Chronic diarrhea resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mugilan Poongkunran M.B.B.S [2]

Definition

Diarrhea is defined based upon the frequency, volume, and consistency of stools. It is more commonly defined as more than three loose stools in 24 hours or when the stool weight is more than 200 g per 24 hours containing more than 200 ml fluid per 24 hours. Chronic diarrhea is defined as a decrease in fecal consistency with or without increased stool frequency for more than 4 weeks. Chronic diarrhea may be divided into watery, fatty (malabsorption), and inflammatory (with blood and pus). Watery diarrhea may be subdivided into osmotic (water retention due to poorly absorbed substances), secretory (reduced water absorption), and functional (hypermotility) types. However, not all chronic diarrhea is strictly classified, because some categories overlap.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

• Human immunodeficiency virus
• Inflammatory bowel disease

Common Causes

Fatty Diarrhea

• Malabsorption syndrome : Bacterial overgrowth, celiac disease, pancreatic insufficiency, short bowel resection, Whipple disease

Inflammatory Diarrhea

• Infection : Amebiasis, Cytomegalovirus, Strongyloides, Tuberculosis, Yersiniosis etc.
• Inflammatory bowel disease
• Ischemic colitis
• Neoplasia : Colon cancer, lymphoma
• Radiation enteritis

Osmotic Diarrhea

• Lactose intolerance
• Other : Antacids, fructose, lactulose, laxatives, magnesium, phosphate, sorbitol ingestion.

Secretory Diarrhea

• Bacterial toxins
• Hormonal : Carcinoid syndrome, diabetes, gastrinoma, hyperthyroidism, medullary carcinoma of thyroid, somatostatinoma, VIPoma
• Irritable bowel syndrome
• Medications : Angiotensin receptor blockers, antibiotics, chemotherapy, colchicine, H2-receptor antagonist, NSAIDs, proton pump inhibitors, SSRIs, laxative (nonosmotic laxatives) etc.
• Postsurgical : Cholecystectomy, gastrectomy, intestinal resection, vagotomy

Management

This management is as per the American Gastroenterological Association guidelines for the evaluation and management of chronic diarrhea.

Adults with chronic diarrhea (> 4 weeks)

History ❑ Onset : Congenital / abrupt / gradual ❑ Pattern : Continuous / intermittent ❑ Duration ❑ Epidemiology : Travel / food / water ❑ Stool characteristics : Watery / bloody / fatty ❑ Fever ❑ Abdominal pain ❑ Weight loss ❑ Fecal incontinence ❑ Aggravating factors : Diet / stress ❑ Mitigating factors : Diet / over-the-counter drugs / use of prescription ❑ Previous evaluations ❑ Iatrogenic : Medication / radiation therapy / surgery ❑ Factitious diarrhea : Eating disorders / laxative ingestion / malingering ❑ Systemic disease : Cancer, diabetes, HIV, hyperthyroidism, other conditions

Physical Examination ❑ General : Nutrition / vitals / volume status ❑ Skin : Flushing / rashes / dermatographism ❑ CVS : Murmur ❑ RS : Wheeze ❑ Thyroid : Mass ❑ Abdomen : Ascitis / hepatomegaly / mass / tenderness ❑ Anorectal : Abscess / blood / fistula / sphincter competence ❑ Extremities : Edema

Routine laboratory tests ❑ CBC and differential : Anemia / eosinophilia / leucocytosis ❑ ESR ❑ Serum electrolytes ❑ Total serum protein and albumin ❑ Thyroid function tests ❑ Urine analysis

Altered diet +/- ORT +/- IVF +/- emperical antibiotic trial in case of specific obvious diagnosis

Stool analysis ❑ Weight ❑ Stool electrolytes / fecal osmotic gap ❑ Stool pH ❑ Fecal occult blood testing ❑ Stool WBC's ❑ Fat output : Quantitative / Sudan stain ❑ Laxative screen

Categorize diarrhea

Chronic osmotic diarrhea

Chronic secretory diarrhea

Chronic inflammatory diarrhea

Chronic fatty diarrhea

Low pH : Carbohydrate malabsorption

High Mg : Inadvertent ingestion or laxative abuse.

Exclude infection ❑ Stool culture ❑ Stool for ova and parasites ❑ Giardia antigen ❑ Bacterial overgrowth : Small bowel aspirate or breath H2 test

Exclude structural disease ❑ Small bowel radiographs ❑ Sigmoidoscopy or colonoscopy with biopsy ❑ CT abdomen ❑ Small bowel biopsy

Exclude structural disease ❑ Small bowel radiographs ❑ CT abdomen ❑ Small bowel biopsy and aspirate for quantitative culture

Dietary review / breath H2 test (lactose) or lactase assay in biopsy

Exclude structural disease ❑ Small bowel radiographs ❑ Sigmoidoscopy or colonoscopy with biopsy ❑ CT abdomen ❑ Biopsy of the proximal small bowel mucosa

Exclude infection ❑ Stool culture : Standard Aeromonas, Plesiomonas, tuberculosis ❑ Clostridium toxin assay ❑ Other specific test : Virus and parasites

Exclude exocrine pancreatic insufficieny ❑ Secretin test ❑ Stool chymotrypsin activity ❑ Bentiromide test ❑ Others : D-xylose absorption tests / Schilling test

Selective testing ❑ Cholestyramine test for bile acid diarrhea ❑ Plasma peptides : Gastrin / calcitonin / vasoactive intestinal polypeptide / somatostatin ❑ urine : 5-hydroxyindole acetic acid / metanephrine / histamine ❑ Others : TSH / ACTH stimulation test / serum protein electrophoresis / serum immunoglobulins

Specific Rx per results / Symptomatic Rx

No confirmatory diagnosis / no specific treatment

Emperical therapy ❑ Adequate hydration : ORS / IVF / parental nutrition ❑ Antimicrobial therapy : Depending upon the prevalence of bacterial or protozoal infection in a specific community or situation ❑ Bile acid binding resins : cholestyramine ❑ Opiates / octreotide

Evaluation of Diagnostic Tests

Spot Stool Analysis

Because a 72-hour stool collection is cumbersome, qualitative tests continue to be used in the clinic.

Occult Blood

• A positive test result suggests the presence of inflammatory bowel disease, neoplastic diseases or celiac sprue and other sprue like syndromes.
• Fecal occult blood positivity can also be associated with laxative-induced diarrhea, pancreatic maldigestion, idiopathic secretory diarrhea, and microscopic colitis.

White Blood Cells

• The standard method of detecting white blood cells (WBCs) in stool is with Wright's staining and microscopy.
• Latex agglutination test is highly sensitive and specific for the detection of neutrophils (lactoferrin) in stool in acute infectious diarrhea and in pseudomembranous colits.
• Calprotectin is a zinc and calcium binding protein that is derived mostly from neutrophils and monocytes and fecal calprotectin may be useful for distinguishing inflammatory from noninflammatory causes of chronic diarrhea.

Sudan Stain for Fat

• Excess stool fat should be evaluated by means of a Sudan stain or by direct measurement.
• The presence of excess fat globules by stain or stool fat excretion >14 g/24 h suggests malabsorption or maldigestion.
• Stool fat concentration of >8% strongly suggests pancreatic exocrine insufficiency.

Fecal Cultures

• In immunocompetent patients, bacterial infections are rarely the cause of chronic diarrhea and routine fecal cultures usually are not usually obtained. However, under specific environmental conditions suspecting Aeromonas or Pleisiomonas species, at least one fecal culture should be performed in the evaluation of these patients. The epidemiological clues raising suspicion for the presence of these organisms include consumption of untreated well water and swimming in fresh water ponds and streams.

• In immunocompromised patients, bacterial cultures ought to be part of the initial diagnostic evaluation, as common infectious causes of acute diarrhea, such as Campylobacter or Salmonella, can cause persistent diarrhea.

• Infections with yeast and fungi have been reported as causes of both nosocomial and community-acquired chronic diarrhea, even in immunocompetent individuals. Protozoa and parasites causes are now analyzed by fecal enzyme-linked immunosorbent assay (ELISA) and chronic viral infections are diagnosed from gastrointestinal mucosal biopsy specimens rather than stool samples.

Quantitative Stool Analysis

A 48- or 72-hour quantitative stool collection is useful in the work-up of chronic diarrhea. Full analysis of the collection includes measurement of weight, fat content, osmolality, electrolyte concentrations, magnesium concentration and output, pH, occult blood, and based upon the history fecal chymotrypsin or elastase activity and laxatives. Several days before and during the collection period, the patient should eat a regular diet of moderately high fat content or a fixed diet for some patients to ensure that adequate amounts of fat and calories are consumed. During the collection period, no diagnostic tests should be done that would disturb the normal eating pattern, aggravate diarrhea, diminish diarrhea, add foreign material to the gut, or risk an episode of incontinence. All but essential medications should be avoided, and any antidiarrheal medication begun before the collection period should be held.

Fecal Weight

• Knowledge of stool weight is of direct help in diagnosis and management in some instances. Stool weights greater than 500 g/day are rarely if ever seen in patients with irritable bowel syndrome and stool weights less than 1000 g/day are evidence against pancreatic syndrome.

• Low stool weight in a patient complaining of “severe diarrhea” suggests that incontinence or pain may be the dominant problem.

• Response to fasting such as complete cessation of diarrhea during fasting is strong evidence that the mechanism of diarrhea involves something ingested (nonabsorbable substance or nutrient causing osmotic diarrhea, or unabsorbed fatty acids or laxatives causing secretory diarrhea).

Stool Osmotic Gap

• The osmotic gap is calculated from electrolyte concentrations in stool water by the following formula : 290 - 2([Na+] + [K+]).
• The osmolality of stool within the distal intestine should be used for this calculation rather than the osmolality measured in fecal fluid, because measured fecal osmolality begins to increase in the collection container almost immediately when carbohydrates are converted by bacterial fermentation to osmotically active organic acids.
• Osmotic diarrheas, where electrolytes account for most of stool osmolality, are characterized by osmotic gaps >125 mOsm/kg, whereas secretory diarrheas where nonelectrolytes account for most of the osmolality of stool water, typically have osmotic gaps <50 mOsm/kg. In mixed cases, such in modest carbohydrate malabsorption (in which most of the carbohydrate load is converted to organic anions that obligate the fecal excretion of cations including Na+ and K+), the osmotic gap may lie between 50 and 125.

Fecal pH

• A fecal pH of < 5.3 indicates that carbohydrate malabsorption (such as that associated with lactulose or sorbitol ingestion) is a major cause of diarrhea.
• A pH of > 5.6 argues against carbohydrate malabsorption as the only cause and malabsorption syndrome that involves fecal loss of amino acids and fatty acids in addition to carbohydrate, have a higher fecal pH.

Fecal Fat Concentration and Output

• The upper limit of fecal fat output measured in normal subjects (without diarrhea) ingesting normal amounts of dietary fat is approximately 7 g/day (9% of dietary fat intake)and values more than this signify the presence of steatorrhea.
• A fecal fat concentration of <9.5 g/100 g of stool more likely to be seen in small intestinal malabsorptive syndromes because of the diluting effects of coexisting fluid malabsorption.
• A fecal fat concentrations of ≥9.5 g/100 g of stool were seen in pancreatic and biliary steatorrhea, in which fluid absorption in the small bowel is intact.

Analysis for Laxatives

Analysis for laxatives should be done early in the evaluation of diarrhea of unknown etiology. The simplest test for a laxative is alkalinization of 3 mL of stool supernatant or urine with one drop of concentrated sodium hydroxide and a pink or red color is a positive result. Stool water can be analyzed specifically for phenolphthalein, emetine and bisacodyl and its metabolites, using chromatographic or chemical tests. Urine can be analyzed for anthraquinone derivatives.

• If stool electrolyte analysis suggests secretory diarrhea (osmotic gap <50), the patient may have ingested a laxative capable of causing secretory diarrhea, such as sodium sulfate or sodium phosphate ingestion.
• If stool electrolyte analysis suggests osmotic diarrhea (osmotic gap >125 mOsm/kg), magnesium (Mg2+) laxatives may have been ingested.
• If fecal osmolality is significantly less than 290 mOsm/kg (the osmolality of plasma), water or hypotonic urine has been added to the stool.
• If the osmolality is far above that of plasma, hypertonic urine may have been added to stool. Urinary contamination can be confirmed by a finding of high monovalent cation concentration (e.g., [Na+] + [K+] > 165, physiologically impossible in stool water) and a high concentration of urea or creatinine in stool water.

Endoscopic Examination and Mucosal Biopsy

Sigmoidoscopy and Colonoscopy

• A strong history and complete examination determine which scopes to be used and chronic conditions like melanosis coli, ulceration, polyps, tumors, Crohn's disease, ulcerative colitis, and amebiasis can be diagnosed by inspection of the colonic mucosa.
• Diseases such as microscopic colitis (lymphocytic and collagenous colitis), amyloidosis, Whipple's disease, granulomatous infections, and schistosomiasis, where the mucosa appears normal need mucosal biopsy and can be diagnosed histologically.

Upper Tract Endoscopy

• The presence of steatorrhea makes a small intestinal malabsorptive disorder to be the likely etiology and an endoscope that allows specimens to be obtained from the proximal and distal duodenum and/or proximal jejunum would be the best investigation of choice.
• Crohn's disease, giardiasis, celiac sprue, intestinal lymphoma, eosinophilic gastroenteritis, hypogammaglobulinemic sprue, Whipple's disease, lymphangiectasia, abetalipoproteinemia, amyloidosis, mastocytosis, and various mycobacterial, fungal, protozoal, and parasitic infections can be diagnosed through upper GI scopy and biopsy.
• An aspirate of small intestinal contents can be sent for quantitative aerobic and anaerobic bacterial culture if bacterial overgrowth is suspected and for microscopic examination for parasites.

Radiography

• Radiographic studies of the stomach and colon may be complementary to endoscopy and colonoscopy because barium-contrast radiograms can better detect fistulas and strictures.

• An unsuspected diagnosis is made by small intestinal radiography. Abnormal findings such as excess luminal fluid, dilation, and an irregular mucosal surface may lead to a suspicion of celiac sprue, Whipple's disease, or intestinal lymphoma which would help in further investigations and making the ultimate diagnosis. Other diseases that might be diagnosed with small intestinal radiography are carcinoid tumors and scleroderma.

• Computed tomography is performed in patients with chronic diarrhea to examine for pancreatic cancer, chronic pancreatitis, inflammatory bowel disease, chronic infections such as tuberculosis, intestinal lymphoma, carcinoid syndrome, and other neuroendocrine tumors.

• Mesenteric or celiac angiography may show evidence of intestinal ischemia caused by atherosclerosis or vasculitis that are rare causes of chronic diarrhea.

Tests for Bacterial Overgrowth

• The gold standard for diagnosis of bacterial overgrowth has been quantitative culture of an aspirate of luminal fluid and specifically a positive jejunal culture (>106 organisms/mL) in chronic diarrhea patients can be considered evidence of clinically significant bacterial overgrowth in the upper small intestine.

• A breath test using [14C] glycocholate is used to test bacterial overgrowth. The radiolabeled conjugated bile acid is deconjugated by the bacteria, and the 14C in the side chain is metabolized to 14CO2, which is exhaled.

• Another 14C-breath test using [14C] xylose, nonradioactive glucose and nonradioactive lactulose have been developed to test bacterial overgrowth.

• An elevated concentration of hydrogen in breath after overnight fasting also has been proposed as an insensitive but specific marker of small intestinal bacterial overgrowth. This elevated hydrogen concentration may also be seen in patients with malabsorption syndrome.

• An abnormal Schilling II test result (radiolabeled B12 given with intrinsic factor) that normalizes after therapy with broad-spectrum antibiotics has also been considered as a test for small intestinal bacterial overgrowth (the so-called Schilling III test).

Empirical therapy

Empirical therapy is used as an initial treatment before diagnostic testing or after diagnostic testing has failed to confirm a diagnosis or when there is no specific treatment or when specific treatment fails to effect a cure.

• Empirical trials of antimicrobial therapy like metronidazole for protozoal diarrhea or fluoroquinolone for enteric bacterial diarrhea if the prevalence of bacterial or protozoal infection is high in a specific community or situation.

• Most cases of diarrhea, except for high-volume secretory states, respond to a sufficiently high dose of opium or morphine. Codeine, synthetic opioids diphenoxylate and loperamide are less potent. However loperamide is generally used because of its less abuse potential.

• The somatostatin analogue octreotide has proven effectiveness in carcinoid tumors and other peptide-secreting tumors, dumping syndrome, and chemotherapy-induced diarrhea.

• Intraluminal agents include adsorbants, such as activated charcoal, and binding resins like bismuth and stool modifiers, such as medicinal fiber.

Do's

• In chronic diarrhea, always assess volume status first and adequate intravascular volume and correcting fluid and electrolyte disturbances take priority over identifying the causative agent.
• Check for warning signs.
• Report to the public health authorities in case of suspected outbreaks.

Don'ts

• Don't treat patients with severe diarrheal dehydration using 5% dextrose with 1/4 normal saline, as using solutions with lower amounts of sodium (such as 38.5 mmol/L in 1/4 saline with 5% dextrose ) would lead to sudden and severe hyponatremia with a high risk of death.
• ORT is contraindicated in the initial management of severe dehydration and also in patients with frequent and persistent vomiting (more than four episodes per hour), and painful oral conditions such as moderate to severe thrush.
• Loperamide should be avoided in patients with significant abdominal pain, fever and bloody diarrhea that suggests inflammatory diarrhea.

References

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