M ALABSORPTION G ROUP A

M ALABSORPTION S YNDROME 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

A PPROACH TO THE P ATIENT Malabsorption

H ISTORY, S YMPTOMS AND I NITIAL P RELIMINARY O BSERVATION Extensive small-intestinal resection for mesenteric ischemia Short bowel syndrome Steatorrhea with chronic alcohol intake and chronic pancreatitis Pancreatic exocrine dysfunction

A CTIVE T RANSPORT OF S ITE - SPECIFIC D IETARY N UTRIENT A BSORPTION Throughout SI (Proximal>Distal) Glucose, amino acids, lipids Proximal SI (esp. duodenum) Calcium Iron Folate Ileum Cobalamin Bile acids

A DAPTATION Morphologic and functional Due to segmental resection Secondary to the presence of luminal nutrients and hormonal stimuli Critical for survival

S TEATORRHEA 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

L ABORATORY T ESTING 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

L ABORATORY 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

D IAGNOSTIC P ROCEDURES Malabsorption

D IAGNOSIS OF M ALABSORPTION 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

S TOOL O SMOTIC G AP Normal: mosmol/kg H 2 0 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 58 Co- 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

C OBALAMIN A BSORPTION 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

S CHILLING T EST 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

S CHILLING T EST 58 Co-Cbl With Intrinsic Factor With Pancreatic Enzymes After 5 Days of Antibiotics Pernicious anemia ReducedNormalReduced Chronic pancreatitis Reduced NormalReduced Bacterial overgrowth Reduced Normal Ileal diseaseReduced

B IOPSY OF S MALL -I NTESTINAL M UCOSA 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

B IOPSY L ESIONS AND F INDINGS

R ESULTS OF D IAGNOSTIC S TUDIES IN D IFFERENT C AUSES OF S TEATORRHEA D-Xylose Test Schilling TestDuodenal Mucosal Biopsy Chronic pancreatitisNormal50% 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 diseaseNormalAbnormalNormal Celiac sprueDecreasedNormalAbnormal: probably "flat" Intestinal lymphangiectasia Normal Abnormal: "dilated lymphatics"

D IFFERENTIAL D IAGNOSIS FOR C HRONIC D IARRHEA : A PPROACH TO A P ATIENT WITH M ALABSORPTION

D ISEASE E NTITIES C AUSING M ALABSORPTION

C ELIAC S PRUE Other names: Nontropical sprue, Celiac disease, gluten-sensitive enteropathy Etiology is not known Environmental – gliadin-associated Immunologic – IgA antigliadin, IgA antiendomysial, IgA anti-tTg antibodies Genetic – HLA-DQ2 allele Protean manifestations  most of which are secondary to nutrient malabsorption

Onset of symptoms occur at ages ranging from first year of life to eighth decade Clinical manifestations: Appear with the introduction of cereals in an infants diet ranges from significant malabsorption to multiple nutrients, diarrhea, steatorrhea, weight loss, consequences of nutrient depletion to absence of any GI symptoms but with evidence of a single nutrient depletion Hallmark: malabsorption and histologic changes

Mechanism of diarrhea: Steatorrhea Secondary lactase deficiency Bile acid malabsorption Endogenous fluid secretion Associated diseases: Dermatitis herpetiformis (DH) DM type 1 IgA deficiency Complications: GI and non GI neoplasms Intestinal ulceration Refractory sprue Collagenous sprue

T ROPICAL S PRUE Affects 5-10% of population in some tropical area Etiology and pathogenesis is uncertain Clinical manifestations: Chronic diarrhea Steatorrhea Weight loss Folate and cobalamin deficiencies

S HORT B OWEL S YNDROME General term for digestive problems that occur after a resection Depends on Segment resected Length of segment Presence of ileocecal valve Extent of colon removal Residual disease Generally, need to lose 2/3 of intestine Usually acquired Can be congenital in children Congenital short bowel After resection, intestine undergoes adaptation.

S HORT BOWEL SYNDROME Diarrhea Steatorrhea Possibility of hyperoxaluria Increase in gallstone risk Increase in gastrin levels Removal of Ileum Bile unabsorbed Stimulates colonic fluid and electrolyte secretion Removal of ileocecal valve Bacterial overgrowth Decrease in intestinal time Removal of intestinal mucosa Lactose intolerance Lipid, fluid and electrolytes are not absorbed Clinical PresentationPathophysiology

S HORT BOWEL SYNDROME K EY P OINTS Follows resection of intestines Generally inadequacy in absorbing food and fluids because of lack of surface area

B ACTERIAL O VERGROWTH S YNDROME Proliferation of colonic type bacteria within small intestine Clinical Manifestation Diarrhea Steatorrhea Macrocytic anemia

B ACTERIAL O VERGROWTH S YNDROME Cobalamin deficiency Increased bacteria = use more B12 Macrocytic Anemia Impaired micelle formation Steatorrhea Due to steatorrhea Due to bacterial enterotoxins Diarrhea Bacterial Overgrowth Functional Stasis Anatomical Stasis Direct Communication between SI and LI PathogenesisEtiology

B ACTERIAL O VERGROWTH S YNDROME K EY POINTS Macrocytic anemia Because of lack of B12 Stasis = allows bacteria to multiply

W HIPPLE ’ S D ISEASE Insidious in presentation Chronic multisystem disease Usually causes Clinical Manifestation Diarrhea Steatorrhea Weight loss Abdominal pain Arthralgia CNS/ cardiac problems

W HIPPLE ’ S D ISEASE More common in men Middle aged caucasian men Fatal if left untreated T. whipplei Gram negative Rod shaped Presence of PAS (+) macrophages in SI lamina propria Steatorrhea caused by SI mucosal injury Lymphatic obstruction EpidemiologyEtiology and Pathogenesis

W HIPPLE ’ S D ISEASE K EY POINTS Rare, SYSTEMIC disease Insidious CNS and cardiac symptoms Dementia = POOR prognosis Caused by damage to mucosa and lymphatic obstruction

P ROTEIN L OSING E NTEROPATHY Group of diseases with Hypoproteinemia and edema WITHOUT Proteinuria/ kidney problems Protein synthesis defects/ liver problems Clinical Manifestation Peripheral edema Diarrhea Steatorrhea

P ROTEIN L OSING E NTEROPATHY Excess protein loss in the GI tract Exceeds the normal 10% protein catabolism Protein Losing enteropathy Mucosal Ulceration Group Non ulcerated mucosa group; altered permeability Lymphatic dysfunction PathogenesisEtiology

P ROTEIN L OSING E NTEROPATHY K EY POINTS Peripheral edema, hypoproteinemia More than >10% total protein breakdown Proteins lost through exudates, altered permeability, lymphatic obstruction

T REATMENT

Disease EntityTreatment Celiac SprueComplete dietary gluten restriction Dietary lactose and fat restriction for more severe cases Tropical SprueBroad spectrum antibiotics and folic acid Tetracycline for 6 months Short Bowel SyndromeOpiates (codeine), Low fat high, high carbohydrate diet Fat soluble vitamins, folate, cobalamin, calcium, iron, magnesium, zinc Bacterial Overgrowth SyndromeSurgical correction on the anatomical blind loop Broad- spectrum antibiotics: Tetracycline, metronidazole, amoxicillin/clavulanic acid and cephalosporins Whipple’s diseaseDouble strength trimethoprin/sulfamethoxazole for 1 year Alt: chloramphenicol Protein losing enteropathyTreat the underlying disease process Low fat diet and MCT’s for the treatment of hypoproteinemia