MALABSORPTİON SYNDROME
Prof. Dr. Tufan KUTLUProf. Dr. Tufan KUTLU
Malabsorption
Malabsorption can be defined as subnormal Malabsorption can be defined as subnormal intestinal absorption of dietary constituents, and intestinal absorption of dietary constituents, and thus excessive loss of nutrients in the stool; it may thus excessive loss of nutrients in the stool; it may be due to a digestive defect, a mucosal be due to a digestive defect, a mucosal abnormality, or lymphatic obstruction.”abnormality, or lymphatic obstruction.”
Characteres of stools in childhood
0-6 months0-6 monthsBreast milkBreast milk 1-12/day1-12/day
yellow to braunyellow to braunpH: 5pH: 5
FormulaFormula 1-7/day1-7/dayyellow to braunyellow to braunpH: 7pH: 7
6 months-1 year6 months-1 year 2-3/day2-3/day braunbraun
>1 year>1 year as adultas adult5-10g/kg/day5-10g/kg/day
DiarrheaDiarrhea Increase in the number of stools or a decrease Increase in the number of stools or a decrease
in their consistencyin their consistency ConstipationConstipation
Decrease in the number of stools or an increase Decrease in the number of stools or an increase in their consistency in their consistency
Malabsorption syndrome
Chronic diarrheaChronic diarrhea Protuberant abdomenProtuberant abdomen VomitingVomiting Weigth lossWeigth loss Short statureShort stature Anorexia..Anorexia..
Digestion of carbohydratesDigestion of carbohydrates
CarbohydratesCarbohydrates Starch 50 %Starch 50 % Sucrose 20-40 %Sucrose 20-40 % Lactose 20-40 %Lactose 20-40 %
MonosaccharidesMonosaccharides GlycoseGlycose GalactoseGalactose FructoseFructose
EnzymesEnzymes Salivary amylaseSalivary amylase Pancreatic amylasePancreatic amylase DisaccharidaseDisaccharidase
Sucrase-isomaltaseSucrase-isomaltase GlucoamylaseGlucoamylase LactaseLactase
Carbohydrate malabsorptionCarbohydrate malabsorption
Sucrase-izomaltase deficiencySucrase-izomaltase deficiency Primary lactase deficiencyPrimary lactase deficiency Late onset lactase deficiencyLate onset lactase deficiency Glycose-galactose malabsorptionGlycose-galactose malabsorption Secondary disaccharidase deficiencySecondary disaccharidase deficiency
Digestion of proteins Digestion of proteins
Gastric asid Enterokinase Pancreatic proteases
Protein malabsorptionProtein malabsorption Kongenital enterokinase deficiency Pancreatic enzyme deficiency Aminoacid transport defects
Digestion of lipidsDigestion of lipids
Gastric lipase
Pancreatic lipase
Bile acids
Absorption
Steatorrhea Pancreatic deficiencyPancreatic deficiency
Congenital Congenital Cystic fibrosisCystic fibrosisShwachman-Diamond syndromeShwachman-Diamond syndromeJohanson-Blizzard syndromeJohanson-Blizzard syndromePearson’s syndromePearson’s syndrome
AcquiredAcquiredChronic pancreatitisChronic pancreatitis
SteatorrheaSteatorrhea
Bile acid deficiencyBile acid deficiency Diminution of synthesis in the liverDiminution of synthesis in the liver Bile duct atresiaBile duct atresia İncrease of bacterial deconjugation İncrease of bacterial deconjugation Diminution of ileal reabsorption (Crohn’s Diminution of ileal reabsorption (Crohn’s
disease, ileal resection, short gut)disease, ileal resection, short gut) Drugs (cholestyramine)Drugs (cholestyramine)
SteatorrheaSteatorrhea
AbetalipoproteinemiaAbetalipoproteinemia Retinitis pigmentosaRetinitis pigmentosa Neurologic symptomsNeurologic symptoms AchantocytosisAchantocytosis Cholesterol very lowCholesterol very low Treatment: no fat, MCT, vitamine ADEK Treatment: no fat, MCT, vitamine ADEK
supplementationsupplementation
HypobetalipoproteinemiaHypobetalipoproteinemia
SteatorrheaSteatorrhea
Intestinal lymphangiectasiaIntestinal lymphangiectasia HypoalbuminemiaHypoalbuminemia LymphopeniaLymphopenia EdemaEdema
Mucosal absorption disordersMucosal absorption disorders Celiac disease Celiac disease Short gutShort gut
Gastrointestinal diseases associated with maldigestion and malabsorption
Intraluminal digestion
Stomach Pernicious anemia
Gastrointestinal diseases associated with maldigestion and malabsorption
Intraluminal digestion
Pankreas Cystic fibrosisShwachman-Diamond syndromeAcute/chronic pancreatitisTyripsinogen deficiencyLipase deficiencyAmylase deficiency
Gastrointestinal diseases associated with maldigestion and malabsorption
Intraluminal digestion
Liverİntestine
Cholestasis syndromesEnterokinase deficiencyShort bowel syndrome
Gastrointestinal diseases associated with maldigestion and malabsorption
Digestion at the enterocyte membrane
Congenital disaccharidase deficiency
Acquired/late-onset disaccharidasedeficiency
LactaseSucrase-isomaltaseTrehalaseLactaseSucrase-isomaltaseGlucoamylase
Gastrointestinal diseases associated with maldigestion and malabsorption
Enterocyte absorption Glucose-galactose malabsorptionCongenital chloride diarrheaAbetalipoproteinemiaHypobetalipoproteinemiaCeliac diseaseShort bowel syndromeMilk/soy protein intoleranceWhipple’s diseaseInflamatory bowel diseaseInfectionsAcrodermatitis enteropathica
Gastrointestinal diseases associated with maldigestion and malabsorption
Uptake into blood and lymph
Miscellaneus disorders
Congestive heart failureConstrictive pericarditisIntestinal lymphangiectasiaIntestinal lymphomaCarsinoid syndromeImmun deficiency syndromesAllergic gastroenteropathyEosinophilic gastroenteropathyDrugs
Presenting symptoms Chronic diarrhea Rectal bleeding Meteorismus Abdominal pain Weigth loss Failure to thrive Constipation Tenesmus
Vomiting Anorexia Pallor Weakness Fever Geophagia
Physical findings
Weigth loss Short stature Protuberant abdomen Ascites Edema Hepatomegaly Splenomegaly
Clubbing Pallor Gingival hipertrophy Aphthous mouth ulcers Arthritis Eritema nodosum Uveitis, episcleritis
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 pathogens
Complete blood count, serum electrolytes, blood urea nitrogen, creatinine, calcium, phosphorus, albumin, total protein
Urinalysis and culture
Diagnostic studies in the evaluation of maldigestion and malabsorption II Sweat chloride test Breath analysis D-Xylose test Serum carotene, folate, B12, and iron levels Fecal alpha-1-antitrypsin level Fecal fat studies or coefficient of fat absorption
studies
Diagnostic studies in the evaluation of maldigestion and malabsorption III
Fat-soluble vitamin levels: A, D, E, K Contrast radiographic studies: upper
gastrointestinal series, or barium enema Gastroscopie/colonoscopie Small intestinal biopsy for histology, and mucosal
enzyme determination
Antibodies
Anti-gliadin ab Anti-endomisium ab Anti-transglutaminase ab Autoantibody p-ANCA, ASCA
Sweat test indications Failure to thrive Chronic diarrhea Rectal prolapsus Neonatal cholestasis Cirrhosis Pancreatitis Recurrent pulmonary infections Nasal polyps Meconium ileus Positive family history
Disorders with sweat test positivity Cystic fibrosis Adrenal insufficiency Protein-calorie malnutrition Neonatal cholestasis G-6-PD deficiency Pancreatitis Glycogen storage diseases Hypoparathyroidism Hypothyroidism Nephrogenic diabetes insipidus Ectodermal dysplasia
Causes of villous atrophy in infants and children Peptic duodenitis Celiac disease Acute gastroenteritis Cow’s milk and soy protein intolerance Eosinophilic gastroenteritis Immunodeficiency: congenital, acquired, AIDS Crohn’s disease Protein-calorie malnutrition Total parenteral nutrition Bacterial overgrowth or stasis Microvillus inclusion disease Autoimmune enteropathy Giardiasis
Relative value of a small-bowel biopsy
Diagnostic biopsy Celiac disease Congenital microvillous atrophy Immunodeficiency Eosinophilic gastroenteritis Crohn’s disease Abetalipoproteinemia Chylomicron retention disease Lymphangiectasia (mucosal type) Diagnostic or non diagnostic Autoimmun enteropathy Crohn’s disease Tropical sprue Isolated IgA deficiency Lymphangiectasia Giardiasis
Nonspesific changes Milk or soy protein intolerance Intractable diarrhea AIDS Malnutrition Drug and radiation-induced lesions Contaminated small-bowel syndrome Graft-versus-host disease
Specialized studies
Schilling test Serum/urine bile acid determination Endoscopic retrograde pancreatography Provocative pancreatic secretion testing
Causes of chronic diarrhea in neonates
Cow’s or soy milk intolerance Glucose-galactose malabsorption Sucrase-isomaltase deficiency Congenital lactase deficiency Necrotizing enterocolitis Infections Cystic fibrosis Shwachman disease Abetalipoproteinemia Chylomicron retention disease
Primary immunodeficiency Short bowel syndrome Intestinal lymphangiectasia Acrodermatitis enteropathica Microvillous inclusion disease Congenital chloride diarrhea Congenital bile salt malabsorption Congenital enterokinase
deficiency
CELİAC DİSEASE
Celiac disease (CD), also called gluten-Celiac disease (CD), also called gluten-sensitive enteropathy, is a permanent sensitive enteropathy, is a permanent intestinal intolerance to dietary wheat gliadin intestinal intolerance to dietary wheat gliadin and related proteins that produces mucosal and related proteins that produces mucosal lesions in genetically susceptible individualslesions in genetically susceptible individuals
Celiac disease
Historical background
Gallen, 250 AD, described celiac diseaseGallen, 250 AD, described celiac disease Samuel Gee, 1888, first description of CD Samuel Gee, 1888, first description of CD Dicke, 1950, role of wheat and rye flour in the Dicke, 1950, role of wheat and rye flour in the
pathogenesis of CD pathogenesis of CD Paulley, 1954, first biopsy (surgical)Paulley, 1954, first biopsy (surgical) Sakula ve Shiner, 1957, peroral intestinal biopsySakula ve Shiner, 1957, peroral intestinal biopsy ESPGHAN criteria, 1970, 1979, 1990, 2012ESPGHAN criteria, 1970, 1979, 1990, 2012
Genetics of celiac disease
Prevalence of CD among first-degree relatives of Prevalence of CD among first-degree relatives of CD patients is approximately 10 %CD patients is approximately 10 %
75 % of monozygotic twins have been found 75 % of monozygotic twins have been found concordant with the disaeseconcordant with the disaese
Association of CD (95 % in CD, 20-30 % in Association of CD (95 % in CD, 20-30 % in controls) with the HLA DQ α/β heterodimer controls) with the HLA DQ α/β heterodimer encoded by the DQA1*0501 and the DQB1*0201 encoded by the DQA1*0501 and the DQB1*0201 genesgenes
Epidemiology
The reported prevalence of The reported prevalence of symptomatic CD is 1 in symptomatic CD is 1 in 1000 live births (1/250 – 1000 live births (1/250 – 1/4000) 1/4000)
The prevalence of The prevalence of asymptomatic CD is 1/200 asymptomatic CD is 1/200 (1/100-1/300)(1/100-1/300)
Pathogenesis
CD is an immunologically mediated small CD is an immunologically mediated small intestinal enteropathy.intestinal enteropathy.
The mucosal lesions shows features suggesting The mucosal lesions shows features suggesting both humoral- and cell-mediated immunologic both humoral- and cell-mediated immunologic overstimulation.overstimulation.
All the evidence available suggests a gluten-All the evidence available suggests a gluten-dependent activation of mucosal immunity in CD.dependent activation of mucosal immunity in CD.
Pathology Partial to total villous atrophyPartial to total villous atrophy Elongated cryptsElongated crypts Increased mitotic index in the Increased mitotic index in the
cryptscrypts Increased intraepitelial lymphocytesIncreased intraepitelial lymphocytes Infiltrations of plasma cells and Infiltrations of plasma cells and
lymphocytes as well as mast cells, lymphocytes as well as mast cells, eosinophils, and basophils in the eosinophils, and basophils in the lamina proprialamina propria
Clinical presentation
VomitingVomiting AnorexiaAnorexia Chronic diarrheaChronic diarrhea Weigth lossWeigth loss IrritabilityIrritability Failure to thriveFailure to thrive Abdominal distentionAbdominal distention Muscle wastingMuscle wasting
Clinical presentation Short statureShort stature Delayed pubertyDelayed puberty AnemiaAnemia Rickets-osteomalasiaRickets-osteomalasia Joint complaintsJoint complaints Cryptogenetic hepatitisCryptogenetic hepatitis EpilepsyEpilepsy
Cerrahpaşa experience;Age at the time of diagnosis
Age (year)Age (year) nn %%
<2<2
>4>4
>10>10
2424
4848
1212
28.628.6
57.157.1
14.314.3
Symptoms
Diarrhea: 85,5 %Diarrhea: 85,5 % Abdominal distention: 41 %Abdominal distention: 41 % Weigth loss: 27,7 %Weigth loss: 27,7 % Failure to thrive: 20,5 %Failure to thrive: 20,5 % Vomiting: 19,3 %Vomiting: 19,3 % Anorexia: 18,1 %Anorexia: 18,1 % Abdominal pain: 13,2 %Abdominal pain: 13,2 % Constipation: 3,6 %Constipation: 3,6 %
Physical findings
Height < 3. p. : 60,7 %Height < 3. p. : 60,7 % Weight < 3. p. : 66,7 %Weight < 3. p. : 66,7 % Hepatomegaly: 38,1 %Hepatomegaly: 38,1 % Clubbing: 17,9 %Clubbing: 17,9 % Ascites: 8,3 %Ascites: 8,3 % Edema: 4,8 % Edema: 4,8 %
Laboratory findings
Anemia: 50 %Anemia: 50 % Trombocytosis: 64.7 %Trombocytosis: 64.7 % Low Fe: 60 %Low Fe: 60 % Low ferritin: 78,4 %Low ferritin: 78,4 %
Associated diseases
Dermatitis herpetiformisDermatitis herpetiformis Down syndromeDown syndrome Autoimmune diseasesAutoimmune diseases
Thyroid diseasesThyroid diseases Addison’s diseaseAddison’s disease SarcoidosisSarcoidosis Insulin-dependent diabetes Insulin-dependent diabetes
mellitusmellitus Autoimmune hepatitisAutoimmune hepatitis Alopecia…Alopecia…
Down syndrome-celiac disease
The prevalence of celiac diseae in Down The prevalence of celiac diseae in Down syndrome: syndrome: 1 - 18 %1 - 18 %
Insulin-dependent diabetes mellitus-celiac disease
The prevalence of celiac diseae in insulin-The prevalence of celiac diseae in insulin-dependent diabetes mellitus: 1,5 - 8 %dependent diabetes mellitus: 1,5 - 8 %
Laboratory findings
AnemiaAnemia TrombocytosisTrombocytosis Folic acid deficiencyFolic acid deficiency BB12 12 deficiencydeficiency
HypoproteinemiaHypoproteinemia HypertransaminasemiaHypertransaminasemia
Diagnosis
Antigliadin antibodiesAntigliadin antibodies Anti-endomysium antibodiesAnti-endomysium antibodies Anti tissue transglutaminase Anti tissue transglutaminase
antibodiesantibodies Small intestinal biopsySmall intestinal biopsy Response to gluten-free dietResponse to gluten-free diet
Diagnosis
ESPGHAN criteriaESPGHAN criteria Finding of villous atrophy with hyperplasia of the Finding of villous atrophy with hyperplasia of the
crypts and abnormal surface epithelium, while the crypts and abnormal surface epithelium, while the patient eating adequate amounts of gluten.patient eating adequate amounts of gluten.
A full clinical remission after witdrawal of gluten A full clinical remission after witdrawal of gluten from the diet.from the diet.
The finding of circulating antibodies to gliadin and The finding of circulating antibodies to gliadin and endomysium at the time of diagnosis and their endomysium at the time of diagnosis and their disappearence on a gluten-free diet, adds weight to the disappearence on a gluten-free diet, adds weight to the diagnosis. diagnosis.
Diagnosis
ESPGHAN criteriaESPGHAN criteria A control biopsy to verify the consequences on A control biopsy to verify the consequences on
the mucosal architecture of the gluten-free diet the mucosal architecture of the gluten-free diet is considered mandatory only in patients with is considered mandatory only in patients with equivocal clinical response to the diet and in equivocal clinical response to the diet and in patients asymptomatic at first presentation. patients asymptomatic at first presentation.
Diagnosis
Gluten challenge is not considered mandatory, Gluten challenge is not considered mandatory, except under unusual circumstances. These except under unusual circumstances. These include situations where there is doupt about the include situations where there is doupt about the initial diagnosis, for exemple when no initial initial diagnosis, for exemple when no initial biopsy was done, or when the biopsy specimen biopsy was done, or when the biopsy specimen was inadequate or not typical of CD. The was inadequate or not typical of CD. The diagnostic challenge may be necessary to exclude diagnostic challenge may be necessary to exclude other causes that could be responsible for the flat other causes that could be responsible for the flat mucosa. mucosa.
Therapy
Gluten-free diet; wheat, rye, Gluten-free diet; wheat, rye, barley and oats should be barley and oats should be excludedexcluded
IronIron Folic acidFolic acid Lactose-free diet Lactose-free diet
Therapy
Gluten-free dietGluten-free diet
Gluten-free bread
Celiac disease-cancer
It has been demonstrated that the risk of developing It has been demonstrated that the risk of developing small intestinal lymphoma is increased in patients taking small intestinal lymphoma is increased in patients taking a reduced-gluten or a normal diet, whereas for patients a reduced-gluten or a normal diet, whereas for patients who have taken a strict gluten-free diet for 5 years or who have taken a strict gluten-free diet for 5 years or more the risk of developing malignancies over all sites is more the risk of developing malignancies over all sites is not increased when compared with the general not increased when compared with the general population.population.
Celiac disease
All the present evidence strongly supports the All the present evidence strongly supports the view that restriction of gliadin should be view that restriction of gliadin should be complete and for life for all patients.complete and for life for all patients.