1
INFANTILE DIARRHEA
CHCUMS
DIVISION OF INFECTIOUS DISEASE AND
GASTROENTEROLOGY
DIARRHEA
2
Background
? Diarrhea is a clinical syndrome of diverse
etiology associated with many influencing
factors.
? It is the most frequent childhood disease
second only to the respiratory infection.
? The major cause of death among world’s
children and the number one killer of children
under five in many developing countries.
3
Disease Burden
Worldwide
? 3-5 billion episodes/year
? 4-5 million deaths/year
Children are the predominant populations.
? 3.2 billion episodes/year in <5y children
? 1.3 million deaths/year in <5y children
In China
? 836 million episodes of diarrhea every year
? 1/4-1/3 of all outdoor patients and a large amount
of hospitalizations of children are due to diarrhea
4
Fluidity
Volume
Number
In pediatrics,diarrhea is
defined as an increase in the
relative to the usual habits of
each individual
of stools
Definition
5
Normal Stool of Children
Breastfed babies,pass stools 3-4 times a day
yellow
loose (soft to runny) but textured
sweet-smelling
Bottlefed babies,once a day
pale yellow or yellowish-brown
bulkier and more formed
pretty pungent
Babies on solids,thicken and darken slightly
have a stronger odor
6
Dehydration
Malnutrition
Mortality
Why diarrhea is more
dangerous for children?
7
Malnutrition and Child Mortality
8
If,Diarrhea + Malnutrition
The RISK of DEATH is 4 fold higher
than that of well nourished children
9
Why children are highly
vulnerable to diarrhea?
Immature digestive system
More nutrition demand
Weakness of defense system
The normal intestinal flora
have not built up well
Bottle feeding
10
Etiology of Diarrhea
11
Etiology of Diarrhea
Infective Non infective
Viruses
Bacteria
Parasites
Fungi
Allergic
Symptomatic
Inappropriate feeding
Food intolerance
Climate
12
Viral Enteropathogens
Viral enteropathogens cause most illnesses
in pediatric population.
? Rotavirus (morn than 50% acute diarrhea)
? Astrovirus
? Norwalk virus
? Coronavirus
? Calicivirus
? Enteric adenovirus (serotypes 40 and 41)
13
Rotavirus
14
The most common cause of childhood diarrhea
second only to the viral enteropathogens
? Escherichia coli
EPEC; ETEC; EITC; EHEC; EAEC
? Campylobacter jejuni
? Shigella species
? Salmonella typhimurium
? Yersinia enterocolitica
? Staphylococcus aureus
? Clostridium difficile
? Vibrio cholerae
Bacterial Enteropathogens
15
Rare etiologic pathogen of diarrhea
? Cryptosporidium parvum
? Entamoeba histolytic
? Giardia lamblia
Parasites Pathogens
16
Rare etiologic pathogen of diarrhea
? Candida albicans
? Aspergillus
? Mucor
Fungous Pathogens
17
The most important infective
causes of acute diarrhea in
developing countries in children
are:
? Rotavirus
? Enterotoxigenic escherichia coli
? Shigella
? Campylobacter jejuni
? Salmonella typhimurium
18
Etiology of Diarrhea
Infective Non infective
Viruses
Bacteria
Parasites
Fungi
Allergic
Symptomatic
Inappropriate feeding
lactose intolerance
Climate
19
? Overfeeding
? Indigestible diet
? Sudden change of formula
? Inappropriate feeding for a milk-fed
baby shifting into solid food
(too much,too early,too rapid…)
? Dietary Diarrhea
Inappropriate feeding:
20
? Allergic Diarrhea
Primary food hypersensitivity,3 months after birth
Second food hypersensitivity:
Infection→ injury and hyperpermeability of intestinal
mucosa → large molecular protein entering
bloodstream → allergic state
Cow's milk protein
Soy bean protein
Egg white
peanuts,meat,and fish etc,
21
? Symptomatic Diarrhea
Diarrhea is only one of the symptoms of primary
disease,Problem is not originally located in
intestinal tract.
?Respiratory tract infection
?Otitis media
?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,
22
? Lack of
DisaccharidaseLactoseIntolerance
Primary Disaccharidase Deficiency is a rare
disease (congenital 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
23
? Climate
Seasonal variation affects the digestive function
of small children, incidence of diarrhea is highest
during the early raniny season
Cold weather causes increasing of enterokinesia
Hot weather causes decreasing of digestive
enzyme and malfunction of digestive tract……
24
Pathophysiological
Mechanisms of Diarrhea
25
Virus Diarrhea- Rotavirus
Enterotoxigenic Enteritis –
ETEC,Vibrio Cholerae
Entero-Invasive Organisms –
Shigella Species,EIEC
Dietary Diarrhea
Pathophysiological
Mechanisms of Diarrhea
26
Pathogenesis of Virus Diarrhea
Virus invades the absorptive enterocytes of villi but spares crypt cells
The viruses replicates and infected enterocytes are destroyed
Rotavirus
27
Pathogenesis of Virus Diarrhea
1- Infected absorptive
enterocytes are killed
causing patchy epithelial cell
destruction and villous
shortening
2- Destroyed absorptive
cells are rapidly replaced by
cells that migrate from the
crypts.
Villi become covered with
immature non-absorptive
secretory cells having:
- no brush border
- no brush border enzymes
Osmotic Diarrhea
28
Pathogenesis 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 inflammatory infiltrate in the lamina propria
Impairment of digestive functions
discreasing hydrolysis of
disaccharides
Impairment of absorptive functions
the transport of water and
electrolytes via glucose and amino
acid co-transporters
An imbalance in the ratio of intestinal
fluid absorption to secretion
Malabsorption of complex
carbohydrates,particularly
lactose
Other 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 diarrhea
Pathophysiological
Mechanisms of Diarrhea
30
Pathogenesis of
Enterotoxigenic Diarrhea
Pathogens:
?Vibrio cholerae (cholera)
?ETEC
?Staphylococcus aureus
?Clostridium difficile
31
enterotoxigenic
organisms
Ingestion small bowel
mucosa and
proliferate
activates
cellular guanylatecyclase
Heat-stable enterotoxin
promote 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
Secretory diarrhea
Pathogenesis of Enterotoxigenic
Diarrhea (Secretory Diarrhea)
32
Pathogenesis of Enterotoxigenic
Diarrhea (Secretory Diarrhea)
1- Enterotoxigenic
Bacteria secrete
Enterotoxins
2- Toxin stimulates the
production of C-AMP
Increased C-AMP
leads to,
3 - Inhibition of
absorption of Na and
Cl from the cells of
villi
4 - Stimulation of
secretion of Cl from
crypt cells
+++---
1
2 3 4
1
3
4
33
Pathogenesis of Enterotoxigenic
Diarrhea (Secretory Diarrhea)
The mucosa is not destroyed during this process
34
An imbalance in the ratio of intestinal fluid absorption to
secretion,so watery stool may occur in clinical observation
Pathogenesis of Enterotoxigenic
Diarrhea (Secretory Diarrhea)
35
Enterotoxigenic Diarrhea
Clinical finding:
1,Watery diarrhea and vomiting develop after an
incubation period of 6 hr- 5 days(2-3days,
average)
2,Low-grade fever occurs in some children
3,Profuse,painless,watery diarrhea,sometimes
with flecks of mucus but no blood
4,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 diarrhea
Pathophysiological
Mechanisms of Diarrhea
37
Invasive Diarrhea
Entero-Invasive Organisms:
? Shigella species
? EIEC (enteroinvasive E,coli)
? Campylobacter jejuni
? Salmonella typhimurium
? Yersinia enterocolitica
The central event in pathogenesis is
invasion of colonic mucosa
38
Pathogenesis of Invasive Diarrhea
Invasive
enteropathogen
Ingestion Gut lumen
Colon and rectum
mucous membrane proper
Extensive destruction of the epithelial layer
Inflammation,Hyperemia,swelling,heavy neutrophil
infiltration,inflammatory exudate
The desquamation,ulceration,and formation of microabscesses
in the colonic mucosa inhibit absorption of water
stools that are frequent and scanty and that contain blood
inflammatory cells and mucus
39
Pathogenesis of
Invasive Diarrhea
40
Invasive Diarrhea
Clinical finding:
1,Stools that are frequent and scanty and
that contain blood inflammatory cells,and
mucus
2,Stool examination,large amount of WBC,
pus cell,and RBC
3,Dehydration 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 diarrhea
Pathophysiological
Mechanisms of Diarrhea
42
Pathogenesis of Dietary Diarrhea
Inappropriate diet
Irritates the bowel
Promote the peristalsis
Water entering the lumen
Decomposed product amineslactic acidacetic acid
Acidity decreasing
Give the chance to the bacteria which
lived in lower part of bowel coming up Endogenous infection
Aggravate the
intestinal
function
disturbance
Indigested food accumulate in the upper part of intestine
Dyspepsia
Indigested food ferment and putrescence
Hyperosmosis
Diarrhea
43
Morphology of Intestinal Mucosa
44
Morphology of Intestinal Mucosa
Villi
covered mainly (90%)
by tall columnar
absorptive cells
(Enterocytes) having
a micrevillar brush
border
Crypts of lieberkuhn
Covered mainly by
short columnar
secretory cells
Goblet cells
without brush border
45
Defense Barriers of the Enterocytes
1,Physical barrier,mucus 2,Bacteriological (flora)
3,Immunological,Secretory IgA
1 2
3
46
Normal Flora
Breast-fed,A Gram-positive population,Bifidobacteria and Lactobacilli
Bottle-fed,A Gram-negative flora,Enterobacteriaceae
47
Clinical
Manifestations
48
Clinical manifestations
? Gastrointestinal symptom
? Systemic symptom
? Dehydration and electrolyte
disturbances
49
Assessment of a child with dehydration &
electrolyte disturbances
50
Dehydration
Excessive loss of water,especially
loss of extracellular fluid,
51
52
53
54
Assessment of a Dehydration
Mild Moderate Severe
Dehydration 5% 5-10% 10-15%
50ml/Kg 50-100ml/Kg 100-120ml/Kg
Mental State Normal Restless,irritable Prostration/Coma
Fontanel Normal Sunken Deeply Sunken
Tear Normal Decrease Absence
Bucal
Mucosa
Moist Dry Very Dry
Tissue
Turgor
Normal Absent Absent
Urine Flow Decrease
Slightly
Decrease Anuria
Shock Absent Absent Present
55
Type of dehydration
Hypotonic
<280 mOsm/L
Isotonic
280~300 mOsm/L
hypertonic
>300 mOsm/L
Serum sodium <130mmol/L 130-150mmol/L <150mmol/L
Skin color
Skin temperature
Skin turgor
Pale
Cold
Absent
Pale
Cold
Normal
Flush
-
Normal
Duration of vomiting
and diarrhea
Very long Long Short
Thirsty No No Yes
Mucous membrane Moist Moist Dry
NS syndroms Lethargy Normal Irritable
Disturbance of
peripheral circulation
Yes No No
56
serum potassium<3.5mmol/L
Etiology
1,Excessive of loss
2,Insufficient intake
3,Distributional disturbance of extracelluar
and intracelluar potassium
Hypopotassaemia
57
(二 ) 低钾血症
Manifestations
（ 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 abnormality
Hypopotassaemia
serum potassium<3.5mmol/L
58
serum calcium<1.88mmol/L
High nervous and muscular excitability
Hypocalcemia
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 disturbance for the severe cases
H+
产生 ↑
Metabolic Acidosis
60
Classification of Diarrhea
based on ……
Severity
Duration
Etiology
61
Classification of Diarrhea
1,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 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 accompany with vomiting
and fever,dehydration and electrolyte disturbance
62
Acute stage,the course of the
diseases less than 2 weeks
Persisting type,the course of
disease more than 2 weeks but
less than 2 months
Chronic stage,the
course of disease more than 2
months
Classification of Diarrhea
63
Persisting 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 retardation
Mortality is high
Troublesome to be controlled,
Adequate calories
Reestablish the normal flora
64
Rotaviruses Infection
65
Rotaviruses infection
History:
First recognized in humans in 1973 by
Australian Scientist Bishop,with a hubbed
wheel appearance under electronmicroscope,
giving their name
Virology:
Double-stranded RNA virus
VP6,A-G group,group A is the most important
group in childhood infection
66
Rotaviruses infection
Peak season:
Deep fall and winter(October-February）
Causing sharply increasing of outdoor patients in autumn
and winter,also named autumn diarrhea
Peak age:
6m-2y,rarely happen in children above 4y
Disease burden:
80% infectious diarrhea in pediatric clinic in autumn and
winter
About 1/4 to 1/3 (more than 800 cases) hospitalized diarrhea
children are caused by rotavirus in our ward every year
67
Rotaviruses infection
Clinical manifestations:
? Onset of sudden fever,respiratory tract symptoms
? Vomiting,watery or soft stool that lack gross blood or
mucus
? Severe dehydration than infection by other viral
pathogens
? Complications and fatalities are related almost exclusively
to the adverse effects of dehydration,electrolyte imbalance,
and acidosis
? Malnutrition is a risk factor for severe consequences
? Disaccharides Intolerance
Laboratory findings:
Specific antigens in stool specimen recommended by WHO
68
Diagnosis
69
Diarrhea?
Watery,loose stools
without or only a minute
amount of WBC
Epidemic data
Stool culture
Serous assay
Stool culture
Serous assay
Shigella species
EIEC
Campylobacter jejuni
Salmonella typhimurium
Yersinia enterocolitica
Virus Diarrhea
ETEC,EPEC
Lots of WBC and RBC,
mucus in stools
Acute stage Persisting or chronic diarrhea
Antibiotic
associate
diarrhea
Infective
Non-infective
Allergic state? Symptomatic diarrhea? Inappropriate feeding?
food intolerance Lack of disaccharidase? Immunodeficience?
Malnutrition? Malabsorption? etc.
Persisting
infection?
Entamoeba
histolytic
Giardia lamblia
Cryptosporidium
Staphylococcus
Clostridium difficile
Candida albicans
70
Treatment
71
Main lines of management
1,Feeding
2,Fluid therapy
3,Drugs
72
1,Feeding during diarrhea
Continue feeding the child
Give as much as the child want
Give small frequent feeds
Encourage anorexic child to eat
73
For breast-fed
Continue breast
feeding as usual
during and after
diarrhea and
rehydration therapy.
1,Feeding during diarrhea
74
For formula-fed
Low lactose of lactose-free formula only in case
of lactose intolerance children (rotavirus)
1,Feeding during diarrhea
75
Children on Mixed Diet
? Continue normal feeding as usual
? Give repeated small frequent feeds
? Avoid too sweetened or oily foods
? Avoid foods containing a high fiber content
1,Feeding during diarrhea
76
2,Fluid therapy
77
3,Drugs in the
management of
Diarrhea
78
Commonly used drugs in diarrhea
?Antimicrobial agents
?Antiparasitics
? Probiotics,lactobacilli,
Bifidobacteria
?Antidiarrheal agents,
adsorbants and mucous
membrane protectors,SMECTA
79
?Antimicrobial agents
1,Antimicrobial agents are not recommended
for viral diarrhea
2,invasive pathogen and toxic pathogen
infection should choose effective
antimicrobial agents
3,antibiotics should be stopped or changed
for the antibiotic associate diarrhea
80
Functions of Normal Flora
Digestion
Production of vitamins
Stimulation of host immune
response Inhibition of pathogen
attachment
Production of pathogen inhibitory
substances
81
Fluid Therapy
82
ORS Therapy in mild to
moderate dehydration
? ORS is the preferred treatment for fluid and
electrolyte losses caused by diarrhoea in
children who have mild to moderate
dehydration
? 50-100ml/kg ORS to be given over a 4-hour
period
? WHO recommended ORS High sodium content
90mmol/l
83
Intravenous fluid therapy
Severely dehydrated or who are in a state of shock
must receive immediate and aggressive intravenous
fluid therapy
Complete correcting of the deficit
Replacing ongoing loss of water and
electrolytes
Supply the physiological maintenance
84
Phase I,Treat shock
(0 - 30 minutes)
Phase II,Initial Rehydration
(? - 8 hours)
Phase III,Continued Replacement
(8 - 24 hours)
10-20ml/kg 0.9% NaCl
Reassess
Improved No Change
Measure plasma electrolytes
Calculate fluid deficit and maintenance
Review plasma electrolytes and fluid status
Initial replacement with saline-dextrose solution
Half the calculated fluid deficit plus maintenance
Replacement with saline-dextrose solution
Half the calculated fluid deficit plus maintenance
Intravenous fluid therapy
85
Intravenous fluid therapy
Mild:50ml/kg
Moderate,50ml-100ml/kg
Severe:100ml-120ml/kg
Hypotonic,2/3 tonic
Isotonic dehydration,? tonic； Hypertonic
dehydration:1/3-1/5 tonic
Duration of fluid therapy,8-12 hours
Shock and severe dehydration,20ml/kg/30min-1hour
at the beginning
Hypertonic dehydration,replace total fluid deficit plus
maintenance slowly over 48-72 hours
Complete correcting of the deficit
86
Intravenous fluid therapy
Replacing ongoing loss of water and electrolytes
10ml-40ml/kg,1/3-1/2 tonic
?Supply the physiological maintenance
70ml-90ml/kg,1/4-1/5 tonic
Complete within 12-16 hours for the two parts
87
Treatment of metabolic
acidosis
For full correction of acidosis,NaHCO3 required
(mmol)= Base deficit x body weight x 0.3
In most cases,metabolic acidosis is self-corrected
once dehydration corrected and hence effective
circulation volume restored
In rare situation,half of the calculated required
NaHCO3 may be given,watch out for Na overload and
pulmonary oedema
88
Potassium Replacement
钾盐的补充应在排尿后给钾
100-300mg/kg.d
divided into 4 times a day
Concentration,0.15-0.3%
Replacement should be maintained for
4-6days
89
Calcium,and Magnesium
replacement
Calcium,10% alcium gluconate
10ml slow iv/gtt
Magnesium,0.2ml/kg iv/gtt Bid-Tid
90
91
The following are causes of
secretory diarrhea:
A,Vibrio cholerae
B,Enteropathogenic escherichia coli
C,Rotavirus
D,Lactose intolerance
E,Shigella species
92
Case history
A 2-year-old gril presents with a history of passing
10-15 water stools and has vomited at least four
times in the last 24 hours,She appears
distressed but otherwise cooperative and drinks
thirstily from a glass of fruit juice but then vomits,
The nurse informs you that her pulse is 96
beats/minute,temperature 37.9 and blood
pressure 100/60mmHg,
Please discuss the management of this child.
INFANTILE DIARRHEA
CHCUMS
DIVISION OF INFECTIOUS DISEASE AND
GASTROENTEROLOGY
DIARRHEA
2
Background
? Diarrhea is a clinical syndrome of diverse
etiology associated with many influencing
factors.
? It is the most frequent childhood disease
second only to the respiratory infection.
? The major cause of death among world’s
children and the number one killer of children
under five in many developing countries.
3
Disease Burden
Worldwide
? 3-5 billion episodes/year
? 4-5 million deaths/year
Children are the predominant populations.
? 3.2 billion episodes/year in <5y children
? 1.3 million deaths/year in <5y children
In China
? 836 million episodes of diarrhea every year
? 1/4-1/3 of all outdoor patients and a large amount
of hospitalizations of children are due to diarrhea
4
Fluidity
Volume
Number
In pediatrics,diarrhea is
defined as an increase in the
relative to the usual habits of
each individual
of stools
Definition
5
Normal Stool of Children
Breastfed babies,pass stools 3-4 times a day
yellow
loose (soft to runny) but textured
sweet-smelling
Bottlefed babies,once a day
pale yellow or yellowish-brown
bulkier and more formed
pretty pungent
Babies on solids,thicken and darken slightly
have a stronger odor
6
Dehydration
Malnutrition
Mortality
Why diarrhea is more
dangerous for children?
7
Malnutrition and Child Mortality
8
If,Diarrhea + Malnutrition
The RISK of DEATH is 4 fold higher
than that of well nourished children
9
Why children are highly
vulnerable to diarrhea?
Immature digestive system
More nutrition demand
Weakness of defense system
The normal intestinal flora
have not built up well
Bottle feeding
10
Etiology of Diarrhea
11
Etiology of Diarrhea
Infective Non infective
Viruses
Bacteria
Parasites
Fungi
Allergic
Symptomatic
Inappropriate feeding
Food intolerance
Climate
12
Viral Enteropathogens
Viral enteropathogens cause most illnesses
in pediatric population.
? Rotavirus (morn than 50% acute diarrhea)
? Astrovirus
? Norwalk virus
? Coronavirus
? Calicivirus
? Enteric adenovirus (serotypes 40 and 41)
13
Rotavirus
14
The most common cause of childhood diarrhea
second only to the viral enteropathogens
? Escherichia coli
EPEC; ETEC; EITC; EHEC; EAEC
? Campylobacter jejuni
? Shigella species
? Salmonella typhimurium
? Yersinia enterocolitica
? Staphylococcus aureus
? Clostridium difficile
? Vibrio cholerae
Bacterial Enteropathogens
15
Rare etiologic pathogen of diarrhea
? Cryptosporidium parvum
? Entamoeba histolytic
? Giardia lamblia
Parasites Pathogens
16
Rare etiologic pathogen of diarrhea
? Candida albicans
? Aspergillus
? Mucor
Fungous Pathogens
17
The most important infective
causes of acute diarrhea in
developing countries in children
are:
? Rotavirus
? Enterotoxigenic escherichia coli
? Shigella
? Campylobacter jejuni
? Salmonella typhimurium
18
Etiology of Diarrhea
Infective Non infective
Viruses
Bacteria
Parasites
Fungi
Allergic
Symptomatic
Inappropriate feeding
lactose intolerance
Climate
19
? Overfeeding
? Indigestible diet
? Sudden change of formula
? Inappropriate feeding for a milk-fed
baby shifting into solid food
(too much,too early,too rapid…)
? Dietary Diarrhea
Inappropriate feeding:
20
? Allergic Diarrhea
Primary food hypersensitivity,3 months after birth
Second food hypersensitivity:
Infection→ injury and hyperpermeability of intestinal
mucosa → large molecular protein entering
bloodstream → allergic state
Cow's milk protein
Soy bean protein
Egg white
peanuts,meat,and fish etc,
21
? Symptomatic Diarrhea
Diarrhea is only one of the symptoms of primary
disease,Problem is not originally located in
intestinal tract.
?Respiratory tract infection
?Otitis media
?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,
22
? Lack of
DisaccharidaseLactoseIntolerance
Primary Disaccharidase Deficiency is a rare
disease (congenital 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
23
? Climate
Seasonal variation affects the digestive function
of small children, incidence of diarrhea is highest
during the early raniny season
Cold weather causes increasing of enterokinesia
Hot weather causes decreasing of digestive
enzyme and malfunction of digestive tract……
24
Pathophysiological
Mechanisms of Diarrhea
25
Virus Diarrhea- Rotavirus
Enterotoxigenic Enteritis –
ETEC,Vibrio Cholerae
Entero-Invasive Organisms –
Shigella Species,EIEC
Dietary Diarrhea
Pathophysiological
Mechanisms of Diarrhea
26
Pathogenesis of Virus Diarrhea
Virus invades the absorptive enterocytes of villi but spares crypt cells
The viruses replicates and infected enterocytes are destroyed
Rotavirus
27
Pathogenesis of Virus Diarrhea
1- Infected absorptive
enterocytes are killed
causing patchy epithelial cell
destruction and villous
shortening
2- Destroyed absorptive
cells are rapidly replaced by
cells that migrate from the
crypts.
Villi become covered with
immature non-absorptive
secretory cells having:
- no brush border
- no brush border enzymes
Osmotic Diarrhea
28
Pathogenesis 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 inflammatory infiltrate in the lamina propria
Impairment of digestive functions
discreasing hydrolysis of
disaccharides
Impairment of absorptive functions
the transport of water and
electrolytes via glucose and amino
acid co-transporters
An imbalance in the ratio of intestinal
fluid absorption to secretion
Malabsorption of complex
carbohydrates,particularly
lactose
Other 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 diarrhea
Pathophysiological
Mechanisms of Diarrhea
30
Pathogenesis of
Enterotoxigenic Diarrhea
Pathogens:
?Vibrio cholerae (cholera)
?ETEC
?Staphylococcus aureus
?Clostridium difficile
31
enterotoxigenic
organisms
Ingestion small bowel
mucosa and
proliferate
activates
cellular guanylatecyclase
Heat-stable enterotoxin
promote 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
Secretory diarrhea
Pathogenesis of Enterotoxigenic
Diarrhea (Secretory Diarrhea)
32
Pathogenesis of Enterotoxigenic
Diarrhea (Secretory Diarrhea)
1- Enterotoxigenic
Bacteria secrete
Enterotoxins
2- Toxin stimulates the
production of C-AMP
Increased C-AMP
leads to,
3 - Inhibition of
absorption of Na and
Cl from the cells of
villi
4 - Stimulation of
secretion of Cl from
crypt cells
+++---
1
2 3 4
1
3
4
33
Pathogenesis of Enterotoxigenic
Diarrhea (Secretory Diarrhea)
The mucosa is not destroyed during this process
34
An imbalance in the ratio of intestinal fluid absorption to
secretion,so watery stool may occur in clinical observation
Pathogenesis of Enterotoxigenic
Diarrhea (Secretory Diarrhea)
35
Enterotoxigenic Diarrhea
Clinical finding:
1,Watery diarrhea and vomiting develop after an
incubation period of 6 hr- 5 days(2-3days,
average)
2,Low-grade fever occurs in some children
3,Profuse,painless,watery diarrhea,sometimes
with flecks of mucus but no blood
4,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 diarrhea
Pathophysiological
Mechanisms of Diarrhea
37
Invasive Diarrhea
Entero-Invasive Organisms:
? Shigella species
? EIEC (enteroinvasive E,coli)
? Campylobacter jejuni
? Salmonella typhimurium
? Yersinia enterocolitica
The central event in pathogenesis is
invasion of colonic mucosa
38
Pathogenesis of Invasive Diarrhea
Invasive
enteropathogen
Ingestion Gut lumen
Colon and rectum
mucous membrane proper
Extensive destruction of the epithelial layer
Inflammation,Hyperemia,swelling,heavy neutrophil
infiltration,inflammatory exudate
The desquamation,ulceration,and formation of microabscesses
in the colonic mucosa inhibit absorption of water
stools that are frequent and scanty and that contain blood
inflammatory cells and mucus
39
Pathogenesis of
Invasive Diarrhea
40
Invasive Diarrhea
Clinical finding:
1,Stools that are frequent and scanty and
that contain blood inflammatory cells,and
mucus
2,Stool examination,large amount of WBC,
pus cell,and RBC
3,Dehydration 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 diarrhea
Pathophysiological
Mechanisms of Diarrhea
42
Pathogenesis of Dietary Diarrhea
Inappropriate diet
Irritates the bowel
Promote the peristalsis
Water entering the lumen
Decomposed product amineslactic acidacetic acid
Acidity decreasing
Give the chance to the bacteria which
lived in lower part of bowel coming up Endogenous infection
Aggravate the
intestinal
function
disturbance
Indigested food accumulate in the upper part of intestine
Dyspepsia
Indigested food ferment and putrescence
Hyperosmosis
Diarrhea
43
Morphology of Intestinal Mucosa
44
Morphology of Intestinal Mucosa
Villi
covered mainly (90%)
by tall columnar
absorptive cells
(Enterocytes) having
a micrevillar brush
border
Crypts of lieberkuhn
Covered mainly by
short columnar
secretory cells
Goblet cells
without brush border
45
Defense Barriers of the Enterocytes
1,Physical barrier,mucus 2,Bacteriological (flora)
3,Immunological,Secretory IgA
1 2
3
46
Normal Flora
Breast-fed,A Gram-positive population,Bifidobacteria and Lactobacilli
Bottle-fed,A Gram-negative flora,Enterobacteriaceae
47
Clinical
Manifestations
48
Clinical manifestations
? Gastrointestinal symptom
? Systemic symptom
? Dehydration and electrolyte
disturbances
49
Assessment of a child with dehydration &
electrolyte disturbances
50
Dehydration
Excessive loss of water,especially
loss of extracellular fluid,
51
52
53
54
Assessment of a Dehydration
Mild Moderate Severe
Dehydration 5% 5-10% 10-15%
50ml/Kg 50-100ml/Kg 100-120ml/Kg
Mental State Normal Restless,irritable Prostration/Coma
Fontanel Normal Sunken Deeply Sunken
Tear Normal Decrease Absence
Bucal
Mucosa
Moist Dry Very Dry
Tissue
Turgor
Normal Absent Absent
Urine Flow Decrease
Slightly
Decrease Anuria
Shock Absent Absent Present
55
Type of dehydration
Hypotonic
<280 mOsm/L
Isotonic
280~300 mOsm/L
hypertonic
>300 mOsm/L
Serum sodium <130mmol/L 130-150mmol/L <150mmol/L
Skin color
Skin temperature
Skin turgor
Pale
Cold
Absent
Pale
Cold
Normal
Flush
-
Normal
Duration of vomiting
and diarrhea
Very long Long Short
Thirsty No No Yes
Mucous membrane Moist Moist Dry
NS syndroms Lethargy Normal Irritable
Disturbance of
peripheral circulation
Yes No No
56
serum potassium<3.5mmol/L
Etiology
1,Excessive of loss
2,Insufficient intake
3,Distributional disturbance of extracelluar
and intracelluar potassium
Hypopotassaemia
57
(二 ) 低钾血症
Manifestations
（ 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 abnormality
Hypopotassaemia
serum potassium<3.5mmol/L
58
serum calcium<1.88mmol/L
High nervous and muscular excitability
Hypocalcemia
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 disturbance for the severe cases
H+
产生 ↑
Metabolic Acidosis
60
Classification of Diarrhea
based on ……
Severity
Duration
Etiology
61
Classification of Diarrhea
1,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 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 accompany with vomiting
and fever,dehydration and electrolyte disturbance
62
Acute stage,the course of the
diseases less than 2 weeks
Persisting type,the course of
disease more than 2 weeks but
less than 2 months
Chronic stage,the
course of disease more than 2
months
Classification of Diarrhea
63
Persisting 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 retardation
Mortality is high
Troublesome to be controlled,
Adequate calories
Reestablish the normal flora
64
Rotaviruses Infection
65
Rotaviruses infection
History:
First recognized in humans in 1973 by
Australian Scientist Bishop,with a hubbed
wheel appearance under electronmicroscope,
giving their name
Virology:
Double-stranded RNA virus
VP6,A-G group,group A is the most important
group in childhood infection
66
Rotaviruses infection
Peak season:
Deep fall and winter(October-February）
Causing sharply increasing of outdoor patients in autumn
and winter,also named autumn diarrhea
Peak age:
6m-2y,rarely happen in children above 4y
Disease burden:
80% infectious diarrhea in pediatric clinic in autumn and
winter
About 1/4 to 1/3 (more than 800 cases) hospitalized diarrhea
children are caused by rotavirus in our ward every year
67
Rotaviruses infection
Clinical manifestations:
? Onset of sudden fever,respiratory tract symptoms
? Vomiting,watery or soft stool that lack gross blood or
mucus
? Severe dehydration than infection by other viral
pathogens
? Complications and fatalities are related almost exclusively
to the adverse effects of dehydration,electrolyte imbalance,
and acidosis
? Malnutrition is a risk factor for severe consequences
? Disaccharides Intolerance
Laboratory findings:
Specific antigens in stool specimen recommended by WHO
68
Diagnosis
69
Diarrhea?
Watery,loose stools
without or only a minute
amount of WBC
Epidemic data
Stool culture
Serous assay
Stool culture
Serous assay
Shigella species
EIEC
Campylobacter jejuni
Salmonella typhimurium
Yersinia enterocolitica
Virus Diarrhea
ETEC,EPEC
Lots of WBC and RBC,
mucus in stools
Acute stage Persisting or chronic diarrhea
Antibiotic
associate
diarrhea
Infective
Non-infective
Allergic state? Symptomatic diarrhea? Inappropriate feeding?
food intolerance Lack of disaccharidase? Immunodeficience?
Malnutrition? Malabsorption? etc.
Persisting
infection?
Entamoeba
histolytic
Giardia lamblia
Cryptosporidium
Staphylococcus
Clostridium difficile
Candida albicans
70
Treatment
71
Main lines of management
1,Feeding
2,Fluid therapy
3,Drugs
72
1,Feeding during diarrhea
Continue feeding the child
Give as much as the child want
Give small frequent feeds
Encourage anorexic child to eat
73
For breast-fed
Continue breast
feeding as usual
during and after
diarrhea and
rehydration therapy.
1,Feeding during diarrhea
74
For formula-fed
Low lactose of lactose-free formula only in case
of lactose intolerance children (rotavirus)
1,Feeding during diarrhea
75
Children on Mixed Diet
? Continue normal feeding as usual
? Give repeated small frequent feeds
? Avoid too sweetened or oily foods
? Avoid foods containing a high fiber content
1,Feeding during diarrhea
76
2,Fluid therapy
77
3,Drugs in the
management of
Diarrhea
78
Commonly used drugs in diarrhea
?Antimicrobial agents
?Antiparasitics
? Probiotics,lactobacilli,
Bifidobacteria
?Antidiarrheal agents,
adsorbants and mucous
membrane protectors,SMECTA
79
?Antimicrobial agents
1,Antimicrobial agents are not recommended
for viral diarrhea
2,invasive pathogen and toxic pathogen
infection should choose effective
antimicrobial agents
3,antibiotics should be stopped or changed
for the antibiotic associate diarrhea
80
Functions of Normal Flora
Digestion
Production of vitamins
Stimulation of host immune
response Inhibition of pathogen
attachment
Production of pathogen inhibitory
substances
81
Fluid Therapy
82
ORS Therapy in mild to
moderate dehydration
? ORS is the preferred treatment for fluid and
electrolyte losses caused by diarrhoea in
children who have mild to moderate
dehydration
? 50-100ml/kg ORS to be given over a 4-hour
period
? WHO recommended ORS High sodium content
90mmol/l
83
Intravenous fluid therapy
Severely dehydrated or who are in a state of shock
must receive immediate and aggressive intravenous
fluid therapy
Complete correcting of the deficit
Replacing ongoing loss of water and
electrolytes
Supply the physiological maintenance
84
Phase I,Treat shock
(0 - 30 minutes)
Phase II,Initial Rehydration
(? - 8 hours)
Phase III,Continued Replacement
(8 - 24 hours)
10-20ml/kg 0.9% NaCl
Reassess
Improved No Change
Measure plasma electrolytes
Calculate fluid deficit and maintenance
Review plasma electrolytes and fluid status
Initial replacement with saline-dextrose solution
Half the calculated fluid deficit plus maintenance
Replacement with saline-dextrose solution
Half the calculated fluid deficit plus maintenance
Intravenous fluid therapy
85
Intravenous fluid therapy
Mild:50ml/kg
Moderate,50ml-100ml/kg
Severe:100ml-120ml/kg
Hypotonic,2/3 tonic
Isotonic dehydration,? tonic； Hypertonic
dehydration:1/3-1/5 tonic
Duration of fluid therapy,8-12 hours
Shock and severe dehydration,20ml/kg/30min-1hour
at the beginning
Hypertonic dehydration,replace total fluid deficit plus
maintenance slowly over 48-72 hours
Complete correcting of the deficit
86
Intravenous fluid therapy
Replacing ongoing loss of water and electrolytes
10ml-40ml/kg,1/3-1/2 tonic
?Supply the physiological maintenance
70ml-90ml/kg,1/4-1/5 tonic
Complete within 12-16 hours for the two parts
87
Treatment of metabolic
acidosis
For full correction of acidosis,NaHCO3 required
(mmol)= Base deficit x body weight x 0.3
In most cases,metabolic acidosis is self-corrected
once dehydration corrected and hence effective
circulation volume restored
In rare situation,half of the calculated required
NaHCO3 may be given,watch out for Na overload and
pulmonary oedema
88
Potassium Replacement
钾盐的补充应在排尿后给钾
100-300mg/kg.d
divided into 4 times a day
Concentration,0.15-0.3%
Replacement should be maintained for
4-6days
89
Calcium,and Magnesium
replacement
Calcium,10% alcium gluconate
10ml slow iv/gtt
Magnesium,0.2ml/kg iv/gtt Bid-Tid
90
91
The following are causes of
secretory diarrhea:
A,Vibrio cholerae
B,Enteropathogenic escherichia coli
C,Rotavirus
D,Lactose intolerance
E,Shigella species
92
Case history
A 2-year-old gril presents with a history of passing
10-15 water stools and has vomited at least four
times in the last 24 hours,She appears
distressed but otherwise cooperative and drinks
thirstily from a glass of fruit juice but then vomits,
The nurse informs you that her pulse is 96
beats/minute,temperature 37.9 and blood
pressure 100/60mmHg,
Please discuss the management of this child.
