2 MalabsorptionMalabsorption can be defined as subnormal intestinal absorption of dietary constituents, and thus excessive loss of nutrients in the stool; it may be due to a digestive defect, a mucosal abnormality, or lymphatic obstruction.”
3 Characteres of stools in childhood 0-6 monthsBreast milk /dayyellow to braunpH: 5Formula 1-7/daypH: 76 months-1 year 2-3/day braun>1 year as adult5-10g/kg/day
4 DiarrheaIncrease in the number of stools or a decrease in their consistencyConstipationDecrease in the number of stools or an increase in their consistency
12 Steatorrhea Bile acid deficiency Diminution of synthesis in the liver Bile duct atresiaİncrease of bacterial deconjugationDiminution of ileal reabsorption (Crohn’s disease, ileal resection, short gut)Drugs (cholestyramine)
13 Steatorrhea Abetalipoproteinemia Hypobetalipoproteinemia Retinitis pigmentosaNeurologic symptomsAchantocytosisCholesterol very lowTreatment: no fat, MCT, vitamine ADEK supplementationHypobetalipoproteinemia
15 Gastrointestinal diseases associated with maldigestion and malabsorption Intraluminal digestionStomachPernicious anemia
16 Gastrointestinal diseases associated with maldigestion and malabsorption Intraluminal digestionPankreasCystic fibrosisShwachman-Diamond syndromeAcute/chronic pancreatitisTyripsinogen deficiencyLipase deficiencyAmylase deficiency
17 Gastrointestinal diseases associated with maldigestion and malabsorption Intraluminal digestionLiverİntestineCholestasis syndromesEnterokinase deficiencyShort bowel syndrome
18 Gastrointestinal diseases associated with maldigestion and malabsorption Digestion at the enterocyte membraneCongenital disaccharidase deficiencyAcquired/late-onset disaccharidasedeficiencyLactaseSucrase-isomaltaseTrehalaseGlucoamylase
19 Gastrointestinal diseases associated with maldigestion and malabsorption Enterocyte absorptionGlucose-galactose malabsorptionCongenital chloride diarrheaAbetalipoproteinemiaHypobetalipoproteinemiaCeliac diseaseShort bowel syndromeMilk/soy protein intoleranceWhipple’s diseaseInflamatory bowel diseaseInfectionsAcrodermatitis enteropathica
20 Gastrointestinal diseases associated with maldigestion and malabsorption Uptake into blood and lymphMiscellaneus disordersCongestive heart failureConstrictive pericarditisIntestinal lymphangiectasiaIntestinal lymphomaCarsinoid syndromeImmun deficiency syndromesAllergic gastroenteropathyEosinophilic gastroenteropathyDrugs
22 Physical findings Weigth loss Short stature Protuberant abdomen AscitesEdemaHepatomegalySplenomegalyClubbingPallorGingival hipertrophyAphthous mouth ulcersArthritisEritema nodosumUveitis, episcleritis
23 Diagnostic studies in the evaluation of maldigestion and malabsorption I Stool examination for blood, leukocytes, reducing substances, C. difficile toxin, ova and parasites and cultures for infectious bacterial pathogensComplete blood count, serum electrolytes, blood urea nitrogen, creatinine, calcium, phosphorus, albumin, total proteinUrinalysis and culture
24 Diagnostic studies in the evaluation of maldigestion and malabsorption II Sweat chloride testBreath analysisD-Xylose testSerum carotene, folate, B12, and iron levelsFecal alpha-1-antitrypsin levelFecal fat studies or coefficient of fat absorption studies
25 Diagnostic studies in the evaluation of maldigestion and malabsorption III Fat-soluble vitamin levels: A, D, E, KContrast radiographic studies: upper gastrointestinal series, or barium enemaGastroscopie/colonoscopieSmall intestinal biopsy for histology, and mucosal enzyme determination
26 Antibodies Anti-gliadin ab Anti-endomisium ab Anti-transglutaminase ab Autoantibodyp-ANCA, ASCA
27 Sweat test indications Failure to thriveChronic diarrheaRectal prolapsusNeonatal cholestasisCirrhosisPancreatitisRecurrent pulmonary infectionsNasal polypsMeconium ileusPositive family history
28 Disorders with sweat test positivity Cystic fibrosisAdrenal insufficiencyProtein-calorie malnutritionNeonatal cholestasisG-6-PD deficiencyPancreatitisGlycogen storage diseasesHypoparathyroidismHypothyroidismNephrogenic diabetes insipidusEctodermal dysplasia
29 Causes of villous atrophy in infants and children Peptic duodenitisCeliac diseaseAcute gastroenteritisCow’s milk and soy protein intoleranceEosinophilic gastroenteritisImmunodeficiency: congenital, acquired, AIDSCrohn’s diseaseProtein-calorie malnutritionTotal parenteral nutritionBacterial overgrowth or stasisMicrovillus inclusion diseaseAutoimmune enteropathyGiardiasis
30 Relative value of a small-bowel biopsy Diagnostic biopsyCeliac diseaseCongenital microvillous atrophyImmunodeficiencyEosinophilic gastroenteritisCrohn’s diseaseAbetalipoproteinemiaChylomicron retention diseaseLymphangiectasia (mucosal type)Diagnostic or non diagnosticAutoimmun enteropathyTropical sprueIsolated IgA deficiencyLymphangiectasiaGiardiasisNonspesific changesMilk or soy protein intoleranceIntractable diarrheaAIDSMalnutritionDrug and radiation-induced lesionsContaminated small-bowel syndromeGraft-versus-host disease
31 Specialized studies Schilling test Serum/urine bile acid determination Endoscopic retrograde pancreatographyProvocative pancreatic secretion testing
32 Causes of chronic diarrhea in neonates Cow’s or soy milk intoleranceGlucose-galactose malabsorptionSucrase-isomaltase deficiencyCongenital lactase deficiencyNecrotizing enterocolitisInfectionsCystic fibrosisShwachman diseaseAbetalipoproteinemiaChylomicron retention diseasePrimary immunodeficiencyShort bowel syndromeIntestinal lymphangiectasiaAcrodermatitis enteropathicaMicrovillous inclusion diseaseCongenital chloride diarrheaCongenital bile salt malabsorptionCongenital enterokinase deficiency
34 Celiac diseaseCeliac disease (CD), also called gluten-sensitive enteropathy, is a permanent intestinal intolerance to dietary wheat gliadin and related proteins that produces mucosal lesions in genetically susceptible individuals
35 Historical background Gallen, 250 AD, described celiac diseaseSamuel Gee, 1888, first description of CDDicke, 1950, role of wheat and rye flour in the pathogenesis of CDPaulley, 1954, first biopsy (surgical)Sakula ve Shiner, 1957, peroral intestinal biopsyESPGHAN criteria, 1970, 1979, 1990, 2012
36 Genetics of celiac disease Prevalence of CD among first-degree relatives of CD patients is approximately 10 %75 % of monozygotic twins have been found concordant with the disaeseAssociation of CD (95 % in CD, % in controls) with the HLA DQ α/β heterodimer encoded by the DQA1*0501 and the DQB1*0201 genes
37 EpidemiologyThe reported prevalence of symptomatic CD is 1 in 1000 live births (1/250 – 1/4000)The prevalence of asymptomatic CD is 1/200 (1/100-1/300)
38 PathogenesisCD is an immunologically mediated small intestinal enteropathy.The mucosal lesions shows features suggesting both humoral- and cell-mediated immunologic overstimulation.All the evidence available suggests a gluten-dependent activation of mucosal immunity in CD.
39 Pathology Partial to total villous atrophy Elongated crypts Increased mitotic index in the cryptsIncreased intraepitelial lymphocytesInfiltrations of plasma cells and lymphocytes as well as mast cells, eosinophils, and basophils in the lamina propria
40 Clinical presentation VomitingAnorexiaChronic diarrheaWeigth lossIrritabilityFailure to thriveAbdominal distentionMuscle wasting
41 Clinical presentation Short statureDelayed pubertyAnemiaRickets-osteomalasiaJoint complaintsCryptogenetic hepatitisEpilepsy
42 Cerrahpaşa experience; Age at the time of diagnosis Age (year)n%<2>4>1024481228.657.114.3
50 Diagnosis Antigliadin antibodies Anti-endomysium antibodies Anti tissue transglutaminase antibodiesSmall intestinal biopsyResponse to gluten-free diet
51 Diagnosis ESPGHAN criteria Finding of villous atrophy with hyperplasia of the crypts and abnormal surface epithelium, while the patient eating adequate amounts of gluten.A full clinical remission after witdrawal of gluten from the diet.The finding of circulating antibodies to gliadin and endomysium at the time of diagnosis and their disappearence on a gluten-free diet, adds weight to the diagnosis.
52 Diagnosis ESPGHAN criteria A control biopsy to verify the consequences on the mucosal architecture of the gluten-free diet is considered mandatory only in patients with equivocal clinical response to the diet and in patients asymptomatic at first presentation.
53 DiagnosisGluten challenge is not considered mandatory, except under unusual circumstances. These include situations where there is doupt about the initial diagnosis, for exemple when no initial biopsy was done, or when the biopsy specimen was inadequate or not typical of CD. The diagnostic challenge may be necessary to exclude other causes that could be responsible for the flat mucosa.
54 TherapyGluten-free diet; wheat, rye, barley and oats should be excludedIronFolic acidLactose-free diet
57 Celiac disease-cancer It has been demonstrated that the risk of developing small intestinal lymphoma is increased in patients taking a reduced-gluten or a normal diet, whereas for patients who have taken a strict gluten-free diet for 5 years or more the risk of developing malignancies over all sites is not increased when compared with the general population.
58 Celiac diseaseAll the present evidence strongly supports the view that restriction of gliadin should be complete and for life for all patients.