Approach to Chronic Diarrhea

8/10/2019 Approach to Chronic Diarrhea

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Approach to Chronic Diarrhea

Jos Geraldo P. Ferraz, MD, PhDGI DivisionMucosal Inflammation Research GroupThe University of Calgary


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Diarrhea

Increased frequency of bowel movements and

reduced consistency/increased fluidity of stool

Number of bowel movements greater than 3/daily,with stool weight > 200g/d

Duration:

Acute(< 2 weeks)

Persistent(> 2 and < 4 weeks)

Chronic(> 4 weeks)


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Diarrhea - Issues

Second (?) cause of death worldwide

Leading cause of death in pediatric population worldwide

Developing vs developed countries

Contamination ( CDC-US ):

76.000.000 americans

325.000 admissions to hospital

5.000 deaths

England: 19.4 cases por 100 p/year

Accurate estimate of number of cases? Reporting?

Prevalence of chronic diarrhea (US)5%


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Chronic Diarrhea - etiology

Chronic intestinal infection Amebiasis

Giardiasis

Tuberculosis

Blastomycosis

Inflammatory Bowel Disease Ulcerative colitisCrohnsdisease

Collagenous colitis

Microscopic colitis

Malabsorption Gastroenteric anastomosis

Pancreatic insufficiency

HyperchlorydriaCeliac disease

Crohnsdisease

Tropical sprue

Abetalipoproteinemia

Intestinal lymphangiectasia

Whipplesdisease


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Carbohydrate malabsorption Lactose, fructose

Sorbitol

Drugs Antibiotics

Anti-hypertensivesAnti-arrhytmics

Diuretics

Chemotherapy

Antacids (Mg)

Ethanol

NSAIDsCaffeine

Colchicine


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Surgery Gastrectomy

Vagotomy

Cholecystectomy

Intestinal resection

Endocrine Adrenal insufficiency

Hyperthyroidism

Hypothyroidism

Diabetes

Laxative abuse Intestinal ischemia

Radiation colitis/proctitis Diverticulitis

Functional diarrhea


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Chronic Diarrheaetiology (rare)

Hormone producing tumors Gastrinoma

VIPoma

Villous adenoma

Medullar thyroid carcinoma

GanglioneuromaPheochromocytoma

Carcinoid tumor

Mastocytosis

Infiltrative/autoimmune Scleroderma

AmyloidosisIntestinal Lymphoma

Immunoproliferative disorders

Food allergy


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Steps/Approach in Chronic Diarrhea

Absorption of nutrients

Regulation of water, electrolyte absorption/secretion

Motility

Inflammation

Liver/pancreatic function

Surface area/mucosal integrity


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Malabsorption - Algorithm

stool analysis

carbohydrates leukocytes/eosinophils

lactose tolerance testimaging

steatorrhea

fecal fat (timed collection)

normal altered

Malabsorption


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Case 1

A.V.F., 52 years old, female

Referred for investigation of chronic diarrhea since Feb 1997

Otherwise well when change in bowel habits ~9 years ago,

characterized by 5-6 daily, explosive, watery BMs, LLQ pain,flatulence, associated with perianal burning. Improvementwith fasting.

Significantly better with reduction in dairy intake.

All symptoms developed following acute, infectious

gastroenteritis in January 1997. No weight loss, no fever orchills

Physical exam was unremarkable

CBC, lytes, fasting glucose, SPE were normal


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J.A.P., 34 years old male

Diagnosed with ileocolonic Crohns disease 8 years ago, with ileal

resection due to fibrostenotic disease. On maintenance 5-ASA at

1.2 g/d

2 year history of chronic diarrhea, characterized by large volume,

oily, 3-4 BMs/d, associated with 15 kg weight loss. Easy bruising,

hair loss, dry skin, weak nails. Denied fecal incontinence.

Significant epigastric pain immediately following meals, withradiation to the back.

DM diagnosed 6 years ago, on insulin. Peripheral neuropathy.

History of EtOH abuse (~100 g /d for over 12 years).

Case 2


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Chronic Diarrhea

Osmotic/secretory

Abdominal distention and pain: intestinal gas

carbohydrate vs. fat malabsorption Strong odour: fat/protein malabsortpion

Ascites: fat malabsorption


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MSK

Muscle spams, weakness, paresthesia: malabsorptionof vit D, Ca, Mg and PO4

Bone disease (osteoporosis, osteopenia,osteomalacia) and fracture: fat malabsorption, Ca, vitD, secondary hyperparathyroidism


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Easy bruising/petechiae: vit K / C

Glossitis: vit B, folate and iron

Edema: albumin, steatorrhea

Dermatitis: vit A, B, Zn and fatty acids

Weak nails, hair loss: steatorrhea, iron def

Iron deficiency

Kidney stones: steatorrhea

Chronic Diarrhea, continued


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Nutrient Absorption

pre-epithelial

epithelial

post-epithelial

Chronic Diarrheadiagnosis


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Chronic DiarrheaLabs - Imaging

CBC, lytes, creatinine, albumin, total protein, INR,fasting glucose, TSH, HIV (if applicable)

Stool culture, O+P, Sudan III, carbs, quantitativefecal fat

Imaging: EGD, sigmoidoscopy, colonoscopy, US, CT,MRI, EUS

Functional tests


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Stool collection: 48-72 h

Analysis:

- stool weight (200 g/d)

- fecal fat (5-7 g/d)

- osmotic gap: 290 - 2 ( [ Na+ ] + [ K+ ] )

125 mOsm osmotic

< 50 mOsm secretory

50 - 125 mOsm mixed/carbohydrate malabsorption

Quantitative Fecal Fat


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Lactose, lactulose, fructose tolerance test

D-Xylose

Schilling

Bacterial overgrowth (glucose, lactulose, D-xylose)

Pancreatic:- secretin- bentyromide

- pancreolauril- fecal elastase- 14C-trioleyn

Function Tests


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Imaging

US (abdomen)- pancreas, lymphadenopathy, thickening of bowel wall

Upper gastrointestinal endoscopy

- biopsies of second portion of duodenum EUS

Colonoscopy and biopsies

SBFT / ACBE

CT

MRI

ERCP


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Malabsorption - Algorythm

stool analysis

carbohydrates leukocytes/eosinophils

lactose tolerance testimaging

steatorrhea

fecal fat (timed collection)

normal altered

Malabsorption


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Steatorrhea

Sudam III

Quantitative Fecal Fat

++ / +++

Steatorrhea excluded

< 5-7 g/d

Steatorrhea

> 5-7 g/d


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Fecal Fat (quantitative)

< 5-7 g/d

No fat malabsorption Steatorrhea

> 5-7 g/d

D-Xylose US/CT abdomen

Assessment of Pancreatic Exocrine Function

Steatorrhea


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D-Xylose

To estimate absorptive capacity of small intestine

Oral administration of D-Xylose (25 g)

20% uptake, measured in urine collected duringfollowing 5h

Serum [ ] > 1.3 mmol / L / 1.73 m2(20 mg/dL)


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D-Xylose

Steatorrhea

Normal

Assessment of

Pancreatic Function

Duodenal biopsies

Altered

H2breath test or empiric antibiotics


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Pancreatic Function Test

Secretin

PABAabsorbed (GI tract) and excreted in urine (6 h, normal 85 mg)

Pancreolaurilfluoroscein hydrolyzed by pancreatic esterase, livermetabolism and urinary excretion- day 01 FD

- day 02 F- results: ratio day 1/2 (normal 20%)

Pancreatic enzyme supplements

Fecal elastase


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Steatorrhea

Pancreatic Function Test

Altered

Pancreatic Exocrine Insufficiency

H2Breath Test or ATB

Normal


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Small Intestinal Bacterial Overgrowth

H2

Fasting H2> 20 ppm

H2 post-ch > 10 ppm

Diagnosis of Small Intestinal Bacterial Overgrowth

Antibiotics

Reduction in Fecal Fat


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0 15 30 45 60 75 90 105 120 135 150 165 180

0

50

100

150

200

Tempo (min)

H2expirado

(ppm)

H2 Breath Test Bacterial Overgrowth


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Lactose Tolerance Test

lactoseglucosegalactoselactase

absorption

glucose (20 mg%)

colon H2

CO2

SCFA

pH

lungs

20 ppm

AUC0-4h3000

diarrhea


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Normal Lactose Tolerance Test

0 15 30 45 60 75 90 105 120 135 150 165 180

0

10

20

Tempo (min)

H2expirado(ppm)


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0 15 30 45 60 75 90 105 120 135 150 165 180

0

50

100

150

200Lactase (+)

Lactase (-)

Tempo (min)

H2expirado(

ppm)

Lactose Tolerance Test


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Case 1

A.V.F., 52 years old, female

Referred for investigation of chronic diarrhea since Feb 1997

Otherwise well when change in bowel habits ~9 years ago,characterized by 5-6 daily, explosive, watery BMs, LLQ pain,flatulence, associated with perianal burning. Improvement withfasting.

Significantly better with reduction in dairy intake.

All symptoms developed following acute, infectious gastroenteritis inJanuary 1997. No weight loss, no fever or chills

Physical exam was unremarkable

CBC, lytes, fasting glucose, SPE were normal


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Case 1

Colonoscopy: normal

Lactose tolerance test: flat response, H2 breath test: AUC 6800

0 15 30 45 60 75 90 105 120 135 150 165 180

0

50

100

150

200Lactase (+)

Lactase (-)

Tempo (min)

H

2expirado(ppm)


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Case 1

Significant improvement on a lactose free diet

Other options: lactase supplements

Potential differential diagnosis to be considered:

Fructose intolerance

Celiac disease IgA/EMA/Duodenal biopsies/Gluten-free diet

Microscopic colitis

Budesonide, bismuth, 5-ASA

IBS (post-infectious?)


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J.A.P., 34 years old male

Diagnosed with ileocolonic Crohns disease 8 years ago, with ileal

resection due to fibrostenotic disease. On maintenance 5-ASA at

1.2 g/d

2 year history of chronic diarrhea, characterized by large volume,

oily, 3-4 BMs/d, associated with 15 kg weight loss. Easy bruising,

hair loss, dry skin, weak nails. Denied fecal incontinence.

Significant epigastric pain immediately following meals, withradiation to the back.

DM diagnosed 6 years ago, on insulin. Peripheral neuropathy.

History of EtOH abuse (~100 g /d for over 12 years).

Case 2


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Case 2

Fibrostenotic ileal Crohns disease/diabetes: small intestinal bacterialovergrowth suspected

Quantitative fecal fat: stool weight = 890 g/d, fecal fat: 32 g

H2 breath test: positive (early H2 peak15 min,= 40 ppm) Tetracycline 500 mg po QID x 14 days

Fecal fat (post-ATB): stool weight: 380 g/d, fecal fat: 16 g/d

CT of abdomen: thickening of terminal ileum, diffuse pancreatic

calcification

Pancreatic insufficiency suspected, Creon 20 initiated

Fecal fat (with Creon): stool weight 280 g/d, fecal fat 8.2 g/d


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Case 2

Maintenance treatment of small intestinal Crohns disease:

Role of oral 5-ASA Steroids: budesonide vs. prednisone Immunomodulators: azathioprine, 6-MP, MTX Biologics: infliximab, adalimumab Fibrostenotic vs. Inflammatory pattern Prevention of recurrence following surgical resection, dose No medication?

Significant, but not complete symptom improvement Short gut vs. inadequate dose of pancreatic enzyme

supplements


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Case 2

Approach to Chronic Diarrhea

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