Acute diarrhea laboratory findings: Difference between revisions
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*Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication]. | *Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication]. | ||
* [[Complete blood count]] ([[CBC]]) | |||
* [[Glucose]] | |||
* [[White blood cells]] ([[WBC]]) | |||
* [[Urinalysis]] | |||
* [[Calcium]] | |||
* [[Thyroid stimulating hormone]] ([[TSH]]) | |||
* [[Liver function tests]] ([[LFT]]s) | |||
* [[Blood urea nitrogen]] ([[BUN]]) / [[creatinine]] | |||
* [[Hepatitis]] serologies | |||
* Stool examinations: | |||
** Stool cultures | |||
** Stool [[electrolyte]]s | |||
** Stool osmolality | |||
** Ova and parasites | |||
** Fecal [[lactoferrin]] | |||
** Fecal [[leukocyte]]s | |||
** Test for ''[[C. difficile]]'' | |||
===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.<ref name="pmid24319453">{{cite journal| author=Viana Freitas BR, Kibune Nagasako C, Pavan CR, Silva Lorena SL, Guerrazzi F, Saddy Rodrigues Coy C et al.| title=Immunochemical fecal occult blood test for detection of advanced colonic adenomas and colorectal cancer: comparison with colonoscopy results. | journal=Gastroenterol Res Pract | year= 2013 | volume= 2013 | issue= | pages= 384561 | pmid=24319453 | doi=10.1155/2013/384561 | pmc=PMC3844264 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24319453 }} </ref> | |||
* Fecal occult blood positivity can also be associated with laxative-induced diarrhea, pancreatic maldigestion, idiopathic secretory diarrhea, and [[microscopic colitis]].<ref name="pmid8602182">{{cite journal| author=Fine KD| title=The prevalence of occult gastrointestinal bleeding in celiac sprue. | journal=N Engl J Med | year= 1996 | volume= 334 | issue= 18 | pages= 1163-7 | pmid=8602182 | doi=10.1056/NEJM199605023341804 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8602182 }} </ref> | |||
=====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]].<ref name="pmid12818275">{{cite journal| author=Kane SV, Sandborn WJ, Rufo PA, Zholudev A, Boone J, Lyerly D et al.| title=Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation. | journal=Am J Gastroenterol | year= 2003 | volume= 98 | issue= 6 | pages= 1309-14 | pmid=12818275 | doi=10.1111/j.1572-0241.2003.07458.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12818275 }} </ref> | |||
* 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.<ref name="pmid20634346">{{cite journal| author=van Rheenen PF, Van de Vijver E, Fidler V| title=Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. | journal=BMJ | year= 2010 | volume= 341 | issue= | pages= c3369 | pmid=20634346 | doi=10.1136/bmj.c3369 | pmc=PMC2904879 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20634346 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21242354 Review in: Ann Intern Med. 2011 Jan 18;154(2):JC1-12] </ref> | |||
=====Sudan Stain for Fat===== | |||
* Excess stool fat should be evaluated by means of a Sudan stain or by direct measurement.<ref name="pmid10761454">{{cite journal| author=Fine KD, Ogunji F| title=A new method of quantitative fecal fat microscopy and its correlation with chemically measured fecal fat output. | journal=Am J Clin Pathol | year= 2000 | volume= 113 | issue= 4 | pages= 528-34 | pmid=10761454 | doi=10.1309/0T2W-NN7F-7T8Q-5N8C | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10761454 }} </ref> | |||
* 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.<ref name="pmid7537217">{{cite journal| author=Rautelin H, Hänninen ML, Sivonen A, Turunen U, Valtonen V| title=Chronic diarrhea due to a single strain of Aeromonas caviae. | journal=Eur J Clin Microbiol Infect Dis | year= 1995 | volume= 14 | issue= 1 | pages= 51-3 | pmid=7537217 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7537217 }} </ref> 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.<ref name="pmid17277989">{{cite journal| author=Friedman M, Ramsay DB, Borum ML| title=An unusual case report of small bowel Candida overgrowth as a cause of diarrhea and review of the literature. | journal=Dig Dis Sci | year= 2007 | volume= 52 | issue= 3 | pages= 679-80 | pmid=17277989 | doi=10.1007/s10620-006-9604-4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17277989 }} </ref> 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.<ref name="pmid8863034">{{cite journal| author=Koontz F, Weinstock JV| title=The approach to stool examination for parasites. | journal=Gastroenterol Clin North Am | year= 1996 | volume= 25 | issue= 3 | pages= 435-49 | pmid=8863034 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8863034 }} </ref> | |||
====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).<ref name="pmid6051321">{{cite journal| author=Fordtran JS| title=Speculations on the pathogenesis of diarrhea. | journal=Fed Proc | year= 1967 | volume= 26 | issue= 5 | pages= 1405-14 | pmid=6051321 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6051321 }} </ref> | |||
=====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.<ref name="pmid1634072">{{cite journal| author=Eherer AJ, Fordtran JS| title=Fecal osmotic gap and pH in experimental diarrhea of various causes. | journal=Gastroenterology | year= 1992 | volume= 103 | issue= 2 | pages= 545-51 | pmid=1634072 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1634072 }} </ref> | |||
=====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.<ref name="pmid1634072">{{cite journal| author=Eherer AJ, Fordtran JS| title=Fecal osmotic gap and pH in experimental diarrhea of various causes. | journal=Gastroenterology | year= 1992 | volume= 103 | issue= 2 | pages= 545-51 | pmid=1634072 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1634072 }} </ref> | |||
=====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.<ref name="pmid6735076">{{cite journal| author=Bo-Linn GW, Fordtran JS| title=Fecal fat concentration in patients with steatorrhea. | journal=Gastroenterology | year= 1984 | volume= 87 | issue= 2 | pages= 319-22 | pmid=6735076 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6735076 }} </ref> | |||
* 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.<ref name="pmid20814209">{{cite journal| author=Hammer HF| title=Pancreatic exocrine insufficiency: diagnostic evaluation and replacement therapy with pancreatic enzymes. | journal=Dig Dis | year= 2010 | volume= 28 | issue= 2 | pages= 339-43 | pmid=20814209 | doi=10.1159/000319411 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20814209 }} </ref> | |||
=====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.<ref name="pmid8193462">{{cite journal| author=Carlson J, Fernlund P, Ivarsson SA, Jakobsson I, Neiderud J, Nilsson KO et al.| title=Munchausen syndrome by proxy: an unexpected cause of severe chronic diarrhoea in a child. | journal=Acta Paediatr | year= 1994 | volume= 83 | issue= 1 | pages= 119-21 | pmid=8193462 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8193462 }} </ref> | |||
* If stool electrolyte analysis suggests osmotic diarrhea (osmotic gap >125 mOsm/kg), magnesium (Mg2+) laxatives may have been ingested.<ref name="pmid2005938">{{cite journal| author=Fine KD, Santa Ana CA, Fordtran JS| title=Diagnosis of magnesium-induced diarrhea. | journal=N Engl J Med | year= 1991 | volume= 324 | issue= 15 | pages= 1012-7 | pmid=2005938 | doi=10.1056/NEJM199104113241502 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2005938 }} </ref> | |||
* 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, [[lymphoma|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.<ref name="pmid24095975">{{cite journal| author=Saad RJ, Chey WD| title=Breath Testing for Small Intestinal Bacterial Overgrowth: Maximizing Test Accuracy. | journal=Clin Gastroenterol Hepatol | year= 2013 | volume= | issue= | pages= | pmid=24095975 | doi=10.1016/j.cgh.2013.09.055 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24095975 }} </ref> | |||
* 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.<ref name="pmid2295385">{{cite journal| author=Corazza GR, Menozzi MG, Strocchi A, Rasciti L, Vaira D, Lecchini R et al.| title=The diagnosis of small bowel bacterial overgrowth. Reliability of jejunal culture and inadequacy of breath hydrogen testing. | journal=Gastroenterology | year= 1990 | volume= 98 | issue= 2 | pages= 302-9 | pmid=2295385 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2295385 }} </ref> | |||
* 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 test|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).<ref name="pmid5762651">{{cite journal| author=| title=Schilling test of vitamin B12 absorption. | journal=Br Med J | year= 1969 | volume= 1 | issue= 5639 | pages= 300-1 | pmid=5762651 | doi= | pmc=PMC1982167 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5762651 }} </ref> | |||
==References== | ==References== |
Revision as of 13:56, 7 February 2018
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
OR
Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
OR
[Test] is usually normal among patients with [disease name].
OR
Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
OR
There are no diagnostic laboratory findings associated with [disease name].
Laboratory Findings
- There are no diagnostic laboratory findings associated with [disease name].
OR
- An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
- [Test] is usually normal among patients with [disease name].
- Laboratory findings consistent with the diagnosis of [disease name] include:
- [Abnormal test 1]
- [Abnormal test 2]
- [Abnormal test 3]
- Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
- Complete blood count (CBC)
- Glucose
- White blood cells (WBC)
- Urinalysis
- Calcium
- Thyroid stimulating hormone (TSH)
- Liver function tests (LFTs)
- Blood urea nitrogen (BUN) / creatinine
- Hepatitis serologies
- Stool examinations:
- Stool cultures
- Stool electrolytes
- Stool osmolality
- Ova and parasites
- Fecal lactoferrin
- Fecal leukocytes
- Test for C. difficile
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.[1]
- Fecal occult blood positivity can also be associated with laxative-induced diarrhea, pancreatic maldigestion, idiopathic secretory diarrhea, and microscopic colitis.[2]
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.[3]
- 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.[4]
Sudan Stain for Fat
- Excess stool fat should be evaluated by means of a Sudan stain or by direct measurement.[5]
- 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.[6] 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.[7] 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.[8]
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).[9]
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.[10]
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.[10]
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.[11]
- 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.[12]
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.[13]
- If stool electrolyte analysis suggests osmotic diarrhea (osmotic gap >125 mOsm/kg), magnesium (Mg2+) laxatives may have been ingested.[14]
- 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.[15]
- 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.[16]
- 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).[17]
References
- ↑ Viana Freitas BR, Kibune Nagasako C, Pavan CR, Silva Lorena SL, Guerrazzi F, Saddy Rodrigues Coy C; et al. (2013). "Immunochemical fecal occult blood test for detection of advanced colonic adenomas and colorectal cancer: comparison with colonoscopy results". Gastroenterol Res Pract. 2013: 384561. doi:10.1155/2013/384561. PMC 3844264. PMID 24319453.
- ↑ Fine KD (1996). "The prevalence of occult gastrointestinal bleeding in celiac sprue". N Engl J Med. 334 (18): 1163–7. doi:10.1056/NEJM199605023341804. PMID 8602182.
- ↑ Kane SV, Sandborn WJ, Rufo PA, Zholudev A, Boone J, Lyerly D; et al. (2003). "Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation". Am J Gastroenterol. 98 (6): 1309–14. doi:10.1111/j.1572-0241.2003.07458.x. PMID 12818275.
- ↑ van Rheenen PF, Van de Vijver E, Fidler V (2010). "Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis". BMJ. 341: c3369. doi:10.1136/bmj.c3369. PMC 2904879. PMID 20634346. Review in: Ann Intern Med. 2011 Jan 18;154(2):JC1-12
- ↑ Fine KD, Ogunji F (2000). "A new method of quantitative fecal fat microscopy and its correlation with chemically measured fecal fat output". Am J Clin Pathol. 113 (4): 528–34. doi:10.1309/0T2W-NN7F-7T8Q-5N8C. PMID 10761454.
- ↑ Rautelin H, Hänninen ML, Sivonen A, Turunen U, Valtonen V (1995). "Chronic diarrhea due to a single strain of Aeromonas caviae". Eur J Clin Microbiol Infect Dis. 14 (1): 51–3. PMID 7537217.
- ↑ Friedman M, Ramsay DB, Borum ML (2007). "An unusual case report of small bowel Candida overgrowth as a cause of diarrhea and review of the literature". Dig Dis Sci. 52 (3): 679–80. doi:10.1007/s10620-006-9604-4. PMID 17277989.
- ↑ Koontz F, Weinstock JV (1996). "The approach to stool examination for parasites". Gastroenterol Clin North Am. 25 (3): 435–49. PMID 8863034.
- ↑ Fordtran JS (1967). "Speculations on the pathogenesis of diarrhea". Fed Proc. 26 (5): 1405–14. PMID 6051321.
- ↑ 10.0 10.1 Eherer AJ, Fordtran JS (1992). "Fecal osmotic gap and pH in experimental diarrhea of various causes". Gastroenterology. 103 (2): 545–51. PMID 1634072.
- ↑ Bo-Linn GW, Fordtran JS (1984). "Fecal fat concentration in patients with steatorrhea". Gastroenterology. 87 (2): 319–22. PMID 6735076.
- ↑ Hammer HF (2010). "Pancreatic exocrine insufficiency: diagnostic evaluation and replacement therapy with pancreatic enzymes". Dig Dis. 28 (2): 339–43. doi:10.1159/000319411. PMID 20814209.
- ↑ Carlson J, Fernlund P, Ivarsson SA, Jakobsson I, Neiderud J, Nilsson KO; et al. (1994). "Munchausen syndrome by proxy: an unexpected cause of severe chronic diarrhoea in a child". Acta Paediatr. 83 (1): 119–21. PMID 8193462.
- ↑ Fine KD, Santa Ana CA, Fordtran JS (1991). "Diagnosis of magnesium-induced diarrhea". N Engl J Med. 324 (15): 1012–7. doi:10.1056/NEJM199104113241502. PMID 2005938.
- ↑ Saad RJ, Chey WD (2013). "Breath Testing for Small Intestinal Bacterial Overgrowth: Maximizing Test Accuracy". Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.2013.09.055. PMID 24095975.
- ↑ Corazza GR, Menozzi MG, Strocchi A, Rasciti L, Vaira D, Lecchini R; et al. (1990). "The diagnosis of small bowel bacterial overgrowth. Reliability of jejunal culture and inadequacy of breath hydrogen testing". Gastroenterology. 98 (2): 302–9. PMID 2295385.
- ↑ "Schilling test of vitamin B12 absorption". Br Med J. 1 (5639): 300–1. 1969. PMC 1982167. PMID 5762651.