INFANTILE

CHCUMS
DIARRHEA

DIVISION OF INFECTIOUS DISEASE AND

GASTROENTEROLOGY

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

worlds

children and the number one killer of children

under five in many developing countries.
2

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
3

Definition
In pediatrics, diarrhea is
defined as an increase in the

F luidity
Volume

of stools

Number
relative to the usual habits of
each individual
4

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

5

Why diarrhea is more

dangerous for children ?

Dehydration
Malnutrition

Mortality
6

Malnutrition and Child Mortality

If: Diarrhea + Malnutrition

The RISK of DEATH is 4 fold higher

than that of well nourished children

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
9

Etiology of Diarrhea

10

Etiology of Diarrhea
Infective

Non
infective

Viruses
Bacteria
Parasites
Fungi

Allergic
Symptomatic
Inappropriate feeding
Food intolerance
Climate
11

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)
12

Rotaviru
s

13

Bacterial Enteropathogens
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

14

Parasites Pathogens
Rare etiologic pathogen of diarrhea

Cryptosporidium parvum
Entamoeba histolytic
Giardia lamblia

15

Fungous Pathogens
Rare etiologic pathogen of diarrhea
Candida albicans
Aspergillus
Mucor

16

The most important infective

causes of acute diarrhea in
developing countries in children
are:
Rotavirus
Enterotoxigenic escherichia coli
Shigella
Campylobacter jejuni
Salmonella typhimurium
17

Etiology of Diarrhea
Infective

Non
infective

Viruses
Bacteria
Parasites
Fungi

Allergic
Symptomatic
Inappropriate feeding
lactose intolerance
Climate
18

Dietary Diarrhea
Inappropriate feeding:
Overfeeding
Indigestible diet
Sudden change of formula
Inappropriate feeding for a milk-fed
baby shifting into solid food
(too much, too early, too rapid)

19

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.
20

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.
21

Lack of
Lactose Intolerance
Disaccharidase

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
22

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

23

Pathophysiological
Mechanisms of
Diarrhea

24

Pathophysiological
Mechanisms of
Diarrhea
Virus Diarrhea- Rotavirus
Enterotoxigenic Enteritis
ETEC, Vibrio Cholerae
Entero-Invasive Organisms
Shigella Species, EIEC
Dietary Diarrhea
25

Pathogenesis of Virus Diarrhea

Rotavirus

Virus invades the absorptive enterocytes of villi but spares crypt cells
The viruses replicates and infected enterocytes are destroyed

26

Pathogenesis of Virus Diarrhea

Osmotic 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
27

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
Malabsorption of complex
carbohydrates, particularly
lactose
Other than degested into
monosaccharide, lactose be lysis
into organic acid, hyperosmosis

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

Watery stool

28

Pathophysiological
Mechanisms of
Diarrhea
Virus Diarrhea- Rotavirus
Enterotoxigenic enteritis
ETEC, Vibrio Cholerae
Entero-Invasive Organisms
Shigella Species, EIEC
Dietary diarrhea
29

Pathogenesis of
Enterotoxigenic Diarrhea

Pathogens:
Vibrio cholerae (cholera)
ETEC
Staphylococcus aureus
Clostridium difficile
30

Pathogenesis of Enterotoxigenic
Diarrhea (Secretory Diarrhea)
enterotoxigenic
organisms

Ingestion

small bowel
mucosa and
proliferate

Heat-stable enterotoxin

Heat-labile enterotoxin

binds to receptors of
epithelial cells
activates

activates

cellular guanylatecyclase

cellular adenylcyclase

increased intracellular
concentrations of cGMP

increased intracellular
concentrations of cAMP

promote the net secretion of water and chloride

decrease absorption of sodium and chloride by villous cells

Secretory diarrhea

31

Pathogenesis of Enterotoxigenic
Diarrhea (Secretory Diarrhea)
1 Enterotoxigenic
1Bacteria secrete
Enterotoxins

2 Toxin stimulates the

2production of C-AMP

Increased C-AMP
leads to :

--2

+++
4

33 - Inhibition of
absorption of Na and
Cl from the cells of
villi
44 - Stimulation of
secretion of Cl from
crypt cells

32

Pathogenesis of Enterotoxigenic
Diarrhea (Secretory Diarrhea)

The mucosa is not destroyed during this process

33

Pathogenesis of Enterotoxigenic
Diarrhea (Secretory Diarrhea)
An imbalance in the ratio of intestinal fluid absorption to
secretion, so watery stool may occur in clinical observation

34

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
35

Pathophysiological
Mechanisms of
Diarrhea
Virus Diarrhea- Rotavirus
Enterotoxigenic enteritis
ETEC, Vibrio Cholerae
Entero-Invasive Organisms
Shigella Species, EIEC
Dietary diarrhea
36

Invasive Diarrhea
The central event in pathogenesis is
invasion of colonic mucosa
Entero-Invasive Organisms:
Shigella species
EIEC (enteroinvasive E. coli)
Campylobacter jejuni
Salmonella typhimurium
Yersinia enterocolitica
37

Pathogenesis of Invasive Diarrhea

Ingestion
Invasive
enteropathogen

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

38

Pathogenesis of
Invasive Diarrhea

39

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
40

Pathophysiological
Mechanisms of
Diarrhea
Virus Diarrhea- Rotavirus
Enterotoxigenic enteritis
ETEC, Vibrio Cholerae
Entero-Invasive Organisms
Shigella Species, EIEC
Dietary diarrhea
41

Pathogenesis of Dietary Diarrhea

Inappropriate diet

Dyspepsia

Indigested food accumulate in the upper part of intestine

Acidity decreasing
Give the chance to the bacteria which
lived in lower part of bowel coming up
Indigested food ferment

and putrescence
Decomposed product amineslactic acidacetic acid
Hyperosmosis
Irritates the bowel
Promote the peristalsis
Water entering the lumen

Endogenous
infection
Aggravate the
intestinal
function
disturbance

Diarrhea
42

Morphology of Intestinal Mucosa

43

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

44

Defense Barriers of the Enterocytes

1

3
2

1. Physical barrier: mucus 2. Bacteriological (flora)

3. Immunological: Secretory IgA
45

Normal Flora

Breast-fed: A Gram-positive population: Bifidobacteria and Lactobacilli

Bottle-fed: A Gram-negative flora: Enterobacteriaceae

46

Clinical
Manifestations

47

Clinical manifestations

Gastrointestinal symptom

Systemic symptom

Dehydration and electrolyte

disturbances
48

Assessment of a child with dehydration &

electrolyte disturbances

49

Dehydration
Excessive loss of water, especially
loss of extracellular fluid.

50

51

52

53

Assessment of a Dehydration
Mild

Moderate

Severe

5%

5-10%

10-15%

50ml/Kg

50-100ml/Kg

100-120ml/Kg

Mental State
Fontanel
Tear
Bucal
Mucosa
Tissue
Turgor
Urine Flow

Normal

Restless, irritable

Prostration/Coma

Normal

Sunken

Deeply Sunken

Normal

Decrease

Absence

Moist

Dry

Very Dry

Normal

Absent

Absent

Decrease
Slightly

Decrease

Anuria

Shock

Absent

Absent

Present

Dehydration

54

Type of dehydration

Serum sodium
Skin color
Skin temperature
Skin turgor
Duration of vomiting
and diarrhea
Thirsty
Mucous membrane
NS syndroms
Disturbance of
peripheral circulation

Hypotonic
<280 mOsm/L

Isotonic
280~300 mOsm/L

hypertonic
>300 mOsm/L

<130mmol/L

130-150mmol/L

<150mmol/L

Pale
Cold
Absent

Pale
Cold
Normal

Flush
Normal

Very long

Long

Short

No

No

Yes

Moist

Moist

Dry

Lethargy

Normal

Irritable

Yes

No

No

55

Hypopotassaemia
serum potassium<3.5mmol/L

Etiology
1.

Excessive of loss

2.

Insufficient intake

3.

Distributional disturbance of extracelluar

and intracelluar potassium

56

()

Hypopotassaemia
serum potassium<3.5mmol/L

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

57

Hypocalcemia

serum calcium<1.88mmol/L

High nervous and muscular excitability

58

Metabolic Acidosis

1 etiology
(1) loss of alkaline substance from GI track
(2) acid substance accumulation in body

H+

H+
2 manifestations:
hyperpnoea increased heart rate serise
lip conscious disturbance for the severe cases
59

Classification of Diarrhea
based on

Severity
Duration
Etiology
60

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
61

Classification of Diarrhea
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
62

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

63

Rotaviruses Infection

64

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
65

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
66

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

67

Diagnosis

68

Diarrhea?

Infective

Persisting or
chronic diarrhea

Acute stage
Watery, loose stools
without or only a
minute amount of WBC
Epidemic data
Stool culture
Serous assay
Virus Diarrhea
ETEC,EPEC

Lots of WBC and RBC,

mucus in stools

Antibiotic
associate
diarrhea

Persisting
infection?

Stool culture
Serous assay
Shigella species
EIEC
Campylobacter jejuni
Salmonella typhimurium
Yersinia enterocolitica

Entamoeba
Staphylococcus
histolytic
Giardia lamblia Clostridium difficile
Cryptosporidium Candida albicans

Non-infective
Allergic state? Symptomatic diarrhea? Inappropriate feeding?
food intolerance Lack of disaccharidase? Immunodeficience?
Malnutrition? Malabsorption ? etc.

69

Treatment

70

Main lines of management

1. Feeding
2. Fluid therapy
3. Drugs

71

 1. Feeding during diarrhea

Continue feeding the child
Give as much as the child want
Give small frequent feeds
Encourage anorexic child to eat

72

 1. Feeding during diarrhea

For breast-fed
Continue breast
feeding as usual
during and after
diarrhea and
rehydration therapy.

73

 1. Feeding during diarrhea

For formula-fed

Low lactose of lactose-free formula only in case

of lactose intolerance children (rotavirus)
74

 1. Feeding during diarrhea

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

75

2. Fluid therapy

76

3. Drugs in the
management of
Diarrhea

77

Commonly used drugs in diarrhea

Antimicrobial agents
Antiparasitics
Probiotics: lactobacilli,
Bifidobacteria
Antidiarrheal agents:
adsorbants and mucous
membrane protectors: SMECTA

78

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
79

Functions of Normal Flora

Digestion
Production of vitamins
Stimulation of host immune
response Inhibition of pathogen
attachment
Production of pathogen inhibitory
substances
80

Fluid Therapy

81

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

82

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

83

Intravenous fluid therapy

Phase I: Treat shock
(0 - 30 minutes)

10-20ml/kg 0.9%
NaCl
Reasse
ss
Improv
ed

No
Change

Measure plasma electrolytes

Phase II: Initial Rehydration

( - 8 hours)

Calculate fluid deficit and maintenance

Initial replacement with saline-dextrose so

Half the calculated fluid deficit plus maint

Phase III: Continued Replacement

(8 - 24 hours)

Review plasma electrolytes and

fluid status

Replacement with saline-dextrose solution

Half the calculated fluid deficit plus maint

84

Intravenous fluid therapy

Complete correcting of the deficit

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
85

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

86

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

87

Potassium Replacement

100-300mg/kg.d
divided into 4 times a day
Concentration: 0.15-0.3%
Replacement should be maintained for
4-6days

88

Calcium, and Magnesium

replacement

Calcium: 10% alcium gluconate

10ml slow iv/gtt
Magnesium: 0.2ml/kg iv/gtt Bid-Tid

89

90

The following are causes of

secretory diarrhea:
Vibrio cholerae
Enteropathogenic escherichia coli
Rotavirus
Lactose intolerance
Shigella species

A.
B.
C.
D.
E.

91

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.
92