2007 AGA GI Fellows Nutrition Course
Malabsorption A Clinical Approach
John K. DiBaise, MD Associate Professor of Medicine Mayo Clinic Arizona
Outline
Normal digestion and absorption Classification of malabsorption Tests of malabsorption Clinical approach to diagnosis
Malabsorption vs. Maldigestion
Decreased intestinal absorption of macronutrients and/or micronutrients
malabsorption defect in mucosal phase maldigestion defect in intraluminal phase
Normal Digestion and Absorption
Mechanical mixing Enzyme and bile salt production Mucosal function Blood supply Intestinal motility Commensal gut flora
Fat Digestion and Absorption
Ebert EC. Dis Month 2001;47:49
Carbohydrate and Protein Digestion and Absorption
Protein
Pancreatic proteases
Oligopeptides
Mucosal peptidases
AA
Digestion
Absorption
Distribution
CHO
Oligosaccharides
Sugars
Pancreatic amylase
Mucosal disaccharidases
Classification of Malabsorption
Luminal Mucosal Postabsorptive Overt Subclinical Asymptomatic
Global/Total Partial Selective CHO Protein Fat
Classification of Malabsorption
Luminal phase
Substrate hydrolysis
Digestive enzyme deficiency/inactivation, inadequate mixing Diminished bile salt synthesis/secretion, increased loss Diminished gastric acid/intrinsic factor, bacterial consumption
Fat solubilization
Luminal availability of nutrients
Mucosal phase
Brush border hydrolysis Epithelial transport
Postabsorptive processing
Enterocyte, lymphatic
Mechanisms of Fat Malabsorption
Pancreatic insufficiency Bile acid deficiency Small intestinal bacterial overgrowth Loss of absorptive surface area Defective enterocyte function Lymphatic disorders
Mechanisms of Carbohydrate Malabsorption
Selective disaccharidase deficiency Disruption of brush border/enterocyte function Loss of mucosal surface area Pancreatic insufficiency
Mechanisms of Protein Malabsorption
Pancreatic insufficiency Disorders with impaired enterocyte function Disorders with decreased absorptive surface Protein-losing enteropathy
Clinical Presentation
Diarrhea Steatorrhea Weight loss
Bloating, distension, gas, borborygmi Anorexia or hyperphagia Nausea, vomiting Abdominal discomfort Muscle atrophy Edema Signs/symptoms of specific vitamin deficiencies
History and Exam
Prior GI surgery h/o chronic pancreatitis h/o liver, GI disorder h/o CTD, diabetes h/o radiation therapy Diet and medications Alcohol/drugs h/o chronic sinus or respiratory infections
Recent travel history Timing of onset Bowel habits/stool characteristics Associated GI and systemic complaints Evidence of malnutrition or micronutrient deficiencies on exam
Overview of Tests for Malabsorption
Blood tests Fecal fat determination Imaging studies Endoscopy with biopsy and aspirate Breath tests D-xylose test, Schilling test, Secretin/CCK test
Screening Laboratory Tests
Blood tests
CBC Electrolytes, Mg, Phos, Ca Albumin, protein Vitamin B12, Folate, Iron Liver tests PT/INR, cholesterol Carotene (?)
Stool tests
Inspection Hemoccult O&P Qualitative fat
everything comes down to poo...
Fecal Fat Determination Quantitative
Gold standard to diagnose maldigestion 72 hour collection optimal Normal < 7 g/day Limited use in clinical practice due to issues with collection/processing
Fecal Fat Determination Qualitative
Random spot sample
Qualitative (Sudan stain) Semi-quantitative (#/size of droplets) Acid steatocrit
Less sensitive for mild-moderate steatorrhea Variable reproducibility Helpful only if abnormal
D-xylose Test
Indicates malabsorption secondary to mucosal dysfunction Oral load with 25 g D-xylose
5 hr urine collection (normal > 4 g) 1 hr and 3 hr serum samples (normal > 20 mg/dl at 1 hr, > 18.5 mg/dl at 3 hr)
Numerous factors affect results Role in clinical practice controversial
? Use in special populations
Vitamin B12 Absorption and Schilling Test
Determine etiology of B12 deficiency 1 mcg radiolabeled cynanocobalamin ingested and 1 mg nonlabeled B12 administered IM 24 hr urine collection Recovery of < 9% abnormal Numerous causes of false positives/negatives
4 Stages of the Schilling Test
Condition Stage 1
(B12) Decreased B12 Malabsorption Pernicious anemia Chronic pancreatitis SIBO TI resection Decreased Decreased Decreased Decreased Normal Decreased Decreased Decreased Normal Decreased Decreased Normal Decreased
Stage 2
(IF)
Stage 3
(enzymes)
Stage 4
(antibx)
Direct Pancreatic Function Tests
Gold standard Quantitative stimulation tests using either secretin or CCK or test (Lundh) meal Requires Dreiling tube placed into duodenum with collection of contents for an hour Analyzed for bicarbonate (secretin) or amylase/lipase/trypsin (CCK) Low concentrations (< 80-90 mEq/L HCO3; < 780 IU/L lipase) consistent with pancr. insuff. Limited by availability, invasiveness, expense
Endoscopic Pancreatic Function Tests
Uses endoscope instead of Dreiling tube
Results not affected by sedation or analgesia
Correlates well with conventional test (in healthy subjects) Number of advantages
More widely available, less costly/ uncomfortable, no radiation exposure
? Practicality of 1 hr endoscopy
Timed specimens at 30/45 min sufficient
Stevens T et al. AJG 2006
Indirect Pancreatic Function Tests
Serum trypsinogen/trypsin Fecal chymotrypsin Fecal elastase-1 Pancreolauryl test Bentiromide test
Tubeless tests
Trial of pancreatic enzymes
Breath Tests
Specific carbohydrate malabsorption
Lactose, fructose, sucrose Hydrogen
Small intestinal bacterial overgrowth
Glucose, lactulose
Hydrogen
Xylose, glycocholate
14C
Fat malabsorption
14C-triolein
Historical interest mainly
Small Bowel Culture
Gold Standard test for SIBO
Abnormal > 105 cfu/ml
Many limitations
Invasive Expensive Contamination Many bacterial uncultivatable Difficulty culturing anaerobes
Imaging Studies
Barium contrast small bowel series
Anatomical lesions, transit Flocculation, decreased folds, segmentation, dilation
CT/MR enterography
Detect bowel and pancreatic lesions
Enteroscopy, VCE, high resolution magnification endoscopy, chromoendoscopy
Imaging Studies
ERCP
Detect ductal abnormalities Other diagnostic/therapeutic applications
MRCP
Detect ductal and parenchymal abnormalities
EUS
Detect ductal and parenchymal abnormalities Allows tissue sampling Interobserver variability problematic
Endoscopy and Small Bowel Biopsy
Visual assessment
Decreased folds, scalloping, mosaic pattern, frosted appearance, inflammatory changes
Histologic assessment
Diagnostic Supportive of diagnosis Normal
Tests of Fat Malabsorption
Fecal fat collection Spot fecal fat 14C-triolein, 13C-triglyceride breath tests Near infrared reflectance analysis (NIRA)
Can measure fecal fat, nitrogen and CHO As accurate but less time consuming then 72 hr fecal fat collection Not widely available
Tests of Carbohydrate Malabsorption
Oral breath tests Quantitative analysis of fecal CHO Stool pH Oral tolerance tests Direct assay of mono- and disaccharidases
Protein-Losing Enteropathy
Characterized by excessive loss of serum proteins into the gut
Hypoproteinemia, hypoalbuminemia, edema, muscle atrophy
May occur as isolated phenomenon or part of global malabsorption Need to r/o malnutrition, nephrosis, liver disease
Conditions Associated with Protein-Losing Enteropathy
Mucosal disease
IBD, Celiac, Whipple s, Tropical sprue, Menetrier s, GI malignancy, chemotherapy, eosinophilic dz, SIBO
Lymphatic obstruction
Lymphangiectasia, lymphoma, constrictive pericarditis, Crohn s, radiation, Fontan procedure
Tests of Protein Malabsorption
Nutrient balance studies with fecal nitrogen measurement Radioisotopic methods
albumin 99mTc-labeled transferrin 125I-labeled albumin
51Cr-labeled
Indirect methods
Fecal E-1 antitrypsin clearance (> 25 mg/d)
Terminal Ileal Resection and Malabsorption
< 100 cm
Bile Acid
> 100 cm
Fat
Take Home Points
Three Major Malabsorptive Conditions
Small bowel mucosal disease Small bowel bacterial overgrowth Pancreatic insufficiency
Take Home Points
Approach to Suspected Malabsorption
History Physical exam Routine screening labs Stool analysis Selective tests based on above findings
H2 breath tests, Celiac Abs, Abd imaging, EGD w/bx, Colon w/bx, PFT, ERCP/MRCP/EUS, Angio, Fecal E1-AT, Fat pad aspirate
Treat based on underlying disease or type of malabsorption
Cases
Case 1
47 yo man h/o alcoholism c/o constant vague abdominal pain, one constipated stool/day and 20 pound weight loss CT scan shows pancreatic atrophy Lab tests
Serum carotene 50 mcg/dl (normal > 80) 72 hr fecal fat 28 g/day (normal < 7) 5 hr urinary D-xylose 7.5 g (normal > 4)
What s the next step?
Further testing? What test(s)? Treatment? With what?
Case 2
36 yo man presents for evaluation of iron deficiency anemia. No GI symptoms. No aspirin/NSAIDs. IgA tTG antibody positive Small bowel biopsy done What result would you expect on the D-xylose test?
Case 3
62 yo woman with h/o prior gastric surgery (Roux-en-Y GJ) for PUD c/o early satiety, diarrhea, foul-smelling breath and weight loss What s the most likely diagnosis? What test(s) can confirm the diagnosis?
Case 4
75 yo man presents with FUO, arthritis and diarrhea Labs show hypoproteinemia Sprue antibodies negative Negative SIBO breath test Small bowel biopsy done What is the diagnosis?
Case 5
22 yo man returns from a prolonged stay in the Philippines c/o diarrhea, fatigue and 5 pound weight loss Hgb 10.5 MCV 104 Folate low D-xylose test decreased Celiac antibodies negative Small bowel biopsy done What s the diagnosis? treatment?
