Source: MKSAP 16



    • Definition:
      • Increase in frequency or liquidity of stool (In the past defined as stool weight >200g/day).
    • Classification
      • <2w = acute
      • 2-4w = subacute
      • >4w = chronic
    • Another way:
      • Osmotic
        • Lower stool volumes (<1L/day), stools stop when stop eating.
        • High Stool Osmotic Gap
      • Secretory
        • Pass liters of stool/day => volume depletion, dehydration, electrolyte disturbances.
        • Will persist despite fasting.
        • Can also check stool 
        • Low osmotic gap
      • Inflammatory
        • Mucous or blood in stool.
        • Fecal leukocytes in stool microscopically.
      • Malabsorptive
        • Umbrella term for any condition that can cause loss of fat or carbohydrates or protein in stool.
        • Crohn's, Celiac, etc..
    • Diarrhea Evaluation.jpg


    Clinical History

    • Travel, medications, surgical hx, family hx, dietary, stool timimg/characterization, weight loss, joint pains, skin lesions, fevers.



    • Stool studies    
      • Stool osmotic gap
        • 290 − 2 × [stool sodium + stool potassium] = GAP (another solute in stool)  (290 = expected osmolality of stool)
          • If GAP > 100 (mmol/Kg or mOsm/kg) = osmotic diarrhea.
          • If GAP < 50 = secretory diarrhea
      • Fecal fat quantification
      • Cultures (for bacterial overgrowth)
    • Upper scope (small bowel cultures for bacterial overgrowth, duodenal biopsies)
    • Lower scope (terminal ilium for crohn's, random biopsies for microscopic colitis, colonic biopsy)
    • NOTE: biopsies should be obtained from duodenum and colon even if endoscopically normal, b/c can still have celiac (duodenum) and microscopic colitis (colon).
    • Other Tests
      • Breath testing (for lactose, fructose, sucrose)
      • Secretagogues (Serum gastrin levels, calcitonin, VIP, tryptase, urine 5-hydroxyindoleacetic acid).


    Acute Diar​rhea

    • Most does not need to be evaluated
    • Indications for evalutation:
      • ​Indications to Evaluate Acute Diarrhea

        • Fever ≥38.5 °C (101.3 °F)
        • Significant abdominal pain
        • Severe diarrhea leading to volume depletion
        • Inflammatory bowel disease
        • Recent antibiotic use
        • Elderly patients
        • Hospitalized patients
        • Pregnant women
        • Immunocompromised patients
        • Food handlers
    • (See above for workup)

    ​Chronic Diarrhea

    • Broad differential.
    • (See above for workup)




    Clues or Risk Factors

    Inflammatory bowel disease



    Ulcerative colitis

    Colonoscopy with biopsies

    Bloody diarrhea, tenesmus

    Crohn disease

    Ileocolonoscopy with biopsies, small-bowel imaging (SBFT, CTE, MRE)

    Weight loss, abdominal pain, perianal disease

    Microscopic colitis

    Colonoscopy with biopsies

    Secretory diarrhea

    Celiac disease

    Serologies (tTG IgA), upper endoscopy with small-bowel biopsies

    Extraintestinal features, family history

    Small intestinal bacterial overgrowth

    Upper endoscopy with small-bowel cultures, hydrogen breath testing

    Bloating, excess flatus, malabsorption

    Carbohydrate malabsorption

    Detailed history, hydrogen breath testing, stool osmotic gap, avoidance trial

    Bloating, excess flatus

    Pancreatic insufficiency

    Features of chronic pancreatitis on imaging (CT, EUS, MRCP), 48- to 72-hour fecal fat quantitation, pancreatic function tests

    Known pancreatic disease/resection, weight loss

    Bile acid malabsorption

    Compatible history, clinical response to cholestyramine

    Terminal ileal resection (<100 cm)

    Bile acid deficiency

    Compatible history, steatorrhea, response to medium-chain triglyceride diet

    Terminal ileal resection (>100 cm)


    Colonoscopy with biopsies (for colonic ischemia), duplex ultrasound or MRA (for chronic mesenteric ischemia)

    Low-flow states, cardiovascular risk factors

    Radiation enteropathy/proctopathy

    Compatible history, small-bowel imaging, colonoscopy with biopsies

    Any previous radiation to abdomen or pelvis

    Irritable bowel syndrome

    Compatible history, fulfills Rome criteria, exclude other diseases

    Symptoms relieved after a bowel movement

    Eosinophilic enteritis

    Eosinophilia on small-bowel biopsies (for mucosal-based disease) or full-thickness bowel biopsy (for submucosal- or serosal-based disease)

    Atopic history, peripheral eosinophilia (not required)

    Whipple disease

    Small-bowel biopsies showing PAS+ macrophages that are acid-fast negative, polymerase chain reaction on any biopsied affected tissue

    Arthralgia, lymphadenopathy, neurologic symptoms


    Detailed history and review of chart

    New medications, initiation of enteral nutrition

    Factitious diarrhea

    Diagnosis of exclusion

    Often high volume and frequency, bulimia, anorexia, weight loss, stool osmolality and osmolar gaps may be helpful (>50 mOsm/kg [50 mmol/kg]), stool magnesium >90 meq/L may be diagnostic


    Malabsorption Syndromes

    • Generalized loss of nutrients (carbohydrates, fat, or protein) in the digestive tract.


    Malabsorption Symptoms Workup Causes
    Fat Malabsorption

    Diarrhea, Wt loss

    Stool: Foul smelling, float, oily appearance

    - Quantitative fecal fat collection (48-72hrs)

      Must intake 100g of fat daily for 7 days.


    - Imaging of pancreas, upper endoscopy

      (small bowel biopsy + cultures)

    - Pancreatic insufficiency

    - Small bowel Disease

     (incl. Celiac, autoimmune

      enteropathy, small intestinal

      bacterial overgrowth +other)



    Diarrhea, Bloating, Extra gas, no weight


    - Clinical history (eliminate item from diet)

    - Hydrogen breath test (correlate w/ sympt)

      (many malabsorb but asymptomatic)

    - **Lactase deficiency**

    - Fructose/Sucrose




    Diarrhea, Edema, ascites, anasarca

    (rare in isolation, usually have other

     malabsorption syndromes)

    - Stool alpha-1-antitrypsin clearance test

    (A1A unique in stool, only protein not

    cleaved by pancreatic enzymes,

    not absorbed or secreted in bowel 

     = true marker of protein loss compare

    to normal range)

    - C. difficile infection

    - IBD, Celiac Dz

    - Whipples Disease

    - Amyloidosis

    - Constrictive pericarditis

    - Lymphangiectasia, 

      Lymphatic obstruction


    Celiac Disease

    • Immunologic response to dietary gliadins in patients who are at risk genetically (presence of HLA-DQ2 or HLA-DQ8)
    • Affects 1% of US.
    • Sensitivity to gluten.
    • Gluten present in wheat, barley, and rye.
      • Often cross-contamination of oats.
    • Symptoms:
      • Diarrhea, bloating, weight loss.
      • Extraintestinal manifestations
        • NOTE: Vitamin B12 deficiency usually concominant -> replacing with HUGE doses (150,000u 2x/week) and B12 is still low. 




        Anemia (low iron, vitamin B12, folate),

        functional asplenia (Howell-Jolly bodies on blood smear)


        Osteopenia/osteoporosis, osteomalacia, arthropathy


        Seizures, peripheral neuropathy, ataxia


        Infertility, recurrent miscarriages


        Dermatitis herpetiformis (Classic)



        Glomerular IgA deposition


        Enamel defects, abnormal liver chemistry tests, vitamin-deficient states

    • Investigations
      • Best serologic screen: Tissue Transglutaminase IgA antibody (Sn 69-93%, Sp 96-100%).
        • Can be false-negative in 5% of pts due to selective IgA deficiency
        • IgG-based TtG (Tissue Transglutaminase), but do not use as screen (poor in non-IgA deficient pts).
      • Definitive Dx: Small Bowel Biopsy.
      • Genetic Testing: Tests for HLA-DQ2 or HLA-DQ8, but high false positive rate
        • Only indicated for patients on gluten-free diet, and refuse to re-introduce gluten.
        • If NEGATVE = DO NOT have Celiac Disease. 
        • If POSITIVE = unclear. (30-40% of population are positive).
      • Therapeutic trial of glutent-free diet: TtG IgA will be normal if gluten intake is stopped. 
    • Management:
      • Avoid gluten-containing products.
        • Includes wheat, barley, rye.
          • Also suggest avoiding oats in first year (due to cross-contamination of oat products).
          • Can re-introduce oats after 1 year once clinically stable. 
      • Can follow TtG levels if needed.
      • If recurrence of symptoms:
        • Can check TtG IgA level to assess gluten in diet.
        • Inavertant or intentional gluten loss is most common cause of recurrence of symptoms.
      • Ongoing Care:
        • Baseline DEXA Scan (BMD risk) recommended
        • Vitamin/Mineral Levels (B12, iron, folate, etc.)
        • Vaccination for encapsulated organisms
          • Esp if have Howell-Jolly bodies on peripheral smear = functionally asplenic
          • Vaccinate: Pneumococcus, Meningicoccus, H. influenzae
    • Associated Conditions: (Share HLA susceptibility)
      • (Can cause recurrent diarrhea in these patients).
      • Microscopic colitis (most common, 70-fold increase in risk).
      • Lactose malabsorption
      • Small-Intestinal Bacterial Overgrowth
      • Pancreatic insufficiency
      • IBD
      • Refractory celiac disease
      • Enteropathy-associated T-cell Lymphoma


    Small Intestinal Bacterial Overgrowth

    • Too many bacteria and alterations in types of bacteria in small bowel.
    • Clincal Features:
      • Diarrhea, bloating, and weight loss.
      • Malabsorption of fat, protein or carbohydrates (combinations).
    • Look for Risk Factors of bowel stasis:
      • Key feature for risk factors is BOWEL STASIS


    • Altered gastric acid (achlorhydria, gastrectomy)
    • Structural Abnormalities (strictures, small-bowel diverticula, blind loops)
    • Intestinal dysmotility (DMII, Neuromuscular disorders).
    • Investigations:
      • Macrocytic anemia
        • with B12 deficiency and folate excess (bacteria consume B12 and make folate + vitamin K).
      • Two ways to test:
        • Lactose Breath Test (or Hydrogen Breath Test) (Lactulose or glucose as substrate, look for early peak of hydrogen on breath) --> small bowel bacteria fementing CHO.
          • Lots of false positive/negative results, affected by transit time, abx use, CHO ingestion.
        • Upper Endoscopy: Small bowel cultures (duodenum or jejunum)
          • Concentration of bacteria >10^5 org/mL of fluid (combination of aerobic/anaerobic).
    • Management:
      • Antibiotics, often require one course of antibiotics x7-10d.  (i.e. cipro/flagyl)
        • Wait to see if symptoms recur, if recur then rotate antibiotics.
      • Can use any antibiotics (amox-clav, fluoroquinolones, tetracycline, metronidazole, rifaximin).
      • If bloating significant symptom, can reduce lactose intake.

    Short Bowel Syndrome

    • Defined as <200cm of remaining small bowel (normal ~600cm, 2/3 lost).
    • Biggest issue is water/electrolyte loss in stool.
      • Always check if colon is in continuity with small bowel.
        • Colon can compensate by increasing absorption of water/electrolytes.
    • Causes:
      • Large Resections of Small Bowel for many reasons:
        • Crohn's Disease, Bowel ischemia, volvulus, abdo trauma, tumors (Desmoid), 
      • Also: radiation enteritis
    • Management:
      • Avoid chronic gastric acid suppression (can worsen diarrhea).
      • Oral rehydration solutions, antidiarrhea agents.
      • May require TPN long term, but continue enteral nutrition (stimulate bowel adaptation).
      • Bowel transplants: very rare, select centers, depends on original dx.  (mostly in kids).
    • Complications:
      • Catheter infections, liver disease, bacterial overgrowth, micronutrient deficiencies.


    Lactose Intolerance

    • Lactase deficiency leading to lactose malabsorption.
    • Lactase is on tips of brush border, prone to injury/loss.
    • Can be affected by any process disturbing brush border: (Celiac, Brohn's etc..)
    • Risk Factors:
      • Primary Deficiency: Ethnic groups with no dairy products in historical background
        • (Blacks, American Indians, Hispanics, Asians).
      • Adult Loss: Europeans: can lose lactase when older.
      • Provoked:  Celiac, Crohn's, radiation enteritis, small bowel resection.
      • Transient: After gastroenteritis (usually self-limited)
    • Symptoms:
      • Osmotic diarrhea, bloating, excess flatus.
      • NOT weight loss, bleeding (if see weight loss, bleeding, likely lactose intolerance is secondary to something).
    • Workup:
      • Dietary history is usually enough.
      • Lactose malabsorption:
        • Hydrogen breath test - lactose as substrate
          • Look for rise in breath hydrogen >20ppm due to colonic bacterial lactose breakdown.
    • NOTE: Patients can malabsorb lactose, but may not be lactose intolerant.
    • Management:
      • Avoid lactose
        • Supplement calcium, vitamin D.
      • Some evidence that CAN ingest equivalent to 1 cup of milk/day (12g of lactose) with no symptoms.
        • Recommended ingest slowly during day and with meals (instead of bolus by itself)
        • Yogurt may be tolerated, as empties from stomach slower than milk
          • (can contain lactase from bacteria).
      • Lactase in milk: reported improvement in symptoms, but dosing not studied.


    Irritable Bowel Syndrome

    • Should not cause weight loss or nocturnal stools (also fevers, night sweats, etc..)
    • These are "alarm features" and other dx should be explored.
    • 7% prevalence in population (<50yo, poor SES)
    • Pathophysiology:
      • Poorly understood
      • Altered motility, inflammation, dysfunctional serotonin syndrome, etc...
    • Risk Factors:
      • History of physical/sexual abuse.
      • Food intolerance, estrogen use
      • Somatization traits, psychologic distress
      • History of Infectious Gastroenteritis
    • Diagnosis:
      • The American College of Gastroenterology
      • Abdominal pain or discomfort that occurs in association with altered bowel habits over >3 months. 
    • Clinical Features:
      • Abdominal discomfort/pain, altered BM + NO ORGANIC CAUSE
      • No ALARM features (fevers, night sweats, weight loss, etc...)
      • Types:
        • Types: (From ROME III)

          1. IBS with constipation (IBS-C)

                —hard or lumpy stools ≥25% and loose (mushy) or watery stools <25% of bowel movements

          2. IBS with diarrhea (IBS-D)

                —loose (mushy) or watery stools ≥25% and hard or lumpy stools <25% of bowel movements

          3. Mixed IBS (IBS-M)

                —hard or lumpy stools ≥25% and loose (mushy) or watery stools ≥25% of bowel movements

          4. Unsubtyped IBS (IBS-U)

               —insufficient abnormality of stool consistency to meet criteria IBS-C, D, or M

          Source: MKSAP 16 / Alimentary Pharmacology & Therapeutics. 26(6). Ersryd A, Posserud I, Abrahamsson H, Simrén MM. Subtyping the irritable bowel syndrome by predominant bowel habit: Rome II versus Rome III; 953-961

    • Diagnosis:
      • American College of Gastroenterology IBS Recommendations: 

        • "Simple definition"  of IBS ---> ALL 3 of:
          • 1.  Abdominal pain or discomfort
          • 2.  Associated with altered bowel habits
          • 3.  Over a period of ≥ 3 months
            (No ALARM symptoms)

        • ALARM Symptoms of IBS:
          • ***Anemia***
          • ***Weight loss***
          • Age of onset >50y
          • Nocturnal Symptoms
          • Abnormal physical exam
          • More obvious ones:
            Rectal Bleeding, IBD, Celiac Disease, Family Hx of Colon Ca

                 *** - Represents symptoms most likely to lead to alternate dx.

      • Must fit clinical features
      • Workup:
        • CBC, ESR/CRP, TSH, stool for O&P.
        • If diarrhea-predominant or mixed... rule out celiac (TTG antibody)
        • What not to do:
          • Abdo imaging and colonoscopy NOT recommended in absence of ALARM symptoms
          • Cultures for small bowel bacterial overgrowth not recommended.
    • Management:
      • Educate Patient (UpToDate or MAYO clinic has good patient info)
        • Advise to try to avoid unnecessary surgeries (high rate of surgery - cholecystectomy etc..)
      • Can do a trial of lactose avoidance.
      • Symptom Treatment Notes



        Insoluble Fibre

        (FIRST LINE)

        - Psyllium, Ispaghula, Calcium polycarbophil

        - Modest improvement in symptoms

          Soluble Fibre

        - Wheat, Bran, Corn

        -  = PLACEBO (no help)


        - Better for IBS-C (accelerate transit)

        - NNT = 3.5


        Low dose Tricyclic


        - Better for IBS-D (anticholinergic --> slows down bowel)

        - NNT = 4


        - Not FDA approved

        - Improves global IBS function (trial shows)

          Osmotic Laxatives - Limited Data (helps frequency, but not abdo pain)
        Diarrhea Loperamide  
          Low dose TCA

         (see above)

          Alosetron (5-HT3 Antagonist)

        - Helps Diarrhea significantly

        - Can cause severe constipation and colonic ischemia 

        - (strictly FDA controlled)


        Fiber (see above)  

        Must have pregnancy test before starting (if childbearing age) and should take contraception. 

        - NOT first line, only if fiber failed.

          SSRI (see above)  
        Abdo Pain

        Hyoscine, Peppermint


        - (All smooth muscle relaxants)

        - Some short-term benefit (Safety not well documented)


        SSRI's, TCA

        (see above)

          NO Opioids!!! - Do not use opioids --> narcotic bowel syndrome, paradoxical worsening.
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