Disorders of Malabsorption

1. Disorders of Malabsorption

2. Malabsorption It is a descriptive term of many diseases and is not a diagnosis Result from either a defect in nutrient digestion in the intestinal lumen or mucosal absorption

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

4. 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

5. 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

6. Specific nutrient malabsorptive disorder Mineral and vitamin malabsorption -Congenital chloride diarrhea -Congenital sodium absorption defect -Acrodermatitis enteropathica -Menke disease -Vitamin D dependent rickets -Vitamin B12 malabsorption

7. Malabsorption Clinical manifestations: -Diarrhea -Abdominal distention -Failure to thrive -edema -digital clubbing -abnormal hair -muscle wasting -stomatitis and glossitis -signs of rickets -skin bruises

8. Malabsorption Diarrhea is the main presentation of malabsorption: Onset: at birth, relation to food Character: offensive, oily, watery,�

9. Evaluation of children with malabsorption CBC and blood film anemia, lymphopenia (lymphangiectasia), neutropenia (shwachman syndrome), acanthocytosis (abetalipoproteinemia) Stool: Leukocytes and occult blood Parasites PH and reducing substances

10. Evaluation of children with malabsorption Celiac serology Albumin level Ca, Mg, zinc Iron level, folic acid level, Vit B12 Vit D, E, A Prothrombin time Upper endoscopy

11. Investigations for Carbohydrate malabsorption Clinitest: Detect reducing substances in the stool stool PH less than 5.6 Carbohydrate reach the bowel where they are degraded to Hydrogen gas+ CO2+ organic acids

12. Investigations for Carbohydrate malabsorption 3-Breath hydrogen test Ingestion of carbohydrate load (sucrose or lactose)1-2g/kg, sugar will not be ingested in the small bowel and passes to the colon and then metabolized by normal flora into hydrogen gas which will be detected in the breath

13. Investigations for Carbohydrate malabsorption 4-Small bowel mucosal biopsies Low mucosal disaccharidase levels in primary disaccharidase deficiency (lactase, sucrase, maltase)

14. Investigations for fat malabsorption Sudan test -Best screening method -Mixing the stool with sudan red stain, fat droplets will separate and be identified, more than 6-8 droplets / low power field is abnormal 72-hr quantitative fecal fat test - The gold standard to confirm steatorrhea Dietary record is used to calculate fat intake for 3 days, stool is collected, excretion of more than 7% is abnormal

15. Investigations for Gastrointestinal Protein loss Dietary and endogenous proteins are almost absorbed Majority of stool nitrogen is derived from gut bacterial proteins Albumin Level: -GI loss of protein manifests as hypoalbuminemia -low albumin occur due to other factors a1-antitrypsin: -Useful screening test for protein losing enteropathy -Unlike albumin, is resistant to digestion in the GIT -High levels in the stool indicate protein losing enteropathy

16. Investigations for Pancreatic Exocrine function Most common is Cystic fibrosis Sweat chloride test Genetic testing Fecal elastase: -Sensitive test to assess exocrine pancreatic function -endoprotease that is human and pancreas specific, not altered by pancreatic enzyme replacement Serum Trypsinogen Duodenal aspirate Analysis of bicarbonate, trypsinogen and lipase after secretin stimulation

17. Cystic Fibrosis Multisystem disorder characterized by obstruction and infection of the airways and by maldigestion Autosomal recessive inheritance CF gene codes for CFTR (CF Transmembrane Regulator) expressed on epithelial surfaces Most common mutation is F508

18. Cystic Fibrosis Gastrointestinal Manifestations: Meconium ileus in newborns (10-20%) specific for CF, manifest in 1st 24-48hrs, picture of intestinal obstruction Rectal prolapse related to steatorrhea, malnutrition, chronic cough

19. Cystic Fibrosis Prolonged neonatal jaundice Mainly obstructive type - Distal intestinal obstruction syndrome (DIOS) accumulation of fecal material in terminal ileum or cecum leading to partial or total obstruction - Intussusception , volvolus, appendicitis

20. Cystic Fibrosis Pancreatic exocrine insufficiency bulky greasy frequent stools, failure to gain weight, abdominal distention ( Malabsorption picture), Liver Disease biliary cirrhosis, fatty liver, biliary colic secondary to cholilithiasis - Pancreatitis

21. Cystic Fibrosis Diagnostic Criteria Clinical features Laboratory evidence: (GIT, Respiratory, - Two positive sweat chloride genitourinary) tests OR OR History of CF in a sibling PLUS - Two CF mutations OR OR Positive newborn - An abnormal nasal potential screening test difference

22. Cystic Fibrosis Management: High calorie diet Pancreatic enzyme replacement max 2500IU/Kg/meal Vitamin and mineral replacement

23. Celiac Disease Permanent intolerance to gluten Mainly affects the small bowel Common period of presentation is between 6 months and 2yr of age

24. Celiac Disease Gluten is mainly found in wheat, rye and barley Gluten leads to sensitization of lamina propria lymphocytes leading to villus atrophy, crypt hyperplasia and damage to surface epithelium

25. Celiac Disease There is genetic predisposition -concordance rate in MZ twins reach 100% - 5-10% of first degree relatives will have celiac disease -associated with HLA(B8, DR7, DR3,DQw2)

26. Celiac Disease Clinical manifestations: Mode of presentation is variable asymptomatic or Picture of malabsorption

27. Celiac Disease Symptoms Diarrhea Failure to thrive Vomiting Irritability Anorexia Large bulky stool Abdominal pain Signs Growth retardation Clubbing Muscle wasting Abdominal distension edema

28. Celiac Disease Associations IgA deficiency Pernicious anemia DM Addison disease Hypothyroidism Alopecia Down syndrome

29. Celiac Disease Diagnosis Serological markers Antigliadin antibodies IgG & IgA Antiendomysial antibodies IgA Anti tissue transglutaminase IgA and IgG

30. Celiac Disease Small bowel biopsy -Short, flat villi -increased number of lymphocytes in the epithelial layer -crypt hyperplasia

31. Celiac Disease Treatment Life long, strict gluten-free diet Improve the appetite, decrease the diarrhea, reverse osteopenia, prevent lymphoma, enhance appropriate growth and puberty