Malabsorption syndrome: pathophysiology and diagnosis. Teaching slides

Malabsorption syndrome: pathophysiology and diagnosis. Teaching slides

1. Malabsorption syndrome Stefano Fiorucci, MD Department of Surgery and Biomedical Sciences University of Perugia

2. Malabsorption Disorders of absorption constitute a broad spectrum of conditions with multiple etiologies and varied clinical manifestations. Almost all of these clinical problems are associated with diminished intestinal absorption of one or more dietary nutrients and are often referred to as the malabsorption syndrome . Malabsorption is a clinical term that encompasses defects occurring during the digestion and absorption of food nutrients Impairment can be of single or multiple nutrients depending on the abnormality. Most, but not all, malabsorption syndromes are associated with steatorrhea , an increase in stool fat excretion of >6% of dietary fat intake. Some malabsorption disorders are not associated with steatorrhea: primary lactase deficiency, a congenital absence of the small intestinal brush border disaccharidase enzyme lactase, is associated with lactose "malabsorption," and pernicious anemia is associated with a marked decrease in intestinal absorption of cobalamin (vitamin B 12 ) due to an absence of gastric parietal cell intrinsic factor required for cobalamin absorption

3. CLASSIFICATION OF MALABSORPTION SYNDROMES Inadequate digestion    Postgastrectomy   Deficiency or inactivation of pancreatic lipase    Exocrine pancreatic insufficiency , chronic pancreatitis , pancreatic cancer , cystic fibrosis , gastrinoma Reduced intraduodenal bile acid concentration/impaired micelle formation    Cholestatic liver diseases    Bacterial overgrowth in small intestine : Afferent loop /stricture/fistulas   Interrupted enterohepatic circulation of bile salts Ileal resection, Crohn disease   Drugs ( bind or precipitate bile salts ) neomycin , cholestyramine , calcium carbonate Impaired mucosal absorption/mucosal loss or defect    Crohn ’s disease    Inflammation, infiltration , or infection : Crohn ’s diseaase , amyloidosis , scleroderma Lymphoma , eophionolic gastroenteritis , celiac sprue, collagenous sprue Whipple disease , radiation enterits , infection includinggiardiasis , grapht vs host   Genetic disorders      Disaccharidase deficiency , agammaglobulinemia , abetalipoproteinemia , Hartnup disease , cystinuria   Impaired nutrient delivery to and/or from intestine : L ymphoma a Lymphangiectasia Lymphatic obstruction   Circulatory disorders Endocrine and metabolic disorders

4. Malabsorption:Causes Exocrine pancreatic insufficiency chronic pancreatitis pancreatic cancer cystic fibrosis Inactivation of pancreatic lipase – Gastrinoma (ZES) drugs ( orlistat )  bile acid (impaired micelle formation) parenchymal liver D. cholestatic liver D. Bacterial overgrowth Anatomic stasis (blind loop, stricture, fistula) Functional stasis (DM, scleroderma) Interrupted interohepatic circulation of bile acid ( ileal resection, crohn’s D.) Drugs(bind or precipitate bile salt) neomycin, chlestyramine Impaired mucosal absorbtion / mucosal loss or defect intestinal resection or bypass inflammation/infiltration/infect. ( celiac sprue , tropical sprue , whippl’s disease, lymphoma, mastocytosis , eosinophilic e., scleroderma, crohn’s D., …) Impaired nutrient transport lymphatic obstruction (lymphoma, lymphangectasia ) CHF Genetic disorders disacharidase defficiency Agamaglobulinemia Abetalipoprotinemia Endocrine/Metabolic disorders DM Hyperthyroidism adrenal insufficiency carcinoid syndrome

5. Malabsorptive disorders can be categorized into 1-Generalized mucosal abnormalities resulting in multiple nutrient malabsorption 2-Specific nutrient disorder (carbohydrate, fat, protein, vitamin and mineral malabsorption)

6. Malabsorptive disorders with generalized mucosal defects Celiac disease Cow’s milk allergy Microvillous inclusion disease Tufting enteropathy Lymphangiectasia Short bowel syndrome Chronic malnutrition Congenital immunodeficiency disorders HIV Parasitic infections Tropical sprue Bacterial overgrowth

7. Specific nutrient malabsorptive disorder Carbohydrate malabsorption - lactase deficiency (congenital, secondary) Congenital sucrase-isomaltase deficiency Glucose- galactose malabsorption Protein malabsorption - Enterokinase deficiency - Amino acid transport defect ( eg;Hartnup disease ) Fat malabsorption - Pancreatic exocrine insufficiency (cystic fibrosis, shwachman diamond syndrome, chronic pancreatitis) - liver and biliary disorders - abetalipoproteinemia

8. Specific nutrient malabsorptive disorder Mineral and vitamin malabsorption - Congenital chloride diarrhea -Congenital sodium absorption defect - Acrodermatitis enteropathica - Menke disease -Vitamin D dependent rickets -Vitamin B 12 malabsorption

9. Mechanisms Luminal phase (processing defect) Digestive enzyme deficiency / inactivation bile salt synthesis; Excretion; loss; bile salt de-conjugation gastric acid; intrinsic factor (p. anemia) Bacterial consumption of nutrients Mucosal phase Epithelial transport defect – inflammations infections Brush border hydrolysis defect congenital/acquired disacharidase deficiency Post-absorptive phase Enterocyte processing – Abetalipoproteinemia Lymphocytic obstruction – intestinal lymphangectasia

10. Clinical manifestations History: Diarrhea/steatorrhoea,Weight loss Symptoms of anaemia Diarrhoea – bulky, floating, malodorous stool – difficult to flush. Weight loss – may be profound, usually associated with anorexia. Anaemia – B12, iron, folate malabsorption. Patient may complain of dizziness, dyspnoea and fatigue

11. Symptom or Sign Mechanism Weight loss/malnutrition Anorexia, malabsorption of nutrients Diarrhea Impaired absorption or secretion of water and electrolytes; colonic fluid secretion secondary to unabsorbed dihydroxy bile acids and fatty acids Flatus Bacterial fermentation of unabsorbed carbohydrate Glossitis, cheilosis, stomatitis Deficiency of iron, vitamin B 12 , folate, and vitamin A   Abdominal pain Bowel distention or inflammation, pancreatitis Bone pain Calcium, vitamin D malabsorption, protein deficiency, osteoporosis Tetany, paresthesia Calcium and magnesium malabsorption Weakness Anemia, electrolyte depletion (particularly K + )   Azotemia, hypotension Fluid and electrolyte depletion Amenorrhea, decreased libido Protein depletion, decreased calories, secondary hypopituitarism Anemia Impaired absorption of iron, folate, vitamin B 12   Bleeding Vitamin K malabsorption, hypoprothrombinemia Night blindness/xerophthalmia Vitamin A malabsorption Peripheral neuropathy Vitamin B 12 and thiamine deficiency   Dermatitis Deficiency of vitamin A, zinc, and essential fatty acid

12. Signs, symptoms Caloric Weight loss with normal appetite Fat Pale,voluminous,greasy offensive diarrhea Protein Edema, muscle atrophy, amenorrhea carbohydrate Abdominal bloating, flatus, w. diarrhea B12 Macrocytic anemia Subacut combined degeneration of sp.cord Folic acid Macrocytic anemia Vit B (general) Cheliosis , glossitis,A.stomatitis , Acrodermatitis Iron Microcytic anemia Ca & Vit D Osteomalacea (bone pain,pathologic #), Tetany Vit A Follicular hyperkeratosis, Night blindness VIt K Bleeding diathesis, Hematoma

13. Malasportion syndrome Diagnosis

14. Endoscopy Gross morphology – gives diagnostic clue Reduced duodenal folds and scalloping of duodenal mucosa – celiac disease Use of vital dyes to identify villous atrophy Biopsy – to establish Dx For patients with documented steatorrhea or chronic Diarrhea Lesions seen – classifid in to three Diffuse,specific e.g. whippl’s Disease Patchy, specific – crohn’s D., lymphoma infectious causes Diffuse,non -specific – celiac sprue , Tropical sprue autoimmune enteropathy Suspected distal pathology - push enteroscopy wireless capsule endoscopy

15. Causes of villous atrophy in the duodenum Celiac disease Tropical sprue Small- bowel bacterial overgrowth Autoimmune enteropathy Hypogammaglobulinemic sprue Drug- associated enteropathy (e.g., olmesartan ) Whipple disease Collagenous sprue Crohn's disease Eosinophilic enteritis Intestinal lymphoma Intestinal tuberculosis Infectious enteritis (e.g., giardiasis ) Graft versus host disease Malnutrition Acquired immune deficiency syndrome enteropathy Small Bowel Biopsy

16. Wireless video-capsule

17. Barium studies Important information about the gross anatomy and morphology of SB Upper GI series with small bowell follow through Duodenal tube double contrast study by passing a tube into proximal SB and injecting barium+ methylcellulose Normal study doesn’t exclude small bowell disease

18. Functional tests for malabsorption ( excluding pancreatic causes ) Steatorrhea Shilling test Lactose test Xylose test Hydrogen breath test

19. Tests for steatorrhea Quantitative test 72hr stool fat collection – gold standard > 6gm/day – pathologic P’ts with steatorrhea - >20gm/day Modest elevation in diarrheal disease (may not necessarily indicate Malabsorption) Qualitative tests Sudan lll stain Detect clinically significant steatorrhea in >90% of cases Acid steatocrit – a gravimetric assay Sensitivity – 100%, specificity – 95% , PPV – 90% NIRA (near infra reflectance analysis) Equally accurate with 72hr stool fat test Allows simultaneous measurement of fecal fat, nitrogen, CHO

20. Schilling test To determine the cause of cobalamine (B 12 ) malabsorbtion Helps to asses the integrity of gastric, pancreatic and ileal functions. Abnormal cobalamine absorbtion in: pernicious anemia, ch. Pancreatitis, Achlorohydria , Bacterial overgrowth, ileal dysfunction The test Administering 58 Co-labeled cobalamine p.o. Cobalamine 1mg i.m . 1 hr after ingestion to saturate hepatic binding sites Collecting urine for 24 hr ( dependant on normal renal & bladder function) Abnormal - <10% excretion in 24 hrs

21. D-xylose test D-xylose A Pentose monosacharide absorbed exclusively at the proximal SB Used to asses proximal SB mucosal function The test After overnight fast, 25 gm D-xylose p.o . Urine collected for next 5 hrs Abnormal test - <4.5 gm excretion show duodenal / jejunal mucosal D. False + ve results: Renal dysfunction Inadequate urine sample Impaired gastric empyting , Ascites Drugs(ASA, indometacin , Neomycin )

22. Steatorrhea and D-Xylose Test Discriminate Maldigestion from Malabsorption MALDIGESTION (pancreatic insufficiency) MALABSORPTION (celiac sprue ) Fecal Fat D-Xylose Excretion Normal Jejunal Biopsy Normal Abnormal “flat”

23. Carbohydrate malabsorbtion Lactose tolerance test P.o. 50 gm lactose Blood glucose at 0,60,120 min. BG <20mg/l + dev’t of Sxs – diagnostic Breath tests hydrogen (also detects bacterial overgrowth) The hydrogen breath tests and lactose tolerance tests have Sensitivity and Specificity >95% in detecting in lactose intolerance i- H2 breath test is easier