approach to Malabsorption Syndrome .pptx

approach to Malabsorption Syndrome

1. M a l a b sorption Syndrome

2. S u p e r v i s e d b y D o c t o r . S a l a h A l l i A L - T a w e e l . T h i s s e m inar c o l lection a n d d o n e b y M o h ammed Saleh Nasher Hazza a n d w a h e e b S a l e h Nasher

3. Learning objectives Outline the function of small intestine. Define malabsorption. Identify the causes and pathogenesis of malabsorption. Explain the clinical manifestations of malabsorption. Review the investigations of malabsorption. Recognize the definition, causes, clinical features, investigations, management and complications of celiac disease. List the causes of subtotal villous atrophy. Define the following: Dermatitis herpetiformis , tropical sprue , small bowel bacterial overgrowth and ileal resection malabsorption .

4. Small intestine: The small intestine extends from the ligament of Treitz to the ileocaecal valve. The average length of the small intestine in an adult is about 7 m. Which divided into three parts: duodenum, jejunum and ileum. Functions of the small intestine are: Digestion: (mechanical, enzymatic and peristaltic) Absorption: the products of digestion, water, electrolytes and vitamins Protection: against ingested toxins Immune regulation

5. 1- Digestion and absorption of fat

6. 2-Digestion and absorption of carbohydrates: Composed of: A- Polysaccharide starch – amylases action-- alpha-limit dextrins – maltose and maltotriose . B- Disaccharides ( sucrose and lactose ) are hydrolyzed by brush border sucrase and lactase enzymes to momosaccharides . C- Monosaccharides glucose, galactose are actively transport and fructose by simple diffusion.

7. 3- Digestion and absorption of proteins

8. MALABSORPTION S y n drome Defin ition : as a clinical C o n dition due to d e f e c tive o r diminished intestinal absorption of one or more o f dietary nutrients. Includes a broad spectrum of conditions with multiple aetiologies and vari a ble clinical manifestation. Aetiology and pathogenesis: due to abnormalities of the three processes of normal digestion. 1-Intraluminal malabsorption a-Reduced nutrient availability Cofactor deficiency (pernicious anemia, gastric surgery) Nutrient consumption (bacterial overgrowth)

9. b-Impaired fat solubilization Reduced bile salt synthesis (hepatocellular disease) Impaired bile salt secretion (chronic cholestasis) Increased bile salt losses (terminal ileal disease) c-Defective nutrient hydrolysis Lipase inactivation (ZE syndrome) Enzyme deficiency (pancreatic insufficiency or cancer) Improper mixing or rapid transit (resection, bypass, hyperthyroidism)

10. 2-Mucosal malabsorption a-Extensive mucosal loss (resection or infarction) b-Diffuse mucosal disease (celiac disease, Crohn's disease, irradiation , infection, infiltrations) c-Brush border hydrolase deficiency (lactase deficiency) d-Epithelial processing ( abetalipoproteinemia ) 3-Postmucosal malabsorption a-Vascular conditions (vasculitis, atheroma) b-Lymphatic conditions ( lymphangiectasia , irradiation, nodal tumor, cavitation, or infiltrations)

11. 4- Multiple Mechanisms : Example : Subtotal gastrectomy leads to premature gastric emptying resulting in impaired mixing of food with bile and pancreatic enzymes, associated with bacterial overgrowth due to hypochlorhydria .

12. E t i ology : A c c o r d ing t o A n a t o mical c a u ses : A - G a s t r i c c a u se s : 1 - g a s t r i c s u r gery : e . g . G a s t r e c t o m y . 2 - G a s t r i c C a r c i noma & p e r n i cious A n e mia : d e c r ease d H C L l e a d i ng t o b a c t e rial o vergrowth i n t h e i n t e s t ine . 3 - Gastr i n o m a : i n c r eased H C L l e a ding t o i n h i bition o f d i g e s t ive e n z y m e s . B - p a n c r ea t i c c a u ses : 1 - c h r o n i c p ancreatitis 2 - C y s t ic fibrosis o f t h e p a n c r eas 3 - p a n c r ea tic c a r c i noma 4 - p a n c r e tectomy C - H e p a t o - b i l i a ry : 1 - A c u te a n d c h r onic l i v e r d i s e ase 2 - o b s tructive jaundice

13. D . S m a l l i n testi n al d i s ease s : m o s t common 1 - C o e l iac d i s ease ( g l u ten sensitiv e e n t e r o p athy ) : i s t h e m o st common c a u se 5 2 % 2 - B a c t erial overgrowth : i s t h e s e c o n d c o m m o n c a u s e 1 2 % . ♦ B a c t e r i a l o v e r g r o w t h → S t a g n a n t ( b l i n d ) l o o p S y n drome d u e to s t r i c t u r e s , d i v e r t i c u l o s i s , d e c r eased m o t i l i ty e . g . D M , h y p o t h yroidism , S y s t e m i c S c l eroderma l e a d t o S t a g n ant o f i n t e s t inal c o n t e n ts w i t h o v e r g rowth o f b a c t eria w i t h d i a r r hea a n d m a l a b sorption

14. 3 - S h o r t b o w e l s y ndrome ( i n t e s tin al r e s e c t ion ) E x c e s s ive i n t e s t inal r e s e c tion w i l l r e d u ce t h e a v a i l able s u r f a ce f o r a b s o r p tion . 4 - i n t e s t inal l y m p h a t ic o b s t r u ction : e . g . W h i p p le's d i s ease & l y m phoma 5 - i n f e c t i o n : e . g . T B , p a r a s ite s e . g G i a r d i a L a m b l i a . A n d H I V e n t e r o p athy . 6 - I n f l ammation : • Crohn's d i s e ase , T r o p ical s p r u e a n d W h i p p le's dis ease s 7 - i r r a diation e n t e r i t i s . 8 - D i s a c c harid a s e d e f i c iency : L a c t a se d e f i ciency → m a l a b sorption o f l a c t ose → b l o a t i n g a n d d i a rrhoea 9 - A m y l o idosis :

15. 1 - I n t e s tinal m o t i l i ty d e f e c t : • i n c r e ase d m o t i l ity : e . g . h y p e r t h yroidism . • d e c r eased m o t i l ity : e . g . D M , h y p o thyroidism & s y s t e m i c Scleroderma . ♦ D r u g s - i n d u c e d : • C h o l e s t y r a m i n e • n e o m y cin • o r l i s t a t ♦ M i s c ellaneous : 1 - h e a r t : c o n g e sti ve heart failure & c o n s t r i c t i v e p e r icarditis . 2 - H y p o g a m m a g l o b u l i n e m i a : i s c o n g e n i tal v i l l u s A t r o p hy .

16. C l i n i cal p i cture o f Mal a b sorption S y n drome : 1 - g e n eral f e a t ures o f m a l a b sorption S y n d rome : ♦ S t e a t o r r hoea ( f a t t y s t o o l ) i s S t o o l b u l k y , g r e a s y , o f f e n sive , d i f f i cult t o f l u s h ♦ d i a r r hea d u e to i m p a i red a b s o r p tion w i t h i n c reased s e c r e t i o n o f w a t e r ♦ W e i ght l o s s d u e t o m a l a b sorption o f f a t ♦ w e a kness d u e to m a l a b sorption o f p r o t e i n s ♦ F l a t u s d u e to b a c t e rial f e r m e n t ation o f u n a b s o rbed c a r b o h y drates . ♦ A b d o m i nal p a i n d u e to d i s t e n sion o r i n f l a m m e d b o w e l . ♦ A b d o m inal d i s t e n sion . ♦ b o r b o r ygmi ( a u d i b le i n t e s t inal s o u n d s . )

17. Fats : Loss of weight.  Proteins : Muscle wasting & nutritional oedema.  Carbohydrates : hypoglycemia. E x c e p t i n p a t . D . M .  Vitamin A : Night blindness.  Vitamin D : Rickets or osteomalacia  Vitamin E : Dermatitis.  Vitamin K : Bleeding tendency  Vitamin B1 : Beri-Beri.  Vitamin B2 : Glossitis & angular stomatitis.  V i t a min B 3 : Pellagra  Vitamin B6 : Peripheral neuropathy.  Vitamin B12 : Megaloblastic anemia & SCD. 2 - S p e c i f i c f e a t ures o f d e f i ciency o f s p e c i f ic f a c t ors .

18.  Folic acid : Megaloblastic anemia.  Iron : Microcytic anemia.  Sodium : Muscle cramps & hypotension  Potassium : Myopathy & arrhythmia  Calcium : Parasthesia & tetany  Magnesium : arrhythmia & tetany.  Water : Dehydration. 3 - Features of the cause : l a t e r o n

19. I n v e stigation o f m a l a b sorption S y n drome A. Investigations to diagnose malabsorption: 1. Fat in the stools:  Normally : fat in the stools is not more than 6 gm/day  In steatorrhea : total fat is increased:  Non-split: in impaired digestion (pancreatic disorder)  Split: in small intestinal diseases. 2. Urinary D-xylose test :-  Method : give 25 gm D- Xylose orally, then collect urine over the next 5 hours.  Normally : urine collected over 5 hours should contain at least 5 gm of D – Xylose.  In steatorrhea : urine collected over 5 hours will contain less than 5 g m of D – Xylose " provided that renal functions are normal "

20. 3. Barium follow through of the small intestine: • Loss of the normal feathery appearance of the jejunum. • Segmentation & flocculation of the barium pattern. • Dilatation of the intestinal lumen. 4. Jejunal Biopsy : √ Recently : taken through the enteroscope. √ Previously : taken by the intestinal biopsy capsule (Crosby capsule).

21. Lesions Pathologic Findings D i f fuse , s p e c i fic Whipple’s disease Lamina propria contains macrophages containing PAS+ material Agammaglobulinemia No plasma cells; either normal or absent villi (“flat mucosa”) Abetalipoproteinemia Normal villi; epithelial cells vacuolated with fat postprandially

22. L e s i o ns p a t c h y , s p e c i fic P a t h o log ic f i n ding Intestinal lymphoma Malignant cells in lamina propria a n d s u b m u cosa Amyloidosis Amyloid deposits Crohn’s disease Noncaseating granulomas

23. l e s i o ns , diffuse , n o n s p ecific P athologic finding Celiac disease Short or absent villi; mononuclear infiltrate; epithelial cell damage; hypertrophy of crypts Tropical sprue Similar to celiac disease Bacterial overgrowth Patchy damage to villi; lymphocyte infiltration Drug-induced enteritis Variable histology

24. B. Investigations to diagnose the cause: 1. Glucose tolerance test: i n small intestinal diseases: flat curve.  In pancreatic causes : diabetic curve. 2. Tests for Bacterial overgrowth:  14 C-glycocholic breath test: Method: measure the 14 CO2 in the breath after oral administration of 14 C- glycocholic. In bacterial overgrowth : 14 CO2 in the breath will increase because more bacteria will act on the 14 C – Xylose.

25. Investigations of bile salt malabsorption ( SeHCAT test): SeHCAT is radiolabeled bile salt in capsule. It’s serum level of less than 15% after ingestion of capsule is abnormal. 4 - Schilling test (vitamin B 12 malabsorption): using a radiolabeled vitamin B 12 as a marker. malabsorption of vitamin B 12 can occur because of lack of intrinsic factor (e.g., pernicious anemia or gastric resection), pancreatic insufficiency , bacterial overgrowth , or ileal disease.

26. C. Investigations for the deficient factors: 1. Blood picture : microcytic or megaloblastic anemia 2. Plasma proteins : hypoproteinemia 3. Serum electrolytes : diminished iron, Na, K, Ca, Mg. 4. Bone X –ray: osteomalacia.

27. Investigation of malabsorption

28. Treatment of Malabsorption S y ndrome : 1. Treatment of the cause: e.g. anti – TB drugs for TB. 2. Replacement of the deficient factors : e.g. parentral vitamins & minerals.

29. COELIAC DISEASE Coeliac disease: is an immunologically mediated inflammatory disorder of the small bowel occurring in genetically susceptible individuals and resulting from intolerance to wheat gluten and similar proteins found in rye, barley and, to a lesser extent, oats. Gluten = Glutenin + Gliadin . Tissue transglutaminase (TTG) is the autoantigen for anti- endomysial antibodies, used in serological diagnosis.

30. E t i o logy o f c o e l iac d i s e ase : I d i o p athic ( u n k n own c a u s e s ) b u t t h e r e a r e E n v i ronmental f a c t o r e . g . g l uten d i e t & v i r a l i n fections e . g . a d e n o v i rus 1 2 G e n etic f a c t o r : d u e t o P r e s e nt H L A D Q 2 / H L A D Q 8 & r e l a tive f i r s t d e g r ee 1 % T w i n s i s 7 5 % I m m u n olog ical f a c t or s .

31. Wheat

32. Barley

33. Rye

34. Oats

35. After being taken up by epithelial cells, gluten peptides are deamidated by the enzyme tissue transglutaminase in the subepithelial layer. They are then able to fit the antigen-binding motif on HLA-DQ2 positive antigen presenting cells. Recognition by CD4+ T cells triggers a Th 1 immune response with generation of pro-inflammatory cytokines (IL-1, IFN- γ and TNF- α). Lymphocytes infiltrate the lamina propria , and increased intraepithelial lymphocytes (IEL), crypt hyperplasia and villous atrophy ensue.

36. Clinical features: Typical features: presents with steatorrhea, with abdominal distension, weight loss, and delayed growth. Atypical features: tiredness, folate or IDA or oral ulcers. Extraintestinal features: depression, arthralgias , osteoporosis, or osteomalacia . Associations: dermatitis herpetiformis, type 1 diabetes mellitus, autoimmune thyroid disease.

37. Bulky, oily, pale and offensive stools which float in the toilet (steatorrhoea) signify fat malabsorption.

38. Investigations; 1- Duodenal or jejunal biopsy: an increase in mucosal lymphocytes and plasma cells (the infiltrative lesion) with partial blunting or total villous flattening. 2-Antibodies: Serum antigliadin (especially IgA ) and Anti- endomysial antibodies IgA Ab. 3-Haematology and biochemistry: Microcytic or macrocytic anaemia from iron or folate deficiency , reduced concentrations of calcium, magnesium, total protein, albumin or vitamin D. 4-Barium follow-through: dilated loops of bowel, diminished folds , flocculation of contrast.

39. Important causes of subtotal villous atrophy Coeliac disease Tropical sprue Dermatitis herpetiformis Lymphoma AIDS enteropathy Giardiasis Hypogammaglobulinaemia Radiation Whipple's disease Zollinger-Ellison syndrome

40. Management: 1-Correct existing deficiencies of iron, folate , calcium and/or vitamin D. 2-Commence a life-long gluten-free diet. Exclusion of wheat, rye, barley and initially oats Introduced rice, maize and potatoes as a sources of carbohydrates. Booklets produced by coeliac societies.

41. Follow up: 1-Regular monitoring: of symptoms, weight and nutrition is essential. 2-Compliance to diet. 3-Good response: improve symptoms with disappearance of anti- endomysial antibodies. 4-Repeat jejunal biopsies: If symptoms do not improved or antibodies remain persistently positive. Complications of celiac disease: 1- Intestinal lymphoma 2- Small bowel carcinoma 3- Squamous carcinoma of the oesophagus 4- Ulcerative jejunoileitis

42. DERMATITIS HERPETIFORMIS: It is skin lesion characterised by crops of intensely itchy blisters over the elbows, knees, back and buttocks , due to IgA Ab deposition, associated with partial villous atrophy on jejunal biopsy, responds to a gluten-free diet , some time with addition of dapsone. TROPICAL SPRUE: Chronic, progressive malabsorption in a patient in or from the tropic, associated with small intestinal infection. Tetracycline 250 mg 6-hourly for 28 days is the treatment of choice, with folic acid supplementation lead to improve symptoms and jejunal morphology.

43. SMALL BOWEL BACTERIAL OVERGROWTH ('BLIND LOOP SYNDROME') The count of coliform organisms in small intestine may be 10 8 -10 10 /ml organisms considered bacterial overgrowth. The normal contain less than 10 4 /ml organisms in the duodenum and jejunum. Due to impair the normal physiological mechanisms controlling bacterial proliferation in the intestine. Patient presents with watery diarrhoea and/or steatorrhoea , with anaemia due to B12 deficiency. Treatment of the underlying cause. Tetracycline is the treatment of choice. Metronidazole or ciprofloxacin is an alternative. Intramuscular vitamin B12 supplementation may be needed in chronic cases.

44. ILEAL RESECTION: Malabsorption that results from ileal resection , for example following surgery for Crohn's disease, that leads to Vitamin B 12 and bile salt malabsorption. Unabsorbed bile salts pass into the colon stimulating water and electrolyte secretion and causing watery diarrhoea . Other consequences of ileal resection shown in the next slide Diarrhoea usually responds to colestyramine . Aluminium hydroxide is an alternative. Parenteral vitamin B12 supplementation is necessary.

45. Consequences of ileal resection

46. Megaloblastic anemia due to vitamin B12 deficiency. A- the tongue is smooth, shiny and loss of papillae. B- blood film: macrocytosis , hypochromia and hypersegmented neutrophil. A B

47. REFERENCES 1 - Davidson's (Principles and Practice of Medicine). 2 - Harrison text book (principles of Internal Medicine). 3 - Cecil Textbook (Textbook of Medicine). 4 - Kumar (Clinical Medicine). 5 - O T H ER B O OKS O F I N T E R N AL MEDICINE A S B O O K D O CTOR O S A M A M A H MOUD A N D B O O K S D O C T OR M A H M OUD A L L A M

48. Thanks