Pediatric malabsorption syndromes

Pediatric Malabsorption Syndromes

1. Dr.Azad A Haleem AL.Mezori DCH, FIBMS Lecturer University Of Duhok College Of Medicine Pediatrics Department 2016 [email protected] Pediatric Malabsorption Syndromes

2. Introduction Which organ is the most important organ in the body? Most people would say the heart or the brain, completely overlooking the gastrointestinal tract (GI tract). The GI tract is imperative for our well being and our lifelong health. A non-functioning GI tract can be the source of many chronic health problems that can interfere with your quality of life and or even death .

3. The old saying "you are what you eat" perhaps would be more accurate if worded "you are what you absorb and digest". we will be looking at the importance of these two functions of the digestive system: digestion and absorption .

4. Digestion is the mechanical and chemical break down of food into small organic fragments. Mechanical digestion refers to the physical breakdown of large pieces of food into smaller. In  chemical digestion , enzymes break down food into the small molecules  before they can be absorbed by the digestive epithelial cells .  The Human diet needs carbohydrates, protein, and fat , as well as vitamins and inorganic components for nutritional balance . Enzyme Produced In Site of Release Carbohydrate Digestion: Salivary amylase Salivary glands Mouth Pancreatic amylase Pancreas Small intestine Maltase Small intestine Small intestine Protein Digestion: Pepsin Gastric glands Stomach Trypsin Pancreas Small intestine Peptidases Small intestine Small intestine Fat Digestion: Lipase Pancreas Small intestine

5. Carbohydrates The digestion of carbohydrates begins in the mouth. The salivary enzyme ( amylase ) food starches into maltose , a disaccharide . In the duodenum. The  chyme  from the stomach enters the duodenum and mixes with the digestive secretions from the pancreas, liver, and gallbladder .

6. Pancreatic juices ( amylase ), breakdown of starch and glycogen  into maltose and other disaccharides. These disaccharides are then broken down into monosaccharides by enzymes called maltases , sucrases , and lactases . The monosaccharides are absorbed across the intestinal epithelium into the bloodstream to be transported to the different cells in the body . Carbohydrates

7. Carbohydrates

8. Protein A large part of protein digestion takes place in the stomach . The enzyme  pepsin digestion proteins by breaking them down into peptides , short chains of four to nine amino acids . In the duodenum , other enzymes (produced by the pancreas) – trypsin , elastase , and chymotrypsin – act on the peptides, reducing them to smaller peptides. Further breakdown of peptides to single amino acids is aided by enzymes called peptidases (those that break down peptides). The amino acids are absorbed into the bloodstream through the small intestine.

9. Proten

10. Lipids Lipid (fat) digestion begins in the stomach with the aid of lingual lipase and gastric lipase . However, the bulk of lipid digestion occurs in the small intestine due to pancreatic lipase . Bile aids in the digestion of lipids, primarily triglycerides, through emulsification. Emulsification is a process in which large lipid globules are broken down into several small lipid globules.

11. Lipases break down the lipids into fatty acids and glycerides . The bile salts surround long-chain fatty acids and monoglycerides , forming tiny spheres called micelles . The long-chain fatty acids and monoglycerides recombine in the absorptive cells to form triglycerides , which aggregate into globules, and are then coated with proteins. These large spheres are called chylomicrons . Chylomicrons contain triglycerides, cholesterol, and other lipids; they have proteins on their surface. Chylomicrons leave the absorptive cells entering the lymphatic vessels. From there, they enter the blood in the subclavian  vein   . Lipids

12. Vitamins Vitamins can be either water-soluble or lipid-soluble. Fat-soluble vitamins are absorbed in the same manner as lipids. Water-soluble vitamins can be directly absorbed into the bloodstream from the intestine.

13. Malabsorption syndromes Malabsorption ; A defect in the absorption of one or more nutrients. Malabsorption syndromes encompass numerous clinical entities that result in chronic diarrhea, abdominal distention, and failure to thrive .

14. Pathophysiology Carbohydrate, fat, or protein malabsorption is caused by a disorder in the intestinal processes of digestion, transport, or both of these nutrients across the intestinal mucosa into the systemic circulation. Either a congenital abnormality in the digestive or absorptive processes or, more commonly, a secondarily acquired disorder of such processes may result in malabsorption .

15. Disorders of Carbohydrate metabolism Disorders of Carbohydrate metabolism can be: congenital : cystic fibrosis and Shwachman -Diamond syndrome, which may cause amylase deficiency; the extremely rare congenital lactase deficiency ; sucrase-isomaltase deficiency; acquired: the most common being lactose intolerance , typically secondary to a damage of the mucosa, such as a viral enteritis conditions that cause mucosal atrophy, such as celiac disease.

16. Disorders of protein metabolism Congenital : cystic fibrosis, Shwachman -Diamond syndrome, and enterokinase deficiency, which cause inadequate intraluminal digestion. Acquired: disorders of protein digestion and/or absorption are nonspecific ( ie , they also affect the absorption of carbohydrates and lipids) and are found in conditions that result in damage to the absorptive intestinal surface , such as extensive viral enteritis, milk protein allergy enteropathy , and celiac disease .

17. Disorders of Lipid metabolism Congenital : cystic fibrosis and Shwachman -Diamond syndrome, which cause lipase and colipase deficiency . congenital primary bile acid malabsorption . Acquired (secondary mostly to disorders of the liver and the biliary tract or to chronic pancreatitis). Clearly, any condition that results in the loss of small intestinal absorptive surface also causes steatorrhea .

18. Classification and etiology Disorders of intraluminal digestion. Disorders of transport in the intestinal mucosal cell. Disorders of transport in the intestinal mucosal cell. Disorders of transport from mucosal cell Systemic diseases associated with malabsorption . Drugs causing malabsorption .

19. Disorders of intraluminal digestion Pancreatic insufficiencies: -cystic fibrosis -chronic pancreatitis -carcinoma of pancreas Bile salt insufficiency: -obstructive jaundice -bacterial overgrowth Rapid transit of food through gut - Gastroenterostomy -partial gastrectomy Increased bile salt loss in faeces -terminal ileal disease- Crohn’s disease -terminal ileal resection Lack of intrinsic factor -pernicious anaemia

20. Disorders of transport in the intestinal mucosal cell: Defect in brush border hydrolysis -lactase deficiency Defect in epithelial transport - coeliac disease -tropical sprue - lymphoma Disorders of transport from mucosal cell Lymphatic obstruction -abdominal lymphoma -tuberculosis - lymphangiectasia Defect in epithelial processing - abetalipoproteinaemia

21. Systemic diseases associated with malabsorption : Addison’s disease Thyrotoxicosis Hypothyroidism Diabetes mellitus Collagen vascular disease. Drugs causing malabsorption : Colchicine & Neomycin-precipitation of bile salts in gut,inhibition of lactase Methotrexate -folic acid antagonist. Cholestyramine -binding bile salts Laxatives

22. Epidemiology Genetically determined syndromes Celiac disease is by far the most common inherited malabsorption syndrome. Cystic fibrosis is the second most common malabsorption syndrome. Acquired syndromes Cow's milk and soy milk protein allergies are common, especially in infants and young children.   A transient and common form of malabsorption in infants results from acute-onset enteritis (mostly viral, specifically rotaviral ), which causes transient lactose intolerance.

23. Gender: Celiac disease is slightly more common in females. Autoimmune enteropathy is an X-linked disorder that only affects males in familial cases. Age: Symptoms of a congenital disease are usually apparent shortly after birth or after a short hiatus once a particular substance is ingested in substantial amounts. Protein sensitivity syndromes to milk or soy protein usually present in infants younger than 3 months. S olid food protein sensitivity syndromes are known to occur in older patients. Epidemiology

24. Diet history : Obtain a complete history of the patient's diet, including the amount and type of fluids, solid foods, and formula ingested. GI tract symptoms: abdominal gaseous distention abdominal pain nausea & vomiting, Dehydration Chronic or recurrent diarrhea Poor appetite, failure to thrive, poor weight gain skin irritation in the perianal area due to acidic stools are characteristic of carbohydrate malabsorption syndromes. Other symptoms Systemic symptoms , including weakness, fatigue, and failure to thrive. Protein sensitivity may be associated with an eczematous rash . folate and B-12 malabsorption result in macrocytic anemia . Patients with abetalipoproteinemia develop retinitis pigmentosa and ataxia because of chronic fat-soluble vitamin malabsorption and deficiency (vitamins A and E). Pediatric Malabsorption Syndromes  Clinical Presentation

25. Laboratory Studies The following laboratory studies are indicated in malabsorption syndromes : Stool analysis CBC liver function tests Total serum protein and albumin Celiac screening Imaging Studies, Barium studies Substance tolerance test Endoscopy Biopsy of Small-Intestinal Mucosa.

26. Stool analysis Reducing substances indicates that carbohydrates have not been properly absorbed. Acidic stool has a pH level of less than 5.5. This indicates carbohydrate malabsorption , even in the absence of reducing substances. Normally, stool bile acids should not be detected . The level of quantitative stool fat and the amount of fat intake should be measured and monitored for 3 days. The presence of large serum proteins in the stool, such as a 1  -antitrypsin, indicates leakage of serum protein and serves as a screening test for protein-losing enteropathy . Examination of the stool for ova and parasites may reveal the presence of  Giardia  species, a known cause of acquired malabsorption syndromes. Testing for other chronic intestinal infections that cause malabsorption , such as  Clostridium difficile or  Cryptosporidium   species may be performed .

27. A CBC : megaloblastic anemia in patients with folate and vitamin B-12 malabsorption Neutropenia in patients with Shwachman -Diamond syndrome (associated with pancreatic insufficiency). In patients with abetalipoproteinemia , blood smears may reveal acanthocytosis . In patients with inflammatory bowel disease , the erythrocyte sedimentation rate, C-reactive protein level, or both are commonly elevated. Total serum protein and albumin levels may be lower than reference range in syndromes in which protein is lost or is not absorbed, particularly in: protein-losing enteropathy and pancreatic insufficiency or enterokinase deficiency. With bile acid malabsorption , levels of the low-density lipoprotein (LDL) cholesterol may be low. In patients with liver or biliary disease , the results of liver function tests may be higher

28. Immunoglobulin G ( IgG ) and immunoglobulin A ( IgA ) antigliadin and IgA antiendomysial antibodies, or especially tissue transglutaminase antibodies, are useful in the diagnosis of gluten-sensitive enteropathy . Recently, a 13C-Sucrose breath test has been proposed as a noninvasive, easy-to-use, integrated marker of the absorptive capacity and integrity of the small intestine .  

29. Procedures Substance tolerance test Attempt to isolate the substance that is causing the malabsorption . Resolution of diarrhea after the suspected substance is removed from the diet and resumption of the diarrhea when the substance is reintroduced are specific signs that the particular substance is not adequately absorbed. Challenging the patient with the suspected malabsorbed substance once the diarrhea has resolved provides a more sensitive test.

30. Carbohydrate malabsorption tolerance test Carbohydrate malabsorption results in bacterial fermentation. This biochemical process releases hydrogen gas that is absorbed into the blood and excreted by the lungs. The amount of carbohydrate administered is typically 2 g/kg, with a maximum dose of 50 g. An increase in the exhaled hydrogen concentration following ingestion of an oral carbohydrate load (>20 ppm ) indicates carbohydrate malabsorption .

31. Endoscopy Gross morphology – gives diagnostic clue Cobblestone appearance – Crohn’s disease. Reduced duodenal folds and scalloping of duodenal mucosa – celiac disease.

32. Biopsy of Small-Intestinal Mucosa primary indications (1) evaluation of a patient either with documented or suspected steatorrhea or with chronic diarrhea (2) diffuse or focal abnormalities of the small intestine defined on a small-intestinal series

33. Lesions seen – classified into three Diffuse,specific : Agammaglobulinemia , Abetalipoproteinemia Patchy, specific Crohn’s disease, Intestinal lymphoma. Diffuse,non -specific celiac sprue , Tropical sprue Bacterial overgrowth

34. Barium studies evaluation of the patient with presumed or suspected malabsorption small-bowel series -a useful examination to look for anatomical abnormalities , such as strictures and fistulas (as in Crohn's disease) or blind loop syndrome (e.g., multiple jejunal diverticula ), and to define the extent of a previous surgical resection

35. Treatment Replacement of nutrients, electrolytes and fluid may be necessary. In severe deficiency, hospital admission may be required for parenteral administration. Pancreatic enzymes are supplemented orally in pancreatic insufficiency . Dietary modification is important in some conditions: Gluten-free diet in coeliac disease. Lactose avoidance in lactose intolerance . Food allergic enteropathy need to be on an elimination diet, avoiding offending food antigens. Antibiotic therapy will treat Small Bowel Bacterial overgrowth ( eg , metronidazole , rifaximin ). cholestyramine : In children with chronic diarrhea secondary to bile acid malabsorption , the use of cholestyramine . Immunosuppressive medications can be used to control autoimmune enteropathy .

36. Diet Carbohydrate intolerance Initiate treatment in patients with severe acquired carbohydrate intolerance by eliminating all dietary carbohydrates until the diarrhea is resolved. Then, slowly reintroduce carbohydrates. In infants , use a glucose polymer ( Polycose )–based formula ( eg , Pregestimil ). In patients with the most severe carbohydrate intolerance , a casein-based formula that contains essential amino acids and medium-chain triglyceride (MCT) oil and no carbohydrates .

37. Fat intolerance MCT oil is used to treat patients with poor weight gain that results from fat malabsorption . MCT oil does not require traditional fat metabolism and, thus, is more easily absorbed directly into the enterocyte and is transported through the portal vein to the liver. Fat-soluble vitamin supplements are required. Supplements in patients with fat malabsorption should also include linoleic and linolenic fatty acids.

38. Alternative formulas ( protein intolerance ) Currently, soy formulas are not considered effective for the prevention or treatment of nutritional allergies. Instead, use hydrolyzed protein formulas . High-degree protein hydrolysate formulas are used to treat infants with a cow's milk allergy , but these formulas may contain residual epitopes capable of provoking a severe allergic reaction . In these infants, use formulas with crystalline amino acids ( eg , Neocate , EleCare ) as the protein source.

39. Prognosis Mucosal atrophy caused by infectious gastroenteritis, food-sensitivity enteropathies , or malnutrition can result in an 80% reduction of intestinal surface area. Once the causative agent is removed, the repair of the small bowel is usually rapid ( 4-6 days ). Some malabsorption syndromes are transient , whereas others simply require a change in diet. Bacterial overgrowth compromises intestinal adaptation and increases the risk of liver disorders .

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