Click here to load reader

Malnutrition Chronic malabsorption disorder

  • View
    27

  • Download
    0

Embed Size (px)

DESCRIPTION

Malnutrition Chronic malabsorption disorder. Prof. András Arató. X. Pathophysiological classification of failure to thrive. Inadequate food intake Loss of ingested food Defective utilization Excess metabolic demand. Inadequate food intake. Intrauterine malnutrition Poverty - PowerPoint PPT Presentation

Text of Malnutrition Chronic malabsorption disorder

  • MalnutritionChronic malabsorption disorder Prof. Andrs Arat

  • X

  • Pathophysiological classification of failure to thriveInadequate food intakeLoss of ingested foodDefective utilizationExcess metabolic demand

  • Inadequate food intakeIntrauterine malnutritionPovertyMaternal depressionInadequate feeding techniqueMacro- or micronutrients deficienciesAnorexia, refusal of foodsDisturbance of swallowingOro-motor dysfunctionCleft palate

  • Loss of ingested food

    VomitingDisturbance of intraluminal digestionIntestinalis malabsorption

  • Defective utilization

    Diseases of central nervous systemChromosomal abnormalities (21, 18, 13 trisomies)Congenital infections Metabolic disorders (respiratory chain)Endocrine disorders (GH deficiency, hypothyreosis)

  • Excess metabolic demandInflammationImmunodeficiencyInfection HyperthyreosisHypoxia (congenital heart disease, lung diseases)

  • Hospital and disease related malnutrition circulus vitiosusDisease relatedIncreased losse.x.malabsorptionIncreased demandFever, inflammation, etc.AnorexiaStress relatedcatabolismHospital relatedProblems with food supplyFasting because ofproceduresDrug relatedAltered healingImpaired muscle functionImmune dysfunctionAltered intestinal functionKolacek S Ann Nestle 2009, 67, 85-93.

  • Screening Tool Risk on Nutritional status and Growth

  • STRONG screening in Hungarian hospitalized childrenThe survay was done by 30 pediatricians nationwideNumber of screened children: 1209 Children belonging to high risk group:184 (15 %)

  • Comparisons between adequately nourishedand malnourished children on executive functionsKar BR et al. Behav Brain Funct 2008, 4, 1-12.VF: verbal fluency DF: design fluency WM: working memory AN: adequately nourished; MN: malnourished

  • Intra-uterine growth delayGrowth hormone deficiencyAcquired hypothyroidismConstitutional delayCaloric deprivation

  • Structure of small intestineCryptVilousMaturationDifferenciationExfoliation (apoptosis)Cell division

  • Pathophysiology of diarrhoeaOsmotic diarrhoeaStops on fastingStool osmolality > 2x[Na+]+[K+] (Na60mmol/l)Ex. Cholera

  • Pathophysiology of diarrhoeaReduction of absorption surfaceIntestinal ressection, enteropathiesReduced time of contact with intestinal mucosaInflamation (Crohns disease)Acceleration do intestinal transit (large intestinal volume)Increased time of transitBacterial overgrowth

  • History of diseaseOnsetRelation to foodsCharacteristics of stools (blood, fat, mucous)EvolutionAssociated signs or symptomsrespiratoryFamily historyallergy, food intolerance, IBDGrowth pattern

  • Evaluation of patientGeneral nutritionSigns of chronic diseaseAbdominal distentionPerianal lesions

  • Early onset diarrhoeaCongenital microvillous atrophyCytoskeleton abnormalitiesCongenital chloridorrheaEnzyme deficiencyLactaseSucrase-isomaltase

  • Reducing sugars in stools?Stool pH?H2 breath test?

  • Lactase deficiencySecondaryTransientSegmentalParcialAdult typeCongenital

  • Typical story...Baby on infant formula (with lactose)Acute diarrhoeaLactose free formula...Diarrhoea worsens... Extensive hydrolisate formula (lactose free)...Diarrhoea continues...could it be cows milk intolerance?

  • Diagnostic stepsStop feeding

    Oral rehydration solution (glucose)Sucrose in water(2g/kg in 10%)

    Diarrhoea stopped!Osmotic!

    No diarrhoea

    Reducing sugars 3+

    = Diagnosis!!

  • Toddlers diarrhoeaPeas and carrots syndrome!Adequate growthNo signs of chronic diseaseInvestigations normalSelf limited

  • Chronic Diarrhoea common causesGiardiasisCystic fibrosisFood intoleranceCoeliac diseaseInflammatory bowel disease

  • Haematologic abnormalities?Coeliac diease Microcytic anaemiaPearson syndromeSideroblastic anaemiaShwachman-Diamond syndromePeriodic neutropenia, anaemia, thrombocytopenia

  • Rare causes of chronic diarrhoea in infantsAbetalipoproteinemiaPearson syndromeShwachman-Diamond syndromeAuto-immune enteropathyIntestinal lymphangiectasia

  • InvestigationsCBCAlbuminMarkers of inflammationESR, CRP, thrombocytosisSweat testGenetic testing (chromosome 7)Stool elastase; stool fatStool calprotectin, lactoferrin, -1-antitrypsinStool microbiologyAnti-tTG antibodies (IgA)pANCA, ASCAAnti-enterocyte antibodies; auto-antibodies

  • Instrumental examinationsBreath tests after intake of different sugarsImage forming examinationsPlain abdominal X-rayDuodenal tubing (digesting enzymes, Giardia)Small intestinal biopsyWith capsule or with endoscopyAnalysis with light or electrone microscopy

  • OCTI

  • Causes of villous atrophyPostenteritis syndromeCows milk allergySoya allergyCoeliac diseaseGiardiasisImmunodeficiency syndromesAutoimmune enteropathy

  • Classification of malabsorption syndromeImpaired intraluminal digestionIntestinal malabsorptionFermentation

    In many cases more factors elicit the malabsoprtion (e.g.bacterial overgrowth)

  • Malabsorption due to impaired intraluminal digestionCFSchwachman syndromeIsolated lipase or colipase deficiencyImpaired bile acid synthesisBile duct atresiaInterrupted enterohepatic circulationileal resectionCrohn diseaseCongenital malabsorption of bile acidsCongenitalis trypsinogen or enterokinase deficiency

  • Intestinal malabsorptionCoeliac diseaseSensitization to food proteins (cows milk, soya, rice, wheat)Giardia infestationPostenteritis syndromeImmunodeficiency syndromesAcrodermatitis enteropathica

  • Intestinal malabsorption II.Bacterial overgrowthCrohn diseaseShort bowel syndromeIntestinal lymphangiectasiaAutoimmune enteropathyCongenital microvillous atrophySelective transport defects

  • Malabsorption due to fermentationDisaccharidase deficienciesLactose (congenital, secondary, adult)Sucrose (congenital, secondary)Izomaltose (primary, secondary)Monosaccharide malabsorptionsGlukose/galactoseFructose (toddlers diarrhoea)

    In the primary forms the small intestine has normal structure

  • Pathological findings in biopsy samplesSpecificDilatated lymphatic vessels in intestinal lymphangiectasiaVacules filled with lipids in abetalipoproteinaemia Non specificDiseases with villous atrophy

  • Postenteritis syndromeAcute diarrhoea lasts more than 2 weeksSmall intestinal damageSecondary lactose malabsorptionSecondary cows milk protein intoleranceTreatmentlactose free dietcows milk free diet

  • Giardia lamblia infestationVery frequentDiagnosis: Stool analysisDuodenal tubing, vegetatve forms can be found only hereTherapy:MetronidazoleThis treatment can be begun without diagnosis (ex juvantibus)

  • Classification of food allergies with gastrointestinal symptoms according to their pathogenesis

    IgE mediatedMixed (IgE and non-IgE)Non-IgE mediatedImmediate gastrointestinal hypersensitivityOrale allergic syndromeAllergic eosinophil oesophagitisAllergic eosinophil gastritisAllergic eosinophil gastroenterocolitisFood allergy caused enteropathyFood allergy caused enterocolitisFood allergy caused proctocolitis

  • Cows milk allergySymptomsSkin, respiratory, gastrointestinalAt the gastrointestinal form partial villous atrophy is characteristicDiagnosisSymptoms cease at elimination and recur at provocationSmall intestinal biopsy is indicated when the differential diagnosis causes difficulties.

  • No improvement of clinical symptomsHistory, physical examination and laboratory tests Therapeutic elimination dietSpec. IgEnegativenegativepositiveNo dietanaphylaxis or clear immediate type reactionCMP elimination& Specific IgEImprovement of the clinical symptomsDiagnostic elimination diet (with eHF or AAF)Late reactions (e.g. atopic eczema): 1 - 2 weeksGI symptoms (e.g. diarrhea, vomiting): 2 - 4 weeksStandardized oral challenge with CMPSpec. IgEpositive

  • Treatment of cows milk allergyCows milk free dietExtensively hydrolized proteins (under 1500 D) Hydrolisate can be prepared from cows milk, collagen and soyaAmino acid mixtureSoya is not indicated as in the enteral form of cows milk protein allergy occurance of soya allergy is also very frequentProbiotics

  • From the formulae containing whole protein to the aminoacid mixture Standard formulaExtensive hydrolysateAminoacids mixture

  • 1st Century A.D.: Aretaeus the Cappadocian(Greek) Work translated by Francis Adams and published by the Sydenham Society in 1856

    Wellcome Institute LibraryLondon

    From: Paveley WF. BMJ 297:1646, 1988

  • Cappadocia Photo of a 15th Century map showing "Capadocia".

  • Arateus The Coeliac Disease

    He named it koiliakos after the Greek word koelia = abdomenIf the stomach be irretentive of the food and if it pass through undigested and crude, and nothing ascends into the body, we call such persons coeliacs.

  • A comprehensive dogmatic system . . . requires the science systematized to be at a standstill, not to say dead. Knowledge is a ferment, expanding on all sides so much and so rapidly as during the past hundred years, [and] must speedily burst the old bottle of any dogmatic system. Medical Lectures. Chapter 14. Samuel Gee (1839-1911)Medical lectures and aphorisms. London, 1902; 3rd edition, 1907.

  • Samuel Gee

    1887: Lectured and published On the Coeliac Affection in St. Bartholomews Hospital Reports: The disease occur in Englishmen returning from the tropics,in children aged 1 5 and adults who never left England. (Gees Disease)

  • Samuel Gee about the therapy of coeliac diseaseMention a child who wonderfully throve when fed upon a quart of the best Dutch mussels daily, but relapsed when the season for mussels was overHe concludes that if a patient be cured at all, it may be by means of diet.

  • Sir Frederick StillUnfortunately one form of starch which seems particularly liable to aggravate the symptoms is bread. I know of no adequate substituteAs far as I have been able to ascertain, in no case did the disease begin while the child was still on breast-feeding

  • Willem Karel Dicke(1905-1962)

    Utrecht University

  • Observations of Dicke

    Noticed his hospitalized coeliac toddlers, who existed on gruel (porridge) in the food scarce days of WWII, improved when wheat flour was not available but rice or potato flour was used. When Swedish planes dropped bread in The Netherlands, his patients who had improved on wheat-free diets, all relapsed.

  • Dickes PhD thesis"Investigation of the harmful effects of certain types of cereal on patients with coeliac disease" At the State University of Utrecht on 30th of May, 1950

  • Definition of Celiac DiseaseCD is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically (mainly HLA) susceptible individuals, characterized by the presence of variable combination of gluten-dependent clinical manifestations, CD specific antibodies, HLA DQ2 and DQ8 haplotypes and enteropathy

  • Gluten-sensitive enteropathy in genetically susceptible individualsThe present definitions of CD are based on:Presence of enteropathyInduction of intestinal lesions (and symptoms) by glutenGenetic susceptibilitySpecific serologic markersDefinition of CD

  • Healthy subjectsLatent coeliac diseaseSilent coeliac diseaseManifest coeliac diseaseMorphology of jejunumVillous atrophyaNormalmucosaDR3-DQ2DR5/7-DQ2DR4-DQ8Genetic inclinationCoeliac iceberg

  • Typical endoscopic picture of normal (a) and coeliac mucosa (b)

  • Normal (a) and coeliac disease (b) small intestinal mucosa

  • Positive EMA test on monkey oesophagus section

  • Intestinal deposits of IgA anti-TG2 antibodiesTG 2IgATG2 + IgA

  • Pathogenetic factors in coeliac diseaseGenetic backgroundGliadinTranszglutaminase

  • Coding of charateristic heterodimer in cis and trans positionSollid LM. Nature Rev. 2002, 2, 647-655

  • GliadinTrigger factor of coeliac diseaseTrigger factors of other autoimmune disease are not known

  • Transglutaminase enzymeIt is ubiquiter in the connective tissues and makes crossbonds between the polypeptid chainsTransglutaminase is the substrate of antiendomysium, az antireticulin and antijejunal antibodiesIn coeliac disease the transglutaminase is the autoantigen

  • Enzymatic actions of transglutaminase enzymeSollid LM. Nature Rev. 2002, 2, 647-655

  • Binding to the A HLA II moleculesVan De Wal Y. Gut 2000, 46, 734-737

  • The effect of transglutaminase to the epitop structure of gliadinVan De Wal Y. Gut 2000, 46, 734-737

  • Coeliac disease as a gluten-sensitive enteropathy (Interlaken 1969) Diagnosis based upon:

    Structurally abnormal jejunal mucosa when taking a diet containing gluten

    Clear improvement of villous structure when taking a gluten-free diet

    Deterioration of the mucosa during challenge

  • History and clinical presentation compatible with CD; in subject < 2 years old r/o other clinical conditions mimicking CDCD-associated serologyRevised ESPGHAN criteria for diagnosis of coeliac disease (1990)Histological findings compatible with CD (hyperplastic villous atrophy)Unequivocal clinical and serological response to GFDCompulsorySupportive

  • Prevalence rate of coeliac disease in IDDMAustria:3% (Schober, 2000)Sweden: 6% (Carlsson, 1999)Spain: 6,45% (Vitoria, 1998)Canada: 5,1% (Fraser-Reynolds, 1998)Italy: 7% (DeVitis, 1996)Finland: 2,4% (Saukkonen, 1996)United Kingdom: 2% (Page, 1994)

  • Possible new treatment modalities in the futurePeptidase supplementation (generate new target sequences for brush border enzymes)Transglutaminase inhibition (unwanted side effects)Binding MHC II binding sitesSilencing of gluten reactive T cells (Treatment with anti-CD3 during gluten challenge)

  • Possible new treatment modalities in the futureCytokine therapy (IL-10, anti-IL15, anti-IFN gamma)Selective adhesion molecule inhibition (Natalizumab)Inhibition of NKG2D (Prevents killing epithelial cells by NK cells

  • Gastrointestinal symptoms in CFNeonatesMeconium ileusProlonged jaundiceInfants and toddlerssteatorrheaslowened weight gainpolyphagia

  • Gastrointestinal symptoms in CFChildhoodMeconium ileus equivalentPortal hypertensionHyperspleniaStricture of colon strictura (when preparated containing enzymes in high concentration are used)

  • Guidelines for diagnosis of CF, J Pediatr 2008;153:S4-S14

  • Causes of false positive sweat testAdrenal insufficiencyNephrogenic diabetes insipidusHypothyreosisMalnutrition, malabsorptionAnorexia nervosaFucosidosisGlycogen storage diseasesFamiliar hypoparathyreosis

  • Standpoints in patientscare in CFDietHigh energy intake (150 % of normal)Increased protein intakeNear normal fat intakeReplace of fat soluble vitaminsEnzimpreparatesMode of intakeDose

    ***************