Malabsorption Group A

1. MalabsorptionGroup A

2. 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

3. Approach to the Patient Malabsorption

4. 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

5. 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

6. Adaptation • Morphologic and functional • Due to segmental resection • Secondary to the presence of luminal nutrients and hormonal stimuli • Critical for survival

7. 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

8. 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

9. 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

10. Diagnostic Procedures Malabsorption

11. 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

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

14. Cobalamin Absorption

15. 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

16. Schilling Test

17. 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

18. Biopsy Lesions and Findings

19. Results of Diagnostic Studies in Different Causes of Steatorrhea

20. Differential Diagnosis for Chronic Diarrhea: Approach to a Patient with Malabsorption

21. Disease Entities Causing Malabsorption

22. Celiac Sprue • Other names: • Nontropicalsprue, 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

23. 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

24. 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 • Collagenoussprue

25. Tropical Sprue • 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

26. Short Bowel Syndrome • 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.

27. Short bowel syndrome Clinical Presentation Pathophysiology • 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

28. Short bowel syndrome Key Points • Follows resection of intestines • Generally inadequacy in absorbing food and fluids because of lack of surface area

29. Bacterial Overgrowth Syndrome • Proliferation of colonic type bacteria within small intestine • Clinical Manifestation • Diarrhea • Steatorrhea • Macrocytic anemia

30. Bacterial Overgrowth Syndrome Pathogenesis Etiology

31. Bacterial Overgrowth Syndrome Key points • Macrocytic anemia • Because of lack of B12 • Stasis = allows bacteria to multiply

32. Whipple’s Disease • Insidious in presentation • Chronic multisystem disease • Usually causes • Clinical Manifestation • Diarrhea • Steatorrhea • Weight loss • Abdominal pain • Arthralgia • CNS/ cardiac problems

33. Whipple’s Disease Epidemiology Etiology and Pathogenesis • 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

34. Whipple’s Disease Key points • Rare, SYSTEMIC disease • Insidious • CNS and cardiac symptoms • Dementia = POOR prognosis • Caused by damage to mucosa and lymphatic obstruction

35. Protein Losing Enteropathy • Group of diseases with Hypoproteinemia and edema WITHOUT • Proteinuria/ kidney problems • Protein synthesis defects/ liver problems • Clinical Manifestation • Peripheral edema • Diarrhea • Steatorrhea

36. Protein Losing Enteropathy Pathogenesis Etiology • Excess protein loss in the GI tract • Exceeds the normal 10% protein catabolism

37. Protein Losing Enteropathy Key points • Peripheral edema, hypoproteinemia • More than >10% total protein breakdown • Proteins lost through exudates, altered permeability, lymphatic obstruction

38. Treatment