PEDIATRICS YEARWISE QUESTION PAPERS

(2008-14)
WITH SOME SPECIAL TOPICS

Edited by:
Prithwiraj Maiti, MBBS
House physician
Department of Internal Medicine, R.G.Kar Medical College
Author: “An Ultimate Guide to Community Medicine”
Author: “A Practical Handbook of Pathology Specimens and Slides”
[Both published by Jaypee Brothers Medical Publishers, India]

Table of contents

Topic Page no.

2008 1-20
2009 21-34
2010 35-47
2011 48-63
2012 64-74
2013 75-94
2014 95-110
PSGN 111-117
Nephrotic syndrome 118-127
Meningoencephalitis 128-147
Thalassemia 148-156
Thyroxin synthesis 157-161
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WBUHS 2008
Pediatrics and Neonatology
Group A
1. What is glomerular filtration? How it is affected in acute poststreptococcal
glomerulonephritis? Describe the underlying pathogenic mechanism for the
clinical picture of acute poststreptococcal glomerulonephritis. (1+3+6)
Glomerular filtration:
 As the blood passes through the glomerular capillaries, the plasma is
filtered through the glomerular capillary walls.
 The filtration barrier is composed of:
a. Capillary endothelium with slit pores
b. Glomerular basement membrane
c. Podocytes of visceral epithelial cells.

ESL: Endothelial surface

layer, GBM: Glomerular
basement membrane,
Qp: Plasma flow rate.
Note that:
𝐺𝐹𝑅~(20% 𝑜𝑓 𝑄𝑝).

 The ultrafiltrate, which is cell free, contains all of the substances in plasma
(electrolytes, glucose, phosphate, urea, creatinine, peptides, low molecular
weight proteins) except proteins having a molecular weight of ≥68 kd
(such as albumin and globulins).
 The filtrate is collected in Bowman's space and enters the tubules, where
its composition is modified by tightly regulated secretion and absorption of
solute and fluid, until it leaves the kidney as urine.
 2

Effect of APGSN on glomerular filtration:

 APSGN is an antibody-antigen disease that occurs as a result of certain
strains of the Group A ß-hemolytic streptococcal infection (type 12 and 49)
and is most commonly seen in children of the 5-12 years age-group.
 The exact mechanism of the pathophysiology for APSGN is not certain. It is
believed that immune complexes develop and become trapped in the
glomerular capillary loop at the basement membrane.
 This produces swelling and occlusion of the capillary lumen and results in
alterations in the glomerular filtration rate.
Morphological alteration in PSGN as seen in different techniques:
Method Description
Light microscopy a. Proliferation of all 3 layers of renal microstructure
(epithelium, mesangium and endothelium)
b. Hypercellularity (owing to infiltration of glomeruli
by PMN cells and proliferation of cells).
Immunofluorescence Granular immune complex deposits (mainly IgG and C3),
in the mesangium and along the GBM.
Electron microscopy Subepithelial electron dense deposits, with appearance
of “humps”.
Note that: Swelling of these humps usually disappear
after 6 weeks of onset.

Underlying pathogenic mechanism for the clinical picture of APSGN:

Usual chief complaints in a patient in APSGN:
1. Decreased urine volume and frequency
2. Periorbital edema, prominent in the morning
3. Hematuria
4. Hypertension (occasional).
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Pathogenesis of clinical features:

1. Edema and hypertension:

Hypercellularity and
Compression of Reduction in GFR
proliferation of all
afferent and efferent and resultant
the 3 layers of renal
renal vessels oliguria
microstructure

Activation of Renin-
Retention of salt and Edema associated
Angiotensin-
water with hypertension
Aldosterone system

a) A complication of this abnormal retention of salt and water is acute

left sided heart failure. Which is suspected by the following
symptoms and signs:
Symptoms and signs of acute LHF
Symptoms Signs
 Acute respiratory distress  Gallop rhythm (S3/ S4)
 Tachypnoea  Basal crepts/ wheeze
 Tachycardia (due to pulmonary edema)

b) Another complication of this hypertension is hypertensive

encephalopathy which is suspected by the following symptoms:
 Headache
 Vomiting
 Convulsion
 Alteration of sense of consciousness.

2. Proteinuria and hematuria:

As a result of immune complex deposition along the glomerular
basement membrane (GBM) and resultant damage to glomeruli, there is
leakage of protein and RBC, which is responsible for the nephritic range
of proteinuria and hematuria characteristic of PSGN.
 4

Group B
2.a. Give an outline of clinical features of neonatal sepsis.
Introduction:
Systemic bacterial infections of newborn infants are termed as neonatal sepsis.
They are the most common cause of neonatal deaths in India. Neonatal sepsis
manifests with vague and ill-defined symptoms and therefore requires high index
of suspicion for early diagnosis.
Symptoms and signs of neonatal sepsis:
 Alteration in the established feeding behavior: It is the most characteristic
early feature of neonatal sepsis. The baby, who had been active and
sucking normally, gradually or suddenly becomes lethargic, inactive,
unresponsive and refuses to suck.
 Appearance of the infant: The infant may appear pale with grayish
circumoral cyanosis and a vacant look.
 Hypothermia: Hypothermia is a common manifestation of septicemia in
preterm babies.
 Apneic spells: Episodes of apneic spells with cyanosis may be the sole
manifestation of septicemia in preterm babies.
 Fever: Term babies may manifest with fever, especially in association with
gram-positive infections and meningitis.
 Other symptoms/ signs:
 Diarrhoea
 Abdominal distension
 Vomiting
 Jaundice
 Hepatosplenomegaly.
Additional localizing features:
The additional localizing features may appear depending upon the spread of
infection to different systems and organs of the baby. Ex:
System Disease Localizing features
Respiratory Pneumonia Fast breathing, chest retraction, grunting
 5

CNS Meningitis Excessive/ high-pitched crying, fever, seizures,

neck retraction, bulging anterior fontanel
Overwhelming sepsis with Shock, bleeding, sclerema*, renal failure
multisystem involvement
*Sclerema is a severe skin condition characterized by diffuse hardening of the
subcutaneous tissue with minimal inflammation in premature ill newborns. It
appears suddenly, first on the thighs and buttocks and then, spreading rapidly,
often affects all parts of the body except the palms, soles and genitalia. The
involved skin is pale, waxy and firm to palpation.
2.b. Describe briefly the complications of low birth weight (LBW) babies.
Types of low birth weight infants:
It is desirable and of practical relevance to make clinical distinction between the
two types of LBW babies.
1. Preterm: A preterm is defined as a baby born alive before 37 weeks of
pregnancy are completed.
2. Small for date: A small for date baby is one whose size is smaller than
normal for the gestational age, most commonly defined as a weight below
the 10th percentile for the gestational age.
The SFD babies are often full term or borderline term in gestation.
Complications of preterm LBW babies
The basic underlying feature of the preterm LBW infant is immaturity of their
organ systems.
Complications Cause
Perinatal asphyxia Preterm babies may not establish respiration satisfactorily at
birth and develop asphyxia requiring expert resuscitation.
Hypothermia All newborn babies keep themselves warm by active metabolism
in the brown fat. The preterm babies lack adequate stores of
brown fat and are, therefore, vulnerable to become hypothermic
at the usual ambient temperatures unless specific measures are
taken to keep them warm.
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Feeding problems Infants born before 34 weeks of gestation do not have

and poor weight gain coordinated sucking and swallowing movements. Therefore, they
are unable to suck at the breast and are liable to get choked.
Respiratory distress Infants born before 34 weeks of gestation have immature lungs
syndrome (RDS) which do not expand well after birth and are, therefore, unable
to perform the function of gas exchange. They are susceptible to
develop RDS which is characterized by rapid and laboured
respirations, chest indrawing, grunting and cyanosis.
Apnea of prematurity Because of the immature respiratory control mechanisms, these
babies have a tendency to manifest apneic spells.
Intraventricular Premature infants have immature vascular beds around cerebral
hemorrhage (IVH) ventricles. The delicate vessels may rupture and cause IVH.
Biochemical Immature metabolic pathways of preterm infants predispose
abnormalities them to the development of:
 Hypoglycemia
 Metabolic acidosis and
 Hyperbilirubinemia.
Infection Preterm babies do not have efficient humoral, cellular and
mucosal immune mechanisms to protect themselves against
infections. So, they are very much prone to infections.
Retinopathy of Excessive oxygen saturation may occur as a result of
prematurity (ROP) unmonitored oxygen therapy during newborn resuscitation.
This ↑SpO2 injures the immature growing retinal blood vessels,
causing ROP which may result in vision loss if left untreated.

Complications of preterm small for date babies

The basic underlying feature of the preterm SFD/ IUGR babies is in-utero
undernutrition and hypoxia.
Complication Cause
Perinatal asphyxia SFD babies may not establish respiration satisfactorily at birth and
develop asphyxia requiring expert resuscitation.
 7

Meconium
aspiration
syndrome (MAS)

Hypothermia Since, they are chronically undernourished in utero, they also lack
adequate brown fat stores. This predisposes them to hypothermia.
Hypoglycemia Insufficient energy store predisposes SFD babies to hypoglycemia.
Polycythemia Placental insufficiency + Intrauterine hypoxia
↓ ↓
Feed intolerance Stimulation of erythropoiesis→ Polycythemia
↓ ↓
Poor weight gain Jitteriness, feeding intolerance, hypoglycemia, hypocalcemia,
hyperbilirubinemia, respiratory distress, cardiac failure.

2.c. Write in short the indications and complications of phototherapy.

Indications of phototherapy:
For preterm babies
Most preterm babies are placed under phototherapy when their total serum
bilirubin (TSB) approaches 10-12 mg/dl.
For term babies
Age of neonate TSB level to start phototherapy
25-48 hours ≥15 mg/dl
49-72 hours ≥18 mg/dl
>72 hours ≥20 mg/dl
 8

Guidelines on continuation of phototherapy:

 Continue breastfeeding every 2-3 hr
 If TSB ≥25 mg/dL, repeat TSB in 2-3 hr
 If TSB 20-25 mg/dL, repeat TSB in 3-4 hr
 If TSB <20 mg/dL, repeat TSB in 4-6 hr
 If TSB continues to fall, repeat TSB in 8-12 hr
 When TSB is <13-14 mg/dL, discontinue phototherapy
 If TSB is not decreasing/ is moving closer to level for exchange transfusion/
the TSB/albumin ratio exceeds recommended limits, consider exchange
transfusion.
Complications of phototherapy:
1. Loose stools
2. Erythematous macular rash
3. Purpuric rash (due to transient porphyrinemia)
4. Overheating
5. Dehydration (due to increased insensible water loss)
6. Hypothermia from exposure
7. Bronze baby syndrome:
 It refers to a dark, grayish brown skin discoloration in infants
undergoing phototherapy, which is not a C/I of phototherapy.
 Almost all infants with this syndrome have significant elevation of
conjugated bilirubin and other evidences of obstructive liver disease.
 The discoloration may be due to photo-induced modification of
porphyrins, which are often present during cholestatic jaundice and
may last for many months.
Group C
3.a. Dietary management of severe protein energy malnutrition (PEM):
It consists of 3 phases:
1. Initial stabilization phase
2. Phase of high energy feeding
3. Phase of rehabilitation.
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Initial stabilization phase

 In this phase a cautious approach is required because of the child’s fragile
physiological state and reduced homeostatic capacity and feeding should
be adjusted to provide energy and protein required only to maintain basic
physiological processes.
- For this purpose, the following regimen is recommended based on
actual weight of the child:
80 cal/kg/day + 0.7 gm protein/kg/day
 The second rule is to offer small amount of feeds of low osmolarity and low
lactose at frequent intervals to avoid the incidence of vomiting,
hypoglycemia and hypothermia.
- For this purpose, the following regimen is recommended:
Day Frequency of feeds Volume/kg/feed Volume/kg/day
1-2 2 hourly 11 ml
3-5 3 hourly 16 ml 130 ml
6-7+ 4 hourly 22 ml
- Milk is the most common nutritional liquid food and is also well
tolerated, except by children with lactose intolerance. The calorie
content of milk can be increased after 1st week by adding oil as follows:
Component Amount
Cow’s milk 300 ml
Sugar 85 gm
Vegetable oil 30 gm
The amount of water added to this formulation would depend on the
desired concentration of calories and proteins required and state of
hydration of the individual child.
- In children with lactose intolerance, low lactose diet/ lactose free diet
should be given:
Type of diet Example
Low lactose diet Dried skimmed milk/ (Milk+ rice)
Lactose free diet Rice-egg/ Cereal pulse/ Soya rice gruel/ Chicken gruel
Alternatively, cards/ card-rice may be given to these children.
 10

Phase of high energy feeding

 After the child passes through the initial phase and shows signs of
improvement, tolerates the prescribed diet, one can then gradually
increase the calorie and protein intake as follows:
150-180 cal/kg/day + 1.5-2.0 gm protein/kg/day
 Some example of high energy foods given in this period are:
1. Besan mix/ ladoo/ panjiri
2. Sooji/ kheer
3. Hyderabad mix
4. Shakti ahar.
Phase of rehabilitation
 Once the child is able to tolerate a high dose of therapeutic nutrition and
has started gaining weight, he or she may be offered solid/semisolid family
foods containing cereals, pulses, vegetables rich in calories and
quantitatively appropriate Bengal gram, groundnuts and dark green leafy
vegetables should be added to regular family foods.
 Oils, sugar and fruits should also be given and minerals and vitamins could
be continued for 5-6 weeks.
 The diet prescribed for the child should be such that the family can provide
within their limited income, can be easily cooked at home, does not perish
easily, is culturally acceptable, as well as locally available.

3.b. Congenital hypothyroidism (CH):

Introduction:
It is the most common preventable cause of mental retardation.
Etiology:
Group Description Prevalence
Thyroid dysgenesis Complete agenesis/ partial agenesis/ 80-85%
ectopic thyroid
Dyshormonogenesis Inborn error of thyroxine synthesis 15%
 11

Transplacental passage of thyrotropin-receptor blocking antibody 2%

(TRBAb). (Note that, thyrotropin and TSH are synonymous.)

 Thyroid dysgenesis is most common cause of congenital hypothyroidism in

non-endemic areas of India. It is important to note that the cause of thyroid
dysgenesis is unknown in most cases and it usually occurs sporadically.
 Iodine deficiency is the most common cause of congenital hypothyroidism
in endemic areas of India.

History:
Points important in history Points to which etiology of CH?
Family history of hypothyroidism Dyshormonogenesis
Recurrent transient hypothyroidism Transplacental TRBAb
Residence in iodine deficient area Iodine deficiency
Maternal intake of anti-thyroid drugs/ CH due to fetal iodine exposure
anti-arrhythmic drugs with ↑I2 content*
*The most common example is Amiodarone.

Clinical features of CH:

 Hoarse cry
 Facial puffiness
 Umbilical hernia
 Hypotonia
 Mottling of skin
 Lethargy.

Indicators of future CH:

 Open posterior fontanel
 Prolonged jaundice
 Prolonged constipation
 Continuous unexplained hypothermia.
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Approach to a child with CH:

Congenital hypothyroidism

Thyroid scan

No uptake Increased uptake Ectopic uptake

Dyshormonogenesis/
USG
Iodine deficiency

Ectopic thyroid
No thyroid gland Normal thyroid gland

Thyroid agenesis Test for TRBAb

+Ve -Ve

Transplacental passage of Defect in TR/ Na+ uptake/

maternal TRBAb TPO/ Thyroglobulin

[TRBAb: Thyrotropin receptor blocking antibody, TR: Thyrotropin receptor, TPO: Thyroid peroxidase.]

Treatment:
 Levothyroxine (T4) given orally is the treatment of choice. As 80% of
circulating T3 is formed by mono-deiodination of T4, serum levels of T4 and
T3 in treated infants return to normal.
 Starting dose of T4 is 10-15 μg/kg/day.
 T4 and TSH level is expected to come to normal within 1 week and 1 month,
respectively with this treatment.
 Lifelong thyroid replacement is required in most cases. But it should be
stopped for 1 month at the age of 3 years in suspected transient CH.
 In case of rare central hypothyroidism (thyroid hormone deficiency due to a
disorder of the hypothalamic-pituitary axis), cortisol replacement should be
done first, followed by thyroid replacement.
 13

3.c. Clinical features of pyogenic meningitis in children:

Symptoms
Classical:
a. Fever,
b. Headache,
c. Photophobia.

Others:
a. Irritability,
b. Lethargy,
c. Mental confusion,
d. Nausea and vomiting,
e. Altered consciousness.

Signs
Classical:
a. Neck rigidity,
b. Kernig sign,
c. Brudzinski sign.
Kernig sign
 This maneuver is usually performed with the patient supine with hips and
knees in flexion.
 Extension of the knees is attempted.
 Inability to extend the patient’s knees beyond 135⁰ without causing pain
constitutes a positive test for Kernig’s sign.
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Brudzinski sign
 With the patient supine, the physician places one hand behind the patient’s
head and places the other hand on the patient’s chest.
 The physician then raises the patient’s head (with the hand behind the
head) while the hand on the chest restrains the patient and prevents the
patient from rising.
 Flexion of the patient’s hips and knees constitutes a positive sign.
 Brudzinski’s neck sign has more sensitivity than Kernig’s sign.

Others:
Skin
a. Erythematous maculopapular rash -> purpura and petechiae (Neisseria)
b. Tache Cerebrale: Stroke skin with a blunt instrument -> 30-60 sec -> raised red
rash.
Central Nervous System
a. Seizures: Focal/ generalized; tonic/ clonic/ tonic-clonic.
b. Respiratory distress,
c. SIADH (Syndrome of inappropriate ADH secretion),
d. Focal neurologic signs:
 Cranial nerve palsies (most common: CN6).
 Hemiparesis/ quadriparesis,
 Visual signs: Papilledema/ visual field defects (due to cortical venous or
arterial thrombosis)
 Auditory signs: Ataxia & hearing loss (due to labyrinthitis)
 Altered state of consciousness: Obtunded/ semicomatose/ comatose.
 15

Systemic Conditions
Signs of cellulitis, septic arthritis, otitis media, pneumonia etc. which may act as
the source of infection.

3.d. Complications of VSD:

Introduction:
90% of the VSD patients will have a spontaneous closure of the defect at the age
of 3 years. But in patients with persistent defect, the following complications may
arise:
1. Pulmonic stenosis (PS)
2. Pulmonary arterial hypertension (PAH):
a. Hyperkinetic type
b. Obstructive type
3. Aortic regurgitation (AR)
4. Infective endocarditis (IE).

Pathogenesis of the complications:

Complication Pathogenesis
PS Hypertrophy of RV infundibulum*
PAH
Hyperkinetic type As the PA receives blood flow from both RV and LV in VSD, the net
flow through PA is increased, causing PAH (see picture below)
Obstructive type Pulmonary arterial musculature remodelling takes place, resulting
in irreversible obstruction to blood flow and resultant PAH
AR Prolapse of right coronary cusp of aortic valve
IE VSD is the commonest congenital lesion complicated by IE. So,
good oral-dental hygiene is emphasized in all patients of VSD.
* Right ventricular infundibulum (also called Conus arteriosus) is a conical pouch
formed from the upper part of the right ventricle and it is the entrance from the
right ventricle into the pulmonary artery.
 16

Treatment of complications:
Medical management
 Treat any co-existing infective endocarditis
 Assess the patient carefully for development of PS/ PAH/ AR.

Surgical management
 Surgical treatment in VSD is indicated if there is associated PS, PAH or AR.
 Operative treatment consists of closure of VSD with the use of a patch.
Group D
4. A 4 year old boy was presented at the emergency room with acute onset of
cough and respiratory distress. He has no fever. His father also suffers from
recurrent episodes of similar problem. The child was admitted 3 times with similar
complications in the preceding 1 year.
a. What is the most probable diagnosis?
b. How will you manage the condition? (1+7)

The most probable diagnosis is an acute exacerbation of asthma.

 17

Explanation:
The positive family history and 3 similar attacks in last 1 year suggests bronchial
asthma. As the child was presented with acute onset of cough and respiratory
distress; it is probably an episode of acute exacerbation.
Management of the condition
Rapid classification of asthma severity:
 The assessment of severity of status asthmaticus is based on clinical
observation of child.
 Becker asthma score/ Pulmonary index score is a quick assessment of
severity of acute asthma by using respiratory rate, wheezing, inspiratory:
expiratory ratio and accessory muscle use.
Score Respiratory Wheezing at I:E ratio Accessory muscle
rate (per min) use
0 <30 None 1:1.5 None
1 30-40 Terminal expiration 1:2 1 site
2 41-50 Entire expiration 1:3 2 sites
3 >50 Inspiration and >1:3 3 sites/ neck
entire expiration strap muscle use
 Interpretation of Becker’s score for acute asthma: <4: mild, 4-6: moderate,
and ≥7: severe (and should be admitted to the ICU).
General management
 Children with status admitted to the PICU require IV access, continuous
pulse oximetry and cardiorespiratory monitoring.
 Sedation should be strictly avoided during acute exacerbations of asthma in
the nonintubated children because of the respiratory depressant effect of
anxiolytic and hypnotic drugs.
 For children who require mechanical ventilation, it is preferable to have an
arterial and central venous access.
Fluid
 Poor fluid intake, increased loss of insensible fluids and vomiting may cause
dehydration in the asthmatic child.
 18

 Fluid replacement should be aimed towards restoration of euvolemia;

isotonic fluids like Ringer’s lactate or normal saline should be used to
correct the dehydration.
Antibiotics
 Antibiotics are not routinely indicated in children with status asthmaticus.
 These should be used in children with evidence of bacterial infection as
indicated by:
 High fever
 Purulent secretions
 Consolidation on X ray film or
 Very high WBC counts.
Oxygen
 Oxygen should be administered by nasal cannula or by mask; in order to
achieve an arterial oxygen saturation ≥95%.
 Oxygen therapy should be titrated using pulse oximetry to maintain
satisfactory oxygen saturation.
Definitive treatment approach protocol
19
 20

[VT: Tidal volume, PEEP: Positive end-expiratory pressure]

Goals of ventilation in status asthmaticus are to maintain:
 Adequate oxygenation,
 Permissive hypercarbia and
 Adjusting minute ventilation (peak pressure, tidal volume and rate) in order
to maintain an arterial pH of >7.2.
Criteria for discharge of the patient from hospital:
 Need for bronchodilators is every 4-6 hourly
 The patient can speak and feed well
 Maintains an oxygen saturation of >95%
 Peak expiratory flow rate is >75% of predicted.
 21

WBUHS 2009
Pediatrics and Neonatology
Group A
1. Give an outline of bilirubin metabolism. Describe the underlying mechanism for
physiological jaundice in the newborn. (6+4)
Bilirubin metabolism:
Formation:
 Most of the bilirubin in the body is formed in the tissues by the breakdown of
hemoglobin (specifically, heme).
 Heme is degraded in a
2-step process, which
can take place in all
nucleated cells.
 In this process bilirubin
and CO are produced in
equimolar amounts.
 CO, which diffuses
from the cell, binds to
hemoglobin in circulating red blood cells to form carboxyhemoglobin (COHb), and
is eventually excreted in breath.
Circulation:
 The bilirubin is bound to albumin in the circulation.
 Some of it is tightly bound, but most of it can
dissociate in the liver and free bilirubin enters liver
cells via a member of the organic anion
transporting polypeptide (OATP) family, and then
becomes bound to cytoplasmic proteins.
 It is next conjugated to glucuronic acid in a
reaction catalyzed by the enzyme UDP-
glucuronosyl transferase. Each bilirubin molecule
reacts with 2 uridine diphosphoglucuronic acid
(UDPG) molecules to form bilirubin diglucuronide
(BG2).
 22

 This glucuronide, which is more water-soluble than the free bilirubin, is then
transported against a concentration gradient most likely by an active transporter
known as multidrug resistance protein-2 (MRP-2) into the bile canaliculi.
Excretion through urine:
 A small amount of the bilirubin glucuronide escapes into the blood, where it is
bound less tightly to albumin than is free bilirubin, and is excreted in the urine.
 Thus, the total plasma bilirubin normally includes free bilirubin plus a small
amount of conjugated bilirubin.
Enterohepatic circulation:
 Most of the bilirubin glucuronide passes via the bile ducts to the intestine.
 The intestinal mucosa is relatively impermeable to conjugated bilirubin but is
permeable to unconjugated bilirubin and to urobilinogens, a series of colorless
derivatives of bilirubin formed by the action of bacteria in the intestine.
 Consequently, some of the bile pigments and urobilinogens are reabsorbed in the
portal circulation.
 Some of the reabsorbed substances are again excreted by the liver
(enterohepatic circulation) into the feces.

Underlying mechanism in physiological jaundice in newborn:

Introduction:

 About 60-70% of healthy newborn babies are likely to develop physiological

jaundice.
 Physiological jaundice appears between 24-72 hours of age
 23

 Its maximum intensity is seen on the 4th-5th days of life

 Peak serum bilirubin level does not exceed 15 mg/dl
 This type of jaundice usually disappears before 14 days of life and does not need
any specific therapy.
Mechanism:
I. Relative polycythemia with reduced lifespan of neonatal RBCs
II. Increased bilirubin load
III. Defective uptake from plasma
IV. Defective conjugation
V. Decreased excretion
VI. Increased enterohepatic circulation.

Group B
2.a. Causes of failure of breastfeeding:
There are 10 steps of successful breastfeeding, failure to adopt any of which may cause
failure of breastfeeding:

1. Have a written breastfeeding policy that is routinely communicated to all health

care staff.
2. Train all health care staff in skills necessary to implement this policy.
3. Inform all pregnant women about the benefits and management of
breastfeeding.
4. Help mothers initiate breastfeeding within half an hour of birth.
5. Show mothers how to breastfeed, and how to maintain lactation even if they
should be separated from their infants:
Good position:
I. The baby’s whole body should face the
mother and be close to her
II. The baby’s head and neck should be
supported, in a straight line with his
body, to face the breast
III. Baby’s abdomen should touch
mother’s abdomen, to be as close as
possible to his mother.
 24

Good attachment:
I. The baby’s mouth is wide open
II. The baby’s chin touches the breast
III. The baby’s lower lip is curled outward
IV. The lower portion of the areola is not visible.

6. Give newborn infants no food or drink other than breast milk, unless medically
indicated.
7. Practice rooming-in - that is, allow mothers and infants to remain together - 24
hours a day.
8. Encourage breastfeeding on demand.
9. Give no artificial teats or pacifiers (also called dummies or soothers) to
breastfeeding infants.
10.Foster the establishment of breastfeeding support groups and refer mothers to
them on discharge from the hospital or clinic.

3.b. Routine care of newborn in the delivery room:

The routine care of newborn in the delivery room can be elaborated under the following
headings:
1. Standard precautions and asepsis at birth
2. Prevention and management of hypothermia
3. Issues regarding clamping of umbilical cord
4. Cleaning of the baby
5. Recording of weight
6. Head to toe examination
7. Initiation of breastfeeding
8. Administration of Vitamin K.
 25

Standard precautions and asepsis at birth:

Maintain ‘5 Cs’ to prevent sepsis at birth:
1. Clean hand: Hand hygiene and use of sterile gloves
2. Clean surface: Use of clean and sterile towel to dry and cover the baby
3. Clean blade: Umbilical cord to be cut with a clean and sterile blade
4. Clean tie: Cord should be clamped with a clean and sterile clamp/ tie
5. Nothing to be applied on the cord: Keep the cord dry.
Prevention and management of hypothermia:
 The temperature of delivery room should be 25⁰C and it should be free from
draft of air
 The baby should be received in a pre-warmed sterile linen sheet at birth
 Any wet linen should not be allowed to remain in contact with the infant
 The infant should be placed in contact with the mother’s abdomen in skin to skin
contact immediately after the birth.
Issues regarding clamping of umbilical cord:

 Umbilical cord clamping must be delayed for 1-2 minutes to allow transfer of
additional amount of blood from placenta to the infant
 The umbilical cord should be clamped at 2-3 cm away from the abdomen using a
commercially available clamp
 The stump should be away from genitals to avoid contamination
 The cord should be inspected every 15-30 min during initial few hours after birth
for early detection of any oozing.
Cleaning of the baby:
 The baby should be dried and cleaned at birth with a clean and sterile cloth
 The cleaning should be gentle as only the blood and meconium to be wipe out
 Wiping must not be vigorous (as it will wash vernix caseosa, the greasy material
on the skin of infant that protect the skin and maintain temperature).
Recording of weight:
A sterile pre-heated sheet should be placed on weighing machine with 10 gm
sensitivity.
 26

Head to toe examination:

 Examine midline structures (cleft lip, neck masses, chest abnormality,
omphalocele, meningocele, cloacal abnormality)
 Identify and document the patency of anal opening
 Examine the baby for any birth injury
 Note the axial temperature of the baby.
Initiation of breastfeeding:
 Start breastfeeding at the earliest point, must within 1 hour
 Assist the mother to put the baby on the breast, irrespective of the mode of
delivery.
Administration of Vitamin K:
 <1 kg baby: 0.5 mg
 >1 kg baby: 1 mg
 Preferable solution to administer: Vitamin K1.

3.c. Clinical features and treatment of scabies in newborn:

Clinical features of scabies:
Features Description
Pruritus Severe, nocturnal
Eruption Usually polymorphic consisting of small pointed papules, papulopustules,
scratching marks; sometimes vesicles and urticarial lesions
Burrows Burrows are the characteristic lesions in scabies. The burrows are grayish
brown, curved/ S-shaped, slightly elevated ridges, about 5 mm in length
Point of entry The most superficial part of the burrow has a slightly scaly appearance
of the mite
Secondary This may complicate neglected scabies and may mask the original disease,
pyogenic therefore, scabies should always be suspected in cases presenting with
infection extensive pyoderma
Distribution The lesions of scabies show a characteristic distribution: Webs and sides
of the fingers, anterior and ulnar sides of the wrist, anterior axillary fold,
anterior abdominal wall, around umbilicus, the waist, lower parts of the
buttocks, inner thighs, ankles, cubital and popliteal fossae.
 27

Treatment of scabies in newborn:

 All individuals in the house are preferably treated simultaneously
 Clothes and bed sheets should be washed or dry-cleaned.
The antiscabetic preparation should be applied from neck to toes:
Preparation Instruction to use
Permethrin dermal Single application washed off after 8-12 hours. A second
cream (2.5-5%) application may be indicated a week later if symptoms do not
improve
Sulfur precipitate Applied daily after a hot bath for 3-4 successive nights
ointment (3-5%)
Gamma benzene Applied after a hot bath; the same clothing is retained for 48
hexachloride (BHC) hours and then a further bath is taken and the clothing and bed
sheets are changed. It must not be prescribed to infants
Benzyl benzoate Applied to the whole body except the head for 3 successive
emulsion (25-33%) nights
Crotamiton 10% It has both an antipruritic effect in addition to scabicidal action.
The patient should take a hot bath and dry himself/herself
carefully on a towel. Crotamiton should then be applied daily
for 2 days followed by a bath on the 3rd day.

Group C
3.a. Rheumatic chorea:
Introduction:
It is one of the major criteria of modified Jones’ criteria to diagnose acute rheumatic
fever (ARF).
 28

Also known as:

1. Sydenham’s chorea
2. Chorea minor
3. St. Vitus Dance.
Description:
 It is found in 15% of the patients with ARF
 It occurs more often in prepubertal girls (8-12 years)
 The changes seen are (serially):
1. Emotional ability and personality changes
2. Loss of motor coordination (deterioration of handwriting)
3. Characteristic spontaneous purposeless movements (usually affecting all 4
limbs)
4. Development of motor weakness (hypotonia).
Prognosis:

 The adventitious movement, weakness and hypotonia continue for an average of

7 months before slowly waning in severity.
 Sydenham's is also associated with psychiatric symptoms with obsessive
compulsive disorder (OCD) being the most frequent manifestation.
Management:
 Antibiotic: A 10-day course of penicillin when Sydenham's Chorea is newly
diagnosed, followed by long-term penicillin prophylaxis
 Treatment of movement disorders: Haloperidol, Pimozide, Clonidine, Valproic
acid, Carbamazepine and Phenobarbitone
 Immunomodulators: Steroids, IV-IG and plasma exchange.
3.b. Laboratory evaluation of ascites of a child:
1. Blood: Hb, TC, DC, CRP
2. Renal function: Na+ K+ Urea Creatinine
3. Liver function test
4. Clotting profile
5. Urine analysis
6. CXR
7. ECG
8. USG
 29

9. Diagnostic peritoneal paracentesis:

I. Physical appearance:
 Turbid: SBP
 Hemorrhagic: TB/ Malignancy.

II. Biochemical properties:

 Serum ascitic albumin gradient (SAAG):
 It is calculated by: the following formula:
𝑆𝐴𝐴𝐺 = (𝑆𝑒𝑟𝑢𝑚 𝑎𝑙𝑏𝑢𝑚𝑖𝑛 − 𝐴𝑠𝑐𝑖𝑡𝑖𝑐 𝑓𝑙𝑢𝑖𝑑 𝑎𝑙𝑏𝑢𝑚𝑖𝑛)
 SAAG >1.1 gm/dL: Suggestive of portal hypertension.
 LDH:
LDH estimation is often helpful in distinguishing spontaneous bacterial
peritonitis from gut perforation. LDH↑ along with ↓glucose, ↑total
protein and multiple organisms on gram stain suggest secondary
bacterial peritonitis.

III. Cytological properties:

 WBC count:
 Neutrophilic leukocytosis: Suggestive of SBP
 Lymphocytic leukocytosis: Suggestive of TB/ Malignancy
 Atypical cells: Malignancy.

IV. Microbiological properties:

 Gram stain
 AFB staining + Mycobacterial culture.

V. Special tests:
 X-PERT TB/ RIF assay:
Detects M.tuberculosis genome + Rifampicin resistance (which is a very
reliable indicator for MDR-TB).
 Adenosine deaminase (ADA):
ADA levels may be high in tubercular ascites. However, it is a
nonspecific marker and results should be interpreted very cautiously.

10. Endoscopy:
If ascites is suspected to be due to cirrhosis/ portal hypertension, then look for GI
varices (endoscopy).
 30

11. Series of other tests may be required to diagnose the underlying cause.

3.c. Tuberculin test:

Introduction:
A tuberculin skin test is done to see if someone has ever been exposed to tuberculosis
(TB). It is also popularly known as Mantoux test.
Preparation:
 Tuberculin is a glycerol extract of the tubercle bacillus.
 Whereas, Purified protein derivative (PPD) tuberculin is a precipitate of species-
nonspecific molecules obtained from filtrates of sterilized, concentrated cultures.

Procedure (Mantoux technique):

 Standard dose: 5 tuberculin units (1 TU = 0.1 ml)

 Mode of administration: Intradermal injection
 Reading: 48-72 hours later
 Inference: A person who has been exposed to the bacteria is expected to mount
an immune response in the skin containing the bacterial proteins.
 Result:

 The reaction is read by measuring the diameter of induration across the

forearm (perpendicular to the long axis) in millimeters.
 If there is no induration, the result should be recorded as "0 mm".
Erythema (redness) should not be measured
 If a person has had a history of a positive tuberculin skin test, or had a
recent tuberculin skin test (within 1 year), another skin test should be
used.

Interpretation of results:

Cutoff size of reaction for a positive Mantoux test in children:

 31

False positive results False negative results

 Non-tuberculous mycobacteria  Infectious mononucleosis
 Previous administration of BCG vaccine  Live virus vaccine within 3 weeks
 Sarcoidosis
 Hodgkin's disease
 Corticosteroid therapy
 Malnutrition
 Immunological compromise

3.d. Vascular purpura:

Introduction:
Vascular purpura/ Henoch-Schonlein purpura (HSP) is the most common vasculitis of
childhood and is characterized by leukocytoclastic vasculitis and IgA deposition in the
small vessels in the skin, joints, GI tract and kidney.
Pathogenesis:
Not well understood, but thought to be composed of the following components:
1. An infectious trigger
2. IgA immune complex deposition
3. Familial (genetic) component.
 32

Clinical features:
Feature Description
Classical rash  It is the hallmark of HSP
 Characterized by palpable purpura starting as pink macules/
wheals and progressing into petechiae, purpura or ecchymoses
 Typically seen in gravity dependent areas (ex: buttock)
 These skin lesions typically last for 3-10 days and may recur
upto 4 months after initial presentation.
GI manifestations Abdominal pain, vomiting, diarrhea, paralytic ileus, melena,
(seen in 80% cases) intussusception, mesenteric ischemia or perforation
Musculoskeletal Self-limiting arthritis (resolves within 2 weeks), usually appearing in
(seen in 75% cases) lower extremities and not leading to deformities
Renal manifestations Hematuria, proteinuria, hypertension, frank nephritis, nephrotic
(seen in 50% cases) syndrome and acute/ chronic renal failure
CNS manifestations Intracerebral hemorrhage, seizures, headaches and behavior changes

Pathology:
 Skin smear shows: Vasculitis of dermal capillaries and postcapillary venules
 Inflammatory exudate contains: Neutrophils and monocytes
 Renal histology: Endocapillary proliferative glomerulonephritis.
Diagnosis:
2 of the following criteria must be present:
1. Palpable purpura
2. Age at onset ≤20 yr
3. Bowel angina (postprandial abdominal pain, bloody diarrhea)
4. Biopsy demonstrating intramural granulocytes in small arterioles +/ venules.
Treatment:
• Mostly supportive: Adequate hydration, nutrition and analgesia
• Empiric use of prednisone (1 mg/kg/day for 1-2 week, followed by taper):
It reduces abdominal and joint pain but does not alter overall prognosis/ prevent
renal disease.
 33

Group D
4. A 4 year old child has been brought to the emergency with convulsions persisting
for more than 30 minutes. How will you diagnose the case? Briefly narrate the
management of the case.
Diagnosis of the case:
It is a case of status epilepticus (SE) because SE is defined as prolonged single seizure/
multiple episodes of seizures lasting >30 minutes without regaining consciousness in
between the episodes.
It should be emphasized that no investigation is necessary to start immediate
management of SE and only when SE in controlled, investigations are to be done to rule
out any provocable cause of seizure.
History:
 Description of the event
 Associated symptoms
 Duration of the post-ictal period (characterized by a state of disorientation)
 Prior history of seizures
 Detailed history of anti-epileptic drug use
 History of neurological development.
Investigations:
Routine investigations:
1. Blood: Hb, TC, DC ESR
2. Renal function: Na+ K+ Urea Creatinine
3. Liver function test.
Special investigations;
1. Serum glucose
2. Serum calcium
3. Malarial parasite
4. Culture (if fever present)
5. Lumber puncture (in case of suspected CNS infections).
Other tests:
1. CT brain (in case of a suspected structural lesion in brain)
 34

2. EEG (in case of suspected non-convulsive SE).

Management of the case:
A. Airway:
 Must be secured. If required apply oropharyngeal suction and intubation
 Prevention of aspiration.
B. Breathing:
 Free flow oxygen
 Ventilation, if required.
C. Circulation:
 Maintain circulatory volume by IV fluid
 Control of body temperature.
D. Drugs:
 To reduce brain edema: IV dextrose, mannitol
 Definitive drugs:
 35

WBUHS Paediatrics (including Neonatology) 2010 Paper

Group A
1. Outline the metabolism of iron in the body. Compare the laboratory findings of
iron deficiency anemia and thalassemia. (4+6)
Iron metabolism:
Absorption:
 Most of the iron in the diet is in the ferric (Fe3+) form, whereas it is the ferrous
(Fe2+) form that is absorbed.
 Some amount of Fe3+ to Fe2+ conversion occurs within the stomach. Gastric
secretions dissolve the iron and permit it to form soluble complexes with vitamin
C and other substances that aid its reduction to the Fe2+ form.
 Rest of the conversion occurs within the duodenum. Fe3+ reductase activity is
associated with the iron transporter in the brush borders of enterocytes.
 Almost all iron absorption occurs in the duodenum. Transport of Fe2+ into the
enterocytes occurs via divalent metal transporter 1 (DMT1).

Within enterocytes:
 Some Fe2+ is again converted to Fe3+ and stored within the enterocytes as
ferritin-Fe3+ complex.
 36

 The rest binds to the basolateral Fe2+ transporter ferroportin (FP) and is
transported to blood. This transport is aided by a protein named hephaestin (Hp).

Within blood:
In the plasma, Fe2+ is converted to Fe3+ and bound to the iron transport protein
transferrin.

Note:
Heme binds to an apical transport protein in enterocytes and is carried into the
cytoplasm. In the cytoplasm, HO2, a subtype of heme oxygenase, removes Fe2+ from
the porphyrin ring of heme and adds it to the intracellular Fe2+ pool.
 37

Storage of iron:
70% of the iron in the body is in hemoglobin, 3% in myoglobin, and the rest in ferritin,
which is present not only in enterocytes, but also in many other cells.
Regulation of iron absorption:
 Iron absorption is regulated by hepcidin, a small circulating peptide that is
synthesized and released from the liver in response to increases in intrahepatic
iron levels.
 Hepcidin inhibits iron transfer from the enterocyte to plasma by binding to
ferroportin and causing it to be endocytosed and degraded.
 Thus, when the body is replete with iron, high hepcidin levels inhibit its
absorption into the blood. Conversely, with low body stores of iron, hepcidin
synthesis falls and this in turn facilitates iron absorption.
 38

Comparison between laboratory findings of iron deficiency anemia & thalassemia:

Parameters Iron deficiency anemia Thalassemia
Hb level ↓ ↓
RBC level ↓ Normal/ ↑
RBC indices
Mean cell volume (MCV) ↓ ↓↓
Mean cell hemoglobin ↓ ↓↓
(MCH)
Red cell distribution width ↑↑ Normal
(RDW)*
Iron status
Serum iron ↓ ↑ (∝ iron overload)
Serum ferritin ↓ ↑ (∝ iron overload)
Transferrin saturation ↓ ↑
Total iron binding capacity ↑ ↓
(TIBC)
*RDW is the coefficient of variation of red cell volume distribution. RDW is the objective
documentation of subjective anisocytosis.
A simplified way to differentiate between these 2 entities:

Microcytic anemia

RDW

Normal Elevated

Favors thalassemia Ferritin level

Normal/ high Low

Favors iron
Favors thalassemia
deficiency anemia
 39

Group B
2.a. Breast milk versus cow’s milk:
 40

2.b. Developmental milestones of 1 year old child

Please see 2012 Paper Group C Question no. 3.d.
2.c. Urinary findings of acute post-streptococcal glomerulonephritis
Please see 2011 Paper Group C Question no. 3.a.
Group C
3.a. Transient tachypnea of newborn.
Introduction:

 Liquid that fills the lung lumen during normal fetal development must be
absorbed into the vascular system soon after birth to permit successful
pulmonary gas exchange.
 This transition occurs rapidly in most infants, but sometimes the process is
delayed, producing the clinical and radiographic features of a condition that is
known as transient tachypnea of the newborn (also called the syndrome of
retained fetal lung liquid).
Risk factors:
1. Term babies born by cesarean section
2. Preterm infant
3. Maternal asthma
4. Maternal diabetes.
Clinical features:
 The disorder typically begins soon after birth with a rapid respiratory rate,
ranging from 60-100 per minute.
 The baby remains alert and active and maintains good color.
 Sometimes sternal and subcostal retractions of the chest wall, grunting during
expiration and occasionally mild cyanosis that disappears with delivery of
supplemental oxygen may be seen.
 Signs and symptoms usually resolve by 3-4 days after birth.
Radiologic appearance:
Findings suggestive of excessive fluid in the lungs:
1. Hyperextended lung fields
2. Prominent pulmonary vascular markings (particularly around the hilum)
 41

3. Thickened interlobar fissure

4. Flattening and depression of diaphragm
5. Fluid may be found in pleural space.
Treatment:
 The condition usually resolves spontaneously without any specific therapy within
2-3 days of life.
 Some infants may require administration of 40% O2 to maintain good color.
 Infants with respiratory distress sometimes benefit from being managed in the
prone, head-up position.
3.b. Clinical presentation and management of acute bronchiolitis.
Introduction:
Acute bronchiolitis is a common serious acute lower respiratory tract infection (LRTI)
caused by respiratory syncytial virus (RSV) in the age group of 1-6 months.
Inflammation of bronchial mucosa leads to edema and mucus plug formation; which
narrows the airway and increases airway resistance both during inspiration and
expiration; which may progress to emphysema and atelectasis. Due to diminished
ventilation and perfusion, hypoxia and retention of CO2 may lead to respiratory failure.
Clinical presentation:
 Few days following an upper respiratory tract infection; breathing becomes fast
and respiratory distress develops.
 Majority of the infants have only mild symptoms and recovers within 3-7 days.
 Those with severe disease, the following features are seen:
 Retraction of lower intercostal spaces and suprasternal notch
 Dyspnea ± cyanosis
 Moderately high fever
 Accessory muscles of respiration are working
 Expiration is prolonged
 Fine crepitations and rhonchi in auscultation
 Breath sounds are faint/ absent
 Respiratory distress is out of proportion to the physical signs
 Hyperinflation results in pushing down of liver and spleen
 If chest is overinflated, increased resonance is noted on percussion.
 42

Management:
 Treatment of acute bronchiolitis is symptomatic. Infants with mild symptoms can
be cared at home in a humidified atmosphere.
 If respiratory distress/ feeding problems occur, the child should be hospitalized
and following treatment are given:
a. Position: The child is kept in a humidified atmosphere in sitting position at an
angle of 30⁰-40⁰ with head and neck elevated.
b. Oxygen:
 Moist oxygen is given continuously even in the absence of cyanosis
 Infants with severe disease should be given 60% moist oxygen
continuously given through a hood
 Pulse oximetry should be done frequently to maintain an oxygen
saturation above 92%.
c. Fluid and electrolyte balance should be maintained.
d. Bronchodilators:
 If the child shows improvement with bronchodilators, then it may be
given every 4-6 hourly
 The bronchodilator of choice is inhaled salbutamol with ipratropium
and epinephrine.
e. Antiviral agent:
 Ribavirin is an antiviral agent which has no role in treating infants with
acute bronchiolitis who were previously healthy.
 But it can shorten the course of disease in infants with:
a. Congenital heart disease
b. Chronic lung disease
c. Immunodeficiency.
 Ribavirin is delivered through a nebulizer 16 hours a day for 3-5 days.
3.c. OPV versus IPV
Points OPV IPV
Potency Low (needs ≥4 doses) High (needs 2-3 doses)
Intestinal immunity (IgA production) High Low
Secondary (herd) immunization Yes No
Purpose Community protection Individual protection
Role in times of epidemic Definite role No role
Reverts to virulence? No Yes, very rarely
Disease in immunocompromised? No Yes
 43

Risk of escape of wild virus Non-existent Possible (if produce with

wild virus seeds)
Possible combination vaccine No Yes (with DPT and Hib)
Price Low High
Injection safety No issue A possible risk
Vaccine associated paralytic polio 1 case/ 2.5 million doses None
(VAPP)

3.d. Phototherapy
Introduction:
Phototherapy remains the mainstay of treating hyperbilirubinemia in neonates. It is
highly effective and carries an excellent safety track record for over 50 years.
Mechanism:
 Phototherapy acts by converting insoluble bilirubin into soluble isomers that is
excreted in urine and feces.
 There are 2 main modes of action:
a. Configurational isomerization: This is a reversible reaction where the Z
isomers are converted into E isomers. This is a not a major reaction.
b. Structural isomerization: This is an irreversible reaction where bilirubin is
converted to lumirubin. This is the major reaction.
 Wavelength of choice: 460- 490 nm (Blue-green light).
 Minimum irradiation level: 30 microwatt/sq.cm./nm.
Types of phototherapy lights:
 CFL lights (most commonly used in India)
 Blue LED lights
 Halogen bulbs
 Fibre-optic light sources.
Guidelines of a successful phototherapy:
 Irradiance of lights should be periodically measured
 Lamps should be changed if they are flickering/ ends are blackened/ irradiance
level falls below the specified level
 Expose maximal surface area of the baby
 Avoid blocking of lights by any equipment/ coverings of the baby
 Ensure good hydration and nutrition of the baby
 44

 Make sure that the light falls on the baby perpendicularly if the baby is in
incubator
 Minimize interruption of phototherapy during feeding sessions/ procedures.
Administering phototherapy:
 Make sure the temperature of the room is 25⁰-28⁰C to prevent hypo/hyper-
thermia of the baby
 Remove all clothes of the baby except the diaper
 Cover the baby’s eyes with an eye-patch that does not block the baby’s nostrils
 Place the naked baby:
o In a cot/ bassinet if the weight is >2kg
o In an incubator/ under radiant warmer if the weight is <2kg
 Keep the distance between the baby and the light between 30-45 cm
 Ensure optimum breastfeeding and during breastfeeding sessions, remove eye-
patch for better mother-child interaction.
Monitoring and stoppage of phototherapy:
 If TSB (total serum bilirubin) ≥25 mg/dL, repeat TSB in 2-3 hr
 If TSB 20-25 mg/dL, repeat TSB in 3-4 hr
 If TSB <20 mg/dL, repeat TSB in 4-6 hr
 If TSB continues to fall, repeat TSB in 8-12 hr
 When TSB is <13-14 mg/dL, discontinue phototherapy
 If TSB is not decreasing/ is moving closer to level for exchange transfusion/ the
TSB: albumin ratio exceeds recommended limits, consider exchange transfusion.

Group D
4. A 7 year old child with H/O exchange transfusion in neonatal period presents with
hematemesis. Physical examination is unremarkable except for splenomegaly (6 cm).
a. What is your differential diagnosis?
b. Describe the steps in the management of this child. (1+7)
My provisional diagnosis is extra-hepatic portal venous obstruction.
Explanation:
 In this question, H/O exchange transfusion is insignificant as exchange
transfusion has many indications other than severe hyperbilirubinemia (severe
anemia, polycythemia, severe electrolyte imbalance etc.).
 45

 Concomitant presence of hematemesis and splenomegaly suggest a common

presentation of portal hypertension, the cause of which may be extra-hepatic or
intra-hepatic.
 In India, the extra-hepatic portal venous obstruction (EHPVO) is the commonest
cause of portal hypertension (50-75%); followed by intra-hepatic portal venous
obstruction (IHPVO: Cirrhosis: 25-35%).
 The common presentations include:
Entity Common clinical presentation
EHPVO Upper GI bleeding (hematemesis/ melena) + Splenomegaly
IHPVO Jaundice + Ascites + Hepatosplenomegaly ± Upper GI bleed
- So, from the clinical presentation, we can conclude that the cause of portal
hypertension in the mentioned patient is extra-hepatic.

Management:
There are 3 parts in the management of a patient with portal hypertension:
1. Emergency management of bleeding
2. Prophylaxis of first episode of bleeding (primary prophylaxis)
3. Prophylaxis of subsequent bleeding episodes (secondary prophylaxis).
Emergency management of bleeding
A. Airway:
 Must be protected, particularly if there is risk of aspiration
 If required: Oropharyngeal suction.
B. Breathing:
 Oxygen
 Ventilation.
C. Circulation:
 1 wide bore cannula in each hand
 IV fluid resuscitation (Preferred fluid of choice: Normal saline)
 In case of severe bleeding: Blood transfusion (maintain a Hb level of 7-9 gm %)
 Treat any co-existing coagulopathy (platelet, vitamin K, fresh frozen plasma).
D. Drugs:
 Reduction of bleeding by splanchnic (and also systemic) vasoconstriction:
o Vasopressin
o Terlipressin
o Glypressin.
 46

 Safer and selective splanchnic vasoconstrictors (with fewer side effects):

o Somatostatin
o Octreotide.
 IV antibiotic therapy in all patients (to reduce the risk of potentially life-
threatening infections).
E. Endoscopy:
Endoscopy confirms the presence of varices and subsequently they can be
treated endoscopically by the 2 following techniques, the mechanism of both of
which is stoppage of bleeding by variceal thrombosis:
 Variceal ligation (banding)
 Injection sclerotherapy:
Intra and para-variceal administration of sclerosing agents:
o Ethanolamine oleate
o Sodium tetradecyl sulfate.
F. Failure of endoscopy/ not feasible:
Balloon tamponade on varices by Sengstaken-Blackmore tube (SSBT): It is a last
resort and highly effective in controlling variceal bleeding; but it is associated
with significant complications (high incidence of re-bleeding and aspiration
pneumonia after removal of the tube).
 47

Prophylaxis of first episode of bleeding (primary prophylaxis)

 Nonselective β blocker:
Propranolol reduces portal pressure by causing splanchnic vasoconstriction and
reducing cardiac output.
 Oral nitrates:
Nitrates reduces portal pressure by reducing hepatic vascular resistance.
Prophylaxis of subsequent bleeding episodes (secondary prophylaxis)
Various options are:
 Variceal ligation
 Sclerotherapy
 Surgical portosystemic shunting
 Transjugular intrahepatic portosystemic shunting (TIPS)
 Liver transplantation.
 48

WBUHS Pediatrics (including Neonatology) 2011

Group A
1. Describe formation, circulation, absorption and composition of CSF. Give an outline
of management of tubercular meningitis of 2 year old child. (1.5×4)+4
Formation of CSF:
Site of formation:
The CSF is formed by the choroid plexus (50%) and directly from the walls of the
ventricles (50%). The choroid plexus is a venous plexus contained within the four
ventricles of the brain.
Physiology:
The continuous formation of CSF by the choroid plexus occurs in 2 stages:
 First, plasma is passively filtered across the choroidal capillary endothelium.
 Next, secretion of water and ions across the choroidal epithelium provides for
active control of CSF composition and quantity.
 HCO3-, Cl- and K+ ions enter the CSF via channels in the epithelial cell apical
membranes.
 Aquaporins provide for water movement to balance osmotic gradients.
 49

Circulation of CSF:
The majority of CSF is produced from within the two lateral ventricles.

Lateral ventricles

Interventricular
foramina of Monro

3rd ventricle

Cerebral aqueduct of
Sylvius

4th ventricle

Foramen of 2 Foramens of
Magendie Luschka

Subarachnoid space Subarachnoid space

of the midline of the lateral side

Absorption of CSF:
 In adults, the main route for reabsorption of CSF is via the arachnoid
granulations, from where it returns to the vascular system by entering the dural
venous sinuses.
 However, in neonates, the arachnoid granulations are not well developed and
sparsely distributed. So, in neonates, lymphatic drainage plays an important role
in CSF absorption. CSF flow along the cranial nerves and spinal nerve roots allow
it to drain into the lymphatic channels.
 50

Composition of CSF:
The reference range for CSF analysis is as follows:
Parameter Value
Appearance and color* Clear, colorless
Opening pressure* 90-180 mm H2O (with patient lying in lateral position)
Glucose 50-80 mg/dL (or > 2/3rd of blood glucose)
Total protein 15-60 mg/dL
Chloride 110-125 mEq/L
Lactate (newborn) 10-40 mg/dL
Lactate (older children) 10-25 mg/dL
pH 7.28 - 7.32
WBC count 0-5
RBC count 0
[*Not needed in this question.]

Management of tubercular meningitis in a 2 year old child:

Chemotherapy
Supportive measures:
i. Mannitol 20% (IV) 5 ml/kg followed by 2ml/kg every 6 hourly for 2 days
ii. Oral glycerol given by nasogastric tube (50% glycerol in 2.5% dextrose)
iii. Intravenous fluids/nasogastric feed, vitamin and mineral supplements
iv. Antiepileptic drugs, if needed.
 51

Anti-tubercular drug regimen:

IAP recommended anti-tubercular drug regimen is:
Regimen Duration
HRZE 2 months
HRE 10 months
Total duration 12 months

IAP recommended doses of drugs are:

Drug Dose (mg/kg/day)
Daily Intermittent
Isoniazid (H) 5 15
Rifampicin (R) 10 15
Pyrazinamide (Z) 25 30
Ethambutol (E) 20 30
Streptomycin (S) 20 30
Prednisone* 1 -
Corticosteroids are preferred in intravenous form during acute phase of illness and then
switched over to oral form and tapered off gradually.
Role of steroid in tubercular meningitis:
 Reduces the intensity of cerebral edema
 Reduces the risk of developing arachnoiditis, fibrosis and spinal block.
Surgery
It has been shown that addition of ventriculo-peritoneal (VP) shunt in children who are
in advanced stage of TBM only adds to more morbidity as survival leaves the child with
lots of neurological deficits. Hence, early diagnosis and prevention are more important
than intervention by VP shunt.
Group B
2.a. Bell’s palsy:
Introduction:
Bell’s palsy is a rapidly developing ipsilateral facial nerve palsy due to inflammation of
the nerve at/near the stylomastoid foramen.
 52

Etiopathogenesis:
 It has been postulated that the inflammation of facial nerve is probably triggered
out by HSV1/VZV infection.
 Rapidly developing inflammatory exudate strangulate the nerve, leading to palsy.
 Because in many cases, there is no permanent structural damage of the nerve,
there is complete functional recovery.
Clinical features:
 Onset: Usually acute/ subacute: develops over few days
 Often there is a preceding H/O exposure to an attack of common cold
 Symptoms and signs:
 Inability to elevate the eyebrows
 Loss of forehead furrowing/ wrinkling
 Inability to frown
 Inability to close the eyelid:
Eyeball is seen to be rolled upwards on attempted closure of eye. This is
called ‘Bell’s phenomenon’. Such an eye is at risk of developing exposure
keratitis.
 Weakness of buccinators leading to following manifestations:
 On puffing out of chick, air leaks through the angle of the mouth of
the affected half
 Loss of nasolabial fold
 Lower eyelid sacs down so that punctum no longer remains in
contact.
 Drooping of the angle of the mouth to the affected side: saliva dribbles
through angle of mouth
 Angle of mouth is deviated towards healthy site when patient attempts to
smile
 Taste on the anterior 2/3rd of the tongue is lost on the involved side in
about 50% of cases; this finding helps to localize the lesion as being
proximal or distal to the chorda tympani branch of the facial nerve.
Treatment:
1. Drugs:
a. Corticosteroid: Oral prednisone (1 mg/kg/day for 1 wk, followed by a 1-wk
taper) started within the first 3-5 days
b. Acyclovir: Although its role is doubtful, many clinicians prefers to prescribe it.
 53

2. Prevention of exposure keratitis:

a. Protective eye-pad
b. Lubricant eye drop/ ointment.
3. Physiotherapy.
Special note: Facial Palsies at Birth:
 Facial palsy at birth is usually a compression neuropathy from forceps application
during delivery and recovers spontaneously in a few days or weeks in most cases.
 Congenital absence of the depressor angularis oris muscle causes facial
asymmetry, especially when an affected infant cries, and is often associated with
other congenital anomalies, especially of the heart. It is not a facial nerve lesion
but is a cosmetic defect.
2.b. KMC: Please see from 2013 Group 2.a.
2.c. Sepsis screen of newborn:
Introduction:
No investigation is required to start treatment in a sick baby who has high probability of
sepsis. But in clinically doubtful cases, a sepsis screen should be performed. It is a panel
of tests, which helps in initiating the treatment strategy.
Components:
Parameters Positive values
Total leukocyte count (TLC) <5000/ cu.mm
Absolute neutrophil count (ANC) <1800/cu.mm
Immature: Total (I:L) neutrophil count >20%
CRP >8 mg/ml
Micro-ESR ≥15 mm in 1st hour

Interpretation:
 If ≥2 parameters are abnormal, it should be considered as a positive sepsis screen
and it is reasonable to start antibiotic therapy.
 If a septic screen is negative in the presence of strong clinical suspicion, it should
be repeated within 12 hours.
 If the screen is still negative, sepsis can be excluded with reasonable certainty.
 54

Special note:
For early onset sepsis (occurring within first 72 hours of life), documentation of
polymorphs in the neonatal gastric aspirate at birth serves as a marker of
chorioamnionitis and it may be taken as one parameter of sepsis screen.
Group C
3.a. Laboratory diagnosis of acute glomerulonephritis
1. Urine analysis
2. Renal function test
3. Serology
4. Blood
5. Chest X Ray
6. USG abdomen.
Investigation Findings
Urine analysis  Urine protein: Mild to moderate proteinuria
 Microscopic examination:
 Presence of dysmorphic/ crenated RBCs and RBC casts are diagnostic
 WBCs, hyaline casts and granular casts are present
Note: Minimal urine findings may be present in children with severe clinical
features.
Renal function  Blood urea-creatinine: Normal/ elevated (due to renal impairment)
tests  Serum Na+: Hyponatremia may be present (due to impairment of free
water excretion)
 Serum K+: Hyperkalemia may be present (due to decreased GFR)
 Total serum protein: May be elevated due to increased γ-globulins.
Serology Following serological tests may be done:
 ASO titre (high in pharyngitis)
 Anti-DNase B (high in streptococcal skin infections)
- These titres decrease to low levels within 4-6 weeks.
Blood  Hemoglobin: May be low due to dilution
 Occasionally, coagulation abnormalities are identified
 Complement: C3 is low in 90% of patients but normalizes within 8-12
weeks. Persistently low C3 levels indicate other forms of GN.
Chest X Ray  It shows pleural fluid and mild cardiomegaly (due to pericardial effusion)
 Gross cardiomegaly may be seen in severe volume overload and is an
impending sign of cardiac failure (a complication of acute GN)
 Consolidation may be seen in presence of streptococcal pneumonia.
 55

USG abdomen  It shows bilaterally enlarged kidneys with mild parenchymal changes
 Free fluid in the abdomen and pleural fluid are other common findings.
Renal biopsy Renal biopsy is not routine done and only done in following indications:
1. Renal function is severely impaired beyond 7-10 days
2. Serum C3 remains depressed beyond 6-8 weeks.

3.b. Febrile convulsion:

Introduction:
Febrile convulsions are the commonest provoked seizures affecting 3-5% of children.
Definition:
Febrile convulsions are defined as convulsions during fever occurring between 6 months
and 5 years of age in absence of any infection of CNS in a neurologically normal child.
Classification/ types:
Febrile convulsions are of 2 types:
1. Simple/ benign
2. Atypical/ complex.
Type of convulsion Description
Simple  Primarily generalized, usually tonic-clonic seizure
 Lasts for <15 min
 Not recurrent within a 24 hour period.
Atypical  Primarily focal seizure
 Lasts for >15 min
 Recurs within 24 hours.

Risk factors for recurrence of febrile seizures and subsequent epilepsy:

1. Atypical febrile seizures
2. Family history of epilepsy
3. Seizure within 1 hour of febrile episode
4. Presence of neurodevelopmental abnormalities.
Differential diagnosis:
 Infections of CNS (meningitis and encephalitis) are important causes of
convulsions associated with fever and easily confused with febrile convulsions.
 56

 To avoid this confusion, a lumbar puncture should be performed in the first

episode of febrile convulsion in infants aged <1 year who are not immunized with
Hib and pneumococcal vaccines/ whose immunization status is unknown, when a
CNS infection is suspected.
Treatment:
 Immediate reduction of temperature with antipyretics
 Hydrotherapy to comfort the patient
 Maintenance of airway, breathing and circulation
 In case of prolonged seizure, IV access should be established to maintain
adequate hydration and administer anticonvulsants
 Anticonvulsant of choice is IV midazolam/ diazepam (0.2-0.3 mg/kg/dose).
Prophylaxis against febrile seizure:
It is of 2 types:
1. Intermittent
2. Continuous.
Type Indication Drug of choice Dose (mg/kg/d) Duration
Intermittent ≥3 episodes of febrile seizures Oral Clobazam 0.75-1.0 3 days
in 3 months OR ≥6 episodes of during fever
febrile seizures in 1 year
Continuous Failure of intermittent Oral sodium 10-20 Duration:
prophylaxis/ recurrent atypical valproate 1-2 year OR
seizures/ when parents are Oral 3-5 upto 5 year
unable to recognize fever onset phenobarbitone of age

3.c. Diet of 1 year old infant.

 Breastfeed as often as the child wants, offer food from the family pot
 Give at least 1½ katori serving at a time, containing:
o Mashed roti/
o Rice bread mixed in thick dal/
o Khichdi with added ghee or oil.
 Add to the serving:
o Cooked vegetables/
o Mashed roti or rice bread mixed in sweetened undiluted milk/
o Sevian or dalia or halwa or kheer prepared in milk/
 57

o Any cereal porridge cooked in milk/

o Mashed boiled or fried potatoes.
 Offer banana/ biscuit/ mango/ papaya as snacks in between the servings.
 Frequency: 5 times a day
 Remember:
Sit by the side of child and help him to finish the serving; wash your child’s hands
with soap and water every time before feeding.
[Note: Please read the table no. 6.2 in page no. 91 in O.P.Ghai (8th edition) for other age
groups]
3.d. Head circumference:
Introduction:
The size of the head is a good indicator of the size of its contents, i.e., the brain and the
ventricles. Any abnormality in the head circumference should alert the doctor towards
any problem with the brain or its related structures.
Measurement:
 Hand ornaments are removed and braids undone.
 Using a non-stretchable tape, the maximum circumference of the head from the
occipital protuberance to the supraorbital ridges on the forehead is measured.
 The crossed tape method, using firm pressure to compress the hair, is the
preferred way to measure head circumference.
 58

Normal values:
Age Normal head circumference (cm)
At birth 34-35 cm
3 months 40 cm
6 months 42-43 cm
1 year 45-46 cm
2 years 47-48 cm
5 years 50-51 cm
Adult head circumference is achieved at around 5-6 years of age.

Abnormalities of head circumference:

 Microcephaly is defined as head circumference, >3SD below the mean for the age
and sex.
 Macrocephaly is defined as a head circumference >2SD above the mean for age
and sex.
Group D
4. A 2 year old child has presented with fever for 20 days. Examination revealed severe
pallor, hepatosplenomegaly and purpuric spots all over the body.
a. Write the differential diagnosis
b. Suggest investigations to reach the final diagnosis. (5+3)

Differential diagnosis:
Malignancy:
1. Acute lymphoblastic leukemia (ALL)
2. Acute myeloid leukemia (AML)
3. Non-Hodgkin lymphoma (NHL).
Infections:
1. Chronic malaria
2. Chronic kala-azar
3. Disseminated (miliary) tuberculosis.
 59

Discussion about the differentials (points in favor of diagnosis):

1. ALL:
 Age of presentation: 2-5 years
 Common clinical features include:
a. Pallor and fatigue
b. Petechiae/ purpura
c. Infections/ fever
d. Lymphadenopathy
e. Hepatosplenomegaly.
2. AML:
 Age of presentation: It can occur at any age but more incidence is seen in
adolescence and during first 4 weeks of life
 Clinically, AML presents similar to the ALL but lymphadenopathy and
hepatosplenomegaly are less common in AML.
3. NHL:
 Age of presentation of NHL in children: Usually >3 years of age
 Children with NHL typically present with extranodular disease involving
mediastinum/ abdomen/ head-neck region and may present with various
features like:
a. Mediastinum: Superior mediastinal syndrome/ Superior vena caval
syndrome/ Pleural or pericardial effusion
b. Abdomen: Abdominal pain/ ascites/ hepatosplenomegaly/ palpable mass/
intestinal obstruction/ intussusception
c. Head-neck region: Cervical adenopathy/ jaw swelling etc.
d. Note that, constitutional symptoms are uncommon in NHL, except in
patients with anaplastic large cell lymphoma (LCL). Many of these patients
have low-grade fever, malaise, anorexia ± weight loss.
4. Chronic malaria:
 Any cases of long term fever should be investigated for malaria as it may
involve any system of the body and present with a very wide variety of clinical
signs and symptoms ranging from its characteristic paroxysm to neurological
manifestations as in cerebral malaria.
 60

5. Chronic kala-azar:
 Age of presentation: Although all age groups are affected, children aged 1-4
years are more susceptible.
 Clinical features:
High grade fever Pallor Hyperpigmentation of
Weight loss Bleeding skin in late stages (face,
Hepatosplenomegaly manifestations (in hands, upper trunk)
Abdominal discomfort form of petechiae, Cough
Lymphadenopathy (<5%) epistaxis, gum Diarrhoea
bleeding etc.) Secondary infections

6. Disseminated tuberculosis:
 Age of presentation: <3 years of age
 Introduction:
The majority of children with TB infection develop no signs and symptoms at
any time. Occasionally, the initiation of the infection is marked by several days
of low grade fever and mild cough. Most children who develop tuberculosis
disease experience pulmonary manifestations, but 25-35% of children have an
extrapulmonary presentation.
 Other clinical features:
Hepatomegaly Fever lasting several weeks with daily
Splenomegaly spikes in morning temperatures
Pancreatitis Hypercalcemia
Multiple organ dysfunction with Cutaneous lesions
adrenal insufficiency Choroidal tubercles
 61

Investigations to reach the final diagnosis

1. Routine investigations:
a. Blood: Hb, TC, DC, Platelet count, CRP/ESR
b. Renal function test: Na+ K+ Urea Creatinine
c. Liver function test: Bilirubin (direct and indirect), albumin, ALT, AST, ALP.
d. Coagulation profile: BT, CT, PT, aPTT
e. Urine analysis: Urinary protein; note any presence of cast, RBC, WBC etc.
f. Chest X Ray
2. Special investigations:
a. Peripheral blood smear examination
b. Bone marrow aspiration and examination
c. Bone marrow biopsy (in selected cases)
d. Lumber puncture and examination of CSF cytology
e. CT and MRI (in selected cases).
3. Specific investigations:
These are specific investigations for suspected specific diseases.
Ex.:
Peripheral thick and thin blood smears for malaria
Smears of tissue aspirate for kala-azar
Sputum smear/ culture/ tissue biopsy in disseminated TB etc.

Interpretation of test results

1. ALL:
 Routine blood investigation: Pancytopenia/ hyper-leukocytosis.
 Confirmation of diagnosis by peripheral blood smear and bone marrow
aspirate.
 Bone marrow showing >25% of lymphoblast is diagnostic of ALL.
 Evaluation of CSF for leukemic blasts to determine CNS involvement is
important for staging of the disease. It must be performed when platelet
count comes close to 100,000/cu.mm.
 Patient with high tumor burden/ tumor lysis syndrome may present with
decreased urine output and azotemia.
 Immunophenotyping may be done to differentiate the cellular linage of ALL
(pre-B cell/ T cell/ mature B cell).
2. AML:
 Routine blood investigation: Pancytopenia/ hyper-leukocytosis.
 62

 DIC may occur with any subgroup of AML (rapidly declining platelet count,
PT↑, aPTT↑, elevation of fibrinogen and FDP in serum).
 Confirmation of diagnosis by peripheral blood smear and bone marrow
aspirate.
 FAB classification of AML:
Classification Description
M0 Undifferentiated
M1 Acute myeloblastic leukemia with minimal maturation
M2 Acute myeloblastic leukemia with maturation
M3 Acute promyelocytic leukemia
M4 Acute myelomonocytic leukemia
M5 Acute monoblastic leukemia
M6 Acute erythroblastic leukemia
M7 Acute megakaryoblastic leukemia
 Staining activity with myeloperoxidase (MPO) and Sudan black is observed in
AML.
 Auer rods (needle shaped accumulation of primary granules) are primarily
found in M2, M3 and M5 subtype.
 Chloroma (localized collection of leukemic cells in CNS/ orbit) may be evident
in CT or MRI of brain.
3. NHL:
 Histology is the primary mean of diagnosis.
 For this purpose, following sites and modes may be selected:
a. Biopsy of accessible lymph node (preferred)
b. Percutaneous needle aspiration of accessible lymph node
c. Examination of pleural fluid/ bone marrow.
4. Chronic malaria:
 Peripheral blood smear:
o The gold standard for diagnosis of malaria is careful investigation of a
properly prepared thick smear as it gives information about parasite
load, prognosis and response to therapy.
o Thick smears help to detect the parasites while thin smears help to
identify the species.
 Rapid diagnostic tests:
o These tests detect malarial antigens (PfHRP2, PMA and pLDH).
o They are quick, easy and simple to perform; but they can’t give any
information about the parasite load and response to therapy; have a
lower sensitivity than peripheral blood smear and a higher cost.
 63

5. Chronic kala-azar:
 Routine investigation may show:
o Blood: Pancytopenia
o LFT: Mild elevation of liver enzymes (ALT & AST) and reversal of
Albumin: Globulin ratio.
 Diagnosis of kala-azar rests on microscopic detection of amastigotes in smears
of tissue aspirate. The sites from where the tissue can be taken are: lymph
node (sensitivity: 60%), liver (sensitivity: 85%) and spleen (sensitivity 97%).
Although splenic aspirate has the highest sensitivity, because of the fear of life
threatening hemorrhage, this procedure is contraindicated if PT> (control +
5sec.) or platelet count <40,000/cu.mm.
 Dipstick ELISA testing of blood from a finger prick for leishmanial anti-K39
antigen has a very high sensitivity and specificity in symptomatic patients. Its
titre decreases after a successful therapy and increases in cases of relapse;
making it a useful test to recognize treatment failure.
6. Disseminated (miliary) TB:
 The chest radiograph is the single most important way of detecting miliary
tuberculosis. It may be normal in 25-50% of patients and may remain that
way for several weeks. It may also exhibit a vast array of abnormalities
including pleural effusions, hilar adenopathy, interstitial infiltrates and
extensive parenchymal consolidation.
 The sputum smear is positive in approximately 30% of patients with miliary
TB, and increases with additional lesions, e.g. cavitation, in up to 70% of
patients.
 Sputum cultures are positive in almost 66% of patients.
 Histologic confirmation of disseminated TB is achieved best by tissue
biopsy of the lung, bone marrow, liver, lymph node, skin or any other
tissue that is clinically involved.
 Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and
transbronchial biopsy (TBB) remains an invaluable tool in the immediate
diagnosis of miliary TB. The definitive diagnostic yield is 73-86%.
 64

Paediatrics including Neonatology

WBUHS 2012
Group A
1. Discuss briefly the synthesis of thyroid hormones. Outline the clinical features
and treatment of cretinism. (5+3+2)
Iodine uptake
 The thyroid is able to concentrate I– against a strong electrochemical gradient.
This is an energy-dependent process and is linked to the Na+-K+ ATPase-
dependent thyroidal I– transporter.
 The ratio of iodide in thyroid to iodide in serum (T:S ratio) is a reflection of the
activity of this transporter. This activity is primarily controlled by TSH and the
T:S ratio in humans on a normal iodine diet is about 25:1.
Iodine oxidation
 The thyroid is the only tissue that can oxidize I– to a higher valence state, an
obligatory step thyroid hormone biosynthesis.
 This step involves a heme-containing peroxidase (thyroperoxidase) and occurs
at the luminal surface of the follicular cell. Thyroperoxidase requires hydrogen
peroxide as an oxidizing agent.

 Once iodination occurs, the iodine does not readily leave the thyroid.
Coupling
 The coupling of two DIT molecules to form T4—or of an MIT and DIT to form
T3—occurs within the thyroglobulin molecule.
 It is assumed that the same thyroperoxidase catalyzes this reaction, which is
supported by the observation that the same drugs which inhibit I– oxidation
also inhibit coupling.

 The formed thyroid hormones remain as integral parts of thyroglobulin until

the latter is degraded.
Deiodination

 A deiodinase removes I– from the inactive MIT and DIT molecules in the
thyroid. This mechanism provides a substantial amount of the I– used in T3
and T4 biosynthesis.
 65

 A peripheral deiodinase in target tissues such as pituitary, kidney, and liver

selectively removes I– from the 5' position of T4 to make T3, which is a much
more active molecule.

Cretinism:
Clinical features:
Cretinism is the most serious consequence of iodine deficiency. It occurs only in
geographic association with endemic goitre.
There are 2 types of cretinism: neurological and myxedematous. There are some
common clinical features and some differentiating clinical features and laboratory
findings, which are as follows: [Reference: Nelson’s Paediatrics]
Neurological cretinism Myxedematous cretinism
Common features
 Mental retardation
 Deaf-mutism
 Neurological symptoms (Ex.: Clonus of the foot, Babinski sign, Patellar
hyper-reflexia).
Differentiating features
Normal growth and pubertal Delayed growth and sexual
development development
Affected persons are goitrous but Absence of goitre (USG shows thyroid
euthyroid atrophy)
No myxedema Myxedema (due to fluid retention)
 66

Little or no impaired thyroid function Serum T4 levels are low and TSH levels
are markedly elevated
Disturbance in stance and gait Not common

Treatment:
 Cretinism is best to prevent than to treat because, once the neuromotor
deficiency and mental retardation ensues; it is irreversible.
 Iodized salt and iodized oil are highly efficacious in preventing iodine
deficiency.

 Recommended daily iodine intake:

Age group RDI (in µg)
Children upto the age of 10 years 40-120
Older children and adults 150
Pregnancy 175
Lactation 200

 Administration of a single intramuscular injection of iodinated poppy seed oil

to women prevents iodine deficiency during future pregnancies for about 5 yr.
 This form of therapy given to children younger than 4 years of age with
myxedematous cretinism results in a euthyroid state in 5 mo.
 Older children respond poorly and adults not at all to iodized oil injections,
indicating an inability of the thyroid gland to synthesize hormone; these
patients require treatment with T4.
Group B
2.a. Management of cyanotic spells in Tetralogy of Fallot.
 Introduction:
 Paroxysmal hypercyanotic spells are a particular problem during the 1st 2
years of life of Tetralogy of Fallot patients.
 The infant becomes hyperpneic and restless. As cyanosis increases, gasping
respirations ensue and syncope may follow.
 The spells occur most frequently in the morning on initially awakening or
after episodes of vigorous crying.
 67

 The onset is usually spontaneous and unpredictable. The spells may last
from a few minutes to a few hours.
 Short episodes are followed by generalized weakness and sleep.
 Severe spells may progress to unconsciousness and, occasionally, to
convulsions or hemiparesis.
 Spells are associated with reduction of an already compromised
pulmonary blood flow, which, when prolonged, results in severe systemic
hypoxia and metabolic acidosis.
 Management:
 Depending on the frequency and severity of hypercyanotic attacks, one or
more of the following procedures should be instituted in sequence:
(1) Placement of the infant on the abdomen in the knee-chest position
while making certain that the infant's clothing is not constrictive,
(2) Administration of oxygen (although increasing inspired oxygen will not
reverse cyanosis caused by intracardiac shunting), and
(3) Injection of morphine subcutaneously in a dose not in excess of 0.2
mg/kg.
 Calming and holding the infant in a knee-chest position may abort
progression of an early spell.
 Because metabolic acidosis develops when arterial Po2 is <40 mm Hg,
rapid correction (within several minutes) with intravenous administration
of sodium bicarbonate is necessary if the spell is unusually severe and the
child shows a lack of response to the foregoing therapy.
 Recovery from the spell is usually rapid once the pH has returned to
normal. Repeated blood pH measurements may be necessary because
rapid recurrence of acidosis may ensue.
 For spells that are resistant to this therapy, intubation and sedation are
often sufficient to break the spell.
 Drugs that increase systemic vascular resistance, such as intravenous
phenylephrine, can improve right ventricular outflow, decrease the right-
to-left shunt, and improve the symptoms.
 β-Adrenergic blockade by the intravenous administration of propranolol
(0.1 mg/kg given slowly to a maximum of 0.2 mg/kg) has also been used.
 68

3.b. Prevention of hypothermia in newborn.

Warm chain
The strategy of prevention of hypothermia in newborn is known as “Warm chain”,
which includes 10 steps as follows:
1. Warm delivery room (>25◦C)
2. Warm resuscitation
3. Immediate drying
4. Skin to skin contact
5. Breastfeeding
6. Bathing postponed
7. Appropriate clothing
8. Mother and baby together
9. Professional alert
10. Warm transportation.
Description:
 Conduct delivery in a warm room.
 Dry baby including head immediately with warm clean towel.
 Wrap baby in pre-warmed linen, cover the heads and the limbs.
 Place the baby skin to skin on the mother on the same bed (rooming -in).
 Practice frequent breastfeeding. Practice KMC in LBW baby.
 Points to remember regarding bathing of the baby:
Timing of bath Procedure
 Small for date/ LBW: Till the  Warm room and warm water.
cord fails/ till the baby  Bathe quickly and gently.
attains a weight of 2.5 kg.  Dry quickly and thoroughly.
 Sick/ admitted in nursery: No  Wrap in a warm, dry towel.
bath.  Dress and wrap infant.
 Term baby: Postponed till  Use a cap.
next day.  Keep close to mother.
 69

 Warm transportation:
Let temperature stabilize before transport.
Document temperature and take remedial measures.
Carry close to chest, if possible in kangaroo position.
Cover adequately.
Use thermocol box with pre-warmed linen/ plastic sheet/ water filled
mattress with thermostat.
 Use incubators and radiant warmers properly to assist sick and small neonates
maintain their normal body temperature.
Reference: National neonatology forum (NNF).

2.c. Diagnosis of Rheumatic arthritis.

Clinical features:
 Commonly involved joints: Larger joints (knee/ ankle/ wrist/ elbow).
 Involved joints are generally hot, red, swollen and exquisitely tender; even the
friction of bedclothes is uncomfortable.
 Pattern of joint involvement: The joint involvement is characteristically
migratory in nature; a severely inflamed joint can become normal within 1-3
days without treatment, as 1 or more other large joints become involved.
 There is usually no residual deformity in affected joints.
 Almost always associated with history of episodes of fever, where the
temperature usually remains below 103◦F and a suspected streptococcal
infection (sore throat/ impetigo etc.).
 A dramatic response to even small doses of salicylates is another
characteristic feature of the arthritis and the absence of such a response
should suggest an alternative diagnosis.
Laboratory investigations:
Aspiration of synovial fluid in acute rheumatic fever shows:
 WBC: 10,000-100,000 WBC/mm3 with a predominance of neutrophils,
 Protein level: 4 gm/dl,
 Glucose level: Normal
 Formation of a mucin clot.
 70

Group C
3.a. Pulsus paradoxus.
 Introduction: A condition when pulse volume decreases with inspiration and
increases with expiration.
 Note: This is a normal phenomenon when it is within physiological limits.
 Mechanism:

Negative ↑ Venous ↑ Venous

Inspiration intrathoracic return to right return to right
pressure atrium ventricle

RV occupies a ↓LV stroke

↓Pulse volume
volume > LV volume

The reverse is true for expiration.

Positive ↓ Venous ↓ Venous

Expiration intrathoracic return to right return to right
pressure atrium ventricle

RV occupies a ↑LV stroke

↑Pulse volume
volume < LV volume

 Method of assessment:
 Blood pressure cuff is applied over arm, cuff pressure is increased till
brachial pulse is obliterated and then cuff pressure is released and
brachial artery is auscultated (as done while measuring BP).
 At one point, the first Korotkov sound appears and it is noted.
 While releasing the cuff pressure, at another point, the Korotkov sound
becomes regular and almost double. This point is noted.
 71

 The difference between these two points is the degree of pulsus

paradoxus.
 Interpretation:
Degree of pulsus paradoxus Interpretation
<10 mm Hg Normal
10-20 mm Hg Pericardial effusion/ Constrictive pericarditis
>20 mm Hg Cardiac tamponade (Severe pericardial effusion
causing impairment of cardiac filling)

3.b. Complications of acute glomerulonephritis.

Complications:
A. Acute left sided heart failure:
It occurs due to volume overload resulting from retention of salt and water
through activation of RAS and associated hypertension.
Suspect by the following signs and symptoms:
 Acute respiratory distress.
 Tachypnoea.
 Tachycardia.
 Gallop rhythm (S3/ S4).
 Basal crepts/ wheeze (due to pulmonary edema).
B. Hypertensive encephalopathy:
It is an uncommon complication of PSGN accompanied by hypertension. It
is suspected by the following symptoms:
 Headache.
 Vomiting.
 Convulsion.
 Alteration of sense of consciousness.
C. Acute renal failure:
It is a rare complication of PSGN resulting from acute kidney injury through
immunological reactions.
Treatment of complications:
A. Left heart failure:
IV Furosemide (1 mg/kg/dose): To relieve pulmonary edema.
B. Hypertensive encephalopathy:
IV antihypertensives.
Antihypertensives of choice:
1) Labetalol,
2) Hydralazine,
 72

3) Sodium Nitroprusside.
4) Diazoxide.
C. Acute renal failure:
Send for dialysis for correction of blood urea nitrogen (BUN): may be peritoneal
dialysis/ hemodialysis.
3.c. Biochemical changes in Rickets:
 Introduction:
A lack of adequate mineralization of growing bones results in rickets.
 Etiology:
Rickets result from deficiency of calcium or phosphorus (as both are
needed for bone mineralization).
Deficiency of calcium results from insufficient amount of vitamin D,
resulting in secondary hyperparathyroidism (+ a high PTH level).
 Some common causes of vitamin D deficiency are:
1. Poor intake of vitamin D rich foods.
2. Inadequate exposure to sunlight.
3. Malabsorption syndromes.
4. Chronic liver disease.
5. Anticonvulsant drugs (Ex.: Carbamazepine, Valproate,
Lamotrigine).
 Biochemical changes in Rickets:
When hypocalcemia occurs in vitamin D deficiency, PTH production is
elevated, causing:
1. Activation of renal 1α-hydroxylase, increasing the amount of
active vitamin D and calcium absorption;
2. Increased resorption of calcium from bone by osteoclasts;
3. Decreased renal calcium excretion; and
4. Increased renal excretion of phosphate.
 So, biochemical investigations in Rickets (from vitamin D deficiency) will show
the following:
Parameters Change in Rickets
Serum calcium Normal/ ↓
Serum phosphate ↓
Serum PTH ↑
 73

Serum 25(OH)D ↓
Serum Alkaline phosphatase ↑
Urine calcium ↓
Urine phosphate ↑

3.d. Milestones of development in a 1 year old child.

 Domains:
1. Gross motor development.
2. Fine motor skill development.
3. Social and adaptive development.
4. Language.
5. Vision and hearing.
 Key gross motor developmental milestones in a 1 year old child:
Age Milestones
3 months Neck holding
5 months Roll over
6 months Sits with support
8 months Sits without support
9 months Stands with support
12 months Stands without support
 Key fine motor skill developmental milestones in a 1 year old child:
Age Milestones
4 months Reach out for objects with both hands (Bi-dextrous reach)
6 months Reach out for objects with one hand (Uni-dextrous reach)
9 months Immature pincer grasp
12 months Mature pincer grasp
 Key social and adaptive developmental milestones in a 1 year old child:
Age Milestones
2 months Social smile (smile after being talked to)
3 months Recognizes mother
6 months Recognizes strangers
9 months Waves “Bye-bye”
12 months Comes when called
 Key language developmental milestones in a 1 year old child:
Age Milestones
1 month Alerts to sound
3 months Musical vowel sounds
 74

4 months Laugh loud

6 months Monosyllables (ma, ba, da)
9 months Disyllables (mama, baba, dada)
12 months 1-2 word with meaning
 Key visual milestones in a 1 year old child:
Age Milestones
1 month Focuses on parents
3-4 months Fixates intently on an object shown to him (grasping with the
eye) as if the child wants to reach the object
4 months Binocular vision well established
6 months Child adjusts his position to follow the object of interest
1 year Can follow rapidly moving objects
 Key hearing milestones in a 1 year old child:
Age Milestones
3-4 months Child turns his head towards the source of sound
5-6 months Child turns his head to one side and then downwards if a sound
is made below the level of ears
7 months Child becomes able to localize sounds made above the ears
10 months Child directly looks at the source of sound diagonally

Group D
4. A 4 years old child presented with pallor, fever, gum bleeding and 1.5 cm palpable
spleen. Mention the diagnostic possibility and investigations to confirm diagnosis.
(3+5)
Diagnostic possibility:
The differential diagnoses should include:
Malignancy:
1. Acute lymphoblastic leukemia (ALL)
2. Acute myeloid leukemia (AML)
Infections:
1. Chronic malaria
2. Chronic kala-azar
3. Disseminated (miliary) tuberculosis.

Please see the 2011 Group D Question no. 4 for rest of the answer.
 75

Paediatrics including neonatology

2013
Group A
1. Pathophysiology of large VSD and the future changes in hemodynamics
if remain untreated. Mention the complications of VSD. Outline the
treatment of VSD with CCF. (5+3+2)
Pathophysiology of large VSD:
Introduction:
VSD is a characterized by a defect in the membranous part of ventricular
septum with variable extension into the muscular septum; causing an
abnormal communication between left and right ventricle; allowing blood to
flow from LV to RV, i.e. along the pressure gradient throughout the entire
period of systole.
Magnitude of the shunt:
 The magnitude of left to right shunt in VSD depends upon 2 factors:
a. Physical size of VSD.
b. (Pulmonary: systemic) vascular resistance.
 In a small VSD (usually <5 mm), the defect is pressure restrictive;
meaning that right ventricular pressure is normal. The higher pressure in
the left ventricle drives the shunt left to right and the size of the defect
limits the magnitude of the shunt.
 In a large VSD (usually >10 mm), the defect is pressure nonrestrictive;
meaning that right and left ventricular pressures are equalized. In these
defects, the direction of shunting and the shunt magnitude are
determined by the ratio of pulmonary to systemic vascular resistance.
Effect of a large shunt:
 Just after birth, the pulmonary vascular resistance remains elevated for
some period, limiting the size of shunt.
 Few weeks after birth, the media of small pulmonary arterioles begins to
involute; so the pulmonary vascular resistance begins to fail and size of
shunt starts to increase.
 Eventually, a large left-to-right shunt develops, and clinical symptoms
become apparent.
 76

Reversal of the shunt: (Eisenmenger syndrome)

 In most cases during early infancy, the major contribution to pulmonary
arterial hypertension (PAH) is the large communication between
ventricles allowing exposure of the pulmonary circulation to systemic
pressure; resulting in large pulmonary blood flow.
 With continued exposure of the pulmonary vascular bed to high systolic
pressure and high flow, pulmonary vascular obstructive disease
eventually develops.
 When the ratio of (pulmonary: systemic) resistance approaches 1:1, the
shunt reverses, signs of heart failure abate, and the patient begins to
show signs of cyanosis. This event is known as “Eisenmenger syndrome”.
Future changes in hemodynamics in a case of untreated VSD: (see picture)
Level Hemodynamic changes Clinical findings
VSD Left to right shunt throughout A loud pan-systolic murmur best
the entire period of systole heard over left 4th intercostal
space. It’s so loud that it is often
audible at other cardiac areas of
heart. (Shunt murmur)
Pulmonary valve Functional pulmonic stenosis Mid systolic murmur at
(abnormal amount of blood pulmonary area
flow through a normal valve) (Flow murmur)
Pulmonary artery PAH Accentuated P2, best heard over
pulmonary area
 77

RV Volume overload (which may Parasternal heave (in case of RV

cause RV failure in late stage) hypertrophy)
LA Volume overload (which may
cause LA failure in late stage)
Mitral valve Functional mitral stenosis Mid diastolic murmur over mitral
(abnormal amount of blood area (Flow murmur)
flow through a normal valve)
LV Volume overload (which may Laterally displaced apex beat (in
cause LV failure in late stage) case of LV hypertrophy)

Heart sounds:
 S1: Masked by murmur.
 S2:
 As the LV has 2 outlets of blood flow: to the aorta and to the RV;
so the blood in the LV empties early; resulting in an early A2.
 As the RV has 2 inlets of blood flow: from the RA and from the LV;
it receives an extra amount of blood and empties late; resulting in
a delayed P2.
 So, the S2 is widely split but varies with respiration in patients
with significant VSD.
 If significant PAH develops, an accentuated P2 may be heard best
over the pulmonary area.
 S3: May be heard in small L to R shunt.
Murmurs:
 Shunt murmur: Pansystolic murmur along lower left sternal border (4th
intercostal space), which may become palpable (then it is called a thrill).
 Flow murmur:
 Pulmonary valve: A mid systolic murmur may be heard over
pulmonary area due to functional pulmonic stenosis.
 Mitral valve: A mid diastolic murmur may be heard over mitral
area due to functional mitral stenosis.
 In clinical practice, these murmurs are very hard to differentiate from
the shunt murmur (pansystolic) as it often masks all other sounds.
Complications of VSD:
1. Pulmonic stenosis
 78

2. PAH
3. Aortic regurgitation
4. Infective endocarditis.
Discussion of complications of VSD
 As told at the very beginning, VSD may be of two types:
a. Perimembranous type of VSD (defect through membranous part of
ventricular septum).
b. Muscular type of VSD (defect through muscular part of the
ventricular septum).
 In >90% of the patients, spontaneous closure of VSD occurs by the age of
3 years. The muscular type of VSD has a higher chance of getting closed.
 There may be outcomes as stated below in case of untreated large VSDs:
a. Pulmonic stenosis (due to hypertrophy of RV infundibulum).
b. Pulmonary arterial hypertension (PAH).
c. Aortic regurgitation (due to prolapse of right coronary cusp of aortic
valve)
 The PAH may be of two types:
a. Hyperkinetic (due to high pulmonary artery blood flow).
b. Obstructive (due to arterial remodelling and resultant obstruction).
In the obstructive type of PAH, the patient becomes inoperable, which is
a danger of significant PAH.
 VSD is the commonest congenital lesion complicated by infective
endocarditis (IE). Maintenance of good oral hygiene is of paramount
importance in reducing the risk of endocarditis.
Treatment of VSD with CCF
Medical management:
Therapies used to manage symptomatic CHF in children with VSDs may include
the following:
1. Increased caloric density of feedings to ensure adequate weight gain -
Occasionally, oral feeds must be supplemented with tube feeds because
a baby in CHF may be unable to consume adequate calories for
appropriate weight gain.
2. Diuretics to relieve pulmonary congestion: Furosemide is usually given in
a dosage of 1-3 mg/kg/day divided in 2 or 3 doses; long-term furosemide
 79

treatment results in hypercalcemia and renal damage and electrolyte

disturbances.
3. Angiotensin-converting enzyme (ACE) inhibitors (ex. Captopril and
Enalapril): These medications reduce both the systemic and pulmonary
pressures, thereby reducing the left-to-right shunt.
4. Digoxin (5-10 µg/kg/day): This may be indicated if diuresis and afterload
reduction do not relieve symptoms adequately.
Operative treatment:
Indication of surgery in VSD:
1. CCF.
2. Large L to R shunt (pulmonary flow: systemic flow > 2:1).
3. Presence of complications (pulmonic stenosis/ PAH/ AR).
Operations of choice:
 The operative treatment of choice of perimembranous VSD is closure of
VSD using a patch. This operation is performed through the RA.
 The procedure of choice in muscular VSDs is catheter closure of VSD.
 In patients with any evidence of PAH, the surgery should be done as
early as possible (otherwise the patient becomes inoperable).
Group B
Write briefly on the following: (5 marks each)
2.a. Kangaroo mother care (KMC):
Introduction:
KMC refers to care of preterm/ low birth weight (LBW) babies by placing the
infant in skin-to-skin contact with the mother/ any other caregiver.
Components:
1. Kangaroo position:
 This consists of skin-to-skin contact between mother and infant;
keeping the infant in a vertical position between the mother’s
breasts and under her cloths.
 Mother should keep herself in a semi-reclining position to avoid
gastric reflux of the infant.
 80

 Head of the baby should be turned to one side and slightly

extended to keep the airway open.
 Hips should be flexed and abducted (frog position).
 Arms should be flexed.
 Baby’s abdomen should at the level of mother’s epigastrium.

2. Kangaroo nutrition: Exclusive breastfeeding.

3. Kangaroo discharge and follow-up: Early home discharge from neonatal
unit in the kangaroo position is one of the most important components
of KMC. Mother requires adequate support and follow-up at home.
Benefits of KMC:
1. Physiological:
a. Protection from cold stress and hypothermia.
b. Stabilization of heart rate, respiratory rate, oxygenation and sleep
pattern.
2. Clinical:
a. Increased milk production in mothers.
b. Weight gain.
c. Thermal protection.
d. Protection against respiratory and nosocomial infections.
e. Emotional bonding between mother and child.
f. Early discharge from the hospital.
Eligibility criteria for KMC:
1. For baby:
a. All stable LBW babies.
b. Sick babies after hemodynamic stabilization.
2. For mother:
a. All willing mothers in good health.
 81

b. Free from any serious illness.

c. Good hygiene.
d. Proper counselling of mother and family members.
e. Family’s support and cooperation.
Initiation of KMC:
Birth weight Initiation
<1200 gm May take days to weeks before KMC can be initiated.
1200-1800 gm May take days before KMC can be initiated.
>1800 gm KMC can be initiated immediately after birth.

Clothing in KMC:
1. For mother: Any light weight front open dress as per local culture is
suitable for KMC.
2. For baby: Baby is dressed with cap, socks, nappy and front open
sleeveless shirt.
Monitoring:
Nursing stuff should monitor the baby especially during initial stages:
 The baby’s position is neither too flexed nor too extended (clear airway).
 Breathing is regular.
 Colour of the baby is pink.
 Baby is maintaining adequate temperature.
Duration:
 Sessions of KMC <1 hour should be avoided because it may be stressful
for the baby.
 Afterwards, sessions should be gradually prolonged upto 24 hours,
interrupted only for changing diapers.
Stopping of KMC:
 When the baby attains a weight of 2500 gm.
 When the baby completes a gestation of 37 weeks.
 When the baby refuses (cry/ try to get out/ get anxious) KMC.
 82

3.b. Clinical features and laboratory investigation of Dengue fever in children.

Clinical features:
Incubation period: 4-10 days.
Febrile phase (last for 2-7 days)
Fever Myalgia Nausea Petechiae
Facial flushing Arthralgia Vomiting Nose bleed
Skin erythema Headache Sore throat Gum bleed
Bodyache Anorexia Conjunctival redness Hepatomegaly

Critical phase (after 3-7 days of onset of fever)

Severe bleeding Severe hepatitis
Shock Encephalitis
[* A sudden fall of platelet count and Myocarditis
rise of hematocrit occur in this phase.] Impaired consciousness

Recovery phase (after 1-2 days in critical phase)

General wellbeing improves Hemodynamic stabilization
Appetite returns Diuresis ensues
In some patients the following features may be seen:
Rash Generalized pruritus
Respiratory distress (due to still Bradycardia
persisting pulmonary edema)

Laboratory investigation in a suspected case of dengue fever:

General investigations
1. Blood:
a. TC & DC: A decreasing leukocyte count (TC) with increasing
lymphocyte count (in DC).
b. Platelet count: Low (<100,000/cu.mm in severe cases).
c. Hematocrit: High (≥20%↑ above normal values in severe cases).
2. Liver function test: Rise in both SGOT and SGPT, with the rise of SGOT
being greater than rise of SGPT.
3. Renal function test: Increased urea: creatinine in severe cases.
 83

4. Serum albumin: Low in patients in shock/ progressing to shock.

5. Serum pH: Acidosis in severe cases.
Radiological investigations
1. X-Ray chest: It may show pleural effusion, commonly at the right side.
2. USG abdomen: It may show ascites or gall bladder edema.
Specific investigations
It is of two types:
1. Direct methods:
a. Virus isolation by culture.
b. Genome detection by PCR.
c. NS1 antigen detection.
2. Indirect methods:
a. IgM detection.
b. IgG detection.
The methods 1a and 1b are not feasible in average medical setup. So these are
not discussed.
NS1 antigen detection:
NS1 antigen is a highly conserved glycoprotein of dengue virus and secreted
during initial periods of illness and its level declines as disease progresses. It
has a specificity of 100% and sensitivity of 90% in first 4 days of illness.
IgM antibody detection:
It becomes detectable at day 5, peaks at day 14 and becomes undetectable by
2-3 months.
IgG antibody detection:
It becomes detectable at day 7, increases slowly and remains detectable at low
levels probably for life.
2.c. Neonatal sepsis screening.
 Septic screening should be done to support the clinical suspicion of
infection before the institution of specific antibacterial therapy.
However, no investigation is required to start treatment in a sick baby
having high probability of sepsis.
 84

 The reliable markers of neonatal septicemia include:

a. Total leukocyte count <5000/ cu.mm,
b. Absolute neutrophils count <1800/ cu.mm,
c. (Immature: mature) total neutrophils ratio >20%,
d. Raised micro-ESR (≥15 mm in 1st hour) and
e. Positive C-reactive protein (>8 mg/ ml).
 Blood culture and CSF examination (by lumbar puncture) are mandatory
before initiating specific antibacterial therapy.
 An X-Ray of the chest should be taken in all cases. It may show scattered
or localized opacities suggestive of patchy consolidation.
 Blood should be examined for glucose, bilirubin, urea and electrolytes.
Premature rupture of membrane:
 In all infants born following premature rupture of membrane/ those
developing respiratory distress soon after-birth; gastric aspirate should
be collected in a heparinized tube and examined under the microscope
after staining with Leishman's stain.
 The presence of >5 neutrophils per high power field/ when their number
exceeds 3 times the number of the epithelial cells, is suggestive of
intrauterine/ congenital pneumonia.
 A bacterial culture should be obtained from liquor amnii (or cervical
swab), gastric aspirate, throat, umbilical stump and blood.
Group C
Write short notes: (5 marks each)
3.a. Utility of growth chart:
1. Growth monitoring: Growth chart is the most useful to monitor the
following aspects of growth of child:
a. Present status of the growth of the child:

Position in the WHO growth chart Status of child growth

At or above the 2nd curve (M-2SD) Normal
At or above 3rd curve (M-3SD) but Moderately underweight
below 2nd curve
Below 3rd curve Severely underweight
b. Direction of the growth of the child:
 85

Direction of growth curve of child Interpretation

Upward Good
Flat Dangerous
Downward Very dangerous
2. As a diagnostic tool: Malnutrition can be detected long before signs and
symptoms of it become apparent.
3. Planning and policy making: Growth chart provides an objective basis
for planning and policy making in relation to child health care at local/
state/ central levels.
4. Educating mothers: The mother can be easily educated in the care of
her own child and she is encouraged for participating more actively in
growth monitoring.
5. Tool for action: Growth chart guides the health worker to take
appropriate intervention [like nutritional interventions and referrals] at
the right time.
6. Tool for evaluation: Growth chart provides an effective tool for
evaluating the effect of the intervention measures.
7. Tool for teaching: The growth chart can be used to teach importance of
adequate feeding/ effects of diarrhea and ARI on child health etc.

3.b. Rabies prophylaxis:

Rabies prophylaxis is of 2 types:
A. Pre-exposure prophylaxis.
B. Post-exposure prophylaxis.
Pre-exposure prophylaxis
 It is offered to individuals at high risk of rabies due to contact with
animals (veterinary doctors, wildlife workers, dog handlers etc.).
 3 doses are recommended to be given intramuscularly on day 0, 7,
21/28.
 A booster dose is required after 1 year and every 5 years thereafter.
 86

Post-exposure prophylaxis
The aim of post exposure prophylaxis is to neutralize the inoculated virus
before it can enter the CNS. Every case of human exposure should be treated
as medical emergency.
The type of post exposure prophylaxis depends on the type/ degree of contact,
which has been classified into 3 categories: They are as follows:

Category of contact with rabid animal Post exposure prophylaxis

Category 1: Touching/ feeding animals, Local treatment of wound
licks on intact skin.
Category 2: Minor scratches/ abrasions Local treatment of wound +
without bleeding, penetration of Immediate vaccination.
uncovered skin.
Category 3: Single/ multiple Local treatment of wound +
transdermal bites/ scratches, licks on Immediate vaccination +
broken skin, contamination of mucous Administration of rabies
membrane with saliva from licks, immunoglobulin.
contact with bats.

Local treatment of Wound

 The purpose of local treatment is to remove as much virus as possible

from the site of inoculation before it can be absorbed on nerve endings.
 It should never be neglected and should be done in every case.
 Local treatment comprises of the following processes:
1. Cleansing:
 Immediately flush and wash the wound[s], scratches and
adjoining areas with plenty of soap and water, preferable
under a running tap, for at least 15 minutes.
 If soap is not available, simply flush the wound with plenty of
water.
 In case of punctured wounds, use catheters to irrigate the
wound.
2. Chemical treatment:
The residual virus remaining in the wound should be inactivated by:
 Alcohol/
 Tincture iodine/
 Povidone iodine.
 87

3. Suturing:
 Bite wounds should not be immediately sutured to prevent
additional trauma which may help spread the virus into deeper
tissues.
 If suturing is necessary, it should be done 48-72 hours later,
applying minimum possible stitches under the cover of rabies
immunoglobulin locally.
4. Antibiotic and anti-tetanus measure:
 It should follow the local treatment mentioned above when
indicated.

POST EXPOSURE VACCINATION

Intramuscular schedules
I. Single site schedule:
One dose of the vaccine should be administered on days 0, 3, 7, 14 and
30. All intramuscular injections must be given into the deltoid region or,
in small children, into the anterolateral area of the thigh muscle. Vaccine
should never be administered in the gluteal region.

II. Abbreviated multisite schedule:

In the abbreviated multisite schedule, the 2-1-1 regimen, one dose is
given in the right arm and one dose in the left arm at day 0, and one
dose applied in the deltoid muscle on days 7 and 21. The 2-1-1 schedule
induces an early antibody response and may be particularly effective
when post-exposure treatment does not include administration of rabies
immunoglobulin (Ex: Category 2).

Intradermal schedule
WHO recommended the following intradermal regimen and vaccines for
use by the intradermal route:

2-site intradermal method:

The regimen is (2-2-2-0-1-1).
The volume per intradermal site is: 0.1 ml.

Post exposure passive immunization

 Rabies immunoglobulin is used for passive immunization as soon as
possible after the initiation of post exposure vaccination.
 88

 It should be mentioned that after 7 days of first dose of vaccine, rabies

immunoglobulin is not recommended because an active antibody
response to rabies vaccine [CCEEV] is presumed to occur after this
period.
 The schedule of rabies immunoglobulin is as follows:
Dose:
20 IU/kg for Human Rabies IG; 40 IU/kg for Equine Rabies IG.
Site of administration:
All/ as much as possible IG should be administered into/ around the
wound.
If any amount remains, it should be administered at a site distant from
the site of vaccination.
Caution:
In case of equine IG, there is a small risk of anaphylaxis due to its
heterogenous origin. So the physician should always be ready with a
syringe of adrenaline before administering it.

3.c. Miliary tuberculosis in children:

 Introduction:
It is characterized by hematogenous spread and progressive
development of innumerable small foci throughout the body.
 Age group: Miliary TB commonly occurs in infants and young children.
 Onset of disease: Sudden.
 Clinical features:
1. Symptoms:
 High grade fever
 Dyspnea
 Rigors
 Alteration of sensorium
 Weight loss.
2. Signs:
 Cyanosis
 89

 Lymphadenopathy
 Hepatosplenomegaly
 Fine crepitation and rhonchi
 Choroid tubercles
 Signs of meningitis may be present in 20-30% of cases.
 Diagnosis:
1. Demonstration of tubercle bacilli/ its components:
a. ZN stain.
b. Special stain.
c. Culture in LJ medium/ BACTEC assay.
d. PCR.
2. Demonstration of host’s response to tubercle bacilli:
Tuberculin test.
3. Radiological investigations:
Demonstration of following features in X-Ray:
a. Airspace consolidation.
b. Lymphadenopathy.
c. Bronchiectasis.
Demonstration of following features in CT-Scan:
a. Low attenuation of lymph nodes.
b. Lymph node calcification.
c. Branching Centrilobular nodules.
d. Miliary nodules.
 Treatment:
{2(HRZE) + 4(HR)}3: 2 months of HRZE and 4 months of HR: thrice weekly
DOTS is recommended under RNTCP.
 90

3.d. Pulse polio immunization.

 Introduction:
Pulse polio is an immunization campaign established by the Govt. of
India in 1995-96 to eradicate polio in India by vaccinating all children
under the age of 5 years against polio virus.
 Objectives:
1. The Pulse Polio Initiative (PPI) aims at covering every individual in the
country. It aspires to reach even children in remote communities
through an improved social mobilisation plan.
2. Not a single child should miss the immunisation, leaving no chance of
polio occurrence.
3. Cases of Acute Flaccid Paralysis (AFP) to be reported in time and stool
specimens of them to be collected within 14 days. Outbreak
Response Immunisation (ORI) to be conducted as early as possible.
4. Maintaining high level of surveillance.
5. Performance of good mop-up operations where polio has
disappeared.
 Steps involved in PPI:
1. Setting up of booths in all parts of the country.
2. Initialising walk-in cold rooms, freezer rooms, deep freezers, ice-lined
refrigerators and cold boxes for ensuring steady supply of vaccine to
booths.
3. Arranging employees, volunteers and vaccines.
4. Ensuring vaccine vial monitor on each vaccine vial.
5. Immunising children with OPV on National Immunisation Days.
6. Identifying missing children from immunisation process.
7. Surveillance of efficacy.
 91

 Current condition:
On 27 March, 2014 WHO South-East Asia Region (including India) was
certified polio-free by an independent commission under the WHO
certification process.

Group D
4. A 4 years old child presented with H/O fever for 7 days and recurrent
convulsion for last 2 days and headache. How will you proceed for diagnosis
clinically and by laboratory investigation? (4+4)

Presenting symptoms:
1. Fever.
2. Recurrent convulsion.
3. Headache.
Take history of any other following symptoms:
1. Lethargy/ irritability.
2. Mental confusion/ altered level of consciousness.
3. Nausea/ vomiting.
4. Photophobia.
Look for following signs:
Classical signs:
1. Kernig sign:
 This manoeuvre is usually performed with
the patient supine with hips and knees in
flexion.
 Extension of the knees is attempted.
 The inability to extend the patient’s
knees beyond 135 degrees without
causing pain constitutes a positive test
for Kernig’s sign.
 92

2. Brudzinski sign:
 With the patient supine, the physician
places one hand behind the patient’s
head and places the other hand on the
patient’s chest.
 The physician then raises the patient’s
head (with the hand behind the head)
while the hand on the chest restrains
the patient and prevents the patient
from rising.
 Flexion of the patient’s lower
extremities (hips and knees)
constitutes a positive sign.
 Brudzinski’s neck sign has more sensitivity than Kernig’s sign.

Associated signs:
 Look for any associated cranial nerve palsies
 Look for hemiparesis/ quadriparesis
 Look for visual signs: Papilledema/ visual field defects
 Look for auditory signs: Ataxia & hearing loss (suggestive of labyrinthitis)
 Look for any erythematous maculopapular rash (suggestive of Neisseria
meningitidis infection).

Look for evidence of any systemic infective conditions:

Look for signs of cellulitis, septic arthritis, otitis media, pneumonia etc.
which may act as the source of infection.

LABORATORY INVESTIGATIONS
The following diagnostic tests/ methods are usually used in general:
1. CSF study by lumber puncture (LP)
2. Serological tests
3. Gram stain and ZN stain
4. Culture and sensitivity testing
5. Radioimaging.
 93

CSF Study

Parameters Normal Pyogenic Viral Tubercular

meningitis meningoencephalitis meningitis
Cell count 0-6 >1000 100-500 50-300
(lymphocyte) (PMN) (Predominantly (lymphocyte)
lymphocytic with
PMN fraction<30%)
Protein 20-40 >100 50-100 >50 at early
(mg/dl) stages, may be
very high in late
stages
Glucose 40-80 Very low, Unaltered <40
(mg/dl) may be 0
RBC 0-2 10-50 in HSV encephalitis (with multifocal seizures).

Serological tests

1. Antibody detection:
For this purpose, 2 types of serum can be used:
a. Acute serum for acute cases (IgM detection).
b. Convalescent serum for chronic cases (IgG detection).
2. In special situations like epidemic, special tests can be applied:
a. NS1 and IgM testing in dengue epidemic.
b. Rapid influenza diagnostic test (RIDT) in influenza epidemic.

Identification of causative organism by Lumbar Puncture

1. Gram stain:
a. Gram +ve organisms (Strep. pneumoniae, Staph. Aureus etc.).
b. Gram –ve organisms (E.coli, Klebsiella, N.meningitidis etc.).
2. ZN stain: For identifying tubercle bacilli.
3. PCR: For identifying causative viral agents.

Radioimaging

 Neuroimaging, especially MRI has become the most sensitive diagnostic

technique for finding damages/ complications already occurred in case
of meningitis.
 94

 The usual nonspecific findings on MRI, which can be found in meningitis

of all etiologies are:
a. Cerebral edema
b. Infarct
c. Hydrocephalus.
 Only the following 2 etiological agents produce specific findings on
neuroimaging:
I. HSV encephalitis: Involvement of temporo-parietal regions
II. Japanese B encephalitis: Involvement of thalamus.
 95

Pediatrics including Neonatology

WBUHS (2014)
Group A
1. Describe the formation and circulation of CSF in brain. Describe the clinical
features of raised ICT in a 6 year old child. Give an outline of treatment of such a
patient. (3+3+4= 10)
Formation and circulation of CSF in brain:
Please see 2011 Group A; 1st part of Question no 1.
Clinical features of raised ICT in a 6 year old child:
Symptoms Description Significance
Headache Persistent headache, especially in early Stretching of dura, venous
morning, often bioccipital or bifrontal sinuses and sensory nerves
Vomiting Usually projectile and often present in Direct pressure on medullary
early morning centers
Diplopia and Raised ICT displaces the brainstem 6th cranial nerve palsy and
lateral gaze─ downwards, stretching the 6th nerve paralysis of lateral rectus
Herniation • Impaired consciousness Severe brain edema and
syndrome • Abnormality of pupil pressure difference in various
• Irregular respiration tissues of brain lead to
• Hypertonicity herniation during which part
• Paresis of brain get impacted in
• Decerebrate or decorticate posture abnormal location
• Altered body temperature
• Cardiovascular collapse.
Cushing’s triad • Irregular respiration
• Bradycardia Brainstem compression
• Hypertension.

Signs Description Significance

MacEwen sign Percussion of skull near the junction of Presence of hydrocephalus/
frontal, temporal and parietal bones will brain abscess
produce a stronger resonant sound
Sunset sign Bilateral downward gaze of eyes Impending herniation
 96

Localizing signs:
These signs help to detect the anatomical location of lesion:
Localizing signs Probable site of lesion
Combined CN6 and CN7 palsy Pons
Head tilt Cerebellum/ posterior fossa
Ataxia Cerebellum/ Spinocerebellar tract/ frontal
lobe/ thalamus
Motor deficit Cerebral cortex/ brainstem/ spinal cord
Seizure Cortical/ subcortical area
Nystagmus Cerebello-vestibular system
Impaired vision in presence of normal Lesion near optic nerve/ chiasma/
refraction radiation/ occipital cortex
Bitemporal hemianopia Compression over optic chiasma
Personality disturbance, impaired Frontal lobe
sphincter control and grasp response

Treatment:
Starting of treatment:
Treatment should be started when there is clinical evidence of raised ICP or sudden
increase in ICP, i.e. >20 mm Hg for >3 minutes or 16-20 mm Hg for >30 minutes.
Modes of treatment:
1. Basic therapy
2. Advanced therapy.
Basic therapy
A: Airway

B: Breathing, Blood pressure

C: Circulation

D: Drugs (for seizure control, acute reduction of ICP,

osmotherapy, sedation and paralysis, steroids)

E: External stimulus prevention

H: Head position, Hyperventilation

T: Temperature control
 97

A. Maintain Airway/ Avoid hypoxia:

 Monitor oxygenation (target SaO2~100%) and apply supplemental O2 as
required.
 If the patient has inadequate respiratory effort/ GCS <8/ rapid clinical
deterioration (signs of herniation, unequal pupils)/ status epilepticus
unresponsive to medications, then intubation should be attempted.
B. Breathing:
Maintain PaO2 >80 mmHg and PaCO2 30-35 mmHg.
Blood pressure:
Maintain mean arterial blood pressure (MAP) in the normal range for age.
C. Circulation:
Keep patient normovolemic, give normal saline. Hypotension, if present should
be treated aggressively.
D. Drugs:
I. Drugs for seizure control:
 Seizure increases cerebral oxygen consumption and diminishes the
capacity to maintain ICP.
 Midazolam 0.1- 0.2 mg/kg/IV given every 5 minutes till seizures are
controlled, load the patient with phenytoin.
II. Drugs for acute reduction of ICP:
Lidocaine helps in acute reduction of pressure (1.5 mg/kg). It should also
be instilled locally before endotracheal tube suctioning to avoid coughing.
III. Drugs for osmotherapy:
Osmotic and loop diuretics may be used:
• Mannitol: In low-dose 0.25-0.5 mg/kg of 20% solution given as bolus and
may be repeated 4-6 hourly.
• Furosemide: 0.5-1.0 mg/kg/IV may be given alone or with osmotic
diuretics.
IV. Sedation and paralysis:
Sedation decreases the sympathetic activity thus reduces hypertension
and plays a key role in management. Paralysis is used during controlled
ventilation.
V. Steroids:
Steroids are used in vasogenic edema (tumor, abscess and organized
subdural hematoma). Dexamethasone: Loading dose 1 mg/kg, then 0.25
mg/kg/IV 6 hourly.
 98

E. External stimulus prevention:

Prevent external stimulus, monitor signs of over stimulation and keep
surrounding noise level less than 90 db.
H. Head position:
• Maintain head in midline position at 15⁰-30⁰ to improve cerebral venous
drainage; lower cerebral blood volume (CBV) will lower ICP.
• While turning the patient keep hip joint flexed <30°.
Hyperventilation:
Maintain mild hyperventilation if required, the effect will start within 30 sec and
peak in 8 minutes. This will lead to vasoconstriction and decrease in cerebral
blood flow thus resulting in acute reduction of raised ICP.
T. Temperature control:
Keep normothermic (36-37°C) as ↑Temperature ↑ CBF ↑ CBV ↑ ICP.

Advanced therapies (ICP monitoring is required)

 Barbiturate coma
 Moderate hypothermia (32-36°)
 Decompressive craniotomy/ durotomy/ lobectomy
 Operative treatment of mass lesions
 Ventricular drainage/ Ventriculo-peritoneal (VP) shunt
 Neuromuscular blocking agents.

Group B
2.a. Hypoglycemia in neonate:
Definition: Hypoglycemia is defined as a blood glucose level of <40 mg/dL or a plasma
glucose level <45 mg/dL.
Risk factors:
1. Inadequate substrate:
a. Small for gestational age
b. Gestation <35 weeks
c. Birth weight <2000 gm.
2. Relative hyperinsulinemia:
a. Infants of diabetic mothers
 99

b. Large for gestational age

c. Rh isoimmunization.
3. Sickness:
a. Hypothermia
b. Sepsis
c. Asphyxia.

Screening for hypoglycemia:

 It is recommended in high risk situations as stated above

 These babies should be screened at 2, 6, 12, 24, 48 and 72 hours after birth using
reagent strips (Dextrostix).
 Babies showing blood sugar value <40 mg/dL on reagent strip should be treated
for hypoglycemia but should have a confirmation of hypoglycemia by a laboratory
test as reagent strips have high false +ve rates.

Clinical features:
Clinically, hypoglycemia may be asymptomatic/ may show a range of clinical features:
Stupor Lethargy
Tremor Difficulty in feeding
Apathy Eye rolling
Cyanosis Episodes of sweating
Convulsions Sudden pallor
Apneic spells Hypothermia
Tachypnea Cardiac arrest (rare)
Weak and high pitched cry
 100

Management of hypoglycemia:

Hypoglycemia

Asymptomatic Symptomatic

Blood sugar Blood sugar Bolus of 10% glucose

>20 mg/dL <20 mg/dL at 2 ml/kg

Immediately followed
Trial of oral feeds IV glucose infusion by glucose infusion at
6 mg/kg/min

Check blood glucose

Test blood sugar after
after 30-45 min and
30-45 min
then 6 hourly

≥2 consecutive values
Repeat hypoglycemic are >50 mg/dL after
>40 mg/dL <40 mg/dL
episodes 24 hour of parenteral
therapy

Frequent feeding for Increase infusion rate

Taper off infusion at
48 hours with 6 by 2 mg/kg/min to a
IV glucose infusion rate of 2 mg/kg/min
hourly monitoring of maximum of 12
every 6 hours
blood sugar mg/kg/min

Monitoring:
Hypoglycemia is linked to long-term adverse effects. These babies should be evaluated
at 3, 6, 9, 12 and 18 months for growth, neurodevelopment and vision and hearing loss.
 101

3.b. Hemorrhagic diseases of newborn:

Basic physiology:
 A moderate decrease in factors II, VII, IX and X normally occurs in all newborn
infants by 48-72 hr after birth, with a gradual return to birth levels by 7-10 days
of age.
 This transient deficiency of vitamin K–dependent factors is probably due to lack
of free vitamin K from the mother and absence of the bacterial intestinal flora
normally responsible for the synthesis of vitamin K.
 Rarely in term infants and more frequently in premature infants, accentuation
and prolongation of this deficiency between the 2nd and 7th days of life result in
spontaneous and prolonged bleeding.
Types:
There are 3 types of hemorrhagic diseases of newborn:
1. Classical disease
2. Early onset disease
3. Late onset disease.
Features Early onset disease Classical disease Late onset disease
Onset 0-24 hr 2-7 days 1-6 mo
Sites of Cephalohematoma, GI, ENT region, Intracranial, GI,
hemorrhage subgaleal, intracranial, intracranial, circumcision, cutaneous, ENT region,
GI, umbilical, intra- cutaneous, injection sites injection sites, thoracic
abdominal
Risk factors Maternal drugs Vitamin K deficiency Cholestasis:
(phenobarbital, Breast-feeding malabsorption of
phenytoin, warfarin, vitamin K (biliary atresia,
rifampin, isoniazid) that cystic fibrosis, hepatitis)
interfere with vitamin K
metabolism
Inherited
coagulopathy
Prevention Avoid high-risk Prevented by parenteral Prevented by parenteral
medications vitamin K at birth and high-dose oral
Administrations of vitamin K during periods
vitamin K (20 mg) to Oral vitamin K regimens of malabsorption or
infant at birth or to require repeated dosing cholestasis
mother before birth over time
 102

Incidence Very rare ≈2% if infant not given Depends on primary

vitamin K disease

2.c. Enumerate the vaccines that can be given to an unimmunized 2 year old child.
IAP recommended general immunization schedule in case of an unimmunized child:

So, applying this table to a 2 year old child, we get the following:
Visit Suggested vaccines
First visit MMR
DTwP1/ DTaP1
OPV1/ IPV1
Hib1
HepB1
Second visit BCG
(after 1 month of first DTwP2/ DTaP2
visit) OPV2
HepB2
Third visit OPV3/IPV2
(after 1 month of MMR
second visit) Typhoid (as third visit in a 2 year old
child will be at 2 year 2 months)
 103

Fourth visit DTwP3/ DTaP3

(6 months after first OPV4/IPVB1
visit) HepB3

Group C
3.a. Modified Jones’ criteria:

Major manifestations:
1. Carditis:
It occurs in 50% of acute rheumatic fever (ARF) patients. It may be
inflammation of one or more layers of heart, which show signs as follows:
Affected layer Sign
Pericarditis Pericardial friction rub/ effusion/ chest pain/ ECG changes
Myocarditis Tachycardia (out of proportion to the severity of fever)
Endocarditis (valvulitis) A murmur indicating MR/ AR is always present
Severe carditis Clinical signs of CHF (Gallop rhythm/ cardiomegaly)
Pancarditis/ Cardiomegaly on chest radiograph
Pericarditis/ CHF
2. Polyarthritis:
 This is the most common manifestation of ARF (70%) and usually involves
large joints (knee, ankles, elbows, wrists).
 Often, more than one joint, either simultaneously or in succession is
involved with a characteristic migratory nature of the arthritis.
 104

 Swelling, heat, redness, severe pain, tenderness and limitation of motion

are common.
 The arthritis responds dramatically to salicylate therapy; if the arthritis
does not respond within 48 hours of the diagnosis of rheumatic fever is
probably incorrect.
3. Chorea:
 Sydenham’s chorea is present in 15% of patients with ARF and is common
in pre-pubertal girls (8-12 years).
 It begins with emotional lability and personality changes.
 Then it progresses through loss of motor coordination, characteristic
spontaneous purposeless movements, followed finally by motor weakness
and hypotonia of muscles; which continue for an average of 7 months
before waning progressively.
4. Erythema marginatum:
 It is seen in <10% of cases and is rare in Indian subcontinent.
 The characteristic nonpruritic serpiginous/ annular erythematous rashes
are most prominent on the trunk and inner proximal portions of the
extremities, but never seen on face.
 The rashes disappear on exposure to cold and reappear when covered with
a warm blanket.
5. Subcutaneous nodules:
 Subcutaneous nodules are found in 2-10% of the cases.
 They are hard, painless, nonpruritic, freely mobile and <2 cm in diameter.
 They are distributed symmetrically, singly or in clusters over the extensor
surfaces of large and small joints, scalp and along the spine.
 They last for weeks and are significantly associated with carditis.
Minor manifestations:
1. Arthralgia refers to a joint pain without the objective changes of arthritis.
Note that, if polyarthritis is already taken as a major criteria, then arthralgia
can’t be taken as a minor criteria.
2. Fever (with a temperature usually of at least 39°C) generally is present early in
the course of rheumatic fever.
3. In laboratory findings, acute phase reactants (elevated CRP levels and ESR) are
objective evidences of an inflammatory process.
4. A prolonged P-R interval on ECG is neither specific for acute rheumatic fever
nor an indication of active carditis.
 105

Evidence of Antecedent Group A Streptococcal Infection:

 A history of sore throat is not an adequate evidence of recent group A
streptococcal infection.
 Positive throat swab cultures or rapid streptococcal antigen tests for group A
streptococci are less reliable than antibody tests, because they do not distinguish
between recent infection and chronic pharyngeal infection.
 Streptococcal antibody tests are the most reliable laboratory evidence of
antecedent streptococcal infection capable of producing rheumatic fever. The
onset of the clinical manifestations of acute rheumatic fever coincides with the
peak of the streptococcal antibody response.
 Some of the most commonly used Streptococcal antibody tests are Anti-
streptolysin O (ASO) titre and Streptozyme test.
3.b. Pneumatocele:
Introduction:
Pneumatoceles are intrapulmonary air-filled cystic spaces.
Age group:
Although pneumatoceles are seen in all age groups, they are most frequently
encountered in infancy.
Causes:

Staph.aureus (commonest)

Strep.pneumoniae

Post-pneumotic (common) H.influenzae

E.coli

Causes of pneumatocele
Klebsiella pneumoniae

Blunt trauma
Special causes
Positive pressure ventilation in
preterm neonates
 106

Clinical presentation:
• Children present with typical features of pneumonia, including cough, fever and
respiratory distress. No clinical findings differentiate pneumonia with or without
pneumatocele formation.
• Occasionally pneumatoceles become large enough to compress adjacent lung
and the mediastinum enough to cause respiratory or cardiovascular symptoms.
Radiologic features:
• When mature, pneumatoceles appear as thin walled cystic spaces within the lung
parenchyma, containing air.
• They tend to appear within the 1st week of infection and usually resolve by 6th
week.

Complications:
1. Rupture of a pneumatocele may cause pneumothorax
2. Secondary infection: Secondarily infected pneumatocele.
Treatment:
• Post-pneumonic pneumatoceles tend to spontaneously resolve providing the
infection is adequately treated with antibiotics.
• Surgical intervention is only required if the pneumatocele causes symptoms due
to mass-effect or ruptures into the pleural space resulting in pneumothorax.
Dx:
I. Bronchogenic cyst
II. Lung abscess
III. TB
IV. Cystic adenomatoid malformation
V. Hyper IgE syndrome.
 107

3.c. Common causes and laboratory diagnosis of iron deficiency anemia in children
Causes of iron deficiency anemia in children:
It can be divided into 4 distinct groups as follows:
1. Decreased intake
2. Increased loss
3. Decreased iron store
4. Increased iron demand.
Group Causes
Decreased intake  Delayed weaning
 Malnutrition and iron poor diet
 Malabsorption syndromes
 Chronic infection and chronic diarrhea
Increased loss • GI bleeding
• Malaria
• Hookworm infestation
• Peptic ulcer, diverticulitis
• Bleeding diathesis
• Fetomaternal hemorrhage
Decreased iron store • Preterms
• Small-for-dates
• Twins
Increased iron demand • Prematurity
• LBW
• Recovery from PEM
• Adolescence

Laboratory diagnosis of iron deficiency anemia:

Parameters Change in iron deficiency anemia
Hb level ↓
RBC level ↓
RBC indices
Mean cell volume (MCV) ↓
Mean cell hemoglobin (MCH) ↓
Red cell distribution width (RDW)* ↑↑
Iron status
Serum iron ↓
 108

Serum ferritin ↓
Transferrin saturation ↓
Total iron binding capacity (TIBC) ↑

*RDW is the coefficient of variation of red cell volume distribution. RDW is the objective
documentation of subjective anisocytosis.
3.d. Causes and clinical features of hyponatremia:
Introduction:
Under normal conditions, serum sodium is tightly regulated in between 135-145 mEq/L.
Hyponatremia is defined a serum sodium concentration of <130 mEq/L. But if the
concentration comes to <120 mEq/L, then it is usually associated with serious clinical
symptoms and must be corrected immediately
Causes:
Some common causes of hyponatremia and their short description:
1. Systemic dehydration
2. Decreased effective plasma volume (in CHF, nephrotic syndrome, cirrhosis,
positive pressure mechanical ventilation, severe asthma)
3. Primary polydipsia (increased water ingestion)
4. Decreased free water excretion (in adrenal insufficiency/ thyroid deficiency)
5. Primary salt loss (of renal and non-renal origin): PKD, CRF, Cystic fibrosis
6. Syndrome of inappropriate ADH secretion: SIADH (excessive administration
of vasopressin in the treatment of central diabetes insipidus, encephalitis,
brain tumors)
7. Cerebral salt wasting (Hypersecretion of Atrial natriuretic peptide [ANP] in
brain tumors, head trauma, hydrocephalus)
8. Runner’s hyponatremia (Excess fluid ingestion during long-distance running
can result in severe hyponatremia due to hypovolemia-induced activation of
Arginine vasopressin [AVP] secretion)
9. Pseudo-hyponatremia (Can result from hypertriglyceridemia, which result in a
relative decrease in serum water content)
10. Factitious hyponatremia (Can result from obtaining a blood sample proximal
to the site of intravenous hypotonic fluid infusion).
 109

Clinical features of hyponatremia:

Mechanism of manifestations:
• Hyponatremia causes a decrease in the osmolality of the extracellular space.
• Because the intracellular space then has a higher osmolality, water moves from
the extracellular space to the intracellular space to maintain osmotic equilibrium.
• The increase in intracellular water causes cells to swell. Although cell swelling is
not problematic in most tissues, it is dangerous for the brain, which is confined
by the skull. Brain cell swelling is responsible for most of the symptoms of
hyponatremia.
• As brain cells swell, there is an increase in intracranial pressure, which impairs
cerebral blood flow.
Manifestations:
• Acute, severe hyponatremia can cause brainstem herniation and apnea;
respiratory support is often necessary.
• Neurologic symptoms of hyponatremia include anorexia, nausea, vomiting,
malaise, lethargy, confusion, agitation, headache, seizures, coma and decreased
reflexes. Patients may have hypothermia and Cheyne-Stokes respirations.
• Hyponatremia can cause muscle cramps and weakness; rhabdomyolysis can
occur with water intoxication.
Group D
4. A 6 year old girl child is admitted with hematuria, moderate edema and headache.
Mention the possible differential diagnosis. How will you evaluate such a case to reach
to a definite diagnosis? (2+6=8)
Although the typical presentation is more suggestive of a picture of acute nephritic
syndrome, the differential diagnoses should include the following:
1. Acute nephritic syndromes
2. Nephrotic syndromes, especially:
a. Membranoproliferative glomerulonephritis (MPGN)
b. Idiopathic Focal segmental glomerulosclerosis (FSGS).
Evaluation of such a case:
Investigation Nephritic syndrome Nephrotic syndrome
Urine analysis  Urine protein: Mild to moderate  Urine protein: Nephrotic range
proteinuria (1+/2+) proteinuria (3+/4+)
 110

 Microscopic examination:  Microscopic examination:

 Presence of dysmorphic/  Gross hematuria/ persistent
crenated RBCs and RBC casts microscopic hematuria suggests
are diagnostic the likelihood of significant
 WBCs, hyaline casts and glomerular lesions
granular casts are present.  Hyaline casts and granular cases
are present.
Renal function  Blood urea-creatinine: Usually  Blood urea-creatinine:
tests normal/ may be elevated (due to  In MCNS, blood urea levels are
renal impairment) normal unless edema is massive
with associated oliguria
 Serum Na+: Hyponatremia may  Persistently elevated urea and
be present (due to impairment of creatinine suggest the presence
free water excretion) of significant renal histologic
 Serum K+: Hyperkalemia may be lesions
present (due to decreased GFR)  Serum albumin: Hypoalbuminemia
 Total serum protein: May be (<2.5 gm/dl)
elevated due to increased  Total serum cholesterol:
γ-globulins. Hyperlipidemia (>200 mg/dl).
Blood  Hemoglobin: May be low due to  Serum IgM: High
hemodilution  Serum IgG: Low
 Complement: C3 is low in 90% of  Complement: C3 level is usually
patients but normalizes within 8- normal; persistently decreased
12 weeks. serum C3 levels indicate MPGN.
Chest X Ray It may show evidence of pericardial Tuberculin test (if positive, a CXR) is
effusion/ gross cardiomegaly (an done to exclude TB (renal TB presents
impending sign of CHF)/ with persistent hematuria and pyuria).
consolidation in strep. pneumonia.
USG To detect free fluid in abdomen and pleura (when undetectable clinically)
 111

Post streptococcal glomerulonephritis (PSGN)

Theory and Viva Questions

General Discussion
1. What are the usual chief complaints in paediatric age group?
a. Oliguria
b. Proteinuria
c. Hematuria
d. Edema.

2. What is the normal urine volume in paediatric age group? What are its
abnormalities?
Urine volume Designation
1-2 cc/kg/hr Normal
< 1cc/kg/hr Oliguria
<0.5 cc/kg/hr Acute renal failure
>4 cc/kg/hr Polyuria

3. What is the normal range of protein in urine? What are its

abnormalities?

The normal range of protein in urine is around 150 mg/24 hours.

Various range of proteinuria may result in abnormal conditions where
urinary protein excretion is increased significantly.

Proteinuria was first quantified according to the 24 hours urinary protein

excretion:

24 hour urinary protein excretion Designation

150 mg/ 24 hours Normal
150 -500 mg/ 24 hours Mild/ nephritic range of proteinuria
500 mg- 2 gm/ 24 hours Moderate range of proteinuria
>2 gm/ 24 hours Severe range of proteinuria
 112

As the process of collecting 24 hours urine sample was hazardous, it is

now replaced by “spot urine protein: creatinine ratio“, which is the most
sensitive method of assessing severity of proteinuria.
Spot urine protein: creatinine ratio Designation
~0.2 Normal
0.2-2.0 Nephritic range of proteinuria
>2.0 Nephrotic range of proteinuria

Another method of assessing the severity of proteinuria in a paediatric

patient is “total urine protein as per body surface area”.
Total urine protein as per body Designation
surface area
~ 4mg/sq.mt./hour Normal
4-40 mg/sq.mt./hour Nephritic range of proteinuria
> 40 mg/sq.mt./hour Nephrotic range of proteinuria

The test which is done bedside to roughly estimate the proteinuria in

paediatric age group is “heat and acetic acid test”.
Procedure:
 Fill 2/3rd of the test tube with urine.
 Heat the upper 2 cm of urine and observe the cloudiness.
 Add 2-3 drops of 10% acetic acid. Cloudiness due to phosphate in
urine will disappear.
 Repeat heating. Persistent cloudiness indicates albumin in urine.
Interpretation:
Observation Grading of proteinuria
No haziness 0
Haziness only on the upper part 1+
Haziness spreading beyond the 2+
upper part
Haziness is observed throughout 3+
the complete length of tube
A segment is precipitated on the 4+
lower portion of the tube

4. What are the types of hematuria?

Hematuria is mainly of 2 types:
 113

a. Frank hematuria: When visible blood is present in urine.

b. Microscopic hematuria: It is characterized by >5 RBC/1cc centrifuged
deposit.

5. What do you mean by generalized edema? What are the usual sites to
detect edema?
Generalized edema is described as edema detected clinically in more
than 1 region.
Usual sites to detect edema:
a. Pedal edema.
b. Sacral edema.
c. Periorbital edema.
d. Scrotal edema (in men).
e. Anterior abdominal wall and other serous civilities of body, i.e.
pleura, peritoneum etc. (seen in extremely severe generalized
edema).

6. Define acute nephritis.

Acute nephritis is a clinical condition characterized by acute onset of
mild to moderate proteinuria and edema with severe oliguria,
sometimes associated with hypertension and hematuria.

PSGN
1. When will you classify a case of acute nephritis as a case of post
streptococcal glomerulonephritis (PSGN).
When there is past history of definitive sore throat/ skin infections
preceding an episode of acute nephritis, then it is classified as a case of
PSGN.

2. What are the responsible stains?

Some of the nephritogenic stains of group A β-hemolytic streptococci are
mainly responsible for PSGN. The commonest are type 12 and type 49.

3. What is the usual age of onset?

5-12 years.
 114

4. What are the nephritogenic antigens described in the initiation of

pathogenesis of PSGN?
The most important 2 nephritogenic antigens responsible for the
pathogenesis of PSGN are:
a. Nephritis associated plasmin receptor (NAPlr) and,
b. Streptococcal pyogenic exotoxin B (SPE-B).

5. What is the characteristic morphologic involvement in PSGN? What is it

called?
The characteristic morphology of PSGN shows:
 Diffuse involvement of almost all glomeruli
 Proliferation of all 3 layers [epithelium, mesangium and
endothelium].
 This characteristic involvement pattern is called “Acute diffuse
proliferative glomerulonephritis”.

6. Describe the morphology of PSGN in brief.

Method Description
Light microscopy a. Proliferation of all 3 layers of renal
microstructure (epithelium,
mesangium and endothelium).
b. Hypercellularity (owing to infiltration
of glomeruli by PMN cells and
proliferation of cells).
c. Subepithelial hump like deposits.
Immunofluorescence Granular immune complex deposits
(mainly IgG and C3), in the mesangium and
along the GBM.
Electron microscopy Subepithelial electron dense deposits, with
appearance of “humps”.
Note that: Swelling of these humps usually
disappear after 6 weeks of onset.

7. What are the chief complaints in a patient with PSGN?

a. Decreased urine volume and frequency
b. Periorbital edema, prominent in the morning
c. Blood in urine
d. Hypertension (occasional).
 115

8. Describe the clinical features of PSGN along with their relevant

pathogenesis. (Final MB Question)

Edema and hypertension:

Hypercellularity and
Compression of Glomerular filtration
proliferation of all the
afferent and efferent rate ↓ and resultant
3 layers of renal
renal vessels oliguria
microstructure

Activation of Renin-
Retention of salt and Edema associated
Angiotensin-
water with hypertension
Aldosterone system

Proteinuria and hematuria:

As a result of immune complex deposition along the glomerular
basement membrane (GBM) and resultant damage to glomeruli, there is
leaking of protein and RBC, which is responsible for nephritic range of
proteinuria and hematuria in PSGN.

9. What are the complications associated with PSGN?

A. Acute left sided heart failure:
It occurs due to volume overload owing to retention of salt and
water through activation of RAS and associated hypertension.
Suspect by the following signs and symptoms:
 Acute respiratory distress
 Tachypnea
 Tachycardia
 Gallop rhythm (S3/ S4)
 Basal crepts/ wheeze (due to pulmonary edema).
B. Hypertensive encephalopathy:
It is an uncommon complication of PSGN accompanied by
hypertension. It is suspected by the following symptoms:
 Headache
 116

 Vomiting
 Convulsion
 Alteration of sense of consciousness.
C. Acute renal failure:
It is a rare complication of PSGN resulting from acute kidney injury
through immunological reactions.

10.What investigations will you do for confirming a diagnosis of PSGN?

 Urine analysis:
a. Specific gravity: High (due to reduced urine volume).
b. Proteinuria: Mild to moderate (1+ - 2+).
c. RBC and RBC cast.
 Renal function tests:
a. Urea creatinine ratio: Raised (it is usually used to assess renal
function).
b. Na+-K+: Na+ is reduced and K+ is grossly elevated.
 Supportive investigations:
a. ASO titre/ Anti DNAase/ Anti Hyaluronidase.
b. Hypo-complement-emia (reduced C3 and CH50 fraction).
c. Culture may reveal a positive result from throat/ skin.
 Renal biopsy:
Indications of renal biopsy in a patient of suspected PSGN:
a. Massive proteinuria.
b. Persistent hematuria.
c. Persistent low level of complement.

11.Outline the management of a confirmed case of PSGN.

It can be divided in 3 parts:
a. Supportive treatment.
b. Definitive treatment.
c. Treatment of complications.

Supportive treatment:
a. Absolute bed rest
b. Restriction of fluid and electrolytes
c. To calculate the fluid required for a patient, the following formula is
used:
 117

𝐹𝑙𝑢𝑖𝑑 𝑟𝑒𝑞𝑢𝑖𝑟𝑒𝑚𝑒𝑛𝑡
𝑚𝑙
= [𝑂𝑏𝑙𝑖𝑔𝑎𝑡𝑜𝑟𝑦 𝑓𝑙𝑢𝑖𝑑 𝑙𝑜𝑠𝑠 (400 𝑏𝑜𝑑𝑦 𝑠𝑢𝑟𝑓𝑎𝑐𝑒 𝑎𝑟𝑒𝑎)
𝑠𝑞. 𝑚𝑡
+ 𝐷𝑎𝑖𝑙𝑦 𝑢𝑟𝑖𝑛𝑒 𝑣𝑜𝑙𝑢𝑚𝑒]
d. If urea creatinine ratio is high enough, then protein is also restricted
in the diet.

Definitive treatment:
a. To treat oliguria, diuretics are used. Commonly used diuretic is
Furosemide (1-2 mg/kg/day).
b. To treat hypertension, which is severe enough, antihypertensive may
be used. Commonly used ones are Nifedipine/ Amlodipine.
- Usually symptoms improve within 7 days.

Treatment of complications:
 Left heart failure: IV Furosemide (1 mf/kg/dose): To relieve pulmonary
edema.
 Hypertensive encephalopathy: IV antihypertensives.
Antihypertensives of choice:
1) Labetalol
2) Hydralazine
3) Sodium Nitroprusside
4) Diazoxide.
 Acute renal failure: Send for dialysis for correction of blood urea nitrogen
(BUN): may be peritoneal dialysis/ hemodialysis.
 118

Nephrotic syndrome
Theory and Viva questions
What do you mean by nephrotic syndrome?
It is a clinical condition characterized by massive proteinuria, hypoalbuminemia
and edema associated with hyperlipidemia.
What do you mean by nephrotic range of proteinuria?
The normal range of protein in urine is around 150 mg/24 hours.
Various range of proteinuria may result in abnormal conditions where urinary
protein excretion is increased significantly.
Proteinuria was first quantified according to the 24 hours urinary protein
excretion:
24 hour urinary protein excretion Designation
150 mg/ 24 hours Normal
150 -500 mg/ 24 hours Mild/ nephritic range of proteinuria
500 mg- 2 gm/ 24 hours Moderate range of proteinuria
>2 gm/ 24 hours Nephrotic range of proteinuria

As the process of collecting 24 hours urine sample was hazardous, it is now

replaced by “spot urine protein: creatinine ratio“, which is the most sensitive
method of assessing severity of proteinuria.
Spot urine protein: creatinine ratio Designation
~0.2 Normal
0.2-2.0 Nephritic range of proteinuria
>2.0 Nephrotic range of proteinuria

Another method of assessing the severity of proteinuria in a paediatric patient

is “total urine protein as per body surface area”.
Total urine protein as per body Designation
surface area
~ 4mg/sq.mt./hour Normal
4-40 mg/sq.mt./hour Nephritic range of proteinuria
> 40 mg/sq.mt./hour Nephrotic range of proteinuria
 119

How will you classify nephrotic syndrome?

1. According to the etiology:
a. Primary/ idiopathic variety (90%): Where the main change is in the
kidney.
b. Secondary variety: When the main change is in organs other than
kidney and kidney is affected secondarily.
 Infections: HBV, HIV, syphilis, leprosy.
 Autoimmune: SLE, HS purpura.
 Metabolic: Diabetic nephropathy (in adults).
 Genetic: Amyloidosis.
 Liver disease: Wilson’s disease.
 Thyroid disorders: Hashimoto’s thyroiditis.
 Drugs: NSAIDs, Penicillin derivatives, ACE inhibitors.
 Tumours: Hodgkin’s disease.
 Miscellaneous: Heavy metal poisoning (Hg/Pb), snakebite.
2. According to the renal histology:
a. Minimal change nephrotic syndrome (80%).
b. Nephrotic syndrome associated with significant lesions.
3. According to the time of onset:
a. Congenital NS (arising within the first 3 months of life).
b. Typical onset NS (2-6 years of life).
c. Atypical onset NS (older children).
4. According to the response to therapy:
a. Steroid sensitive NS.
b. Steroid dependent NS.
c. Steroid resistant NS.
What are the pathological features of minimal change nephrotic syndrome?
Renal biopsy findings of minimal change NS include:
1. Light microscopy: Normal morphology of glomerular capillary loops,
mesangial matrix and cells.
2. Electron microscopy: Nonspecific obliteration of epithelial foot processes
(also called podocytes).
3. Immunofluorescence: Otherwise normal with occasional mesangial
deposition of IgM.
 120

What is the mechanism of proteinuria in NS? What is the special feature of

proteinuria in NS?
Majority of NS patients have a primary abnormality in the epithelial foot
processes (podocytes), which is responsible for the alteration in the
permeability of the glomerular filter, resulting in proteinuria.
The special feature of proteinuria in NS is that it is highly selective in nature.
What do you mean by “highly selective” proteinuria?
𝐶𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒 𝑜𝑓 𝐻𝑖𝑔ℎ 𝑚𝑜𝑙𝑒𝑐𝑢𝑙𝑎𝑟 𝑤𝑒𝑖𝑔ℎ𝑡 𝑝𝑟𝑜𝑡𝑒𝑖𝑛𝑠
[𝐸𝑥. : 𝐼𝑔𝐺]
𝑃𝑟𝑜𝑡𝑒𝑖𝑛 𝑠𝑒𝑙𝑒𝑐𝑡𝑖𝑣𝑖𝑡𝑦 =
𝐶𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒 𝑜𝑓 𝐿𝑜𝑤 𝑚𝑜𝑙𝑒𝑐𝑢𝑙𝑎𝑟 𝑤𝑒𝑖𝑔ℎ𝑡 𝑝𝑟𝑜𝑡𝑒𝑖𝑛𝑠
[𝐸𝑥. : 𝐴𝑙𝑏𝑢𝑚𝑖𝑛]
A low “Protein selectivity” ratio indicates highly selective proteinuria as in
minimal change nephrotic syndrome.
Which are the proteins lost in the highly selective proteinuria in NS?
The proteins which are lost selectively in NS patients are:
Clinically important:
1. Albumin (leading to hypoalbuminemia)
2. Immunoglobulins (leading to reduced immunity & repeated infections).
Clinically less important:
3. Transferrin
4. Thyroxin binding globulin (and so, nephrotic infants are often picked up
in neonatal thyroid screening).
What is the mechanism of edema in NS?

Reduced plasma
Highly selective Interstitial edema
Hypoproteinemia colloidal oncotic
proteinuria and hypovolemia
pressure

Retention of Na+ Activation of RAS

Edema
and water axis
 121

What are the clinical features of NS?

1. Edema: It is insidious in onset, usually periorbital edema occurs first and
then pedal edema ensues. The edema is soft and pits easily on pressure.
Gradually edema becomes generalized; with sometimes ascites,
hydrothorax and hydrocele complicating the picture.
2. Usually there is no significant rise in BP, hematuria and fall in urine
output; which if present, suggest significant glomerular lesions.

What are the differential diagnoses of generalized edema?

1. Severe protein energy malnutrition (PEM)
2. Protein losing enteropathy
3. Heart failure
4. Hepatic failure
5. Acute glomerulonephritis
6. Angioedema/ Urticaria.

What is the mechanism of hypercholesterolemia in NS?

There are 2 mechanisms:
 122

1. Increased synthesis of lipoproteins.

2. Reduced activity of lipoprotein lipase.
In NS, there is a gross loss of protein from body. The liver tries to compensate
this loss by increasing the synthesis of protein. The proteins which are
synthesized by the liver in this attempt mainly include the lipoproteins. The
activity of lipoprotein lipase (LPL) is also reduced in NS patients. Both of these
factors result in hyperlipidemia/ hypercholesterolemia.

What investigations will you want to do to confirm a diagnosis of NS?

1. Urine analysis:
 It will reveal nephrotic range of proteinuria (>2 gm/24 hours or
>40 mg/sq.mt./day).
 In 80% of cases, hematuria is not present. If present, it is
suggestive of significant glomerular lesions.
2. Renal function test:
 Blood urea: creatinine ratio usually remains normal in minimal
change disease.
 If it goes high, then it is suggestive of hypovolemia and fall in renal
perfusion.
3. Blood study:
 Hypoalbuminemia (defined as serum albumin level <2.5 gm/dl).
 Hyperlipidemia ( defined as a serum cholesterol >200mg/dl).
 ESR ↑ (often >100mm/1hr).
4. Other associated tests:
 Tuberculin test/ chest X ray.
 HBV/ HIV testing.
 Antinuclear antibody testing (in suspected case of SLE).
 C3/ ASO titre (in case of persistent hematuria, suspected PSGN).
 Urine culture (in suspected case of UTI).
5. Renal biopsy:
It is indicated in the following cases:
 Age of onset <12 months.
 Gross/ persistent microscopic hematuria.
 Persistent low blood C3 level.
 Persistent hypertension.
 123

 Impaired renal function.

 Partial/ no response to steroid therapy.

How will you manage a case of NS?

It can be divided into 2 parts:
a. General management.
b. Specific treatment.
General management
 High protein diet (1.5-2.0 gm/kg).
 Salt restriction (1-2 gm/day, only the amount used in usual cooking is
allowed, with no extra salt intake).
 Fluid restriction (daily fluid intake is limited to [Obligatory fluid loss (400
ml/ sq.mt body surface area) + 24 hours urine volume]).
 Diuretics are used only in cases of significant edema. They should be
used cautiously. The starting diuretics of choice is Furosemide,
Spironolactone may be added with caution in case of massive edema.
Specific treatment
 The treatment option of choice is corticosteroid.
 The only 2 agents with proven benefits are Prednisolone and
Prednisone.
 The duration and dosage of steroid therapy depends on the response
towards therapy.
 Before going into details of specific treatment, we should look at some
definitions regarding NS:
Definitions regarding Nephrotic Syndrome (According to IAP)
Remission Urine albumin nil or trace/ proteinuria < 4mg/sq.mt./hr
for 3 consecutive early morning specimens.
Relapse Urine albumin 3+ or 4+/ proteinuria > 40 mg/sq.mt/hr for
3 consecutive early morning specimens, having been in
remission previously.
Frequent ≥2 relapses in initial 6 months/ >3 relapses in any 12
relapse months.
Infrequent <2 relapses in initial 6 months/ ≤3 relapses in any 12
relapse months.
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Steroid 2 consecutive relapses when on alternate day steroids/

dependence within 14 days of its discontinuation.
Steroid Absence of remission despite therapy with daily
resistance Prednisolone at a dose of 2 mg/kg/day for 4 weeks.

 The treatment protocol are as follows:

Group Strategy/ duration (Agent of choice Prednisolone/ Prednisone)

1st episode 2 mg/kg/day (maximum 60 mg/day) in 2-3 divided doses for a
duration of 6 weeks.
Followed by,
1.5 mg/kg/day (maximum 40 mg/day) single dose on alternate
days for a duration of 6 weeks.
Then discontinued.
Infrequent 2 mg/kg/day until remission (urinary protein is nil/ trace for 3
relapse consecutive days).
Followed by,
1.5 mg/kg/day single dose on alternate days for a duration of 4
weeks.
Then discontinued.
Frequent Following treatment of a relapse, prednisolone is gradually
relapse/ tapered to maintain the patient in remission on alternate day
steroid dose of 0.5-0.7 mg/kg, which is administered for 9-18 months.
dependence A close monitoring of growth and blood pressure and
evaluation for features of steroid toxicity is essential. If the
prednisolone threshold to maintain remission is higher than 0.5
mg/kg on alternate days or if features of corticosteroid toxicity
are seen, additional use of the following immunomodulators as
steroid sparing agents is suggested:
1. Levamisole,
2. Cyclophosphamide,
3. Cyclosporin,
4. Tacrolimus,
5. Mycophenolate.
Note:
Be careful while using cyclosporine/ tacrolimus as they have the
side effect of nephrotoxicity; so periodic renal function
assessment is of utmost importance.
Note:
Recent case series and a controlled trial support the use of
 125

Mycophenolate as a steroid sparing agent. The lack of renal,

hemodynamic and metabolic toxicity with this agent makes it
an attractive alternative to calcineurin inhibitors (cyclosporine/
tacrolimus).

What are the symptoms of steroid toxicity?

 Growth retardation
 Short stature
 Cushingoid feature
 Hypertension
 Osteoporosis
 Subcapsular cataract.
 126

What are the complications of NS and how will you manage those?
Complications of NS:
1. Edema
2. Infections
3. Thrombotic complications
4. Hypovolemia and acute renal failure.
Complications Comments Management
Edema  Salt restriction.
 Fluid restriction.
 Significant edema: Furosemide.
 Massive edema: Furosemide +
Spironolactone.
 Intractable cases where serum albumin
levels are extremely low: Infusion of
albumin.
Infections* Strep.pneumoniae  Treat the infection accordingly (Ex.:
Peritonitis/ Cellulitis/ Pneumonia/
Meningitis).
Varicella  Oral Acyclovir for 7 days.
 IV Acyclovir in severe cases.
Thrombotic High risk:  LMW Heparin followed by oral
complications  Aggressive use of anticoagulant.
(Renal/ diuretics,
pulmonary/  Venepuncture of
cerebral deep veins and
thrombosis/  Hypovolemia.
embolism)
Hypovolemia and Occurs in case of:  Discontinue diuretics.
acute renal failure#  Severe relapse.  Admission and rapid infusion of normal
 After administration saline 10-20 ml/kg over 20-30 minutes.
of diuretics.  Patients who don’t respond to 2 bolus
infusions should receive infusion of
albumin.

* Immunization with pneumococcal and varicella vaccines is advised once the

patient is off steroids for 4 weeks.
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#Features of hypovolemia:

Clinical features:
a. Abdominal pain,
b. Lethargy,
c. Dizziness,
d. Leg cramps,
e. Hypotension,
f. Tachycardia,
g. Delayed capillary refill,
h. Low volume pulse,
i. Cold clammy distal extremity.
Suggestive laboratory features:
a. Elevated ratio of urea: creatinine
b. High hematocrit
c. Urinary sodium <20 mEq/L
d. Urinary K+ index> 0.6.

References:
1. Essential Paediatrics, 8th Edition, O.P.Ghai.
2. Revised guideline of management of steroid sensitive nephrotic
syndrome, 2008, Indian paediatric nephrology group, Indian Academy of
Paediatrics (IAP).
 128

Meningitis/ Meningoencephalitis in children

Theory and Viva questions
Enumerate the aetiological agents of meningeal involvement in children.
Meningitis in children can be classified I mainly 2 types according to the
etiological agents:
a. Bacterial etiology: Mainly meningitis in nature
b. Viral etiology: Mainly encephalitis in nature.
c. Tubercular: Mainly meningoencephalitis in nature.
Bacterial etiology
Causative agents according to age:
Age Causative agent (Most common agents)
0-3 months  E.coli
 Strep.pneumoniae
3 months- 3 year  H.influenzae (type b)
 Strep.pneumoniae
3 year- 10 year  Strep.pneumoniae
 N.meningitidis
>10 year  N.meningitidis
 Strep.pneumoniae

Viral etiology

Viral agents

DNA virus RNA virus

HSV1 Enterovirus type 9 and 71

HSV2 Polio

VZV Coxsackie virus

CMV Measles/ Mumps/ Rubella

EBV Influenza (at times of epidemic)

 129

Note:
It should be noted that in the western and north-east states of India, one of
the major causes of viral meningoencephalitis is Japanese B Encephalitis virus.

What are the possible sources of infection to meninges/ brain?

1. Pneumonia
2. Empyema
3. Pyoderma
4. Osteomyelitis
5. Head injury
6. Sinusitis
7. Mastoiditis.

Describe the pathogenesis of meningitis/ meningoencephalitis.

The following 4 points should be kept in mind in case of a meningitis/
meningoencephalitis:
a. Inflammation of meninges.
b. Inflammation of brain.
c. Vasculitis.
d. Exudate formation.
Inflammation of meninges
For understanding this, one should review the anatomy of meningeal layers.
The human meninges contains 3 layers as
follows (from outward to inward, mnemonic
is DAP):
1. Dura matter,
2. Arachnoid matter,
3. Pia matter.
Pia matter contains nerve fibres.
So in case inflammation extends to pia-
matter, the following events result:
 130

Inflammation of pia matter

Inflammation of nerve roots within pia

Meningeal irritation signs

[Sub question: What are the signs of meningeal irritation and how will you
demonstrate it clinically?
Signs of meningeal irritation are also collectively called the triad of
“meningism” consisting of:
a. Neck rigidity
b. Photophobia and,
c. Headache.
Demonstration of signs of meningeal irritation:
1. Kernig sign:
 This manoeuvre is usually
performed with the patient
supine with hips and knees in
flexion.
 Extension of the knees is
attempted.
 The inability to extend the
patient’s knees beyond 135
degrees without causing pain
constitutes a positive test for
Kernig’s sign.

2. Brudzinski sign:
 With the patient supine, the physician places one hand behind the
patient’s head and places the other hand on the patient’s chest.
 131

 The physician then raises the patient’s head (with the hand behind
the head) while the hand on the chest restrains the patient and
prevents the patient from rising.
 Flexion of the patient’s lower extremities (hips and knees)
constitutes a positive sign.
 Brudzinski’s neck sign has more sensitivity than Kernig’s sign.

Inflammation of brain

Bacterial endotoxin/ cell wall/ teichoic

acid

Cellular response by releasing

TNF/ Cytokines/ PAF

Damage to brain cells

Necrosis
 132

Inflammation of blood vessels (vasculitis)

Vasculitis

Thrombosis of cerebral arteries and veins

End artery involvement

Infarction of vital areas of brain

Exudate formation

Protein rich exudate formation

Blockage of narrow passages of brain (Ex.: Foramen of

Cerebeal edema
Monro/ Foramen of Luska)

Increased intracranial tension (ICT) Blockage of CSF circulation

Obstructive hydrocephalus

Problem in re-absorption of CSF through arachnoid

granulations

Communicating hydrocephalus (Image below)

 133

What are the clinical signs and symptoms of this condition?

Symptoms
Classical:

a. Fever
b. Headaches
c. Photophobia.

Others:

a. Irritability
b. Lethargy
c. Mental confusion
d. Nausea and vomiting
e. Altered consciousness.

Signs

Classical:

a. Kernig sign
b. Brudzinski sign.
 134

Others:

Skin

a. Erythematous maculopapular rash -> purpura and petechiae (Neisseria)

b. Tache cerebrale - stroke skin with a blunt instrument -> 30-60 sec ->
raised red rash.

Central Nervous System

a. Seizures: Focal/ generalized; tonic/ clonic/ tonic-clonic

b. Respiratory distress
c. SIADH (Syndrome of inappropriate ADH secretion),
d. Focal neurologic signs:
 Cranial nerve palsies
 Hemiparesis
 Quadriparesis
 Visual signs: Papilledema/ visual field defects (due to cortical venous
or arterial thrombosis)
 Auditory signs: Ataxia & hearing loss (due to labyrinthitis)
 Altered state of consciousness:
 Obtunded,
 Semicomatose,
 Comatose.

Systemic Conditions:
Signs of cellulitis, septic arthritis, otitis media, pneumonia etc. which may
act as the source of infection.

Name some of the sequelae/ complications of meningitis.

1. Involvement of frontal lobe-------- Behavioural change.

2. Involvement of occipital lobe------- Cortical blindness.
3. Cranial nerve palsy:
a. CN 2: Blindness.
b. CN 3/4/6: Diplopia/ squint.
c. CN 9/10/11/12: Bulbar palsy.
4. Basal ganglia involvement: Hypotonia. (as basal ganglia controls the
tone of muscles in our body).
 135

Describe the diagnostic tests usually used to diagnose meningitis and etiology.

The following diagnostic tests/ methods are usually used in general:

1. CSF study by lumber puncture (LP)
2. Serological tests
3. Gram stain and ZN stain
4. Culture and sensitivity testing
5. Radioimaging.

CSF Study

Parameters Normal Pyogenic Viral Tubercular

meningitis meningoencephalitis meningitis
Cell count 0-6 >1000 100-500 50-300
(lymphocyte) (PMN) (predominantly (lymphocyte)
lymphocytic with
PMN fraction<30%)
Protein 20-40 >100 50-100 >50 at early
(mg/dl) stages, may be
very high in late
stages
Glucose 40-80 Very low, Unaltered <40
(mg/dl) may be 0
RBC 0-2 10-50 in HSV encephalitis (with multifocal seizures).

Serological tests

1. Antibody detection:
For this purpose, 2 types of serum can be used:
a. Acute serum for acute cases (IgM detection).
b. Convalescent serum for chronic cases (IgG detection).
2. In special situations like epidemic, special tests can be applied:
a. NS1 and IgM testing in dengue epidemic.
b. Rapid influenza diagnostic test (RIDT) in influenza epidemic.

Identification of causative organism by LP

1. Gram stain:
a. Gram +ve organisms (Strep. pneumoniae, Staph. Aureus etc.).
b. Gram –ve organisms (E.coli, Klebsiella, N.meningitidis etc.).
2. ZN stain: For identifying tubercle bacilli.
 136

3. PCR: For identifying causative viral agents.

Radioimaging
 Neuroimaging, especially MRI has become the most sensitive diagnostic
technique for finding damages/ complications already occurred in case
of meningitis.
 The usual nonspecific findings on MRI, which can be found in meningitis
of all etiologies are:
a. Cerebral edema.
b. Infarct.
c. Hydrocephalus.

The CT scan reveals edema

of the right frontal lobe
(white arrows) with
moderate hydrocephalus
(double-headed arrow).
There is a low-attenuation
lesion in the left anterior
thalamus (yellow arrow).

 Only the following 2 etiological agents produce specific findings on

neuroimaging:
a. HSV encephalitis: Involvement of temporo-parietal regions.

MR image showing
high signal in the
temporal lobes
 137

b. Japanese B encephalitis: Involvement of thalamus.

MRI of a JE patient
showing bilateral thalamic
hyperintensity

Outline the management strategy of a suspected case of meningitis.

Management

Supportive Initial empirical

Specific therapy
treatment therapy

Supportive treatment:

 Mannitol: To reduce intracranial tension immediately.

 Head end elevation to 15-30°: To encourage jugular venous return.
 Antipyretics: To control fever.
 Short term mechanical hyperventilation: To recover cerebral
autoregulation (which is impaired in meningitis).
 Seizure control:
a. Diazepam/ Lorazepam.
b. Phenytoin sodium (Loading dose and Maintenance dose
subsequently).
 Diuretics (Furosemide): To treat/ prevent cerebral edema
 138

 Steroids (Dexamethasone): To reduce the incidence of neurologic

complications
 Maintain fluid electrolyte balance: To prevent incidence of SIADH.

Initial empirical therapy:

Before the specific etiologic agent has been discovered, the initial empirical
therapy of choice recommended is (IV):
a. Ceftriaxone/ Cefotaxime + Vancomycin or,
b. Ampicillin + Chloramphenicol.
If fever/ signs of meningeal irritation still persist after 48 hours of therapy, then
a LP should be done and choice of antibiotics should be reviewed.

Specific therapy:
It is based on diagnostic confirmation of etiologic agent on LP:

Etiologic agent Specific therapy Duration

Meningococcus/ Penicillin/ Ceftriaxone/ 10-14 days
Pneumococcus Cefotaxime
Listeria Ampicillin
H. influenzae Ceftriaxone/ Cefotaxime
Staph. aureus Vancomycin 3 weeks
(MRSA suspected case)
Gram negative bacilli Ceftriaxone/ Cefotaxime/
Ceftazidime
Tubercle bacilli HRZES A minimum of
12 months
HSV1/ HSV 2/ VZV Acyclovir 14-21 days
CMV Ganciclovir 2 weeks
 139

Tubercular Meningitis

What do you mean by “chronic” meningitis?

When the duration of the meningitis is > 4 weeks, it is called “chronic”.

Give 2 examples of chronic meningitis?

1. Tubercular meningitis.
2. Inadequately treated pyogenic meningitis.

Describe the pathogenesis of tubercular meningitis?

 There is a primary focus in every tubercular infection.
Ex.:
Lung,
Intestine,
Cervical lymph nodes etc.
 From the primary focus, tubercle bacilli spread through lympho-
hematogenous routes/ through dissemination into blood stream.
 Finally the bacilli lodge into the meninges.
 The time between the first bacterial lodge into meninges and
development of symptoms of meningitis is usually between 3 months to
1 year.
 The initial inflammatory reaction of meninges to tubercle bacilli is PMN
in nature (Polymorphonuclear [PMN] cells like neutrophils), however,
after 1-2 days, it changes to lymphocytic nature.

Describe the extension of disease from meninges to other brain areas.

 The primary site affected in tubercular meningitis is sub-pial space of
outer cortex (It is the space beneath the pia matter that separates pia
from glia limitans).
 The foci initially formed in sub-pial space are called “Rich’s foci”.
 140

Subpial space

 From the subpial space, the infection spreads into the following routes:

Subpial space

Subarachnoid space

Inflammation

Thick gelatinous material

(composed of fibrin and protein)

Base of the brain Formation of a thick coat in the CSF space

Obstruction of foramen of Magna/ Luska Defective absorption and accumulation of CSF

Obstructive hydrocephalus Communicating hydrocephalus

 141

What are the other mechanisms by which tubercular meningitis affects our
brain?
Vasculitis:
 The pia mater allows blood vessels to pass through and nourish the
brain. The perivascular space created between blood vessels and pia
mater functions as a lymphatic system for the brain. So, in case of any
inflammation occurring in the pia, vasculitis occurs.

 This vasculitis affects mainly medium and small sized vessels and called
periarteritis (affecting the outer portion of the artery).
 This reaction is severe around the circle of Willis.
 It gradually gives rise to thrombosis formation and segmental infarction
of brain.
 The areas of brain most commonly having infarction are:
a. Thalamus
b. Basal ganglia
c. Internal capsule.
Cerebral edema:
The brain tissue immediately underlying the tuberculous exudate shows
various degrees of oedema, perivascular infiltration, and a microglial reaction,
a process known as ‘border zone reaction’.
 142

What are the pathological variations of TB meningitis?

Pathological classification of TB meningitis

Tuberculous Spinal
Typical TM Serous TM
encephalopathy meningitis

Types Description
Typical Characteristic CSF findings and clinical features.
Serous It is a hypersensitivity reaction to tuberculoprotein.
It has an acute presentation although shows minimum CSF changes.
Tuberculous Exclusively present in infants and children.
encephalopathy There is no meningeal irritation/ focal neurological signs.
But there is a diffuse cerebral disorder.
Spinal Associated with Pott’s disease of spine. It is a leading cause of
paraplegia (impairment of motor/ sensory function in lower
extremities) in developing countries.

What are the clinical features of tuberculous meningitis?

There are 3 stages in the evolution of clinical signs and symptoms of TBM:
Stages Clinical signs and symptoms
Nonspecific stage This stage lasts for 1-4 weeks; the usual nonspecific symptoms
are:
 Low grade fever
 Evening rise of temperature
 Lethargy
 Anorexia
 Headache
 Night sweats
 Poor feeding and abdominal pain in infants etc.
Stage of meningitis There are 2 types of signs seen in this stage:
 Meningeal irritation signs:
1. Neck rigidity
2. Kernig’s sign
3. Brudzinski’s sign.
 143

 Focal neurological signs:

1. Loss of sphincter control
2. Convulsion.
Stage of Profound loss of consciousness with:
encephalitis  Rise of temperature
 Unequally dilated pupil
 Altered respiratory pattern (Cheyne-Stroke’s breathing)
 As coma deepens, the following types of rigidity may
appear:
1. Decorticate rigidity
2. Decerebrate rigidity.

What do you mean by decorticate and decerebrate rigidity?

 Basically upper motor neurones (UMN) are divided into 2 groups:
1. Flexor biased UMNs: Corticospinal tracts and rubrospinal tracts
2. Extensor biased UMNs: Reticulospinal and vestibulospinal tracts.
 Therefore lesions involving UMN tracts above the midbrain (cerebral
hemisphere, internal capsule and thalamus) result in decorticate
rigidity with extension of lower limbs and some flexion of upper limbs
(as rubrospinal tract remains intact).
 144

 Lesions involving UMN tracts below the midbrain (causing brainstem

damage) result in decerebrate rigidity with extensions of both the limbs
due to unopposed extensor biased upper motor neurons.

 Progression from decorticate to decerebrate rigidity is an ominous sign,

as it indicates that the lesion is progressing from the cortex to the
brainstem, and decerebration is usually fatal.
 145

Describe the course of tubercular meningitis in short according to stages.

Stage 1

Full recovery in
100% treated

Stage 2

75% recovery if Sequelae in 25%

treated patients treated

Hydrocephalus/ Motor deficits (Hemiplegia/ Paraplegia/ Quadriplegia etc)/

Alteration of special sense (deafness/ blindness etc.)/ Low IQ/ Behavioural
disorders/ Bulbar palsy/ Facial palsy/ Hypothalamic syndrome (eats
vigorously)/ Diabetes incipidus/ Minimal brain dysfunction.

Stage 3

50-60% mortality 40-50% sequelae

 146

How will you diagnosis a case of tubercular meningitis?

CSF study by lumber puncture:
 Colour: Clear transparent/ yellow (xanthochromia).
 Cobweb coagulum formation (lymphocytes and tubercle bacilli
enmeshed in a dense framework made up of fibrin).
 CSF may be kept in a refrigerator for some hours to facilitate cobweb
coagulum formation.
 Cell count: 50-150 (infiltrate is predominantly lymphocytic in nature).
 Protein: 100-300 mg/dl; sometime high levels as 3-5 gm/dl may be seen.
Other diseases where a similar high protein content in CSF is seen are:
a. Froin syndrome
b. GB syndrome
c. Spinal block syndrome.
But, in these diseases, the cell count in CSF is usually close to normal
(unlike tubercular meningitis).
 BACTEC test may give results within 1-2 days. So may be preferred in
diagnostic purpose.
 Adenosine Deaminase test (ADA) is a sensitive and specific test for
diagnosis of tubercular meningitis.
Radioimaging:
Radio-imaging by CT/ MRI may show any of the following abnormalities:
a. Basal exudates
b. Infarct commonly seen in thalamus/ basal ganglia/ internal capsule
c. Hydrocephalus: May be obstructive/ communicating
d. Cerebral edema.
 147

Tell the general lines of management of a case of tubercular meningitis.

Supportive treatment:
1. Adequate nutrition
2. Nasogastric tube feeding
3. Proper fluid therapy to prevent dehydration
4. Anticonvulsant drugs (Diazepam/ Lorazepam) at times of convulsion
5. Care of the skin
6. Frequent posture change
7. Passive physiotherapy initially, then change it to active
8. Antiemetic drugs in case of vomiting
9. Anticonvulsants in case of seizures
10.Steroid (Prednisolone: 1-1.5 mg/kg/day for 4-6 weeks). It has 2 roles:
a. Reduction of cerebral edema
b. Reduction of neurological sequelae.

Specific therapy:
2 months of (HRZ+ E/S) + 10 months of (HR).
Total duration of treatment is recommended for at least 12 months.
 148

Thalassemia
Theory and Viva questions

1. What does “Thalassemia” mean?

Thalassa: The sea (The disease was first found on the basin of
Mediterranean sea).
Emia: Related to blood.

2. What is the normal chain composition of adult human Hb and its

variations?

The normal adult Hb is HbA. It comprises of 2 α chains and 2 β chains.

The normal fetal Hb is HbF. It comprises of 2 α chains and 2 γ chains.
Another variety of Hb is HbA2. It comprises of 2 α chains and 2 δ chains.

3. What do you know about the pathogenesis of Thalassemia?

Thalassemia is an inherited disorder of haemoglobin synthesis.
 It results from an alteration of globin chain formation, which causes
a decreased rate of globin chain formation.
Ex:
In α-thalassemia, fewer α-globin chains are produced and in β-
thalassemia, fewer β-globin chains are produced.
 This results in an imbalance between rate of production of α and β
globin chains; leading finally to an early destruction of RBCs and
severe anemia.
Ex.:
In α-thalassemia, the haemoglobin within RBC contains fewer α-
globin chains and more β-globin chains; leading to unstable
tetramer formation and early destruction of RBCs.
In β-thalassemia, the haemoglobin within RBC contains fewer β-
globin chains and more α-globin chains; leading to RBC membrane
damage and early destruction of RBCs.

4. Are the common symptoms of β-thalassemia major manifest from birth?

No, the symptoms usually appear after 3-6 months of birth. In some
patients, the symptoms may even appear after 3-5 years of age.
 149

5. Why the symptoms of β-thalassemia major manifest usually at the age of 3-

6 months?

Usually at the age of 3-6 months, there is a cessation in the production of

fetal Hb (HbF). So the symptoms start manifesting at that time.

6. What are usually the first chief complains of the patient?

a. Progressive pallor,
b. Malaise,
c. Inability to feed,
d. Repeated episodes of infection/ cough and cold/ fever etc.

7. Is there a possibility to get jaundice in a patient with thalassemia?

Yes, there may be mild- moderate jaundice in thalassemia.

8. What are the mechanisms of jaundice in thalassemia and what are the
possible causes?

 Mechanism of jaundice in thalassemia:

a. Ineffective erythropoiesis (major mechanism),
b. Intravascular hemolysis (minor mechanism).

 Possible causes of jaundice in thalassemia:

a. Iron overload due to repeated blood transfusions,
b. Infection by HBV (mainly), HCV, HIV, Syphilis, P.falciparum etc.
c. Formation of anti-RBC antibody from repeated blood
transfusions.

9. Is there a possibility to get edema in a patient with thalassemia?

Yes.

10. What are the causes of edema in a thalassemia patient?

 From severe anemia in the patient,
 From a pre-existent heart problem in the patient.
 150

11. What are the other symptoms of anemia found usually in a thalassemia
patient?
 Irritability,
 Reduced physical activity,
 Intolerance to exercise,
 Malaise,
 Dizziness.
 Fainting.

12. How can you grade pallor and Hb level?

Grade of pallor How to detect? Roughly estimated Hb level

Mild Contrast of palmar crease colour >9 gm/dl
> Colour of palmar surface
Moderate Contrast of palmar crease colour 6-9 gm/dl
= Colour of palmar surface
Severe Contrast of palmar crease colour <6 gm/dl
< Colour of palmar surface

13. How you can confirm a diagnosis of thalassemia?

I will do the following tests to confirm a diagnosis of thalassemia:

1) Peripheral blood smear:
A picture of microcytic hypochromic anemia with the following
characteristic features:
 Target cell: A RBC with central condensation of Hb and a
peripheral thin rim of Hb. Between these two layers, there is a Hb
free zone.
 Normoblast.
 Reticulocytes.

2) Red cell indices:

MCV ↓, MCH ↓, MCHC ↓.
RDW is usually normal but it may vary widely.
The RDW and MCV can be used simultaneously to detect some major
causes of anemia:*
 151

RDW MCV Interference

Normal Normal Normal
Normal Low Thalassemia
High Low Iron deficiency anemia
High Normal Aplastic anemia
High High Megaloblastic anemia

3) Hemoglobin electrophoresis:
It will show a rise of fetal Hb (HbF sometimes may rise upto 90% of total
Hb). It will also show a rise in HbA2 (may be >3.5 gm%).

4) Iron parameters:
Serum Iron: High.
Serum ferritin: High.
Free red cell protoporphyrin: High.
TIBC (Total iron binding capacity): Low.

5) RBC half-life estimation by adding difluorophosphate and Sodium

chromate will show a reduced half-life of RBC (may decrease to 25-30
days where normal is 60 days).

6) X-Ray Skull:
It will show “hair on end” appearance.
Mechanism: Normally the brain is kept in a bony covering which has an
outer and an inner table. Within these 2 tables, there are numerous
trabeculi, which are surrounded by blood vessels.
In thalassemia, the hyperactive bone marrow expands in all parts of
body, as in brain. For this expansion, the tables are spaced and within
them, the trabeculi are stretched and straightened. This straightening
of trabeculi is responsible for the “hair on end” appearance in the X-Ray
skull of a patient of thalassemia.

7) Other radiological signs of thalassemia:

a. Squaring of metacarpals.
b. Mossaic pattern of trabeculi of carpal bones.
c. Osteoporosis of spine.
 152

14. How a case of diagnosed thalassemia is managed? (With all relevant

questions answered)
There are 2 components in the mainstay of treatment of thalassemia:
a. Packed cell transfusion.
b. Chelation therapy.
Packed cell transfusion
Why packed cells are chosen prior to whole blood?
Packed cells are chosen prior to whole blood in case of a blood transfusion
in a thalassemia patient because the volume of packed cells are much less
than whole blood.
So, thalassemia patients, who are already experiencing a hypervolemic
condition (because of a hyperdynamic circulatory state from chronic
anemia), may develop an episode of cardiac failure if whole blood is
transfused to the patient (due to a sudden volume overload on the heart).
When the treatment of thalassemia should be initiated? Is there any
exception?
As soon as the diagnosis is confirmed, treatment is initiated.
EXCEPT, If the age of onset is > 18 months of age, then the patient is at first
observed to rule out thalassemia intermedia.
Below which Hb level, regular transfusion is indicated and why?
If Hb level is <7 gm%, then regular transfusion regimen is indicated
because:
a. Chance of hemosiderosis rises significantly below this level.
b. Cosmetic deformities (especially over the face) will worsen.
c. The child will show reduced physical activity, malaise, intermittent fever
and other signs of anemia.
What are the different regimens of blood transfusion in thalassemia
patients?
Regimen name Set to control blood Hb to which level?
Palliative 8.5 gm %
Hyper-transfusion 12 gm %
Moderate transfusion# 9.0 – 11.5 gm %
# It is the preferred option in India.
 153

What are the criteria for blood transfusion in thalassemia?

Blood transfusion in thalassemia should follow the criteria given below:
a. It should be group and type specific.
b. Hematocrit value of the transfused blood should be 65%-75%.
c. The blood should be washed with triple saline (to remove any pre-
existing antibody attached to the RBC membrane).
d. It should be cross matched by “Coomb’s test”.
e. It should be as fresh as possible (not more than 4-5 day old).
What do you mean by “leuco-depletion”? What are the advantages of
“leuco-depletion” in a thalassemia patient and what are the methods?
Leuco-depletion is defined as removal of WBCs from a given sample of
blood.
The main advantage of leuco-depletion in transfusing a thalassemia patient
is that the chance of non-febrile transfusion reaction is decreased in the
leuco-depleted blood.
The various methods of thalassemia are:
a. Laminar flow,
b. Cold centrifuge,
c. Leucocyte filter,
d. Frozen cells.
What should be the rate of transfusion in a thalassemic patient?
 10-15 ml/kg packed cells every 3-4 weeks.
 The interval of 3-4 weeks is preferred because after 1 unit of PRBC
transfusion, the Hb level in the patient rises by approx. 3 gm% and
the rate of decrease of Hb level in a thalassemic patient is approx. 1
gm% every week. So, by the end of 3 weeks, there will be need for
transfusion.
 In a patient with any kind of cardiac dysfunction, the rate of
transfusion should not exceed 2-3 ml/kg body weight/hour because
of the risk of volume overload.
What are the different infections that may occur in a repeatedly transfused
patient?
a. HBV
b. HCV
 154

c. HIV
d. Yersinia (more often a complication of chelation therapy)
e. Malaria.
Chelation therapy
What are the causes of iron overload in a thalassemic patient?
a. More iron absorption from the gut (due to anemia),
b. Repeated transfusions,
c. Possible lack of excretory mechanism of iron from body.
What are the chelating agents commonly used now a days?

Chelating agents

Parenteral Oral

Desferoxamine Deferiprone

Bidentate (having 2 arms to bind iron) Hexadentate (having 6 arms to bind iron)

Mainly removes iron from blood Mainly removes iron from tissue

Dose: 40-60 mg/kg/day is infused over a period of 8-12 hours

Dose: 75 mg/day
during the night for a total duration of 5-6 days a week

Side effect: ARDS, Neurotoxicity Side effect: Arthritis, Neutropenia, Agranulocytosis

Nowadays, a third chelating agent called Deferasirox is being used to

remove both extracellular and intracellular iron (from both blood and
tissues). The recommended dose is 30 mg/kg/day. Important side effects
include renal and liver toxicity.
 155

Splenectomy
What do you mean by “hypersplenism”?
Hypersplenism is defined as significantly enlarged spleen with
pancytopenia in peripheral blood.
When will you suspect hypersplenism in a thalassemia patient?
When the requirement of packed cells in a thalassemic patient rises to
>250 ml/kg/year, hypersplenism is suspected.
What are the causes of “hypersplenism” in a thalassemia patient?
a. Inadequate/ irregular transfusion
b. Chronic liver disease by HBV/HCV contracted through blood borne
infections
c. Allo-immunization.
What are the important points that should be kept in mind before a
splenectomy is attempted?
a. Pneumococcal and H.influenzae (type b) vaccination.
b. The age of the child should be above 5 years (as the incidence and
severity of H.influenzae infection is much more and severe in children
aged <5 years).
c. Lifelong prophylaxis against infections.

15. What are the complications of thalassemia?

Most of the complications of thalassemia result from toxic effects of iron
overload on different organs in the body. The iron overload is often a result
of irregular blood transfusions.
a. Cardiomyopathy: Due to direct cardiac damage,
b. Cirrhosis: Due to damage to hepatocytes,
c. Diabetes: Due to destruction of pancreatic β-cells,
d. Growth hormone deficiency: From damaging effect on pituitary cells.
e. Hypothyroidism: From damaging effect on thyroid gland.
f. Osteoporosis and fracture: Due to increased fragility of bones.

16. What are the different pharmacological agents now being tried to treat
thalassemia?
Pharmacological agent Mechanism of action
Hydroxyurea This agent increases the synthesis of γ-chains, so
 156

the amount of HbF in circulation increases (α2γ2),

which has a higher Hb transport capacity; thus
reducing needs for repeated transfusions.
5 Aza- Cytidine Induction of fetal Hb synthesis through expression
of silenced genes, normalization of bone marrow
and reduced need for repeated transfusions.
Vitamin C It may be given orally 1-2 hours before
administering Desferoxamine because it causes a
redistribution of body iron from tissue to blood,
upon which Desferoxamine can act faster.
Folic acid It may be used along with the transfusion-chelation
dual therapy because it reduces hyperactivity of
bone marrow by supplementing the process of DNA
synthesis.

17. What are the screening tests that may be applied in a mass scale to control
thalassemia?
a. NESTROF test,
b. Universal hemoglobin electrophoresis.
c. Chorionic villi biopsy/ Amniocentesis.

18. How the NESTROF test is performed and how interpretation is drawn?
NESTROF= NAKED EYE SINGLE TUBE RED CELL OSMOTIC FRAGILITY TEST.
Note:
A 0.9% sodium chloride solution is isotonic with plasma. When osmotic
fragility is normal, red cells begin to hemolyze when suspended in 0.5%
saline; 50% lysis occurs in 0.40–0.42% saline, and lysis is complete in 0.36%
saline.
 2 test tubes are taken.
 In one tube, 2 ml 0.36% buffered saline solution is put.
 In the other tube, 2 ml distilled water is put.
 In either tube, patient’s blood is added.
 In a normal person, patients RBC will be completely lysed by the
hypotonicity of the solution. This lysis process will be seen as a
haziness of the solution.
 In a patient with thalassemia, patients RBC will not be lysed by even
lower concentrations of normal saline.
 157

Thyroid hormone synthesis (Steps with Description)

IODINE TRAPPING
 Iodine present in the plasma is actively taken up through the basolateral
surface of the thyrocytes into the thyroid gland against both chemical and
electrical gradient.
 The resting membrane potential (RMP) of acinar (follicular) cells is about -
50 mV. So, when electronegative iodine is taken up into these cells, it has to
be transported against an electrical gradient.
 The basolateral membrane of thyrocytes facing the capillaries contain a
symporter that transport 2 Na+ and 1 I- ion into the cell with each cycle.
o This Na+/I- symporter (NIS) is capable of producing intracellular I-
concentration that is 20-40 times greater than plasma. So, normal
(thyrocytes: plasma) iodine concentration becomes about (20-40):1.
 So, for uptake of I- into thyrocytes, I- has to be transported against a
chemical concentration gradient also.
 The problem of facing these chemical and electrical gradient effectively is
solved with the help of secondary active transport system involving the NIS
symporter and Na+ K+ ATPase pump.
o The energy provided by Na+ K+ ATPase pump is utilized by NIS
symporter to transport 1 I- into the thyrocytes.

Note:
TSH induces both NIS expression
and penetration of NIS in the
basolateral membrane where it
can mediate sustained iodide
uptake.
 158

IODINE TRANSPORT AND EXIT INTO LUMEN

 The absorbed iodide migrates into the luminal (apical) membrane of the
cell and enters the lumen containing colloid, where the initial steps of
thyroid hormone synthesis take place.
 The exit/ transport of I- through the apical membrane is mediated by Cl-/I-
exchanger known as “Pendrin”.

OXIDATION OF IODIDE
At the interface between thyrocyte
and colloid, the absorbed iodide is
oxidized to iodine atoms. This
reaction is mediated by Thyroid
peroxidase, which is a membrane
bound enzyme found in apical
membrane. Hydrogen peroxide is
required for this reaction.
 159

ORGANIFICATION OF IODINE/ IODINATION

 As soon as the iodine is produced, it is incorporated into the C3 position of
the tyrosine residue attached to the thyroglobulin molecule in the colloid.
The resultant compound is mono-iodo-tyrosine (3’-MIT).
 Then 3’-MIT is next iodinated on the C5 to form di-iodo-tyrosine (3, 5 DIT).
 Both the reactions are mediated by Thyroid peroxidase enzyme.

𝐼2 + 𝑇𝑦𝑟𝑜𝑠𝑖𝑛𝑒 = 3′ 𝑀𝐼𝑇
𝐼2 + 3′ 𝑀𝐼𝑇 = 3,5 𝐷𝐼𝑇
Note: This process of organification is inhibited by thiouracil compounds.
COUPLING REACTION
 In coupling reaction, 2 DIT molecules undergoes oxidative condensation to
form thyroxine/ T4/ Tetra-iodo-thyronine with the elimination of alanine
side chain from the molecule that forms the outer ring.
 T3/ Tri-iodo-thyronine is formed by condensation of MIT with DIT.
 A small amount of rT3 (Reverse T3) is also formed probably by
condensation of DIT with MIT. rT3 is biologically inert.
 All he reactions are mediated by Thyroid peroxidase.
3,5 𝐷𝐼𝑇 + 3,5 𝐷𝐼𝑇 = 3,5,3′ , 5′ 𝑇4 + 𝐴𝐿𝐴𝑁𝐼𝑁𝐸
3′ 𝑀𝐼𝑇 + 3,5𝐷𝐼𝑇 = 3,5,3′ 𝑇3 + 𝐴𝐿𝐴𝑁𝐼𝑁𝐸
3′ 𝑀𝐼𝑇 + 3,5 𝐷𝐼𝑇 = 3, 3′ , 5′ 𝑟𝑇3 + 𝐴𝐿𝐴𝑁𝐼𝑁𝐸

RELEASE OF THYROID HORMONES

 Thyroid hormone so produced remain a part of thyroglobulin molecule until
needed. So, colloid represents a reservoir of thyroid hormone and humans
can ingest a diet completely devoid of iodine upto 2 months before a
decline in the circulating level of thyroid hormone is seen.
 When there is a need for thyroid hormone secretion, the colloid containing
hormone is internalized by thyrocytes through receptor mediated
 160

endocytosis. The receptor in thyroglobulin mediating this uptake is called

megalin, which is present in the apical membrane.

 The endocytotic vesicles are then fused with lysosomes to form endo-
lysosome containing hormones.
 Proteolytic enzymes within the lysosome hydrolyses the peptide bonds of
thyroglobulin and attached iodinated residues releasing MIT, DIT and free
T3, T4.
 161

 The free T4 and T3 are released into cytosol and thence capillaries and
transported through blood.
 MIT and DIT are not secreted. They are deiodinated by a microsomal
iodotyrosine deiodinase liberating iodine and tyrosine which are then
recycled. But this enzyme has no action on iodo-thyronines. So, T3 and T4
remains intact and released into circulation.

DEIODINATION
T3 is an active hormone where T4 is prohormone as a source of T3. There are 3
types of deiodinase: