INFANTILE DIARRHEA

CHCUMS

DIVISION OF INFECTIOUS DISEASE AND GASTROENTEROLOGY

1

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

Fluidity
Volume Number
of stools

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

Allergic Viruses Symptomatic Bacteria Inappropriate feeding Parasites Food intolerance Climate Fungi
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

Rotavirus

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

Allergic Viruses Symptomatic Bacteria Inappropriate feeding Parasites lactose intolerance Climate Fungi
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 cellular guanylatecyclase increased intracellular concentrations of cGMP activates cellular adenylcyclase 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 1 Enterotoxigenic 1Bacteria secrete Enterotoxins 2 Toxin stimulates the 2production of C-AMP

--2 3 4

Increased C-AMP leads to :

+++

3 - Inhibition of 3 absorption of Na and Cl from the cells of villi 4 - Stimulation of 4 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) Low-grade fever occurs in some children Profuse, painless, watery diarrhea, sometimes with flecks of mucus but no blood Fluid and electrolyte losses, tachycardia, tachypnea, a sunken anterior fontanel, progress to circulatory collapse
35

2. 3. 4.

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 Stool examination: large amount of WBC, pus cell , and RBC

2.

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 and putrescence Decomposed product amineslactic acidacetic acid Hyperosmosis
Indigested food ferment

Endogenous infection Aggravate the intestinal function disturbance

Irritates the bowel Promote the peristalsis Water entering the lumen

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
Dehydration Mental State Fontanel Tear Bucal Mucosa Tissue Turgor Urine Flow Shock
5% 50ml/Kg Normal Normal Normal Moist

Moderate
5-10% 50-100ml/Kg Restless, irritable Sunken Decrease Dry

Severe
10-15% 100-120ml/Kg Prostration/Coma Deeply Sunken Absence Very Dry

Normal
Decrease Slightly Absent

Absent
Decrease Absent

Absent
Anuria Present
54

Type of dehydration
Hypotonic <280 mOsm/L
Serum sodium Skin color Skin temperature Skin turgor Duration of vomiting and diarrhea Thirsty Mucous membrane NS syndroms Disturbance of peripheral circulation

Isotonic 280~300 mOsm/L 130-150mmol/L Pale Cold Normal Long No Moist Normal

hypertonic >300 mOsm/L <150mmol/L Flush Normal Short Yes Dry Irritable

<130mmol/L Pale Cold Absent Very long No Moist Lethargy

Yes

No

No
55

Hypopotassaemia
serum potassium<3.5mmol/L

Etiology
1. 2. 3. Excessive of loss Insufficient intake Distributional disturbance of extracelluar and intracelluar potassium

56

Hypopotassaemia serum potassium<3.5mmol/L

Manifestations 1low nervous and muscular excitability nervous excitability downcast, lethargy muscular excitability weaknessbyporesalexia of tendon jerk, paralysis

()

GI smooth muscle excitability paralytic ileus

2cardiovascular 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+ 2 manifestations: hyperpnoeaincreased heart rateserise lip conscious disturbance for the severe cases
59
H+

Classification of Diarrhea based on

Severity Duration Etiology

60

1. Mild diarrhea:

Classification of 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

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

Diarrhea?
Persisting or chronic diarrhea Persisting infection? Lots of WBC and RBC, mucus in stools Stool culture Serous assay Shigella species EIEC Campylobacter jejuni Salmonella typhimurium Yersinia enterocolitica

Antibiotic associate diarrhea

Virus Diarrhea ETEC,EPEC

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 Reassess

Improved

No Change

Measure plasma electrolytes Calculate fluid deficit and maintenance

Phase II: Initial Rehydration ( - 8 hours)

Initial replacement with saline-dextrose solution Half the calculated fluid deficit plus maintenance

Review plasma electrolytes and fluid status

Phase III: Continued Replacement (8 - 24 hours)

Replacement with saline-dextrose solution Half the calculated fluid deficit plus maintenance

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: tonicHypertonic dehydration:1/3-1/5 tonic Duration of fluid therapy8-12 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/kg1/4-1/5 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:

A. Vibrio cholerae B. Enteropathogenic escherichia coli C. Rotavirus D. Lactose intolerance E. Shigella species
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