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

OsmoticOsmoticNa<70mEq/litreNa<70mEq/litreOsmolality> (Na+K)x2Osmolality> (Na+K)x2pH <5pH <5Reducing substancesReducing substancesVolume<200ml/dayVolume<200ml/dayCeases when oral Ceases when oral intake is stoppedintake is stopped

SecretorySecretoryNa>70mEq/litreNa>70mEq/litreOsmolality=(Na+K)x2Osmolality=(Na+K)x2pH>6pH>6No reducing No reducing substancessubstancesVolume>200ml/dayVolume>200ml/day

Differentiating between Osmotic Differentiating between Osmotic and Secretory Diarrhoeaand Secretory Diarrhoea

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 ))

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

Bile acid Bile acid malabsorptionmalabsorptionCongenital Congenital electrolyte electrolyte transport defecttransport defectHormoneHormone--secreting tumours secreting tumours e.g., e.g., VIPomaVIPoma, , GastrinomaGastrinoma,Carcinoid, ,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 deficiencydeficiency

Overfeeding (<6mth)Overfeeding (<6mth)

GI infectionsGI infectionsCoeliac diseaseCoeliac diseaseCMP/Soy allergyCMP/Soy allergyInflammatory diseases Inflammatory diseases 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 = 95mOsm95mOsm•• drags drags 300 ml300 ml waterwater

LACTOSE MALABSORPTION

GALACTOSE

GLUCOSE

LACTOSElactase

+

* USING GLUCOSE BY-PASSES NEED FOR LACTASE

* NO NEED TO CHANGE PROTEIN OR FAT

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 Incidence 1 in 300 in Ireland and 1 in 500500--2000 in Australia (2000 in Australia (seroprevseroprev 1%)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 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)

ESPGHAN CRITERIA 1969, 1974ESPGHAN CRITERIA 1969, 1974

ABNORMAL MUCOSA ON GLUTENABNORMAL MUCOSA ON GLUTEN

HISTOLOGICAL RESPONSE TO GLUTENHISTOLOGICAL RESPONSE TO GLUTEN--FREE FREE DIETDIET

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 statureshort stature

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%Short stature, anaemia, personality Short stature, anaemia, personality problemsproblems

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

AntigliadinAntigliadin Abs: IgA(specific) and 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--endomysialendomysial (IgA based) quoted as (IgA based) quoted as having a sensitivity and specificity having a sensitivity and specificity approaching 97%approaching 97%AntiAnti--tissue tissue transglutaminasetransglutaminase sensitivity 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 there is doubt surrounding the there is doubt surrounding the DxDx, , 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 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

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

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 and loss ileocaecalileocaecal valve) and abnormal valve) and abnormal host defence host defence

Clinical FeaturesClinical Features

ClassicClassic: fat malabsorption and : fat malabsorption and anaemiaanaemia

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 fatNonNon--Invasive: Breath testsInvasive: Breath testsInvasive: Duodenal aspiration and Invasive: Duodenal aspiration and cultureculture

The practical reality of chronicThe practical reality of chronicdiarrhoeadiarrhoea

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

TypeType –– fluidity, number, size, fluidity, number, size, colourcolour and smelland smell

Liquid stools in congenital chlorideLiquid stools in congenital chloride diarrhoeadiarrhoeaNoisily with flatus in cases of sugar Noisily with flatus in cases of sugar malabsorptionmalabsorptionLoose and bulky in Loose and bulky in CoeliacCoeliac diseasediseasePasty, 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 Offensive smell in CoeliacCoeliac diseasediseaseUndigested food, foul smelling, alt with normal stools in Undigested food, foul smelling, alt with normal stools in well nourished toddler in Toddler’swell nourished toddler in Toddler’s diarrhoeadiarrhoea

HistoryHistory

TimingTimingNeonatal (congenital causes)Neonatal (congenital causes)Introduction or elimination of cow’s Introduction or elimination of cow’s milk proteins, wheat, lactose or milk proteins, wheat, lactose or sucrosesucrose

Causes of neonatalCauses of neonatal diarrhoeadiarrhoeaCongenital lactase deficiencyCongenital lactase deficiencyCongenital glucoseCongenital glucose--galactosegalactose deficiencydeficiencyCongenital chlorideCongenital chloride diarrhoeadiarrhoeaCongenital bileCongenital bile--acid acid malabsorptionmalabsorptionCongenital defective Congenital defective jejunaljejunal Na/H Na/H exchangeexchangeCongenital Congenital enterokinaseenterokinase deficiencydeficiencyCongenital Congenital microvillousmicrovillous atrophyatrophyIntestinal pseudoIntestinal pseudo--obstructionobstructionHirschsprung’sHirschsprung’s diseasedisease

HistoryHistory

Associated symptomsAssociated symptomsAnorexia (intestinal Anorexia (intestinal malabsorptionmalabsorption))Increased appetite (CF)Increased appetite (CF)Thirst (severe and fluidThirst (severe and fluid diarrhoeadiarrhoea))Abdominal pain, bloating Abdominal pain, bloating (fermentation)(fermentation)Weakness (Weakness (CoeliacCoeliac disease)disease)

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

MICROSCOPYMICROSCOPYwbc, rbc, mucuswbc, rbc, mucus•• colitiscolitiscystscysts•• giardiagiardiafatty acid crystalsfatty acid crystals•• mucosal damagemucosal damagefat globulesfat globules•• pancreatitispancreatitis

BIOCHEMISTRYBIOCHEMISTRYReducing Reducing substancessubstancesTryptic activityTryptic activity•• low = low = pancreatic pancreatic

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

secretionsecretion

Other investigationsOther investigations

FBE FBE –– IBD, increased IBD, increased eosinophilseosinophils in in cow/soy milk intolerance or parasitescow/soy milk intolerance or parasitesLFTsLFTs-- assess liver disease, U/Esassess liver disease, U/EsTSH to rule out hyperthyroidismTSH to rule out hyperthyroidismBreath test Breath test –– sugar sugar malabsorptionmalabsorptionBaBa meal and follow through meal and follow through –– IBD or IBD or anatomical problemsanatomical problems

EndoscopyEndoscopy and biopsyand biopsy

To exclude:To exclude:CoeliacCoeliac disease disease GiardiaGiardiaAbetaproteinemiaAbetaproteinemia (fat fill (fat fill enterocytesenterocytes))LymphangiectasiaLymphangiectasia ((villivilli distorted by distorted by ectaticectaticlymphaticslymphatics))SensitisationSensitisation to food proteins (cow, soy, to food proteins (cow, soy, wheat)wheat)Inflammatory bowel diseaseInflammatory bowel disease