1、1INFANTILE DIARRHEACHCUMSDIVISION OF INFECTIOUS DISEASE AND GASTROENTEROLOGYINFANTILE DIARRHEA.2Backgroundn Diarrhea is a clinical syndrome of diverse etiology associated with many influencing factors.n It is the most frequent childhood disease second only to the respiratory infection.n The major ca
2、use of death among worlds children and the number one killer of children under five in many developing countries.3Disease Burden Worldwiden 3-5 billion episodes/yearn 4-5 million deaths/year Children are the predominant populations.n 3.2 billion episodes/year in 5y childrenn 1.3 million deaths/year
3、in 5y children In China n 836 million episodes of diarrhea every yearn 1/4-1/3 of all outdoor patients and a large amount of hospitalizations of children are due to diarrhea.4 F Fluidityluidity Volume Volume Number NumberIn pediatrics,diarrhea is defined as an increase in the relative to the usual h
4、abits of each individualof stoolsof stoolsDefinition.5Normal Stool of ChildrenBreastfed babies:pass stools 3-4 times a day yellow loose(soft to runny)but textured sweet-smellingBottlefed babies:once a day pale yellow or yellowish-brown bulkier and more formed pretty pungentBabies on solids:thicken a
5、nd darken slightly have a stronger odor.6Dehydration MalnutritionMortalityWhy diarrhea is more dangerous for children?.7Malnutrition and Child Mortality.8If:Diarrhea+MalnutritionThe RISK of DEATH is 4 fold higher than that of well nourished children.9Why children are highly vulnerable to diarrhea?l
6、Immature digestive systeml More nutrition demandl Weakness of defense systeml The normal intestinal flora have not built up well l Bottle feeding.10Etiology of Diarrhea.11Etiology of DiarrheaInfectiveNon infective Viruses Bacteria Parasites Fungi Allergic Symptomatic Inappropriate feeding Food intol
7、erance Climate.12Viral EnteropathogensViral enteropathogens cause most illnesses in pediatric population.n Rotavirus(morn than 50%acute diarrhea)n Astrovirusn Norwalk virus n Coronavirus n Calicivirusn Enteric adenovirus(serotypes 40 and 41).13RotavirusRotavirus.14The most common cause of childhood
8、diarrhea second only to the viral enteropathogensn Escherichia coli EPEC;ETEC;EITC;EHEC;EAECn Campylobacter jejuni n Shigella speciesn Salmonella typhimurium n Yersinia enterocolitican Staphylococcus aureus n Clostridium difficilen Vibrio choleraeBacterial Enteropathogens.15Rare etiologic pathogen o
9、f diarrhean Cryptosporidium parvum n Entamoeba histolyticn Giardia lamblia Parasites Pathogens.16Rare etiologic pathogen of diarrhean Candida albicansn Aspergillusn Mucor Fungous Pathogens.17The most important infective causes of acute diarrhea in developing countries in children are:u Rotavirusu En
10、terotoxigenic escherichia coliu Shigellau Campylobacter jejuniu Salmonella typhimurium.18Etiology of DiarrheaInfectiveNon infective Viruses Bacteria Parasites Fungi Allergic Symptomatic Inappropriate feeding lactose intolerance Climate.19u Overfeedingu Indigestible dietu Sudden change of formulau In
11、appropriate feeding for a milk-fed baby shifting into solid food (too much,too early,too rapid)n Dietary DiarrheaInappropriate feeding:.20n Allergic DiarrheaPrimary food hypersensitivity:3 months after birth Second food hypersensitivity:Infection injury and hyperpermeability of intestinal mucosa lar
12、ge molecular protein entering bloodstream allergic state Cows milk protein Soy bean protein Egg white peanuts,meat,and fish etc.21n Symptomatic Diarrhea Diarrhea is only one of the symptoms of primary disease.Problem is not originally located in intestinal tract.Respiratory tract infection Otitis me
13、dia Some infectious diseases,etc.Always be mild,and recover with the primary disease getting better The younger the children,the more chance to get a symptomatic diarrhea accompanied by other diseases.22n Lack of DisaccharidaseLactose IntolerancePrimary Disaccharidase Deficiency is a rare disease(co
14、ngenital defects of carbohydrate hydrolysis).Second Diaccharidase Deficiency:Rotavirus infection Injures the enterocytes of villi Transient disaccharidase deficiency Malabsorption of lactose in the milk Typical loose and watery stools.23n ClimateSeasonal variation affects the digestive function of s
15、mall children:incidence of diarrhea is highest during the early raniny seasonCold weather causes increasing of enterokinesiaHot weather causes decreasing of digestive enzyme and malfunction of digestive tract .24Pathophysiological Mechanisms of Diarrhea.25 Virus Diarrhea-Rotavirus Enterotoxigenic En
16、teritis ETEC,Vibrio Cholerae Entero-Invasive Organisms Shigella Species,EIEC Dietary DiarrheaPathophysiological Mechanisms of Diarrhea.26Pathogenesis of Virus DiarrheaVirus invades the absorptive enterocytes of villi but spares crypt cellsThe viruses replicates and infected enterocytes are destroyed
17、Rotavirus.27Pathogenesis of Virus Diarrhea1-Infected absorptive enterocytes are killed causing patchy epithelial cell destruction and villous shortening2-Destroyed absorptive cells are rapidly replaced by cells that migrate from the crypts.Villi become covered with immature non-absorptive secretory
18、cells having:-no brush border-no brush border enzymesOsmotic Diarrhea.28Pathogenesis of Virus Diarrhea(Osmotic Diarrhea)Rotaviruses attach and replicate in the mature enterocytes at the tips of small intestinal villi Destroy villus tip cells,variable degrees of villus blunting mononuclear inflammato
19、ry infiltrate in the lamina propria Impairment of digestive functionsdiscreasing hydrolysis of disaccharidesImpairment of absorptive functionsthe transport of water and electrolytes via glucose and amino acid co-transporters An imbalance in the ratio of intestinal fluid absorption to secretionMalabs
20、orption of complex carbohydrates,particularly lactoseOther than degested into monosaccharide,lactose be lysis into organic acid,hyperosmosis Watery stool.29 Virus Diarrhea-Rotavirus Enterotoxigenic enteritis ETEC,Vibrio Cholerae Entero-Invasive Organisms Shigella Species,EIEC Dietary diarrheaPathoph
21、ysiological Mechanisms of Diarrhea.30Pathogenesis of Enterotoxigenic Diarrhea Pathogens:Vibrio cholerae(cholera)ETEC Staphylococcus aureus Clostridium difficile.31 enterotoxigenic organismsIngestion small bowel mucosa and proliferate activates cellular guanylatecyclase Heat-stable enterotoxin promot
22、e the net secretion of water and chloride increased intracellular concentrations of cAMP activates cellular adenylcyclase binds to receptors of epithelial cells Heat-labile enterotoxin decrease absorption of sodium and chloride by villous cells increased intracellular concentrations of cGMP Secretor
23、y diarrheaPathogenesis of Enterotoxigenic Diarrhea(Secretory Diarrhea).32Pathogenesis of Enterotoxigenic Diarrhea(Secretory Diarrhea)1-Enterotoxigenic Bacteria secrete Enterotoxins2-Toxin stimulates the production of C-AMP Increased C-AMP leads to:3-Inhibition of absorption of Na and Cl from the cel
24、ls of villi4-Stimulation of secretion of Cl from crypt cells+-12341234.33Pathogenesis of Enterotoxigenic Diarrhea(Secretory Diarrhea)The mucosa is not destroyed during this process.34An imbalance in the ratio of intestinal fluid absorption to secretion,so watery stool may occur in clinical observati
25、on Pathogenesis of Enterotoxigenic Diarrhea(Secretory Diarrhea).35Enterotoxigenic Diarrhea Clinical finding:Watery diarrhea and vomiting develop after an incubation period of 6 hr-5 days(2-3days,average)Low-grade fever occurs in some childrenProfuse,painless,watery diarrhea,sometimes with flecks of
26、mucus but no blood1.Fluid and electrolyte losses,tachycardia,tachypnea,a sunken anterior fontanel,progress to circulatory collapse.36 Virus Diarrhea-Rotavirus Enterotoxigenic enteritis ETEC,Vibrio Cholerae Entero-Invasive Organisms Shigella Species,EIEC Dietary diarrheaPathophysiological Mechanisms
27、of Diarrhea.37Invasive DiarrheaEntero-Invasive Organisms:Shigella species EIEC(enteroinvasive E.coli)Campylobacter jejuni Salmonella typhimurium Yersinia enterocoliticaThe central event in pathogenesis is invasion of colonic mucosa.38Pathogenesis of Invasive DiarrheaInvasive enteropathogenIngestion
28、Gut lumenColon and rectum mucous membrane proper Extensive destruction of the epithelial layer Inflammation:Hyperemia,swelling,heavy neutrophil infiltration,inflammatory exudateThe desquamation,ulceration,and formation of microabscesses in the colonic mucosa inhibit absorption of waterstools that ar
29、e frequent and scanty and that contain blood inflammatory cells and mucus.39Pathogenesis of Invasive Diarrhea.40Invasive DiarrheaClinical finding:Stools that are frequent and scanty and that contain blood inflammatory cells,and mucus Stool examination:large amount of WBC,pus cell,and RBC1.Dehydratio
30、n and electrolyte disturbances are less frequent because of less loss of digestive fluid.41 Virus Diarrhea-Rotavirus Enterotoxigenic enteritis ETEC,Vibrio Cholerae Entero-Invasive Organisms Shigella Species,EIEC Dietary diarrheaPathophysiological Mechanisms of Diarrhea.42Pathogenesis of Dietary Diar
31、rheaInappropriate dietIrritates the bowel Promote the peristalsisWater entering the lumen Decomposed product amineslactic acidacetic acid Acidity decreasingGive the chance to the bacteria which lived in lower part of bowel coming up Endogenous infection Aggravate the intestinal function disturbance
32、Indigested food accumulate in the upper part of intestineDyspepsia Indigested food ferment and putrescenceHyperosmosisDiarrhea.43Morphology of Intestinal Mucosa.44Morphology of Intestinal MucosaVillicovered mainly(90%)by tall columnar absorptive cells(Enterocytes)having a micrevillar brush borderCry
33、pts of lieberkuhnCovered mainly by short columnar secretory cellsGoblet cellswithout brush border.45Defense Barriers of the Enterocytes1.Physical barrier:mucus 2.Bacteriological(flora)3.Immunological:Secretory IgA123.46Normal FloraBreast-fed:A Gram-positive population:Bifidobacteria and Lactobacilli
34、 Bottle-fed:A Gram-negative flora:Enterobacteriaceae.47Clinical Manifestations.48Clinical manifestationsu Gastrointestinal symptomu Systemic symptomu Dehydration and electrolyte disturbances .49Assessment of a child with dehydration&electrolyte disturbances.50DehydrationExcessive loss of water,espec
35、ially loss of extracellular fluid.51.52.53.54Assessment of a DehydrationMildModerateModerateSevereSevereDehydration5%5-10%10-15%50ml/Kg50-100ml/Kg100-120ml/KgMental StateNormalRestless,irritableProstration/ComaFontanelNormalSunkenDeeply SunkenTearNormalDecreaseAbsenceBucal MucosaMoistDryVery DryTiss
36、ue TurgorNormalAbsentAbsentUrine FlowDecrease SlightlyDecreaseAnuriaShockAbsentAbsentPresent.55Type of dehydrationHypotonic300 mOsm/LSerum sodium130mmol/L130-150mmol/L150mmol/LSkin colorSkin temperatureSkin turgorPaleColdAbsentPaleColdNormalFlush-NormalDuration of vomiting and diarrheaVery longLongS
37、hortThirstyNoNoYesMucous membraneMoistMoistDryNS syndromsLethargyNormalIrritableDisturbance of peripheral circulationYesNoNo.56 serum potassium3.5mmol/LEtiology Excessive of loss Insufficient intake1.Distributional disturbance of extracelluar and intracelluar potassiumHypopotassaemia.57(二二)低钾血症低钾血症M
38、anifestations（1）low nervous and muscular excitability nervous excitability ：downcast,lethargy muscular excitability：weakness、byporesalexia of tendon jerk,paralysis GI smooth muscle excitability ：paralytic ileus（2）cardiovascular system：cardiac dysrhythmia,low heart sound,electrocardiographic abnormal
39、ityHypopotassaemia serum potassium3.5mmol/L.58 serum calcium1.88mmol/L High nervous and muscular excitabilityHypocalcemia.59 1 etiology (1)loss of alkaline substance from GI track (2)acid substance accumulation in body H+排除 2 manifestations:hyperpnoea、increased heart rate、serise lip、conscious distur
40、bance for the severe cases H+产生Metabolic Acidosis.60Classification of Diarrhea based on Severity Duration Etiology.61Classification of Diarrhea1.Mild diarrhea:Most of the cases are non-infectious diarrhea Frequency of stool often less than 10 times/day Yellowish loose stool,sour smell with a few of
41、mucusfat drop in microscopic exam General condition is good,self-limited on several days 2.Moderate diarrhea:3.Severe diarrhea:Most of the cases are infectious diarrhea(rotavirus,shigella)Frequency of stool often more than 10 times/day Watery stool,plenty of mucus.General condition is poor,usually a
42、ccompany with vomiting and fever,dehydration and electrolyte disturbance.62Acute stage:the course of the diseases less than 2 weeksPersisting type:the course of disease more than 2 weeks but less than 2 monthsChronic stage:the course of disease more than 2 monthsClassification of Diarrhea.63Persisti
43、ng and ChronicPersisting and Chronic Diarrhea Complicate reasons:Persisting infection,Allergic state,Lack of disaccharidase,Immunodeficience,Broad spectrum antibiotic usage,Malnutrition,Malabsorption,etc.Pathogenesis is not clear Great dangerous:Malnutrition and growth retardationMortality is high T
44、roublesome to be controlled:Adequate caloriesReestablish the normal flora .64Rotaviruses Infection.65Rotaviruses infection First recognized in humans in 1973 by Australian Scientist Bishop,with a hubbed wheel appearance under electronmicroscope,giving their name Double-stranded RNA virusVP6:A-G grou
45、p,group A is the most important group in childhood infection.66Rotaviruses infection Deep fall and winter(October-February）Causing sharply increasing of outdoor patients in autumn and winter,also named autumn diarrhea6m-2y,rarely happen in children above 4y80%infectious diarrhea in pediatric clinic
46、in autumn and winterAbout 1/4 to 1/3(more than 800 cases)hospitalized diarrhea children are caused by rotavirus in our ward every year.67Rotaviruses infection u Onset of sudden fever,respiratory tract symptomsu Vomiting,watery or soft stool that lack gross blood or mucus u Severe dehydration than in
47、fection by other viral pathogensu Complications and fatalities are related almost exclusively to the adverse effects of dehydration,electrolyte imbalance,and acidosisu Malnutrition is a risk factor for severe consequencesu Disaccharides Intolerance Specific antigens in stool specimen recommended by
48、WHO.68Diagnosis.69Diarrhea?Watery,loose stools without or only a minute amount of WBC Epidemic dataStool cultureSerous assayStool cultureSerous assayShigella species EIEC Campylobacter jejuni Salmonella typhimurium Yersinia enterocoliticaVirus Diarrhea ETEC,EPECLots of WBC and RBC,mucus in stools Ac
49、ute stagePersisting or chronic diarrheaAntibiotic associate diarrheaInfective Non-infective Allergic state?Symptomatic diarrhea?Inappropriate feeding?food intolerance Lack of disaccharidase?Immunodeficience?Malnutrition?Malabsorption?etc.Persisting infection?Entamoeba histolytic Giardia lamblia Cryp
50、tosporidiumStaphylococcus Clostridium difficileCandida albicans.70Treatment.71Main lines of managementFeedingFluid therapyDrugs.72 1.Feeding during diarrhea Continue feeding the child Give as much as the child wantGive small frequent feedsEncourage anorexic child to eat.73 For breast-fedContinue bre
