorption

  • Vasculitis

  • Drugs

  • Neuroendocrine tumors

    • Gastrinoma

    • VIPoma

    • Somatostatinomas

    • Mastocytosis

    • Carcinoid syndrome

    • Medullary carcinoma of thyroid

  • Neoplasia: villous adenoma, colon cancer, lymphoma

  • Idiopathic secretory diarrhea

Disordered motility

  • Post-vagotomy

  • Post-sympathectomy

  • Diabetic neuropathy

  • Hyperthyroidism

  • Addison’s disease (adrenal insufficiency)

  • Irritable bowel syndrome

2.2. Osmotic Diarrhea

Excess amounts of poorly absorbed substances that remain in the intestinal lumen may cause osmotic diarrhea. Large amounts of these substances (e.g. lactose, lactulose, magnesium) contain osmotically active solutes which obligate retention of water in the lumen of the intestine by virtue of their osmotic effects.

Electrolyte absorption (Na+, K+, Cl-, HCO3-) is unaffected by these osmotically-active substances therefore stool water contains very little unabsorbed sodium and potassium. This is the basis for the measurement and calculation of the fecal osmotic gap , a diagnostic test in the evaluation of patients with chronic diarrhea.

The fecal osmotic gap estimates the difference between luminal osmolality and the osmolality of luminal contents contributed by fecal electrolytes. Luminal osmolality is approximately equal to body fluid osmolality (290 mosm/kg H2O) since the colon cannot maintain an osmotic gradient against plasma. Furthermore, fecal osmolality may be measured directly but this measurement should NOT be used in the calculation of the fecal osmotic gap: fecal osmolality begins to rise almost immediately as it sits in the collection container. This rise is due to monosaccharide conversion by bacterial fermentation to several osmotically active organic acids. The osmolality of luminal contents contributed by fecal electrolytes is calculated by multiplying the sum of the Na+ and K+ concentrations measured in a stool sample by 2 (to account for the anions that accompany these cations). Therefore:

Fecal osmotic gap = 290 mosm/kg H2O – 2 ([Na+] + [K+]) mmol/L

In patients with pure osmotic diarrhea the fecal osmotic gap should be large (> 125 mosm/kg H2O). In patients with secretory diarrhea (see Table 1) the osmotic gap should be small (<50 mosm/kg H2O).

Measurement of the pH of feces may also be helpful in assessing osmotic diarrhea. Carbohydrate induced diarrhea, such as lactase deficiency, typically has a low pH whereas magnesium induced diarrhea has a high pH.

The hydrogen breath test (also occasionally utilized in the assessment of bacterial overgrowth syndrome, discussed below) may be used to detect lactose intolerance. A oral dose of lactose is administered and, in patients with lactase deficiency, excess H2 is produced by colonic bacterial fermentation of the unabsorbed carbohydrate. H2 diffuses into the general circulation and is liberated in expired air. In general, a rise of over 20 ppm (parts per million) in exhaled hydrogen at 3-6 hours after ingestion of the substrate is abnormal.

Important examples of osmotic diarrhea include lactose malabsorption and ingestion of excess magnesium as in magnesium hydroxide. Lactose intolerance is due to congenital or, more commonly, acquired deficiency in the brush border disaccharidase lactase. This leads to malabsorption of lactose – the sugar contained in dairy products. Lactose remains in the intestinal lumen and acts as a strong osmotic substance. This leads to symptoms of flatulence, bloating, and diarrhea. Lactase deficiency is particularly common in Asians, African-Americans, Native Americans, Jews, Hispanics, Southern Europeans, and Mediterraneans. Over one-half of the world's population is affected. Lactose intolerance is treated by avoidance of lactose containing foods and/or supplementing oral intake of dairy products with liquid or tablet form of the lactase enzyme.

2.3. Malabsorption, Maldigestion, and Fatty Diarrhea

Abnormalities of absorption may have several pathophysiologic mechanisms as outlined below. Although all three major nutrients (fat, carbohydrate, and protein) may be malabsorbed, clinical symptoms usually only develop with carbohydrate and fat malabsorption. Some disorders that cause fat, carbohydrate, and protein malabsorption may not cause diarrhea. The student is directed to the review section on normal physiology of digestion and absorption prior to studying this section.

  1. Luminal Phase

    1. Reduced nutrient availability

      1. Cofactor deficiency

      2. Nutrient consumption

    2. Impaired fat solubilization

      1. Reduced bile salt

      2. Impaired bile salt secretion

      3. Bile salt inactivation

      4. Impaired CCK release

      5. Increased bile salt losses

    3. Defective nutrient hydrolysis

      1. Lipase

      2. Enzyme deficiency

      3. Improper mixing or rapid transit

  2. Mucosal Phase

    1. Extensive mucosal loss

    2. Diffuse mucosal disease

    3. Enterocyte defects

      1. Microvillous inclusion disease

      2. Brush border hydrolase deficiency

      3. Transport defects

      4. Epithelial processing

  3. Transport Phase

    1. Vacular

    2. Lymphatic

Nutrients may be malabsorbed due to defects in digestion during the luminal phase of nutrient absorption.

Intralumenal maldigestion may occur at several levels:

  1. Reduced nutrient availability:

    1. Patients who lack intrinsic factor, the cofactor necessary for vitamin B12 absorption, due to autoimmune atrophic gastritis (atrophic gastritis due to an autoimmune process where antibodies target the H+-ATPase on parietal cells causing parietal cell loss; parietal cells produce intrinsic factor in addition to HCl) leading to pernicious anemia. Patients are unable to absorb B12.

    2. Bacterial overgrowth syndrome (discussed below) leads to nutrient consumption by bacteria.

  2. Impaired fat solubilization

    1. Reduced bile salt synthesis due to severe liver disease (cirrhosis) and impaired bile salt secretion due to chronic cholestasis (intrinsic liver disease which causes bile duct damage or extrahepatic bile duct obstruction): bile salts are thus not available to form micelles to aid in fat solubilization for absorption.

    2. Bile salts may be inactivated in the intestinal lumen by overgrowth of bacteria in the small bowel bacterial overgrowth syndrome . The normal concentration of bacteria in the proximal small intestine is less than 104 cfus/ml (colony forming units per ml). In patients with conditions that predispose to intestinal stasis either by anatomic or motility abnormalities (see Predisposing conditions favoring bacterial overgrowth table below) or in patients with abnormal connections between loops of proximal and distal bowel, bacteria may overgrow in the proximal small intestine. These excess bacteria deconjugate bile salts leaving them unconjugated and unable to participate in micelle formation. This leads to malabsorption of fat and symptoms of abdominal pain, diarrhea, and bloating. It may also lead to malabsorption of the fat soluble vitamins A, D, E, K. Clinically, vitamin K deficiency is detected by measuring the prothrombin time (PT) in blood. If prolonged this may suggest vitamin K deficiency as several of the proteins in the coagulation cascade rely on vitamin K for their formation.

Table 2. Predisposing Conditions Favoring Bacterial Overgrowth

Intestinal Stasis

Anatomic

Intestinal strictures (secondary to Crohns disease, radiation, or malignancy, for example)

Small intestinal diverticulosis (seen in scleroderma

Surgical procedures creating blind loops (end-side entero-enteric anastomoses, Billroth II anastomoses, jejuno-ileal bypass)

Motility disorders

Scleroderma

Diabetes mellitus (diabetic autonomic neuropathy)

Idiopathic intestinal pseudoobrstruction

Abnormal connections between proximal and distal bowel

Resection of ileocecal valve

Fistulas (gastrocolic, jejunocolic due to Crohns, peptic ulcer disease, cancer)

  1. Diagnosis of bacterial overgrowth

    1. Direct aspiration of luminal contents at the time of endoscopy (not routinely performed) and cultured

    2. Hydrogen breath tests. A substrate (a carbohydrate such as glucose, lactulose, lactose, or fructose) is administered and then expired air is then analyzed for hydrogen (H2) content. An “early” peak (30-60 minutes after ingestion) in the H2 concentration in expired air is detected if the substrate is metabolized by excessive small intestinal bacteria. A “late” peak (2-3 hours after ingestion) is typically seen when malabsorbed substrate reaches the colon and is metabolized by normally present colonic bacteria.

  2. Treatment of bacterial overgrowth:

    1. Correction of predisposing factor if possible (i.e., correction of surgical abnormality or treatment of underlying disease)

    2. Correction of nutritional deficiencies

    3. Antibiotics

  1. Increased bile salt losses
    Surgical resection of or extensive inflammatory disease in the terminal ileum (as seen in Crohn’s disease) may lead to malabsorption of bile acids. The loss of bile acids in the stool leads to relative bile salt deficiency resulting in impaired fat solubilization.

  1. Defective nutrient hydrolysis

    1. Zollinger Ellison syndrome – excess HCl (acid) production may inactivate gastric lipase and proteolytic pancreatic exocrine enzymes.

    2. Pancreatic enzyme deficiency – due to chronic pancreatitis or a malignancy obstructing the outflow of pancreatic juices into the duodenum.

    3. Improper mixing – due to surgical resection such as post-gastrectomy (Billroth I or Billroth II anastomoses for example)

    4. Rapid intestinal transit - diabetic neuropathy or hyperthyroidism (disordered motility)

Malabsorption : Mucosal abnormalities:

Many diseases may interrupt the mucosal integrity and thus the absorptive surface of the intestine leading to malabsorption. The small bowel mucosa may be damaged due to prior radiation treatment, vascular insufficiency, or from inflammatory or infectious conditions. As mentioned above, inflammatory diseases such as Crohn’s disease disrupt the mucosa leading to malabsorption. Celiac sprue is a diffuse mucosal disease of the small bowel which leads to villous atrophy and subsequent nutrient malabsorption.

Celiac sprue or gluten sensitive enteropathy is a chronic disease with a characteristic although not specific mucosal lesion of the small intestine which impairs nutrient absorption and with removal of all wheat gliadins (the toxic alcohol-soluble gluten fractions) from the diet there is resolution of the mucosal abnormality and improvement in nutrient absorption.

  • Pathology: Small intestinal villous atrophy and increases in lamina propria lymphocytes.

  • Epidemiology: Whites (highest incidence in Northern Europeans, particularly Ireland) although celiac sprue has been documented in Asians from India and Pakistan.

  • Clinical presentation: Varied – often depending on extent and degree of villous atrophy. Classically, crampy abdominal pain, diarrhea, flatulence, bloating, weight loss, steatorrhea. Also: Iron deficiency anemia, osteoporosis (vitamin D malabsorption), peripheral neuropathy (B12 deficiency), easy bruising (vitamin K malabsorption), edema (malabsorption of protein).

  • Diagnosis :

    • Biopsy of small intestine during upper endoscopy for pathologic evaluation

    • Serology:

      • Anti-gliadin antibodies (IgA and IgG)

      • Anti-endomysial antibodies (IgA) – these IgA antibodies are reactive with the lining of visceral smooth muscle (i.e., the endomysium). Sensitivity and specificity is very high with these antibodies compared to anti-gliadin in the detection of celiac sprue. It is unclear if these antibodies play a role in the pathogenesis of celiac sprue.

      • It was recently (1997-1998) discovered that tissue transglutaminase is the antigen recognized by endomysial antibodies. There is now an ELISA that can be used to measure tissue transglutaminase antibodies with high specificity and sensitivity.

  • Treatment :

    • The mainstay of treatment for celiac sprue is a gluten free diet. This diet is incredibly restrictive necessitating the evaluation by a dedicated nutritionist. Gliadins (the alcohol soluble fraction of gluten – the major wheat storage protein) and prolamins (alcohol soluble fractions of rye, barley, and oat storage proteins) of rye, barley, and possibly oats are toxic to celiac sprue patients. For more details on the gluten free diet the Celiac Sprue association website is particularly helpful: http://www.csaceliacs.org/basics.html .

      Other aspects of treatment include nutrient supplementation: iron, B12, calcium, vitamin D, vitamin K.

  • Pathogenesis of celiac sprue :

    • Genetic factors: >95% of patients carry HLA-DQ2 or –DQ8; 10% of first degree relatives have celiac sprue

    • Environmental agent – gliadin component of gluten

    • Autoimmune response to gliadin and prolamin peptide fragments.

    • Diarrhea caused by malabsorbed substances including electrolytes, protein, and fat

    • Presumed pathophysiology: Gliadin is absorbed into the lamina pro Congenital defects of ion absorptive processes pria and presented to T cells by antigen presenting cells in conjunction with HLA-DQ2 or DQ8. Tissue transglutaminase deamidates gliadin peptides which generates acidic, negatively charged residues which binds the T cell receptor more strongly. This leads to a more pronounced T cell response. These activated lymphocytes generate a cytokine response (TNF-α, interleukin-4, interferon-γ), which lead to damaged villi and inflammation.

    • See illustration in N Engl J Med 2002; 346: 180-188

  • Celiac Sprue : associated diseases: Dermatitis herpetiformis, pruritic blistering skin eruption associated with IgA deposits in skin

    • Small intestinal lymphoma (increased risk of lymphoma in patients with celiac sprue: risk may be lessened with adherence to gluten free diet)

Post-absorptive/Transport Phase Abnormalities Resulting in Malabsorption

  • Defective chylomicron synthesis in a-beta lipoproteinemia

  • Submucosal infiltration in the intestinal wall due to lymphoma or amyloidosis

  • Lymphatic obstruction in intestinal lymphangiectasia

2.4. Inflammatory Diarrhea

Diarrheal diseases that fit into this category are discussed in detail in the section on inflammatory bowel diseases and in the infectious disease section on infectious diarrhea. Briefly, in addition to mucosal disruption resulting in enterocyte damage and abnormal absorption of nutrients and electrolytes, inflammatory processes may result in discharge of mucus, proteins, and blood into the intestinal lumen.

2.5. Secretory Diarrhea

Secretory diarrhea is caused by abnormal ion transport in intestinal epithelial cells usually resulting in decreased absorption of electrolytes. The major solutes in the intestinal lumen of patients with secretory diarrhea are Na+, K+, Cl-, and HCO3- therefore electrolytes account for most of the luminal osmolality. Consequently, the fecal osmotic gap {290 – 2([Na+] + [K+])} is small, usually less than 50 mosm/kg H2O. In addition, because this type of diarrhea is due to abnormalities in ion transport, the diarrhea usually persists despite fasting. However, reliance on this clinical history point (i.e., diarrhea which continues despite fasting) can be troublesome: most patients with secretory diarrhea (defined as a small fecal osmotic gap) still absorb most of the 9-10L of fluid entering the jejunum each day – they just do not absorb almost all of it as in normal circumstances. Therefore, one may argue that the term secretory diarrhea is a misnomer and should really be called “non-osmotic” diarrhea.

There are four main categories of disease resulting in secretory diarrhea:

  1. Congenital defects of ion absorptive processes

    1. Congenital chloridorrhea results from defective or absent Cl-/HCO3- exchanger in the ileum and colon. This results in excess Cl- loss in the stool and metabolic alkalosis.

    2. Congenitally defective or absent Na+/H+ exchanger leads to excess Na+ in the stool and metabolic acidosis

  2. Intestinal resection

    1. Decreased absorptive surface for not only nutrients but also electrolytes and fluid

    2. Combined malabsorption and secretory component

  3. Diffuse mucosal disease with destruction of enterocytes or reduction in enterocyte function

    1. Similar pathophysiology to intestinal resection – also may cause nutrient malabsorption in addition to electrolyte malabsorption (defective ion transport)

  4. Abnormal mediators: result in changes in intracellular signaling pathways

    1. Changes in cAMP (cyclic adenosine monophosphate), cGMP (cyclic guanosine monophosphate), calcium, and/or protein kinases. These changes lead to a decrease in Na+ absorption or an increase in Cl- secretion.

    2. Mediators

    3. Other mediators: bacterial toxins

    4. Other mediators: non-osmotic laxatives (see Table 1)

    5. More mediators: fatty acids – byproducts of fat malabsorption which reach colon and stimulate colonic secretion.

    6. More mediators: bile acids – bile acids not absorbed in ileum due to ileal resection or severe ileal disease (such as in Crohn’s disease) can also act as a cathartic in the colon and stimulate secretion of fluid and electrolytes.

    7. Final mediators: circulating agents released by neuroendocrine tumors (rare). (See Table 3)

Table 3. Neuroendocrine Tumors and Secretory Diarrhea

Condition

Mediator

Mechanism of Diarrhea

Other Manifestations

Zollinger-Ellison syndrome

Gastrin

Acid inactivation of pancreatic enzymes and bile salts

Intestinal fluid and electrolyte secretion

Acid-induced damage to intestinal mucosa

Increased motility

Severe peptic ulcer disease

Erosive esophagitis

Tumor in pancreas or duodenum

Carcinoid syndrome

Serotonin, substance P, Bradykinin, Motilin, Prostaglandins

Increased motility

Intestinal fluid and electrolyte secretion

Flushing

Wheezing

Right-sides heart failure

Hypotension

Medullary Carcinoma of the Thyroid

Calcitonin, Prostaglandins

Intestinal fluid and electrolyte secretion

Increased motility

Thyroid module or enlargement

Pancreatic Cholera

VIP (Vasocactive intestinal peptide)

Intestinal fluid and electrolyte secretion

Hypokalemia

Achlorhydria

Flushing

Hypotension

Glucagonoma

Glucagon

Intestinal fluid and electrolyte secretion

Necrolytic erythema migrans (rash)

Diabetes

Anemia

Cheilitis/glossitis

Tumor in pancreas

Somatostatinoma

Somatostatin

Decreased intestinal nutrient absorption

Steaorrhea due to decrease pancreatic secretion

Diabetes

Dyspepsia

Cholelithiasis

Pancreatic tumor

Systemic Mastocytosis

Histamine

Intestinal fluid and electrolyte secretion

Gastric hypersecretion

Villous atrophy

Flushing

Nausea/vomiting

Abdominal pain

Dermatographism

2.6. Disordered Motility

Conditions which cause altered gastric, small intestinal, or colonic motor activity may cause diarrhea by limiting the time for the normal digestive and absorptive processes to take place. That is, food boluses are propelled rapidly through the intestinal lumen decreasing the contact time at absorptive epithelial cells.

Patients with autonomic diabetic neuropathy or hyperthyroidism may have altered intestinal motility leading to diarrhea. Patients who have had a vagotomy and/or partial gastrectomy are also prone to altered motility. Abnormal motility also likely contributes to diarrhea in patients with the irritable bowel syndrome.

Irritable bowel syndrome (IBS), one of the most common syndromes identified in gastroenterology clinics, is felt to be due to heightened visceral sensation and altered intestinal motility. Typically, symptoms include intermittent, non-localizing abdominal pain with an altered bowel pattern. That is, patients alternate from being constipated to having diarrhea. This is often associated with a sensation of incomplete evacuation after bowel movements or the passage of mucus in the stool. IBS does not cause blood in the stool, fevers, nocturnal symptoms of diarrhea, or weight loss. There are set criteria for the diagnosis of IBS based on the clinical history alone and most gastroenterologists may suspect and can diagnose IBS without diagnostic testing, but endoscopic procedures, blood work, or gastrointestinal x-rays are often performed to rule out other diseases. Treatment is usually symptomatic (anti-diarrheals, anti-spasmodics, fiber supplementation, avoidance of laxatives).

Slow motility may also result in diarrhea: Slow intestinal transit may result in intestinal stasis leading to bacterial overgrowth (discussed above).

2.7. Diagnostic Tests in the Evaluation of Diarrhea

  • Differentiate between acute and chronic diarrhea: Clinical history

  • Stool specimens for routine and specialized microbiologic cultures

  • Stool specimens for stool electrolytes to calculate fecal osmotic gap

  • “Spot” stool specimen for fecal fat (Sudan stain)

  • 24-72 hour stool collections to assess fecal weight and fecal fat

  • Stool specimens for detecting excess laxative ingestion

  • Blood tests to evaluate for :

    • Anemia

    • Electrolyte disturbances

    • Renal dysfunction

    • Prothrombin time (vitamin K)

    • Albumin

    • Iron, Folate, vitamin B12

  • Tests for Malabsorption :

    • Fat malabsorption:

      • Sudan stain

      • 72 hour stool collection (abnormal: greater than 7 grams of fat)

    • Carbohydrate Malabsorption:

      • D-xylose absorption test: xylose, a sugar absorbed in the duodenum and jejunum, is administered orally. It is not completely metabolized and is therefore excreted in the urine in its intact form. Therefore, it may be measured in the urine. In patients with mucosal intestinal disease the d-xylose will not be absorbed and will therefore have low levels in the urine (<4g after a 25g dose). Caveats: 1) The test requires normal renal function. Therefore, the test is not useful in patients with renal failure. 2) Bacteria in the intestine may also utilize xylose as a nutrient source therefore limiting what is available for absorption. Therefore, patients with bacterial overgrowth syndrome may have a falsely abnormal d-xylose test.

      • H2tests: A carbohydrate is administered orally to the patient (lactose, fructose) and then the patient’s expired air is measured for H2. The test relies on colonic (or small intestinal, in the case of small intestinal bacterial overgrowth syndrome) bacterial fermentation of non-absorbed carbohydrate.

      • Test for pancreatic insufficiency:

        • Invasive: secretin stimulation test. Secretin is administered intravenously and pancreatic juice is aspirated from the duodenum and analyzed for bicarbonate and amylase levels. Low levels indicate pancreatic exocrine insufficiency.

        • Non-invasive: measurement of fecal chymotrypsin and/or fecal elastase

      • Test to evaluate B12 deficiency:

        • Schilling test

  • Upper Endoscopy, Colonoscopy

2.8. Treatment of Diarrhea

Depends on underlying cause. In general, do not use anti-diarrheal agents that slow motility in patients with infectious diarrhea.