8-GASTROENTESTINAL LECTURE Malabsorption syndrum.pptx

GIT LECTURE 8

1. Malabsorption syndrom Dr jabbar jasim

2. Malabsorptive Syndromes Impairment of intraluminal digestion, mucosal absorption, or nutrient delivery to the systemic circulation caused by many different diseases, drugs, or nutritional products.

3. Malabsorption Does not always cause diarrhea. Clinical signs of vitamin or mineral deficiencies may occur in the absence of diarrhea. Most digestion and absorption of nutrients occurs in the small intestine. Diarrhoea and weight loss in patients with a normal diet should always lead to the suspicion of malabsorption . Dietary fat is the nutrient most difficult to absorb. Fat is predominantly insoluble in the aqueous milieu of the intestine and critically depends on all phases of An intraluminal, or digestive, phase ; A mucosal, or absorptive, phase; and A delivery, or postabsorptive, phase . An abnormality at any site of this process can cause steatorrhea . Steatorrhoea : Bulky, pale and offensive stools which float in the toilet indicate fat malabsorption.

4. CLINICAL CONSEQUENCES or signs OF MALABSORPTION OF NUTRIENTS, WATER, AND ELECTROLYTES Nutrient Malabsorbed Clinical Manifestation Protein Wasting, edema Carbohydrate and fat Diarrhea, abdominal cramps and bloating, weight /growth retardation Fluid and electrolytes Diarrhea, dehydration Iron Anemia, cheilosis, angular stomatitis Calcium/vitamin D Bone pain, fractures, tetany Magnesium Paresthesias , tetany Vitamin B12/folate Anemia, glositis,cheilosis,paresthesias ,) ataxia (vitamin B12 only Vitamin E Paresthesias , ataxia, retinopathy Vitamin A Night blindness, xerophthalmia , hyperkeratosis, diarrhea Vitamin K Ecchymoses Riboflavin Angular stomatitis, cheilosis Zinc Dermatitis, hypogeusia, diarrhea

5. If history suggestive of malabsorption we should examine the patient for clinical sings resulted of nutrient deficiency and then we should send for routine blood tests to confirm malabsorption . Routine blood tests associated with malabsorption Hematological 1) Microcytic anaemia (iron deficiency) 2) Macrocytic anaemia (folate or B12 deficiency) 3) Increased prothrombin time (vitamin K deficiency) Biochemical 1) Hypoalbuminaemia . 2) Hypocalcaemia. 3)Hypomagnesaemia. 4)Deficiencies of phosphate, zinc. After that we should search for the cause of malabsorption with further investigations

6. History Examination (clinical signs) Routie blood tests Further investigations searching for the cause

7. CAUSES OF MALABSORPTION Conditions Causes of malabsorption Mechanism of Malabsorption :- Partial gastrectomy with gastrojejunostomy Impaired mixing Gastric bypass surgery Chronic pancreatitis Impaired lipolysis Pancreatic cancer Congenital pancreatic insufficiency Congenital co-lipase deficiency Gastrinoma Severe chronic liver disease Impaired micelle formation Cholestatic liver disease Bacterial overgrowth Crohn's disease Ileal resection Gastrinoma

8. Congenital, primary, and secondary lactase deficiency Impaired mucosal absorption Congenital enterokinase deficiency Abetalipoproteinemia Giardiasis Celiac disease Tropical sprue Agammaglobulinemia Amyloidosis AIDS-related (infections, enteropathy ) Causes of malabsorption

9. Radiation enteritis Graft-versus-host disease Whipple's disease Eosinophilic gastroenteritis Megaloblastic gut Collagenous sprue Ulcerative jejunitis Lymphoma Bacterial overgrowth Short-bowel syndrome Mastocytosis Impaired mucosal absorption

10. Congenital intestinal lymphangiectasia Impaired nutrient delivery Lymphoma Tuberculosis Constrictive pericarditis Severe congestive heart failure Hypoparathyroidism Unknown Adrenal insufficiency Hyperthyroidism Carcinoid syndrome Causes of malabsorption

11. 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. . Clinical features:- it can presents at any age, In infancy it occurs after weaning on to cereals and typically presents with diarrhoea , malabsorption and failure to thrive . In older children it may present with non-specific features such as delayed growth. Features of malnutrition are often found on examination and mild abdominal distension may be present. Affected children have both growth and pubertal delay, leading to short stature in adulthood. In adults peak onset is in the fifth decade and females are affected slightly more than males. The presentation is highly variable, depending on the severity and extent of small bowel involvement. Some patients have florid malabsorption while others develop non-specific symptoms such as tiredness, weight loss, folate deficiency or iron deficiency anaemia . Other recognised presentations include oral ulceration, dyspepsia and bloating.

12. DISEASE ASSOCIATIONS OF COELIAC DISEASE Insulin-dependent diabetes mellitus (2-8%) Thyroid disease (5%) Primary biliary cirrhosis (3%) Sjögren's syndrome (3%) IgA deficiency (2%) Pernicious anaemia Inflammatory bowel disease Sarcoidosis Myasthenia gravis Neurological complications- encephalopathy, cerebellar atrophy, peripheral Neuropathy, epilepsy Dermatitis herpetiformis Down's syndrome Enteropathy-associated T-cell lymphoma Small bowel carcinoma Squamous carcinoma of oesophagus Ulcerative jejunitis Pancreatic insufficiency Microscopic colitis Splenic atrophy

13. Investigations: in addition to routine investigations for coeliac disease we should do the following investigations:- Duodenal or jejunal biopsy Endoscopic small bowel biopsy is the gold standard, The histological features are usually characteristic but other causes of villous atrophy should also be considered Sometimes the villi appear normal but there are excess numbers of intraepithelial lymphocytes present . IMPORTANT CAUSES OF SUBTOTAL VILLOUS ATROPHY Coeliac disease Tropical sprue Dermatitis herpetiformis Lymphoma AIDS enteropathy Giardiasis Hypogammaglobulinaemia Radiation Whipple's disease Zollinger -Ellison syndrome

14. Antibodies( serological ):- IgA anti­endomysial antibodies are detectable in most untreated cases and are sensitive and specific. IgG antibodies must be analysed in patients with coexisting IgA deficiency. . TTG{ Tissue transglutaminase} assays have replaced other blood tests in many countries as they are easier to perform, semi-quantitative and more accurate in patients with IgA deficiency. These antibody tests constitute a valuable screening tool in patients with diarrhoea but are not a substitute for small bowel biopsy; they usually become negative with successful treatment. Other investigations Barium follow-through X-rays dual energy X-ray absorptiometry ( DEXA scanning) to look for evidence of metabolic bone disease.

15. Management life long gluten free diet with correction of existing deficiencies of iron, folate, calcium and/or vitamin D. , The exclusion of wheat, rye, barley and initially oats these contain gluten. Rice, maize and potatoes are satisfactory sources of complex carbohydrates. The most common reason for failure to improve with dietary treatment is accidental or unrecognised gluten ingestion. Jejunal or duodenal biopsies when to be repeat ; should be reserved for patients who do not symptomatically improve or whose antibodies remain persistently positive. while patients who have an excellent clinical response, with disappearance of circulating anti- endomysial antibodies, probably do not need. Refractory coeliac require treatment with corticosteroids or immunosuppressive drugs to induce remission although dietary compliance should be carefully assessed in patients who fail to respond but if their diet is satisfactory and also we should exclude other conditions such as pancreatic insufficiency or microscopic colitis also complications of coeliac disease such as ulcerative jejunitis or enteropathy-associated T-cell lymphoma.

16. Prognosis and complications There is an increased risk of malignancy Enteropathy-associated T-cell lymphoma. Small bowel carcinoma. Squamous carcinoma of the oesophagus . A few patients develop ulcerative jejunoileitis ; fever, pain, obstruction or perforation. Metabolic bone disease is common in patients with long-standing, poorly controlled coeliac disease.

17. DERMATITIS HERPETIFORMIS This is characterised by crops of intensely itchy blisters over the elbows, knees, back and buttocks . Almost all patients have partial villous atrophy on jejunal biopsy, even though they usually have no gastrointestinal symptoms. In contrast, fewer than 10% of coeliac patients have evidence of dermatitis herpetiformis. Treatment The rash usually responds to a gluten-free diet but some patients require additional treatment with dapsone (100-150 mg daily).

18. TROPICAL SPRUE defined as chronic, progressive malabsorption in a patient in or from the tropics, associated with abnormalities of small intestinal structure and function. The Aetiology : The epidemiological pattern and occasional epidemics suggest that an infective agent or agents may be involved, Although no single bacterium has been isolated, the condition often begins after an acute diarrhoeal illness. Small bowel bacterial overgrowth with Escherichia coli , Enterobacter and Klebsiella is frequently seen. Clinical features: diarrhoea , abdominal distension, anorexia, fatigue and weight loss, in visitors to the tropics the onset of severe diarrhoea may be sudden and accompanied by fever. When the disorder becomes chronic, the features of megaloblastic anaemia ( folic acid malabsorption ) and other deficiencies including ankle oedema, glossitis and stomatitis are common. Remissions and relapses may occur.

19. Diagnosis :- Endoscopic biopsy resemble those of coeliac disease. Partial villous atrophy is more common than subtotal villous atrophy. Management Tetracycline 250 mg 6-hourly for 28 days is the treatment of choice and brings about long-term remission or cure. folic acid (5 mg daily) improve symptoms and jejunal morphology. In some cases treatment must be prolonged before improvement occurs, and occasionally patients must leave the tropics.

20. Whipple's disease : is a multisystemic disease and almost any organ can be affected, sometimes long before gastrointestinal involvement becomes apparent The disease is caused by infection with the Gram-positive bacillus Tropheryma whipplei which is resident within macrophages 'foamy' macrophages in small intestinal mucosa which stain positive with periodic acid-Schiff (PAS). The Villi are widened and flattened; densely packed macrophages occur in the lamina propria, these may obstruct lymphatic drainage causing fat malabsorption.

21. Clinical features of Whipple's disease most commonly affected are Middle-aged men . Gastrointestinal (> 70%) : Diarrhoea (75%), steatorrhoea , weight loss (90%), Bloating protein-losing enteropathy, ascites, hepatosplenomegaly (< 5%) Musculoskeletal (65%) Seronegative large joint arthropathy, sacroiliitis

22. Haematological (60%) Anaemia , lymphadenopathy Neurological (10-40%) Apathy, fits, dementia, myoclonus, meningitis, cranial nerve lesions Cardiac ( 10% ) Pericarditis, myocarditis, endocarditis, coronary arteritis Other (40%) Fever, pigmentation .

23. Whipple's disease is often fatal if untreated Treatment Intravenous ceftriaxone 2 g daily for 2 weeks, followed by oral co-trimoxazole for at least 1 year Relapse occurs in up to 30% of patient usually neurological in which case the same therapy is repeated or else treatment with doxycycline and hydroxychloroquine .

24. Small bowel bacterial overgrowth (blind loop syndrome) The normal duodenum and jejunum contain less than 10 4 / mL organisms which are usually derived from saliva. Coliform organisms never exceeds 10 3 / ml In bacterial overgrowth there may be 10 8 -10 10 / ml organisms. Disorders which impair the normal physiological mechanisms controlling bacterial proliferation in the intestine predispose to bacterial overgrowth .

25. Examples Mechanism Pernicious anaemia Partial gastrectomy Long-term PPI therapy Hypo- or achlorhydria Scleroderma Diabetic autonomic neuropathy Chronic intestinal pseudo-obstruction Impaired intestinal motility Gastric surgery (blind loop after Billroth II operation) Jejunal diverticulosis Enterocolic fistulas (e.g. Crohn's disease) Extensive small bowel resection Strictures (e.g. Crohn's disease) Structural abnormalities Hypogammaglobulinaemia ( IgA and IgM levels in serum and jejunal secretions are reduced)causing bacterial overgrowthand recurrent gastrointestinal infections (particularly giardiasis). Impaired immune function Causes of small bowel bacterial overgrowth

26. Clinical features of bacterial overgrowth Patient presents with watery diarrhea and/or steatorrhoea with anaemia due to B12 deficiency, these arise because of :- Deconjugation of bile acids ( certain bacteria, e.g., Bacteroides , deconjugate conjugated bile acids to unconjugated bile acids. Unconjugated bile acids will be absorbed more rapidly than conjugated bile acids, and, as a result, the intraduodenal concentration of bile acids will be reduced.) , this will impairs micelle formation, And because of bacterial utilization of vitamin B12. symptoms from the underlying intestinal cause.

27. Investigations Serum vitamin B12 concentration is low, folate levels are normal or elevated because the bacteria produce folic acid. Barium follow-through or small bowel enema may reveal blind loops or fistulas. Endoscopic duodenal biopsies exclude mucosal disease such as coeliac disease. Jejunal contents for bacteriological examination can be aspirated at endoscopy; the laboratory analysis requires anaerobic and aerobic culture techniques. Glucose hydrogen or 14 C-glycocholic acid breath tests In these tests breath samples are serially measured after oral ingestion of the test material, bacteria within the small bowel cause an early rise in breath hydrogen from glucose or 14 C from 14 C-glycocholate.

28. 5- Serum immunoglobulins reduced in Hypogammaglobulinaemia 6- Reduced or absent plasma cells and nodules of lymphoid tissue also in Hypogammaglobulinaemia .

29. Treatment The underlying cause of small bowel bacterial overgrowth should be addressed Tetracycline 250 mg 6-hourly for 7 days, 50% of patients do not respond so alternative is:- Metronidazole 400 mg 8-hourly or ciprofloxacin 250 mg 12-hourly Intramuscular vitamin B12 supplementation is needed in chronic cases. Antidiarrhoeal drugs ( diphenoxylate 5 mg 8-hourly orally or loperamide 2 mg 4-6-hourly orally ) for those with motility disorders. In hypogammaglobulinaemia treatment should focus on control of giardiasis and, if necessary, immunoglobulin infusions.

30. Ileal resection usually found after surgery for Crohn's disease which cause malabsorption. Vitamin B12 and bile salt malabsorption develops, Unabsorbed bile salts pass into the colon, stimulating water and electrolyte secretion and resulting in diarrhoea . If hepatic synthesis of new bile salts cannot keep pace with faecal losses, fat malabsorption occurs. The faecal losses of bile salts lead to formation of lithogenic bile & leading to gallstones.

31. Renal calculi rich in oxalate develop( normally, oxalate in the colon is bound to and precipitated by calcium. Unabsorbed bile salts preferentially bind calcium, leaving free oxalate to be absorbed with subsequent development of urinary oxalate calculi ) Patients have urgent watery diarrhoea or mild steatorrhoea . Investigations: Contrast studies of the small bowel and tests of B12 ( Schilling test ) and bile acid absorption. Treatment: Parenteral vitamin B12 supplementation. Diarrhoea usually responds well to colestyramine , a resin which binds bile salts in the intestinal lumen, Aluminium hydroxide is an alternative therapy.

32. Comparison of Different Types of Fatty Acids   Long-Chain Medium-Chain Short-Chain Carbon chain length < 12 8---12 > 8 Present in diet In large amounts In small amounts No Origin In diet as triglycerides Only in small amounts in diet as triglycerides Bacterial degradation in colon of nonabsorbed carbohydrate to fatty acids Primary site of absorption Small intestine Small intestine Colon Requires pancreatic lipolysis Yes No No Requires micelle formation Yes No No Presence in stool Minimal No Substantial

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