Malabsorption syndrome......................pptx

malabsorbtion

1. MALABSORPTION SYNDROME- in s h o r t GHPD , B I R D E M

2. Malabsorption Maldigestion: refers to impaired hydrolysis of luminal contents. Malabsorptoin: refers to impaired transport across the mucosa. In clinical practice,malabsorption is used to describe the end result of either defect. Malabsorption may involve a broad range of nutrients (Panmalabsorption) or only an indivudual nutrient or class of nutrients (specific malabsorption).

3. Each day, the average person consumes 2000 to 3000 kcal of food. Most of this caloric load is in the form of polymers or other complex compounds that must be broken down into smaller molecules, to be transported across the small intestinal mucosa. Thus, proteins are cleaved into dipeptides and amino acids, starches are split into monosaccharides, and fats are broken down into fatty acids and monoglycerides.

4. A typical Western diet ingested by an adult includes approximately 100 g. of fat, 400 g of carbohydrate, 100 g of protein, 2 L of fluid, and the required sodium, potassium, chloride, calcium, vitamins, and other elements. Salivary, gastric, intestinal, hepatic, and pancreatic secretions add an additional 7–8 L of protein-, lipid-, and electrolyte-containing fluid to intestinal contents.

5. This massive load is reduced by the small and large intestines to less than 200 g of stool that contains less than 8 g of fat, 1–2 g of nitrogen, and less than 20 mM each of Na+, K+, Cl–, HCO3–, Ca2+, or Mg2+. If there is impairment of any of the many steps involved in the complex process of nutrient digestion and absorption, intestinal malabsorption may ensue.

6. Nearly 200 conditions are associated with defects in this process and can produce substantial disability.

7. Malabsorption can be sorted pathophysiologically into conditions that are associated with Impaired luminal hydrolysis. Impaired mucosal function (mucosal hydrolysis, uptake and packaging). Impaired removal of nutrients from the mucosa. Pathophysiology

8. A.Imapired luminal hydrolysis or solubilization. Pancreatic exocrine insufficiency. Bile acid deficinecy. Zollinger Ellison syndrome. Post gastrectomy malabsorption. Rapid intestinal trnasit. Small bowel bacterial overgrowth. Causes of malabsorption

9. B.Impaired mucosal hydrolysis, uptake or packaging I.Brush border or metabolic disorder lactase deficiency Sucrose-isomaltase deficiency Glucose –galactose malabsoption II.Mucosal disease Celiac sprue Collageneous sprue Nongranulomatous ulcerative jejunoileitis Eosinophilic gastroenteritis Causes of malabsorption

10. Mucosal disease contd. Systemic mastocytosis Immunoproliferative small intestinal disease(IPSID) Lymphoma Crohn’s disease. Radiation enteritis Amyloidosis III. Infectious disease Tropical sprue Whipple’s disease Parasitic disease Mycobacterium avium intracellulare AIDS enteropathy Causes of malabsorption

11. IV.After intestinal resection. C. Impaired removal of nutrients: Lymphangiectasia. Chronic mesenteric ischemia. Causes of malabsorption

12. Systemic disease Associated with malabsorption

13. PATHOPHYSIOLOGY

14. From a pathophysiologic point of view, mechanisms causing malabsorption can be divided into premucosal (luminal) factors, mucosal factors, and postmucosal factors (vascular and lymphatic) FATS DEFECTIVE MIXING For sufficient digestion and absorption of lipids, dietary fat must adequately mix with digestive secretions. Gastric resections or gastrointestinal motility disorders that result in rapid gastric emptying or rapid intestinal transit, such as autonomic neuropathy resulting from diabetes mellitus or amyloidosis, can cause fat malabsorption consequent to impaired gastrointestinal mixing of dietary fat.

15. REDUCED SOLUBILIZATION OF FAT Fat malabsorption due to decreased formation of micelles occurs if the luminal concentrations of conjugated bile acids are lower than the critical concentration required for forming micelles. DECREASED LIPOLYSIS If exocrine pancreatic function is severely reduced, impairment of pancreatic lipase and colipase secretion results in decreased luminal hydrolysis of dietary fat. Even when pancreatic enzyme concentrations are normal, reduced pancreatic lipase activity due to a low luminal pH, excessive calcium ingestion, or ingestion of the specific lipase inhibitor orlistat can cause pancreatic steatorrhea.

16. DECREASED MUCOSAL ABSORPTION AND CHYLOMICRON FORMATION Generalized mucosal diseases, such as celiac disease or tropical sprue, often are associated with fat malabsorption. Defective uptake of free fatty acids and monoglycerides results from reduced mucosal surface area because of villus shortening, reduced enterocyte function, and mucosal inflammation. DEFECTIVE LYMPHATIC TRANSPORT OF CHYLOMICRONS Impairment of lymphatic transport of chylomicrons is a cause for postmucosal malabsorption of dietary fat. Decreased lymphatic transport can result from congenital diseases such as primary intestinal lymphangiectasia or from obstruction of lymphatic vessels due to metastatic solid tumors, lymphoma, Whipple's disease, retroperitoneal fibrosis.

17. PROTEINS AND AMINO ACIDS Defective digestion or absorption of dietary proteins has to be differentiated from excessive loss of serum proteins into the gastrointestinal tract, which is termed protein-losing enteropathy DEFECTIVE INTRALUMINAL PROTEOLYSIS Protein digestion may be impaired in patients who have undergone partial or total gastric resection, presumably as a result of poor mixing with digestive secretions, although gastric pepsin deficiency could be contributory. Defective proteolysis also occurs with exocrine pancreatic insufficiency. DEFECTIVE MUCOSAL HYDROLYSIS OF PEPTIDES AND DECREASED ABSORPTION OF OLIGOPEPTIDES AND AMINO ACIDS Generalized mucosal diseases, such as celiac disease and tropical sprue, result in global malabsorption

18. CARBOHYDRATES DEFECTIVE INTRALUMINAL HYDROLYSIS OF CARBOHYDRATES Pancreatic α-amylase normally is secreted in excess into the intestinal lumen. In mild forms of pancreatic insufficiency, carbohydrate digestion usually is at least partially preserved, but severe pancreatic insufficiency results in clinically apparent carbohydrate malabsorption and diarrhea due to decreased luminal hydrolysis of ingested starch. MUCOSAL DEFECTS OF CARBOHYDRATE DIGESTION AND ABSORPTION The most common cause of carbohydrate malabsorption is late-onset lactose malabsorption due to decreased levels of the intestinal brush border enzyme lactase . Acquired malabsorption of carbohydrates occurs commonly after extensive intestinal resections, in diffuse mucosal diseases such as celiac disease or Crohn's disease, or temporarily after self-limited gastrointestinal infections .

19. VITAMINS FAT-SOLUBLE VITAMINS Diseases causing malabsorption of dietary fat commonly cause malabsorption of fat-soluble vitamins. Fat-soluble vitamins also are malabsorbed in diffuse diseases of the mucosal surface area, in diseases affecting chylomicron formation and transport, [21] and in exocrine pancreatic insufficiency. WATER-SOLUBLE VITAMINS Vitamin B 12 (Cobalamin) Decreased release of dietary vitamin B 12 from food sources because of impaired pepsin and acid secretion, as in atrophic gastritis [24] or use of acid inhibitory drugs such as proton pump inhibitors, [25] usually results in only mild cobalamin malabsorption without clinical consequences. By contrast, deficiency of gastric intrinsic factor secretion, as occurs in pernicious anemia or after gastric resections.

20. Diseases and conditions affecting the ileal mucosa, such as Crohn's disease or ileal resection, lead to a reduction of specific absorptive sites for the intrinsic factor-vitamin B 12 complex. Folate Folate malabsorption occurs with mucosal diseases affecting the proximal small intestine, such as celiac disease, Whipple's disease, and tropical sprue. MINERALS CALCIUM Severe calcium malabsorption can occur in diseases that affect the small intestinal mucosa, such as celiac disease. In these disease states, calcium absorption is impaired directly because of the reduction of the intestinal surface area and indirectly because of formation of insoluble calcium soaps with malabsorbed long-chain fatty acids.

21. IRON Iron deficiency is common in patients with gastric resection or with celiac disease. Reduction in the mucosal surface area of the small intestine as a result of diffuse mucosal disease, intestinal resection, or intestinal bypass also can result in impaired iron absorption.

22. MECHANISMS THAT COMPENSATE FOR MALABSORPTION. ROLE OF THE COLON The colon has the capacity to absorb a limited number but a wide variety of substances and nutrients including sodium, chloride, water, oxalate, short chain fatty acids, calcium, and vitamin K. the nutritive role of the colon in patients with severe malabsorption is clinically relevant. Colonic preservation of malabsorbed nutrients also can result in symptoms and complications of malabsorption, such as colonic hyperabsorption of oxalate, which contributes to formation of renal stones.

23. Colonic Salvage of Incompletely Absorbed Carbohydrates Carbohydrates that reach the colon cannot be absorbed by the colonic mucosa, but they can be metabolized by the colonic bacterial flora. Metabolism by anaerobic bacteria results in the breakdown of oligosaccharides and polysaccharides to mono- and disaccharides, which are metabolized further to lactic acid; short-chain (C2 to C4) fatty acids (SCFAs) such as acetate, propionate, and butyrate; and to odorless gases, including hydrogen, methane, and carbon dioxide. Because SCFAs have caloric values between 3.4 and 5.95 kcal/g, their colonic absorption can contribute positively to overall calorie balance. In patients with short bowel syndrome, colonic salvage of malabsorbed carbohydrates can save up to 700 to 950 kcal/day,

24. Not all SCFAs are absorbed by the colon, and those that are not absorbed contribute to osmotic diarrhea. The beneficial effects of colonic bacterial carbohydrate metabolism may be accompanied by side effects due to gas production.

25. Role of the Colon in Fat Malabsorption Long-chain triglycerides or fatty acids, which constitute most dietary fat, cannot be absorbed by the human colon. Long-chain fatty acids bind calcium in the colon, thereby increasing the amount of sodium oxalate that is absorbed. Fatty acids with chain lengths longer than 12 carbons can cause diarrhea, because they increase mucosal permeability and inhibit colonic absorption of fluid and electrolytes. An increase in colonic permeability due to long-chain fatty acids also may be a contributing factor for the increased colonic oxalate absorption seen in patients with steatorrhea and hyperoxaluria.

26. CALCIUM OXALATE KIDNEY STONES Fat malabsorption secondary to bile acid deficiency in patients with extensive ileal resection is associated with an increased risk of oxalate kidney stones if the colon is preserved. Oxalate in food usually precipitates as calcium oxalate in the intestinal lumen and is lost in the stool. Lipolysis in patients with SBS and fat malabsorption is normal, and unabsorbed long-chain fatty acids compete with oxalate for available luminal calcium. Consequently, a larger amount of free oxalate is lost to the colon, where it is absorbed and ultimately excreted by the kidney.

27. Symptoms and signs of Malabsorption

28. Clinical findings in intestinal malabsorption. Organ System Clinical Feature Cause Gastrointestinal tract Diarrhea Nutrient malabsorption; small intestinal secretion of fluid and electrolytes; action of unabsorbed bile acids and hydroxy-fatty acids on colonic mucosa Weight loss Nutrient malabsorption; decreased dietary intake Flatus Bacterial fermentation of unabsorbed dietary carbohydrates Abdominal pain Distention of bowel, muscle spasm, serosal and peritoneal Glossitis, stomatitis, Iron, riboflavin, niacin deficiency cheilosis

29. Musculoskeletal system Osteopenic bone disease Calcium, vitamin D malabsorption Osteoarthropathy Not known Tetany Calcium, magnesium, and vitamin D deficiency Endocrine system Amenorrhea, impotence, infertility Generalized malabsorption and malnutrition Secondary hyperparathyroidism Protracted calcium and vitamin D deficiency

30. Skin Purpura Vitamin K deficiency Follicular hyperkeratosis Vitamin A, zinc, essential fatty acids, and dermatitis niacin deficiency Edema Protein-losing enteropathy, malabsorption of dietary protein Hyperpigmentation Secondary hypopituitarism and adrenal insufficiency Nervous system Xerophthalmia, night blindness Vitamin A deficiency Peripheral neuropathy Vitamin B12, thiamine deficiency

31. Night Blindness (Vitamin A) Anaemiairon, Folate,B12 Angular stomatits,glossitis (iron,folate,B12) Bleeding gums (vitamin C) Acrodermatitis enteropathica (Zinc) Koilonychia (iron) Parasthesia,tetany (calcium,Magnesium) clubbing Osteomalacia,rickets (Calcium,Vitamin D) Muscle wasting (Protein) Proximal myopathy (vitamin D) Peripheral neuropathy (B12) Peripheral edema (hypoalbuminaemia) Folicular hyperkeratosis (Vitamin A) Possible Physical consequences of Malabsorption

32. Routine Blood tests Biochemical screening tests Prothombin time Complete blood count Microcytic anaemia Macrocytic anaemia Lymphopenia Thrombocytosis Hypokalaemia Low Blood urea nitrogen Low Serum Creatinine Low serum Calcium Low serum Albumin Extended Laboratory tests for malabsorption

33. Immunologic Markers Immunoglobulins IgA deficiency, immunodeficiency syndromes Autoantibodies (e.g., ANA) Connective tissue diseases Antimitochondrial autoantibodies Primary biliary cirrhosis ACTH, cortisol Abnormal values in Addison's disease 5-Hydroxyindoleacetic acid in urine Elevated in carcinoid syndrome Gastrin * Elevated in Zollinger-Ellison syndrome Glucagon * Elevated in glucagonoma Serum TSH Decreased in hyperthyroidism; increased in hypothyroidism Somatostatin * Elevated in somatostatinoma (normal in duodenal somatostatinoma) Tissue transglutaminase antibodies, EMA Celiac disease

34. `1. Stool studies— Careful inspection of the stool by the physician is an important component of the malabsorption evaluation. Steatorrheic. The simplest approach to detect the presence of fat malabsorption is a qualititative examination of stool. A spot specimen is smeared on a microscope slide and is gently heated with a drop of glacial acetic acid for a few seconds to allow fat droplets to form. A fat-soluble stain, such as Sudan III, is then applied and the slide is examined under the microscope. Stained fat droplets are sought and the number of droplets is assessed semiquantitatively. This test is regularly positive (more than five droplets per high power field) when substantial steatorrhea is present.

35. Sudan stain of stool for fat. The positive stain (left) shows larger globules of unabsorbed fat (arrows).

36. Quantitative determination of fat in a pooled 48- or 72-hour stool collection, although cumbersome, remains the definitive test for steatorrhea. The van de Kamer method . Ideally the patient should be placed on an 80–100-g fat diet for a day or two before the stool collection is begun and maintain that intake throughout the collection period . a stool fat concentration over 9.5% suggests intraluminal maldigestion whereas a stool fat concentration less than 9.5% suggests mucosal disease as intestinal fluid secretion and malabsorptions of other nutrients dilute stool fat in the latter situation.

37. Measurements of the pancreatic enzyme, elastase, in the stool assayed is useful for detecting severe pancreatic exocrine deficiency. Stool samples should be evaluated for ova and parasites and for specific parasitic antigens in patients with suspected malabsorption, especially if diarrhea is present. Several protozoal diseases, including giardiasis, cryptosporidiosis, microsporidiosis, and Isospora belli infection, can produce significant malabsorption.

38. Test of fat absorption Qualitative fecal fat (>5 fat droplets/HPF) Quantitaive fecal fat (>7gm/24 hrs) May be normal with mild or moderate steatorrhoea Useful for follow up, affected by stool weight Rest for protein absorption Fecal nitrogen excretion Alpha antitrypsine clearance Adds little to assessment. Useful to identify protein losing enteropathy. Laboratory tests for malabsorption

39. Tests of carbohydrate absorption Quantitative excretion tests(anthrone) Stool PH<5.5 Osmotic gap in stool water Stool reducing substance D- Xylose absorption test Oral glucose, sucrose, lactose tolerance tests Breath hydrogen tests Does not account for colonic salvage Charecteristics for carbohydrate malabsorption Not specific May be positive with reducing substances other than carbohydrate Measure urine and blood concentration, low results suggestsproximal intestinal dysfunction May be misleading in patients with diabetes mellitus, bacterial overgrowth. Simple and inexpensive test for malabsorption of specific of a specific substance

40. Specific oral absorption tests and breath tests—The D-xylose absorption test may help to differentiate malabsorption caused by small intestinal mucosal disease from malabsorption due to impaired intraluminal digestion or lymphatic obstruction. This pentose sugar requires no intraluminal processing and is absorbed by facilitated diffusion. After administration of a 25-g dose orally to a well-hydrated patient, 5 g or more are normally excreted in the urine over 5 hours and blood levels should reach 25 mg/dL 2 hours after the test dose. Low urine excretion and blood levels suggest disease of the mucosa of the proximal small intestine such as celiac sprue.

41. Hydrogen Breath Test To screen for intestinal lactase or, less commonly, sucrase deficiency, either breath hydrogen excretion or blood glucose can be measured following an orally administered test dose of lactose or sucrose. If lactose is malabsorbed, it travels to the distal small intestine where the bacterial flora metabolize the sugar releasing hydrogen, which is excreted by the lungs and can be readily measured in the breath. After a test dose of 2 g/kg (25 g maximum) a rise of less than 10 parts per million (PPM) is normal whereas a rise to 20 PPM suggests lactase deficiency.

42. Schilling test with intrinsic factor Low urinary recovery Dual lebeled study Suggests ileal dysfunction, may be abnormal with pancreatic exocrine insufficiency and bacterial overgrowth. Corrects for pancreatic exocrine insufficiency Tests for bile acid malabsorption Fecal bile acid excretion Radiolebeled bile acid excretion 75SeHCAT retention selenium-75-homotaurocholic acid test [14C]Glycocolic acid breath test Gold standard but difficult to assay Correlates with fecal bile acid excretion Sensitive indicator of ileal bile acid malabsorption Abnormal with small bowel overgrowth or bile acid malabsorption.

43. Tests for small bowel bacterial overgrowth [14C]Xylose breath test Glucose breath hydrogen test Quantitative culture of jejunal aspirate (>10 x 10000/ml) Sensitivity may be low Inexpensive some false negative Gold standard for this diagnosis. Tests for exocrine pancreatic insufficiency Stool chymotrypsin concentration Dual lebeled schilling test Low concentration in presence of steatorrhoea highly suggestive in pancreatic insuficinecy. Complex test Secretin/CCK test Involve intubation,complex analysis.

44. The Schilling Test The Schilling test can be used clinically to distinguish between gastric and ileal causes of vitamin B 12 deficiency. The Schilling test is performed by administering a small oral dose of radiolabeled vitamin B 12 and, simultaneously or within one or two hours, a large intramuscular flushing dose of nonradiolabeled vitamin B 12 . The unlabeled B 12 saturates vitamin B 12 carriers; thus, any radioactive vitamin B 12 absorbed by the intestine is excreted in the urine. If less than 7% to 10% of the administered dose is recovered in urine within 24 hours, vitamin B 12 malabsorption is confirmed. To specify the site of vitamin B 12 malabsorption, a second phase of the Schilling test is performed subsequently with oral administration of intrinsic factor. In patients with pernicious anemia, the results of the Schilling test normalize after oral administration of intrinsic factor.

45. Patients with pancreatic exocrine insufficiency might have an abnormal result on the Schilling test, with or without added intrinsic factor, but results normalize with addition of pancreatic enzymes . In small bowel bacterial overgrowth the results of the Schilling test can improve after antibiotic therapy . In ileal disease or following ileal resection, abnormal results of the Schilling test persist despite intrinsic factor.

46. Imaging for diaqgnosis of malabsorption Plain X- ray abdomen: Pancreatic calcifications. USG : Biliary obstruction, and chronic pancreatits Small Bowel Follow-through and Small Bowel Enteroclysis: The principal role of small bowel radiologic series in evaluating malabsorption is to identify focal or diffuse abnormalities and alterations that predispose to bacterial overgrowth, including diverticula, stagnant loops of intestine, generalized intestinal hypomotility or dilatation, intestinal fistulas, and tumor. Abdominal Computed Tomography: CT scanning is useful to detect focal intestinal lesions, such as thickening of the small bowel wall in Crohn's disease or small intestinal lymphoma, intestinal fistula, and dilated bowel loops.

47. 5. MRI 6. EUS 7. MRCP

48. Endoscopy: 1. Upper GI endoscopy with duodenal biopsy 2. VCE: Videocapsule endoscopy: Can see the mucosal abnormality but has limitation of taking biopsy. 3. Balloon enteroscopy: Single or double bvaloon.

49. Endoscopy Endoscopic inspection of the duodenal mucosa can provide clues to some causes of malabsorption. Aphthae suggest Crohn's disease, and small, diffuse, white, punctate lesions can be seen in primary or secondary lymphangiectasia. Mosaic-like scalloping of duodenal folds and reduction in the number of duodenal folds are highly suggestive of villus atrophy in celiac disease.

50. Celiac disease

51. Focal lymphangiectasias

52. Contnd Interpretation of pathologic findings on small bowel biopsy in malabsorption

53. Contnd

54. Treatment 1. Correction of deficiency 2. Treat the underlying cause.

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