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 Vitamin K 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 Iron 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

2 x (stool [Na+] + [stool K+]) ≤ stool osmolality Stool Osmotic Gap Useful in differentiating secretory from osmotic diarrhea 2 x (stool [Na+] + [stool K+]) ≤ stool osmolality 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

Radiologic Examination 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 Abnormal Findings <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 Chronic Pancreatitis Achlorydia 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 Test 58Co-Cbl With Intrinsic Factor With Pancreatic Enzymes After 5 Days of Antibiotics Pernicious anemia Reduced Normal Chronic pancreatitis Bacterial overgrowth Ileal disease

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 Steatorrhea D-Xylose Test  Schilling Test Duodenal Mucosal Biopsy Chronic pancreatitis Normal 50% abnormal; if abnormal, normal with pancreatic enzymes Bacterial overgrowth syndrome Normal or only modestly abnormal Often abnormal; if abnormal, normal after antibiotics Usually normal Ileal disease Abnormal Celiac sprue Decreased Abnormal: probably "flat" Intestinal lymphangiectasia 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)