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Acute and chronic Acute and chronic diarrhoea in childhooddiarrhoea in childhood

A/Prof Katie Allen, A/Prof Katie Allen, Department of GastroenterologyDepartment of GastroenterologyDepartment of AllergyDepartment of AllergyRCHRCH

Diarrhoea, vomiting and Diarrhoea, vomiting and dehydration in childhooddehydration in childhood

Talk OverviewTalk Overview

What is the definition of diarrhoeaWhat is the definition of diarrhoeaWhat are the mechanisms of What are the mechanisms of diarrhoeadiarrhoeaWhat are the causes of vomiting What are the causes of vomiting What are the causes of vomiting What are the causes of vomiting and diarrhoeaand diarrhoeaAcute versus chronic diarrhoeaAcute versus chronic diarrhoeaDiscussion of common diarrhoeal Discussion of common diarrhoeal conditions (acute and chronic)conditions (acute and chronic)Management of dehydration and Management of dehydration and acute diarrhoeaacute diarrhoea

Diarrhoeal disease in childhoodDiarrhoeal disease in childhood

2 million deaths annually worldwide2 million deaths annually worldwide15% of all child deaths15% of all child deaths•• 6% of child deaths in Europe6% of child deaths in Europe•• 18% of all child deaths in SE Asia18% of all child deaths in SE Asia

>90% of all deaths occur in developing >90% of all deaths occur in developing nationsnations

What is diarrhoea ?What is diarrhoea ?

It is an increase in the frequency, It is an increase in the frequency, volume and fluid content of stoolvolume and fluid content of stoolWhat is normal ? What is normal ?

Breast fedBreast fed babies can pass 1 stool q babies can pass 1 stool q Breast fedBreast fed babies can pass 1 stool q babies can pass 1 stool q 10/7 or 10 stools/day, 10/7 or 10 stools/day,

bottle fedbottle fed infants pass 2infants pass 2--3 pasty stools 3 pasty stools per day and per day and

older childrenolder children 11--2 formed stools /day 2 formed stools /day or 1 stool q 2/7 or 1 stool q 2/7

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Gastrointestinal absorptionGastrointestinal absorption

Causes of acute diarrhoea and Causes of acute diarrhoea and vomitingvomiting

Gastrointestinal infectionsGastrointestinal infectionsFood poisoningFood poisoningMechanical Mechanical •• obstruction, intussusceptionobstruction, intussusception

AppendicitisAppendicitisHaemolytic Uraemic SyndromeHaemolytic Uraemic SyndromeOther infectionOther infection•• UTI, sepsisUTI, sepsis

Food allergy (cow’s milk intolerance, Coeliac)Food allergy (cow’s milk intolerance, Coeliac)

Remember medications can cause Remember medications can cause diarrhoeadiarrhoea

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Causes of acute Causes of acute vomitingvomiting

All the aboveAll the abovePyloric stenosisPyloric stenosisAppendicitisAppendicitisRaised intracranial pressureRaised intracranial pressureMeningitisMeningitisMetabolic diseaseMetabolic disease

Infectious diarrhoeaInfectious diarrhoea

ViralViral•• Rotavirus, adenovirus, small round virusesRotavirus, adenovirus, small round viruses

BacterialBacterialC l b t j j iC l b t j j i•• Campylobacter jejuniCampylobacter jejuni

•• Shigella, Salmonella, S aureus, Clostridium Shigella, Salmonella, S aureus, Clostridium perfringens, E coliperfringens, E coli

ParasiticParasitic•• Giardia, CryptosporidiaGiardia, Cryptosporidia

History of travel and exposure to History of travel and exposure to unsecured water supply is unsecured water supply is

important to obtainimportant to obtain

Mechanisms of acute infectious Mechanisms of acute infectious diarrhoeadiarrhoea

Villus damageVillus damage•• virusesviruses

Enterotoxin productionEnterotoxin production•• V choleraeV cholerae, ETEC, Salmonella, , ETEC, Salmonella, C jejuni, S aureus, Cl C jejuni, S aureus, Cl

perfringens, Cl difficile, Y enterocoliticaperfringens, Cl difficile, Y enterocolitica

AdherenceAdherence•• EPEC, EPEC, G lamblia, Y enterocoliticaG lamblia, Y enterocolitica

Cytotoxin productionCytotoxin production•• STEC, STEC, S dysenteriae, C jejuni, Cl difficileS dysenteriae, C jejuni, Cl difficile

InvasionInvasion•• EIEC, EIEC, C jejuniC jejuni, Cryptosporidium, , Cryptosporidium, Y enterocoliticaY enterocolitica

RotavirusRotavirus

WheelWheel--like like DoubleDouble--stranded RNAstranded RNA

80nm diameter80nm diameter~80nm diameter~80nm diameter

Photo: FP Williams, US EPA

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Rotavirus Rotavirus -- epidemiologyepidemiology

Most common cause of diarrhoeal illness Most common cause of diarrhoeal illness in childrenin children600,000 deaths/year worldwide600,000 deaths/year worldwideM t lit 0 5%M t lit 0 5% d h d tid h d tiMortality <0.5% Mortality <0.5% -- dehydrationdehydration

Autumn and winter monthsAutumn and winter monthsAll children exposed by age 5All children exposed by age 5

Rotavirus Rotavirus -- PathophysiologyPathophysiology

Damage to tips of villus cells, leading to:Damage to tips of villus cells, leading to:

•• Loss of absorptive capacityLoss of absorptive capacitywater and electrolyte transport linked to glucosewater and electrolyte transport linked to glucosewater and electrolyte transport linked to glucose water and electrolyte transport linked to glucose and amino acid cotransporters on luminal surface and amino acid cotransporters on luminal surface of enterocyteof enterocyte

•• Loss of digestive capacityLoss of digestive capacitydisaccharidases on cell surfacedisaccharidases on cell surface

Rotavirus Rotavirus -- Clinical featuresClinical features

Most prominent in 6Most prominent in 6--24 months age group24 months age groupIncubation 2Incubation 2--3 days3 daysMay be coryzal prodromeMay be coryzal prodromeFeverFeverVomiting and DiarrhoeaVomiting and Diarrhoea

Diagnosis confirmed by stool immunoflouresenceDiagnosis confirmed by stool immunoflouresence

Other viral gastroenteritisOther viral gastroenteritis

AdenovirusAdenovirusNot seasonal, more prolonged diarrhoeaNot seasonal, more prolonged diarrhoea

Small round virusesSmall round viruses•• AstrovirusAstrovirus•• AstrovirusAstrovirus

Milder than rotavirusMilder than rotavirus•• CalicevirusCalicevirus

Localised outbreaks in older children. Short Localised outbreaks in older children. Short incubation period and duration of symptomsincubation period and duration of symptoms

Other infectious cause?Other infectious cause?

Unlikely to be viral gastroenteritis if:Unlikely to be viral gastroenteritis if:•• Bloody stoolBloody stool

S t i illS t i ill•• Severe systemic illnessSevere systemic illness•• Severe abdominal painSevere abdominal pain•• Prominent / bilious / projectile vomitingProminent / bilious / projectile vomiting•• Prolonged history (> 2 weeks)Prolonged history (> 2 weeks)

Causes of bloody diarrhoeaCauses of bloody diarrhoea

Infectious colitis (eg salmonella) Infectious colitis (eg salmonella) (any age)(any age)Allergic colitis and gastroenteritis (< Allergic colitis and gastroenteritis (< Allergic colitis and gastroenteritis (< Allergic colitis and gastroenteritis (< 6 mth old) (eg food protein induced 6 mth old) (eg food protein induced enterocolitits)enterocolitits)Inflammatory bowel disease (> 2yo) Inflammatory bowel disease (> 2yo) (Crohn’s disease, ulcerative colitis)(Crohn’s disease, ulcerative colitis)Meckel’s diverticulumMeckel’s diverticulum

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Chronicity of presentation is Chronicity of presentation is importantimportant

Acute presentation (1Acute presentation (1--5 days)5 days)usually viral and selfusually viral and self--limitinglimiting

Subacute presentation (1Subacute presentation (1--2 weeks)2 weeks)think giardia and bacterial gastrothink giardia and bacterial gastro

Chronic presentation (weeksChronic presentation (weeks--months)months)consider food allergy (including consider food allergy (including

Coeliac disease), lactose intoleranceCoeliac disease), lactose intolerance

Management of dehydrationManagement of dehydration

Management of diarrhoea and Management of diarrhoea and vomitingvomiting

Assess whether acute or chronicAssess whether acute or chronic

If If acuteacute: assess whether surgical or : assess whether surgical or gginfectious infectious -- if acute then management if acute then management of hydration and metabolites is keyof hydration and metabolites is key

If If chronic:chronic: assess whether failure to assess whether failure to thrive or not thrive or not –– if chronic then if chronic then management of weight and management of weight and micronutrients is keymicronutrients is key

DehydrationDehydrationClinical signsClinical signs•• Recent weight lossRecent weight loss•• Skin turgorSkin turgor•• Peripheral perfusionPeripheral perfusion•• Peripheral perfusionPeripheral perfusion•• Dry mucous membranesDry mucous membranes•• Sunken eyesSunken eyes•• Sunken fontanelleSunken fontanelle•• Acidotic breathingAcidotic breathing•• AcidosisAcidosis•• Tachycardia and hypotensionTachycardia and hypotension

DehydrationDehydrationMild (<4%) Moderate (4-6%) Severe (>6%)

Appearance Alert Restless, irritable Lethargic

Skin turgor Normal Slow (1-2s) Very slow (>2s)

Perfusion Normal Cool ColdPerfusion Normal Cool Cold

M membranes Moist Dry Dry

Eyes Normal Sunken Sunken

Breathing Normal Normal Deep acidotic

Blood pressure Normal Normal Hypotension

Heart rate Normal Normal Rapid, feeble

Treatment of dehydrationTreatment of dehydration

Treat shockTreat shockOral rehydration in mild or moderately Oral rehydration in mild or moderately dehydrateddehydrated

O l h d ti l ti i th NGO l h d ti l ti i th NG•• Oral rehydration solution via mouth or NG Oral rehydration solution via mouth or NG tubetube

•• Continue to feed in additionContinue to feed in addition

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Oral Rehydration SolutionsOral Rehydration Solutions

Salt and sugar solutions utilise glucoseSalt and sugar solutions utilise glucose--linked cotransporter in small intestinelinked cotransporter in small intestine

E t t

Na

Glucose

Lumen Enterocyte

Oral Rehydration TherapyOral Rehydration Therapy

Mild / no dehydration:Mild / no dehydration:•• Increase frequency of usual fluidsIncrease frequency of usual fluids•• frequent, small volume drinksfrequent, small volume drinks•• Avoid hypertonic solutions (fruit juice fizzyAvoid hypertonic solutions (fruit juice fizzy•• Avoid hypertonic solutions (fruit juice, fizzy Avoid hypertonic solutions (fruit juice, fizzy

drinks)drinks)•• Avoid lowAvoid low--calorie drinkscalorie drinks

Oral Rehydration TherapyOral Rehydration Therapy

Moderate dehydration:Moderate dehydration:•• NasogastricNasogastric•• Calculate fluid deficit and fluid requirementCalculate fluid deficit and fluid requirement•• Replace deficit over 6 hoursReplace deficit over 6 hours•• Replace deficit over 6 hoursReplace deficit over 6 hours•• Give daily maintenance (full 24 hour Give daily maintenance (full 24 hour

requirement) over next 18 hoursrequirement) over next 18 hours•• Allow for ongoing losses (diarrhoea)Allow for ongoing losses (diarrhoea)•• Continue to offer food and usual drinksContinue to offer food and usual drinks

Photo: Trevor Duke, RCH

Rehydration TherapyRehydration Therapy

Severe dehydrationSevere dehydration•• Intravenous accessIntravenous access•• Intravenous fluid resuscitationIntravenous fluid resuscitation

20ml/Kg 0 9% NaCl20ml/Kg 0 9% NaCl20ml/Kg 0.9% NaCl20ml/Kg 0.9% NaClRepeat to restore circulationRepeat to restore circulation

•• Rehydration Rehydration -- oral/intravenousoral/intravenousORS or 0.45% NaCl, 5% Dextrose, 20mmol/l ORS or 0.45% NaCl, 5% Dextrose, 20mmol/l KClKClDeficit over 6 hoursDeficit over 6 hoursMaintenance amount over next 18 hoursMaintenance amount over next 18 hours

Rehydration therapyRehydration therapy

Severe dehydration (continued)Severe dehydration (continued)

•• Check electrolytes and acidCheck electrolytes and acid--base in base in severely dehydrated childrenseverely dehydrated childrenseverely dehydrated childrenseverely dehydrated childrenchildren with altered conscious statechildren with altered conscious statethe very youngthe very youngthose with other abnormalitiesthose with other abnormalities

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Photo: Trevor Duke, RCH

Rehydration therapyRehydration therapy

Calculation exampleCalculation example•• 10 Kg infant, moderately dehydrated10 Kg infant, moderately dehydrated•• Deficit over 6 hoursDeficit over 6 hours

5% f b d i ht 0 5K5% f b d i ht 0 5K5% of body weight = 0.5Kg5% of body weight = 0.5Kg= 500ml= 500ml500ml in 6 hours = 84ml/hr500ml in 6 hours = 84ml/hr

•• 24 hour maintenance over 18 hours24 hour maintenance over 18 hours100ml/Kg = 1000ml100ml/Kg = 1000ml1000ml in 18 hours = 55ml/hr1000ml in 18 hours = 55ml/hr

Other treatmentsOther treatments

Antibiotic treatment is rarely necessaryAntibiotic treatment is rarely necessary•• ShigellaShigella•• YersiniaYersinia•• GiardiaGiardiaGiardiaGiardia•• Cl difficileCl difficile•• (Campylobacter)(Campylobacter)•• (Salmonella)(Salmonella)

Antiemetics not usefulAntiemetics not usefulAntidiarrhoeals not usefulAntidiarrhoeals not useful

Family and contact hygeine is Family and contact hygeine is importantimportant

Metabolic derangementMetabolic derangement

Metabolic acidosisMetabolic acidosis•• ketosis, bicarbonate loss, inadequate tissue ketosis, bicarbonate loss, inadequate tissue

perfusionperfusionHypernatraemia (Na >150mmol/l)Hypernatraemia (Na >150mmol/l)Hypernatraemia (Na >150mmol/l)Hypernatraemia (Na >150mmol/l)•• Excessive water loss, Na administrationExcessive water loss, Na administration

Hyponatraemia (Na < 130mmol/l)Hyponatraemia (Na < 130mmol/l)•• Excessive water administration, Na lossExcessive water administration, Na loss

Criteria for admissionCriteria for admission

ShockShockModerate or severe dehydrationModerate or severe dehydrationComplicatedComplicated•• Hyper/hyponatraemia, short gut syndrome, Hyper/hyponatraemia, short gut syndrome,

immunocompromised hostimmunocompromised hostVery youngVery youngSocial concernsSocial concerns

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Reasons to think againReasons to think again

Bilious, bloodstained or projectile vomitingBilious, bloodstained or projectile vomitingAbdominal distension, tendernessAbdominal distension, tendernessHigh feverHigh feverPersistent tachycardia or hypotensionPersistent tachycardia or hypotension

Overview of treatment for acute Overview of treatment for acute diarrhoeal diseasediarrhoeal disease

ResuscitationResuscitationDiagnosisDiagnosisAssessment of hydrationAssessment of hydrationStart rehydrationStart rehydrationAdmit to hospital?Admit to hospital?Continue feedsContinue feedsReassessReassess

Photo: Trevor Duke, RCHPhoto: Trevor Duke, RCH

Chronic DiarrhoeaChronic Diarrhoea

OverviewOverview

Physiology of GI absorptionPhysiology of GI absorptionDefinition of chronic diarrhoeaDefinition of chronic diarrhoeaCategories of causesCategories of causesAlgorithm for diagnosisAlgorithm for diagnosisSpecific diseases Specific diseases Practical tipsPractical tips

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Review GI physiology in GanongReview GI physiology in Ganong

Gastrointestinal absorptionGastrointestinal absorption Fat digestion and absorptionFat digestion and absorption

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Mechanism of Mechanism of abetalipoproteinaemiaabetalipoproteinaemia

Protein digestion and absorptionProtein digestion and absorption Digestion of carbohydratesDigestion of carbohydrates

What is diarrhoea ?What is diarrhoea ?

It is an increase in the frequency, It is an increase in the frequency, volume and fluid content of stoolvolume and fluid content of stoolWhat is normal ? What is normal ?

Breast fedBreast fed babies can pass 1 stool q babies can pass 1 stool q Breast fedBreast fed babies can pass 1 stool q babies can pass 1 stool q 10/7 or 10 stools/day, 10/7 or 10 stools/day,

bottle fedbottle fed infants pass 2infants pass 2--3 pasty stools 3 pasty stools per day and per day and

older childrenolder children 11--2 formed stools /day 2 formed stools /day or 1 stool q 2/7 or 1 stool q 2/7

NORMAL STOOLS IN INFANTSNORMAL STOOLS IN INFANTS

1st week 8-28 days 1-12 mth 13-24 mth

No. / 24 hr Range

4.0 1-12

2.2 0-6

1.8 0-5

1.7 0-3

Mean wt Range (g)

4.3 0.5-48

11 0.3-40

17 2-98

35 4-180

Stool water 73% 73% 75% 74%

Lemoh and Brooke

Arch Dis Childh

1979, 54:719

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Definition of Chronic DiarrhoeaDefinition of Chronic Diarrhoea

History of diarrhoea >2/52History of diarrhoea >2/52Aetiology is based on physiological Aetiology is based on physiological principles and include osmotic, secretory, principles and include osmotic, secretory, inflammatory or GI dysmotilityinflammatory or GI dysmotilityy y yy y yCan result in electrolyte and nutritional Can result in electrolyte and nutritional deficienciesdeficienciesToddlers Diarrhoea and Overflow Toddlers Diarrhoea and Overflow constipation (less common now) are the constipation (less common now) are the commonest causes commonest causes

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Fat globules implies impaired Fat globules implies impaired digestiondigestion Impaired intraluminal digestion IImpaired intraluminal digestion I

Affecting Affecting allall nutrientsnutrientsCYSTIC FIBROSISCYSTIC FIBROSIS

Shwachman syndrome (panc hypoplasia Shwachman syndrome (panc hypoplasia Shwachman syndrome (panc hypoplasia, Shwachman syndrome (panc hypoplasia, neutropenia and metaphysial chondrodysplasia)neutropenia and metaphysial chondrodysplasia)

JohansonJohanson--Blizzard syndromeBlizzard syndromePearson syndromePearson syndromeCystinosisCystinosis

Impaired intraluminal digestion IIImpaired intraluminal digestion II

Affecting Affecting fatfat absorptionabsorptionBiliary atresiaBiliary atresiaImpaired enterohepatic circ Impaired enterohepatic circ •• (eg ileal resection or Crohn’s disease)(eg ileal resection or Crohn’s disease)

Blind loopBlind loop

Isolated lipase or colipase defyIsolated lipase or colipase defyImpaired bile acid synthesisImpaired bile acid synthesis

Impaired intraluminal digestion IIIImpaired intraluminal digestion III

Affecting Affecting proteinsproteinsCongenital trypsinogen defyCongenital trypsinogen defyCongenital enterokinase defyCongenital enterokinase defy

Fatty acid crystals implies impaired Fatty acid crystals implies impaired absorption absorption –– capable of partial hydrolysiscapable of partial hydrolysis

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OsmoticOsmoticNa<70mEq/litreNa<70mEq/litreOsmolality> (Na+K)x2Osmolality> (Na+K)x2pH <5pH <5

SecretorySecretoryNa>70mEq/litreNa>70mEq/litreOsmolality=(Na+K)x2Osmolality=(Na+K)x2pH>6pH>6

Differentiating between Osmotic Differentiating between Osmotic and Secretory Diarrhoeaand Secretory Diarrhoea

Reducing substancesReducing substancesVolume<200ml/dayVolume<200ml/dayCeases when oral Ceases when oral intake is stoppedintake is stopped

No reducing No reducing substancessubstancesVolume>200ml/dayVolume>200ml/day

Differential Diagnosis of Differential Diagnosis of SecretorySecretoryDiarrhoeaDiarrhoea

Infection with Infection with toxigenic toxigenic organisms organisms (e.g., (e.g., Cholera, Cholera, E. Coli,E. Coli, Salmonella Salmonella ))

S titi d S titi d

Bile acid Bile acid malabsorptionmalabsorptionCongenital Congenital electrolyte electrolyte

Surreptitious drug Surreptitious drug administration administration e.g., e.g., laxativeslaxatives

yytransport defecttransport defectHormoneHormone--secreting tumours secreting tumours e.g., VIPoma, e.g., VIPoma, Gastrinoma,Carcinoid, Gastrinoma,Carcinoid, PheochromocytomaPheochromocytoma

MastocytosisMastocytosis

Differential Diagnosis of Differential Diagnosis of OsmoticOsmoticDiarrhoeaDiarrhoea

Osmotic LaxativesOsmotic LaxativesCHO malabsorption CHO malabsorption e.g., Glue.g., Glu--Gal transport Gal transport defect, lactase and defect, lactase and isomaltaseisomaltase--sucrase sucrase

GI infectionsGI infectionsCoeliac diseaseCoeliac diseaseCMP/Soy allergyCMP/Soy allergyInflammatory diseases Inflammatory diseases

isomaltaseisomaltase sucrase sucrase deficiencydeficiencyOverfeeding (<6mth)Overfeeding (<6mth)

AutoAuto--immune immune enteropathyenteropathyBacterial overgrowthBacterial overgrowth

AbetaliproteinaemiaAbetaliproteinaemialymphangiectasialymphangiectasia

SUGAR MALABSORPTIONSUGAR MALABSORPTION

Average diet 350 g CHOAverage diet 350 g CHOAssume 5% gets to colonAssume 5% gets to colon18 g monosaccharides = 18 g monosaccharides = 95 O95 O95mOsm95mOsm•• drags drags 300 ml300 ml waterwater

LACTOSE MALABSORPTION

GLUCOSE

LACTOSElactase

+GALACTOSE

* USING GLUCOSE BY-PASSES NEED FOR LACTASE

* NO NEED TO CHANGE PROTEIN OR FAT

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Lactose intoleranceLactose intolerance

Primary (congenital) Primary (congenital) –– rarerare

Secondary (acquired)Secondary (acquired)T T tt i f ti d t i f ti d t •• Temporary Temporary –– postpost--infectious damage to infectious damage to villous (eg rotavirus or giardia)villous (eg rotavirus or giardia)

•• Permanent Permanent –– 97% of Africans and 97% of Africans and AsiansAsians

Coeliac DiseaseCoeliac Disease

A disease of the proximal SI characterised A disease of the proximal SI characterised by an abnormal small intestinal mucosa by an abnormal small intestinal mucosa and associated with a permanent and associated with a permanent intolerance to glutenintolerance to glutenNot seen in Asian and infrequent in the Not seen in Asian and infrequent in the Black populationBlack populationIncidence 1 in 300 in Ireland and 1 in 500 Incidence 1 in 300 in Ireland and 1 in 500 in Australia (seroprev 1%)in Australia (seroprev 1%)DQ2,7 can be used for family screeningDQ2,7 can be used for family screening

PathogenesisPathogenesis

Gluten induced T cell mediated Gluten induced T cell mediated immune response within the lamina immune response within the lamina propria following a yet to be defined propria following a yet to be defined sensitization processsensitization processsensitization processsensitization processHumoral immunity appears to play a Humoral immunity appears to play a limited role in the pathogenesis of limited role in the pathogenesis of this disorderthis disorderWheat, rye, barley (unlikely oats) Wheat, rye, barley (unlikely oats)

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ESPGHAN CRITERIA 1969, 1974ESPGHAN CRITERIA 1969, 1974

ABNORMAL MUCOSA ON GLUTENABNORMAL MUCOSA ON GLUTEN

HISTOLOGICAL RESPONSE TO GLUTENHISTOLOGICAL RESPONSE TO GLUTEN--FREE FREE DIETDIETDIETDIET

HISTOLOGICAL RELAPSE ON GLUTEN HISTOLOGICAL RELAPSE ON GLUTEN CHALLENGECHALLENGE

ESPGHAN CRITERIA 1990ESPGHAN CRITERIA 1990

ABNORMAL MUCOSA ON GLUTENABNORMAL MUCOSA ON GLUTEN

FULL CLINICAL REMISSION ON DIETFULL CLINICAL REMISSION ON DIET

Exceptions where diagnostic doubt:Exceptions where diagnostic doubt:•• < 2 years of age at presentation< 2 years of age at presentation•• asymptomatic: family members asymptomatic: family members

diabetes diabetes short short

staturestature

Clinical PresentationClinical Presentation

Chronic diarrhoea, FTT 9Chronic diarrhoea, FTT 9--18 months 18 months of age and before 9 months presents of age and before 9 months presents with mainly vomitingwith mainly vomitingConstipation in 10%Constipation in 10%Constipation in 10%Constipation in 10%Short stature, anaemia, personality Short stature, anaemia, personality problemsproblems

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Atypical PresentationAtypical PresentationNeurologicalNeurological: Seizures in 5% of adults, : Seizures in 5% of adults,

cerebellar ataxia, dementia, peripheral cerebellar ataxia, dementia, peripheral neuropathy, myopathy, cerebral neuropathy, myopathy, cerebral calcification and folate deficiency calcification and folate deficiency

Dermatitis Herpetiformis:Dermatitis Herpetiformis:chronic pruritic papulovesicular rash over chronic pruritic papulovesicular rash over

extensor surfaces and Ig A deposits in the extensor surfaces and Ig A deposits in the skin with mild biopsy findingsskin with mild biopsy findings

Elevated transaminase levelsElevated transaminase levels

Clinical AssociationsClinical Associations

Immune: Ig A deficiency, IDDM, Immune: Ig A deficiency, IDDM, Thyroiditis, CAH, Ig A nephropathy, Thyroiditis, CAH, Ig A nephropathy, fibrosing alveolitis, CMP enteropathyfibrosing alveolitis, CMP enteropathy

Other: Down syndrome, CF, Other: Down syndrome, CF, AlphaAlpha--11--antitrypsin deficiency, antitrypsin deficiency,

Screening testsScreening tests

Antigliadin Abs: IgA(specific) and Antigliadin Abs: IgA(specific) and IgG(sensitive) with false positive results in IgG(sensitive) with false positive results in GI infections, IBD and other allergic GI infections, IBD and other allergic disordersdisordersAntiAnti--endomysial (IgA based) quoted as endomysial (IgA based) quoted as having a sensitivity and specificity having a sensitivity and specificity approaching 97%approaching 97%AntiAnti--tissue transglutaminase sensitivity tissue transglutaminase sensitivity and specificity of 98%, again IgA based and specificity of 98%, again IgA based assayassay

DiagnosisDiagnosis

Abnormal SI mucosaAbnormal SI mucosaClinical response to glutenClinical response to gluten--free dietfree diet3 biopsies rarely required unless 3 biopsies rarely required unless th i d bt di th D th i d bt di th D there is doubt surrounding the Dx, there is doubt surrounding the Dx, less then 2 yrs at time of diagnosis, less then 2 yrs at time of diagnosis, no previous biopsy and teenagers no previous biopsy and teenagers who plan to start a normal dietwho plan to start a normal diet

LongLong--term complicationsterm complications

OsteoporosisOsteoporosisMalignant GI disease: Birmingham Malignant GI disease: Birmingham study demonstrated an increased study demonstrated an increased risk of lymphoma GI cancer and risk of lymphoma GI cancer and risk of lymphoma, GI cancer and risk of lymphoma, GI cancer and other malignancyother malignancyGluten free and not reduced gluten Gluten free and not reduced gluten containing diet protected against the containing diet protected against the development of these malignancies development of these malignancies

Lactose intoleranceLactose intolerance

Primary (congenital) Primary (congenital) –– rarerare

Secondary (acquired)Secondary (acquired)T T tt i f ti d t i f ti d t •• Temporary Temporary –– postpost--infectious damage to infectious damage to villous (eg rotavirus or giardia)villous (eg rotavirus or giardia)

•• Permanent Permanent –– 97% of Africans and 97% of Africans and AsiansAsians

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LACTOSE MALABSORPTION

GLUCOSE

LACTOSElactase

+GALACTOSE

* USING GLUCOSE BY-PASSES NEED FOR LACTASE

* NO NEED TO CHANGE PROTEIN OR FAT

Coeliac DiseaseCoeliac Disease

A disease of the proximal SI A disease of the proximal SI characterised by an abnormal small characterised by an abnormal small intestinal mucosa and associated intestinal mucosa and associated with a permanent intolerance to with a permanent intolerance to glutenglutenNot seen in Asian and infrequent in Not seen in Asian and infrequent in the Black populationthe Black populationIncidence 1 in 300 in Ireland and 1 Incidence 1 in 300 in Ireland and 1 in 500 in Australiain 500 in Australia

Clinical PresentationClinical Presentation

Chronic diarrhoea, FTT 9Chronic diarrhoea, FTT 9--18 months 18 months of age Constipation in 10%of age Constipation in 10%Short stature, anaemia, irritability, Short stature, anaemia, irritability, dental hypoplasiadental hypoplasiadental hypoplasiadental hypoplasia

Cows milk protein allergyCows milk protein allergy2% of children <2yo2% of children <2yoUsually occurs with within days to weeks Usually occurs with within days to weeks of starting cow’s milk (eg formula)of starting cow’s milk (eg formula)Can occur in breast fed babiesCan occur in breast fed babiesSymptoms of diarrhoea, vomiting, Symptoms of diarrhoea, vomiting, irritability, ezcemairritability, ezcemaUsually settles with extensively hydrolysed Usually settles with extensively hydrolysed formula (eg Peptijunior, Alfare)formula (eg Peptijunior, Alfare)1010--20% also intolerant of soy formula20% also intolerant of soy formula

Bacterial OvergrowthBacterial OvergrowthColonic flora proliferate in the SI in areas Colonic flora proliferate in the SI in areas of stasis and leads to a clinical syndrome of stasis and leads to a clinical syndrome characterized by anaemia and steatorrheacharacterized by anaemia and steatorrhea

F t di i t th d l t F t di i t th d l t Factors predisposing to the development Factors predisposing to the development of bacterial overgrowth include anatomical of bacterial overgrowth include anatomical abnormalities, motility disorders, excess abnormalities, motility disorders, excess bacterial load (e.g., achlorhydria, fistula bacterial load (e.g., achlorhydria, fistula and loss ileocaecal valve) and abnormal and loss ileocaecal valve) and abnormal host defence host defence

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Clinical FeaturesClinical Features

ClassicClassic: fat malabsorption and : fat malabsorption and anaemiaanaemia

SystemicSystemic: Arteritis vesicopustular : Arteritis vesicopustular SystemicSystemic: Arteritis, vesicopustular : Arteritis, vesicopustular rash, Raynaud’s, nephritis, hepatitisrash, Raynaud’s, nephritis, hepatitis

OtherOther: Weight loss, short stature, : Weight loss, short stature, abdominal pain, PLE, osteomalacia, abdominal pain, PLE, osteomalacia, night blindness and ataxia night blindness and ataxia

Diagnostic testsDiagnostic tests

RadiologyRadiologyLaboratory: 72Laboratory: 72--hr faecal fat and hr faecal fat and Sudan stain for fatSudan stain for fatNN I i B th t tI i B th t tNonNon--Invasive: Breath testsInvasive: Breath testsInvasive: Duodenal aspiration and Invasive: Duodenal aspiration and cultureculture

The practical reality of chronic The practical reality of chronic diarrhoeadiarrhoea

A good history is invaluable!A good history is invaluable!

TypeType –– fluidity, number, size, colour and smellfluidity, number, size, colour and smell

Liquid stools in congenital chloride diarrhoeaLiquid stools in congenital chloride diarrhoeaNoisily with flatus in cases of sugar malabsorptionNoisily with flatus in cases of sugar malabsorptionLoose and bulky in Coeliac diseaseLoose and bulky in Coeliac diseaseLoose and bulky in Coeliac diseaseLoose and bulky in Coeliac diseasePasty, yellowish and cheesy smell in exocrine pancreatic Pasty, yellowish and cheesy smell in exocrine pancreatic insufficiencyinsufficiencyAcidic smell due to fermentationAcidic smell due to fermentationOffensive smell in Coeliac diseaseOffensive smell in Coeliac diseaseUndigested food, foul smelling, alt with normal stools in Undigested food, foul smelling, alt with normal stools in well nourished toddler in Toddler’s diarrhoeawell nourished toddler in Toddler’s diarrhoea

HistoryHistory

TimingTimingNeonatal (congenital causes)Neonatal (congenital causes)Introduction or elimination of cow’s Introduction or elimination of cow’s

ilk t i h t l t ilk t i h t l t milk proteins, wheat, lactose or milk proteins, wheat, lactose or sucrosesucrose

5/01/2011

20

Causes of neonatal diarrhoeaCauses of neonatal diarrhoeaCongenital lactase deficiencyCongenital lactase deficiencyCongenital glucoseCongenital glucose--galactose deficiencygalactose deficiencyCongenital chloride diarrhoeaCongenital chloride diarrhoeaCongenital bileCongenital bile--acid malabsorptionacid malabsorptionCongenital defecti e jej nal Na/H Congenital defecti e jej nal Na/H Congenital defective jejunal Na/H Congenital defective jejunal Na/H exchangeexchangeCongenital enterokinase deficiencyCongenital enterokinase deficiencyCongenital microvillous atrophyCongenital microvillous atrophyIntestinal pseudoIntestinal pseudo--obstructionobstructionHirschsprung’s diseaseHirschsprung’s disease

HistoryHistory

Associated symptomsAssociated symptomsAnorexia (intestinal malabsorption)Anorexia (intestinal malabsorption)Increased appetite (CF)Increased appetite (CF)Thirst (severe and fluid diarrhoea)Thirst (severe and fluid diarrhoea)Abdominal pain, bloating Abdominal pain, bloating (fermentation)(fermentation)Weakness (Coeliac disease)Weakness (Coeliac disease)

What you can learn from What you can learn from one faecal specimen!one faecal specimen!

MICROSCOPYMICROSCOPYwbc, rbc, mucuswbc, rbc, mucus•• colitiscolitiscystscysts

BIOCHEMISTRYBIOCHEMISTRYReducing Reducing substancessubstancesTryptic activityTryptic activityyy

•• giardiagiardiafatty acid crystalsfatty acid crystals•• mucosal damagemucosal damagefat globulesfat globules•• pancreatitispancreatitis

•• low = low = pancreatic pancreatic insufficiencyinsufficiency

Stool electrolytesStool electrolytes•• Na > 70 = Na > 70 = active active

secretionsecretion

Other investigationsOther investigations

FBE FBE –– IBD, increased eosinophils in IBD, increased eosinophils in cow/soy milk intolerance or parasitescow/soy milk intolerance or parasitesLFTsLFTs-- assess liver disease, U/Esassess liver disease, U/EsTSH t l t h th idiTSH t l t h th idiTSH to rule out hyperthyroidismTSH to rule out hyperthyroidismBreath test Breath test –– sugar malabsorptionsugar malabsorptionBa meal and follow through Ba meal and follow through –– IBD or IBD or anatomical problemsanatomical problems

Endoscopy and biopsyEndoscopy and biopsy

To exclude:To exclude:Coeliac disease Coeliac disease GiardiaGiardiaAbetaproteinemia (fat fill enterocytes)Abetaproteinemia (fat fill enterocytes)Abetaproteinemia (fat fill enterocytes)Abetaproteinemia (fat fill enterocytes)Lymphangiectasia (villi distorted by ectatic Lymphangiectasia (villi distorted by ectatic lymphatics) lymphatics) Sensitisation to food proteins (cow, soy, Sensitisation to food proteins (cow, soy, wheat)wheat)Inflammatory bowel diseaseInflammatory bowel disease