Chronic Diarrhea Neil Stollman MD San Francisco General Hospital University of California San Franci

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Chronic DiarrheaNeil Stollman MDSan Francisco
General HospitalUniversity of California San
Francisco
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Case Discussion

• You are in GI (or Medicine) Clinic at SFGH
• Its 455 and being the hard-working
  eager-to-learn Fellow/Resident that you are you
  pick up the last chart (hoping of course for a
  nice simple heme stoolno such luck)
• The patient is a 37 year old man referred from
  his PCP with (gulp) chronic diarrhea.
  
• Undeterred you dive right in...

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WHAT IS CHRONIC DIARRHEA

• Dictionary Abnormal frequency and liquidity of
  fecal evaluations
  
• Scientist Increased stool weight (above ULN
  fecal weight eg. 200 gm/day)
  
• Patients Generally a) dont weigh their stool
  and b) consider consistency mostly in reporting
  diarrhea

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And for how long..

• No consensus
• Should be long enough to allow most cases of
  acute diarrhea (generally self limited and
  infectious) to run their course
  
• Reasonable 4-6 weeks

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Background stuff...

• Differentiate from
• Irritable Bowel Syndrome
• Fecal incontinence may be reported by patient as
  diarrhea and should be specifically queried as
  w/u entirely different
  
• Prevalence
• Children worldwide 3-20
• Adults in US probably about 5
• 3000000 lost work days and 350M annually

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OK back to the patient..

• What elements of his history will be relevant
  and/or may be helpful in elucidating the cause of
  his problem

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Chronic DiarrheaClues in the history

• Characteristics congenital abrupt or gradual in
  onset watery bloody fatty
  
• Continuous or intermittent nocturnal
  incontinence response to fasting
  
• Duration
• Travel history
• Potentially contaminated food or water exposure
• Family members ill
• Hx eating disorder 20 gain malingering
  (suggests factitious)

• Abdominal Pain (IBD IBS ischemia)
• Weight loss (malabsorption CA ischemia
• Aggrevating factors eg. diet stress
• Mitigating factors eg. diet meds
• Previous evaluations
• Systemic Diseases eg. thyroid DM CVD AIDS
  CA
  
• Medication history
• Hx XRT surgery

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Physical Examination

• Rarely yields definitive cause but gives
  important information about extent of fluid and
  nutritional depletion.
  
• Flushing rashes on skin mouth ulcers
• Thyroid wheezing arthritis heart murmers
  hepatomegaly ascites edema
  
• Anorectal exam sphincter tone contractility
  perianal fistulas/abscess

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Routine Lab tests

• CBC evaluate for anemia leukocytosis
  (suggesting inflammation) eosinophilia
  (suggesting neoplasm allergy CVD parasite
  eosinophilic enteritis)
• Chemistries fluid/electrolyte status
  nutritional status liver dz

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Therapeutic trial

• If specific dx is obvious might stop here and
  initiate a specific therapeutic trial ie. stop
  potentially offending drug empiric antibiotics
  for parasites (eg. metronidazole) or bacteria
  (eg. cipro) in situations in which infectious
  diarrhea is highly suspicious.
• Need specific end-point to avoid delaying
  further evaluation

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OK back to our patient.

• Complete history physical examination and
  routine lab tests are unrevealing.
  
• What are potential further evaluations that you
  would consider

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Stool analysis (stool is the tool!)

• Can be quantitative or spot
• Potential studies for initial evaluation
• Stool FOBT
• Stool WBC
• Stool fat
• Stool culture (bacterial) and micro (OP)
• Stool Na/K for osmotic gap osmolality
• Stool pH
• Laxative screening

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Stool occult blood

• Utility of guaiac card testing in evaluation of
  chronic diarrhea not well established.
  
• Unclear sensitivity and specificity
• May be positive due to rectal irritation or other
  occult lesion rather than from primary diarrheal
  process.
  
• Probably not very useful

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Stool WBC

• Usually done with Wrights staining and
  microscopy.
  
• Operator dependent with false positives and
  negatives
  
• utility of latex agglutination test for PMN
  product lactoferrin. Highly sensitive for
  detection of PMNs in acute infectious diarrhea
  and PMC

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Stool fat

• Qualitative usually done with Sudan Stain also
  very operator-dependent
  
• Quantitative eg. concentration or fat / 100
  gm stool. (food diary required many patients
  curb food intake during diarrhea)
  
• Normals (w/o diarrhea) ULN 7gm/d (9 of intake)
• BUT diarrhea itself can cause secondary
  steatorrhea even when fat digestion and
  absorption are intact thus levels of 7-14 gm/day
  not specific.
• 14 gm/day fairly specific for fat
  maldigestion/malabsorption (eg. pancreatic or
  biliary steatorrhea SB mucosal dz)

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Stool Culture

• Although bacterial infection rarely causes
  chronic diarrhea (esp if immunocompetent) can be
  easily excluded with stool culture
  
• Special media required for Aeromonas and
  Pleisiomonas (suspect if untreated well water or
  fresh-water swimming)
  
• Cryptosporidia and Microsporidia CAN infect
  immunocompetent hosts
  
• Selectively consider micro for OP ELISA for
  Giardia-specific antigen C. diff toxin

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Stool electrolytes / osmolar gap

• Bowel is freely permeable membrane normal stool
  osmolality must be near that of serum ie. 290
  mOsm/kg
  
• For calculation of osmotic gap we use 290 rather
  than measured total stool Osm which increases in
  collection container rapidly as carbohydrates
  are converted by bacterial fermentation to
  osmotically active organic acids

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Stool electrolytes / osmolar gap II

• Osmotic Gap 290 - 2 (Na K) (which accounts
  for associated anions)
  
• Secretory diarrhea unabsorbed electrolytes
  retain water in lumen
  
• Gap
• Osmotic diarrhea non-electrolytes retain water
  in lumen
  
• Gap 125 mOsm/kg in pure osmotic diarrhea

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Stool Osmolarity III

• Measured Osmolality - shouldnt be used to
  calculate gap but may have occasional utility
  
• Low osmolality (contamination of stool specimen with water or
  dilute urine or presence of gastrocolic fistula
  and ingestion of hypotonic fluid.
• High osmolality (290) may occur during storage
  contamination by concentrated urine gastrocolic
  fistula and ingestion of hypertonic fluid or
  ingestion of large amounts of poorly absorbed
  carbohydrate (eg. lactulose sorbitol)

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Stool pH

• Stool pH malabsorption eg lactulose or sorbitol.
  
• In generalized malabsorption in which fats and
  amino acids are also malabsorbed the fecal pH
  may be higher or normal

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Stool screen for laxatives

• Simple test for phenolphthalein (now off market
  in US) involves alkalinization of stool with
  NaOH causing pink color
  
• If no gap may be NaPO4 or NaSO4 ingestion
• Suspect if high stool Na low Cl-
• Can measure fecal sulfate or phosphate
• If increased gap may be Mg ingestion
• Suspect if stool Mg 45 mmol/L
• ethics of room search for laxatives

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• Any blood or urine tests of value in this
  situation

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Urine tests in chronic diarrhea

• May aid in laxative identification
• 5-HIAA (for carcinoid syndrome)
• VMA metanephrines (pheochromocytoma)
• Histamine (mast cell disease foregut carcinoids)

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Blood tests in chronic diarrhea

• Serum VIP (pancreatic cholera syndrome) suspect
  if chronic secretory diarrhea volume 1L/day
  low serum K
  
• Calcitonin (medullary thryoid CA)
• Gastrin (ZES)
• Celiac disease
• IgG antigliadin Abs most sensitive
• antiendomysial Abs most specific
• E. histolytica titers

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To scope or not to scopelower

• AGA Guidelines F/S generally best initial test
  although when suspicion for IBD is high weight
  loss gross or occult GIB abnormal TI suspected
  or F/S negative colonoscopy is reasonable
• Can dx melanosis IBD amebiasis grossly and
  microscopic colitis (lymphocytic eosinophilic
  collagenous) amyloidosis Tb with biopsy
  (random 4-quadrant Q10-20 cm even in normal
  gross exam)

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To scope or not to scopeupper

• EGD w/ SB Bx can diagnose Crohns sprue
  giradiasis amyloid Whipples lymphangiectasia
  abetalipoproteinemia and many mycobacterial
  fungal protozoan and parasitic infections.
• Increased yield if steatorrhea or FOBT
• Duodenal bx adequate in most cases

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Any role for Radiology

• No formal studies but SBFT probably has some
  role.
  
• Enteroclyis not better than oral SBFT for this
  indication
  
• Mesenteric angiography if ischemia (vasculitis
  atherosclerosis) suspected
  
• Abd CT not generally useful unless pancreatic
  dysfunction suspected or neuroendocrine tumor by
  blood tests

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Physiological Tests-Mucosal absorption

• D-xylose test ingest 25g of D-xylose and assess
  5-hour urine collection (serum level (
• With normal renal function low urine or serum
  levels suggests diseased small bowel mucosa eg
  Crohns sprue etc

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Physiological Tests-Ileal absorption

• Ileum absorbs B12 NaCl and bile acids
• Schilling II (labeled B12 IF) may be useful in
  evaluation of chronic diarrhea
  
• Intestinal perfusion-not useful
• Bile acid malabsorption can be tested by
  measuring bile acids in quantitative stool
  collection nuclear med studies (Se75-HCAT) but
  not standardized or widely available many use a
  therapeutic trial of cholestyramine as indirect
  test

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Physiological Tests-Breath Tests

• Most use substances labeled with 14C or 13C or
  non-labeled fermentable sugar
  
• Metabolism of these compounds produces
  isotopically-labeled CO2 or unlabeled H2 that can
  be detected in expired air

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Breath Tests-Lactose Malabsorption

• Therapeutic trial of lactose-free diet OK
• Lactose Hydrogen Breath Test malabsorbed lactose
  gets fermented in colon to organic acids and
  gases including H2 which is then absorbed
  excreted by lungs measured by chromatography.
• Controversy over dose (12.5gm 25gm 50gm most
  use 25g) and cutoff for positive result (most use
  increase of 20ppm above baseline w/in 4 hours)
  
• 10 of pts dont have colonic flora that can
  produce H2 and may have false negative tests

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Breath Tests-Bacterial Overgrowth

• Overgrowth causes diarrhea mainly by
  deconjugating bile acids so they cant form
  micelles and fat malabsorption occurs
  
• Gold Standard quantitative culture of luminal
  fluid (106 organisms ). Not standardized and
  cumbersome to do.

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Breath Tests-Bacterial Overgrowth II

• 14C-labeled glycocholate (conjugated BA gets
  deconjugated and 14C02 exhaled)-not widely
  available
  
• 14C-xylose (1gm)-if SB bacteria metabolize get
  early release of 14C02-also not widely available
  
• Can also use non-labeled glucose (50g) or
  lactulose and look for early breath H2 peak or
  Schilling III abnormal result that corrects
  after antibiotics

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Physiological Tests-tests of pancreatic exocrine
function

• Intubation tests (measuring HCO3 and enzymes
  after secretin/CCK) difficult and rarely done
  
• Bentiromide agent gets digested by chymotrypsin
  releasing PABA absorbed and excreted in urine.
  dose) is abnormal. Limited by urine collection
  and renal insufficiency.
• Can measure stool chmotrypsin trypsin lipase
  and elastase (newest kid on the block hot now)

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Recommended Approach-AGA

• Detailed history physical examination routine
  labs done initially as outlined.
  
• If points strongly to specific diagnosis
  specific confirmatory tests or empiric therapy
  may be warranted.
  
• In still unclear quantitative stool collection
  best next test evaluating
  
• stool weight
• presence / absence of steatorrhea
• osmotic or secretory classification

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Flow chart
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Secretory diarrhea
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Osmotic diarrhea
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Inflammatory diarrhea
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Fatty diarrhea
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Diff Dx after stool collection.

• Osmotic diarrhea
• Mg2 PO43- SO42-
• CHO malabsorption
• Fatty diarrhea
• Mucosal disease
• Short bowel syndrome
• Bacterial overgrowth
• Ischemia
• Pancreatic or biliary maldigestion
• Inflammatory diarrhea
• IBD PMC
• Bacterial viral parasitic infections
• Ischemia

• Secretory diarrhea
• Non-osmotic laxatives
• Bacterial toxins
• Cholerrheic diarrhea
• IBD collagenous microscopic colitis
• Vasculitis
• Drugs poisons
• Motility post-vagotomy diabetic hyperthyroid
  IBS
  
• Neuroendocrine tumors
• Addisons disease
• Neoplasia

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Finally when all else fails..

• Empiric therapy may be used as
• Temporizing Rx before testing complete
• After testing has failed to confirm Dx
• When Dx made but no specific Rx available or
  fails to affect cure
  
• Symptomatic treatment options
• Oral rehydrating solutions
• Bile-acid binding agents bismuth fiber
• Opiates diphenoxylate loperamide codeine MTO
• Somatostatin analogue (limited success in AIDS
  and SBS second-line agent)