Evaluation and Differential

Diagnosis of Chronic Diarrhea

and Malabsorption

Ralph A. Giannella, MD

University of Cincinnati

October 23, 2009

Villus and Crypt Na and Cl Transport

Glucose Na
Na Cl Classification of Diarrhea
X

cAMP Na Na Inflammatory
Cl Glucose Secretory
Villus Na
Osmotic
Fatty
Cl Lumen functional
Crypt

cAMP
Cl
Adapted from: Banwell JB: Infectious Diarrhea. SL Gorbach, ed. Blackwell. 1986. p 4

Features of Secretory and Osmotic

Causes of Inflammatory Diarrhea
Diarrheas
Intestinal infections (Campylobacter,
Salmonella, Shigella, E. coli) Secretory Large volume
Persists during fasting
C. difficle colitis 270 - ((Na) + (K)) X 2 = < 20
Inflammatory bowel disease (ulcerative
colitis, Crohns disease) Osmotic Stool volume < 1 L/day
Stool volume during fasting
Other Colitides (radiation, ischemia) 270 - ((Na) + (K)) X 2 = > 50
Osmotic gap
 Causes of Secretory Diarrhea Causes of Osmotic Diarrhea
Infections and enterotoxins Ingestion of poorly absorbed solutes
(Cholera toxin, E. coli LT & ST, Staph Magnesium compounds
toxin, HIV and rotaviruses etc) Antacids
Sorbitol, mannitol
Humoral agents (Gastrin, Serotonin, VIP,
Calcitonin, prostaglandins etc) Maldigestion of food
Pancreatic insufficiency (F)
Laxatives (commercial, altered bile salts Lactase deficiency
and fatty acids) Malabsorption
Others (diabetes, drugs, microscopic colitis, Mucosal defects
idiopathic etc) Bacterial overgrowth

Fatty Diarrhea Other Diarrheal Disorders

Celiac serology, EGD with small Hospital-acquired diarrhea
Exclude structural bowel biopsy, aspirate for O&P Microscopic colitis
disease and quantitative culture, CT
enterography Drug-induced diarrhea
Negative Post-cholecystectomy diarrhea
Diabetic diarrhea
r/o Pancreatic Fecal elastase
CT scan, ERCP, EUS
Post-travelers diarrhea
insufficiency
Post-infectious IBS
Fine KD, Schiller LR. Discussed in the handout
Gastroenterology
116:1464, 1999.

Malabsorption Disorders Mechanism of Fat Absorption

Pancreatic insufficiency
Pancreas Liver Jejunal Mucosa Lymphatics
Small bowel bacterial overgrowth Lipolysis Micellar Absorption Delivery
Celiac disease Solubilization
with Bile salts
Ileal resection
Fatty acid bile salt esterification
Giardiasis
FA
Short Bowel syndrome FA Lacteals
TG
BMG TG To tissues
Tropical sprue
Chylomicron
Whipples disease BMG formation

Wilson and Dietschy Gastroenterology 1971

Normal Enteroheptic Circulation of Bile Salts
Classification of Malabsorption
Cholesterol
0.5 gm/day Pancreatic Enzymes (chronic pancreatitis, Z-E
B.S syndrome)
Bile >4. mM
Salts Bile Salts (biliary obstruction, bacterial
Jejunum overgrowth, ileal disease)

B.S. Pool Size Mucosal Disease (resection, radiation enteritis,

Ileum
4.0 gm
Na ischemia, celiac disease, Whipples disease)

Lymphatic Disease (lymphangiectasia,

Colon lymphoma)
0.5 gm B.S.
excreted/day

Fat Malabsorption Sudan Stain D-Xylose Test in Malabsorption

Qualitative test for fat 5-carbon sugar absorbed in small intestine

Microscopic examination of stool Can distinguish small bowel from pancreatic
disease
Positive with > 15 gms/day
Abnormal test indicates SB disease or SBBO
False positive mineral oil
False negative mild fat False positives (Renal disease, ascites,
malabsorption delayed gastric emptying, vomiting)

Value of Small Bowel Biopsy Celiac Disease-Atypical

Biopsy is always Biopsy may be
diagnostic diagnostic Presentations (No GI symptoms)
Whipples disease Lymphoma
Iron deficiency anemia
MAI
Agammaglobulinemia Giardia Osteopenia
Cryptosporidia Amenorrhea or infertility
abetalipoproteinemia Collagenous sprue Isolated hypertransaminasemia
Lymphangiectasia
Neuropathy
Amyloidosis
Scleroderma Neuropsychiatric manifestations

Note absence of celiac disease

 False Negative Anti-EMA and tTG
Tests for Celiac Disease
Assays
Anti-gliadin antibody (AGA)
IgA deficiency

Anti-endomysial antibody (Anti EMA) Mild enteropathy (positivity correlates

immunohistochemistry with degree of enteropathy)

Tissue transglutaminase (tTG)- Elisa

(95+% specific; 70-90% sensitive; usually the Children less than 2
first test done)

HLA Haplotype and Celiac Disease Consequences of Ileal Disease or

HLA-DQ2 in 95% of patients with celiac sprue Resection
HLA-DQ8 found in most of the remaining pts
Vitamin B12 malabsorption
Steatorrhea
25% of Western population are DQ2 or DQ8, Diarrhea
therefore most with DQ2/DQ8 do not have Gall stones
celiac disease Renal stones
Small bowel bacterial overgrowth
A haplotype negative for DQ2 or DQ8 rules out
celiac disease (99% confidence)

Bile Salt Diarrhea

Length of Ileal Resection and
Steatorrhea Cholesterol
70 0.8 gm/day
B.S.
60 Bile Salts >4 mM
Fecal50 Jejunum
fat 40 Patient may Patient may have
g/day have Bile Salt Fatty acid diarrhea B.S. Pool Size
30
diarrhea 4.0 gm Ileum
20 Na
10

50 150 200 Colon

100 0.8 gm B.S.
Length of Ileal resection cm excreted/day
 Fatty Acid Diarrhea
Bacterial Overgrowth Syndrome
Cholesterol
1.2 gm/day
B.S. Classic presentation
Bile Salts < 4 mM
Macrocytic anemia (Vit B12 def)
Jejunum
Steatorrhea
B.S. Pool Size Diarrhea
2.5 gm Ileum
Na+ Common Presentation
gas, bloating, diarrhea, abdominal
Colon distress
>1.2 gm B.S.
excreted/day

Small Bowel Bacterial Overgrowth Diagnosis of Bacterial Overgrowth

Clinical suspicion-anemia, steatorrhea,
diarrhea, predisposing intestinal lesion
Metabolic Effects of Document malabsorption of fat,
Misplaced Flora xylose, or vit B12
R/O mucosal disease, pancreatic
Steatorrhea Macrocytic Anemia Malabsorption disease, ileal disease
(Deconjugation
of Bile salts)
(bacterial consumption of (mucosal damage etc)
vitamin B12)
Specific tests (quantitative culture,
glucose hydrogen breath test)