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Topic
Protein Energy Malnutrition (PEM)
Growth and Development: 0-2 years
Some Paediatric behaviour problems
Delivery room management of Newborn
Neonatal resuscitation
FEVER
Fever of Uncertain Origin (FUO)
Floppy infant syndrome
Acute bacterial meningitis beyond neonatal period
Encephalitis & encephalopathy
Anemia
Malaria
Measles (rubeola)
Mumps
AFB / Poliomyelitis
Tetanus
Childhood tuberculosis
Prevention and management of acute diarrhea
ARI/Pneumonia
Rheumatic fever
Diphtheria
Intestinal protozoan infections
Cerebral palsy
Pertusis
Trisomy syndrome
Down syndrome
Trisomy 18; 13
Neonatal sepsis
Neonatal hyperbilirubinemia
Vaccine preventable disease/ immunization
Prematurity/ IUGR
Hyaline membrane disease
Meconium aspiration syndrome
Diabetes mellitus
Mental Retardation

Short stature

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Protein Energy Malnutrition (PEM)

Definition:
The World Health Organization (WHO) defines malnutrition as the cellular
imbalance between the supply of nutrients and energy and the bodys demand for
them to ensure growth, maintenance, and specific functions.
Introduction:
Protein energy malnutrition has been identified as a major health and
nutritional problem in India. Young children (0-6 years) require more protein for
each kilogram of body weight than adults. So they are more vulnerable to
malnutrition. It is not only an important cause of childhood morbidity and
mortality, but also leads to permanent impairment of physical and mental
growth of those who survive.
1. Incidence:
The incidence of protein energy malnutrition in India in preschool children is 1-2%.
Nearly 80% of the cases of PEM are the "intermediate ones", that is the mild and
moderate cases which usually go unrecognized. Nutritional Marasmus is more
frequent than Kwashiorkor.
2. Etiology:
The most common cause of malnutrition is poverty. PEM is primarily due to:
1. An inadequate intake of food both in quantity and quality
2. Infections
1. Diarrhoea
3. Measles
2. Respiratory Infections
4. Intestinal worm infestation
These infections increase requirements for calories, proteins and other
nutrients, while decreasing their absorption and utilization.
3. The other factors causing PEM are:
1. Poor environmental
7. Social and cultural feeding
conditions
practices
2. Large family size
8. Low birth weight
3. Poor maternal health and
9. Malabsorption states
10.Short bowel syndrome
nutritional status
11.Small bowel bacterial
4. Failure of lactation
5. Premature termination of
overgrowth
12.Celiac disease
breast feeding
13.Immunodeficiency states
6. Delayed weaning
14.Enzyme and transport
defects

3. Early detection of PEM:

The first indicator of PEM is underweight for age. The most practical method to
detect this is to maintain growth charts. The extent of weight loss and growth rate
varies with severity of PEM.
1. Early stages of PEM : Failure to maintain weight or growth rate
2. Progressive PEM : Loss of weight, loss of subcutaneous fat and muscle
mass and dysfunction of many vital organs
3. Severe PEM: increasing failure of homeostatic mechanisms of body and
damage to immune
defenses may lead to infection, shock and death.
Types of PEM:
1. Marasmus
3. Marasmic Kwashiorkor
2. Kwashiorkor
Clinical features of PEM
Features
Clinical
Muscle wasting
Fat wasting
Edema
Weight for
height
Mental changes
Clinical
Appetite
Diarrhea
Features
Skin changes
Hair changes
Hepatic
enlargement

Marasmus

Kwashiorkor
Always Present
Obvious
Sometimes hidden by edema and fat
Severe loss of subcutaneous Fat often retained but not firm
fat
None
Present in lower leg and usually in face
and lower arms
Very low
Low but may be masked by edema
Sometimes quiet and
apathetic
Usually good
Often
Marasmus
Usually none
Seldom
None

Irritable, moaning, apathetic

Sometimes present
Poor
Often
Kwashiorkor
Diffuse pigmentation, sometimes flaky
paint dermatosis
Sparse, easily pulled out
Sometimes due to accumulation of fat

Biochemical / Pathology
Features

Marasdmus

Kwoshiorkor

Serum albumin
Urinary urea per g
creatinine
Hydroxyproline / creatinine
ratio
Plasma / amino acid ratio
Anemia
Liver biopsy

Normal or slightly
decreased
Normal or decreased

Low (less than 3g/100

ml blood)
Low

Low

Low

Normal
Uncommon
Normal or atrophic

Elevated
Common
Fatty changes

Classification of PEM:
IAP classification:
Nutritional
Grade
Normal
Grade 1
Grade 2
Grade 3
Grade 4

Percentage of standard weight

for age
> 80%
71 80%
61 70%
51 60%
Less than 50%

Waterlows classification:
Parameter
Weight / Age %
Weight / Height
%
Weight / Age %

Normal
100
100

Wasted
70
70

Stunted
70
100

100

100

84

Gomez classification:
It is based on weight retardation.
Normal nutritional status
Between 90 and 110%
1st degree, mild malnutrition
Between 75 and 89%
nd
2 degree, moderate
Between 60 and 74%
malnutrition
3rd degree, severe
Under 60%
malnutrition
Diagnosis of Malnutrition:
Nutritional anthropometry:

5
This is a valuable index of assessment of nutritional status. 2/3 of children with PEM
does not present with clinical signs but are diagnosed by anthropometry.
1. Weight for age:
most sensitive method when recorded serially. A decrease in weight gain /
loss in weight can be seen within 1 month.
2. Height for age:
compares the child's height with the expected height for the age.
3. Weight for height:
this compares a child's weight with the expected weight of the same
height. It is useful for differentiating between acute and chronic
malnutrition.
4. Acute malnutrition:
child is wasted i.e. weight for age and height is low but height for age is
normal.
5. Chronic malnutrition:
child is stunted i.e. weight for age is low and height for age is low.
6. Mid upper arm circumference (MUAC):
Normal MUAC for a child between 1-5 years of age is greater than 13.5 cm.
If the MUAC is 12.5-13.5, the child has mild to moderate malnutrition and if
it is less than 12.5 cm it is suggestive of severe malnutrition. This is useful
for screening a large number of children but less useful in long term growth
monitoring.
7. Chest/ Head circumference
Chest circumference = Head circumference at one year of age.
Chest circumference > Head circumference after 2 years of age.
In PEM, chest circumference is less than Head circumference even after 2
years of age.
8. Skin fold thickness:
It is an indication of the availability of caloric stores in the form of
subcutaneous fat. Sites for measurement are triceps and subscapular
region.
9. The most important measurement for malnutrition is the growth
curve: weight for age is plotted as percentiles curves and growth is monitored
over a period of time; it is also called road to health chart

Marasmus:
1. It results from inadequate intake of energy or both energy and proteins
2. Usual age is less than 1 year
3.
4.

Marasmus is typically observed in infants who are breastfeeding when the amount of milk is markedly
reduced or, more frequently, in those who are artificially fed
It is a form adaptation syndrome to chronic underlnutrition

5. Hence it is a non oedematous form

6. There is severe wasting skin becoming wrinkled and loose
7. Buccal pad of fat is lost giving a wise mans appearance
8. Infant have constipation or starvation diarrhoea
9. Flat or distended abdomen with visible peristalsis
10.Subnormal temperature and low pulse
Kwashirokor:
1. Lethargy, apathy, irritability are the initial features
2. Muscle wasting and edema
3. Hepatomegaly
4. Skin:
a. Depigmentataion
b. Dry and crackling: flaky paint and paddy field dermatitis
5. Hair signs:
a. Easy pluckability
b. Brownish
c. Flag sign
6. Theories of Causes of edema:
a. Reduced albumin synthesis
b. Aflatoxin poisoning
c. Impaired renal function
d. Decreaed Na- K ATPase acivity
e. Increased free radicals; methionine levels are low which is a precursor
of glutathione an antioxidant
Complications of PEM:
1. Dehydration and diarrhea
2. Hypothermia
3. Hypoglycemia
4. Infections
5. Congestive cardiac failure
6. Vitamin deficiency
7. Multiple nutritional deficiencies
8. Electrolyte imbalance
Management:
Goals:
1. To minimize weight loss
2. To maintain body mass
3. To encourage body mass growth
Principles:
1. Patient evaluation: Severity of PEM systemic infections, associated
nutritional deficits
2. Intake of food: Culturally acceptable and affordable food must be promoted.
3. Prevention of complications and death: By careful surveillance & prompt
action.

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4. Attempt to eliminate epidemiological factors
Management of mild to moderate PEM:
This is managed at home by parents and monitored through weekly home
visits by paramedical personnel, visits to the hospital or nutritional
rehabilitation centre every week. The goal is to provide adequate calories to
replace losses & to promote growth.
Caution: The calories and proteins should be gradually built up.
Recommendations:

Energy 120-150 kcal/kg/day

Protein 2-3 gm/kg/day

Foods advocated:

Double or triple mixes of cereals and pulses like dal, rice, khichdi,
seasonal green leafy vegetables, root vegetables, sugar, jaggery, milk, milk
products and nuts like groundnuts.

Oil / ghee or butter are added to increase calories.

Frequent small feeds with calories and proteins distributed

proportionately are encouraged.
Miscellaneous:

Parents should be educated regarding the hygienic way of preparing and

handling food;
personal hygiene and importance of safe and clean
drinking water.

Basic advice regarding ORS (oral rehydration solution) use for diarrhoea,
vitamin supplements, treatment of infections and infestations should be
given

Zinc supplements are given to promote growth once positive nutrition

balance starts (increase in weight gain)
Child must be immunized as per schedule.
Severe PEM:
Hospital Management:
Resuscitation : 6 - 24 hours
Acute Phase : 1 day - 1 week
Rehabilitation : 2nd - 3rd weeks
Resuscitation - Treatment of Complications:
Dehydration:
Assessment: Fluid and sodium given should not exceed 75% of allowances
calculated on the basis of weight.
Hypothermia:
It is common in Marasmus. It is usually a sign of infection, hypoglycemia or
severe energy deficit. The child is kept warm, given frequent feeds and
antibiotics for infection.
Hypoglycemia:
It is defined as a blood sugar of less than 50 mg/dl.
More common in Marasmus
1-2 ml/kg of 10% dextrose as bolus; then maintenance with 10%
dextrose and saline over 24 hours.
Infection:

8
Broad-spectrum antibiotics are given.
Anemia:
5-10ml/kg of packed red blood cells is transfused if hemoglobin is less
than 5 mg/dl.
Xerophthalmia:
If child is > 1 year or > 10 kg, vitamin A 100,000 units are given IM on
days 1, 2 and 28.
If child is less than 1year or less than 10 kg, 1/2 the above dose is
given.
Congestive Cardiac Failure:
It is common after day 3 of the acute phase usually in Kwashiorkor.
Oxygen and Diuretics must be given.
Hypomagnesemia:
It is corrected with 1 ml of magnesium sulfate given IM every 12 hours
for 1-3 days.
Hypocalcemia:
It is corrected with 1-2 ml/kg of calcium gluconate IV.
Acute Phase: Involves Dietary Management:
Rule 1:
Calculations are to be based on actual weight (not the expected weight). Near
maintenance requirement is provided i.e., approximately 80 cal/kg/day and 0.7
gm/kg/day of protein.
Rule 2:
Offer small feeds at frequent intervals (to avoid vomiting, hypoglycemia and
hypothermia).
Rule 3:
Step up intake gradually so that by the end of the first week, the child is able
to take approximately 100 kcal/kg/day and 1 gm/kg/day of protein. Intragastric
/ NG tube feeding or total parenteral nutrition may be required. Milk is the
most common liquid nutritious food and is usually well tolerated except in
lactose intolerance. (Curd is usually well tolerated). Fluid volume is calculated
at approximately 120 ml/kg/day.
High Energy Feeding:
After the initial phase and some signs of improvement, calorie intake is
gradually increased to approximately 150 - 180 kcal/kg/day. Milk intake is
gradually decreased and intake of semisolids and solids is increased. Protein
intake is increased to approximately 1.5 - 2 gm/kg/day.
Rehabilitation:
Once the child is able to tolerate a high dose of therapeutic nutrition and has
started gaining weight, offer solid/semisolid family foods containing cereals,
pulses and vegetables.
Bengal gram, groundnuts and green leafy vegetables should be added.
Oils, sugar, fruit should be given and vitamins and minerals should be
continued for 5-6 weeks.
Recovery And Follow Up:
Recovery is assessed by:
1. Improvement of general condition, alertness and smile.

9
2. Return of appetite.
3. Gain in weight of 50-70 gms/day.
4. Disappearance of edema (7-10 days) and hepatomegaly.
5. Rise in serum albumin over the first 2 weeks of therapy
Recovery is complete when the child reaches his/her standard weight, which
usually takes 6-8 weeks.
Prognosis:
Mortality 10-30%
Long term sequelae: Irreversible stunting and mental impairment.
Preventive Measures:
The following is adapted from the 8th FAO/WHO expert committee on nutrition
for the prevention of PEM in the community.
Health Promotion:
1. Measures directed towards pregnant and lactating women i.e. education
and distribution of supplements.
2. Promotion of breast-feeding.
3. Development of low cost weaning food: The child should be made to eat
more food at frequent intervals.
4. Measures to improve family diet.
5. Nutrition education: Promotion of correct feeding practices.
6. Home Economics
7. Family planning and spacing of births
8. Family environment
Specific Protection:
1. The child's diet must contain protein and energy rich food. Milk, eggs
and fresh fruits should be given, if possible.
2. Immunization
3. Food fortification
Early Diagnosis And Treatment:
1. Periodic surveillance.
2. Early diagnosis of any lag in growth.
3. Early diagnosis and treatment of infections and diarrhoea.
4. Development of supplementary feeding programmes during epidemics.
5. Deworming of heavily infested children.
Rehabilitation:
1. Nutritional rehabilitation services
2. Hospital treatment
3. Follow-up care.

10

Growth and Development

1. Percentile - A percentage scale from 0 to 100 that is associated with an item to
show which percentage of the distribution is above and below the item.
2. Standard deviation:
The dark blue zone represents observations within one standard deviation
to either side of the mean, which accounts for about 68.2% of the
population. Two standard deviations from the mean (medium and dark
blue) account for about 95.4%, and three standard deviations (light,
medium, and dark blue) about 99.7%

3. What is child development?

Child development refers to how a child becomes able to do more complex
things as they get older. Development is different than growth. Growth only
refers to the child getting bigger in size.
1. Gross motor: using large groups of muscles to sit, stand, walk, run,
etc., keeping balance, and changing positions.
2. Fine motor: using hands to be able to eat, draw, dress, play, write,
and do many other things.

11
3. Language: speaking, using body language and gestures,
communicating, and understanding what others say.
4. Cognitive: Thinking skills: including learning, understanding, problemsolving, reasoning, and remembering.
5. Social: Interacting with others, having relationships with family,
friends, and teachers, cooperating, and responding to the feelings of
others.
4. Growth is increase in size of the body (physical maturation)
5. Development is physiological and psychological maturation
6. What are developmental milestones?
Developmental milestones are a set of functional skills or age-specific tasks
that most children can do at a certain age range.

Growth and development - 0 to 2 years

Introduction:
1. There are definite and predictable pattern of growth and development that
are continuous, orderly and progressive.
Crawl Creep Walk
Babbles Words Sentences
Scribble Writing
2. Directional Pattern:
a. Cephalocaudal Pattern ( Head to Tail)
b. Proximal to Distal (Midline to peripheral)
c. Mass to specific (Differentiation)
3. Need for growth and development monitoring.
To find the deviation as soon as possible

To bring possible remedies.

4. Factors affecting growth and development:
Genetic make up
Sex
Race
Nutrition
Environment
Fetal:
1. Embryonic period: 8 weeks; by this time all major organ systems have developed;
CNS has developed and vulnerable for teratogenic and hypoxic insults
2. Fetal period:
1. 10 weeks: face recognizable; rotation of gut
2. 12 weeks: gender of genitals becomes visible; budding of bronchi and
bronchioles
3. 20-24: primitive alveoli and surfactants begin to form
4. 26 weeks: eye opening
5. III trimester: respond to external stimuli by body movements and heart rate
changes; habituation with repetitive stimuli
3. Nweborn:
1. Wt: 3.4 kg; boys heavier;
2. Length: 50 cm (20)
3. HC: 35 cm (14 )
4. Eye: Focal length: 8-12; nearsighted from breast to mothers face;
preference for faces
5. Hearing: developed well; preferential turn toward female voice

12
6. Gaze back at mother
7. Autonomic instability: flushing, mottling, perioral pallor, hiccupping,
vomiting, uncontrolled limb movements and inconsolable crying
8. Behavioural state:
i. Quiet sleep: not arousable by heel stick
ii. Active sleep: arousable but gets habituated by repeated heel stick
iii. Drowsy: repeated heel stick pushes the infant to fussy or crying
state
iv. Alert: fixate on object or face and follow horizontally and vertically;
turn toward a novel sound
v. Fussy
vi. Crying
4. 0-2 months:
1. Physical:
i. Weight:
1. Wt loss by 10% of birth weight in first week; regains it in 2
week
2. Gains 30 gm /day in first month (fastest growth in life)
ii. Uncontrolled writhing and purposeless closing and opening of hands
iii. Active moro response; tonic neck posture
iv. Involuntary smiling
v. 6 behavioural states; sleep and wakefulness evenly distributed and
later sleep period more in nights
vi. Eye gaze, head turning, sucking under some control
vii. Visual preference to human face
viii. Turns towards mother voice indicating some recognition memory
2. Cognitive:
i. Recognizes facial expression like smile
ii. Habituates to repeated stimuli
iii. Increase attention to changing stimulus
iv. Discriminates rhythmic patterns in native vz non native language
3. Emotional:
i. Crying in response to wet diaper
ii. Cries while hungry and relief after feeding
5. 2-6 months:
1. physical:
i. Weight gain is 20 gm/day in 3-4 months and birth weight is doubled
at the end of 4 months
ii. Disappearance of asymmetric tonic neck reflex and hands are
brought to midline to examine objects
iii. Grasp reflex disappear to hold and release objects voluntarily
iv. Gains control over trunk muscles that helps in intentional rolling over
v. Holds heads with bopping 3 mo, steadily at 4-5 mo while sitting and
start taking spoon feeding
vi. Can gaze across at things
vii. Achieves greater degree of regular sleep-wake cycle; shorter than in
adults and wake frequently during nights
2. Cognitive:
i. Starts shifting attention from breast feeding mother to other things
around
ii. Starts exploring his own body by hands
3. Emotional development and communication:
i. Shows anger, fear and joy for appropriate stimuli

13
ii. Says inga - 3 mo
iii. Loughs aloud - 4 mo
iv. Excited at sight of food- 4 mo
v. Shows facial imitation and hand games
vi. Show sadness when parents are unavailable
6. 6-12 months:
1. Physical:
i. At 1 year the birth weight triples; length increase by 50%; HC
increases by 10 cm
ii. Sits supported 6-7 mo; without support 10 mo; pivots while sitting 910 mo; examines several objects at a time
iii. Crawl and pulling to stand 8 mo
iv. Thumb finger grasp 8-9 mo; pincer grasp by 12 mo;
v. Walks by 1 yr
vi. Mandibular central incisors erupt
2. Cognitive:
i. Objects are passed from hand to hand, banged, dropped and
mouthed
ii. Looks down for a ball that has been dropped and gives up if not
seen- 4-7 mo
iii. At 9 mo, search for objects if hidden- object permanence
iv. Plays peek-a-boo; pat-a-cake and waves bye bye -10 mo
3. Emotional:
i. Look anxiously at stranger, clings to mother stranger anxiety
ii. Cry to call mother in next room
iii. Tantrums appear as a drive for autonomy and mastery
4. Communication:
i. Understands and responds to vocal and facial expressions-7 mo
ii. Shows toy to parents to share the joy - 9 mo
iii. Utter syllables like ma, da, pa babbling 8-10 mo
iv. Responds to name
v. Uses a first true word for the object permanence or a person
vi. Says mama, dada-12 mo
7. The second year: 12-18 mo
1. Physical:
i. Growth rate slows and appetite declines
ii. Relatively short legs and long torsos with exaggerated lumbar
lordosis and protruding abdomen
iii. Brain growth and myelinisation increase head circumference by 2 cm
iv. Walks independently with genu varus (bow leg) and gets corrected
over few months
v. Stops, pivots and stoops without toppling over
vi. Increasing dexterity ( reaching, grasping and releasing) and mobility
2. Cognitive:
i. Stacks blocks
ii. Uses things for intended purposes: combs for hair, cups for drinking
iii. Symbolic play: pretends to drink from an empty cup
iv. Imitates parent or older children
3. Emotional:
i. Orbit around parents- going away and return to parents now and
then
ii. Exhibit temper tantrums reflecting their inability to verbally
communicate their emotional states

14
4. Linguistic:
i. Receptive language precedes expressive language
ii. Ploysylabic jargon
iii. Responds appropriately by words like no, bye-bye, give-me etc -12
mo
iv. Names body parts and uses 4-6 words correctly- 15 mo
8. Second year: 18-24 mo:
1. Physical:
i. Gains 5 and 5 lb
ii. At 24 mo they their adult height
iii. 90% head circumference achieved in 2 yr
2. Cognitive:
i. Uses a stick to get a toy out of reach 18 mo
ii. Can wind a mechanical toy
iii. Symbolic play: Feeds a toy from empty plate
3. Emotional:
i. Shows separation anxiety when parents are missing
ii. Uses a toy or blanket (transitional object) while sleeping to represent
absent parent
iii. Looks at the mirror and remove an unusual thing from his nose
iv. Hand over a broken toy to parents to fix
v. Says himself no, no when touches a forbidden object
4. Linguistic:
i. 15-20 words at 18 mo and 50-100 words at 2 years
ii. Combine two words
iii. Understands 2 step commands like give the ball and take the shoes

Some Paediatric behaviour problems

1.Pica :
Definition:
Repeated or chronic ingestion of non-nutritive substances such as plaster,
charcoal, clay, ashes, paint and earth.
Trichotillomanania is injestion of hair leading to bezoar
cautopyreiophagia is ingestion of burnt match heads
Mouthing activity up to 2 yrs normal
Pica after 2 years should be investigated
Causes:
1. Mental retardation
2. Lack of parental nurturing
3. Nutritional deficiencies in iron, calcium, zinc, and other nutrients (eg,
thiamine, niacin, vitamins C and D)
4. Low socioeconomic groups
5. Autism
6. Kleine-Levin syndrome :
? autoimmune hypothalamic dysfunction
Paroxysmal,
Adolescent boys
Self limiting
Hypersomnalence, hyperphagia, hypersexuality

15
7. Stress: Maternal deprivation, parental separation, parental neglect, child
abuse, and insufficient amounts of parent/child interactions have been
associated with pica.
8. Pregnancy
Risk:
1.
2.
3.
4.

Lead poisoning
Iron deficiency anemia
Parasitic infestation
Such as hyperkalemia following cautopyreiophagia (ingestion of burnt
match heads).
5. geophagia (soil or clay ingestion) has been associated with soil-borne
parasitic infections, such as toxoplasmosis and toxocariasis
6. Toxocariasis (visceral larva migrans, ocular larva migrans) and
ascariasis are the most common soil-borne parasitic infections
associated with pica.
7. Symptoms of toxocariasis are diverse and appear to be related to the
number of larvae ingested and the organs to which the larvae migrate.
8. Physical findings associated with visceral larva migrans may include
fever, hepatomegaly, malaise, coughing, myocarditis, and encephalitis.
9. Ocular larva migrans can result in retinal lesions and loss of vision.
10.displace normal dietary intake or interfere with the absorption of
necessary nutritional substances.
11.Dental effects: Pica has been reported to result in severe tooth abrasion,
abfraction, and surface tooth loss
Tests:
1. screening of blood:
lead concentrations
intestinal parasites
Anemia
2. Abdominal radiography
3. Upper and lower GI barium examinations
4. Repeated imaging at regular intervals to track changes in location of
ingested materials
5. Upper GI endoscopy to diagnosis bezoar formation, identify associated
lesions, or both
Treatment:
1. Address any identified nutritional deficiencies; however, nutritional and
dietary approaches have demonstrated success related to the prevention
of pica in only a very limited number of patients.
2. Treatment involves behaviour and development, environmental, and family
education approaches. Other successful treatments include associating the
pica behaviour with bad consequences or punishment (mild aversion
therapy) followed by positive reinforcement for eating the right foods.
3. Medications may help reduce the abnormal eating behaviour, if pica occurs
as part of a developmental disorder such as mental retardation.

2.Enuresis:

16
Discharge of urine into clothes after the developmental age when bladder
control should be established i.e. beyond 5 years.
Definition: discharge of urine twice a week for 3 consecutive months
Prevalence:
At 5 yrs:
5-7% male; 3% in females
At 10 yeras: 3% male and 2 % female
At 18 yrs:
1% male; nil in female
Etiology:
1. Familial pattern
2. Gene in chr 22
3. Reduced Argenine vasopressin secretion;
4. Enuresis can be divided into primary enuresis (PE) and secondary enuresis
(SE). A child who has experienced a minimum 6-month period of
continence before the onset of the bedwetting is considered to have SE.
5. Enuresis is reported in 43% of children of enuretic fathers, 44% of children
of enuretic mothers, and 77% of children when both the mother and father
had enuresis
6. Arousal to the sensation of a full or contracting bladder involves
interconnected anatomic areas, including the cerebral cortex, reticular
activating system (RAS), locus ceruleus (LC), hypothalamus, pontine
micturition center (PMC), spinal cord, and bladder. The RAS controls depth
of sleep, the LC controls arousal, and the PMC initiates the command for a
detrusor contraction. Various neurotransmitters are involved, including
noradrenaline, serotonin, and antidiuretic hormone (ADH).
a. Factors that cause nocturnal polyuria in children with enuresis
include the following:
i. Fluid ingestion before bedtime
ii. Food consumption before bedtime
iii. Low nocturnal secretion of ADH
iv. Increased nocturnal solute excretion
v. Excess intake of caffeine
7. Small functional bladder capacity is a pathophysiologic factor for enuresis
8. functional bladder capacity (FBC) was positively correlated with nighttime
urine output.8 Children with enuresis possibly maintain a smaller nocturnal
bladder volume
9. external urethral sphincter might fall below a critical level during sleep and
thereby trigger a detrusor contraction
10.Cystitis is a common cause of enuresis and an aggravating factor
associated with other causes.
11.Various common situations predispose to a psychological cause, including
birth of a new sibling, parental divorce or separation, a death in the family,
child abuse, or any other cause of social dysfunction at home or school
12.Constipation can cause both PE and SE and is a common aggravating factor
that should be considered when other causes are present
13.As many as 37% of children with cerebral palsy have enuresis.
14.Patients with myelomeningocele almost always have enuresis
15.SE may be a symptom of an unobserved overnight major motor convulsion
in a child with a known seizure disorder.

17
16.Diabetes mellitus is also associated with abnormalities in the afferent
sensory pathways to the bladder, which may contribute to enuresis.
17.Diabetes insipidus may be central or nephrogenic. Central diabetes
insipidus may result from an intracranial tumor, head trauma, encephalitis,
or meningitis. Nephrogenic diabetes insipidus may result from any cause of
renal failure, diffuse renal cortical or medullary damage, hypokalemia,
hypercalcemia, or nephrotoxic drugs.

Studies:
Laboratory Studies:
Urinalysis:
1. Urinalysis is the most important screening test in a child with enuresis.
2. Children with cystitis usually have WBCs or bacteria evident in the
microscopic urinalysis.
3. Children with overactive bladder or dysfunctional voiding, urethral
obstruction, neurogenic bladder, ectopic ureter, or diabetes mellitus are
predisposed to cystitis.
4. If the urinalysis findings suggest cystitis, urine should be sent for culture
and sensitivity.
5. Urethral obstruction may be associated with RBCs in the urine.
6. The presence of glucose suggests diabetes mellitus.
7. A random or first-morning specific gravity greater than 1.020 excludes
diabetes insipidus.
8. Portable bladder ultrasonography is available to assess residual urine when
the patient is in the office. The residual volume of urine is normally less
than 5 mL.
9. MRI of the spine is indicated in any patient with an abnormal neurologic
examination finding of the lower extremitie
Treatment:
1. Children with enuresis benefit from a caring and patient attitude by their
parents; punishment has no role. A positive approach by the physician is also
important to instill confidence and enhance compliance.
2. The child should be encouraged to void upon awakening, approximately every
1.5-2 hours, before leaving home or school for any reason, and always before
bed. Children should be encouraged to void regularly at school and at least
twice per day at school
3. Children should be instructed to drink liberal amounts during the day, not to
drink to excess with the evening meal
4. Parents should be asked to take the child to the bathroom to void prior to
bedtime
5. Alarm therapy is reported to improve bedwetting by increasing nocturnal
bladder capacity or by enhanced arousal. The alarm should be attached at
bedtime to the underwear or pajamas in a position chosen to promptly sense
wetness
6. Desmopressin acetate therapy:
o The tablet and oral disintegrating tablet (not available in the United
States) have similar efficacy.

18
The intranasal formulation has a black box warning by the FDA and is no
longer recommended
o The recommended starting dose for the tablet is 0.2 mg, administered 1
hour before bedtime
o hyponatremic-related seizures associated with the use of desmopressin
o A maximum of 1 cup of fluid should be offered at the evening meal, no
more than 1 cup between mealtime and bedtime, and nothing to drink
within 2 hours prior to bedtime.
7. Anticholinergic therapy:
o helpful in some patients, especially those with overactive bladder,
dysfunctional voiding, or neurogenic bladder
o These medications reduce uninhibited detrusor contractions, increase
the threshold volume at which an uninhibited detrusor contraction
occurs, and enlarge the functional bladder capacity.
o These medications should not be administered during a fever because a
decrease in sweating is an anticholinergic effect
o The dosage of oxybutynin is 2.5-5 mg administered at bedtime
8. Imipramine therapy:
o imipramine is effective to reduce bedwetting.
o The usual dose, taken 1-2 hours before bedtime, is 25 mg for patients
aged 6-8 years and 50-75 mg for older children and adolescents.
o Adverse effects include constipation, difficulty initiating voiding,
irritability, drowsiness, reduced appetite, and personality changes.
Imipramine overdose can be fatal, and a cautionary warning is
necessary with every prescription
o

3.Infantile colic:

Features:
1. Severe paroxysmal crying in late afternoon
2. Knees drawn up; fists clenched; pass flatus or stools or urinate; No response to
soothing
3. 2 weeks - 2 hr/day ; 6 weeks - 3 hr/day ; 3 months- 1 hr/day ; Continue till 4-5
months in 30-40%
4. Wessel criteria:
i.
Well fed
ii.
Healthy
iii.
Cries more than : 3 hrs / day; 3 days / week;
3 weeks
5. Some responds to elimination of cow milk from mother of infant diet
6. Colic remains a diagnosis of exclusion
7. Rule out:
a. Corneal abrasion
b. Hair wrapped around toes and fingers
c. Strangulated hernia
d. Torsion of testis or appendix of the testis
e. Lactose intolerance
f. Trauma
g. UTI
h. GE reflux
i. Bronchiolitis

19

Causes:
Causes include the following:
1.
Gastroesophageal reflux, overfeeding, underfeeding,
2.
Milk protein allergy, and early introduction of solids.
3.
Parental anxiety and parental stress has been a subject of many studies.
Postpartum depression may lead to stress in parents, which may be transferred to
the infant, resulting in excess crying.
4.
Other causes include inexperienced parents or incomplete or no burping after
feeding.
5.
Recent epidemiologic evidence suggests that exposure to cigarette smoke and its
metabolites may be related to colic. Maternal smoking during pregnancy may be
associated with colic.4
6.
Some evidence has linked persistent crying in young infants to food allegy. 5 an
association between colic and cow's milk allergy (cma) has been postulated. 6
7.
data from one study suggested an association between low birth weight and
increased incidence of colic.
8.
Recently, some reports have focused on intestinal microflora and its association
with colic.8 lower counts of intestinal lactobacilli were observed in infants with colic
compared with infants without colic
Treatment:
1. Dicyclomine hydrochloride is an anticholinergic drug that has been proven in
clinical trials to be effective in the treatment of colic. However, because of
serious, although rare, adverse effects (eg, apnea, breathing difficulty,
seizures, syncope), its use cannot be recommended.
2. Wessel and colleagues suggested an association between family and infantile
tension whjich need to be addressed.
3. A maternal low-allergens diets (ie, low in dairy, soy, egg, peanut, wheat, shell
fish) may offer relief
4. Lactobacillus reuteri endogenous to the human GI tract was found to relieve
colic symptoms in breastfed infants
5. Simethicone is a nonabsorbable medication that changes the surface tension of
gas bubbles, Experimental evidence does not support its use in colic.
6. Sedatives, such as phenobarbital, chloral hydrate, and alcohol (gripe water)
should never be used, however tempting.
7. Herbal remedies have been used in many cultures. Only a handful of studies of
herbal products have been conducted, and additional studies of their safety
and efficacy are needed.
4.Thumb Sucking:
1. Thumb sucking is a behavior found in humans, chimpanzees
2. sucking is one of a babys natural reflexes and completely typical for babies and
young children.[3] As a child develops the habit, it will usually develop a "favorite"
finger to suck on
3. Most thumb-suckers stop gradually by the time they are five years old
4. Most children stop sucking on thumbs, pacifiers or other objects on their own
between two and four years of age.

20
5. The only time it might cause concern is if it goes on beyond 6 to 8 years of age. At

this time, it may affect the shape of the oral cavity or dentition.
Tips from the American Dental Association:
1. Praise children for not sucking, instead of scolding them when they do.
2. If a child is sucking its thumb when feeling insecure or needing comfort, focus
instead on correcting the cause of the anxiety and provide comfort to your child.
3. If a child is sucking on its thumb because of boredom, try getting the child's
attention with a fun activity.
4. Involve older children in the selection of a means to cease thumb sucking.
5. The pediatric dentist can offer encouragement to a child and explain what could
happen to its teeth if it does not stop sucking.
6. Only if these tips are ineffective, remind the child of its habit by bandaging the
thumb or putting a sock/glove on the hand at night.
Summary of Best Practices Recommendations:
1. American Academy of Paediatrics : Most children suck their thumbs or fingers at

some time in their early life. The only time it might cause concern is if it goes on
beyond 6 to 8 years of age or affects the shape of the child's mouth and the
position of teeth.
2. American Dental Association : Children suck on objects as a natural reflex;
however, during and after the eruption of the permanent teeth, such sucking may
cause problems with the skeletal development of the mouth and alignment of the
teeth.

5.Food refusal:
1. Young children may go through periods of fussy eating. They have a short period
where they dont want to eat certain foods
2. Food refusal might be a normal part of growing up for some children; but it also
could be sometimes indicating early stage anorexia.
3. Growing child wants to be more independent. They may declare it by refusing to
eat.
4. It can be difficult for families to get the balance between freedom and parental
control.
5. Parents need to avoid becoming anxious because the toddler can respond to this
by becoming more adamant in not wanting to eat.
6. Young children like routine so parents need to have a regular meal schedule.
7. Parents should try and eat with their toddler. It is also suggested that parents offer
encouragement and praise if their child eats well.
8. Meal time should be fun and relaxed with no other distractions.
9. Parents should not try and rush their child as some can be quite slow eaters; it is
recommended that twenty-five minutes is an acceptable amount of time.
6. Breath holding spell
1. Incidence 0.1 to 5%
2. Age 6 mo to 6 years
3. Reflexive holding of breath in expiration following a period of provoked cry
4. Becomes silent, apneic, turns pale (pallid) or blue (cyanotic)
5. Loss of consciousness and opisthotonus, body jerks, urination and frank
convulsions may occur

21
6. Resolves spontaneously
7. DD: Spells occur in:
Seizures, CNS tumors, familial dysautonomia etc
8. Management:
i.
Reassure parents
ii.
Ignore spells and monitor for any complications
iii.
Support the child but do not become submissive
iv.
Unconsciousness:
v.
Place the child on his side
vi.
Maintain airway
vii.
Atropine .01 mg / kg SC for bradycardia or asystole
7. Temper Tantrums
1. 1-4 years; once a week in 50-80% of this age group
2. Clinical:
i.
Child throws himself down, kick and scream; holds his breath
ii.
A manifestation achieving autonomy and mastery over the environment
iii.
Annoying at home, embarrassing in public
3. Cause: not mature enough to cope with difficulties
4. Management
i.
Minimize the need to say no by comfortable environment
ii.
Distraction
iii.
Reward
iv.
Fight the battle that needs to won and avoid conflicts
v.
Allow him to achieve mastery and autonomy
vi.
Set reasonable limits
5. After an attack
i.
Stay nearby; do not abandon
ii.
No threats
iii.
Do not use negative terms
iv.
Do not let him hurt himself
v.
Do not hold a grudge after the event
vi.
Psychiatry in resistant cases
8. Attention deficit / hyper active disorder
1. Neuro deveolpmental disorder; 2-10% of school children
2. Triad:
i.
Impulsivity: act without thinking first, not learning from past mistakes
ii.
Inattention:
iii.
Hyperactivity
3. Impulsivity
i.
Act without thinking first,
ii.
Not learning from past mistakes
iii.
Speak When they're supposed to be quiet
iv.
Cut in line
v.
Can't wait their turn in line or in a game

22
vi.

Cognitively impulsive ADHD kids will make a multiple number of guesses in

a short period of time.
4. Inattention
i.
No attention to details
ii.
Short attention span
iii.
Easy distractibility
iv.
Forgetfulness
v.
Failure to listen when spoken to
vi.
Failure to engage in tasks
5. Hyperactivity
i.
Fidgetiness
ii.
Difficulty in remaining seated in class
iii.
Excessive running and climbing
iv.
Not awaiting turns
v.
Excessive talking : Answer before question is complete
6. Etiology
a. Genetic : multifactorial
b. Associated with :
i. Fragile X syndrome
ii. Williams syndrome
iii. Angel man syndrome
iv. Klinefelter
v. Turner
vi. Fetal alcohol syndrome
c. Perinatal:
i. CNS trauma/ infections/ toxins
ii. Prematurity/ asphyxia
iii. Hyperthyroidism
7. Management
a. Disorder diminish between 10-25 years
b. Medications
c. Behavioral intervention strategies
d. Parent training
e. ADHD and school
II.
Medications
a. Stimulants:
i. Stimulant: Methyl phenindate; amphetamine
ii. Non stimulant: Atomoxetine ; Clonidine
b. School-Based Interventions:
i. Help teachers meet childrens educational needs by teaching them
skills to manage the childrens ADHD behaviours in the classroom
9. Dyslexia
1. Definition: Difficulty to read, while intelligence is normal
2. Etiology:
Genetic
Familial

23
3. Epidemiolgy: 5-10% school children
4. Pathogenesis:
a. Defect in left temporo - parieto-occipital brain regions which does not
function properly while reading
b. Clinical
i. Difficulty in text reading slow readers
ii. Under achiever in school
iii. Difficulty in comprehending
iv. Difficulty in writing
v. Inability to memorize
vi. Difficulty in spelling
vii. Difficulty in doing simple mathematical problems
viii. Difficulty Learning any new language
5. Diagnosis
i.
It is a clinical diagnosis
ii.
Family history
iii.
Teacher observation
iv.
Oral reading to measure reading accuracy and fluency using set of
graded readers under timed conditions
v.
Compare with peers
6. Celebrity Dyslexics
i.
Alexander Graham Bell Inventor
ii.
Agatha Christie Writer
iii.
Leonardo da Vinci Artist
iv.
Thomas Edison Inventor
v.
Albert Einstein - Scientist
vi.
Bill Gates - Microsoft Chairman
vii.
Michael Faraday - Chemist and Physicist
7. Treatment
i.
Special school and teachers
ii.
Help group
iii.
Phonic instructions: sound for letters
iv.
Guided repeated oral reading
v.
Accommodation rather than remediation
8. Prognosis:
Schooling and early intervention may help near normal achievements
10. Autism Spectrum Disorder
1. Pervasive Neurologic disorder with
i.
qualitative impairment of:
a. Social interaction
b. Communication
c. Reciprocity
d. Imagination and play
ii.
Stereotyped behavior, activity and interest
2. Etiology
i.
Unknown

24

3.

4.

5.

6.

7.

ii.
Strong genetic basis- multifactorial
iii.
Diagnosed by 3 mo
iv.
Variable severity- spectrum
v.
58.7 per 10 000 children
vi.
MMR vaccine- not proved
Observations:
i.
Structural changes in cingulate gyrus
ii.
Early accelerated brain growth and followed by slow growth
clinical
i.
Abnormal eye contact
ii.
Failure to orient to name
iii.
Failure to use gesture to point or show
iv.
Failure to smile
v.
Lack of sharing
vi.
Lack of peer play
vii.
Absence of imaginary play
viii.
Unusual use of language
DD
i.
Fragile X syndrome
ii.
Tuberous sclerosis
iii.
Angel man syndrome
Diagnosis:
i.
Screening using checklist
ii.
20% have microcephaly
iii.
Treatment
iv.
Behavior therapy
v.
Special scooling
vi.
Drugs:
i.
Clomipramine (tricyclic antidepressant)
ii.
Clonidine
iii.
Stimulants: amphetamine; methylphenidate
Prognosis:
i.
May be able to live self sufficient, employed and live in community
ii.
Schizophrenia is a complication

25

Delivery room management of Newborn

1. NORMAL BIRTH
Spontaneous onset;
Low-risk throughout labour and delivery.
Spontaneous delivery with or without ARM
The vertex position
Between 37 and 42 completed weeks
Mother and infant are in good health
2. The three Ps:
1. The powers : uterine contractions and maternal efforts
2. The passage : adequate birth canal
3. The passenger: healthy fetus
3. Definition of fetal distress:
1. Compromised blood flow to the fetus
2. Altered foetal heart rate or rhythm
3. Changes in blood chemistry.
4. Practical definition:
Fh does not return to normal 30 sec. after uterine contraction
Fh remains below 100/mt. between contractions

26
5. Causes
1. Maternal:
1. Microvascular ischaemia (PIH)
2. Low oxygen carried by rbc (severe anemia)
3. Acute bleeding (placenta previa, placental abruption)
4. Shock and acute infection
2. Placental-umbilical cord factors:
1. Obstructed of umbilical blood flow
2. Dysfunction of placenta
3. Post maturity
3. Fetal factors:
1. Malformations of cardiovascular system
2. Intrauterine infection
6. Ante partum assessment
1. Fetal movement (fm)

FM or fetal kicks
10 kicks in 4-6 hour window period

kicks recorded as x in the corresponding time

2. Fetal heart monitoring
Non stress test
Contraction stress test
3. Biophysical profile
4. Liquor amnii

7. FH:
1. Tools:
Monaural (pinard's) stethoscope,
Hand-held ultrasound doppler apparatus.
Cardioto chograph-CTG
8. FHR

27
Early gestation:

FH high under sympathetic control

Later gestation:

decrease in fhr after para sympathetic maturation

Fetal heart patterns
1. Basal fetal heart rate
Normal
120-160/mt
Bradycardia
< 120
Tachycardia
> 160
2. Beat to beat variability : 5 between contractions
3. Acceleration : 15/mt lasting for 15 sec.
4. Baseline bradycardia
Mean FHR < 110 bpm
Etiology:
Heart block
Occiput posterior or transverse position,
Fetal hypoxia.
Xylocain during pudental block
5. Accelerations
Accelerations- transient increase in fhr of 15 bpm or more lasting for 15
sec. Good outcome.
Causes:

Early
Fetal anemia
hypoxia

Fetal infection

Maternal fever
6. Deceleration
FHR below the baseline level of more than 15 bpm and lasting for 15 sec.
Early:
Synchronous with uterine contraction
Caused by head compression and vagal stimulation
Variable :
Slowing oh fh even after uterine relaxation
Caused by cord compression of the umbilical cord
Late:
Prolonged and persists after uterine contraction
Caused by fetal hypoxia
7. Stress test
1. Uterine contraction spontaneous or induced by nipple stimulation or
oxytocin challenge.
2. Positive:
3 contractions in 10 minutes followed by late deceleration

28

Prolonged deceleration:

Biophysical profile
5x2= 10 points
1. Fetal breathing - 30 seconds of sustained fetal breathing in 30 minutes

29
2. Fetal movement - 3 or more gross body movements in 30 minutes
3. Fetal tone - one episode of limb motion from flexion to extension to flexion
4. Amniotic fluid - pocket of fluid measuring at least one centimeter
5. FH 120-160 / mt
Amniotic membrane and liquor amnii:
1. Absent membrane endangers fetal life
2. Meconium stained amniotic fluid indicates established fetal distress
Fetal PH
1. A microtechnique of sampling blood from the fetal scalp
2. Ph < 7.25 indicates fetal distress

Neonatal resuscitation
Perinatal physiology: sequence of events during birth:
1. First cry
6.
2. Lung expansion
3. Clearing of lung fluid
7.
4. Air exchange
5. Termination of Rt to Lt shunts
8.
9.
Circulatory transition
Fatal transitional neonatal

Compromised by factors:
1.
Fetal
2.
Placental
Fetal factors
1. Premature delivery
2. Pulmonary hypoplasia
3. Intra uterine infections
4. CHD

Increase in Po2 from 25 to 60

mm Hg
Decrease in pulmonary
vascular resistance
Increase in Lt atrial flow
Increase in systemic bp

3.

Maternal

5. Hydrops fetalis
6. Chromosomal anomalies
7. Maternal sedation

30
Placental
1.
Infections
4. Cord prolapse
2. Premature seperation
5. True knots
3. Nucal cord
Maternal
1. CPD
2. Prolonged labour:
Combined duration of the first and second stage of labour is more 18
hours
Delayed dilatation of the cervix
Inadequate descent of the presenting part
3. Ante partum hemorrhage
4. Diabetes
5. PIH
6. PROM
Goals of resuscitation :
1. Establish spontaneous
3. Adequate cardiac output
respiration
4. Adequate arterial po2
2. Minimize thermal loss
Equipments
1. Radiant warmer
7. ET 2.5,3,3.5
2. O2
8. Umb. catheter 6-8 g
3. Ambu bag and mask- 750 ml
9. Drugs
4. Mucous sucker- bulb and dee
i. Epinephrin- 1 in 10 000
lee
ii. Na bicarbonate
5. Neonatal stethoscope
iii. Naloxone
6. Laryngoscope and 0,1 blades;
iv. Normal saline iv
batteries
v. 10% GDW
Universal precaution
1. Cap
4. Gloves
2. Mask
5. Imperviuos gown
3. Goggles
Resuscitation :
1. Place infant on warm table
5. Do not stimulate larynx
2. Towel dry and wrap
6. Chin up and head tilt
3. Place head in 15 extension
position
4. Suction mouth first then
nostrils

Apgar score:
Test

0 Points

1 Point

2 Points

31
Activity (Muscle Tone)

Absent

Arms & legs

extended

Pulse (Heart Rate)

Absent

Below 100 BPM Above 100 BPM

Grimace (Response
Stimulation or Reflex
Irritability)

No
Response

Facial grimace

Appearance (Skin Color)

Blue-gray, Pink body and

Normal over entire
pale all over blue extremities body Completely
pink

Respiration (Breathing)

Absent

Slow, irregular

Active movement
with flexed arms &
legs

Sneeze, cough, pulls

away

Good, crying

Primary vz secondary apnoea:

Primary apnea:
When infant is asphyxiated:
Responds with a increased respiratory rate.
Becomes apnic, followed by a drop in heart rate
Increase in blood pressure.
responds to stimulation and 02 therapy with spontaneous respiration
Secondary apnea
When asphyxia is allowed to continue:
The infant responds with a period a gasping respirations,
Falling heart rate, and blood pressure.
Takes a last breath and then enters the secondary apnea period.
Will not respond to stimulation and death will occur unless resuscitation
begins immediatelY.
Resuscitataion :
1. Apgar 8-10:
1. Pink; HR >100; no breathing; ? Primary apnea
2. Stimulation: flick the sole or run the back two attempts: Good response:
follow normal care
3. No response - ? Sec apnea
1. Apgar 5-7:
1. Blue; hr 100; breath regularly; breath regularly
2. O2 by mask 5l/mt
3. Baby turns pink
2. Apgar 3-4 :
1. Apneic; hr < 100; blue and pale: Sec. Apnea
2. Bag and mask with 100% o2
3. Pressure: first 40 cm water then 20 cm water
4. Rate 40/mt.
5. Turns pink and eupneic
3. Apgar 1-3:
Hr < 100:

32
1. Intubate
2. 100 % o2
Hr < 60:
3. Cardiac massage with bag: 3:1 ratio
4. Cardiac massage
4. Medication:
1. Cathedrize umb. Vein with saline filled cath.
2. Epinephrin 1:10000 .1 to .3 ml/kg
3. Normal saline 10 ml/kg
4. Bicarbonate 4 ml/kg of .5 mg/ml
5. Dopamine drip: 5-20 mic.g/kg/mt
5. Meconium aspiration:
1. No bag and mask
2. Vigorous suction
3. Intubation & suction of meconium through ET

FEVER

1. Normal temperature:
1. Adult core (rectal) temp: 36.4 c to 36.9 c with .4 c fluctuation
2. Infants rectal temp:
37 c and .8 c fluctuation during sleep
3. Circadian rhythm:
lowest at 4 am; highest temp at 6 pm
4. External temp
.5 less than core temp
2. Fever definition:
core temp >38 c
3. Thermometers:
1. Mercury:
i. Axillary; oral
ii. Rectal
iii. Low reading
2. Eletronic: Tympanic
3. Crystal : Forehead
4. Fever mechanism:

33
1. Thermoregulatory centre in ant hypothalamus is set to higher level by
i. Endogenous Pyrogens: cytokines; interferon; tumour necrosis factor
ii. Exogenous Pyrogens:
1. Microbes microbial toxins stimulation of
macrophagesendogenous pyrogens
2. Bacterial endotoxin stimulates Thermostat directly
3. Antigen antibody complex also stimulates endogenopus
pyrogens
2. Pyrogens stimulate preoptic area of hypothalamus to release prostaglandin
E2 which acts on the hypothalamus to raise the set point;
3. The hypothalamus maintains the set point at the elevated level until it is
reset downward by the disappearance of endogenous pyrogens or the
inhibition of prostaglandin synthesis (e.g., by antipyretic agents).
4. Thermoregulatory response of the body:
i. Vasodilatation or constriction
ii. Increase or decrease in sweating
iii. Vasopressin altering the volume of ECF
iv. Increase in muscle contractions-shivering
v. Behaviour: to move to warm or cool place
vi. Chills may be provoked by antipyretics that cause sudden decrease
of body temperature.
5. Circadian rhythm:
i. 1c less in early morning
ii. 1c more in evening
5. Causes of fever:
1. Infections
2. Vaccines
3. Tissue injury: infarction, pulmonary embolism, trauma etc
4. Malignancy : lymphoma, leukemia, hepatoma
5. Autoimmune disorders: Rheumatoid arthritis, Rheumatic fever, SLE
6. Drugs: cocaine, atropine, Amphotericin B and drug fever
7. Inflammation: ulcerative colitis, regional ileitis
8. Granulomatous disease: sarcoidosis: sarcoidosis is a noncaseating
granuloma that is formed in response to an exaggerated immune reaction
mediated by T-helper cells. The etiology is unknown, although increased
immunoglobulin M (IgM) and hyperglobulinemia against various infectious
agents are present.
9. Endocrine: thyrotoxicosis, pheochromocytoma (from adrenal medulla)
10.Metabolic : uremia, gout
11.Genetic disorders:
1. Nephrogenic Diabetes Incipitus
2. Reiley Dey syndrome: Riley-Day syndrome, is an autosomal recessive
disorder seen predominantly in Jews of eastern European descent.
Patients present with sensory and autonomic disturbances; a decreased
ability to feel pain or temperature sensations; inappropriate blood
pressure and body temperature fluctuations; trouble with feeding,
swallowing and gastrointestinal motility; hypotonia; developmental
delays; recurrent pneumonias (from aspiration); scoliosis and kyphosis;
increased sweating; transient skin blotching; and decreased stature.

34
3. congenital icthyosis
4. Hereditary periodic fevers:
1. Familial Mediteranean fever: The salient features of FMF include brief
recurrent episodes of peritonitis, pleuritis, and arthritis, usually with
accompanying fever. FMF occurs within families and is much more
common in individuals of Mediterranean descent than in persons of
any other ethnicity.mutation in chromosome 16 cause decrease in
pyrin that is necessary for inhibition of inflammatory mediators;
autosomal recessive
2. Tumor necrosis factor (TNF) receptorassociated periodic syndrome
(TRAPS)
3. Muckle-Wells syndrome (MWS): periodic episodes of skin rash, fever,
and joint pain. Progressive hearing loss and kidney damage; gene
mutations that cause Muckle-Wells syndrome result in a hyperactive
cryopyrin protein and an inappropriate inflammatory response; These
proteins are involved in the immune system, helping to regulate the
process of inflammation
4. Hyperimmunoglobulinemia D with periodic fever syndrome (HIDS)
5. Cyclic neutropenia: autosomal dominant; People with cyclic
neutropenia experience periodic neutropenia with subsequent
infections, followed by peripheral neutrophil count recovery
12. Factious fever:
1. Mnchausen syndrome is a term for psychiatric disorders known as
factitious disorders wherein those affected feign disease, illness
2. The syndrome name derives from Baron Mnchhausen ( 17201797)
who purportedly told many fantastic and impossible adventures about
himsel
3. Mnchausen syndrome by proxy is a more commonly known name
for Factitious Disorder by Proxy where a person deliberately causes
injury or illness to another person (most often his/her child)
12.Psycogenic fever?
13.Unknown etiology:
i. Kawasaki:
1. It is a self-limited acute vasculitic syndrome of unknown
etiology,
2. abnormality of immune system initiated by the infectious insult
3. Peak in 1-2 years; uncommon in < 3 mo and > 8 yrs
4. Fever, erythema of mouth, palms and soles and unilateral Cx
adenopathy
14.
Single spike:
i. Blood transfusion
ii. Drug infusion
iii. Surgical procedures and manipulations
iv. Catheterization
15.More than 41C
i. Usually non-infectious
ii. Hypothalamic dysfunction
iii. Malignant hyperthermia

35
6.

7.

8.

9.

iv. Heat stroke

Beneficial effects of fever:
1. Fever is established as a phylogenetically ancient host response that is
conserved highly in all mammals
2. It is an adaptive response and not a disease
3. the animals find the warmest spot in the environment and remain there
while their body temperature increases in response to the external stimulus
4. it decereases microbial reproduction
5. increases the rate of immune reactions
6. stimulates lymphocyte production
7. increase in interferon production
8. increase phagocytic activity
9. increases serum ferritin level that inhibits microbial growth
Adverse effects:
1. Increase:
i. O2 consumption
ii. CO2 production
iii. Cardiac output
iv. Increased in heart beats by 10 to 15 beats for 1
.;
v. CCF in anemia and CHD
vi. Pulmonary insufficiency in chronic lung disease
vii. Metabolic complications in diabetes
2. Febrile seizures in 6 months to 5 years
3. In epilepsy, prone for severe seizures
4. Dehydration
5. A fever greater than 106 degrees Fahrenheit can result in brain damage and
death
6. Increase the catabolism of proteins leading to loss of protein of 300 to
400grams per day
7. TNF- alpha and IL-1 cause the release of b-endorfins in the brain that
produce delirium
8. Herpes labialis. Increased body temperature may activate latent virus of
herpes simplex
9. High fever in pregnancy may be teratogenic
Temperature less than 36C:
1. Overwhelming sepsis
2. Hypothyroidism
3. Over use of antipyretics
Types of fever:
1. Intermittent: fever intervened by normal temperature
2. Continuous: less than .5 C variation
3. Remittent: more than .5 C variation
4. Relapsing:
i. Fever every 1&3 day: tertian
ii. Fever every 1&4 day: quartan
iii. Fever that occur daily: quotidian
5. Biphasic: camelback fever:
i. Poliomyelitis
ii. Leptospirosis
iii. Dengue

36
iv. Yellow fwver
v. Colorodo tick fever
6. Periodic fever:
i. Familial Mediteranean fever
ii. Tumor necrosis factor (TNF) receptorassociated periodic syndrome
(TRAPS)
iii. Muckle-Wells syndrome (MWS)
iv. Cyclic neutropenia
10.Physiological alterations:
1. Tacypnea
2. Tachycardia
3. Pulse-temperature dissociation:
i. Typhoid
ii. Brucellosis
iii. Leptospirosis
iv. Myocarditis with heart block
11.Treatment :
1. Less than 39C in healthy child need not be treated if febrile fits is not
anticipated
2. Antipyeretics:
i. Acts by inhibiting cyclooxygenase in hypothalamus and decreasing
PGE2
ii. Paracetamol: 10 to 15 mg/kg / dose; hepatic toxicity
iii. Aspirin contraindicated as it can precipitate Reye syndrome
iv. Ibupfofen: 5-10 mg; reduce renal blood flow
3. Non pharmacological:
i. Tapid sponging
ii. Ventilation
iii. Hydration
iv. Ice cooling in hyperpyrexia

37

Fever of Uncertain Origin (FUO)

1. Definition: Petersdorf and Beeson (1961):
i. Fever higher than 38.3oC on several occasions recorded by
health personnel
ii. Duration of fever 3 weeks as outpatient
iii. One week of study in hospital (as inpatient)
2. New Definition: Durack and Street in 1987
i. Eliminated the in-hospital evaluation requirements 3
outpatient visits, or 3 days in hospital.
3. Petersdorf in 1992 acknowledged the change in criteria and suggested a change
that 1 week hospital stay be changed to intelligent and intensive
investigationfor 1 week either in hospital or as outpatient
4. Expanded definitions:
i.
Classical PUO
iv. HIV-Associated PUO
ii. Nosocomial PUO
v. Transplant associated PUO
iii. Neutropenic PUO
5. Fever without a focus:
Acute onset of fever and present for less than a week without localizing symptoms
and signs and with no apparent infectious or noninfectious causes.
6. Hyperpyrexia: temperature more than 41C:
7. Clues for FUO evaluation:
i. Age:
1. <6years: respiratory, genitourinary tract infection, osteomyelitis, JRA,
rarely leukemia
2.
Adolescents: tuberculosis, inflammatory bowel disease, autoimmune
disease, lymphomas
ii. Exposure:
1. Wild or domestic animals: Zoonosis, leptospirosis
2. Pica: Toxocara, Toxoplasma
3. Visit to endemic area: malaria
4. Eye drops: atropine fever
iii. Genetic disorder in family: Nephrogenic Diabetes Incipitus; Reiley Dey etc

38
iv. Absence of sweating:
1. Nephrogenic diabetes insipitus
2. Unhydrotic ectodermal dysplasia
3. Familial dysautonomia(Reily Dey)
v. Red weeping eyes: polyarteritis nodosa
vi. Palpebral conjunctivitis:
1. Measles
2. Cocksackie
3. TB
4. Infectious mononucleosis
vii. Bulbar conjunctivitis:
1. Kawaski
2. Leptospirosis
viii. Conjunctival hemorrhage: infective endocarditis
ix. Uveitis:
1. Sarcoidosis
2. JRA
3. SLE
x. Chorioretinitis:
1. CMV
2. Toxoplasma
xi. Proptosis: orbital cellulitis
xii. Lack of tears:
1. Familial dysautonomia(Reily Dey)
2. Sjogren syndrome: ("Sicca syndrome") is an autoimmune disorder in
which immune cells attack and destroy the exocrine glands[2] that produce
tears and saliva. The hallmark symptoms of the disorder are dry mouth
and dry eyes
xiii. Sinus tenderness: sinusitis
xiv. Fever blisters: rules out enteric fever; staph infection
xv. Conjested pharynx:
1. Infectious mononucleosis
2. Kawaski
xvi. Bone pain and tenderness:
1. Osteomyelitis
2. Leukemia
xvii. Referred pain over trapezium: subdiaphramatic abscess
xviii. Tenderness per rectum: pelvic abscess
8. Lab:
i. CBC:
3. Poly < 5000:
a. no bacterial etiology
b. enteric fever
4. Poly>10000 and > bands : bacterial sepsis
ii. ESR:
5. > 30 mm: infallamatory conditions
6. >100 mm:
c. Autoimmune
d. TB
e. Kawasaki
iii. Blood culture: aerobic, anerobic, enteric and AFB
iv. Urine culture: mid stream of suprapubic

39
5. Mantoux: positive primary TB; Negative in sarcoidosis
6. Xray : Chest, sinus and mastoid
7. Bone marrow: Leukemia and MP
8. Lyumphnode: biopsy or FNAC: TB and lymphoma
9. Ultimate causes:

10.

11.

Infections

30 - 40 %

Malignancies

20 25 %

Collagen Vascular
Disease

10 20 %

Miscellaneous

15 20 %

Undiagnosed

10 15 %

Treatment:
1. Avoid empirical trials; it obscures diagnosis of infective endocarditis ,
meningitis etc
2. ATT if the child is critically ill and TB is suspected
Prognosis:
1. Children with FUO has better prognosis than adults
2. More often FUO is due to atypical presentation of a common illness
3. In 25% cases the diagnosis remains unclear

40

Floppy infant syndrome

1. Definition: Refers to an infant with generalised hypotonia presenting at birth or in
early life.
2. HISTORY:
a. Fetal movements are dinished in utero
b. The incidence of breech presentation is higher in foetuses with
neuromuscular disorders as turning requires adequate fetal mobility.
c. Birth anoxia, as hypoxic-ischaemic encephalopathy remains an important
cause of neonatal hypotonia.
d. Neonatal seizures and an encephalopathic state offer further proof that the
hypotonia is of central origin.
e. The onset of the hypotonia is also important as it may distinguish between
congenital and aquired aetiologies.
f. Enquire about consanguinity and identify other affected family members in
order to reach a definitive diagnosis, using a detailed family pedigree to
assist future genetic counselling.
3. Clinical clues on neurological examination:
a. There are two approaches to the diagnostic problem.
i. The first is based on identifying the neuro-anatomical site of the
lesion or insult. Careful neurological examination should, in most
cases, localise the site of the lesion to the upper motor neuron (UMN)
or lower motor neuron (LMN) unit
ii. The second is to determine whether or not the hypotonia is
accompanied by weakness. Weakness is uncommon in UMN
hypotonia except in the acute stages. Hypotonia with profound
weakness therefore suggests involvement of the LMN. Assessment of
muscle power of infants is generally limited to inspection.
b. Useful indicators of weakness are:
i. Ability to cough and clear airway secretions (cough test). Apply
pressure to the trachea and wait for a single cough that clears
secretions. If more than one cough is needed to clear secretions, this
is indicative of weakness.
ii. Poor swallowing ability as indicated by drooling and oropharyngeal
pooling
of secretions.
iii. The character of the cry infants with consistent respiratory
weakness have a weak cry.
iv. Paradoxical breathing pattern intercostal muscles paralysed with
intact
diaphragm.

41
v. Frog-like posture and quality of spontaneous movements poor
spontaneous movements and the frog-like posture are characteristic
of LMN conditions.
vi. Excessive head lag will be evident on pull to sit.
vii. Minimal support with a sensation of slipping through the hands
during vertical suspension testing and inverted U position on ventral
suspension are further indicators
c. A distinct pattern of weakness may favour certain aetiologies:
i. Axial weakness is a significant feature in central hypotonia.
ii. Generalised weakness with sparing of the diaphragm, facial muscles,
pelvis and sphincters suggests anterior horn cell involvement.
iii. With myasthenic syndromes, the bulbar and oculomotor muscles
exhibit a greater degree of involvement.
iv. Progressive proximal symmetrical weakness suggests a
dystrophinopathy. Signs of proximal weakness in the older infant
include a lordotic posture, Trendelenburg gait (waddling) and Gower
sign. A striking distribution of weakness of the face, upper arms and
shoulders suggests fascioscapulohumeral muscular dystrophy.
v. Distal muscle groups are predominantly affected with peripheral
neuropathies. Signs suggesting distal weakness in an older infant
would include weakness of hand grip, foot drop and a high stepping,
slapping gait.
vi. Toungue:
1. Examine the tongue for size and fasciculations. Fasciculations,
irregular twitching movements, generally indicate an
abnormality of the anterior horn cells. Do not examine the
tongue while the infant is crying.
2. The co-existence of atrophy would strongly favour a
denervative aetiology.
3. Enlargement of the tongue may suggest a storage disorder
such as Pompes disease.
vii. An ECG may be helpful in demonstrating baseline fasciculations of
the intercostals muscles.
viii. The presence of a facial diplegia (myopathic facies; mask like)
suggests either a congenital myopathy or myasthenia gravis.
ix. Respiratory and bulbar weakness can accompany both conditions.
x. Fluctuation in strength would favour myasthenic syndromes
xi. Where clinical evaluation suggests complex multisystem involvement
(i.e.hypotonia plus) inborn errors of metabolism should be excluded.
THE FLOPPY STRONG CHILD
1. The presence of facial dysmorphism should alert the doctor to the possibility of an
underlying syndrome or genetic disorder.
a. Conditions that need to be excluded include:
i. Trisomy 21
ii. Prader-Willi: obesity; small hands and feet, almond shaped eyes,
narrow bifrontal diameter and hypogonadism. DNA methylation study
which will detect 99% of cases.

42
iii. Zellweger syndrome: high forehead, wide patent fontanelles and
sutures, shallow orbital ridges, epicanthus and micrognathia.
Neurological manifestations are dominated by severe hypotonia with
depressed or absent tendon reflexes, and poor sucking and
swallowing. Hepatomegaly and liver dysfunction are consistent
findings.
b. A karyotype is a must in the dysmorphic hypotonic child. This can be
combined with FISH testing if Prader-Willi syndrome is suspected. Cranial
MRI will identify patients with structural CNS malformations, neuronal
migration defects and those with white matter changes (congenital
muscular dystrophies in particular).
2. Hypotonia may also be prominent in connective tissue diseases such as Ehlers
Danlos or Marfans syndrome. An excessive range of joint mobility, unusual joint
postures, and the ability to do various contortions of the limbs and/or
hyperelasticity of the skin are important diagnostic clues.
3. Although metabolic disorders are well recognised as the cause for central
hypotonia, because of the rarity of the conditions, the diagnostic yield is low. Very
long-chain fatty acids (VLCFA) testing should be performed if a peroxisomal
disorder such as Zellweger is suspected.
SUSPECTED PERIPHERAL CAUSE
1. genetic analysis: of the muscular dystrophies, spinal muscular atrophies and
hereditary neuropathies.
2. Examples include:
a. spinal muscular atrophy: polymerase chain reaction (PCR) testing for a
deletion of the survivor motor neuron (SMN) gene and
b. congenital myotonic dystrophy: expansion of cytosine thymine guanine
(CTG) triplet repeats.
c. Duchenne muscular dystrophy: DNA Xp21 deletion testing (PCR assays) can
confirm the diagnosis in 65% of males with and 80% of males with Beckers
muscular dystrophy.
d. Only in the remaining cases is muscle biopsy still advocated.
e. Muscle enzymes levels (creatine kinase assay) are rarely helpful in the
floppy infant, with the exception of muscle disorders where creatine kinase
values are elevated, such as congenital muscular dystrophies and in some
of the congenital structural myopathies.
3. Electromyography (EMG):
Neuropathic disease:
An action potential amplitude that is twice normal due to the increased
number of fibres per motor unit because of reinnervation of denervated
fibres
An increase in duration of the action potential
A decrease in the number of motor units in the muscle (as found using
motor unit number estimation techniques)
Myopathic disease:
A decrease in duration of the action potential
A reduction in the area to amplitude ratio of the action potential

43
A decrease in the number of motor units in the muscle (in extremely severe
cases only)
4. Nerve conduction studies are useful in the investigation of hereditary motor
sensory neuropathies and distinguishing axonal from demyelinating disorders.
5. Molecular DNA testing can then be used for specific demyelinating disorders.
6. Muscle biopsy:
a. Variation in size and shape of muscle fibers
b. Increase in connective tissue
c. Fatty infiltration
d. Areas of degeneration and regeneration
e. Inflammatory changes
f. Centralized nuclei

PRINCIPLES OF MANAGEMENT
1. Regular physiotherapy will prevent contractures.Occupational therapy is important
in facilitating activities of daily living.
2. Vigorous treatment of respiratory infections is indicated.
3. Annual flu vaccination is necessary.
4. Annual orthopaedic review is required to monitor for scoliosis and to exclude hip
dislocation/ subluxation.
5. Feeding intervention by nasogastric tube or gastrostomy will benefit the
undernourished child. Maintenance of ideal weight is important, as excessive
weight gain will exacerbate existing weakness.
6. Children with neuromuscular disorders deserve special attention when it comes to
anaesthesia. The anaesthetist should be forewarned about the possibility of an
underlying muscle disease even if the child has very mild or non-existing
symptoms. A family history of muscle disease or mild hyper-CK-aemia may be of
importance.
7. Muscle relaxants should only be used if essential because of their more profound
and prolonged effect in myopathic children.
8. All children with neuromuscular disease should also be considered potentially
susceptible to malignant hypothermia (the strongest correlation is with central
core disease) and implicating agents should therefore be avoided.
9. Ethical considerations such as the appropriateness of cardiopulmonary
resuscitation in the event of cardiac arrest or acute respiratory failure need to be
addressed sensitively.
Clincical clues and investigations of the more common phenotypes of the
floppy weak infant
Spinal cord transection or
Haemangioma or tuft of hair in midline
MRI spinal cord
disease Scoliosis
Syringomyelia or other forms
Evidence of bladder or bowel dysfunction
MRI spinal cord
of spinal dysraphism
Mixed deep tendon reflexes with absent
abdominal and anal reflexes

44

Spinal muscular atrophy

Tongue atrophy and fasciculations
Baseline fasciculations
Paradoxical breathing pattern
survival
Severe proximal muscle weakness with
(SMN) gene by PCR
absent tendon reflexes testing
Preserved social interaction
Peripheral neuropathy
nerve conduction

ECG:
Deletion of the
motor neuron

Weakness predominantly distal

Motor

In most cases absent deep tendon reflexes studies

Pes cavus
Sural nerve biopsy
Molecular DNA
testing if
available for specific
demyelinating
disorders
Myasthenia gravis
to acethylcholine

Greater involvement of oculomotor and

Response

bulbar muscles
esterase
inhibitors
True congenital myasthenia due to receptor Single-fibre EMG
defects is rare
Serum antibodies
to
Exclude transient neonatal form from
acethylcholine
receptors
maternal history
Electrodiagnostic
studies not
universally positive in
young
patients
Infantile botulism
organism from

Acute onset descending weakness,

cranial neuropathies, ptosis,

unreactive pupils, dysphagia,
in the stool
constipation

Isolation of
stool culture
Presence of toxin

Congenital muscular
Hypotonia, weakness and contractures
Creatine kinase usually
dystrophy
at birth
elevated

45
Associated brain and eye problems
structural and

Brain

MRI

for

white
matter
abnormalities
Muscle biopsy: merosin
stain
Congenital myotonic
DNA testing by
dystrophy
CTG

Polyhydramnios with reduced fetal

movements

Molecular

determining number of

Inverted V-appearance of the mouth

repeats (normal
range 5 - 39
Examination of mothers face shows inability repeats)
to bury her eyelashes and grip myotonia
EMG of the
mother
Premature cataract surgery in the mother
Congenital structural
EMG usually not
myopathy

Slender stature

CK

and

Hypotonia with feeding problems at birth

helpful
Weakness that is often non-progressive
Muscle biopsy is
critical for
Nemaline myopathy: often associated with
definitive
diagnosis.
feeding problems
ECG when nemaline
and
Central core: most often associated with
desmin
myopathies are
malignant hyperthermia
suspected
Myotubular myopathy: Ptosis and
The genetic basis
for several
extraocular palsies consistent
of the congenital
myopathies
clinical features
has
now
been
determined

Glycogen storage disease

Enlarged heart in a very floppy weak
Blood
smear vacuolated
Pompes disease
newborn
lymphocytes
Unexplained cardiac failure
Urine
oligosaccharides
Tongue may appear large
Typical ECG and ECHO
changes
Acid maltase assay in
cultured fibroblasts

46
Muscle

biopsy usually

not
necessary

47

Acute bacterial meningitis beyond neonatal period

1. Introduction
Meningitis is an inflammatory process of the membranes of brain and spinal
cord and CSF
Potentially serious infection of CNS
Increased mortality
High rate of complications
Long term morbidity
2. Etiology
Age: Less than 2 months:
Maternal flora:
Group B Streptococcus
Listeria monocytogenes
H.influenza. B
2 mo to 12 yrs:
Pneumococcus
Meningococci
Hi.b
Altered immunity
Psuedomonas
Staphylococcus
Salmonella
Predisposing factors
3. Predisposing factors:
Altered immune defense
Splenic dysfunction (sickle cell)
Asplenia syndrome
CSF leak :
o Fracture skull
o Dermal sinus
Pre auricular sinus
Pilonidal sinus
o Spinal Meningocoel
CSF shunt infection
1. Pathophysiology
a. Transmission:
i. Droplet: Person to person Colonization of nasopharynx
Bacteremia
ii. Hematogenous spread from:
1. ASOM

48
2.
3.
4.
5.
6.

Sinusitis
Pneumona
Osteomyelitis
Endocarditis
Abscess

2. Pathology
a. Meningeal exudation
b. Ventriculitis
c. Vasculitis
d. Thrombosis
e. Increase in ICP
f. Cranial neuropathy
g. Hydrocephalus
h. Subdural effusion
3. Clinical manifestations
a. Rarely dramatic onset and sudden death in 24 hrs
b. Insidious onset:
i. Fever
ii. Head ache
iii. Photophobia
iv. Irritability
v. Lethargy
vi. Altered sensorium
vii. Convulsions
viii. Coma
4. Clinical signs
i. Nugal rigidity
ii. Kernig sign : Flexion of hip to 90 and extension of knee produce
pain
iii. Brudzinki sign: Flexion of neck produces flexion of hip and knees
iv. Bulging fontannel
v. Sutural widening
vi. Iv , vi, vii, viii cranial nerve palsy
vii. Focal deficits
viii. Tache cerebrale: Stroke skin with a blunt instrument 30-60 sec
raised red rash
ix. Convulsions
5. Causes for Convulsions
i. Cerebritis
ii. Ventriculitis
iii. Cerebral abscess
iv. Infarction
v. Syndrome of Inappropriate ADH secretion & electrolyte
disturbances
vi. Hypoglycemia
vii. Vascular thrombosis

49

6.

7.

8.

9.

viii. Subdural effusion

Lumbar puncture
a. Normal CSF
i. Colour:
clear
ii. Glucose:
60% of blood level; 50 to 80 mg/dl
iii. Protein:
15-35 mg/dl
iv. Chloride:
116-122
v. Pressure:
100-200 mm of water
vi. Cells:
< 5 lymp
vii. CSF in meningitis
b. Bacterial
1. Pressure:
>200 mm H2O
2. Colour:
opalescent
3. Cells:
200-2000 WBC/ml (pmn)
4. Protein:
>130 mg/dl
5. Glucose:
<2.5 mmol/l
c. Viral
1. Cells:
0-200 WBC/ml (lym)
2. Protein:
<40 mg/dl
3. Glucose:
2.5-3.6 mmol/l
Contra indication for L.P:
a. Increased intra cranial pressure
b. Shock
c. Skin infection at the site
d. Thrombocytopenia
e. Suspected brain abscess
Intra cranial pressure
a. Normal <160 mm of water
b. ICP > 300 mm of water
c. Causes:
i. Cell death cytotoxins
ii. Increased permeability cytokines
iii. CSF obstruction arachnoiditis; venriculitis
iv. Water retention syndrome of inappropriate ADH (SIADH)
v. Symptoms of ICP
d. Head ache and vomiting
e. 3 0r 6 nerve palsy
f. Bradycardia
g. Irregular respiration
h. Papilledema
Complications
a. Hydrocephalus
i. Arachnid adhesions
ii. Fibrosis of aqueduct
iii. Obstruction of foramen of Megendie and Luschka
b. Subdural effusion:

50
i. Common in H.influenza
ii. Collection of fluid in subdural space
iii. Bulging fontanel
iv. Sutural widening
v. Increase in head circumference
vi. Convulsions and
vii. fever
10.
Complications
a. Epilepsy
b. Cr n palsies
c. Stroke
d. Dural sinus thrombosis
e. SIADH
f. Deafness
g. Mental retardation
h. DIVC
11.
Syndrome Of Inappropriate ADH Secretion
a. Failure of osmoreceptors in the hypothalamus
b. Excessive release of ADH from the post pituitary
c. Fluid retention
d. Delusional hyponatremia
e. Headache
f. Convulsions
12.
Meningococcemia
Neisseria meningitides:
a. Waterhouse-friderichsen syndrome:
i. Hemorrhagic adrenalitis with adrenocortical insufficiency
ii. Overwhelming bacterial infection
iii. Shock
iv. Disseminated i ntravascular coagulation(DIC)
v. Widespread purpura
b. Petechiae over skin
13.
Prognosis of meningitis
a. Mortality 10 %
b. High in pneumococcal
c. High in < 6 yrs of age
d. High in convulsions persisting for than 4 days
14.
Treatment
a. Blood and CSF c&s
b. Vancomycin 60 mg/kg in 4 % doses
c. Cefotaxim 200 mg/kg in 4 % doses
d. Ceftrioxone 100 mg/kg in single dose
e. Choremphenicol 100 mg/kg in 4 % doses
f. Listeria: ampicillin 200 mg/kg in 4 % doses
g. Duration: 10-14 days
h. Steroids:

51

15.

16.

i. Helps in suppressing inflammation

ii. Dexamethazone .15 mg/kg dose 6 hrly for 2 days
i. SIADH
i. IVF reduced to to 2/3 dose
j. ICP
i. Hyperventilation with o2
ii. IV lasix 1 mg/kg
k. Convulsions:
i. IV diazepam .1 to .2 mg/kg/dose
ii. Phenytoin 15 to 20 mg/kg/ loading followed by 5 mg/kg
maintenance
Prognosis
a. 10 % mortality
b. More in pneumoccocal
c. More in children < 6 yrs
d. Convulsions persisting for more than 4 days has poor prognosis
Prevention
a. Hib vaccine
b. Menigococcal vaccine
c. Expossure to infection:
i. Rifampicin 10 mg/kg for 4 days

52

ENCEPHALITIS & ENCEPHALOPATHY

1. Introduction:
Potentially serious infection or inflammation of CNS
Increased mortality
High rate of complications
Long term morbidity
2. Definitions:
Meningitis:
o Inflammatory process of the membranes of brain and spinal cord and csf
Encephalitis: aseptic meningitis syndrome
o Inflammation of the brain parenchyma
Meningoencephalitis:
o Inflammation of the meninges and brain parenchyma
Cerebritis:
o Bacterial infection of brain tissue, and abcess formation
Encephalopathy:
o Generalized disorder of cerebrum without CSF pleocytosis
3. Encephalitis:
a. Features:
i.
Inflammation of meninges and brain
ii.
CSF inflammatory cells
iii.
No organisms in Gm stain
iv.
Bacterial culture negative
b. Etiology :
Enterovirus:
i.
Poliomyelitis
ii.
Coxsackie
iii.
Echo (ev9)
Arbo virus:
i.
Westnile
ii.
St.louiz
iii.
Japanease encephalitis
iv.
Tick-borne virus
Herpez:
i.
Hsv i, ii, vi
ii.
Varicella zoster
Cmv
Epstein bar virus
Mumbs
Rabies
Rubella
Vaccine virus

53
i.
Polio, mumps, measles
Acanthamoeba: swimming pool & contact lens
2. JAPANESE ENCEPHALITIS :
A flavi virus (single-stranded rna)
Transmission - c. Tritaeniorhynchus, culex vishnui (india),
Amplifying hosts - pigs and aquatic birds ( egrets, herons)
Subclinical: resolve in a few days
Clinial: neurotoxic effects in brain cells and neural stem cells.
major neurologic sequelae including seizure disorders, motor or cranial
nerve paresis, or movement disorders.
Case-fatality rates range from 1 % to 60%.
3. Encephalitis:
Pathogenesis:
Local replication in the skin or mucosa
Hematogenous dissemination -JE
Neuronal retrograde dissemination- rabies : peripheral nerve; HSV :
alfactory tract
primary viremia leads to seeding of the reticuloendothelial system
Secondary viremia leads to seeding of other sites, including the CNS
Pathology
Variable degrees of meningitis, cerebral oedema, congestion, and
haemorrhage
Perivascular cuffing: the accumulation of lymphocytes or plasma cells in
a dense mass around the vessel.
Demyelination
Hydranencephaly: brain tissue replaced by sacs filled with csf
Neuronal damage
Gliosis
4. CLINICAL FEATURES
CLINICAL SPECTRUM
Subclinical - iceberg
Variable severity
Mild illness with complete recovery or coma and sudden death

TYPICAL ILLNESS:
Head ache, fever, irritability
nausea, vomiting
Retro bulbar pain
Photophobia
Altered sensorium
Convulsions
Stupor
Coma

54

PARALYSIS
Static , Progressive or Fluctuating
Flaccid or spastic
Bladder bowel dysfunction
Emotional outbursts
Cerebral edema and elevated ICP
EEG:
Slow wave patterns

CT/MRI:
Brain edema; necrosis
Focal lesions in HSV
ENCEPHALOPATHY:
1. Etiology:
Infections:
Tb, enteric fever, shigella
Hiv
Toxic:
Co, lead, aspirin, alcohol

Metabolic:
Bilirubin, uraemia, hypoglycemia
Hypoxia
Hypoxic ischemic encephalopathy
Hypertension
Nephritis
Hereditory:
Mitochondrial encephalopathy
Myoclonic encephalopathy of childhood
Slow virus (prions)
Creutzfeldt-jakob disease
Kuru

Subacute sclerosing pan encephalitis(sspe)

Leukemia
Punch drunk syndrome (traumatic)
1. REYE SYNDROME:
Acute non inflammatory encephalopathy and hepatic failure.
After a viral illness like influenza and varicella
Associated with the use of aspirin during the illness
Inborn errors of metabolism may be a predisposing factor
Mitochondrial dysfunction
Follows an apparent recovery from viral illness
2. Stages of Reye syndrome
Stage 1 - vomiting, sleepiness, and lethargy

55
Stage 2 - restlessness, irritability, disorientation, delirium,
Stage 3 - obtunded, comatose, decorticate rigidity,
Stage 4 - deep coma, decerebrate rigidity, fixed and dilated pupils, loss of
oculovestibular
reflexes,
Stage 5 - seizures, flaccid paralysis, absent deep tendon reflexes, no pupillary
response, and
respiratory arrest
3. DIAGNOSIS OF REYE SYNDROME
Altered level of consciousness; convulsions
Increase in SGOT, SGPT and ammonia
Hypoglycemia
normal CSF but increase in ICP
No jaundice
Brain biopsy with cerebral edema without inflammation
Mortality > 40%

56

Anemia
Introduction:
1. Stem cell is the precursor of RBCs
2. Erythropoiesis: erythropoietin directs stem cells into the production of myeloid
precursors:
a. Proerythroblast early erythroblast late erythro blast normoblast
reticulocytepolychromatic cells RBC

3. Erythropoietin (epo)
a. Hormone produced by the kidney in nb and by liver in fetus
b. Promotes the formation of red blood cells
c. Kidney cells make and release erythropoietin in response to hypoxia
d. Action through mrna
4. Red blood cell distribution width:
a. A measure of the variation of RBC size.
b. Red blood cells of unequal sizes, is known as anisocytosis.
c. Normal rdw is 11 - 14%.
d. Iron deficiency anaemia shows an increased rdw.
e. Rdw = ( standard deviation of mcv mean mcv) 100
5. Normoblasts:
a. Full metabolic functions
b. Low o2 carrying capacity
c. Looses nucleus by extrusion

57

6. Reticulocytes
a. 1% of the red cells
b. Develop and mature into RBC
c. Have a reticular network of ribosomal rna
d. Visible with methylene blue

7. Poikilocytosis
Difference in shape of RBCs:eg.
i. Microcytes
ii. Spherocutes
iii. Ovalocytes
iv. Tear drop cells

8. RBC:
a.
b.
c.
d.
e.
f.
g.
h.

Looses nucleus to accommodate Hb

Increased 02 carrying capacity
Flexible disc
Contain 40 enzymes
No mitochondria
ATP by anaerobic and pentose pathway
Energy needed to keep iron in ferrous state and to neutralize oxidants
60-90 days life span

58
i.

Utilize glucose without insulin

9. Normal values
1. HB%: male:
2. RBC count:
3.
4.
5.
6.

13.8 to 17.2 gm/dl; female: 12.1 to 15.1 gm/dl

male: 4.7 to 6.1 million cells/mcl;
Female: 4.2 to 5.4 million cells/mcl
Mcv:
80 to 100 femtoliter(fl)
Mch:
27 to 31 picograms/cell
Mchc:
32 to 36 grams/dl
Packed cell volume (pcv): 48% for men and 38% for women.

Anemia:
10.
Definition: hg% < 2 standard deviations below the mean for age with
1. Reduced HB%
2. Reduced PCV
3. Reduced RBC count
11.
Anaemia is a sign of an underlying pathology (it is not a diagnosis)
12. Classification of anemia:
I. Etiologic classification
v. 1. Impaired RBC production
vi. 2. Excessive destruction
vii. 3. Blood loss
Ii. Morphologic classification
viii. 1. Macrocytic anemia
ix. 2. Microcytic hypochromic anemia
x. 3. Normochromic normocytic anemia
Types of RBCs
1. Normocytic
2. Microcytic
3. Macrocytic
12.
Iron deficiency anaemia
i. Calculation of daily requirement:
1. Iron content of newborn is .5gm ; adult is 5 gm
2. 0.8 mg should be absorbed daily for 15 years to reach this value.
3. Loss of iron is 1 mg/day through hair, epithelium and neils

59
4. 1 mg /day is the daily requirement
5. Only 10% is absorbed from the gut
6. Hence 10 mg is the daily requirement
ii. Causes so iron deficient anemia:
30% of world population is anemic
Newborn:
1. Early cord clamping < 2 mts.
2. Blood sampling
Infants:
1. Milk has less iron
2. Lack of cereal diet
3. Cows milk allergry
4. Peptic ulcer
5. Meckels diverticulitis
6. Rectal polyp
7. Hemaangioma
8. Chronic diarrhea
Adolescents:
1. Growth spurt
2. Menstrual loss
3. Iron chelators- eg. Tea
4. Iron deficient food- faddism
5. Peptic ulcer
6. Hook warm
7. Helicobacter pylori infection of stomach
13.
Symptoms:
1. Chronic anemia is compensated
2. Acute or severe anemia: symptoms develop
3. Pallor
4. Tiredness, easy fatigability and irritability
5. Generalized muscle weakness
6. Phagophagia and pica
7. School failure
8. Loss of hair
9. Cardiac de compensation
14.
Physiologicl anemia of infancy:
1. Fetus lives in sterile condition and less need for wbc
2. Lives in hypoxic condition and hence need for RBCs more
3. Site of production of RBC from fetus to nb:
a. Yolk sac (mesoblastic erythropoiesis)
b. Liver (hepatic erythropoiesis)
c. Bone marrow ( myeloid erythropoiesis)
4. Normal values in NB:
1. Newborn:
I.
Pcv: 45-65%
II.
Reti. Count: 2-8%
III.
Hb: 16-18gm%
2. 6-8 weeks (Physiological anemia of infancy)

60
i. Hb: 10 gm%
ii. Pcv 30%
3. Causes of physiological anemia:
i. Decreased RBC life span
ii. Decreased eryhtropoietin
iii. Rapid increase in body weight
15. Lab tests:
1. HB%
2. Pcv
3. Serum ferritin
4. Serum iron
5. Iron binding capacity
6. Blood smear study
7. Stool occult blood
8. Bone marrow
16.
Differential diagnosis of Microcytic hypochromic anemia:
1. Thalassemia trait & Hb E disease
a. Hb A2 increased
b. Hb F increased
c. Serum iron and IBC normal
2. Lead poisoning:
a. Basophilic stippling
b. Free erythro protoporphyrin (FEB) increased
3. Sideroblastic anemia:
a. Amino levulinic acid synthase deficiency
b. Defective heme synthesis
c. Sideroblasts in peripheral smear
4. Atransferrinemia
a. No stainable iron in normoblasts
Basophilic stippling:

17.

Treatment:
1. Ferrous sulphate best absorbed
a. Bad taste,
b. Gastric upset
c. Constipation
d. Contains 20 % elemental iron
e. 4-6 mg / kg in 3 divided doses
f. Treat for 8 weeks

Sideroblasts:

61

18.

b. Response:
a. Hb raises by .5 gm / day
b. Reticount increases
2. Blood transfusion:
a. Rarely necessary
b. Precipitates ccf
c. Give 2-3 ml/kg packed cells
Prevention:
a. Iron fortified formula
b. Reduce milk intake to 500 ml/day
c. Iron rich food:
a. Vegetarian: leafy vegetables; cereals
d. Non vegetarians:
a. liver, meat, kidney etc
e. Avoid iron chelators
a. Tea, coffee, phytates in green leaves

Malaria
Questions:
1. Describe the clinical features, investigations and treatment of a child
suffering from cerebral malaria. Sep 2002
2. S.n:
a. Management of cerebral malaria. Oct. 2003
b. Toxicity of antimalarial drugs. Aug 2004
c. Black water fever. Nov. 2001
1.
Definition:

62

2.

3.

4.

5.

6.

7.

Malaria is an acute and chronic illness characterized by paroxysms of fever, chills,

sweats, fatigue, anemia and splenomegaly.
Etiology:
Caused by intracellular parasite plasmodium protozoa; 4 species:
1. Falciparum
2. Malariae
3. Ovale
4. Vivax
Transmitted by:
1. Female anopheles mosquitoes
2. Blood transfusion
3. Contaminated needles
4. Trans placental to fetus
5. Organ transplant
Epidemiology:
1. Occurs in > 100 countries
2. P. Falcifarum and p.malariae are found in most places
3. P. Vivax is the predominant type in india
Pathogenesis:
1. Asexual phase in human; sexual phase in female anopheles mosquito
2. Thrive in different cells and different host species
3. Two step process in human to amplify the no of parasites
4. The exoerythrocytic phase begins with inoculation of sporozoites by female
anopheles mosquitoes
5. Schizonts develop in hepatocytes and released into blood stream as merozoites
(1-2 weeks).
6. P.falciparum and p.malaiae have only one phase in hepatocytes.
7. P.ovale and p.vivax release merozoites after 6-9 days; hepatic phase persists
up to 5 years to cause relapse.
8. Merozoites enter RBCs to develop into ring forms and then to trophozoites
9. Trophozoites multiply and released as merozoites by rupturing RBCs.
10.Some trophozoites in RBC develop into gametocytes to enter sexual cycle in
mosquitos.
Pathologic process:
1. Fever during release of merozoites from RBC
2. Anemia due to:
1. Haemolysis
2. Sequestration of RBCs in spleen
3. Bone marrow suppression
Immunopathology:
1. Intracellular parasites killed by macrophages, RES (spleen); extracellular
parasites killed by antibody mediated immunity
2. Immunity is not complete; does not eradicate or prevent reinfection;
prevents only severity of disease.
3. Immune mediated disorders:
1. Immune complex formation
2. Immune depression
3. Cytokine mediated tissue hypoxia
4. Hyper gammaglobulinemia

63

8.

9.

5. Cyto adherence of infected erythrocytes in capillary

endothelium and vascular obstruction due to falcifarum sp with
leakage of blood, fluid and proteins and result in tissue
hypoxia.
6. Hypoglycaemia lactic acidosis due to anaerobic metabolism
7. No sufficient immunity after infection and hence re infections
can occur
8. Cumulative effects of above factors lead to multi organ failure
9. Hb F resist p.falciparum; hence newborn shows resistance to
malaria
10.Severe disease in pregnancy and infancy
Resistance to malaria:
c. Hb s resists malarial infection in general
d. Lack of blood group duffy resists p.vivax
e. Hb.f and ovalocytes resist p.falciparum
f. Newborn is resistant due to hb.f and maternal antibodies.
g. 3 m to 5 yrs: lack of immunity and develop severe disease
h. Severe disease in pregnancy
Clinical features:
i.
Incubation:
1. P.falciparum
9-14 days
2. P.vivax
12-17 days may go up to 12 months or more.
3. Hypnozoites are responsible for long incubation and late relapses in
these two species of malaria.
i. P.ovale
16-18 days
ii. P.malariae
6-12 months
ii.
Prodrome:
i. 2-3 days
ii. Headache
iii. Fatigue
iv. Anorexia
v. Myalgia
vi. Mild fever
vii. Pain chest and abdomen and joints
iii.
Illness:
i. Paroxysms of fever alternate with wellness
ii. Fever coincides with rupture of RBCs and release of merozoites
iii. Chills, swaets, headache, myalgia, nausea, vomiting, diarrhea,
pallor, and jaundice.
iv. Periodicity:
1. P.vivax and ovale
every 48 hrs
2. P.malairae
every 72 hrs
3. P.falciparum
less periodicity
4. Mixed infections
iv.

Children:
i. High fever
ii. Drowsiness
iii. Lethargy
iv. Cyanosis

less periodicity

64

10.

11.

v. Hepatoslenomegaly
vi. Convulsions
vii. Hypoglycaemia
viii. Hyperkalemia
ix. Acidosis
x. Dehydration
v.
Recrudescence:
relapse of fever due to dormant parasites
a. From liver:
p. Vivax and p.ovale
b. From RBC: p.malariae
vi.
P.falciparum features:
a. Intense parasitemia > 60% (others only 2%) due to invasion of both
mature and immature RBCs;
b. High fatality
vii.
P.vivale:
a. Can cause death due to splenic rupture
b. Relapse from hepatic phase from 6 m to 5 yrs
viii.
P.malariae:
a. Low parasitemia
b. Infects only mature RBCs
c. Mildest form of malaria
d. Chronic infection
e. Recrudescence even after 30 yrs
ix.
P.ovale:
a. Least common
b. Acute and chronic
c. Can occur in conjunction with P.falciparum
Congenital malaria:
1. Abortion
2. Still birth
3. Prematurity and IUGR
4. Neonatal death
5. Affected NB may show fever, pallor, jaundice, and hepatosplenomegaly.
Cerebral malaria:
1. Pathophysiology:
i. Cerebral malaria is the most important complication of falciparum
malaria.
ii. The basic underlying defect seems to be clogging of the cerebral
64icrocirculation by the parasitized red cells.
iii. This results in sequestration of the parasites in these deeper blood
vessels.
iv. Obstruction to the cerebral microcirculation results in hypoxia and
increased lactate production due to anaerobic glycolysis.
v. Eeg may show non-specific abnormalities.
vi. Ct scan of the brain is usually normal.
vii. White retina is characteristic of malarial retinopathy.
2. Clinical features:
i. High-grade fever and failure to eat and drink.
ii. Vomiting and cough are common.

65
iii.
iv.
v.
vi.
vii.

12.

Coma persists more than 30 minutes after a convulsion

Deep breathing due to acidosis
Cold, clammy skin due to shock
Opisthotonus posture, mimicking either tetanus or meningitis.
Neurological signs:
a. Symmetrical upper motor neuron and brain stem disturbances
b. Diconjugate gaze, decerebrate and decorticate postures.
c. Unarosable coma
d. Corneal reflex and 'doll's eye' movements may be absent.
e. Retinal haemorrhages and exudates are rarer than in adults.
f. CSF examination in cerebral malaria is usually normal;
g. Increase in pressure, protein level and cell-count (mostly
lymphocytes, 50cells/ml) may be seen.
3. Other features:
i. Exclusion of other causes of encephalopathy, i.e. Viral or bacterial.
ii. Severe anaemia
iii. Acute renal failure
iv. Pulmonary oedema or adult respiratory distress syndrome (ards).
v. Hypoglycaemia
vi. Circulatory collapse, shock, hypotension
vii. Spontaneous bleeding/disseminated intravascular coagulation.
viii. Jaundice
Diagnosis:
a. All fever in endemic areas is due to malaria unless proved otherwise.
b. P.falciparum: ring forms with double chromatic dots; RBC with more than
one parasites
c. Microscopy:
Thick smear
1. Make thick smear by joining the 3 drops of blood and spreading it with
corner of another slide. Correct thickness is attained when newsprint is
barely legible through the smear.
2. It should be 10 mm diameter; 10 mm away from the edge of the slide;
contains 10 layers of RBCs and 10 wbcs should be visible per oil immersion
field of microscope.
Thin smear
1. With the edge of the slide spread a new drop of blood to the surface of the
first slide. Air dry, allowing 10 minutes for the thin smear.
2. It is uniformly spread over the slide. It is tongue shaped. Thin enough so
that a newsprint can be read through the smear. Consists of a single layer
of RBCs.
3. After drying, only thin smear is fixed by dipping thin smear into methanol
for 5 seconds.
Staining:
1. Giemza staining:
Dry; fix thin smear with methanol and not thick smear; add 3% giemza
stain; allow 30-45 mts; wash with water; dry.
2. Jsb stain:

66
After dehemoglobinisation by treating with dw for 10 mts, dip the thick
smear in jsb ii stain two to three times.
Wash it by dipping in buffer water two to three times. Then keep the thick
film dipped in jsb i stain for 40-60 seconds. Wash it with buffer water. Drain,
dry and examine.

13.

14.

Rapid diagnostic tests:

1. Immunochromatographic tests:
Are based on the capture of the parasite antigens from the peripheral blood
using specific antibodies.
The tests can target the histidine-rich protein 2 of P. Falciparum, a panmalarial plasmodium aldolase, and the parasite specific lactate
dehydrogenase.
These RDTs do not require a laboratory, electricity, or any special
equipment.
If the target antigen is present in the blood, a labelled antigen/antibody
complex is formed and permits visualization as coloured lines.
2. Quantitative buffy coat (qbc) test:
Qbc test, is a new method for identifying the malarial parasite in the
peripheral blood. It involves staining of the centrifuged and compressed red
cell layer(buffy coat) with acridine orange and its examination under uv
light source.
Treatment:
1. Uncomplicated malaria:
Drugs
Tab. Chloroquine
Primaquin

Dose
Day 0: (first day of treatment) 10 mg/ kg of bw single
dose
Day 1: 10 mg/ kg of bw single dose
Day 2: 5 mg/ kg of bw single dose
Single dose of 0.25 mg/ kg body weight daily for 14 days

2. Chloroquin resistant malaria:

ACT (artesunate
combination treatment)

4 mg/ kg bw of artesunate daily for 3 days plus 25 mg/

kg bw of sulphadoxine + 1.25 mg/ kg bw of
pyrimethamin
on
the
first
day
(or)
Oral quinine 10 mg/ kg bw daily for 3 days with tab
doxycline (100 mg)
(or)
Tab. Mefloquin (25 mg/ kg bw, but total dose does not
exceed 1000 mg)
(and)

67
Tab. Primaquin in single dose of 0.75 mg/ kg bw
3. Severe and complicated malaria and cerebral malaria:

Iv quinine

Artemisinin
Derivatives

Quinine salt 20 mg/ kg bw on admission (iv infusion or divided

im injection) followed by maintenance dose of 10 mg/ kg bw 8
hourly; infusion rate should not exceed 5 mg/ kg bw per hour.
The parenteral treatment should be given for minimum of 48
hours and once the patient tolerates oral therapy, quinine 10 mg/
kg bw three times a day with doxyclycline 100 mg once a day or
clindamycin in pregnant women and children under 8 years of
age, shouldbe given to complete 7 days of treatment in patient
treated with parenteral quinine.
Or
(b) artesunate: 2.4 mg/ kg body weight iv or im given on
admission, then at 12 hours and 24 hours, then once a day for 7
days;
Or
(c) artemether: 3.2 mg/ kg body weight im given on admission
then 1.6 mg/ kg body weight per Day for 7 days;
Or
(d) arteether: 150 mg daily im for 3 days in adults only (not
recommended for children);
Followed by full course of act to patients completed
treatment with artemisinin derivatives (b, c and d).

15. Treatment of complications:

1.
Corticosteroids are contraindicated as they cause prolonged coma and
increased mortality.
2.
Anemia is treated with RBC packed cells 10 ml/kg with frusemide
3.
Shock is treated with normal saline
11.

Blackwater fever:
1. Black water fever (bwf) is a severe clinical syndrome and complication of
falciparum malaria characterized by intra vascular haemolysis ,
haemoglobinuria and kidney failure .
2. Black water fever is caused by heavy parasitization of red blood cells with
plasmodium falciparum . When the red blood cells burst, hemoglobin leaks
into the blood plasma .
3. This free hemoglobin damages the glomerulus in the kidney, and begins to
leak into the urine where it causes further damage to the tubules of the
kidney.
4. Within a few days of onset there are chills, with rigor, high fever, jaundice,
vomiting, rapidly progressive anemia and the passage of dark red or black
urine.
5. The cause of hemolytic crises in this disease is unknown. There is rapid and
massive destruction of red blood cells with the production of hemoglobinemia

68

12.

, hemoglobinuria, intense jaundice, anuria (passage of less than 50 milliliter

of urine in a day), and finally death in the majority of cases.
6. The most probable explanation for blackwater fever is an autoimmune
reaction.
7. Blackwater fever is much less common today than it was before 1950. It may
be that quinine plays a role in triggering the condition, and this drug is no
longer commonly used for malaria prophylaxis.
8. The treatment is antimalarial chemotherapy, intravenous fluid and
sometimes supportive care such as intensive care and dialysis.
Toxicity of antimalarial drugs:
a. Quinine:
i. Cinchonism.:
1. Tinnitus (a hearing impairment), rashes, vertigo, nausea, vomiting
and abdominal pain are the most common symptoms.
2. Neurological effects are experienced in some cases due to the drug's
neurotoxic properties.
3. These actions are mediated through the interactions of quinine
causing a decrease in the excitability of the motor neuron end plates.
4. This often results in functional impairment of the eight cranial nerve,
resulting in confusion, delirium and coma.
5. Quinine can cause hypoglycaemia through its action of stimulating
insulin secretion; this occurs in therapeutic doses and therefore it is
advised that glucose levels are monitored in all patients every 4
6 hours. This effect can be exaggerated in pregnancy and therefore
additional care in administering and monitoring the dosage is
essential.
6. Repeated or over-dosage can result in renal failure and death through
depression
of the respiratory system.
b. Chloroquine:
i. Cause dizziness, headache, diplopia, disturbed visual accomodation,
dysphagia, nausea, malaise, and pruritus of palms, soles and scalp.
ii. It can also cause visual hallucinations, confusion, and occasionally frank
psychosis.
iii. It can exacerbate epilepsy and psoriasis.
iv. It can cause retinal toxicity after 3-6
v. Intra muscular injections of chloroquine can cause hypotension and
cardiac arrest, particularly in children.
c. Pyrimethamine:
a. Can cause occasional skin rashes and depression of hematopoiesis.
b. Excessive doses can produce megaloblastic anemia.
d. Sulfonamides:
a. Can cause agranulocytosis;
b. Aplastic anemia;

69
c. Hypersensitivity reactions like rashes, fixed drug eruptions, erythema
multiforme of the steven johnson type, exfoliative dermatitis, serum
sickness;
d. Liver dysfunction abnormalities;
e. Anorexia, vomiting
f. Acute hemolytic anemia can also occur.
g. The drug is contraindicated in patients with known hypersensitivity to sulfa,
infants below 2 months of age, patients with advanced renal disease and
first and last trimesters of pregnancy.
e. Mefloquin:
a. Nausea, vomiting, abdominal pain and dizziness can occur in doses
exceeding 1 g.
b. Less frequently it can cause nightmares, sleeping disturbances,
dizziness, ataxia, sinus bradycardia, sinus arrhythmia, postural
hypotension,
c. 'Acute brain syndrome' consisting of fatigue, asthenia, seizures and
psychosis.
d. Mefloquine should be used with caution in patients with heart block,
patients taking beta blockers, patients with history of epilepsy and
psychiatric disease.
e. It should be avoided in first trimester of pregnancy and pregnancy
should be avoided within 3 months of taking the drug.
f. Contraindications:
1. It should not be used for prophylaxis in pregnancy, particularly
during the first trimester.
2. It is contraindicated in patients with history of seizures, severe
neuropsychiatric disturbances, or adverse reactions to quinoline
antimalarials like chloroquine and quinine.
3. It should not be used concomitantly with these drugs for
increased risk of cardiotoxicity and risk of convulsions.
4. Mefloquine is reported to increase the risk of seizures in patients
taking valproate.
f. Artemisinin derivatives :
a. The most common toxic effects that have been identified are nausea,
vomiting, anorexia, and dizziness;
b. Neutropenia, anemia, hemolysis, and elevated levels of liver enzymes,
have been noted rarely.
c. Neurotoxicity is the greatest concern regarding artemisinins, since the
administration of high doses in laboratory animals has led to severe and
irreversible changes in the brain.
d. In humans, an episode of ataxia was reported after treatment with oral
artesunate, and one casecontrol study showed hearing loss after the
use of artemetherlumefantrine.
e. Treatments during the first trimester, showed similar levels of congenital
abnormalities, stillbirths, and abortions
f. Embryotoxic effects, which have been demonstrated in animals.

70
g. Primaquine:
a. At larger doses, it may cause occasional epigastric distress and
abdominal cramps.
b. Mild anemia, cyanosis and methemoglobinemia may also occur.
c. Severe methemoglobinemia can occur rarely in patients with deficiency
of nadh methemoglobin reductase.
d. Granulocytopenia and agranulocytosis are rare complications.
e. Patients with deficiency of glucose 6-phosphate dehydrogenase will
develop hemolytic anemia on taking usual doses of primaquine. If a
patient is known to be severely G6PD deficient, then primaquine should
not be given.
MEASLES (Rubeola)
1. Aetiology:
1. single stranded RNA with lipid envelope
2. genus: Morbilivirus; Family: Paramyxoviridae
3. human are the only host
2. Epidemiology:
1. Measles is one of the most infectious viruses known to man. Rarely will an unimmunized
2. Child escape.
3. Measles virus infection was annually responsible for approximately 6 million
deaths of infants and children globally.
4. Moreover, measles virus was responsible for more deaths than any other single
agent.
5. A review of community based studies of published measles outbreak
investigations found a median case fatality ratio of 3.7%, range 0 to 23.9%.
6. Vaccine from 1963 changed the epidemiology.
7. Incidence rate per 100,000 population varies from 0-142.7, CFR varies between 01.9%.
3. Transmission:
1. By droplets through respiratory mucosa and rarely conjunctiva.
2. Infective period: 3 days before and 5 days after rashes appear.
4. Pathology:
1. Necrosis of respiratory epithelium
2. Lymphocytic infiltration
3. Small vessel vasculitis of skin and mucosa
4. giant cells (up to 26 nuclei)
5. Fused cells with more than 100 nuclei called Warthin-Finkaldey giant cells
5.Pathogenesis:
4 phases
1. Incubation:
Infection of mucosa lympadenopathy viremeia RES
secondary viremia reach body surface to form exanthema
2. Prodrome:
mild fever, conjunctivitis, coryza, cough and photophobia.
3. Enanthem:
1. Koplick spots 1-4 days before exanthem;
2. inner cheek between premolars

71
3. also rarely on conjunctiva and vaginal mucosa
4. Exanthem:
1. Symptoms abate as rash appears
2. Begins at 5-6 days after fever
3. First seen around hairline and behind ears
4. Maculopapular
5. Spreads downwards to trunk and limbs
6. Finally confluence and fade over 7 days
7. Leaves brawny desquamation of skin
6.Subclinical measles:
1. In immune persons
2. Mild or absent rashes
3. No shedding of virus
7.Lab findings:
1. Dcreased WBCs
2. Decreased Lymphocytes
3. ESR normal
4. CRP not elevated
8.Diagnosis:
1. Koplick spot with typical rash
2. Specific IgM increased
3. Increasing titre of paired IgG serology
4. Viral detection via culture or reverse transcriptionPCR
9. D.D
1. Differential diagnosis includes rubella, scarlet fever, drug rashes serum
sickness, roseola infantum, infectious mononucleosis, erythema infectiosum
and echovirus and coxsackievirus infections and Kawasaki syndrome.
2. Rubella: A recognizable prodrome is absent, fever and other constitutional
symptoms are absent or less severe, post auricular and sub occipital lymph
nodes are enlarged (and usually tender), and duration is short.
3. Drug rashes: A drug rash often resembles the measles rash, but a prodrome is
absent, there is no cephalocaudal progression or cough, and there is usually a
history of recent drug exposure.
4. Roseola infantum: The rash resembles that of measles, but it seldom occurs in
children > 3 yr. Initial temperature is usually high, Koplik's spots and malaise
are absent, and defervescence and rash occur simultaneously.
5. Kawasaki syndrome: increased polymorphs; thrombocytosis; increased acute
phase reactants.
10. Complications:
1. Mortality more in
1. <5 and > 20 yrs.
2. Vit.A def. And malnutrition.
3. Immune def.
4. malignancy
2. Measles precipitates Vit.A def
3. Giant cell pneumonia: Also known as Hecht's pneumonia, this is a deadly but
fortunately rare complication of measles. It tends to strike children who are
immunodeficient as from leukemia or HIV/AIDS. The postmortem examination

72
(autopsy) shows multinucleated giant cells lining the alveoli (air sacs) of the
lungs.
4. Post measles bacterial pneumonias esp staph.
5. Bronchiolitis obliterans: rare and life-threatening form of non-reversible
obstructive lung disease in which the bronchioles are plugged with granulation
tissue. Causes death.
6. Croup, tracheitis and bronchiolitis.
7. Sinusitis and mastoiditis.
8. Retropharyngeal abscess
9. Activation of PC
10.Gastro enteritis and dehydration
11.Appendicitis due to lymphoid hyperplasia
12.Febrile seizures in 3%
13.Encephalitis 1 in 1000
14.Black measles: black measles, a rare, severe, often fatal, form of measles in
which hemorrhage into the skin lesions and mucous membranes is associated
with a sudden rise in temperature, convulsions, delirium, stupor, coma, and
marked respiratory distress. Called also hemorrhagic measles.
15.Myocarditis
16.Prgnancy: leads to fetal death, and neonatal mortality
17.Subute sclerosing pan encephalitis (SSPE)
1. Subacute sclerosing panencephalitis (SSPE) is a rare chronic,
progressive encephalitis that affects primarily children and young adults,
caused by a persistent infection of immune resistant measles virus
(which can be a result of a mutation of the virus itself). 1 in 100,000
people infected with measles develop SSPE.
2. Clinically: Insiduos onset, suble changes in behaviour, school failure
3. Three stages:
i. Irritability; Reduced attention span; Temper outbursts
ii. Massive myoclonus; no loss of consciousness
iii. Disappearance of myoclonus ; Choreo athetosis; Immobility;
Dystonia; Lead pipe rigidity; dementia; stupor; coma; death.
4. Diagnosis:
1. Clinical; myoclonus and consciousness
2. Measles antibody in CSF
3. EEG : Characteristic periodic activity (Rademecker complex)
4. Brain biopsy: eosinophilic inclusion bodies in the cytoplasm nuclei of
neurons and glial cells
5. Treatment:
Combinations of treatment for SSPE include:
Oral inosine pranobex (oral isoprinosine) combined with
intrathecal (injection through a lumbar puncture into the spinal
fluid) or intraventricular interferon alpha.
Oral inosine pranobex (oral isoprinosine) combined with interferon
beta.
Intrathecal interferon alpha combined with intravenous ribavirin.
Prognosis: death in 3 years
11. Treatment of Measles:
1. No antiviral drugs

73
2. Hydration, antipyretics, O2
3. Ventilator support
4. Vit A 1-2 L units
5. IV ribaverin tried in immune def.
12.Prognosis: death 1 in 1000; 15 % in immune def.
13.Prevention:
1. Measles 9 month
2. MMR in 15 months (?autism)
14.Post exposure:
1. Measles vaccine within 72 hrs
2. IM/IV IgG within 6 days

74

MUMPS
Etiology:
Single stranded RNA; Family Para myxoviridae; Genus Rubula virus
Human beings are the only host
Epidemiology:
Age: 5-9 yrs; epidemic at 4 yrs ; significant reduction after vaccination
Infectivity: 7 days before and 7 after parotid swelling appears
Pathology:
Can involve Salivary glands; CNS; Testes; Thyroid; Ovaries; Heart; Kidneys; Liver;
Joints.
Infection epithelium lymphnode viremia target tissues necrosis with
lymphocytic infiltration focal ischemia healing
Clinical features:
Incubation 12-25 days
Asymptomatic
Non specific symptoms
Typical illness:
o Prodrome: 1- 2 days of fever; headache and vomiting;
o Unilateral or bilateral (70%) swelling of parotids; tenderness; ear pain
o Parotid swelling:
Angle of lower jaw obscured
Ear lobe lifted up and out
Stensen duct opening red and swollen
Sub mandibular glands can be involved
Lymphatic obstruction leads to edema over sternum
o Fever resolves in 3 days swelling in 7 days
Diagnosis:
1. Increase in serum amylase
2. Leucopenia
3. Relative lymphocytosis
4. Viral isolation
5. PCR
6. Paired serology: rise in titre of acute and convalescent sera of IgG by
a. Compliment fixation
b. Hemagglutination
c. Enzyme immuno assay and ELIZA
d. Ig M by EIA demonstrates recent infection
D.D:
1. Parotid swelling occurs in influenza; CMV; E.B virus; HIV; staph infection(poly
increased)
2. Sialidinitis due to calculus

75
3. Sjogren syndrome: autoimmune disorder in which immune cells attack and destroy
the exocrine glands[2] that produce tears and saliva. The hallmark symptoms of the
disorder are dry mouth and dry eyes (part of what are known as sicca symptoms).
4. SLE: a chronic autoimmune connective tissue disease that can affect any part of
the body.SLE is one of several diseases known as "the great imitators" because it
often mimics or is mistaken for other illnesses.
5. Parotid tumour
Complications:
1. Meningitis
2. Encephalitis
3. Gonadal atrophy
4. Rare: optic neuritis; nephritis, pancreatitis
5. Nerve deafness
6. Thrombocytopenia
7. Transverse myelitis
8. Pregnancy: fetal loss
9. 30% gonadal involvement; sterility if bilateral; oopheritis can mimic appendicitis
10.Pancreatitis diabetes
11.Myocarditis
12.Thyroiditis myxaedema
Treatment:
Non specific; pain killers and rest
Prognosis:
good rarely death due to encephalitis
Prevention:
MMR at 15 m and 5 yrs; contra indicated in egg and neomycin allergy , pregnancy
and HIV

Acute Flaccid Paralysis

76
1. Definition:
1. Flaccid paralysis occurring over hours or few days with:
1. Hypotonia
2. Hyporeflexia
3. Loss of power
4. Wasting if persists for longer period
2. WHO definition for polio surveillance:
Flaccid paralysis of less than 4 weeks duration in children less than 15 years
2. It involves lower motor neuron complex:
1. Anterrior horn cell:
a. Viral: poliomyelitis
b. Immune mediated: acute transverse myelitis
2. Nerve trunk:
a. Immune mediated: Guillain-Barre
b. Toxin: Diphtheria; porphyria
c. Traumatic: IM injections
3. Neuromuscular junction:
a. Tick toxin
b. Botulinum
4. Muscles:
a. Myositis
5. Metabolic:
a. Familial periodic paralysis: autosomal recessive; abnormal K levels;
episodic paralysis
3. Clinical:
1. Fever
2. Rapid progression often of ascending paralysis
3. Cranial nerve involvement
4. Sensory disturbances
5. Recovery
Signs and
symptoms

Polio

Guillain-Barr
syndrome

Traumatic
neuritis

Transverse
myelitis

Installation
of
paralysis
Fever at
onset

24 to 48 hours
onset to full
paralysis
High, always
present
at onset of flaccid
paralysis, gone the
following day
Acute, usually
asymmetrical,
principally proximal

From hours to
ten
days
Not common

From hours to
four
days
Commonly
present
before, during
and after flaccid
paralysis
Asymmetrical,
acute
and affecting
only

from hours to
four days

Flaccid
paralysis

Generally
acute,
symmetrical
and

rarely present

acute, lower
limbs,
symmetrical

77
Muscle tone

Deeptendon
reflexes

Reduced or absent
in
affected limb
Decreased to
absent

distal
Global
hypotonia
Globally absent

one limb
Reduced or
absent
in affected limb
Decreased to
absent

Hypotonia in
lower Limbs
Absent in
lower
limbs early;
hyperreflexia
late
Anesthesia of
lower limbs
with
sensory level

Sensation

Severe myalgia,
backache, no
sensory
changes

Cramps,
tingling,
hypoanaesthesi
a of
palms and soles

Pain in gluteus,
hypothermia

Cranial
nerve
involvement

Only when bulbar

involvement is
present

Absent

Absent

Respiratory
insufficiency

Only when bulbar

involvement is
present

Absent

Sometimes

Autonomic
signs
& symptoms

Rare

Often present,
affecting nerves
VII,
IX, X, XI, XII
in severe cases,
enhanced by
bacterial
pneumonia
Frequent
blood pressure
alterations,
sweating,
blushing and
body
temperature
fluctuations

Hypothermia in
affected limb

Present

Cerebrospinal
fluid
Bladder
dysfunction
Nerve
conduction
velocity:
third
week

Inflammatory

Albumincytologic
dissociation
Transient

Normal

normal or mild
inf.
Cells
Present

Abnormal: anterior
horn cell disease
(normal during the
first 2 weeks)

Abnormal:
slowed
conduction,
decreased
motor
amplitudes

Abnormal: axonal
damage

normal or
abnormal,no
diagnostic
value

EMG at
three
weeks

Abnormal

Normal

Normal

Normal

Absent

Never

78
Sequel at
three
months and
up to
a year

Severe,
asymmetrical
atrophy, skeletal
deformities
developing later

Symmetrical
atrophy of
distal
muscles

Moderate
atrophy,
only in affected
lower limb

flaccid diplegia
atrophy after
years

4. Investigations:
1. CSF
2. MRI spine
3. Viral isolation: throat swap; stools
4. EMG
5. Nerve conduction studies
6. Elevation muscle enzymes
6. AFP surveillence:
1. Non-polio AFP rate in children <15 years of age. (Target > 1/100,000)
2. Reported AFP cases investigated 48 hours of report (Target 80%)
3. Reported AFP cases with 2 stool specimens collected 14 days since
onset. (Target 80%) If no more than two months have elapsed since the
onset of paralysis, collect two stool specimens from the patient with an
interval of 24-48 hours between collections.
4. Reported AFP cases with a follow-up exam at least 60 days after paralysis
onset to verify the presence of residual paralysis or weakness. (Target
80%)
5. Specimens arriving at national laboratory 3 days of being sent (Target
90%)
6. Specimens with a turn-around time 28 days (Target 80%).The turnaround time is the time between specimen receipt and reporting of
results
7. Stool specimens from which non-polio enterovirus was isolated (Target >
10%).
8. Classify the AFP cases.
9. Suspected polio or AFP is a temporary classification which within twelve
weeks of paralysis onset, the expert committee should reclassify the case
as confirmed polio, polio-compatible, or discarded.

POLIOMYELITIS
1. Virus:
1.
2.
3.
4.

Single stranded RNA; Family: Picarnoviridae; genus:Enterovirus

Type 1,2,3 are antigenically different
Humans are the only host
PV1 is highly localized to regions in India, Pakistan, Afghanistan, and
Egypt,West and Central Africa. Wild poliovirus type 2 has probably been
eradicated; it was last detected in October 1999 in Uttar Pradesh, India.[22]
Wild PV3 is found in parts of only five countries (Nigeria, Niger, Pakistan,
India, and Sudan).[20]

79
2. Transmission:
1.
Excreted from GIT and transmitted by feco oral method and disease occurs
in CNS
3. Epidemiology:
1.
90-95% subclinical or abortive
2.
5 % non paralytic illness
3.
1in 1000 paralytic polio in infants; 1 in 100 in adolescents.
4.
Poor sanitation and overcrowding predisposes transmission
5.
Infectivity: 2 weeks before and several weeks after the onset of illness.
4. Pathogenesis:
1.
Enter cells with specific polio receptors in GIT epithelium regional
lymphadenopathy pimary viremia RES & CNS through nerve endings
spinal motor neurons multiply Release by cell death
2.
Vaccine virus similar course but no replication in CNS
3.
Vaccine virus after acquiring neurovirulance can produce similar illness
(VAPP)
5. Pathology:
1.
Motor neurons of spinal cord invaded; poly and lymphocytic infiltration and
inflammation; edema; more neuronal loss due to inflammatory edema.
2.
Anterior horn cell, internuncial neurons and dorsal ganglion can be invoveld;
3.
Vermis of cerebellum, substantia nigra, red nucleus of pons, thalamus,
hypothalamus, pallidum and motor cortex can be involved to variable
extent.
6. Immunity:
1.
Infants 0-4 months have transplacental Ig.G
2.
Type specific immunity by natural and vaccine virus through IgG
3.
GIT gets IgA for surface immunity.
7. Incubation:
1.
8-12 days or longer.
8. Clinical Course:
1.
Abortive:
1.
Mild influenza like illness; fever, malice, head ache and
anorexia.
2.
Recovery in 2-3 days.
2.
Non Paralytic:
1.
Minor illness: as above
2.
Major illness:
1. Neck stiffness
2. Stiffness of muscles of trunk and limbs- spinal rigidity
3. Fleeting bladder paralysis
4. Constipation
5. Loss of head control
6. Depressed tendon reflexes
7. Loss of abdominal and cremastric reflexes
8. No sensory disturbances
3.
Paralytic Polio: i in 100 cases
1. Spinal
2. Bulbar
3. Spino bulbar
4. Polio encephalitis
4.
Spinal:

80
1.
2.

5.

Phase I: Similar to abortive polio

Phase II:
1. Apparent recovery from phase I followed by
2. Fever, head ache, muscle pain, paresthesias, muscle spasm
3. Asymmetrical and spotty paralysis
4. Proximal more than distal muscle groups
5. Diaphragm and intercostals paralysis
6. Reduced DTR
7. Bladder and bowel dysfunction
8. Provocation paralysis following IM inj.
9. Sensation is intact
10.
Recovery 6-12 months

Bulbar:
1.
May occur alone
2.
Nasal voice due to palatal palsy
3.
Pooling of saliva
4.
Irregular respiration
5.
Diminished cough reflex
6.
Deviation of uvula
7.
Increase in BP
8.
Hyperpyrexia
9.
Cardiac arrhythmias
10. Skin mottling due to vasomotor instability
11. Aphonia due to vocal cord paralysis
12. Weakness of hyoid muscle and rope sign by pulling hyoid
backwards
13. Cranial nerve palsies
6.
Polio encephalitis:
1. Irrritabilty
2. drowsiness
3. Coma
4. Tremors
5. Seizures
7.
Ventilatory insufficiency: due to
1. Pharyngeal and laryngeal weakness
2. Intercostal and diaphragmatic paralysis
3. Dysfunction of respiratory centres
4. Early diagnosis:
1. Anxious expression
2. Working of ala nasii
3. Week cough reflexes
4. Paradoxical abdominal movements
5. Deltoid weakness as the area is adjacent to phrenic nerve in
spinal cord
9. Diagnosis:
1.
Fever, asymmetry and spotty paralysis without sensory involvement.
2.
2 Stool specimens in 24-48 hrs apart for viral solation
3.
DNA sequence for wild, vaccine and non polio viruses
4.
CSF: early polymorphic leukocytosis; later lymphocytosis
5.
Paired serology for increasing titre.
10.DD:
1.
AFP:

81
1.
VAPP
2.
Guillain Barre Syndrome: symmetric; ascending with sensory
involvement
3.
Transverse myelitis
4.
Traumatic paralysis
11. Treatment:
1.
Symptomatic
2.
Pain killers
3.
Bed rest
4.
No Im inj and surgery; tonsillectomy can lead to bulbar polio
5.
Hot tub baths
6.
Splinting in neutral positions
7.
Phsiotherapy after pain subsides
8.
Air way maintenance
9.
Tracheostomy
10.
Ventilatory support
12.Prevention:
1.
The first inactivated virus vaccine was developed in 1952 by Jonas Salk, and
announced to the world on April 12, 1955. [47] The Salk vaccine, or
inactivated poliovirus vaccine (IPV), is based on poliovirus grown in a type
of monkey kidney tissue culture (Vero cell line), which is chemically
inactivated with formalin.[15] After two doses of IPV (given by injection), 90%
or more of individuals develop protective antibody to all three serotypes of
poliovirus, and at least 99% are immune to poliovirus following three doses.
[4]
2.

Subsequently, Albert Sabin developed another live, oral polio vaccine (OPV).
It was produced by the repeated passage of the virus through non-human
cells at sub-physiological temperatures. Three doses of live-attenuated OPV
produce protective antibody to all three poliovirus types in more than 95%
of recipients.
13.Eradication:
1. High infant immunization coverage with four doses of oral polio vaccine (OPV)
in the first year of life in developing and endemic countries, and routine
immunization with OPV and/or IPV elsewhere.
2. Organization of National immunization days to provide supplementary doses
of oral polio vaccine to all children less than five years of age.
3. Active surveillance for wild poliovirus through reporting and laboratory testing
of all cases of acute flaccid paralysis[7] among children less than fifteen years of
age.
4. Targeted "mop-up" campaigns once wild poliovirus transmission is limited to a
specific focal area.
5. Pulse Polio is an immunization campaign established by the government of
India in 1994 to eradicate poliomyelitis (polio) in India by vaccinating annually
all children under age five against poliovirus.
Every child receives a dose of Oral Polio Vaccine (OPV), a live, attenuated
virus which colonises the gastrointestinal tract. This virus competitively inhibits
the wild, disease-causing poliovirus. Not only does this prevent pernicious
infection in the host, it precludes transmission of the wild poliovirus to other

82
hosts. Since poliovirus cannot survive outside a host for more than two weeks,
theoretically it would be eradicated, resulting in the eradication of
poliomyelitis.

TETANUS
Questions:
1. Describe the clinical features, complications, prevention and management of
tetanus. Nov 2001
2. S.N: Neonatal tetanus. Feb 2007
Definition:
Tetanus is an acute, spastic paralytic illness caused by the neurotoxin of
Clostridium tetani
Bacteriology:
Clostridium tetani is a motile, gram positive, spore-forming, obligate anaerobe;
drum stick appearance in microscopy.
Ubiquitous and found in soil, dust, alimentary tract of animals.
Produce a single toxin tetanospasmin
Does not invade tissues and no inflammation
Epidemiology:
Ubiquitous; found in 90 developing countries; causes neonatal and maternal
mortality.
Causes of infection:
1. Penetrating injury by dirty nail,
9. Compound fractures
10.Frost bite
splinter, glass piece etc.
11.Gangrene
2. IM injection by drug abusers
12.Intestinal surgery
3. Contaminated surgical
13.Ritual scarificationinstruments
circumcision, female genital
4. Animal bites-dog, bats etc
5. Abscess including dental
mutilation
14.Insect
bites
abscess
15.Septic
abortion
6. Chronic middle ear infection
16.Unclean delivery
7. Burns
17.No obvious cause
8. Chronic ulcers
Pathogenesis:
Tetanus occurs after introduction of spores which germinate and multiply without
tissue invasion; release toxin after cell lysis; toxin binds at the neuromuscular junction;
enters motor nerves; retrograde axonal transport; enters the a-motor neuron; passes on
to adjacent inhibitory interneuron; prevents the release of g-amino butyric acid
(GABA)leading to sustained muscle contraction without relaxation.
Mechanism:
Tetanospamin is a Zinc containing enzyme protein; it inactivates synaptobrevin
that helps fusion of synaptic vesicles with terminal cell membrane

83
Clinical features:
Incubation: 2-14 days or even more. Generalized and localized tetanus:
Features of Generalized tetanus:
1. Trismus or lock jaw due to masseter spasm.
2. Headache, restlessness, irritability.
3. Stiffness, difficulty in chewing and swallowing
4. Neck muscle spam
5. Facial muscle spasm leading to risus sardonicus (Origin: L. Risus= laughter +
Sardinia = herb fr, ref. to effects of Strychnos nux-vomica)
6. Opisthotonus (body arches in such a way only heel and occiput touch the
surface due to total contraction of opposing muscles acquiring an equilibrium
position.
7. Laryngeal and respiratory muscle spasm leading to asphyxia
8. Consciousness is intact; pain is preserved; anxious look.
9. Tetanic seizures characterized by sudden severe tonic contractions of the
muscles with fists clinching, flexion, and adduction of the arms and
hyperextension of legs. The spasm progresses in severity and duration. The
spasms are triggered by light, sound and touch.
10.Urinary retention due to bladder sphincter spasm.
11.Autonomic disturbances like tachycardia, dysarrythmias, labile hypertension,
sweating and cutaneous vasoconstriction.
12.Severe progression of symptoms in the first week, stabilization in 2nd week,
amelioration in 3rd week.
Neonatal Tetanus (m tetanus neonatorum):
1. Spores contaminate umbilical stump due to unclean instrument or applicants
like cow dung.
2. Manifests in 3-12 days
3. Progressive difficulty in feeding
4. Diminished movements, stiffness and rigitity.
5. Progressive spasms
6. opisthotonus
Localized tetanus:
1. Results in painful spasms of muscles adjacent to the wound
2. May precede generalized tetanus
3. Cephalic tetanus, a rare form involves bulbar musculature due to
contaminated wound on head, nose or otitis media. It is characterized by
retracted eyelids, deviated gaze, trismus, risus sardonicus, spastic tongue, and
pharyngeal spasm.
Diagnosis:
1. One disease in Medicine that allows confirmation by clinical features. Typical
spasm with normal sensorium.
2. Leukocytosis
3. Normal CSF
4. Normal EEG and EMG.
5. Smear for C.tetani is usually negative.
6. In 1/3 cases isolation of organism is possible.
D.D:
1. Unmistaken diagnosis is possible
2. Trismus is seen in pharyngeal abscess and brain stem encephalitis.

84
3. Rabies has typical hydrophobia.
4. Strychnine poisoning has spasm but no Trismus.
5. Hypocalcaemia has laryngeal and carpopedal spasm but no Trismus
6. Epilepsy may mimic tetanus but normal sensorium in later condition.
Treatment:
1. Wound debridement and cleaning to clear tetanus bacilli and anaerobic
conditions.
2. Human tetanus immunoglobin 3000-6000 units as IM; infiltration around wound
not considered necessary now. Intra thecal not effective.
3. Intravenous immunoglobin as an alternative if TIG is not available.
4. Another alternative is tetanus antitoxin; 50,000 to 100 000 U half IM and half
IV. After sensitivity tests.
5. Penicillin G100000 U/kg in 4 divided IV doses for 10-14 days.
6. IV metronidazole 500 mg 8 hrly for adults.
7. Erythromycin and tetracycline for allergic patients.
8. Diazepam 0.1 to 0.2 mg/kg iv every 3-4 hrs later titrated to need.
9. Intra thecal baclofen in intensive care settings.
10.Vecuronium and pancuronium followed by ventilation improves ultimate
survival.
11.Autonomic instability is treated by b-blockers and morphine.
Supportive care:
1. Dark and secluded settings protected from sound, light and touch.
2. Suction of secretions
3. Maintenance of nutrition and hydration with electrolytes.
4. Avoid infection, ulceration and constipation.
Complications:
1. Aspiration pneumonia
2. Intramuscular haematomas.
3. Bone fractures
4. Renal failure due to myoglobinuria.
5. Hyperpyrexia
6. Cardiac arrhythmias
7. Venous thrombosis
Prognosis:
1. Synapses regenerate in spinal cord and recovers slowly.
2. No antibodies are formed and hence TT immunization is necessary.
3. High mortality in younger age groups.
4. Better prognosis in long incubation and localized tetanus.
5. Cephalic tetanus has poor prognosis
6. Long term sequelae include cerebral palsy, mental retardation.
7. Mortality: Generalized tetanus=5to 35%; neonatal tetanus=10-75%
Prevention:
1. DTP vaccination in early childhood
2. Boosters every 10yrs
3. Antenatal TT
4. TT and TIG 250 IU in tetanus prone wounds
5. Wound cleaning after injury.

85

CHILDHOOD TUBERCULOSIS
1.

EPIDEMIOLOGY
2.
world
1. 95% in developing countries
2. 1/3 of world population affected
3. 2 billion case load
4. 8 million new cases annually
5. 1 million die annually
6. In 98% portal of entry is lung
7. 8 % MDR TB
8. HIV co epidemic
1. India
1. 3.8 million cases
2. 4,400 die every day
3. 0.8 % among U5
4. All age 1.6%
5. 40% under 16 infected
6. 105% of them develop disease
7. MDR 3%
1. Taxonomy of Mycobacteria
1.Tuberculous
1. M.tuberculosis
2. M.bovis
3. M.africanum
4. M.microti
5. M.canetti
2. M. leprae
3. Non Tuberculous (anonymous)
I. Photochromogens:
M. kansasii (Pathogen)
II. Scoto chromogens:
M. scrofulaceum (Pathogen)
M. aquae (Saprophyte)
III. Non Chromogens
M.avium complex (Pathogen)
IV. Rapid Growers
M. fortuitum (Pathogen)
2. Mycobacterium tuberculosis
1. Bacteriology:
Non spore forming
Non motile

86
Pleomorphic
Gram positive
Curved rods
Obligate aerobes
facultative intracellular parasite
2. Transmission:
airborne droplet from an adult with TB cavity and forceful cough
no transmission by children because:
1. paucibacillary
2. less cough
3. less tussive force
3. Clinical spectrum: Two groups
1. Infected asymptomatic Mx +
2. Tubercular disease
1. Clinical
2. Bacteriological
3. Radiological

Immunological- phlectenular conjunctivitis; erythema

nodosum
4. Clinical types:
1. Primary TB:
Latent tuberculosis
Primary complex
Progressive primary complex
Disseminated tuberculosis
Reactivation tuberculosis
2. Secondary TB: adult type
No
1
2

5
6
4.

Primary TB
No prior immune sensitization
Disease spreads to regional
gland and further disseminates
to different organs
Delayed hypersensitivity
develops during the course of
disease hence less tissue
destruction
Sub pleural focus develops
anywhere in the lung- Ghon
focus
Casseation and cavitation less
common
Lesions leal by calcification

Adult TB
Very strong existing immunity
Localization of the disease to the
affected organ
More tissue destruction due to delayed
hypersensitivity

Apical region commonly affected due

to more Oxygen availability- simon
focus
Casseation and cavitatation more
pronounced
Healing by fibrosis

Pathogenesis:
1. An adult with tuberculous cavity coughs with enough tussive force

87
2. Child gets the infection; portal of entry is lung;
3. incubation 4-8 weeks;
4. Bacteria settle in a well ventilated sub pleural lung for eg. Rt middle or
lower lobe and this is called Ghon Focus
5. bacteria multiply in alveoli
6. Neutrophils try to eliminate bacilli but are not able to eliminate the bacteria
due to resistant bacterial wall
7. Monocytes enter the scene and engulf the bacteria but not able to do intra
cellular killing due to tough bacterial wall
8. Monocytes form special giant cells called Langhan type of giant cells and
epithelioid cells (macrophages)
9. Lymphocytes invade the area and get sensitized; CD4 cells secrete specific
lymphokines which activate CD8 cells which lyse bacilli loaded monocytes
and macrophages kill the bacteria. Delayed hypersensitivity is developed
by CD4 cells and Mantoux becomes positive by the end of 4-6 weeks.
10.
Delayed hypersensitivity is responsible for tissue destruction such as
casseation and cavitation and also allergic reactions like phlectanular
keratoconjunctivitis and erythema nodosum.
5. Course after infection:
1. Immune host:
1. mostly killed by macrophages
2. some survive in macrophages
3. Heals with calcification or
4. develops into focal tuberculous pneumonia and progress further
progressive tuberculosis; disseminated tuberculosis;
reactivation tuberculosis
5. Lymphadenopathy:
6. carried via lymphatic to regional lymph nodes
7. regional adenitis:
a. heals with calcification or
b. enlarge further to produce:
1.
bronchial compression collapse or emphysema
2.
rupture into bronchus endobronchial tuberculosis
3. rupture into nearby vessels lympho haematogenous
dissemination disseminated TB bacteria settle in for
future reactivation tuberculosis
1. kidney
2. brain
3. bone
4. liver etc
6. Progressive tuberculosis:
1. Primary focus heals with calcification if immunity is good
2. In susceptible child it enlarges into:
i. tuberculous pneumonia Casseation and cavity formation
ii. Lympho hematogenous spread: settle in:

88
a.
b.
c.
d.
e.

Apices of lung
kidney
brain
bone
liver etc for future reactivation tuberculosis

7. Disseminated TB
Pathogenesis
1. Lympho hematogenous spread
2. Brain; TBM
3. Liver
4. Kidney
5. Bone and joints
8. Reactivation TB
1.
Varying periods of dormancy
2. > 7 years of age Usually adolescents
3. Upper lobe infiltration ( more O2 and blood)- Simon focus
4. Casseation and cavitations
5. Pleurisy
6. Pericarditis
7. Tuberculoma

89

9. Time line :

10. Immunity
1. Mainly Cell mediated immunity; Humeral immunity less role
2. Bacilli land on well ventilated subpleural area of lung
3. Neutrophils migarate first but could not fight due to resistant bacterial cell wall
4. Monocytes come for second line defense engulf the bacteria but could not kill ;
form epithelioid cells- multinucelate giant cells
5. Third comes T lymphocytes; CD4 get sensitized and release cytokines

90
6.
7.
8.
9.

CD4 release cytokines which activate CD8 cytotoxic cells

CD8 lyse monocyte and release bacteria
Activated macrophages ultimately kill the bacteria
After sensizitization of T lymphocytes, granuloma formation occurs to prevent
spread of infection
10.TB granuloma:

11. Clinical features

i. Latent Tuberculosis
1. Asymptomatic
2. Mx + ve
3. CXR normal
4. No clinical signs
5. 40 % develop symptomatic TB
6. Maximum progression in first 2 yrs
7. Reactivation during adolescence
ii. Clinical features in symptomatic primary tuberculosis:
1. Fever
2. Cough
3. Malaise
4. Night sweats
5. Malaise
6. Anorexia
7. Weight loss
iii. External markers
1. Wasting
2. Lanugo hair
3. Long eye lashes
4. Phlectenular conjunctivitis
5. Scrofuloderma
6. Sinus ulcers
7. Lupus vulgares
8. Tuberculids
9. Skin TB
10.Scrfuloderma
11.Veruka and lupus vulgares

91
12. TB in Prgnancy
1. Prematurity
2. IUGR
3. Increased peri natal mortality
4. Congenital TB in NB is rare
13. Investications
1. Mantoux:
1.
Mantoux skin test:
1. Basis: Delayed cellular hypersensitivity
2. 0.1 ml intradermal
3. 5 TU of PPD Tween 80
4. Read after 48-72 hrs
5. Early reaction not positive
6. Delayed reaction is positive
2. False positive:
1. Non tuberculous mycobacteria
2. BCG ( up to 5 yrs; <10 mm)
3.
False Negative:
1. Anergy
2. Infant
3. Malnutrition
4. Suppressed immunity
5. Vaccine: Measles; MMR
6. Measles infection
7. Miliary TB
8. Technical error
4.
Mantoux reading :
positive reaction:
1. Contact history ; Symptoms of PC
}
2. HIV
}
3. Immuno supression
}
> 5 mm
4. High prevalence area
>10 mm
5. Low prevalence area
> 15 mm
6. Recent Mx conversion
>10 mm
7. Serial Mantoux in a patient:
becomes positive
2. Bacterial isolation and culture:
1. Gastric aspirate- 3 consecutive morning samples
2. Bronchoscopy and aspirate
3. Negative culture and smear do not rule out TB
4. AFB staining:
Ziehl-Neelsen stain
1. Heat fix
2. Smear with carbol fuchsin
3. Steam 5 mts
4. Rinse
5. Add 3% acid alcohol - 5 minutes

92
6. Rinse
7. Methylene blue-1 mt
8. Rinse
9. Dry
10.Bright red purple bacilli

5. Auramine-rhodamine florescent stain.

1. Requires a fluorescent microscope.
2. The fluorochrome dyes used
3. The fluorescing mycobacteria are seen as bright yellow-orange
bacilli against a dark background.
6. Culture:
Lowenstein-Jensen medium:
1. Egg medium
2. glycerol enhances the growth of M.tuberculosis
3. also used in drug susceptibility testing
4. > 3 weeks for growth
5. > 4 weeks for sensitivity
6. rough, tough and buff colonies

3.

CXR

Primary focus

Miliary TB
Calcified hilar adenitis
Calcified hilar adenitis

Miliary

93

4.

Other tests
Interferon release by T cells towards MT antigens
Quantiferon TB c-gold
T Spot- TB
Elispot (elliza identifies T cells specific for TB)
14.Other forms of TB:
1.
Lymphadenopathy:
Scrofula
More in M.bovis
Firm, non tender, matted, fixed
Also caused by Atypical mycobacteria;
Mx positive
Fine needle aspiration cytology (FNAC) for AFP culture and smear
2.
Upper respiratory tract:
1. Laryngitis
2. CSOM
3.
Pleurisy and pericarditis
4.
Miliary TB:
1.
Choroid tubercles
2.
Miliary mottling in CXR
5.
CNS:
1. TB Meningitis
2. Tuberculoma

94
6.
7.
8.
9.

Abdominal Tuberculosis
TB arthritis, osteomyelitis
Renal and genital : rare
TB & HIV :
1. 30% more in HIV
2. Mx ve
3. Rapid progression
4. Lymphocytosis favours viral replication-vicious cycle
5. Rifampicin toxicity increased by ART

15: Treatment of Primary TB:

1. Pulmonary: 2HRZ/4HR
a. INH, Rifampicin and pyrazinamide for 2 months
b. INH, Rifampicin for next 4 months
2. MDR TB:
a. Add ehtambutol and SM
3. DOTS: Directly Observed Therapy, Short-course
a. 2 months drugs under direct observation by health worker
b. Intermittent course
i. Basis for Intermittent Chemotherapy
In vitro experiments have shown that after a culture of M.
tuberculosis has
been exposed to certain drugs for
sometimes, it takes several days (the lag period), before
multiplication starts again
ii. Higher dosing in intermittent treatment increase peek plasma
levels
4. Indications for Corticosteroids:
a. TBM
b. Tuberculoma
c. Endobronchial TB
d. Pericarditis
e. Miliary TB
16.Prevention :
BCG:
1. Live attenuated vaccine prepared from mycobacterium bovis - Bacillus
Calmette Gurin
2. Heat and light sensitive vaccine
3. Add 1 cc NaCl to vial; 0.05 ml intradermal; left arm; no spirit for cleaning
4. Time: Within 14 days after birth
5. Reaction:
a. 2 to 3 weeks - papule
b. 5 weeks - 4-8 mm in diameter
c. 6-12 weeks - shallow ulcer covered with a crust.
d. Healing with round scar 2-10 mm in diameter.
e. Scar not a must
6. Complications:

95
1.
2.
3.
4.

BCG Abcess
Keloid
Adenitis
Spread of tubercular disease

7.

Contraindications:
1. symptomatic HIV
2. Immunocompromised child
3. Mx + ve child
8. Prevents serious forms of TB in infancy
9. 50% effective in Primary TB
10. 80% protective in CNS TB
11. No protection for adults as effect wanes after 5 years
11. Also used for diagnosis as accelerated BCG reaction
17. NB & TB Mother
Neonate:
INH for 3 months
Isolation for MDR TB
Pregnancy:
Pyrazinamide teratogenic
Isoniacid, Rifampicin and ethambutol

Prevention and management of acute diarrheal diseases

1. Definition:
The passing of 3 or more watery or loose stools in a 24-hour period.
2. Three types:
1. acute watery diarrhea
2. Persistent diarrhea
3. Dysentery
4. Diarrhea in severe malnutrition
3. Acute watery diarrhoea (including cholera):
1. Lasts several hours or days:

96
2. Weight loss if feeding is not continued;
3. Dehydration,
4. Acute bloody diarrhoea (dysentery): Features:
1. Damage of the intestinal mucosa
2. Sepsis and
3. Malnutrition
5. Persistent diarrhoea, >14 days or longer:
Leads to Malnutrition
6. Diarrhoea with severe malnutrition (marasmus or kwashiorkor): Features:
1. Severe systemic infection,
2. Dehydration,
3. Heart failure
4. Vitamin and mineral deficiency.
7. Global problem:
1. million u5 children die of diarrheal diseases.
2. 19% of all deaths among children ages 0-4.
3. 85% occur in the first year of life.
4. At least 3 episodes per year
5. Diarrhea and malnutrition set a vicious cycle
8. Etiological agents :
1. Bacterial:
1. Enterotoxigenic e. Coli
2. Shigellae
3. Salmonellae
4. Vibrio cholerae
5. Campylobacter jejuni
6. Clostridium difficile
2. Viral: Rotavirus
3. Parasitic agents: Cryptosporidium
4. Protozoans : Amoeba; Giardia
Transmission:
1. Rota virus, shigella and e.coli
: person to person
2. Cholera
: food and water
3. Salmonella and camphylobacter
: food poison
4. Clostridium difficile
: antibody associated
Pathogenesis:
1. Toxin
2. Invasion
3. Osmotic
4. Increased motility
Toxin
1. Rota virus:
a. Activates intracellular signal transduction
b. Inhibits na, cl coupled transport
c. Eflux of cl
2. E.coli:

97
a. Activates adenylate cyclase
b. Increases intracellular cyclic AMP
c. Pumps out Na and Cl
3. Shigella:
Invasion, mucosal destruction and exudation
4. E.coli: types:
a. ETEC:
Fimbrial adherence ; toxin mediated chloride shift
b. EPEC:
Adherence and effacement; cell injury
c. EIEC:
Shigella toxin; invasion cell necrosis
d. EHEC:
Hemolytic uremic syndrome
Osmotic :
Eg: lactose intolerance; unabsorbed food produce osmotic pressure to water
into lumen
Motility disorder:
Eg: irritable bowel syndrome
Risk factors
1. Age
2. Measles
3. Malnutrition
4. Breast feeding
5. Formula feeding
6. Vit.A deficiency
7. Zinc deficiency
8. Race lactase deficiency in Caucasians
9. Human races the five human races, Ethiopian. American. Caucasian.
Mongolian. Esquimaux.
Zinc:
Biochemical functions :
1. Component of enzymes like: carbonic unhydrase, alcohol dehydrogenase, alkaline
Phosphatase, carboxy peptidase, superoxide dismutase etc.
2. Essential for insulin storage and secretion by b cells.
3. It is required for maintaining vit a level in serum.
4. It is required for wound healing by unknown mechanism.
5. Gusten is a zinc containing protein and is important for taste sensation.
6. Zinc plays important roles in growth and development, the immune response,
neurological function, and reproduction.
Zinc in diarrhoea
1. Improved absorption of water and electrolytes by the intestine,
2. Faster regeneration of gut epithelium,
3. Increased levels of enterocyte brush border enzymes,
4. Enhanced immune response,
Behavioral factors:

98
1. Failure to breast-feed exclusively for the first 4-6 months of life
2. Using infant bottles
3. Unsafe water
4. Improper hand washing
5. Open air defecation
Malnutrition and diarrhea:
Diarrhea produce malnutrition; malnutrition in turn produce immune deficiency
and increases diarrheal episodes and hence a vicious cycle is set up.
Signs and symptoms
1. No dehydration: there are no signs or symptoms.
2. Mild dehydration increases:
1. 5% of body weight is lost as water
2. Thirst, restless or irritable behaviour,
3. Decreased skin turgor,
4. Sunken eyes, and
5. Sunken fontanel (in infants).
3. In severe dehydration,10%
1. Hypo volaemic shock,
2. Diminished consciousness,
3. Lack of urine output,
4. Cool moist extremities,
5. A rapid and feeble pulse
6. Low blood pressure,
7. Peripheral cyanosis.
8. Death
At risk model:
I.
90% no dehydration; self limiting
II.
9 %: some dehydration
III.
1 %: severe dehydration
Treatment :
1. ADD with no dehydration:
a. Mother care
b. Continue breast feeding
c. Give extra ha fluids- HAF
i. Juices
ii. Buttermilk
iii. Rice water; coconut water
iv. Rice, cereal, dhal kanji
d. Give more food
e. Home available fluid (HAF)
Oral rehydration solution
Zinc supplementation
Nutritional support
Probiotics
Antibiotics
Ort: Reduced osmolarity

99
Sodium chloride 2.6 gms/litre
Sodium 75 mmol/litre
Glucose, anhydrous 13.5
Glucose, 75
Potassium chloride 1.5
Potassium 20 Chloride 65
Trisodium citrate/dihydrate 2.9
Citrate 10
Total weight 20.5
Total osmolarity 245
No dehydration:
Give as much fluid as the child wants until diarrhoea stops. As a guide, after each
loose stool, give:
a. Children under 2 years of age: 50-100 ml (a quarter to half a large cup)
of fluid;
b. Children aged 2 up to 10 years: 100-200 ml (a half to one large cup);
c. Older children and adults: as much fluid as they want.
Some dehydration:
75 to 100 ml/kg in 4 hours
Continue as in no dehydration
Diarrhoea treatment
i. Zinc:
1. 10 mg for <6m 20 mg for >6 m for 14 days
ii. Probiotics:
1. Produce microbial lactase
2. Competes with pathogenic bacteria
3. Increase immune effect
4. Provide acidity
5. Protects cancer and allergy?
iii. Drugs:
1. No benefits
2. Co-trimoxazole in cholera
3. Nitazoxanide for giardia ? Rota virus
4. Shigella: quiolones; furazolidine
iv. Treatment
1. Vomiting:
a. Ondensitran 2 mg stratum
2. Racecodotril:
a. Enkephalinaze inhibitor
b. Anti secretory
c. Under evaluation
3. Intravenous management
i. Treat shock:
1. 20 ml / kg nacl in 20 minutes
ii. Treat dehydration:
1. 50-100 ml/kg n gns for next 8 hours
iii. Maintenance:
1. Pms 100 ml/kg/24 hrs
Electrolytes

100
Hyponatremia:
<130 m.eq/l
3% nacl for rapid correction
Hypernatremia:
>150 m.eq /l
Ors
Hypokalemia:
<3 m.eq/l
Iv potassium
Hyperkalemia:
1. >6 meq/l
Acidosis
Alkalosis
Complications
1. Shock kidney- arf
2. Intra cerebral thrombosis
3. Hemolytic uremic syndrome
Lab
1. Electrolytes
2. Stool microscopy
3. Stool culture
Prevention strategies
1. Breast feeding
2. Improved weaning practices
3. Proper use of water
4. Hand washing
New developments
super-ors
Rotavirus vaccine

4. Hypoglycemia
5. Paralytic ileus
6. Pem
4. Stool reducing substance
5. Cbc

5. Disposing feces properly

6. Effectiveness of measles
vaccination

ARI / PENEUMONIA
Definitions:
Acute respiratory tract infection: infection of R.S for less than 14 days
URI: up to larynx including middle ear
LRI: from trachea to pleura
Pneumonia:
Inflammation of parenchyma of lungs; often focal involving some lobes
Bronchopneumonia:
Acute inflammation of the walls of the bronchioles with peribronchial
inflammation of lung parenchyma; bilateral and symmetrical involvement
Epidemiology: 19% of under 5 deaths are due to pneumonia

101

Etiology of Pneumonias:
1. Infection: viral, bacterial, fungal, parasitic
2. Aspiration: food; gastric juice
3. Foreign body bronchus
4. Hydrocarbons: kerosene ingestion
5. Lipoid substance: oil baths and nasal instillation of oil
6. Hypersensitivity : airy and grain products, animal dander and protein
7. Drugs: anticancer drugs like methotrexate
8. Radiation: x ray treatment for cancers
Leading Etiologic Agents of Pneumonia Infants and Children:
Common pathogens:

Age

Bacterial pathogens

Viral Pathogens

Neonate

Group B Streptocaccus
Gram-negative bacilli
( E.coli, K.pneumoniae,
Proteus sp, others)
S.aureus

RSV
Herpes simplex virus
CMV
Adenovirus

1-3 mo.

S.pneumoniae
H.Infuenzae type b

RSV

4 mo.-5
yrs

S.pneumoniae
H.Influenzae type b

Parainflenza virus1 and 3,

Adenovirus
Influenza viruses A and B

5 yrs and
older

S.pneumoniae

Other

C.trachomatis

M.pneumoniae
C.pneumoniae

102
Pathogenesis:
Lower respiratory tract is kept sterile by:
1. Immune defense by leukocytes and Ig.A antibodies
2. Mucous coat
3. Ciliary clearance
4. Cough
Viral pneumonias: progression:
1. Droplet infection
7. Cellular debris
2. Spreads along the
8. Airway narrowing
airways
9. Airway obstruction
3. Infects epithelium
10. Atelectasis
4. Cell injury
11. Ventilation perfusion
5. Edema
mismatch
6. Exudation
12. Hypoxia
Bacteriral pneumonias
1. Pathogensis:
Viral invasion Surface defense knocked down Altered secretions
bacterial invasion Inflammation consolidation
2. Streptococcus peumoniae:
Focal often lobar pneumonia
3. G.A. Streptococcus:
Diffuse often involves pleura
4. Staphylococcus:
Unilateral ; extensive; hemorrhagic necrosis;
cavitation;
pneumatoceles; empyema
5. Mycoplasma:
Patchy; edema; airway obstruction; coin shadow
9. Pathology
1. Congestion (1-2 days)
2. Red hepatization (2nd-4th day)
3. Gray hepatization (4th-6th day)
4. Resolution (8th-9th day)
5. All 4 phases may be seen in different parts of the same lung.
10. Recurrent pneumonia:
1. 2 episodes in a year
2. 3 episodes in life time
Causes:
1. Cystic fibrosis
6. Sequestration
2. HIV
7. Con emphysema
3. Immunodeficiency
8. TEF
4. Immotile cilia syndrome
9. Bronchiectasis
(Kartagener syndrome)
10. Neuromuscular
5. Foreign body
incoordination
Clinical features:
1. Starts as upper respiratory
5. Grunt
catarrh
6. Cyanosis
2. Fever
7. Chest retraction
3. Chills
8. Working of accessory
4. Tachypnoea
muscles of respiration

103

9. Crackles and wheeze

10.Restlessness
11. Infants :
1. Diarrhea
2. Vomiting
12. WHO classification of ARI:
a. No pneumonia: Normal breathing
b. Pneumonia: Increased respiratory rate:
infants:
> 60
2-12 months
> 50
1-5 years
> 40
c. Severe Pneumonia:
1. Chest retraction
d. Severe disease:
1. Cyanosis
2. Unconsciousness
Diagnosis:
Lab:
creased in bacterial
al
13. CXR:
Sun ray appearance
Airbronchogram
Lobar consolidation
14. Treatment
Amoxicillin
Cloxacillin
Cefuroxim axitil
Azithrocyn
15. Poor response:

Antibiotic resistance

Viral

Aspiration
16.
Complications
Septicemia
Meningitis
Osteomyelitis
Metastasis

11.Delirium
12.Pleuritic pain
3. Abdominal distension
4. Incessant cry

2. Grunting
3. convulsions

Perbronchial cuffing
Silhouette sign

Levofloxacin
Gatrifloxacin
Aminoglycosides

Immunodeficiency
Cystic fibrosis

Empyema
Death due to sepsis; resp.failure
and other complications

104

Rheumatic Fever
1. Historical aspects:
1600
Sydenham - - Described Chorea
1812
Charles Wells - - Assoc of rheumatism with carditis and
subcutaneous nodules
1889
Walter B. Cheadle - Classic description of ARF

1944

Duckett Jones presented his paper on Diagnosis of ARF in

Chicago; described Jones criteria of Rheumatic fever

2. Age incidence: 5-15 years

Peak incidence around 8 years
School children are susceptible population; Prevalence = 5.3/ 1000 school
children
3. Sex Incidence: Male : female equally affected
4. Predisposing factors:
Poor socioeconomic status
Overcrowding and poor housing
malnutrition
Poor sanitation and hygiene

105
Lack of health facility
Genetic predisposition-HLA DR-3
Immune response gene seen in 15% of population
5. Etiology
Group A b hemolytic streptococcus
Common strains are M 1,3,5,6,18 and 24
Only pharyngeal infection predispose to Rheumatic fever
Attack rate is .3 to 3%
6. Etiopathogenesis
i. Group A b-hemolytic streptococcus- antigenicity:
Cell Wall Components:
M moiety protein (rheumatogenic component)
Hyaluronic acid capsule
Extracellular products:
Streptolysin S, streptolysin O, hyaluronidase,
Deoxyribonuclease B; erythrogenic toxins (strep pyrogenic exotoxins
ii. Sequence of events
i.
Pharyngeal infection of Gr. A b hemolytic streptococcus
ii.
Sensitization of B lymphocytes by streptococcal antigens
iii.
Formation of anti sreptococcal antibodies in the host
iv.
Formation of immune complexes that cross react with myocardial
sarcolemma proteins
v.
Myocardial and valvular inflammation

106

7. Clinical features
After a latent period of 2-3 weeks symptom complex develops with one or
more of the following:
Cardidtis
Polyarthritis
Sydenham chorea
Erythema marginatum
Subcutaneous nodules
Polyarthralgia
Fever
8. Carditis
Pancarditis-pericardium, myocardium, endocrdium or valves
Mitral valve most commonly affected and more in female
Aortic valve (incompetence) more in male
Pulmonary and tricuspid valves less common
Pericarditis +effusion
Carey Cooms murmur(mid diastolic)
9. Signs of carditis:
1. High pulse rate
2. Changingmurmurs; Carey Cooms murmur (mid diastolic)
3. Cardiomegaly
4. Prolonged P-R interwal
5. Pericardial rub
6. Cardiac failure
10.

Polarthritis:
1. Migratory or flitting
2. Present in 80% patients
3. Large joints (knees, hip, wrists, elbows, shoulders)
4. Limitation of movements; swollen but no effusion
5. Small joints spared

107
11.

12.

13.

14.

Sydenham Chorea
1. Usually appear after months or years following GABHS infection
2. May be the only manifestation in some
3. Common in females
4. Lasts up to 3 months
5. Involuntary purposeless movement
6. Emotional lability
7. Ataxia
8. Slurred speech
9. Muscular weakness
10.Difficulty in walking, writing
11.Adder sign
12.Milkmaid sign
13.Pendular knee jerk
14.Pronator sign
15.All disappear during sleep
16.Carditis can develop still later
Erythema marginatum
1. In 7 %
2. Macular
3. Serpigenous
4. Erythematous
5. Central clearance
6. Trunk and limbs involved
7. Face spared
8. Not well seen in our population
9. Carditis often associated
Subcutaneous nodules
1. In 5 %
2. Occur in severe cases
3. Seen over elbows, joints, scalps, spinal column
4. Size: few mm to 2 cm
5. Non tender
6. Movable under the skin
Diagnosis: 2major or 1majorandtwominor of modified criteria
Original Jones Criteria - 1944
1. Major:
1. Carditis
2. Arthralgia
3. Chorea
4. Subcute. Nodules
5. Hx of prev ARF
6. or rheumatic H.D.
2. Minor :
1. Fever
2. Abdominal Pain

108
3.
4.
5.
6.
7.

Precordial Pain
E. Marginatum
Epistaxis
Pul Findings
Lab findings - ESR, WBCs
8. Anemia, ECG changes.
Modified Jones criteria - 1992
Major:
1. Carditis - Echo of MV
2. Migratory Polyarthritis
3. Erythema Marginatum
4. Sydenhams Chorea
5. Subcutaneous Nodules
Minor:
1. Arthralgia
2. Fever
3. ECG prolonged P-R
4. Previous Rheumatic fever or heart disease:
5. Lab - ESR, CRP, ASO,
6. + Strep Culture
15. Other tests
1. WBC count : neutrophils count is high
2. ESR: greatly elevated >100 mm /hr
3. CRP is positive
4. ECG: prolonged P-R interval (first degree heart block)
5. CXR
16.
Differential diagnosis
1. Juvenile Rheumatoid arthritis
2. Systemic lupus erythematosus
3. Reactive arthritis

DIPHTHERIA
1. Definition:
i. Acute toxic infection caused by corynebacterium diphtheriae
ii. Diphtheria in Greek means a piece of leather
iii. I st infection in history conquered by the principles of bacteriology,
immunology and public health.
2. Etiology:
i. corynebacterium diphtheriae are aerobic, nonencapsulated, non-spore
forming, non motile, pleomorphic, gram positive bacilli
ii. Mitis, intermedius and gravis, belfanti are serotypes.
iii. Produce exotoxin after encoded by a bacteriophage
iv. C.ulcreans less commonly produce similar disease.
3. Pathogenesis:

109
i. Transmission by droplets sometimes by contact with skin lesion
ii. Asymptomatic carriers also spread the disease
iii. Children under 15 are susceptible
iv. Remain in superficial layers of respiratory mucosa and multiply
v. Induce cell necrosis by toxin
4. Psuedomembrane:
i. Cell necrosis, fibrin, leukocytes, epithelial cells , RBCs and bacilli together
form a dense membrane
ii. Adherent to underlying tissues
iii. Bleeds on peeling
iv. Usually seen on tonsil and posterior fornix.
v. Nasal , laryngeal , conjunctival and cutaneous lesions possible
vi. Cervical glands enlarge to form bull neck
vii. Exotoxin affects heart, kidneys and CNS
Diphtheritic membrane and bull neck

Clinical features
i. Incubation 2-5 days
ii. Nasal:
Membrane in nares and upper lip
iii. Faucial:
Membrane on tonsils, fornix, palate, pharynx and uvula
Cervical nodes enlarge
iv. Laryngeal:
Membrane on larynx and can spread to trachea and bronchi
Hoarseness, stridor and croup
6. Other sites:
i. Cutaneous:
Non healing ulcers with grey brown membrane
Spreads to others
Provides immunity to host
ii. Eye:
5.

110

7.

8.

9.

10.

11.

Ulcerative conjunctivitis
iii. Vulvo vaginitis
iv. Otitis externa
Diagnosis:
i. Culture from lesions
ii. Smear to identify organisms
iii. Toxigenicity to be determined ( Elek test)
iv. PCR for toxin gene
Complications:
i.
Cardiomyopathy(10-24%)
2nd week
Tachycardia
Prolonged P-R interwal
ST-T changes
Heart blocks
CCF
ii.
Neuropathy
Occurs after 2-3 weeks
Palatal palsy
Occulomotor
Strabismus
ciliary paralysis
Blurred vision
Loss of accommodation
Peripheral neuritis
muscle weakness
Diaphragmatic paralysis
DD
i. Infectious mononucleosus
ii. Vincents angina
iii. Streptococcal pharyngitis
iv. herpes
Treatment :
i. Antidiphtheritic serum after sensitivity tests
Nasal: 10 to 20000 U IM
Faucial: 15 to 25000 U IM/IV
Laryngeal 20 to 40000 IM/IV
Severe forms: 40 to 100 000 U half IM ; half IV
ii. Drugs:
Crystalline penicillin 25 to 50 000 U /kg IV in 3 doses for 14 days
Erythromycin is an alternative
iii. Tracheostomy
iv. ECG monitoring
v. Nutrition and hydration
Prognosis :

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i. Mortality 30-50% reduced to 5-10% by effective management
ii. ADS within 72 hrs reduce mortality
iii. Mortality high in facial and laryngeal diphtheria
12. Prevention:
i. Antibiotic prophylaxis to carries
ii. Diphtheria vaccine 5 doses before 5 yrs
iii. Adult vaccine by 11-12 yrs

Intestinal Protozoan infections

Enteric protozoan:
Introduction:
i.

ii.

1. Types:

General features:
1. A disease of open air defecation; poor hand washing and anal sex
2. HIV, immune deficient disorders a special risk
3. Epidemics among Children in orphanage
Prevention:
1. Sanitation- sanitary latrines
2. Safe water
3. Cooked food
4. Peeled vegetables and fruits
5. Hand washing
6. Avoid food sold by street vendors.

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Invasive:

Amoebiasis
Noninvasive:

Giardiasis
Cryptosporidiasis
Cyclosporiasis

2. Amebiasis:
a. Types:
i. Entamoeba dispar
ii. Entamoeba histolytica
b. Epidemiology
1. Man is the only host
2. 10% of world population is infected
3. 100 000 people die each year
4. Endemic in countries with poor hygiene and sanitation
5. 90 % E.histolytica and 100 % of E.dispar infections are
asymptomatic
6. All age groups are affected
7. No sex difference
8. Childhood amebiasis is relatively less common
9. 30% homosexuals pass cysts in stools
10.More common among asylums
11.Significant problem in HIV
c. Transmission
i. By faecal contamination of drinking water and foods
ii. Direct contact with contaminated hands or objects
iii. Homosexual contact.
iv. Geophagy is a common route of infection
v. Faeco oral transmission: 5 Fs
Finger
Food
Fluid
Flees
Fomites
d. Clinical manifestations:
a. Asymptomatic carrier state
b. Acute amoebic dysentery (proctocolitis)
c. Amoebic liver abscess
d. Amoeboma
e. Lung abscess
f. Cerebral abscess
g. Poor host defense is still a mystery
e. Amebic dysentery:
a. Initially watery diarrhea with fever and dehydration; diffuse
abdominal pain
b. Later recurrent episodes of bloody diarrhea
c. Can lead to fulminant colitis with increased mortality;

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d. Flask shaped ulcers in colon
e. Intestinal perforation and peritonitis
f. Less commonly colonic strictures and peri anal ulcers
f. Ameboma:
a. Localized amebic infection
b. Usually in caecum or ascending colon
c. Clinically a palpable painful abdominal mass in lower right abdominal
quadrant
g. Extra intestinal amebiasis:

a. Liver

abscess:
Fever
Right upper quadrant tenderness
Referred pain to right shoulder
Hepatomegaly
Jaundice and diarrhea rare
Can rupture into pleural cavity or peritoneal cavity
peritonoitis
b. Lung abscess:
Hematogenous spread
Caugh
Dyspnea
Pleuritic pain
Pleural effusion
c. Other complications:
Cerebral abscess - hematogenous
Genitourinary amebiasis rupture of abscess
Pericarditis- hematogenous or rupture of abscess
h. Diagnosis:
i. Live motile trophozoites containing rbcs in wet preparation of
minimum 3 stool samples

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ii. Specific antigen detection differentiates from E.dispar-Enzyme
immuno assay

115
5. Lab findings:
i. Live motile parasites in stools and duodenal aspirates
ii. Detection of cysts in stools
iii. Giardia antigen detection (ELIZA)
6. Treatment:
i. Metronidazole: 5 mg/kg 3 times/day for 5 days
ii. Tinidazole: 50 mg/kg single dose
iii. Nitazoxanide 100 to 200 mg BD for 3 days
iv. Furazolidine 1.5 mg 4 times/day for 7-10 days
7.

Cryptosporidiasis: Cryptosporidium parvum

a. Introduction:

Cerebral palsy
1. Definiton: group of motor syndromes resulting from disorders of early brain
development and manifesting as chronic, static impairment of muscle tone,
power, coordination and movements often associated with epilepsy and
abnormalities of speech, vision, intellect etc
2. Prevalence: 2 per 1000
3. Etiology:
a. Only 10% are due to intrapartum asphyxia
b. Intrauterine infections
c. LBW/Preterm who have more chances of intracranial haemorrhage
d. Maternal sepsis (UTI) and fever>38C
4. Pathology: periventicular leukomalacia

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5.

a. Enhanced vulnerability of immature oligodendroglia (myelin producing cells

of the central nervous system) to oxidative stress caused by
ischemia/infection/inflammatory insults
b. Loss of volume of periventricular white matter& cystic changes,
c. ventricular dilatation
d. thinning of carpus callosum
Classification:
Motor
syndrome
Spastic
diplegia

Pathology

Etiology

PVL

Spastic
quadriplegia
Hemiplegia

PVL; multicystic
encephalomalacia
Malformations
Stroke in utero or neonatal

Extrapyramida
Athetoid,dyskin
etic

Putamen,thalamus, basal
ganglia undergo pathologic
changes

Prematurity; Ischemia ;
Infection ;
Endocrine and Metabolic
Endocrine; Metabolic;
Genetic;
Developmental; PVL
Genetic; Developmental;
PVL
Asphyxia; Kernicterus;
Mitochondrial; Metabolic;
Genetic

6. Spastic hemiplegia:
a. Arm more involved than legs
b. Show hand preference in early stage
c. Walking may be delayed up to 2yrs
d. Circumduction gait
e. Growth arrest in affected limbs
f. Equinovarus deformity of foot
g. Tiptoe walking
h. Ankle clonus and Babinski sign
i. Increased DTR
j. Weekness of hand and foot dorsiflexors
k. 1/3 have epilepsy
l. have mental retardation
m. Family history may be suggestive of inherited clotting disorders in some
n. CT scan:
i. Focal cerebral infarction: thromboembolic disorder: anticardiolipin
antibodies
ii. Calcification: intrauterine infection
7. Spastic diplegia:
a. Clinical:
i. Bilateral spasticity of legs greater than arms
ii. First noticed when infant begins to crawl
iii. While crawling infant drags the legs (commando crawl)
iv. Application of diaper is difficult
v. Child is unable to sit
vi. Brisk reflexes, ankle clonus, bilateral Babinski
vii. Scissoring posture on suspension by axillae
viii. Walking is delayed
ix. Equinovarus deformity with tiptoe walking

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x. Less growth of lower limbs and normal development of upper torso
xi. Inteliigence is normal
xii. Seizures are meinimal
b. Pathology: Periventicular leukomalacia near internal capsule
c. MRI: shows specific regional abnormalities
8. Spastic quadriplegia:
a. Clinical:
i. Most severe form
ii. Marked motor involvement of all four limbs
iii. Severe mental retardation and seizures
iv. Supranuclear bulbar palsy (psuedobulbar) with difficulty in
swallowing and frequent aspiration pneumonias
v. Increased tone in all limbs
vi. Decreased movements
vii. Hyper reflexia
viii. Plantar extensor
ix. Later: flexion contractures in limbs
x. Speech and visual abnormalities
xi. May have athetosis
b. Pathology: PVL and cystic changes in cortex
9. Athetoid CP (extrapyramidal CP):
a. Clinical:
i. Less common
ii. More likely associated with birth asphyxia
iii. Limbs are hypotonic
iv. Poor head control
v. Difficulty in feeding, tongue thrust and drooling are prominent
vi. Speech is slurred
vii. Seizures are uncommon
viii. Intellect is preserved
b. Pathology: The lesions have a marbled appearance caused by neuronal loss and an
overgrowth of myelin in the putamen, caudate, and thalamus. It is describes as status
marmoratus; similarity with kernicterus

c.
10.Diagnosis:
a. Static disorder in contrast to progressive disorders of degeneration and
muscular dystrophy
b. MRI will rule out cervical spinal cord lesions like tumors and anomalies of
base of the skull
c. Chromosomal disorders will have abnormal karyotype
d. Screening for metabolic disorders
11.Treatment:
a. Multidisciplinary approach
b. Parental guidance
c. Physiotherapy
d. Occupational therapy
e. Tendon release
f. Aplliances
g. Rhizotomy for spasticity
h. Ophthalmic management
i. Drugs:
i. Oral dantrolene sodium, benzodiazepines and baclofen for spasticity

118
ii. Injection of botulinum toxin in muscle groups and salivary glands
iii. Levodopa for dystonia

Pertusis
1. Etiology:
Bordetella pertusis: epidemic and sporadic causes
Bordetella parapertusis: sporadic cases
B.bronchiseptica: animal pathogen
2. Epidemiology:
World over 60 million cases and 500,000 deaths
Vaccine caused >99% reduction in incidence
1-6 yr more susceptible
More cases in older children
3. Pathogenesis
Gram negative coccobacilli
Droplet infection
Colonize only ciliated epithelium
Local epithelial damage
Pertusis toxin mechanism unclear; inhibits immune functions of host
4 . Clinical manifestations

119
Incubation 3-12 days
Catarrhal:
1-2 weeks; fever; rhinorrhea; lacrimation and conjunctival suffusion
Paroxysmal:
2-6 weeks
Initial dry intermittent cough
Machine gun burst of uninterrupted cough
Loud whoop
Vomiting
Clutches a comforting adult
convalescent stage :
2 weeks
Symptoms regress
Infants:
No stages
No typical cough or whoop
After a trigger may develop signs of choking, cyanosis and apnea.
Paroxysm may continue intermittently for a longer period
SIDS
Immunized children and adults:

No distinct stages
Whoop not apparent
Uninterrupted cough
Post tussive emesis
Lasts for 3 weeks
Physical findings
Uninformative in many
Secondary infection may show signs of pneumonia
Conjunctival hemorrhage and petechiae on the face
Swollen eye lids
Diagnosis
Cough with whoop
Absence of fever and lung signs
Lymphocytosis
Normal CXR
Pharyngeal swap culture:

Bordet Gengou medium

Colonies like mercury droplets
PCR from throat swaps
Serum for agglutinins
Treatment :
Azithromycin 10 mg/kg od for 5 days
Erythromycin for > 1 m infants (causes pyloric stenosis In NB )
Air way maintenance
Quiet environment
Mist inhalation

4.

5.

6.

7.

8.

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Small frequent feeding
9. Isolation: up to 5 days of treatment
10.Complications:
Apnea
Secondary infections
Otitis media
CNS hemorrhage
Hernia
Laceration of lingual frenulum
SIDS
Pertusis encephalopathy
11.Prevention:
DPT (DTwP)
Acellular pertusis vaccine (DTaP)
Tdap for adolescents

TRISOMY SYNDROMES
1. Common types:
i. Trisomy 21 - Down syndrome
ii. Trisomy 18 - Edward syndrome
iii. Trisomy 13 - Patau syndrome
2. Genetics-some basics:
Human cells has 23 pairs of chromosomes diploid cells
Human egg and sperm cells contain 23 chromosomes- haploid cells
23 pairs+ or 1 or more chromosomes aneuploid
3 copies of same chromosome present in a cell is called trisomy
Mostly anomalies are lethal and end in abortion
3. Types of genetic disorders
i.
Single-gene (Mendellian or monogenic disorders): mutations occur in one
gene:
cystic fibrosis, Marfan syndrome
could be dominant , recessive or X linked
ii.
Polygenic or Multifactorial : mutations in multiple genes+ environmental :
cleft palate , CHD and diabetes.
iii.
Mitochondrial Disorders: mutations in the mitochondrial DNA;:
Leber's Hereditary Optic neuropathy.

121
4. Types of genetic disorders
5. Chromosomal disorders:
i.
Sructural:
Deletion
Translocation
Invertion
Ring formation
ii.
Numerical: (aneuploidy) autosomal and sex chromosomal
Monosomy
Trisomy
Mosaicism
iii.
Mechanism of Trisomy formation
Non disjunction:
Normal
Non disjunction

6. Roberstonian Translocation :

7. Mosaicisism
Occurs at mitosis of zygote

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Down syndrome
1. Incidence:
i.
1/750 births
ii.
Double this incidence at conception
iii.
Advanced maternal age (>35yrs)
iv.
97% maternal origin
v.
95% nondisjunction
vi.
4% translocation
vii.
1% mosicism
2. DOWN syndrome: Phenotype
1. Hypotonia
2. Brchycephaly
3. Mid facial hyperplasia
4. Upslanted palpebrum
5. Epicanthic folds
6. Brushfield spots in iris
7. Protruding toungue
8. CHD: endocardial cushion
defect; VSD
9. Mental retardation
10.Postreior fontannel
8. Additional features:
1. Excessive skin at nape of
the neck
2. Epilepsy and febrile fits
3. Cataract
4. Low set small ears
9. Associations:

11.Hypoimmunity
12.Short stature
13.Short and broad hand
14.Simian crease
15.Single flexor crease in little
finger
16.Incurving of little finger
17.Ulnar loops
18.Proximal triradius
19.Sandal cleft in foot
20.Brushfield spots in iris
5.
6.
7.
8.

Accident proneness
Quiet infants
Friendly
Love music

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1.
2.
3.
4.

Duodenal atresia
Leukemias
Hypothyroidism
Infertility

5. Deafness
6. Atlanto axial instability
7. Diabetes mellitus

TRISOMY 21: Genetic counseling

1. 21-21 translocation carrier-100%
5. 1in 200 chance for mother > 35
risk
yrs
2. 14-21 carrier 15% risk
6. 1in 2000 chance for mother < 25
3. Father as carrier risk is 1 in 200
yrs
4. 1in100 chance for mother > 40
yrs
Prenatal diagnosis:
1.
Triple test or Triple screen:
In trisomy 21, second-trimester maternal serum levels:
1. Alpha-fetoprotein
} 25 percent lower
2. Unconjugated estriol }
3. Human chorionic gonadotropin is two times higher than normal.
2. Ultrasound
1.
Increased nuchal fold thickness (nuchal translucency), caused by
subcutaneous edema at the base of the occiput
2.
Fetal echocardiogram at 20 weeks to detect serious cardiac malformations.
3.
An ultrasound at 28 to 32 weeks to monitor growth and detect duodenal
atresia.

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3. Cytogenetics
1. cytogenetic analysis of cells obtained by one of three invasive procedures :
First trimester amniocentesis
Second-trimester amniocentesis
Chorionic villus sampling
2. Karyotype analysis - requires seven to 10 days.
3. Fluorescent in situ hybridization (FISH) for rapid diagnosis
4. TREATMENT
1.
Referral to support groups
2.
Referral to organizations that advocate for Down syndrome.
3.
A positive outlook should be encouraged.
4.
Medical care
5.
Early intervention for CHD, Cataracts and other defects.
6.
Special education and vocational counselling
7.
Prevention of accidents
5. Prognosis
1. Mosaics have less severe features
2. Deaths due to overwhelming infections; Accidents; Maliganancy ; CHD

TRISOMY 18: Edward syndrome

1. Incidence: 1 in 6000 births
2. Features:
1. Low birth weight
8. Hyper tonicity
2. Closed fists
9. Short sternum
3. Overlapping fingers
10.Rocker bottom feet
4. Narrow hip
11.Micro cephaly
5. CHD
12.Prominent occiput
6. Renal defects
13.Micrognathia
7. Mental retardation
3. 95% die in infancy

TRISOMY 13: Patau syndrome

1. Incidence:
i.
1 in 12000 births
2. Feautures:
1. Cleft lip

2. Polydactyly

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3.
4.
5.
6.
7.
3. Patau

Hypotelorism
Bulbous nose
Low set malformed ears
Brain malformation
Scalp defects-alopecia
syndrome

8. Absent ribs
9. Genital defects
10.Visceral defects
11.Microptholmia

Neonatal Sepsis Septicaemia

1. Definition: neonatal sepsis is a clinical syndrome of systemic illness accompanied by
bacteremia occurring in the first of life.
2. Incidence:
2% in - utero
10% in neonates
Twofold higher incidence in Male
3-10 times higher incidence in LBWT and Preterm
3. Clinical Types:
a. Early Onset Sepsis- within 1 week: pathogens in the genital tract colonize
on skin, umbilical cord, respiratory and GIT mucosa or through placenta in
the perinatal period
b. Late onset Sepsis after 1 week of life; pathogens acquired through human
contacts or nosocomial
4. Definition of sepsis:
1. Bacteremia- presence of bacteria in blood
2. Septicemia :
Bacterial multiplication elaboration of toxin Toxemia Inflammatory
response morbidity mortality
5. Risk Factors:
a. Preterm and MBW
b. Rupture of membranes
c. Maternal infection
d. Resuscitation

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6.

7.

8.

9.

e. Invasive monitoring
f. Galactosemia: E.coli sepsis
g. Male sex
h. Bottle feeding
i. Cultural practices like oil bath, blowing into mouth
Normal immunity:
Microbial entry Neutrophils move in Chemotaxis opsonization
phagocytosis killing
Immune status in NB:
a. Ig G and complement level are less in preterm and prone for GBS sepsis
b. Neutrophils: reduced phagocyic activity against Gm negative bacteria like
E.Coli
c. Monocyte-macrophage system : chemotaxis is impaired
d. Lymphocyte: Natural killer cells have reduced cytotoxic activity and prone
for viral infections like HSV
Transmission
a. Antenatal: Transplacental
b. Intranatal: Trans vaginal
c. Postnatal:
i. Breastfeeding (HIV) / formula feeding : enteric group
ii. Nursery acquired
iii. Community acquired
Early onset sepsis:
a. causes:
1.
Transplacental (TORCHS)
1. Cytomegalovirus }
2. Rubella
}
3. HSV
}
(viral)
4. HIV
}
5. Treponema pallidum
(spirochete)
6. Toxoplasma gondi
(protozoa)
2.
Trans vaginal:
1. Chorioamnionitis due to :
a. PROM (>18 hrs);
b. MRO aspiration of infected fluid
3. Postnatal:
2. Resuscitation procedures
a. Endotracheal tube
b. Suction apparatus
c. Umbilical catheterization
b. Early Pathogens (first week):
1. Transplacental: (TORCHS)
a. Toxoplasma
d. HSV; HIV
b. Rubella;
e. Syphilis;
c. CMV;
f. Listeria monocytogenes
2. Transvaginal:

127
a. GBS;
b. E.Coli;
c. Gonococci;
3. Postnatal:
a. Staph aureus;
b. Klebsiella;
c. Salmonella;
Early onset sepsis :
Ascending infection

11. Late onset sepsis:

Causes:
Nursery:
Nosocomial
Cross infection
Breastfeeding: HIV
Community acquired
Late Pathogens:
Nursery:
GBS
Enterics/Enterococcus
HSV
Enterovirus, RSV, Flu
Coomunity:
GBS, E. coli and other Gram-negative species
CDC data:

d. Chlamydia
e. HSV; HIV

d. Psuedomonas.
e. Parainfluenza;
f. adenovirus
Vertical transmission

128

12. Pathogenesis:
Colonization in skin, mucous membranes
Multiplication and spread
Bactremia
Lungs, Brain, blood,Kidneys
Inflammatory response
Pnumonia, meningitis, septicemia, UTI
Overwhelming sepsis
Septic shock
Death
13. Signs and symptoms:
General
Vague and nonspecific; subtle or insiduos
Temperature irregularity:
Hypothermia more common than fever
Hyperthermia in viral infection like Herpes
Change in behavior:
Lethargy and poor suck
Irritability
Change in tone
Skin:
Pallor and circumoral cyanosis
Skin mottling
Petichiae
Rash
Sclerema
Jaundice
Feeding:
Feeding intolerance
Vomiting
Diarrhea
Abdominal distension; + or Visible bowel loops
Metabolic:
Hypoglycaemia
Hyperglycemia
Metabolic acidosis
Focal sepsis:

129

14.

DD:
1.
2.
3.
4.
5.
6.

Cellulitis
Umbilical sepsis
Impetigo
Osteomyelitis
Septic arthritis
Meningitis
Otitis media
Systemic:
GIT: diarrhea and vomiting
R.S: Dyspnea, tachypnea, grunting, chest retraction
CNS: convulsions; inactivity, high pitched cry, bulging fontanel
Vacant look
Feeble cry; Apneic spells
Abd: Hepatosplenomegaly
RDS
Transient tachypnea
Intra cerebral haemorrhage
Inborn errors of metabolism
GI perforation
Disseminated herpes

14. Complications:
Hypoglycemia
Acidosis
Hypotension
Anemia
Disseminated intra vascular coagulation
Hyperbilirubinemia
Organ failures
15. Septic screening
Gastric aspirate
> 5 polys per HPF; C/S
Maternal vaginal swap
For GPS; C/S
TC
< 5000 / cml
Bandemia
> 20 %
Thrombocytopenia
Acidosis
Micro ESR
> 15 mm
CRP
> 8 mg/L
Cytokins and procalcitonin:
elevated
CSF
C/S; microscopy
Blood : Glucose; Bilirubin; Urea; electolytes
Blood culture
CXR:
Hyperventilation
Thymic atrophy

130

Pear shaped heart

Distended abdomen (foot ball sign)

16. Treatment
IV fluids : glucose and electrolytes
Fresh blood: provides polys, thrombocytes, complements and opsonins
Exchange blood transfusion: to remove toxins
IV Gamma Globulins: 500 mg/kg
Antibiotics:
GBS & E.Coli:
Ampicillin 100 mg/kg Or Cefotaxim 100 mg mg/kg with
Gentamycin 5 mg/kg
Vancomycin 10 mg/kg
Staph:
Cefotaxim with Gentamycin
17. Prognosis
Mortality is > 20 %
Mortality increases with coexisting complications:
Tracheo esophegeal fistula
Meningo myelocoel
Meconium aspiration
Respiratory Distress syndrome

18. Prevention
Maternal screening for GBS, HSV, HIV, Syphilis,Gono
Antibiotic prophylaxis to antenatal mother who are identified carriers of GBS
Antibiotic prophylaxis to neonate
Hand washing
Barrier nursing
Aseptic techniques in resuscitation and nursery care
Colostrum and exclusive breast feeding
Caesarian section for proved vaginal sepsis like HSV

131

NEONATAL HYPERBILIRUBINEMIA
Bilirubin
It is an end product of heme catabolism
Anti oxidants like Vit.E, Catalase, superoxide dismutase are deficient in NB
Bilirubin is a powerful antioxidant
Peroxyl scavenger
It protects NB from oxygen toxicity
Formation of Bilirubin
is liberated from
Senile RBCs
Defective RBCs
Structure - sickle cell; Thalassemia
Enzymes - G6PD
Membrane - Spherocytosis
Ineffective erythropoiesis
Bilirubin production:
RBC Macrophages in Bonemarrow + Reticuloendothelial system (spleen)
hemoglobin Heme + Globin ; Heme Biliverdin + Iron Bilirubin (indirect)
Bilirubin di glucuronide (direct)
Direct and indirect bilirubin
van den bergh test
To detect bilirubin in serum
Ehrlichs diazo reagent containing sulphanilic acid and sodium nitrite
Dirct: Serum + reagent reddish purple
Indirect: Serum + reagent + alcohol reddish purple
Bilirubin metabolism:

Heme

132
Blood :
Liver :

Bilirubin carried by Z protein enters liver

Bilirubin conjugated to b.diglucuronide by
Diphospho glucuronyl transferase
Intestine:
Con. Bilirubin secreted through bile into intestine
Bacteria converts it into stercobilinogen
Epithelial glucuronidase converts it back into
unconjugated bilirubin
Enterohepatic Circulation: Unconjugated
bilirubin
reabsorbed
and
transported to liver
Classification of Hyperbilirubinemia
1) Physiological
2) Pathological
1. Indirect:
I.
Hemolytic
Immune (Coombs Positive)
ABO
Rh
Nonimmune
Enzyme defect- G6PD
Membrane defect: Spherocytosis
Hemoglobin defect: Thalasemia
II.
Non Hemolytic

Breast milk

Criggler najar

Gilbert

Infection
2. Direct:
I.
Dubin Jhonson
II.
Rotar
III.
Infection
IV.
Biliary Obstruction
PHYSIOLOGICAL JAUNDICE: Icterus neonatorum
Criteria:
1) Jaundice after 24 hrs of life
2) Increase by less than 5 mg/dl/day
3) Maximum 12 mg/dl in tern and 15 mg in preterm
4) Peak in 3-5 days and subside in 7 days in term and 14 days in preterm
5) Direct less than 1 mg
Causes of physiological jaundice:
1) Increased Hb%
2) Low UDPGT
3) Decreased intestinal flora
4) Decreased intestinal motility
5) Increased enterohepatic circulation
Exaggerated physiological jaundice :

again

133
1)
2)
3)
4)
5)
6)
7)

Preterm
Trisomy 21
Cretinism
Male
Asian race
Hemorrhage: cephalhematoma
Oxytocin drip in mother

Pathologic jaundice
1. Immune Hemolytic - Erythroblastosis fetalis

ABO incompatibility:
Features:
A1 more antigenic
O - A1 severe incompatibility due to Ig.G antibodies produced by
mother with O Gr
ABO in 20 % pregnancies
Among them 20 % develop icterus
Overall incidence is 1-2 %
First pregnancy can be affected
Less jaundice but anemia may be significant
< 10% may go for exchange transfusion
2/3 of haemolytic jaundice are ABO incompatibility
ABO diagnosis:
Grouping
Week Coombs positive
spherocytes in blood smear
Indirect Bilirubin elevated to moderate level
Polychromazia
Reti. count increased
ABO treatment :
Phototherapy
Packed cell transfusion
Rarely exchange transfusion

Rh Incompatibility :
Features:
More than 60 antigens in RBC
Rh factor is one
Rh factor has many antigens:
D, C,E, Kell, Kidd, K, M, Duffy
90 % Rh disease due to D antigen
C&E 10%
Rh Sensitization:
Rh ve Mother sensitized by fetal Rh + RBC by feto maternal transfusion
that occurs during:
Normal Delivery
Internal versions

134
Invasive procedures
Abortions
Tubal pregnancies
Abdominal injury

1 ml of fetal blood can produce adequate sensitization

Ig M and IgG antibodies are produced
Ig G crosses placenta into fetal circulation
Adheres to fetal RBC
Produce haemolysis by compliment activation
Increasing severity by successive pregnancies
ABO incompatibility will reduce severity of Rh incompatibility
Clinical features
Only 5 % develop hemolytic disease due to:
Less chance for feto maternal transfusion
variable maternal response
less no of pregnancies
ABO incompatibility
Among them 15% are mild
Rest varying severity
Hydrops Fetalis:
Intra uterine hemolysis
Severe anemia
Hypoproteinemia
Anasarca
CCF
IUD
Rh disease in NB:
Indirect hyperbilirubinemia within 24 hrs
Fast rise to threshold levels
Anemia
Hypoglycemia
Kernicterus
Kernicterus:
Bilirubin deposited in
basal ganglia,
brainstem,
Hippocampus
Olfactory nuclei
cerebellum etc
Neuronal loss due damage to cell membrane and interference to O2
utilization
Early stage:
Lethargy
Poor feeding
Loss of moro
High pitched cry

135
Hypertonia
Opisthotonus
Bulging fontanell
Convulsions
Spasticity
Death
Chronic stage:
Hypotonia
Mental retardation
Seizures
Squint
Ataxia
Deafness
Diagnosis of Rh:
Cord Blood:
Group and Rh type
Strong positive direct Coombs test
Hb% low
UC bilirubin elevated
Polychromazia
Increased reti count
Nucleated RBCs
Maternal:
Anti D Ig.G elevated
Ultrasound:
Scalp edema
Hepato splenomegaly
Increased middle cerebral artery flow
Umbilical cord blood sampling:
Hb
Grouping, typing
Bilirubuin estimation
Treatment:
Aim:
1) Prevent IUD
2) Prevent Kernicterus
Fetal:
O ve Packed cell transfusion
Neonate:
Packed cells transfusion for anemia
Albumin therapy to improve bilirubin transport to liver and bound bilirubin is
non toxic
Phototherapy
Exchange transfusion
IV Immunoglobulin
Casein decreases enterohepatic circulation by inhibiting glucuronidase

136
Tin or zinc proto or meso porphyrin inhibits heme oxygenase
Phenobarbitone increases glucuronyl transferase enzyme activity; more
useful in Crigler Najjar type II and Gilbert
Exchange Transfusion:
Indications:
Threshold level for Kernicterus:
>20 mg for term and
> 15 mg for preterm
Cord Hb% <10
Cord bilirubin > 5mg
Exchange transfusion:
O ve fresh blood cross matched with infant and mothers sera
Double volume: 85X2/kg ml
20 ml exchanged each time via umbilical venous catheter placed at IVC or
hepatic vein
Removes 80% sensitized cells and mat. antibodies and 50 % of bilirubin
Complications:
Sudden death
Necrotizing enterocolitis
Portal vein thrombosis
Sepsis
Anemia
Electrolyte changes
Hypocalcemia
Thrombocytopenia
Phototherapy :
Light in blue-green spectrum 425-475 nm
Blue florescent tubes
Converts Unconjugated bilirubin in the skin to water soluble stereoisomer
30-40% bilirubin can be reduced in the first24 hrs
Started at 5mg less of exchange levels
Eyes covered
Complications:
Loose stools
Bronze baby syndrome
Purpueric rash
Hypo or hyperthermia
Elevation of direct bilirubin
Non immune hemolytic jaundice
Breastmilk and jaundice:
1. Breast feeding associated jaundice:
a. Inadequate breast milk with starvation leading to increased
enterohepatic circulation
b. Bilirubin in meconium is absorbed due to lack of meconium clerence
2. Breast milk jaundice:

137
a. Prolonged indirect hyperbilirubinemia beyond 2 week
b. 10-30% of infants affected
c. Gilbert syndrome may be associated in some - Defects in uridine
diphosphate-glucuronyl transferase activity
d. An unusual metabolite of progesterone (pregnane-3-alpha 20 beta-diol),
a substance in the breast milk that inhibits uridine diphosphoglucuronic
acid (UDPGA) glucuronyl transferase
e. Increased concentrations of nonesterified free fatty acids that inhibit
hepatic glucuronyl transferase
f. Increased enterohepatic circulation of bilirubin due to (1) increased
content of beta glucuronidase activity in breast milk and, therefore, the
intestines of the breastfed neonate and (2) delayed establishment of
enteric flora in breastfed infants
g. Reduced hepatic uptake of unconjugated bilirubin due to a mutation in
the solute carrier organic anion transporter protein SLCO1B1.
h. Inflammatory cytokines in human milk, especially interleukin (IL)-1 beta
and IL-6, are increased in individuals with breast milk jaundice and are
known to be cholestatic and reduce the uptake, metabolism, and
excretion of bilirubin.
Hereditary spherocytosis:
Autosomal dominant
Membrane proteins spectrin and ankyrin are defective
Spherical shape of rbc
Osmotic fragility test + ve
Splenectomy is the cure
G-6 PD deficiency:
Enzyme defect : Low level of G6PD
X-linked inheritance
Mild form of Non Hemolytic Jaundice
Aggravated by Gilbert syndrome if coexisting
Crigler-Najjar:
Type I :
autosomal recessive
Lack of UDPGT
Type II:
autosomal dominant
Milder form
Phenobarbitone useful
Gilbert Syndrome:
Autosomal dominant
Decreased hepatic UDPGT
10 % population affected
Prolongs physiological and breast milk jaundice
Rare forms
Lucy - Driscol syndrome:
Indirect hyperbilirubinemia

138

Dubin-Jhonson:

Rotar:

Due to unknown inhibitor of bilirubin conjugation

Direct Hyperbilirubinemia
Greenish yellow skin
Pale stools
Hepatomegaly
Causes:
TORCHS
Con.Biliary atresia
Hep.A,B
Insipissated bile syndrome
Conjugated bilirubin not excreted into bile
Direct hyperbilirubinemia
Autosomal recessive
Pigmentation of liver
Same as Dubin-Jhonson without liver pigmentation

VPD - vaccine-preventable disease

Definitions:
An infectious disease for which an effective preventive vaccine exists.
If a person dies from it, the death is considered a vaccine-preventable
death.
1.4 million U5 deaths were from vaccine-preventable diseases.
With 100% immunization, one out of seven deaths could be prevented
The 8 targeted VPDs in India are:
Diphtheria,
Poliomyelitis,
Hepatitis B,

Tetanus,
Measles,
Tuberculosis,
Pertusis,
JE
six killer diseases:
1. Polio,
4. Pertusis (whooping cough),
2. Diphtheria,
5. Measles and
3. Tuberculosis,
6. Tetanus.
Fully immunized child: A child who received
1. One dose of BCG,
2. Three doses of DPT and OPV
3. One dose of measles before one year of age
4. This gives a child the best chance for survival
Historical: Small pox:
1. The first vaccine having been sent by Jenner himself and used in Bombay in
1802.

139
2. The pilot projects began during 1960
3. WHO certified India to be free of smallpox in March 1977.
4. The global eradication of smallpox is arguably the greatest achievement of
twentieth century medicine
Milestones in the Immunization Program in India:
1978: Expanded Program of Immunization (EPI) introduced after smallpox
eradication: BCG, DPT, OPV, Typhoid; limited to mainly urban areas
1985: Universal Immunization Program (UIP) introduced; Expanded to entire
country; Measles added;
1990: Vitamin-A supplementation
1992: Child Survival and Safe Motherhood Program
1995: Polio National Immunization Days
1997: Reproductive and Child Health Program (RCH I)
2005: RCH-II and the National Rural Health Mission (NRHM)

BCG:
1. Live attenuated vaccine prepared from mycobacterium bovis - Bacillus Calmette
Gurin
2. Heat and light sensitive vaccine
3. Add 1 cc NaCl to vial;0.05 ml intradermal; left arm; no spirit for cleaning
4. Within 14 days after birth
5. 2 to 3 weeks - papule
1. 5 weeks - 4-8 mm in diameter
2. 6-12 weeks - shallow ulcer covered with a crust.
3. Healing with round scar 2-10 mm in diameter.
4. Scar not a must
5. Prevents serious forms of TB in infancy
6. complications
1. Abcess
2. Keloid
3. Adenitis
4. Spread of tubercular disease
7. Contraindication:
1. HIV
2. Immunocompromised child
3. Mx + ve child
OPV:
1. Live attenuated whole virus vaccine
2. Trivalent- types I, II & III
3. Light and heat sensitive
4. From NB Up to 5 years of age
5. 4 doses at 6,10,14 weeks and 16-24 months
6. Pulse polio for U5 children as and when planned
7. Neurovirulance vaccine associated poliomyelitis
8. Contraindications: > 5 years; severe immune deficiency; severe diarrhea
DPT:

140
1. Diphteria and tetanus: toxoid
2. Pertusis: whole cellular inactivated bacteria
3. 6,10,14 and 16-24 months
4. Should not freeze
5. Intramuscular vaccine- preferably antero lateral thigh
6. Site of injection
7. DPT-Vaccine reactions
8. Local redness and swelling, induration,
9. Fever
10.Prolonged crying
11.Febrile convulsions
12.Hypotonichyporesponsive episodes
13.Pertusis contrindicated in:
1. Incessant crying for more than 3 hours
2. Fever more than 40.5c
3. Hypotonichyporesponsive episodes
4. Progressive neurological disease
5. > 6 years of age
Double antigen-DT :
1. Diphtheria and tetanus toxoid
2. 4 to 5 years age
3. No specific contraindications
4. Pain swelling and fever can occur
TT :
1. 6,10,14, 1 years, 4-5 years, 10, 16 years and later every ten years
2. Antenatal 2 doses at 1 month interval
3. Pain, eryythema, tenderness and induration
4. No specific contraindications
5. No need for TT in trivial injuries
Measles:
1. Live attenuated virus
2. .5 ml subcutaneous
3. Completion of 9 months
4. Mild fever and cold few days later
5. Toxic shock syndrome
6. contraindications:
1. Neomycin and egg allergy
2. Immune compromised children
Optional vaccines:
Mumps, measles and rubella vaccine (MMR):
1. Mumps can cause sterility, myocarditis and encephalitis
2. Rubella can cause fetal malformation- Congenital rubella syndrome with
CHD and mental retardation
3. MMR is given at 15 completed months
4. Adverse effects and contraindications similar to measles
5. ? autism

141
Hepatitis B vaccination:
1. Sexual and perinatal, needle stick transmission
2. Severe acute & chronic active hepatitis, hepatic carcinoma
3. HbB positive mother, NB to receive:
3. HbB vaccine at birth
4. HbB immune globulin 100 IU within 2-3 days
4. Normal schedule: 0,1,6 months or 6,10,14 weeks along with DPT
5. Child dose .5 ml; adult dose 1 ml IM, no boosters
6. May have Pain and fever
Haemophilus influenza Type B:
1. Produce otitis media, pneumonia and meningitis in children
2. Capsular polysaccharide vaccine
3. < 6 months:6,10,14 weeks combined with DPT
4. > 6 months: 2 doses at 1 month interwal
5. >15 months: 1 dose
6. Booster at 18 months
7. > 5 years: No need for vaccine
8. IM ; safe vaccine ; mild fever and pain
Typhoid vaccine:
1. Oral and IM vaccines
2. 50-80% protection
3. To be repeated every 3 years
4. Optional vaccine
5. safe
Rota virus vaccine:
1. Rota virus causes acute gastroenteritis in infants; more morbidity and
mortality
2. Rota shield withdrawn
3. Rota Teq available; oral vaccine
4. 2 ml at 2,4,6 months
5. Not to give in < 12 & > 32 weeks of age
6. ? Intussusception
7. Costly
Pneumococcal vaccine:
1. Produce meningitis, otitis media
2. PCV -7 .5ml IM at 2,4,6,and 12 months
Varicella (chickenpox):
1. 0.5 ml subcutaneous from 1-12 years
2. 2 doses at 1 month interval for >13 years
3. Adverse effects and contraindications similar to measles
Influenza:
1. Live attenuated nasal vaccine; .5 ml divided and sprayed into each
nostril; not to be given in asthmatic children
2. Killed IM vaccine; .25 ml < 3 yrs; .5 ml > 3 yrs
3. Two doses < 9 years
4. ? Guillain Barre syndrome

142
Vaccination:General precautions:
1. Screen the child for fitness
2. Verify the doses already given
3. No need to repeat schedule for gaps in dosage
4. Asepsis
5. Multiple doses to be used in 4 hours
6. Maintain Cold chain
7. Verify vaccine
8. Choose the correct root of administration
Precaution and contraindications:
1. Congenital disorders
7. Steroid therapy
2. Previous h/o anaphylaxis
8. High fever
3. Egg protein allergy
9. Severe illness
4. Allergy to preservatives
10.Bleeding disorders Epilepsy
5. Cancers
11.Febrile seizures
6. Symptomatic HIV
12.Breath holding spells

Prematurity/IUGR
1. Definitions:
Preterm: Infants delivered before 37 completed wks of gestation
Low-birth-weight infant: infant with birth weight lower than 2500g (up to and
including 2499g), regardless of gestational age.
Very low-birth-weight infant: infant with birth weight lower than 1500g (up to
and including 1499g), regardless of gestational age.
Extremely low-birth-weight infant: infant with birth weight lower than 1000g
(up to and including 999g), regardless of gestational age.

IUGR or SGA: birth weight below the 10 th percentile or > 2 SD below the mean
for gestational; impaired growth of the foetus due to foetal disorders, maternal
conditions (e.g. maternal malnutrition) or placental insufficiency.
1. Incidence:

Any baby at birth may be classified based on gestation into preterm, term or postterm
and on the birth weight into small-for- dates (SFD) appropriate-for-dates (AFD), and largefor-dates (LFD

LBW: 30% of all newborn; Preterm: 10-12% of deliveries

Infant mortality rises from five times normal at 37 weeks of gestational age to 45
times normal at 32 weeks of gestational age. Most of the problems associated
with prematurity occur in infants with birth weights of 1,500 g or less, usually in
those born at less than 32 weeks of gestational age.
Prematurity is associated with:
1. Inability of uterus to retain fetus
2. Interference with the course of pregnancy
3. Premature rupture of membranes

143

4. Premature separation of placenta

5. Unknown stimulus for uterins contractions before term
IUGR is associated with:
1. Interference with circulation and efficiency of placenta
2. Interference with growth of fetus
3. Interference with health of mother
IUGR is a noemal fetal response to nutyritional or oxygen deprivation

3.
Causes of prematurity:
1. Fetal:
i.
Fetal distress
ii.
Multiple gestation
iii.
Erythroblastosis
iv.
Non immune hydrops
V.
Chromosomal defects
2. Placental:
i.
Placental dysfunction
ii.
Placenta previa
iii.
Abruption placentae
3. Utrine:
I. Bicornuate uterus
II. Cx incompetence
4. Maternal:
i.
Teenage mothers
ii.
Low maternal weight,
iii.
Cervical incompetence,
iv.
Antepartum hemorrhage,
v.
Previous fetal loss,
vi.
Previous preterm delivery.
vii. Preterm labor is medically induced for the sake of the baby as in the case of
Rh isoimmunisation or maternal diabetes mellitus
viii. The cause of a majority of preterm deliveries, however, remains unknown.
ix.
Preeclampsia
x.
Chronic illness
1.
CHD
2.
Renal disease
xi.
Infection:
1.
Listeria
2.
GBS
3.
UTI
4.
Bacterial vaginosis
5.
Chorioamnionitis
xii. Drug abuse:
1.
Cocaine
2.
Alcohol
3.
Smoking

144
xiii. Others:
1.
PROM
2.
Polyhydramnios
3.
Trauma
xiv. Poor socioeconomic status
xv. Teen pregnancy
xvi. Maternal anemia and malnutrition
xvii. Illegitimate pregnancy
xviii. Short pregnancy interwal
xix. Grand multi
5. Causes of IUGR:
I.
Poor nutritional status of the mother
II.
Frequent pregnancies
III.
Mothers with a weight of less than 40 kg and a height of less than 145
cm
IV.
Insufficient nutritional intake during pregnancy also has an adverse effect
on fetal weight.
V.
Maternal hypertension, pre-eclampsia, post-maturity, frequent
pregnancies, multiple pregnancy, anemia, malaria and tobacco use are
other causes of intrauterine growth retardation.
VI.
Chronic maternal diseases of heart, kidneys, lungs or liver may also lead
to intrauterine growth retardation.
5.
Assesment of Gestational age:
1. Prenatal assesment:
i. Calculated from first day of LMP
ii. Date of first quickening (16-18 weeks)
iii. Ultrasound measurements (before 20 weeks): The biparietal
diameter on a routine basis has been found to predict gestational
age to within 5 days as long as measurements are taken within 15
-19 weeks of gestation
iv. Symphysio-fundal height measurements; 1 cm is equal to one
week from the 18th to 20th week of gestation. At 20 weeks, the
fundus is at the umbilicus and at term it is at the xiphoid process.
v. Amniotic fluid creatinine levels < 1.8mg/100mls are seen in 90% of
fetuses before 36 weeks while values > 1.8mg/100mls are seen in
up to 98% of foetuses after 36 weeks.
vi. By 35 weeks, on the average, the L/S ratio is about 2:1,

indicating lung maturity.

2. Post natal assessment:
i. Rapid delivery room assessment: Farr and later elaborated by
Finnstrom

145
S.N
o
1
2
3
4

Physical criteria

< 37 weeks

> 37 weeks

Creases in sloe of
feet
Breast nodule
Scalp hair
Ear lobe
Male:Teste and
scrotum

Present in anterior 1/3

only
< 4mm
Fine and wolly
Less cartilage
Testes partially
descended; few
rugosity and less
pigmentation of
scrotum
prominent clitoris;
labium minora
expopsed

Present over entire

surface
>7 mm
Coarse and silky
Thick cartilage
Teste fully descended;
fully pigmented; full
rugacity

5
Female:

Majora cover clitoris

and minora

ii. Neurological criteria: Amiel Tison described neurological

evaluation of the maturity of the newborn using study of passive
tone.
iii. Cobination of physical and neurological criteria: Dubowitz was the
first to combine the assessment of physical and neurological
criteria and it is the most widely used in clinical practice to assess
gestational age; Ballard et al simplified the Dubowitz method by
leaving out characteristics which are affected by illness of the
newborn baby or its in-utero position. They combined the eleven
physical criteria described by Farr8 and subsequently by Dubowitz
into six observations. They also combined the most useful
neurological criteria used by Amiel-Tison involving passive rather
than active muscle tone and including resting posture, angles of
flexion, resistance to extension and passive recoil.
iv. New Ballard scale: The New Ballard Score is an extension of the
above to include extremely pre-term babies i.e. up to 20 weeks.
1. Consists of six physical and six neuromuscular criteria
2. Score 10 corresponds to 20 weeks and score 50 corresponds
to 44 weeks
3. Accuracy is + or 2 weeks
4. Performed in < 12 hours after birth for < 26 weeks preterm
5. Gives allowance to sick neonates
6. Neurological criteria:
a. Posture
b. Square window
c. Arm recoil

146
d. Popliteal angle
e. Scarf sign
f. Heel to ear
7. Physical criteria:
a. Skin color and texture
b. Lanugo hair
c. Plantar creases
d. Breast nodule and areola
e. Eye lids and ear
f. Genitalia
3. Direct opthalmoscopy:
a. < 27 weeks: cornea is opaque
i. >34 weeks: atrophy of vessels of lens from center to periphery;
Disappearance of the anterior lens capsule vascularity between
the twenty seventh and thirty-fourth weeks of gestation: Assessing
vascularity of the lens was done within the first 24 hours of birth
with
1. Grade 4: Anterior lens capsule vascularity covers the entire
anterior lens surface [27-28 weeks].
2. Grade 3: Early vascular atrophy with central clearing [29
30 weeks].
3. Grade 2: More clearing with thinning of peripheral vessels
[31-32 weeks]
4. Grade 1: Few peripheral thin vessels with none reaching the
centre [33-34 weeks].
4. Other methods:
a. Femur length:
b. Foot length
c. Ultrasound studies of cerebellum and cerebrum
d. Fetal scapular length
e. Skin color examination by photo-calorimeter
6. Physical criteria:
SIGN

SCORE
-1

Skin

Sticky, friable,
transparent

gelatinous, red,
translucent

smooth pink,
visible veins

Lanugo

none

sparse

abundant

thinning

bald areas

mostly bald

Plantar
Surface

heel-toe
40-50mm: -1
<40mm: -2

>50 mm
no crease

faint red marks

anterior
transverse crease
only

creases ant.
2/3

creases over
entire sole

Breast

imperceptable

barely
perceptable

flat areola
no bud

stippled areola
1-2 mm bud

raised areola
3-4 mm bud

full areola
5-10 mm bud

Eye / Ear

lids fused
loosely: -1
tightly: -2

lids open
pinna flat
stays folded

sl. curved pinna;

soft; slow recoil

Genitals
(Male)

scrotum flat,
smooth

scrotum empty,
faint rugae

Genitals
(Female)

superficial peeling cracking, pale parchment, deep

&/or rash, few
areas, rare
cracking, no
veins
veins
vessels

well-curved pinna;
formed & firm
soft but ready
instant recoil
recoil

testes in upper
testes descending,
canal,
few rugae
rare rugae

thick cartilage
ear stiff

testes down,
good rugae

testes pendulous,
deep rugae

clitoris
prominent
prominent
majora & minora majora large,
prominent & labia clitoris & small
clitoris &
equally prominent minora small
flat
labia minora enlarging minora

majora cover
clitoris & minora

5
leathery,
cracked,
wrinkled

SIGN
SCORE

147
TOTAL PHYSICAL MATURITY SCORE

Neurological Criteria:
SIGN

SCORE
-1

SIGN
SCORE

Posture

Square
Window

Arm
Recoil

Popliteal
Angle

Scarf Sign

Heel To
Ear
TOTAL NEUROMUSCULAR SCORE

Maturity rating:

Classification of IUGR:
1. Symmetric IUGR:
a. Head circumference, length, and weight are equally affected- <10%
b. Ealier onset and associated with diseases affecting cell number :
chromosomal, genetic, malformations, tretogenic, infectious, PIH
etiologies

148
2. Asymmetric IUGR:
a. Only weight is reduced - <10%
b. Relative sparing of head growth
c. Late onset
d. Associated with poor maternal nutrition or late onset PET, PIH
Problems associated with prematurity:
I. Major problems:
1. Morbidity is inversely proportional to birthweight
2. RDS occurs in 80% in 500-750 gm while it is 25% in 1250-1500 gms
3. Intraventricular hemarrahge range from 25% to 3%
4. Sepsis 24%
5. Bronchopulmonary dysplasia 23%
6. Necrotizing enterocolitis 7%
II.
Physiologic handicaps:
1. Poor sucking, swallowing and breathing; immatrure gag reflex and
frequent aspiration of feeds
2. Lack of body fat; decreased ability to maintain body temperature
3. Surfactant deficiency and inefficient respiratory mechanics
4. Immature respiratory control and apnea-bradycardia
5. Persistence of PDA and pulmonary conjestion
6. Immature cerebral vasculature- subendymal and intraventricular
hemorrhage and periventricular leukomalacia
7. Impaired digestion and absorption
8. Immature renal function
9. Increased susceptibility to infection
10.
Immature metabolic activities- hypoglycaemia and hypocalcemia
III.
Problems of IUGR:

1. The neonatal complications in the small-for-date babies are slightly different. The

IV.

basic underlying problem among them is in-utero undernutrition and

hypoxia. They have small placentae.
2. The stress of labor may lead to fetal distress, meconium passage in utero
and birth asphyxia.
3. Since, they are chronically undernourished in utero, they also lack
adequate brown fat stores. This predisposes them to hypothermia.
4. They also develop hypoglycemia because of insufficient energy stores.
5. They too are candidates for neonatal sepsis because of the ill effects of
chronic intrauterine stress on the immune system.
6. Small-for-dates infants are more likely to have malformations than their
normal counterparts.
7. They also face feeding difficulties, though to a lesser extent than the
preterm babies.
Referral:
1. The indications for hospitalization of a neonate include the following:
1. Birth weight less than 1800 gm
2. Gestation less than 34 weeks
2. Neonate who is not able to take feeds from the breast
3. A sick neonate (irrespective of the birth weight or gestation)

149

V.

Thermoregulation:
1. Thermoregulation is a very important aspect of neonatal care. Those
least able to tolerate hypothermia include the preterm and/or growth
restricted infant and the infant with asphyxia or respiratory difficulties.
Hypothermia: body temperature below 36.5C.
2. Optimal temperature is to maintain infant core temp between 36.5 to 37
C
3. Humidity is 40-60 %; 100% during O2 and intubation
4. Mechanisms of Heat Loss and Preventive measures:
a. Evaporation:
i. Loss of heat when water evaporates from the skin and
respiratory tract
ii. Highest immediately after birth and with bathing
iii. Dry baby quickly and remove wet towels/blankets
iv. Humidify 02
b. Convection:
i. Heat lost to surrounding moving air
ii. Depends on difference in air temperature, speed of
movement of the air, and amount of skin exposure
iii. Cover babys head
iv. Dress baby
v. Keep out of drafts
vi. Warm 02
vii. Raise surrounding (ambient) temperature
c. Radiation:
I. Heat lost to surrounding colder solid objects (not in direct
contact) independent of air temperature
II. Keep incubator, warmer, cot away from outside walls and
windows
III. Dress baby
IV. Use double walled incubator or plexiglass heat shield in the
incubator
V. For infants with temperature control problems, cover three
sides of the incubator with aluminum foil (shiny side in)
d. Conduction
I. Heat loss to cold solid objects in direct contact
II. Baby will gain heat if placed on warm surface
III. Prewarm incubator/radiant warmer to ensure warm mattress
IV. Cover x-ray plates and scales
v. Prewarm hands, stethoscopes, blankets and other
equipment

150

3. Kangaroo mother care (KFC)

i. Kangaroo mother care is care of preterm infants carried skin-toskin with the mother. It is a powerful, easy-to-use method to
promote the health and well-being of infants born preterm as well
as full-term. Its key features are:
early, continuous and prolonged skin-to-skin contact
between the mother and the baby;
exclusive breastfeeding (ideally);
it is initiated in hospital and can be continued at home;
small babies can be discharged early;
mothers at home require adequate support and follow-up;
it is a gentle, effective method that avoids the agitation
routinely experienced in a busy wardwith preterm infants.
ii. Position:

The baby should be placed between the mothers breasts in an upright position.

The head should be turned to one side and in a slightly

upturned position. This position helps in breathing of and allows
eye-to-eye contact between the mother and her baby.
The legs and arms should be folded.
Babys abdomen should be at the level of the mothers upper
abdomen.
Support the baby bottom with a sling/binder.
Feeding
Holding the baby near the breast stimulates milk production.
Mother should express milk while the baby is still in KMC
position.
The baby could be fed with paladai, cup, spoon or tube,
depending on the condition of the baby.

151

VI.

VII.

Monitoring of
Preterm/LBW:
1. Pulse
oximetry for Pa O2, HR
2.
Transcutaneous PO2 and PCO2
3.
Electrolytes, glucose, Ca, bilirubin from
umb
artery sampling of blood
Nutrition:
I.
Desired weight gain 15gm/week;
II. Linear
and head circumference growth 1 cm/week
15
gm/day
III.
Calories: 120 Kcal/kg/day;
IV. IV GDW 10% (>1500 gm) or 5% (<1500 gm) 80-100ml/day
V. Aminoacid solution 3 g/kg/day via umb vein
VI. Trophic feeds: breast feed/EBM/donor BM/ formula <10 ml/kg/day in day
1 with slow increments to full requirement in 1 week
VII. Nutrient supplement:
a. 1. Calcium and phosphorus (140-160 mg/kg/d & 70-80 mg/kg/d
respectively for infants on EBM)
b. 2. Vitamin D (400 IU/day), vitamin B complex and zincb (about
0.5mg/day) usually in the form of Multivitamin drops
c. Folate (about 50 mcg/kg/day)
d. Iron (2 mg/kg/day)
VIII. Choice of feeding:
< 28 weeks: No proper sucking; No gut motility
Intravenous fluids
28-31 weeks: Sucking bursts develop; No coordination between
suck/swallow OG tube
feeding with spoon/paladai
feeding and occasional breathing
32-34 weeks: Slightly mature sucking pattern; Coordination begins
Feeding by spoon/paladai/cup
>34 weeks: Mature sucking pattern; more coordination between
breathing and swallowing Breastfeeding
VIII. Apnea of prematurity:
1. Definition: respiratory pause lasting for more than 20 sec or long enough
to produce cyanosis and bradycardia.
2. Causes:

152
a.
b.
c.
d.
e.
f.
g.
h.
i.

Hypoxia
Infection
Hypoglycaemia
Intracranial hemorrhage
Seizures
Drugs: morphine
Vagal Response to passage of feeding tube
NEC
Apnea of prematurity:
i. Immaturity of respiratory center
ii. Immaturity of mechanisms that maintain airway patency
3. Occurs in the first 2 weeks of life
4. Evalution: for any underlying cause
5. Treatment:
a. Caffeine citrate: 20 mg/kg loading; 5-10 mg/kg/day maintenance
b. Nasal CPAP
6. Prognosis:
a. May continue post term
b. Some may develop SIDS
IX. PDA:
I. Persists in those who have:
a. <28 weeks of gestation
b. HMD
c. surfactant therapy
II. Clinical:
a. Hyperdynamic precardium
b. Wide pulse pressure
c. Systolic murmur
III. Treatment:
a. Medical:
i. Prophylaxis: Indomethacin 0.1mg/kg/iv q 24 hr for 3-5

days from day 1

ii. Therapeutic: Indomethacin 0.2mg/kg/iv q 12 hr upto 3
doses; closure in 2/3

iii. Side effect: oliguria

iv. Contrindicvations:
1. Hyperkalemia
2. Creatinine >2mg/dl
3. Thrombocytopenia
v. Alternate drug:
1. Ibuprofen 10 mg/kg loading and 5 mg/kg 2
doses /daily
X. NEC:

a. Emergency in NB; 10% in less than 1500 gm; mortality rates of 50%
or more depending on severity.

153

b. Multifactorial:
i.

ii.

iii.

iv.
v.
vi.

ischemic insult damages the intestinal lining, leading to increased

intestinal permeability and leaving the intestine susceptible to
bacterial invasion. once feedings are begun, ample substrate is
present for proliferation of luminal bacteria, which can penetrate
the damaged intestinal wall, producing hydrogen gas.
The initial ischemic insult may result from:
1. vasospasm of the mesenteric arteries, which can be
produced by an anoxic insult triggering the primitive diving
reflex that markedly diminishes intestinal blood flow.
2. Intestinal ischemia may also result from low blood flow
during an exchange transfusion, during sepsis, or from the
use of hyperosmolar formulas.
3. Similarly, congenital heart disease with reduced systemic
blood flow or arterial O2 desaturation may lead to intestinal
hypoxia/ischemia and predispose to NEC.
Necrosis begins in the mucosa and may progress to involve the full
thickness of the intestinal wall, causing perforation with
subsequent peritonitis and often free intra-abdominal air.
Perforation occurs most commonly in the terminal ileum; the colon
and the proximal small bowel are involved less frequently.
The gas may collect within the intestinal wall (pneumatosis
intestinalis) or enter the portal veins.
Sepsis occurs in 33% of infants, and death may occur.
NEC may occur as clusters of cases or as outbreaks in neonatal
ICUs. Some clusters appear to be associated with specific
organisms (eg, Klebsiella , Escherichia coli , coagulase-negative
staphylococci), but often no specific pathogen is identified.

c. Symptoms:
i.
ii.
iii.
iv.
v.

Infants may present with feeding difficulties,

bilious emesis,
ileus manifested by abdominal distention, or
gross or microscopic blood in stool.
Sepsis may be manifested by lethargy, temperature instability,
increased apneic spells, and metabolic acidosis.

d. Diagnosis
i. Screening the stools of enterally fed premature infants for occult
blood or reducing substances may help diagnose NEC early.
ii. Early x-rays may be nonspecific and reveal only ileus.
iii. X-ray signs diagnostic of NEC are pneumatosis intestinalis and
portal vein gas.
iv. Pneumoperitoneum indicates bowel perforation and an urgent
need for surgery.

e. Treatment

154
i.
ii.
iii.
iv.
v.
vi.

f.

Stoppage of feedings
NGT
Fluid resuscitation
Broad-spectrum antibiotics
TPN
Possibly surgery

Prevention:

i. Risk may be decreased by delaying feedings for several days to

weeks in tiny or sick premature infants while providing TPN;
ii. Breast milk seems to offer protection. For this and other reasons,
breast milk should be encouraged for enteral feeding.
iii. Umbilical catheters, if required, should be placed below the renal
arteries.
iv. Polycythemia should be treated promptly.
v. Recent evidence suggests that probiotics (eg, Bifidus infantis,
Lactobacillus acidophilus) may help prevent NEC
XI. Intraventricular hemorrhage:
1. 20-30% incidence in < 31 weeks of GA; < 1500 gm
2. Bleeding commonly occurs in lateral ventricles
3. Ischemic damage to capillaries lead to rupture and hemorrhage
4. Most within 24 hours and all before 4 days
5. Symptoms: coma, decerebrate posturing, fixed pupils, bulging fontanelle,
hypotension, acidosis,apnea
6. Diagonosis: ultrasound
a. Grading of hemorrhage:
i. In germinal matrix only- no mortality
ii. In ventricles without enlargement- no mortality
iii. With ventricular enlargement- 10-20% mortality
iv. Intra parenchymal-10-20% mortality
7. Treatment:
a. Volue and blood replacement
b. O2
c. Ventilation
d. Shunt for hydrocephalus
8. Prevention: maternal steroid; indomethacin for baby
9. Prognosis:
a. Mortality 10-20%
b. Hydrocephalus
c. Neurologic sequelae (PVL)
XII. Retinopathy of prematurity:
1. Incompletely vascularised and premature retina
2. 60% in those weighing <1250 gm
3. Only 6% warrant intervention

155
4. Triggered by injury to developing retinal vessels abnormal vasularization,
fibrovascular tissue growth into vitreous, scarring, folding and
detachment of retina
5. Routine eye exam in <1500 gms at 4 weeks
6. Laser therapy
XII. Late preterm:
I. 34 to 37 weeks of gestation
II. 12.8% of all births; 70% of preterms
III. Causes:
i. Obstetric induction of labour
ii. Increase in Caesarian section
iii. Multiple births
IV. Issues:
i. RDS
ii. Feeding problems
iii. Hyperbilirubinemia and kernicterus
iv. Apnea
v. Hypoglycaemia
vi. Seizures
vii. Sepsis
viii. hypothermia
V. Management:
i. Extended hospitalization
ii. EBM supplements

156

Hyaline Membrane Disease (RDS type I)

1. Definition:
a. A preterm neonate showing progressive respiratory difficulty including
tachypnea >60/mt, chest retractions, and cyanosis within 48-96 hours of
life
b. Chesr radiograph shows uniform reticulogranular pattern and peripheral
air bronchogram
2. Incidence:
a. Inversely proportional to gestational age and birth weight
b. 44% between 500 to 1500 gms weight
c. Accounts for 6% neonatal deaths prior to surfactant era
3. Pathophysiology:
a. Surfactant:
i. The lungs of preterm babies with RDS are both anatomically and
biochemically immature; they neither synthesize nor secrete
surfactant well
ii. Its synthesis begins at 24 weeks
iii. Surfactant is a complex system
of lipids, proteins and glycoproteins which are produced in
specialized lung cells called Type II cells or Type II pneumocytes. The
surfactant is packaged by the cell in structures called lamellar
bodies, and extruded into the air-spaces.
iv. Surfactant recovered by alveolar wash from most mammals
contains 70-80% phospholipids, 8-10% protein, and 10% neutral
lipids, primarily cholesterol. Dipalmitoyl phosphatidylcholine (DPPC),
or lecithin, is functionally the principle phospholipid.

v. it decreases surface tension and maintains alveolar expansion; lack

of surfactant causes alveolar collapse; exudation of proteineseous
substance and epithelial debris which form hyaline membrane
vi. Decrease in surfactant by:
1. Asphyxia
2. Fetal hyperinsulinemia ( maternal diabetes)
vii. Increase by:
1. Antenatal corticosteroids

157

2. Stress induced by PIH, IUGR and twin gestation

b. Compliant chest wall:
i. Chest wall is weak and compliant
ii. Negative intrathoracic pressure during inspiration make the chest
wall retract more than expand
c. Negative intrathoracic pressure : Preterm baby is not able create
sufficient negative intrathoracic pressure during inspiration
d. Shnts: Presence of Rt to Lt shunt through PDA or Foramen ovale causes
more hypoxia and pulmonary edema
4. Risk factors for RDS:
a. Increased risk:
i. Prematurity
ii. Male sex
iii. Caesarian without labor pain
iv. Perinatal asphyxia
v. Chorioamnionitis
vi. Multiple gestation
vii. Maternal diabetes: too much insulin in a baby's system due to
maternal diabetes can delay surfactant production
viii. Familial predisposition
b. Decreased risk:
i. Chronic intrauterine distress
ii. PROM
iii. Maternal hypertension
iv. IUGR/SGA
v. Corticosteroids
vi. Thyroid hormone
vii. Tocolytic agents (b2 agonist, oxytocin antagonists, NSAID etc)
5. Clinical presentation:
a. History of:
i. Preterm delivary
ii. Preinatal asphyxia
iii. Progressive dyspnea since birth
b. Progressive respiratory distress
c. Increasing oxygen requirement
d. Tachypnea
e. Grunting
f. Nasal flaring
g. Chest retraction
h. Cyanosis
6. Diagnosis:
a. The lecithin/sphingomyelin ratio was less than 2 ; phosphatidylglycerol
was not present in amniotic fluid or tracheal fluids at birth; negative
bubble stability test
b. CXR:
i. Uniform reticular pattern or ground glass appearance
ii. Air bronchogram
c. Lab:
i. pAo2 < 50mm Hg; saturation < 85%
ii. PcO2 > 45 mm of Hg

158

iii.
iv.
v.
vi.
vii.

pH < 7.25
Septic work up for gr. B. strepto and H.inf which mimic RDS
Serum glucose as hypoglycemia mimics RDS
Serum electrolytes and Ca
Echo for PDA and PFO
7. Management:
a.
Prevention:
i. Antenatal corticosteroids:
1. Antenatal steroid given to mother reduces neonatal deaths
in first 48 hours due to:
a. RDS
b. Intraventricular hemorrhage
c. Necrotising enterocolitis
2. 12 mg betamethazone Im two doses 24 hour apart
(dexamethazone produces PVL and not recommended)
ii. Antenatal fetal monitoring for asphyxia, LS ratio for lung maturity
ultrasonography foe fetal maturity and appropriate measures to
prevent preterm labour and fetal hypoxia
iii. Tocolytic agents to prevent preterm labor
iv. Erythromycin 500 mg 6 hourly should be given to mothers with
preterm pre-labor rupture of the membranes as this reduces the risk
of preterm delivery
b. General Recommendations:
1. The lowest concentration of oxygen possible should be used
during resuscitation,
provided there is an adequate heart rate
response (100/min) as this reduces cerebral vasoconstriction and
may reduce mortality.
2.
CPAP: Start resuscitation with CPAP of at least 56 cm water via
mask or nasal prongs to stabilize the airway and establish
functional residual volume.
3.
If positive pressure ventilation is needed for resuscitation, aim to
avoid excessive tidal volumes by incorporating resuscitation
devices which measure or limit the peak inspiratory pressure as
this might reduce the risk of lung injury.
4.
Intubation should be reserved for babies who have not responded
to positive pressure ventilation by mask or those requiring
surfactant therapies.
5.
Pulse oximetry may be used to guide oxygen delivery during
resuscitation, aiming to avoid hyperoxic peaks. It must be
remembered that normal saturations during transition after birth
may be between 5080% .
6. INSURE: intubate surfactant,extubate CPAP.
c. Surfactant treatment:
i. Surfactant replacement therapy, either as a rescue treatment or a
prophylactic natural surfactant therapy, reduces mortality
ii. Surfactant can be extracted from animal lung lavage and from
human amniotic fluid or produced from synthetic materials.
iii. Two basic strategies for surfactant replacement:

159

1. Prophylactic or preventive treatment in which surfactant is

iv.
v.
vi.

vii.

Viii.

administered at the time of birth or shortly thereafter to

infants who are at high risk for developing RDS
2. Rescue or therapeutic treatment in which surfactant is
administered after the initiation of mechanical ventilation in
infants with clinically confirmed RDS
Prophylactic surfactants with in 15 mts of birth to all preterm < 30
weeks
Relacement therapy: preferably within 2 hours after birth
Dosages:
1. The synthetic surfactants are no longer available.
2. The two surfactants currently available are Beractant
(Survanta ,a natural bovine surfactant) and Poractant
(Curosurf a natural porcine surfactant). Both are used for
prophylaxis and rescue treatment.
3. Initial and subsequent dose of Survanta is 100 mg/kg
4. Initial dose of Curosurf is 100-200 mg/kg and subsequent
doses of 100 mg.
5. Have varied from 25 mg to 200 mg phospholipids/kg body
weight as single doses in the different clinical trials.
6. It may well be that lower doses would be appropriate for
prophylaxis
7. No benefit in administering surfactant > 24 hours age or
using more than 2 doses
8. Positioning of the neonate for administration varies with the
type of surfactant used. Exosurf requires the infant head to
be turned from left to right with administration, while
survanta requires 4 positions for each aliquots. These
involve the neonate head down and turned left to right, and
head up left to right. The neonate will remain in each
position for 30 seconds while dosing. With survanta the
dose is given in 4 increments with each position change.
The dosing increment should be given over 2-3 seconds, in
the endo-tracheal tube just beyond the end in the trachea.
9. Surfactant is given as continuos infusion via side port on the
ET or as aliquots via a catheter placed through ET
10.
Repeat doses are given after 6-12 hours if necessary.
Side effects of surfactant therpy:
1. Small risk of pulmonary hemorrhage
2. Secondary lung infection
3. Pneumothorax
Contraindications:
1. congenital anomalies incompatible with life
2. respiratory distress in infants with laboratory evidence of lung
maturity

160
Ix. Hazards/complications:
1. Procedural complications resulting from the administration of
surfactant include
1 plugging of endotracheal tube (ETT) by surfactant;
2 hemoglobin desaturation and increased need for
supplemental O2
3 bradycardia due to hypoxia;
4 tachycardia due to agitation, with reflux of surfactant into
the ETT;
5 pharyngeal deposition of surfactant;
6 administration of surfactant to only one lung;
7 administration of suboptimal dose secondary to
miscalculation or error in reconstitution.
2. Physiologic complications of surfactant replacement therapy
include
1 apnea
2 pulmonary hemorrhage
3 mucus plugs
4 increased necessity for treatment for PDA
5 marginal increase in retinopathy of prematurity
6 barotrauma resulting from increase in lung compliance
following surfactant replacement and failure to change
ventilator settings accordingly.
viii. Other uses of surfactant therapy:
1. Severe pneumonias
2. Meconium aspiration syndrome
3. Persistance of pulmonary hypertension

4. Pulmonary hemorrhage
5. Adult RDS
d. Fluid maintenance and nutritional support
e. Antibiotics;Sedation
8. Prognosis: depends on birth weight

161

MECONIUM ASPIRATION SYNDROME

1. Definition:
1. (Faranhoff): respiratory distress in infant born through meconium stained
amniotic fluid whose symptoms can not be otherwise explained.
2. Hallmark:
a.
Poor lung compliance
b.
Hypoxemia
c.
Typical radiographic findings
2. Incidence:
1. Meconium aspiration is 10-15 % of all deliveries
2. MAS (pneumonia) is 5 % of meconium aspirations
3. Meconium:
1. First intestinal discharge of NB
2. Composed of epithelial cells, fetal hair, mucus and bile
3. Intrauterine stress may cause passage meconium in amniotic fluid
4. Meconium inactivates surfactant
4.
Pathophysiology:
1. Meconium directly alters the amniotic fluid, reducing antibacterial activity
and subsequently increasing the risk of perinatal bacterial infection.
2. Meconium is irritating to fetal skin, thus increasing the incidence of
erythema toxicum.
3. Aspiration induces hypoxia via 4 major pulmonary effects:
a.

Airway obstruction:

i. Complete obstruction of the airways by meconium results in

atelectasis.
ii. Partial obstruction causes air trapping and hyperdistention of
the alveoli, commonly termed the ball-valve effect.
iii. The gas that is trapped (hyperinflating the lung) may rupture
into the pleura (pneumothorax), mediastinum
(pneumomediastinum), or pericardium (pneumopericardium).
b. Surfactant dysfunction:
i. Meconium deactivates surfactant and may also inhibit
surfactant synthesis.

162
ii.

several constituents of meconium, especially the free fatty

acids (eg, palmitic, stearic, oleic), have a higher minimal
surface tension than surfactant and strip it from the alveolar
surface, resulting in diffuse atelectasis.
c. Chemical pneumonitis:
i. Enzymes, bile salts, and fats in meconium irritate the airways and parenchyma,
causing a release of cytokines (including tumor necrosis factor (tnf)-, interleukin
(il)-1, i-l6, il-8, il-13) and resulting in a diffuse pneumonitis that may begin within a
few hours of aspiration.

Pulmonary hypertension:
i. To complicate matters further, many infants with meconium
aspiration syndrome (MAS) have primary or secondary
persistent pulmonary hypertension of the newborn (PPHN) as a
result of chronic in utero stress and thickening of the pulmonary
vessels.
ii. Right to left shunting at PDA and PFO
iii. PPHN further contributes to the hypoxemia caused by
meconium aspiration syndrome.
e. Infection: although meconium is sterile, its presence in the air
passages can predispose to pulmonary infection.
4. Clinical manifestation:
a. Respiratory distress within first hour
b. Tachypnea, chest retraction and grunting and cyanosis
c. Pneumothorax and or peumomediastinum
d.

d.
e.
f.

Barrel chest in the presence of air trapping

Meconium staining of vernix,cord, skin and neils

Decreased air entry, rales, ronchi and wheeze

5. Lab:
a. Acid-base status :
a. Ventilation-perfusion (V/Q) mismatch
b. Metabolic acidosis from perinatal stress is complicated by
respiratory acidosis from parenchymal disease and persistent
pulmonary hypertension of the newborn (PPHN).
c. ABG measurement of pH, partial pressure of carbon dioxide
(pCO2), partial pressure of oxygen (pO2), and continuous
measurement of oxygenation by pulse oximetry are necessary
for appropriate management.
b. Serum electrolytes: Obtain sodium, potassium, and calcium
concentrations at 24 hours of life in infants with meconium aspiration
syndrome because the syndrome of inappropriate secretion of
antidiuretic hormone (SIADH) and acute renal failure are frequent
complications of perinatal stress.
c. CBC count
a. In utero or perinatal blood loss, as well as infection, contributes
to postnatal stress.
b. Hemoglobin and hematocrit levels must be sufficient to ensure
adequate oxygen-carrying capacity.

163
c. Thrombocytopenia increases the risk for neonatal hemorrhage.
d. Neutropenia or neutrophilia with left shift of the differential may
indicate perinatal bacterial infection.
e. Polycythemia may be present secondary to chronic or acute
fetal hypoxia. Polycythemia is associated with decreased
pulmonary blood flow and may exacerbate the hypoxia
associated with meconium aspiration syndrome and PPHN.
d. Imaging Studies:
a. Chest radiography:
i. Hyperinflation and flattened diaphragm
ii. Patchy infiltrates
iii. Pneumothorax
iv. pneumomediastinum

6. Treatment:
a. Prevention:
i. Fetal monitoring and intervention for impending fetal distress
ii. Avoid postmaturity
iii. When meconium is detected, amnioinfusion with warm, sterile
saline is theoretically beneficial to dilute the meconium in the
amniotic fluid- not practiced now
b. Delivery room:
i. The current AAP guidelines are as follows:
1. If the baby is not vigorous (defined as depressed
respiratory effort, poor muscle tone, and/or heart rate
<100 beats/min): Use direct laryngoscopy, intubate, and
suction the trachea immediately after delivery. Suction
for no longer than 5 seconds. If no meconium is
retrieved, do not repeat intubation and suction. If
meconium is retrieved and no bradycardia is present,

164
reintubate and suction using meconium trap aspirator. If
the heart rate is low, administer positive pressure
ventilation and consider suctioning again later.
2. If the baby is vigorous (defined as normal respiratory
effort, normal muscle tone, and heart rate >100
beats/min): Do not electively intubate. Clear secretions
and meconium from the mouth and nose with a bulb
syringe or a large-bore suction catheter.
3. In both cases, the remainder of the initial resuscitation
steps should ensue, including drying, stimulating,
repositioning, and administering oxygen as necessary.
c. Nursery care:
i. ontinued care in the neonatal ICU (NICU)
ii. optimal thermal environment to minimize oxygen consumption.
iii. Minimal handling is necessary because these infants are easily
agitated. This can cause right-to-left shunting, leading to
hypoxia and acidosis. Sedation is often necessary to decrease
agitation.
iv. Oxygen therapy via hood or positive pressure by CPAP is crucial
in maintaining adequate arterial oxygenation. Mechanical
ventilation is required by approximately 30% of infants with
meconium aspiration syndrome.
v. Oxygen saturations should be maintained at 90-95%.
vi. Surfactant therapy is now commonly used to replace displaced
or inactivated surfactant and as a detergent to remove
meconium. Although surfactant use does not appear to affect
mortality rates, it may reduce the severity of disease and
progression to extracorporeal membrane oxygenation (ECMO). 9
Studies are ongoing to evaluate the potential role of pulmonary
lavage with surfactant.
vii. High-frequency oscillation and jet ventilation are alternative
effective therapies
viii. For treatment of persistent pulmonary hypertension of the
newborn (PPHN), inhaled nitric oxide is the pulmonary
vasodilator of choice.
ix. Maintaining systemic blood pressure greater than pulmonary
blood pressure, thereby decreasing the right-to-left shunt
x. Ensure adequate oxygen carrying capacity by maintaining the
hemoglobin concentration above 13 g/dL.
xi. Corticosteroids are not recommended.
xii. Culture and Broad spectrum antibiotics and
xiii. ECMO is used if all other therapeutic options have been
exhausted.
7. Prognosis:
a. Significant mortality
b. Improves with surfactant, HFV and nitric oxide

165
<5% for ECMO
d. Survivors may develop bronchopulmonary dysplasia, chronic lung
disease, neurologic sequelae
c.

Diabetes mellitus
1.

Definition:
Diabetes mellitus (DM) is a chronic metabolic disorder caused by an absolute or
relative deficiency of insulin with hyperglycaemia as a cardinal biochemical feature
2.
Classification:
1. Type 1 Diabetes Mellitus : insulin dependent; ketoacidosis is common
2. Type 2 Diabetes Mellitus : non insulin dependent; ketoacidosis is uncommon
3. Secondary diabetes mellitus: Cystic fibrosis; Cushing syndrome
4. Impaired glucose tolerance: intermediate between normal and diabetic
state; risk factor for future diabetes and coronary disease
3.
Type 1 Diabetes Mellitus :
1. Overall incidence is .2 to .3 %
2. 10% of all cases of DM
3. 40% of them are < 20 years old
4. Annual rate of increase of cases is 3-4%
5. Peak presentation: 5-7 years ( exposure to infectious agents) and at puberty
( increased GH)
6. Genetics:
i. Immune mediated damage to the insulin producing B cells due to
genetic predisposition
ii. Association with HLA-DR3 and DR4
iii. Association with DQ 1 gene (absence of aspartic acid in HLA DQ
chain responsible for activating autoimmune cascade)
7. Environment:
i. Increasing prevalence of autoimmune provactive factors:

166
1. An unknown adverse factor
2. Frequent childhood infections (hygiene theory)
3. Toxins from vegetables and early infant diet
4. Enterovirus infection
ii. Decreasing prevalence of protective factors:
1. Breastfeeding
2. Herd immunity to virus transferred to fetus
8. Viral infections of cells:
i. Coxackie B3 and B4
ii. Cytomegalo virus
iii. Rubella (10-12% congenital rubella develop DM)
iv. Mumps
9. Vaccination: role not established
10. Seasonal association:
i. New cases in adolescent population are recognized in autumn and
winter probably coinciding with some viral infections like Mumps etc
11. Puberty:
i. Pubertal peek incidence occurs earlier in girls due to estrogen
regulated IL6 gene
12. Diet: (controversial provocation of autoimmunity)
i. Cow milk protein- molecular mimicry with cells
ii. Nitrates from vegetables and meat
iii. Early exposure to cereals
13. Body mass index:
i. Highe BMI is an independant risk factor for both Types of DM
ii. Insulin resistance is a function of fat mass
14. Chemicals:
i. Drugs like alloxan, strptozotocin, pentamidine, and vacor are
cytotoxic to cells
ii. Vacor and strptozotocin can also induce autoimmunity
15. Pathogenesis:
i. T cell mediated autoimmune disease leading to destruction of cells
over a period of time
ii. Some cells regenerate providing honeymoon phase
iii. Develop multiple antibodies for cells
iv. Molecular mimicry between viral proteins and cells
v. Cytokines secreted during viral infections upregulate autoimmune
reactions
vi. Psycho social stress in infants may increase hormonal levels and
neuronal signals which increase insulin resistance, insulin requirement
and immune destruction
vii. Overall steps: T cell primingt cell proliferation cells destruction
16. Pathophysiology:
i. Insulin performs storage and retrieval of cellular fuel
ii. Secretion is modulated by neural, hormonal and substrate mediated
mechanisms
iii. Moderate Insulinopenia glucose utilization by tissues is reduced
hyperglycemia develops after food;
iv. Severe insulinopenia glycogenolysis and gluconeogenesis by liver
fasting hyperglycemia

167
v. Hyperglycemia osmotic dieresis + loss of calories and electrolytes
persistent dehydration hyper secretion stress hormones:
epinephrine, cortisol, growth hormone and glucagon further
glycogenolysis, guconeogenesis, lipolysis,ketogenesis and increase in
lipid concentration
vi. Glucagon shunts free fatty acids into ketone body formation
vii. Acidosis, hyperosmolality, diminished cerebral O2 utilization coma
17. Clinical manifestations:
i. Symptoms steadily increases with decreasing cell mass
ii. Worsening insulinopenia progressive hyperglycaemiaeventual
ketoacidosis
iii. Polyuria, nocturia, plydipsia, glycosuria (caloriuria) and hyperphagia
but with weight loss
iv. Monilial vaginitis in female child
v. Ketoacidososis: DKA
18. Diagnosis:
i. Non fasting blood glucose > 200 gm/dl with polyuria, glycosuria and
ketonuria
ii. HbA1c
iii. Tests for other autoimmune disorders:
1. IgA: celiac disease
2. Antithyroid peroxidase, antithyroglobulin antibodies: Thyroiditis
19. Treatment:
i. Patient and family education: regarding symptoms, drug dosing and
diet and glucose monitoring
ii. Insulin:
1. Facilitates cellular entry of glucose; decreases neoglucogenesis;
turns off ketone production
2. Dose:
a. Prepubertal: 0.7 U/kg/day
b. Midpuberty: 1 U/kg/day
c. Postpuberty: 1.2 U/kg/day
3. Dosing:
a. Twice-daily combinations of short-acting and
intermediate-acting insulin.
b. Multiple injection regimens, using once-daily or twicedaily injections of long-acting or intermediate-acting
insulin and short-acting insulins given at each meal
c. A combination of the above 2 regimens, with a morning
injection of mixed insulin, an afternoon premeal injection
of short-acting insulin and an evening injection of
intermediate-acting or long-acting insulin
d. Dosage adjusted over a trial period to cover before meal
and after the meal
4. Insulin pump:
a. Continuous subcutaneous insulin infusion (CSII) using an
insulin pump
b. Useful mfor adolescents
c. Can be programmed with blood glucose levels and
insulin needs are adjusted by pump computer
5. Inhaled insulin therapy:

168
a. Preprandial inhaled insulin and bed time long acting
insulins are being tried with promising results
6. Oral insulin: oralin; promising trial are underway
20. Diabetic Ketoacidosis:
i. Commonest cause of death due ti DM
ii. Induced by stress, infection, omitting insulin dose
iii. Ketoacidososis: DKA
1. 20% of present with symptom before dianosis
2. Very low insulin levels
3. Ketoacids produce abdominal discomfort, nausea, vomiting and
further dehydration
4. Signs of dehydration are masked as intravasular volume is
maintained at the expense of intracellular volume
5. Deep heavy rapid breathing: Kussmauls respiration
6. Fruity odour due to acetone
7. Increased ion gap, decreased sodium bicarbonate and pH
8. Confusion leading to coma
iv. Complications:
1. Cerebral edema
2. Hypokalemia
3. Septic shock
4. Hypoglycaemia
5. Cerebral hemorrhge
6. Pancreatitis
v. Problems to be managed:
1. Dehydration/shock
2. Acidosis
3. Hypokalemia
4. Hypoglycaemia
5. Hyperosmolality
6. Cerebral edema
7. infecftion
vi. Diagnosis:
1. Hyperglycaemia (BG > 200mg/dL or 11 mmol/l)
2. pH < 7.3
3. Bicarbonate < 15 mmol/l
4. More than 3% dehydration
5. Clinical:
a. Vomiting
b. Drowsiness
c. Clinical acidosis
vii. Management: Milwaukee protocol
1. Insulin therapy
2. Fluid replacement
3. Treatment of underlying cause
viii. Insulin:
1. Insulin to drive glucose into cells; it is given as infusion .
1U/kg/hour
ix. Intravenous fluids to correct dehydration:
1. Shock treatment:
a. 0-1 hour: 0.9 % K NaCl 10-20 ml /kg or RL as bolus
2. Treatment for dehydration:

169
a. 2 nd hour: 0.45% NaCl
b. Total Requirement for 48 hours = Maintenance + Deficit
fluid already given
c. Maitenance: 100 ml/kg first 10 kg wt; plus 50 ml/kg for
next 10 kg; plus 25ml/kg for remaining body weight
d. Deficit: 85 ml/kg
e. 5% GDW added when glucose level falls below 250 mg/dl
f. Potassium 20 meq/L as Kphosphate and 20 meq/L as K
acetate
g. Bicarbonate is not necessary as fluid and insulin correct
acidosis
3. Hourly rate = 48 hr maintenance + deficit resuscitation fluid
already given
48
a. Example :
A 20 kg 6 year old boy who is 8% dehydrated, and who has
already had 20ml/kg saline, will require:
8 % x 20 kg = 1600 mls deficit plus 55ml x 20kg = 1100
mls maintenance each 24 hours
1100 mls
= 3800 mls
minus 20kg x 20ml = 400 mls resus fluid 3400 mls over
48 hours = 71 mls/hour
21. Non ketotic hyperosmolarncoma:
i. Rare in children
ii. Blood sugar >800 mg/dL
iii. No ketosis
iv. Severe dehydration
v. Altered sensorium
vi. Treatment:
1. Insulin infusion
2. NS in 1st 12 hour to replace 50% of volume deficit; remainder
in next 24 hour
3. When blood glucose is < 300 mg/dL .2% NS with 5 % GDW with
20 mEq/L of Potassium
22. Nutrition in DM:
i. Food :
1. 20% brealfast; 20% lunch; 30% dinner; 10% in between snacks
2. Carbohydrate: 55%
(70% complex Carbohydrate;) more
fibers
3. Fat: 30% polyunsaturatyed: saturated 1.2:2; begetable fat
4. Protein: 15%
ii. Wight in normal range to be m,aintained
23. Self monitoring:
i. Blood glucose- 4 times daily to monitor glycemic control and insulin
dose
ii. HbA1c represent the fraction of haemoglobin to which glucose has
been nonenzymatically attached in the blood stream and expressed
as a percentage of total Hb; it reflects the average blood glucose

170
concentration from the preceding 2-3 months. It is an index of long
term glycemic control. It is elevated in Thalassemia (HbF) and lowered
in Sickle cell disease; values 6 to 7.9% represent good metabolic
control
24. Exercise: helps utilization of glucose by muscles and glucoregulation;
planned exercise decreases
insulin requirement by 10-15% and prolonged
exercise by 50%; exercise induced hypoglycaemia is avoided by
carbohydrate exchange
25. Benefits of good glycemic control: Reduces complications such as
retinopathy, nephropathy, and neuropathy
26. Hypoglycemia:
i. Symptom according to blood levels
ii. Mild: pallor, sweating, apprehension, tremor and tachycardia
iii. Moderate: drowsiness,confusion
iv. Severe: seizure and coma
v. Treatment:
1. Beverage or candy
2. Glucagon .5 mg IM
3. IV glucose
27. Somogyi phenomenon:
i. Early morning hypoglycaemia due to exaggerate counteregulatory
response
28. Brittle diabetes: refers to fluctuating blood glucose levels due to
environmental factors such family stress in young girls
4. Type II DM:
1. Polygenic disease plus environmental factors:
i. Low physical activity
ii. Hyperclaoric and lipid rich diet
iii. Obescity causing:
1. Insulin resistance
2. Increased hepatic glucose production
3. Decreased insulin secretion
2. Incidence: 7/ 100 000 among children; increase due to obesity epidemic
3. Genetic basis:
i. Polygenic
ii. Acanthosis nigircans is a marker
iii. Hisutism with polycystic ovary is associated with Type II DM
iv. Gigantism
4. Prveniton:
i. Avoid:
1. heavy snacking
2. Emotional eating
3. TV, computer cued eating
ii. Life style interventions
5. Treatment:
i. Initial insulin therapy
ii. Metformin 500 mg bd with meals

171

Mental retardation (Intellectual disability)

1. Definitions:
a. Group of disorders of adaptive and intellectual function with an age of
onset before completion of maturity < 18 yeras
b. Deficits in cognitive and adaptive functioning greater than 2 standard
deviation below the for the population on standardized testing
c. Intelligence quotient of less than 70; adaptive skills less than 2 SD below
the mean
2. Cognition:
a. The word cognition is defined as the act of knowing or knowledge.
b. E.g. of cognitive skill:
i. Concentration: When a person focuses his attention for any length
of time, we refer to it as concentration.
ii. Perception: perception means interpretation; perception correlates
with previous experience
iii. Memory:
1. Receptive memory: This refers to the ability to note the
physical features of a given stimulus such as the shapes or
sounds associated with the letters of the alphabet to be able
to recognize it at a later time.
2. Sequential memory: This refers to the ability to recall stimuli
in their order of observation or presentation
3. Rote memory: This refers to the ability to learn certain
information as a habit pattern e.g. Spelling, multiplication
table etc ; memorization by repetition, often without an
understanding
4. Long-term memory: This refers to the ability to retrieve
information of things learned in the past.

172
5. Short-term memory: Short-term memory lasts from a few
seconds to a minute
iv. Logical thinking: a learned mental process in which one uses
reasoning consistently to come to a conclusion.eg.
1. Learning Algebra
2. Logical thinking allows a child to reject quick and easy
answers, such as I dont know, or this is too difficult
3. Adaptive behaviour:
a. The age-appropriate behaviors necessary for people to live independently
and to function safely and appropriately in daily life.
b. Includes real life skills such as grooming, dressing, safety, safe food
handling, school rules, ability to work, money management, cleaning,
making friends, social skills, and personal responsibility expected of his
age
c. adaptive behaviour covers three types of skills:
1. Conceptual skills: language and literacy; money, time, and number
concepts;
2. Social skills: interpersonal skills, social responsibility, the ability to
follow rules, obey laws, and avoid being victimized
3. Practical skills: occupational skills, schedules/routines, safety, etc
4. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
Revision (DSM-IV-TR) defines mental retardation as follows:
1. Significantly subaverage intellectual functioning - An intelligence quotient
(IQ) of approximately 70 or below
2. Concurrent deficits or impairments in adaptive functioning in at least 2 of
the following areas: communication, self-care, home living,
social/interpersonal skills, use of community resources, self-direction,
functional academic skills, work, leisure, health, and safety
3. Onset before age 18 years
5. Etiology:
S.N
O
1
2

Cause

Chromosomal
abnormalities:
Genetic syndromes

Brain abnormality

Inborn errors:

Examples

1.
2.

Trisomy;
Klinefelter etc

3. Fragile X syndrome;
4. Prader Willi
5.
Rubinstein-Taybi
syndrome
6.
Hydrocephalus;
7.
meningomyelocoel;
8.
lissencephaly
1.
2.

PKU;
Tay-Sachs

Percent
age of
case
22
21

9
8

173
5
6

Congenital
infections:
Familial

Perinatal:

Post natal:

Unknown

3.
4.

HIV;
TORCHS

5.
6.
7.
8.
9.
10.
11.
12.
13.
14.

Environment;
genetic
HIE; meningitis;
IVH;
PVL;
fetal alcohol syndrome
Trauma;
meningitis;
hydrocephalus
Cerebral palsy

4
6
4
5
21

1. Trisomy 21:
1. hypotonia, upward slanting of palpebral fissures, round face,

micrognathia,
2. single palmar crease, brachycephaly
2. Prader-Willi syndrome:
1. Prader-Willi syndrome (PWS) is a disorder caused by a deletion or
disruption of genes in the proximal arm of chromosome 15 or by
maternal disomy in the proximal arm of chromosome 15.
2. Commonly associated characteristics of this disorder include

diminished fetal activity, obesity, hypotonia, mental retardation, short

stature, hypogonadotropic hypogonadism, strabismus, and small
hands and feet.
3. Tuberous sclerosis:
1. Mutation in a gene affecting the formation of the ectodermal layer

of the embryo.
2. Angiofibromas on the cheeks (adenoma sebaceum),
3. Caf au lait spots
4. White leafy macule
5. Mental retardation,
6. Epilepsy begins as infantile spasms,
2. Rubinstein-Taybi syndrome:
1. This is an autosomal-dominant inherited condition, with the
majority of cases representing new deletions or point mutations of
the CREB-binding protein gene (16p13.3).
2. Broad terminal phalanges, beaked nose, down-slanting palpebral
fissures, epicanthal folds, and microcephaly characterize this
syndrome.
3. Behavioral aspects include variable degrees of impulsivity,
distractibility, instability of mood, and stereotypies.
4. Phenylketonuria (PKU):
1. 1 in 10,000 live births;
2. Diminished activity of phenylalanine hydroxylase, which leads to a
high serum phenylalanine level, affecting myelination of the CNS

174
3. Mental retardation, hypertonia, hyperreflexia, musty odour in urine

and sweat. Seizures; tremors; eczema; psychotic manifestations.

3. X-linked mental retardatio: Fragile X syndrome:
1. Most common
2. X linked, with dominant inheritance, and the penetrance is lower in
females.
3. Constriction at the location xq 27.3, it appears as if the
chromosome is fragile and a part of it is breaking off.
4. Trinucleotide CGG repeat expansion (>200 repeats) and unaffected
carriers with the premutation (60-200 repeats ) are present as the
basic defect
5. Include an oblong face, prominent ears and jaw, and
macroorchidism.
6. Most have moderate mental retardation
7. Hyperactivity and social withdrawal
4. Rett's Syndrome:
1. Rett syndrome is a neurodevelopmental disorder of the grey
matter of the brain that affects females more commonly than
males.
2. The clinical features include small hands and feet and a
deceleration of the rate of head growth (including microcephaly in
some).
3. Repetitive hand movements, such as wringing and/or repeatedly
putting hands into the mouth, are also noted.
4. It is caused by mutant gene in X chromosome
5. Maternal infections:
1. Congenital rubella:
1. Mental retardation,
2. Microcephaly,
3. Hearing and vision impairment,
4. Congenital heart disease, and
5. Behaviour problems
2.
Congenital cytomegalovirus infection:
May result in microcephaly, sensorineural hearing loss, and
psychomotor retardation
3. Congenital toxoplasmosis:
Hydrocephalus, microcephaly, psychomotor retardation, vision
and hearing impairment
4. Human immunodeficiency virus:
Microcephaly, progressive neurological deterioration, mental
retardation, cerebellar symptoms
5. Toxic substances: Fetal alcohol syndrome (FAS).
1. Dysmorphic features,
2. Prenatal and postnatal growth retardation,
3. Microcephaly;
4. Mental and motor retardation,

175
5. Hyperactivity, and attention deficit.
6. Herpes simplex type 2P:
1. The neonate is infected during the delivery and may develop

encephalitis within 2 weeks.

2. Poor outcome, ie, microcephaly, profound mental retardation,

and neurological deficits.

6. Brain defects:
1. Lissencephaly:
2. Hydrocephalus/menigomyelocoel
7. Pathogenesis:
1. CREB (cAMP response element-binding) is a cellular transcription factor;
2. CREB-binding protein (CBP) interact with numerous transcription
factors and act to increase the expression of their target genes
3. CREB regulates BDNF (Brain-derived neurotrophic factor),
4. Mutation of the gene encoading for the CREB-binding protein results in
severe mental retardation seen in Rubinstein-Taybi syndrome
8. Pathology:
1. No or mild changes in CNS
2. Microcephaly in some
3. Grey matter heterotrophia: clumps of grey matter being located in the
wrong part of the brain due to defects in induction
4. Tightly packed neurons
5. Defects in dentritic and synaptic organization
9. Clinical Manifestations:
1. MR is usually idendified at 3 yeras
2. Dysphorphism is the earliest sign of mental retardation
3. Microcephaly
4. Cerebral palsy, seizures, autism
5. Failure to meet age appropriate mile stones
6. Hypotonia or hypertonia
7. Language delay :
1. including expressive language (speech) and receptive language
(understanding).
2. Red flags include no mama/dada/babbling by 12 months, no 2word phrases by age 2, and parents reporting they are concerned
that the child may be deaf.
8. Fine motor/adaptive delay
1. Significant delays in activities such as self-feeding, toileting, and
dressing are typically reported in children with MR/ID.
2. Prolonged, messy finger feeding and drooling are signs of oralmotor incoordination.
9. Cognitive delay:
1. Difficulties with memory, problem-solving and logical reasoning.
2. Difficulty following directions (particularly multipart directions).
10. Social delays:
1. Lack of interest in age-appropriate toys and delays in imaginative
play and reciprocal play with age-matched peers.
11. Gross motor:

176
clumsiness
12. Behavioral disturbances:
1. Difficult temperaments, hyperactivity, disordered sleep
2. Aggression, self-injury, defiance, inattention, hyperactivity and
stereotypic behaviors.
11. Developmental assessment
1. Parents' Evaluation of Developmental Status (PEDS),
2. Ages and Stages Questionnaires (ASQ) and Child Development
Inventories (CDI).
3. The most common psychological tests for children include:
1. Wechslers scale
2. The Bayley Scales of Infant Development-III,
3. The Stanford-Binet Intelligence Scale
4. Vineland adaptive behaviour scale
12.
Laboratory findings:
1. DNA analysis of the FraX promoter region
2. Karyotype:
a. Chromosomal abnormalities (trisomy 21 and others) may account for
as many as 50% of those affected by severe to profound MR.
b. Sex chromosome aneuploidy is seen in as many as 5% of children with
mild MR or learning disabilities.
3. FISH probes are clinically indicated, as follows:
a. Prader-Willi/Angelman syndrome
b. Cri du chat syndrome
4. Metabolic labs:
a. Plasma amino acids (aminoacidopathies)
b. Urinary organic acids (organic acidopathies)
c. Urinary mucopolysaccharides and oligosaccharides
(mucopolysaccharidoses)
d. Plasma 7-DHC (Smith-Lemli-Opitz syndrome)
e. Thyroid function tests
f. Very-long-chain fatty acids (peroxisomal disorders)
g. Creatine kinase (in the assessment of profound central hypotonia
versus myopathy)
13. Imaging:
1. Brain MRI
1. Brain imaging should be conducted in any child with global
developmental delays or MR/ID. The yield will be higher in the setting
of an abnormal neurologic examination (eg, microcephaly, focal
neurologic finding and/or facial dysmorphisms).
2. Brain MRI is generally preferred over CT scan because the former has
greater resolution and enhanced detection of abnormalities in the
progression and timing of myelination, demyelination, and heterotopic
gray matter.
3. Head CT scan:
1. calcifications with TORCH infections
2. Tuberous sclerosis
1.

177
3. Craniosynostosis
4. Skeletal films: assessment of growth.

14. D.D:
Autism
Borderline intellectual functioning
Child Abuse & Neglect, Posttraumatic Stress Disorder
Depression
Learning Disorder,
Rett's Syndrome
13. Complications:
1. Individuals with severe to profound MR/ID experience a decreased life
expectancy related to the underlying etiology or additional complicating
neurologic disorders, such as epilepsy.
2. Neurologic dysfunction resulting in immobility, significant oral motor
incoordination, dysphagia, and aspiration confers a greater risk of
premature death than MR/ID itself.
3. Respiratory disease is the most prevalent cause of death among
individuals with profound MR/ID
4. Attention deficit/hyperactivity disorder (ADHD) is diagnosed in 8-15% of
children and 17-52% of adults with MR.
5. Self-injurious behaviors require treatment in 3-15%, particularly in the
severe range of MR/ID.
6. Schizophrenia may have a prevalence of 3% in individuals with MR/ID,
compared to 0.8% in the general population.
7. The rates of transmittable diseases, including sexually transmitted
diseases (STDs), hepatitis B, and Helicobacter pylori infection, are
increased significantly among individuals with MR/ID.
8. One in 5 individuals with MR/ID also has cerebral palsy (CP).
9. As many as 20% of individuals with MR/ID have seizures.
10. GI complications with MR/ID include feeding dysfunction, excess
drooling, reflux esophagitis, and constipation .
11. GU complications with MR/ID include urinary incontinence and poor
menstrual hygiene.
14. Prevention:
1. Prevention of:
1. Alcohol abuse
2. Teen pregnancy
3. Head trauma
2. Safe sex
3. Immunization to prevent CNS infections
4. New born screening for metabolic disorders- PKU; hypothyroidism
5. Antenatal screening for trisomy
15. Treatment:
1. MR is not treatable
2. The complex habilitation plan for the individual requires input from care
providers from multiple disciplines, including special educators, language
therapists, behavioral therapists, occupational therapists, and community
1.
2.
3.
4.
5.
6.

178
services that provide social support and respite care for families affected
by MR/ID
3. Attention to Sexuality/abuse
4. No specific pharmacologic treatment is available for cognitive impairment
in the developing child or adult with MR/ID.
5. Medications, when prescribed, are targeted to specific comorbid
psychiatric disease or behavioral disturbances. Stimulants,
antidepressants etc
16. Prognosis:
1. Mild retardation: Near normal life in adulthood
2. Life expectancy is not adversely affected
3. Severe forms may be able to lead life with medical and social support

179

Short stature
1.

Definition:

a. Short stature is defined as a height less than two standard deviation of the

2.

3.

4.

mean for age or below the third percentile for height on national standards
for that population.
b. The child is significantly below the midparental or target height
c. The child is consistently having a poor growth velocity below 2 SD
Height measurement:
a. Measure standing height in triplicate using a calibrated wall-mounted
stadiometer.
b. One well-accepted device is available from Harpenden Ltd of Wales
Parameters for the assessment of growth:
1. Target height
2. Growth velocity
3. Bone age
4. Body proportions
5. Arm span
6. Weight-for-Height Ratio
Target height:
a. Mid parental height (average height of parents in cm) plus 6.5 cm for boys
and minus 6.5 cm for girls
b. Child achieves within 8 cm of midparental height
c. A range 8 cm above or below this predicted height is considered within the
3rd to 97th percentile.
d. A child whose current height percentile differs greatly from his or her target

percentile is considered inappropriately short for his or her genetic

potential
5.
Growth velocity:
a. Growth velocity is change in height (cm) / year.
b. Growth velocity is 25 cm in first year; 12.5 cm in second year; 6 cm/year till
puberty
c. Height:
i. At birth: 50 cm
ii. 1 year: 75 cm
iii. 4 years: 100 cm
iv. 8 years: 125 cm
v. 12 years: 150 cm
d. Height that plots stably along a given percentile on the growth chart reflects
normal growth velocity. Crossing percentiles in the downward or upward
directions reflects abnormally low or accelerated growth velocities
respectively
e. Calculate growth velocity as the change in standing height over at least 6
months (in children) or in length over at least 4 months (in infants).
f. Poor linear growth is defined as linear growth velocity more than 2 SDs
below the mean
6. Skeletal maturation: Bone age:

180
a. The appearance of representative epiphyseal centers obtained on

radiography is compared with age appropriate published standards.

b. The main clinical methods for skeletal bone age evaluation are the Greulich

and Pyle (GP) and the Tanner e Whitehouse (TW2) method.

c. Xrays:

7.

i. knee: < 3yers

ii. wrist: < 6 yers
iii. Elbow: > 6 yers
d. Familial short stature (FSS) is associated with normal skeletal maturation
e. Bone age is usually delayed in children with constitutional growth delay,
malnutrition, and endocrine causes of short stature (eg, hypothyroidism,
cortisol excess, growth hormone deficiency)
Body proportions:
a. The upper-to-lower body segment (U/L) ratio:
i. It indicates whether the short stature is proportionate or
disproportionate.
ii. The lower segment is obtained by measuring the distance between
the upper border of the symphysis pubis and the floor in a standing
patient
iii. The upper segment is determined by subtracting the lower segment
from the standing height.
iv. The resulting U/L ratio is compared with normal values for age and sex
v. The U/L ratio normally declines progressively from birth, reaching a
nadir during early puberty. With the onset of pubertal growth, the U/L
ratio increases slightly until epiphyseal fusion.
vi. The ratio:
1. At birth: 1.7
2. 3 years: 1.3
3. 6 years: 1.1
4. 10 yeras:
1
vii. Decreased U/L ratio for age:
1. Skeletal dysplasias involving primarily the spine (eg,
spondylodysplasias)
2. Eunichoidism
3. Delayed or incomplete puberty (eg, Klinefelter or Kallmann
syndrome)
viii. Increased U/L ratio
1. Those dysplasias involving especially the long bones (eg,
achondroplasia)
2. Because puberty is associated with relatively greater truncal
than limb growth, an increased U/L ratio for age may be seen in
precocious puberty.
b. Arm span:
i. is approximately equal to height in children 8 years of age or older.
Arm span can be measured as the distance from left fingertips to right
fingertips in a patient standing, arms spread, against a wall.
ii. Arm span can be used as a surrogate for height measurement and for
monitoring growth velocity in children who have scoliosis, spina bifida,
or leg contractures or after spinal irradiation.

181
c. Weight-for-Height Ratio:

8.

9.

i. Obescity in endocrine disorders:

1. GH deficiency
2. Thyroid hormone deficiency
3. Glucocorticoid excess (Cushings disease)
ii. Thin for stature in systemic disorders like:
1. Malnutrition
2. Chronic illness etc
Practical Classification of short stature:
a. Proportional:
i. Equal height weight ratio: GHD
ii. Weight more than height: Cretinism, GH deficiency,GH insensitivity,
hypothyroidism, or glucocorticoid excess,
iii. Height more than weight: Chronic illness, mal nutrition
b. Disproportional:
i. Short limb: achondroplasia and other chondrodysplasias
ii. Short trunk: Hurler, Morquio
Classification of short stature:
a. Physiological:
i. Familial short stature
ii. Constitutional growth delay
b. Pathological:
i. Endocrine disorders:
1. Growth hormone deficiency
a. Genetic causes:
i. Receptor mutation
ii. Gene deletion
iii. GH resistance
b. Congenital: associated with septo-opic dysplacia and
ectopic pituitary
c. Acuired:
i. Parental deprivation syndrome
ii. Craniopharyngeoma
iii. Histiocytosis
iv. Germinoma
v. Cranial irradiation
d. Idiopathic:
i. Isolated GH deficiency
ii. Combined pituitary hormone deficiency
2. Insulin like growth factor-1 deficiency
3. Hypothyroidism
4. Cushing syndrome
5. Precocious puberty
6. Diabetes mellitus
7. Psuedo hypoparathyroidism
ii. Rickets
iii. IUGR
iv. Inborn errors of metabolism:
1. Mucopolysachharidoses
2. Other storage disorders
v. Intrinsic disease of bone:
1. Achondroplasia

182
2. Fibrous dysplasia
vi. Chromosomal:
1. Autosomal:
a. Down
b. Prader-Willi
c. Noonan
2. Sex chromosome:
a. Turner
vii. Chronic illness:
1. CHD
2. Inflammatory bowel disease
3. Chronic infection and infestation
4. Hematologic: Thalassemia
5. Pulmonary : cystic fibrosis; Bronchial asthma
6. Renal disease
7. Cancers
10. Familial Short stature:
a. Short parents
b. Normal weight and length at birth
c. Growth velocity is decreased in first two years and then resumes normal
growth
d. Bone age and puberty are normal
e. Adult height is appropriate for the family
11. Constitutional growth delay:
a. Normal parents
b. Normal weight and length at birth
c. Growth pattern is similar to FSS
d. Delay in bone age
e. Delay in onset of puberty
f. Growth is decreased in first 3 years
g. But growth continues beyond the average period of growth
h. Finally reaches the target height
12.Disproportionate short stature:
a. Skeletal dysplasias:
Achondroplasia:
In people with achondroplasia, the cartilage cells developed into bone more
slowly than normal. This happens especially in the long bones of the arms
and legs, leading to shorter bones and shorter overall height. Therefore, the
trunk or torso of people with achondroplasia is relatively normal in length
but the arms and legs are short.
fibroblast growth factor receptor-3(FGFR3) is defective
13.Short stature with syndromic features:
1. Trisomy 21: hypotonia, upward slanting of palpebral fissures, round face,
micrognathia, single palmar crease, brachycephaly
2. Turner's syndrome: webbed neck, low hairline, broad chest, increased carrying
angle, hypertelorism, posteriorly rotated ears
3. Russell-Silver syndrome: triangular face, asymmetry, clinodactyly; maternal
uniparental disomy (UPD) on chromosome 7

4. Prader-Willi syndrome: obesity, small hands and feet, hypotonia,

hypogonadism, down-turned mouth

183
5. DiGeorge syndrome: minor facial dysmorphism, cleft palate
6. Noonan's syndrome: hypertelorism, backward rotated ears
14. Growth Hormone Deficiency:
a. Hypopituitarism :
i. Incidence is 1 in 4000-10,000
ii. Multiple hormone deficiency- 20%
iii. Isolated growth hormone deficiency- 13%
b. Growth hormone:
i. Secreted by ant.pituitary; stimulated by GHRH; inhibited by
somatostatin
ii. GH released in response to sleep, exercise and hypoglycaemia
iii. Promotes growth by stimulating insulin like growth factor: IGF1
iv. Deficiency is due to:
1. Mutation :
a. Septo optic dysplasia:
i. incomplete development of septum pallucidum,
ii. optic nerve hypoplasia,
iii. Midline abnormalities in brain
iv. Nystagmus
v. Visual impairment
vi. Ant and post hormone deficiency
2. Isolated pituitary hypoplasia
3. Acquired pituitary defects:
i. Craniopharyngeoma
ii. Germinoma
iii. Histiocytosis
iv. Tuberculosis
v. Sarcoidosis
vi. Toxoplasmosis
vii. Meningitis
viii. Trauma- shaken baby syndrome
ix. ICBI(birth injuries)
4. Isolated GHD and insensitivity:
a. Abnormalities of receptors
b. GH genes
c. X linked genes
d. Acquired:
i. Radiation
ii. Meningitis
iii. Hiostiocytosis
iv. Trauma
e. Insensitivity:
i. Laron syndrome
c. Clinical manifestations:
i. Congenital hypopituitorism:
1. Normal length at birth
2. Growth rate below 25%
3. Hypoglycaemia, prolonged jaundice and apnoea and cyanosis
and seizures at birth
4. Microphallus in boys
5. Round head, broad and short face
6. Small saddle shaped nose; nasolacrimal folds

184
7. Bulging eyes
8. Small chin
9. Crowded teeth
10.High pitched voice
11.Proportional extremities
12.Delay or absent sexual maturation
13.Delayed skeletal age
14.Normal intelligence
d. Lab findings:
i. Low levels of GH in response to stimulation by insulin, argentine,
clonidine, glucagon
ii. Levels of IGF1
iii. Levels of TSH, ACTH,
e. X-Ray:
i. CT: supracellar calcification- craniopharyngeoma
ii. Bony erosion: histiocytosis
iii. MRI:
Triad: small ant pituitary, hypolastic pituitary stalk, ectopic post
pituitary bright spot
iv. Delay in bone age
f. Treatment:
i. Subcutaneous recombinant GH for 7 days- total dose .1 to.3 mg?kg
ii. IGF 1 for resistant cases

Leukemias
Dr.p.natarajan
Definition
Common malignancy in pediatrics
41% of all malignancies < 15 years
4.1 % per 100 000 children annually
Definition:
A group, of malignant diseases in which a genetic abnormality in
hematopoietic cells gives rise to clonal proliferation of cells

185
Increased proliferation
Decreased apoptosis
Distruption of marrow function
Ending in marrow failure
Acute lymphoblastic leukemia - ALL
ALL 77%; AML 11%; CML 2-3%; rest unclassified
Age: 2-6 years; More in males
Higher incidence in:
Down
Bloom
Fanconi
Turner
Klinefilter
Ataxia telangiectasia (Immune deficiency)
100% monozygotic; 50% in dizygotic twins
Etiology
Unknown
Radiation
Epstein Barr virus?
Advanced maternal age
Alkylating agents
Pathogenesis
Malignant transformation of a single clone of cells belonging to lymphoid or
myeloid series due to a genetic damage to DNA;
This is followed by proliferation of affected clone
Chromosomal translocation: e.g: Philadelphia Chromosome t(9;22) in CML
Surface markers:
85% are derived from B cells
15% from T cells
Philadiphia chromosome
The ABL gene on chromosome 9 is mistakenly transferred to chromosome 22 and
attaches to the BCR gene.
This creates a new fusion gene called BCR-ABL which leads to leukemic process.
Clinical features
Initially non specific
Anorexia, fatigue, irritability
Low grade fever
Bone and joint pain
Recurrent URI
On progression: Pallor, epistaxis, purpura and fever
On examination:
Anemia
Purpura and peticheal hemorrhages
Lymphadenopathy
Splenomegaly
Less hepatomegaly

186
Bone tenderness
Joint swelling
CNS
CNS:
Increased ICT
Papilloedema
Retinal hemorrhages
Cranial nerve palsy
R.S:
Obstructive airway signs
Large mediastinal mass in adolescent boys with T cell leukemia
Diagnosis
Peripheral blood:
Anemia
Thrombocytopenia
TC: < 10 000/ L
Most cells look like atypical lymphocytes but are actually part of malignant
clone
Convent party appearance
Bone marrow:
Hyper cellular marrow; more myeloid series
>25% lymphoblasts
CSF: leukocytosis
Lab:
Increase in uric acid
Increase in LDH
Cxr:
Mediastinal widening;
Tracheal compression
Abd.Us:
Kidney infiltartion
Intra abdominal lymphadenopathy
X ray long bones:
Periosteal elevation
Growth arrest lines
D.D
Aplastic anemia
Myelofibrosis
Infectious mononucleosus
Rheumatoid arthritis
Leukemoid reaction
Treatment
Fatal without treatment
Favorable prognostic factors are:
Age 3 to 7 yr; female
WBC count < 25,000/L

187
French-American-British (FAB) L1 morphology
Leukemic cell karyotype with > 50 chromosomes and t(12;21)
No CNS disease at diagnosis
Speed of response to treatment

Unfavourable factors
A leukemic cell karyotype with chromosomes that are normal in number but
abnormal in morphology (pseudodiploid)
Presence of the Philadelphia (Ph) chromosome t(9;22)
Increased age in adults
B-cell immunophenotype
Risk groups
Standard (low) risk: Includes children aged 1 to 9 years who have a white blood
cell count of less than 50,000/L at diagnosis.
High risk: Includes children younger than 1 year or older than 9 years and children
who have a white blood cell count of 50,000/L or more at
standard protocols
On going trials
Treatment
The 4 general phases of chemotherapy for ALL include
Remission induction
CNS prophylaxis
Post remission consolidation or intensification
Maintenance
Induction therapy:
To kill the leukemia cells in the blood and bone marrow.
To put leukemia into remission.
Consolidation /intensification therapy:
It begins once the leukemia is in remission. The purpose of consolidation /
intensification therapy is to kill any remaining leukemia cells that may not be
active but could begin to regrow and cause a relapse.
Maintenance therapy:
This is the third phase of treatment. Its purpose is to kill any remaining
leukemia cells that may regrow and cause a relapse
CNS prophylaxis: CNS sanctuary therapy
to kill cells in CNS so that they will not produce CNS leukemia/ CNS relapse
Phase 1. Remission induction
Treatment for 4 weeks
Weekly vincristine : 1.5 mg/m2/iv
Prednisolone 40 mg/m2/oral/divided dose
L-Asparaginase 10 000U/m2/IM biweekly
Daunomycin weekly for high risk cases
Phase II: CNS prophylaxis
Triple intrathecal therapy for 2 yr old child

188
Methtrexate
10 mg
Hydrocortisone
10 mg
Cytosine arabinoside 10 mg
Weekly X 6 followed by every 2 months for 2 years
CNS radiation: now avoided
Maintenance therapy
continued for 2 -3 years
6 Mercaptopurine 50 mg/m2/daily/oral
Methotrexate 20 mg/m2/week iv/oral
Reinforcement therapy for 30-36 months
Vincrystine 1.5 mg/m2/IV/monthly
Prednisolone 40 mg/m2/day/oral/ 7 days a month
Remission
Disappearence of clinical signs
No leukemic cells in peripheral smear
marrow smear contain less than 5 % blast cells
Neutrophil and thrombocyte counts return to normal
Relapse:
marrow
CNS
Testis

Hemolytic Anemias
Definition
Hemolysis is the premature destruction of erythrocytes
Hemolytic anemia results when bone marrow activity cannot compensate for
the erythrocyte loss.
Introduction
RBC survival time 110-120 days
0.85% senile rbcs removed every day
Hemolytic anemia:
1. RBC life span is short
2. RBC count falls
3. Erythropoietin level increases
4. Increased RBC production-

189

1.
2.
3.
4.
5.
6.
7.
8.

1.

2.

1.
2.
3.
4.
5.
6.
7.
8.

5. Erythroid hyperplasia of marrow

6. Extramedullary erythropoiesis
7. Reticulocytes in peripheral smear
8. Reticuloytes
Elevate Reticulocyte count
Methylene blue stain
1% of RBC is normal
Elevated in:
1. Hemolytic anemia
2. Acute Blood loss
3. For short period after correction of deficiency of:
1. Iron
2. B12
3. Folic acid
Other evidences of hemolysis
Indirect hyperbilirubinemia
Increased serum lactic dehydrogenase
Increased urinary and fecal urobilinogen
Bilirubin gall stones
Decreased hemophexin and haptoglobin which get bound to Heme
Increased free Hb- pink plasma
CO released from Hb and appear in expired air
Aplastic crisis during certain infections like parvo virus
Classification
Cellular: mostly inherited except paroxysmal nocturnal hemoglobinuria
1. Membrane defect- spherocytosis
2. Enzyme defect- G6PD; pyruvate kinase
3. Hemoglobin defect- Thalasemias; Hb S
Extracellular: mostly acquired except abetalipoproteinemia with acanthocytosis
1. Antibody factors-autoimmune; isoimmune
2. Plasma factors- abetalipoproteinemia, toxins
3. Mechanical factors- hemolytic uremic syndrome
Membrane defects
Hereditary spherocytosis
Skeletal protein defect- spectrin, ankyrin, protein 3
Northern European ancestry: 1: 5000
Autosomal dominant
Micro spherocytes and reticulocytes in smear
No significant anemia
Increased osmotic fragility
Splenomegaly: splenectomy is the cure
DD: ABO incompatibilty
Microspherocytes
Elliptocytosis
Elliptocytes in smear
Mild or no hemolysis

190

Jaundice
Splenomegaly
abnormalities in spectrin, but a few have abnormalities in protein 4.1
Autosomal dominant
Splenectomy is cure
Hemoglobinopathy
800 variants of Hb
Hb genes are locatecd in Chromosome 16p for alpha & 11p for beta chains
Hb consists 2 pairs of globin chains
Embryo: Gower Hb 2 2
Fetal: Hb F 2 2

Hb. A: 2 alpha and 2 beta chains

Hb A2: 2 alpha and 2 delta
NB has more Hb F
At 6 months, Hb contains :
Hb A 95%; Hb A2 3.55; Hb F 2.5%
Hb A
Quantitative deficiency of globin chains:
eg. Thalasemias
a. thalasemia: alpha chains are less
b thalasemia: beta chains are less
Qualitative defect in globin chains:
eg. Hb S, C, E
Thalasemias
Mutations leading to decreased production of globin chains either alpha or beta
with variable severity
thalassemia:
Low leles of Hb A
More Hb F
More Hb A2
thalassemia:
More Barts Hb (4) and Hb H (4)
HbF is less and fetal survival is difficult

Demographics: Thalassemia
Found most frequently in the Mediterranean, Africa, Western and Southeast
Asia, India and Burma
Distribution parallels that of Plasmodium falciparum

Thalassemia types
1. Alfa thalassemia
2. Beta thalasemia:
1. Major - homozygous
2. Minor (trait) - heterozygous
3. Intermedia
3. Delta/Beta thalassemia

191
4. Hereditary persistentce of fetal hemoglobin (HPFH)
Thalassemia Major
Cooleys anemia
Homozygous 0
Symptomatic in infancy
Require blood transfusion in early life
Typical facies:
Maxillary hyperplasia
Flat nasal bridge
Frontal bossing
Pathologic fractures
Marked hepatosplenomegaly
Hypersplenism
Fatique and lethargy
Mild jaundice
Hemosiderosis (increased absorption; release)
Growth retardation
Complications of hemosiderosis
Hypothyroidism
Gonadal failure
Hypoparathyroidism
Diabetes mellitus
CCF
Cardiac arrhythmias
Lab findings
1. Elevated HbF and A2 in Hb electrophoresis
2. Severe anemia <5 gm%
3. Few reticulocytes <8%
4. Numerous nucleated RBCs
5. Microcytosis
6. Target cells
7. Unconjugated bilirubin increased
8. Elevated serum ferritin
9. Saturation of transferrin
10.Erythroid hyrplsia of marrow
Target cells
Osmotic Fragility Test
RBCs are incubated in varying concentrations of a hypotonic solution of sodium
chloride (NaCl) at 37oC
Normal cells begin to haemolyse at NaCl concentrations of approximately 0.50%
In positive test lysis is usually completed by 0.4-0.5%, starting at higher NaCl
concentrations

Secondary Laboratory Investigation

Cellulose Acetate Hb Electrophoresis
- A2/C

A+

192
Normal

Hemoglobin electrophoresis
Lanes 1 and 5 : hemoglobin standards.
Lane 2 : normal adult.
Lane 3 : normal neonate.
Lane 4 : homozygous Hb S
Lanes 6 and 8: heterozygous sickle cell
Lane 7 is a SC disease
Imaging
Treatment
Red cell phenotyping matched for rh and kell antigens
Transfusions to maintain 9 to 10 gm% Hb levels (hypertransfusion)
Iron store is determined by liverbiopsy
For iron chelation:
Vit C supplementation
Deferoxamine s/c over 10-12 hr, 4-5 days a week or
oral deferasirox
Thalassemia intermedia
Clinical severity is between thalassemia trait and thalassemia major.
The diagnosis is a clinical
Hemoglobin level of at least 6-7 g/dl
Without the need for regular blood transfusions.
Thalassemia minor
Heterozygous for beta thalassemia.
Mild anemia very closely resembling iron-deficiency anemia.
More severe than trait
Have a normal blood iron level
No treatment is necessary
In particular, iron is neither necessary nor advised.
Thalassemia Trait
Milder than thalassemia minor
heterzygous
Suspected in people with family history
Resembles iron deficiency anemia
Hb F and A2 are elevated
Thalassemia trait have some level of protection from Malaria; common in
people from regions where Malaria occurs.
Thalassemia
4 genes for globin
Deletion of 1 gene: silent carrier
Deletion of 2 genes: Thalassemia trait
Deletion of 3 genes: Hb H disease-4
All 4 absent: Thalassemia major- hydrops fetalis
Clinical
4: Barts Hb is raised in NB
silent carrier: normal

193

Trait:
microcytic anemia mimicking iron deficiency
Barts Hb is raised in NB >3-8%
Hb H: gamma chain tetramer
Barts Hb is raised in NB to > 25%
Microcytosis , anamia, splenomegaly, gall stones, mild jaundice
Major:
Fetal hydrops
Transfusion dependance if survives
Sickle cell disease
Hb S: thymine replaces adenine in 6 codon of chain due to mutation
glutamtic acid, an
Amino acid, at position no.6 of b-globin chain of haemoglobin is replaced by
valine.
Autosomal recessive
Trait and disease states
Sickle ccells
Primarily affects africans and african americans
Abnormal shape and flexibility.
The sickling is promoted by conditions which are associated with low oxygen
levels
Hemolysis, anemia and jaundice
Aplastic crisis parvo virus
Bacterial sepsis - pnumoccocal
Intravascular blocking by sickle cell-vaso occlusive crisis: bone infarction, acute
chest syndrome etc
Diagnosis:
Hb elecrophoresis
Sickling Test
A drop of patients blood is mixed with sodium metabisulphate (a
reducing agent that deoxygenates blood) and examined under a
microscope after 30min
Treatment:
Penicillin prophylaxis
Transfusion
splenectomy

Acute renal Failure

Definition
It is a clinical syndrome of sudden deterioration of renal function in which
kidney is unable to maintain fluid and electrolyte homeostasis and
characterized by an increase in:
blood urea nitrogen (BUN)
serum creatinine values,
hyperkalemia,
metabolic acidosis,

194

hypertension.

Incidence:
2-3 % pediatric intensive care
Etiologic classification
1. Prerenal:
2. Dehydration
3. Hemorrhage
4. Septic Shock
5. Hypoalbuminemia : Redistribution of extracellular fluid
6. CCF
2. Renal:
1. Glomerulonephritis :
1. Post streptococcal
2. SLE
3. Henoch - Schonlein Purpura
4. Membranoproliferative
2. Hemolytic uremic syndrome
3. Acute tubular necrosis
4. Cortical necrosis
5. Renal vein thrombosis
6. Acute interstitial nephritis
7. Tumor infiltration
8. Tumor lysis syndrome
3. Post renal:
1. Posterior urethral valve
2. Urolithiasis
3. Hemorrhagic cystitis
4. Neurogenic bladderr
Prerenal ARF :
1. Inadequate renal perfusion
2. Decreased GFR
3. No kidney disease
4. Correction of hypovolemia in time cures the condition
5. If not corrected in time renal parenchymal damage occurs
ARF : Renal
1. Renal parenchymal damage: glomerulonephritis
2. Hemolytic uremic syndrome:
1. Triad:
1. Uremia (ARF)
2. Microangiopathic hemolytic anemia
3. Thrombocytopenia
2. Common secondary to Shigella and E.Coli infection; toxin
produces capillary endothelial cell injury
3. Acute tubular necrosis
4. Ischemic ATN:
1. Prolonged prerenal state

195
2. Obstetric complications
3. Sepsis
4. Surgery (e.g., open heart surgery, repair of abdominal aortic
aneurysm)
5. Nephrotoxic ATN:
1. Aminoglycosides
2. Amphotericin B
3. Cisplatin (anticancer)
4. Radioisotopic contrast media
4. Tumor lysis syndrome:
Obstruction of the tubules by uric acid
crystals following
chemotherapy of leukemia
5. Acute interstitial nephritis:
The interstitium is the tissue that surrounds and imbeds the glomeruli and
tubules
Inflammation caused by an hypersensitivity reaction to a medication, including
antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs )
Post renal ARF
1. Obstructive uropathy:
1. Congenital:
1. Posterior urethral valve
2. Cong. Bilateral pelvi ureteric obstruction
2. Bilateral conditions acquired:
1. Nephrolithiasis
2. Obstruction by tumor
3. Hemorrhagic cystitis
4. Neurogenic bladder (reflux; infection)
5. Multiple myeloma
ARF: Clinical features
History
1. Vomiting and diarrhea - prerenal
2. Recent pharyngitis post streptococcal
3. Exposure to nephrotoxic drugs
4. Hydronephrosis diagnosed antenataly
5. Dribbling of urine with supra pubic swelling - PUV
Physical examination
1. Tachycardia and poor peripheral perfusion - prerenal
2. Edema and cardiac gallop post sreptococcal
3. Rash and arthritis: SLE; HSP
4. Bilatreal renal mass: obstructive uropathy
Some definitions
1. Proteinuria: >150 mg/24 hour
2. Haematuria: > 5 RBCs/HPF on 3 urine tests
3. Oliguria: < 0.5 ml/kg/hour; <1ml/kg/hr in infants
4. Uremia:

196
Illness accompanying kidney failure proceeding to decreased mental acuity and
coma
5. Azotemia:
Refers to high levels of urea, the abnormality can be measured
chemically but is not yet so severe as to produce symptoms.
6. BUN:
Measurement of urea content of blood; urea is split into Co2 and
ammonia and ammonia is measured which is the nitrogen part of urea: 515 mg/dL
Lab findings
1. Anemia: dilutional; hemolytic in HUS
2. Leukopenia: SLE
3. Thrombocytopenia: HUS
4. Hyponatremia: dilutional
5. Metabolic acidosis
6. Elevated BUN, creatinine, uric acid, potassium, phosphates
7. Low C3: PSGN, SLE
8. Hematuria: Renal-Glomerular
9. WBCs in urine: interstitial disease
10.eosinophils: drug induced interstitial nephritis
11.Prerenal:
1. Sp.gravity : > 1020
2. U Osm
: > 500 mOsm/kg
3. U Na
: < 20 mEq/L
12.Renal:
1. Sp.gravity : < 1010
2. U Osm
: < 350 mOsm/kg
3. U Na
: > 40 mEq/L
RIFLE classification
Grading of severity
Imaging
1. CXR: cardiomegaly; pulmonary congestion
2. Ultrasound:
1. Hydronephrosis
2. Hydroureter
3. Renal biopsy
Treatment
Medical
1. Bladder catheter to estimate urine output
2. Correction of hypovolemia: 20 ml/kg NaCl over 30 mts
3. Diuretic challenge after correction of hypovolemia to rule out prerenal
condition:
1. Mannitol
0.5 gm/kg - single dose
2. Furosemide
2-4 mg/kg
3. Or Bumetanide
0.1 mg/kg
4. Dopamine:
2-3 g/kg/mt

197
4.

Persisting ARF after diuretic challenge:

1. Fluid restriction:
400 ml/m2 / 24 hr+ equivalent of urine
output
5. Management of Hyperkalemia
1. Serum K: >6 mEq / L
2. Produces cardiac arrhythmia; cardiac arrest, death
3. ECG:
1. Peaked T wave; 2.widening QRS; 3. ST
depression 4. ventricular arrhytmia; 5. cardiac
arrest
1. Treatment:
1. Oral kayexalate (resin) 1 g/kg/ 2 hourly
2. 10% Calcium gluconate1 ml/kg iv over 3- 5mts :
counteracts myocardial irritability due to
hyperkalemia
3. Sodium bicarbonate 1-2 mEq/kg IV over 5-10 mts:
1. Insulin 0.1 u/kg with glucose 50% 1 ml/kg over 1 hour:
Both shift potassium from intravascular to
intracellular compartment
6. Metbolic acidosis
1. Causes: Retention of H ions, phoasphate, and sulphate
2. Severe acidosis contributes to hyperkalemia
3. It is corrected by IV sodabicarb to raise pH to 7.2
4. Full correction may precipitate hypocalcemic tetany- alkalotic tetany:
As the pH of blood increases, the protein in the blood becomes more
ionised into anions. This causes the free calcium present in blood to
bind strongly with protein
7. Hypocalcemia
1. Treated by reducing serum phosphorus level and not by IV Ca to avoid Ca
deposition in tissues
2. Low phosphate diet
3. Phosphate binders:
1. Calcium carbonate
2. Calcium acetate
8. Hyponatremia
1. Dilutional and hence fluid restriction
2. 3% Na Cl for convulsions
9. Uremic platelet dysfunction: GI bleeding is treated by H2 blocker
10.Hypertension:
1. Slat tretsriction
2. Isradipine 0.05-0.15 mg/kg/dose
3. Amlodipine, propranolal etc
4. IV nitroprusside 1 10 g/kg infusion for encephalopathy
4. Diazepam for seizures
11.Other measures:
1. Washed red cell transfusion for anemia

198
2.

Dietary restriction:
1. Sodium
2. Potassium
3. Phosphate
4. Protein

12.Dialysis
1. Indication:
1. Pulmonary edema due to volume overload
2. Persistent hyperkalemia
3. Severe metabolic acidosis
4. Uremic coma and Seizures
5. BUN > 100 mg/dL
6. Dialysis
2. Intermittent hemodialysis large venous catheter attached to
extracorporeal circuit
3. Peritoneal dialysis:
hyperosmolar dialysate is infused into peritoneal cavity
via
trancutaneous catheter and drained by
gravity after 45 mts;
done in cycles
4. Continuous renal replacement therapy (CRRT)
double lumen catheter in subclavian or femoral vein; connected to
CRRT circuit;
continuos passage of blood across highly permeable filter
13.Prognosis
1. Depends on underlying disease
2. Renal limited ARF: 1% mortality
3. Multiorgan failure: 90% mortality
4. Better recovery from prerenal causes
5. Poor recovery from bilateral renal vein thrombosis and rapidly
progressing glomerulonephritis
14.Acute versus chronic renal failure
1. CRF ism due to congenital or acquired defects
2. Inability to concentrate urine- polyuria
3. Failure to thrive
4. Anemia
5. Rickets
6. Hypertension
7. Platelet dysfunction and bleeding
8. End stage disease: uremia

199

Leukemias
Definition
Common malignancy in pediatrics
41% of all malignancies < 15 years
4.1 % per 100 000 children annually
A group, of malignant diseases in which a genetic abnormality in hematopoietic
cells gives rise to clonal proliferation of cells:
Increased proliferation
Decreased apoptosis
Distruption of marrow function
Ending in marrow failure

Acute lymphoblastic leukemia - ALL

ALL 77%; AML 11%; CML 2-3%; rest unclassified

Age: 2-6 years; More in males
Higher incidence in:
Down
Bloom
Fanconi
Turner
Klinefilter
Ataxia telangiectasia (Immune deficiency)
100% monozygotic; 50% in dizygotic twins
Etiology
Unknown

200
Radiation : in utero, diagnostic, therapeutic
Epstein Barr virus?
Advanced maternal age
Alkylating agents
Benzene
Pathogenesis:
Malignant transformation of a single clone of cells belonging to lymphoid
series due to a genetic damage to DNA;
This is followed by proliferation of affected clone
Chromosomal translocation: e.g: Philadelphia Chromosome t (9;22)
Surface markers:
85% are derived from B cells
15% from T cells
ALL Morphologic Classification - The French-American-British (FAB) Cooperative
Working Group
L1: Lymphoblats: 85%
1. small cells
2. high nucleus-to-cytoplasm ratio
3. indistinct nucleoli
4. cytoplasm is scanty
L 2: Lymphoblast - 14 %
1. larger, often in a more
2. heterogeneous population, with a
3. lower nucleus-to-cytoplasm ratio
4. prominent nucleoli
L3 Lymphoblasts 1 %
1. heterogeneous group of cells
2. deeply basophilic cytoplasm
3. prominent cytoplasmatic vacuolization.
Philadiphia chromosome
1. The ABL gene on chromosome 9 is mistakenly transferred to
chromosome 22 and attaches to the BCR gene.
2. This creates a new fusion gene called BCR-ABL which leads to
leukemic process.
Clinical features
1. Initially non specific
2. Anorexia, fatigue, irritability
3. Low grade fever
4. Bone and joint pain
5. Recurrent URI
6. On progression: Pallor, epistaxis, purpura and fever
On examination:
1. Anemia
2. Purpura and peticheal hemorrhages
3. Lymphadenopathy
4. Splenomegaly

201
5.
6.
7.
8.

Less hepatomegaly
Bone tenderness
Joint swelling
CNS:
1. Increased ICT
2. Papilloedema
3. Retinal hemorrhages
4. Cranial nerve palsy
9. R.S:
1. Obstructive airway signs
2. Large mediastinal mass in adolescent boys with T cell leukemia
Diagnosis
Peripheral blood:
1. Anemia
2. Thrombocytopenia
3. TC: < 10 000/ L
4. Most cells look like atypical lymphocytes but are actually part of
malignant clone
5. Convent party appearance
Bone marrow:
1. Hyper cellular marrow; more myeloid series
2. >25% lymphoblasts
3. CSF: leukocytosis
Lab:
Increase in uric acid
Increase in LDH
Cxr:
Mediastinal widening;
Tracheal compression
Abd.Us:
Kidney infiltartion
Intra abdominal lymphadenopathy
X ray long bones:
Periosteal elevation
Growth arrest lines
D.D
Aplastic anemia
Myelofibrosis
Infectious mononucleosus
Rheumatoid arthritis
Leukemoid reaction
Treatment
Fatal without treatment

Favourable prognostic factors are:

1. Age 3 to 7 yr; female
2. WBC count < 25,000/L

202
3. French-American-British (FAB) L1 morphology
4. Leukemic cell karyotype with > 50 chromosomes and t (12;21)
5. No CNS disease at diagnosis
6. Speed of response to treatment
Unfavourable factors
1. A leukemic cell karyotype with chromosomes that are normal in number
but abnormal in morphology (pseudodiploid)
2. Presence of the Philadelphia (Ph) chromosome t(9;22)
3. Increased age in adults
4. B-cell immunophenotype
Risk groups

Standard (low) risk: Includes children aged 1 to 9 years who have a white blood
cell count of less than 50,000/mL at diagnosis.
High risk: Includes children younger than 1 year or older than 9 years and
children who have a white blood cell count of 50,000/mL or more at diagnosis
Treatment Protocols
standard protocols

Childrens Cancer and Leukaemia Group (CCLG),

Children's Cancer Group (CCG)
Paediatric Oncology Group (POG).
Recently, these two groups have joined together to form the Children's
Oncology Group (COG).
Many ongoing trials
Most favorable trial will become standard protocol
Treatment
The 4 general phases of chemotherapy for ALL include
1. Remission induction
2. CNS prophylaxis
3. Post remission consolidation or intensification
4. Maintenance
Induction therapy:
To kill the leukemia cells in the blood and bone marrow.
To put leukemia into remission.
Consolidation /intensification therapy:
It begins once the leukemia is in remission. The purpose of
consolidation / intensification therapy is to kill any remaining leukemia
cells that may not be active but could begin to regrow and cause a
relapse.
Maintenance therapy:
This is the third phase of treatment. Its purpose is to kill any remaining
leukemia cells that may regrow and cause a relapse
CNS prophylaxis: CNS sanctuary therapy
to kill cells in CNS so that they will not produce CNS leukemia/ CNS
relapse
Phase 1.:Remission induction
Treatment for 4 weeks

203
Weekly vincristine : 1.5 mg/m2/iv
Prednisolone 40 mg/m2/oral/divided dose
L-Asparaginase 10 000U/m2/IM biweekly
Daunomycin weekly for high risk cases
Phase II: CNS prophylaxis
Triple intrathecal therapy
e.g.for 2 yr old child
Methtrexate
10 mg
Hydrocortisone
10 mg
Cytosine arabinoside
10 mg
Weekly for 6 weeks followed by every 2 months for 2 years
CNS irradiation: craniospinal irradiation for high risk groups
Maintenance therapy
continued for 2 -3 years
6 Mercaptopurine 50 mg/m2/daily/oral
Methotrexate 20 mg/m2/week iv/oral
Reinforcement therapy for 30-36 months
Vincrystine 1.5 mg/m2/IV/monthly
Prednisolone 40 mg/m2/day/oral/ 7 days a month
Remission
70-80 %
Disappearance of clinical signs
No leukemic cells in peripheral smear
marrow smear contain less than 5 % blast cells
Neutrophil and thrombocyte counts return to normal
Relapse
Marrow: presence of 25% lymphoblasts in a bone marrow
aspirate following the first complete remission ;15-20 %
CNS: presence of morphologically identified lymphoblasts on
smears of CSF 5-10 %
Testis: evidence of lymphoblastic infiltration in one or both testes;
1-2 %
Supportive care
Urate oxidase and allopurinol may be given to reduce the uric acid level
following tumor lysis syndrome
Erythrocyte and platelet transfusion
Prophylaxis for pneumocystis carinii
Psychological support
Prognosis
5 year survival is 80% with aggressive therapy
Minimal residual Disease:
Refers to the burden of leukemic cells at end of induction
It has a prognostic value
High MRD at the end induction suggests a poor prognosis
Other treatment options:
Bone marrow transplant

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Stem cell transplant

Acute Myelogenous Leukemia

AML

11 % of childhood leukemia
Etiology:
1. Ionizing radiation
2. Alkylating agents
3. Syndromes:
Trisomy 21
Fanconi Anemia
Bloom
Diamond-Blackfan
Neurofibromatosis Type I
4. children who live near nuclear power plants or high-voltage power lines ?

5. the risk of AML was slightly increased in people who smoked compared
with those who did not smoke.
6. Antecedent hematologic disorders that predispose patients to AML
include:
7. Aplastic anemia,
8. Myelofibrosis,
9. Paroxysmal nocturnal hemoglobinuria
10.Polycythemia vera
11.myelodysplastic syndrome
Epidemiology
Acute myeloid leukemia affects all races nearly equally.
Male and female distributions are nearly equal
More in the first year of life
For the rest of the first decade of life, ALL is more common by a ratio of 4:1.
Equal during adolescence, and the incidence increases in adulthood.
Pathogenesis
1. acute myeloid leukemia is most commonly associated with the development of
fusion genes resulting from chromosome translocations.
2. Many translocations are characteristic of a particular subtype of acute leukemia
3. Multiple genetic mutations are often required for the complete leukemic
transformation.
Clinical features

205
1.
Hemorrhage due to thrombocytopenia
2.
Fever due to infections
3.
This infiltration may manifest as adenopathy, hepatomegaly and
splenomegaly.
4. Mediastinal mass may cause symptoms of respiratory insufficiency or
superior vena cava syndrome
5.
Abdominal masses obstruct the GI or urogenital tracts.
6.
Nodules of myeloblasts, called chloromas, in the skin, orbit, CNS or any
other organ.
7.
Monoblastic leukemia is often associated with gingival hyperplasia
8.
Unexplained persistent fevers
9.
Weight loss and cachexia are unusual
10.
Bone pain is less common in patients with acute myelocytic
leukemia
11.
Pathologic fractures of the extremity
12.
Compression fractures cause back pain and dysfunction of the
lower extremity (eg,
weakness, loss of bladder and bowel
function).
13.
Elevated intracranial pressure,
14.
Visual complaints.
15.
Involvement of cranial nerves, most often the facial nerve and the
abducens nerve
16.
Intracranial hemorrhage
17.
Splenomegaly is sometimes massive
18.
Typhlitis can mimic signs of appendicitis
19.
Severe anemia may lead to congestive heart failure.
20.
Skin nodules are firm, raised, and often bluish-purple in
color- blueberry muffin
Work up
1. Anemia is usually normocytic
2. Platelet counts of less than < 20,000/l
3. WBC counts may be decreased or elevated.
4. Hyperleukocytosis with WBC counts of more than >100,000/l
5. Primitive granulocyte or monocyte precursors are observed on peripheral
smears. Numbers of mature neutrophils are usually diminished.
6. Auer rods (thin, needle-shaped eosinophilic cytoplasmic inclusions) in blast
cells
7. Serum uric acid and lactic dehydrogenase levels are elevated
8. Serum muramidase (lysozyme) levels are increased
9. Evidence of disseminated intravascular coagulation
10.Auer rods
Auer rods can be seen in the blasts of acute myeloid leukemia
They are composed of fused lysosomes and contain peroxidase,
lysosomal enzymes
Imaging and bone marrow Studies
chest radiography to rule out mediastinal masses

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metaphyseal bands at the distal femurs
Bone marrow: hyperplastic marrow with monotonous sheets of leukemic blasts.
FAB classification

Treatment
The Children's
(COG):
Induction
2

M0

Minimally differentiated
myeloblastic leukemia

M1

Acute
myeloblastic
without maturation

M2
M3
M4

acute

leukemia,

Oncology Group

Acute myeloblastic leukemia, with Remission:

granulocytic maturation
cycles of
Acute promyelocytic leukemia (APL) induction therapy
with infusions of :
Acute myelomonocytic leukemia

M4e Myelomonocytic together with bone

o
marrow eosinophilia
M5

Acute monoblastic leukemia

M6

Acute erythroid leukemias

M7

Acute megakaryoblastic leukemia

M8

Acute basophilic leukemia

daunomycin, cytosine arabinoside, etoposide (ADE therapy).

Maintenance:
sequential cycles of chemotherapy are administered by using
combinations of :
cytosine arabinoside and etoposide,
mitoxantrone and cytosine arabinoside, and, finally,
high-dose cytosine arabinoside with L-asparaginase.
Supportive:
Marrow transplant
Stem cell transplant
Transfusion support
Management of Hyperkalemia and hyper phosphatemia with associated
hypocalcemia
broad-spectrum antibacterial, antiviral, and antifungal antibiotics;

207

Pediatric HIV
1. History:
HIV was +ve
1. in 1959 : plasma sample taken from an adult male in Congo.
2. in 1969 : in tissue samples from an African-American teenager who died in
St. Louis.
3. In 1976 : in tissue samples from a Norwegian sailor.
4. ? So first case of HIV infection occurred around 1930 in West Africa
(computer generated model)
5. HIV is a descendant of simian (monkey) immunodeficiency virus (SIV).
6. SIV bear a very close resemblance to HIV
'Patient Zero'.
1. Patient Zero was a Canadian flight attendant called Gaetan Dugas who
traveled extensively worldwide.
2. Analysis of several of the early cases of AIDS showed that the infected
individuals were either direct or indirect sexual contacts of the flight
attendant.
2. Global data-2009:
1. The history of AIDS is a short one. As recently as the 1970s, no one was
aware of this deadly illness
2. 33.3 million people are living with HIV, 2.6 million added/year
3. 1.8 million die of AIDS.
4. 2.5 million children living with HIV 400,000 added / year
5. 30 children die as a result of AIDS
6. 16 million children have lost one or both parents to AIDS.
7. Most children living with HIV almost 9 in 10 live in sub-Saharan Africa,
the region of the world where AIDS has taken its greatest toll.
3. Estimated number of people living with HIV/AIDS in India, 2007:
1. People living with HIV/AIDS 2.31 million
2. Adult (15 years or above) HIV prevalence 0.34%
3. 39% are female and 3.5% are children.
4. Women attending antenatal clinics : 0.48%.
5. People attending std clinics: 3.6%
6. Female sex workers: 5.1%
7. Injecting drug users: 7.2%
8. Men who have sex with men: 7.4 %
4. Etiology
1. Family: Retroviridae
2. Genus: Lentivirus
3. HIV I: contains 2 copies of single stranded RNA
4. HIV II: common among monkeys; rare in Ped.HIV difficult to identify with
HIV I tests; specific antibody test or III generation ELIZA should be used
for testing
5. Epdemiology

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6. Infection
1. HIV 1: Gp 120 carries a binding site to CD4 molecule with co recptors like
CC5 of T Cell and gain entry into cell ; a
2. Viral RNA enters into cell cytoplasm
3. Viral RNA transcribes viral DNA copies using reverse transcriptase
4. DNA copies enters chromosomal DNA to form provirus
5. Proviral DNA encodes production of viral RNA viral proteins assembly
buds out of cell as new HIV 1 virus
6. Virus attacks young CD4 cells
7. Viral release by CD4 cell lysis
8. Gradual decrease in CD4 population
7. HIV transmission
1. Virtually vertical (MTCT)
2. Rarely through:
1. blood products, clotting factors- 3-6%
2. Homosexual contacts in adolescent boys
3. Heterosexual contact in adolescent girls
4. IV drug use
3. Transmission by household contacts is nonexistent
8. Risk factors for MTCT
1. Preterm < 34 weeks
2. Low CD4 count in mother
3. Birt weight < 2500 gms
4. Rupture of membranes for > 4 hours
5. Mothers viral load > 1000 copies/mL

209

9.

10.

11.

12.

13.

6. Vaginal delivery
7. Instrumental delivery
8. Caserian + ART to infant decrease transmission by 87 %
Mother To Child Transmission
1. Transmission rate is 12-30 %
2. Intra uterine: 30-40 %
3. Intrapartum: 60-70 %
4. Breastfeeding:
Transplacental
1. PCR is positive in fetal tissue by 10 weeks of gestation
2. In situ hybridization and immuno cytochemistry identify virus in fetal
tissue in 1st trimester
3. Viral detection soon after birth
Intrapartum
1. Infected blood, cervico vaginal secretions in birth canal conjunctiva,
skin abrasions, gastric mucosa
2. Infected infant negative for viral detection in first week of life
3. First born twin 3 times more infected
Breast feeding
1. Both virus and viral laden cells are present breast milk
2. Mother infected before pregnancy: 14 %
3. Mother infected postnatally: 29 %
4. Benefit of breastfeeding outweighs the risk of HIV in developing countries
5. WHO: breastfeed first 6 months and rapid weaning thereafter
Pathogenesis
1. Virus enters via mucosal breaks
2. Carried by dentritic cells (antigen presenting cells) to lymph gland
3. Virus infects T helper (CD4) cells, monocytes and macrophages
4. CD 4 receptors are also present in:
1. Micrglia
2. Astrocytes
3. oligodentroglia
2. Placental villus cells
5. Co receptor CXCR 4 and CCR 5 are also necessary for viral attachmnt
6. Persons who lack CCR5 are highly protected from HIV
7. Lymphocyte proliferation against viral antigen produce generalized
lymphadenopathy
8. Younger the CD4 cells the more they are invaded
9. HIV is peculiar that it uses CD4 cells meant for eliminating them as host
cells
10.CD4 cell count decreases and viraemia increases in 3-6 weeks producing
flulike illness
11.Then by 2-4 months body mounts up cellular and humoral immune
defense to reduce viraemia
12.Now there is a symptom free period only for a short period to be
followed by gradual reduction CD4 cells and appearance of symptom
complex
13.Mechanisms of CD4 cell death:

210
1. Lysis by virus
2. Syncytia formation
3. Autoimmune cell destruction
4. Apoptosis
14.Monocytes resists killing and act as reservoirs for HIV
15.CD8 T cells suppress viral replication by blocking CCR 5
16.Decrease in CD4 population and increase in immune response leads to
clinical latency
17.The virus switch to more virulent phenotypes and more T cells are killed
heralding AIDS disease
14. Course of illness
1. Rapid course and death in 6-9 months- 15-25 %; in transplacental
transmission and is due to underdeveloped immune system in fetus
2. Slow progression with survival up to 6 years; 60-80% ; occurs in intra
partum infection
3. Long term survivors: < 5%; occurs in good immune system and
attenuated virus
4. CD4 < 1500 / mm is equivalent < 200 / mm in adults as infants
normally have lymphocytosis
5. Skin sensitivity tests are usually negative
6. B cell activation produce hypergammaglobulinemia in some patients
7. Antibodies specific for HIV are less and protection is also less
15. Clinical manifestations
1. Normal at birth
2. Initially symptoms are nonspecific
3. Lymphadenopathy
4. hepatosplenomegaly
5. failure to thrive
6. chronic diarrhea
7. wasting
8. Recurrent bacterial infections
9. Chronic parotid swelling
10.Recurrent pneumonia
16. Clinical categories
Category N: asymptomatic
Category A:
Any 2 of the following:
1. Lymphadenoapthy
2. Parotitis
3. Hepatomegaly
4. Splenomegaly
5. Dermatitis
6. Recurrent sinusitis
7. Otitis
Category B
1. Lymphocytic interstitial pneumonia

211
2. Oropharngeal thrush > 2 mo
3. Chronic diarrhea
4. Fever > 1 mo
5. Hepatitis
6. Herpes simplex
7. Pneumonitis
8. Varicella
9. Cardiomegaly
10.neuropathy
Category C
1. With 2 serious bacterial infections: sepsis, meningitis, pneumonia
in 2 years
2. Esophageal candidasis
3. Cryptococcoal infection
4. Encephalopathy
5. Malignancies
6. Disseminated TB
7. Pneumocystis pneumonia
8. Cerebral toxoplasmosis
9. Severe wasting
17. Immunologic category -CD 4 counts / L:
Immunity
1. No suppression
2.
Moderate
suppression
3.
suppression

Severe

< 12 yr

1-5 yr

6-12 yr

>1500

>1000

>500

750-1500

500-1000

200-500

< 750

< 500

< 200

18. Combined categorization:

A1; A2; A3 etc
19. Oppurtunitic infections:
1. Pneumocysti carinii pneumonia- PCP
1. Most common OI in Ped. HIV ; Common in 3-6 mo of age
2. It accounts for 57% of AIDS-defining conditions
3. High Mortality at 1 yr
4. Fever, tacypnaea, hypoxemia
5. CXR: interstitial infiltrates
6. Diagnosis: staining of bronchial aspirtae for PC
7. Treatment:
1. IV TMP-SMZ; IV corticosteroids; Oral maintenance for 21 days
2. Pentamidine: 4 mg/kg/day, single dose IV for 21 deays
8. Prophylaxis: TMP-SMZ

212
1. Age (Year)

CD4 Count (Absolute Count/Micro-Litre)

2. 1-5
<500
3. 6-12
<200
2. Non-tuberculosis mycobacterial infections:
1. Mycobacterium avium complex, M. kansasii, M. chelonei & M.
fortuitum
2. Slowly progressive. High-grade fever, weight loss, abdominal pain
and anemia are common.
3. Night sweats, diarrhea, malaise, hepatomegaly, osteomyelitis,
meningo encephalitis and intra abdominal and soft tissue
abscesses also occur with this infection.
4. Treatment: Clarithromycin or Azithromycin with Ethambutol and/or
Rifabutin
3. Tuberculosis:
1. Most common HIV-related OI;
2. High incidence of drug-resistant tuberculosis
3. Depletion and dysfunction of CD4 cells with defects in the function
of macrophages and monocytes
4. Miliary TB, hepatosplenomegaly, lymphadenopathy, TBM, and
genito-urinary tuberculosis may occur.
5. Mx is usually negative; positive if the induration is 5 mm
6. PCR test has high sensitivity and specificity. 4-drug regimen of
Isoniazid, Rifampin, Pyrazinamide and Ethambutol .
7. Duration of treatment is for 6-12 months for pulmonary , 12
months for extra-pulmonary disease.
8. ART & ATT :
1. In a patient with CD4 count less than 200, ART to be started
two weeks
to two months after starting of tuberculosis therapy.
2. If CD4 count is higher, ART after induction phase of
tuberculosis is complete
4. VIRAL INFECTIONS
HERPES SIMPLEX 1 & 2:
1. Recurrent self-limited cluster of orolabial ulcers with severe
stomatitis and cutaneous dissemination
2. Oral Acyclovir 80 mg/kg/day in 3-4 divided doses for 10 days
VARICELLA ZOSTER VIRUS (VZV):
1. Persistent lesions for more than one month after onset
2. pneumonia, hepatitis and encephalitis
3. IV Acyclovir 1500 mg/m2/day in 3 divided doses for 7-10 days;
4. Oral therapy 80 mg/kg/day in 4 divided
Herpes zoster :
1. Dormant form of vzv
2. Multidermatomal infection,

213
3. Disseminated zoster with over 20 lesions outside the primary
dermatomal eruption,
4. Bilateral involvement with rash,
5. Retinitis and rarely pneumonitis,
6. Consumptive coagulopathy,
7. Hepatitis,
8. Marked constitutional symptoms
9. Encephalitis.
10.Post-herpetic neuralgia is more common.
11.Intra-venous acyclovir 30 mg/kg, daily in 3 doses.
12.Oral acyclovir 80 mg/kg/d in 4 div doses
CYTOMEGALOVIRUS (CMV):
1. CMV infection is an AIDS defining condition.
2. More than 90% of HIV-infected pregnant women are CMV-infected;
mother infects child pre or post natally
3. Chorioretinitis visual loss and retinal detachment
4. diarrhoea, abdominal pain
5. Pneumonitis
6. Encephalitis: It manifests as sub-acute dementia complex.
7. Ganciclovir 10 mg/kg/day in 2 divided doses, intra-venously, over
1-2 hours for 14-21 days
8. Life-long prophylaxis with Ganciclovir (5 mg/kg/d IV 5 days per
week)
4. TOXOPLASMA GONDII INFECTION
1. Women transmits toxoplasma to the foetus
2. Low-birth weight, microcephaly hydrocephalus, hepatosplenomegaly and
chorioretinitis.
3. Cns : headache, fever, changes in the mental status, seizures;
hemiparesis, ataxia and cranial nerve palsies.
4. Multiple ring-enhancing lesions-granulomas is seen on the mri or the ct
scan of the brain.
5. The drugs used are sulfadiazine & pyrimethamine.
6. Folinic acid for prevention of drug-induced suppression of the bone
marrow.
5. CANDIDA INFECTIONS
1. Oral thrush and diaper dermatitis are common
2. Esophageal candidiasis present with substernal or abdominal pain,
dysphagia and weight loss.
3. Disseminated infection may manifest as sepsis and shock.
4. Nystatin, Amphotericin B and Azoles.
5. For esophageal candidiasis, Fluconazole is the drug of choice.
Amphotericin for treating for resistant cases
6. DIARRHEA
1. Diarrhoea may persist for several days leading to wasting and cachexia.
2. Cryptosporidium: Paramomycin
3. Isospora: Oral TMP-SMX

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4. Cyclospora: Oral TMP-SMX
5. Microsporidium : Albendazole 400 mg twice a day
6. Entamoeba Histolytica: Metronidazole
7. Giardia Lamblia: Metronidazole Furazolidone Tinidazole
20. Differences in pediatric and adult hivinfection:
1. Progression of disease is more rapid
2. Immune system is more immature with higher CD 4 counts
3. Recurrent invasive bacterial infections are more common
4. Disseminated CMV, Candida, Herpes Simplex and Varicella Zoster are more
common
5. LIP occur almost exclusively in children
6. CNS infections are common
7. Peripheral neuropathy, myopathy are rare in children
21.Skin manifestations in hiv-infected children:
Infectious Disorders
and Lesions

Non-Infectious Disorders and Lesions

Viral Infections:
Herpes simplex, Herpes
zoster,
Molluscum contagiosum,
Warts

Atopic dermatitis; Seborrheic dermatitis,

Generalized dermatitis, Nutritional
Deficiency

Fungal Infections:
Candida, Tinea,
Onchomycosis

Eczema, Psoriasis, Drug eruptions

Bacterial:Impetigo

Vasculitis

Other: Scabies

Alopecia

22.Hematological abnormalities:
Abnormality
Anemia

Mechanism
Auto-immune; Suppression of the bone marrow by
drugs Nutritional deficiency (folic acid, Vitamin B12,
micronutrients)

Thrombocytopeni Immune-mediated, Nutritional deficiency (Vitamin

a
B12 deficiency)
Neutropenia

Immune-mediated destruction

215

23.Other
1.
2.
3.

Lymphopenia

Bone marrow suppression due to altered cytokine

production, CD4+ apoptosis induced by HIV
replication

Eosinophilia

Shifting of immune response from Th1 to Th2

cytokine profile

manifestations:
Cardiac: Myopathy
CNS: HIV Encephalopathy; peripheral neuropathy
Nephropathy: due to virus, immune complex mediated vasculitis, or
opportunistic infections
4. Respiratory: Lymphoid Interstitial Pneumonitis (LIP)
1. Cough and Tachypnea
2. Diffuse bilateral reticulondular or interstitial infiltrates on chest
radiograph
5. Malignancy:
1. Non-Hodgkins lymphoma, leiomyomas and leiomyosarcomas
and leukemia
2. Kaposis sarcoma is rare
24.Diagnosis
1. Viral Culture: 100% specific; costly and needs sophisticated laboratory set
up
2. Polymerase Chain Reaction (PCR) RNA/DNA:
1. Two PCRs have to be positive, done beyond one month
and at least one of them after age of 3 months.
2. Detect nearly 100% of infected newborns
3. Enzyme Linked Immunosorbent Assay (ELISA)
1. I Generation ELISA: antigen from crude viral lysate
2. II generation: part of virus
3. III Generation ELISA: synthetic peptides as the antigen
4. Rapid tests
ELIZA
1. Current kids are 100% sensitive and specific.
2. detection of anti-HIV antibodies in patients sera.
3. The ELISA is performed by the use of purified antigen, bound to a plate
containing small wells.
4. The latest ELISA is the Rapid Test with results in 10 mts
5. Eliza test should be confirmed by Western Blot or repeated Eliza with
different antigens
ELIZA : method
1. HIV antigens pre-coated onto an ELISA plate
2. HIV antibodies of patient will bind to the HIV antigens on the plate.
3. Anti-human immunoglobulin is coupled to an enzyme is now added which
binds to human HIV antibodies

216
4. Chromogen or substrate is then added which changes color when cleaved by
the enzyme attached to the second antibody
Western Blot Analysis (WBA)
1. Plasma electrophoresis on a strip pre-impregnated with various HIV antigens
(i.e. p24, p28, gp41, gp120, gp160,).
2. show bands of all these antibodies depending on their presence in the
samples
3. In India, it is not mandatory to do WBA
25.Management Care immediately after birth
1. Cord clamped soon; no milking;
2. Early baby bathing
3. Single dose NVP to mother during labour and to the baby within 72 hours
after birth.
4. Exclusive replacement feeding is afass acceptable, feasible, affordable,
sustainable and safe
5. Quick weaning at 6 mo
6. CTX prophylaxis from age of 46 weeks; 5 mg/kg/day
7. Growth monitoring
8. Screen for infections
26.When to start ART in children, guided by CD4
1. < 11 month infants : if CD4 < 1500 cells/mm3
2. 1235 months : if CD4 < 750 cells/mm3
3. 3659 months : if CD4 <350 cells/mm3
4. > 5 years old : < 350 cells/mm3 especially if symptomatic; or
5. Before CD4 drops below 200 cells/mm3.
27.ARV regimens
1. Zidovudine (AZT) + Lamivudine (3TC) + Nevirapine NVP
2. Stavudine (D4T) + Lamivudine (3TC) + Nevirapine (NVP)
3. Vaccine:
1. if the HIV-infected child is asymptomatic or mildly symptomatic
vaccinations should be given.
2. Withold vaccine (live vaccines) for HIV-infected children who are
symptomatic and severely immuno-compromised.
28.Prevention
1. Transmission from the mother to child is likely to be about 15-45%.
2. There is 16.2% greater risk of mother-to-infant transmission of HIV when
children are breast-fed as opposed to formula-fed.
3. Single dose NVP 200mg given at the onset of labour and
4. single dose of syrup NVP 2mg/kg weight to the baby within 72 hours
decreases risk of transmission by 13.1% (breast feeding)..
5. Transmission of the HIV virus occurs most commonly during the first few
months after birth
6. Avoid manipulations like amniocentesis and external cephalic version
increase the risk of transmission of HIV.

217
7. Long duration of rupture of membranes increase the transmission risk. It has
been estimated that with every hour, the risk of transmission increases by
2%.
8. Placental disruption and infections also adversely affect transmission.
9. Invasive fetal monitoring should be avoided, as should all invasive obstetric
procedures.
10.Where facilities are available, elective LSCS should be offered.
11. If instrumental delivery is necessary, then forceps are a better option than
vacuum suction cup delivery.
12.Emergency LSCS is associated with high transmission
13.In India normal delivery is recommended unless the woman has obstetric
reasons
14.When replacement feeding (infant formula) is acceptable, feasible,
affordable, sustainable and clean water is available, HIV-infected mothers
should avoid breastfeeding completely.
15. Otherwise, exclusive breastfeeding is recommended during the first months
of life, with early abrupt weaning at 3-4 months or 6 months of age