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Approach to Chronic Diarrhea

Jos Geraldo P. Ferraz, MD, PhD


GI Division
Mucosal Inflammation Research Group
The University of Calgary

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)

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%

Chronic Diarrhea - etiology


Chronic intestinal infection

Amebiasis
Giardiasis
Tuberculosis
Blastomycosis

Inflammatory Bowel Disease

Ulcerative colitis
Crohns disease
Collagenous colitis
Microscopic colitis

Malabsorption

Gastroenteric anastomosis
Pancreatic insufficiency
Hyperchlorydria
Celiac disease
Crohns disease
Tropical sprue
Abetalipoproteinemia
Intestinal lymphangiectasia
Whipples disease

Chronic Diarrhea - etiology


Carbohydrate malabsorption

Lactose, fructose
Sorbitol

Drugs

Antibiotics
Anti-hypertensives
Anti-arrhytmics
Diuretics
Chemotherapy
Antacids (Mg)
Ethanol
NSAIDs
Caffeine
Colchicine

Chronic Diarrhea - etiology


Surgery

Gastrectomy
Vagotomy
Cholecystectomy
Intestinal resection

Endocrine

Adrenal insufficiency
Hyperthyroidism
Hypothyroidism
Diabetes

Laxative abuse

Intestinal ischemia

Radiation colitis/proctitis

Diverticulitis

Functional diarrhea

Chronic Diarrhea etiology (rare)

Hormone producing tumors

Gastrinoma
VIPoma
Villous adenoma
Medullar thyroid carcinoma
Ganglioneuroma
Pheochromocytoma
Carcinoid tumor
Mastocytosis

Infiltrative/autoimmune

Scleroderma
Amyloidosis
Intestinal Lymphoma
Immunoproliferative disorders

Food allergy

Steps/Approach in Chronic Diarrhea

Absorption of nutrients
Regulation of water, electrolyte absorption/secretion
Motility
Inflammation
Liver/pancreatic function
Surface area/mucosal integrity

Malabsorption - Algorithm

stool analysis
normal

altered

carbohydrates
fecal fat (timed collection)

leukocytes/eosinophils

lactose tolerance test

Malabsorption

imaging

steatorrhea

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
with fasting.
Significantly better with reduction in dairy intake.
All symptoms developed following acute, infectious
gastroenteritis in January 1997. No weight loss, no fever or
chills
Physical exam was unremarkable
CBC, lytes, fasting glucose, SPE were normal

Case 2
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, with
radiation to the back.
DM diagnosed 6 years ago, on insulin. Peripheral neuropathy.
History of EtOH abuse (~100 g /d for over 12 years).

Chronic Diarrhea
Osmotic/secretory
Abdominal distention and pain: intestinal gas
carbohydrate vs. fat malabsorption

Strong odour: fat/protein malabsortpion


Ascites: fat malabsorption

MSK
Muscle spams, weakness, paresthesia: malabsorption
of vit D, Ca, Mg and PO4
Bone disease (osteoporosis, osteopenia,
osteomalacia) and fracture: fat malabsorption, Ca, vit
D, secondary hyperparathyroidism

Chronic Diarrhea, continued


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
diagnosis

Nutrient Absorption
pre-epithelial

epithelial
post-epithelial

Chronic Diarrhea
Labs - Imaging

CBC, lytes, creatinine, albumin, total protein, INR,


fasting glucose, TSH, HIV (if applicable)
Stool culture, O+P, Sudan III, carbs, quantitative
fecal fat
Imaging: EGD, sigmoidoscopy, colonoscopy, US, CT,
MRI, EUS
Functional tests

Quantitative Fecal Fat


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

Function Tests
Lactose, lactulose, fructose tolerance test
D-Xylose
Schilling
Bacterial overgrowth (glucose, lactulose, D-xylose)
Pancreatic:
- secretin
- bentyromide
- pancreolauril
- fecal elastase
- 14C-trioleyn

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

Malabsorption - Algorythm

stool analysis
normal

altered

carbohydrates
fecal fat (timed collection)

leukocytes/eosinophils

lactose tolerance test

Malabsorption

imaging

steatorrhea

Steatorrhea
Sudam III

++ / +++
Quantitative Fecal Fat

< 5-7 g/d

> 5-7 g/d

Steatorrhea excluded

Steatorrhea

Steatorrhea
Fecal Fat (quantitative)

< 5-7 g/d

No fat malabsorption

D-Xylose

> 5-7 g/d

Steatorrhea

US/CT abdomen
Assessment of Pancreatic Exocrine Function

D-Xylose

To estimate absorptive capacity of small intestine


Oral administration of D-Xylose (25 g)

20% uptake, measured in urine collected during


following 5h
Serum [ ] > 1.3 mmol / L / 1.73 m2 (20 mg/dL)

Steatorrhea
D-Xylose

Altered

Normal

Assessment of
Pancreatic Function

Duodenal biopsies

H2 breath test or empiric antibiotics

Pancreatic Function Test


Secretin
PABA
absorbed (GI tract) and excreted in urine (6 h, normal
85 mg)
Pancreolauril
fluoroscein hydrolyzed by pancreatic esterase, liver
metabolism and urinary excretion
- day 01 FD
- day 02 F
- results: ratio day 1/2 (normal 20%)
Pancreatic enzyme supplements
Fecal elastase

Steatorrhea
Pancreatic Function Test

Normal

Altered

Pancreatic Exocrine Insufficiency

H2 Breath Test or ATB

Small Intestinal Bacterial Overgrowth


H2

Fasting H2 > 20 ppm


H2 post-ch > 10 ppm

Antibiotics

Reduction in Fecal Fat

Diagnosis of Small Intestinal Bacterial Overgrowth

H2 Breath Test Bacterial Overgrowth

H2 expirado (ppm)

200
150
100
50
0
0

15

30

45

60

75

90 105 120 135 150 165 180

Tempo (min)

Lactose Tolerance Test


lactose

lactase

glucose
galactose

absorption

glucose (20 mg%)

colon

H2
CO2
pH

SCFA

lungs
20 ppm

AUC0-4h 3000
diarrhea

Normal Lactose Tolerance Test

H2 expirado (ppm)

20

10

0
0

15

30

45

60

75

90

105 120 135 150 165 180

Tempo (min)

Lactose Tolerance Test

H2 expirado (ppm)

200

Lactase (+)
Lactase (-)

150
100
50
0
0

15

30

45

60

75

90

105 120 135 150 165 180

Tempo (min)

Other Tests
HIV, CMV
EMA/IgA/TTG (celiac)
1-antitrypsin in stool (protein loosing enteropathy)
gastrin (Zollinger-Ellison), calcitonin (thyroid ca),
glucagon (glucagonoma), VIP (VIPoma), PTH
5-hydroxy-indol acetic acid (5-HIAA, carcinoid), metanephrines in
urine (pheo), hystamine (mastocytosis, carcinoid)
Immunoglobulins (nodular lymphoid hyperplasia, commom
variable immunodeficiency)
Small intestinal biopsy (celiac, Whipples)

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 with
fasting.
Significantly better with reduction in dairy intake.
All symptoms developed following acute, infectious gastroenteritis in
January 1997. No weight loss, no fever or chills
Physical exam was unremarkable
CBC, lytes, fasting glucose, SPE were normal

Case 1
Colonoscopy: normal
Lactose tolerance test: flat response, H2 breath test: AUC 6800

H2 expirado (ppm)

200

Lactase (+)
Lactase (-)

150
100
50
0
0

15

30

45

60

75

90

105 120 135 150 165 180

Tempo (min)

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?)

Case 2
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, with
radiation 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
Fibrostenotic ileal Crohns disease/diabetes: small intestinal bacterial
overgrowth suspected

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


H2 breath test: positive (early H2 peak 15 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

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

Case 2