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Introduction
Malabsorption
Malabsorption Syndrome
• Diminished intestinal absorption of one or more dietary nutrients
• Not an adequate final diagnosis• Most are associated with steatorrhea– Increase in stool fat excretion of >6% dietary fat
intake
Approach to the Patient
Malabsorption
History, Symptoms and Initial Preliminary Observation
• Extensive small-intestinal resection for mesenteric ischemia– Short bowel syndrome
• Steatorrhea with chronic alcohol intake and chronic pancreatitis– Pancreatic exocrine dysfunction
Active Transport of Site-specific Dietary Nutrient Absorption
• Throughout SI (Proximal>Distal)– Glucose, amino acids, lipids
• Proximal SI (esp. duodenum)– Calcium– Iron– Folate
• Ileum– Cobalamin– Bile acids
Adaptation
• Morphologic and functional• Due to segmental resection• Secondary to the presence of luminal
nutrients and hormonal stimuli• Critical for survival
Steatorrhea
• Quantitative stool fat determination (72 hours)– Gold standard
• Qualitative Sudan III stain– Does not establish degree of fat malabsorption– For preliminary screening studies
• Blood, breath, and isotropic test– Do not directly measure fat absorption– Excellent sensitivity only with obvious steatorrhea– Not survived transition from research laboratory to
commercial application
Laboratory Testing
• Vitamin D malabsorption– Evidence of metabolic bone disease– Elevated serum ALP– Reduced serum calcium
• Vitamin K malabsorption– Elevated prothrombin time– Without liver disease– No intake of anti-coagulants
Laboratory testing
• Cobalamin/Folate malabsorption– Macrocytic anemia
• Iron malabsorption– Iron deficiency anemia– No occult bleeding from GIT– Non-menstruating female– Exclusion of celiac sprue• Iron is absorbed in the proximal SI
Diagnostic Procedures
Malabsorption
Diagnosis of Malabsorption
• Effect of prolonged (>24h) fasting on stool output– Osmotic diarrhea• Decrease in stool output: Presumptive evidence that
diarrhea is related to malabsorption
– Secretory diarrhea• Persistence of stool output: Not due to nutrient
deficiency
Stool Osmotic Gap
• Normal: 290-300 mosmol/kg H20 • Significant osmotic gap
– Suggests the presence of anions other than Na and K are present in the stool, presumably the cause of diarrhea
• Diff >50: osmotic gap present, dietary nutrient is not absorbed
• Diff <25: dietary nutrient is not responsible for the diarrhea
Useful in differentiating secretory from osmotic diarrhea
2 x (stool [Na+] + [stool K+]) ≤ stool osmolality
Schilling Test Urinary D-Xylose Test Radiologic Examination
Use
-determine the cause for cobalamin malabsorption-assess the integrity of stomach, pancreas, and colon
-test for carbohydrate absorption-assessment of proximal small-intestinal mucosal function
-evaluation of the patient with presumed or suspected malabsorption
Procedure
-performed by administering 58Co-labeled cobalamin orally and collecting urine for 24 h
- performed by giving 25 g D-xylose and collecting urine for 5 h
-performed with the examination of the esophagus to duodenal bulb-insufficient barium is given to the patient
AbnormalFindings <10% excretion in 24 h <4.5 g excretion Ex. strictures & fistulas
(Crohn’s disease),
Disadvantage- infrequently performed because of the unavailability of human intrinsic factor
- diminished use due to ease of obtaining a mucosal biopsy by endoscopy and false-negative rate
-abnormalities are rarely seen with current barium suspensions, skilled personnel required
Cobalamin Absorption
Dietary cobalamin in
meat
Bound to R-binder protein
in stomach
Complex bound in acid milieu in
the stomach
Uptake of cobalamin in receptors in
brush border of ileal enterocytes
Pancreatic protease
enzymes split cobalamin and binding protein
Cobalamin enters the
proximal small intestine and
binds to intrinsic factor
Schilling Test• Pernicious Anemia
– Atrophy of gastric parietal cells lead to absence of gastric acid and intrinsic factor secretion
• Chronic Pancreatitis– Deficiency of pancreatic proteases to split the cobalamin-R binder
complex• Achlorydia
– Absence of another factor secreted with acid that is responsible for splitting cobalamin from the proteins in food
• Bacterial Overgrowth syndromes– Bacterial utilization of cobalamin
• Ileal dysfunction– Impaired cobalamin – intrinsic factor uptake
Schilling Test58Co-Cbl
With Intrinsic Factor
With Pancreatic Enzymes
After 5 Days of Antibiotics
Pernicious anemia Reduced Normal Reduced Reduced
Chronic pancreatitis Reduced Reduced Normal Reduced
Bacterialovergrowth Reduced Reduced Reduced Normal
Ileal disease Reduced Reduced Reduced Reduced
Biopsy of Small-Intestinal Mucosa
• Essential in the evaluation of a patient with documented steatorrhea or chronic diarrhea
• Preferred method to obtain histologic material of proximal small-intestinal mucosa
• Indications:– Evaluation of a patient either with documented or
suspected steatorrhea or with chronic diarrhea– Diffuse or focal abnormalities of the small
intestine defined on a small-intestinal series
Biopsy Lesions and Findings
Results of Diagnostic Studies in Different Causes of SteatorrheaD-Xylose Test Schilling Test Duodenal
Mucosal BiopsyChronic pancreatitis
Normal 50% abnormal; if abnormal, normal with pancreatic enzymes
Normal
Bacterial overgrowth syndrome
Normal or only modestly abnormal
Often abnormal; if abnormal, normal after antibiotics
Usually normal
Ileal disease Normal Abnormal NormalCeliac sprue Decreased Normal Abnormal:
probably "flat"Intestinal lymphangiectasia
Normal Normal Abnormal: "dilated lymphatics"
Differential Diagnosis for Chronic Diarrhea: Approach to a Patient with Malabsorption
CC: Diarrhea 1 month duration
Prolonged fast (>24h)
Osmotic Diarrhea (>50 osmotic gap
difference)
SI Mucosal Biopsy
Diagnosis: Cause of Malabsorption
Secretory Diarrhea (<25 osmotic gap
difference)